SBO Probiotics Women's 25 Billion CFU [Discontinued] by Ancient Nutrition

POSSIBLY EFFECTIVE

• Constipation. Oral Bacillus coagulans seems to be beneficial for constipation. Details: Clinical research in individuals with mild intermittent constipation shows that taking B. coagulans SNZ 1969 (CTCBIO, Inc.) 1 billion colony-forming units (CFUs) daily for 8 weeks reduces colonic transit time, increases the number of weekly complete spontaneous bowel movements, and improves bowel discomfort when compared with placebo. Colonic transit time was reduced by at least 25% in 58% of patients taking B. coagulans, compared with 32% of patients taking placebo (107613). Other clinical research in patients with functional constipation shows that taking B. coagulans Unique IS2 (Unique Biotech Limited) 2 billion CFUs daily for 4 weeks modestly increases the number of bowel movements and reduces abdominal pain and pain with defecation when compared with placebo. Also, 98% of patients achieved normal stool consistency, compared with 74% of those taking placebo (107612). Adding lactulose 10 grams to this regimen increases stool frequency when compared with placebo, but not when compared with lactulose alone. However, normal stool consistency was achieved earlier and by more patients in those taking lactulose plus B. coagulans when compared with lactulose alone. The combination was also more beneficial for reducing defecation pain, abdominal pain, and sensations of incomplete evacuation (107614). Also, a small clinical study in adults with constipation-dominant functional bowel disorders shows that taking a specific supplement containing B. coagulans 1 billion CFUs twice daily for 4 weeks modestly improves abdominal pain and abdominal distention, as well as discomfort and effort during defecation, when compared with baseline (104232). However, the validity of the findings in this study is limited by the lack of a comparator group.
• Irritable bowel syndrome (IBS). Oral Bacillus coagulans seems to be beneficial for IBS. Details: Clinical research in adults with diarrhea-predominant IBS shows that taking B. coagulans daily for 56-90 days improves quality of life and decreases bloating, nausea, vomiting, abdominal pain, and stool frequency when compared with placebo. Improvements in headache, anxiety, and constipation have also been shown (92730,92735,92740,105169). In addition, meta-analyses show that taking B. coagulans reduces overall symptom, straining, and/or abdominal pain severity when compared with placebo (107594,110866). In one study, taking B. coagulans for 80 days resulted in no symptoms in 63% of individuals, compared with only 21% of those taking placebo (105169). Doses used in some of this clinical research have included a specific B. coagulans MTCC5856 product (Lactospore, Sabinsa Corporation) 2 billion colony-forming units (CFUs) daily for 90 days (92730), another specific B. coagulans product (GanedenBC30, Ganeden Biotech Inc.) 300 million to 2 billion CFUs daily for 8 weeks (92735,92740), B. coagulans LBSC (Advanced Enzyme Technologies Ltd.) 2 billion CFUs three times daily for 80 days (105169), or B. coagulans Unique IS2 2 billion CFUs daily for 8 weeks (110866). Other clinical research in adults with IBS shows that taking a specific combination product (Colinox, DMG Italia SRL) containing B. coagulans and simethicone after each meal three times daily for 4 weeks improves bloating and discomfort, but not pain, when compared with placebo (92726).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Antibiotic-associated diarrhea. Although there has been interest in using oral Bacillus coagulans for antibiotic-associated diarrhea, there is insufficient reliable information about the clinical effects of B. coagulans for this condition.
• Athletic performance. It is unclear if oral Bacillus coagulans is beneficial for athletic performance. Details: A small clinical trial shows that taking an inactivated B. coagulans GBI-30, 6086 product (Staimune, Kerry, Inc) 1 billion cells daily for 2 weeks does not improve jump power or muscle endurance when compared with placebo (107610). This study might not have been adequately powered to detect differences between groups. A larger study in resistance-trained males shows that taking B. coagulans Unique IS-2 2 billion colony-forming units daily for 60 days in combination with 20 grams of an 80% whey protein concentrate modestly improves some measures of power and muscle strength when compared with taking whey protein alone. However, some measures of strength were not improved, and there was no effect on maximum oxygen consumption, muscle hypertrophy, or body composition (110878).
• Cancer. Although there has been interest in using oral Bacillus coagulans for cancer prevention, there is insufficient reliable information about the clinical effects of B. coagulans for this purpose.
• Cirrhosis. Oral Bacillus coagulans has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with liver cirrhosis who are at increased risk for developing spontaneous bacterial peritonitis (SBP) shows that taking a combination of B. coagulans, Enterococcus faecalis, Clostridium butyricum, and Bacillus mesentericus three times daily, in conjunction with norfloxacin for 6 months, does not reduce the risk of developing SBP when compared with norfloxacin alone (92731).
• Clostridioides difficile infection. Although there has been interest in using oral Bacillus coagulans for C. difficile infection, there is insufficient reliable information about the clinical effects of B. coagulans for this purpose.
• Depression. Although there has been interest in using oral Bacillus coagulans for depression, there is insufficient reliable information about the clinical effects of B. coagulans for this condition.
• Diabetes. Oral Bacillus coagulans has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with type 2 diabetes shows that taking B. coagulans GBI-30, 6086 (GanedenBC30) 100 billion CFUs, Lactobacillus acidophilus 1 billion colony-forming units (CFUs), Lacticaseibacillus rhamnosus 10 billion CFUs, 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. There was no effect on plasma lipids (107731).
• Diarrhea. It is unclear if oral Bacillus coagulans is beneficial for acute diarrhea or diarrhea-dominant functional bowel disorders. Details: Clinical research in infants 6-24 months of age with acute diarrhea of various causes shows that taking B. coagulans 120 million colony-forming units (CFUs) twice daily for up to 5 days in conjunction with oral rehydration solution does not decrease duration, frequency, or volume of diarrhea when compared with oral rehydration solution and placebo (92738). However, a small clinical study in adults with acute diarrhea shows that taking a specific supplement (Lactic Acid Bacillus) containing B. coagulans 2 billion CFUs, three times daily for 7 days, reduces diarrhea and improves abdominal pain when compared with placebo (100853). Preliminary clinical research in adults with diarrhea-dominant functional bowel disorders shows that taking a specific supplement containing B. coagulans 1 billion CFUs twice daily for 4 weeks reduces abdominal pain, abdominal distention, discomfort and effort during defecation, and the number of stools classified as diarrhea when compared with baseline (104232). The validity of these findings is limited by the lack of a comparator group.
• Dyspepsia. It is unclear if oral Bacillus coagulans is beneficial for dyspepsia. Details: Several small studies show that B. coagulans can improve symptoms of dyspepsia (104231,104232,104233,107611). In one study, 1 billion colony-forming units (CFUs) were taken twice daily for 4 weeks, resulting in an improvement in abdominal pain and abdominal distention when compared with placebo (104232). Some studies have used B. coagulans in combination with other probiotics. In adults with functional dyspepsia, taking a combination of B. coagulans MY01 and Bacillus subtilis MY02 as 1.25 billion CFUs each twice daily for 8 weeks improves postprandial distress scores of at least 0.7 in 48% of patients, compared with only 20% of those taking placebo (107611). A small clinical study in older adults aged 55-75 years with indigestion, abdominal pain, and flatulence shows that taking a probiotic syrup containing B. coagulans 500 million CFUs with digestive enzymes (alpha amylase 25 mg, pepsin 10 mg, and lipase 1.5 mg) 5 mL twice daily for 5 days reduces symptoms of dyspepsia when compared with placebo (104233). Also, a small study in adults with non-specific gastrointestinal discomfort shows that taking a specific combination supplement (SNZ TriBac, Sanzyme Biologics) containing B. coagulans SNZ 1969, Bacillus clausii SNZ 1971, and B. subtilis SNZ 1972, 2 billion CFUs daily for 30 days, decreases self-reported symptoms of burping, belching, and sour taste when compared with placebo (104231). It is unclear if these effects are due to B. coagulans, other ingredients, or the combinations.
• Flatulence. It is unclear if oral Bacillus coagulans is beneficial for flatulence. Details: Clinical research in children aged 6-8 years shows that taking B. coagulans GBI-30, 6086 (GanedenBC30, Ganeden, Inc.) 1 billion colony-forming units (CFUs) daily for 3 months modestly decreases the incidence of flatulence when compared with taking placebo (107615). However, preliminary clinical research in patients with postprandial intestinal gas-related symptoms shows that taking a specific combination supplement (Digestive Advantage Gas Defense Formula, Ganeden Biotech) containing this same strain of B. coagulans and an enzyme blend daily for 4 weeks does not improve bloating or gas when compared with placebo (92736).
• Gingivitis. Although there has been interest in using oral Bacillus coagulans for gingivitis, there is insufficient reliable information about the clinical effects of B. coagulans for this condition.
• Helicobacter pylori. It is unclear if oral Bacillus coagulans is beneficial for H. pylori. Details: In patients with H. pylori, preliminary clinical research shows that taking B. coagulans (Donghai Pharmaceutical Co Ltd) 1050 mg three times daily for 8 weeks results in a 20% eradication rate 1-2 weeks after treatment. This was as effective as taking Clostridium butyricum 1050 mg twice daily, alone or in combination with B. coagulans (105168). This study is limited by lack of blinding and the lack of a placebo group. Also, it is unclear how B. coagulans compares to standard H. pylori eradication treatments.
• HIV/AIDS. Although there has been interest in using oral Bacillus coagulans for HIV/AIDS, there is insufficient reliable information about the clinical effects of B. coagulans for this condition.
• Hypercholesterolemia. Although there has been interest in using oral Bacillus coagulans for cholesterol reduction, there is insufficient reliable information about the clinical effects of B. coagulans for this purpose.
• Inflammatory bowel disease (IBD). Although there has been interest in using oral Bacillus coagulans for IBD, there is insufficient reliable information about the clinical effects of B. coagulans for this purpose.
• Necrotizing enterocolitis (NEC). It is unclear if oral Bacillus coagulans is beneficial or safe for NEC prevention. Details: Preliminary clinical research in infants with a gestational age of less than 33 weeks or a very low birth weight shows that taking B. coagulans 350 million colony-forming units daily until hospital discharge does not reduce the risk of NEC or death when compared with placebo. However, taking B. coagulans reduced the incidence of feeding intolerance in these newborns (92733). 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). It is unclear if oral Bacillus coagulans is beneficial for NAFLD. Details: Preliminary clinical research in adults with NAFLD shows that taking 1 capsule containing B. coagulans 1 billion colony-forming units plus 400 mg inulin for 8 weeks may be beneficial for treating inflammation associated with NAFLD when compared with placebo. However, this combination did not improve lipid profiles or glycemic indices. Inulin was used in this study as a prebiotic to ensure bacterial growth in the gut lumen (104230).
• Postoperative ileus. It is unclear if oral Bacillus coagulans is beneficial for postoperative ileus. Details: A small clinical study in patients undergoing gynecological laparoscopic surgery shows that taking B. coagulans TBC169 105 million or 175 million colony-forming units the night before surgery, and then every 8 hours starting 8 hours after surgery, reduces time to first flatus by up to 10 hours when compared with placebo. There were also modest reductions in the rates of postoperative gastrointestinal adverse events such as nausea, vomiting, distension, and ileus. However, there was no difference in time to first defecation or length of hospital stay (110879).
• Rheumatoid arthritis (RA). It is unclear if oral Bacillus coagulans is beneficial for RA. Details: Preliminary clinical research in adults with RA shows that taking B. coagulans GBI-30, 6086 (GanedenBC30, Ganeden Biotech Inc.) 2 billion colony-forming units daily for 60 days, in conjunction with standard therapy, reduces overall pain when compared with placebo. However, it does not reduce the number of painful or swollen joints or improve activities of daily living (92734).
• Rotaviral diarrhea. It is unclear if oral Bacillus coagulans is beneficial for rotaviral diarrhea. Details: Preliminary clinical research in newborns shows that taking B. coagulans 100 million colony-forming units daily for one year reduces the incidence of acute rotaviral diarrhea. Taking B. coagulans decreases the incidence of diarrheal episodes by around 5 per year and reduces duration of diarrhea by around 3 days per episode when compared with placebo. However, taking B. coagulans does not reduce the occurrence of mild to moderate dehydration (92729).
• Small intestinal bacterial overgrowth (SIBO). Oral Bacillus coagulans has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with SIBO who were previously treated for 3 weeks with broad spectrum antibiotics shows that taking a specific probiotic product (Lactol, Bioplus Life Sciences Pvt. Ltd.) containing B. coagulans spores and fructo-oligosaccharides twice daily on 15 days per month for 6 months, in conjunction with minocycline, modestly decreases stomach pain and flatulence (91145).
• Travelers' diarrhea. Although there has been interest in using oral Bacillus coagulans for travelers' diarrhea, there is insufficient reliable information about the clinical effects of B. coagulans for this condition.
• Upper respiratory tract infection (URTI). It is unclear if oral Bacillus coagulans is beneficial for URTI prevention. Details: Clinical research in children aged 6-8 years shows that taking B. coagulans GBI-30, 6086 (GanedenBC30, Ganeden, Inc.) 1 billion colony-forming units (CFUs) daily for 3 months modestly decreases the incidence of some URTI symptoms, including nasal congestion, bloody nasal mucus, itchy nose, and hoarseness, but not others such as dry cough and sore throat, when compared with placebo (107615). More evidence is needed to rate Bacillus coagulans for these uses.

