Vital Flora Adult 55+ Daily Probiotic Shelf Stable by Brenda Watson's Vital Planet

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if apple juice consumption is beneficial in patients with Alzheimer disease. Details: A small clinical study in adults with moderate to severe Alzheimer disease shows that drinking 4 ounces of apple juice twice daily for one month does not improve cognitive function when compared with baseline. However, according to caregiver assessment, it seems to improve aspects of mood and behavior, such as anxiety, depression, apathy, delusion, and agitation, when compared with baseline (94422). The validity of this finding is limited by the lack of a comparator group.
• Cancer. It is unclear if apple consumption is beneficial for preventing cancer. Details: Some population research has found that eating one or more apples daily may be associated with a decreased risk of esophageal, colorectal, larynx, or breast cancer when compared with eating less than 1 apple daily (31688). Also, a case-control study in adults with lung cancer has found that increased apple consumption may be associated with a reduced risk of lung cancer (3470).
• Dental plaque. It is unclear if apple consumption is beneficial for reducing dental plaque. Details: A small clinical study in healthy patients shows that eating an apple is less effective for reducing plaque than brushing teeth. Eating an apple actually increases plaque when compared with baseline, although it decreases the measure of bacterial vitality (99447).
• Diabetes. It is unclear if consumption of powdered, dehydrated apple is beneficial in patients with type 2 diabetes. Details: A small clinical study in patients with type 2 diabetes shows that substituting 26-52 grams of white wheat flour in bread with powdered, dehydrated apple and consuming the bread daily for up to 4 weeks does not improve fasting blood glucose or postprandial glucose levels when compared with a low-fiber white bread control (13141).
• Diarrhea. It is unclear if apple juice consumption is beneficial in infants with severe diarrhea. Details: A clinical study in infants with severe diarrhea shows that drinking apple juice 15 mL/kg twice daily during episodes of diarrhea results in more fecal loss when compared with drinking water (31687).
• Metabolic syndrome. Although there has been interest in using apple for metabolic syndrome, there is insufficient reliable information about the clinical effects of apple for this purpose.
• Muscle strength. Oral apple extract has only been evaluated in combination with other ingredients; its effects when used alone is unclear. Details: Small clinical studies in resistance trained males show that taking a specific blend of ancient peat and apple extract (elevATP, VDF FutureCeuticals Inc.) 150 mg daily as a liquid with liposomes (QuSomes, BioZone Laboratories Inc.) for 12 weeks modestly increases lower body and total strength, improves lower body power output, and increases cross-sectional area of muscle when compared with placebo (94418,94419).
• Obesity. It is unclear if apple consumption is beneficial in patients with overweight or obesity. Details: A small clinical study in females with hypercholesterolemia and overweight or obesity shows that eating apples three times daily for 12 weeks is associated with weight loss of 1.2 kg, compared with weight loss of 0.9 kg in those consuming oat cookies (17997). More evidence is needed to rate apple for these uses.

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POSSIBLY EFFECTIVE

• Colic. Oral Bifidobacterium lactis seems to be beneficial for colic. Details: Clinical research in infants with colic shows that taking B. lactis BB-12 (Chr. Hansen, Hoersholm or Bifidolactis Infant, Sofar SpA) drops providing 1 billion colony-forming units (CFUs) daily for 3 or 4 weeks modestly reduces the daily number of crying episodes by about 2.5 when compared with placebo. The proportion of infants with at least a 50% reduction in crying time from baseline was 61% to 80%, compared with 22% to 32% of those taking placebo. Use of B. lactis also resulted in increased sleep time, reduced crying duration, and improved physical and emotional functioning of the caregiver. Stool frequency was decreased in one study, but was not changed in the other (107583,107587).
• Constipation. Oral Bifidobacterium lactis seems to be beneficial for constipation. Details: A meta-analysis of clinical research shows that taking B. lactis increases bowel movement frequency by about 1.5 stools weekly in adults with functional constipation. Specific strains used include LMG P-21384 as 5 billion colony-forming units (CFUs) daily, Bi-07 as 100 million CFUs daily, DN-173 010 as 12.5 billion CFUs daily, and GCL2505 as 10 billion CFUs daily for 2-4 weeks (95342). Another meta-analysis of clinical research in adults with chronic constipation shows that taking B. lactis modestly increases stool frequency when compared with taking placebo. However, there was no effect of taking B. lactis on treatment success, stool consistency, severity of straining or bloating, or gut transit time. Due to the small number of studies, the effect of B. lactis on other symptoms of constipation is unclear from this analysis (110874). A third meta-analysis shows that two specific strains of B. lactis, HN019 and DN-173 010, have medium to large effects on intestinal transit time in mainly healthy adults (110983). The effect of these strains on intestinal transit time in patients with constipation is unclear from this analysis. Clinical research in patients with low defecation frequency also shows that taking the specific B. lactis strain BB-12 (Chr. Hansen A/S) 1-10 billion CFUs daily for 4 weeks increases the odds of improved defecation frequency by about 1.3-fold when compared with placebo (92264). It is possible that any beneficial effect is limited to patients with more severe constipation. One clinical study in patients with functional constipation shows that taking the specific B. lactis strain HN019, 1 or 10 billion CFUs daily for 4 weeks, has no effect on bowel movements when compared with placebo. However, in a post-hoc analysis of patients with three or less weekly stools, this strain of B. lactis modestly increased bowel movements when compared with placebo (98737). Another clinical study in patients with mild chronic constipation shows that taking B. lactis NCC2818 15 billion CFUs daily for 4 weeks does not affect gut transit time, stool output, or symptoms when compared with placebo (102411). B. lactis has also been examined in combination with other ingredients. One small clinical trial using a specific combination product (ID-HWS1000) containing B. lactis IDCC 4301, Bifidobacterium breve IDCC 4401, Lacticaseibacillus casei IDCC 3451, Lactiplantibacillus plantarum IDCC 3501, Lacticaseibacillus rhamnosus IDCC 3201, Lactococcus lactis IDCC 2301, xylooligosaccharide, and dietary fiber as nondigestible maltodextrin, oat fiber, and psyllium husk fiber daily for 4 weeks modestly increases stool frequency and improves symptoms of functional constipation in adults when compared with placebo (107517). Another small clinical trial shows that taking yogurt 180 mL providing B. lactis HN019, L. acidophilus NCFM, and polydextrose (Litesse) daily for 2 weeks modestly improves clinical response and reduces transit time when compared with taking a control yogurt. However, there was no effect on the number of daily bowel movements (90275). Other studies have used B. lactis UABla-12, Bl-04, Bi-07, and/or HN019 in combination with Bifidobacterium bifidum UABb-10, Bifidobacterium longum UABl-14, Lactobacillus acidophilus DDS-1, and fructo-oligosaccharides (FOS) for 4 weeks (110970) or Lactobacillus acidophilus NCFM and Lacticaseibacillus paracasei Lpc-37 for 2 weeks (110979). However, there was a general lack of support for symptom improvement from these studies.
• Irritable bowel syndrome (IBS). Oral Bifidobacterium lactis seems to be beneficial for reducing symptoms of IBS when used alone. Its benefits when used in combination with other probiotics are unclear. Details: Clinical research in adults with IBS shows that taking B. lactis UABla-12 10 billion colony-forming units (CFUs) daily for 6 weeks modestly reduces the severity of abdominal pain when compared with placebo. Also, 28% of patients responded to treatment by having more than a 30% reduction in pain severity, compared with only 16% of those taking placebo. There were also improvements in abdominal distention, duration of pain, and bowel habits (107581). Additional clinical research in children aged 4-16 years shows that taking B. lactis B19 10 billion CFUs daily for 4 weeks reduces bloating, feelings of abdominal fullness, and difficulty with defecation in 25% to 50% of patients with IBS (95350). Some research has also evaluated B. lactis in combination with other probiotics. Clinical research shows that taking a product (Duolac Care) containing B. lactis, Bifidobacterium breve, Lactobacillus acidophilus, Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Streptococcus thermophilus twice daily for 4 weeks can relieve symptoms in 72% of patients with IBS (95353). Another clinical study in patients with diarrhea-predominant IBS shows that taking a specific multi-species probiotic (NordBiotic, MBM Biotix) containing B. lactis BL040, B. breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, L. acidophilus LA120, Lacticaseibacillus casei LC130, L. plantarum LP140, and Streptococcus thermophilus ST250 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516). However, multiple studies show that taking capsules or drinking fermented milk containing a combination of B. lactis BB-12, L. paracasei, and L. acidophilus La510 as 26 billion CFUs total twice daily for 2-6 months does not improve gastrointestinal symptoms in patients with IBS (90236,94696,94697).
• Respiratory tract infections. Most clinical research shows that taking Bifidobacterium lactis alone or in combination with other probiotics may reduce the risk of respiratory infections in otherwise healthy individuals. In patients who are not otherwise healthy, most clinical research shows that taking oral B. lactis has not demonstrated benefit. Details: Clinical research in infants aged 6 to 12 months shows that taking B. lactis HN019 one million colony-forming units (CFUs) per gram of follow-on formula daily for 12 weeks reduces the incidence of confirmed (9.4% vs. 0.0%) and parentally reported (25.0% vs. 9.4%) upper respiratory tract infections when compared to formula without added probiotics. Infants consumed an average of 141 grams of formula daily (110988). Another clinical trial in one month old infants shows that taking B. lactis BB-12 10 billion CFUs daily for an average of about 15 months reduces the proportion of children with respiratory tract infections until age 2 by 13% when compared with taking placebo. The frequency of recurrent respiratory tract infections was not different between groups (95381). In contrast, other clinical research in children attending day care shows that taking B. lactis BB-12 one billion CFUs daily for 3 months does not reduce the duration or incidence of respiratory tract infections (95382). Most research in children also shows that taking B. lactis in combination with other ingredients reduces the risk of respiratory infections. One clinical study shows that children ages 3-5 years who attend day-care centers have significantly fewer influenza-like respiratory symptoms when given milk containing a specific combination of 5 billion CFUs each of B. lactis and Lactobacillus acidophilus (HOWARU Protect, Danisco). Children taking this product seem to have a 45% lower risk of experiencing fever, cough, and rhinorrhea when compared with placebo. The duration of symptoms was also 2 days shorter. These patients were also less likely to use an antibiotic for their symptoms (16847). A clinical study in healthy children aged 3-10 years shows that taking 12.5 billion CFUs daily of a specific combination of B. lactis CUL34 (Lab4), Bifidobacterium bifidum CUL20, and L. acidophilus CUL21 and CUL60, plus vitamin C 50 mg daily reduces the risk of cough by 16% and sore throat by 20% and modestly reduces school absenteeism and antibiotic use when compared with placebo. However, nasal symptoms, fever, and wheezing were not reduced (106943). Another clinical study in children 3-12 years of age with a sick household member shows that taking a combination product (Up4-Junior, UAS Laboratories) containing B. lactis UABLA-12 4 billion CFUs and L. acidophilus DDS-1 1 billion CFUs with fructo-oligosaccharides 50 mg daily for 2 weeks modestly shortens the duration of respiratory infections, but does not reduce the risk of developing an infection, when compared with placebo (98439). In healthy children ages 3-6 years, taking a combination of B. lactis BB-12 and Enterococcus faecium L3 (iNatal Ped, Pharmextracta SpA) 2 billion CFUs each daily for 3 months reduces the incidence of upper respiratory tract infections by 84% compared with children not taking probiotics. The duration of infections was reduced by 50% (110991). The effect of B. lactis on respiratory tract infections has also been examined in adults. In healthy overweight adults or adults with obesity, taking 50 billion CFUs of a specific combination of B. lactis (Lab4P), B. bifidum, L. acidophilus, and Lactiplantibacillus plantarum for 24 weeks reduces the overall likelihood of having upper respiratory tract infection symptoms, such as sneezing, cough, and blocked nose, by approximately 40% when compared with placebo (103439). In college students, clinical research shows that taking B. lactis BB-12 and Lacticaseibacillus rhamnosus LGG one billion CFUs each daily for 12 weeks reduces the duration of upper respiratory tract infection by about 2 days when compared with placebo. Symptom severity was reduced by 34%. There was also a small reduction in the number of missed school days, but not work days (110993). Some research has investigated the effects of B. lactis on respiratory tract infection outcomes in patients who are not otherwise healthy. One clinical trial in children hospitalized with an acute respiratory tract infection shows that taking B. lactis Probio-M8 20 billion CFUs daily from admission until 4 weeks after discharge modestly reduces the duration of nasal, throat, and general aching symptoms when compared with taking placebo. Taking B. lactis also modestly reduced the proportion of patients requiring hospitalization of at least 7 days (110984). Despite these findings, another clinical trial in children and adolescents who are hospitalized shows that taking B. lactis 100 million CFUs daily during a hospital stay does not reduce the incidence or duration of respiratory infections, including common cold, rhinitis, sinusitis, and others, when compared with placebo (92265). Also, in older adults in long-term care, taking a combination of B. lactis BB-12 and Lacticaseibacillus rhamnosus 13-16 billion CFUs daily does not reduce the incidence of upper or lower respiratory infections when compared with placebo over a 12-month period, and increases the use of antibiotics for lower respiratory tract infections by 2.2 days (103425).

POSSIBLY INEFFECTIVE

• Dental caries. Oral Bifidobacterium lactis does not seem to be beneficial for preventing dental caries in young children. Details: Clinical research in infants shows that giving B. lactis BB-12 DSM 15954 (Chr. Hansen A/S) 5 billion colony-forming units (CFUs) daily, starting at age 1-2 months and continuing for an average of 15 months, through a sustained-release pacifier or tablet does not reduce the incidence of dental caries at age 4 when compared with placebo (107588).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children aged 6-17 years with allergic rhinitis shows that taking a specific combination product (Inatal ped Pharmaextracta) containing B. lactis BB-12 DSM 15954 and Enterococcus faecium L3 LMG P-27496 2 billion colony-forming units (CFUs) each with oligofructose daily for 3 months prior to a high allergen exposure period the period modestly reduces symptoms of allergic rhinitis and the need for corticosteroids and/or oral antihistamines when compared with baseline (107582). However, other clinical research shows that drinking 250 mL of fermented milk containing B. lactis BB-12 50 billion CFUs, Lacticaseibacillus rhamnosus GG 50 billion CFUs, and Lactobacillus acidophilus La-5 5 billion CFUs from 36 weeks' gestation until 3 months postpartum does not reduce the incidence of allergic rhinitis in the child at 6 years of age when compared with placebo milk (96893).
• Antibiotic-associated diarrhea. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 6 clinical trials in hospitalized or outpatient adults shows that taking B. lactis in combination with up to 8 other probiotic strains reduces the risk of antibiotic-associated diarrhea by 30% when compared with taking placebo (107635). However, individual clinical trials have mixed results. Some specific combination products containing B. bifidum have shown benefit for antibiotic-associated diarrhea (AAD). One such product is Ecologic AAD, which contains B. lactis NIZO 3680, Bifidobacterium bifidum NIZO 3804, Enterococcus faecium NIZO 3886, L. acidophilus NIZO 3678 and NIZO 3887, Lacticaseibacillus paracasei NIZO 3672, Lactiplantibacillus plantarum NIZO 3684, Lacticaseibacillus rhamnosus NIZO 3689, and Ligilactobacillus salivarius NIZO 3675. Another evaluated product contains B. lactis BB-12 5.9 billion CFUs daily, L. rhamnosus GG 5.2 billion CFUs, and L. acidophilus La-5 8.3 billion CFUs daily. However, other combinations do not appear to be beneficial. These include B. lactis BB-12 and L. acidophilus LA-5; B. lactis BB-12 and L. rhamnosus; B. lactis, B. bifidum, and L. acidophilus; and B. lactis W51, B. bifidum W23, L. acidophilus W37, L. acidophilus W55, L. paracasei W20, L. plantarum W62, L. rhamnosus W71, and L. salivarius W24 (90239,92255,94692,95348,95405,103425,110969). It is too soon to know which combinations might be most beneficial, if any, for preventing AAD.
• Atopic dermatitis (eczema). It is unclear if oral Bifidobacterium lactis is beneficial for the prevention or treatment of atopic dermatitis. Details: Some research has evaluated B. lactis for TREATING atopic dermatitis. One very small clinical study shows that giving infants a formula containing B. lactis BB-12 (Chr. Hansen A/S) 30-80 billion colony-forming units (CFUs) daily helps reduce the severity of eczema and the markers for allergic responses, including soluble CD4 in serum and eosinophilic protein X in urine when compared with baseline (3458). However, preliminary clinical research shows that giving B. lactis CNCM I-3446 10 billion CFUs to infants as an adjunct to standard topical treatment daily for 3 months does not reduce eczema severity when compared with placebo (90256). B. lactis has also been investigated in combination with other ingredients. In children, taking B. lactis as part of a multi-ingredient formulation for 8 or 12 weeks modestly reduces symptom severity and the need for topical corticosteroids when compared with placebo (107531,110995). In these studies, 1 billion CFUs of a 1:1:1 combination of B. lactis CECT 8145, Lacticaseibacillus casei CECT 9104, and Bifidobacterium longum CECT 7347 daily was used in children ages 4-17 years for 12 weeks (107531) or B. lactis UABLA-12 was taken in combination with Lactobacillus acidophilus DDS-1 for a total of 10 billion CFUs daily along with fructo-oligosaccharide 100 mg (DDS Junior) daily for 8 weeks by children ages 1-3 years (110995). B. lactis-containing probiotics have also been investigated for PREVENTING atopic dermatitis. A meta-analysis of small- to medium-sized studies shows that providing mixed strains of lactobacilli and bifidobacteria to infants during pregnancy and/or in early infancy prevents atopic dermatitis in the child by approximately 40% over the next 0.5-2 years (107503). Although this analysis was not limited to studies examining the effects of B. lactis, seven of the nine studies used B. lactis as part of a combination product. Individual studies included in the analysis have shown that taking a combination of B. lactis, Bifidobacterium bifidum, Ligilactobacillus salivarius, and Lacticaseibacillus paracasei during pregnancy from approximately 35 weeks' gestation until birth, and then giving this combination to the infant after birth until 6 months of age, does not reduce the incidence of eczema at age 2 years, although it does appear to reduce the risk of atopic sensitization by 57% (90234). A secondary analysis of a clinical study included in this analysis in infants aged 8-14 months found that taking a daily mixture of B. lactis and Lacticaseibacillus rhamnosus 1 billion CFUs each daily for 6 months is associated with a lower incidence of eczema when compared with placebo (102286). Also, some clinical research shows that supplementation with 250 mL of fermented milk containing B. lactis BB-12, Lacticaseibacillus rhamnosus GG, and Lactobacillus acidophilus La-5 starting at 36 weeks' gestation and continuing until 3 months postpartum, without supplementation in the infant, reduces the overall occurrence of atopic dermatitis in the child at 2 years of age. At 6 years of age, the effect appears to be inconclusive (96893).
• Bipolar disorder. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with bipolar disorder who were recently hospitalized for a manic episode shows that taking a combination probiotic containing B. lactis BB-12 and Lacticaseibacillus rhamnosus GG 100 million colony-forming units daily for 24 weeks reduces the risk of rehospitalization when compared with placebo. The hazard ratio for the first rehospitalization due to worsening of psychiatric symptoms was 0.37 for the combination probiotic group when compared with placebo. Among patients who were re-hospitalized, taking the combination probiotic reduced the mean duration of rehospitalization by 5.4 days when compared with placebo (96896).
• Cancer. Although there has been interest in using oral Bifidobacterium lactis for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of B. lactis for this condition.
• Canker sores. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small study shows that taking a combination of B. lactis, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, and Lactobacillus acidophilus reduces pain, but does not affect the number of lesions or healing time, when compared with placebo. Also, another small study shows that using lozenges providing inulin 0.13 gram along with B. lactis and L. acidophilus 1.5 billion colony-forming units each reduces pain, but does not affect ulcer size or healing, when compared with Oracure gel (105146).
• Child development. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: An 11-year follow-up study evaluating B. lactis and Lacticaseibacillus rhamnosus taken daily during pregnancy from 35 weeks' gestation until birth, or six months after birth if breastfeeding, and then giving the same supplement to the infant until 2 years of age, does not affect neurocognitive outcomes such as attention, intelligence, executive function, depression, and anxiety when compared with those taking placebo (102287).
• Clostridioides difficile infection. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in inpatients aged 65 years or older shows that taking a combination of B. lactis, Bifidobacterium bifidium, and Lactobacillus acidophilus 60 billion colony-forming units daily for 21 days does not reduce the incidence of C. difficile diarrhea when compared with placebo (92255). Other combinations also do not appear to be beneficial, including a combination of B. lactis Bi-04, B. lactis Bi-07, Lactobacillus acidophilus, and Lacticaseibacillus paracasei, as well as a combination of B. lactis Bb-12, Lacticaseibacillus rhamnosus GG, and L. acidophilus La-5 (95364).
• Critical illness (trauma). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in multi-trauma patients requiring ventilation shows that taking a combination probiotic containing B. lactis twice daily for 15 days modestly reduces the risk of sepsis, as well as the length of stay in the ICU and hospital, when compared with placebo. The product contained B. lactis BB12 1.75 billion colony-forming units (CFUs) in combination with Lactobacillus acidophilus LA-5 1.75 billion CFUs, Lactiplantibacillus plantarum 500 million CFUs, and Saccharomyces boulardii 1.5 billion CFUs. Half of the dose was given onto the oropharynx and half via a nasogastric tube (107524).
• Dental plaque. It is unclear if Bifidobacterium lactis is beneficial for preventing dental plaque. Details: Preliminary clinical research shows that consuming a yogurt supplemented with B. lactis DN-173010 100 million colony-forming units daily between breakfast and lunch for 4 weeks does not prevent gingivitis or plaque when compared with a placebo yogurt. However, following a non-brushing period of 5 days, both gingivitis and plaque were modestly reduced in individuals consuming the B. lactis-containing yogurt (98502). Clinical research in adolescent boys aged 13-15 years with mild to moderate gingival inflammation shows that taking two lozenges containing B. lactis BB-12 (Chr. Hansen A/S) and Lacticaseibacillus rhamnosus GG (Probiotical SpA) twice daily for 4 weeks does not reduce plaque when compared with placebo. However, there was a benefit on levels of some salivary and plaque pathogenic bacteria. Each lozenge provided B. lactis BB-12 470 million colony-forming units (CFUs) and L. rhamnosus 440 million CFUs (107574). Conversely, a small clinical trial in healthy adults shows that taking four lozenges daily providing a total daily dose of 2 billion CFUs each of B. lactis BB-12 DSM 15954 (Chr. Hansen A/S) and L. rhamnosus GG ATCC 53103 (Probiotical SpA) for 4 weeks modestly reduces plaque when compared with placebo (107572).
• Diabetes. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of four clinical trials shows that taking probiotics during pregnancy is unlikely to prevent gestational diabetes and increases the risk of pre-eclampsia by 85% when compared with placebo. Although the specific effects of B. lactis are unclear from this analysis, three of the included studies used B. lactis in combination with Lacticaseibacillus rhamnosus (105185). Other clinical research that has found no benefit has used B. lactis BB-12 and L. rhamnosus GG at least 1 billion CFUs daily from 16-20 weeks' gestation until 28 weeks' gestation, or B. lactis 420 DSM 22089 (Dupont Nutrition & Health) and L. rhamnosus HN001 ATCC SD5675 as 10 billion CFUs each daily throughout pregnancy, with or without fish oil (102284,105144). Conversely, one small clinical study in adults with gestational diabetes shows that taking a combination of B. lactis BB-12, Streptococcus thermophilus STY-31, Lactobacillus acidophilus LA-5, and Lactobacillus delbrueckii subsp. bulgaricus LBY-27 for 8 weeks, starting at 24-28 weeks' gestation, modestly reduces fasting blood glucose and improves insulin sensitively when compared with placebo (96892). In children aged 8-17 years with type I diabetes, taking B. lactis Bb12 DSM 15954 and L. rhamnosus GG ATCC 53103 1 billion CFUs daily for 6 months does not reduce insulin requirements or levels of glycated hemoglobin over 12 months when compared with placebo. In addition, C-peptide levels and the maintenance of residual pancreatic beta-cell function were not affected (107518). A small clinical trial in adults with type 2 diabetes shows that taking fermented goat milk 120 grams containing one billion colony-forming units each of B. lactis BB-12 and Lactobacillus acidophilus La-5 daily for 6 weeks modestly reduces levels of glycated hemoglobin and low-density lipoprotein (LDL) cholesterol, but not fasting blood glucose or insulin resistance, when compared with conventional fermented milk containing Streptococcus thermophilus TA-40 (110973).
• Diarrhea. It is unclear if oral Bifidobacterium lactis is beneficial for the treatment or prevention of diarrhea. Details: The European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388). However, B. lactis is not a specific focus of the guidelines and most evidence is low quality. Clinical research shows that B. lactis reduces the duration of acute diarrhea in children by about one day (107636). In older adults in long-term care, clinical research shows that taking a combination of B. lactis BB-12 and Lacticaseibacillus rhamnosus 13-16 billion colony-forming units daily does not reduce the incidence or duration of diarrhea over a 12-month period when compared with placebo (103425).
• Familial hypercholesterolemia. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children 6-18 years of age with high cholesterol shows that taking a probiotic containing B. lactis MB 2409, Bifidobacterium bifidum MB 109, and Bifidobacterium longum BL04 daily for 12 weeks decreases total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels by 2% to 3% and increases HDL cholesterol levels by about 2% when compared with placebo. However, these changes might not be considered clinically significant (98736).
• Generalized anxiety disorder (GAD). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients newly diagnosed with GAD shows that taking sertraline 25 mg plus probiotics daily for 8 weeks may modestly reduce some symptoms of anxiety when compared with sertraline alone. However, the reduction in anxiety score was small and change was not consistent between rating scales. Also, the quality of life was not improved. The probiotics provided a total of 18 billion colony-forming units of B. lactis, Bifidobacterium longum, Bifidobacterium bifidum, and Lactobacillus acidophilus (110977).
• Gingivitis. It is unclear if oral Bifidobacterium lactis is beneficial for gingivitis. Details: Preliminary clinical research shows that consuming a yogurt supplemented with B. lactis DN-173010 100 million colony-forming units (CFUs) daily between breakfast and lunch for 4 weeks does not prevent gingivitis or plaque when compared with a placebo yogurt. However, following a non-brushing period of 5 days, both gingivitis and plaque were modestly reduced in individuals consuming the B. lactis-containing yogurt (98502). Another clinical trial following cleaning in patients with gingivitis shows that taking lozenges containing B. lactis HN019 (HOWARU Bifdo LYO 40 DCU-S, Danisco) one billion CFUs twice daily for 8 weeks increases the proportion of patients without generalized gingivitis by almost 50%, and modestly reduces bleeding with probing and gingivitis severity, compared with placebo lozenges. There was no effect on plaque (110992). B. lactis has also been investigated in combination with other ingredients. Clinical research in adolescent boys aged 13-15 years with mild to moderate gingival inflammation shows that taking two lozenges containing B. lactis BB-12 (Chr. Hansen A/S) and Lacticaseibacillus rhamnosus GG (Probiotical SpA) twice daily for 4 weeks modestly reduces gingivitis when compared with placebo. Each lozenge provided B. lactis BB-12 480 million colony-forming units (CFUs) and L. rhamnosus 440 million CFUs (107574). A small clinical trial in healthy adults shows that taking four lozenges daily providing a total daily dose of 2 billion CFUs each of B. lactis BB-12 DSM 15954 (Chr. Hansen A/S) and L. rhamnosus GG ATCC 53103 (Probiotical SpA) for 4 weeks modestly reduces plaque and gingivitis when compared with placebo (107572).
• Helicobacter pylori. It is unclear if oral Bifidobacterium lactis is beneficial for H. pylori; some research suggests that B. lactis may minimize the adverse effects of H. pylori eradication therapy, but not all research agrees. Details: Preliminary clinical research shows that adding B. lactis B94 7 billion colony-forming units (CFUs) daily to sequential H. pylori eradication therapy for 2 weeks results in an eradication rate of 87%, compared with 71% of those taking placebo or using no control along with sequential eradication therapy. Use of B. lactis also reduced treatment non-compliance due to diarrhea during the first week and reduced symptoms such as loss of appetite, nausea, and abdominal pain. In order to have one beneficial outcome, 6.2 patients would need to take B. lactis. There was no overall effect on non-compliance related to diarrhea or to skin rash (107589). Another clinical study shows that taking a specific combination of B. lactis and a lactobacilli species (Ferzym, Specchiasol) 5 billion CFUs daily for one week during standard triple therapy and one week thereafter reduces some treatment-related adverse effects such as taste disturbances and diarrhea, although it does not seem to improve compliance (12763). However, there was no difference in eradication rates or symptom relief in children aged 6-16 years taking B. lactis B94 5 billion CFUs daily plus inulin 900 mg for 14 days along with standard triple therapy (107590). Discrepancies may be related to the population studied or to the B. lactis strain, the other ingredients, or the type of H. pylori treatment used in the available research.
• Hypercholesterolemia. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of nine small to moderate-sized clinical studies shows that taking a combination of B. lactis and Lactobacillus acidophilus reduces levels of total cholesterol when compared with placebo (107591). Populations in the included clinical trials enrolled patients with hypercholesterolemia, type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), metabolic syndrome, and others. The benefits of B. lactis in patients with hypercholesterolemia are unclear.
• Inflammatory bowel disease (IBD). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking 10 billion colony-forming units each of B. lactis BB-12 and Lactobacillus acidophilus LA-5 twice daily for 12 weeks does not increase the proportion of patients with a reduction in weekly bowel frequency of at least 50% when compared with placebo. Also, there was no effect of this combination on stool consistency or abdominal symptoms. However, there were some modest benefits when compared with baseline (110999). This study was small and may have been underpowered to detect differences.
• Malnourishment-related diarrhea. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children aged 6 months to 4 years of age hospitalized with severe acute malnutrition shows that taking B. lactis BB-12 and Lacticaseibacillus rhamnosus LGG 5 billion colony-forming units each daily during hospitalization and for 8-12 weeks as an outpatient does not affect diarrhea incidence or severity or the number of days with diarrhea during hospitalization. However, the number of days with diarrhea as an outpatient was reduced by 2.2 days (110996).
• Malnutrition. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children aged 6 months to 4 years of age hospitalized with severe acute malnutrition shows that taking B. lactis BB-12 and Lacticaseibacillus rhamnosus LGG 5 billion colony-forming units each daily during hospitalization and for 8-12 weeks as an outpatient does not affect pneumonia incidence, duration, or severity, weight gain, duration of hospitalization, or other outcomes (110996).
• Metabolic syndrome. It is unclear if oral Bifidobacterium lactis is beneficial for metabolic syndrome. Details: In patients with metabolic syndrome, preliminary clinical research shows that taking fermented milk 80 mL providing B. lactis HN019 27.2 billion colony-forming units daily for 45 days reduces body mass index by approximately 4% and low-density lipoprotein (LDL) cholesterol by approximately 14% when compared with no treatment. There was no effect on waist circumference, glucose control, or other blood lipids (105154).
• Necrotizing enterocolitis (NEC). It is unclear if oral Bifidobacterium lactis is beneficial or safe for NEC prevention. Details: Meta-analyses of clinical research generally show that giving various bifidobacteria species alone does NOT reduce the risk of NEC or all-cause mortality. However, only a few of the studies included in these analyses have used B. lactis (95344,95351,103437,105164). A systematic review of four studies using B. lactis shows that although NEC incidence is reduced by 89% in one study, a significant reduction was not identified in the other studies when compared with placebo (107592). A network meta-analysis of two clinical studies shows that taking a combination probiotic containing B. lactis Bb-12, Bifidobacterium longum subsp. infantis Bb-02, and Streptococcus thermophilus TH-4, reduces the risk of NEC by 71% when compared with control (102437). Despite these findings, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, B. lactis is not specifically recommended (103003,111609,111611).
• Neonatal jaundice. It is unclear if oral Bifidobacterium lactis is beneficial for neonatal jaundice. Details: Clinical research in newborns with jaundice shows that taking B. lactis CP-9 5 billion colony-forming units twice daily during conventional phototherapy treatment reduces the duration of phototherapy by about 13 hours and modestly improves the decline in serum bilirubin when compared with taking placebo. A sub-analysis shows that this benefit is limited to full-term, and not preterm, newborns (110987).
• Nonalcoholic fatty liver disease (NAFLD). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children with NAFLD, clinical research shows that taking a specific combination (Prokid, Gostaresh Milad Pouya Company) containing B. lactis DSMZ 32269 6 billion colony-forming units (CFUs), Lactobacillus acidophilus ATCC B3208 3 billion CFUs, Lacticaseibacillus rhamnosus DSMZ 21690 2 billion CFUs, and Bifidobacterium bifidum ATCC SD6576 2 billion CFUs daily for 12 weeks normalizes liver sonography findings in 53% of children, compared with 17% of those taking placebo. In addition, levels of alanine aminotransferase and aspartate aminotransferase are reduced by 30% and 25%, respectively. There was no effect on body mass index or blood lipids when compared with placebo (105156). However, other research in adults with NAFLD shows that taking probiotic yogurt 100 grams fortified with vitamin D 1000 IU plus B. lactis Bb-12 and L. acidophilus 40 million CFUs daily for 3 months does not improve fasting blood glucose levels, insulin levels, blood pressure, or anthropometric indices when compared with unfortified yogurt (105174).
• Obesity. It is unclear if oral Bifidobacterium lactis is beneficial for weight loss. Details: Clinical research in overweight and obese adults shows that taking B. lactis 420 10 billion colony-forming units (CFUs) daily for 6 months does not reduce body fat or body weight when compared with placebo (95356). However, in individuals with abdominal obesity, clinical research shows that taking B. lactis CECT 8145 (Ba8145) 10 billion CFUs for 3 months modestly decreases body mass index (BMI) when compared with placebo. Also, taking heat-killed B. lactis CECT 8145 (Ba8145) 10 billion CFUs modestly decreases waist circumference when compared with placebo. Sub-group analyses show that these benefits occur only in females, and there was no effect of these products on the visceral or subcutaneous fat areas when compared with placebo (105551). Another clinical trial shows that taking 10 billion colony-forming units each of B. lactis 420 and Lacticaseibacillus rhamnosus HN001 daily, alone and with fish oil providing eicosapentaenoic acid 0.22 grams and docosahexaenoic acid 1.9 grams (Croda Europe Ltd.), during pregnancy and for 6 months postpartum, reduces the odds of overweight at 24 months by approximately 64% or 78%, respectively, when compared with taking placebo (110336). When taken in combination with Lactobacillus acidophilus LA02, B. lactis BS01 2 billion CFUs daily for 6 weeks does not reduce body weight or body fat when compared with placebo in young, healthy individuals, only some of whom were overweight (103438). In contrast to these findings, clinical research shows that taking 50 billion CFUs of a specific combination of B. lactis, Bifidobacterium bifidum, L. acidophilus, and Lactiplantibacillus plantarum (Lab4P) for 24 weeks reduces body weight by an additional 1.3 kg more than placebo (103439). Heat-killed B. lactis has also been investigated in combination with other ingredientd. Clinical research shows that taking enriched seafood sticks 50 grams daily providing heat-inactivated B. lactis CECT 8145 5 billion colony-forming units, inulin 1.7 grams, and eicosapentaenoic acid plus docosahexaenoic acid 370 mg daily for 12 weeks does not reduce body weight, body fat, blood pressure, or most lipid or glycemic indices, when compared to taking conventional seafood sticks. There was a modest decrease in insulin levels in males (110997).
• Oropharyngeal candidiasis. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In older adults in long-term care, clinical research shows that taking a combination of B. lactis BB-12 and Lacticaseibacillus rhamnosus 13-16 billion colony-forming units daily does not reduce the incidence of oropharyngeal candidiasis when compared with placebo over a 12-month period (103425).
• Otitis media. It is unclear if oral Bifidobacterium lactis is beneficial for preventing otitis media. Details: Clinical research in one month old infants shows that taking B. lactis BB-12 10 billion colony-forming units daily for an average of about 15 months does not reduce the proportion of children with otitis media by two years of age when compared with taking placebo (95381).
• Periodontitis. It is unclear if oral Bifidobacterium lactis is beneficial for periodontitis. Details: In patients with periodontitis, a small clinical trial shows that taking B. lactis HN019 lozenges providing 1 billion colony-forming units twice daily (HOWARU1 Bifido LYO 40 DCU-S, DuPont Danisco Sweeteners Oy) for 30 days after scaling and root planing modestly improves some measures of periodontitis 60 days after treatment completion, including pocket depth and clinical attachment, when compared with using placebo lozenges. In addition, although the risk for disease progression was not improved when compared with placebo, there was a reduction in the need for additional therapy in at least three sites (105157,105158,107622).
• Postoperative bowel function. It is unclear if oral Bifidobacterium lactis is beneficial for improving postoperative bowel function. Details: Clinical research in patients undergoing colorectal polyp resection shows that taking B. lactis MH-02 2 billion colony-forming units daily for 7 days postoperatively does not reduce total postoperative gastrointestinal symptom severity when compared with taking placebo. However, the time to recovery of bowel function was reduced by about 0.7 days and there were modest improvements in defecation difficulty (110985).
• Postpartum depression. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a combination of B. lactis 420 DSM 22,089 and Lacticaseibacillus rhamnosus HN001 ATCC SD5675 (Dupont Nutrition & Health) 10 billion CFUs daily, alone or with fish oil providing eicosapentaenoic acid (EPA) 0.44 grams and docosahexaenoic acid (DHA) 3.8 grams daily, does not reduce symptoms of postpartum depression or anxiety when compared with placebo. Supplements were started in the second trimester of pregnancy and continued until 6 months after delivery (107496).
• Prader-Willi syndrome (PWS). It is unclear if oral Bifidobacterium lactis is beneficial for PWS. Details: A small clinical trial in children with PWS shows that taking B. lactis BPL1 CECT8145 (Archer Daniels Midland Co-Biópolis) 10 billion colony-forming units (CFUs) daily for 12 weeks does not improve fat mass, abdominal adiposity, lipid profile, blood pressure, or glucose control when compared with placebo. However, there was a small improvement in insulin levels and measures of insulin resistance. Also, abdominal adiposity was modestly improved in a sub-group of patients over age 4.5 years, the age at which excessive weight gain typically starts in this population (105149). Other clinical research in children with PWS shows that taking B. lactis BL-11 (Beijing Huayuan Academy of Biotechnology) 30 billion CFUs twice daily for 12 weeks does not affect weight or psychological outcomes, including behavior, communication, and motor skills, when compared with placebo. However, height and overall clinical impression were modestly improved (107585).
• Pregnancy-induced nausea and vomiting. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles comprised of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units (CFUs) of B. lactis Bl-04, Lactiplantibacillus plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Lacticaseibacillus paracasei DSM 13434 and Lpc-37, Ligilactobacillus salivarius Ls-33, Levilactobacillus brevis Lbr-35, Lactobacillus acidophilus La-14, and Lacticaseibacillus casei Lc-11, along with inulin 200 mg (107199).
• Prematurity. It is unclear if oral Bifidobacterium lactis is beneficial for preventing infections in premature infants. Details: A small clinical trial in very low birth weight premature infants shows that taking B. lactis BB-12 two billion colony-forming units per kg six times daily from birth for 6 weeks does not reduce the incidence of nosocomial infections when compared with taking placebo (110994). This study may have been too small to detect differences.
• Psoriasis. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with psoriasis shows that taking a mixture of probiotics for 8 weeks modestly improves overall disease symptoms and feelings of depression when compared with placebo. The percentage of patients achieving at least a 50% or 75% reduction in overall symptom score was 40% and 24%, respectively, compared with 16% and 8% of those taking placebo. The probiotic was taken twice daily and provided a total daily dose of 2.6 billion colony-forming units (CFUs) of B. lactis, Bifidobacterium bifidum, Bifidobacterium longum, and Lactobacillus acidophilus (107498).
• Radiation-induced diarrhea. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with cervical cancer receiving radiotherapy with or without chemotherapy shows that taking a specific product (Biogurt, Fame Pharmaceuticals) containing B. lactis BB-12 and Lactobacillus acidophilus LA-5 1.75 billion lyophilized live colony-forming units in a capsule three times daily throughout radiation treatment reduces the risk of diarrhea by 28% when compared with placebo. Taking probiotics also reduced the use of loperamide when compared with placebo (102285).
• Rheumatoid arthritis (RA). Although there has been interest in using oral Bifidobacterium lactis for RA, there is insufficient reliable information about the clinical effects of B. lactis for this condition.
• Rotaviral diarrhea. It is unclear if oral B. lactis is beneficial for rotaviral diarrhea. Details: Small clinical studies show that giving B. lactis BB-12 alone or along with Streptococcus thermophilus may help reduce the incidence of diarrhea and rotavirus shedding in infants and children up to 36 months old (3169).
• Ulcerative colitis. Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial shows that taking a specific product (Probio-Tec AB-25) containing B. lactis BB-12 and Lactobacillus acidophilus La-5 is not beneficial for preventing relapse in patients with ulcerative colitis when compared with placebo (95338).
• Urinary tract infections (UTIs). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients in adults and children; its effect when used alone is unclear. Details: In children aged 4 months to 5 years with a previous UTI, clinical research shows that taking a specific combination (Complete Probiotic Platinum) of B. lactis 750 million colony-forming units (CFUs), Bifidobacterium bifidum 200 million CFUs, Lactobacillus acidophilus 750 million CFUs, and Lacticaseibacillus rhamnosus 50 million CFUs per kg twice daily for 18 months increases the median time to the first incidence of recurrence by approximately 3 months and increases the percentage of children without a UTI during the study period from 83% to 97% (103436). However, in older adults in long-term care, taking a combination of B. lactis BB-12 and L. rhamnosus 13-16 billion CFUs daily does not reduce the incidence of UTI when compared with placebo over a 12-month period (103425).
• Ventilator-associated pneumonia (VAP). Oral Bifidobacterium lactis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking B. lactis BB12 1.75 billion colony-forming units (CFUs), Lactobacillus acidophilus LA-5 1.75 billion CFUs, Lactiplantibacillus plantarum 500 million CFUs, and Saccharomyces boulardii 1.5 billion CFUs twice daily for 15 days reduces the risk of VAP to 12%, compared with 28% of patients taking placebo. Half of the dose was given onto the oropharynx and half via a nasogastric tube (107524). More evidence is needed to rate Bifidobacterium lactis for these uses.

(Read more about BIFIDOBACTERIUM ANIMALIS SUBSP. LACTIS)

POSSIBLY EFFECTIVE

• Irritable bowel syndrome (IBS). Oral Bifidobacterium bifidum seems to be beneficial for reducing symptoms of IBS. Details: Clinical research shows that taking live or heat-inactivated B. bifidum MIMBb75 is beneficial for improving gastrointestinal symptoms in patients with IBS (105155,105160). Taking 1 billion colony-forming units (CFUs) daily for 4 weeks results in an overall responder rate of 57%, compared with 21% in the placebo group. There were specific improvements in abdominal pain, bloating, and urgency (105160). When taking the heat-inactivated form of B. bifidum MIMBb75 (SYN-HI-001) 1 billion cells daily for 8 weeks, 34% of patients experienced at least a 30% improvement in abdominal pain and overall relief of symptoms in at least 4 of the 8 weeks, compared with only 19% of those taking placebo (105155). A clinical study in patients with diarrhea-predominant IBS shows that taking a specific combination product (NordBiotic, MBM Biotix) containing B. bifidum BF030, Bifidobacterium breve BB010, Bifidobacterium longum BL020, Bifidobacterium animalis subsp. lactis BL040, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, Lactobacillus acidophilus LA120, Lacticaseibacillus casei LC130, Lactiplantibacillus plantarum LP140, and Streptococcus thermophilus ST250 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life, when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516).
• Respiratory tract infections. Most clinical research shows that taking Bifidobacterium bifidum may reduce the risk of respiratory infections in otherwise healthy individuals. Details: One clinical study shows that taking B. bifidum R0071 3 billion colony-forming units (CFUs) daily for 6 weeks decreases the percentage of college students who experience at least one day of cold or flu by about 35% when compared with placebo. The number of cold or flu episodes is also decreased by 32% when compared with placebo (90272). Some studies have evaluated probiotics containing B. bifidum along with other species. One study shows that taking a specific combination (Infloran) of B. bifidum and Lactobacillus acidophilus 1 billion CFUs each twice daily for 3 months reduces the number of school-aged children who experience cold-related fever, cough, or school absence when compared with placebo (90286). In healthy children aged 3-10 years, clinical research shows that taking 12.5 billion CFUs daily of a specific combination of B. bifidum CUL20, L. acidophilus CUL21 and CUL60, and Bifidobacterium animalis subsp. lactis CUL34 (Lab4) plus vitamin C 50 mg daily reduces the risk of cough by 16% and sore throat by 20% and modestly reduces school absenteeism and antibiotic use when compared with placebo. However, nasal symptoms, fever, and wheezing were not reduced (106943).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in healthy adults over 65 years shows that taking a total of one billion colony-forming units (CFUs) of B. bifidum BGN4 and Bifidobacterium longum BORI daily for 12 weeks modestly improves mental flexibility when compared with placebo. However, there were no benefits on cognitive function, including language, memory, or attention (110968).
• Allergic rhinitis (hay fever). Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with seasonal allergies shows that taking B. bifidum G9-1 0.15 billion colony-forming units CFUs), Bifidobacterium longum MM-2 0.15 billion CFUs, and Lactobacillus gasseri KS-13 1.2 billion CFUs twice daily for 8 weeks during allergy season modestly improves quality of life, specifically nasal symptoms, when compared with taking placebo. However, eye symptoms were not improved (110972).
• Alzheimer disease. Although there has been interest in using oral Bifidobacterium bifidum for Alzheimer disease, there is insufficient reliable information about the clinical effects of B. bifidum for this condition.
• Antibiotic-associated diarrhea. Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical trial shows that taking a total of 60 billion colony-forming units (CFUs) of B. bifidum CUL20 NCIMB 30153, Bifidobacterium lactis CUL 34 NCIMB 30172, and Lactobacillus acidophilus CUL60 NCIMB 30157 and CUL 21 NCIMB 30156 daily for 21 days does not reduce the risk of antibiotic-associated diarrhea when compared with placebo (92255). An additional large clinical trial in children aged 3 months and up shows that taking B. bifidum in combination with other probiotics does not reduce the risk of antibiotic-associated diarrhea when compared with taking placebo, when the more stringent definition is considered excluding diarrhea of other etiologies. However, the risk of diarrhea of any etiology is reduced by 35%. The probiotic supplement provided a total of 10 billion CFUs of B. bifidum W23, Bifidobacterium animalis subsp. lactis W51, Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, Lacticaseibacillus rhamnosus W71, and Ligilactobacillus salivarius W24 daily from the first day of antibiotic treatment until 7 days after treatment ended (110969). A meta-analysis of 4 clinical trials in hospitalized or outpatient adults shows that taking B. bifidum in combination with up to 8 other probiotic strains does not reduce the risk of antibiotic-associated diarrhea when compared with placebo (107635).
• Atopic dermatitis (eczema). Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of B. bifidum, Ligilactobacillus salivarius, Lacticaseibacillus paracasei, and Bifidobacterium animalis subsp. lactis during pregnancy, from approximately 35 weeks' gestation until birth, and then giving this same combination to the infant after birth until 6 months of age, does not reduce the incidence of eczema at age 2 years, although it does appear to reduce the risk of atopic sensitization by 57% when compared with placebo (90234).
• Bacterial vaginosis. Although there has been interest in using oral Bifidobacterium bifidum for bacterial vaginosis, there is insufficient reliable information about the clinical effects of B. bifidum for this condition.
• Cancer. Although there has been interest in using oral Bifidobacterium bifidum for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of B. bifidum for this condition.
• Clostridioides difficile infection. It is unclear if oral Bifidobacterium bifidum is beneficial for preventing C. difficile infection. Details: Preliminary clinical research in patients undergoing elective colon cancer surgery shows that taking B. bifidum does not prevent C. difficile infection when compared with taking no additional treatment. All patients received a single intravenous dose of antibiotics before surgery. B. bifidum (Biofermin) provided 10 billion colony-forming units daily for 7 days before surgery and for 10 days after surgery starting on postoperative day 5 (110982). B. bifidum has also been investigated in combination with other probiotics. A large clinical study in hospitalized adults aged 65 years or older shows that taking a combination of B. bifidum, Bifidobacterium animalis subsp. lactis, and Lactobacillus acidophilus as 60 billion colony-forming units (CFUs) daily for 21 days does not reduce the incidence of C. difficile diarrhea when compared with placebo (92255). Also, taking B. bifidum and L. acidophilus is not beneficial for reducing the incidence of C. difficile diarrhea when compared with placebo (95364). However, one small clinical study shows that taking B. bifidum along with L. acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Streptococcus thermophilus as 12 billion CFUs total daily, starting 1 day after beginning antibiotic treatment, reduces the risk of C. difficile diarrhea by about 72% in adult inpatients (95364).
• Colic. Although there has been interest in using oral Bifidobacterium bifidum for colic, there is insufficient reliable information about the clinical effects of B. bifidum for this condition.
• Common cold. Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in healthy adults shows that taking B. bifidum, in combination with other probiotics and vitamins/minerals, daily for at least 3 months reduces the duration of common cold episodes by approximately 2 days when compared with taking a placebo providing only the vitamins/minerals. However, there was no difference in the number of common cold episodes. The probiotic supplement provided B. bifidum MF 20/5 5 million colony-forming units (CFUs), Bifidobacterium longum SP 07/3 5 million CFUs, and Lactobacillus gasseri PA 16/8 40 million CFUs (Tribion Harmonis) daily (110978).
• Constipation. It is unclear if oral Bifidobacterium bifidum is beneficial for constipation. Details: Clinical research shows that taking B. bifidum CCFM16 (Jiangsu WECARE-Probiotics Biotechnology Co., Ltd) 2 billion colony-forming units (CFUs) daily for 28 days does not improve patient-described symptoms of constipation or increase the number of weekly spontaneous bowel movements when compared with placebo. However, 42% of patients taking B. bifidum had at least 3 spontaneous bowel movements weekly, compared with 12% of those taking placebo. Stool consistency was also improved (107579). B. bifidum has also been investigated in combination with other probiotics and ingredients in clinical research in adults with chronic constipation. One study shows that taking B. bifidum in combination with Bifidobacterium longum, B. longum subsp. infantis, Lactobacillus acidophilus, Lacticaseibacillus casei, and Lactobacillus delbrueckii subsp. lactis (Hexbio) as 30 billion CFUs twice daily for 7 days increases the number of weekly bowel movements by about 2 when compared with placebo (90266). Another study shows that taking B. bifidum UABb-10 300 million CFUs daily for 4 weeks in combination with Bifidobacterium longum UABl-14 300 million CFUs, Bifidobacterium animalis subsp. lactis UABla-12 7.8 billion CFUs, Lactobacillus acidophilus DDS-1 6.6 billion CFUs, and fructo-oligosaccharides (FOS) 7 mg does not improve symptoms of constipation when compared with a placebo providing FOS (110970).
• Dental plaque. It is unclear if oral Bifidobacterium bifidum is beneficial for dental plaque. Details: A small clinical study in children ages 8-10 years shows that eating 110 grams of probiotic fruit yogurt (Activia Çilekli Meyveli, Danone) containing B. bifidum DN-173 010 1.1 trillion colony-forming units daily for 2 weeks does not reduce dental plaque when compared with a placebo fruit yogurt (102410). This study was limited by small size and the use of a sweet yogurt, which might increase dental plaque.
• Depression. Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with major depression shows that taking Bifidobacterium bifidum, Lacticaseibacillus casei, and Lactobacillus acidophilus daily for 8 weeks reduces symptoms of depression measured on the Beck Depression Inventory (BDI) when compared with placebo (99780). However, the validity of the results from this study is limited by incomplete reporting. For example, patient baseline BDI scores were not reported.
• Diabetes. It is unclear if oral Bifidobacterium bifidum is beneficial for diabetes. Details: Clinical research in patients with gestational diabetes shows that taking freeze-dried B. bifidum, Lactobacillus acidophilus, and Lacticaseibacillus casei, each as 2 billion colony-forming units (CFUs) per gram daily for 6 weeks, decreases fasting plasma glucose levels by 5-9 mg/dL and reduces insulin resistance and insulin levels when compared with placebo (95416,98430). In contrast, a large clinical trial shows that taking B. bifidum sp9 cs at least 6 billion CFUs, L. acidophilus LA1 at least 7.5 billion CFUs, and Bifidobacterium longum sp54 cs at least 1.5 billion CFUs daily from 14-24 weeks' gestation does not reduce the incidence of gestational diabetes when compared with taking placebo (107520). Limited evidence has also assessed the effects of B. bifidum for type 2 diabetes. A small clinical trial in patients taking metformin shows that taking B. bifidum G9-1 (Biofermin) 72 mg three times daily for 10 weeks modestly improves symptoms of diarrhea and constipation when compared with baseline. However, there was no effect on levels of fasting blood glucose or glycated hemoglobin (110975). A small clinical study shows that taking a combination of B. bifidum, L. acidophilus, and Streptococcus thermophilus daily for 12 weeks does not reduce levels of fasting blood glucose or glycated hemoglobin when compared with placebo (107521).
• Diabetic nephropathy. Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with diabetic nephropathy who are not taking antidiabetes drugs shows that taking a combination of B. bifidum, Lactobacillus acidophilus, and Streptococcus thermophilus daily for 12 weeks modestly reduces the ratio of microalbuminuria/creatinine (mAlb/Cr), a marker of kidney damage, when compared with placebo. However, there was no effect on the estimated glomerular filtration rate (eGFR) (107521).
• Diarrhea. It is unclear if oral Bifidobacterium bifidum is beneficial for diarrhea. Details: The European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388). However, B. bifidum is not a specific focus of the guidelines and most evidence on the use of this species is low quality.
• Exercise-induced respiratory infections. Although there has been interest in using oral Bifidobacterium bifidum for preventing exercise-induced respiratory infections, there is insufficient reliable information about the clinical effects of B. bifidum for this use.
• Familial hypercholesterolemia. It is unclear if oral B. bifidum is beneficial for familial hypercholesterolemia. Details: Preliminary clinical research in children 6-18 years of age with high cholesterol shows that taking a probiotic containing B. bifidum MB 109, Bifidobacterium animalis subsp. lactis MB 2409, and Bifidobacterium longum BL04 daily for 12 weeks reduces total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels by 2% to 3% and increases HDL cholesterol levels by about 2% when compared with placebo. However, these changes might not be considered clinically significant (98736).
• Generalized anxiety disorder (GAD). Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients newly diagnosed with GAD shows that taking sertraline 25 mg plus probiotics daily for 8 weeks may modestly reduce some symptoms of anxiety when compared with sertraline alone. However, the reduction in anxiety score was small and change was not consistent between rating scales. Also, the quality of life was not improved. The probiotics provided a total of 18 billion colony-forming units of B. bifidum, Bifidobacterium longum, Bifidobacterium animalis subsp. lactis, and Lactobacillus acidophilus (110977).
• Helicobacter pylori. Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One preliminary clinical trial in children with symptomatic H. pylori infection shows that taking a combination probiotic containing B. bifidum and Lactobacillus acidophilus daily for 6 weeks, in conjunction with triple therapy, increases the H. pylori eradication rate by an additional 19% when compared with triple therapy alone (90602). However, other individual clinical trials have shown that taking B. bifidum, L. acidophilus, Lacticaseibacillus rhamnosus, and Streptococcus faecium may not improve eradication rates when taken with triple therapy consisting of furazolidone, tetracycline, and lansoprazole (90279).
• HIV/AIDS. Although there has been interest in using oral Bifidobacterium bifidum for HIV/AIDS, there is insufficient reliable information about the clinical effects of B. bifidum for this condition.
• Hyperlipidemia. Although there has been interest in using oral Bifidobacterium bifidum for hyperlipidemia, there is insufficient reliable information about the clinical effects of B. bifidum for this condition.
• Necrotizing enterocolitis (NEC). It is unclear if oral Bifidobacterium bifidum is beneficial or safe for NEC prevention. Details: Meta-analyses of clinical research generally show that giving various bifidobacteria species alone does NOT reduce the risk of NEC or all-cause mortality (95344,95351,103437,105164). However, giving bifidobacteria in combination with lactobacilli or Enterococcus faecalis to preterm infants appears to reduce the risk of NEC and giving bifidobacteria with a prebiotic appears to reduce the risk of mortality (3162,90252,95351,102419,103437,103448,104157,105162,105164). The effects of B. bifidum, specifically, are unclear. Also, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, B. bifidum is not specifically recommended (103003,111609,111611).
• Nonalcoholic fatty liver disease (NAFLD). Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children with NAFLD, clinical research shows that taking a specific combination (Prokid, Gostaresh Milad Pouya Company) of B. bifidum ATCC SD6576 2 billion colon-forming units (CFUs), Lactobacillus acidophilus ATCC B3208 3 billion CFUs, Lacticaseibacillus rhamnosus DSMZ 21690 2 billion CFUs, and Bifidobacterium animalis subsp. lactis DSMZ 32269 6 billion CFUs daily for 12 weeks normalizes liver sonography findings in 53% of children, compared with 17% of those taking placebo. In addition, levels of alanine aminotransferase and aspartate aminotransferase decreased by 30% and 25%, respectively. There was no effect on body mass index or blood lipids when compared with placebo (105156). However, a small clinical trial in adults shows that taking a combination of B. bifidum BMCM 02290, Bifidobacterium longum BCMC 02129, B. longum BCMC 02120, Lactobacillus acidophilus BCMC 12,130, Lacticaseibacillus casei BCMC 12,313, and Lactobacillus delbrueckii subsp. lactis BCMC 12,451 as 30 billion CFUs twice daily for 6 months has no beneficial effects on hepatic steatosis or fibrosis, liver enzyme levels, blood lipids, or fasting blood glucose levels when compared with placebo (107523).
• Nonalcoholic steatohepatitis (NASH). Although there has been interest in using oral Bifidobacterium bifidum for NASH, there is insufficient reliable information about the clinical effects of B. bifidum for this condition.
• Obesity. Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking 50 billion CFUs of a specific combination of B. bifidum, Bifidobacterium animalis subsp. lactis, Lactobacillus acidophilus, and Lactiplantibacillus plantarum (Lab4P) for 24 weeks reduces body weight by an additional 1.3 kg more than placebo (103439).
• Oropharyngeal candidiasis. Although there has been interest in using oral Bifidobacterium bifidum for oropharyngeal candidiasis, there is insufficient reliable information about the clinical effects of B. bifidum for this condition.
• Pharyngitis. Although there has been interest in using oral Bifidobacterium bifidum for pharyngitis prevention, there is insufficient reliable information about the clinical effects of B. bifidum for this condition.
• Polycystic ovary syndrome (PCOS). Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with PCOS, clinical research shows that taking a combination of B. bifidum T1 (IBRC-M10771), Lactobacillus acidophilus T16 (IBRC-M10785), and Lacticaseibacillus casei T2 (IBRC-M10783) 2 billion colony-forming units each, plus inulin 800 mg, daily for 12 weeks modestly reduces serum insulin and triglyceride levels and improves insulin resistance and insulin sensitivity when compared with placebo. There was no effect on levels of cholesterol or fasting glucose (105159). Another clinical trial shows that 31.3% of patients with PCOS taking B. bifidum in combination with other probiotics daily for 6 months had regular menstrual cycles compared with 12.5% of those taking placebo. There were also modest improvements in testosterone levels and waist circumference, but not other hormones, insulin resistance, body weight, or most measures of quality of life. The product provided B. bifidum UBBB-55, Lactiplantibacillus plantarum UBLP-40, Lacticaseibacillus casei UBLC-42, and Limosilactobacillus fermentum UBLF-31, one billion colony-forming units (CFUs) each, as well as Lactobacillus acidophilus UBLA-34, Lacticaseibacillus rhamnosus UBLR-58, Limosilactobacillus reuteri UBLRu-87, 2 billion CFUs each, and fructo-oligosaccharides (FOS) 100 mg daily for 2 months and then twice daily for 4 months. All patients also underwent dietary and lifestyle changes (110974).
• Postoperative infection. It is unclear if oral Bifidobacterium bifidum is beneficial for preventing postoperative infection. Details: Preliminary clinical research in patients undergoing elective colon cancer surgery shows that taking B. bifidum does not prevent surgical site or other infection or leakage when compared with taking no additional treatment. All patients received a single intravenous dose of antibiotics before surgery. B. bifidum (Biofermin) provided 10 billion colony-forming units daily for 7 days before surgery and for 10 days after surgery starting on postoperative day 5 (110982).
• Pouchitis. Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study shows that taking a specific product (Trilac, Allergon AB) containing B. bifidum 600 million colony-forming units (CFUs), Lactobacillus acidophilus 600 million CFUs, and Lactobacillus delbrueckii subsp. bulgaricus 400 million CFUs per capsule, taken in doses of 2 capsules three times daily for 9 months, can reduce pouchitis severity and the number of patients experiencing pouchitis when compared to baseline (90296).The validity of these findings is limited by the lack of a comparator group.
• Prematurity. It is unclear if oral Bifidobacterium bifidum is beneficial for growth and development of premature infants. Details: Clinical research in very low birthweight premature infants shows that taking B. bifidum OLB6378 2.5 billion colony-forming units (CFUs) in two divided doses daily until body weight reached 2000 grams or 4.4 pounds reduces the time to established enteral feeding by 1.1 days when compared with taking placebo. There was no effect on other outcomes, including growth, length of hospital stay, mortality, or morbidities (110971).
• Psoriasis. Oral B. bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with psoriasis shows that taking a mixture of probiotics for 8 weeks modestly improves overall symptoms and feelings of depression when compared with placebo. The percentage of patients achieving at least a 50% or 75% reduction in overall symptom score was 40% and 24%, respectively, in those taking the probiotic mixture, compared with 16% and 8% of those taking placebo. Each probiotic capsule was used twice daily and provided a total daily dose of 2.6 billion colony-forming units (CFUs) of B. bifidum, Bifidobacterium animalis subsp. lactis, Bifidobacteruim longum, and Lactobacillus acidophilus (107498).
• Radiation-induced diarrhea. Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients undergoing pelvic radiotherapy with weekly cisplatin shows that taking B. bifidum (Infloran) and Lactobacillus acidophilus as 1 billion colony-forming units (CFUs) each twice daily, from seven days before starting radiotherapy and continuing during radiotherapy, reduces the incidence of moderate to severe diarrhea and the need for antidiarrheal medication when compared with placebo. Moderate to severe diarrhea occurred in 9% of patients taking probiotics, compared with 45% of those taking placebo (107580).
• Rheumatoid arthritis (RA). Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with moderate-to-severe RA shows that taking capsules containing freeze-dried strains of B. bifidum, Lactobacillus acidophilus, and Lacticaseibacillus casei daily for 8 weeks does not reduce RA severity, the number of tender or swollen joints, or joint pain when compared with placebo (95418).
• Ulcerative colitis. Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some preliminary clinical research shows that taking a fermented milk (Yakult, Yakult Honsha Co., Ltd.) containing B. bifidum, Bifidobacterium breve, and Lactobacillus acidophilus as an adjunct to standard maintenance therapy might help prevent relapse in ulcerative colitis patients when compared with a control group (12775,14338). Preliminary clinical research in patients with moderate to severe symptoms taking mesalazine 1200 mg daily shows that taking an unknown dose of B. bifidum BGN4 twice daily along with Lactobacillus acidophilus and Ligilactobacillus salivarius (Acronelle, Bromatech srl, Milan, Italy) for 2 years modestly improves patient- and physician-scales of overall symptoms when compared with taking mesalazine alone. There were also improvements in stool frequency and rectal bleeding (110981).
• Urinary tract infections (UTIs). Oral Bifidobacterium bifidum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children aged 4 months to 5 years with a previous UTI, clinical research shows that taking a specific combination (Complete Probiotic Platinum) of B. bifidum 200 million colony-forming units (CFUs), Bifidobacterium animalis subsp. lactis 750 million CFUs, Lactobacillus acidophilus 750 million CFUs, and Lacticaseibacillus rhamnosus 50 million CFUs per kg twice daily for 18 months increases the median time to the first incidence of recurrence by approximately 3 months and increases the percentage of children without a UTI during the study period from 83% to 97% when compared with placebo (103436). More evidence is needed to rate Bifidobacterium bifidum for these uses.

