S.Bifido Biotic with B. longum BB536 by Orthoplex White

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about BIFIDOBACTERIUM LONGUM)

LIKELY EFFECTIVE

• Diarrhea. In children, oral Saccharomyces boulardii reduces the duration of acute diarrhea and the duration of hospitalization for acute diarrhea when taken alone or in combination with zinc. It is unclear if it is beneficial for chronic diarrhea in children or for diarrhea in adults. Details: Most clinical research shows that S. boulardii reduces the duration of acute diarrhea in children by about one day (92815,102422,103454,107636,111103). Diarrhea caused by rotaviruses or nonspecific causes was reduced by about 18 and 22 hours, respectively (92815). In regions where malnourishment or zinc deficiency is common, zinc is often given alongside oral rehydration therapy (ORT) as part of standard treatment. Individual clinical studies in infants and children with acute diarrhea show that giving S. boulardii (LesunBerry Sundyota Numandis) 150-250 mg once or twice daily, or 10 billion colony-forming units (CFUs) daily, for 5 days reduces the duration of diarrhea and the time to first semi-solid stool by about 12-29.5 hours when compared with ORT and possibly zinc (72147,95412,98397,98729,103451). In one clinical trial, approximately 83% of children adding S. boulardii to standard treatment with ORT and zinc were considered as recovered after 3 days, compared with 16% of children taking placebo with standard treatment (103451). Also, a meta-analysis shows with high certainty that taking a combination of S. boulardii and zinc reduces the duration of diarrhea in children by about 39 hours. This is 21 to 23 hours faster than either product taken alone (103454). Other clinical research in infants and children aged 6-24 months with persistent diarrhea shows that giving S. boulardii 1750 billion to 175 trillion CFUs twice daily for 5 days reduces the number of stools and the duration of diarrhea (72132). Other clinical research in young children with acute diarrhea shows that taking S. boulardii CNCM-I 3799 5 billion CFUs in combination with Bacillus subtilis CU-1 1 billion CFUs (Swiss Garnier Biotech) daily for 5 days reduces the duration of diarrhea by about 5.3 hours when compared with placebo. When administration is started within 24 or 48 hours of diarrhea onset, the combination product reduced diarrhea duration by 25.2 hours and 13.8 hours, respectively (107605). S. boulardii might also be beneficial for chronic diarrhea of various etiologies. In children receiving routine treatment for diarrhea lasting for at least 2 weeks, preliminary clinical research shows that taking S. boulardii for 14 days was effective in 91% of children, compared with 68% of those given only routine treatment. Efficacy was defined as having 1-2 stools daily or normal stool characteristics. The time to recovery was also reduced by approximately 35 hours; however, this was about 11 hours longer than those given probiotics containing an unknown mixture of bifidobacteria, lactobacilli, and enterococcus. S. boulardii 0.25 grams daily was used in children under three years of age; older children took this dose twice daily (107603). In hospitalized children with acute diarrhea, taking S. boulardii seems to reduce hospital length of stay by around 20-22 hours when compared with control (102422,111103). Also, a small clinical study in critically ill adults shows that administering S. boulardii 500 mg four times daily in tube feedings for 21 days or until enteral feedings were stopped reduces the occurrence of diarrhea when compared with placebo (4349). However, one clinical study in otherwise healthy adults in Mexico and India, taking loperamide 2 mg with simethicone 125 mg up to 8 times over 2 days was more effective for reducing diarrhea than taking S. boulardii 250 mg twice daily for 5 days (98400).