(Read more about BACILLUS COAGULANS)

POSSIBLY EFFECTIVE

• Dyslipidemia. Oral Indian gooseberry seems to be beneficial for dyslipidemia. Details: Meta-analyses of 12 small clinical studies in healthy adults or patients with dyslipidemia, diabetes, hypertension, or metabolic syndrome show that taking Indian gooseberry fruit extract or powder 0.5-3 grams daily or Indian gooseberry fruit 12 grams daily for 2-12 weeks reduces total cholesterol by around 39 mg/dL, low-density lipoprotein (LDL) cholesterol by around 15-34 mg/dL, and triglycerides by around 22-52 mg/dL when compared with control groups. Results are conflicting whether Indian gooseberry increases high-density lipoprotein (HDL) cholesterol (111567,111568). Subgroup analysis suggests that Indian gooseberry is more effective at doses greater than 1 gram daily and in adults with triglycerides above 150 mg/dL (111568). Clinical research in patients with dyslipidemia shows that taking Indian gooseberry whole fruit extract (Tri-low, Arjuna Natural Ltd.) 500 mg twice daily for 12 weeks reduces triglyceride and low-density lipoprotein (LDL) cholesterol levels by 34% and 20%, respectively, compared with 15% and 5%, respectively, in patients taking placebo (99238).
• Gastroesophageal reflux disease (GERD). Oral Indian gooseberry seems to be beneficial for reducing symptoms of GERD. Details: Clinical research in adults who have had non-erosive symptoms of GERD for at least 3 months shows that taking Indian gooseberry fruit extract 1000 mg twice daily for 4 weeks reduces the frequency and severity of heartburn and regurgitation by about 63% and 50%, respectively, compared with reductions of 24% and 5%, respectively, in patients taking placebo (99240).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Oral Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy, middle-aged females shows that drinking 50 mL of a juice containing Indian gooseberry extract 30-60 mg and lingonberry extract 25-50 mg daily for 12 weeks improves skin elasticity, thickness, wrinkles, and hydration when compared with placebo (102856). It is unclear if these effects are due to Indian gooseberry, lingonberry, or the combination. Another small clinical study in healthy, middle-aged females shows that applying a topical emulsion containing extracts of Indian gooseberry 3% and gotu kola 3% twice daily for 60 days improves skin hydration, some measures of skin wrinkles, and elasticity of the cheek but not the eye when compared with placebo (111571). It is unclear if these effects are due to Indian gooseberry, gotu kola, or the combination.
• Androgenic alopecia. Topical Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In individuals with self-perceived hair loss, preliminary clinical research shows that applying a hair product containing Indian gooseberry modestly improves hair growth rate and density, as well as hair thinning, when compared with baseline. Patients used a leave-in product containing Indian gooseberry (Saberry), coconut water solids (Cococin), gamma-L-glutamyl-selenomethionine (Peptiselect), and other ingredients as 3.5 mL in females and 2 mL in males, once daily for 3 months (105353).
• Cancer. Although there is interest in using oral Indian gooseberry for cancer, there is insufficient reliable information about the clinical effects of Indian gooseberry for this purpose.
• Cardiovascular disease (CVD). It is unclear if oral Indian gooseberry is beneficial for the prevention of CVD. Details: A meta-analysis of 9 small clinical studies in adults who are healthy or have CVD risk factors shows that taking Indian gooseberry fruit extract or powder 500-1500 mg daily for 2-12 weeks reduces low-density lipoprotein (LDL) cholesterol by around 15 mg/dL, very low-density lipoprotein (VLDL) cholesterol by around 5 mg/dL, triglycerides by around 22 mg/dL, and high-sensitivity C-reactive protein when compared with control groups. However, the meta-analysis suggests that Indian gooseberry does not improve high-density lipoprotein (HDL) cholesterol, systolic blood pressure, or diastolic blood pressure (111567). The validity of these findings is limited by small sample sizes and considerable heterogeneity among the included studies.
• Coronavirus disease 2019 (COVID-19). It is unclear if oral Indian gooseberry is beneficial for the treatment of COVID-19 in hospitalized adults. Details: A small clinical trial in adults hospitalized with COVID-19 shows that receiving Indian gooseberry powder 2 grams twice daily for 10 days does not impact RT-PCR positivity rate at day 10 when compared with placebo. Additionally, there were no clear trends in clinical improvement in patients receiving Indian gooseberry when compared with placebo. All patients in this study also received oral hydroxychloroquine and lopinavir/ritonavir (110012).
• Diabetes. Several small or limited-quality clinical studies suggest that oral Indian gooseberry may modestly improve glycemic control and blood lipid levels in patients with type 2 diabetes. Details: A moderate-sized, open-label study in adults with newly-diagnosed type 2 diabetes and dyslipidemia shows that taking Indian gooseberry extract, standardized to 10% beta-glucogallin, 2 grams daily for 90 days reduces glycated hemoglobin (HbA1c), fasting blood glucose, and postprandial blood glucose when compared to baseline, with superior effects on fasting blood glucose and postprandial blood glucose when compared with metformin 500 mg (111569). A smaller clinical study in patients with type 2 diabetes on stable doses of metformin shows that taking Indian gooseberry fruit extract (Capros, Natreon Inc) 500 mg twice daily for 12 weeks reduces HbA1c by around 0.5% and improves low-density lipoprotein (LDL) cholesterol, triglyceride, and high-density lipoprotein (HDL) levels when compared with placebo. Taking a lower dose, 250 mg twice daily, does not seem to improve HbA1c but has a modest effect on lipid levels (105356). Another small clinical study in patients with type 2 diabetes using various antidiabetes drugs shows that taking powdered Indian gooseberry fruit 1 gram, 2 grams, or 3 grams daily for 3 weeks modestly reduces fasting and 2-hour postprandial blood glucose levels and improves lipid levels when compared to baseline (105355). The validity of these findings is limited by the lack of a comparator group.
• Hangover. It is unclear if oral Indian gooseberry is beneficial for hangover prevention. Details: A small clinical trial shows that taking Indian gooseberry leaf extract (Phyllpro) 750 mg daily for 10 days prior to alcohol intoxication modestly reduces some hangover symptoms 10 hours later, including nausea, headache, lack of appetite, and dizziness, when compared with placebo. Blood alcohol levels after 12 hours were also reduced. However, the overall hangover score was not significantly different between groups (99846).
• Hepatitis B. Although there is interest in using oral Indian gooseberry for hepatitis B, there is insufficient reliable information about the clinical effects of Indian gooseberry for this condition.
• Hypercholesterolemia. Small studies suggest that oral Indian gooseberry might help to reduce low-density lipoprotein (LDL) cholesterol levels. Details: Preliminary clinical research shows that taking Indian gooseberry might reduce levels of LDL cholesterol in patients with hypercholesterolemia. One preliminary clinical study shows that taking Indian gooseberry 50 grams for 4 weeks decreases LDL cholesterol by 15% when compared to baseline (2077). Other preliminary clinical research shows that taking Indian gooseberry fruit extract (Amlamax, Arjuna Natural Ltd.) 500 mg or 1000 mg daily for 6 months reduces levels of LDL cholesterol by about 13% when compared with baseline (99241). Also, one small study shows that taking an Indian gooseberry fruit juice powder 500 mg daily for 6 weeks modestly decreases LDL cholesterol and triglyceride levels when compared with baseline (99242). Some preliminary clinical research also shows that Indian gooseberry reduces LDL cholesterol in obese individuals. One small study shows that taking Indian gooseberry fruit extract (Capros, Natreon Inc.) 500 mg twice daily for 12 weeks reduces LDL cholesterol by 16 mg/dL in this population when compared to baseline (92515). However, the validity of these studies is limited by the lack of comparator groups.
• Hypertension. It is unclear if oral Indian gooseberry is beneficial for hypertension. Details: In patients with uncontrolled hypertension using standard therapies, clinical research shows that taking Indian gooseberry dried fruit powder 500 mg three times daily for 8 weeks reduces systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 16% and 12%, respectively, from baseline, which is significantly greater than reductions seen with placebo. The frequency of response to treatment, based on a reduction in SBP or DBP of at least 10 mmHg or 5 mmHg, respectively, was also increased from up to 50% to at least 83% of patients (105352). However, other clinical research in adults with cardiovascular risk factors shows that taking Indian gooseberry 500-1500 mg twice daily for 2-12 weeks does not reduce SBP or DBP more than placebo (105354,111567).
• Irritable bowel syndrome (IBS). Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small, open-label study of adults with IBS shows that taking 7 grams of an Unani medicinal product called Jawarish Shahi, containing Indian gooseberry, terminalia, coriander, cardamom, and willow bark, twice daily for 45 days reduces the severity of IBS, as measured by improvements in abdominal pain and distension, bowel habits, and quality of life, when compared to baseline (111570). The validity of these findings is limited by insufficient blinding and the lack of a comparator group. It is unclear if these effects are due to Indian gooseberry, other ingredients, or the combination.
• Metabolic syndrome. It is unclear if oral Indian gooseberry is beneficial for metabolic syndrome. Details: Preliminary clinical research in adults with metabolic syndrome shows that taking a specific Indian gooseberry extract (Capros, Natreon Inc.) 250 mg twice daily for 12 weeks reduces total cholesterol by nearly 10%, low-density lipoprotein (LDL) cholesterol by 15%, and triglycerides by 10%, and increases high-density lipoprotein (HDL) cholesterol by about 7% when compared with placebo. Additionally, taking this product as 500 mg twice daily reduces total cholesterol by 14%, LDL cholesterol by 26%, and triglycerides by 19%, and increases HDL cholesterol by 22% when compared with placebo. Both doses also seem to improve markers of endothelial function, oxidative stress, and systemic inflammation (102857).
• Obesity. It is unclear if oral Indian gooseberry is beneficial for improving weight loss or metabolic parameters in adults with obesity. Details: Preliminary clinical research in overweight or obese individuals shows that taking Indian gooseberry fruit extract (Capros, Natreon Inc.) 500 mg twice daily for 12 weeks reduces low-density lipoprotein (LDL) cholesterol by 16 mg/dL when compared to baseline. However, there was no effect on other lipids or on blood pressure, body weight, or body mass index (92515). The validity of these findings is limited by the lack of a comparator group.
• Oral mucositis. It is unclear if oral Indian gooseberry is beneficial in patients with radiation-induced mucositis. Details: A retrospective observational study in patients with head and neck cancer receiving radiotherapy suggests that rinsing the mouth with Indian gooseberry 1% and povidone-iodine twice daily is associated with delayed development of mucositis and intolerable mucositis and a decreased incidence of intolerable mucositis when compared with povidone-iodine alone (111566). The validity of these findings is limited by the retrospective study design.
• Osteoarthritis. Oral Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with knee osteoarthritis suggests that specific Ayurvedic formulas containing Indian gooseberry may be equivalent to glucosamine sulfate 2 grams daily or celecoxib 200 mg daily for reducing pain. Two capsules containing Indian gooseberry 166.66 mg/capsule, ginger 33.33 mg/capsule, and Tinospora cordifolia 73.33 mg/capsule, with or without Boswellia serrata 100 mg/capsule, taken three times daily for 24 weeks, were used. All four treatments reduced active pain by about 28% to 38%, functional pain by 19% to 29%, and functional difficulty by 18% to 25%, with no significant between-group differences in the observed improvements (89557). It is not clear if these effects are due to Indian gooseberry, the other ingredients, or the combination.
• Periodontitis. It is unclear if subgingival Indian gooseberry is beneficial for periodontitis. Details: Clinical research in patients with chronic periodontitis shows that the subgingival application of a sustained-release Indian gooseberry fruit 10% gel following scaling and root planing does not affect plaque or gingivitis development over 2-3 months when compared with placebo. However, there was a modest benefit on periodontal destruction based on probing pocket depth (105358).
• Vitiligo. Oral Indian gooseberry has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with vitiligo shows that taking 1 tablet containing Indian gooseberry 100 mg, vitamin E 10 mg, and carotenoids 4.7 mg orally 3 times daily for 6 months, in combination with conventional topical therapy and/or phototherapy, increases re-pigmentation in the head, neck, and trunk and decreases signs of inflammation when compared with conventional treatment alone (92513). More evidence is needed to rate Indian gooseberry for these uses.

