WellBelly [Discontinued] by Natrol

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

• 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

• Celiac disease. Although there has been interest in using oral lipase for celiac disease, there is insufficient reliable information about the clinical effects of lipase for this purpose.
• Dyspepsia. It is unclear if oral lipase is beneficial for improving symptoms of postprandial distress syndrome. Details: A small clinical trial shows that taking a specific acid-resistant lipase (Amano Enzyme USA) 280 mg immediately before a high-fat meal does not reduce postprandial bloating and nausea when compared with placebo in individuals with postprandial distress syndrome (101900).
• Inflammatory bowel disease (IBD). Although there has been interest in using oral lipase for IBD, there is insufficient reliable information about the clinical effects of lipase for this purpose.
• Prematurity. It is unclear if adding a specific form of lipase, recombinant human bile salt-stimulated lipase (rhBSSL), to infant formula improves outcomes in premature infants. Some research suggests a potential increased risk for adverse effects. Details: Human breast milk contains rhBSSL, but it is inactivated when breast milk is pasteurized for donation. Clinical research in infants born before 32 weeks' gestation shows that adding rhBSSL as 8700 units per 100 mL formula or pasteurized breast milk, for 4 weeks does not increase growth velocity, body length, or head circumference over the next 12 months when compared with formula or pasteurized breast milk devoid of lipase. However, the infants who were small for gestational age (SGA), which made up approximately 15% of the study population, grew by an additional 1.9 grams/kg daily on average when compared with placebo (101940). More evidence is needed to rate lipase for these uses.

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Proteolytic enzymes represent a wide group of enzymes that are used alone or in combination. See specific monographs for effectiveness information.

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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.

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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.

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There is insufficient reliable information available about the safety of lipase.

CHILDREN: POSSIBLY UNSAFE
when recombinant human bile salt-stimulated lipase (rhBSSL) is used orally by premature infants. Adding rhBSSL to infant formula or pasteurized breast milk increases the risk for serious gastrointestinal adverse effects in premature infants (101940).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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POSSIBLY SAFE ...when used orally and appropriately. Various proteolytic enzymes have been safely used orally in clinical research (716,964,965,968,969,6252,6253,10622,11457,18281,18284) (91104,91105,91106,91111,96449). Side effects are typically mild to moderate and most often include gastrointestinal effects. See specific monographs for more detailed information related to the safety of individual proteolytic enzymes. ...when used topically and appropriately. Various proteolytic enzymes have been safely used topically in clinical research (67835,67843,67845,91113). Some proteolytic enzymes might cause allergic reactions when used topically. See specific monographs for more detailed information related to the safety of individual proteolytic enzymes.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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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.

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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.

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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).

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General ...Orally and intravaginally, Lactobacillus acidophilus is generally well tolerated.
Most Common Adverse Effects:
Orally: Mild gastrointestinal adverse effects.
Intravaginally: Vaginal discharge.
Serious Adverse Effects (Rare):
Orally: There is concern that L. acidophilus may cause infections in some people.

Dermatologic ...Orally, in one clinical trial, a combination of Lactobacillus acidophilus La-5, Lacticaseibacillus paracasei subsp. paracasei F19, and Bifidobacterium animalis subsp. lacltis BB-12 was associated with two cases of rash, one with itching. However, it is not clear if these adverse effects were due to L. acidophilus, other ingredients, the combination, or if the events were idiosyncratic (90236).

Gastrointestinal ...Orally, taking Lactobacillus acidophilus in combination with other probiotics may cause gastrointestinal side effects including epigastric discomfort (90239), abdominal pain (90239,90291,111785), dyspepsia (90239), flatulence (107497,107520), bloating (107497,111785), diarrhea (111785), vomiting (107537), and burping (90239); however, these events are uncommon.

Genitourinary ...Intravaginally, cream containing Lactobacillus acidophilus has been shown to cause increased vaginal discharge in about 5% of patients, compared to about 1% of patients receiving placebo cream (90237). Vaginal burning was reported by one person using intravaginal L. acidophilus and Limosilactobacillus fermentum in a clinical trial (111781).

Immunologic ...Since Lactobacillus acidophilus preparations contain live and active microorganisms, there is some concern that they might cause pathogenic infection in some patients. L. acidophilus has been isolated in some cases of bacteremia, sepsis, splenic abscess, liver abscess, endocarditis, necrotizing fasciitis, pancreatic necrosis, and meningoencephalitis. Most of these cases are thought to be due to the translocation of bacteria from other locations in the body in which they occur naturally, such as the oral cavity and gastrointestinal tract (107543,111782,111792). L. acidophilus endophthalmitis has been reported rarely (111787,111795). In one case, it was related to intravitreal injections for age-related macular degeneration in a 90-year-old female with an intraocular lens (111787). In another, it occurred following cataract surgery (111795).

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General ...No adverse effects have been reported in adults. However, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Gastrointestinal adverse effects, such as necrotizing enterocolitis, when recombinant human bile salt-stimulated lipase is used in premature infants.

Gastrointestinal ...Orally, when added to the formula or pasteurized breast milk consumed by premature infants, recombinant human bile salt-stimulated lipase (rhBSSL) can cause gastrointestinal adverse effects, including abdominal distension, flatulence, constipation, colic, abdominal pain, gastroenteritis, vomiting, regurgitation, and rectal bleeding (101940). Premature infants receiving rhBSSL also had a slightly higher rate of necrotizing enterocolitis (NEC) when compared with those receiving placebo. After review by a panel of experts, it was determined that the rate of confirmed or suspected NEC in infants consuming rhBSSL was 3.3%, compared with 0.5% in those receiving placebo. Although this rate of NEC is lower than the historical rate of occurrence in premature infants (11%), a possible increased risk for NEC cannot be ruled out (101940).

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General ...Orally, proteolytic enzymes are generally well tolerated. See specific monographs for detailed safety information related to individual proteolytic enzymes.
Most Common Adverse Effects:
Orally: Gastrointestinal upset.
Serious Adverse Effects (Rare):
Topically: Allergic reactions.

Gastrointestinal ...Orally, some patients taking proteolytic enzymes may have gastrointestinal complaints (101517).

Immunologic ...Proteolytic enzymes are commonly found in laundry detergents and pre-spotter products. Rarely, protease specific IgE positive tests possibly related to these products have occurred. Exposure may be airborne or topical (102705). In addition, in case reports, occupational exposure to the airborne proteolytic enzyme pepsin has resulted in allergic rhinoconjunctivitis or asthma (102706,102707).

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