POSSIBLY EFFECTIVE

• Antibiotic-associated diarrhea. Oral Saccharomyces boulardii seems to be beneficial for the prevention of antibiotic-associated diarrhea (AAD) in most patients. Details: Most clinical research shows that taking S. boulardii orally can help prevent AAD in adults and children (4350,4353,4355,8511,14334,14381,72198,72138,72145,72190)(72198,90263,90299) and decrease the risk of AAD by 37% to 63% (14334,14458,90263,90299,92813,94692,95348,107635). For every 9-13 patients treated, one fewer will develop AAD (14334,14458,92813,94692,95348). In children, S. boulardii 250 mg once or twice daily (equivalent to about 5-10 billion colony-forming units (CFUs)) during antibiotic treatment was used (72145,92813,94692). In adults, S. boulardii 250-500 mg taken 2-4 times a day, usually not to exceed 1000 mg daily, has been most commonly used during antibiotic treatment (4353,4355,14334,14381,90263,92813,95348). However, not all research agrees. A large clinical study in adults shows that taking a specific S. boulardii product (Perenterol forte) 250 mg twice daily, starting on the same day as initiation of systemic antibiotics and continuing for 7 days after stopping antibiotics, does not reduce the occurrence of AAD when compared with placebo (98730). Another clinical study in elderly patients shows that taking S. boulardii 5 billion CFUs twice daily, starting within 48 hours of antibiotic treatment and continuing for 7 days after stopping antibiotics, does not reduce the incidence of AAD when compared with placebo (95361). These negative findings might be related to the age and clinical status of the included patients.
• Clostridioides difficile infection. Oral Saccharomyces boulardii seems to be beneficial for preventing C. difficile infection. In combination with vancomycin or metronidazole, oral S. boulardii seems to be beneficial for preventing recurrence of C. difficile infection. Details: Among patients treated for C. difficile infection, about 6% to 25% experience at least one recurrent episode (95390). Taking S. boulardii 500 mg twice daily (equivalent to 20 billion colony-forming units (CFUs) daily) orally, in combination with vancomycin or metronidazole, reduces the risk of C. difficile diarrhea recurrence in adults with a history of recurrence (4352,4354,14334,72194). S. boulardii has also been evaluated for preventing a first occurrence of C. difficile diarrhea due to antibiotic use. Most results shows that taking S. boulardii 10-30 billion CFUs daily orally, in conjunction with antibiotics, can reduce the risk of developing C. difficile diarrhea by 53% to 61% in adults and children (14334,18088,72145,95364,95370). However, a meta-analysis of available clinical research shows that taking S. boulardii reduces the risk of C. difficile diarrhea by 75% in children, but does not reduce this risk in adults (92813). Observational research in acutely hospitalized elderly patients found that taking S. boulardii during antibiotic treatment is associated with a 58% reduced rate of C. difficile infection (98398). In contrast, a retrospective observational study in hospitalized elderly patients found no difference in C. difficile infection rates between patients receiving S. boulardii 250 mg twice daily along with broad spectrum antibiotics and those receiving broad spectrum antibiotics alone (98731). Due to this conflicting evidence, the current guidelines from the Infectious Diseases Society of America (IDSA) do not make a recommendation for the use of probiotics, including S. boulardii, for the primary prevention of C. difficile infection (107538).
• Helicobacter pylori. Oral Saccharomyces boulardii seems to be beneficial for reducing adverse effects associated with standard therapy for H. pylori eradication. It is unclear if it is beneficial for increasing eradication rates. Details: Meta-analyses of up to 17 clinical studies in adults and children with H. pylori infection show that taking S. boulardii 100-1000 mg daily for 1-4 weeks along with standard H. pylori eradication therapy increases eradication rates by 9% to 11% when compared to standard treatment with placebo (92814,102423). For every 12 patients treated with adjunct S. boulardii and standard treatment, one additional patient will have successful eradication when compared to using standard treatment alone (92814). However, most trials have been conducted in patients on standard triple therapy. Several more recent clinical trials show that taking S. boulardii 250-500 mg twice daily does not increase the eradication rate of 14-day quadruple therapy when compared with placebo (107606,110570,111101). Another recent clinical study shows that taking S. boulardii 30 million colony forming units (CFUs) 