(Read more about INDIAN GOOSEBERRY)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral maitake mushroom for allergic rhinitis, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Cancer. Although there has been interest in using oral maitake mushroom for cancer, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Chemotherapy-induced anemia. Although there has been interest in using oral maitake mushroom for preventing chemotherapy-induced anemia, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Chemotherapy-induced diarrhea. Although there has been interest in using oral maitake mushroom for preventing chemotherapy-induced diarrhea, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Chemotherapy-related fatigue. Although there has been interest in using oral maitake mushroom for preventing chemotherapy-related fatigue, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Chemotherapy-induced leukopenia. Although there has been interest in using oral maitake mushroom for preventing chemotherapy-induced leukemia, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Chemotherapy-induced nausea and vomiting (CINV). Although there has been interest in using oral maitake mushroom for preventing CINV, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral maitake mushroom for CFS, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral maitake mushroom for COVID-19, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Diabetes. Although there has been interest in using oral maitake mushroom for diabetes, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• HIV/AIDS. Although there has been interest in using oral maitake mushroom for HIV/AIDS, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Hyperlipidemia. Although there has been interest in using oral maitake mushroom for hyperlipidemia, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Hypertension. Although there has been interest in using oral maitake mushroom for hypertension, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Laryngeal cancer. It is unclear if maitake mushroom is beneficial for improving quality of life in patients with laryngeal cancer. Details: Clinical research in patients with laryngeal or pharyngeal cancer undergoing chemo-radiation treatment shows that taking maitake mushroom polysaccharides D-fraction 1 gram 3 times daily during treatment modestly improve survival over 5 years and prevents the decline in overall quality of life when compared with taking placebo (111935).
• Myelodysplastic syndromes. Although there has been interest in using oral maitake mushroom for myelodysplastic syndromes, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Obesity. Although there has been interest in using oral maitake mushroom for obesity, there is insufficient reliable information about the clinical effects of maitake mushroom for this purpose.
• Pharyngeal cancer. It is unclear if maitake mushroom is beneficial for improving quality of life in patients with pharyngeal cancer. Details: Clinical research in patients with laryngeal or pharyngeal cancer undergoing chemo-radiation treatment shows that taking maitake mushroom polysaccharides D-fraction 1 gram 3 times daily during treatment modestly improve survival over 5 years and prevents the decline in overall quality of life when compared with taking placebo (111935).
• Polycystic ovary syndrome (PCOS). Maitake mushroom may have some benefit in PCOS, but it does not appear to be as effective as clomiphene. Details: Preliminary clinical research in patients with PCOS shows that taking three tablets of a specific combination product (SX-Fraction, Maitake Products, Inc.), each containing maitake mushroom powder 250 mg plus maitake SX-fraction (a glycoprotein-rich extract) 18 mg, three times daily starting on the first day of menses for up to 28 weeks, can improve ovulation cycle rates, but does not appear to be as effective as clomiphene. After 12 weeks of treatment, patients taking the maitake mushroom product had an ovulatory cycle rate of about 42% compared with about 70% in those taking clomiphene 50 mg daily. However, 13 out of 15 patients who failed monotherapy with maitake mushroom or clomiphene alone ovulated when both maitake mushroom and clomiphene were used for 4 cycles (17131). More evidence is needed to rate the effectiveness of maitake mushroom for these uses.

(Read more about MAITAKE MUSHROOM)

