Polyflora O by D'Adamo Personalized Nutrition

POSSIBLY EFFECTIVE

• Diarrhea. Low-quality evidence shows that oral cooked green bananas might be helpful for the management of acute and persistent diarrhea due to various causes in children. Details: Many clinical studies in children aged 5 months to 5 years with acute diarrhea of various etiologies shows that consuming cooked green bananas with or without rice for up to 14 days increases recovery rates by 30% to 266% when compared with control (93451,93462,93463,106469). Consuming cooked green bananas also reduced the need for rehydration therapy and the incidence of dehydration (93462,93463,106469). Clinical trials used cooked green bananas 50-100 grams per day in children aged 6-12 months, 100-200 grams per day in children aged 12-24 months, and 300 grams per day aged 24 months to 5 years (93451,93462,93463,106469). A moderate size, open label clinical study among children aged 6-35 months hospitalized with persistent diarrhea in Bangladesh shows that consuming a diet of green banana mixed with rice suji increases the number of children who recover within 5 days when compared with a full-strength rice suji diet but is equivalent to the standard treatment (control) of 75% strength rice suji diet (112150). Duration of hospital stay is also similar with green banana and 75% strength rice suji and shorter than with full strength rice suji. There is also less relapse at home among children who had been given the green banana rice suji diet in hospital compared with the 75%-strength rice suji. The validity of the study is limited by the lack of blinding. Clinical research also shows that bananas might be beneficial for diarrhea associated with enteral feeding in adults with critical illness. Adding banana flakes (Kanana Banana, Corpak Co) 1-3 tablespoons every 8 hours to the feeding tube seems to be as effective as routine medical treatment involving feeding rate adjustments and use of antidiarrheal agents for reducing symptoms and duration of diarrhea. After 7 days of treatment, 57% of patients in the banana group were free of diarrhea compared with only 24% of patients in the group receiving routine treatment (93453).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral banana flower for allergic rhinitis, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Athletic performance. It is unclear if oral banana is beneficial for athletic performance. Details: Preliminary clinical research in trained male cyclists shows that consuming 0.4 grams/kg carbohydrate orally from ripe bananas with water 10-20 minutes prior to a 75 km cycling time trial, and 0.15-0.2 grams/kg carbohydrate from bananas with water every 15 minutes during the trial, modestly improves cycling time and oxygen consumption when compared with water alone. This regimen is equally effective to the same dose of carbohydrate from a 6% carbohydrate beverage (Gatorade) (93459,93465). However, another study from the same group of researchers found conflicting results with the use of carbohydrates from banana for this purpose (100995). It is possible that the consumption of carbohydrates in general, not the use of bananas specifically, is beneficial for athletic performance. However, other preliminary clinical research in trained male runners shows that consuming a banana and drinking plain water does not improve the time to run 10 km on a treadmill when compared with plain water alone. No benefit was seen with the consumption of other carbohydrate drinks when compared with plain water; it is possible that the duration of exercise was too short to identify an improvement in performance (93457). Further research is needed to clarify the benefits of banana, if any, for athletic performance.
• Burns. It is unclear if topical banana leaf is beneficial in patients with burns. Details: Preliminary clinical research in adults and children with partial thickness burns shows that daily changes of a banana leaf dressing with povidone iodine reduces pain during dressing changes. Furthermore, wound healing is as effective as a boiled potato peel bandage with povidone iodine, with no increased need for skin grafting (93454). When compared with Vaseline gauze dressing for 8 days following skin graft treatment for burns in adults, banana leaf dressing increases speed of epithelization from 11.7 days to 8.7 days, and improves average pain, pain during dressing removal, and ease of dressing removal. By the 8th day, complete epithelization was present in 57% of the wounds dressed with banana leaves when compared with 0% of the wounds dressed with Vaseline gauze (93455).
• Cancer. Although there has been interest in using topical banana green fruit for cancer, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Constipation. It is unclear if oral green banana is beneficial in patients with constipation. Details: Preliminary clinical research in children with functional constipation shows that consuming cooked green bananas, 30 grams daily for 8 weeks, improves stool consistency and abdominal pain and reduces straining and pain during defecation when compared with baseline. Consuming cooked green bananas with a conventional laxative such as polyethylene glycol plus electrolytes or sodium picosulfate also appears to decrease the dose of laxative needed in these children when compared with baseline (100996). The validity of these findings is limited by the lack of a comparator group.
• Contraception. Although there has been interest in using oral banana root for contraception, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Cough. Although there has been interest in using oral banana flower for cough, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Depression. It is unclear if oral banana is beneficial in patients with depression. Details: A large cross-sectional study in the general Chinese adult population has found that moderate, but not high, banana consumption is associated with a lower likelihood of depressive symptoms in males. However, high banana consumption is associated with a higher likelihood of depressive symptoms in females (106471).
• Diabetes. It is unclear if oral banana starch is beneficial in patients with diabetes. Details: Two small clinical studies in adults with type 2 diabetes shows that taking banana starch 24-57.2 grams orally daily for 4-28 days does not improve serum glucose levels, glucose variability, glucose control scores, or insulin levels when compared with control starches (110619,93448).Other preliminary clinical research in obese patients with type 2 diabetes shows that taking banana starch 24 grams in 240 mL of water each day for 4 weeks reduces body weight when compared with a taking soymilk powder in water. However, banana starch did not improve lipid levels or body fat (93448). Other preliminary clinical research in patients with type 2 diabetes shows that taking desiccated banana 250 grams daily for 12 weeks does not improve lipid levels or glycemic response when compared to baseline (93452).
• Exercise-induced muscle soreness. It is unclear if oral banana is beneficial for exercise-induced muscle soreness. Details: Preliminary clinical research in trained cyclists shows that consuming 0.4 grams/kg of carbohydrates orally from mini-yellow bananas with water 20 minutes prior to a 75 km cycling time trial, and 0.2 grams/kg of carbohydrates from banana every 15 minutes during the trial, decreases muscle soreness ratings 1.5 hours after the time trial when compared with water alone. Consuming carbohydrates from Cavendish bananas in the same manner did not decrease delayed onset muscle soreness, although cyclists reported less muscle cramping with both types of bananas when compared with water (100995). It is unclear whether carbohydrates from banana are any more effective than other carbohydrate sources or whether these results are generalizable to other types of exercise.
• Gastroesophageal reflux disease (GERD). Although there has been interest in using oral banana fruit for GERD, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Hangover. Although there has been interest in using oral banana fruit for hangover, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Headache. Although there has been interest in using topical banana leaves for headache, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Hypercholesterolemia. It is unclear if oral banana is beneficial in patients with hypercholesterolemia. Details: Preliminary clinical research shows that taking desiccated banana 500 grams orally daily for 12 weeks reduces levels of total cholesterol by 7.5% when compared with baseline in patients with hypercholesterolemia. Taking 250 grams daily does not seem to reduce total cholesterol levels; however, high-density lipoprotein (HDL) cholesterol levels increase by 14.5% (93452). The validity of these findings is limited by the lack of a comparator group.
• Hypertension. Although there has been interest in using oral banana fruit for hypertension, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Hypokalemia. Although there has been interest in using oral banana fruit for hypokalemia, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Inflammatory bowel disease (IBD). Although there has been interest in using oral banana fruit for IBD, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Joint pain. Although there has been interest in using oral banana flower for joint pain, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Kidney stones (nephrolithiasis). Oral banana stem has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with calculi of at least 5 mm shows that taking a specific Ayurvedic product (Herbmed) containing banana stem 250 mg and Crateva nurvala 250 mg orally daily for 3 months moderately improves symptoms associated with urinary calculi and reduces the size of the calculi by 11% to 33% when compared with baseline (93460). It is not clear if this is due to banana stem, Crateva nurvala, or the combination. Also, the validity of this finding is limited by the lack of a comparator group.
• Menorrhagia. Although there has been interest in using oral banana fruit for menorrhagia, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Obesity. It is unclear if oral banana is beneficial in patients with obesity. Details: Preliminary clinical research in obese patients with type 2 diabetes shows that taking banana starch 24 grams in 240 mL of water orally each day for 4 weeks reduces body weight by 1 kg more when compared to a control group consuming soymilk powder in water (93448).
• Peptic ulcers. Although there has been interest in using oral banana fruit for peptic ulcers, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Shigellosis. It is unclear if oral green banana is beneficial in patients with shigellosis. Details: Clinical research in children 6-60 months of age who are being treated with antibiotics for shigellosis shows that eating cooked green banana 250 grams per liter of a rice-based diet for 5 days improves symptoms of diarrhea, including the presence of fecal mucus and blood, when compared with a rice-based diet alone. Adding banana to the diet decreased the number of daily stools by 70% in those consuming banana compared to 50% in children consuming the rice diet alone (93461).
• Skin grafts. Although there has been interest in using topical banana leaves for skin grafts, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Smoking cessation. Although there has been interest in using oral banana fruit for smoking cessation, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Stroke. Although there has been interest in using oral banana fruit for stroke, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Tuberculosis. Although there has been interest in using oral banana flower for tuberculosis, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Vaginitis. Although there has been interest in using oral banana root for vaginitis, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Vitamin A deficiency. Although there has been interest in using oral banana fruit for vitamin A deficiency, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Warts. Although there has been interest in using topical banana leaves or peels for warts, there is insufficient reliable information about the clinical effects of banana for this purpose.
• Wound healing. Although there has been interest in using topical banana leaves, peels, or green fruit for wound healing, there is insufficient reliable information about the clinical effects of banana for this purpose. More evidence is needed to rate banana for these uses.