3 times daily for 4 weeks in combination with clarithromycin-based triple therapy does not increase H. pylori eradication rate when compared with triple therapy alone (108138). The role of S. boulardii monotherapy in patients failing standard H. pylori eradication therapy has also been evaluated. A small clinical study in Chinese adults who required rescue therapy after failing to respond to standard therapy shows that taking S. boulardii 500 mg twice daily for 2 weeks increases the rate of H. pylori eradication 14-fold when compared with no treatment. For every 4 patients treated, 1 more had eradication when compared with no treatment. However, in patients that did not respond to S. boulardii rescue therapy, adding S. boulardii to standard therapy did not further increase the rate of H. pylori eradication when compared with standard therapy alone (110569). Clinical research also shows that S. boulardii may reduce the adverse effects of H. pylori eradication therapy (12763,72161,102421,107606,111101). Adding S. boulardii 100-1000 mg daily for 1-4 weeks to H. pylori eradication therapy reduces the risk of treatment-related diarrhea and nausea by up to 67% and 40%, respectively, when compared with placebo or no treatment (92814,102423,107606). The reduced adverse effects might have contributed to the 67% reduction in discontinuation of standard treatment in patients using adjunct S. boulardii in five of the clinical studies that measures this outcome (102423).
• Necrotizing enterocolitis (NEC). Oral Saccharomyces boulardii seems to reduce the risk of NEC in hospitalized preterm infants. However, guidance among regulatory agencies and clinical organizations varies. Details: Although two older meta-analyses show that giving S. boulardii to preterm infants during the first week of life does not reduce the risk of NEC or all-cause mortality (95344,95351), a more recent meta-analysis of 10 moderate-quality clinical trials shows benefit. S. boulardii, usually 100-200 mg/kg daily, starting within the first week after birth and continuing throughout hospitalization, reduced the risk of NEC by 44% when compared with placebo or no treatment. There were also reductions in feeding intolerance and the number of days in the hospital, but no effect on sepsis or mortality (103452). Despite these findings, guidance among regulatory agencies and clinical organizations varies with respect to the use of probiotics in very low birth weight infants under 1000 grams. The US Food and Drug Administration (FDA) warns that preterm infants given probiotics are at risk of serious infections caused by the bacteria or fungi contained in probiotics due to cases reported in this group of infants (111610). Also, The American Academy of Pediatrics does not support the routine administration of probiotics to preterm infants, particularly those with a birth weight below 1000 grams, due to conflicting data on safety and efficacy and potential for harm in this vulnerable population (111608). The Canadian Paediatric Society, the American Gastroenterological Association, and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition state that probiotic combinations may be of benefit in reducing the incidence of NEC in preterm neonates over 1000 grams. However, Saccharomyces boulardii is not specifically recommended (103003,111609,111611).
• Rotaviral diarrhea. In children, oral Saccharomyces boulardii seems to reduce the duration of rotaviral diarrhea. Details: Clinical studies in children ages 3 months to 5 years with acute rotaviral diarrhea show that giving S. boulardii 200-250 mg twice daily for 5 days reduces the duration of diarrhea by about 1 day and reduces the risk of still having diarrhea 3 days after beginning the intervention by about 55% (95335,95391). Also, a meta-analysis of clinical research shows that giving S. boulardii to infants and children with acute rotaviral diarrhea reduces the duration of diarrhea by about 18 hours (92815). However, giving S. boulardii does not seem to reduce fever or vomiting, the need for parenteral rehydration, or the number of patients who experience diarrhea for more than 7 days (95335).
• Travelers' diarrhea. Most research suggests that oral Saccharomyces boulardii can help to reduce the risk of traveler's diarrhea. Details: A meta-analysis which included four large clinical studies evaluating the use of S. boulardii CNCM I-745 500-1000 mg daily for 1-3 weeks in adults traveling to different parts of the world found a 21% reduction in relative risk of travelers' diarrhea when compared with placebo (101445). Also, some early research shows that taking S. boulardii 250-1000 mg daily orally for 1 month seems to help prevent travelers' diarrhea (155,72183).