POSSIBLY INEFFECTIVE

• Hyperlipidemia. Preliminary clinical studies show that oral reishi mushroom does not improve lipid levels in patients with hyperlipidemia or type 2 diabetes. Details: Preliminary clinical research shows that taking reishi mushroom extract 1440 mg daily for 12 weeks does not significantly improve the lipid profile in patients with hyperlipidemia (70776). Also, a meta-analysis shows that taking reishi mushroom extract 1400-4000 mg daily for 12-16 weeks does not reduce total cholesterol or low-density lipoprotein (LDL) cholesterol in patients with type 2 diabetes (91435).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral reishi mushroom for aging, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Altitude sickness. Although there has been interest in using oral reishi mushroom for altitude sickness, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Alzheimer disease. A small clinical study suggests that oral reishi mushroom does not improve Alzheimer disease symptoms. Details: Preliminary clinical research in patients with Alzheimer disease shows that taking reishi mushroom powder 1000 mg three times daily for 6 weeks does not improve memory, language skills, or quality of life when compared with placebo (97942).
• Asthma. Although there has been interest in using oral reishi mushroom for asthma, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Benign prostatic hyperplasia (BPH). Preliminary clinical research suggests that oral reishi mushroom extract can help reduce some lower urinary tract symptoms in patients with BPH. Details: Clinical research in patients with mild to moderate lower urinary tract symptoms (LUTS) associated with BPH, urinary incontinence, overactive bladder, or other conditions, shows that taking reishi mushroom extract 6 mg orally once daily for up to 12 weeks moderately improves total symptom severity measured on the International Prostate Symptom Score (IPSS) scale, when compared with placebo (91436,91437). A higher dose of 60 mg daily is not more effective than the 6 mg dose, and a lower dose of 0.6 mg daily is not more effective than placebo (91437). Reishi mushroom extract does not improve peak urine flow rate, residual urine volume, prostate volume, or quality of life when compared with placebo (91436,91437). The relevance of these results is unclear since not all of the patients with LUTS had BPH.
• Bronchitis. Although there has been interest in using oral reishi mushroom for bronchitis, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Cancer. It is unclear if oral reishi mushroom is beneficial when used in conjunction with chemotherapy. Details: A meta-analysis of 9 clinical trials using various reishi mushroom products in combination with chemotherapy found that complete and partial responses increased by 30% with combination therapy when compared with chemotherapy alone. However, there was no difference in overall survival (102915). The reliability and applicability of these results are unclear since the trials looked at several different types of cancer, used varying doses and durations of therapy, and were all conducted in China or other Asian countries.
• Cancer-related fatigue. It is unclear if oral reishi mushroom is beneficial in patients with breast cancer and fatigue. Details: Results from a small clinical study in breast cancer patients show that taking reishi mushroom powder 1000 mg orally three times daily for 4 weeks can improve cancer-related fatigue when compared with placebo (91438). However, it is not clear if the improvement is clinically meaningful.
• Cardiovascular disease (CVD). It is unclear if oral reishi mushroom is beneficial for reducing CVD risk factors. Details: A meta-analysis of 5 low-quality studies in adults with diabetes shows that taking reishi mushroom 1400-3000 mg daily for 12-16 weeks does not reduce CVD risk factors, including total and low-density lipoprotein (LDL) cholesterol, triglycerides, blood pressure, and body mass index, when compared with placebo (91435).
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral reishi mushroom for CFS, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Chronic kidney disease (CKD). Although there has been interest in using oral reishi mushroom for CKD, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Colorectal adenoma. Limited clinical research suggests that oral reishi mushroom extract may be beneficial for reducing colorectal adenoma size. Details: Preliminary clinical research in patients with colorectal adenomas shows that taking reishi mushroom extract 1500 mg orally in two divided doses daily for 12 months reduces the number and size of adenomas when compared with no treatment (70774).
• Coronary heart disease (CHD). It is unclear if oral reishi mushroom is beneficial for CHD. Details: Preliminary clinical research shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg orally three times daily for 12 weeks reduces symptoms of CHD, such as chest pain, palpitations, and shortness of breath, in a greater percentage of patients when compared with placebo (70800).
• Diabetes. Evidence on the use of oral reishi mushroom in patients with type 2 diabetes is conflicting. Details: A meta-analysis of clinical research in patients with type 2 diabetes shows that taking reishi mushroom extract 1400-4000 mg daily for 12-16 weeks does not reduce glycated hemoglobin (HbA1c) or plasma lipids (91435). However, one preliminary clinical study in patients with type 2 diabetes shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg three times daily for 12 weeks reduces HbA1c, but not fasting blood glucose, when compared with placebo (70801).
• Fibromyalgia. It is unclear if oral reishi mushroom is beneficial for fibromyalgia. Details: A small clinical trial in patients with fibromyalgia shows that taking reishi mushroom (MundoReishi Salud S.L.) powder 3 grams twice daily for 6 weeks does not improve mood, quality of life, anthropometric measures, blood pressure, or glycemic or lipid parameters when compared with placebo (108309,108310). However, the study may have been underpowered to detect any differences between groups.
• Genital herpes. Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with recurrent genital herpes shows that taking 4.4 grams of a mixture of hot water extracts of reishi mushroom, terminalia, Job's tears, Wisteria floribunda, Trapa natans, and Elfvingia applanata orally once daily for 2 days, then 2.2 grams daily thereafter until outbreak resolution, decreases the time to outbreak resolution by 6 days when compared with previous outbreaks (91434).
• Gulf war syndrome. It is unclear if oral reishi mushroom is beneficial for Gulf war syndrome. Details: A very small exploratory clinical trial in adults with Gulf war syndrome shows that taking reishi mushroom extract (JHS Natural Products, Mushroom Science) 1600 mg in two divided doses daily for 30 days does not improve symptoms when compared with placebo. Also, symptoms modestly worsened after an additional 30 days of treatment at a dose of 3200 mg daily (108311).
• Hepatitis B. One small clinical study suggests that a specific reishi mushroom extract may reduce hepatitis B activity and improve liver function. Details: Preliminary clinical research shows that taking a specific reishi mushroom extract (Ganopoly, Encore International Co.) 1800 mg orally three times daily for 12 weeks reduces levels of hepatitis B viral DNA and hepatitis B surface antigen, which are markers of hepatitis B activity, and normalizes aminotransferase levels in a greater percentage of patients when compared with placebo (70799).
• Herpes labialis (cold sores). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with recurrent herpes labialis shows that taking 4.4 grams of a mixture of hot water extracts of reishi mushroom, terminalia, Job's tears, Wisteria floribunda, Trapa natans, and Elfvingia applanata orally once daily for 2 days, then 2.2 grams daily thereafter until outbreak resolution, decreases the time to outbreak resolution by almost 4 days when compared with previous outbreaks (91434).
• Herpes zoster (shingles). Although there has been interest in using oral reishi mushroom for herpes zoster, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Human papillomavirus (HPV). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with oral HPV shows that taking a combination of reishi and coriolus mushroom powders, 400 mg orally daily for 2 months, clears HPV in 88% of patients when compared with baseline (91433). The validity of this finding is limited by the lack of a comparator group.
• Hypertension. Limited research suggests that oral reishi mushroom may be beneficial in some types of hypertension. Details: Preliminary clinical research shows that taking reishi mushroom extract 1440 mg daily for 12 weeks does not lower blood pressure in patients with hypertension (70776). However, in other clinical research, taking reishi mushroom extract 330-1440 mg daily for 1-6 months reduces blood pressure in patients with stage II or essential hypertension, but not in those with mild hypertension or diabetes (70786,70802,91435).
• Influenza. Although there has been interest in using reishi mushroom for influenza, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Insomnia. Although there has been interest in using reishi mushroom for insomnia, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Lung cancer. Small clinical studies suggest that oral reishi mushroom does not reduce the size of lung tumors. Details: A meta-analysis of preliminary clinical research shows that taking reishi mushroom does not reduce the size of lung tumors. However, it may stimulate immune function and improve quality of life in lung cancer patients when compared with control (70779).
• Peptic ulcers. Although there has been interest in using oral reishi mushroom for peptic ulcers, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose.
• Rheumatoid arthritis (RA). Oral reishi mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with active RA who are taking disease-modifying antirheumatic drugs shows that taking reishi mushroom extract 4 grams in combination with San Miao San (containing 2.4 grams each of atractylodes, phellodendron, and Achyranthes bidentata) daily for 24 weeks does not increase the percentage of patients achieving a 20% response based on the American College of Rheumatology (ACR) criteria or modify blood markers of disease and inflammation when compared with placebo (70767).
• Stress. Although there has been interest in using oral reishi mushroom for stress, there is insufficient reliable information about the clinical effects of reishi mushroom for this purpose. More evidence is needed to rate reishi mushroom for these uses.

(Read more about REISHI MUSHROOM)

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)

POSSIBLY EFFECTIVE

• Cognitive function. Oral sage seems to be beneficial for improving cognitive function in healthy adults. The benefits of sage aromatherapy are unclear. Details: Clinical research shows that taking a specific product providing common sage polyphenols and Spanish sage terpenoids (Cognivia), either as a single dose or daily for 29 days, modestly improves working memory and accuracy when compared with placebo. A single dose of this product contains common sage leaf extract 400 mg and Spanish sage essential oil 200 mg (105337). In addition, preliminary clinical research shows that Spanish sage essential oil 25-50 mcL orally as a single dose seems to dose-dependently enhance some measures of cognitive performance in young adults by a small amount (10811,72609,72616,72660). When used as aromatherapy, essential oils of common sage, but not Spanish sage, seem to improve quality of memory and secondary memory. Neither species improves speed of memory or working memory when used as aromatherapy. In this study, five drops of common sage essential oil and 5 mL water were placed on a warmed stone and allowed to diffuse for 5 minutes prior to exposure (72658).
• Hyperlipidemia. Oral sage seems to be beneficial for reducing low-density lipoprotein (LDL) cholesterol and triglyceride levels. Details: Clinical research in adults with mixed hyperlipidemia types shows that taking common sage leaf extract 500 mg, standardized to quercetin 2.16%, three times daily for 2 months reduces LDL cholesterol and triglyceride levels by about 20% and 23%, respectively, and increases high-density lipoprotein (HDL) cholesterol levels by 20%, when compared with placebo (72662). Also, preliminary clinical research in adults with type 2 diabetes and hypercholesterolemia shows that taking common sage leaf extract 500 mg three times daily for 3 months lowers total cholesterol by 17%, LDL cholesterol by 36%, and triglycerides by 56%, and increases HDL cholesterol by 28%, when compared with placebo (91971).
• Menopausal symptoms. Oral sage seems to be beneficial for reducing menopausal symptoms. Details: Clinical research shows that taking a thujone-free common sage extract (Menosan, A.Vogel AG) 280 mg daily for 4 weeks reduces overall symptoms of menopause by 39% when compared with placebo. About 41% of patients taking common sage had at least a 50% reduction in symptoms, compared with 8% of those taking placebo. Hot flushes, sleep problems, joint and muscle discomfort, irritability, and physical and mental exhaustion were improved, whereas urogenital symptoms such as sexual desire and vaginal dryness were not (105338). Other clinical research shows that taking common sage extract 300 mg daily for 3 months moderately reduces overall symptoms of menopause after about 10 weeks when compared with placebo. However, there was no effect on vaginal dryness, physical and mental exhaustion, or urinary incontinence (103379). Another small clinical study shows that taking a specific thujone-free common sage extract (Sage Menopause, Bioforce AG) 280 mg daily for 56 days reduces daily hot flash frequency by 40% and reduces hot flash intensity when compared with baseline (17177). The validity of these findings is limited by the lack of a comparator group.