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POSSIBLY EFFECTIVE

• Irritable bowel syndrome (IBS). A specific strain of oral brewer's yeast seems to be beneficial for some IBS symptoms. Details: A meta-analysis of results from two clinical studies shows that taking the specific brewer's yeast strain CNCM I-3856 500 mg or 1000 mg daily, standardized to 8 billion colony-forming units (CFUs) per gram, for up to 12 weeks might reduce abdominal pain and discomfort and improve stool consistency in patients with constipation-predominant IBS. It seems to take at least one month for any benefits to occur (95611). Another small clinical study shows that taking the same product as 2 billion CFUs twice daily in addition to standard treatment for 8 weeks modestly improves abdominal pain and stool consistency when compared with standard treatment alone. Benefits were evident within 4 weeks and were found in patients with diarrhea-predominant, constipation-predominant, and mixed-type IBS (105170). Additionally, a large clinical trial in patients with constipation-predominant IBS shows that taking the same brewer's yeast product 8 billion CFUs daily for 8 weeks increases the likelihood of abdominal pain response, defined as a 30% or greater reduction in average daily abdominal pain scores, by 33% and improves quality of life scores when compared with placebo. However, no improvements in bloating, flatulence, stool frequency, or stool consistency were reported (111108).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using oral or topical brewer's yeast for acne, there is insufficient reliable information about the clinical effects of brewer's yeast for this condition.
• Allergic rhinitis (hay fever). It is unclear if oral dried, inactive brewer's yeast is beneficial for allergic rhinitis. Details: Preliminary clinical research in adults with seasonal allergies shows that taking a specific dried, inactive brewer's yeast preparation (EpiCor, Embria Health Sciences) 500 mg once daily for 12 weeks reduces the median severity of nasal congestion by 14%, the median severity of rhinorrhea by 19%, and the median number of days with nasal congestion by 12.5 days during weeks of highest pollen counts when compared with placebo. However, taking this brewer's yeast preparation does not appear to reduce ocular symptoms or sneezing. Also, it does not appear to improve nasal or ocular symptoms during weeks in which pollen counts are lower (92821).
• Clostridioides difficile infection. Although there has been interest in using oral brewer's yeast for C. difficile infection, there is insufficient reliable information about the clinical effects of brewer's yeast for this condition.
• Diarrhea. Although there has been interest in using oral brewer's yeast for diarrhea, there is insufficient reliable information about the clinical effects of brewer's yeast for this condition.
• Furuncles (boils). Although there has been interest in using oral brewer's yeast for furuncles, there is insufficient reliable information about the clinical effects of brewer's yeast for this condition.
• Hypercholesterolemia. It is unclear if oral brewer's yeast is beneficial for hypercholesterolemia. Details: Preliminary clinical research shows that taking brewer's yeast 20 grams, containing chromium 48 mcg, daily for 8 weeks decreases levels of total cholesterol by 24-26 mg/dL and increases levels of high-density lipoprotein (HDL) cholesterol by 5-6 mg/dL when compared to baseline in normocholesterolemic and hypercholesterolemic patients (37178).
• Influenza. It is unclear if oral dried, inactive brewer's yeast is beneficial for influenza. Details: Preliminary clinical research shows that taking a specific dried, inactive brewer's yeast preparation (EpiCor, Embria Health Sciences) 500 mg daily for 12 weeks reduces the incidence of common cold or flu-like symptoms by 10% to 20% when compared with placebo in adults with no history of influenza vaccination. Taking this preparation does not appear to reduce the duration or severity of cold or flu-like symptoms that do occur in these patients (92822). However, in patients recently vaccinated for influenza, clinical research shows that taking this same preparation 500 mg daily for 12 weeks reduces the risk of developing symptoms of the common cold or flu by about 11% and reduces the duration of symptoms that develop by 0.85 days when compared with placebo (16117).
• Premenstrual syndrome (PMS). Oral brewer's yeast has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that taking a specific combination product (Sillix Donna, Giuliani) containing folic acid, vitamin B6, vitamin E, various minerals, and brewer's yeast might help reduce scores on the Menstrual Distress Questionnaire (MDS) when compared to baseline (7845). It is unclear if this benefit is due to brewer's yeast or the vitamins and minerals also contained in the preparation. More evidence is needed to rate brewer's yeast for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Breast cancer-related hot flashes. Oral chicory has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study of breast cancer survivors who use estrogen deprivation therapy shows that taking 5 mL of chicory and fumitory syrup 3 times daily for 4 weeks significantly decreases the frequency and severity of hot flashes when compared with placebo. Hot flash frequency and severity were both reduced by around 57% in the treatment group, as compared with a 10% reduction in the placebo group (110724). The use of a per-protocol analysis limits the validity of these findings. Additionally, it is unclear if these findings are due to chicory, fumitory, or the combination. Cancer. Although there has been interest in using oral chicory for the treatment or prevention of cancer, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Constipation. Although there has been interest in using oral chicory for constipation, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Diabetes. Although there has been interest in using oral chicory for diabetes, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Dyspepsia. Although there has been interest in using oral chicory for dyspepsia, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Hyperlipidemia. Although there has been interest in using oral chicory for hyperlipidemia, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Hypertension. Although there has been interest in using oral chicory for hypertension, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Neonatal jaundice. It is unclear if oral chicory solution is beneficial in neonates with jaundice. Details: A moderate-sized clinical study of nursing mothers shows that taking 50 mL of chicory 10% distillate every 12 hours for 3 days reduces bilirubin levels of breastfed neonates with jaundice by around 0.3 mg/dL when compared with placebo (110723). However, it is unlikely that these findings are clinically significant.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral chicory seed is beneficial in patients with NAFLD. Details: A small clinical trial in patients with NAFLD shows that taking chicory seed 9 grams infused in hot water daily for 12 weeks reduces body mass index (BMI) by 0.66 kg/m2 when compared with placebo. When combined with turmeric 3 grams daily, serum alkaline phosphatase was decreased. Although levels of other liver enzymes decreased when compared to baseline, changes were not significant when compared with placebo. Also, taking chicory seed did not affect plasma lipid levels (102350).
• Osteoarthritis. It is unclear if oral chicory root extract is beneficial in patients with osteoarthritis. Details: A small clinical study in patients with knee or hip osteoarthritis shows that taking chicory root extract 600 mg three times daily for 3 months does not improve pain, stiffness, or functional ability when compared with placebo (93647). However, this small study was likely underpowered to detect differences between groups. More evidence is needed to rate the effectiveness of chicory for these uses.

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POSSIBLY EFFECTIVE

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

POSSIBLY INEFFECTIVE

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

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about LACTICASEIBACILLUS RHAMNOSUS)

POSSIBLY EFFECTIVE

• 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.

(Read more about LACTOBACILLUS ACIDOPHILUS)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Common cold. Preliminary clinical research shows that taking a specific larch arabinogalactan extract (ResistAid, Lonza Ltd.) 4.5 grams daily for 12 weeks does not significantly decrease the number, intensity, or symptoms of common colds when compared with placebo in patients who frequently suffer from colds. However, larch arabinogalactan appears to increase the percentage of patients who experience no cold episodes. About 42% of patients receiving larch arabinogalactan extract had no cold episodes, compared to only 28% of patients receiving placebo (93104).
• Hyperlipidemia. Preliminary clinical research shows that taking larch arabinogalactan 8.4 grams daily for 6 months, or 15-30 grams daily for 6 weeks, does not significantly lower total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B (apo B), apolipoprotein A-1, body weight, blood pressure, or glucose levels in healthy people (15617,15620). It is not known if larch arabinogalactan lowers lipid levels in patients with hyperlipidemia. More evidence is needed to rate larch arabinogalactan for these uses.