POSSIBLY INEFFECTIVE

• Sepsis. In preterm infants, oral Saccharomyces boulardii does not seem to be beneficial for sepsis prevention. Details: A meta-analysis of 5 clinical trials shows that giving preterm infants S. boulardii, usually 100-200 mg/kg daily, does not reduce the risk of sepsis when compared with placebo or no treatment (103452).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if oral Saccharomyces boulardii is beneficial for acne. Details: Preliminary clinical research shows that taking a specific strain of S. boulardii called CBS 5926 (Perenterol, Cell Tech Pharma) daily for 5 months results in a subjective improvement in 80% of patients, compared with only 26% of those in the placebo group (7140).
• Cholera. It is unclear if oral Saccharomyces boulardii is beneficial for cholera. Details: A small clinical study in patients with cholera shows that taking S. boulardii 250 mg, alone or in combination with bismuth subsalicylate 524 mg every 6 hours, does not reduce cholera symptoms when compared with bismuth subsalicylate alone or with placebo (98733). However, this study might not have been adequately powered to detect a difference in outcomes.
• Cognitive function. It is unclear if oral Saccharomyces boulardii is beneficial for cognitive function. Details: In healthy medical students, taking S. boulardii CNCM I-1079 (LacidoEnter, Institut Rosell) 5 billion colon-forming units daily for 30 days does not improve exam performance or reduce stress related to the exam when compared with placebo (103450).
• Constipation. It is unclear if oral Saccharomyces boulardii is beneficial in children with constipation. Details: A moderately sized open-label clinical study in children aged 6 months to 12 years with functional constipation shows that taking S. boulardii 500-750 mg daily for 12 weeks reduces the rate of treatment success, defined as 3 or more bowel movements per week without incontinence, by 69% and 81% when compared with lactulose alone or lactulose and S. boulardii combination therapy, respectively. While no differences in stool frequency, stool consistency, incontinence frequency, or painful defecations were reported, more children taking S. boulardii discontinued the study and/or required a change in treatment during the study period (111102).
• Crohn disease. It is unclear if oral Saccharomyces boulardii is beneficial for this condition. Details: Preliminary clinical research shows that taking S. boulardii 250 mg three times daily for up to 9 weeks reduces the frequency of bowel movements in patients with Crohn disease (7646). One preliminary clinical study shows that patients with Crohn disease in remission who take S. boulardii 1 gram daily combined with mesalamine (5-aminosalycilic acid, 5-ASA) 1 gram twice daily have a lower rate of relapse when compared with patients who take only mesalamine 1 gram three times daily after 6 months of treatment (14379). However, other clinical research shows that taking S. boulardii 1 gram daily for 1 year after achieving remission with steroids or salicylates does not increase the time to relapse or decrease symptom severity in patients with non-severe Crohn disease (92807). Possible reasons for the discrepancies include concomitant use of salicylates, severity of Crohn disease, and duration of treatment.
• Critical illness (trauma). It is unclear if oral Saccharomyces boulardii is beneficial for reducing complications in critically ill, hospitalized patients. Details: A small clinical study in critically ill patients shows that administering S. boulardii 500 mg four times daily in tube feedings for 21 days or until enteral feedings were stopped reduces the occurrence of diarrhea when compared with placebo (4349). Also, clinical research in multi-trauma patients requiring ventilation shows that taking a combination probiotic containing S. boulardii for 15 days modestly reduces the risk of sepsis, as well as the length of stay in the ICU and hospital, when compared with placebo. The combination product was taken twice daily and contained S. boulardii 1.5 billion colony-forming units (CFUs) in combination with Lactobacillus acidophilus LA-5 1.75 billion CFUs, Lactiplantibacillus plantarum 500 million CFUs, and Bifidobacterium animalis subsp. lactis BB12 1.75 billion CFUs. Half of the dose was given into the oropharynx and half via a nasogastric tube (107524).
• Cystic fibrosis. It is unclear if oral Saccharomyces boulardii is beneficial for cystic fibrosis. Details: Taking a specific strain of S. boulardii (Saccharomyces cerevisiae Hansen CBS 5926) 250 mg three times daily orally for 21 days does not seem to decrease Candida albicans gastrointestinal colonization in patients with cystic fibrosis (7652).