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POSSIBLY INEFFECTIVE

• Age-related cognitive decline. Oral Bifidobacterium breve does not seem to improve cognition in older adults. Details: A small clinical study in patients over 65 years of age shows that taking a sachet (Morinaga Milk Industry Co., Ltd) containing lyophilized powder of B. breve M-16V and B-3 and Bifidobacterium longum BB536 and M-63 as 12.5 billion colony-forming units each with water daily for 12 weeks does not improve cognition as measured on the Montreal Cognitive Assessment (MoCA) when compared with placebo (102412). While the results of this study may have been limited by the small population size, a larger clinical study in adults ages 50-80 years with subjective memory complaints also shows that using the same product for the same duration does not improve cognition when compared with placebo (102414).
• Sepsis. Oral Bifidobacterium breve does not seem to prevent sepsis in preterm infants. Details: One large, well-designed clinical study in preterm infants shows that taking B. breve BBG-001 up to about 90 billion colony-forming units (CFUs) daily in formula does not reduce the risk of sepsis when compared with placebo (92256). An additional smaller clinical trial also shows that taking B. breve M-16V 3 billion CFUs daily does not reduce the risk of sepsis (111008).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in children ages 4-17 years with allergic rhinitis and intermittent asthma related to Parietaria officinalis pollen shows that taking a combination of B. breve M-16 V one billion colony-forming units (CFUs), Bifidobacterium longum subsp. infantis M-63 one billion CFUs, and B. longum subsp. longum BB536 3 billion CFUs daily for 8 weeks modestly improves symptoms of rhinitis and quality of life when compared to taking placebo. There was no difference in the use of rescue medication (111001).
• Antibiotic-associated diarrhea. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in hospitalized patients with antibiotic-associated diarrhea shows that taking a combination of B. breve 50 million colony-forming units (CFUs) and Lacticaseibacillus casei 20 million CFUs three times daily does not reduce the average duration of diarrhea, the frequency of healing, or relapse rates, when compared with taking placebo (111006).
• Asthma. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical trial in children ages 3-14 years with asthma shows that taking a combination of B. breve B632 (DSM 24706) and Ligilactobacillus salivarius LS01 (DSM 22775) one billion colony-forming units (CFUs) each twice daily for 8 weeks and then once daily for 8 weeks modestly reduces the number of asthma exacerbations. The odds of having one or two asthma exacerbation was more than three fold in children taking placebo when compared with children taking probiotics. There was no effect on the duration of exacerbation or use of corticosteroids (111004).
• Atopic dermatitis (eczema). Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a total of 10 billion colony-forming units (CFUs) daily of a combination of B. breve M-16V and Bifidobacterium longum subsp. longum BB536 from about 4 weeks before the expected due date until delivery and then giving 5 billion CFUs of this combination daily to the infant for 6 months reduces the odds of developing atopic dermatitis by up to 77% before 18 months of age when compared with no probiotic (111015).
• Atopic disease. Although there has been interest in using oral Bifidobacterium breve for preventing and treating atopic disease, there is insufficient reliable information about the clinical effects of B. breve for this use.
• Celiac disease. Although there has been interest in using oral Bifidobacterium breve for celiac disease, there is insufficient reliable information about the clinical effects of B. breve for this condition.
• Chemotherapy-related infection. Although there has been interest in using oral Bifidobacterium breve for preventing chemotherapy-related infections, there is insufficient reliable information about the clinical effects of B. breve for this purpose.
• Clostridioides difficile infection. Although there has been interest in using oral Bifidobacterium breve for C. difficile infection, there is insufficient reliable information about the clinical effects of B. breve for this condition.
• Cognitive impairment. It is unclear if oral Bifidobacterium breve is beneficial for cognitive impairment. Details: Clinical research in older adults with suspected mild cognitive impairment shows that taking B. breve A1 (MCC1274) 20 billion colony-forming units daily for 16 weeks improves some measures of cognitive function, including immediate and delayed memory, as well as visual spatial ability, by moderate amounts when compared with placebo. However, there was no effect on language or attention (103447). However, taking the same dose for 24 weeks does not improve most measures of cognitive function (111002).
• Colic. It is unclear if oral Bifidobacterium breve is beneficial for colic. Details: Preliminary clinical research in infants with colic shows that adding B. breve CECT7263 200 million colony-forming units (CFUs) daily, or a combination of B. breve with Limosilactobacillus fermentum CECT5716 as 100 million CFUs each daily, to human milk, formula, or water for 28 days reduces the time spent crying per week by approximately 160-200 minutes from baseline. Taking B. breve is at least as effective as taking simethicone 20 mg four times daily (105150). Other clinical research shows that taking B. breve B632 and BR03 100 million CFUs each daily for 3 months modestly reduces daily crying duration when compared with taking placebo (111010). B. breve has also been investigated for colic prevention. Clinical research in infants without colic at baseline shows that adding B. breve CECT7263 10 million CFUs per gram to formula modestly reduces the number of infants crying more than three hours daily when compared with a control formula. At 6 weeks of age, 12% of infants taking formula supplemented with B. breve cried more than 3 hours daily, compared with 29% of those using the control formula. At 4 months of age, frequency of crying more than 3 hours daily was low and not significantly different between groups (105151). However, this study was not specifically designed to examine the effects of B. breve on colic frequency as the infants did not have colic at baseline.
• Constipation. Most early research shows that oral Bifidobacterium breve seems to be beneficial for constipation. Details: Preliminary clinical research in children aged 3-16 years with functional constipation shows that taking a specific B. breve powder (Yakult, Yakult Honsha Co., Ltd.) 1-100 billion colony-forming units (CFUs) daily for 4 weeks increases defecation frequency by about 4 times per week, decreases episodes of fecal incontinence by about 7.5 episodes per week, and improves stool consistency and episodes of abdominal pain (17726). Multi-strain probiotics containing bifidobacteria have also been evaluated for constipation. In children with chronic constipation, preliminary clinical research shows that taking a combination of B. breve M-16 V, Bifidobacterium longum M-63, and B. longum BB536 daily for 8 weeks in addition to polyethylene glycol (PEG), does not improve symptoms or increase the rate of clinical remission when compared with PEG alone (107600). However, one meta-analysis of clinical research in adults with functional constipation shows that taking B. breve DSM 16604 and Lactiplantibacillus plantarum LMG P-21021 as 5 billion CFUs total daily for 30 days improves bowel movement frequency by about 1.5 stools weekly when compared with placebo (95342). Also, a small clinical trial shows that taking a specific combination product (ID-HWS1000) containing Lacticaseibacillus rhamnosus IDCC 3201, L. plantarum IDCC 3501, Lacticaseibacillus casei IDCC 3451, Bifidobacterium animalis subsp. lactis IDCC 4301, Bifidobacterium breve IDCC 4401, Lactococcus lactis IDCC 2301, xylooligosaccharide, and dietary fiber as nondigestible maltodextrin, oat fiber, and psyllium husk fiber modestly increases stool frequency and improves symptoms of functional constipation in adults when compared with placebo (107517).
• Depression. It is unclear if oral Bifidobacterium breve is beneficial for depression. Details: A small clinical trial in patients with major depressive disorder shows that taking B. breve CCFM1025 10 billion colony-forming units (CFUs) daily for 4 weeks modestly improves symptoms of depression when compared with placebo (107602).
• Diabetes. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients for various forms of diabetes; its effect when used alone is unclear. Details: One small clinical study in patients with type 2 diabetes shows that taking a specific combination product (Familact probiotics, ZistTakhmir Co.) containing B. breve and other probiotics daily for 6 weeks does not reduce fasting blood glucose or plasma insulin levels when compared with placebo. This product contains B. breve 30 billion colony-forming units (CFUs), B. longum 7 billion CFUs, Lactobacillus acidophilus 2 billion CFUs, Lacticaseibacillus casei 7 billion CFUs, Lactocaseibacillus rhamnosus 1.5 billion CFUs, Lactobacillus delbrueckii subsp. bulgaricus 200 million CFUs, and Streptococcus thermophilus 1.5 billion CFUs (99790). In adults with gestational diabetes, one clinical study shows that taking a specific product (Visbiome, ExeGi Pharma) containing B. breve and various other probiotics as a total of 112.5 billion CFUs twice daily for 8 weeks does not affect levels of fasting blood glucose or glycated hemoglobin (HbA1c) when compared with placebo. However, there were small improvements in insulin levels and insulin resistance (107549). A combination probiotic containing B. breve has also been evaluated in children 2-12 years of age with new-onset type 1 diabetes. One clinical study shows that taking Visbiome as 112.5 billion CFUs daily for 3 months modestly decreases HbA1c and insulin requirements when compared with placebo. Also, about three times as many children achieved remission, defined as insulin requirements of less than 0.5 U/kg daily and HbA1c levels of less than 7%. However, C-peptide levels and the maintenance of residual pancreatic beta-cell function were not affected when compared with placebo (107497). It is unclear if any benefits are due to B. breve, other probiotics, or the combinations.
• Diarrhea. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing B. breve, Lacticaseibacillus casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum, and Streptococcus thermophilus daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). A large clinical trial in infants aged 4-6 months shows that taking an infant formula fermented with B. breve C50 and Streptococcus thermophilus 065 (Calisma) for about 5 months does not affect the incidence or duration of diarrhea episodes when compared with a standard infant formula. However, there was a modest reduction in severity of diarrhea episodes, based on reductions in proportions of infants with dehydration, consultations with medical providers, and need for oral rehydration (111106). This formula did not provide live B. breve.
• Exercise-induced muscle soreness. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in resistance-trained males shows that taking B. breve BR03 and Streptococcus thermophilus FP4 as 10 billion colony-forming units total daily for 3 weeks prior to resistance training modestly attenuates range of motion decrements, but does not seem to significantly decrease overall muscle soreness, when compared with placebo (95415).
• Helicobacter pylori. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In adults with H. pylori infection and peptic ulcer disease, adding a combination product containing seven strains of probiotics (Balance by Protexin Co) daily for 14 days to quadruple therapy with omeprazole, bismuth subcitrate, amoxicillin, and clarithromycin does not improve H. pylori eradication or symptoms when compared with quadruple therapy alone. This product provided B. breve, Lacticasebacillus casei, L acticasebacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum, and Streptococcus thermophilus (90291).
• Irritable bowel syndrome (IBS). Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study shows that taking a specific combination product (Visbiome, ExeGi Pharma) containing B. breve and other probiotics as 450 billion CFUs daily for 8 weeks decreases bloating in patients with diarrhea-predominant IBS (IBS-D) (11379). However, adding this product as 900 billion CFUs daily to a sham diet or a low-FODMAP diet for 4 weeks does not improve IBS symptoms when compared with placebo (98741). Other clinical research shows that taking a different product (Duolac Care) containing Lactobacillus acidophilus, Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, Bifidobacterium breve, Bifidobacterium animalis subsp. lactis, Bifidobacterium longum, and Streptococcus thermophilus twice daily for 4 weeks can relieve symptoms in 72% of patients with IBS (95353). In addition, a clinical study in patients with IBS-D shows that taking a specific combination probiotic (NordBiotic, MBM Biotix) containing B. breve BB010, Lactobacillus acidophilus LA120, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, Lacticaseibacillus casei LC130, Lactiplantibacillus plantarum LP140, B. longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium animalis subsp. lactis BL040, and Streptococcus thermophilus ST250 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life, when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516).
• Metabolic syndrome. Although there has been interest in using oral Bifidobacterium breve for metabolic syndrome, there is insufficient reliable information about the clinical effects of B. breve for this condition.
• Necrotizing enterocolitis (NEC). It is unclear if oral Bifidobacterium breve is beneficial or safe for preventing NEC. Details: One large, well-designed clinical study in preterm infants shows that taking B. breve BBG-001 up to about 90 billion colony-forming units daily in formula does not reduce the risk of NEC when compared with placebo (92256). In a systematic review, four studies show that using B. breve does not reduce the incidence of NEC in most infants. However, in one of the included studies, although there was no effect on the incidence of NEC stage 2 in the total group or in infants born at less than 28 weeks' gestation, the incidence was reduced in infants born at less than 34 weeks' gestation. Also, other preliminary clinical research shows that giving B. breve alone or with Lacticaseibacillus casei reduces the incidence of NEC (107592,107595). Guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, B. breve is not specifically recommended (103003,111609,111611).
• Nonalcoholic fatty liver disease (NAFLD). Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with NAFLD shows that taking two sachets daily for 3 months of a specific combination product (VSL#3) containing B. breve and other probiotics does not affect body mass index or most glycemic or lipid parameters when compared with taking placebo. However, there was a modest decrease in triglyceride levels and liver enzymes (111009).
• Obesity. It is unclear if oral Bifidobacterium breve is beneficial for obesity. Details: Clinical research in children aged 6-18 years with obesity and insulin resistance shows that adding B. breve BR03 (DSM 16604) and B632 (DSM 24706) 1 billion colony-forming units (CFUs) each daily for 8 weeks to advice on the Mediterranean diet and exercise modestly improves insulin sensitivity when compared with placebo. However, there was no difference between groups in body mass index (BMI) or blood pressure when compared with diet and exercise advice alone (107598). Additional clinical research in overweight, but non-obese, adults based on BMI shows that taking B. breve B-3 5 billion CFUs daily for 12 weeks modestly reduces body fat mass and waist and hip circumference when compared with taking placebo. However, there was no effect on body fat percentage or lipid endpoints (111003).
• Postoperative recovery. Although there has been interest in using oral Bifidobacterium breve for improving postoperative recovery, there is insufficient reliable information about the clinical effects of B. breve for this purpose.
• Pouchitis. Oral Bifidobacterium breve has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that continuous treatment with a specific combination product (Visbiome, ExeGi Pharma) containing B. breve and other probiotics as 6 grams (300-500 billion live bacteria per gram) daily for up to a year seems to maintain remission of pouchitis in 85% of patients (6087,12769).
• Radiation-induced diarrhea. Although there has been interest in using oral Bifidobacterium breve for preventing radiation-induced diarrhea, there is insufficient reliable information about the clinical effects of B. breve for this purpose.
• Respiratory tract infections. Although there has been interest in using oral Bifidobacterium breve for preventing respiratory tract infections, there is insufficient reliable information about the clinical effects of B. breve for this purpose.
• Rotaviral diarrhea. Although there has been interest in using oral Bifidobacterium breve for rotaviral diarrhea, there is insufficient reliable information about the clinical effects of B. breve for this condition.
• Short bowel syndrome. Although there has been interest in using oral Bifidobacterium breve for short bowel syndrome, there is insufficient reliable information about the clinical effects of B. breve for this condition.
• Ulcerative colitis. It is unclear if oral Bifidobacterium breve is beneficial for ulcerative colitis. Details: Some clinical research has evaluated B. breve-containing probiotics for increasing remission rates in patients with ulcerative colitis. The best evidence is for a specific combination product (Visbiome, ExeGi Pharma). Doses of 3 grams (equivalent to 900 billion colony-forming units (CFUs)) once or twice daily has been used in combination with conventional treatment. In children aged 1-16 years, doses of 450-1800 billion CFUs for up to one year have been used (3261,14370,14371,16841,95337). A meta-analysis of clinical research shows that taking this probiotic can increase remission rates by about 1.7-fold when compared with placebo in adults and children with active ulcerative colitis (95337). There is also evidence that it is beneficial for improving remission rates in patients who do not adequately respond to conventional treatment (14371). Additionally, some preliminary clinical research shows that this specific product, taken as an adjunct to standard maintenance therapy, might help prevent relapse (3261,16841). Other preliminary clinical research shows that taking Visbiome or a fermented milk (Yakult, Yakult Honsha Co., Ltd.) containing B. breve, Bifidobacterium bifidum, and Lactobacillus acidophilus as an adjunct to standard maintenance therapy might help prevent relapse in ulcerative colitis patients (3261,12775,14338,16841). However, other research shows that taking B. breve Yakult is not beneficial for preventing ulcerative colitis relapse (98740). More evidence is needed to rate Bifidobacterium breve for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abdominal pain. It is unclear if oral Bifidobacterium longum is beneficial for abdominal pain or discomfort. Details: Clinical research in adults with abdominal pain, discomfort, and bloating shows that taking B. longum 35624 (Align) one billion colony-forming units daily for 4 weeks does not reduce symptom severity or the frequency of pain and discomfort when compared with placebo. However, there was a 72% increased odds of having at least one day free of abdominal bloating or distension. Individuals in this study had not been seeing a physician but had symptoms at least twice a week for 3 months (111858).
• Acute radiation syndrome. It is unclear if oral Bifidobacterium longum is beneficial for acute radiation syndrome. Details: A small clinical study shows that antibiotic-resistant B. longum can help improve short-term survival in the treatment of radiation sickness. In combination with prophylactic antibiotics, B. longum appears to inhibit colonization and overgrowth of intestinal opportunistic pathogens, preventing post-irradiation sepsis. This study used B. longum 10 billion colony-forming units daily in 10 mL of milk for 30 days, starting approximately 10 days after irradiation (3457).
• Age-related cognitive decline. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients over 65 years of age shows that taking a sachet (Morinaga Milk Industry Co., Ltd) containing lyophilized powder of B. longum BB536 and M-63, along with B. breve M-16V and B-3 as 12.5 billion colony-forming units (CFUs) each with water daily for 12 weeks does not improve cognition as measured on the Montreal Cognitive Assessment (MoCA) when compared with placebo (102412). While the results of this study may have been limited by the small population size, a larger clinical study in adults ages 50-80 years with subjective memory complaints also shows that using the same product for the same duration does not improve cognition when compared with placebo (102414). Additional clinical research in healthy adults over 65 years shows that taking a total of one billion CFUs of B. longum BORI and Bifidobacterium bifidum BGN4 daily for 12 weeks modestly improves mental flexibility when compared with placebo. However, there were no benefits on cognitive function, including language, memory, or attention (110968).
• Allergic rhinitis (hay fever). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with seasonal allergies shows that taking B. longum MM-2 0.15 billion colony-forming units CFUs), Bifidobacterium bifidum G9-1 0.15 billion CFUs, and Lactobacillus gasseri KS-13 1.2 billion CFUs twice daily for 8 weeks during allergy season modestly improves quality of life, specifically nasal symptoms, when compared with taking placebo. However, eye symptoms were not improved (110972). Also, a small clinical trial in children ages 4-17 years with allergic rhinitis and intermittent asthma related to Parietaria officinalis pollen shows that taking a combination of B. longum BB536 3 billion CFUs, B. longum M-63 1 billion CFUs, and Bifidobacterium breve M-16 V 1 billion CFUs, daily for 8 weeks modestly improves symptoms of rhinitis and quality of life when compared to taking placebo. There was no difference in the use of rescue medication (111001).
• Antibiotic-associated diarrhea. It is unclear if oral Bifidobacterium longum is beneficial for preventing antibiotic-associated diarrhea (AAD); the available research is conflicting. Details: One preliminary clinical study shows that taking B. longum can reduce stool frequency, abdominal discomfort, and stool clostridial spore count when used in patients concurrently taking erythromycin (1233). However, other research shows that taking B. longum with clindamycin does not significantly reduce diarrhea (14334). A small clinical trial in children aged 5 months to 16 years shows that taking a combination of B. longum PL03, Lacticaseibacillus rhamnosus KL53A, and Lactiplantibacillus plantarum PL02 twice daily during antibiotic treatment does not reduce the rate of AAD when compared with placebo. However, there was a modest reduction in the number of stools each day (107553).
• Asthma. It is unclear if oral Bifidobacterium longum is beneficial for asthma. Details: Clinical research in patients with asthma shows that taking B. longum 35624 (Alimentary Health Ltd) one billion colony-forming units twice daily for 4 weeks does not reduce asthma severity or inhaler use or improve pulmonary function when compared with taking placebo. However, in a small sub-set of patients with uncontrolled symptoms, well-controlled asthma occurred in 93% of patients taking B. longum compared with 36% of those taking placebo. This benefit was maintained for an additional 4 weeks in 57% of patients. Some measures of pulmonary function were improved (111856).
• Athletic performance. It is unclear if oral Bifidobacterium longum is beneficial for athletic performance. Details: In athletes, preliminary clinical research shows that taking B. longum OLP-01 15 billion colony-forming units in three divided doses daily for 5 weeks with training and de-training does not affect the distance run in 12 minutes when compared with placebo (103446).
• Atopic dermatitis (eczema). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Research evaluating B. longum-containing probiotics for preventing atopic dermatitis has been mixed. One clinical study shows that taking a combination of B. longum plus Lacticaseibacillus rhamnosus or Lacticaseibacillus paracasei, beginning about 2 months before expected delivery and continuing through breastfeeding until the infant is 2 months old, reduces the risk of eczema in the infant (90285). Preliminary clinical research also shows that taking a total of 10 billion colony-forming units (CFUs) daily of a combination of B. longum BB536 and Bifidobacterium breve M-16V from about 4 weeks before the expected due date until delivery and then giving 5 billion CFUs of this combination daily to the infant for 6 months reduces the odds of developing atopic dermatitis by up to 77% before 18 months of age when compared with no probiotic (111015). In addition, in children ages 4-17 years, taking 1 billion CFUs of a 1:1:1 combination of B. longum CECT 7347, Lacticaseibacillus casei CECT 9104, and Bifidobacterium animalis subsp. lactis CECT 8145 for 12 weeks modestly reduces symptom severity and the need for topical corticosteroids when compared with placebo (107531). However, in infants with a family history of allergic disease, giving human milk containing B. longum BL999 10 million CFUs and L. rhamnosus 20 million CFUs daily for the first 6 months of life does not seem to reduce the incidence of eczema or atopic sensitization (35396).
• Bronchopulmonary dysplasia. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One large observational study in premature infants suggests that taking B. longum 1-1.5 billion colony-forming units with L. acidophilus during the first month of life for the prevention of necrotizing enterocolitis is not associated with a reduced risk of bronchopulmonary dysplasia. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Cancer. Although there has been interest in using oral Bifidobacterium longum for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of B. longum for this condition.
• Celiac disease. It is unclear if oral Bifidobacterium longum is beneficial for celiac disease. Details: Preliminary clinical research in children aged 2-17 years with celiac disease shows that taking B. longum CECT 7347 1 billion colony-forming units (CFUs) daily along with a gluten-free diet for 3 months does not improve gastrointestinal symptoms, including diarrhea, constipation, abdominal pain, or vomiting, when compared with placebo (92266). Also, a small clinical trial in adults with persistent symptoms of celiac disease while following a gluten-free diet shows that taking B. longum NLS-SS (Natren Life Start 2, Natren Inc., USA) 4 billion CFUs three times daily for 3 weeks does not reduce symptoms when compared with taking placebo. However, there was a modest benefit in patients with the greatest initial clinical burden (111857). This study might have been too small to detect differences between groups.
• Chemotherapy-related infection. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with leukemia receiving chemotherapy shows that taking B. longum in combination with Lactobacillus acidophilus (Morinaga Bifidus), with or without Enterococcus faecalis (Levenin), does not reduce the risk of Candida infection when compared to control (35434).
• Clostridioides difficile infection. Although there has been interest in using oral Bifidobacterium longum for C. difficile infection, there is insufficient reliable information about the clinical effects of B. longum for this condition.
• Cognitive function. It is unclear if oral Bifidobacterium longum is beneficial for improving cognitive function. Details: A small clinical trial in healthy adults ages 60-75 years without cognitive impairment shows that taking B. longum BB68S 50 billion colony-forming units (CFUs) daily for 8 weeks modestly improves cognitive function, including immediate and delayed memory, visuospatial/constructional memory, and attention, when compared with taking placebo. There was no effect on language or some other measures (111776). A small clinical trial in healthy adults shows that taking a product containing a combination of B. longum R0175 70 million CFUs, Lactobacillus helveticus R0052 2 billion CFUs, and Lactiplantibacillus plantarum R1012 800 million CFUs (Puraflor, GSK Consumer Healthcare, Milano, Italy) daily for 4 weeks does not affect cognitive performance during acute stress when compared with placebo. The probiotics were provided in combination with inulin 500 mg, potassium 50 mg, magnesium 45 mg, glutathione 20 mg, lactoferrin 10 mg, and zinc 9 mg (110923). The effects of B. longum alone are not clear from this study. Also, a larger clinical trial is needed to confirm these results.
• Colic. Although there has been interest in using oral B. longum for colic, there is insufficient reliable information about the clinical effects of B. longum for this condition.
• Common cold. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in healthy adults shows that taking B. longum, in combination with other probiotics and vitamins/minerals, daily for at least 3 months reduces the duration of common cold episodes by approximately 2 days when compared with taking a placebo providing only the vitamins/minerals. However, there was no difference in the number of common cold episodes. The probiotic supplement provided B. longum SP 07/3 5 million colony-forming units (CFUs), Bifidobacterium bifidum MF 20/5 5 million CFUs, and Lactobacillus gasseri PA 16/8 40 million CFUs (Tribion Harmonis) daily (110978).
• Constipation. It is unclear if oral Bifidobacterium longum is beneficial for constipation. Details: B. longum BB536 in doses of 2-20 billion colony-forming units (CFUs) has been evaluated for constipation in adults, but results are conflicting and modest at best (35413,35424). Multi-strain probiotics containing B. longum have also been evaluated. Clinical research in adults with chronic constipation shows that taking a multi-strain probiotic (Hexbio) containing B. longum, Bifidobacterium bifidum, Lactobacillus acidophilus, Lacticaseibacillus casei, and Lactobacillus delbrueckii subsp. lactis 30 billion CFUs twice daily for 7 days increases the number of weekly bowel movements by about 2 when compared with placebo (90266). However, another study shows that taking B. bifidum UABb-10 300 million CFUs daily for 4 weeks in combination with Bifidobacterium longum UABl-14 300 million CFUs, Bifidobacterium animalis subsp. lactis UABla-12 7.8 billion CFUs, Lactobacillus acidophilus DDS-1 6.6 billion CFUs, and fructo-oligosaccharides (FOS) 7 mg does not improve symptoms of constipation when compared with a placebo providing FOS (110970). Also, in children with chronic constipation, preliminary clinical research shows that taking a combination of B. longum M-63, B. longum BB536, and B. breve M-16 V daily for 8 weeks in addition to polyethylene glycol (PEG) does not improve symptoms or increase the rate of clinical remission when compared with PEG alone (107600). B. longum has also been investigated for constipation prevention in infants. Clinical research in healthy term infants less than 3 months of age shows that consuming infant formula without B. longum for 12 weeks results in a 5.2-fold increased odds of having constipation when compared with consuming a formula supplemented with B. longum CECT7210 10 million CFUs per gram (111825).
• Coronavirus disease 2019 (COVID-19). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small, retrospective study in patients with severe COVID-19 symptoms shows that taking a combination of probiotics in three divided doses daily modestly reduces the duration of diarrhea when compared to standard treatments alone. The probiotic treatment consisted of B. longum 60 million colony-forming units (CFUs), Streptococcus thermophilus 6 million CFUs, and Lactobacillus delbrueckii subsp. bulgaricus 6 million CFUs, given in three divided doses daily (107200).
• Depression. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in patients with mild to moderate symptoms of major depressive disorder shows that taking a total of 10 billion colony-forming units (CFUs) of B. longum and Lactobacillus helveticus daily modestly improves symptoms of depression when compared with placebo, but not when compared with the prebiotic galactooligosaccharide. All patients had been taking antidepressants for at least 3 months (102506). Also, preliminary clinical research in treatment-naïve patients with moderate depression shows that taking 0.3 billion CFUs of B. longum in combination with 2.7 billion CFUs of L. helveticus daily modestly improves symptoms of depression and sleep quality when compared with baseline (105129). However, a larger clinical trial in untreated patients with depression shows that taking a total of 3 billion CFUs of B. longum and L. helveticus does not improve symptoms of depression when compared with placebo. The majority of these patients had a history of prior antidepressant usage (110922). All studies used B. longum R0175 and L. helveticus R0052 (Lallemand Health Solutions Inc.) daily for 8 weeks.
• Diabetes. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with type 2 diabetes shows that taking a specific combination product (Familact probiotics, ZistTakhmir Co.) containing B. longum and other probiotic bacteria daily for 6 weeks does not reduce fasting blood glucose or plasma insulin levels when compared with placebo. This product contains B. longum 7 billion colony-forming units (CFUs), Bifidobacterium breve 30 billion CFUs, Lactobacillus acidophilus 2 billion CFUs, Lacticaseibacillus casei 7 billion CFUs, Lactocaseibacillus rhamnosus 1.5 billion CFUs, Lactobacillus delbrueckii subsp. bulgaricus 200 million CFUs, and Streptococcus thermophilus 1.5 billion CFUs (99790). Also, a large clinical trial shows that taking B. longum sp54 cs at least 1.5 billion CFUs daily, L. acidophilus LA1 at least 7.5 billion CFUs daily, and Bifidobacterium bifidum sp9 cs at least 6 billion CFUs daily from 14-24 weeks' gestation does not reduce the incidence of gestational diabetes when compared with placebo (107520).
• Diarrhea. It is unclear if oral Bifidobacterium longum is beneficial for diarrhea treatment or prevention. Details: Clinical research in healthy term infants less than 3 months of age shows that consuming infant formula supplemented with B. longum CECT7210 for 12 weeks does not reduce the overall number of diarrhea episodes or the proportion of infants with a diarrhea episode when compared with consuming control infant formula. The probiotic formula provided 10 million colony-forming units (CFUs) per gram (111825). The number of episodes of diarrhea may have been too small to detect differences between groups. B. longum has also been investigated for diarrhea treatment. A small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing B. longum, B. breve, Lacticaseibacillus casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, and Streptococcus thermophilus daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). In adults with acute diarrhea, clinical research shows that taking one capsule providing at least 20 million CFUs each of B. longum and Lactobacillus gasseri (Omniflora) three times daily for up to 6 days is as effective as taking Enterococcus faecium SF 68 75 million CFUs three times daily, used as an active comparator, for reducing the duration of diarrhea. However, complete recovery occurred in a modestly greater proportion of patients. All patients also received oral rehydration solution (111854).
• Familial hypercholesterolemia. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children 6-18 years of age with high cholesterol shows that taking a probiotic containing B. longum BL04, Bifidobacterium animalis subsp. lactis MB 2409, and Bifidobacterium bifidum MB 109 daily for 12 weeks reduces total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels by 2% to 3% and increases HDL cholesterol levels by about 2% when compared with placebo. However, these changes might not be considered clinically significant (98736).
• Generalized anxiety disorder (GAD). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients newly diagnosed with GAD shows that taking sertraline 25 mg plus probiotics daily for 8 weeks may modestly reduce some symptoms of anxiety when compared with sertraline alone. However, the reduction in anxiety score was small and change was not consistent between rating scales. Also, the quality of life was not improved. The probiotics provided a total of 18 billion colony-forming units of B. longum, Bifidobacterium bifidum, Bifidobacterium animalis subsp. lactis, and Lactobacillus acidophilus (110977).
• Hepatic encephalopathy. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with hepatic encephalopathy shows that taking an unspecified amount of B. longum W11 in combination with fructo-oligosaccharides (Zirfos) 2.5 grams daily for 90 days modestly reduces serum ammonia levels and improves performance on various neuropsychological tests measuring abstract reasoning, memory, motor speed, language, etc., when compared with taking a placebo consisting of B vitamins (111847).
• Helicobacter pylori. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of clinical research in adults shows that taking combination products containing both lactobacilli and bifidobacteria in conjunction with standard therapy increases the odds of H. pylori eradication by approximately 2-fold when compared with standard therapy alone. These combinations also reduce the odds of disease-related side effects by approximately 70% when compared with standard therapy alone. Six of the ten studies in the meta-analysis included B. longum, with two specifying the inclusion of two B. longum subspecies (90601). However, one clinical study has evaluated a combination product containing seven strains of probiotics in adults with H. pylori infection and peptic ulcer disease. In this study, adding this specific probiotic (Balance by Protexin Co) daily for 14 days to quadruple therapy with omeprazole, bismuth subcitrate, amoxicillin, and clarithromycin does not improve H. pylori eradication or symptoms when compared with quadruple therapy alone. This product provided B. longum, B. breve, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Streptococcus thermophilus (90291). The lack of effect might be attributed to the shorter duration of therapy or the different composition and dose of probiotics.
• Hyperlipidemia. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in individuals with total cholesterol of 190 mg/dL or higher shows that taking fermented milk 375 grams containing B. longum BB536 and Lactobacillus acidophilus 145 for 4 weeks reduces low-density lipoprotein (LDL) cholesterol levels when compared with yogurt. However, high-density lipoprotein (HDL) cholesterol levels seem to be reduced as well (35401).
• Irritable bowel syndrome (IBS). Although most research shows that taking Bifidobacterium longum in combination with other probiotics is beneficial for IBS, the effect of B. longum alone is unclear. Details: Some clinical research shows that consuming B. longum (35624; Align or Bifantis) in daily doses of 100 million colony-forming units (CFUs) as capsules or 1 billion CFUs as capsules or a malted milk drink for 4-8 weeks reduces overall disease severity, abdominal pain, bloating, and bowel movement difficulty, an improves quality of life in patients with IBS when compared with placebo or to baseline. These benefits seem to occur within one week of treatment (13054,95392,111773). However, not all research agrees. A meta-analysis of a small number of clinical studies shows that although this strain reduces overall symptom severity, taking B. longum does not increase the frequency of global responders or reduce abdominal pain when compared with placebo (107594). Also, although a meta-analysis of two studies shows that taking B. longum 35624 along with multiple other probiotics reduces abdominal pain and bloating/distension, a meta-analysis of three clinical trials shows that taking B. longum 35624 alone does not improve these symptoms or bowel habit satisfaction (107593). Also, one clinical trial shows that taking B. longum R0175 10 billion CFUs daily for 8 weeks does not improve symptoms of IBS when compared with placebo (103440). One clinical study shows that taking B. longum NCC3001 10 billion CFUs once daily for 6 weeks increases the percentage of patients with IBS who experience a clinically meaningful improvement in anxiety and depression symptoms by about 2-fold when compared with placebo. A clinically meaningful improvement was defined as an increase in Hospital Anxiety and Depression (HAD) scale score of at least 2 points (95417). Some research has evaluated B. longum in combination with other probiotics. Clinical research shows that taking a specific product (Duolac Care) containing B. longum, Bifidobacterium breve, Bifidobacterium animalis subsp. lactis, Lactobacillus acidophilus, Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Streptococcus thermophilus twice daily for 4 weeks can relieve symptoms in 72% of patients with IBS (95353). In addition, a clinical study in patients with diarrhea-predominant IBS shows that taking another specific combination probiotic (NordBiotic, MBM Biotix) containing B. longum BL020, B. breve BB010, B. animalis subsp. lactis BL040, Bifidobacterium bifidum BF030, Lactobacillus acidophilus LA120, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, Lacticaseibacillus casei LC130, and Lactiplantibacillus plantarum LP140, and Streptococcus thermophilus ST250 2.5 billion CFUs daily twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516).
• Japanese cedar pollinosis. It is unclear if oral Bifidobacterium longum is beneficial for this condition. Details: Some clinical research shows that taking powder containing B. longum BB536 50 billion colony-forming units twice daily for 4-13 weeks during pollen season reduces runny nose, nasal blockage, and overall symptom score when compared with placebo in patients with Japanese cedar pollen allergy (35382). However, other clinical research shows that taking this same strain daily for 13 weeks does not reduce runny nose or nasal blockage when compared with placebo (35379). There is also conflicting evidence regarding the effect of B. longum on eye symptoms, with some evidence showing no beneficial effect and other evidence suggesting reduced eye symptoms (35382,35384). Also, B. longum BB536 does not seem to improve nasal itching, sneezing, or throat symptoms associated with Japanese cedar pollinosis (35379,35382,35384).
• Lactose intolerance. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with persistent symptoms related to lactose intolerance despite a lactose-free diet, a small clinical trial shows that taking a combination of B. longum BB536 4 billion colony-forming units (CFUs), Lacticaseibacillus rhamnosus HN001 1 billion CFUs, and vitamin B6 1.4 mg (Zircombi) daily for 30 days modestly improves symptoms of bloating and constipation, but not abdominal pain, when compared with placebo (105153).
• Necrotizing enterocolitis (NEC). It is unclear if oral Bifidobacterium longum is beneficial or safe for NEC prevention. Details: Although some research disagrees, most clinical research and meta-analyses of clinical research show that giving bifidobacteria alone does NOT reduce the risk of NEC or all-cause mortality (92256,95344,95351,103437,105164). However, giving bifidobacteria in combination with lactobacilli or Enterococcus faecalis to preterm infants appears to reduce the risk of NEC by up to 87% and giving bifidobacteria with a prebiotic appears to reduce the risk of mortality (3162,90252,95351,102419,103437,103448,104157,105162,105164). A network meta-analysis of two clinical studies shows that taking a combination probiotic containing B. longum Bb-02, Bifidobacterium animalis subsp. Lactis Bb-12, and Streptococcus thermophilus TH-4, reduces the risk of NEC by 71% when compared with control (102437). Despite these findings, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, B. longum is not specifically recommended (103003,111609,111611). The effects of B. longum specifically are unclear.
• Nonalcoholic fatty liver disease (NAFLD). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with NAFLD shows that taking a combination product (Hexbio) containing B. longum BCMC 02129, B. longum BCMC 02120, Bifidobacterium bifidum BMCM 02290, Lactobacillus acidophilus BCMC 12,130, Lacticaseibacillus casei BCMC 12,313, and Lactobacillus delbrueckii subsp. lactis BCMC 12,451 as 30 billion colony-forming units twice daily for 6 months has no beneficial effects on hepatic steatosis or fibrosis, liver enzyme levels, blood lipids, or fasting blood glucose levels when compared with placebo (107523).
• Nonalcoholic steatohepatitis (NASH). Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with NASH shows that taking a specific combination probiotic capsule (Lactiale, Farmak) containing B. longum, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, and Streptococcus thermophilus 100 million colony-forming units in total, with fructo-oligosaccharides (FOS), once daily for 12 weeks does not improve liver enzyme levels or hepatic steatosis when compared with control (102415). However, other clinical research in patients with NASH undergoing lifestyle modification shows that taking an unspecified amount of B. longum in combination with FOS (Zirfos) daily for 24 weeks modestly reduces disease activity and steatosis, as well as levels of aspartate aminotransferase, low-density lipoprotein (LDL) cholesterol, insulin resistance, and inflammatory factors when compared with placebo. There was no effect on body mass index, high-density lipoprotein (HDL) cholesterol, triglycerides, other glycometabolic indices, or other measures of liver function (111849). It is unclear whether any benefits are related to B. longum, FOS, or the combination.
• Obesity. Although there has been interest in using oral Bifidobacterium longum for weight loss, there is insufficient reliable information about the clinical effects of B. longum for this use.
• Oral mucositis. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in patients with locally advanced nasopharyngeal cancer undergoing radiochemotherapy shows that taking a specific probiotic product (Bifico, Shanghai Sine Pharmaceutical Co. Ltd.) containing B. longum, Lactobacillus delbrueckii subsp. lactis, and Enterococcus faecium three capsules twice daily for up to 7 weeks modestly reduces the incidence of severe oral mucositis when compared with placebo (102413).
• Periodontitis. Although there has been interest in using oral Bifidobacterium longum for periodontitis, there is insufficient reliable information about the clinical effects of B. longum for this condition.
• Postoperative infection. It is unclear if oral Bifidobacterium longum is beneficial for preventing postoperative infections. Details: Preliminary clinical research shows that taking B. longum BB536 50 billion colony-forming units daily for 7-14 days before colorectal surgery and then postoperatively for 14 days does not reduce the incidence of postoperative infections, the need for additional antibiotics, or the duration of hospital stay when compared with no intervention. However, hospital stay was reduced by 18 days in a sub-set of patients who had received preoperative chemoradiotherapy (111772).
• Prematurity. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One large observational study in infants fed strictly human milk, but not strictly formula or a combination, suggests that taking B. longum 1-1.5 billion colony-forming units with L. acidophilus during the first month of life for the prevention of necrotizing enterocolitis is associated with a modest increased weight gain velocity. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Psoriasis. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with psoriasis shows that taking a mixture of probiotics for 8 weeks modestly improves overall symptoms and feelings of depression when compared with placebo. The percentage of patients achieving at least a 50% or 75% reduction in overall symptom score was 40% and 24%, respectively, in those taking the probiotic, compared with 16% and 8% of those taking placebo. Each probiotic capsule provided a total daily dose of 2.6 billion colony-forming units (CFUs) of B. longum, Bifidobacterium bifidum, Bifidobacterium animalis subsp. lactis, and Lactobacillus acidophilus (107498).
• Radiation-induced diarrhea. Although there has been interest in using oral Bifidobacterium longum for radiation-induced diarrhea prevention, there is insufficient reliable information about the clinical effects of B. longum for this condition.
• Respiratory tract infections. It is unclear if oral Bifidobacterium longum is beneficial for preventing respiratory tract infections. Details: One clinical study shows that taking B. longum R0033 3 billion colony-forming units (CFUs) daily for 6 weeks does not reduce the percentage of college students who experience at least one day of cold or flu or the overall number of cold or flu episodes when compared with placebo (90272). However, preliminary clinical research in children aged 2-6 years shows that taking B. longum B536, 5 billion CFUs daily on 5 days each week for 10 months, reduces the duration of sore throat by 46% and modestly decreases the frequency of respiratory illnesses when compared with placebo. There was also a nonsignificant trend toward reduced fever and runny nose duration in the treatment group; however, the study was not adequately powered to detect a difference in these outcomes (98738).
• Retinopathy of prematurity. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One large observational study in premature infants suggests that taking L B. longum 1-1.5 billion colony-forming units with L. acidophilus during the first month of life for the prevention of necrotizing enterocolitis is not associated with a reduced risk of retinopathy of prematurity. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Rotaviral diarrhea. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in hospitalized infants with rotaviral infection shows that giving a probiotic formula containing B. longum BORI and Lactobacillus acidophilus AD031 2 billion colony-forming units per gram twice daily for 3 days reduces the duration of diarrhea by about 1.2 days when compared with placebo; however, it does not reduce the duration of fever or the frequency of diarrhea or vomiting (95334).
• Sepsis. Oral Bifidobacterium longum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One large observational study in infants fed a mix of human milk and formula, but not strictly human milk or formula, suggests that taking B. longum 1-1.5 billion colony-forming units with L. acidophilus during the first month of life for the prevention of necrotizing enterocolitis is associated with a 31% reduction in the development of clinical sepsis. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Ulcerative colitis. It is unclear if oral Bifidobacterium longum is beneficial for ulcerative colitis. Details: A small clinical trial in patients with mild to moderate ulcerative colitis symptoms and using stable doses of standard treatment shows that taking at least 200 billion colony-forming units B. longum 536 three times daily for 8 weeks does not increase the proportion of patients in remission or reduce symptom severity when compared with taking placebo (111851). Given the high rate of response in the group given only standard treatment, this study may have been too small to detect differences between groups. More evidence is needed to rate Bifidobacterium longum for these uses.

(Read more about BIFIDOBACTERIUM LONGUM)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. Observational research suggests that higher dietary intake of cassava flour is linked with a 9% reduced risk for developing type 2 diabetes when compared with lower dietary intake (99803).
• Diarrhea-related dehydration. Preliminary clinical research suggests that salt solutions from cassava might be effective for treating diarrhea-related dehydration in children (25884,25885). In one trial, taking a cassava salt solution significantly reduced stool output and duration of diarrhea compared to the World Health Organization/Oral Rehydration Solution (WHO/ORS) in children with dehydration caused by diarrhea (25885). However, while cassava salt solution appears to be effective for the management of mild to moderate diarrhea-related dehydration in children, its low electrolyte content makes it unsuitable for treating severe dehydration with electrolyte depletion (25884). More evidence is needed to rate cassava for these uses.