(Read more about LARCH ARABINOGALACTAN)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Antibiotic-associated diarrhea. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in hospitalized adults shows that consuming a 97 mL drink (Actimel, Danone) containing S. thermophilus 100 million colony-forming units (CFUs)/mL, Lacticaseibacillus casei 100 CFUs/mL, and Lactobacillus delbrueckii subsp. bulgaricus 10 million CFUs/mL twice daily while taking antibiotics reduces the odds of developing AAD by 75% when compared with a milkshake without probiotics (16740). However, a meta-analysis of 6 clinical trials in hospitalized or outpatient adults, including the study above, shows that taking S. thermophilus in combination with 2-7 other probiotic strains does not reduce the risk of antibiotic-associated diarrhea when compared with placebo (107635). The validity of these findings is limited by the high degree of heterogeneity across the studies, including variations in the study populations, study durations, and probiotic combinations assessed. The use of a combination product containing S. thermophilus has also been studied in infants 6-26 months of age. A small clinical study in these patients shows that taking a formula containing S. thermophilus 1 million CFUs and Bifidobacterium animalis subsp. lactis 10 million CFUs daily for 15 days reduces the risk of AAD by 48% when compared with taking regular formula (102427).
• Bacterial vaginosis. Intravaginal Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with recurrent bacterial vaginosis shows that using a specific probiotic capsule (Probaclac Vaginal, Nicar Laboratories, Inc) containing S. thermophilus 0.8 billion stabilized lactic ferments, Lacticaseibacillus rhamnosus 6.8 billion stabilized lactic ferments, and Lactobacillus acidophilus 0.4 billion stabilized lactic ferments intravaginally once daily for two one-week periods, with a one week rest period in between, reduces the odds of bacterial vaginosis recurrence by 77% when compared with control (102438).
• Child growth. It is unclear if oral Streptococcus thermophilus is beneficial for improving child growth. Details: A preliminary clinical study in malnourished children ages 6 months to 3 years shows that consuming a powdered milk formula with S. thermophilus and Bifidobacteria bifidum Bb12 400-600 mL daily for 6 months does not impact weight or height when compared with the same formula with B. bifidum Bb12 alone (102434). The validity of this study was limited by short duration and variability in the children's age.
• Clostridioides difficile infection. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in hospitalized adults shows that taking S. thermophilus along with Bifidobacterium bifidum, Lactobacillus acidophilus, and Lactobacillus delbrueckii subsp. bulgaricus, 12 billion colony-forming units (CFUs) total daily, starting 1 day after beginning antibiotic treatment, reduces the risk of C. difficile diarrhea by about 72% when compared with placebo (95364).
• Colic. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in breastfed infants aged 15-120 days with colic shows that receiving a synbiotic sachet containing 1 billion colony-forming units total of S. thermophilus, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Bifidobacterium breve, as well as fructo-oligosaccharides (Protexin Healthcare) daily for 30 days reduces daily crying by 50% or more in 87% of infants, compared with an average 46% reduction in the placebo group (102430).
• Constipation. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in adults with functional constipation or constipation-predominant irritable bowel syndrome shows that taking a 26-gram chocolate supplement containing S. thermophilus MG510 300 million colony-forming units (CFUs)/gram and Lactiplantibacillus plantarum LRCC5193 100 million CFUs/gram daily for 4 weeks does not increase bowel movements when compared with placebo. However, it may modestly improve stool consistency (102440).
• Coronavirus disease 2019 (COVID-19). Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small, retrospective study in patients with severe COVID-19 symptoms suggests that taking a combination of probiotics in addition to standard treatments modestly reduces the duration of diarrhea when compared with standard treatments alone. The probiotic treatment consisted of S. thermophilus 6 million colony-forming units (CFUs), Lactobacillus delbrueckii subsp. bulgaricus 6 million CFUs, and Bifidobacterium longum 60 million CFUs, given in three divided doses daily (107200).
• Diabetes. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with type 2 diabetes shows that taking a specific combination product (Familact probiotics, ZistTakhmir Co.) containing S. thermophilus and other probiotic bacteria daily for 6 weeks does not reduce fasting blood glucose or plasma insulin levels when compared with placebo. This product contains S. thermophilus 1.5 billion colony forming units (CFUs), Lactobacillus acidophilus 2 billion CFUs, Lacticaseibacillus casei 7 billion CFUs, Lacticaseibacillus rhamnosus 1.5 billion CFUs, Lactobacillus delbrueckii subsp. bulgaricus 200 million CFUs, Bifidobacterium breve 30 billion CFUs, and Bifidobacterium longum 7 billion CFUs (99790). Other clinical research in adults with diabetes shows that taking a combination of S. thermophilus, L. acidophilus, and Bifidobacterium bifidum daily for 12 weeks does not reduce levels of fasting blood glucose or glycated hemoglobin (HbA1c) when compared with placebo (107521). However, S. thermophilus in combination with other probiotics might be beneficial for gestational diabetes. A small clinical study in patients with gestational diabetes shows that taking a total of 4 billion CFUs of a freeze-dried combination of S. thermophilus STY-31, L. acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, and L. delbrueckii subsp. bulgaricus LBY-27 for 8 weeks, starting at 24-28 weeks' gestation, modestly reduces fasting blood glucose and improves insulin sensitivity when compared with placebo (96892). Also, other clinical research in patients with gestational diabetes shows that taking a specific product containing S. thermophilus and other probiotics (Visbiome, ExeGi Pharma) as a total of 112.5 billion CFUs twice daily for 8 weeks does not affect levels of fasting blood glucose or HbA1c when compared with placebo. However, there were small improvements in insulin levels and insulin resistance (107549). A combination probiotic containing S. thermophilus has also been evaluated in children 2-12 years of age with new-onset type 1 diabetes. One clinical study shows that taking Visbiome as 112.5 billion CFUs daily for 3 months modestly decreases HbA1c and insulin requirements when compared with placebo. Also, about three times as many children achieved remission, which was defined as insulin requirements of less than 0.5 U/kg daily and HbA1c of less than 7%. However, C-peptide levels and the maintenance of residual pancreatic beta-cell function were not affected when compared with placebo (107497).