• Exercise-induced muscle soreness. Oral Saccharomyces boulardii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In rugby players, preliminary clinical research shows that taking S. boulardii (SBFloractiv, Bioceuticals) 250 mg for 9 weeks of international competition reduces muscle soreness and leg heaviness by a small amount more than placebo (103453). This was part of a 17-week study involving a multi-ingredient probiotic product (Ultrabiotic 60, Bioceuticals) providing 60 billion colony-forming units of Lactobacilli, Bifidobacterium, and Streptococci. When S. boulardii was added to this probiotic mixture, improvements were similar to those seen with the probiotic mixture alone.
• Heart failure. It is unclear if oral Saccharomyces boulardii is beneficial for heart failure. Details: A small clinical study in patients with NYHA Class II or III heart failure shows that taking S. Boulardii 1000 mg daily for 3 months is associated with an improved left ventricular ejection fraction (LVEF) and decreased left atrial diameter when compared with baseline (98399). The validity of these findings is limited by the lack of statistical comparison to the placebo group. However, a larger preliminary clinical trial in a similar population given standard care shows that taking the same dose of S. Boulardii CNCM I-745 does not improve LVEF or the distance walked in 6 minutes when compared with standard care alone (107608).
• HIV/AIDS-related diarrhea. It is unclear if oral Saccharomyces boulardii is beneficial for this condition. Details: Preliminary clinical research shows that taking S. Boulardii orally up to 3 grams daily seems to help reduce HIV-related diarrhea, although the details of this research are unclear (72168,72195).
• Hypercholesterolemia. It is unclear if oral Saccharomyces boulardii is beneficial for hypercholesterolemia. Details: Preliminary clinical research shows that taking S. Boulardii 14 billion colony-forming units twice daily for 8 weeks does not affect lipid parameters when compared to baseline in patients with hypercholesterolemia (98732). The validity of these findings is limited by the lack of a comparator group.
• Intestinal parasite infection. It is unclear if oral Saccharomyces boulardii is beneficial for intestinal parasite infection. Details: Preliminary clinical research in patients with amebiasis or infection with Entamoeba histolytica shows that taking a specific S. Boulardii product (Ultra-levure, Biocodex) 250 mg three times daily orally in combination with a conventional antibiotic regimen (metronidazole and iodoquinol) for 4 weeks improves diarrhea duration and abdominal pain when compared with conventional antibiotic treatment alone (72131).
• Irritable bowel syndrome (IBS). It is unclear if oral Saccharomyces boulardii is beneficial for IBS. Details: One clinical study in patients with diarrhea-predominant (IBS-D) or mixed-type IBS shows that taking S. boulardii (Bioflor, Kuhnil) 200 billion colony-forming units daily for 4 weeks improves quality of life about 2.2-fold more than placebo. However, taking this product does not seem to improve abdominal pain and discomfort, stool consistency, urgency, bloating, or other symptoms of this condition (95359). Similarly, a meta-analysis of a small number of clinical studies shows that taking S. boulardii CNCM I-745 does not reduce the severity of abdominal pain when compared with placebo; however, it may increase the frequency of abdominal pain relief (107594). Another clinical study shows that taking S. boulardii 200 mg orally three times daily for 30 days along with mesalazine 800 mg three times daily does not improve symptoms of IBS-D better than mesalazine alone (92808). However, the results of this latter study are limited by the fact that a blinded placebo was not provided to the control group.
• Low birth weight. It is unclear if oral Saccharomyces boulardii is beneficial for growth in low birth weight infants. Details: Preliminary clinical research in preterm infants with low birth weight shows that giving a specific S. boulardii supplement (Bioflor, Biocodex) 50 mg/kg twice daily, in addition to infant formula for at least 7 days and up to 28 days after birth, increases weight gain and feeding tolerance when compared to consuming infant formula alone (98734).