(Read more about CASSAVA)

POSSIBLY EFFECTIVE

• Urinary tract infections (UTIs). Cranberry products may possibly reduce the risk of repeat, symptomatic UTI in females with recurrent UTI, in children, and in people susceptible to UTI following kidney transplant, urogenital surgery, or radiation therapy near the urogenital system. While some positive evidence exists, most research suggests that cranberry products do not seem to reduce the risk of UTI in older adults in institutions, pregnant patients, or adults with neuromuscular dysfunction of the bladder. Cranberry is not recommended for the treatment of UTI in any population. Details: Cranberry appears to reduce the risk of UTI in some populations but not others. In healthy females at an increased risk of UTI or history of recurrent UTI, meta-analyses of clinical trials show that cranberry products decrease the overall risk of recurrent or first-time UTI by 26% to 35% (46473,92578,96739,111407). In 2019, the American Urological Association published guidelines stating that, based on low certainty evidence, clinicians may offer cranberry tablets or juice as prophylaxis for females with recurrent UTIs. Due to a lack of compelling evidence for any specific product, the guidelines recommend choosing formulations based on availability and tolerability (100855). In 2020, the US Food and Drug Administration (FDA) approved qualified health claims stating that consuming cranberry juice in doses of at least 8 ounces daily, or cranberry supplements in doses of at least 500 mg daily, may help reduce the risk of recurrent UTI in healthy females. However, the FDA has concluded that there is limited scientific evidence to support these claims (103302). The benefits of cranberry for prevention of UTI during pregnancy are unclear. Subgroup analysis of meta-analyses suggest that cranberry supplementation does not reduce the risk of UTI in pregnant adults compared with placebo or no treatment (100855,111407). A preliminary clinical study shows that drinking cranberry juice 240 mL three times daily until delivery does not reduce the frequency of asymptomatic bacteriuria or symptomatic UTI during pregnancy, although the study was not adequately powered to detect a difference in these outcomes (16415). In contrast, one preliminary clinical trial shows that UTI frequency was reduced in 70.5% of those ingesting cranberry juice 250 mL four times daily, compared with only 32% of those taking placebo (93670). In children, a meta-analysis shows that taking cranberry products probably reduces the risk of subsequent symptomatic UTIs by up to 54% compared with placebo or no treatment, but does not specify a particular formulation (111407). Clinical trials show that daily consumption of cranberry syrup (Pharmatoka), cranberry juice (Cranberry UR-50, Kikkoman Company) 100 mL, cranberry-lingonberry juice 50 mL, and cranberry extract (Anthocran) 120 mg reduce the risk of UTI recurrence in children (46452,96733,96737,108055). In contrast, another clinical trial shows that drinking cranberry juice (Ocean Spray Cranberries, Inc) 5 mL/kg daily for 6 months does not reduce the incidence of recurrent UTI when compared with placebo, although it does decrease the total number of UTI episodes and length of antimicrobial therapy per child (46470). In older, institutionalized adults, a meta-analysis of 5 studies evaluating the effectiveness of cranberry products shows little or no benefit in preventing symptomatic, culture-verified UTIs (111407). A clinical study in females residing in long-term care (LTC) facilities shows that taking a specific cranberry supplement (Ellura, Pharmatoka) once daily for 1 year does not reduce the incidence of UTI or asymptomatic bacteriuria (92517). However, clinical trials of cranberry products in elderly patients in LTC facilities suggest that cranberry may be more effective in patients at a higher risk for UTIs, such as those with diabetes, long-term catheterization, or recurrent UTIs (90041,108055), and in patients with E. coli-related UTIs (46389,46472). In one small study, providing all patients living in a LTC facility with 4 ounces of cranberry juice or six tablets of a specific concentrated cranberry product (Azo-Cranberry, i-Health, Inc.) daily for 13 months decreased the facility's overall monthly UTI rate from 27.7 to 20.7 (46492). In another clinical trial, taking cranberry juice cocktail (Ocean Spray Cranberries, Inc) 300 mL daily for 6 months decreased the rate of asymptomatic bacteriuria plus pyuria by 13% in older females living in institutional settings (7008). In another clinical trial, taking a cranberry capsule 500 mg, standardized to 1.8% PACs, twice daily for 12 months decreased the risk of UTI by around 26% in patients at high-risk for UTI, including those with catheters, diabetes, or at least one UTI in the previous 12 months (90041). Meta-analyses and clinical research show that cranberry products do not reduce the risk of UTI associated with neurogenic bladder, neuromuscular dysfunction, or insufficient bladder emptying in adults or children (2811,6759,11980,46379,46425,46473,90044,92578,96737,108055,111407). However, one study found benefit in patients with neurogenic bladder due to spinal cord injury taking cranberry capsules (Cran-Max, Proprietary Nutritionals, Inc.) 500 mg daily (46443). Cranberry products have also been evaluated in a variety of other high-risk populations, with mixed results. A meta-analysis of 7 studies shows that cranberry products reduce the risk of UTIs in people with increased susceptibility to UTI due to an intervention (e.g., kidney transplant, radiotherapy to urogenital system, or urogenital surgery) when compared with placebo (111407). Cranberry extracts do not seem to reduce the risk of UTIs in individuals undergoing hysterectomy and/or anterior vaginal repair (46465), pelvic floor surgery (104245), or in patients with multiple sclerosis (46496,111407). Taking cranberry powder capsules (NurtiCran90, Petefa AB) 550 mg three times daily for 5 days does not reduce the UTI rate at days 5 or 14 when compared with placebo in postoperative females with hip fracture receiving a urinary catheter; however, the study was not adequately powered to detect a difference in this outcome (96734). Other preliminary clinical research in elderly males with benign prostatic hyperplasia and a recent UTI shows that taking a standardized cranberry extract (Anthocran) 120 mg daily for 60 days reduces the UTI recurrence rate by about 62% when compared with placebo (96735). Cranberry supplements have been studied in a variety of formulations, but it is unclear whether certain cranberry formulations are better than others (111407). Most positive studies utilized oral cranberry EXTRACTS in tablet, powder, or capsule form (6760,17210,46366,46432,93669,111407). Some products (Cranberry Supreme, GNC; Cranpac, IPCA Laboratories), taken as 200 mg twice daily, were standardized to provide 100-120 mg of proanthocyanidins (PACs) daily (46432). Some of these studies used capsules containing 400 mg cranberry solids twice daily (6760) or Natural Cranberry Extract (Solgar Vitamin and Herb Co.) 800 mg twice daily (17210). However, a clinical study in healthy females with a history of UTIs shows that taking a specific cranberry extract product (Urophenol; Diana Food) does not reduce the risk of symptomatic UTI when taken at a dose of 120 mg twice daily, standardized to 15% PACs, or at a dose of 1 mg twice daily, standardized to 1% PACs. A subgroup analysis suggests that the high dose may have modest benefit in those with less than 5 UTIs a year (108054). Cranberry JUICE or syrup has yielded mixed results for the prevention of UTI in patients with a history of recurrent UTIs, with some showing significant benefit (8253,46366,96736,111407). These studies used cranberry juice 240-250 mL 1-3 times daily (46366,96736), cranberry syrup, or a combination beverage containing cranberry juice plus lingonberry juice (Maija) 50 mL daily (8253). However, other studies found no significant improvement when compared with placebo (17524,46471,90047), although some of these studies may have been inadequately powered to detect a difference (17524,46471). Cranberry products have also been compared with other treatments including antibiotics and probiotics for preventing recurrent UTI, but the results are unclear. A meta-analysis suggests that cranberry products reduce the risk of symptomatic UTIs compared to probiotics. The analysis also showed no difference in the risk of UTI between cranberry products and antibiotics, but the precision of included studies was poor (111407). In one study, taking cranberry extract capsules (Cran-Max; Proprietary Nutritionals, Inc) 500 mg daily for 6 months was as effective as trimethoprim 100 mg daily in elderly females with recurrent UTI (16720). However, taking this same cranberry product twice daily for 12 months was less effective than trimethoprim-sulfamethoxazole 480 mg once daily in younger premenopausal individuals (17176). Additional research in children with vesicoureteral reflux (VUR) shows that daily consumption of cranberry products results in UTI recurrence rates equivalent to those obtained with prophylactic antibiotics. Cranberry juice (Cranberry UR-50, Kikkoman Company) 100 mL daily was equally effective to cefaclor 5-10 mg/kg daily; cranberry syrup (Pharmatoka) 0.2 mL/kg daily was equally effective to trimethoprim 0.2 mL/kg daily (96737).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral cranberry is beneficial for age-related cognitive decline. Oral cranberry may be beneficial for improving visual episodic memory in healthy, elderly adults, but its effects on other aspects of cognition are unclear. Details: A clinical study in healthy adults aged 50-80 years shows that taking a freeze-dried cranberry powder 4.5 grams twice daily (standardized to provide 281 mg proanthocyanidins daily), provided as a sachet and added to food or beverage for 12 weeks, improves visual episodic memory performance during a memory and recall test (Rey Complex Figure Test), but does not appear to affect other measures such as attention, orientation, fluency, language, processing speed, or short-term memory, when compared with placebo (108564). Cranberry supplementation also does not appear to affect grey matter structure; however, due to the low number of patients who completed a baseline and follow-up MRI, this study may not have been adequately powered to detect a difference between groups.
• Benign prostatic hyperplasia (BPH). Preliminary clinical research suggests that oral cranberry is beneficial for reducing BPH symptoms. Details: Preliminary clinical research shows that taking powdered dried cranberry fruit 500 mg three times daily for 6 months improves lower urinary symptoms and reduces prostate specific antigen (PSA) levels when compared with no treatment in patients 45 years of age or older with elevated PSA levels, a negative prostate biopsy, and clinically confirmed non-bacterial prostatitis (17126). Another small study in those 45 years of age and older without elevated PSA levels shows that taking a specific dried cranberry powder (Flowens, Naturex-DBS, LLC) 250-500 mg daily for 6 months reduces lower urinary tract symptoms and improves voiding and storage symptoms when compared with placebo (96738).
• Cancer. Although there has been interest in using oral cranberry for cancer, there is insufficient reliable information about the clinical effects of cranberry for this condition.
• Cardiovascular disease (CVD). Although some research suggests that oral cranberry may modestly improve some CVD risk factors, it is unclear if it is beneficial for CVD prevention. Details: A meta-analysis of 10 clinical studies shows that cranberry juice or cranberry extract seems to reduce systolic blood pressure by 3.6 mmHg and body mass index by 0.3 kg/m2 when compared with placebo. However, these improvements are unlikely to be clinically significant, and cranberry does not appear to improve diastolic blood pressure, lipid levels, glycemic control, or waist circumference (102849). The generalizability of these results is limited, as the study populations ranged from healthy adults to those with type 2 diabetes, metabolic syndrome, or coronary heart disease. A clinical crossover study in patients who are overweight or obese and have elevated blood pressure shows that drinking cranberry juice 250 mL twice daily for 8 weeks reduces ambulatory diastolic blood pressure by 2 mmHg during daytime hours, but does not improve systolic blood pressure, glycemic control, or lipid levels, when compared with placebo (108059). The validity of these findings is limited due to short duration of treatment and broad heterogeneity of patient baseline characteristics.
• Catheter-related infections. Although there has been interest in using oral cranberry for catheter-related infections, there is insufficient reliable information about the clinical effects of cranberry for this condition.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral cranberry for CFS, there is insufficient reliable information about the clinical effects of cranberry for this condition.
• Diabetes. It is unclear if oral cranberry is beneficial for diabetes. Details: A small clinical trial shows that taking cranberry supplements orally does not improve fasting serum glucose, glycated hemoglobin (HbA1C), fructosamine, triglycerides, high-density lipoprotein (HDL) cholesterol, or low-density lipoprotein (LDL) cholesterol levels in patients with type 2 diabetes (11328).
• Helicobacter pylori. There is conflicting evidence regarding the use of oral cranberry for Helicobacter pylori eradication, either as a standalone treatment or in combination with standard triple therapy. Details: Two small clinical studies show that taking cranberry juice 480-500 mL, containing 88 mg proanthocyanidins (PACs), daily in two divided doses for 2-3 months can modestly increase the H. pylori eradication rate at 8 weeks, but not at 2 weeks, when compared with placebo. However, the eradication rate was only 20% or less, which is much lower than that obtained with conventional triple therapy (46388,104248). Lower doses, as either cranberry juice or cranberry powder, do not seem to improve H. pylori eradication rates. Cranberry juice containing only 23 mg or 44 mg PACs or cranberry powder containing 36 mg or 72 mg PACs did not demonstrate benefit when compared with placebo (104248). Cranberry juice has also been studied in combination with standard triple therapy. Preliminary clinical research shows that taking cranberry juice 250 mL daily for 3 weeks along with omeprazole, amoxicillin, and clarithromycin for one week does not increase the eradication rate when compared with triple therapy plus placebo. However, the combination treatment increased the rate of H. pylori eradication when only females were considered (46439). A meta-analysis of 4 small clinical studies, including three studies already discussed, shows that taking cranberry, either as a juice or a dried powder, does not improve H. pylori eradication rate when compared with placebo, regardless of treatment duration (108060). The validity of these findings is limited by the high heterogeneity of the included studies and incomplete reporting. In asymptomatic children aged 6-16 years old with H. pylori, one clinical study shows that drinking cranberry juice 200 mL, with live or heat-killed Lactobacillus johnsonii 80 mL, daily for 3 weeks eradicates H. pylori in 15% to 22% of patients, compared with 1.5% of those receiving placebo. However, these rates are lower than those typically obtained with conventional triple therapy (46441).
• Hyperlipidemia. Oral cranberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Drinking a combination of cranberry, blueberry, apple, and chokeberry juice 300 mL daily for 6 weeks appears to decrease total cholesterol and increase high-density lipoprotein (HDL) cholesterol when compared to baseline in females with overweight or obesity and at least one risk factor for cardiovascular disease (111233). However, the validity of the study is limited by its small size, short duration, and lack of a comparator group. It is unclear if these effects are due to cranberry, other ingredients, or the combination.
• Kidney stones (nephrolithiasis). It is unclear if oral cranberry is beneficial for reducing the risk of kidney stones. Details: Although some preliminary clinical research shows that drinking cranberry juice 500 mL diluted in 1500 mL water daily for 2 weeks can decrease urinary excretion of oxalate in healthy males, which suggests a decreased risk of kidney stone formation (46371), other preliminary clinical research shows that both cranberry juice and concentrated cranberry extracts can increase urinary oxalate levels, suggesting an increased risk of stone formation (7074,46393).
• Memory. It is unclear if oral cranberry is beneficial for memory. Details: Preliminary clinical research in cognitively intact older adults shows that taking cranberry juice 16 ounces twice daily for 6 weeks does not improve memory when compared with placebo (46390).
• Metabolic syndrome. It is unclear if oral cranberry is beneficial for metabolic syndrome. Details: Preliminary clinical research shows that drinking cranberry juice 240 mL twice daily for 8 weeks can increase plasma antioxidant capacity when compared with placebo in adults with metabolic syndrome. However, cranberry juice does not appear to affect blood pressure, blood glucose, serum lipids, or markers of inflammation when compared with placebo in these patients (46467).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral cranberry is beneficial for NAFLD. Details: Preliminary clinical research in adults with NAFLD shows that adding cranberry extract 288 mg daily to a weight loss diet for 12 weeks does not appear to affect body weight, liver enzymes, lipid levels, or steatosis grade when compared with placebo. Cranberry extract may moderately reduce insulin levels and insulin resistance (104249). However, the clinical impact of these reductions is unclear. Another clinical trial in adults with NAFLD shows that taking dried cranberry powder 144 mg daily after lunch for 6 months improves steatosis grade as measured by ultrasound, insulin sensitivity, and levels of total cholesterol and triglycerides, but does not affect liver enzyme levels, when compared with placebo. All patients also consumed a reduced-calorie diet and an undefined dose of supplemental vitamin E (108058).
• Obesity. Oral cranberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in females with overweight or obesity and at least one risk factor for cardiovascular disease shows that drinking a combination of cranberry, blueberry, apple, and chokeberry juice 300 mL daily for 6 weeks does not reduce body weight, body mass index (BMI), or blood pressure but might improve total cholesterol and high-density lipoprotein (HDL) cholesterol when compared to baseline (111233). However, the validity of these findings is limited by the small study size, short duration, and lack of a comparator group. It is unclear if these effects are due to cranberry, other ingredients, or the combination.
• Overactive bladder. It is unclear if oral cranberry is beneficial for overactive bladder. Details: Preliminary clinical research in otherwise healthy females shows that taking dried cranberry powder 500 mg daily for 24 weeks can reduce daily micturition by 16% and urgency episodes by 57% when compared with placebo. Patients taking cranberry powder also reported an improvement in their own perception of their bladder condition when compared with placebo (104246). Limitations of this study include a short duration, lack of a run-in period, and high drop-out rate, which interfered with the ability to meet power.
• Periodontitis. Topical cranberry extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with chronic periodontitis shows that applying a topical combination gel product containing cranberry extract 2.5 grams and garcinia extract after scaling and root planing reduces plaque index, gingival index, probing pocket depth, clinical attachment level, and salivary biomarkers of periodontal disease when compared with scaling and root planing alone and similarly to scaling and root planing with tetracycline fibers (112272). It is unclear if these effects are due to cranberry, garcinia, or the combination.
• Peristomal lesions. Although there has been interest in using oral cranberry for peristomal lesions, there is insufficient reliable information about the clinical effects of cranberry for this condition.
• Prostate cancer. It is unclear if cranberry is beneficial for preventing prostate cancer recurrence. Details: Clinical research shows that taking cranberry powder (Pacran, Naturex) 1500 mg for a mean of 30 days prior to radical prostatectomy for prostate cancer does not improve prostate tissue markers when compared with taking placebo. However, levels of prostate tissue antigen decreased by approximately 22% when compared with baseline (105127).
• Radiation-induced cystitis. Evidence for the use of cranberry juice in the prevention of radiation-induced cystitis is conflicting. Details:One small clinical study in individuals with prostate cancer shows that taking 200 mg of a cranberry extract standardized to 30% proanthocyanidins (Monoselect Macrocarpon; PharmExtracta) once daily during external beam radiotherapy for 6-7 weeks reduces the risk of lower UTI by 64% when compared with placebo (92579). However, other preliminary clinical research shows that taking cranberry capsules, standardized to contain a total of 72 mg proanthocyanidins, daily during radiation treatment for prostate cancer and for two weeks post-treatment, does not improve pain, burning, nocturia, or urinary flow symptoms from radiation-induced cystitis when compared with a beetroot placebo (104247). Additionally, preliminary clinical research in patients receiving radiotherapy for bladder or cervical cancer shows that consuming cranberry juice 250 mL daily for 2 weeks does not seem to reduce the incidence of UTIs (46469).
• Rheumatoid arthritis (RA). It is unclear if oral cranberry is beneficial in RA. Details: A clinical study in adults with RA shows that drinking reduced-calorie cranberry juice 250 mL twice daily in addition to taking fish oil 1 gram three times daily for 90 days improves disease activity score (DAS28-CRP) when compared with no supplementation. However, this combination was similarly effective to patients taking fish oil alone, suggesting that any benefits may be due to fish oil, as opposed to cranberry juice (108057). In contrast, another small study in adults with RA shows that drinking reduced-calorie cranberry juice 500 mL daily for 90 days does not improve disease activity score or clinically relevant biologic markers of RA such as rheumatoid factor, anti-cyclic citrullinated peptide antibodies, erythrocyte sedimentation rate, or C-reactive protein when compared with a control group (112273).
• Upper respiratory tract infection (URTI). It is unclear if oral cranberry is beneficial for the prevention or treatment of URTIs. Details: Clinical research shows that drinking a cranberry juice beverage 450 mL daily for 70 days does not decrease the incidence of cold or flu, but may reduce cold and flu symptoms, when compared with placebo in healthy adults (90046).
• Urinary odor. It is unclear if oral cranberry is beneficial for urinary odor. Details: Preliminary clinical research shows that cranberry juice cocktail might reduce urinary odors when given orally on a regular basis to patients with urinary incontinence (3333,3334,8254). Cranberry juice cocktail up to 237 mL three times daily for up to 4 weeks has been used (3334). More evidence is needed to rate cranberry for these uses.

(Read more about CRANBERRY)

POSSIBLY EFFECTIVE

• Constipation. Oral guar gum may improve symptoms and stool frequency in adults and children with constipation. Details: Several small clinical studies in adults show that taking partially hydrolyzed guar gum increases stool frequency and relieves straining and pain when compared to baseline. Studied doses include 4-12 grams daily for up to 8 weeks or 11 grams twice daily for up to 3 weeks (12548,25073,93619). Small clinical studies in children with constipation also show that taking guar gum 3-5 grams daily for 4 weeks or partially hydrolyzed guar gum 6 grams daily for 2-15 months moderately increases bowel movement frequency and decreases abdominal pain when compared to baseline (93605,101889). While these improvements appear to be similar to those reported in children treated with lactulose (93605), a direct comparison is lacking.
• Diarrhea. Oral guar gum may reduce the duration of diarrhea in adults and children. Details: Two small clinical studies in patients in the intensive care unit show that adding guar gum 2% or 22 grams/L to enteral feeding formula reduces the number of liquid stools and decreases the percentage of days with diarrhea by around 70% when compared with control enteral formula (10325,54239). A larger clinical trial in children with acute watery diarrhea due to infections also shows that taking guar gum reduces the duration of diarrhea by around 16 hours when compared with a control (54210). Another clinical study in children with persistent watery diarrhea also shows that adding guar gum 20 grams/L daily for 7 days to a comminuted chicken diet improves the odds of diarrhea resolution after 7 days by 3-fold when compared with the chicken diet alone (54243).
• Hypercholesterolemia. Oral guar gum, taken alone or with other dietary fibers, may reduce cholesterol levels in patients with hypercholesterolemia. Details: Several small clinical trials in patients with hypercholesterolemia show that taking guar gum 15-18 grams in single or divided doses daily for up to 24 months lowers cholesterol levels when compared with baseline levels or placebo (4971,10897,54314,54318,54333). Additionally, a meta-analysis of 25 small clinical studies in patients with hypercholesterolemia, diabetes, hypertension, or metabolic syndrome shows that guar gum reduces total cholesterol by around 20 mg/dL and low-density lipoprotein (LDL) cholesterol by around 17 mg/dL, but does not reduce triglyceride levels, when compared with controls. Subgroup analyses suggest that improvements in total and LDL cholesterol are greater in patients with hypercholesterolemia and in those taking at least 15 grams of guar gum daily (107930). Additional clinical evidence shows that taking guar gum along with other dietary fibers can reduce cholesterol levels. Taking 20 grams of a mixture containing guar gum, pectin, and a small amount of the insoluble fibers from soy, pea, and corn bran daily for 36 weeks lowers total and LDL cholesterol, but does not affect high-density lipoprotein (HDL) cholesterol or triglyceride levels (12547,54335). Also, taking a specific product containing guar gum and psyllium (Minolest) 16.5 grams daily for 3 months reduces total and LDL cholesterol when compared with placebo, but does not affect triglyceride levels (54206). Taking 15 grams of a combination of guar gum, psyllium, pectin, and carob gum daily for 6 months also appears to reduce total and LDL cholesterol when compared to baseline (8431).
• Hypertension. Oral guar gum may modestly reduce systolic and diastolic blood pressure, although these reductions may not be considered clinically significant. Details: Several small clinical trials in patients with hypertension show that taking guar gum 7-10 grams with each meal daily for up to 6 weeks modestly reduces systolic and diastolic blood pressure when compared with placebo (54232,54304,54320). However, guar gum does not appear to be as effective for reducing blood pressure as psyllium husk (54260). A meta-analysis of clinical trials in adults also shows that taking guar gum 1-30 grams daily for 6 weeks to 6 months reduces systolic and diastolic blood pressure by approximately 1 mmHg when compared with placebo or no intervention. However, many patients included in these trials did not have hypertension at baseline. Sub-analyses suggest that the effects of guar gum on blood pressure may be larger in patients with hypertension. The validity of this meta-analysis is limited by high heterogeneity (105507).
• Irritable bowel syndrome (IBS). Oral guar gum may improve bowel function and abdominal pain in adults and children with IBS. Details: Clinical trials in adults with IBS show that taking guar gum 5-10 grams daily for 12 weeks improves abdominal pain, bowel function, and quality of life when compared with baseline or wheat bran (10326,54245). A small clinical study in children 8-16 years of age with chronic abdominal pain and IBS shows that taking partially hydrolyzed guar gum 5 grams daily for 4 weeks decreases symptom frequency and normalizes bowel movements when compared with placebo. However, it does not improve abdominal pain (93615). Another small clinical trial in children 1-18 years of age with IBS shows that taking a specific guar gum product (Resource Optifibre, Nestle HealthCare Nutrition) for at least 6-8 weeks improves stool consistency and abdominal pain when compared to baseline (93621).

POSSIBLY INEFFECTIVE

• Obesity. Oral guar gum may not improve body weight in patients with obesity. Details: Several small clinical trials in overweight or obese adults show that taking guar gum 10.5-20 grams in divided doses daily for up to 14 months does not reduce body weight or improve satiety when compared with placebo or other controls (54212,54260,54353,54360). Additionally, a meta-analysis of 11 small clinical studies of various patient populations, including postmenopausal adults and those with hyperlipidemia or diabetes, shows that taking guar gum 7.5-21 grams daily for 3 weeks to 6 months does not reduce body weight when compared with placebo (8305).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anal fissures. It is unclear if oral guar gum is beneficial in patients with anal fissures. Details: A small clinical study in patients with chronic anal fissures treated with topical application of glyceryl trinitrate shows that taking partially hydrolyzed guar gum 5 grams daily as maintenance therapy for a total of 10 months increases success rate by 53% and decreases the risk for recurrence of anal fissures by 52% when compared with control (93617).
• Autism spectrum disorder. It is unclear if oral guar gum is beneficial in children with autism spectrum disorder. Details: A very small clinical study in children 4-9 years of age with autism and constipation shows that taking partially hydrolyzed guar gum (Sunfiber, Taiyo Kagaku Co. Ltd.) 6 grams daily for 2-15 months moderately improves irritability, but not other measures of behavior, when compared to baseline (101889). The validity of this finding is limited by the lack of a comparator group.
• Chemotherapy-induced diarrhea. It is unclear if oral guar gum is beneficial for the prevention or treatment of chemotherapy-induced diarrhea. Details: A clinical study in patients receiving 5-fluorouracil chemotherapy for colorectal cancer shows that adding guar gum (Novasource GI control, Novartis Nutrition) 11 grams daily on cycle days 7-14 for 24 weeks to treatment with Lacticaseibacillus rhamnosus GG does not reduce the rate of severe diarrhea or other abdominal complaints when compared with no treatment or L. rhamnosus GG alone (16736).
• Cholera. It is unclear if oral guar gum is beneficial for improving diarrhea in patients with cholera. Details: A small clinical study in adults with cholera treated with doxycycline shows that adding guar gum 25-50 grams to oral rehydration solution for 2 days does not reduce the duration of diarrhea, but might reduce stool weight over the first 24 hours, when compared with oral rehydration solution alone (54262).
• Cholestasis. Small clinical studies suggest that oral guar gum may not improve symptoms of cholestasis during pregnancy. Details: Two small clinical studies in patients with cholestasis during pregnancy show that taking a specific granulated guar gum product (Guarem, Orion Pharmaceutical) 5-15 grams daily until delivery does not reduce the intensity of pruritus or improve liver function when compared with placebo (54209,54356).
• Diabetes. Small clinical studies suggest that oral guar gum might improve postprandial glucose levels in patients with type 1 diabetes; whether guar gum is effective for improving glycemic control in patients with type 2 diabetes is unclear. Details: Two small clinical studies in patients with type 1 diabetes show that taking guar gum 5 grams with meals four times daily for 4-6 weeks lowers postprandial glucose levels when compared with placebo (10896,12545). However, clinical trials in patients with type 2 diabetes show conflicting results. Several very small clinical studies suggest that taking guar gum 5-7.6 grams with each meal daily for up to 48 weeks lowers blood glucose when compared with baseline levels or placebo in patients with type 2 diabetes (12540,12541,12542,12543,12544). However, other small clinical trials in these patients show that taking guar gum 5-7 grams with each meal for up to 3 months does not improve glycemic control (54270,54275,54320,54326). The reasons for these discrepant findings are unclear; however, all of the studies in patients with type 2 diabetes were very small and likely underpowered to identify significant treatment effects. In addition to glycemic control, the effect of guar gum on serum lipids in patients with diabetes has also been evaluated. A meta-analysis of 11 small clinical studies in patients with type 2 diabetes with or without hypercholesterolemia shows that taking guar gum 5-30 grams daily for up to 6 months reduces total cholesterol by around 20 mg/dL and low-density lipoprotein (LDL) cholesterol by around 15 mg/dL. Doses of guar gum 20 grams daily or greater also appear to reduce triglyceride levels by around 13 mg/dL, while lower doses have no effect (107929).
• Influenza. It is unclear if oral guar gum is beneficial for the prevention of influenza. Details: Observational research in hospitalized patients has found that taking partially hydrolyzed guar gum 5.2 grams daily for the duration of a hospital stay is associated with a lower risk of influenza when compared with those not taking guar gum. One additional case of influenza appears to be prevented for every 14 patients taking guar gum over placebo (107928).
• Malnourishment-related diarrhea. It is unclear if oral guar gum is beneficial in children with malnourishment-related diarrhea. Details: A small clinical study in children aged 6-36 months with acute watery diarrhea related to malnutrition shows that adding guar gum 15 grams/L to oral rehydration solution reduces the duration of diarrhea by around 18 hours when compared with oral rehydration solution alone (93616).
• Postprandial hypotension. Small clinical studies suggest that oral guar gum may be beneficial for the prevention of postprandial hypotension in older females and patients with type 2 diabetes. Details: A small clinical study in older females with postprandial hypotension shows that taking guar gum 9 grams along with a meal decreases the risk of postprandial hypotension by 75% when compared with placebo (93618). Another small clinical study in patients with type 2 diabetes shows that taking guar gum 9 grams prior to a meal reduces the risk of postprandial decreases in blood pressure when compared to baseline (12540).
• Small intestinal bacterial overgrowth (SIBO). It is unclear if oral guar gum is beneficial in patients with SIBO. Details: A small clinical study in patients with SIBO shows that taking guar gum 5 grams daily along with rifaximin 1200 mg daily for 10 days increases the chance for eradication of SIBO by 37% to 40% when compared with rifaximin alone. However, overall clinical improvement appears to be similar for guar gum plus rifaximin and rifaximin alone (93622). More evidence is needed to rate guar gum for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Antibiotic-associated diarrhea. Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a specific L. casei-containing combination product (Bio-K+ CI1285) may be beneficial for preventing antibiotic-associated diarrhea. This combination product provides L. casei LBC80R, Lactobacillus acidophilus CL1285 and Lacticaseibacillus rhamnosus CLR2 as 100 billion colony-forming units (CFUs) daily (25494,95402,95403) However, taking L. casei might not help with the treatment of antibiotic-associated diarrhea. Clinical research in hospitalized patients with antibiotic-associated diarrhea shows that taking a combination of L. casei 20 million CFUs and Bifidobacterium breve 50 million CFUs 3 times daily does not reduce the average duration of diarrhea, the frequency of healing, or relapse rates, when compared with taking placebo (111006).
• Atopic dermatitis (eczema). Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children under two years of age with atopic dermatitis who are on a cow's milk protein elimination diet, clinical research shows that taking a specific mixture (Latopic, Biomed S.A.) providing 1 billion colony-forming units (CFUs) of L. casei ôOCK 0919 50%, Lacticaseibacillus rhamnosus ŁOCK 0900 25%, and L. rhamnosus ôOCK 0908 25% for 3 months increases the odds of a 30% or greater improvement in symptom scores by about 2.6-fold when compared with placebo. However, there was no difference in the absolute symptom scores between groups. Beneficial effects of this combination were greater in children confirmed to have allergen sensitization (107510). Other clinical research in children ages 4-17 years shows that taking 1 billion CFUs of a 1:1:1 combination of L. casei CECT 9104, Bifidobacterium lactis CECT 8145, and Bifidobacterium longum CECT 7347 for 12 weeks modestly reduces symptom severity and the need for topical corticosteroids when compared with placebo (107531).
• Cancer. Although there has been interest in using oral Lacticaseibacillus casei for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of L. casei for this condition.
• Clostridioides difficile infection. Some early research suggests that oral Lacticaseibacillus casei may be beneficial for preventing a first C. difficile infection. However, the quality of evidence is generally poor, and taking oral L. casei does not seem to be beneficial for the prevention of C. difficile recurrence. Details: Evidence from clinical and observational research investigating the effect of L. casei on C. difficile occurrence or recurrence is weak. Most studies use this species in combination with one or more additional probiotic species, including a specific product (Bio-K+ Cl1285) providing L. casei LBC80R and Lactobacillus acidophilus CL1285 and a specific product (Bio-K+ 50 Billion; Bio-K Plus International) providing L. casei LBC80R, L. acidophilus CL1285, and Lacticaseibacillus rhamnosus CLR2 as 50 or 100 billion CFUs daily (25494,90231,90934,95369,95403,107529). Observational research has found that providing a specific combination (Bio-K+ 50 Billion; Bio-K Plus International) of L. casei LBC80R, L. rhamnosus CLR2, and L. acidophilus CL1285 as 50-100 billion colony-forming units (CFUs) daily for 5 days to patients who are on antibiotics for at least 2 days reduces the hospital-wide incidence of C. difficile by approximately 40%. The incidence rate was decreased by at least 50% in the highest risk individuals taking this combination (107529). Current guidelines from the Infectious Diseases Society of America (IDSA) state that there is insufficient information to recommend administration of probiotics for the primary prevention of C. difficile-associated diarrhea (107538).
• Constipation. Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Combinations of probiotics containing L. casei appear to increase stool frequency and improve symptoms of functional constipation in adults. These combinations include Hexbio, containing L. casei, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. lactis, Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium longum subsp. infantis 30 billion CFUs twice daily for 7 days (90266), and ID-HWS1000, containing L. casei IDCC 3451, Lactiplantibacillus plantarum IDCC 3501, Lacticaseibacillus rhamnosus IDCC 3201, Bifidobacterium animalis subsp. lactis IDCC 4301, Bifidobacterium breve IDCC 4401, Lactococcus lactis IDCC 2301, xylooligosaccharide, and dietary fiber as nondigestible maltodextrin, oat fiber, and psyllium husk fiber (107517).
• Depression. Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with major depression shows that taking L. casei, Lactobacillus acidophilus, and Bifidobacterium bifidum daily for 8 weeks reduces symptoms of depression measured on the Beck Depression Inventory (BDI) when compared with placebo (99780). However, the validity of the results from this study is limited by incomplete reporting. For example, patient baseline BDI scores were not reported.
• Diabetes. It is unclear if oral Lacticaseibacillus casei is beneficial for treatment of type 2 or gestational diabetes. Details: In patients with gestational diabetes, clinical research shows that taking a combination of freeze-dried L. casei, Lactobacillus acidophilus, and Bifidobacterium bifidum each as 2 billion colony-forming units (CFUs) per gram daily for 6 weeks improves fasting blood glucose levels and glycemic control when compared with placebo (95416,98430). Furthermore, a sub-analysis of a meta-analysis of clinical research investigating the effects of L. casei as part of multi-ingredient probiotic and prebiotic products shows that taking products containing L. casei modestly reduces fasting insulin levels and improves insulin resistance in this population. There were also modest reductions in triglyceride levels; however, the effects on fasting blood glucose were not significant (111796). It is unclear from these studies if any beneficial effects are related to L. casei, L. acidophilus, Bifidobacterium bifidum, or the combination. Limited evidence from mainly small clinical trials has also assessed the effects of L. casei for type 2 diabetes. In one study, taking L. casei 100 million CFUs daily for 8 weeks reduces fasting blood glucose by about 28 mg/dL when compared with placebo. There was no effect on glycated hemoglobin; however, the duration was inadequate to demonstrate an effect (99786). In another study, taking a specific product (Familact) containing L. casei and six other probiotic strains daily for 6 weeks reduces fasting blood glucose, but does not affect plasma insulin, when compared with placebo (99790).
• Diarrhea. Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing L. casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum subsp. infantis, Bifidobacterium breve, and Streptococcus thermophilus daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). Although The European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388), both guidelines note that most evidence is low quality.
• Helicobacter pylori. It is unclear if oral Lacticaseibacillus casei is beneficial for H. pylori eradication in adults or children. Details: Clinical research in adults shows that taking L. casei along with six other probiotics in conjunction with bismuth quadruple therapy does not seem to improve H. pylori eradication rates when compared with placebo and bismuth quadruple therapy (90291). Also, taking a combination of L. casei and Lactobacillus acidophilus without any standard H. pylori therapies does not improve H. pylori eradication rates (12766). However, a clinical study in children shows that taking a fermented milk product containing L. casei DN-114 001 for 14 days along with triple therapy comprised of omeprazole, amoxicillin, and clarithromycin for 7 days improves the H. pylori eradication rate to approximately 85%, compared with 61% of those given triple therapy alone (107544).
• HIV/AIDS. Although there has been interest in using oral Lacticaseibacillus casei for HIV/AIDS, there is insufficient reliable information about the clinical effects of lactobacillus for this condition.
• Hyperlipidemia. It is unclear if oral Lacticaseibacillus casei is beneficial for hyperlipidemia. Details: In patients with primary hyperlipidemia, clinical research shows that taking L. casei 200 million colony-forming units in combination with red yeast rice twice daily for 8 weeks does not have beneficial effects on low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglyceride levels, when compared with taking red yeast rice alone. Taking L. casei seems to modestly reduce diastolic blood pressure in this population; however, it is unclear if these changes are clinically significant (112517).
• Hypertension. It is unclear if oral Lacticaseibacillus casei is beneficial for lowering blood pressure. Details: A meta-analysis of 18 clinical trials shows that taking various species of lactobacilli as 100 million to 1.5 trillion colony-forming units daily for 3-24 weeks reduces systolic and diastolic blood pressure by 3 mmHg and 1.5 mmHg, respectively, when compared with placebo in various populations. However, sub-group analyses of three clinical trials show that these benefits do not occur in clinical research investigating the effects of L. casei, specifically (105135).
• Irritable bowel syndrome (IBS). Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in patients with diarrhea-predominant IBS shows that taking a specific multi-species probiotic (NordBiotic, MBM Biotix) containing L. casei LC130, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, Lactobacillus acidophilus LA120, Lactiplantibacillus plantarum LP140, Bifidobacterium breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium animalis subsp. lactis BL040, and Streptococcus thermophilus ST250 as 2.5 billion colony-forming units (CFUs) total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life, when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516). However, clinical research shows that taking another multi-species combination of L. casei LBC80R, L. acidophilus CL1285, and L. rhamnosus CLR2 50 billion CFUs each daily for 3 months does not improve symptoms in patients with IBS when compared with placebo (99789).
• Lyme disease. Although there has been interest in using oral Lacticaseibacillus casei for Lyme disease, there is insufficient reliable information about the clinical effects of lactobacillus for this condition.
• Necrotizing enterocolitis (NEC). It is unclear if oral Lacticaseibacillus casei is beneficial or safe for NEC prevention. Details: Most meta-analyses of clinical research show that giving lactobacilli enterally reduces the risk of NEC and/or severe NEC in preterm, mainly very low birth weight (VLBW), infants. Some meta-analyses support the use of lactobacilli in combination with bifidobacteria, as opposed to lactobacilli alone for reducing the risk of NEC. However, the effects of L. casei specifically are unclear (95344,95351,103437,103445,104157,105162,105164). Also, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, L. casei is not specifically recommended (103003,111609,111611).
• Nonalcoholic fatty liver disease (NAFLD). Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults with NAFLD shows that taking a combination of L. casei BCMC 12,313, Lactobacillus acidophilus BCMC 12,130, Lactobacillus delbrueckii subsp. lactis BCMC 12,451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum subsp. infantis BCMC 02129, and Bifidobacterium longum BCMC 02120 as 30 billion colony-forming units twice daily for 6 months has no beneficial effects on hepatic steatosis or fibrosis or on levels of liver enzymes, blood lipids, or fasting blood glucose, when compared with placebo (107523).
• Polycystic ovary syndrome (PCOS). Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with PCOS, clinical research shows that taking a combination of L. casei T2 (IBRC-M10783), Lactobacillus acidophilus T16 (IBRC-M10785), and Bifidobacterium bifidum T1 (IBRC-M10771) as 2 billion colony-forming units (CFUs) each, plus inulin 800 mg, daily for 12 weeks modestly reduces serum insulin and triglyceride levels and improves insulin resistance and insulin sensitivity when compared with placebo. However, it does not alter cholesterol or fasting blood glucose levels (105159). Clinical research also shows that 31.3% of patients with PCOS taking L. casei in combination with other probiotics daily for 6 months had regular menstrual cycles compared with 12.5% of those taking placebo. There were also modest improvements in testosterone levels and waist circumference, but not other hormones, insulin resistance, body weight, or most measures of quality of life. The product provided L. casei UBLC-42 1 billion CFUs, along with Lactiplantibacillus plantarum UBLP-40, Lactobacillus acidophilus UBLA-34, Lacticaseibacillus casei UBLC-42, Limosilactobacillus fermentum UBLF-31, Lacticaseibacillus rhamnosus UBLR-58, Limosilactobacillus reuteri UBLRu-87, Bifidobacterium bifidum UBBB-55, and fructo-oligosaccharides (FOS) daily for 2 months and then twice daily for 4 months. All patients also underwent dietary and lifestyle changes (110974).
• Pregnancy-induced nausea and vomiting. Oral Lacticaseibacillus casei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles comprised of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units (CFUs) of L. casei Lc-11, Lactiplantibacillus plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Lacticaseibacillus paracasei DSM 13434 and Lpc-37, Ligilactobacillus salivarius Ls-33, Levilactobacillus brevis Lbr-35, Lactobacillus acidophilus La-14, and Bifidobacterium animalis subsp. lactis Bl-04, along with inulin 200 mg (107199).
• Rheumatoid arthritis (RA). Small clinical studies suggest that taking Lacticaseibacillus casei might be beneficial for RA. Details: Two small clinical studies in patients with RA show that taking L. casei 01 as 100 million colony-forming units daily for 8 weeks reduces tender and swollen joints and increases the number of patients who experience moderate symptom improvement when compared with placebo (90230,90297). However, one small clinical study in patients with moderate-to-severe RA shows that taking capsules containing freeze-dried strains of L. casei, Lactobacillus acidophilus, and Bifidobacterium bifidum daily for 8 weeks does not reduce RA severity, the number of tender or swollen joints, or joint pain when compared with placebo (95418).
• Rotaviral diarrhea. It is unclear if Lacticaseibacillus casei is beneficial for rotaviral diarrhea. Details: Although the World Gastroenterology Organization has not made a recommendation (98471), the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388). However, these guidelines note that most evidence is low quality and is not specific to rotavirus infection. Furthermore, these guidelines were released prior to the publication of the most recent, high-quality studies showing no benefit with the use of certain probiotics (98427,98428). Research on the use of L. casei, specifically, for this purpose is lacking.
• Short bowel syndrome. Although there has been interest in using oral Lacticaseibacillus casei for short bowel syndrome, there is insufficient reliable information about the clinical effects of L. casei for this condition.
• Small intestinal bacterial overgrowth (SIBO). It is unclear if oral Lacticaseibacillus casei is beneficial for the treatment of SIBO. Details: A small clinical study in children with chronic diarrhea due to SIBO shows that taking a combination of lyophilized L. casei 1.5 grams and Lactobacillus acidophilus 1.5 grams by mouth twice daily for 21 days decreases average daily stools by 1.5, but does not improve other symptoms, when compared with placebo (91143). Disparate study findings may be due to many factors, including differences in patient populations evaluated and use of different probiotic formulations. More evidence is needed to rate Lacticaseibacillus casei for these uses.

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POSSIBLY EFFECTIVE

• Allergic rhinitis (hay fever). Oral live or heat-killed Lacticaseibacillus paracasei seems to improve some symptoms of allergic rhinitis in adults and children. Details: Clinical research in adults with persistent allergic rhinitis due to grass pollen despite treatment with loratadine shows that taking L. paracasei LP-33 as 2 billion colony-forming units (CFUs) daily for 5 weeks can improve quality of life by almost 18% when compared with placebo. The improvement in quality of life appears to be related to improvements in eye-related symptoms, but not nasal symptoms (90242). In children with perennial allergic rhinitis due to dust mites, taking L. paracasei LP-33 10 billion CFUs daily for 30 days improves quality of life related to overall symptom severity or level of bother by 28% and 23%, respectively, when compared to placebo. However, quality of life related specifically to nasal and eye-related symptoms was not improved when compared with placebo (107532). In children ages 2-5 years with allergic rhinitis, clinical research shows that taking fermented milk (Danone) containing L. paracasei DN-114 011 10 billion CFUs daily does not increase the time free from rhinitis episodes, the mean duration of episodes, or the cumulative number of episodes, when compared with taking a control milk. However, the number of episodes was reduced between months 3-9. The fermented milk was made with the yogurt cultures Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus (112512). Heat-killed L. paracasei has also been investigated. One clinical trial in adults with chronic allergy symptoms shows that taking heat-killed L. paracasei IJH-SONE68 1040 mg or 500,000 cells daily for 12 weeks modestly improves self-reported symptoms, including frequencies of sneezing and blowing, watery eyes, and head dullness, when compared with taking placebo. There was no effect on nasal congestion or itchy eyes (111939). Also, clinical research in children aged 5 years and older with perennial allergic rhinitis due to dust mites shows that taking heat-killed L. paracasei LP-33 10 billion cells daily for 30 days improves quality of life related to overall symptom severity or level of bother by 18% and 22%, respectively, when compared with placebo. Efficacy was not inferior to live L. paracasei LP-33 (107532).
• Atopic dermatitis (eczema). Oral live Lacticaseibacillus paracasei, alone or in combination with other probiotics, seems to be beneficial for the treatment of atopic dermatitis in infants and children and for preventing atopic dermatitis when provided to the infant after exposure during pregnancy. Small clinical trials suggest that heat-killed L. paracasei does not seem to be beneficial for the treatment of atopic dermatitis. Details: In children aged 1-18 years, clinical research shows that taking L. paracasei 2 billion colony-forming units (CFUs) daily, alone or with Limosilactobacillus fermentum 2 billion colony-forming units (CFUs) daily each, for 3 months modestly reduces symptoms of atopic dermatitis when compared with placebo (98440). However, another clinical trial shows that administering formula containing lyophilized L. paracasei CNCM I-2116 to infants aged 3-6 months does not reduce atopic dermatitis severity or the prevalence of atopic dermatitis after 12 weeks of treatment (90256). Heat-killed L. paracasei has also been investigated. In adults treated with conventional topical corticosteroid and tacrolimus, a small clinical trial shows that taking heat-killed L. paracasei K71 200 billion cells daily for 12 weeks does not improve skin symptom severity, quality of life, or use of topical medication, when compared with taking placebo (111947). Also, in infants ages 4-30 months with atopic dermatitis, clinical research shows that, in addition to topical fluticasone propionate cream, taking heat-treated L. paracasei GM-080 daily for 16 weeks does not further improve symptoms when compared with using the topical fluticasone propionate cream alone (102406). Other clinical research has investigated the effects of L. paracasei in combination with other probiotics for the PREVENTION of atopic dermatitis. A combination of L. paracasei, Ligilactobacillus salivarius, Bifidobacterium animalis subsp. lactis, and Bifidobacterium bifidum, a total of 10 billion CFUs daily provided from 36 weeks' gestation and then to the infant until age 6 months, reduces the prevalence of atopic dermatitis at age two by approximately 60% (90234). Similar findings occurred in clinical research investigating the effect of L. paracasei ST11 and B. longum BL999 (ST11+BL999) for the last 2 months of pregnancy and first 2 months of breastfeeding (90234,90285).
• Common cold. A combination of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum seems to be beneficial for reducing the incidence or severity of the common cold. The effects of L. paracasei alone are unclear. Details: Clinical research in healthy individuals shows that taking an acidified milk drink providing L. paracasei (L. casei 431) 1 billion colony-forming units (CFUs) daily for 21 days before and after receiving the seasonal influenza vaccination does not affect the number, duration, or severity of common cold or influenza-like illness episodes when compared with taking placebo. However, there was a modest reduction in the duration of illness 4-6 weeks after vaccination (111937). L. paracasei has also been examined in combination with L. plantarum. Clinical research shows that taking L. plantarum HEAL 9 (DSM 15312) and L. paracasei 8700:2 (DSM 13434) (Probi Defendum, Probi AB) 1 billion CFUs daily for 12 weeks reduces the incidence of the common cold by about 12% and reduces the number of symptomatic days from 8.6 to 6.2 when compared with placebo (17119). Additional clinical research in adults at increased risk of a common cold shows that taking this same combination for 12 weeks does not reduce the incidence of developing a common cold when compared with placebo. However, symptom severity was modestly reduced. Also, each episode was reduced by an average of 1.1 days (107557). A more recent clinical study in adults at increased risk of developing a common cold shows that taking the same combination does not reduce symptom severity or the absolute number of common cold episodes when compared with placebo. However, in individuals with at least one cold, the mean number of colds was reduced by 0.12 over the 12-week period. In addition, there were modest overall reductions in the incidence of recurring colds and the use of analgesics (107555). A smaller clinical trial using the same product at the same dose and duration has also been conducted in children aged 1-6 years in daycare. The severity of nasal congestion/runny nose was modestly reduced when compared with placebo in this population. However, there were no differences between groups in the overall incidence, severity, or duration of common colds or upper respiratory tract infections or the number of days absent from daycare (107556). This latter trial was terminated prior to the completion of the planned patient recruitment for reasons unrelated to adverse effects, which may have impacted the findings. L. paracasei has also been investigated as part of fermented milk. A clinical trial in elderly nursing home residents shows that drinking two bottles of fermented milk containing L. paracasei Shirota daily for 6 months does not reduce the risk of developing respiratory symptoms when compared with placebo milk (96885). However, a small clinical study in healthy, male, middle-aged office workers shows that drinking a fermented milk made with L. paracasei Shirota for 12 weeks reduces the incidence and duration of the common cold by 59% when compared with a control milk (98426). Also, a clinical study in children aged 3-6 years attending daycare shows that drinking a fermented milk product containing L. paracasei (Actimel, Danone) 200 grams daily for 3 months reduces the risk of developing the common cold, the most common upper respiratory tract infection in these children, by around 18% when compared with a control milk product. The fermented milk product did not affect medication use or sick leave from daycare (96882).

POSSIBLY INEFFECTIVE

• Constipation. Oral Lacticaseibacillus paracasei does not seem to be beneficial for constipation. Details: Meta-analyses of two or three clinical trials in adults with functional constipation show that taking L. paracasei Shirota 6.5-30 billion colony-forming units daily for 4 weeks does not appear to improve gut transit time or increase the number of stools (95342). Also, clinical research in patients with constipation shows that taking a combination of L. paracasei Lpc-37 2.5 billion colony-forming units daily for 2 weeks along with Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis strains Bl-04, Bi-07, and HN019, does not improve bloating, abdominal pain, intestinal transit time, frequency of bowel movements, or stool consistency when compared with placebo. There was a small beneficial effect on flatulence (110979).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if topical heat-killed Lacticaseibacillus paracasei is beneficial for acne. Details: Preliminary clinical research in patients with mild to moderate acne shows that topical application with a lotion providing the cell-free supernatant of L. paracasei MSMC 39-1 twice daily for 4 weeks is as effective as a lotion containing 2.5% benzoyl peroxide for decreasing redness and the inflammatory acne lesion count. There was no effect of either lotion of non-inflammatory acne lesion count (111945). This study is limited by the lack of blinding to lotion type.
• Alcohol-related liver disease. It is unclear if oral Lacticaseibacillus paracasei is beneficial in patients with alcohol-related liver disease. Details: Clinical research in patients with alcohol-related liver disease shows that taking fermented milk providing L. paracasei Shirota daily for 60 days reduces levels of triglycerides and low-density lipoprotein (LDL) cholesterol by 27% and 24%, respectively, compared with taking placebo. There was also an improvement in liver function, based on modest improvements in various liver markers, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, and bilirubin. Patients consumed L. paracasei 20 billion colony-forming units daily (111958).
• Antibiotic-associated diarrhea. It is unclear if oral Lacticaseibacillus paracasei is beneficial for preventing antibiotic-induced diarrhea. Details: Most clinical research has investigated the effect of L. paracasei in combination with other probiotics. A meta-analysis of 3 clinical trials in hospitalized or outpatient adults shows that taking L. paracasei in combination with up to 8 other probiotic strains reduces the risk of AAD by 40% when compared with taking placebo (107635). One of these studies, a small clinical trial in patients taking amoxicillin 500 mg twice daily for 7 days, used a specific combination probiotic (Ecologic AAD) twice daily for 14 days. The product provided L. paracasei NIZO 3672, Bifidobacterium bifidum NIZO 3804, Bifidobacterium animalis subsp. lactis NIZO 3680, Enterococcus faecium NIZO 3886, Lactobacillus acidophilus NIZO 3678 and NIZO 3887, Lactiplantibacillus plantarum NIZO 3684, Lacticaseibacillus rhamnosus NIZO 3689, and Ligilactobacillus salivarius NIZO 3675 as 1 billion colony-forming units (CFUs) each daily (95405). In addition, one small clinical study in hospitalized adults shows that consuming a 97 mL drink (Actimel, Danone) containing L. paracasei 100 CFUs/mL, Streptococcus thermophilus 100 million CFUs/mL, and Lactobacillus delbrueckii subsp. bulgaricus 10 million CFUs/mL twice daily while taking antibiotics reduces the odds of developing AAD by 75% when compared with a milkshake without probiotics (16740). However, an additional large clinical trial in children aged 3 months and up shows that taking L. paracasei in combination with other probiotics does not reduce the risk of antibiotic-associated diarrhea when compared with taking placebo, when the more stringent definition is considered excluding diarrhea of other etiologies. However, the risk of diarrhea of any etiology is reduced by 35%. The probiotic supplement provided a total of 10 billion CFUs of L. paracasei W20, Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Bifidobacterium bifidum W23, Bifidobacterium animalis subsp. lactis W51, Lactiplantibacillus plantarum W62, Lacticaseibacillus rhamnosus W71, and Ligilactobacillus salivarius W24 daily from the first day of antibiotic treatment until 7 days after treatment ended (110969). It is unclear if any benefits are due to L. paracasei, the other ingredients, or their combination. L. paracasei has also been investigated alone. In hospitalized patients with spinal cord injury, preliminary clinical research shows that 17.1% of patients taking L. paracasei Shirota 6.5 billion CFUs daily in a probiotic drink (Yakult light) developed diarrhea compared with 54.9% of those given only routine care. L. paracasei was taken during antibiotic treatment and for an additional 7 days (111955). This study is limited by a lack of blinding.
• Antituberculosis treatment-associated adverse effects. It is unclear if oral Lacticaseibacillus paracasei is beneficial for preventing adverse effects associated with antituberculosis treatment. Details: Preliminary clinical research shows that taking L. paracasei Shirota 10 billion or 20 billion colony-forming units (CFUs) daily during standard antituberculosis treatment does not reduce the incidence of liver injury when compared with antituberculosis treatment alone. However, there was a modest decrease in the incidence of elevated alkaline phosphatase in patients taking 20 billion CFUs daily and a modest decrease in the incidence of elevated bilirubin in patients taking 10 billion CFUs daily. There was no effect on other liver markers (107509). Other preliminary clinical research shows that taking this same dose daily for 2 months during standard antituberculosis treatment reduces the rate of any gastrointestinal adverse event to 29% to 38% of patients, compared with 50% of those taking antituberculosis treatment alone. In addition, the duration of symptoms was shorter. However, when individual gastrointestinal adverse events were evaluated, only the incidence and duration of vomiting and appetite loss were reduced; the incidence of nausea, diarrhea, flatulence, and constipation were unaffected (107542).
• Asthenopia (eye strain). It is unclear if oral heat-killed Lacticaseibacillus paracasei is beneficial for asthenopia. Details: Preliminary clinical research shows that taking heat-killed L. paracasei 50 mg daily for 8 weeks does not decrease eye fatigue induced by blue-light emitting devices when compared with placebo. However, a subgroup analysis shows that in patients who report eye fatigue at baseline, subjective symptoms of eye fatigue and eye redness are reduced after exposure to blue-light emitting devices (98429).
• Asthma. It is unclear if oral Lacticaseibacillus paracasei is beneficial for asthma. Details: A small clinical study in children with asthma shows that taking L. paracasei GMNL-133 (LP) 2 billion colony-forming units (CFUs), Limosilactobacillus fermentum GM-090 (LF) 2 billion CFUs, or both strains together daily for 3 months seems to modestly reduce asthma severity and increase Childhood Asthma Control Test (C-ACT) scores when compared with placebo (99785). In children ages 2-5 years with asthma, clinical research shows that taking fermented milk (Danone) containing L. paracasei DN-114 011 10 billion colony-forming units daily does not increase the time free from asthma episodes, the mean duration of episodes, or the cumulative number of episodes, when compared with taking a control milk. The fermented milk was made with the yogurt cultures Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus (112512).
• Cancer. Although there has been interest in using oral Lacticaseibacillus paracasei for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Canker sores. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial shows that taking a combination of L. paracasei, Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium animalis subsp. lactis modestly reduces pain, but not the number of lesions or healing time, when compared with placebo (107548).
• Clostridioides difficile infection. Although there has been interest in using oral Lacticaseibacillus paracasei for C. difficile infection prevention, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Colic. Although there has been interest in using oral Lacticaseibacillus paracasei for colic, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Colorectal cancer. It is unclear if oral Lacticaseibacillus paracasei is beneficial for colorectal cancer prevention. Details: Clinical research in patients with previous removal of colorectal tumors shows that taking at least 1.5 billion colony-forming units L. paracasei Shirota 3 times daily for 4 years does not prevent the development of new colorectal tumors when compared with not taking L. paracasei. However, taking L. paracasei reduces the occurrence of colorectal tumors with moderate or severe atypia by 35%. Half of the patients included in this research were also consuming wheat bran biscuits (111959).
• Dental caries. It is unclear if oral Lacticaseibacillus paracasei is beneficial for dental caries prevention. Details: Preliminary clinical research shows that giving infants a weaning cereal containing L. paracasei F19 (Semper AB) from 4 months of age until 13 months of age does not reduce the risk of dental caries in the primary or permanent teeth by the age of 3, 6, or 9 years (90260).
• Depression. Although there has been interest in using oral Lacticaseibacillus paracasei for depression, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Diabetes. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with gestational diabetes shows that taking a specific product containing L. paracasei and other probiotics (Visbiome, ExeGi Pharma) as a total of 112.5 billion colony-forming units (CFUs) twice daily for 8 weeks does not affect levels of fasting blood glucose or glycated hemoglobin (HbA1c) when compared with placebo. However, there were small improvements in insulin levels and insulin resistance (107549). This same combination probiotic has also been evaluated in children 2-12 years of age with new-onset type 1 diabetes. One clinical study shows that taking Visbiome as 112.5 billion CFUs daily for 3 months modestly decreases HbA1c and insulin requirements when compared with placebo. Also, about three times as many children achieved remission, defined as insulin requirements of less than 0.5 U/kg daily and HbA1c of less than 7%. However, C-peptide levels and the maintenance of residual pancreatic beta-cell function were not affected when compared with placebo (107497).
• Diarrhea. It is unclear if oral Lacticaseibacillus paracasei is beneficial for the treatment of diarrhea. Details: While the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388), both guidelines note that most evidence is low quality. Also, evidence related to the use of L. paracasei, specifically, is limited. One large clinical study shows that taking a fermented milk product containing L. paracasei DN-114 001 (e.g., DanActive, Dannon) 100 million CFUs per milliliter for up to 4 months helps to prevent acute, non-rotaviral diarrhea in children ages 6-24 months (14374).
• Exercise-induced muscle damage. It is unclear if oral Lacticaseibacillus paracasei is beneficial for exercise-induced muscle damage. Details: Clinical research in adults shows that taking L. paracasei L-PS23 20 billion colony-forming units or heat-killed L. paracasei HK-PS23 20 billion cells daily modestly reduces muscle strength loss and improves measures of muscle recovery in the 48 hours following exercise-induced muscle damage when compared with taking placebo. L. paracasei was taken for 6 weeks prior to inducing muscle damage and continued for an additional 48 hours (111940).
• Exercise-induced respiratory infections. It is unclear if oral Lacticaseibacillus paracasei is beneficial for preventing respiratory infections related to exercise. Details: Clinical research in endurance athletes shows that taking a probiotic supplement containing L. paracasei Shirota (LCS, Yakult) 65 billion colon-forming units (CFUs) twice daily for 20 weeks does not reduce the risk of developing an upper respiratory tract infection when compared with placebo. Taking this probiotic also does not reduce the duration or severity of respiratory infections in this population (98431). However, other clinical research shows that taking L. paracasei Shirota 6.5 billion CFUs daily for 4 months during winter endurance training modestly reduces the proportion of athletes with at least 1 week with upper respiratory tract illness symptoms by 27%, and the total number of episodes by 0.9, when compared with taking placebo. There was no difference in symptom severity or duration (111950).
• Fractures. It is unclear if oral Lacticaseibacillus paracasei is beneficial for the healing of fractures. Details: A clinical study in elderly adults with distal radius fracture shows that consuming 100 mL of skim milk containing L. paracasei Shirota 12 billion colony-forming units twice daily for 3 months modestly improves hand function, pain, and daily life activities when compared with skimmed milk placebo (102407). This study is limited by the fact that, although subjective measures showed improvement, there was no consistent improvement in objective measures.
• Helicobacter pylori. It is unclear if oral Lacticaseibacillus paracasei is beneficial in children with H. pylori infection. Details: Clinical research in H. pylori-colonized children aged 6 to 17 years shows that taking a fermented dairy product containing live or heat-killed L. paracasei ST11 (Chamyto, Nestle'-Chile SA, Santiago, Chile) 1.6 billion cells or colony-forming units 5 days each week for 4 weeks does not reduce H. pylori colonization when compared with the beverage without L. paracasei. The beverages were fermented with Lactobacillus helveticus (110934).
• HIV/AIDS. Although there has been interest in using oral Lacticaseibacillus paracasei for HIV/AIDS, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Hypercholesterolemia. It is unclear if oral Lacticaseibacillus paracasei is beneficial for hypercholesterolemia. Details: A small clinical trial in patients with hypercholesterolemia shows that taking 10.5 billion colony-forming units of L. paracasei TISTR 2593 daily for 90 days reduces levels of low-density lipoprotein cholesterol by about 11% when compared with taking placebo. There was no effect on total or high-density lipoprotein cholesterol or triglyceride levels (111938).
• Insomnia. It is unclear if oral Lacticaseibacillus paracasei is beneficial for improving sleep quality. Details: A small clinical trial in students shows that taking fermented milk containing L. paracasei Shirota daily for 11 weeks, starting 8 weeks prior to a stressful standardized examination, modestly reduces feelings of sleepiness upon rising and increases sleep length when compared with a non-fermented placebo milk. Objective measures of sleep latency were also reduced. There was no effect on total sleep time or sleep efficacy (111949).
• Irritable bowel syndrome (IBS). It is unclear if oral Lacticaseibacillus paracasei is beneficial for IBS. Details: One clinical study shows that taking a specific multi-species probiotic (Visbiome, ExeGi Pharma) containing L. paracasei and seven other probiotics as 450 billion colony-forming units (CFUs) daily in two divided doses for 8 weeks improves abdominal bloating, but not abdominal pain, flatulence, or number of stools, in patients with diarrhea-predominant IBS (IBS-D) (11379). However, adding this product as 900 billion CFUs daily to a sham diet or a low-FODMAP diet for 4 weeks does not improve IBS symptoms when compared with placebo (98741). Another clinical study in patients with IBS-D shows that taking a specific multi-species probiotic (NordBiotic, MBM Biotix) containing L. paracasei LPC100, Lacticaseibacillus rhamnosus LR110, Lactobacillus acidophilus LA120, Lacticaseibacillus casei LC130, and Lactiplantibacillus plantarum LP140, Bifidobacterium breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium animalis subsp. lactis BL040, and Streptococcus thermophilus ST250 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516). However, other clinical research shows that taking L. paracasei HA-196 10 billion CFUs daily or L. paracasei Shirota 13 billion CFUs daily for 8 weeks or a combination of L. paracasei, L. acidophilus, and B. animalis subsp. lactis BB-12 (Cultura) 13-20 billion CFUs daily for 6 months does not improve most symptoms of IBS (90236,94696,94697,103440,111952). L. paracasei has also been examined in combination with other ingredients. In patients 60 years and older with IBS, taking L. paracasei DKGF1 100 billion CFUs daily with Opuntia humifusa extract more than doubles the proportion of patients with improvements in self-reported overall symptoms during more than 2 of the 4 weeks of treatment when compared with taking placebo. Response rates for abdominal pain and psychological well-being were also improved. However, there were no differences between groups for response rates related to improvements in gas or bloating (111943).
• Japanese cedar pollinosis. It is unclear if oral Lacticaseibacillus paracasei is beneficial for Japanese cedar pollinosis. Details: Clinical research in patients with Japanese cedar pollinosis shows that taking L. paracasei KW3110 at least one trillion colony-forming units daily for 12 weeks starting 1 month before the start of the pollen season does not improve nasal symptoms during peak season when compared with taking placebo (111948).
• Lower respiratory tract infections. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children ages 3-6 years shows that taking taking fermented milk (DanActive, Dannon) containing L. paracasei DN-114 011 20 billion colony-forming units daily for 90 days does not prevent lower respiratory tract infections when compared with taking a control non-fermented milk. The fermented milk was made with the yogurt cultures Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus (112515).
• Lyme disease. Although there has been interest in using oral Lacticaseibacillus paracasei for Lyme disease, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Migraine headache. It is unclear if oral Lacticaseibacillus paracasei is beneficial for migraine treatment. Details: Clinical research in patients with moderate to severe vestibular symptoms associated with migraine headaches shows that taking L. paracasei Shirota 20 billion colony-forming units daily for 4 months modestly reduces symptoms of vertigo and dizziness. The number of attacks with vertigo each week was reduced by 1.6, compared with 0.9 in patients taking placebo. Both vertigo and dizziness severity, as well as feelings of anxiety and depression, were also modestly reduced (111951). Although changes in these endpoints were statistically significant after 4 months, there were no differences between endpoints after 2 months, and the clinical significance is unclear.
• Necrotizing enterocolitis (NEC). It is unclear if oral Lacticaseibacillus paracasei is beneficial or safe for NEC prevention. Details: Most meta-analyses of clinical research show that giving lactobacilli enterally reduces the risk of NEC and/or severe NEC in preterm, mainly very low birth weight (VLBW), infants. Some meta-analyses support the use of lactobacilli in combination with bifidobacteria, as opposed to lactobacilli alone for reducing the risk of NEC. However, the effects of L. paracasei, specifically, are unclear (95344,95351,103437,103445,104157,105162,105164). Also, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, L. paracasei is not specifically recommended (103003,111609,111611).
• Nonalcoholic fatty liver disease (NAFLD). Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with NAFLD shows that taking 2 sachets daily for 3 months of a specific combination product (VSL#3) containing L. paracasei and other probiotics modestly decreases triglyceride levels and liver enzymes when compared with taking placebo. However, there was no change in body mass index or most glycemic or lipid parameters (111009). The effect of L. paracasei alone is unclear from this study.
• Osteoarthritis. It is unclear if oral Lacticaseibacillus paracasei is beneficial for osteoarthritis. Details: A large clinical trial in patients with mild to moderate symptoms of knee osteoarthritis shows that taking skim milk containing L. paracasei Shirota 6 billion colony-forming units twice daily for 6 months modestly improves stiffness, pain, and function when compared with taking skim milk placebo (111953). More research is needed to determine whether L. paracasei Shirota is as effective as standard medications.
• Pain (acute). It is unclear if oral Lacticaseibacillus paracasei is beneficial for acute pain. Details: Clinical research in patients with a single rib fracture shows that taking skim milk containing L. paracasei Shirota 6 billion colony-forming units daily for 1 month modestly reduces pain during deep breathing, coughing, and turning over when compared with taking skim milk placebo. Good pain relief during these situations, defined as a decline in maximal pain intensity of 3 points on a 10-point scale, occurred in 42.1% to 61.6% of patients, compared with 25.9% to 47.3% of patients taking placebo. However, there was no effect on sleep quality (111957).
• Parkinson disease. It is unclear if oral Lacticaseibacillus paracasei is beneficial for Parkinson disease. Details: Clinical research in patients with Parkinson disease shows that taking fermented milk providing L. paracasei Shirota 10 billion colony-forming units daily for 12 weeks reduces the use of laxatives by 0.37 or 15% per week and modestly improves stool consistency and symptoms of constipation when compared with taking an acidified milk placebo. There were also modest improvements in non-motor symptoms, anxiety, and depression, but not overall disease severity or dopaminergic therapy requirement (111956).
• Postoperative infection. Although there has been interest in using oral Lacticaseibacillus paracasei for preventing postoperative infections, there is insufficient reliable information about the clinical effects of L. paracasei for this purpose.
• Pouchitis. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that continuous oral treatment for one year with a specific combination product (Visbiome, ExeGi Pharma) containing L. paracasei and other probiotics, 6 grams (300-500 billion live bacteria per gram) daily, for up to 12 months seems to maintain remission in 85% of patients with pouchitis (6087,12769).
• Pregnancy-induced nausea and vomiting. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units (CFUs) of L. paracasei DSM 13434 and Lpc-37, Lactiplantibacillus plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Ligilactobacillus salivarius Ls-33, Levilactobacillus brevis Lbr-35, Lactobacillus acidophilus La-14, Lacticaseibacillus casei Lc-11, and Bifidobacterium animalis subsp. lactis Bl-04, along with inulin 200 mg (107199).
• Prostatitis. It is unclear if oral Lacticaseibacillus paracasei is beneficial for prostatitis. Details: Preliminary clinical research in adults with chronic bacterial prostatitis who are receiving antibiotic treatment shows that taking L. paracasei CNCM I-1572 (L. casei DG) one capsule twice daily for 6 months improves clinical symptoms over baseline in 73% of patients and also reduces symptomatic recurrence and antibiotic use (105133). The validity of these findings is limited by the lack of a comparator group.
• Proton pump inhibitor-induced gastrointestinal (GI) symptoms. It is unclear if oral Lacticaseibacillus paracasei is beneficial for preventing GI symptoms in patients using proton pump inhibitors. Details: Preliminary clinical research in patients with gastroesophageal reflux disease shows that taking L. paracasei F19 (Genefilus F19, Siffra Farmaceutici S.r.l., Italy) 24 billion colony-forming units 3 times a week for 3 or 6 months during treatment with pantoprazole 40 mg daily modestly reduces stool frequency and the severity and proportion of patients with flatulence and bloating when compared with taking placebo (111941).
• Radiation-induced diarrhea. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients undergoing pelvic radiotherapy shows that taking 96 mL fermented milk (Danone) 3 times daily containing L. paracasei DN-114 001 100 million colony-forming units per gram starting one week before the initiation of radiation treatment does not delay the development of diarrhea when compared with taking a control sterilized milk product. The fermented milk was continued throughout treatment and made with the yogurt cultures Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus (112513).
• Rotaviral diarrhea. It is unclear if oral Lacticaseibacillus paracasei is beneficial for rotaviral diarrhea. Details: The current guidelines related to the treatment of viral diarrhea are conflicting. While the World Gastroenterology Organization has not made a recommendation (98471), the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388). However, these guidelines note that most evidence is low quality and is not specific to rotavirus infection. Furthermore, these guidelines were released prior to the publication of the most recent, high-quality studies showing no benefit with the use of certain probiotics (98427,98428). Also, research on the use of L. paracasei, specifically, is lacking.
• Sarcopenia. Although there has been interest in using oral Lacticaseibacillus paracasei for sarcopenia prevention, there is insufficient reliable information about the clinical effects of L. paracasei for this purpose.
• Short bowel syndrome. Although there has been interest in using oral Lacticaseibacillus paracasei for short bowel syndrome, there is insufficient reliable information about the clinical effects of L. paracasei for this condition.
• Small intestinal bacterial overgrowth (SIBO). It is unclear if oral Lacticaseibacillus paracasei is beneficial for the treatment of SIBO. Details: One preliminary clinical study in adults with irritable bowel syndrome and a recent diagnosis of SIBO shows that consuming 65 mL of a specific product (Yakult, Yakult Ltd.) providing 6.5 billion colony-forming units (CFUs) of L. paracasei Shirota by mouth daily for 6 weeks modestly improves flatulence, but not other symptoms, when compared to baseline (91144).
• Ulcerative colitis. Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: The best evidence of benefit is for a specific combination product (Visbiome, ExeGi Pharma). Doses of 3 grams (equivalent to 900 billion colony-forming units (CFUs)) once or twice daily have been used in combination with conventional treatment. In children aged 1-16 years, doses of 450-1800 billion CFUs for up to one year have been used (3261,14370,14371,16841,95337). A meta-analysis of clinical research shows that taking this product as an adjunct to standard ulcerative colitis treatment can increase remissions rates in adults and children by about 1.7-fold when compared with standard treatment alone (95337). There is also evidence that it is beneficial for improving remission rates in patients who do not adequately respond to conventional treatment (14371).
• Upper respiratory tract infection (URTI). Oral Lacticaseibacillus paracasei has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children ages 3-6 years shows that taking taking fermented milk (DanActive, Dannon) containing L. paracasei DN-114 011 20 billion colony-forming units daily for 90 days reduces the incidence of URTIs by 18% when compared with taking a control non-fermented milk. The fermented milk was made with the yogurt cultures Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus (112515).
• Wound healing. It is unclear if oral Lacticaseibacillus paracasei is beneficial for the treatment of SIBO. Details: Clinical research in patients with a recent episiotomy shows that taking L. paracasei (L. casei 431) 1.5 billion colony-forming units daily for 14 days modestly improves wound severity, including redness, swelling, and discharge, 5 and 15 days after birth when compared with taking placebo. There was no effect on wound pain (112519). More evidence is needed to rate Lacticaseibacillus paracasei for these uses.