POSSIBLY INEFFECTIVE

• Postoperative pain. Using an oral rinse containing common sage does not seem to be beneficial for reducing postoperative pain. Details: A large open-label clinical trial in children and adults shows that using a common sage oral rinse 6 times daily in combination with ibuprofen or diclofenac is less effective than benzydamine hydrochloride, a local anesthetic, for reducing pain following tonsillectomy and/or adenoidectomy. Furthermore, treatment with common sage oral rinse is associated with an increased risk of postoperative infection in adults when compared with benzydamine hydrochloride (72700).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if a single oral dose of common sage is beneficial for age-related cognitive decline. Details: Clinical research in healthy, older adults shows that taking a single dose of common sage extract 333 mg improves accuracy of attention and some measures of memory when compared with placebo. However, not all doses were effective and some measures of cognitive function were not affected (72642).
• Alzheimer disease. It is unclear if oral sage is beneficial for Alzheimer disease. Details: Preliminary clinical research shows that taking extracts of common sage and Spanish sage orally seems to improve cognitive function in patients with mild to moderate Alzheimer disease when used for up to 4 months (10334,10810). In one study, a fixed dose of common sage hydroalcoholic extract, equivalent to 1 gram of sage per day, was used for 4 months (10810). In the other, an extract of Spanish sage titrated up to 2.5 mg three times daily for 6 weeks was used (10334). These studies are limited by their short duration and small numbers of participants.
• Androgen deprivation therapy (ADT)-associated hot flashes. It is unclear if oral sage is beneficial for ADT-associated hot flashes. Details: Preliminary clinical research in patients with prostate cancer receiving ADT shows that taking common sage extract 150 mg three times daily with meals for 4 weeks reduces hot flash severity by 48% and hot flash frequency by 42% when compared with baseline. These improvements were maintained with an additional 8 weeks of treatment (91970). The validity of these findings is limited by the lack of a comparator group.
• Athletic performance. It is unclear if oral sage is beneficial for improving athletic performance. Details: In young, healthy, physically active adults, taking a specific supplement (Cognivia, Nexira) containing 400 mg common sage leaf extract and 200 mg Spanish sage oil, orally 2 hours prior to a 40-minute stationary cycling session at 80% of maximum aerobic power, lowers perceived exertion scores and improves working memory and reaction times when compared with placebo (108961).
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if topical sage is beneficial for the treatment or prevention of CINV. Details: A small clinical study in patients undergoing chemotherapy shows that using common sage oil 2 mL topically during 15-minute sessions of Swedish abdominal massage twice daily for 3 days modestly reduces nausea severity scores, but does not affect vomiting frequency, when compared with massage alone (107023).
• Dental plaque. It is unclear if rinsing the mouth with sage is beneficial for reducing plaque. Details: Preliminary clinical research shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), is as effective as normal saline for reducing dental plaque. However, there was no effect on tongue plaque. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Diabetes. It is unclear if oral sage is beneficial for diabetes. Details: A small clinical study in adults with type 2 diabetes shows that taking common sage leaf extract 500 mg three times daily for 3 months lowers fasting blood glucose by 32% and glycated hemoglobin (HbA1c) by 23% when compared with placebo (91971). However, another small clinical study in patients with type 2 diabetes shows that taking common sage extract 150 mg three times daily for 3 months does not lower fasting blood glucose or HbA1c when compared with placebo, although there is a modest reduction in 2-hour postprandial blood glucose levels (105340). A meta-analysis of 3 small studies, including the 2 described above, shows that taking common sage, 150-500 mg three times daily for 2-3 months, modestly reduces fasting blood glucose and 2-hour postprandial blood glucose levels, as well as HbA1c, when compared with placebo (108962). These studies were all conducted in Iran; it is unclear if these findings are generalizable to other geographic locations.
• Dry mouth. It is unclear if rinsing the mouth with common sage is beneficial for dry mouth. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in conjunction with standard care involving brushing and an oral gel (Biotene), is as effective as normal saline for improving overall oral health and modestly more effective than normal saline for improving dry mouth. The rinse was made by steeping 2.5 grams dried sage leaf in 100 mL boiled water for two minutes (105339).
• Gingivitis. Sage has only been evaluated as a mouthwash in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in elderly individuals shows that rinsing the mouth with a mouthwash containing sage, marshmallow, calendula, tormentil, horse chestnut, neem, and myrrh, once daily for 30 seconds for 6 weeks, is no more effective than placebo for improving plaque and gingival bleeding (105341).
• Herpes labialis (cold sores). It is unclear if topical sage is beneficial for herpes labialis. Details: Clinical research shows that topical application of a cream containing either sage alone or sage with rhubarb, starting within 1 day of the first symptoms and continuing for 10-14 days, heals herpes labialis legions in 7.6 days or 6.7 days, respectively, compared to a healing time of 6.3 days with acyclovir cream. The combination of sage and rhubarb also improves the time to healing and reduces pain when compared with sage alone. The cream provided 23 mg sage extract, with or without 23 mg rhubarb extract, per gram and was applied every 2-4 hours while awake (10437).
• Lung cancer. It is unclear if dietary sage is beneficial for lung cancer prevention. Details: Epidemiological research has found that regularly consuming sage is associated with a 54% lower risk of developing lung cancer when compared with those who do not use sage as a spice (72593).
• Oral mucositis. It is unclear if rinsing the mouth with sage is beneficial for oral mucositis. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a rinse containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), does not improve oral mucositis when compared with baseline or normal saline rinse. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Pharyngitis. It is unclear if inhaling a spray containing sage, with or without other ingredients, is beneficial for pharyngitis. Details: Clinical research in patients with acute viral pharyngitis shows that inhaling three puffs (140 mcL) of a specific spray (Valverde Salvia Rachenspray) containing common sage extract 15%, six to nine times daily for 3 days, reduces throat pain intensity over 2 hours when compared with placebo. However, sprays containing common sage extract 5% or 30% do not seem to be more effective than placebo for reducing throat pain (72619). Other preliminary clinical research in patients with sore throat due to acute pharyngitis or tonsillitis shows that applying a combination spray product containing common sage leaf tincture 430 mg/mL, Echinacea flowering aerial parts tincture 863.3 mg/mL, and Echinacea root tincture 45.5 mg/mL, every 2 hours up to 10 times daily for up to 5 consecutive days improves symptoms as effectively as a chlorhexidine-lidocaine spray (20077).
• Polycystic ovary syndrome (PCOS). It is unclear if oral sage is beneficial for PCOS. Details: Clinical research shows that taking common sage extract 330 mg daily for 8 weeks modestly reduces body mass index (BMI), diastolic blood pressure, and fasting blood glucose, and modestly improves measures of insulin resistance, when compared with placebo in individuals with PCOS. However, there was no effect on waist to hip ratio or systolic blood pressure (103380).
• Sunburn. It is unclear if topical sage is beneficial for sunburn prevention. Details: Clinical research shows that a single application of a hydrophilic ointment containing common sage extract 2% to the skin immediately after exposure to ultraviolet light reduces the development of skin redness when compared with placebo (72638).
• Swallowing dysfunction. It is unclear if rinsing the mouth with sage is beneficial for swallowing dysfunction. Details: Preliminary clinical research in patients receiving palliative cancer care shows that rinsing the mouth with 10-15 mL of a solution containing common sage, twice for 30 seconds four times daily for 4 days, in addition to standard oral care with brushing and use of an oral gel (Biotene), does not improve swallowing when compared with baseline or normal saline rinse. The rinse was made by steeping 2.5 grams of dried sage leaf in 100 mL boiled water for two minutes (105339).
• Tonsillitis. Sage has only been evaluated in a spray in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with sore throat due to acute pharyngitis or tonsillitis shows that applying a combination spray product containing common sage leaf tincture 430 mg/mL, Echinacea flowering aerial parts tincture 863.3 mg/mL, and Echinacea root tincture 45.5 mg/mL, every 2 hours up to 10 times daily for up to 5 consecutive days improves symptoms as effectively as a chlorhexidine-lidocaine spray (20077).
• Tonsillopharyngitis. It is unclear if oral sage is beneficial for treating tonsillopharyngitis. Details: A moderate-sized observational study in patients aged 12-75 years old with acute tonsillopharyngitis suggests that taking lozenges containing sage extract 378.5 mg and echinacea extract 5 times daily for 4 days reduces throat pain and tonsillopharyngitis symptoms when compared to baseline, both acutely within 90 minutes and after 4 days of treatment (111530). The validity of these findings is limited by the lack of a comparator group. Also, it is unclear if these effects are due to sage, echinacea, the combination, or natural resolution of the condition. More evidence is needed to rate sage for these uses.

(Read more about SAGE)

POSSIBLY INEFFECTIVE

• Dental Plaque. A solution containing an extract of shiitake mushroom is less effective than fluoride mouthwash for reducing dental plaque. Details: Clinical research shows that rinsing the mouth with a solution containing shiitake mushroom extract does not reduce dental plaque when compared with placebo and appears to be less effective than fluoride mouth rinse (Meridol) (94250).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral shiitake mushroom for aging, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Atherosclerosis. Although there has been interest in using oral shiitake mushroom for atherosclerosis, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Breast cancer. Although there has been interest in using oral shiitake mushroom for breast cancer, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Cancer. It is unclear if oral shiitake mushroom is beneficial in patients with cancer. Details: Although some small clinical studies in patients with gastric or colon cancer have found that patients taking the shiitake mushroom extract AHCC 3-6 grams daily have better survival rates and quality of life when compared with historical population data, other observational research has not found a benefit for patients with head, neck, lung, or breast cancer when compared with baseline (30421,30425,30454). The validity of these studies is limited by lack of a comparator group.
• Chemotherapy-induced anemia. It is unclear if oral shiitake mushroom is beneficial in patients with chemotherapy-induced anemia. Details: A small clinical study in adults receiving chemotherapy for pancreatic cancer shows that taking the shiitake mushroom extract AHCC 6 grams daily for 8-12 weeks does not reduce the rate of grade 2 to 3 anemia when compared with placebo (110131).
• Chemotherapy-induced leukopenia. It is unclear if oral shiitake mushroom is beneficial in patients with chemotherapy-induced leukopenia. Details: Preliminary clinical research in patients with breast cancer receiving chemotherapy shows that taking the shiitake mushroom extract AHCC significantly reduces chemotherapy-related neutrophil events and lipid abnormalities when compared with standard care (94829).Observational research in patients with resectable pancreatic ductal adenocarcinoma has found that taking this product orally 3 grams daily throughout 2 cycles of neoadjuvant gemcitabine improves the neutrophil-to-lymphocyte ratio and nutritional scores when compared with standard of care (106783). In contrast, other clinical research in patients with pancreatic or biliary tract cancer receiving gemcitabine chemotherapy shows that taking AHCC 6 grams daily for two months does not seem to affect neutropenia, thrombocytopenia, or hepatic dysfunction when compared with standard of care. However, taking AHCC did reduce C-reactive protein and increase hemoglobin and albumin when compared to standard of care (30424).
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if oral shiitake mushroom is beneficial in patients with CINV. Details: Preliminary clinical research in patients being treated for head and neck cancers shows that taking the shiitake mushroom extract AHCC 3 grams daily, beginning 3 days prior to chemotherapy and continuing until one week after chemotherapy, reduces gastric side effects and the need for antiemetic therapy when compared with baseline (30425). The validity of these findings is limited by the lack of a comparator group.
• Chemotherapy-induced taste changes. It is unclear if oral shiitake mushroom is beneficial for the prevention of taste changes due to chemotherapy. Details: A small clinical study in adults receiving chemotherapy for pancreatic cancer shows that taking the shiitake mushroom extract AHCC 6 grams daily for 8-12 weeks reduces the rate of patient-reported taste disorders by 27% when compared with placebo (110131). Although patients in the AHCC group had modest improvements in some nutritional parameters when compared with the placebo group, it is unclear if any changes would be considered clinically significant.
• Common cold. Although there has been interest in using oral shiitake mushroom for the common cold, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral shiitake mushroom for COVID-19, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Diabetes. Although there has been interest in using oral shiitake mushroom for diabetes, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Genital herpes. Although there has been interest in using oral shiitake mushroom for genital herpes, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Hepatitis C. It is unclear if oral shiitake mushroom is beneficial in patients with hepatitis C. Details: Preliminary clinical research in adults with chronic hepatitis C shows that taking the shiitake mushroom extract AHCC 6 grams daily for 6 months does not significantly reduce alanine aminotransferase (ALT) or hepatitis C virus RNA levels when compared with placebo (30419).
• HIV/AIDS. Although there has been interest in using oral shiitake mushroom for HIV/AIDS, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Human papillomavirus (HPV). It is unclear if oral shiitake mushroom is beneficial in patients with HPV. Details: A small clinical study in adult females with persistent high-risk HPV shows that taking the shiitake mushroom extract AHCC 3 grams daily leads to clearance of HPV RNA and DNA in 64% of patients after 6 months of treatment, compared to 11% of patients taking placebo (110129). The validity of these findings is limited by lack of statistical comparison between groups.
• Hypercholesterolemia. It is unclear whether oral shiitake mushroom is beneficial for lowering blood lipid levels. Details: Clinical research in adults with borderline high levels of cholesterol or triglycerides shows that consuming bars providing shiitake mushroom for 66 days modestly reduces triglyceride levels, but does not affect levels of low-density lipoprotein (LDL) cholesterol or high-density lipoprotein (HDL) cholesterol, when compared with placebo bars. Each bar provided dried shiitake mushroom 3.5 grams daily and the number of bars consumed daily was based on body mass index (108300). The effect of shiitake mushroom in patients with hypercholesterolemia, specifically, is unclear due to the heterogenous patient population.
• Hypertension. Although there has been interest in using oral shiitake mushroom for hypertension, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Impaired glucose tolerance (prediabetes). Oral shiitake mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with prediabetes shows that taking freeze-dried shiitake mushroom 0.96 grams in combination with chokeberry 1.36 grams, Panax ginseng 1.64 grams, and nattokinase 0.8 grams (Chakreis, YD Nutraceuticals Ltd.) twice daily for 12 weeks does not affect glycated hemoglobin, fasting blood glucose, or oral glucose tolerance test results when compared with placebo. However, there were some modest beneficial effects on insulin resistance and fasting insulin and liver transaminase levels (108301).
• Influenza. Although there has been interest in using oral shiitake mushroom for influenza, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Liver cancer. Small, low-quality clinical studies suggest that oral shiitake mushroom extract may improve overall survival in patients with liver cancer. Details: Preliminary clinical research in patients with advanced hepatic cancer shows that taking the shiitake mushroom extract AHCC orally 6 grams daily for a median of 3.5 months along with supportive care increases the median survival time by 2 months when compared with placebo. Taking AHCC also improved quality of life scores when compared with placebo (30359). Population research in patients with hepatocellular carcinoma has also found that taking AHCC 3 grams daily for up to 9 years after surgical resection reduces tumor recurrence and mortality by 48% and 56%, respectively, when compared with control (30353). In another small, open label clinical study of adults with advanced hepatocellular carcinoma, tumor recurrence occurred in 52% of patients who took AHCC 1 gram three times daily for 2 years after surgical resection (110130). The interpretation of these results is limited by the lack of a control group.
• Obesity. Although there has been interest in using oral shiitake mushroom for obesity, there is insufficient reliable information about the clinical effects of shiitake mushroom for this purpose.
• Prostate cancer. It is unclear whether shiitake mushroom has a role in preventing disease progression. Details: Preliminary clinical research shows that taking shiitake mushroom extract does not prevent disease progression, as determined by prostate-specific antigen (PSA) levels, when compared with baseline (10451). More evidence is needed to rate shiitake mushroom for these uses.