• Neonatal jaundice. It is unclear if oral Saccharomyces boulardii is beneficial for neonatal jaundice prevention or treatment. Details: One clinical study shows that S. boulardii 250 mg dissolved in 10 mL of water and given orally once daily for 2 days reduces the percentage of term infants who develop jaundice by 4% and reduces the percentage of these infants who require phototherapy by 12% when compared with placebo (95413). It is not known if S. boulardii reduces the risk of neonatal jaundice in at-risk infants, such as preterm infants or those with fetal-maternal blood group incompatibility. Giving S. boulardii along with phototherapy does not improve bilirubin levels or decrease the duration of required phototherapy in preterm and term infants with hyperbilirubinemia (92806).
• Obesity. Oral Saccharomyces boulardii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in obese patients shows that taking S. boulardii 5 billion colony-forming units with superoxide dismutase 400 IU twice daily for 60 days does not reduce body weight, body mass index, or measures of hunger and satiety when compared with placebo (106848).
• Periodontitis. Although there has been interest in using oral Saccharomyces boulardii for periodontitis, there is insufficient reliable information about the clinical effects of S. boulardii for this condition.
• Postoperative infection. It is unclear if oral Saccharomyces boulardii prevents postoperative infection. Details: A small clinical study in patients undergoing resection of the colon shows that taking S. boulardii 100 mg daily for at least 7 days before surgery, along with conventional prophylaxis with antibiotics, does not reduce the risk of postoperative infection when compared with conventional treatment alone (111105). However, this study may have been underpowered to detect differences for this outcome.
• Postoperative recovery. It is unclear if oral Saccharomyces boulardii improves postoperative recovery. Details: A small clinical study in patients undergoing resection of the colon shows that taking S. boulardii 100 mg daily for at least 7 days before surgery, along with conventional prophylaxis with antibiotics, does not reduce length of hospital stay when compared with conventional treatment alone (111105). However, this study may have been underpowered to detect differences for this outcome.
• Small intestinal bacterial overgrowth (SIBO). It is unclear if oral Saccharomyces boulardii is beneficial for SIBO. Details: A small clinical study in patients with SIBO and systemic sclerosis shows that adding S. boulardii 200 mg twice daily for 14 days to metronidazole 500 mg twice daily for 7 days eradicates SIBO to a greater degree than metronidazole alone (102420). However, another small clinical study in patients with SIBO and diarrhea-predominant irritable bowel syndrome shows that taking S. boulardii 250 mg twice daily while receiving dietary advice for 15 days does not increase the rate of SIBO eradication when compared with dietary advice alone (111104). However, this study may have been underpowered to detect differences for this outcome.
• Ulcerative colitis. It is unclear if oral Saccharomyces boulardii is beneficial for ulcerative colitis. Details: Preliminary clinical research shows that taking S. boulardii 250 mg three times daily can reduce symptoms in patients with mild-to-moderate ulcerative colitis who experience a flare up despite maintenance treatment with mesalamine (5-aminosalycilic acid, 5-ASA) 1 gram three times daily (14380). The validity of this finding is limited by the lack of a comparator group.
• Urinary tract infections (UTIs). Although there has been interest in using oral Saccharomyces boulardii for UTIs, there is insufficient reliable information about the clinical effects of S. boulardii for this condition.
• Vaginal candidiasis. Although there has been interest in using oral Saccharomyces boulardii for vaginal candidiasis, there is insufficient reliable information about the clinical effects of S. boulardii for this condition.
• Ventilator-associated pneumonia (VAP). Oral Saccharomyces boulardii has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in multi-trauma patients requiring ventilation shows that taking a combination probiotic containing S. boulardii for 15 days reduces the risk of VAP when compared with placebo. VAP occurred in 12% of patients receiving the probiotic preparation, compared with 28% receiving placebo. The combination product was taken twice daily and contained S. boulardii 1.5 billion colony-forming units (CFUs), Lactobacillus acidophilus LA-5 1.75 billion CFUs, Lactiplantibacillus plantarum 500 million CFUs, and Bifidobacterium animalis subsp. lactis BB12 1.75 billion CFUs. Half of the dose was given into the oropharynx and half via a nasogastric tube. (107524). More evidence is needed to rate Saccharomyces boulardii for these uses.