(Read more about LACTICASEIBACILLUS PARACASEI)

POSSIBLY EFFECTIVE

• Antibiotic-associated diarrhea. Oral Lacticaseibacillus rhamnosus GG seems to reduce the risk of antibiotic-associated diarrhea (AAD) in adults and children. Details: Meta-analyses of clinical research show that taking L. rhamnosus GG (Culturelle) can reduce the risk of AAD in adults and children (4371,4372,7306,8511,14334,90299,95348). This strain appears to reduce the risk of AAD by about 60% to 71% (14334,90299,95348,95398). Although some contradictory evidence exists (7306), a meta-analysis of clinical research shows that taking this strain is beneficial in both inpatient and outpatient populations (90299). In children, it has been used as 10-20 billion colony-forming units (CFUs) once daily or 20 billion CFUs twice daily, given throughout the conventional antimicrobial treatment period (4371,4372,8511,14334). In adults, it has been used as 6-40 billion CFUs daily (14334,95348). However, some research suggests that this strain may only be effective in children, not adults (95389). The effect of L. rhamnosus has also been examined in combination with other products. A meta-analysis of 5 clinical trials in hospitalized or outpatient adults shows that taking L. rhamnosus, usually in combination with other probiotic strains, reduces the risk of AAD by 29% when compared with taking placebo (107635). A number of combination products containing L. rhamnosus have demonstrated benefit for preventing AAD, including L. rhamnosus CLR2, Lactobacillus acidophilus CL1285, and Lacticaseibacillus casei LBC80R (Bio-K+ Cl1285) 100 billion CFUs daily (95402,95403,25494); L. rhamnosus R0011 7.6 billion CFUs and Lactobacillus helveticus R0052 0.4 billion CFUs daily (Lacidofil STRONG, Lallemand Health Solutions) (96891); and Bifidobacterium bifidum NIZO 3804, Bifidobacterium animalis subsp. lactis NIZO 3680, Enterococcus faecium NIZO 3886, L. acidophilus NIZO 3678 and NIZO 3887, Lacticaseibacillus paracasei NIZO 3672, Lactiplantibacillus plantarum NIZO 3684, L. rhamnosus NIZO 3689, and Ligilactobacillus salivarius NIZO 3675 (Ecologic AAD) (95405). However, some combination products containing L. rhamnosus have not demonstrated benefit with respect to AAD prevention. In older adults in long-term care, taking a combination of L. rhamnosus and Bifidobacterium animalis subsp. lactis (BB-12) daily does not reduce the incidence or number of days with AAD over a 12-month period when compared with placebo (103425). In a small clinical trial in children aged 5 months to 16 years, taking a combination of L. rhamnosus KL53A, L. plantarum PL02, and Bifidobacterium longum PL03 twice daily during antibiotic treatment does not reduce the rate of AAD when compared with placebo. However, there was a modest reduction in the number of stools each day (107553). An additional large clinical trial in children aged 3 months and up shows that taking L. rhamnosus in combination with other probiotics does not reduce the risk of antibiotic-associated diarrhea when compared with taking placebo, when the more stringent definition is considered excluding diarrhea of other etiologies. However, the risk of diarrhea of any etiology is reduced by 35%. The probiotic supplement provided a total of 10 billion CFUs of L. rhamnosus W71, Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, Ligilactobacillus salivarius W24, Bifidobacterium bifidum W23, and Bifidobacterium animalis subsp. lactis W51 daily from the first day of antibiotic treatment until 7 days after treatment ended (110969).
• Atopic dermatitis (eczema). Oral live Lacticaseibacillus rhamnosus, alone or in combination with other probiotics, seems to be beneficial for the treatment of atopic dermatitis in infants and children. It also seems to be beneficial for preventing atopic dermatitis when taken by the infant after exposure during pregnancy, but it is unclear if taking L. rhamnosus only during pregnancy or lactation is beneficial for preventing atopic dermatitis. Details: A meta-analysis of the available clinical research shows that various species of lactobacilli reduce the severity of atopic dermatitis in infants and children up to 36 months of age. Children with moderate to severe disease seem to obtain greater benefit from supplementation than those with mild disease (98436). One specific strain has shown benefit. Clinical research in infants shows that taking L. rhamnosus GG in extensively hydrolyzed whey formula providing approximately 30 billion colony-forming units (CFUs) per kg daily modestly reduces symptom severity when compared with taking placebo (107528). Other clinical research in children ages 6-36 months shows that taking L. rhamnosus GG 10 billion CFUs daily for 12 weeks more than doubles the proportion of patients with a clinically important reduction in severity when compared with taking placebo. These benefits lasted for at least 4 weeks post-supplementation. The number of days without rescue medication was reduced by about 3 days (112491). Some clinical research also shows that L. rhamnosus GG (Culturelle) might be beneficial for reducing symptoms of atopic dermatitis in infants who are allergic to cow's milk (4369). L. rhamnosus has also been shown to have beneficial effects when used in combination with other probiotics. Examples include a specific mixture (Latopic, Biomed S.A.) providing 1 billion CFUs of L. rhamnosus ŁOCK 0900 25%, L. rhamnosus ŁOCK 0908 25%, and Lacticaseibacillus casei ŁOCK 0919 50% for 3 months in children under 2 years of age (107510), and a combination of lyophilized L. rhamnosus 19070-2 and Limosilactobacillus reuteri DSM 122460 as 10 billion CFUs of each strain twice daily for 6 weeks in children aged 1-13 years (12773). Heat-killed L. rhamnosus has also been evaluated. In children aged 1-12 years with moderate atopic dermatitis, taking heat-killed L. rhamnosus IDCC 3201 (RHT3201) 10 billion CFUs daily for 12 weeks modestly reduces overall symptom severity when compared with placebo. However, these benefits were not shown in the intention to treat analysis. Also, the use of topical corticosteroids was not reduced (107527). Limited research has also evaluated oral L. rhamnosus for the treatment of atopic dermatitis in adults. One clinical study shows that taking 1 billion CFUs each of L. rhamnosus LRH020, Lactiplantbacillus plantarum PBS067, and L. reuteri PBS072 for 56 days modestly reduces the severity of symptoms and improves skin smoothness and moisturization for up to an additional 28 days when compared with placebo (107506). Other research has investigated the effects of L. rhamnosus for the PREVENTION of atopic dermatitis. A meta-analysis of clinical research shows that perinatal use of L. rhamnosus alone or in combination with other probiotics reduces the incidence of atopic dermatitis by up to 40% in children up to 2 years of age or 6-7 years of age. However, this benefit did not occur in children ages 4-5 years or 10-11 years. In these studies, L. rhamnosus was used prenatally and then possibly postnatally during lactation and/or supplemented to the newborn (112494). The reason for the age-related discrepancy is unclear; however, the number of studies investigating the effect of L. rhamnosus in children over 2 years of age was small. When lactobacilli-based probiotics are used during gestation and then supplemented to the newborn during the first 2-24 months of life, additional meta-analyses of clinical research show that this reduces the risk of the child developing atopic dermatitis by up to 40%. Most of the studies included in these analysis used L. rhamnosus GG or HN001 alone or in combination with other probiotics (90247,107503). Regimens used in some clinical research include L. rhamnosus HN001 as 6 billion CFUs daily from 35 weeks' gestation until 6 months after delivery in adults or 6 billion CFUs daily from birth to 2 years old (90603), L. rhamnosus HN001 starting at 14 weeks' gestation and continuing until 6 months postpartum (98437), as well as combinations of L. rhamnosus and Bifidobacterium animalis subsp. Lactis 1 billion CFUs daily for 6 months (102286), L. rhamnosus LPR and Bifidobacterium longum BL999 (90285), and L. rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis subsp. Lactis BB-12 in fermented milk starting at 36 weeks' gestation and continuing until 3 months' postpartum (96893). Some research has investigated differences between the various perinatal dosing schedules. Subgroup analyses of clinical research show that the incidence of atopic dermatitis is reduced by 48% and 34% in infants receiving L. rhamnosus prenatally and then during lactation OR via direct supplementation, respectively. However, the incidence of atopic dermatitis was not reduced in infants receiving L. rhamnosus prenatally and then during lactation AND via direct supplementation (112494). The reason for this discrepancy is unclear but may be related to the different forms of supplementation, levels found in the body, and/or the age of the child at diagnosis (98437,112494).
• Atopic disease. Taking oral Lacticaseibacillus rhamnosus GG during pregnancy and when breastfeeding, or giving it to the infant, seems to prevent atopic disease in infants and children. Details: Clinical research shows that L. rhamnosus GG (Culturelle), 10-20 billion colony-forming units (CFUs) daily taken orally 2-4 weeks before delivery and continued for the first 3-6 months of breastfeeding, prevents atopic disease (e.g., asthma, allergic rhinitis, and eczema) in infants with a family history of atopy. It appears to be equally effective when taken while breastfeeding or when taken by the bottle-feeding infant (7743,8515,11381). For the bottle-feeding infant, L. rhamnosus GG was given as 10-20 billion CFUs daily in formula (Nutramigen LGG, Mead Johnson Nutrition) for the first 3-36 months of life (7743,8515). The preventive effect of this strain in at-risk infants appears to extend up to 7 years of age (11381,99791). Other research shows that L. rhamnosus HN001, 6 billion CFUs daily taken from 35 weeks' gestation and then continued in the infant until 2 years of age, reduces the risk of atopic dermatitis by 43% and rhinoconjunctivitis by 62% when compared with placebo at 4 years of age (90603). These preventive effects appear to extend up to 11 years of age (99791). Clinical research in infants with cow's milk allergy also shows that adding L. rhamnosus GG to a hydrolyzed casein infant formula (Nutramigen LGG, Mead Johnson Nutrition) reduces the overall occurrence of other allergic manifestations when compared with casein infant formula alone. Approximately 4 infants need to take this supplemented formula in order to prevent one allergic manifestation, such as eczema, rash, asthma, and runny nose or eyes. The tolerance to cow's milk allergy is also improved over the next 3 years (96889). However, not all strains or methods of administration appear to be beneficial. Intake of L. rhamnosus HN001 only during gestation and postpartum, without supplementation in the infant, does not reduce the infant's risk of developing atopic manifestations by 12 months of age when compared with placebo. This strain was not detected in breastmilk and did not alter breastmilk protein or cytokine concentrations, which might explain these disparate findings (98437).

POSSIBLY INEFFECTIVE

• Critical illness (trauma). Enteral Lacticaseibacillus rhamnosus does not seem to be beneficial for patients with critical illness. Details: A large clinical trial in critically ill patients on mechanical ventilation shows that giving L. rhamnosus GG 10 billion colony-forming units (CFUs) enterally twice daily for a median of 9 days and up to 60 days does not reduce the risk of developing ICU-acquired infections or diarrhea or alter mortality or length of stay when compared with placebo. Also, in 15 patients, L. rhamnosus GG was isolated from sterile sites, including the blood, peritoneal or pleural fluid, hepatic or intra-abdominal abscess, or urine. Death occurred in two cases (107499).
• Peanut allergy. Oral Lacticaseibacillus rhamnosus does not seem to be beneficial for increasing the efficacy of peanut oral immunotherapy in children. Details: Clinical research in children aged 1-10 years with peanut allergy shows that taking L. rhamnosus ATCC 53103 20 billion colony-forming units (CFUs) daily for 18 months does not increase the efficacy of peanut oral immunotherapy in inducing desensitization or maintenance of sustained unresponsiveness to peanuts over the next 8 weeks. Taking L. rhamnosus decreased the number of gastrointestinal and respiratory adverse events; however, hypersensitivity and urticaria occurred more frequently in children aged 6-10 years taking L. rhamnosus (107525).
• Ventilator-associated pneumonia (VAP). Most research shows that enteral Lacticaseibacillus rhamnosus does not prevent VAP and might increase the risk of L. rhamnosus infection. Details: A large clinical trial in critically ill patients on mechanical ventilation shows that giving L. rhamnosus GG 10 billion colony-forming units (CFUs) enterally twice daily for a median of 9 days and up to 60 days does not reduce the risk of developing VAP when compared with placebo. Also, in 15 patients, L. rhamnosus GG was isolated from sterile sites, including the blood, peritoneal or pleural fluid, hepatic or intra-abdominal abscess, or urine. Death occurred in two cases (107499). In contrast, a small clinical study in critically ill patients suggests that administering L. rhamnosus GG (Culturelle) 2 billion CFUs twice daily might reduce the incidence of VAP to 19%, compared with 40% in the placebo group. In this study, half of the dose was given onto the oropharynx and half via a nasogastric tube (17116).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abdominal pain. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for abdominal pain. Details: A meta-analysis of clinical research in children 4-18 years old with functional abdominal pain shows that taking L. rhamnosus GG does not reduce abdominal pain when compared with placebo (105130).
• Age-related cognitive decline. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for age-related cognitive decline. Details: In healthy middle-aged and older adults, clinical research shows that taking L. rhamnosus GG (Culturelle) 10 billion colony-forming units daily for 3 months does not improve cognitive function when compared with placebo. However, there was some benefit in a sub-group of individuals with cognitive impairment (105134).
• Allergic rhinitis (hay fever). Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that drinking 250 mL of fermented milk containing L. rhamnosus GG 50 billion colony-forming units (CFUs), Lactobacillus acidophilus La-5 5 billion CFUs, and Bifidobacterium animalis subsp. lactis BB-12 50 billion CFUs from 36 weeks' gestation until 3 months postpartum does not reduce the incidence of allergic rhinitis in the child at 6 years of age when compared with placebo milk (96893).
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral Lacticaseibacillus rhamnosus for ADHD prevention or treatment, there is insufficient reliable information about the clinical effects of L. rhamnosus for this purpose.
• Bacterial vaginosis. Oral and vaginal Lacticaseibacillus rhamnosus have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: A clinical trial shows that using vaginal capsules (EcoVag Vaginal Capsules, Bifodan A/S) containing L. rhamnosus and Lactobacillus gasseri, 100 million to 1 billion colony-forming units (CFUs) of each strain per capsule, following conventional treatment for 10 days in three subsequent menstrual cycles, increases the time from cure to relapse when compared with placebo. However, cure rates were not significantly improved in the first month of treatment (16745). Oral L. rhamnosus has also been evaluated. The available clinical research has investigated the use of a specific strain, GR-1 in combination with Limosilactobacillus reuteri RC-14. Some research suggests that this combination does not modify vaginal or fecal microbiota or improve cure or recurrence rates in patients also treated with metronidazole vaginally, when compared with taking placebo (111996,111998). Doses in these studies included at least 1 billion CFUs daily of L. rhamnosus plus L. reuteri for 30 days in otherwise healthy premenopausal adults (111996) or 2 billion CFUs of L. rhamnosus and L. reuteri twice daily for 6 months in patients with HIV (111998). However, other clinical research in patients with bacterial vaginosis suggests that taking this combination of probiotics might be beneficial for improving cure rates and improving the vaginal microbiota. In these studies, cure rates increased from 40%-50% with placebo to approximately 88% with the L. rhamnosus and L. reuteri combination. In addition to a single dose of tinidazole 2 grams or metronidazole treatment, 2 billion CFUs each of L. rhamnosus and L. reuteri were used daily for about 1 month in these studies (111997,112508). The reasons for these discrepancies are unclear but may be related to the differences in patient populations, geographical locations, and/or dosing of the product. The effect of L. rhamnosus GR-1 and L. reuteri RC-14 for the prevention of bacterial vaginosis has also been investigated. One clinical study shows that taking capsules containing 2.5 billion CFUs of this combination daily from 9-14 weeks' gestation until delivery does not affect the rate of bacterial vaginosis when compared with placebo (102292). In patients with HIV treated with metronidazole 400 mg twice daily for 10 days, taking 2 billion CFUs of L. rhamnosus and L. reuteri twice daily for 6 months does not improve the recurrence rates when compared with taking placebo (111998).
• Bipolar disorder. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that taking at least 100 million colony-forming units of a combination of L. rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 for 24 weeks after discharge from the hospital for mania reduces the time to first rehospitalization when compared with placebo. The hazard ratio for the first rehospitalization due to worsening of psychiatric symptoms was 0.37 for the combination probiotic group when compared with placebo. Among patients who were re-hospitalized, taking the combination probiotic reduced the mean duration of rehospitalization by 5.4 days when compared with placebo (96896).
• Cancer. Although there has been interest in using oral Lacticaseibacillus rhamnosus for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Canker sores. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for canker sore prevention or treatment. Details: A systematic review and meta-analysis of mainly small and preliminary clinical trials shows that oral lactobacilli have a small effect on pain from canker sores. However, only two studies in the analysis used L. rhamnosus. One individual study shows that taking L. rhamnosus Lcr35 1.5 billion colony-forming units (CFUs) daily for 3 months has no effect on the number of canker sores. Another small study shows that taking a combination of L. rhamnosus, Lacticaseibacillus paracasei, Lactobacillus acidophilus, and Bifidobacterium animalis subsp. lactis reduces pain, but does not affect the number of lesions or healing time, when compared with placebo (105146). The individual studies were small and may have been underpowered to detect a difference between groups.
• Chemotherapy-induced diarrhea. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for preventing chemotherapy-induced diarrhea. Details: Preliminary clinical research in patients with colorectal cancer receiving chemotherapy with 5-fluorouracil shows that taking L. rhamnosus GG (Culturelle) 10-20 billion colony-forming units (CFUs) daily in two divided doses orally during 24 weeks of chemotherapy, with or without guar gum, reduces severe diarrhea, abdominal discomfort, and the number of chemotherapy dose reductions required when compared with not taking L. rhamnosus GG (16736).
• Child development. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: An 11-year follow-up study shows that taking L. rhamnosus and Bifidobacterium animalis subsp. lactis daily from 35 weeks' gestation until birth, or for six months after birth if breastfeeding, followed by supplementation of the child until two years of age, does not affect neurocognitive outcomes such as attention, intelligence, executive function, depression, and anxiety, when compared with placebo (102287).
• Clostridioides difficile infection. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for the prevention of C. difficile infection. Details: Observational research has found that providing a specific combination (Bio-K+ 50 Billion; Bio-K Plus International) of L. rhamnosus CLR2, Lactobacillus acidophilus CL1285, and Lacticaseibacillus casei LBC80R, as 50-100 billion colony-forming units (CFUs) daily for 5 days to patients who are on antibiotics for at least 2 days reduces the hospital-wide incidence of C. difficile by approximately 40%. The incidence rate was decreased by at least 50% in the highest risk individuals taking this combination (107529). Conversely, individual clinical studies included in some meta-analyses suggest that L. rhamnosus is not effective for the primary prevention of C. difficile infections; however, the number of patients with C. difficile in the individual studies is likely too small for an adequate comparison (14334,90231). Current guidelines from the Infectious Diseases Society of America (IDSA) state that there is insufficient information to recommend administration of probiotics for the primary prevention of C. difficile-associated diarrhea (107538). While some preliminary clinical research shows that taking L. rhamnosus GG might reduce the risk of C. difficile diarrhea recurrence (4392,4394), meta-analyses of more recent, higher-quality clinical data show that this strain is not effective for this purpose (14334,18088,90934,95368,95370).
• Cognitive function. It is unclear if oral Lacticaseibacillus rhamnosus improves cognitive function in young adults. Details: A small clinical trial shows that taking L. rhamnosus JB-1 as 1 billion colony-forming units daily for 4 weeks does not improve cognitive function when compared with placebo in healthy young adults (105148).
• Cognitive impairment. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for cognitive impairment. Details: In middle-aged and older adults with cognitive impairment, a small clinical trial shows that taking L. rhamnosus GG (Culturelle) 10 billion colony-forming units daily for 3 months results in an improved cognitive function score when compared with placebo (105134).
• Colic. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for colic. Details: A small clinical trial in exclusively breastfed infants with colic shows that taking L. rhamnosus ATCC 53103 5 billion colony-forming units (CFUs) daily for 28 days reduces full-force crying time by a median of 135 minutes when compared with taking placebo (112000). Other clinical research in infants aged 4-12 weeks with colic shows that taking a combination of L. rhamnosus and Limosilactobacillus reuteri (FloraActive) 250 million CFUs with fructo-oligosaccharides 3.33 mg and vitamin D3 200 IU daily for 28 days reduces mean crying time by 2.7 hours by the end of the study, compared to a 1.9-hour reduction in the vitamin D group (99783). However, another small clinical study in infants shows that taking L. rhamnosus GG 10 billion CFUs with inulin 225 mg daily starting within 4 days of birth does not prevent colic symptoms or diagnosis at 4 months when compared with inulin alone (112497). This study was a secondary analysis of a trial designed to investigate the effect of L. rhamnosus on atopic disease prevention.
• Common cold. Although there has been interest in using oral Lacticaseibacillus rhamnosus for preventing the common cold, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Constipation. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for constipation. Details: A small clinical study in children less than 5 years old with functional constipation shows that taking L. rhamnosus Lcr35 800 million CFUs twice daily for 4 weeks does not improve stool frequency when compared with placebo (95340). However, a small clinical trial shows that taking a combination of L. rhamnosus IDCC 3201, Lactiplantibacillus plantarum IDCC 3501, Lacticaseibacillus casei IDCC 3451, Bifidobacterium animalis subsp. lactis IDCC 4301, Bifidobacterium breve IDCC 4401, Lactococcus lactis IDCC 2301, xylooligosaccharide, and dietary fiber as nondigestible maltodextrin, oat fiber, and psyllium husk fiber (ID-HWS1000) modestly increases stool frequency and improves symptoms of functional constipation in adults when compared with placebo (107517). It is unclear if these effects are due to L. rhamnosus, other ingredients, or the combination.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral Lacticaseibacillus rhamnosus for reducing symptoms of COVID-19, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Crohn disease. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for preventing Crohn disease recurrence. Details: A small clinical trial in adults shows that taking L. rhamnosus GG (Culturelle) 6 billion colony-forming units (CFUs) twice daily for one year does not prevent recurrence of Crohn disease after surgery (12767). Another small clinical trial in children and young adults shows that taking L. rhamnosus 10 billion CFUs twice daily for up to two years in addition to standard therapy does not prolong remission when compared with placebo (107539).
• Cystic fibrosis. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for cystic fibrosis. Details: Clinical research in children aged 2-16 years with cystic fibrosis shows that taking L. rhamnosus GG 6 billion colony-forming units (CFUs) daily for 12 months does not reduce the odds of having at least one pulmonary exacerbation, the odds of hospitalization over 12 months, or the total number of exacerbations or hospitalizations when compared with placebo (107570).
• Dental caries. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for dental caries prevention. Details: A large clinical trial in children aged 1-6 years shows that providing milk containing L. rhamnosus GG ATCC 53103 (Gefilus, Valio Ltd., Riihimaki Dairy) five days a week for 7 months does not reduce the overall odds of developing dental caries when compared with placebo. However, there was a 44% reduction in caries odds when caries risk was taken into consideration. The milk provided at least 500,000 colony-forming units (CFUs) per mL, with each child consuming 42-584 mL daily (107571). However, a meta-analysis of this and other large clinical trials in preschool children shows that taking L. rhamnosus in juice or milk modestly reduces the incidence of dental caries and prevents tooth decay progression when compared with taking placebo (112507). The effect of L. rhamnosus added to milk has also been investigated in adults. Clinical research in middle-aged and older adults with at least two primary root caries lesions shows that taking L. rhamnosus LB21 200 million CFUs in milk, either alone or with added fluoride 5 ppm, once daily for 15 months modestly reduces lesion severity when compared with placebo milk. However, the milk containing L. rhamnosus in the absence of fluoride was less effective than either the combination or the milk containing fluoride only (107573). The validity of this study is limited by a dropout rate of 38%.
• Dental plaque. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adolescent males aged 13-15 years with mild to moderate gingival inflammation shows that taking two lozenges containing L. rhamnosus GG (Probiotical SpA) and Bifidobacterium animalis subsp. lactis BB-12 (Chr. Hansen A/S) twice daily for 4 weeks does not reduce plaque when compared with placebo. However, here was a benefit on levels of some salivary and plaque pathogenic bacteria. Each lozenge provided L. rhamnosus 440 million colony-forming units (CFUs) plus B. animalis subsp. lactis BB-12 480 million CFUs (107574). A small clinical trial in healthy adults shows that taking four lozenges daily providing a total daily dose of 2 billion CFUs each of L. rhamnosus GG ATCC 53103 (Probiotical SpA) and B. animalis subsp. lactis BB-12 DSM 15954 (Chr. Hansen A/S) for 4 weeks modestly reduces plaque and gingivitis when compared with placebo (107572). Another small clinical trial in adults with moderate gingival inflammation shows that taking a tablet providing 50 million CFUs each of L. rhamnosus PB01 DSM 14869 and Latilactobacillus curvatus EB10 DSM 32307 twice daily after brushing for 4 weeks does not improve plaque or bleeding during probing when compared with placebo (107575).
• Denture stomatitis. Although there has been interest in using oral Lacticaseibacillus rhamnosus for denture stomatitis, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Diabetes. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for treatment of type 1 or type 2 diabetes. Oral L. rhamnosus is unlikely to be beneficial for the prevention of gestational diabetes and may actually increase the risk for other complications. Details: One small clinical study in patients with type 2 diabetes shows that taking a specific combination product (Familact probiotics, ZistTakhmir Co.) containing L. rhamnosus and other probiotic bacteria daily for 6 weeks does not reduce fasting blood glucose or plasma insulin when compared with placebo. This product contains L. rhamnosus 1.5 billion colony-forming units (CFUs), Lactobacillus acidophilus 2 billion CFUs, Lacticaseibacillus casei 7 billion CFUs, Lactobacillus delbrueckii subsp. bulgaricus 200 million CFUs, Bifidobacterium breve 30 billion CFUs, Bifidobacterium longum 7 billion CFUs, and Streptococcus thermophilus 1.5 billion CFUs (99790). A meta-analysis of clinical research shows that taking lactobacilli, usually L. rhamnosus, during pregnancy is unlikely to PREVENT gestational diabetes and increases the relative risk of pre-eclampsia by 85% when compared with placebo (105185). Studies have used L. rhamnosus HN001 6 billion CFUs daily from 14-16 weeks' gestation to 24-30 weeks' gestation (96888), L. rhamnosus GG and Bifidobacterium animalis subsp. lactis (BB-12) at least 1 billion CFUs daily from 16-20 weeks' gestation until 28 weeks' gestation, or L. rhamnosus HN001 ATCC SD5675 and B. animalis subsp. lactis 420 DSM 22089 (Dupont Nutrition & Health) 10 billion CFUs each daily throughout pregnancy, with or without fish oil (102284,105144). Limited evidence has also assessed the effects of L. rhamnosus for type 2 diabetes. Taking L. rhamnosus 10 billion CFUs, L. acidophilus 1 billion CFUs, and Bacillus coagulans GanedenBC30 (GBI-30, 6086) 100 billion CFUs with fructo-oligosaccharides 500 mg daily for 12 weeks modestly reduces fasting blood glucose and insulin and improves measures of insulin resistance when compared with placebo (107536). Some research has also assessed the effects of L. rhamnosus in combination with other probiotics in children 8-17 years old with new onset type 1 diabetes. One clinical study shows that taking L. rhamnosus GG ATCC 53103 and Bifidobacterium animalis subsp. lactis Bb12 DSM 15954 1 billion CFUs daily for 6 months does not reduce insulin requirements or glycated hemoglobin over 12 months when compared with placebo. Additionally, C-peptide levels and the maintenance of residual pancreatic beta-cell function were not affected when compared with placebo (107518).
• Diarrhea. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for the prevention or treatment of acute diarrhea. Details: L. rhamnosus GG (e.g., Culturelle) 6 billion CFUs twice daily, given prophylactically at hospital admission, seems to reduce the risk of non-rotaviral diarrhea in infants and children ages 1-36 months (7741). Furthermore, giving 37 billion CFUs of this strain daily, 6 days weekly for 15 months, can reduce the occurrence of diarrhea from all causes in undernourished children aged 6-24 months (4373). However, in older adults in long-term care, taking a combination of L. rhamnosus and Bifidobacterium animalis subsp. lactis (BB-12) 13-16 billion CFUs daily does not reduce the incidence or duration of diarrhea over a 12-month period when compared with placebo (103425). A small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing L. rhamnosus, Lacticaseibacillus casei, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium infantis, Bifidobacterium breve, and Streptococcus thermophilus daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). L. rhamnosus has yielded inconsistent results in the treatment of acute gastroenteritis, which is defined as three or more episodes of watery stools per day, with or without vomiting, for fewer than 3-7 days. While the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388), both guidelines note that most evidence is low quality. Furthermore, these guidelines were published prior to the completion of the recent high-quality studies showing no benefit with L. rhamnosus GG, alone or in combination with Lactobacillus helveticus (98427,98428,103441,110925). These studies in children 3 months to 4 years of age with acute gastroenteritis show that taking either L. rhamnosus GG (e.g., Culturelle) 1 billion CFUs or a combination product containing L. rhamnosus GG 3.8 billion CFUs and L. helveticus 200 million CFUs twice daily for 5 days does not reduce the risk of a moderate to severe episode of acute gastroenteritis in the 14-28 days after starting the probiotic when compared with placebo (98427,98428,103441,110925). These products also did not reduce the incidence or severity of diarrhea or vomiting, the number of unexpected healthcare visits (98427,98428,103441,110925), the number of day care days missed, or the rate of household transmission (98427) when compared with placebo, regardless of the causative pathogen. Additional clinical research shows that treatment with L. rhamnosus GG 1 billion CFUs twice daily for 5 days does not reduce the severity or duration of diarrhea in otherwise healthy children 6 months to 6 years of age (90280).
• Gingivitis. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adolescent males aged 13-15 years with mild to moderate gingival inflammation shows that taking two lozenges containing L. rhamnosus GG (Probiotical SpA) and Bifidobacterium animalis subsp. lactis BB-12 (Chr. Hansen A/S) twice daily for 4 weeks modestly reduces gingivitis when compared with placebo. Each lozenge provided L. rhamnosus 440 million colony-forming units (CFUs) plus B. animalis subsp. lactis BB-12 480 million CFUs (107574). A small clinical trial in healthy adults shows that taking four lozenges daily providing a total daily dose of 2 billion CFUs each of L. rhamnosus GG ATCC 53103 (Probiotical SpA) and B. animalis subsp. lactis BB-12 DSM 15954 (Chr. Hansen A/S) for 4 weeks modestly reduces plaque and gingivitis when compared with placebo (107572). However, a small clinical trial in adults with moderate gingival inflammation shows that taking a tablet providing 50 million CFUs each of L. rhamnosus PB01 DSM 14869 and Latilactobacillus curvatus EB10 DSM 32307 twice daily after brushing for 4 weeks does not improve plaque or bleeding with probing when compared with placebo (107575).
• Group B streptococcal colonization. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of two clinical trials shows that taking L. rhamnosus GR-1 and Limosilactobacillus reuteri RC-14, starting at 35-37 weeks' gestation and continuing until delivery, does not improve GBS clearance during pregnancy. However, a well-designed study included in this analysis shows that taking 4 billion CFUs daily more than doubles the number of patients testing negative for GBS at delivery (105165). In addition, a small clinical trial shows that taking this combination as 2.5 billion colony-forming units (CFUs) each daily for 12 weeks, starting at weeks 23-25 of gestation, does not prevent the rate of GBS vaginal/rectal colonization at 35-37 weeks' gestation (107567).
• Helicobacter pylori. It is unclear if oral Lacticaseibacillus rhamnosus in combination with standard therapies for H. pylori can improve eradication rates or reduce the risk of adverse effects; the available research is conflicting. Details: Most clinical research in adults has shown that L. rhamnosus does not improve H. pylori eradication rates when used in combination with Lactobacillus acidophilus, Bifidobacterium bifidum, and Streptococcus faecium and taken with triple therapy consisting of furazolidone, tetracycline, and lansoprazole (90279), when used in combination with six other probiotics species and taken with bismuth quadruple therapy (90291), or when L. rhamnosus GG is used with triple therapy consisting of rabeprazole, clarithromycin, and tinidazole (12763). However, a large, more recent study shows that taking L. rhamnosus GG in combination with Bifidobacterium animalis subsp. lactic BB-12 (Normia, JGL; Christian Hanssen) twice daily for 14 days with triple therapy results in eradication in 87% of patients, compared with 73% of those taking triple therapy and placebo (107514). L. rhamnosus has also been evaluated for reducing the risk of adverse effects from H. pylori treatment. In two studies in which L. rhamnosus is taken along with other probiotics, the rate of adverse effects is not reduced when compared with placebo (90279,90291). However, when L. rhamnosus GG is used alone, or in combination with Bifidobacterium animalis subsp. lactis BB-12, triple therapy-related adverse effects are modestly reduced when compared with placebo (12763,107514). There was no longer a difference in adverse events between probiotic therapy and placebo during the 2-4 weeks of follow up (12763).
• HIV/AIDS. Although there has been interest in using oral Lacticaseibacillus rhamnosus for HIV/AIDS, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Hypercholesterolemia. Although there has been interest in using oral Lacticaseibacillus rhamnosus for hypercholesterolemia, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Hypertension. Although there has been interest in using oral Lacticaseibacillus rhamnosus for hypertension, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Irritable bowel syndrome (IBS). It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for IBS; the available research is conflicting. Details: A meta-analysis of clinical research shows that L. rhamnosus reduces abdominal pain, but does not improve the frequency of pain relief, in patients with IBS (107594). In contrast, a small clinical trial shows that taking L. rhamnosus GG 10 billion CFUs daily for 8 weeks does not improve symptoms of IBS (12771). L. rhamnosus has also been evaluated in combination with other probiotics. Clinical research shows that taking a product (Duolac Care) containing L. rhamnosus, Bifidobacterium animalis susbp. lactis, Bifidobacterium breve, Lactobacillus acidophilus, Lactiplantibacillus plantarum, and Streptococcus thermophilus twice daily for 4 weeks can relieve symptoms in 72% of patients with IBS (95353). A clinical study in patients with diarrhea-predominant IBS (IBS-D) shows that taking a specific multi-species probiotic (NordBiotic, MBM Biotix) containing L. rhamnosus LR110, L. acidophilus LA120, L. plantarum LP140, Lacticaseibacillus paracasei LPC100, Lacticaseibacillus casei LC130, B. breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium animalis subsp. lactis BL040, and Streptococcus thermophilus ST250 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life, when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516). However, other clinical research shows that taking a combination of L. rhamnosus CLR2, L. acidophilus CL1285, and L. casei LBC80R 50 billion CFUs each daily for 3 months does not improve symptoms of IBS in the whole study population, although it may have some benefit in specific sub-groups (99789).
• Lactose intolerance. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for lactose intolerance. Details: In patients with persistent symptoms related to lactose intolerance despite a lactose-free diet, a small clinical trial shows that taking a combination product (Zircombi) containing L. rhamnosus HN001 1 billion CFUs, Bifidobacterium longum BB536 4 billion CFUs, and vitamin B6 1.4 mg daily for 30 days modestly improves symptoms of bloating and constipation, but not abdominal pain, when compared with placebo (105153).
• Malnourishment-related diarrhea. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children aged 6 months to 4 years of age hospitalized with severe acute malnutrition shows that taking L. rhamnosus LGG and Bifidobacterium lactis BB-12 5 billion colony-forming units each daily during hospitalization and for 8-12 weeks as an outpatient does not affect diarrhea incidence or severity or the number of days with diarrhea during hospitalization. However, the number of days with diarrhea as an outpatient was reduced by 2.2 days (110996).
• Malnutrition. Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children aged 6 months to 4 years of age hospitalized with severe acute malnutrition shows that taking L. rhamnosus LGG and Bifidobacterium lactis BB-12 5 billion colony-forming units each daily during hospitalization and for 8-12 weeks as an outpatient does not affect pneumonia incidence, duration, or severity, weight gain, duration of hospitalization, or other outcomes (110996).
• Metabolic syndrome. Although there has been interest in using oral Lacticaseibacillus rhamnosus for metabolic syndrome, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Necrotizing enterocolitis (NEC). It is unclear if oral Lacticaseibacillus rhamnosus is beneficial or safe for NEC prevention. Details: Most meta-analyses of clinical research show that giving lactobacilli enterally reduces the risk of NEC and/or severe NEC in preterm, mainly very low birth weight (VLBW), infants. Some meta-analyses support the use of lactobacilli in combination with bifidobacteria, as opposed to lactobacilli alone for reducing the risk of NEC (95344,95351,103437,103445,104157,105162,105164). However, research on the use of L. rhamnosus, specifically, is limited. Large retrospective reports suggest that taking L. rhamnosus GG does not significantly reduce the risk of NEC in preterm, VLBW infants. The most recent report suggests that the use of L. rhamnosus is associated with an almost 2-fold increased incidence of NEC when compared with not using L. rhamnosus (17121,112501). Also, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, L. rhamnosus is not specifically recommended (103003,111609,111611).
• Neurogenic bladder. Although there has been interest in using intravesical Lacticaseibacillus rhamnosus for reducing urinary symptoms associated with neurogenic bladder, there is insufficient reliable information about the clinical effects of L. rhamnosus for this purpose.
• Nonalcoholic fatty liver disease (NAFLD). Oral Lacticaseibacillus rhamnosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children with NAFLD, clinical research shows that taking a specific combination product (Prokid, Gostaresh Milad Pouya Company) containing L. rhamnosus DSMZ 21690 2 billion colony-forming units (CFUs), Lactobacillus acidophilus ATCC B3208 3 billion CFUs, Bifidobacterium animalis subsp. lactis DSMZ 32269 6 billion CFUs, and Bifidobacterium bifidum ATCC SD6576 2 billion CFUs daily for 12 weeks normalizes liver sonography findings in 53% of children, compared with 17% of those taking placebo. In addition, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are reduced by 30% and 25%, respectively. There was no effect on body mass index or blood lipids when compared with placebo (105156).
• Obesity. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for weight loss. Details: Clinical research in adults with obesity shows that taking L. rhamnosus 162 million colony-forming units (CFUs) twice daily for 24 weeks does not reduce body weight or fat mass when compared with placebo. However, when only females are considered, L. rhamnosus seems to reduce body weight by an additional 1.8 kg when compared with placebo (90289). Another clinical trial shows that taking 10 billion CFUs each of L. rhamnosus HN001 and Bifidobacterium animalis subsp. lactis 420 daily during pregnancy and for 6 months postpartum, alone or with 2 capsules daily of fish oil (Croda Europe Ltd.), reduces the odds of the infant being overweight at 24 months by at least 78% when compared with taking placebo (110336). It is unclear if this effect is related to L. rhamnosus, B. lactis, or their combination.
• Oropharyngeal candidiasis. Although there has been interest in using oral Lacticaseibacillus rhamnosus for oropharyngeal candidiasis, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Osteoarthritis. Although there has been interest in using oral Lacticaseibacillus rhamnosus for osteoarthritis, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Otitis media. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for preventing otitis media in children. Details: Preliminary clinical research in children aged 1-6 years who attend daycare shows that taking milk containing L. rhamnosus GG (Culturelle) does not reduce the incidence of otitis media infections when compared with placebo (8565).
• Periodontitis. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for periodontitis. Details: A meta-analysis of 2 small clinical trials in patients with periodontitis shows that using oral L. rhamnosus as an adjunctive therapy to scaling and root planing does not improve clinical attachment or reduce probing pocket depth when compared with control (107622). Similarly, a small clinical trial in patients with stage III periodontitis following scaling and root planing shows that taking L. rhamnosus SP1 (Macrofood S.A.) as 20 million colony-forming units (CFUs) daily for 3 months does not improve plaque, probing pocket depth, bleeding on probing, or clinical attachment, when compared with placebo (107576). However, all studies were small and might not have been adequately powered to detect differences between groups.
• Polycystic ovary syndrome (PCOS). It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for PCOS. Details: A small clinical trial in overweight or obese patients with PCOS who are consuming an energy-restricted diet shows that taking L. rhamnosus 12 billion colony-forming units (CFUs) daily for 20 weeks does not increase weight loss or have beneficial effects on blood lipid levels when compared with placebo (107577). However, this study was small and may not have been adequately powered to detect a difference between groups. Another clinical trial shows that 31.3% of patients with PCOS taking L. rhamnosus in combination with other probiotics daily for 6 months had regular menstrual cycles compared with 12.5% of those taking placebo. There were also modest improvements in testosterone levels and waist circumference, but not other hormones, insulin resistance, body weight, or most measures of quality of life. The product provided L. rhamnosus UBLR-58 2 billion CFUs along with Bifidobacterium bifidum UBBB-55, Lactobacillus acidophilus UBLA-34, Lactiplantibacillus plantarum UBLP-40, Lacticaseibacillus casei UBLC-42, Limosilactobacillus fermentum UBLF-31, Limosilactobacillus reuteri UBLRu-87, and fructo-oligosaccharides (FOS) daily for 2 months and then twice daily for 4 months. All patients also underwent dietary and lifestyle changes (110974). It is unclear if any benefits are due to L. rhamnosus, the other probiotics, or their combination.
• Postoperative bowel function. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for improving postoperative bowel function. Details: A small preliminary clinical trial shows that taking L. rhamnosus GG (Dicoflor 60, Vitis pharma, Warsaw, Poland) 6 million colony-forming units twice daily for 30 days following major pancreatic surgery reduces the time to first passing gas and stool, by about 1.1 and 2 days, respectively, when compared with receiving standard nutrition only (112495).
• Postoperative infection. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for preventing postoperative infections. Details: A small preliminary clinical trial shows that taking L. rhamnosus GG (Dicoflor 60, Vitis pharma, Warsaw, Poland) 6 million colony-forming units twice daily for 30 days following major pancreatic surgery does not reduce the incidence of postoperative infections when compared with receiving standard nutrition only (112495).
• Postoperative recovery. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for improving postoperative recovery. Details: A small preliminary clinical trial shows that taking L. rhamnosus GG (Dicoflor 60, Vitis pharma, Warsaw, Poland) 6 million colony-forming units twice daily for 30 days following major pancreatic surgery reduces the length of hospital stay by 2 days when compared with receiving standard nutrition only (112495).
• Postpartum depression. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for postpartum depression. Details: Clinical research shows that taking L. rhamnosus HN001 6 billion colony-forming units (CFUs) daily from 14-16 weeks' gestation does not reduce the rate of clinically significant depression when compared with placebo. However, taking this product modestly reduces feelings of postpartum depression and anxiety, and 47% fewer patients experienced clinically significant anxiety between 1-2 months' postpartum when compared with placebo (107541). Other clinical research shows that taking a combination of L. rhamnosus HN001 ATCC SD5675 and Bifidobacterium animalis subsp. lactis 420 DSM 22,089 (Dupont Nutrition & Health) 10 billion CFUs daily, alone or with fish oil providing eicosapentaenoic acid (EPA) 0.44 grams and docosahexaenoic acid (DHA) 3.8 grams daily, does not reduce symptoms of postpartum depression or anxiety when compared with placebo. Supplements were started in the second trimester of pregnancy and continued until 6 months after delivery (107496).
• Pouchitis. Although there has been interest in using oral Lacticaseibacillus rhamnosus for pouchitis, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Respiratory tract infections. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for respiratory tract infections; the available research is conflicting. Details: The evidence related to the use of L. rhamnosus for respiratory tract infections is mixed. A meta-analysis of clinical research shows that administering L. rhamnosus GG to infants and children reduces the risk of upper respiratory tract infections (URTIs) by about 38%. However, this analysis shows that giving this strain to infants and children does not reduce the risk of overall respiratory infections or the risk of lower respiratory tract infections (95347). Also, the evidence from individual clinical trials is mixed. One large clinical trial shows that children ages 1-6 years who attend daycare centers get fewer and less severe respiratory infections when given approximately 260 mL milk daily containing L. rhamnosus GG (Culturelle) 0.5-1 million colony-forming units (CFUs) per mL (8565). However, other clinical research in infants aged 6 to 12 months shows that taking L. rhamnosus HN001 one million colony-forming units (CFUs) per gram of follow-on formula daily for 12 weeks does not reduce the incidence of confirmed or parentally reported upper respiratory tract infections when compared with formula without added probiotics. Infants consumed an average of 141 grams of formula daily (110988). Also, a large clinical trial in children aged 2-6 years shows that taking L. rhamnosus GG 1 billion CFUs daily for 16 weeks does not reduce the incidence of physician-diagnosed URTIs when compared with taking placebo. There was also no difference in the number of children, days, or days absent with a URTI (112492). L. rhamnosus has also been investigated in combination with other probiotics. In college students, clinical research shows that taking L. rhamnosus GG and Bifidobacterium lactis BB-12 one billion CFUs each daily for 12 weeks reduces the duration of upper respiratory tract infection by about 2 days when compared with placebo. Symptom severity was reduced by 34%. There was also a small reduction in the number of missed school days, but not work days (110993). Conversely, in older adults in long-term care, taking a combination of L. rhamnosus and Bifidobacterium animalis subsp. lactis (BB-12) 13-16 billion CFUs daily does not reduce the incidence of upper or lower respiratory tract infections when compared with placebo over a 12-month period, and actually increases the use of antibiotics for lower respiratory tract infections by 2.2 days (103425).
• Rheumatoid arthritis (RA). It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for RA. Details: A small clinical trial in patients with RA shows that taking L. rhamnosus GG ATCC 53103 (Gefilus, Valio Ltd.) 10 billion colony-forming units (CFUs) twice daily for 12 months does not reduce symptoms when compared with placebo (107533). An additional small clinical trial shows that taking a total of 2 billion colony-forming units (CFUs) daily of a combination of L. rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 (Chr Hansen) for 14 weeks does not improve symptom severity when compared with placebo (107569). Both studies were small and may not have been adequately powered to detect differences between groups.
• Rotaviral diarrhea. It is unclear if oral Lacticaseibacillus rhamnosus is beneficial for rotaviral diarrhea. Details: Some meta-analyses of clinical research and several small clinical trials show that L. rhamnosus GG (Culturelle) can reduce the duration of diarrhea in infants and children with rotavirus infection (1253,4369,4377,8568,112504). These studies were conducted prior to the availability of the rotavirus vaccine. Conversely, large, high-quality studies conducted after the introduction of the rotavirus vaccine do not show benefits (98427,98428,112504). Clinical research in children 3 months to 4 years of age with acute gastroenteritis, including rotaviral gastroenteritis, shows that taking either L. rhamnosus GG (Culturelle) or a combination product containing L. rhamnosus GG 3.8 billion CFUs and Lactobacillus helveticus 200 million CFUs twice daily for 5 days does not reduce the risk of a moderate to severe episode of acute gastroenteritis in the 14 days after starting the probiotic when compared with placebo (98427,98428,110925). Taking these probiotic products also does not reduce the incidence or severity of diarrhea or vomiting, the number of unexpected healthcare visits (98427,98428,110925), the number of daycare days missed, the rate of household transmission (98427), or the pathogen load (103441) when compared with placebo. Approximately 48% to 65% of the children enrolled in these studies were vaccinated against rotavirus, but it is not clear if this altered the study outcomes (98427,98428,103441). More research is needed to evaluate the effect of lactobacillus in the treatment of rotaviral diarrhea in children who have not been vaccinated against rotavirus. Although L. rhamnosus GG and other species have shown modest benefit in preliminary clinical studies in children who have not received the rotavirus vaccine, the evidence is conflicting, and not all of the evaluated patients had confirmed rotavirus infection (102295). The current guidelines related to the treatment of viral diarrhea are also conflicting. While the World Gastroenterology Organization has not made a recommendation (98471), the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388). However, these guidelines note that most evidence is low quality and is not specific to rotavirus infection. Furthermore, these guidelines were released prior to the publication of the most recent, high-quality studies showing no benefit with the use of L. rhamnosus (98427,98428). Recent guidelines by the American Gastroenterology Association conditionally recommend against the use of probiotics for the treatment of acute infectious gastroenteritis in children (103003).
• Short bowel syndrome. Although there has been interest in using oral Lacticaseibacillus rhamnosus for short bowel syndrome, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Small intestinal bacterial overgrowth (SIBO). Although there has been interest in using oral Lacticaseibacillus rhamnosus for SIBO, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Stress. It is unclear if oral Lacticaseibacillus rhamnosus GG is beneficial for stress. Details: Preliminary clinical research in university students shows that taking L. rhamnosus HN001 6 billion colony-forming units (CFUs) daily for 8-13 weeks during the semester does not reduce stress or anxiety during exams when compared with taking placebo (112496).
• Travelers' diarrhea. It is unclear if oral Lacticaseibacillus rhamnosus GG is beneficial for the prevention of travelers' diarrhea; the available research is conflicting. Details: Clinical research shows that taking L. rhamnosus GG (Culturelle) 2 billion colony-forming units daily orally, starting two days prior to a trip and continuing until the end of the trip, seems to reduce the occurrence of diarrhea in child and adult travelers (4374,10216). However, a meta-analysis which included two small clinical studies evaluating the use of L. rhamnosus GG in adults traveling to different parts of the world found no benefit for the prevention of travelers' diarrhea when compared with placebo (101445). The effectiveness of this strain can vary significantly based upon the destination of travel. Destinations in the same country can have different results, probably due to differences in bacteria and other microorganisms at different locations (10216).
• Ulcerative colitis. Although there has been interest in using oral Lacticaseibacillus rhamnosus for ulcerative colitis, there is insufficient reliable information about the clinical effects of L. rhamnosus for this condition.
• Urinary tract infections (UTIs). It is unclear if oral or intravaginal Lacticaseibacillus rhamnosus is beneficial for the prevention or treatment of UTIs. Details: Some small clinical studies show that intravaginal use of L. rhamnosus might provide modest benefit for preventing UTI (6094,6095). These trials used suppositories containing 0.5 gram (1.6 billion colony-forming units (CFUs)) of L. rhamnosus and Limosilactobacillus fermentum twice weekly for 2 weeks, then once a month for 2 months (6095) or a vaginal solution containing L. rhamnosus 100 billion viable bacteria/mL in a dose of 1 mL twice weekly (6094). However, some research indicates that L. rhamnosus is ineffective in establishing vaginal colonization, regardless of the route of administration (90257). This may explain why studies which have evaluated the use of L. rhamnosus as a single agent for this indication have failed to show benefit (4581). Oral L. rhamnosus has also been evaluated for the prevention of UTI recurrence. Clinical research in postmenopausal adults shows that an oral combination of L. rhamnosus GR-1 and Limosilactobacillus reuteri RC-14, standardized to at least 1 billion CFUs and taken twice daily for 12 months, demonstrates similar efficacy to trimethoprim/sulfamethoxazole 480 mg once daily for reducing the number of symptomatic UTIs. Although this combination was not associated with the increase in antimicrobial resistance that occurred with the use of antibiotic prophylaxis, the antibiotic delayed the median time to first recurrence by two-fold and reduced the number of confirmed microbiological infections when compared with lactobacillus (90235). In children aged 4 months to 5 years with a previous UTI, clinical research shows that taking a specific combination (Complete Probiotic Platinum) of L. rhamnosus, Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium animalis subsp. lactis for 18 months increases the median time to the first incidence of recurrence by approximately 3 months and increases the percentage of children without a UTI during the study period from 83% to 97% (103436). However, in older adults in long-term care, taking a combination of L. rhamnosus and Bifidobacterium animalis subsp. lactis (BB-12) 13-16 billion CFUs daily does not reduce the incidence of UTI when compared with placebo over a 12-month period (103425).
• Vaginal candidiasis. It is unclear if oral or intravaginal Lacticaseibacillus rhamnosus is beneficial for the prevention or treatment of vaginal candidiasis. Details: A combination of L. rhamnosus and Bifidobacterium longum (Lactobac) given orally, or a combination of L. rhamnosus, Lactobacillus delbrueckii, Lactobacillus acidophilus, and Streptococcus thermophilus (Femilac) given intravaginally, does not seem to reduce the risk of vaginal candidiasis infection following use of antibiotics (12108). However, there is preliminary evidence that individuals with candidiasis who use intravaginal suppositories containing 1 billion colony-forming units of L. rhamnosus GG twice daily for 7 days in combination with conventional treatment might have subjective improvement in symptoms (4397). More evidence is needed to rate Lacticaseibacillus rhamnosus for these uses.