(Read more about SHIITAKE MUSHROOM)

POSSIBLY EFFECTIVE

• Cancer. Taking PSK, a constituent of turkey tail mushroom, as an adjunct to standard cancer therapy may improve response rates and survival in some patients with cancer. Very limited data suggests that whole turkey tail mushroom is not beneficial. Details: The PSK constituent of turkey tail mushroom has been used as an adjunct to standard cancer therapy in Japan for several decades, in doses ranging from 1 to 3.6 grams daily (94076). It has been used in a dose of 3 grams daily for 24-36 months for breast (1648,1650,1654,1656), colorectal (1657,1660,70165,70167,70168,70171,70173,70174,70176,70190)(94076), esophageal (1649), gastric (1640,1651,1652,1657,1658,1659,1660,70161,70170,70175)(70179,70181,70183,70186,70189,70191,70194,70198), hepatic (1655,70188), and lung cancers (1653,70180,70184), as well as for leukemia (70200,70206). It has also been used in a dose of 1 gram daily for up to 72 months for colorectal cancer (94076), 1 gram three times daily for 1 month for nasopharyngeal cancer (1661,70195), and 2 grams/m2 per day in 3 divided doses, rotating in cycles with chemotherapy, for gastric cancer (1659,70194,70195). A meta-analysis of 13 clinical trials including over 2500 patients with esophageal, gastric, colon, rectal, breast, or nasopharyngeal cancer, shows that taking PSK in addition to conventional therapy reduces 5-year mortality by 9% when compared with conventional therapy alone. When individual cancer types are considered, the benefit of PSK is most evident in patients with breast, gastric, colon, or rectal cancer (94076). Another meta-analysis of 14 clinical trials shows that taking PSK, polysaccharide peptide (PSP), or turkey tail mushroom in combination with chemotherapy is associated with a 17% lower risk of mortality in some, but not all, types of cancer when compared with chemotherapy alone. However, overall there was no difference in relapse-free survival or total clinical efficacy, defined as complete responses plus partial responses (102915). The reliability and relevance of these meta-analyses is unclear since the trials looked at several different types of cancer, used varying doses and durations of therapy with different turkey tail mushroom extracts, and were all conducted in China or other Asian countries. Research on the use of whole turkey tail mushroom rather than the constituent PSK for treating cancer is limited. A small clinical study in 15 patients with inoperable hepatocellular carcinoma shows that taking turkey tail mushroom 2.4 grams daily for 6-12 weeks does not improve time to progression, progression-free survival, overall survival, or quality of life when compared with placebo (96568). However, this study was likely underpowered to detect any differences.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cervical dysplasia. Intravaginal turkey tail mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A specific vaginal gel (Papilocare, Procare Health) containing turkey tail mushroom, neem, carboxymethyl-beta-glucan, hyaluronic acid, gotu kola, aloe, and alpha-glucan oligosaccharide has been examined in preliminary clinical and observational research in patients with human papillomavirus (HPV)-related cervical lesions. One clinical study shows that topical application for 6 months is associated with a normal Pap smear in 85% of patients, compared with 65% of those receiving only regular monitoring. Benefits were greatest in high-risk patients (108305). In patients over 40 years of age, treatment with this gel resulted in a normal Pap smear in 92% of patients, compared with 50% of those receiving only regular monitoring (111905). Both studies also showed improvements in cervical re-epithelization and HPV clearance (108305,111905). Observational research has also been conducted. One observational study in patients with high-risk HPV infection has found that using this same product is associated with 4.8-, 2.3-, and 5.1-fold increased odds of HPV DNA clearance, remission at colposcopy, and remission with cytology at 6 months, respectively, when compared with untreated patients (108306). In another observational study, using this product for 6 or 12 months is associated with repair of cervical low-grade lesions and a normalized cytology and colposcopy in about 75% of patients. HPV clearance was achieved in 71.6% of patients (111904). Doses of gel administration have varied. The gel is usually applied once daily for 21 days, followed by 7 days with no treatment, and then alternate days for up to 2-12 months (108305,108306,111904,111905). It is occasionally applied once daily for 21 days, followed by 7 days with no treatment, repeated for 3 months, and then alternated days for 3 months (108305).
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral turkey tail mushroom for CFS, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Genital herpes. Although there has been interest in using oral turkey tail mushroom for genital herpes, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Hepatitis. Although there has been interest in using oral turkey tail mushroom for hepatitis, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Muscle strength. Although there has been interest in using oral turkey tail mushroom for muscle strength, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Tinea corporis. Although there has been interest in using oral turkey tail mushroom for tinea corporis, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral turkey tail mushroom for URTI, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose.
• Urinary tract infections (UTIs). Although there has been interest in using oral turkey tail mushroom for UTIs, there is insufficient reliable information about the clinical effects of turkey tail mushroom for this purpose. More evidence is needed to rate turkey tail mushroom for these uses.

(Read more about TURKEY TAIL MUSHROOM)

POSSIBLY EFFECTIVE

• Mastalgia. Meta-analyses of small clinical studies show that vitex agnus-castus moderately reduces breast pain due to cyclic mastalgia. Details: Two small meta-analyses of low-to-moderate quality clinical studies in patients with cyclic mastalgia show that taking vitex agnus-castus moderately reduces breast pain when compared with placebo (101981,111753). The validity of these findings is limited by the heterogeneity of the included studies. Doses of vitex agnus-castus dried fruit extract range from 3.2-40 mg daily, for 2-6 months (90617,96250,101981,111753). Vitex agnus-castus is commonly used in proprietary products, alone or in combination with other herbs (Agnucaston/Cyclodynon, Bionorica AG, Femicur, Mastodynon, Bionorica AG, Monoselect Agnus, ZE 440) (13395).
• Premenstrual syndrome (PMS). Clinical research shows that vitex agnus-castus produces modest improvements in PMS symptoms. Details: Clinical research shows that taking vitex agnus-castus fruit extract orally for 2-6 menstrual cycles seems to reduce symptoms of PMS, especially breast pain or tenderness (mastalgia), edema, constipation, irritability, depressed mood, anxiety, anger, and headache (7055,7076,7078,7079,13394,15065,41483,41489,41490,41494,90619,101981). Doses of fruit extracts have varied from 3.5-40 mg daily, usually for 2-3 menstrual cycles (7055,7076,7078,7079,15065,41483,41489,41490,90619,96435). A meta-analysis of the available clinical research, including 17 studies involving 2,401 patients, shows that taking vitex agnus-castus is comparable to fluoxetine or oral contraceptives, and modestly more effective than placebo, for reducing the symptoms of PMS. A sub-group analysis indicates that efficacy is not impacted by the dose or form used, although the dried powdered berries appear to be ineffective. The low quality of the included studies and the high level of bias and heterogeneity limit the validity of these findings (96435). Another meta-analysis limited to three randomized controlled trials shows that taking vitex agnus-castus increases the likelihood of PMS symptom remission by 2.6-fold over placebo (101979). Some clinical studies have used a specific dried extract of vitex agnus-castus fruit (Agnolyt, Madaus AG) (7076). Other studies used a specific fruit extract known as Ze 440 (Prefemin, Zeller AG), which is standardized to casticin content (7078,90619). Additional studies have used the fruit extract BNO 1095 (Agnucaston/Cyclodynon, Bionorica AG) (15065,41483,41489,41490).