• Diabetic nephropathy. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with diabetic nephropathy who are not taking antidiabetes drugs shows that taking a combination of S. thermophilus, Lactobacillus acidophilus, and Bifidobacterium bifidum 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 Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in children aged 3-36 months with acute diarrhea shows that taking a combination probiotic (Lactogermina) containing 1 billion colony-forming units (CFUs) each of S. thermophilus, Lactobacillus delbrueckii subsp. Bulgaricus, and Lactobacillus acidophilus, plus 500 million CFUs of Bifidobacterium bifidum daily for 5 days, in addition to oral rehydration solution, reduces the duration of diarrhea by 37 hours when compared with oral rehydration solution alone (102426). In addition, a small clinical study in children with dysentery being treated with ceftriaxone shows that taking a specific combination probiotic sachet (Kidilact, Zisttakhmir Company) containing S. thermophilus, Lacticaseibacillus casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum, and Bifidobacterium breve daily for 5 days modestly reduces the duration of diarrhea, hospitalization, and blood in diarrhea when compared with control (102417). It is unclear if these effects are due to S. thermophilus, the other ingredients, or the combination. S. thermophilus has also been evaluated for the prevention of acute diarrhea. A large clinical trial in infants aged 4-6 months shows that taking a fermented formula containing S. thermophilus and Bifidobacterium breve daily for 5 months does not reduce the risk of acute diarrhea or hospitalization for diarrhea, nor does it improve the duration of diarrhea episodes when compared with standard infant formula. However, infants receiving this probiotic had less severe episodes of diarrhea, required fewer medical consultations and prescriptions for oral rehydration solution, and had a lower risk of dehydration (111106). It is unclear if these effects are due to S. thermophilus, Bifidobacterium breve, or the combination.
• Exercise-induced muscle soreness. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in resistance-trained males shows that taking S. thermophilus FP4 and Bifidobacterium breve BR03 10 billion colony-forming units total daily for 3 weeks prior to resistance training modestly attenuates range of motion decrements following resistance training, but does not improve range of motion, muscle soreness, or exercise recovery, when compared with placebo (95415).
• Helicobacter pylori. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In adults with H. pylori infection and peptic ulcer disease, adding a combination product containing seven strains of probiotics (Balance by Protexin Co), including S. thermophilus, daily for 14 days to quadruple therapy with omeprazole, bismuth subcitrate, amoxicillin, and clarithromycin does not improve H. pylori eradication or symptoms when compared with quadruple therapy alone (90291).
• HIV/AIDS. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children ages 2-12 years with HIV shows that receiving a specific probiotic formula (NAN2 probiotico, Nestle) containing a total of 25 billion colony-forming units of S. thermophilus and Bifidobacterium bifidum daily for 2 months modestly increases CD4 counts, but does not reduce diarrhea, when compared with a standard formula (102436).
• Irritable bowel syndrome (IBS). Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Products containing S. thermophilus and other probiotics (Duolac Care; LacClean Gold-S, Cell Biotech, Co. Ltd) as a total of 5 billion colony-forming units (CFUs) twice daily for 4 weeks have shown some benefit in adults with IBS (95353,102439). S. thermophilus-containing probiotics also seem to help specifically in patients with diarrhea-predominant IBS (IBS-D). Duolac Care contains S. thermophilus, Lactobacillus acidophilus, Lacticaseibacillus plantarum, Lacticaseibacillus rhamnosus, Bifidobacterium breve, Bifidobacterium animalis subsp. lactis, and Bifidobacterium longum 10 billion CFUs and was taken twice daily for 8 weeks (102429). Other research has shown benefit with a specific product (Visbiome, ExeGi Pharma) containing S. thermophilus and other probiotics taken as 450 billion CFUs daily for 8 weeks (11379). However, adding this product as 900 billion CFUs daily to a sham diet or a low-FODMAP diet for 4 weeks does not improve IBS symptoms when compared with placebo (98741). Other clinical research shows that taking a specific product (NordBiotic, MBM Biotix) containing S. thermophilus ST250, L. acidophilus LA120, L. rhamnosus LR110, Lacticaseibacillus paracasei LPC100, Lactocaseibacillus casei LC130, and Lactiplantibacillus plantarum LP140, as well as B. breve BB010, B. longum BL020, B. bifidum BF030, and B. animalis subsp. lactis BL040 as 2.5 billion CFUs total twice daily for 8 weeks improves overall symptom severity, as well as quality of life, pain severity, and pain frequency, 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).