(Read more about LACTICASEIBACILLUS RHAMNOSUS)

POSSIBLY EFFECTIVE

• Atopic dermatitis (eczema). Oral Lactiplantibacillus plantarum seems to be beneficial for the treatment of atopic dermatitis. Details: Clinical research in children aged 1-13 years shows that taking L. plantarum CJLP133 50 billion colony-forming units (CFUs) twice daily for 12 weeks modestly reduces overall symptom severity when compared with placebo. However, there was no effect on the use of topical corticosteroids (90259). In adults with mild to moderate atopic dermatitis, a small clinical trial also shows that taking L. plantarum IS-10506 20 billion colony-forming units daily for 8 weeks modestly reduces overall symptom severity when compared with placebo (111992). L. plantarum has also been investigated in combination with other ingredients. Some clinical research shows that taking 1 billion CFUs each of L. plantarum PBS067, Limilactobacillus reuteri PBS072, and Lacticaseibacillus rhamnosus LRH020 daily for 56 days modestly reduces the severity of symptoms and improves skin smoothness and moisturization for up to an additional 28 days when compared with placebo (107506).
• Common cold. A combination of Lactiplantibacillus plantarum and Lacticaseibacillus paracasei seems to be beneficial for reducing the incidence or severity of the common cold. The effects of L. plantarum alone are unclear. Details: Clinical research shows that taking L. plantarum HEAL 9 (DSM 15312) and L. paracasei 8700:2 (DSM 13434) (Probi Defendum, Probi AB) 1 billion colony-forming units (CFUs) daily for 12 weeks reduces the incidence of the common cold by about 12% and reduces the number of symptomatic days from 8.6 to 6.2 when compared with placebo (17119). Additional clinical research in adults who are at an increased risk for the common cold shows that taking this same combination for 12 weeks does not reduce the incidence of developing a cold when compared with placebo. However, symptom severity was modestly reduced. Also, each episode was reduced by an average of 1.1 days (107557). A more recent clinical study in a similar population shows that taking the same combination does not reduce symptom severity or the absolute number of common cold episodes when compared with placebo. However, in individuals with at least one cold, the mean number of colds was reduced by 0.12 over the 12-week period. In addition, there were modest overall reductions in the incidence of recurring colds and the use of analgesics (107555). A smaller clinical trial using the same product at the same dose and duration has also been conducted in children aged 1-6 years in daycare. The severity of nasal congestion/runny nose was modestly reduced when compared with placebo in this population. However, there were no differences between groups in the overall incidence, severity, or duration of common colds or upper respiratory tract infections or the number of days absent from daycare (107556). This latter trial was terminated prior to the completion of the planned patient recruitment for reasons unrelated to adverse effects, which may have impacted the findings.
• Hypercholesterolemia. Oral Lactiplantibacillus plantarum seems to be modestly beneficial for lowering cholesterol levels. Details: Meta-analyses of a small number of clinical trials shows that taking L. plantarum can reduce total cholesterol and low-density lipoprotein (LDL) cholesterol in patients with or without hypercholesterolemia. In one publication these reductions were by about 14 mg/dL and 11 mg/dL, respectively (95399,107591). One of the studies included in the analyses utilized a mixture of three strains of L. plantarum (CECT 7527, 7528, and 7529, AB-LIFEe), containing a total daily dose of 1.2 billion colony-forming units (CFUs) daily for 12 weeks (90255). However, a more recent study shows that taking L. plantarum ECGC 13110402 as 2 billion CFUs twice daily for 12 weeks does not affect total or LDL cholesterol levels when compared with placebo (107559). Taking L. plantarum does not appear to improve high-density lipoprotein (HDL) cholesterol or triglyceride levels in most studies (90255,95399). However, one study shows that taking L. plantarum ECGC 13110402 as 2 billion CFUs twice daily for 12 weeks modestly increases levels of HDL cholesterol, with no effect on triglyceride levels, when compared with placebo (107559).
• Irritable bowel syndrome (IBS). Some research shows that Lactiplantibacillus plantarum, alone or as part of specific combination products, may be beneficial for IBS. Details: Most meta-analyses and clinical studies in patients with IBS show that taking L. plantarum 299v improves at least one or more measures of symptom relief, including the frequency of global response or symptom relief, straining, abdominal pain and/or flatulence when compared with placebo (10419,16746,90249,107594,110866). Another small and preliminary clinical trial in patients with diarrhea-predominant IBS shows that taking L. plantarum APsulloc 331261 (GTB1) daily for 4 weeks results in adequate global relief of symptoms in 94.4% of patients compared with 62.5% of patients taking placebo. The frequency of diarrhea, and both severity and frequency of abdominal pain and bloating were also improved (111978). However, contrasting findings exist. One clinical trial shows that taking L. plantarum 299v 50 billion colony-forming units (CFUs) daily for 4 weeks does not relieve abdominal pain, bloating, or rectal emptying when compared with taking placebo (111969). Two small clinical trials also found no benefit of using L. plantarum 299v for 4 or 8 weeks (12770,111976). However, these latter studies may have been underpowered to detect differences. L. plantarum 299v has been taken as a beverage (ProViva) containing 50 million colony-forming units (CFUs) or as capsules containing 10 billion CFUs daily for 4 weeks (10419,16746,90249). L. plantarum APsulloc 331261 (GTB1) has been taken in doses of 10 billion CFUs daily for 4 weeks (111978). Some clinical research has also shown that specific combination probiotics may be beneficial. One clinical study shows that taking a specific multi-species probiotic (Visbiome, ExeGi Pharma) containing L. plantarum and seven other probiotics as 450 billion CFUs daily in two divided doses for 8 weeks improves abdominal bloating, but not abdominal pain, flatulence, or number of stools, in patients with diarrhea-predominant IBS (IBS-D) (11379). Another clinical study in patients with IBS-D shows that taking a specific multi-species probiotic (NordBiotic, MBM Biotix) containing L. plantarum LP140, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, Lactobacillus acidophilus LA120, Lacticaseibacillus casei LC130, Bifidobacterium breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium animalis subsp. lactis BL040, and Streptococcus thermophilus ST250 2.5 billion CFUs daily twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life, when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516).
• Respiratory tract infections. Oral Lactiplantibacillus plantarum seems to prevent respiratory tract infections. Details: Clinical research in healthy adults shows that taking L. plantarum DR7 (GN Pharmaceuticals Sdn. Bhd.) 1 billion CFUs daily for 12 weeks reduces the duration of nasal symptoms by about 5 days when compared with placebo. There was also a modest decrease in the frequency of upper respiratory tract infections (URTIs) (102290). Also, in overweight adults or adults with obesity, taking 50 billion CFUs of a specific combination of L. plantarum, Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium animalis subsp. lactis (Lab4P) for 24 weeks reduces the overall likelihood of having URTI symptoms, such as sneeze, cough, and blocked nose, by approximately 40% when compared with placebo (103439).
• Ulcerative colitis. Oral Lactiplantibacillus plantarum, alone or in combination with other probiotics, seems to improve remission rates and prevent symptom relapse when used in combination with standard therapy. Details: The best evidence of benefit is for a specific multi-species probiotic (Visbiome, ExeGi Pharma). Doses of 3 grams (equivalent to 900 billion colony-forming units (CFUs)) once or twice daily have been used in combination with conventional treatment. In children aged 1-16 years, doses of 450-1800 billion CFUs for up to one year have been used (3261,14370,14371,16841,95337). A meta-analysis of clinical research shows that taking this product as an adjunct to standard ulcerative colitis treatment can increase remission rates in adults and children by about 1.7-fold when compared with standard treatment alone (95337). Most research also shows that taking this product prevents relapse in people who are already in remission (3261,16841,95337). Other preliminary clinical research shows that taking 250 mL of a different product containing L. plantarum 299v (Profermin) 100 million CFUs/mL twice daily for 8 weeks reduces the severity of flare-up symptoms and increases the rate of remission by about 2-fold when compared with treatment with a specific nutritional beverage (Fresubin Original, Fresenius Kabi) (90271).

POSSIBLY INEFFECTIVE

• Antibiotic-associated diarrhea. Taking Lactiplantibacillus plantarum alone does not seem to reduce the risk of antibiotic-associated diarrhea (AAD) in adults and children. However, it might reduce the risk of loose stools. It is unclear if L. plantarum is beneficial for AAD when taken in combination with other probiotics. Details: Clinical research in children aged 1-11 years shows that taking L. plantarum 299v (ProViva) 10 billion colony-forming units (CFUs) daily during antibiotic treatment and for an additional week does not reduce general abdominal symptoms, the overall incidence of loose or watery stools, or the incidence of AAD (defined as at least three loose or watery stools within a 24 hour period) when compared with placebo (95395). Also, a small clinical trial in adults shows that taking L. plantarum 10 billion CFUs daily does not reduce the incidence of AAD when compared with placebo. However, there was a modest reduction in the incidence of having at least one loose or watery stool during the antibiotic treatment period. Although the risk of nausea was reduced, there was no effect of L. plantarum on vomiting or abdominal pain. In this study, L. plantarum was provided in a drink (200 mL) containing blueberries and oat gruel which was started within 48 hours of the initiation of antibiotics and continued for a week after completion (107552). Combination products have also been investigated with mixed results. A meta-analysis of 3 clinical trials in hospitalized or outpatient adults shows that taking L. plantarum alone or in combination with up to 8 other probiotic strains does not reduce the risk of AAD when compared with taking placebo (107635). Clinical research in adults shows that taking a total of 5 billion CFUs twice daily for 14 days of a specific product (Ecologic AAD) providing L. plantarum NIZO 3684, Bifidobacterium bifidum NIZO 3804, Bifidobacterium animalis subsp. lactis NIZO 3680, Enterococcus faecium NIZO 3886, Lactobacillus acidophilus NIZO 3678 and NIZO 3887, Lacticaseibacillus paracasei NIZO 3672, Lacticaseibacillus rhamnosus NIZO 3689, and Ligilactobacillus salivarius NIZO 3675 modestly reduces the risk of having at least three bowel movements daily and/or having stools with a loose consistency for at least two days during antibiotic treatment (95405). An additional large clinical trial in children aged 3 months and up shows that taking a total of 10 billion CFUs of this same product does not reduce the risk of antibiotic-associated diarrhea when compared with taking placebo, when the more stringent definition is considered excluding diarrhea of other etiologies. However, the risk of diarrhea of any etiology is reduced by 35%. The probiotic supplement was taken from the first day of antibiotic treatment until 7 days after treatment ended (110969). In a small clinical trial in children aged 5 months to 16 years, taking a combination of L. plantarum PL02, Bifidobacterium longum PL03, and Lacticaseibacillus rhamnosus KL53A twice daily during antibiotic treatment does not reduce the rate of AAD when compared with placebo. However, there was a modest reduction in the number of stools each day (107553). The total number of cases of AAD was extremely low in this study, making it difficult to draw conclusions. It is unclear whether any benefit in these trials was related to L. plantarum, another probiotic, or their combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if oral Lactiplantibacillus plantarum is beneficial for acne. Details: A small clinical trial shows that taking L. plantarum CJLP55 (KCTC 11401BP) 10 billion colony-forming units daily for 12 weeks modestly reduces the total and inflammatory lesion count, as well as acne severity, when compared with placebo. There were also modest improvements in skin sebum levels and hydration (107511).
• Aging skin. It is unclear if oral Lactiplantibacillus plantarum is beneficial for aging skin. Details: A small clinical study in healthy, middle-aged and older adults shows that taking L. plantarum HY7714 10 billion colony-forming units daily improves skin hydration and reduces wrinkle depth when compared with placebo (102294).
• Athletic performance. It is unclear if oral Lactiplantibacillus plantarum is beneficial for athletic performance. Details: Small clinical trials in healthy young adults without professional athletic training show that taking L. plantarum is beneficial for athletic performance. Taking L. plantarum TWK10 30-100 billion colony-forming units (CFUs) daily for 6 weeks modestly increases time to exhaustion when compared with taking placebo (111963,111984). In one study, this benefit was found to be dose-dependent (111963). There was also a modest increase in muscle mass (111963) but no differences in ratings of perceived exertion (111984). However, some conflicting evidence exists. In one small clinical trial, taking L. plantarum PS128 60 billion CFUs twice daily for 4 weeks before running a half-marathon does not affect the time to run the half-marathon when compared with taking placebo (111970). Also, in female athletes with low iron stores but without iron-deficiency anemia, a small clinical trial shows that taking L. plantarum 299v 10 billion CFUs with iron 20 mg daily for 12 weeks does not improve physical performance, based on parameters such as work efficiency, time to exhaustion, or perceived exertion, when compared with taking iron alone (111987). These studies may have been underpowered to detect differences between groups. L. plantarum has also been investigated for beneficial effects on recovery of exercise capacity following an endurance event. In one clinical trial, taking L. plantarum PS128 60 billion CFUs twice daily for 4 weeks before running a half-marathon results in a modest increase in lower extremity muscle strength 72 hours after the event when compared with taking placebo. However, there was no difference in anaerobic power or aerobic capacity (111970). This study may have been underpowered to detect differences between groups.
• Autism spectrum disorder. It is unclear if oral Lactiplantibacillus plantarum is beneficial for autism spectrum disorder. Details: A small clinical trial in males aged 7-15 years with autism spectrum disorder shows that taking L. plantarum PS128 daily for 4 weeks does not improve behavior or social response when compared with placebo. However, the probiotic modestly reduced specific behaviors, including opposition and defiance, in a subgroup of children aged 7-12 years (107540).
• Bacterial vaginosis. Oral or vaginal Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A combination product containing L. plantarum has been tried in patients with both bacterial vaginosis and aerobic vaginitis, which typically occurs after unsuccessful treatment of bacterial vaginosis with antibiotics. A clinical study in these patients shows that taking a specific combination product (prOVag, IBSS BIOMED S.A.) containing a total of 100 million colony-forming units (CFUs) of L. plantarum 57B, Limosilactobacillus fermentum 57A, and Lactobacillus gasseri 57C daily for 10 days in conjunction with standard metronidazole treatment increases the duration of symptom-free remission to 71 days, compared with 47 days in those taking metronidazole alone (99784). Also, a preliminary clinical trial shows that vaginal application with a tablet providing at least one billion CFUs of a combination of L. plantarum, Levilactobacillus brevis, and Ligilactobacillus salivarius (Florisia) might be beneficial for the treatment of bacterial vaginosis. Using this combination for 8 days reduces the proportion of patients with bacterial vaginosis by about 79% when compared with baseline. Taking this product does not seem to be more beneficial than using a pH lowering vaginal product (110951).
• Cancer. Although there has been interest in using oral Lactiplantibacillus plantarum for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Celiac disease. Although there has been interest in using oral Lactiplantibacillus plantarum for celiac disease, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Clostridioides difficile infection. It is unclear if oral Lactiplantibacillus plantarum is beneficial for C. difficile prevention. Details: A small clinical trial in hospitalized patients shows that taking L. plantarum 299v as part of a fermented oatmeal gruel, as 80 billion colony-forming units (CFUs) twice daily for three days and 40 billion CFUs twice daily until ICU departure, reduces the likelihood of C. difficile colonization. C. difficile was detected in the feces of 19% of patients taking placebo, compared with 0% of the patients taking L. plantarum (107554). Some research shows that taking L. plantarum 299v might be effective for preventing C. difficile diarrhea recurrence (11378). Current guidelines from the Infectious Diseases Society of America (IDSA) state that there is insufficient information to recommend administration of probiotics for the primary prevention of C. difficile-associated diarrhea (107538).
• Cognitive function. It is unclear if oral Lactiplantibacillus plantarum is beneficial for improving cognitive function. Details: The effect of L. plantarum has been investigated on cognitive function in adults with mild to moderate stress. Clinical research in this population shows that taking L. plantarum DR7 1 billion colony-forming units (CFUs) or L. plantarum P8 20 billion CFUs daily for 12 weeks modestly improves some measures of cognitive function, including memory, social emotional cognition, and verbal learning and memory when compared with taking placebo. However, there were no improvements in most measures and the clinical significance is unclear. Also, sub-analyses suggest that individual benefits may be limited to specific age groups or genders (111964,111967). L. plantarum has also been investigated in combination with other ingredients. A small clinical trial in healthy adults shows that taking a product containing a combination of L. plantarum R1012 800 million CFUs, Bifidobacterium longum R0175 70 million CFUs, and Lactobacillus helveticus R0052 2 billion CFUs (Puraflor, GSK Consumer Healthcare, Milano, Italy) daily for 4 weeks does not affect cognitive performance during acute stress when compared with placebo. The probiotics were provided in combination with inulin 500 mg, potassium 50 mg, magnesium 45 mg, glutathione 20 mg, lactoferrin 10 mg, and zinc 9 mg (110923). The effects of L. plantarum alone are not clear from this study. Also, a larger clinical trial is needed to confirm these results.
• Cognitive impairment. It is unclear if oral Lactiplantibacillus plantarum is beneficial for improving cognitive impairment. Details: Clinical research in older adults with mild cognitive impairment shows that taking heat-killed L. plantarum OLL2712 5 billion cells daily for 12 weeks modestly improves visual memory, but not verbal or composite memory, in most individuals when compared with taking placebo. Some preliminary evidence suggests that dietary intake of cholesterol or fat-soluble vitamins may impact the efficacy of heat-killed L. plantarum (111980). More research is needed to determine the relationship between normal dietary patterns and the clinical effects of heat-killed L. plantarum. Also, the effect of live L. plantarum is unclear.
• Colic. Although there has been interest in using oral Lactiplantibacillus plantarum for colic, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Constipation. Oral Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some combinations products containing L. plantarum have been shown to increase stool frequency and improve symptoms of functional constipation in adults. These include L. plantarum LMG P-21021 and Bifidobacterium breve DSM 16604 5 billion CFUs daily for 30 days (95342) and a combination of L. plantarum IDCC 3501, Lacticaseibacillus casei IDCC 3451, Lacticaseibacillus rhamnosus IDCC 3201, Bifidobacterium lactis IDCC 4301, Bifidobacterium breve IDCC 4401, Lactococcus lactis IDCC 2301, xylooligosaccharide, and dietary fiber as nondigestible maltodextrin, oat fiber, and psyllium husk fiber (ID-HWS1000) (107517).
• Coronavirus disease 2019 (COVID-19). Oral Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In symptomatic COVID-19 outpatients, clinical research shows that taking a total of 2 billion colony-forming units (CFUs) of a specific combination of L. plantarum KABP022, KABP023, and KAPB033 and Pediococcus acidilactici KABP021 (AB21) daily for 30 days increases the rate of complete remission after 30 days by approximately 89% when compared with placebo. There was also a modest reduction in days with specific symptoms, including fever, cough, headache, and some gastrointestinal symptoms (107526).
• Critical illness (trauma). It is unclear if oral Lactiplantibacillus plantarum is beneficial for critical illness. Details: Clinical research in patients in intensive care shows that taking L. plantarum 299v 20 billion colony-forming units (CFUs) daily for 60 days does not affect the number of days alive, the rate of nosocomial infections, or the number of patients discharged by day 60 when compared with placebo (105136). However, a meta-analysis of four clinical trials in critically ill patients on antibiotics shows that taking L. plantarum alone or with other probiotics reduces the risk of infections by 30% when compared with not taking L. plantarum (105143). Also, other clinical research shows that taking L. plantarum 500 million CFUs, Lactobacillus acidophilus LA-5 1.75 billion CFUs, Bifidobacterium lactis BB12 1.75 billion CFUs, and Saccharomyces boulardii 1.5 billion CFUs twice daily for 15 days modestly reduces the risk of sepsis, as well as the length of stay in the ICU and hospital, when compared with placebo (107524).
• Depression. Oral Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with mild to moderate depression shows that taking L. plantarum HEAL9 1 billion colony-forming units with S-adenosylmethionine (SAMe) 200 mg daily for 6 weeks modestly reduces self-reported symptoms of depression when compared with taking placebo (111966). It is unclear if any beneficial effects were due to L. plantarum, SAMe, or their combination.
• Diabetes. Oral Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with gestational diabetes shows that taking a specific product containing L. plantarum and seven other probiotics (Visbiome, ExeGi Pharma) as a total of 112.5 billion colony-forming units (CFUs) twice daily for 8 weeks does not affect levels of fasting blood glucose or glycated hemoglobin (HbA1c) when compared with placebo. However, there were small improvements in insulin levels and insulin resistance (107549). In children aged 2-12 years with new-onset type 1 diabetes, taking this same combination product as 112.5 billion CFUs daily for 3 months modestly decreases HbA1c and insulin requirements when compared with placebo. Also, about three times as many children achieved remission, defined as insulin requirements of less than 0.5 U/kg daily and HbA1c less than 7%. C-peptide levels and the maintenance of residual pancreatic beta-cell function were not changed when compared with placebo in either study (107497).
• Diarrhea. It is unclear if oral Lactiplantibacillus plantarum is beneficial for acute or chronic diarrhea. Details: A small clinical trial in patients with unspecified chronic diarrhea shows that taking L. plantarum CCFM1143 3.52 billion colony-forming units (CFUs) daily for 30 days modestly reduces stool frequency when compared with baseline. However, it is unclear if it is more beneficial than placebo. There was no effect on abdominal symptoms or quality of life (107500). Another small clinical trial in patients with functional diarrhea shows that taking L. plantarum CJLP243 10 billion CFUs daily for 2 months results in adequate relief, defined as at least a 30% reduction in frequency of diarrhea, in 90% of patients when compared with 42% of patients taking placebo (111977). While the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388), both guidelines note that most evidence is low quality, and this recommendation is not specific to L. plantarum.
• Helicobacter pylori. Oral Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with H. pylori infection shows that taking 1 billion colony-forming units each of L. plantarum and Pediococcus acidilactici along with a 10-day triple or nonbismuth quadruple concomitant eradication regimen does not improve eradication rates or reduce side effects associated with the eradication therapy when compared with taking placebo (111983). The effect of L. plantarum alone is unclear from this study.
• Hepatic encephalopathy. Although there has been interest in using oral Lactiplantibacillus plantarum for hepatic encephalopathy, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• HIV/AIDS. Although there has been interest in using oral Lactiplantibacillus plantarum for HIV/AIDS, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Hypertension. It is unclear if oral Lactiplantibacillus plantarum is beneficial for hypertension. Details: A meta-analysis of clinical research shows that taking L. plantarum reduces systolic and diastolic blood pressure by 1.6 mmHg and 1 mmHg, respectively, when compared with placebo in various populations. Studies in the analyses included L. plantarum alone or with other probiotics, in doses ranging from 1 billion colony-forming units (CFUs) daily to 1.5 trillion CFUs daily for 2-12 weeks (107558). However, the effects of L. plantarum in patients with diagnosed hypertension are unclear.
• Hypertriglyceridemia. It is unclear if oral Lactiplantibacillus plantarum is beneficial for hypertriglyceridemia. Details: A clinical trial in patients with hypertriglyceridemia shows that taking 2 grams of a powdered supplement containing L. plantarum KY1032 and Latilactobacillus curvatus HY7601 50 billion colony-forming units daily for 12 weeks reduces triglycerides by 18%, compared with a 0% reduction in patients taking placebo (102289).
• Impaired glucose tolerance (prediabetes). It is unclear if oral live or heat-killed Lactiplantibacillus plantarum is beneficial for prediabetes. Details: Clinical research in patients with prediabetes shows that taking yogurt containing heat-killed L. plantarum OLL2712 at least 5 billion cells daily for 12 weeks modestly reduces levels of glycated hemoglobin (HbA1c) when compared with taking yogurt without L. plantarum. However, the clinical significance is unclear. There was no effect on fasting blood glucose or insulin levels (111988). A small clinical trial shows that taking live L. plantarum HAC01 as 4 billon colony-forming units (CFUs) daily for 8 weeks modestly reduces HbA1c when compared with placebo. There was also a difference in 2-hour postprandial glucose levels; however, this difference seems to be related to an increased level in the placebo group. Also, there was no effect on fasting blood glucose or insulin levels, measures of insulin resistance, or plasma lipid levels (107512). The clinical significance of the change in HbA1c in this study is unclear since the supplementation period was only 8 weeks.
• Insomnia. It is unclear if oral Lactiplantibacillus plantarum is beneficial for insomnia. Details: A small clinical trial in patients with self-reported insomnia shows that taking L. plantarum PS128 (Bened Biomedical Co. Ltd.) 60 billion colony-forming units (CFUs) each evening for 30 days does not improve overall sleep quality or insomnia severity when compared with placebo. However, there were some improvements in feelings of depression and fatigue, as well as a reduction in awakening during deep sleep, when compared with placebo (107508).
• Iron deficiency anemia. It is unclear if oral Lactiplantibacillus plantarum is beneficial for improving iron status when taken in combination with iron supplements. Details: In female athletes with low iron stores or iron deficiency, but without iron-deficiency anemia, a small clinical trial shows that taking L. plantarum 299v 10 billion CFUs with iron 20 mg daily for 12 weeks does not reduce the prevalence of iron deficiency or improve iron storage or hemoglobin levels when compared with taking iron alone (111987). The effect of L. plantarum on iron deficiency anemia is unclear.
• Lactose intolerance. Although there has been interest in using oral Lactiplantibacillus plantarum for lactose intolerance, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Lyme disease. Although there has been interest in using oral Lactiplantibacillus plantarum for Lyme disease, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Malnutrition. Although there has been interest in using oral Lactiplantibacillus plantarum for children with malnutrition, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Metabolic syndrome. Oral Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in elderly patients with metabolic syndrome shows that taking a combination of L. plantarum PBS067-DSM 24,937, Lactobacillus acidophilus PBS066-DSM 24,936, and Limisilactobacillus reuteri PBS072-DSM 25,175 as 2 billion colony-forming units (CFUs) each, along with the prebiotics inulin and fructo-oligosaccharides, daily for 60 days reduces the number of patients diagnosed with metabolic syndrome by 23%, compared with a 10% reduction in those taking placebo. In the probiotic group, there were modest improvements in waist circumference and levels of fasting plasma insulin, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and inflammatory mediators when compared with placebo. However, there were no significant differences in fasting blood glucose or blood pressure. All patients in this study were on a Mediterranean-like standard diet (107560).
• Necrotizing enterocolitis (NEC). It is unclear if oral Lactiplantibacillus plantarum is beneficial or safe for NEC prevention. Details: Most meta-analyses of clinical research show that giving lactobacilli enterally reduces the risk of NEC and/or severe NEC in preterm, mainly very low birth weight (VLBW), infants. Some meta-analyses support the use of lactobacilli in combination with bifidobacteria, as opposed to lactobacilli alone for reducing the risk of NEC. However, the effects of L. plantarum, specifically, are unclear (95344,95351,103437,103445,104157,105162,105164). Also, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, L. plantarum is not specifically recommended (103003,111609,111611).
• Nonalcoholic fatty liver disease (NAFLD). Oral Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with NAFLD shows that taking two sachets daily for 3 months of a specific combination product (VSL#3) containing L. plantarum and other probiotics modestly decreases triglyceride levels and liver enzymes when compared with taking placebo. However, there was no change in body mass index or most glycemic or lipid parameters (111009).
• Obesity. It is unclear if oral live or heat-killed Lactiplantibacillus plantarum are beneficial for weight loss. Details: The effect of L. plantarum has been investigated in adults with overweight or obesity. Some clinical research shows that taking L. plantarum K50 2 billion colony-forming units (CFUs) twice daily for 12 weeks does not affect body weight, body mass index (MI), fat mass, or abdominal fat area when compared with taking placebo. However, triglyceride and total cholesterol levels were modestly decreased (111973). Other research shows beneficial effects on weight loss. One clinical trial shows that taking L. plantarum LMT1-48 20 billion CFUs daily for 12 weeks decreases body weight by 0.9 kg, and modestly reduces BMI and waist circumference, when compared with taking placebo. There were also modest beneficial effects on insulin resistance and insulin levels, but not plasma lipids (111979). Additional clinical research shows that taking L. plantarum Dad-13 2 billion CFUs in skimmed milk powder daily for 90 days reduces body weight by about 1.4 kg when compared to baseline. However, it is unclear if it is more beneficial than placebo. Also, there was no effect on lipid profile (111965). The slight discrepancies between these studies may be related to the different strains and doses used. L. plantarum has also been investigated in combination with other probiotics in adults with overweight or obesity. Clinical research shows that taking 50 billion CFUs of a specific combination of L. plantarum, Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium animalis subsp. lactis (Lab4P) for 24 weeks reduces body weight by an additional 1.3 kg more than placebo (103439). Other clinical research shows that taking 5 billion CFUs each of L. plantarum KY1032 and Latilactobacillus curvatus HY7601 daily for 12 weeks modestly reduces body weight, BMI, and visceral fat mass and circumference when compared with taking placebo. Body weight was reduced by 0.47 kg compared with an increase in 0.93 kg in adults taking placebo. There were no differences between groups in blood insulin or lipid levels (111972). Heat-killed L. plantarum has also been investigated. Clinical research in overweight adults shows that taking heat-killed L. plantarum L-137 (HK L-137) for 12 weeks does not reduce BMI when compared with placebo. However, levels of aspartate aminotransferase and alanine aminotransferase were reduced. Taking heat-killed L. plantarum also seems to suppress the increase in total and low-density lipoprotein (LDL) cholesterol levels seen in those taking placebo (107534). Other clinical research in overweight adults shows that taking yogurt containing heat-killed L. plantarum OLL2712 5 billion cells daily for 12 weeks prevents increases in total abdominal fat and fasting plasma glucose when compared with taking control yogurt. Body weight, BMI, and blood lipids were not different between groups (111995).
• Osteoporosis. Although there has been interest in using oral Lactiplantibacillus plantarum for osteoporosis, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Parkinson disease. It is unclear if oral Lactiplantibacillus plantarum is beneficial for Parkinson disease. Details: A small preliminary clinical trial in patients with Parkinson disease on standard treatment shows that taking L. plantarum PS128 60 billion colony-forming units each night for 12 weeks modestly improves motor function when compared with baseline. There was no improvement in non-motor symptoms including tremor and rigidity (107515).
• Periodontitis. Oral and topical Lactiplantibacillus plantarum have only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients undergoing scaling and root planing shows that a single topical application with a gel containing a combination of L. plantarum (CECT7481) and Levilactobacillus brevis (CECT7480) into the periodontal pocket, followed by taking one lozenge containing these probiotics daily for 3 months, does not reduce the number of diseased sites when compared with placebo. Although there was a two-fold increased odds of healing of gingival bleeding in patients using the probiotic product, the odds of having persisting diseased sites was modestly increased. The gel provided 6 billion colony-forming units (CFUs) each of L. plantarum and L. brevis. One lozenge provided 1.2 billion CFUs of each (110961).
• Polycystic ovary syndrome (PCOS). Oral Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that 31.3% of patients with PCOS taking L. plantarum in combination with other probiotics daily for 6 months had regular menstrual cycles compared with 12.5% of those taking placebo. There were also modest improvements in testosterone levels and waist circumference, but not other hormones, insulin resistance, body weight, or most measures of quality of life. The product provided L. plantarum UBLP-40 1 billion colony-forming units along with Lactobacillus acidophilus UBLA-34, Lacticaseibacillus casei UBLC-42, Limosilactobacillus fermentum UBLF-31, Lacticaseibacillus rhamnosus UBLR-58, Limosilactobacillus reuteri UBLRu-87, Bifidobacterium bifidum UBBB-55, and fructo-oligosaccharides (FOS) daily for 2 months and then twice daily for 4 months. All patients also underwent dietary and lifestyle changes (110974).
• Postoperative infection. Although there has been interest in using oral Lactiplantibacillus plantarum for preventing postoperative infection, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Pouchitis. Oral Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Continuous oral treatment for one year with a specific combination product (Visbiome, ExeGi Pharma) containing L. plantarum and other probiotics, as 6 grams (300-500 billion live bacteria per gram) daily for up to one year, seems to maintain remission of pouchitis in 85% of patients (6087,12769). Another small clinical trial in patients with poor pouch function related to pouchitis or functional disorders shows that taking 5 billion colony-forming units each of L. plantarum 299 and Bifidobacterium infantis Cure 21 twice daily for 3 weeks does not improve pouch function or disease activity when compared with taking placebo (111993). However, this study may have been underpowered to detect differences. The effect of L. plantarum alone is unclear from these studies.
• Pregnancy-induced nausea and vomiting. Oral Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units (CFUs) of L. plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Lacticaseibacillus paracasei DSM 13434 and Lpc-37, Ligilactobacillus salivarius Ls-33, Levilactobacillus brevis Lbr-35, Lactobacillus acidophilus La-14, Lacticaseibacillus casei Lc-11, and Bifidobacterium lactis Bl-04, along with inulin 200 mg (107199).
• Radiation-induced diarrhea. Although there has been interest in using oral Lactiplantibacillus plantarum for preventing radiation-induced diarrhea, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Rheumatoid arthritis (RA). Although there has been interest in using oral Lactiplantibacillus plantarum for RA, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Rotaviral diarrhea. It is unclear if oral Lactiplantibacillus plantarum is beneficial for rotaviral diarrhea. Details: The current guidelines related to the treatment of viral diarrhea are conflicting. While the World Gastroenterology Organization has not made a recommendation (98471), the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388). However, these guidelines note that most evidence is low quality and is not specific to rotavirus infection. Furthermore, these guidelines were released prior to the publication of the most recent, high-quality studies showing no benefit with the use of specific probiotics (98427,98428). Research specifically on the use of L. plantarum is limited. One small preliminary clinical trial in children hospitalized for rotaviral enteritis shows that taking L. plantarum (LRCC5310) modestly reduces the number of children with diarrhea and the number of defecation events on day 3 when compared with not receiving any probiotics. The total period and severity of diarrhea were also reduced. However, the numbers were small, and it is unclear if any benefits were clinically significant. There were no differences between groups in the length of hospital stay or the proportion of patients with persistent vomiting. (111981).
• Short bowel syndrome. Although there has been interest in using oral Lactiplantibacillus plantarum for short bowel syndrome, there is insufficient reliable information about the clinical effects of L. plantarum for this condition.
• Stress. It is unclear if oral live or heat-killed Lactiplantibacillus plantarum is beneficial for stress. Details: Clinical research in adults with stress shows that taking L. plantarum DR7 1 billion colony-forming units (CFUs) daily or L. plantarum P8 20 billion CFUs daily for 12 weeks does not reduce most measures of stress, anxiety, or depression, when compared with taking placebo. However, one trial suggests that there may be some benefit on anxiety in adults under age 30 (111964,111967). Heat-killed L. plantarum has also been investigated. A small clinical trial in patients undergoing temporary stress shows that taking L. plantarum SNK12 100 or 300 billion cells daily for 4 weeks modestly improves total mood when compared with taking placebo (111985).
• Tourette syndrome. It is unclear if oral Lactiplantibacillus plantarum is beneficial for Tourette syndrome. Details: A small clinical trial in children aged 5-18 years with Tourette syndrome shows that taking L. plantarum PS128 DSM 28632 (Bened Biomedical Co., Ltd.) 30 billion colony-forming units (CFUs) twice daily for two months does not reduce the severity of tics or other symptoms of Tourette syndrome when compared with placebo (107501). This study may have been underpowered to detect a difference between groups for many endpoints.
• Urinary tract infections (UTIs). It is unclear if intravaginal Lactiplantibacillus plantarum is beneficial for the prevention of UTIs. Details: One large, non-randomized, clinical study in otherwise healthy patients with recurrent bacterial vaginosis shows that intravaginal use of L. plantarum P 17630 daily for 6 days, then weekly for 16 weeks, does not reduce the risk of recurrent UTI when compared with control (98435).
• Vaginal candidiasis. It is unclear if oral or vaginal Lactiplantibacillus plantarum is beneficial for vaginal candidiasis. Details: Clinical research in females with a history of recurrent vulvovaginal candidiasis shows that taking L. plantarum P17630 modestly improves redness and swelling when compared with taking placebo. The dose of L. plantarum was 5 billion colony-forming units daily for 3 treatment cycles of 15 days, each cycle separated by 15 days (111986). The findings of this study are limited by the slight differences in redness between the groups at baseline. A retrospective study found that intravaginal application with L. plantarum P17630 following clotrimazole treatment is associated with maintenance of symptom resolution in 90% of patients after 3 months, when compared with 68% of those using a control lubricant. All patients applied a 2% clotrimazole vaginal cream each night for 3 days. L. plantarum 100 million CFUs or the control lubricant were then applied once daily for 6 days and then once a week for 4 weeks (111991). Vaginal lactobacilli colonization increased in both studies (111986,111991).
• Ventilator-associated pneumonia (VAP). Oral Lactiplantibacillus plantarum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking L. plantarum 500 million colony-forming units (CFUs), Lactobacillus acidophilus LA-5 1.75 billion CFUs, Bifidobacterium lactis BB12 1.75 billion CFUs, and Saccharomyces boulardii 1.5 billion CFUs twice daily for 15 days reduces the rate of VAP to 12%, compared with 28% in patients taking placebo. Half of the dose was given onto the oropharynx and half via a nasogastric tube (107524). More evidence is needed to rate Lactiplantibacillus plantarum for these uses.

(Read more about LACTIPLANTIBACILLUS PLANTARUM)

POSSIBLY EFFECTIVE

• Antibiotic-associated diarrhea. Most research shows that oral Lactobacillus acidophilus, alone or in combination with other probiotics, seems to reduce the risk of antibiotic-associated diarrhea (AAD) in adults. Details: A meta-analysis of 18 clinical trials in hospitalized or outpatient adults shows that taking L. acidophilus alone or in combination with up to 8 other probiotic strains reduces the risk of AAD by 34% when compared with taking placebo (107635). One small clinical trial in elderly adults shows that AAD occurred in 17% of those taking L. acidophilus (Florajen Acidophilus) 20 billion colony-forming units (CFUs) three times daily, compared with 37% of those taking placebo (95400). A number of combination products have also demonstrated benefit for preventing AAD, including Bio-K+ Cl1285 which provides L. acidophilus CL1285, Lacticaseibacillus casei LBC80R, and Lacticaseibacillus rhamnosus CLR2 as 100 billion CFUs daily (25494,95402,95403); L. acidophilus and Bifidobacterium animalis subsp. lactis (90239); and Ecologic AAD which provides L. acidophilus NIZO 3678 and NIZO 3887, Lacticaseibacillus paracasei NIZO 3672, Lactiplantibacillus plantarum NIZO 3684, L. rhamnosus NIZO 3689, Ligilactobacillus salivarius NIZO 3675, Bifidobacterium bifidum NIZO 3804, Bifidobacterium animalis subsp. lactis NIZO 3680, and Enterococcus faecium NIZO 3886 (95405). However, some combination products have not demonstrated benefit. Clinical research shows that taking a combination of L. acidophilus and bifidobacteria or a combination of L. acidophilus and Lactobacillus delbrueckii subsp. bulgaricus (Lactinex) is not beneficial (90231,90239,92255,95385). An additional large clinical trial in children aged 3 months and up shows that taking L. acidophilus in combination with other probiotics does not reduce the risk of antibiotic-associated diarrhea when compared with taking placebo, when the more stringent definition is considered excluding diarrhea of other etiologies. However, the risk of diarrhea of any etiology is reduced by 35%. The probiotic supplement provided a total of 10 billion CFUs of L. acidophilus W37, Bifidobacterium bifidum W23, Bifidobacterium animalis subsp. lactis W51, Lactobacillus acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, Lacticaseibacillus rhamnosus W71, and Ligilactobacillus salivarius W24 daily from the first day of antibiotic treatment until 7 days after treatment ended (110969).
• Bacterial vaginosis. Most clinical research shows that intravaginal application of Lactobacillus acidophilus may be helpful for the treatment of bacterial vaginosis. It is unclear if oral L. acidophilus is beneficial for the treatment or prevention of bacterial vaginosis. Details: One clinical trial shows that intravaginal suppositories containing 100 million to 1 billion colony-forming units (CFUs) of L. acidophilus (Vivag, Pharma Vinci A/S) given twice daily for 6 days improve bacterial vaginosis resolution rates when compared with placebo (13177). Another clinical trial shows that using 1-2 vaginal tablets containing viable L. acidophilus 10 million CFUs and estriol 0.03 mg per tablet (Gynoflor, Medinova) daily for 6 days increases cure rates when compared with placebo (13176). However, using this product in combination with metronidazole 400 mg twice daily for 7 days does not improve outcomes when compared with metronidazole alone (90237). Preliminary clinical research in patients with clinically defined bacterial vaginosis shows that daily intravaginal application with a douche providing L. acidophilus 1 billion CFUs per mL for 6 days might have beneficial effects on the vaginal flora. When compared with 52.5% of patients with bacterial vaginosis based on bacterial flora at baseline, 7.5% met this criteria 14 days after treatment had been completed (111788). Oral L. acidophilus has also been evaluated. Preliminary clinical research shows that eating yogurt 125 mL daily enriched with L. acidophilus for 2 months might slightly decrease the incidence of recurrent bacterial vaginosis (1245). L. acidophilus has also been investigated in an oral formulation in combination with other probiotics. Clinical research in patients with bacterial vaginosis cured within the past 48 hours shows that taking a product containing L. acidophilus in combination with other probiotics results in recurrence of vaginosis in 18.3% of patients, a statistically significant reduction compared with 32.1% of those using placebo. The mean time to recurrence was approximately 23 days longer in patients taking the lactobacilli. The product contained L. acidophilus 1.08 billion CFUs along with Lactobacillus crispatus LMG S-29995 and Levilactobacillus brevis (Lactogyn, Vésale Pharma, Belgium), and was taken twice daily for 7 days and then once daily for up to an additional 120 days (110950).
• Helicobacter pylori. Oral Lactobacillus acidophilus, usually in combination with other probiotics, seems to improve H. pylori eradication when used along with standard therapies. It is unclear if heat-killed L. acidophilus is beneficial for H. pylori eradication. Details: A meta-analysis of clinical studies utilizing probiotic products containing L. acidophilus shows that these products can improve H. pylori eradication rates 1.14- to 1.24-fold when taken in combination with triple therapy consisting of a proton-pump inhibitor (PPI), clarithromycin, and amoxicillin. Based on these results, about 7-11 patients would need to be treated in order for one additional patient to achieve complete remission (95394). Only one of the trials in this analysis investigated L. acidophilus alone; an additional 8 used L. acidophilus in combination with other probiotics. Individual clinical trials have shown that a combination of L. acidophilus, Enterococcus faecalis, and Bacillus subtilis 30 million colony-forming units (CFUs) total, taken in three divided doses daily, from 2 weeks prior tol 2 weeks after triple therapy increases H. pylori eradication when compared with triple therapy alone (90248). In children, a combination of L. acidophilus (strain 5) 94 million CFUs and Bifidobacterium bifidum (strain 12) 8.6 million CFUs in combination with a PPI, clarithromycin, and amoxicillin or metronidazole has been used daily for 2 weeks, followed by the probiotics alone for an additional 4 weeks (90602). However, other individual clinical trials have shown that L. acidophilus in combination with Lacticaseibacillus rhamnosus, Bifidobacterium bifidum, and Streptococcus faecium may not improve eradication rates when taken with triple therapy consisting of furazolidone, tetracycline, and lansoprazole (90279). Also, taking L. acidophilus along with six other probiotics in conjunction with bismuth quadruple therapy does not seem to improve H. pylori eradication rates when compared with placebo and bismuth quadruple therapy (90291). Also, taking L. acidophilus and L. casei without any standard H. pylori therapy does not improve H. pylori eradication rates in adults (12766). Heat-killed L. acidophilus has also been investigated in adults with H. pylori. Taking a lyophilized and inactivated culture of L. acidophilus (Lacteol Fort) containing 5 billion cells, 3 times daily for 10 days, modestly increases the eradication rate in patients using triple therapy of rabeprazole, clarithromycin, and amoxicillin for 7 days (8562).
• Irritable bowel syndrome (IBS). Some research shows that oral live Lactobacillus acidophilus, taken alone or in combination with other probiotics, may be beneficial for IBS. The effects of non-viable, heat-killed L. acidophilus are unclear. Details: Clinical research in adults with IBS shows that taking L. acidophilus DDS-1 10 billion colony-forming units (CFUs) daily for 6 weeks modestly reduces the severity of abdominal pain when compared with placebo. Also, 52% of patients experienced a more than 30% reduction in pain severity, compared with 16% of those taking placebo. There were also improvements in abdominal distention and duration of pain; however, there were no changes in bowel habits (107581). A meta-analysis shows that taking L. acidophilus improves the rate of symptom relief and reduces bloating severity when compared with placebo. However, other symptoms were not improved (110866). L. acidophilus has also been examined in combination with other probiotics. One clinical study shows that taking a specific combination product (Visbiome, ExeGi Pharma) containing L. acidophilus and 7 other species as 450 billion CFUs daily in two divided doses for 8 weeks improves abdominal bloating, but not abdominal pain, flatulence, or number of stools, in patients with diarrhea-predominant IBS (IBS-D) (11379). Another clinical study in patients with IBS-D shows that taking a specific multi-species probiotic (NordBiotic, MBM Biotix) containing L. acidophilus LA120, Lacticaseibacillus rhamnosus LR110, Lacticaseibacillus paracasei LPC100, Lacticaseibacillus casei LC130, Lactiplantibacillus plantarum LP140, Bifidobacterium breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium animalis subsp. lactis BL040, and Streptococcus thermophilus ST250 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as pain severity, pain frequency, and quality of life, when compared with placebo. Symptom severity was rated as mild by approximately 60% of those taking the probiotic mixture, compared with 30% of those taking placebo (107516). A small clinical trial shows that taking L. acidophilus NCFM plus Lactobacillus helveticus Lafti L10 (Lallemand Health Solutions) 5 billion CFUs each daily for 8 weeks modestly reduces flatus and overall symptoms, but not abdominal pain or bloating, when compared with taking placebo (111785). However, other probiotic compounds containing L. acidophilus have not demonstrated benefit in most patients with IBS. These include L. acidophilus NCFM 10 billion CFUs daily for 12 weeks; L. acidophilus, L. paracasei, and Bifidobacterium animalis subsp. lactis BB-12 (Cultura) 13-20 billion CFUs daily for 6 months; or L. acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2 50 billion CFUs each daily for 3 months (90236,94696,94697,95365,99789). Further research is needed to determine which IBS subtype, if any, is most likely to benefit. Heat-killed L. acidophilus has also been investigated in patients with IBS. One clinical study shows that taking capsules containing heat-killed L. acidophilus (Lacteol Fort) 20 billion colony-forming units (CFUs) daily for 6 weeks improves abdominal pain, bloating, and number and quality of stools when compared with placebo (7744). Also, in patients with IBS-D, observational research has found that use of heat-killed L. acidophilus (Lacteol LB) two capsules daily for one month modestly reduces pain and bloating and improves quality of life. The average weekly number of stools decreased by approximately 4.75. Also, the number of patients with watery stools was reduced from 54% at baseline to 19% (107535).