POSSIBLY INEFFECTIVE

• Fractures. Limited evidence suggests that vitex agnus-castus does not improve fracture healing rates. Details: Clinical research shows that taking a specific vitex agnus-castus dried fruit extract (Agnugol, Goldaru Pharmacy Company) 4 mg, alone or in combination with magnesium oxide (Nature Made Company) 250 mg, daily for 8 weeks does not improve long bone fracture healing when compared with placebo (90618).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using oral vitex agnus-castus for acne, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Aging skin. Vitex agnus-castus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical trial in postmenopausal adults with wrinkles shows that taking one capsule orally daily of a combination of vitex agnus-castus 400 mg, evening primrose oil 500 mg, soy isoflavones 100 mg, and black cohosh 520 mg (Estosalus, Max Biocare Pty Ltd) for 12 weeks improves skin elasticity, skin smoothness, and wrinkle density scores when compared with placebo (109440).
• Amenorrhea. Although there is interest in using oral vitex agnus-castus for amenorrhea, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Anxiety. Although there is interest in using oral vitex agnus-castus for anxiety, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Benign prostatic hyperplasia (BPH). Although there is interest in using oral vitex agnus-castus for BPH, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Dementia. Although there is interest in using oral vitex agnus-castus for dementia, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Dysmenorrhea. It is unclear if oral vitex agnus-castus is beneficial in patients with dysmenorrhea. Details: Preliminary clinical research in patients with primary dysmenorrhea shows that taking a specific vitex agnus-castus extract (Agnucaston, Bionorica AG) daily for 3 months reduces pain, as measured on a visual analog scale, similarly to ethinyl estradiol 0.03 mg / drospirenone 3 mg (Yasmin) taken daily (104975).
• Fibrocystic breast disease. Although there is interest in using oral vitex agnus-castus for fibrocystic breast disease, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Hyperprolactinemia. Although there is interest in using oral vitex agnus-castus for hyperprolactinemia, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Infertility. It is unclear if oral vitex agnus-castus is beneficial for female infertility. Details: Preliminary clinical research in infertile females with oligomenorrhea or amenorrhea shows that taking homeopathic vitex agnus-castus (Phyto Hypophyson L, Steierl-Pharma GmbH) 50 drops orally three times daily for 3 months does not increase the chance of getting pregnant (41470). Also, one small clinical study in those with infertility due to secondary amenorrhea or luteal insufficiency shows that taking a vitex agnus-castus preparation (Mastodynon, Bionorica GmbH, Neumarkt/Opf.) 30 drops twice daily for at least 3 months does not increase the chance of pregnancy when compared with placebo, although the study was likely inadequately powered to detect a difference (7077).
• Insect repellent. Limited research suggests that topical vitex agnus-castus has insect repellent activity. Details: Preliminary clinical research shows that applying a carbon dioxide extract of vitex agnus-castus seeds seems to repel ticks and fleas for 6 hours, mosquitoes for 3-8 hours, and biting flies for 3 hours (13396). It is unclear how this compares with commonly used insect repellants.
• Insomnia. Although there is interest in using oral vitex agnus-castus for insomnia, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Lactation. Although there is interest in using oral vitex agnus-castus for stimulating lactation, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Menopausal symptoms. Clinical research suggests that vitex agnus-castus can relieve some menopausal symptoms; however, most research uses vitex agnus-castus in combination with other treatments. Details: Clinical research shows that taking vitex agnus-castus extract 15 mg twice daily for 8 weeks improves some menopausal symptoms, including anxiety and vasomotor dysfunction, by 76% and 88%, respectively, when compared with baseline. However, there was no effect on depression or sexual dysfunction (101980). Vitex agnus-castus has also been studied as a component of combination products. Preliminary clinical research shows that taking a combination of vitex agnus-castus, equivalent to 1000 mg dried fruit, black seed powder 500 mg, and citalopram 20 mg daily for 8 weeks reduces vasomotor, psychosocial, and physical symptoms of menopause when compared with citalopram alone (100325). Other preliminary clinical research shows that taking one capsule orally daily of a combination of vitex agnus-castus 400 mg, evening primrose oil 500 mg, soy isoflavones 100 mg, and black cohosh 520 mg (Estosalus, Max Biocare Pty Ltd) for 12 weeks moderately reduces the severity of hot flashes, sweating, sleep problems, depressed mood, and irritability when compared with placebo. There was no effect on plasma lipids, joint discomfort, anxiety, exhaustion, or sexual problems (105102). It is unclear if these effects are due to vitex agnus-castus, other ingredients, or the combination.
• Menorrhagia. It is unclear if oral vitex agnus-castus is beneficial in patients with menorrhagia. Details: A meta-analysis of two moderate quality clinical trials in patients who had heavy menstrual periods shows that taking vitex agnus-castus does not reduce menstrual bleeding over the next 1-2 menstrual cycles when compared with placebo (101982). However, preliminary clinical research in patients using an intrauterine device (IUD) shows that taking vitex agnus-castus three times daily for 8 days, starting on the first day of menstruation, and repeated for four consecutive menstrual cycles, reduces the amount of bleeding by approximately 48% when compared with baseline. This reduction was similar to the effects of mefenamic acid 250 mg daily after 4 months, although treatment with mefenamic acid was superior during the first three months (90620).
• Migraine headache. Although there is interest in using oral vitex agnus-castus for migraine headache, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Polycystic ovary syndrome (PCOS). Vitex agnus-castus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with oligomenorrhea due to PCOS shows that taking a traditional combination product (Aslagh) containing equivalent amounts of essential oils of vitex agnus-castus fruit, fennel, and wild carrot seeds orally daily for 3 months, either alone or in combination with metformin, improves rates of menstrual bleeding and menstrual cyclicity similarly to metformin alone. All three groups experienced a significant improvement from baseline. Aslagh was taken as two, 500-mg capsules twice daily, except during menses; metformin was titrated over one week to a dose of 500 mg three times daily (108974).
• Premenstrual dysphoric disorder (PMDD). Limited evidence suggests that vitex agnus-castus might improve symptoms of PMDD. Details: In a clinical trial, vitex agnus-castus 20-40 mg daily for 8 weeks was similar to fluoxetine 20-40 mg daily for relieving symptoms of PMDD. About 58% of patients responded to vitex agnus-castus, compared to about 68% of patients taking fluoxetine. Vitex agnus-castus was more effective for physical symptoms such as breast tenderness, swelling, cramps, and food cravings (12207,41493).
• Rheumatoid arthritis (RA). Although there is interest in using oral vitex agnus-castus for RA, there is insufficient reliable information available about the clinical effects of vitex agnus-castus for this condition.
• Sexual dysfunction. It is unclear if oral vitex agnus-castus is beneficial in patients with sexual dysfunction. Details: Preliminary clinical research in healthy females under 44 years of age with sexual dissatisfaction shows that taking a specific vitex agnus-castus product (Agnugol, Goldaru Herbal Pharmaceutical Company) 3.2-4.8 mg orally once daily for 16 weeks modestly improves scores of sexual satisfaction, function, arousal, and desire when compared with placebo (109437). Additionally, a moderate-sized clinical study in females 50-69 years old with sexual dysfunction conducted in Iran shows that taking vitex agnus-castus 40 drops daily for 8 weeks improves sexual dysfunction scores from mild dysfunction to no dysfunction at 6 and 8 weeks when compared with placebo but does not improve scores at 4 weeks (112361). More evidence is needed to rate the effectiveness of vitex agnus-castus for these uses.

(Read more about VITEX AGNUS-CASTUS)

POSSIBLY SAFE ...when taken orally and appropriately. Bacillus coagulans spores in doses up to 6 billion colony-forming units (CFUs) daily have been used with apparent safety in clinical studies for up to 3 months (92726,92730,92734,92735,92736,92739,92740,104231,105169)(107611,107612,107614). Lower doses of B. coagulans up to 100 million CFUs daily have been used with apparent safety in clinical studies for up to one year (92738). There is insufficient reliable information available about the safety of non-viable, heat-killed B. coagulans formulations when used orally.

CHILDREN: POSSIBLY SAFE
when taken orally and appropriately. Bacillus coagulans spores in doses up to 100 million colony-forming units (CFUs) daily have been used with apparent safety in clinical studies in infants of most ages for up to one year (92729,92733,92738) and in doses of one billion CFUs in children aged 6-8 years for 3 months (107615). There is insufficient reliable information available about the safety of Bacillus coagulans 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 BACILLUS COAGULANS)

LIKELY SAFE ...when consumed in amounts commonly found in foods (6,2076).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Indian gooseberry fruit extract has been used safely in doses of up to 1000 mg daily for up to 6 months, 1500 mg daily for up to 8 weeks, or 2000 mg daily for up to 4 weeks (92515,99238,99240,99241,102855,102857,105352,105354,105356). Indian gooseberry leaf extract has been used with apparent safety at a dose of 750 mg daily for 10 days (99846). ...when used topically and appropriately. An emulsion containing Indian gooseberry extract 3% and other ingredients has been applied safely to the skin twice daily for up to 60 days (111571).

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

(Read more about INDIAN GOOSEBERRY)

POSSIBLY SAFE ...when used orally and appropriately as extracts. A maitake mushroom extract 3 mg/kg twice daily has been used safely for up to 12 weeks (92843). Doses up to 5 mg/kg twice daily of another maitake mushroom extract have been used safely for up to 3 weeks (61239). Maitake mushroom polysaccharides (MMP) 1-1.5 grams daily have also been used safely for up to 2 years (8188).

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

(Read more about MAITAKE MUSHROOM)

POSSIBLY SAFE ...when an extract of reishi mushroom is used orally and appropriately for up to one year (12,5485,70767,70774,70786,70799,70800,70801,70802). ...when whole powdered reishi mushroom is used orally and appropriately for up to 16 weeks (70776,70799,70800,70801,91433,91435,91436,91437,108309).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using

(Read more about REISHI MUSHROOM)

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)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Sage is approved for use as a food in the United States (4912).

POSSIBLY SAFE ...when used orally in medicinal doses, short-term. Common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) have been used with apparent safety when taken orally in doses of 280 mg daily for up to 8 weeks (10334,10810,17177,105338). ...when used topically. Common sage (Salvia officinalis) has been used with apparent safety as a single agent or in combination products for up to one week (10437,72619,107023). ...when the essential oil is inhaled as aromatherapy, short-term (72658).

POSSIBLY UNSAFE ...when used orally in high doses or long-term (12,1304). Some species of sage, including common sage (Salvia officinalis), contain a thujone constituent that can be toxic if consumed in large enough quantities (12,1304).

PREGNANCY: LIKELY UNSAFE
when used orally. The constituent thujone can have menstrual stimulant and abortifacient effects (19).

LACTATION: POSSIBLY UNSAFE
when used orally; sage is thought to reduce the supply of mother's milk (19).

(Read more about SAGE)

LIKELY SAFE ...when consumed in typical food amounts (6).

POSSIBLY SAFE .... ..when the shiitake mushroom extract AHCC is used orally and appropriately. AHCC 4.5-6 grams daily has been used with apparent safety in clinical trials lasting up to 6 months (22926,30419). Population research identified no safety concerns with the use of AHCC 3 grams daily for up to 9 years (30353,94830).

POSSIBLY UNSAFE ...when shiitake mushroom powder is used orally in medicinal amounts. Ingestion of shiitake mushroom powder 4 grams daily for 10 weeks can cause eosinophilia (1149). ...when uncooked shiitake mushroom is ingested. The lentinan component, which is broken down by heat, can cause toxic reactions, including shiitake dermatitis (94354).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid consuming greater than food amounts.

(Read more about SHIITAKE MUSHROOM)

LIKELY SAFE ...when turkey tail mushroom is used orally and appropriately (5477). ...when polysaccharide krestin (PSK) and polysaccharide peptide (PSP) isolates of turkey tail mushroom are used orally and appropriately (1635,1636,1640,1641,1648,1649,1650,1651,1652,1653,1654) (1655,1656,1657,1658,1659,1660,1661,1662,70167,70168,70171,70188,70200,94076). There is insufficient reliable information available about the safety of turkey tail mushroom when used topically or intravaginally.