(Read more about SACCHAROMYCES BOULARDII)

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

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

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

(Read more about BIFIDOBACTERIUM LONGUM)

LIKELY SAFE ...when used orally and appropriately for up to 15 months (155,4347,4350,4351,4352,4353,4354,7140,7646,7652),(12763,14334,14379,14380,14381,72194,72198).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in children of most ages (4347,4356,14334,72145,92806,98734,103451,107603,107605,111102)(111103). There is insufficient reliable information available about the safety of Saccharomyces boulardii in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

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

(Read more about SACCHAROMYCES BOULARDII)

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

(Read more about BIFIDOBACTERIUM LONGUM)

ANTIFUNGALS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking antifungals with Saccharomyces boulardii might decrease the effectiveness of Saccharomyces boulardii.  Details S. boulardii is a live yeast. Therefore, simultaneously taking antifungals might kill a significant number of the organisms (4363).

(Read more about SACCHAROMYCES BOULARDII)

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

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

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

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

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

(Read more about BIFIDOBACTERIUM LONGUM)

General ...Orally, Saccharomyces boulardii is generally well tolerated.
Serious Adverse Effects (Rare):
Orally: There is concern that Saccharomyces boulardii may cause fungemia in certain patients.

Gastrointestinal ...Rarely, oral use of Saccharomyces boulardii has caused gastrointestinal complaints, such as abdominal cramps, flatulence, nausea, vomiting, and decreased appetite (98731,107608).

Immunologic ...Rarely, oral use of Saccharomyces boulardii has been associated with fungemia in both immunocompromised and immunocompetent patients (1247,4357,4358,4360,7329,14459,72121,72126,72142,92809,95357,95363)(96277,105171,107604,107607). Numerous cases of Saccharomyces fungemia have been reported in critically ill intensive care unit (ICU) patients, particularly those with indwelling or central venous catheters, those receiving enteral feeding, or those receiving broad-spectrum antibiotics. Most infections occurred when packets of Saccharomyces were used or when Saccharomyces capsules were opened at the bedside (12776,12777,14459,95358,95360,95362,95363,105171). Admission to the ICU and extended length of stay increase the risk of developing Saccharomyces fungemia (107604). In a hospitalized 1-year-old patient with severe malnutrition and multiple invasive devices, Saccharomyces cerevisiae fungemia developed 2 days after receiving a probiotic containing S. boulardii 200 mg twice daily for 4 days (96277). In addition, there are two case reports of S. cerevisiae fungemia in hospitalized and intubated older patients with COVID-19 who had been given S. boulardii for diarrhea (105171).
The true incidence of fungemia is difficult to determine with S. boulardii. Most clinical laboratories are unable to differentiate between S. boulardii and S. cerevisiae, which might come from other sources (7353). In two case reports of patients in the ICU, there was a 100% alignment of fungal ribosomal DNA ITS sequences between the strains found in the blood of the infected patients and the strains of S. boulardii that had been administered (105171). In a large analysis of hospitalized patients, the incidence rate of Saccharomyces fungemia was 0.11% of those given S. boulardii and did not occur in patients not given this probiotic. Packets or capsules opened at a distance from the patient in the hospital were included in this analysis (107604).
Positive Saccharomyces cultures have also been obtained rarely from other sites, such as the abdominal region and the oral or respiratory tract (107607).
An elevated erythrocyte sedimentation rate may occur when S. boulardii is used to treat Crohn disease (7646), but this effect may be a natural part of the disease process.

(Read more about SACCHAROMYCES BOULARDII)