POSSIBLY INEFFECTIVE

• Atopic disease. Oral Lactobacillus acidophilus does not seem to be beneficial for preventing atopic disease in children. Details: A meta-analysis of clinical research shows that administering L. acidophilus during pregnancy, when breastfeeding, or to newborn infants might actually increase the risk of atopic sensitization (90251). However, the number of studies included in this analysis was limited.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A preliminary clinical study shows that taking a specific probiotic product containing L. acidophilus 5 billion colony-forming units (CFUs), Lactobacillus delbrueckii subsp. bulgaricus 5 billion CFUs, and Bifidobacterium bifidum 20 billion CFUs (Trenev Trio/Healthy Trinity, Natren) twice daily along with minocycline once every evening for 12 weeks improves inflamed and non-inflamed acne lesions in 82% of patients, compared to only 67% of patients treated with either the probiotic combination or minocycline alone (90270).
• Acute respiratory distress syndrome (ARDS). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in premature infants shows that taking 6 billion CFUs of a combination of L. acidophilus NCDO 1748 and Bifidobacterium bifidum NCDO 2203 (UFC Inforan, Switzerland) from 7 days of age until 34 weeks postmenstrual age or discharge does not reduce the odds of ARDS when compared with a control group of infants not given these probiotics. The infants in this study were born at less than 32 weeks gestation and had a birthweight of less than 1500 grams (111794). This study is limited by the lack of randomization to treatment group; placement was based on year of birth.
• Allergic rhinitis (hay fever). It is unclear if oral Lactobacillus acidophilus is beneficial for allergic rhinitis prevention or treatment. Details: A small clinical trial in patients with perennial allergic rhinitis shows that taking heat-treated milk fermented with L. acidophilus L-92 100 mL daily for 8 weeks modestly reduces nasal symptoms and mucus, but not ocular symptoms, when compared with taking an acidified placebo milk. The milk provided approximately 30 billion L. acidophilus cells (25488). The effect of L. acidophilus as a probiotic is unclear from this study. Other clinical research shows that drinking 250 mL of fermented milk containing L. acidophilus La-5 5 billion colony-forming units (CFUs), Lacticaseibacillus rhamnosus GG 50 billion CFUs, and Bifidobacterium animalis subsp. lactis BB-12 50 billion CFUs from 36 weeks' gestation until 3 months postpartum does not reduce the incidence of allergic rhinitis in the child at 6 years of age when compared with placebo milk (96893).
• Asthma. It is unclear if oral Lactobacillus acidophilus can improve lung function in people with asthma. Details: A small clinical crossover study in patients with moderate asthma shows that consuming live active yogurt 225 grams, providing L. acidophilus 760 million colony-forming units (CFUs) per gram, twice daily for 1 month does not affect measures of lung function when compared with yogurt not containing L. acidophilus. All yogurt contained Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus (1244).
• Atopic dermatitis (eczema). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of the available clinical research shows that intake of lactobacilli and bifidobacteria-based probiotics during gestation, followed by giving the probiotic to the newborn for the first 2-6 months of life, reduces the risk of developing atopic dermatitis by 40% over the next 6-24 months when compared with placebo, regardless of family history of atopy. However, only four of 10 studies included in the analysis used L. acidophilus as part of the probiotic combination; the results from these individual, small studies support the overall findings of the meta-analysis (107503). Some clinical research also shows that supplementation with 250 mL of fermented milk containing L. acidophilus La-5, Lacticaseibacillus rhamnosus GG, and Bifidobacterium animalis subsp. lactis BB-12 starting at 36 weeks' gestation and continuing until 3 months' postpartum, without supplementation in the infant, reduces the overall occurrence of atopic dermatitis in the child at 2 years of age. However, at 6 years of age, the effect appears to be inconclusive (96893). In children ages 1-3 years with moderate to severe atopic dermatitis, taking 5 billion colony-forming units (CFUs) of a combination of L. acidophilus DDS-1 and Bifidobacterium animalis subsp. lactis UABLA-12 along with fructo-oligosaccharides (FOS) (DDS Junior) twice daily for 8 weeks modestly reduces symptom severity and the need for topical corticosteroids when compared with placebo (110995).
• Bronchopulmonary dysplasia. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One large observational study in premature infants suggests that taking L. acidophilus 1 to 3 billion CFUs with Bifidobacterium longum subsp. infantis during the first month of life for the prevention of necrotizing enterocolitis was not associated with a reduced risk of bronchopulmonary dysplasia. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Cancer. Although there has been interest in using oral Lactobacillus acidophilus for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• Canker sores. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A systematic review and meta-analysis of mainly small and preliminary clinical trials shows that taking lactobacilli probiotics has a small effect on pain from canker sores. However, the dose and duration of probiotic and the specific species, as well as endpoints and results from individual studies, are mixed. One small study shows that taking a combination of L. acidophilus, Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, and Bifidobacterium animalis subsp. lactis reduces pain, but not the number of lesions or healing time, when compared with placebo. Another study shows that using lozenges providing inulin 0.13 gram along with L. acidophilus and B. animalis subsp. lactis 1.5 billion colony-forming units each reduces pain, but does not affect ulcer size or healing, when compared with Oracure gel (105146). Many of the individual studies may have been underpowered to detect a difference between groups.
• Cholestasis. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in premature infants shows that the risk of developing cholestasis is reduced from 22% to 6% in those given a blend of L. acidophilus, bifidobacteria, and Enterococcus faecalis (Peifeikang powder, Shanghai Xinyi Pharmaceutical Company) at least 5 million colony-forming units three times daily, from birth until implementation of total parenteral nutrition, when compared with infants not given this powder. In the infants that developed cholestasis, the severity was reduced, resulting in a reduction in the rate of cholestatic liver injury, feeding intolerance, and necrotizing enterocolitis. The number of days to reach full enteral feeding, days to normal weight gain, and days of hospitalization were reduced by approximately 2.8, 2.1, and 1.7 days, respectively (103448).
• Clostridioides difficile infection. It is unclear if oral Lactobacillus acidophilus is beneficial for preventing C. difficile occurrence or recurrence. Details: Current guidelines from the Infectious Diseases Society of America (IDSA) state that there is insufficient information to recommend administration of probiotics for the primary prevention of C. difficile-associated diarrhea (107538). Evidence from clinical and observational research investigating the effect of L. acidophilus on C. difficile occurrence or recurrence is weak. Most studies use this species in combination with one or more additional probiotic species, including as Bio-K+ CI1285, containing L. acidophilus CL1285 and L. casei LBC80R, and as Bio-K+ 50 Billion, containing L. acidophilus CL1285, Lacticaseibacillus casei LBC80R, and Lacticaseibacillus rhamnosus CLR2 (25494,90231,90934,95369,95403,107529). Observational research has found that providing the Bio-K+ 50 Billion product as 50-100 billion colony-forming units (CFUs) daily for 5 days to patients who are on antibiotics for at least 2 days reduces the hospital-wide incidence of C. difficile by approximately 40%. The incidence rate was decreased by at least 50% in the highest risk individuals taking this combination (107529).
• Colic. Oral inactivated Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in infants with colic shows that giving a specific multi-ingredient product (Colimil Plus, Milte Italia SPA) containing inactivated L. acidophilus 1 billion colony-forming units, lemon balm 65 mg, and German chamomile 9 mg twice daily for 4 weeks reduces crying time similarly to Limosilactobacillus reuteri DSM 17938 100 million CFUs daily (96278). It is unclear how L. acidophilus compares with no treatment.
• Common cold. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in school children shows that taking a combination of L. acidophilus and Bifidobacterium bifidum (Infloran, Berna) 1 billion colony-forming units each twice daily for 3 months reduces the absolute percentage of school absence due to cold symptoms by 30% when compared with placebo (90286).
• Constipation. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that stool frequency is increased and symptoms of functional constipation in adults are improved with the use of a specific combination product (Hexbio) providing L. acidophilus, Lacticaseibacillus casei, Lactobacillus delbrueckii subsp. lactis, Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium longum subsp. infantis 30 billion colony-forming units (CFUs) twice daily for 7 days (90266). However, most other probiotic compounds containing L. acidophilus have not demonstrated benefit in most patients with constipation. One small clinical trial shows that taking yogurt 180 mL providing L. acidophilus NCFM, Bifidobacterium animalis subsp. lactis HN019, and polydextrose (Litesse) daily for 2 weeks modestly improves clinical response and reduces transit time when compared with taking a control yogurt. However, there was no effect on the number of daily bowel movements (90275). Other studies show that taking Lactobacillus acidophilus DDS-1 6.6 billion CFUs daily for 4 weeks in combination with Bifidobacterium longum UABl-14, Bifidobacterium animalis subsp. lactis UABla-12, Bifidobacterium bifidum UABb-10, and fructo-oligosaccharides (FOS) 7 mg does not improve symptoms of constipation when compared with a placebo providing FOS (110970). Also, there was a general lack of support for symptom improvement following the intake of Lactobacillus acidophilus NCFM 10 billion CFUs daily with Lacticaseibacillus paracasei Lpc-37 and Bifidobacterium animalis subsp. lactis strains Bl-04, Bi-07, and HN019 daily for 2 weeks (110979).
• Critical illness (trauma). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in critically ill, hospitalized adults shows that taking L. acidophilus LA-5 1.75 billion colony-forming units (CFUs), Lactiplantibacillus plantarum 500 million CFUs, Bifidobacterium animalis subsp. lactis BB12 1.75 billion CFUs, and Saccharomyces boulardii 1.5 billion CFUs twice daily for 15 days modestly reduces the risk of sepsis, as well as the length of stay in the ICU and hospital, when compared with placebo (107524).
• Denture stomatitis. Although there has been interest in using oral Lactobacillus acidophilus for denture stomatitis, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• Depression. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with major depression shows that taking L. acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum daily for 8 weeks reduces symptoms of depression measured on the Beck Depression Inventory (BDI) when compared with placebo (99780). However, the validity of the results from this study is limited by incomplete reporting. For example, patient baseline BDI scores were not reported.
• Diabetes. Oral Lactobacillus acidophilus in combination with other probiotic species seems to be beneficial for the treatment of gestational diabetes, although it is unclear if it is beneficial for treatment of type 1 or type 2 diabetes. Oral L. acidophilus is unlikely to be beneficial for the prevention of gestational diabetes. Details: Although some individual studies disagree, meta-analyses of clinical research in patients with gestational diabetes show that taking probiotics, most often L. acidophilus in combination with other species, improves glycemic indices such as fasting blood glucose and insulin sensitivity when compared with placebo (102288,104156). Also, one meta-analysis of clinical research shows that taking probiotics specifically containing L. acidophilus in combination with other species modestly improves these glycemic indices, as well as levels of total cholesterol and triglycerides, but not low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol (111796). Some doses used in available studies include a combination of freeze-dried L. acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum each as 2 billion colony-forming units (CFUs) per gram daily for 6 weeks (95416,98430), a total of 4 billion CFUs of a combination of L. acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, Streptococcus thermophilus STY-31, and Lactobacillus delbrueckii subsp. bulgaricus LBY-27 for 8 weeks starting at 24-28 weeks' gestation (96892), and a specific product containing L. acidophilus and 7 other probiotics (Visbiome, ExeGi Pharma) as a total of 112.5 billion CFUs twice daily for 8 weeks (107549). Meta-analyses in patients with gestational diabetes show that taking probiotics such as L. acidophilus does not reduce the risk for caesarean section birth, neonatal hypoglycemia, large for gestational age birth, or hypertensive disorders such as pregnancy-induced hypertension, pre-eclampsia, or eclampsia (102288,104156,111796). However, one meta-analysis of clinical research shows that taking probiotics specifically containing L. acidophilus modestly reduces neonatal birth weight, but not maternal weight gain (111796). Taking L. acidophilus does not seem to be effective for PREVENTING gestational diabetes. A large clinical trial shows that taking L. acidophilus LA1 7.5 billion CFUs, Bifidobacterium longum sp54 cs 1.5 billion CFUs, and Bifidobacterium bifidum sp9 cs 6 billion CFUs daily from 14-24 weeks' gestation does not reduce the incidence of gestational diabetes when compared with taking placebo (107520). Research on the use of L. acidophilus for type 2 diabetes is mixed. Taking a combination of L. acidophilus, Bifidobacterium bifidum, and Streptococcus thermophilus daily for 12 weeks does not reduce levels of fasting blood glucose or glycated hemoglobin (HbA1c) when compared with placebo (107521). One clinical study shows that taking L. acidophilus along with six other probiotic strains (Familact) daily for 6 weeks reduces fasting blood glucose, but does not affect plasma insulin, when compared with placebo (99790). A small clinical trial shows that taking fermented goat milk 120 grams containing one billion CFUs each of L. acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 daily for 6 weeks modestly reduces levels of HbA1c and low-density lipoprotein (LDL) cholesterol, but not fasting blood glucose or insulin resistance, when compared with conventional fermented milk containing Streptococcus thermophilus TA-40 (110973). However, other clinical research shows that taking L. acidophilus 1 billion CFUs, along with Lacticaseibacillus rhamnosus, Bacillus coagulans GanedenBC30 (GBI-30, 6086), and fructo-oligosaccharides 500 mg daily for 12 weeks modestly reduces fasting blood glucose and insulin and improves measures of insulin resistance when compared with placebo (107731). Another clinical trial shows that taking yogurt 200 grams daily containing L. acidophilus 4.65 million CFUs per gram along with Bifidobacterium animalis subsp. lactis modestly reduces levels of HbA1c, triglyceride, and LDL cholesterol, but not fasting glucose, when compared with a placebo yogurt (111798). A combination probiotic containing L. acidophilus has also been evaluated in children 2-12 years of age with new-onset type 1 diabetes. One clinical study shows that taking a specific combination product (Visbiome, ExeGi Pharma) providing 112.5 billion CFUs daily for 3 months modestly decreases HbA1c and insulin requirements when compared with placebo. Also, about three times as many children achieved remission, defined as insulin requirements of less than 0.5 U/kg daily and HbA1c less than 7%. However, C-peptide levels and the maintenance of residual pancreatic beta-cell function were not affected when compared with placebo (107497).
• Diabetic nephropathy. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with diabetic nephropathy not taking antidiabetes drugs shows that taking a combination of L. acidophilus, Bifidobacterium bifidum, and Streptococcus thermophilus daily for 12 weeks modestly reduces the ratio of microalbuminuria/creatinine (mAlb/Cr), a marker of kidney damage, when compared with placebo. However, there was no effect on the estimated glomerular filtration rate (eGFR) (107521).
• Diarrhea. Oral heat-killed L. acidophilus seems to reduce the duration of diarrhea in adults and children. Oral live L. acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing live L. acidophilus, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum subsp. infantis, Bifidobacterium breve, and Streptococcus thermophilus daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). Heat-killed L. acidophilus has also been investigated for the treatment of diarrhea. A meta-analysis of four small clinical studies in infants and children ages 1 month to 4 years shows that taking heat-killed L. acidophilus LB 20-30 billion colony-forming units (CFUs) daily for up to 5 days along with oral or intravenous rehydration therapy can modestly reduce the duration of diarrhea, primarily of non-rotaviral origin (90295). Also, preliminary clinical research in patients with functional chronic diarrhea shows that taking heat-killed L. acidophilus LB (Lacteol Fort, Laboratoire du Lacteol du Dr Boucard) as two capsules twice daily for a total of 20 billion cells daily for 4 weeks reduces daily stool frequency by 3.5, compared with a reduction of 1.2 in patients taking five chewable capsules three times daily of an unspecified strain of L. acidophilus (Lacidophilin, Tai Ge Pharma Ltd). Stool consistency, pain, distention, and total efficacy, defined as a decrease in mean symptoms by at least 40%, were also further improved in patients taking the heat-killed product (107537). However, other clinical research in children ages 6 months to 12 years hospitalized with acute diarrhea shows that taking 15 billion heat-killed L. acidophilus (Lactrol, Raptakos) cells daily for 3 days along with oral rehydration solution (ORS) does not have beneficial effects on duration of diarrhea, frequency of stools, or length of hospital stay, when compared with ORS alone (111789). The European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388) However, L. acidophilus is not a specific focus of the guidelines and most evidence is low quality.
• Generalized anxiety disorder (GAD). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients newly diagnosed with GAD shows that taking sertraline 25 mg plus probiotics daily for 8 weeks may modestly reduce some symptoms of anxiety when compared with sertraline alone. However, the reduction in anxiety score was small and change was not consistent between rating scales. Also, the quality of life was not improved. The probiotics provided a total of 18 billion colony-forming units of L. acidophilus, Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium animalis subsp. lactis (110977).
• Hepatic encephalopathy. Although there has been interest in using oral Lactobacillus acidophilus for hepatic encephalopathy, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• HIV/AIDS. Although there has been interest in using oral Lactobacillus acidophilus for HIV/AIDS, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• Hypercholesterolemia. It is unclear if oral Lactobacillus acidophilus is beneficial for lowering cholesterol levels; the available research is conflicting. Details: Two meta-analyses of clinical research show that taking fermented milk products containing L. acidophilus can reduce total cholesterol by about 14-19 mg/dL in adults with or without hypercholesterolemia. However, the effect of L. acidophilus on both total and LDL cholesterol levels is conflicting from available research (95396,95397,95399). Clinical trials included in these meta-analyses evaluated patients with hypercholesterolemia, type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), metabolic syndrome, and others. Taking L. acidophilus does not appear to improve high-density lipoprotein (HDL) cholesterol or triglyceride levels (95396,95397,95399). Doses used in some studies have included fermented milk products providing L. acidophilus 39 million to 2 billion CFUs daily, alone or along with other probiotic species, for up to 6 weeks (95396). One small clinical trial in patients with hypercholesterolemia shows that taking L. acidophilus LA-1 60 billion colony-forming units (CFUs) three times daily for 6 weeks does not affect serum lipids when compared with taking placebo (111791). A meta-analysis of nine small to moderate-sized clinical studies shows that taking a combination of L. acidophilus and Bifidobacterium animalis subsp. lactis reduces levels of total cholesterol when compared with placebo (107591). However, it is unclear if this is due to L. acidophilus, Bifidobacterium animalis subsp. lactis, or their combination.
• Hypertension. Although there has been interest in using oral Lactobacillus acidophilus for hypertension, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• Inflammatory bowel disease (IBD). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial in patients with collagenous colitis shows that taking 10 billion colony-forming units each of L. acidophilus LA-5 and Bifidobacterium longum subsp. lactis BB-12 twice daily for 12 weeks does not increase the proportion of patients with a reduction in weekly bowel frequency of at least 50% when compared with placebo. Also, there was no effect of this combination on stool consistency or abdominal symptoms. However, there were some modest benefits when compared with baseline (110999). This study was small and may have been underpowered to detect differences.
• Intraventricular hemorrhage. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in premature infants shows that taking 6 billion CFUs of a combination of L. acidophilus NCDO 1748 and Bifidobacterium bifidum NCDO 2203 (UFC Inforan, Switzerland) from 7 days of age until 34 weeks postmenstrual age or discharge does not reduce the odds of intraventricular hemorrhage when compared with a control group of infants not given these probiotics. The infants in this study were born at less than 32 weeks gestation and had a birthweight of less than 1500 grams (111794). This study is limited by the lack of randomization to treatment group; placement was based on year of birth.
• Lactose intolerance. It is unclear if oral Lactobacillus acidophilus is beneficial for lactose intolerance. Details: One small clinical trial shows that consuming 400 mL of a non-fermented milk product containing L. acidophilus 530 million colony-forming units (CFUs)/mL daily does not reduce symptoms of lactose intolerance or hydrogen breath test results when compared with milk without L. acidophilus (16737). Another small preliminary clinical trial shows that taking L. acidophilus BG2FO4 10 billion CFUs twice daily for 7 days does not reduce lactose-induced gastrointestinal symptoms or improve lactose digestion based on breath hydrogen when compared with baseline (111783). However, another clinical trial shows that adding various L. acidophilus strains 800 million to 1 billion CFUs/mL to non-fermented milk improves hydrogen breath tests in patients with lactose intolerance (16738).
• Lyme disease. Although there has been interest in using oral Lactobacillus acidophilus for Lyme disease, there is insufficient reliable information about the clinical effects of L. acidophilus for this condition.
• Metabolic syndrome. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in elderly patients with metabolic syndrome shows that taking a combination of L. acidophilus PBS066-DSM 24,936, Lactiplantibacillus plantarum PBS067-DSM 24,937, and Limosilactobacillus reuteri PBS072-DSM 25,175 as 2 billion colony-forming units (CFUs) each, with inulin and fructo-oligosaccharides daily for 60 days, reduces the number of patients diagnosed with metabolic syndrome by 23%, compared with a 10% reduction in those taking placebo. In the probiotic group, there were modest improvements in waist circumference and levels of fasting plasma insulin, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and inflammatory mediators when compared with placebo. However, there were no significant differences between groups for fasting blood glucose or blood pressure. All patients in this study were on a Mediterranean-like standard diet (107560).
• Necrotizing enterocolitis (NEC). It is unclear if oral Lactobacillus acidophilus is beneficial or safe for NEC prevention. Details: Most meta-analyses of clinical research show that giving lactobacilli enterally reduces the risk of NEC and/or severe NEC in preterm, mainly very low birth weight (VLBW), infants. Some meta-analyses support the use of lactobacilli in combination with bifidobacteria, as opposed to lactobacilli alone for reducing the risk of NEC. However, only a small number of the individual studies included in these analyses have investigated the effects of L. acidophilus, which was used as part of a combination probiotic and/or prebiotic product in all cases (95344,95351,103437,103445,104157,105162,105164). Also, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, L. acidophilus is not specifically recommended (103003,111609,111611).
• Nonalcoholic fatty liver disease (NAFLD). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children with NAFLD, clinical research shows that taking a specific combination product (Prokid, Gostaresh Milad Pouya Company) containing L. acidophilus ATCC B3208 3 billion colony-forming units (CFUs), Lacticaseibacillus rhamnosus DSMZ 21690 2 billion CFUs, Bifidobacterium animalis subsp. lactis DSMZ 32269 6 billion CFUs, and Bifidobacterium bifidum ATCC SD6576 2 billion CFUs daily for 12 weeks normalizes liver sonography findings in 53% of children, compared with 17% of those taking placebo. In addition, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are reduced by 30% and 25%, respectively. There was no effect on body mass index or blood lipids when compared with placebo (105156). Another clinical trial shows that taking two sachets daily for 3 months of a specific combination product (VSL#3) containing L. acidophilus and other probiotics modestly decreases triglyceride levels and liver enzymes when compared with taking placebo. However, there was no change in body mass index or most glycemic or lipid parameters (111009). However, taking L. acidophilus in combination with other probiotics does not seem to be beneficial in adults with NAFLD. Clinical research shows that taking yogurt 100 grams, containing L. acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12 40 million CFUs and vitamin D 1000 IU, daily for 3 months does not improve fasting blood glucose levels, insulin levels, blood pressure, or anthropometric indices when compared with unfortified yogurt (105174). Also, a small clinical trial shows that taking a combination of L. acidophilus BCMC 12,130, Lacticaseibacillus casei BCMC 12,313, Lactobacillus delbrueckii subsp. lactis BCMC 12,451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum subsp. infantis BCMC 02129, and Bifidobacterium longum BCMC 02120 30 billion colony-forming units twice daily for 6 months has no beneficial effects on hepatic steatosis or fibrosis or on levels of liver enzymes, blood lipids, or fasting glucose, when compared with placebo (107523).
• Nonalcoholic steatohepatitis (NASH). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with NASH shows that taking 1 billion colony-forming units each of L. acidophilus ATCC SD5221 and Bifidobacterium animalis subsp. lactis HN019 daily for 6 months does not have beneficial effects on severity of liver fibrosis or steatosis, metabolic markers, or inflammation when compared with taking placebo. The effect of this combination on liver enzymes was mixed (111797).
• Obesity. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In combination with Bifidobacterium animalis subsp. lactis BS01, taking L. acidophilus LA02 2 billion colony-forming units (CFUs) daily for 6 weeks does not reduce body weight or body fat when compared with placebo in young, healthy females, only some of whom were overweight (103438). However, another clinical study shows that taking 50 billion CFUs of a specific combination of L. acidophilus, Lactiplantibacillus plantarum, Bifidobacterium bifidum, and B. animalis subsp. lactis (Lab4P) for 24 weeks reduces body weight by an additional 1.3 kg more than placebo (103439).
• Polycystic ovary syndrome (PCOS). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with PCOS, clinical research shows that taking a combination of L. acidophilus T16 (IBRC-M10785), Lacticaseibacillus casei T2 (IBRC-M10783), and Bifidobacterium bifidum T1 (IBRC-M10771) 2 billion colony-forming units each, plus inulin 800 mg, daily for 12 weeks modestly reduces serum insulin and triglyceride levels and improves insulin resistance and insulin sensitivity when compared with placebo. However, it does not alter cholesterol or fasting glucose levels (105159). Another clinical trial shows that 31.3% of patients with PCOS taking L. acidophilus in combination with other probiotics daily for 6 months had regular menstrual cycles compared with 12.5% of those taking placebo. There were also modest improvements in testosterone levels and waist circumference, but not other hormones, insulin resistance, body weight, or most measures of quality of life. The product provided Lactobacillus acidophilus UBLA-34 2 billion CFUs along with Bifidobacterium bifidum UBBB-55, Lactiplantibacillus plantarum UBLP-40, Lacticaseibacillus casei UBLC-42, Limosilactobacillus fermentum UBLF-31, Lacticaseibacillus rhamnosus UBLR-58, Limosilactobacillus reuteri UBLRu-87, and fructo-oligosaccharides (FOS) daily for 2 months and then twice daily for 4 months. All patients also underwent dietary and lifestyle changes (110974).
• Postoperative infection. Although there has been interest in using oral Lactobacillus acidophilus for preventing postoperative infections, there is insufficient reliable information about the clinical effects of lactobacillus for this purpose.
• Pouchitis. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Continuous oral treatment for one year with a specific concentrated formulation of L. acidophilus and other probiotics (Visbiome, ExeGi Pharma) as 6 grams (300-500 billion live bacteria per gram), daily for up 12 months seems to maintain remission of pouchitis in 85% of patients (6087,12769). Also, one small clinical study shows that taking a specific product (Trilac, Allergon AB) containing L. acidophilus 600 million colony-forming units (CFUs) per capsule, Lactobacillus delbrueckii subsp. bulgaricus 400 million CFUs per capsule, and Bifidobacterium bifidum 600 million CFUs per capsule, taken in doses of two capsules three times daily for 9 months, can reduce pouchitis severity and the number of patients experiencing pouchitis when compared to baseline (90296). The validity of these findings is limited by the lack of a comparator group.
• Pregnancy-induced nausea and vomiting. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units (CFUs) of L. acidophilus La-14, Lactiplantibacillus plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Lacticaseibacillus paracasei DSM 13434 and Lpc-37, Ligilactobacillus salivarius Ls-33, Levilactobacillus brevis Lbr-35, Lacticaseibacillus casei Lc-11, and Bifidobacterium animalis subsp. lactis Bl-04, along with inulin 200 mg (107199).
• Prematurity. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In premature infants, clinical research shows that taking a blend of L. acidophilus, bifidobacteria, and Enterococcus faecalis (Peifeikang powder, Shanghai Xinyi Pharmaceutical Company), at least 5 million colony-forming units (CFUs) three times daily from birth until implementation of total parenteral nutrition, reduces the rate of development of extrauterine growth retardation from 15% to 8% when compared with those not receiving this blend (103448). Other preliminary clinical research in premature infants shows that taking 6 billion CFUs of a combination of L. acidophilus NCDO 1748 and Bifidobacterium bifidum NCDO 2203 (UFC Inforan, Switzerland) from 7 days of age until 34 weeks postmenstrual age or discharge reduces the odds of neurodevelopment impairment at 24 months corrected age by 70% when compared with a control group of infants not given these probiotics. The odds of having moderate to severe impairment were also reduced. The infants in this study were born at less than 32 weeks gestation and had a birthweight of less than 1500 grams (111794). This study is limited by the lack of randomization to treatment group; placement was based on year of birth. Observational research has also been conducted. One large observational study in infants fed strictly human milk, but not strictly formula or a combination, suggests that taking L. acidophilus 1 to 3 billion CFUs with Bifidobacterium longum subsp. infantis during the first month of life for the prevention of necrotizing enterocolitis was associated with a modest increased weight gain velocity. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Psoriasis. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with psoriasis shows that taking a mixture of probiotics for 8 weeks modestly improves overall symptoms and feelings of depression when compared with placebo. The percentage of patients achieving at least a 50% or 75% reduction in overall symptom score was 40% and 24%, respectively, in those taking the probiotic mixture, compared with 16% and 8% of those taking placebo. Each probiotic capsule was used twice daily and provided a total daily dose of 2.6 billion colony-forming units (CFUs) of L. acidophilus, Bifidobacterium bifidum, Bifidobacterium animalis subsp. lactis, and Bifidobacterium longum (107498).
• Radiation-induced diarrhea. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with cervical cancer receiving radiotherapy with or without chemotherapy shows that taking a specific product (Biogurt, Fame Pharmaceuticals) containing L. acidophilus LA-5 and Bifidobacterium animalis subsp. lactis BB-12 as 1.75 billion lyophilized colony-forming units (CFUs) as a capsule three times daily throughout treatment reduces the risk of diarrhea by 28% when compared with placebo. The treatment group also used less loperamide (102285). Another small clinical trial in patients undergoing pelvic radiotherapy with weekly cisplatin shows that taking L. acidophilus and Bifidobacterium bifidum (Infloran, Laboratio Farmaceutico SIT) as 1 billion CFUs each, twice daily from seven days before starting radiotherapy and continuing during radiotherapy, reduces the incidence of moderate to severe diarrhea and the need for antidiarrheal medication when compared with placebo. Moderate to severe diarrhea occurred in 9% of patients using the probiotics, compared with 45% of those taking placebo (107580).
• Respiratory tract infections. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children ages 3-5 years who attend daycare centers shows that taking a combination milk product containing 5 billion colony-forming units (CFUs) each of L. acidophilus and Bifidobacterium animalis (HOWARU Protect, Danisco) reduces the risk of experiencing fever, cough, and rhinorrhea by 45% when compared with placebo. Patients taking this combination experienced an average 2-day shorter duration of symptoms and were significantly less likely to use an antibiotic for their symptoms. Patients who took L. acidophilus without bifidobacterium also had a reduction in fever, cough, and use of antibiotics, but not rhinorrhea (16847). In healthy children aged 3-10 years, clinical research shows that taking 12.5 billion CFUs daily of a specific combination of L. acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20, Bifidobacterium animalis subsp. lactis CUL34 (Lab4), and vitamin C 50 mg daily reduces the risk of cough by 16% and sore throat by 20%, and modestly reduces school absenteeism and antibiotic use when compared with placebo. However, nasal symptoms, fever, and wheezing were not reduced (106943). A different combination product containing L. acidophilus DDS-1 1 billion CFUs and B. animalis subsp. lactis UABLA-12 4 billion CFUs (Up4-Junior, UAS Laboratories) with fructo-oligosaccharides 50 mg has also been evaluated. Clinical research in children 3-12 years of age with a sick household member shows that taking this product daily for 2 weeks modestly shortens the duration of respiratory infections, but does not reduce the risk of developing an infection, when compared with placebo (98439). In overweight adults or adults with obesity, taking 50 billion CFUs of a specific combination of L. acidophilus, Lactiplantibacillus plantarum, B. bifidum, and B. animalis subsp. lactis (Lab4P) for 24 weeks reduces the overall likelihood of having upper respiratory tract infection symptoms, such as sneezing, cough, and blocked nose, by approximately 40% when compared with placebo (103439).
• Retinopathy of prematurity. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in premature infants shows that taking 6 billion CFUs of a combination of L. acidophilus NCDO 1748 and Bifidobacterium bifidum NCDO 2203 (UFC Inforan, Switzerland) from 7 days of age until 34 weeks postmenstrual age or discharge does not reduce the odds of retinopathy of prematurity when compared with a control group of infants not given these probiotics. The infants in this study were born at less than 32 weeks gestation and had a birthweight of less than 1500 grams (111794). This study is limited by the lack of randomization to treatment group; placement was based on year of birth. Also, one large observational study in premature infants suggests that taking L. acidophilus 1 to 3 billion CFUs with Bifidobacterium longum subsp. infantis during the first month of life for the prevention of necrotizing enterocolitis was not associated with a reduced risk of retinopathy of prematurity. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Rheumatoid arthritis (RA). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with moderate-to-severe RA shows that taking capsules containing freeze-dried strains of L. acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum daily for 8 weeks does not improve RA severity, the number of tender or swollen joints, or joint pain when compared with placebo (95418).
• Rotaviral diarrhea. It is unclear if oral Lactobacillus acidophilus is beneficial for rotaviral diarrhea. Details: One preliminary clinical study shows that taking a combination of L. acidophilus AD031 2 billion colony-forming units (CFUs) and Bifidobacterium longum BORI 20 billion CFUs twice daily for 3 days reduces the duration of rotaviral diarrhea by an average of 3 days when compared with placebo (95334). However, one clinical study using a lower dose and different strain of L. acidophilus (La-14) 200 million CFUs twice daily for 5 days shows that this regimen does not reduce the duration of watery diarrhea or affect the viral load in children aged 9 months to 5 years with confirmed norovirus or rotavirus infection (96887). A small clinical study shows that heat-killed L. acidophilus LB 20-30 billion cells daily for up to 4 days can modestly reduce the duration of diarrhea in infants and children, some of which had confirmed rotavirus (90295).
• Sepsis. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in premature infants shows that taking 6 billion CFUs of a combination of L. acidophilus NCDO 1748 with Bifidobacterium bifidum NCDO 2203 (UFC Inforan, Switzerland) from 7 days of age until 34 weeks postmenstrual age or discharge reduces the odds of late onset sepsis by 55% when compared with a control group of infants not given these probiotics. The infants in this study were born at less than 32 weeks gestation and had a birthweight of less than 1500 grams (111794). This study is limited by the lack of randomization to treatment group; placement was based on year of birth. One large observational study in infants fed a mix of human milk and formula, but not strictly human milk or formula, suggests that taking L. acidophilus 1 to 3 billion CFUs with Bifidobacterium longum subsp. infantis during the first month of life for the prevention of necrotizing enterocolitis was associated with a 31% reduction in the development of clinical sepsis. The infants in this study were born between 22-29 weeks gestation and had a birthweight of less than 1500 grams (111771).
• Short bowel syndrome. Although there has been interest in using oral Lactobacillus acidophilus for short bowel syndrome, there is insufficient reliable information about the clinical effects of lactobacillus for this condition.
• Small intestinal bacterial overgrowth (SIBO). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with chronic diarrhea due to SIBO shows that taking a combination of lyophilized L. acidophilus 1.5 grams and Lacticaseibacillus casei 1.5 grams by mouth twice daily for 21 days decreases average daily stools by 1.5, but does not improve other symptoms, when compared with placebo (91143). Also, one preliminary clinical study shows that taking a total of 2 billion CFUs of L. acidophilus and Lacticaseibacillus rhamnosus (Lacidofil) daily for 4 weeks does not prevent the development of SIBO in children that started treatment with omeprazole 20 mg daily for epigastric pain (90262).
• Travelers' diarrhea. It is unclear if oral Lactobacillus acidophilus is beneficial for the prevention of travelers' diarrhea. Details: A meta-analysis which included three clinical studies evaluating the use of L. acidophilus in adults traveling to different parts of the world found no benefit for the prevention of travelers' diarrhea when compared with placebo (101445). The effectiveness of this species may vary significantly based upon the destination of travel. Destinations in the same country can have different results, probably due to differences in bacteria and other microorganisms at different locations (10216).
• Ulcerative colitis. Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: The best evidence of benefit is for a specific combination product (Visbiome, ExeGi Pharma). Doses of 3 grams (equivalent to 900 billion colony-forming units (CFUs)) once or twice daily have been used in combination with conventional treatment. In children aged 1-16 years, doses of 450-1800 billion CFUs for up to one year have been used (3261,14370,14371,16841,95337). A meta-analysis of clinical research shows that taking this product as an adjunct to standard ulcerative colitis treatment can increase remission rates in adults and children by about 1.7-fold when compared with standard treatment alone (95337). Preliminary clinical research in patients with moderate to severe symptoms taking mesalazine 1200 mg daily shows that taking an unknown dose of L. acidophilus twice daily along with Bifidobacterium bifidum BGN4 and Ligilactobacillus salivarius (Acronelle, Bromatech srl, Milan, Italy) for 2 years modestly improves patient- and physician-scales of overall symptoms when compared with taking mesalazine alone. There were also improvements in stool frequency and rectal bleeding (110981). Although some contradictory evidence exists (3261,16841), most research shows that taking Visbiome or a combination of L. acidophilus LA-5 and Bifidobacterium animalis subsp. lactis BB-12 (Probio-Tec AB-25) does not prevent relapse in people who are already in remission (95337,95338).
• Urinary tract infections (UTIs). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children aged 4 months to 5 years with a previous UTI, clinical research shows that taking a specific combination of L. acidophilus, Lacticaseibacillus rhamnosus, Bifidobacterium bifidum, and Bifidobacterium animalis subsp. lactis (Complete Probiotic Platinum) for 18 months increases the median time to the first incidence of recurrence by approximately 3 months and increases the percentage of children without a UTI during the study period from 83% to 97% (103436).
• Vaginal candidiasis. It is unclear if oral or intravaginal Lactobacillus acidophilus is beneficial for vaginal candidiasis. Details: In a small preliminary clinical trial in patients with recurrent vulvovaginal candidiasis who had undergone a week of oral fluconazole treatment followed by intravaginal L. acidophilus LA 02 and Limosilactobacillus fermentum LF10, 72.4% of patients demonstrated a lack of clinical recurrence over a 7 month observational period. All patients took fluconazole 200 mg three times in the first week followed by intravaginal application with at least 0.4 billion colony-forming units each of L. acidophilus LA 02 and Limosilactobacillus fermentum LF10, along with arabinogalactan and fructo-oligosaccharides (FOS) on alternate days for 10 days and then once weekly for 10 weeks (111781). However, a combination of L. acidophilus, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii, and Streptococcus thermophilus (Femilac) given intravaginally, does not seem to reduce the risk of vaginal candidiasis infection following use of antibiotics (12108). There is also some evidence that eating yogurt enriched with L. acidophilus daily does not reduce the risk of recurrent vaginal candidiasis (1245).
• Ventilator-associated pneumonia (VAP). Oral Lactobacillus acidophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking L. acidophilus LA-5 1.75 billion colony-forming units (CFUs), Lactiplantibacillus plantarum 500 million CFUs, Bifidobacterium animalis subsp. lactis BB12 1.75 billion CFUs, and Saccharomyces boulardii 1.5 billion CFUs twice daily for 15 days reduces the risk of VAP to 12%, compared with 28% in those taking placebo. Half of the dose was given onto the oropharynx and half via a nasogastric tube (107524). More evidence is needed to rate Lactobacillus acidophilus for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A preliminary clinical study shows that taking a specific probiotic product containing L. delbrueckii 5 billion colony-forming units (CFUs), Lactobacillus acidophilus 5 billion CFUs, and Bifidobacterium bifidum 20 billion CFUs (Trenev Trio/Healthy Trinity, Natren) twice daily along with minocycline once every evening for 12 weeks improves inflamed and non-inflamed acne lesions in 82% of patients, compared to only 67% of patients treated with either the probiotic combination or minocycline alone (90270).
• Allergic rhinitis (hay fever). Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children ages 2-5 years with allergic rhinitis, clinical research shows that taking a fermented milk (Danone) daily containing yogurt cultures L. delbrueckii subsp. bulgaricus 1 billion colony-forming units and Streptococcus thermophilus, as well as L. paracasei DN-114 011, does not increase the time free from rhinitis episodes, the mean duration of episodes, or the cumulative number of episodes, when compared with taking a control milk. However, the number of episodes was reduced between months 3-9 (112512).
• Antibiotic-associated diarrhea. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in hospitalized adults shows that consuming a 97 mL drink (Actimel, Danone) containing and L. delbrueckii 10 million colony-forming units/mL along with Lacticaseibacillus paracasei and Streptococcus thermophilus, twice daily while taking antibiotics reduces the odds of developing antibiotic-associated diarrhea by 75% when compared with a milkshake without probiotics (16740).
• Asthma. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children ages 2-5 years with asthma, clinical research shows that taking a fermented milk (Danone) daily containing yogurt cultures L. delbrueckii subsp. bulgaricus 1 billion colony-forming units and Streptococcus thermophilus, as well as L. paracasei DN-114 011, does not increase the time free from asthma episodes, the mean duration of episodes, or the cumulative number of episodes, when compared with taking a control milk (112512).
• Clostridioides difficile infection. Although there has been interest in using oral Lactobacillus delbrueckii for C. difficile prevention, there is insufficient reliable information about the clinical effects of L. delbrueckii for this purpose.
• Colic. Although there has been interest in using oral Lactobacillus delbrueckii for colic, there is insufficient reliable information about the clinical effects of L. delbrueckii for this purpose.
• Common cold. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in children aged 3-6 years attending daycare shows that drinking a fermented milk product containing L. delbrueckii, Lacticaseibacillus paracasei, and Streptococcus thermophilus (Actimel, Danone) 200 grams daily for 3 months reduces the risk of developing the common cold, the most common upper respiratory tract infection in these children, by around 18% when compared with a control milk product. The fermented milk product did not affect medication use or sick leave from daycare (96882).
• Constipation. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that stool frequency is modestly increased and symptoms of functional constipation in adults, such as stool consistency and straining, are improved with the use of a specific combination product (Hexbio) providing L. delbrueckii, Lactobacillus acidophilus, Lacticaseibacillus casei, Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium longum subsp. infantis 30 billion colony-forming units twice daily for 7 days (90266).
• Coronavirus disease 2019 (COVID-19). Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small, retrospective study in patients with severe COVID-19 symptoms shows that taking a combination of probiotics modestly reduces the duration of diarrhea when compared to standard treatments alone. The probiotic treatment consisted of L. delbrueckii 6 million colony-forming units (CFUs), Bifidobacterium longum 60 million CFUs, and Streptococcus thermophilus 6 million CFUs given in three divided doses daily (107200).
• Diabetes. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with type 2 diabetes shows that taking a specific combination product (Familact probiotics, ZistTakhmir Co.) containing L. delbrueckii and other probiotic bacteria daily for 6 weeks does not reduce fasting blood glucose or plasma insulin levels when compared with placebo. This product contains L. delbrueckii 200 million colony-forming units, along with Bifidobacterium longum, Bifidobacterium breve, Lactobacillus acidophilus, Lacticaseibacillus casei, Lactocaseibacillus rhamnosus, and Streptococcus thermophilus (99790). Oral L. delbrueckii has also been investigated for gestational diabetes. One small clinical study in adults with gestational diabetes shows that taking a combination of L. delbrueckii LBY-27, Bifidobacterium lactis BB-12, Streptococcus thermophilus STY-31, and Lactobacillus acidophilus LA-5 for 8 weeks, starting at 24-28 weeks' gestation, modestly reduces fasting blood glucose and improves insulin sensitively when compared with placebo (96892).
• Diarrhea. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in children aged 3-36 months with acute diarrhea shows that taking a combination probiotic (Lactogermina) containing 1 billion colony-forming units (CFUs) each of L. delbrueckii, Streptococcus thermophilus, and Lactobacillus acidophilus, plus 500 million CFUs of Bifidobacterium bifidum twice daily for 5 days, in addition to oral rehydration solution, reduces the duration of diarrhea by 37 hours when compared with oral rehydration solution alone (102426). Also, a small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing live L. delbrueckii, Lactobacillus acidophilus, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Bifidobacterium longum subsp. infantis, Bifidobacterium breve, and Streptococcus thermophilus daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). Although The European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388), both guidelines note that most evidence is low quality.
• Helicobacter pylori. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking 100 million colony-forming units (CFUs) total of L. delbrueckii along with six other probiotics (Balance, Protexin Co., UK) twice daily in conjunction with bismuth quadruple therapy does not seem to improve H. pylori eradication rates when compared with placebo and bismuth quadruple therapy (90291). Other clinical research shows that taking yogurt providing L. delbrueckii 100,000 CFUs and Streptococcus thermophilus for one week prior to triple therapy treatment for H. pylori infection increases the eradication rate by up to 10% when compared with a placebo yogurt and triple therapy. However, taking the yogurt was not effective for reducing medication-related adverse effects (112555).
• Irritable bowel syndrome (IBS). Although there has been interest in using oral Lactobacillus delbrueckii for IBS, there is insufficient reliable information about the clinical effects of L. delbrueckii for this purpose.
• Lactose intolerance. Although there has been interest in using oral Lactobacillus delbrueckii for lactose intolerance, there is insufficient reliable information about the clinical effects of L. delbrueckii for this purpose.
• Nonalcoholic fatty liver disease (NAFLD). Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with NAFLD shows that taking a total of 500 million colony-forming units of L. delbrueckii and Streptococcus thermophilus daily for 3 months modestly reduces liver enzyme levels when compared to baseline (102424). This study was limited by a lack of statistical comparison to the placebo group. Another small clinical trial shows that taking a combination of L. delbrueckii BCMC 12,451, Lactobacillus acidophilus BCMC 12,130, Lacticaseibacillus casei BCMC 12,313, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum subsp. infantis BCMC 02129, and Bifidobacterium longum BCMC 02120 30 billion colony-forming units twice daily for 6 months has no beneficial effects on hepatic steatosis or fibrosis or on levels of liver enzymes, blood lipids, or fasting glucose, when compared with placebo (107523).
• Nonalcoholic steatohepatitis (NASH). Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small open-label clinical trial in patients with NASH shows that taking a combination probiotic containing a total of 100 million colony-forming units of L. delbrueckii, Streptococcus thermophilus, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, and Bifidobacterium longum, plus fructo-oligosaccharides once daily for 12 weeks modestly reduces liver stiffness and alanine aminotransferase, but does not affect steatosis or other liver enzyme levels, when compared with control (102415).
• Oral mucositis. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in patients with locally advanced nasopharyngeal cancer undergoing radiochemotherapy shows that taking a specific probiotic product (Bifico, Shanghai Sine Pharmaceutical Co. Ltd.) containing L. delbrueckii, Bifidobacterium longum, and Enterococcus faecium 3 capsules twice daily for up to 7 weeks modestly reduces the incidence of severe oral mucositis when compared with placebo (102413). A small clinical study in patients with Candida-associated oral mucositis shows that, in addition to topical antifungal therapy, taking four 500-mg lozenges, with each lozenge containing L. delbrueckii 500,000 colony-forming units (CFUs), Streptococcus thermophilus 500,000 CFUs, and Bifidobacterium longum 5 million CFUs, 3 times daily for 4 weeks does not reduce symptoms to a greater extent than topical antifungal therapy alone (102432).
• Pouchitis. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study shows that taking a specific product (Trilac, Allergon AB) containing L. delbrueckii 400 million colony-forming units (CFUs), Lactobacillus acidophilus 600 million CFUs, and Bifidobacterium bifidum 600 million CFUs per capsule can reduce pouchitis severity and the number of patients experiencing pouchitis when compared to baseline. This product was taken in doses of 2 capsules 3 times daily for the first month followed by 1 capsule twice daily for 8 months (90296). The validity of these findings is limited by the lack of a comparator group.
• Pregnancy-induced nausea and vomiting. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles of six days with probiotics and 2 days without. Each capsule contained a total of 10 billion colony-forming units of L. delbrueckii Lb-87, Ligilactobacillus salivarius Ls-33, Lactobacillus acidophilus La-14, Lactiplantibacillus plantarum 299v and DSM 15312, Lacticaseibacillus paracasei DSM 13434 and Lpc-37, Levilactobacillus brevis Lbr-35, Lacticaseibacillus casei Lc-11, and Bifidobacterium animalis subsp. lactis Bl-04, along with inulin 200 mg (107199).
• Radiation-induced diarrhea. Oral Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients undergoing pelvic radiotherapy shows that taking 96 mL fermented milk (Danone) 3 times daily, containing L. delbrueckii, Streptococcus thermophilus, and Lacticaseibacillus paracasei DN-114 001 starting one week before the initiation of radiation treatment does not delay the development of diarrhea when compared with taking a control sterilized milk product. The fermented milk was continued throughout treatment (112513).
• Vaginal candidiasis. Vaginal Lactobacillus delbrueckii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that a combination of L. delbrueckii, Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, and Streptococcus thermophilus (Femilac) given intravaginally, does not seem to reduce the risk of vaginal candidiasis infection following use of antibiotics when compared with placebo (12108). More evidence is needed to rate Lactobacillus delbrueckii for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral Lactobacillus gasseri is beneficial for allergic rhinitis. Details: Clinical research in children ages 6-12 years with allergic rhinitis and asthma shows that taking L. gasseri PM-A0005 2 billion colony forming units (CFUs) twice daily for 8 weeks modestly improves allergic rhinitis symptoms when compared with taking placebo. However, there was no difference in the proportion of patients with symptom improvement or in symptom severity (112580). L. gasseri has also been examined in combination with other probiotics. Clinical research in patients with seasonal allergies shows that taking L. gasseri KS-13 1.2 billion CFUs, Bifidobacterium bifidum G9-1 0.15 billion CFUs, and Bifidobacterium longum MM-2 0.15 billion CFUs twice daily for 8 weeks during allergy season modestly improves quality of life, specifically nasal symptoms, when compared with taking placebo. However, eye symptoms were not improved (110972). It is unclear if any effect in this study is due to L. gasseri, the other probiotics, or the combination.
• Aspirin-associated gastric damage. It is unclear if oral Lactobacillus gasseri can reduce the risk of aspirin-associated gastric damage. Details: A small clinical study in adults taking aspirin 81 mg daily for at least 1 month shows that taking L. gasseri OLL2716 2 billion colony-forming units twice daily in yogurt for 6 weeks reduces the number of mucosal breaks and the number of reddened lesions of the small bowel when compared with placebo (95592).
• Asthma. It is unclear if oral Lactobacillus gasseri is beneficial for asthma. Details: Clinical research in children ages 6-12 years with allergic rhinitis and asthma shows that taking L. gasseri PM-A0005 2 billion colony-forming units (CFUs) for 8 weeks modestly improves pulmonary function and daytime asthma symptoms when compared with taking placebo (112580).
• Bacterial vaginosis. Oral and vaginal Lactobacillus gasseri have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: A clinical trial shows that using vaginal capsules (EcoVag Vaginal Capsules, Bifodan A/S) containing L. gasseri and Lacticaseibacillus rhamnosus, 100 million to 1 billion colony-forming units (CFUs) of each strain per capsule, following conventional treatment for 10 days in three subsequent menstrual cycles, increases the time from cure to relapse when compared with placebo. However, cure rates were not significantly improved in the first month of treatment (16745). Also, a combination product containing L. gasseri has been tried in patients with both bacterial vaginosis and aerobic vaginitis, which typically occurs after unsuccessful treatment of bacterial vaginosis with antibiotics. A clinical study in these patients shows that taking a specific combination product (prOVag, IBSS BIOMED S.A.) containing a total of 100 million CFUs of L. gasseri 57C, Lactiplantibacillus plantarum 57B, and Limosilactobacillus fermentum 57A daily for 10 days in conjunction with standard metronidazole treatment increases the duration of symptom-free remission to 71 days, compared with 47 days in those taking metronidazole alone (99784).
• Common cold. Oral Lactobacillus gasseri has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in healthy adults shows that taking L. gasseri, in combination with other probiotics and vitamins/minerals, daily for at least 3 months reduces the duration of common cold episodes by approximately 2 days when compared with taking a placebo providing only the vitamins/minerals. However, there was no difference in the number of common cold episodes. The probiotic supplement provided L. gasseri PA 16/8 40 million colony-forming units (CFUs), Bifidobacterium longum SP 07/3 5 million CFUs, and Bifidobacterium bifidum MF 20/5 5 million CFUs (Tribion Harmonis) daily (110978).
• Diarrhea. Oral Lactobacillus gasseri has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In adults with acute diarrhea, clinical research shows that taking one capsule providing at least 20 million colony-forming units (CFUs) each of L. gasseri and Bifidobacterium longum (Omniflora) three times daily for up to 6 days is as effective as taking Enterococcus faecium SF 68 75 million CFUs three times daily, used as an active comparator, for reducing the duration of diarrhea. However, complete recovery occurred in a modestly greater proportion of patients. All patients also received oral rehydration solution (111854).
• Dyspepsia. It is unclear if oral Lactobacillus gasseri is beneficial for dyspepsia. Details: Clinical research in patients with functional dyspepsia shows that taking L. gasseri OLL2716 1 billion colony-forming units daily in yogurt for 12 weeks does not affect the overall patient impression of gastric symptoms, or the severity of most individual symptoms, when compared with control yogurt. However, the proportion of patients with an elimination of symptoms was 35.2% compared with 17.3% of those consuming the control yogurt (112584).
• Gastroparesis. It is unclear if oral Lactobacillus gasseri is beneficial for gastroparesis. Details: A small clinical trial in patients with mild to moderate delayed gastric emptying shows that taking L. gasseri OLL2716 1 billion colony-forming units daily in yogurt for 12 weeks does not affect the overall condition or the average time to gastric emptying of a liquid test meal when compared with placebo yogurt. However, the odds of having a clinically relevant improvement in gastric emptying rate were increased by about 4-fold. Patients with severe gastroparesis were excluded from this study (112575). This study may have been inadequately powered to detect some differences between groups.
• Gout. It is unclear if oral Lactobacillus gasseri is beneficial for gout. Details: A small clinical trial in patients with hyperuricemia and/or gout shows that taking L. gasseri PA-3 8.5 billion colony-forming units daily in a yogurt beverage for 8 weeks does not reduce serum uric acid levels in most individuals when compared with control yogurt. Patients discontinued urate lower medications starting 4 weeks prior to this study (112593). This study may have been inadequately powered to detect differences between groups.
• Helicobacter pylori. It is unclear if oral Lactobacillus gasseri is beneficial for H. pylori symptoms or eradication. Details: Preliminary clinical research in patients with H. pylori infections shows that taking L. gasseri OLL2716 1 billion colony-forming units twice daily in yogurt for 4 weeks, starting 3 weeks prior to triple therapy, results in an 82.6% overall eradication rate compared to 69.3% of those given only triple therapy (90244). The validity of this study is limited by the lack of blinding.
• Irritable bowel syndrome (IBS). It is unclear if oral Lactobacillus gasseri is beneficial for IBS. Details: A small clinical trial in patients with IBS shows that taking L. gasseri CP2305 130 million colony-forming units daily in fermented milk powder for 4 weeks modestly reduces IBS symptom severity, and improves fecal characteristics and the number of bowel movements, when compared with placebo (112594).
• Japanese cedar pollinosis. It is unclear if oral heat-killed Lactobacillus gasseri is beneficial for Japanese cedar pollinosis. Details: Clinical research in patients with Japanese cedar pollinosis shows that taking tablets containing heat-killed L. gasseri OLL2809 10 billion cells daily for 8 weeks does not reduce symptoms in the overall population when compared with placebo. However, in the patients with the highest Japanese cedar pollen-specific IgE, nasal symptoms and the specific IgE levels were modestly reduced (112589).
• Menopausal symptoms. It is unclear if oral heat-killed Lactobacillus gasseri is beneficial for menopausal symptoms. Details: Clinical research in females ages 40-60 years shows that taking tablets containing heat-killed L. gasseri CP2305 10 billion cells daily for 6 consecutive menstrual cycles modestly improves perimenopausal symptoms when compared with placebo. The proportion of individuals with improvements in overall symptoms increased by up to 36%. However, the effect of taking L. gasseri on specific symptoms is unclear due to discrepant findings between questionnaires. The individuals in this study had mild climacteric symptoms and regular menstrual cycles (112582).
• Obesity. Most research shows that oral Lactobacillus gasseri is beneficial for weight loss. However, it is unclear if any benefits are clinically significant. Details: Clinical research in adults with overweight or obesity shows that taking L. gasseri BNR17 1 billion or 10 billion colony-forming units (CFUs) daily in divided doses for 12 weeks does not reduce body weight, body mass index (BMI), total fat percentage, or waist or hip circumference when compared with placebo, although it did produce a modest reduction in visceral adipose tissue. There was no effect on lipid or glycemic indices (98433). Other clinical research in adults with increased visceral fat shows that taking L. gasseri SBT2055 200 million or 2 billion CFUs daily in fermented milk for 12 weeks modestly reduces visceral fat area, BMI, fat mass, and waist and hip circumference when compared with a fermented milk lacking in L. gasseri (112588). However, it is unclear whether any improvements are clinically significant.
• Stress. It is unclear if oral heat-killed Lactobacillus gasseri is beneficial for acute or chronic stress. Details: A small clinical trial in adults with acute stress shows that taking heat-killed L. gasseri CP2305 10 billion cells daily in fermented milk for 5 weeks modestly improves sleep quality when compared with a placebo milk. In males, but not females, there was also a modest improvement in stress-associated diarrhea, sleep latency, and sleep duration (112581). This study may have been inadequately powered to detect some differences between groups. Another small clinical trial in adults with chronic stress shows that taking tablets containing this strain of heat-killed L. gasseri 10 billion cells daily for 24 weeks modestly reduces feelings of anxiety and depression and improves sleep quality when compared with placebo (102297). More evidence is needed to rate Lactobacillus gasseri for these uses.

(Read more about LACTOBACILLUS GASSERI)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral Lactobacillus helveticus is beneficial in patients with allergic rhinitis. Details: Clinical research in adults with mild to moderate perennial allergy shows that taking 100 grams daily of a milk fermented with L. helveticus SBT2171 (LH2171) and Streptococcus thermophilus for 16 weeks, modestly improves the severity of a stuffy nose, as well as the proportion of patients with an improvement or disappearance of overall symptoms, when compared with taking milk fermented only with S. thermophilus. However, there was no significant difference between groups on subjective feelings of sneezing, runny nose, itchy eyes, or tearing severity, or on symptoms as evaluated by the physician. The fermented milk provided at least one billion colony-forming units (CFUs) of L. helveticus (110926).
• Antibiotic-associated diarrhea. Oral Lactobacillus helveticus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a combination of L. helveticus R0052 0.4 billion colony-forming units (CFUs) and Lacticaseibacillus rhamnosus R0011 7.6 billion CFUs (Lacidofil STRONG, Lallemand Health Solutions) daily during antibiotic treatment reduces the duration of diarrhea-like defecations by one day when compared with taking placebo. However, there was no effect on the proportion of participants experiencing diarrhea-like defecations or the consistency or daily frequency of bowel movements (96891).
• Cognitive function. Oral Lactobacillus helveticus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in healthy adults shows that taking a product containing a combination of L. helveticus R0052 2 billion colony-forming units (CFUs), Lactiplantibacillus plantarum R1012 800 million CFUs, and Bifidobacterium longum R0175 70 million CFUs (Puraflor, GSK Consumer Healthcare, Milano, Italy) daily for 4 weeks does not affect cognitive performance during acute stress when compared with placebo. The probiotics were provided in combination with inulin 500 mg, potassium 50 mg, magnesium 45 mg, glutathione 20 mg, lactoferrin 10 mg, and zinc 9 mg (110923). The effects of L. helveticus alone are not clear from this study. Also, a larger clinical trial is needed to confirm these results.
• Depression. Oral Lactobacillus helveticus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in patients with mild to moderate symptoms of major depressive disorder shows that taking a total of 10 billion colony-forming units (CFUs) of L. helveticus and Bifidobacterium longum daily modestly improves symptoms of depression when compared with placebo, but not when compared with the prebiotic galactooligosaccharide. All patients had been taking antidepressants for at least 3 months (102506) Also, preliminary clinical research in treatment-naïve patients with moderate depression shows that taking 2.7 billion CFUs of L. helveticus in combination with 0.3 billion CFUs of B. longum daily modestly improves symptoms of depression and sleep quality when compared with baseline (105129). However, a larger clinical trial in untreated patients with depression shows that taking a total of 3 billion CFUs of L. helveticus and B. longum does not improve symptoms of depression when compared with placebo. The majority of these patients had a history of prior antidepressant usage (110922). All studies used L. helveticus R0052 and B. longum R0175 (Lallemand Health Solutions Inc.) daily for 8 weeks.
• Diarrhea. Oral Lactobacillus helveticus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children 3 months to 4 years of age with acute gastroenteritis shows that taking a combination product containing L. helveticus R0052 200 million colony-forming units (CFUs) and Lacticaseibacillus rhamnosus GG R0011 3.8 billion CFUs twice daily (Lacidofil , Lallemand Health Solutions) for 5 days does not reduce the risk of a moderate to severe episode of acute gastroenteritis in the 14-28 days after starting the probiotic when compared with placebo. These products also did not reduce the number of unexpected healthcare visits. The efficacy of these products does not seem to depend on the duration of symptoms, the frequency of diarrhea, or the type of infection (98428,103441,110925).
• Exercise-induced respiratory infections. It is unclear if oral Lactobacillus helveticus is beneficial for preventing exercise-induced respiratory infections. Details: A small clinical trial in athletes shows that taking L. helveticus Lafti L10 (Lallemand Health Solutions) 20 billion colony-forming units (CFUs) daily for 14 weeks during winter modestly decreases the duration of upper respiratory infections by approximately 3.4 days when compared with taking placebo. The number of symptoms was reduced by 2. However, there was no difference between groups in the severity or incidence of upper respiratory tract infections (98438).
• Irritable bowel syndrome (IBS). It is unclear if oral Lactobacillus helveticus is beneficial for patients with constipation-predominant IBS. Details: Preliminary clinical research in adults with constipation-predominant IBS shows that consuming a 350-mL sterilized probiotic beverage containing L. helveticus, with or without polydextrose 5.85 grams, once daily for 7 days modestly reduces intestinal transit time when compared with baseline. There were also improvements in symptoms of constipation, including straining, passing of hard stools, and incomplete evacuation (106480). The sterilized L. helveticus beverage without polydextrose was used as the control beverage in this study. Thus, the effect of viable or non-viable L. helveticus is unclear.
• Rotaviral diarrhea. Oral Lactobacillus helveticus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in children 3 months to 4 years of age with acute gastroenteritis shows that taking a combination product containing L. helveticus R0052 200 million colony-forming units (CFUs) and Lacticaseibacillus rhamnosus GG R0011 3.8 billion CFUs twice daily for 5 days does not increase the speed of stool rotaviral clearance in the 28 days after starting the probiotic when compared with placebo (103441). Approximately 48% to 65% of the children enrolled in these studies were vaccinated against rotavirus, but it is not clear if this altered the study outcomes (98428,103441). More evidence is needed to rate Lactobacillus helveticus for these uses.