• Necrotizing enterocolitis (NEC). Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Also, it is unclear if oral S. thermophilus is safe for use in preterm infants. Details: A network meta-analysis of two clinical studies shows that taking a combination probiotic containing S. thermophilus TH-4, Bifidobacterium longum subsp. infantis Bb-02, and Bifidobacterium animalis sups. Lactis Bb-12 reduces the risk of NEC by 71% when compared with control (102437). It is unclear if these effects are due to S. thermophilus, the other ingredients, or the combination. Also, 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 very preterm or very low birth weight infants under 1000 grams (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).
• Nonalcoholic fatty liver disease (NAFLD). Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with NAFLD shows that taking a total of 500 million colony-forming units of S. thermophilus and Lactobacillus delbrueckii subsp. bulgaricus daily for 3 months modestly reduces liver enzyme levels when compared to baseline (102424). This study was limited by a lack of statistical comparison to the placebo group. Another small clinical study in patients with NAFLD shows that taking a specific product (VSL#3) containing S. thermophilus and seven other probiotic strains, two sachets each morning for 3 months, modestly reduces liver enzyme levels and measures of hepatic steatosis when compared with placebo (111105). It is unclear if these findings are due to S. thermophilus, other ingredients, or the combination.
• Nonalcoholic steatohepatitis (NASH). Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small open-label clinical trial in patients with NASH shows that taking a combination probiotic containing a total of 100 million colony-forming units of S. thermophilus, Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactobacillus delbrueckii subsp. bulgaricus, and Bifidobacterium longum, plus fructo-oligosaccharides once daily for 12 weeks modestly reduces liver stiffness and alanine aminotransferase, but does not affect steatosis or other liver enzyme levels, when compared with control (102415).
• Oral mucositis. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with Candida-associated oral mucositis shows that, in addition to topical antifungal therapy, taking four 500-mg lozenges, with each lozenge containing S. thermophilus 500,000 colony-forming units (CFUs), Bifidobacterium longum 5 million CFUs, and Lactobacillus delbrueckii subsp. bulgaricus 500,000 CFUs, three times daily for 4 weeks does not reduce symptoms to a greater extent than topical antifungal therapy alone (102432).
• Otitis media. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in children 7-13 months of age with a recent history of otitis media shows that taking a combination of S. thermophilus NCC 2496 10 million colony-forming units (CFUs)/gram, Streptococcus salivarius DSM 13084 25 million CFUs/gram, and Lacticaseibacillus rhamnosus LPR CGMCC 1.3724 10 million CFUs along with the prebiotics raftilose or raftiline daily for 12 months does not reduce the risk of otitis media recurrence or antibiotic use when compared with regular formula alone (90241).
• Pouchitis. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that continuous oral treatment for one year with a specific combination product (Visbiome, ExeGi Pharma) containing S. thermophilus and other probiotics, 300-500 billion live bacteria per gram, for up to 12 months seems to maintain remission in 85% of patients with pouchitis (6087,12769).
• Rotaviral diarrhea. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in hospitalized infants shows that giving S. thermophilus 14 million colony-forming units (CFUs) daily with Bifidobacterium BB-12 100 or 190 million CFUs daily, either for 8 months or the duration of hospital stay, reduces the incidence of diarrhea and rotavirus shedding (161,3169).
• Sepsis. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in very preterm infants shows that taking a probiotic combination containing 1 billion colony-forming units of S. thermophilus, Bifidobacterium longum subsp. infantis, and Bifidobacterium animalis subsp. lactis does not reduce mortality or late-onset sepsis when compared with placebo (102428).
• Small intestinal bacterial overgrowth (SIBO). Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with SIBO shows that taking a specific combination probiotic (Duolac Gold, Cell Biotech Co., Ltd) containing S. thermophilus, Bifidobacterium bifidum, Bifidobacterium animalis subsp. lactis, Bifidobacterium longum, Lactobacillus acidophilus, and Lacticaseibacillus rhamnosus 5 billion colony-forming units in lyophilized powder form daily for 4 weeks reduces SIBO and gastrointestinal symptoms when compared with placebo (102431).
• Ulcerative colitis. Oral Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Research shows that taking combination probiotics containing S. thermophilus might increase remission rates in patients with ulcerative colitis. The best evidence of benefit is for a specific combination product (Visbiome, ExeGi Pharma). Doses of 3 grams (equivalent to 900 billion colony-forming units (CFUs)) once or twice daily have been used in combination with conventional treatment. In children aged 1-16 years, doses of 450-1800 billion CFUs for up to one year have been used (3261,14370,14371,16841,95337). A meta-analysis of clinical research shows that taking this product as an adjunct to standard ulcerative colitis treatment can increase remissions rates in adults and children with ulcerative colitis by about 1.7-fold when compared with standard treatment alone (95337). There is also evidence that it is beneficial for improving remission rates in patients who do not adequately respond to conventional treatment (14371). Additionally, some preliminary clinical research shows that this specific product, taken as an adjunct to standard maintenance therapy, might help prevent relapse (3261,16841).
• Vaginal candidiasis. Intravaginal Streptococcus thermophilus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that a specific combination product (Femilac) containing S. thermophilus, Lacticasebacillus rhamnosus, Lactobacillus delbrueckii, and Lactobacillus acidophilus, given intravaginally, does not seem to reduce the risk of vaginal candidiasis infection following use of antibiotics when compared with a control group (12108). More evidence is needed to rate Streptococcus thermophilus for these uses.