(Read more about LACTOBACILLUS HELVETICUS)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol-related liver disease. Although there has been interest in using oral Levilactobacillus brevis for alcohol-related liver disease, there is insufficient reliable information about the clinical effects of Levilactobacillus brevis for this condition.
• Bacterial vaginosis. Oral or vaginal Levilactobacillus brevis have only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with bacterial vaginosis cured within the past 48 hours shows that taking a product containing L. brevis in combination with other probiotics results in recurrence of vaginosis in 18.3% of patients, a statistically significant reduction compared with 32.1% of those taking placebo. The mean time to recurrence was approximately 23 days longer in patients taking the lactobacilli. The product contained L. brevis 1.08 billion colony-forming units (CFUs), Lactobacillus acidophilus 1.08 billion CFUs, and Lactobacillus crispatus LMG S-29995 3.24 billion CFUs (Lactogyn, Vésale Pharma, Belgium), and was taken twice daily for 7 days and then once daily for up to an additional 120 days (110950). A preliminary clinical trial shows that vaginal application with a tablet providing at least one billion colony-forming units of a combination of L. brevis, Lactiplantibacillus plantarum, and Ligilactobacillus salivarius (Florisia) might be beneficial for the treatment of bacterial vaginosis. Using this combination for 8 days reduces the proportion of patients with bacterial vaginosis by about 79% when compared with baseline. Taking this product does not seem to be more beneficial than using a pH lowering vaginal product (110951).
• Behcet disease. It is unclear if oral Levilactobacillus brevis is beneficial for oral ulcers in patients with Behcet disease. Details: Preliminary clinical research in patients with Behcet disease shows that taking lozenges containing an unknown amount of L. brevis (Inersan, VSL Pharmaceuticals) six times daily for 7 days reduces the average number of oral ulcers by about 1.5 when compared with baseline. Benefits lasted for at least one week after treatment was stopped (110959). This trial is limited by the lack of a control group.
• Common cold. It is unclear if oral Levilactobacillus brevis is beneficial for the common cold. Details: Preliminary clinical research in school children shows that consuming a commercially available probiotic test drink (Kagome) containing L. brevis KB290 6 billion colony-forming units per bottle five days per week for 8 weeks does not appear to reduce the incidence of common cold when compared with not consuming the drink (90238).
• Dental caries. It is unclear if oral Levilactobacillus brevis is beneficial for caries prevention. Details: Clinical research in children aged 4-14 years at risk of dental caries shows that taking lozenges containing L. brevis CD2 (Inersan, CD Investments srl) 2 billion colony-forming units twice daily for up to 60 days modestly reduces bleeding on probing when compared with taking a placebo lozenge. However, the effect of taking L. brevis on the prevention of dental caries was not investigated (110953,110958).
• Dry skin. It is unclear if topical Levilactobacillus brevis extract is beneficial for dry skin. Details: A small clinical trial shows that topical application with a cream providing a water-soluble non-viable extract of L. brevis 0.88 mg twice daily to the leg for 4 weeks modestly reduces symptoms such as scaling, roughness, redness, and cracking when compared with baseline. The proportions of patients experiencing a reduction in skin roughness, redness, scaling, and skin dryness were increased numerically when compared with placebo; however, it is unclear which differences are statistically or clinically significant (110955).
• Genital herpes. It is unclear if intravaginal Levilactobacillus brevis is beneficial for genital herpes. Details: A small preliminary clinical trial in adults with acute recurrent genital herpes shows that applying a specific capsule containing 3 different L. brevis strains into the vagina twice daily for 6 months resolves symptoms after 4.4 days, compared with 3 days in those taking acyclovir 400 mg twice daily. The difference between groups was not significant; however, the study may not have been large enough to detect a difference between groups. The dose used was 2 billion colony-forming units of L. brevis strain CD2 (Inersan, VSL Pharmaceuticals, Inc.), L. brevis strain KB290 (Japan Collection of Microorganisms: JCM 17312), and L. brevis strain SBC8803 (Frontier Laboratories of Value Creation Sapporo Breweries) twice daily (99787). The validity of these findings is unclear due to the use of an acyclovir dose that is typically intended for prevention, but not treatment, of acute genital herpes.
• Gingivitis. Although there has been interest in using oral Levilactobacillus brevis for gingivitis, there is insufficient reliable information about the clinical effects of Levilactobacillus brevis for this condition.
• Influenza. It is unclear if oral Levilactobacillus brevis is beneficial for influenza prevention. Details: Preliminary clinical research in school children shows that consuming a commercially available probiotic test drink (Kagome) containing heat-killed L. brevis KB290 6 billion colony-forming units (CFUs) per bottle five days per week for 8 weeks during flu season reduces the incidence of influenza from 24% in the non-test drink group to 16% in the test drink group (90238). A large clinical trial in healthy Japanese adults shows that drinking 200 mL of a beverage containing L. brevis KB290 at least 10 billion CFUs and beta-carotene 7.4-12.4 mg daily for 12 weeks during influenza season does not reduce the risk of influenza or fever when compared with placebo. However, in a subgroup analysis of patients under 40 years of age, the risk of influenza was reduced by around 53% when compared with placebo (107287). It is unclear if these findings are due to L. brevis, beta-carotene, or the combination.
• Insomnia. It is unclear if oral Levilactobacillus brevis is beneficial for insomnia. Details: A small preliminary clinical trial in adults with poor sleep quality shows that taking heat-killed L. brevis SBC8803 25 mg daily for 10 days modestly reduces periods of waking based on sleep diaries when compared with placebo. However, other subjective or objective measures of sleep quality were not significantly improved (110963). This study was small and may have been underpowered to detect differences between groups.
• Irritable bowel syndrome (IBS). It is unclear if oral Levilactobacillus brevis is beneficial for IBS. Details: A small clinical trial in patients aged 6 years and up with IBS shows that taking L. brevis KB290 at least 10 billion colony-forming units (CFUs) daily for 4 weeks does not improve IBS symptoms, such as number of bowel movements per week, volume of feces, or physical sensations, when compared with taking placebo. However, frequency of abdominal pain was modestly reduced when compared with taking placebo and there was a modest improvement in the frequency of watery or mushy feces when compared with baseline (110941). A small clinical trial in healthy adults with minor diarrhea-predominant IBS-like symptoms shows that taking a combination of L. brevis KB290 at least 25.7 billion cells including at least 10 billion CFUs, along with beta-carotene 4.0-4.5 mg, daily for 12 weeks modestly improves the intensity of abdominal pain and reduces stool frequency when compared with taking placebo. There were no differences between groups in improvements in stool consistency, incomplete evacuation, or other symptoms (110960). Although this study included adults with diarrhea-predominant IBS-like symptoms, patients diagnosed with IBS were excluded, limiting the generalizability of the study.
• Oral mucositis. It is unclear if oral Levilactobacillus brevis is beneficial for oral mucositis. Details: Clinical research in patients with head and neck cancer shows that taking a lozenge containing L. brevis CD2 two billion colony-forming units six times daily from the first day of radiation/chemotherapy and until one week after treatment reduces the relative proportion of patients with grade III and IV oral mucositis by about 30% when compared with placebo. However, the proportion of patients that develop grade I or II mucositis is similar (90290). However, preliminary clinical research in patients receiving radiotherapy shows that taking these same lozenges during the same time frame does not reduce the incidence or grade of severe oral mucositis or the need for enteral nutrition when compared with use of a sodium bicarbonate mouthwash three times daily (110956).
• Periodontitis. It is unclear if oral or topical Levilactobacillus brevis are beneficial for periodontitis. Details: A small preliminary clinical trial shows that taking lozenges containing L. brevis (VSL Pharmaceuticals) 200 mg four times daily for four days improves or results in a complete recovery of clinical parameters including gingival inflammation, plaque, calculus, temperature sensitivity, and bleeding, when compared with baseline (110957). However, this study is limited by the lack of a control group. A small clinical trial in patients undergoing scaling and root planing shows that a single topical application with a gel containing a combination of L. brevis (CECT7480) and Lactiplantibacillus plantarum (CECT7481) into the periodontal pocket, followed by taking one lozenge containing these probiotics daily for 3 months, does not reduce the number of diseased sites when compared with placebo. Although there was a two-fold increased odds of healing of gingival bleeding in patients using the probiotic product, the odds of having persisting diseased sites was modestly increased. The gel provided 6 billion colony-forming units (CFUs) each of L. brevis and Lactiplantibacillus plantarum. One lozenge provided 1.2 billion CFUs of each (110961).
• Pregnancy-induced nausea and vomiting. Oral Levilactobacillus brevis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics containing L. brevis during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units (CFUs) of L. brevis Lbr-35, Lactobacillus acidophilus La-14, Lactiplantibacillus plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Lacticaseibacillus paracasei DSM 13434 and Lpc-37, Ligilactobacillus salivarius Ls-33, Lacticaseibacillus casei Lc-11, and Bifidobacterium animalis subsp. lactis Bl-04, along with inulin 200 mg (107199).
• Traumatic oral ulcers. It is unclear if oral Levilactobacillus brevis is beneficial for prevention of traumatic oral ulcers. Details: A small clinical trial in patients aged 14 years and older shows that taking L. brevis CD2 (BioGrowing Co., Ltd, China) as soluble tablets providing four billion colony-forming units three times daily for 21 days starting the day of fixed orthodontic appliance placement reduces the number of days with lesions by 2.4 days or about 50%, and modestly reduces pain, when compared with taking placebo. However, quality of life was not improved (110962).
• Vaginal candidiasis. Although there has been interest in using vaginal Levilactobacillus brevis for vaginal candidiasis, there is insufficient reliable information about the clinical effects of Levilactobacillus brevis for this condition. More evidence is needed to rate Levilactobacillus brevis for these uses.

(Read more about LEVILACTOBACILLUS BREVIS)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Antibiotic-associated diarrhea. Oral Ligilactobacillus salivarius has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical trial in children aged 3 months and up shows that taking L. salivarius in combination with other probiotics does not reduce the risk of antibiotic-associated diarrhea when compared with taking placebo, when the more stringent definition is considered excluding diarrhea of other etiologies. However, the risk of diarrhea of any etiology is reduced by 35%. The probiotic supplement provided a total of 10 billion colony-forming units (CFUs) of L. salivarius W24, Bifidobacterium bifidum W23, Bifidobacterium animalis subsp. lactis W51, Lactobacillus acidophilus W37, L. acidophilus W55, Lacticaseibacillus paracasei W20, Lactiplantibacillus plantarum W62, and Lacticaseibacillus rhamnosus W71, daily from the first day of antibiotic treatment until 7 days after treatment ended (110969). A small clinical trial in patients taking amoxycillin shows that taking a specific product (Ecologic AAD) for 14 days modestly reduces diarrhea-like bowel movements, defined as a frequency of at least 3 per day and/or a very soft or watery consistency, when compared with taking placebo. The product used in this study provides a total of 5 billion CFUs twice daily of L. salivarius NIZO 3675, Lactobacillus acidophilus NIZO 3678 and NIZO 3887, Lacticaseibacillus paracasei NIZO 3672, Lactiplantibacillus plantarum NIZO 3684, Lacticaseibacillus rhamnosus NIZO 3689, Bifidobacterium bifidum NIZO 3804, Bifidobacterium animalis subsp. lactis NIZO 3680, and Enterococcus faecium NIZO 3886 (95405).
• Asthma. Oral Ligilactobacillus salivarius has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical trial in children ages 3-14 years with asthma shows that taking a combination of L. salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706) one billion colony-forming units (CFUs) each twice daily for 8 weeks and then once daily for 8 weeks modestly reduces the number of asthma exacerbations. The odds of having one or two asthma exacerbations was more than three fold in children taking placebo when compared with children taking probiotics. There was no effect on the duration of exacerbation or use of corticosteroids (111004).
• Atopic dermatitis (eczema). It is unclear if oral Ligilactobacillus salivarius is beneficial for atopic dermatitis. Details: L. salivarius LS01 (DSM 2275) has been investigated for the treatment of atopic dermatitis in adults. A small clinical trial shows that taking L. salivarius LS01 1 billion colony-forming units (CFUs) twice daily for 16 weeks modestly reduces symptom severity and improves skin-related quality of life when compared to baseline. However, it is unclear if L. salivarius is beneficial when compared with taking placebo (112541). Another small clinical trial shows that taking a preparation containing L. salivarius LS01 5 billion CFUs daily, along with Streptococcus thermophilus ST10 and tara gum, daily for 1 month modestly improves symptoms when compared with taking placebo (112544). It is unclear if this effect is due to L. salivarius, other ingredients, or the combination. L. salivarius has also been investigated in children with atopic dermatitis. In children up to 11 years of age, a small clinical trial shows that taking L. salivarius LS01 (DSM 22775) daily reduces symptom severity and itch intensity when compared with baseline. Benefits persisted for 4 weeks after treatment. Children took 2 billion CFUs daily for 8 weeks followed by 1 billion CFUs daily for an additional 8 weeks (112540). However, it is unclear if these changes are due to the product or natural changes of the condition. Other clinical research has investigated the effects of L. salivarius in combination with other probiotics for the prevention of atopic dermatitis. A combination of L. salivarius, Lacticaseibacillus paracasei, Bifidobacterium animalis subsp. lactis, and Bifidobacterium bifidum, a total of 10 billion CFUs daily provided from 36 weeks' gestation and then to the infant until age 6 months, reduces the prevalence of atopic dermatitis at age two by approximately 60% (90234). It is unclear if this effect is due to L. salivarius, other ingredients, or the combination.
• Bacterial vaginosis. Vaginal Ligilactobacillus salivarius has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A preliminary clinical trial shows that vaginal application with a tablet providing at least one billion CFUs of a combination of L. salivarius, Lactiplantibacillus plantarum, and Levilactobacillus brevis (Florisia) might be beneficial for the treatment of bacterial vaginosis. Using this combination for 8 days reduces the proportion of patients with bacterial vaginosis by about 79% when compared to baseline. Taking this product does not seem to be more beneficial than using a pH lowering vaginal product (110951).
• Dental caries. It is unclear if oral heat-killed or viable Ligilactobacillus salivarius is beneficial for preventing dental caries. Details: Preliminary clinical research in children ages 3-6 years shows that chewing tablets containing heat-killed L. salivarius (HM6 Paradens) (Acidolac Dentifix Kids, Polpharma, Poland) 10 mg twice daily for 2 weeks reduces the prevalence and incidence of dental caries over 12 months by an intermediate to large amount when compared with usual care with toothbrushing twice daily (112538).
• Diabetes. It is unclear if oral Ligilactobacillus salivarius is beneficial for gestational diabetes. Details: Clinical research in patients with newly diagnosed gestational diabetes or impaired glucose tolerance at less than 34 weeks gestation shows that taking L. salivarius UCC118 1 billion colony-forming units daily until delivery does not affect levels of fasting glucose, the need for pharmacological therapy, or birthweight of the infant, when compared with taking placebo. There were also no clinically relevant benefits on plasma lipid levels. All patients were given dietary advice and regular follow-up care (96894).
• Exercise-induced respiratory infections. It is unclear if oral Ligilactobacillus salivarius is beneficial for preventing exercise-induced respiratory infections. Details: A small clinical trial in athletes shows that taking L. salivarius 20 billion colony-forming units daily for 16 weeks during spring endurance training does not reduce the proportion of patients developing upper respiratory tract symptoms for at least a week or the number of episodes, when compared with taking placebo (112542). However, the study may have been inadequately powered to detect a difference between groups.
• Halitosis. It is unclear if oral Ligilactobacillus salivarius is beneficial for halitosis. Details: A small clinical trial shows that taking a dissolving tablet containing L. salivarius WB21 (Wakamoto Pharmaceutical, Japan) 670 million colony-forming units (CFUs) and xylitol 3 times daily for 2 weeks reduces the concentration of volatile sulfur compounds, but does not reduce halitosis or tongue coating, when compared with taking placebo (112551). Also, another small clinical trial shows that chewing a dissolving gum containing L. salivarius G60 1 billion CFUs with inulin 1 gram every 12 hours after meals for 10 days, but not L. salivarius alone, modestly reduces halitosis and improves quality of life when compared with taking placebo. There was no effect on tongue coating (112548). However, these studies may have been inadequately powered to detect a difference between the L. salivarius alone and placebo groups. In contrast, one small and preliminary clinical trial shows that taking a dissolving tablet containing L. salivarius WB21 (Wakamoto Pharmaceutical, Japan) 670 million CFUs and xylitol 3 times daily modestly reduces oral malodor when compared to baseline. L. salivarius was taken by patients with physiologic or pathological halitosis for 2 or 4 weeks, respectively (112549). The validity of this study is limited by the lack of a comparator group.
• Irritable bowel syndrome (IBS). Although there has been interest in using oral Ligilactobacillus salivarius for IBS, there is insufficient reliable information about the clinical effects of L. salivarius for this condition.
• Mastitis. It is unclear if oral Ligilactobacillus salivarius is beneficial for mastitis prevention or treatment. Details: A small clinical study shows that taking L. salivarius PS2 1 billion colony-forming units (CFUs) daily from 27-32 weeks' gestation until childbirth reduces mastitis rate by 56% when compared with placebo in patients with a history of infectious mastitis. Milk bacterial counts and breast pain in patients that did develop mastitis were also modestly reduced (102291). L. salivarius has also been investigated in the treatment of infectious mastitis. Taking L. salivarius CECT5713 1 billion CFUs daily for 3 weeks results in breast pain recovery and mastitis recurrence in 85% and 7.1% of patients, respectively, compared with 29% and 30.7% of those taking an antibiotic. Milk bacterial counts were also reduced in patients taking L. salivarius (112524). The validity of this study is limited by the lack of blinding. Also, the type of antibiotic used was dependent on the primary care provider.
• Otitis media. It is unclear if oral Ligilactobacillus salivarius is beneficial for otitis media prevention. Details: A small and preliminary clinical trial in children with recurrent otitis media shows that taking L. salivarius PS7 1 billion colony-forming units daily for 6 months reduces the number of acute otitis media episodes by 84% when compared to the 6-month period prior to supplementation (112545). The validity of this study is limited by the lack of a direct comparator group and the use of historical data as comparison.
• Periodontitis. It is unclear if oral Ligilactobacillus salivarius is beneficial for periodontitis. Details: Small clinical trials in patients with mild to moderate periodontitis show that taking L. salivarius does not affect plaque severity, pocket depth, or bleeding on probing when compared with taking placebo (112537,112550). However, there seems to be a modest benefit in some parameters in smokers (112550). These studies have used a tablet providing L. salivarius WB21 (Wakamate Ds, Wakamoto Pharmaceutical Co., Japan) 670 million CFUs 3 times daily for 8 weeks (112550) or a suspension providing an unknown quantity of L. salivarius SGL03 (Salistat SGL03) daily for 30 days (112537). This product (Salistat SGL03) also provided unknown quantities of gluco-oligosaccharides, lactoferrin, essential oils of lemon and rosemary, and vitamin D.
• Pregnancy-induced nausea and vomiting. Oral Ligilactobacillus salivarius has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical trial shows that taking probiotics during pregnancy reduces the severity and duration of nausea and vomiting by 16% to 54%. There was also a small benefit on stool hardness. A specific probiotic (Probiotics 10, Nature's Bounty) was taken as 2 capsules daily for two back-to-back cycles of six days with probiotics and two days without. Each capsule contained a total of 10 billion colony-forming units of L. salivarius Ls-33, Lactobacillus acidophilus La-14, Lactiplantibacillus plantarum 299v and DSM 15312, Lactobacillus delbrueckii subsp. bulgaricus Lb-87, Lacticaseibacillus paracasei DSM 13434 and Lpc-37, Levilactobacillus brevis Lbr-35, Lacticaseibacillus casei Lc-11, and Bifidobacterium animalis subsp. lactis Bl-04, along with inulin 200 mg (107199).
• Ulcerative colitis. Oral Ligilactobacillus salivarius has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with moderate to severe symptoms taking mesalazine 1200 mg daily shows that taking an unknown dose of L. salivarius twice daily along with Bifidobacterium bifidum BGN4 and Lactobacillus acidophilus (Acronelle, Bromatech srl, Milan, Italy) for 2 years modestly improves patient- and physician-scales of overall symptoms when compared with taking mesalazine alone. There were also improvements in stool frequency and rectal bleeding (110981). More evidence is needed to rate Ligilactobacillus salivarius for these uses.

(Read more about LIGILACTOBACILLUS SALIVARIUS)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. It is unclear if oral Limosilactobacillus fermentum is beneficial for asthma. Details: A small clinical study in children aged 6 and up with asthma shows that taking L. fermentum GM-090 2 billion colony-forming units (CFUs), Lacticaseibacillus paracasei GMNL-133 2 billion CFUs, or both strains together daily for 3 months seems to modestly reduce asthma severity and increase Childhood Asthma Control Test (C-ACT) scores when compared with placebo (99785).
• Atopic dermatitis (eczema). It is unclear if oral Limosilactobacillus fermentum is beneficial for atopic dermatitis. Details: In children aged 1-18 years with atopic dermatitis, clinical research shows that taking L. fermentum GM-090 2 billion colony-forming units (CFUs), alone or with L. paracasei GMNL-133 2 billion CFUs daily each, for 3 months modestly reduces symptom severity when compared with placebo (98440).
• Bacterial vaginosis. Oral Limosilactobacillus fermentum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A combination product containing L. fermentum has been tried in patients with both bacterial vaginosis and aerobic vaginitis, which typically occurs after unsuccessful treatment of bacterial vaginosis with antibiotics. A clinical study in these patients shows that taking a specific combination product (prOVag, IBSS BIOMED S.A.) containing a total of 100 million colony-forming units of L. fermentum 57A, Lactiplantibacillus plantarum 57B, and Lactobacillus gasseri 57C daily for 10 days in conjunction with standard metronidazole treatment increases the duration of symptom-free remission to 71 days, compared with 47 days in those taking metronidazole alone (99784).
• Colic. Oral Limosilactobacillus fermentum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in infants with colic shows that adding a combination of L. fermentum CECT5716 and Bifidobacterium breve as 100 million colony-forming units (CFUs) each daily, to human milk, formula, or water for 28 days reduces the time spent crying per week by approximately 160 minutes from baseline. Taking this combination is at least as effective as taking simethicone 20 mg four times daily (105150).
• Exercise-induced respiratory infections. It is unclear if oral Limosilactobacillus fermentum is beneficial for preventing respiratory infections in athletes. Details: Clinical research in male and female athletes shows that taking L. fermentum VRI-003 (PCC, Probiomics Ltd, Australia) 1 billion colony-forming units (CFUs) daily for 11 weeks does not reduce the number, duration, or severity of self-reported upper respiratory tract symptoms when compared with placebo (112564). A small clinical study in elite male athletes shows that taking 12 billion CFUs of this same strain for 4 weeks reduces the number of days of respiratory symptoms in general by 58% compared with placebo. There was no effect on symptom severity, the number of episodes, or the number reporting an episode (112567). Whether L. fermentum is beneficial for specifically preventing lower respiratory tract infections is unclear and might depend on sex of the participant. One clinical trial in males shows that taking L. fermentum VRI-003 1 billion CFUs daily for 11 weeks modestly reduces the severity, number, and duration of lower respiratory tract symptoms when compared with placebo. However, in females, although there is a modest reduction in symptom severity, the number and duration of these symptoms increased (112564). The reasons for these discrepant findings are unclear but may be explained by differences in doses, treatment durations, number of individuals, and populations studied.
• Influenza. It is unclear if oral Limosilactobacillus fermentum is beneficial for preventing influenza in vaccinated adults. Details: A small clinical trial shows that taking L. fermentum CECT5716 10 billion colony-forming units daily for 2 weeks prior to and following influenza vaccination does not reduce the incidence of influenza-like illness over the following 4 months when compared with placebo. However, the number of episodes was modestly reduced in the 5th month following vaccination (112570). This study may have been inadequately powered to detect a difference between groups.
• Mastalgia. It is unclear if oral Limosilactobacillus fermentum is beneficial for mastalgia. Details: Clinical research in patients with painful breastfeeding shows that taking L. fermentum CECT5716 daily for 3 weeks modestly decreases breast pain, and possibly Staphylococcus counts, when compared with placebo. L. fermentum was taken in doses of 3 billion CFUs, 6 billion CFUs, or 9 billion CFUs daily. These patients had painful breastfeeding and high mammary Staphylococcus counts, without acute mastitis (112568).
• Mastitis. It is unclear if oral Limosilactobacillus fermentum is beneficial for mastitis treatment or prevention. Details: Most research has been conducted in patients with mastitis. In patients with breast abscess related to lactational mastitis, clinical research shows that taking L. fermentum CECT5716 3 billion colony-forming units (CFUs) daily for 4 weeks following needle aspiration does not increase pain relief or reduce the recurrence rate of mastitis when compared with placebo. However, the rate of breastfeeding discontinuation due to mastitis recurrence was reduced by about 87% (112563). Taking L. fermentum CECT5716 1 billion CFUs daily for 3 weeks results in breast pain recovery and mastitis recurrence in 88% and 10.5% of patients, respectively, compared with 29% and 30.7% of those taking an antibiotic. Milk bacterial counts were also reduced in patients taking L. fermentum (112524). The validity of this study is limited by the lack of blinding. Also, the type of antibiotic used was dependent on the primary care provider. Research has also been conducted to determine the effect of L. fermentum on mastitis prevention. Clinical research shows that taking L. fermentum CECT5716 3 billion CFUs daily for 16 weeks starting within 6 days of childbirth reduces the clinical mastitis incidence rate by 51% when compared with placebo. The incidence of breast pain was also modestly reduced (112575).
• Obesity. It is unclear if oral Limosilactobacillus fermentum is beneficial for obesity. Details: Clinical research in adults with a body mass index (BMI) between 25 kg/m² and 31.9 kg/m² shows that taking L. fermentum MG4231 and MG4244 (MED-02) 5 billion colony-forming units daily for 12 weeks modestly reduces body weight, body fat mass, and body fat percentage, when compared with placebo. There was no difference in waist or hip circumference, BMI, or blood lipids (112562).
• Polycystic ovary syndrome (PCOS). Oral Limosilactobacillus fermentum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical trial shows that 31.3% of patients with PCOS taking L. fermentum in combination with other probiotics daily for 6 months had regular menstrual cycles compared with 12.5% of those taking placebo. There were also modest improvements in testosterone levels and waist circumference, but not other hormones, insulin resistance, body weight, or most measures of quality of life. The product provided L. fermentum UBLF-31 1 billion colony-forming units along with Lactobacillus acidophilus UBLA-34, Bifidobacterium bifidum UBBB-55, Lactiplantibacillus plantarum UBLP-40, Lacticaseibacillus casei UBLC-42, Lacticaseibacillus rhamnosus UBLR-58, Limosilactobacillus reuteri UBLRu-87, and fructo-oligosaccharides (FOS) daily for 2 months and then twice daily for 4 months. All patients also underwent dietary and lifestyle changes (110974).
• Urinary tract infections (UTIs). Vaginal Limosilactobacillus fermentum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial shows that 21% of patients with an acute UTI using vaginal suppositories containing L. fermentum B-54 and Lacticaseibacillus rhamnosus GR-1 had a recurring UTI compared with 47% of those using control suppositories. The probiotic suppositories, providing 1.6 billion colony-forming units of this combination, were used twice weekly for 2 weeks following a 3-day antibiotic course, then once a month for 2 months (6095).
• Vaginal candidiasis. Vaginal Limosilactobacillus fermentum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In a small preliminary clinical trial in patients with recurrent vulvovaginal candidiasis who had undergone a week of oral fluconazole treatment followed by intravaginal L. fermentum LF10 and Lactobacillus acidophilus LA 02, 72.4% of patients demonstrated a lack of clinical recurrence over a 7 month observational period. All patients took fluconazole 200 mg three times in the first week followed by intravaginal application with at least 0.4 billion colony-forming units of each probiotic, along with arabinogalactan and fructo-oligosaccharides (FOS) on alternate days for 10 days and then once weekly for 10 weeks (111781). The validity of this study is limited by the lack of a comparator group. More evidence is needed to rate Limosilactobacillus fermentum for these uses.

(Read more about LIMOSILACTOBACILLUS FERMENTUM)

POSSIBLY EFFECTIVE

• Abdominal pain. Oral Limosilactobacillus reuteri seems to reduce abdominal pain in children 4 years and older. It is unclear if any species are beneficial in adults. Details: Clinical research in children aged 4-18 years with abdominal pain shows that taking L. reuteri DSM 17938 as 100 or 200 million colony-forming units (CFUs) daily for 8-12 weeks, but not 4 weeks, reduces abdominal pain severity and increases the number of days without pain when compared with placebo (17120,96898,105130,113510,112528,112530). A meta-analysis of clinical research shows that some benefit seems to be maintained 4 weeks after follow-up. However, the benefit on pain severity is smaller with study durations of 8-12 weeks. In addition, there was no change in the number of children with no symptoms at the end of the intervention period (105130). Although some individual research disagrees (96898), most research shows that there was no effect of L. reuteri DSM 17938 on pain frequency (105130,112528). Most of the available clinical trials are small and well-designed studies in larger populations are still needed.
• Colic. Oral Limosilactobacillus reuteri seems to be beneficial for colic. Details: Clinical research shows that giving L. reuteri DSM 17938 (Probiotic Drops, BioGaia AB) for 21-28 days can reduce daily crying time and fecal excretion of Escherichia coli in breastfed infants. Symptoms appear to improve within one week of treatment (17118,17530,90240,90294,96278,98432,107505). Meta-analyses of clinical research show that L. reuteri reduces crying time in infants with colic (107505,113504). One recent meta-analysis of clinical research investigating the effect of L. reuteri, usually as DSM 17938 or ATCC55730, shows that crying time is reduced by approximately 80 minutes daily when compared with control or placebo. There was also an increase in treatment efficacy, defined as a reduction in average daily crying time of at least 50%, when compared with control or placebo. However, the quality of research is poor and there was low confidence in the findings (107505). In some clinical studies, taking L. reuteri DSM 17938 reduced colic symptoms more effectively than simethicone 60 mg once or twice daily over a period of 28 days (17530,96278). Some evidence suggests that this specific strain is also effective in reducing daily crying time in formula-fed infants when given for 28-90 days (90264,96278). L. reuteri strain DSM 17938 (Probiotic Drops, BioGaia AB) 100 million colony-forming units (CFUs) daily was used in these studies (17118,17530,90240,90264,90294,96278). However, results from one large study suggest that this strain does not reduce crying duration in breastfed infants and worsens crying time and fussiness in formula-fed infants (90293). Reasons for this discrepancy are unclear. However, patients in the latter study were recruited from an emergency room and may have had more severe colic than patients treated in other studies. Another large clinical trial in formula-fed infants with colic shows that feeding a partially hydrolysed lactose-reduced formula containing an unspecified amount of L. reuteri DSM 17938 daily for 4 weeks might increase crying time when compared with a standard formula. However, it is unclear if this is related to L. reuteri or other changes in the formulation of the formula (112529). Some research has evaluated L. reuteri in combination with Lacticaseibacillus rhamnosus. Clinical research in infants aged 4-12 weeks with colic shows that taking this combination (FloraActive) 250 million CFUs with fructo-oligosaccharides 3.33 mg and vitamin D3 200 IU daily for 28 days reduces mean crying time by 2.7 hours by the end of the study, compared to a 1.9-hour reduction in the vitamin D group (99783). Some research has evaluated whether taking L. reuteri during pregnancy is beneficial for preventing colic. Clinical research shows that taking L. reuteri LR92 DSM 26866 (Prokid) 100 million CFUs daily during the last 4 weeks of pregnancy modestly reduces infant colic severity and frequency in the first 5 months when compared with taking placebo. Infants from mothers receiving placebo were 2.36-fold more likely to have symptoms of colic (112533).
• Constipation. Oral Limosilactobacillus reuteri seems to be beneficial for functional constipation. Details: The best evidence of benefit in patients with functional constipation is with L. reuteri DSM 17938 (95339,95341,95343,113503,113507). Taking this product in doses of 100 million colony-forming units (CFUs) daily in children and 100 million CFUs 2-4 times daily in adults for 4-8 weeks reduces abdominal discomfort, abdominal pain, bloating, and incomplete defecation, and might increase the number of bowel movements per week, when compared with placebo (95339,95341,95343,113507). In infants and children under 6 years of age, taking L. reuteri DSM 17938 100 million CFUs twice daily for 4 weeks is as effective as taking magnesium oxide 30 mg/kg daily for improving the frequency of defecation from baseline. However, there is no further beneficial effect when these products are taken together (113503). However, some clinical research shows that taking L. reuteri might not be beneficial in children also given other medications for constipation. One clinical trial in children ages 3-7 years given macrogol starting 10 grams daily shows that taking L. reuteri DSM 17938 100 million CFUs daily for 8 weeks does not increase the number of bowel movements or reduce abdominal pain or pain during defecation when compared to macrogol alone (112531). A small clinical study in children shows that taking L reuteri DSM 17983 100 million CFUs daily in combination with lactulose 1-3 mL/kg daily for 12 weeks is no more effective than lactulose alone for improving pain, stool frequency, and consistency (112525). However, it is unclear if this study was powered adequately to detect differences between groups.
• Diarrhea. Most research shows that oral Limosilactobacillus reuteri modestly reduces the duration of acute diarrhea in children under 5 years of age. It is unclear if oral L. reuteri is beneficial for diarrhea prevention in these children. Details: Most clinical research shows that taking L. reuteri DSM 17938 (BioGaia drops, BioGaia AB) up to 100 billion colony-forming units (CFUs) daily for up to 7 days, along with oral or intravenous rehydration therapy, can modestly reduce the duration of diarrhea, primarily of non-rotaviral origin, usually in infants and children ages 3 months to 5 years (7751,7753,90246,95336,107636). In one study, the duration of watery diarrhea in hospitalized children was reduced by 1.2 days when compared with placebo and persistence of watery diarrhea after 3 days was reduced by about 40%. Although the diarrhea relapse rate was also reduced by 64%, the duration of hospital stay was not affected. About 60% of the children in this study had diarrhea of rotaviral origin (113508). However, some research disagrees. One clinical trial in children under 5 years shows that taking L. reuteri DSM 17938 200 million CFUs daily for 5 days does not reduce the duration of diarrhea when compared with taking placebo, although the duration of hospitalization was modestly reduced. About 38% of the children in this study had diarrhea of rotaviral origin (112526). The European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388); however, both guidelines note that most evidence is low quality. L. reuteri has also been examined for diarrhea prevention. One clinical trial in healthy children ages 3-36 months shows that taking L. reuteri DSM 17938 (BioGaia drops, BioGaia AB) 100 million CFUs daily for 3 months modesty reduces the frequency and duration of diarrhea by 35% and 1.1 days respectively, as well as day care absenteeism, when compared with taking placebo. Benefits persisted for an additional 3 months (113506). However, taking L. reuteri might not prevent hospital-acquired diarrhea. In children ages 1-48 months, taking 100 million or 1 billion CFUs of this strain during hospitalization for reasons other than diarrhea does not reduce the occurrence or duration of diarrhea or the length of hospital stay when compared with taking placebo (112523,112534).
• Helicobacter pylori. Oral Limosilactobacillus reuteri seems to reduce the adverse effects associated with H. pylori symptoms and standard treatment regimens. It is unclear if oral L. reuteri improves the rate of H. pylori eradication. Details: Clinical research in adults shows that taking a mixture of two strains of L. reuteri (DSM 17938 and ATCC PTA 6475; e.g., Gastrus, BioGaia AB) 100 million colony-forming units (CFUs) of each strain once daily for about 14 weeks before and after triple therapy does not increase the eradication rate when compared with placebo. However, there was a reduction in the frequencies of some treatment side effects, including abdominal pain, epigastric pain, bloating, and diarrhea (90253). Other clinical research in adults also shows that taking a mixture of L. reuteri DSM 17938 and ATCC PTA 6475 daily for 30 days starting with a 10-day regimen of quadruple therapy does not increase the eradication rate when compared with taking placebo. However, abdominal pain and distension were reduced in 47% to 121% more patients, respectively. The proportion of patients with other gastrointestinal symptoms did not differ between groups (113505). Other research suggests that taking L. reuteri improves the rate of H. pylori eradication as well as adverse effects associated with standard treatment. Clinical research in adults undergoing levofloxacin-based therapy shows that taking L. reuteri (Reuflor Italchimici Pomezia) 100 million CFUs three times daily for 14 days during eradication therapy and 1 week thereafter results in an eradication rate of 80%, compared with 60% in those taking placebo. Nausea and diarrhea associated with the use of eradication therapy were also modestly reduced, but there was no effect on other adverse effects associated with treatment (107563). Other clinical research in adults shows that taking L. reuteri DSM 17 938 and ATCC PTA 6475 (Gastrus, BioGaia, Sweden) 200 million CFUs each once daily for 10 days with proton pump inhibitor, metronidazole, and tetracycline triple therapy is as effective as taking twice daily bismuth quadruple therapy for H. pylori eradication and improving gastrointestinal symptoms (112522). L-reuteri has also been investigated in children. A small clinical trial in children undergoing sequential therapy shows that taking L. reuteri ATCC 55730 (SD2112) (Reuterin, Noos) 100 million CFUs daily does not increase the eradication rate when compared with placebo. However, overall gastrointestinal symptoms, such as abdominal distension, eructation, and halitosis, were modestly reduced (107564). Heat-killed L. reuteri has also been investigated in adults with H. pylori. Clinical research shows that taking heat-killed L. reuteri DSM17648 (Vita Medical Science & Technology CO., LTD) 10 billion cells daily for 4 weeks, with the latter 2 weeks in combination with triple therapy comprised of esomeprazole, amoxicillin, and clarithromycin twice daily, does not improve H. pylori eradication rate. However, gastrointestinal symptoms, including abdominal distention and diarrhea, were modestly improved (107504). However, taking non-viable L. reuteri DSM17648 in combination with Lactobacillus acidophilus, Lacticaseibacillus casei, and Bifdobacterium animalis subsp. lactis (Phyloshot) twice daily does not increase the eradication rate of 14-day quadruple therapy or reduce adverse effects when compared with taking placebo (111101).
• Hypercholesterolemia. Oral Limosilactobacillus reuteri seems to be modestly beneficial for lowering cholesterol levels. Details: Meta-analyses of two clinical trials show that taking L. reuteri can reduce total cholesterol by about 22 mg/dL and low-density lipoprotein (LDL) cholesterol by about 20 mg/dL in patients with or without hypercholesterolemia (95399). The included studies used a specific yogurt or specific capsules containing L. reuteri (strain NCIMB 30242; Cardioviva, Micropharma Limited) 2.9-50 billion colony-forming units (CFUs) daily for 6-9 weeks (90268,90269). Taking L. reuteri does not appear to improve high-density lipoprotein (HDL) cholesterol or triglyceride levels in most studies (90268,90269,95399).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Antibiotic-associated diarrhea. It is unclear if oral Limosilactobacillus reuteri is beneficial for antibiotic-associated diarrhea (AAD) in adults and children. Details: A small clinical trial in hospitalized adults shows that taking L. reuteri ATCC 55730 100 million colony-forming units (CFUs) twice daily for 4 weeks reduces the frequency of AAD to 8%, compared with 50% in those taking placebo. There was no difference between groups for other gastrointestinal adverse effects (95401). However, in children, taking L. reuteri DSM 17938 200 million CFUs twice daily during antibiotic treatment was no more effective than placebo for reducing the frequency of AAD or other gastrointestinal adverse effects (102293).
• Atopic dermatitis (eczema). It is unclear if oral L. reuteri is beneficial for the treatment or prevention of atopic dermatitis. Details: Some research has evaluated L. reuteri for the TREATMENT of atopic dermatitis. A small clinical trial in children aged 1-13 years shows that taking a combination of lyophilized L. reuteri DSM 122460 and Lacticaseibacillus rhamnosus 19070-2, 10 billion CFUs of each strain twice daily for 6 weeks, improves subjective symptoms of atopic dermatitis in 56% of patients, compared with 15% of those taking placebo. However, there were no differences between groups for overall clinical scores or use of topical corticosteroids (12773). Clinical research in adults with atopic dermatitis shows that taking 1 billion CFUs each of L. reuteri PBS072, Lactiplantibacillus plantarum PBS067, and L. rhamnosus LRH020 for 56 days modestly reduces the severity of symptoms and improves skin smoothness and moisturization for up to an additional 28 days when compared with placebo (107506). Other research has investigated the effects of L. reuteri for the PREVENTION of atopic dermatitis. Clinical research shows that taking L. reuteri ATCC 55730 as 100 million CFUs daily during the last month of gestation and then through the first year of life reduces the incidence of IgE-associated atopic dermatitis to 8% at 1-2 years of age, compared to 20% of those taking placebo. However, there was no effect on the overall incidence of atopic dermatitis (16741).
• Atopic disease. It is unclear if oral Limosilactobacillus reuteri is beneficial for the prevention of atopic disease in infants. Details: Clinical research shows that providing L. reuteri ATCC 55730 100 million colony-forming units (CFUs) daily during the last month of gestation and then through the first year of life reduces the prevalence of IgE-associated eczema and skin prick positivity at age 2 years when compared with placebo (16741) but does not reduce the risk of atopic disease, including asthma, allergic rhinoconjunctivitis, eczema, and skin prick reactivity at 7 years of age (90203).
• Bacterial vaginosis. Oral Limosilactobacillus reuteri has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: The available clinical research has investigated the use of a specific strain, L. reuteri RC-14, in combination with Lacticaseibacillus rhamnosus GR-1. Some research suggests that this combination does not modify vaginal or fecal microbiota or improve cure or recurrence rates in patients also treated with metronidazole vaginally, when compared with taking placebo (111996,111998). Doses in these studies included at least 1 billion CFUs daily of L. reuteri plus L. rhamnosus for 30 days in otherwise healthy premenopausal adults (111996) or 2 billion CFUs of L. reuteri and L. rhamnosus twice daily for 6 months in patients with HIV (111998). However, other clinical research in patients with bacterial vaginosis suggests that taking this combination of probiotics might be beneficial for improving cure rates and improving the vaginal microbiota. In these studies, cure rates increased from 40%-50% with placebo to approximately 88% with the L. reuteri and L. rhamnosus combination. In addition to a single dose of tinidazole 2 grams or metronidazole treatment, 2 billion CFUs each of L. reuteri and L. rhamnosus were used daily for about 1 month in these studies (111997,112508). The reasons for these discrepancies are unclear but may be related to the differences in patient populations, geographical locations, and/or dosing of the product. The effect of L. reuteri RC-14 and L. rhamnosus GR-1 for the prevention of bacterial vaginosis has also been investigated. A clinical study shows that taking capsules containing L. reuteri RC-14 and L. rhamnosus GR-1 as 2.5 billion CFUs daily from 9-14 weeks' gestation until delivery does not affect the rate of bacterial vaginosis when compared with placebo (102292). In patients with HIV treated with metronidazole 400 mg twice daily for 10 days, taking 2 billion CFUs of L. reuteri and L. rhamnosus twice daily for 6 months does not improve the recurrence rates when compared with taking placebo (111998).
• Cancer. Although there has been interest in using oral Limosilactobacillus reuteri for cancer prevention or treatment, there is insufficient reliable information about the clinical effects of L. reuteri for this condition.
• Canker sores. It is unclear if Limosilactobacillus reuteri lozenges are beneficial for canker sores. Details: A small clinical trial shows that sucking on a lozenge containing L. reuteri DSM17938 and ATCC PTA 5289 (ProDentis, BioGaia AB) 500 million CFUs twice daily for 90 days does not improve pain or severity of canker sores when compared with placebo (105145).
• Clostridioides difficile infection. It is unclear if oral Limosilactobacillus reuteri is beneficial for C. difficile prevention. Details: Current guidelines from the Infectious Diseases Society of America (IDSA) state that there is insufficient information to recommend administration of probiotics for the primary prevention of C. difficile-associated diarrhea (107538). The benefits of L. reuteri specifically for this purpose are unclear.
• Cystic fibrosis. It is unclear if oral Limosilactobacillus reuteri is beneficial for cystic fibrosis. Details: Clinical research in children and young adults with cystic fibrosis shows that taking L. reuteri 10 billion colony-forming units daily for 6 months reduces the percentage of patients experiencing pulmonary exacerbations from 37% to 3% and upper respiratory tract infections from 20% to 3% when compared with placebo (90245).
• Dental caries. It is unclear if oral Limosilactobacillus reuteri is beneficial for dental caries prevention. Details: Preliminary clinical research shows that taking L. reuteri 100 million colony-forming units (CFUs) daily, from 4 weeks prior to expected delivery and until birth, and then continuing the supplement in the infants until 12 months of age, appears to decrease the prevalence of caries in the primary (baby) teeth of the child by the age of 9 years (90292).
• Dental peri-implantitis. It is unclear if oral Limosilactobacillus reuteri is beneficial for dental peri-implantitis. Details: A small clinical trial in patients with mild to moderate dental peri-implantitis shows that taking L. reuteri DSM 17938 and ATCC PTA 5289 (ProDentis, BioGaia, Sweden) one hundred million colony-forming units (CFUs) daily for 24 weeks starting a week after scaling and a 3-day course with antibiotics does not improve most measures of dental health when compared with taking antibiotics alone (113509). Another small clinical trial in patients with peri-implantitis shows that taking the same dose of L. reuteri DSM 17938 and ATCC PTA 5289 (PerioBalance, Sunstar Suisse SA, Switzerland) daily as a lozenge for 30 days as adjuvant to non-surgical mechanical debridement modestly improves pocket depth and bleeding on probing at implant level for up to 2 months after treatment when compared with mechanical therapy alone. There was no difference between groups in general bleeding on probing or plaque severity (112532). A meta-analysis of these and one other small study shows that taking L. reuteri DSM 17938 and LR ATCC PTA 5289 is modestly favored when compared with taking placebo in these patients when pocket depth, bleeding, and plaque are all taken into consideration, but not when analyzed separately (112527). However, the individual studies were small and it is unclear if they were adequately powered. Also, the clinical relevance of any benefit is unclear.
• Dental plaque. It is unclear if oral Limosilactobacillus reuteri is beneficial for dental plaque prevention. Details: Preliminary clinical research shows that taking L. reuteri, from 4 weeks prior to expected delivery until birth, and then continuing the supplement in the infants until 12 months of age, does not reduce dental plaque in the primary (baby) teeth of the child by the age of 9 years (90292). The available evidence related to the use of L. reuteri for plaque in adults is mixed. In a systematic review, four of the available eight studies showed some benefit on plaque when compared with placebo. However, the meta-analysis included only two studies investigating the use of L. reuteri, in tablets or lozenges for 7-8 weeks, and found no benefit for plaque. Overall, there was moderate evidence suggesting a lack of effect of L. reuteri on dental plaque (105147).
• Diabetes. It is unclear if oral Limosilactobacillus reuteri is beneficial for type 2 diabetes. Details: A small clinical trial in patients with type 2 diabetes using no antidiabetes medications shows that taking L. reuteri ADR-1 M207154 4 billion colony-forming units (CFUs) daily for 6 months modestly reduces glycated hemoglobin (HbA1c) when compared with placebo. These benefits lasted for an additional 3 months after treatment cessation. However, there was no effect on blood pressure or levels of blood glucose, insulin, or lipids. Taking heat-killed L. reuteri ADR-3 M209263 20 billion cells daily for 6 months modestly reduces systolic blood pressure when compared with placebo. However, there was no effect on HbA1c or other glycemic, lipid, or blood pressure indices (107565). Also, another small clinical trial in patients with type 2 diabetes who are using insulin and other antidiabetes therapy shows that taking L. reuteri DSM 17938 (BioGaia) 100 million or 10 billion CFUs daily for 12 weeks has no effect on HbA1c, insulin sensitivity, blood lipids, blood pressure, liver health, adiposity, or microbiota composition when compared with placebo (107566).
• Diverticulitis. It is unclear if oral Limosilactobacillus reuteri is beneficial for diverticulitis. Details: A small clinical study in patients with acute uncomplicated diverticulitis shows that taking L. reuteri 4659 50 million colony-forming units twice daily for 10 days in addition to standard antibiotic therapy modestly reduces abdominal pain, inflammatory markers, and duration of hospitalization when compared with placebo and standard antibiotic therapy (102299).
• Gingivitis. It is unclear if oral Limosilactobacillus reuteri is beneficial for gingivitis. Details: In a systematic review, four of the available eight studies on probiotics showed some benefit on gingivitis when compared with placebo. However, the meta-analysis included only two studies investigating the use of L. reuteri, in tablets or lozenges for 7-8 weeks, and found no benefit for gingivitis. Overall, there was moderate evidence suggesting a lack of effect of L. reuteri on gingivitis (105147). Also, a small clinical trial in patients with gingivitis in the third trimester of pregnancy shows that taking two lozenges daily providing L. reuteri ATCC PTA 5289 and DSM 17938 (BioGaia AB) until birth modestly reduces the severity of gingivitis and dental plaque within two days of birth when compared with placebo. Each lozenge provided at least 100 million colony-forming units (CFUs) of each strain (107568).
• Group B streptococcal colonization. Oral Limosilactobacillus reuteri has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of two clinical trials shows that taking L. reuteri RC-14 and Lacticaseibacillus rhamnosus GR-1, starting at 35-37 weeks' gestation and continuing until delivery, does not improve GBS clearance during pregnancy. However, a well-designed study included in this analysis shows that taking 4 billion CFUs daily more than doubles the number of patients testing negative for GBS at delivery (105165). In addition, a small clinical trial shows that taking this combination as 2.5 billion colony-forming units (CFUs) each daily for 12 weeks starting at 23-25 weeks' gestation does not prevent the rate of GBS vaginal/rectal colonization at 35-37 weeks' gestation (107567).
• HIV/AIDS. Although there has been interest in using oral Limosilactobacillus reuteri for HIV/AIDS, there is insufficient reliable information about the clinical effects of L. reuteri for this condition.
• Hypertension. Although there has been interest in using oral Limosilactobacillus reuteri for hypertension, there is insufficient reliable information about the clinical effects of L. reuteri for this condition.
• Irritable bowel syndrome (IBS). It is unclear if oral Limosilactobacillus reuteri is beneficial for IBS. Details: A small clinical trial in adults with IBS shows that taking L. reuteri ATCC 55730 (BioGaia AB, Sweden) 100 million colony-forming units (CFUs) twice daily for 6 months does not reduce symptoms such as bloating, abdominal pain, constipation, or diarrhea, when compared with taking placebo. For the first 7 days, 100 million CFUs were taken 4 times daily. Patients had constipation-predominant, diarrhea-predominant, or mixed-type IBS (112535). However, this study may have been inadequately powered to detect a difference between groups.
• Lactose intolerance. It is unclear if oral L. reuteri is beneficial for lactose intolerance. Details: Preliminary clinical research shows that taking L. reuteri (Reuterin, Nóos) 400 billion colony-forming units (CFUs) twice daily for ten days before a lactose breath test increases the normalization rate and reduces gastrointestinal symptoms when compared to placebo. Of those taking L. reuteri, 35% achieved a normal lactose breath test, compared with 0% of those taking placebo. However, taking the medication tilactase 15 minutes before the lactose breath test was more effective, with 80% of patients achieving a normal test and a greater reduction in severity of gastrointestinal symptoms (107507).
• Low birth weight. It is unclear if oral Limosilactobacillus reuteri is beneficial for improving outcomes in very low birth weight (VLBW) infants. Details: An observational follow-up of a clinical study in VLBW infants found that adding L. reuteri (Biogaia AB) 100 million CFUs to a daily feed until hospital discharge does not improve motor, sensory, or cognitive outcomes by up to 2 years of age when compared with a control group (99779).
• Lyme disease. Although there has been interest in using oral Limosilactobacillus reuteri for Lyme disease, there is insufficient reliable information about the clinical effects of L. reuteri for this condition.
• Metabolic syndrome. It is unclear if oral Limosilactobacillus reuteri is beneficial for metabolic syndrome. Details: A small clinical crossover study in patients with metabolic syndrome shows that taking L. reuteri 5 billion colony-forming units (CFUs) daily for 12 weeks does not impact weight, blood pressure, blood glucose levels, or lipid parameters when compared with placebo (102300). This study might have been confounded by the short (6-week) washout period between treatments. L. reuteri has also been evaluated in combination with other ingredients. Clinical research in elderly patients with metabolic syndrome shows that taking a combination of L. reuteri PBS072-DSM 25,175, Lactiplantibacillus plantarum PBS067-DSM 24,937, and Lactobacillus acidophilus PBS066-DSM 24,936 as 2 billion CFUs each, along with the prebiotics inulin and fructo-oligosaccharides, daily for 60 days results in a 23% reduction in the number of patients continuing to be diagnosed with metabolic syndrome, compared with a 10% reduction in those taking placebo. In the probiotic group, there were modest improvements in waist circumference and levels of fasting plasma insulin, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and inflammatory mediators when compared with placebo. However, there were no significant differences in fasting blood glucose or blood pressure. All patients in this study were on a Mediterranean-like standard diet (107560). It is unclear whether any benefits are due to L. reuteri, one of the other ingredients, or their combination.
• Necrotizing enterocolitis (NEC). It is unclear if oral Limosilactobacillus reuteri is beneficial or safe for NEC prevention. Details: Most meta-analyses of clinical research show that giving lactobacilli enterally reduces the risk of NEC and/or severe NEC in preterm, mainly very low birth weight (VLBW), infants. Some meta-analyses support the use of lactobacilli in combination with bifidobacteria, as opposed to lactobacilli alone for reducing the risk of NEC (95344,95351,103437,103445,104157,105162,105164). Although there is limited evidence on the effects of L. reuteri, specifically, on the incidence and severity of NEC, a large clinical trial of infants with a gestational age of 32 weeks or less and a birth weight of 1500 grams or less shows that providing L. reuteri DSM 17938 100 million colony-forming units (CFUs) daily in formula or breastmilk, from the start of first feeding until discharge, does not reduce the frequency of NEC or death over a period of 7 days when compared with placebo. However, there was a modest reduction in the frequency of sepsis and the duration of hospital stay was reduced by approximately 8 days (90281). Guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, L. reuteri is not specifically recommended (103003,111609,111611).
• Nonalcoholic fatty liver disease (NAFLD). Although there has been interest in using oral Limosilactobacillus reuteri for NAFLD, there is insufficient reliable information about the clinical effects of L. reuteri for this condition.
• Obesity. Although there has been interest in using oral Limosilactobacillus reuteri for obesity, there is insufficient reliable information about the clinical effects of L. reuteri for this condition.
• Oropharyngeal candidiasis. Although there has been interest in using oral Limosilactobacillus reuteri for oropharyngeal candidiasis, there is insufficient reliable information about the clinical effects of L. reuteri for this condition.
• Osteopenia. It is unclear if oral Limosilactobacillus reuteri is beneficial for osteopenia. Details: A small clinical trial in females aged 75-80 years with osteopenia shows that taking L. reuteri 6575 (BioGaia AB, Sweden) 10 billion colony-forming units daily for 12 months reduces bone mineral density loss in the tibia by at least 50% when compared with taking placebo. There were no differences between groups in bone density loss at the hip, femoral neck, or spine (112521).
• Peri-implant mucositis. It is unclear if oral Limosilactobacillus reuteri is beneficial for peri-implant mucositis. Details: A small clinical trial in patients with dental peri-implant mucositis shows that taking L. reuteri DSM 17938 and ATCC PTA 5289 (PerioBalance, Sunstar Suisse SA, Switzerland) one hundred million colony-forming units (CFUs) daily as a lozenge for 30 days as adjuvant to non-surgical mechanical debridement modestly improves bleeding on probing for up to 2 months after treatment when compared with mechanical therapy alone. There was no difference between groups in general bleeding on probing or pocket depth, or plaque severity (112532). A meta-analysis of this and 3 other small studies shows that taking L. reuteri DSM 17938 and LR ATCC PTA 5289 is modestly favored when compared with taking placebo in these patients when pocket depth, bleeding, and plaque are all taken into consideration, but not when analyzed separately (112527). However, the individual studies were small and it is unclear if they were adequately powered. The clinical relevance of any benefit is unclear from these studies.
• Periodontitis. It is unclear if oral Limosilactobacillus reuteri is beneficial for periodontitis. Details: A meta-analysis of small clinical trials in patients with periodontitis shows that using L. reuteri as a tablet or lozenge as an adjunctive therapy to scaling and root planing modestly improves clinical outcome, including clinical attachment, probing pocket depth and bleeding, when compared with control (107622). However, studies included in this analysis were small. One small clinical study in the analysis shows that taking a specific lozenge (Prodentis, Biogaia) containing L. reuteri DSM17938 and ATCC PTA5289, 100 million colony-forming units (CFUs) each, twice daily for 28 days does not improve clinical attachment levels of the gum, probing pocket depths, bleeding, or dental plaque when compared with placebo (102298). Another small clinical trial shows that taking this same lozenge for 12 weeks does not affect pocket depth, clinical attachment, gingival recession, or bleeding when compared with taking placebo. However, there seems to be a small beneficial effect on pocket depth in deep pockets and fewer patients were at high risk for disease progression (112511). The individual studies may have been inadequately powered to detect a difference between groups.
• Polycystic ovary syndrome (PCOS). Oral Limosilactobacillus reuteri has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical trial shows that 31.3% of patients with PCOS taking L. reuteri in combination with other probiotics daily for 6 months had regular menstrual cycles compared with 12.5% of those taking placebo. There were also modest improvements in testosterone levels and waist circumference, but not other hormones, insulin resistance, body weight, or most measures of quality of life. The product provided L. reuteri UBLRu-87 2 billion colony-forming units along with Bifidobacterium bifidum UBBB-55, Lacticaseibacillus rhamnosus UBLR-58, Lactobacillus acidophilus UBLA-34, Lactiplantibacillus plantarum UBLP-40, Lacticaseibacillus casei UBLC-42, Limosilactobacillus fermentum UBLF-31, and fructo-oligosaccharides (FOS) daily for 2 months and then twice daily for 4 months. All patients also underwent dietary and lifestyle changes (110974). It is unclear if any benefits are due to L. reuteri, the other probiotics, or their combination.
• Prader-Willi syndrome (PWS). It is unclear if oral Limosilactobacillus reuteri is beneficial for PWS. Details: Preliminary clinical research in young adults and children aged 6 months and older with PWS shows that taking L. reuteri LR-99 30 billion colony-forming units twice daily for 12 weeks has modest beneficial effects on social communication, social interaction, and fine motor function when compared with placebo. However, there were no effects on most other symptoms including cognition, speech, emotional response, communication, gross motor function, and other behaviors. Taking L. reuteri reduced body mass index (BMI) when compared with baseline; however, it is unclear whether this change was significant when compared with placebo (107513).
• Psoriasis. Although there has been interest in using oral Limosilactobacillus reuteri for psoriasis, there is insufficient reliable information about the clinical effects of L. reuteri for this condition.
• Respiratory tract infections. It is unclear if oral Limosilactobacillus reuteri is beneficial for preventing respiratory tract infections. Details: One clinical trial in healthy children ages 3-36 months shows that taking L. reuteri DSM 17938 (BioGaia drops, BioGaia AB) 100 million CFUs daily for 3 months modesty reduces the frequency and duration of respiratory tract infections, as well as day care absenteeism, when compared with taking placebo. The total number of respiratory tract infection episodes was reduced by approximately 54%, and the mean duration by 1.3 days. Benefits persisted for an additional 3 months (113506).
• Rheumatoid arthritis (RA). Oral Limosilactobacillus reuteri has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with RA shows that taking a total of 2 billion colony-forming units daily of a combination of L. reuteri RC-14 and Lacticaseibacillus rhamnosus GR-1 for 14 weeks does not improve symptom severity when compared with placebo (107569).
• Rotaviral diarrhea. It is unclear if oral Limosilactobacillus reuteri is beneficial for rotaviral diarrhea. Details: The current guidelines related to the treatment of viral diarrhea are conflicting. While the World Gastroenterology Organization has not made a recommendation (98471), the European Society for Pediatric Infectious Diseases recommends probiotics in hospitalized children with diarrhea (98469) and the Infectious Disease Society of America (IDSA) recommends probiotics for the outpatient treatment of acute diarrhea (95388). However, these guidelines note that most evidence is low quality and is not specific to L. reuteri or rotavirus infection. Although some research disagrees (112526), some clinical studies show that taking L. reuteri DSM 17938 (BioGaia drops, BioGaia AB) up to 100 billion colony-forming units (CFUs) daily for up to 7 days can modestly reduce the duration of diarrhea in infants and children, a portion of which had confirmed rotavirus (7751,7753,95336,113508). In one study, the duration of watery diarrhea in hospitalized children was reduced by 1.2 days when compared with placebo and persistence of watery diarrhea after 3 days was reduced by about 40%. Although the diarrhea relapse rate was also reduced by 64%, the duration of hospital stay was not affected. About 60% of the children in this study had diarrhea of rotaviral origin (113508). However, taking L. reuteri might not prevent hospital-acquired rotaviral diarrhea. In children ages 1-48 months, taking 100 million CFUs of this strain during hospitalization for reasons other than diarrhea does not reduce the occurrence of rotaviral infection when compared with taking placebo (112534).
• Short bowel syndrome. Although there has been interest in using oral Limosilactobacillus reuteri for short bowel syndrome, there is insufficient reliable information about the clinical effects of L. reuteri for this condition.
• Ulcerative colitis. It is unclear if giving Limosilactobacillus reuteri by enema is beneficial for ulcerative colitis. Details: A small clinical trial in children with mild to moderate active symptoms taking oral mesalazine shows that giving L. reuteri ATCC 55730 (Reuflor Italchimici SpA, Italy) 10 billion colony-forming units each evening by enema for 8 weeks modestly reduces overall disease activity when compared with a placebo enema. A clinical response, defined as a reduction in disease activity by 2 points, and clinical remission occurred in 100% and 31% of children, respectively, compared with 53% and 0% of children given the placebo (113511).
• Urinary tract infections (UTIs). Oral Limosilactobacillus reuteri has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in postmenopausal adults shows that taking an oral combination of L. reuteri RC-14 and Lacticaseibacillus rhamnosus standardized to at least 1 billion colony-forming units (CFUs) twice daily for 12 months demonstrates similar efficacy to trimethoprim/sulfamethoxazole 480 mg once daily for reducing the number of symptomatic UTIs. Although this probiotic combination was not associated with the increase in antimicrobial resistance that occurred with the use of antibiotic prophylaxis, the antibiotic delayed the median time to first recurrence by two-fold and reduced the number of confirmed microbiological infections when compared with the probiotics (90235). More evidence is needed to rate Limosilactobacillus reuteri for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. Although there has been interest in using oral pea protein for diabetes, there is insufficient reliable information about the clinical effects of pea protein for this purpose.
• Exercise-induced muscle damage. It is unclear if oral pea protein is beneficial for exercise-induced muscle damage. Details: A small clinical study in healthy, untrained males shows that taking a specific type of pea protein (Nutralys S85 Plus, Roquette) 0.3 grams/kg 3 times daily for 5 days after a 90-minute whole-body high-intensity eccentric exercise bout does not reduce surrogate markers of exercise-induced muscle damage, including creatine kinase, lactate dehydrogenase, and myoglobin, when compared with whey protein or water (104758). However, the study may have been inadequately powered to detect a difference between groups and is further limited by double-blinding restricted only to the protein supplements. The water control did not match the taste, texture, or calorie content of the protein supplements. Another small clinical trial in healthy, physically active older adults shows that taking pea protein 25 grams daily for 10 days prior to and 3 days after a single 20-30 km endurance walk does not improve markers of muscle damage when compared with placebo and may be less effective when compared with whey protein (111729).
• Exercise-induced muscle soreness. It is unclear if oral pea protein is beneficial for exercise-induced muscle soreness. Details: A small clinical study in healthy, untrained males shows that taking a specific type of pea protein (Nutralys S85 Plus, Roquette) 0.3 grams/kg 3 times daily for 5 days after a 90-minute whole-body high-intensity eccentric exercise bout does not reduce exercise-induced muscle soreness when compared with whey protein or water (104758). However, the study may have been inadequately powered to detect a difference between groups and is further limited by double-blinding restricted only to the protein supplements. The water control did not match the taste, texture, or calorie content of the protein supplements. Another small clinical trial in healthy, physically active older adults shows that taking pea protein 25 grams daily for 10 days prior to and 3 days after a single 20-30 km endurance walk does not improve muscle soreness when compared with whey protein or placebo (111729).
• Hyperlipidemia. Although there has been interest in using oral pea protein for hyperlipidemia, there is insufficient reliable information about the clinical effects of pea protein for this purpose.
• Hypertension. It is unclear if oral pea protein hydrolysate is beneficial for hypertension. Details: A small clinical study in adults with elevated blood pressure shows that taking a pea protein hydrolysate 3 grams daily for 3 weeks reduces systolic blood pressure by 6 mmHg when compared with placebo. Taking the same product at a dose of 1.5 grams daily does not reduce blood pressure (94973).
• Irritable bowel syndrome (IBS). Oral pea protein has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small open-label study in patients with diarrhea-predominant IBS shows that taking two tablets of a specific product (Gelsectan, Noventure) containing pea protein, grape seed extract tannins, xyloglucan, and xylo-oligosaccharides (doses unknown) before breakfast and dinner daily for 6 months improves IBS-related symptoms, including diarrhea, pain, bloating, defecatory frequency, stool consistency, and defecatory urgency when compared to baseline (108881). The validity of this study is limited by a lack of placebo control group.
• Muscle strength. Clinical research on the impact of oral pea protein on muscle strength is mixed. Its effects might be similar to whey protein. Pea protein may be more effective in individuals with lower baseline muscle strength. Details: A clinical trial in physically active, but non-resistance trained, young male adults participating in a 12-week upper body resistance training program shows that taking a specific type of pea protein isolate (Nutralys, Roquette) 25 grams twice daily over the training program does not augment training-induced increases in muscle thickness or strength when compared with whey protein or isocaloric placebo. However, a post hoc analysis of participants with the lowest muscle strength at baseline shows that pea protein supplementation increases bicep muscle thickness more than placebo and to a similar degree as whey protein (95426). Additionally, a very small clinical study in trained adults shows that taking pea protein 24 grams twice daily during an 8-week high-intensity functional training program improves muscle strength to a similar degree as whey protein, while neither supplement appears to impact muscle thickness or body mass (102013). The small study size and lack of an isocaloric, protein-free control limits conclusions that can be drawn from this study.
• Obesity. Although there has been interest in using oral pea protein for obesity, there is insufficient reliable information about the clinical effects of pea protein for this purpose.
• Postoperative recovery. Oral pea protein has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults undergoing gastrointestinal resection due to cancer shows that consuming a beverage (Providextra, Fresenius Kabi) containing pea protein hydrolysate 11% and carbohydrates 89% the night before (400 mL) and the morning of surgery (200 mL) reduces postoperative hospital stay by almost 2-fold when compared with conventional preoperative fasting (94933). It is unclear if these findings are due to pea protein, carbohydrates, or the combination. More evidence is needed to rate pea protein for these uses.

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LIKELY SAFE ...when used orally in food amounts. Eating apples and consuming apple juice is safe for most people. Apples are a common food source (3470,3472). However, eating apple seeds should be avoided because they can be toxic (6).

CHILDREN: LIKELY SAFE
when used orally in food amounts. Eating apples and consuming apple juice is safe for most people. Apples are a common food source (3470,3472).

CHILDREN: POSSIBLY SAFE
when apple pectin is used orally and appropriately, short-term. Preliminary clinical research suggests that combination products containing apple pectin and German chamomile (Diarrhoesan) are safe when used in infants for up to one week (19705,19706).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of apple in amounts greater than those found in foods during pregnancy and lactation; avoid using.

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LIKELY SAFE ...when used orally and appropriately. Bifidobacterium lactis has been safely used alone or in combination with other probiotics in clinical trials lasting up to 12 weeks (92255,98502,105158,107572,107581,107586,110979,110985,110986,110992)(110993,110998,110999).

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Bifidobacterium lactis has been safely used alone or in combination with other probiotics in infants and children for up to 15 months (3169,3458,92265,95381,95382,98736,105149,107582,107583,107585)(107587,107590,110984,110987,110988,110991,110994,110995). A combination probiotic containing B. lactis and Lactobacillus acidophilus (HOWARU Protect, Danisco) has been used safely for up to 6 months in children aged 3-5 years (16847). A specific combination of B. lactis, Bifidobacterium bifidum, and L. acidophilus (Complete Probiotic Platinum) has also been used safely for up to 18 months in children aged 4 months to 5 years (103436). In addition, in children ages 4-17 years, 1 billion CFUs of a 1:1:1 combination of B. lactis CECT 8145, Lacticasebacillus casei CECT 9104, and Bifidobacterium longum CECT 7347 has been used safely for 12 weeks (107531). There is insufficient reliable information available about the safety of B. lactis in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION:
Insufficient reliable information available. A meta-analysis of four clinical trials shows that taking probiotics during pregnancy increases the relative risk of pre-eclampsia by 85% when compared with placebo. Although the specific effects of Bifidobacterium lactis are unclear from this analysis, three of the included studies used B. lactis in combination with Lacticaseibacillus rhamnosus (105185). More information is needed to determine if certain patients are at increased risk.

(Read more about BIFIDOBACTERIUM ANIMALIS SUBSP. LACTIS)

LIKELY SAFE ...when used orally and appropriately. Bifidobacterium bifidum has been safely used alone or in combination with other probiotics in clinical trials lasting up to one year (1731,12775,14338,92255,107580,110972,110974,110978). There is insufficient reliable information available about the safety of non-viable, heat-killed B. bifidum formulations when used orally.

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Bifidobacterium bifidum has been safely used alone or in combination with other probiotics in clinical trials in infants and children for up to 18 months (161,90286,90602,98736,103436,110971,110976,110924). There is insufficient reliable information available about the safety of B. bifidum in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY: POSSIBLY SAFE
when Bifidobacterium bifidum is used orally and appropriately, short-term. A combination of B. bifidum, Lactobacillus acidophilus, and Lacticaseibacillus casei has been used with apparent safety for 6 weeks starting at 24-28 weeks' gestation (95416,98430).

LACTATION:
There is insufficient reliable information available about the safety of Bifidobacterium bifidum during lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about BIFIDOBACTERIUM BIFIDUM)

LIKELY SAFE ...when used orally and appropriately. Bifidobacterium breve has been safely used alone or in combination with other probiotics in clinical trials lasting up to one year (3261,6087,11379,12769,12775,14338,14370,14371,103447,111002)(111003,111005).

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Bifidobacterium breve has been safely used alone or in combination with other probiotics in infants and children for up to 12 months (17726,35377,92256,103449,105150,105151,107497,107598,111001)(111004,111008,111015). Cases of bacteremia have occurred rarely in children (107597). There is insufficient reliable information available about the safety of B. breve in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given B. breve or other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of Bifidobacterium breve during pregnancy or lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about BIFIDOBACTERIUM BREVE)

LIKELY SAFE ...when used orally and appropriately. Bifidobacterium longum has been safely used alone or in combination with other probiotics in clinical trials lasting up to one year (1233,12108,13054,14334,35382,35403,35424,103440,103446,105129)(107593,110968,110972,111773,111776,111847,111851,111854,111857,111858).

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Bifidobacterium longum has been safely used alone or in combination with other probiotics in infants and children for up to 4 months (3162,35377,35383,35393,35406,35407,92266,98736,107531,110924)(110976,111001,111015,111825,111833,111848). There is insufficient reliable information available about the safety of B. longum in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given these and other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION: POSSIBLY SAFE
when used orally and appropriately, short-term. A combination of Bifidobacterium longum and Lacticaseibacillus rhamnosus has been used with apparent safety throughout pregnancy (105128,105144). A combination of B. longum BB536 and Bifidobacterium breve M-16V has been used with apparent safety from about 4 weeks before the expected due date until delivery (111015). Also, a combination of B. longum and Lacticaseibacillus paracasei has been used with apparent safety from 2 months prior to delivery until 2 months after delivery during lactation (90285).

(Read more about BIFIDOBACTERIUM LONGUM)

LIKELY SAFE ...when used orally in food amounts that have been processed appropriately to remove cyanogenic glycosides. Cassava flour that contains no more than 10 ppm of cyanide is considered safe by the World Health Organization (25869,26585). Grating and crushing are considered to be appropriate processing methods to remove cyanide from bitter or sweet cassava root. Sweet cassava may be processed by boiling, steaming, baking, or frying (25841,26585). Boiling, steaming, baking, or frying are not considered to be sufficient processing methods to remove cyanide from bitter cassava (26585).

POSSIBLY UNSAFE ...when used orally in food amounts that have not been processed appropriately to remove cyanogenic glycosides. Regularly consuming uncooked cassava or cassava that has not been processed appropriately, especially as part of a protein-deficient diet, increases exposure to cyanogenic glycosides (25844). Heap fermentation or sun drying are not considered to be appropriate processing methods for removing cyanide from bitter or sweet cassava root (26585). Boiling, steaming, baking, or frying are not considered to be appropriate processing methods for removing cyanide from bitter cassava (26585). There is insufficient reliable information available about the safety of using cassava in medicinal amounts.

CHILDREN: POSSIBLY SAFE
when used orally in food amounts. Cassava is commonly consumed as a food with apparent safety. However, regular cassava consumption by children has been associated with inadequate intake of vitamin A, zinc, and iron (26175). Also, cassava may contain cyanogenic glycosides, and children are at a higher risk of cyanide poisoning from cassava compared to adults (25843).

CHILDREN: POSSIBLY UNSAFE
when used orally as a food in large quantities. Epidemiological research has found that children who eat more than 700 grams of cassava daily may have a higher risk of developing konzo, a paralytic disease, than those who eat less than 150 grams daily (25860).

PREGNANCY: POSSIBLY UNSAFE
when used orally as a food, especially in large quantities. Animal research suggests that consuming milled cassava powder as 80% of the diet during the first 15 days of pregnancy can cause teratogenic effects, including intrauterine growth restriction, limb defects, and abnormally small brain (microencephaly) (26171). Also, epidemiological evidence suggests that pregnant women who regularly consume dietary cassava in the form of gari during pregnancy have higher levels of thiocyanate, which has negative effects on fetal birthweight, compared to those who do not consume cassava (26172). ...when applied intravaginally. Inserting 2-3 cm of cassava stalk into the vagina has been used to induce abortion and labor (26174).

LACTATION: POSSIBLY UNSAFE
when used orally in food amounts, especially in large quantities. Excess consumption of cassava during lactation may increase the risk of exposing the infant to thiocyanate, which can negatively affect thyroid function in the infant (26586).

(Read more about CASSAVA)

LIKELY SAFE . .when used orally and appropriately. Cranberry juice up to 300 mL daily and cranberry extracts in doses up to 800 mg twice daily have been safely used in clinical trials (3333,3334,6758,6760,7008,8252,8253,8254,8995,11328) (16415,16720,17100,17126,17176,17210,17524,46379,46388,46389)(46390,46425,46439,46443,46465,46456,46466,46467,46469,46471)(46496,46499,90044,102847,111407).

CHILDREN: LIKELY SAFE
when cranberry juice is consumed in amounts commonly found in the diet (2811,6759,46441,46452,46470,111407). There is insufficient reliable information available about the safety of cranberry when used in medicinal amounts in children.

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in the diet. There is insufficient reliable information available about the safety of cranberry when used therapeutically during pregnancy or lactation; avoid using.

(Read more about CRANBERRY)

LIKELY SAFE ...when used orally and appropriately. Guar gum has been safely used in doses up to 15 grams daily for up to two years (10326,10897,12541,12543,12544,12548,54212,54245,54260,54275)(54333,93617,93619,93622,101888). Doses up to 20 grams daily have been safely used for up to 51 weeks (10896,12545,12547,54314). Guar gum has Generally Recognized as Safe (GRAS) status as a food additive in the US (4912).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. Guar gum has been safely used in doses of 4-5 grams daily for 4 weeks in children 6-16 years of age (93605,93615). Guar gum 3 grams daily for 4 weeks has been safely used in children 4-6 years of age (93605).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately in medicinal amounts. Guar gum has been safely used at doses of 5-15 grams daily for up to 4 weeks during pregnancy (54209,54356).

LACTATION:
There is insufficient reliable information available about the safety of using medicinal amounts of guar gum during lactation; avoid using.

(Read more about GUAR GUM)

LIKELY SAFE ...when used orally and appropriately. Lacticaseibacillus casei has been safely used alone or in combination with other ingredients in studies lasting up to 8 weeks (90230,112517).

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Lacticaseibacillus casei has been safely used alone in studies lasting up to 4 months (14373,107544). Also, a specific mixture (Latopic, Biomed S.A.) providing 1 billion CFUs of L. casei ŁOCK 0919 50%, Lacticaseibacillus rhamnosus ŁOCK 0900 25%, and L. rhamnosus ŁOCK 0908 25% has been used with apparent safety for 3 months in children under 2 years of age (107510). In addition, in children ages 4-17 years, a 1:1:1 combination of L. casei CECT 9104, Bifidobacterium animalis subsp. lactis CECT 8145, and Bifidobacterium longum CECT 7347 providing 1 billion CFUs has been used with apparent safety for 12 weeks (107531). There is insufficient reliable information available about the safety of L. casei in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. A combination of Lacticaseibacillus casei, Lactobacillus acidophilus, and Bifidobacterium bifidum has been used with apparent safety for 6 weeks, starting at 24-28 weeks' gestation (95416,98430).

LACTATION:
There is insufficient reliable information available about the safety of Lacticaseibacillus casei during lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about LACTICASEIBACILLUS CASEI)

LIKELY SAFE ...when live or heat-killed Lacticaseibacillus paracasei are used orally and appropriately. Live L. paracasei alone or in combination with other probiotics has been safely used in studies lasting up to 4 years (6087,14370,14371,35393,35407,103440,105133,107555,107557,110979)(111937,111938,111940,111943,111948,111950,111951,111953,111954,111955)(111958,111959,112512,112513,112518,112519). Non-viable, heat-killed L. paracasei has been safely used in studies lasting up to 3 months (111939,111940,111947). There is insufficient reliable information available about the safety of live or non-viable, heat-killed L. paracasei when used topically.

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Lacticaseibacillus paracasei alone or in combination with Limosilactobacillus fermentum has been used with apparent safety for up to 3 months in children 1-18 years old (98440). Also, live or heat-killed L. paracasei LP-33 has been used with apparent safety for 30 days in children aged 5 years and older (107532). In children ages 2-12 years, a specific combination product (Visbiome, ExeGi Pharma) containing L. paracasei and seven other probiotics has been used safely for 3 months (107497). Also, L. paracasei has been used with apparent safety in combination with Lactiplantibacillus plantarum for up to 12 weeks (107556). L. paracasei DN-114 011 has been taken safely for 90 days in children ages 3-6 years in fermented milk (DanActive, Dannon) (112515). There is insufficient reliable information available about the safety of L. paracasei in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION: POSSIBLY SAFE
when used orally and appropriately. A combination of Lacticaseibacillus paracasei and Bifidobacterium longum from 2 months prior to delivery until 2 months after delivery has been used with apparent safety (90285).

(Read more about LACTICASEIBACILLUS PARACASEI)

LIKELY SAFE ...when used orally and appropriately. Lacticaseibacillus rhamnosus has been safely used alone or in combination with other probiotics in studies lasting up to 6 months (4367,12108,35393,105134,107569,107572,107573,107575,107577,111793)(111996,111997,111998,112493,112496,112503,112508). ...when used intravaginally and appropriately. L. rhamnosus has been used safely in studies lasting from one week to six months (4397,12108,90283,111999). There is insufficient reliable information available about the safety of non-viable, heat-killed L. rhamnosus formulations when used orally.

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. The strain Lacticaseibacillus rhamnosus GG has been used safely in studies lasting from five days to 36 months (4369,4372,4373,4377,7741,8565,8566,8567,8568,14334)(90280,96889,98427,98428,99782,107518,107539,107571,110988,112000)(112491,112492,112494,112502). L. rhamnosus LOCK 0900 has been used safely in combination with other probiotics for 3 months (107510). There is insufficient reliable information about the safety of non-viable, heat-killed L. rhamnosus formulations in children when taken orally. Also, there is insufficient reliable information available about the safety of L. rhamnosus in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given L. rhamnosus and other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. Lacticaseibacillus rhamnosus GG has been used with apparent safety starting 2-4 weeks before delivery (7743,8515). L. rhamnosus HN001 has been used from 14-16 weeks' gestation until 6 months post-delivery (96888,98437). The combination of L. rhamnosus with Bifidobacterium longum has been used from 2 months prior to delivery until 2 months after delivery or throughout pregnancy (90285,105128,105144). The combination of L. rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 has been used for up to two trimesters during pregnancy (102292,107562). A combination of L. rhamnosus, Lactobacillus jensenii, Lactobacillus crispatus, and Lactobacillus gasseri has been used safely for 3-4 weeks from 32-36 weeks' gestation (105131). A meta-analysis of four clinical trials shows that taking probiotics during pregnancy increases the relative risk of pre-eclampsia by 85% when compared with placebo. Although the specific effects of L. rhamnosus are unclear from this analysis, two of the included studies used L. rhamnosus GG and one used L. rhamnosus HN001 (105185). More information is needed to determine if certain patients are at increased risk.

LACTATION: POSSIBLY SAFE
when used orally and appropriately. Lacticaseibacillus rhamnosus GG has been used with apparent safety when breastfeeding for up to six months (7743,8515) and L. rhamnosus HN001 has been used from 14-16 weeks' gestation until 6 months post-delivery (96888,98437). A combination of L. rhamnosus and Bifidobacterium longum has been used with apparent safety from 2 months prior to delivery until 2 months after delivery (90285).

(Read more about LACTICASEIBACILLUS RHAMNOSUS)

LIKELY SAFE ...when live Lactiplantibacillus plantarum is used orally and appropriately. L. plantarum has been safely used alone or in combination with other probiotics in studies lasting up to 9 months (6087,14370,14371,90255,105136,107515,107552,107555,107557,107559)(110961,111963,111966,111973,111976,111979,111983,111986,111990,111994).

POSSIBLY SAFE ...when heat-killed Lactiplantibacillus plantarum is used orally and appropriately. Non-viable L. plantarum strains have been safely used in doses of 50 mg daily for 4 weeks, 10 mg daily for up to 12 months, or up to 300 billion cells daily for up to 12 weeks (107530,111985,111988,111995). ...when L. plantarum is used intravaginally and appropriately. L. plantarum P17630 has been used with apparent safety daily for 6 days, then weekly for 16 weeks (98435). Also, L. plantarum 57B has been used with apparent safety along with Limosilactobacillus fermentum and Lactobacillus gasseri as part of a specific product (InVag) for up to 7 days (111961).

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Lactiplantibacillus plantarum has been safely used in children aged 7-15 years for up to 4 weeks (107540), in healthy newborns for 7 days (111989), and in children up to age 5 years for up to 90 days (111975,111981,111982). Also, L. plantarum has been used safely as a component of a combination probiotic product (Visbiome, ExeGi Pharma) in children aged 2-12 years for up to 3 months (107497) or in combination with Lacticaseibacillus paracasei for up to 12 weeks (107556). There is insufficient reliable information available about the safety of L. plantarum in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. Lactiplantibacillus plantarum (Lp299v, DSM 9843) has been used with apparent safety in doses of 10 billion colony-forming units (CFUs) daily in combination with iron, ascorbic acid, and folic acid daily from 10-12 weeks' gestation until delivery (107550).

LACTATION:
There is insufficient reliable information available about the safety of Lactiplantibacillus plantarum during lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about LACTIPLANTIBACILLUS PLANTARUM)

LIKELY SAFE ...when used orally and appropriately. Lactobacillus acidophilus has been safely used as part of multi-ingredient probiotic products in studies lasting up to nine months (1731,6087,14370,14371,90231,90296,92255,103438,12775,107581)(110950,110970,110979,110998,111785,111793). ...when used intravaginally and appropriately. L. acidophilus has been used safely in studies lasting up to 12 weeks (12108,13176,13177,90265). There is insufficient reliable information available about the safety of non-viable, heat-killed L. acidophilus formulations when used orally.

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Lactobacillus acidophilus has been safely used for up to 5 days (96887). Also, combination probiotics containing L. acidophilus have been used with apparent safety in various doses and durations. L. acidophilus has been combined with Bifidobacterium animalis (HOWARU Protect, Danisco) for up to 6 months in children 3-5 years old (16847), with Bifidobacterium bifidum for 6 weeks (90602,96890), with Bifidobacterium bifidum and Bifidobacterium animalis subsp. lactis (Complete Probiotic Platinum) for 18 months in children 4 months to 5 years of age (103436), and in a specific product (Visbiome, ExeGi Pharma) containing a total of 8 species for 3 months in children 2-12 years old (107497). There is insufficient reliable information available about the safety of L. acidophilus in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. A combination of Lactobacillus acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum has been used with apparent safety for 6 weeks, starting at 24-28 weeks' gestation (95416,98430).

LACTATION:
There is insufficient reliable information available about the safety of Lactobacillus acidophilus during lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about LACTOBACILLUS ACIDOPHILUS)

POSSIBLY SAFE ...when used orally. In the United States, most yogurt is made via bacterial fermentation with Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus (12778). Probiotic species similar to L. delbrueckii have not been associated with serious safety concerns when used appropriately in healthy adults. Most clinical trials have used L. delbrueckii in combination with other probiotics. It is unclear which specific dose and duration of use for L. delbrueckii as a probiotic may be most appropriate.

CHILDREN:
There is insufficient reliable information available about the safety of Lactobacillus delbrueckii as a probiotic in children of any age. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of Lactobacillus delbrueckii during pregnancy and lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about LACTOBACILLUS DELBRUECKII)

POSSIBLY SAFE ...when live or heat-killed Lactobacillus gasseri is used orally and appropriately. Live L. gasseri has been safely used in studies lasting up to 12 weeks (90244,95592,98433,110972,111854,112575,112584,112588,112591,112593). Also, heat-killed L. gasseri has been safely used in studies lasting up to 6 months (102297,112582,112589). ...when used vaginally and appropriately. L. gasseri has been safely used in studies lasting up to 10 days (16745,111961,111999).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in children ages 6-12 years. Lactobacillus gasseri has been safely used alone in a study lasting 8 weeks (112580). There is insufficient reliable information available about the safety of L. gasseri in children of other ages, including in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of Lactobacillus gasseri during pregnancy and lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about LACTOBACILLUS GASSERI)

POSSIBLY SAFE ...when used orally and appropriately. Lactobacillus helveticus has been safely used alone or in combination with other probiotics in doses of up to 20 billion colony-forming units (CFUs) daily in clinical trials lasting up to 14 weeks (96891,98438,102506,105129,110922,110926). There is insufficient reliable information available about the safety of non-viable, heat-killed L. helveticus formulations when used orally.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in children of most ages. Lactobacillus helveticus R0052 has been used safely alone or in combination with other probiotics in doses of up to 3 billion colony-forming units (CFUs) in children aged 3 months to 4 years in clinical trials lasting 5 days to 8 weeks (98428,110924). There is insufficient reliable information available about the safety of L. helveticus in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608). There is insufficient reliable information about the safety of non-viable, heat-killed L. helveticus formulations in children when taken orally.

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of Lactobacillus helveticus during pregnancy and lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about LACTOBACILLUS HELVETICUS)

POSSIBLY SAFE ...when used orally and appropriately. Levilactobacillus brevis has been safely used in doses of up to 12 billion colony-forming units (CFUs) daily in clinical trials lasting up to 3 months (107287,110941,110950,110956,110960,110961,110962). ...when used vaginally and appropriately. L. brevis has been safely used in doses of up to 2 billion CFUs twice daily for 6 months (99787). There is insufficient reliable information available about the safety of non-viable, heat-killed L. brevis formulations when used orally or topically.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in children of most ages. Levilactobacillus brevis has been used safely in children aged 4-14 years in doses of up to 4 billion colony-forming units (CFUs) daily for up to 2 months (90238,110953,110958) or 10 billion CFUs for 4 weeks (110941). There is insufficient reliable information available about the safety of L. brevis in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608). There is insufficient reliable information about the safety of non-viable, heat-killed L. brevis formulations in children when taken orally.

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of Levilactobacillus brevis during pregnancy and lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about LEVILACTOBACILLUS BREVIS)

POSSIBLY SAFE ...when used orally and appropriately. Ligilactobacillus salivarius has been safely used in studies lasting up to 16 weeks (112543,112544,112548,112550). There is insufficient reliable information available about the safety of L. salivarius when used vaginally.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in children of most ages. Ligilactobacillus salivarius has been safely used alone or in combination with other probiotics in studies lasting up to 16 weeks (111004,112540). There is insufficient reliable information available about the safety of L. salivarius in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. Ligilactobacillus salivarius has been safely used from about 30 weeks' gestation or diagnosis of gestational diabetes until delivery (96894,102291).

LACTATION:
There is insufficient reliable information available about the safety of Ligilactobacillus salivarius during lactation. However, there are currently no reasons to expect safety concerns when used appropriately.

(Read more about LIGILACTOBACILLUS SALIVARIUS)

POSSIBLY SAFE ...when used orally and appropriately. Limosilactobacillus fermentum has been safely used alone and in combination with other probiotics in studies lasting up to 12 weeks (112503,112562,112570). ... when used intravaginally and appropriately. L. fermentum has been used safely daily for up to 7 days and biweekly and/or monthly in studies lasting up to 10 weeks (6095,111961).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in children of most ages. Limosilactobacillus fermentum has been safely used alone and in combination with other probiotics in studies lasting up to 6 months (98440,105150,112569,112573,112574). There is insufficient reliable information available about the safety of L. fermentum in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY:
There is insufficient reliable information available about the safety of Limosilactobacillus fermentum during pregnancy. However, there are currently no reasons to expect safety concerns when used appropriately.

LACTATION: POSSIBLY SAFE
when used orally and appropriately. Limosilactobacillus fermentum CECT5716 has been used with apparent safety when breastfeeding for up to 16 weeks (112566).

(Read more about LIMOSILACTOBACILLUS FERMENTUM)

LIKELY SAFE ...when used orally and appropriately. Limosilactobacillus reuteri has been safely used alone or in combination with other probiotics in studies lasting up to 6 months (7752,90250,90253,105145,107507,107565,107566,107569,112511,113505)(112521,112522,112532,112535).

CHILDREN: LIKELY SAFE
when used orally and appropriately in children of most ages. Limosilactobacillus reuteri has been safely used for up to 4 weeks in infants and young children and for up to 12 weeks in older children (7751,8566,8567,17118,17530,90203,90240,90246,90264,90281)(90293,90294,105130,107505,107564,113503,113506,113507,113508,113510)(112523,112525,112526,112528,112529,112530,112534). There is insufficient reliable information available about the safety of L. reuteri in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608). There is insufficient reliable information available about the safety of L. reuteri when used rectally.

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately (102292,107561,107562).

LACTATION: POSSIBLY SAFE
when used orally and appropriately. Although clinical research during lactation is lacking, no safety concerns have been shown in clinical research involving infants up to 3 months of age (17118,17530,90240,90264,90281,90293,90294).

(Read more about LIMOSILACTOBACILLUS REUTERI)

LIKELY SAFE ...when used orally in food amounts. Pea protein is commonly consumed as a food (94935,94970,94981).

POSSIBLY SAFE ...when pea protein is used orally in medicinal amounts, short term. Pea protein has been used with apparent safety in doses of up to 50 grams daily for up to 12 weeks (95426,94934,102013,104758,104759). ...when pea protein hydrolysate is used orally, short term. A pea protein hydrolysate has been used with apparent safety at doses of up to 3 grams daily for up to 3 weeks (94973).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in amounts greater than those found in food.

(Read more about PEA PROTEIN)

ALISKIREN (Tekturna, Rasilez) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of aliskiren.  Details Pharmacokinetic research shows that coadministration of apple juice 200 mL along with aliskiren 150 mg decreases the bioavailability of aliskiren by 63% (17670). Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney (7046,94413). It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction (17603,17604).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, consuming apple juice with antidiabetes drugs might interfere with blood glucose control.  Details Clinical research suggests that consuming apples or drinking apple juice can raise blood glucose levels, with the effects of drinking apple juice being more significant than consuming apples (31699).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Consuming apple juice with antihypertensive drugs might interfere with blood pressure control.  Details Some clinical evidence suggests that consuming apple and cherry juice can increase blood pressure in elderly patients (31680).

ATENOLOL (Tenormin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of atenolol.  Details Pharmacokinetic research shows that coadministration of apple juice 600-1200 mL decreases levels of atenolol by 58% to 82% in a dose-dependent manner (17999). Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney (7046). It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction (17603,17604).

FEXOFENADINE (Allegra) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = B Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of fexofenadine.  Details Pharmacokinetic research shows that coadministration of apple juice 400-1200 mL along with fexofenadine 60-120 mg decreases bioavailability of fexofenadine by up to 78% (7046,94413). Coadministration with smaller quantities of apple juice (150 mL or less) does not appear to affect the bioavailability of fexofenadine (94421). Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney (7046,94413). It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction (17603,17604).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D There is some concern that concomitant consumption of apple juice might decrease oral absorption and blood levels of lithium.  Details In one case report, a patient had an undetectable serum lithium level when lithium citrate was administered with apple juice. When lithium was administered with an alternative beverage, the lithium level became detectable and the patient demonstrated clinical improvement (105342).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of OATP substrates.  Details Research shows that consuming apple juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP (7046,17605). Fexofenadine, atenolol, and aliskiren are substrates of OATP. Clinical research shows that coadministration of apple juice decreases bioavailability of fexofenadine by up to 78% (7046,94413), aliskiren by 63% (17670), and atenolol by up to 82% (17999). These effects appear to increase with larger quantities of apple juice. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction (17603,17604).

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ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Bifidobacterium lactis with antibiotic drugs might decrease the effectiveness of B. lactis.  Details Since B. lactis preparations usually contain live and active organisms, simultaneously taking antibiotics might kill a significant number of the organisms (1740,22802). Tell patients to separate administration of antibiotics and B. lactis preparations by at least 2 hours.

(Read more about BIFIDOBACTERIUM ANIMALIS SUBSP. LACTIS)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Bifidobacterium. bifidum with antibiotic drugs might decrease the effectiveness of B. bifidum.  Details Since B. bifidum preparations usually contain live and active organisms, simultaneously taking antibiotics might kill a significant number of the organisms (1740,22802). Tell patients to separate administration of antibiotics and B. bifidum preparations by at least 2 hours.

(Read more about BIFIDOBACTERIUM BIFIDUM)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Bifidobacterium breve with antibiotic drugs might decrease the effectiveness of B. breve.  Details Since B. breve preparations usually contain live and active organisms, simultaneously taking antibiotics might kill a significant number of the organisms (1740,22802). Tell patients to separate administration of antibiotics and B. breve preparations by at least 2 hours.

(Read more about BIFIDOBACTERIUM BREVE)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Bifidobacterium longum with antibiotic drugs might decrease the effectiveness of B. longum.  Details Since B. longum preparations usually contain live and active organisms, simultaneously taking antibiotics might kill a significant number of the organisms (1740,22802). Tell patients to separate administration of antibiotics and B. longum preparations by at least 2 hours.

(Read more about BIFIDOBACTERIUM LONGUM)

(Read more about CASSAVA)

ATORVASTATIN (Lipitor) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cranberry might increase levels and adverse effects of atorvastatin.  Details In one case report, a patient taking atorvastatin experienced upper back pain, rhabdomyolysis, and abnormal liver function after drinking cranberry juice 16 ounces daily for 2 weeks. Theoretically, this may have been caused by inhibition of cytochrome P450 3A4 (CYP3A4) enzymes by cranberry juice, as atorvastatin is a CYP3A4 substrate. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice (90042). Patients taking atorvastatin should avoid large quantities of cranberry juice.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, cranberry might increase the levels and adverse effects of CYP2C9 substrates. However, research is conflicting.  Details There is contradictory evidence about the effect of cranberry on CYP2C9 enzymes. In vitro evidence suggests that flavonoids in cranberry inhibit CYP2C9 enzymes (10452,11115,90048). However, clinical research shows that cranberry juice does not significantly affect the levels, metabolism, or elimination of the CYP2C9 substrates flurbiprofen or diclofenac (11094,90048). Also, in patients stabilized on warfarin, drinking cranberry juice 250 mL daily for 7 days does not significantly increase the anticoagulant activity of warfarin, a CYP2C9 substrate (15374). Additional pharmacokinetic research shows that cranberry juice does not increase peak plasma concentrations or area under the concentration-time curve of warfarin (15393).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cranberry might increase the levels and adverse effects of CYP3A4 substrates.  Details A case of upper back pain, rhabdomyolysis, and abnormal liver function has been reported for a patient taking atorvastatin, a CYP3A4 substrate, in combination with cranberry juice 16 ounces daily for 2 weeks. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice (90042). Also, animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine, a CYP3A4 substrate, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control (46420).

DICLOFENAC (Voltaren, others) Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, cranberry might modestly increase the levels and adverse effects of diclofenac.  Details In vitro evidence suggests that cranberry juice inhibits diclofenac metabolism by human liver microsomes (90048). However, drinking cranberry juice does not seem to affect diclofenac metabolism in humans (90048).

NIFEDIPINE (Procardia) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cranberry might increase the levels and adverse effects of nifedipine.  Details Animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine treatment, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control (46420). This interaction has not been reported in humans.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, cranberry might increase the levels and adverse effects of warfarin. However, research is conflicting.  Details There is contradictory evidence about the effect of cranberry juice on warfarin. Case reports have linked cranberry juice consumption to increases in the international normalized ratio (INR) in patients taking warfarin, resulting in severe spontaneous bleeding and excessive postoperative bleeding (10452,12189,12668,21187,21188,21189,46378,46396,46411)(46415,90043). Daily consumption of cranberry sauce for one week has also been linked to an increase in INR in one case report (16816). In a small study in healthy young males, taking a high dose of 3 grams of cranberry juice concentrate capsules, equivalent to 57 grams of fruit daily, for 2 weeks produced a 30% increase in the area under the INR-time curve after a single 25-mg dose of warfarin (16416). However, 3 very small clinical studies in patients stabilized on warfarin reported that cranberry juice 250 mL once or twice daily for 7 days (27% cranberry juice or pure cranberry juice) or 240 mL once daily for 14 days does not significantly increase INR or affect plasma warfarin levels (15374,17124,90045). The reasons for these discrepant findings are unclear. It is possible that the form and dose of cranberry may play a role, as cranberry extracts and juices contain different constituents. Additionally, an in vitro study evaluating 5 different cranberry juices found varying effects, with only a cranberry concentrate, and not diluted cranberry juices, inhibiting CYP2C9. However, this concentrate did not inhibit CYP2C9 activity in humans (108062).

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DIGOXIN (Lanoxin) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = B Guar gum might slow digoxin absorption, but it does not seem to impact how much digoxin is absorbed overall.  Details Two small studies in healthy volunteers show no change in the overall extent of digoxin absorption, although early absorption was slowed, when taken with guar gum (533,25074).

ETHINYL ESTRADIOL Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, guar gum might reduce the absorption of ethinyl estradiol, potentially decreasing its effectiveness.  Details Animal research shows that taking guar gum with ethinyl estradiol decreases ethinyl estradiol absorption (12421). However, this effect has not been reported in humans.

METFORMIN (Glucophage) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Guar gum might reduce the absorption of metformin, potentially decreasing its effectiveness.  Details A small study in healthy volunteers shows that guar gum reduces the absorption rate of metformin (532,12546).

ORAL DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Guar gum might reduce the absorption of some oral drugs, potentially decreasing their effectiveness.  Details Clinical research shows that guar gum reduces or slows absorption of medications such as penicillin and metformin (532,533). To avoid changes in absorption, take guar gum 30-60 minutes after oral medications.

PENICILLIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Guar gum might reduce the absorption of penicillin, potentially decreasing its effectiveness.  Details A small clinical study in healthy volunteers shows that taking guar gum with penicillin results in decreased penicillin absorption and reduced penicillin levels (533).

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ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lacticaseibacillus casei with antibiotic drugs might decrease the effectiveness of L. casei.  Details L. casei preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. casei preparations by at least two hours.

(Read more about LACTICASEIBACILLUS CASEI)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lacticaseibacillus paracasei with antibiotic drugs might decrease the effectiveness of L. paracasei.  Details L. paracasei preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. paracasei preparations by at least two hours.

(Read more about LACTICASEIBACILLUS PARACASEI)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lacticaseibacillus rhamnosus with antibiotic drugs might decrease the effectiveness of L. rhamnosus.  Details L. rhamnosus preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. rhamnosus preparations by at least two hours.

(Read more about LACTICASEIBACILLUS RHAMNOSUS)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lactiplantibacillus plantarum with antibiotic drugs might decrease the effectiveness of L. plantarum.  Details L. plantarum preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. plantarum preparations by at least two hours.

(Read more about LACTIPLANTIBACILLUS PLANTARUM)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lactobacillus acidophilus with antibiotic drugs might decrease the effectiveness of L. acidophilus.  Details L. acidophilus preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. acidophilus preparations by at least two hours.

(Read more about LACTOBACILLUS ACIDOPHILUS)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lactobacillus delbrueckii with antibiotic drugs might decrease the effectiveness of L. delbrueckii.  Details Lactobacillus delbrueckii preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. delbrueckii preparations by at least two hours.

(Read more about LACTOBACILLUS DELBRUECKII)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lactobacillus gasseri with antibiotic drugs might decrease the effectiveness of L. gasseri.  Details Lactobacillus gasseri preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. gasseri preparations by at least two hours.

(Read more about LACTOBACILLUS GASSERI)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Lactobacillus helveticus with antibiotic drugs might decrease the effectiveness of L. helveticus.  Details Lactobacillus helveticus preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. helveticus preparations by at least two hours.

(Read more about LACTOBACILLUS HELVETICUS)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Levilactobacillus brevis with antibiotic drugs might decrease the effectiveness of L. brevis.  Details Levilactobacillus brevis preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. brevis preparations by at least two hours.

(Read more about LEVILACTOBACILLUS BREVIS)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Ligilactobacillus salivarius with antibiotic drugs might decrease the effectiveness of L. salivarius.  Details Ligilactobacillus salivarius preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. salivarius preparations by at least two hours.

(Read more about LIGILACTOBACILLUS SALIVARIUS)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Limosilactobacillus fermentum with antibiotic drugs might decrease the effectiveness of L. fermentum.  Details Limosilactobacillus fermentum preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. fermentum preparations by at least two hours.

(Read more about LIMOSILACTOBACILLUS FERMENTUM)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking Limosilactobacillus reuteri with antibiotic drugs might decrease the effectiveness of L. reuteri.  Details L. reuteri preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms (1740). Tell patients to separate administration of antibiotics and L. reuteri preparations by at least two hours.

(Read more about LIMOSILACTOBACILLUS REUTERI)

(Read more about PEA PROTEIN)

General ...Orally, apple fruit is well tolerated. Apple seeds, which contain cyanide, may cause serious adverse effects when consumed in large amounts.
Most Common Adverse Effects:
Orally: Bloating, flatulence.
Serious Adverse Effects (Rare):
Orally: Allergic reactions, including anaphylaxis. Ingestion of large amounts of apple seeds may cause cyanide poisoning, leading to death.

Gastrointestinal ...Orally, apple products, including whole apples, apple puree, and apple juice, may cause bloating and flatulence in some people (104184).

Immunologic ...Patients allergic to other fruits in the Rosaceae family, including apricot, almond, plum, peach, pear, and strawberry, can also be allergic to apples (7129). Rarely, the allergy has resulted in anaphylaxis (94425).

Other ...Orally, ingestion of large amounts of apple seeds, which contain hydrogen cyanide (HCN), may cause cyanide poisoning, leading to death. One death is attributed to ingestion of a cupful of apple seeds. To release cyanide, seeds must be hydrolyzed in the stomach, and several hours may elapse before poisoning symptoms occur (6).

(Read more about APPLE)

General ...Orally, Bifidobacterium lactis seems to be well tolerated by most patients.
Most Common Adverse Effects:
Orally: Diarrhea.
Serious Adverse Effects (Rare):
Orally: There is concern that probiotics may cause infections in some people.

Dermatologic ...In clinical research, two cases of rash, one with itching, were reported by patients taking a combination of Bifidobacterium lactis BB-12, Lacticaseibacillus paracasei F19, and Lactobacillus acidophilus La5. However, it is not clear if these adverse effects were due to B. lactis, other probiotics, or the combination, or if the events were idiosyncratic (90236).

Gastrointestinal ...Bloating and flatulence have been reported with probiotic use; however, these adverse effects have not been reported from ingestion of Bifidobacterium lactis in particular. When taken orally, B. lactis can cause diarrhea and other gastrointestinal complaints in children (3169,95381,105149). Gastrointestinal complaints including worsening diarrhea, abdominal pain, constipation, stomach burn, and flatulence have been reported rarely (110986,110999).

Immunologic ...There have been cases of Bifidobacterium bacteremia in critically ill patients (102416,107599). These cases are rare and none seem to be due to Bifidobacterium lactis alone.
A specific preparation (NBL probiotic ATP, Nobel) containing B. lactis, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, fructo-oligosaccharides, galacto-oligosaccharides, colostrum, and lactoferrin was found to be a significant risk factor for vancomycin-resistant Enterococcus colonization in premature infants. Although there was no direct link to determine causation, it was hypothesized that the probiotic mixture helped to mediate the acquisition and transfer of antibiotic resistance genes (96890).

(Read more about BIFIDOBACTERIUM ANIMALIS SUBSP. LACTIS)

General ...Orally, Bifidobacterium bifidum seems to be well tolerated by most patients.
Serious Adverse Effects (Rare):
Orally: There is concern that probiotics may cause infections in some people.

Gastrointestinal ...Bloating and flatulence have been reported with probiotic use; however, these adverse effects have not been reported from ingestion of Bifidobacterium bifidum in particular. One case of vomiting and fever has been reported in a clinical study for a single child taking B. bifidum and Lactobacillus acidophilus. It is unclear if the probiotics were the causal agent (90286).

Immunologic ...There have been cases of Bifidobacterium sepsis in critically ill patients (102416,107599). However, these cases are rare and none seem to be due to Bifidobacterium bifidum.

(Read more about BIFIDOBACTERIUM BIFIDUM)

General ...Orally, Bifidobacterium breve seems to be well tolerated by most patients.
Serious Adverse Effects (Rare):
Orally: There is concern that B. breve may cause bacteremia in certain patients.

Gastrointestinal ...Bloating and flatulence have been reported with probiotic use; however, these adverse effects have not been reported from ingestion of Bifidobacterium breve in particular.

Immunologic ...There have been rare cases of Bifidobacterium bacteremia related to probiotic use in critically ill infants and adults (102416,107597,107599). In addition, cases of B. breve bacteremia have occurred in preterm infants or young children using probiotics (102416,107597). In a review of 298 term and preterm infants who were admitted to the neonatal intensive care unit of a hospital in Japan and received B. breve BBG-01 over a five-year period, bacteremia occurred in six patients (2%). Concomitant conditions included gastrointestinal perforation, food-induced enterocolitis syndrome, adhesive ileus, ileal volvulus, and aspiration pneumonia following esophageal atresia repair (107597). In one case report, B. breve BBG-01 was provided to an infant starting two days after birth and the day of surgery for an omphalocele. The infant also had bilious gastric fluid with elevated inflammatory markers. It is thought that the intestinal surgical repair might have led to the translocation of the ingested B. breve (107596).
Some cases of B. breve bacteremia do not seem to be directly related to probiotic use. There have been rare cases of B. breve bacteremia and necrotizing fasciitis in patients with type 2 diabetes. One patient had pre-existing chronic diabetic foot ulcers and the other had abscesses near the groin (111007,111011). A childhood history of frequent consumption of fermented beverages containing B. breve was thought to have resulted in B. breve in the intestinal flora of one of these patients, aged 42 years (111011). However, it is unclear if consumption of an unknown quantity of B. breve more than 20 years previously would play a role in this outcome. There is also a rare case of ventriculoperitoneal shunt B. breve infection possibly related to poor oral hygiene and dentition (111014).

(Read more about BIFIDOBACTERIUM BREVE)

General ...Orally, Bifidobacterium longum seems to be well tolerated by most patients.
Serious Adverse Effects (Rare):
Orally: There is concern that B. longum may cause bacteremia in certain patients.

Gastrointestinal ...When taken orally, abdominal discomfort, pain, and distension have been reported rarely (111773,111847,111856). Flatulence has been reported rarely with Bifidobacterium longum when used alone or in combination with other species of probiotics (107520,111773). Other rare gastrointestinal side effects have included constipation and gastrointestinal motor disorder (111773).

Immunologic ...There have been rare cases of Bifidobacterium bacteremia in critically ill infant and adult patients (102416,107599). Various cases of Bifidobacterium longum bacteremia, sometimes presenting as sepsis, have occurred in preterm infants using probiotics (102416,111610,111612,111850,111852,111853). In one case report, a 15-month-old female infant with congenital heart defects and recent surgery to replace a mechanical heart valve developed Bifidobacterium sepsis after being treated with IV antibiotics, extracorporeal membrane oxygenation (ECMO), and oral probiotics containing B. longum. It was thought that ECMO contributed to translocation of bifidobacteria from the gut and into the blood (102416). In 5 cases, very-low birthweight preterm infants developed B. longum bacteremia following the use of a specific probiotic product providing B. longum and Lactobacillus acidophilus (Infloran) for the prevention of necrotizing enterocolitis; antibiotic treatment was required in at least some of the cases (111850,111852,111853). Cases of sepsis related to B. longum have also occurred in adults; however, association with supplementation is unlikely. In one case, sepsis with B. longum occurred following acupuncture. This was likely due to needle contamination and not to supplementation (1236). In another case, a 71-year-old male with liver cirrhosis and prostate cancer developed B. longum lumbar vertebrodiscitis. The source was thought to be translocation from the intestine (111859). A 42-year-old male developed B. longum peritonitis secondary to intestinal perforation (111855).

Pulmonary/Respiratory ...When taken orally, a dry cough has been reported by a single patient in a clinical trial (111851).

Other ...When taken orally, weight gain has been reported by a single patient in a clinical trial (111773).

(Read more about BIFIDOBACTERIUM LONGUM)

General ...Orally, cassava may cause cyanide poisoning. Cassava, especially the bitter variety, contains cyanogenic glycosides. If not removed during processing, these constituents are converted to cyanogens. Symptoms of cyanide poisoning can include vomiting, nausea, stomach pains, and diarrhea, as well as dizziness, weakness, and headache. (26585). Cassava intake has also been associated with an increased risk of hypothyroidism and endemic goiter. This adverse effect is attributed to cyanogens, which can disrupt thyroid hormone production by decreasing iodine absorption (25841,25843,25844). The risk of these adverse effects is especially high for patients who consume cassava as part of a protein-deficient diet (25841,25843,25844). Consumption of cassava that has not been processed to remove the cyanogens has also been associated with an increased risk of developing paralytic diseases, tropical pancreatitis, and tropical ataxic neuropathy (25844,25854,25856,25859,25860,25861,25863,25864). Rarely, cassava has been reported to cause allergic reaction (99802,99806,99807).

Endocrine ...Orally, cassava has been associated with an increased risk of hypothyroidism and endemic goiter, particularly when consumed after poor processing or along with a protein-deficient diet (25846,25850,25852). Cassava, especially the bitter varieties, contains cyanogenic glycosides. If not removed during processing, these constituents are converted to cyanogens, which disrupt thyroid hormone production by decreasing iodine absorption (25841,25843,25844). In humans, consuming boiled cassava leaves 200 grams twice daily can decrease serum levels of the thyroid hormones triiodothyronine (T3) and thyroxine (T4) after only 9 days (25847).
There is also some concern that people who regularly consume cassava may have an increased risk of developing tropical pancreatitis, a form of pancreatitis that is primarily seen in tropical countries. However, this association has not been consistently observed (25854,25856).