(Read more about STREPTOCOCCUS THERMOPHILUS)

LIKELY SAFE ...when used in the amounts commonly found in food.

POSSIBLY SAFE ...when the leaves are applied topically and appropriately (93456). There is insufficient reliable information available about the safety of the other parts of the banana plant when used orally or topically as a medicine.

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

(Read more about BANANA)

POSSIBLY SAFE ...when used orally and appropriately, short-term (7845,16117). A specific dried, inactive brewer's yeast preparation (EpiCor, Embria Health Sciences) has been used with apparent safety at a dose of 500 mg once daily for 12 weeks (92821,92822). A specific living brewer's yeast strain CNCM I-3856 has been used with apparent safety at a dose of 500-1000 mg daily (standardized to 8 billion colony-forming units per gram) for up to 12 weeks (95611,105170,111108). There is insufficient reliable information available about the safety of the long-term use of brewer's yeast or about the safety of using brewer's yeast topically.

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

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

(Read more about BREWER'S YEAST)

LIKELY SAFE ...when consumed in amounts commonly found in food. Chicory and chicory extract have Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. Chicory root extract has been used with apparent safety at doses of 600 mg three times daily for one month (93647). Chicory seed has been used with apparent safety as a hot water infusion of 4.5 grams twice daily for 12 weeks (102350). There is insufficient reliable information available about the safety of chicory when used orally, long-term, or when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive amounts. Chicory may induce menstruation or miscarriage (19).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about CHICORY)

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

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

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

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

(Read more about LACTICASEIBACILLUS RHAMNOSUS)

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

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

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

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

(Read more about LACTOBACILLUS ACIDOPHILUS)

LIKELY SAFE ...when used orally in amounts found in foods. Larch arabinogalactan has Generally Recognized As Safe (GRAS) status in the US (3529).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Larch arabinogalactan has been safely used at doses of 1.5-8.4 grams daily for up to 6 months (15617,15618,17370,93102,93104,104281). Higher doses of 15-30 grams daily have been used with apparent safety for up to 6 weeks (15620). There is insufficient reliable information available about the safety of larch arabinogalactan when used long-term.

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

(Read more about LARCH ARABINOGALACTAN)

LIKELY SAFE ...when used orally and appropriately. Streptococcus thermophilus in combination with other probiotic strains has been safely used in clinical trials lasting up to one year (162,1233,1731,3261,6087,11379,12769,14370,14371,16740,102440).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. Streptococcus thermophilus in combination with other probiotic species has been used with apparent safety in children of most ages for up to one year (161,3169,16841,90241,102426,102436,111106). There is insufficient reliable information available about the safety of Streptococcus thermophilus 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, short-term. A combination of Streptococcus thermophilus, Lactobacillus acidophilus, Bifidobacterium animalis, and Lactobacillus delbrueckii has been used with apparent safety for 8 weeks starting at 24-28 weeks gestation (96892).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about STREPTOCOCCUS THERMOPHILUS)

LEVODOPA Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Taking banana may reduce the effectiveness of levodopa.  Details A case report describes apparent wearing off in a patient with Parkinson disease after eating a banana every day. The wearing off subsided after removing dietary bananas (110618).

(Read more about BANANA)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Taking brewer's yeast with antidiabetes drugs might increase the risk of hypoglycemia.  Details Clinical research shows that taking chromium-containing brewer's yeast can decrease levels of blood glucose in diabetic patients being treated with antidiabetes drugs (37157).

ANTIFUNGALS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking antifungals with some brewer's yeast products might decrease the effectiveness of brewer's yeast.  Details Some brewer's yeast products contain live yeast. Therefore, simultaneously taking antifungals might kill a significant number of the organisms (4363).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking brewer's yeast with lithium might cause additive effects and side effects.  Details Some brewer's yeast products contains lithium (37179).

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = D Theoretically, taking brewer's yeast with MAOIs might increase the risk of hypertension.  Details Brewer's yeast contains tyramine. Taking brewer's yeast with MAOIs might increase the risk for hypertensive crisis (2).

(Read more about BREWER'S YEAST)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, chicory might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal and in vitro research shows that chicory extracts have antidiabetic effects (93650,108543).

(Read more about CHICORY)

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

(Read more about LACTICASEIBACILLUS RHAMNOSUS)

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

(Read more about LACTOBACILLUS ACIDOPHILUS)

(Read more about LARCH ARABINOGALACTAN)

(Read more about STREPTOCOCCUS THERMOPHILUS)

General ...Orally, bananas are well tolerated when consumed as food.
Most Common Adverse Effects:
Orally: Bloating, cramping, gas.
Topically: Urticaria.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis, intestinal obstruction.

Endocrine ...In one case report, an adolescent girl who consumed nothing other than 20 bananas daily developed hyperkalemia and hyperdopaminemia. These changes in the blood resulted in pseudoaldosteronism and dysthymia (93780).

Gastrointestinal ...Orally, banana starch isolated from green bananas has resulted in bloating, gas, cramping, and softer feces (93448,93449,110619). When consumed prior to exercise, fullness and bloating during exercise have been reported (93459). In children, nausea, vomiting, and abdominal distension have been reported when banana is used in the treatment of diarrhea (93461). Cases of intestinal obstruction due to banana seeds have been reported (93777).
In one case report, food protein-induced enterocolitis syndrome (FPIES) has been associated with banana consumption (93778).

Immunologic ...Orally, banana has been reported to cause allergic reaction, including urticaria and redness, abdominal pain and nausea, dyspnea (93779,93781,93782,93797,93798,93803), and anaphylaxis (93783,93793,93802,93803). Topically, contact urticara has also been reported (93784). Skin testing is not always accurate, even for patients with severe banana allergy (93793).

Psychiatric ...Orally, high banana consumption has been associated with a higher likelihood of depressive symptoms in females, but not males, in a cross-sectional study of the general Chinese adult population (106471).

(Read more about BANANA)

General ...Orally, brewer's yeast seems to be well tolerated in most patients when used short-term.
Most Common Adverse Effects:
Orally: Flatulence, migraine.
Serious Adverse Effects (Rare):
Orally: There is concern that brewer's yeast may cause fungemia in some people. It may also cause anaphylaxis in sensitive individuals.

Gastrointestinal ...Orally, brewer's yeast can cause intestinal discomfort and flatulence in hypersensitive individuals (2). Anal irritation and abdominal pain have been reported rarely (105170).

Immunologic ...Allergic reactions to brewer's yeast can occur in hypersensitive individuals. Symptoms include itching, urticaria, local or general exanthemas, and Quincke's edema (2). Rarely, anaphylaxis may occur. In one case, a 33-year-old male experienced dyspnea, chest tightness, and throat tightness shortly after ingesting a few sips of craft beer brewed using brewer's yeast. The patient took diphenhydramine, and symptoms improved prior to his arrival in the emergency department. While the patient had no history of hypersensitivity to other beers from the same brewery, a positive skin test and oral challenge suggested that he was sensitive to the specific strain of brewer's yeast uniquely used only in the offending beer (111107).

Neurologic/CNS ...Orally, brewer's yeast can cause migraine-like headaches in sensitive individuals (2).

(Read more about BREWER'S YEAST)

General ...Orally, chicory seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, belching, bloating, and flatulence.

Dermatologic ...Occupational exposure to chicory may cause skin rash, contact dermatitis, or generalized pruritus (41609,93649). The sesquiterpene lactones of the plant may be the allergens (41609). Chicory may cause an allergic reaction in individuals sensitive to the Asterceae/Compositae family (25416). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Gastrointestinal ...Orally, fructo-oligosaccharides, such as those extracted from chicory, can cause flatulence, belching, abdominal pains, intestinal sounds and bloating, which occur commonly, but are mild at doses of 10 grams daily (740,745,750,8509,93716).

Immunologic ...Occupational exposure to chicory may cause allergic reactions. Dyspnea and anaphylaxis have also been reported in a patient with regular occupational exposure to chicory. This patient also experienced contact dermatitis and generalized pruritus (93649).

Pulmonary/Respiratory ...Occupational exposure to chicory may cause asthma and rhinoconjunctivitis (41617,93648). Dyspnea and anaphylaxis have also been reported in a patient with regular occupational exposure to chicory. This patient also experienced contact dermatitis and generalized pruritus (93649).

(Read more about CHICORY)

General ...Orally, Lacticaseibacillus rhamnosus is generally well tolerated.
Most Common Adverse Effects:
Orally: Mild gastrointestinal adverse effects.
Serious Adverse Effects (Rare):
Orally: There is concern that L. rhamnosus may cause infections in some people.

Gastrointestinal ...Orally, taking Lacticaseibacillus rhamnosus alone or in combination with other probiotics may cause gastrointestinal side effects including diarrhea (90235); however, these events are uncommon. In one small clinical study in infants with suspected cow's milk allergy who were receiving extensively hydrolyzed whey formula, diarrhea occurred in 5 of 13 infants receiving non-viable, heat-killed L. rhamnosus, compared with 0 of 14 infants receiving live L. rhamnosus and 0 of 8 infants receiving placebo (107528).
A 31-year-old male developed severe L. rhamnosus GG stomatitis and oral ulcers while undergoing induction chemotherapy for acute myeloid leukemia. The strain in the ulcers was determined to be the same strain that had been consumed in dairy products (112506).

Immunologic ...Since Lacticaseibacillus rhamnosus preparations contain live and active microorganisms, there is some concern that they might cause pathological infection in some patients. Some lactobacilli species have been isolated in some cases of bacteremia, sepsis, splenic 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 system, in ill and/or immunocompromised patients, or in patients otherwise at risk of infection. However, there are also rare case reports of pathological infections possibly to intake of L. rhamnosus products in these populations (4380,4390,4391,4398,8561,13008,13070,90298,103444,105138)(105139,105141,107543,111613,112499,112505,112509,112536).
Case reports exist of bacteremia or sepsis associated with L. rhamnosus use in infants and children. In infants, some cases have occurred following the use of L. rhamnosus for the treatment or prevention of diarrhea. These cases include a severely ill 6-week-old infant given L. rhamnosus GG (Culturelle) for antibiotic-associated diarrhea (13008), a 6-day old with intrauterine growth restriction given L. rhamnosus GG to prevent antibiotic-associated diarrhea (112509), a 3-month-old infant given L. rhamnosus GG for the prevention of antibiotic-associated diarrhea, and a 18-day-old preterm, very-low-birthweight infant given L. rhamnosus GG for the prevention of necrotizing enterocolitis (111613). In other cases, infants with short bowel syndrome have developed bacteremia (13008,112536). One case report involved an 11-month-old infant receiving L. rhamnosus for 5 weeks through a gastrostomy tube for rotaviral diarrhea (13070). Lactobacillus sepsis has also occurred in a 6-year-old child with cerebral palsy following use of L. rhamnosus GG (Culturelle) for intermittent diarrhea (13008). A 17-year-old male with ulcerative colitis developed bacteremia following once daily use of L. rhamnosus GG 1 billion colony-forming units (CFUs) (Culturelle, ConAgra Foods) (90298).
There are also cases of L. rhamnosus bacteremia or sepsis in adults. Fatal L. rhamnosus septicemia has been reported in an immunocompromised patient consuming yogurt and taking prolonged courses of multiple broad spectrum antibiotics (8561). A 50-year-old male developed L. rhamnosus endocarditis following daily use of a probiotic product providing at least 5 billion CFUs of L. rhamnosus. Although the patient was considered healthy, the role of a previous diagnosis of an unspecified heart murmur or an untreated deep gingival cut 3 months prior to endocarditis diagnosis may have increased the risk of infection (105139). A 56-year-old immunocompetent female developed L. rhamnosus GG bacteremia. She was hospitalized with an indwelling catheter following a motor vehicle accident and had been given this strain following the onset of diarrhea via a nasogastric tube as per hospital protocol (112499). There is also a case of L. rhamnosus sepsis in a male in his late 60s with a bioprosthetic aortic valve. He was taking L. rhamnosus for ulcerative colitis and developed sepsis along with aortic valve endocarditis and septic emboli to the brain (112505).
A specific probiotic preparation (NBL probiotic ATP, Nobel) containing L. rhamnosus, Lacticaseibacillus casei, Lactiplantibacillus plantarum, Bifidobacterium animalis subsp. lactis, fructo-oligosaccharides, galacto-oligosaccharides, colostrum, and lactoferrin was found to be a significant risk factor for vancomycin-resistant Enterococcus colonization in premature infants. Although there was no direct link to determine causation, it was hypothesized that the probiotic mixture helped to mediate the acquisition and transfer of antibiotic resistance genes (96890).

(Read more about LACTICASEIBACILLUS RHAMNOSUS)

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).

(Read more about LACTOBACILLUS ACIDOPHILUS)

General ...Orally, larch arabinogalactan is generally well tolerated (3530,17370,93102). Some people can experience bloating and flatulence (3530).

Gastrointestinal ...Orally, larch arabinogalactan can cause bloating and flatulence (3530).

(Read more about LARCH ARABINOGALACTAN)

General ...Streptococcus thermophilus is well tolerated. Serious adverse effects have not been reported in clinical research.
Serious Adverse Effects (Rare):
Orally: There is concern that probiotics may cause infections in some people.

Immunologic ...Since many probiotic preparations contain live and active microorganisms, there is some concern that they might cause pathogenic infection in some patients. Bacteremia and sepsis have been reported in patients with indwelling or central venous catheters or patients who are severely ill and/or immunocompromised, including preterm infants, that were using probiotic products (4380,8561,13008,13070,90298,102416,103444,105138,105140,105141)(107543,107597,107599,111610,111612,111613,111850,111852,111853). However, reports of pathogenic colonization in relatively healthy patients with intact immune systems who do not have indwelling or central venous catheters are extremely rare (4380,4389,4390,4391,4393,4398,105139,107543,107545,107546)(107547).

(Read more about STREPTOCOCCUS THERMOPHILUS)