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

(Read more about TURKEY TAIL MUSHROOM)

LIKELY SAFE ...when the fruit extract is used orally and appropriately, short-term. Vitex agnus-castus fruit extract has been used safely in studies at doses up to 40 mg daily, for up to 3 months (7055,7076,7077,7078,7079,12207,13393,15065,90617,90618,96435). There is insufficient reliable information available about the safety of vitex agnus-castus seeds when used orally or topically.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally. Theoretically, the hormonal effects of vitex agnus-castus might adversely affect pregnancy or lactation (10979,11456,13393,109439). Animal research shows that taking vitex agnus-castus fruit extract when planning to become pregnant or during pregnancy may increase the risk of infertility, low fetal body weight, abortion, and stillbirth (109439); avoid using.

(Read more about VITEX AGNUS-CASTUS)

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

(Read more about BACILLUS COAGULANS)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, Indian gooseberry may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs; however, research is conflicting.  Details Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking Indian gooseberry 500 mg along with clopidogrel 75 mg or ecosprin 75 mg, as a single dose or for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg or ecosprin 75 mg alone (92514). Until more is known, use caution when taking Indian gooseberry in combination with anticoagulant/antiplatelet drugs.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Taking Indian gooseberry with antidiabetes drugs might increase the risk of hypoglycemia.  Details Clinical research shows that taking Indian gooseberry fruit or fruit extract alone or in conjunction with antidiabetes medications can lower blood glucose levels (31025,105355,105356,111569). Dose adjustments to diabetes medications might be necessary.

ASPIRIN Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, Indian gooseberry may increase the risk of bleeding if used with aspirin; however, research is conflicting.  Details Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with ecosprin 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus ecosprin 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with ecosprin 75 mg alone (92514).

CLOPIDOGREL (Plavix) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, Indian gooseberry may increase the risk of bleeding if used with clopidogrel; however, research is conflicting.  Details Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with clopidogrel 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus clopidogrel 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg alone (92514).

(Read more about INDIAN GOOSEBERRY)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, combining maitake mushroom with antidiabetes drugs might increase the risk of hypoglycemia.  Details Clinical research shows that taking maitake mushroom polysaccharide (MMP) can lower blood glucose levels in patients with types 2 diabetes (8188).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining maitake mushroom with antihypertensive drugs might increase the risk of hypotension.  Details Animal research shows that maitake mushroom can lower blood pressure (1213,1214,61226).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D There is limited evidence that maitake mushroom may increase the anticoagulant effects of warfarin.  Details In a case report, a patient previously stabilized on warfarin developed an elevated international normalized ratio (INR) of 5.1 after taking maitake mushroom (Grifron-Pro Maitake D-Fraction) 1 drop/kg daily in three divided doses for one week. The elevated INR resolved after holding warfarin for two days, then reducing the dose by 11%. It is thought that the beta-glucan constituent of maitake mushroom might cause warfarin dissociation from proteins, resulting in increased free warfarin levels and increased warfarin effects (17209).

(Read more about MAITAKE MUSHROOM)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, high doses of reishi mushroom might increase the risk of bleeding.  Details A dose of 1.5 grams daily of reishi mushroom does not seem to decrease platelet aggregation, but a higher dose of 3 grams daily does (5476,13235).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, reishi mushroom might have additive effects with antidiabetes drugs.  Details Animal research suggests that reishi mushroom decreases blood sugar (70769). However, in patients with type 2 diabetes, taking reishi mushroom does not reduce fasting glucose levels, and its effects on glycated hemoglobin are inconsistent (70801,91435).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of reishi mushroom with antihypertensive drugs might increase the risk of hypotension.  Details Reishi mushroom has shown hypotensive activity in animal research (5488,70784). Clinical evidence suggests that reishi mushroom reduces blood pressure in some, but not all, patients with hypertension (70786,70802).

(Read more about REISHI MUSHROOM)

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)

ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might decrease the clinical effects of anticholinergic drugs.  Details In vitro evidence suggests that common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) can inhibit acetylcholinesterase and might increase acetylcholine levels (31438,39566,72603,72616).

ANTICONVULSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might interfere with the clinical effects of anticonvulsant drugs.  Details Some species of sage can cause convulsions when consumed in large quantities (10812).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking sage with antidiabetes drugs might increase the risk of hypoglycemia.  Details In patients with polycystic ovary syndrome (PCOS) or inadequately controlled type 2 diabetes, common sage (Salvia officinalis) has demonstrated hypoglycemic activity (91971,103380). However, other clinical research in patients with inadequately controlled type 2 diabetes shows that common sage extract does not lower fasting blood glucose levels (105340).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase or decrease the effects of antihypertensive drugs.  Details Animal research suggests that common sage (Salvia officinalis) can cause prolonged blood pressure reduction (4152). However, clinical research suggests that Spanish sage (Salvia lavandulaefolia) can increase blood pressure in some people with hypertension (10334). Until more is known, use with caution.

BENZODIAZEPINES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking sage might increase the sedative and adverse effects of benzodiazepines.  Details In vitro evidence suggests that certain components of common sage (Salvia officinalis) can bind to benzodiazepine receptors (72588). This effect has not been reported in humans.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might have additive effects when used with cholinergic drugs.  Details In vitro evidence suggests that common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) can inhibit acetylcholinesterase and might increase acetylcholine levels (31438,39566,72603,72616).

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.  Details Some constituents of sage have CNS depressant activity (10334).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C19.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C19 (10848). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C9.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C9 (10848). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2D6.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2D6 (10848,19430). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might decrease the levels and clinical effects of drugs metabolized by CYP2E1.  Details Animal research suggests that drinking common sage (Salvia officinalis) tea increases the expression of CYP2E1 (72627). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP3A4.  Details In vitro evidence suggests that aqueous extracts of sage can inhibit CYP3A4 (10848,72641). So far, this interaction has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might interfere with hormone therapy.  Details In vitro evidence suggests that geraniol, a constituent of Spanish sage (Salvia lavandulaefolia), exerts estrogenic activity (39572). The clinical significance of this effect is unclear.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sage might increase levels of drugs transported by P-glycoprotein.  Details In vitro research suggests that common sage (Salvia officinalis) can inhibit the multi-drug transporter protein, P-glycoprotein (72641). This effect has not been reported in humans.

(Read more about SAGE)

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, shiitake mushroom might increase levels of drugs metabolized by CYP2D6.  Details In vitro studies suggest that the shiitake mushroom extract AHCC might induce the CYP2D6 enzyme (30369,30420). This effect has not been reported in humans.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking shiitake mushroom might decrease the effects of immunosuppressive therapy.  Details In vitro evidence suggests that shiitake mushroom extracts stimulate immune function (30351,30358,30360,30361,30366,30367,30368,30371,30376,30379,30381,30382,30416,30418) (74769,74783,74876,94245).

(Read more about SHIITAKE MUSHROOM)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking turkey tail mushroom with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research suggests that turkey tail mushroom and a polysaccharide component can have hypoglycemic effects (108307,111907).

CYCLOPHOSPHAMIDE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, the polysaccharide peptide (PSP) component of turkey tail mushroom might increase exposure to cyclophosphamide.  Details Some animal research shows that the PSP component of turkey tail mushroom can increase the area under the concentration-time curve (AUC) of cyclophosphamide by 44% to 50% and the half-life by 34% to 43% (96569). This interaction could potentially increase the effects and adverse effects of cyclophosphamide. However, it is not known whether PSP affects the levels of the active metabolites of cyclophosphamide that are responsible for its clinical activity.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, the polysaccharide peptide (PSP) component of turkey tail mushroom might inhibit CYP2C9.  Details Laboratory research suggests that the PSP component of turkey tail mushroom dose-dependently inhibits CYP2C9 (94075). Theoretically, taking PSP with drugs metabolized by CYP2C9 might increase drug levels and the risk of adverse effects. However, this has not been reported in humans.

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, the polysaccharide peptide (PSP) component of turkey tail mushroom might interfere with the absorption of tamoxifen.  Details Animal research suggests that PSP increases the time to reach maximum concentration of a single dose of tamoxifen by about 9.5 hours, or 228%. When repeated doses of tamoxifen were given, the time to reach maximum concentration was increased by about 5.6 hours, or 93%. However, PSP did not affect the maximum concentration or the area under the curve of tamoxifen (108308).

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ANTIPSYCHOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, vitex agnus-castus could interfere with the activity of antipsychotic drugs.  Details Vitex agnus-castus might interfere with the action of dopamine antagonists such as antipsychotic drugs due to its dopamine agonist effects (7014,7015).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, vitex agnus-castus could interfere with oral contraceptives.  Details Vitex agnus-castus might interfere with the efficacy of oral contraceptives due to possible hormone modulating activity (10979,11456).

DOPAMINE AGONISTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, vitex agnus-castus could interfere with dopamine agonists.  Details Vitex agnus-castus might potentiate the actions of dopaminergic agonists due to possible dopaminergic effects (10122).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, vitex agnus-castus could interfere with the activity of estrogens.  Details Vitex agnus-castus has hormone modulating activity that can interfere with the efficacy of hormone replacement therapy (10979,11456).

METOCLOPRAMIDE (Reglan) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dopaminergic effects of vitex agnus-castus could interfere with metoclopramide.  Details Vitex agnus-castus might interfere with the action of dopamine antagonists such as metoclopramide due to its possible dopaminergic effects (7014,7015).

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General ...Orally, Bacillus coagulans is well tolerated.
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).

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General ...Orally, Indian gooseberry seems to be well tolerated.

Dermatologic ...Orally, itching has been reported by one individual in a clinical trial (105354).

Gastrointestinal ...Orally, epigastric discomfort or dyspepsia have been reported by up to four individuals in clinical trials (105354,105356).

Hepatic ...In clinical research, increased serum glutamic pyruvic transaminase (SGPT) levels, with otherwise normal liver function, occurred in patients taking Ayurvedic formulations containing ginger, Tinospora cordifolia, and Indian gooseberry, with or without Boswellia serrata. The SGPT levels normalized after discontinuing the treatments (89557). It is unclear if these hepatic effects were due to Indian gooseberry or other ingredients contained in the formulations.

Musculoskeletal ...Orally, musculoskeletal pain has been reported by three individuals in a clinical trial (105354).

Neurologic/CNS ...Orally, fatigue has been reported by one individual in a clinical trial (105354).

Pulmonary/Respiratory ...Orally, breathlessness has been reported by one individual in a clinical trial (105354).

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General ...Orally, maitake mushroom is generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal effects, including diarrhea and epigastric pain.

Dermatologic ...In a clinical trial, one patient experienced rash and pruritus after two doses of maitake mushroom polysaccharide extract. The allergic reaction cleared without intervention (61239).

Gastrointestinal ...In clinical research of a polysaccharide extract from maitake mushroom, one patient reported nausea (61239) and 2 out of 26 reported epigastric pain (17131). In a clinical trial of a liquid extract from maitake mushroom, 2 out of 21 patients experienced diarrhea, and one experienced nausea. One patient withdrew from the study due to diarrhea (92843).

Immunologic ...In a clinical trial of a liquid extract from maitake mushroom, 4 out of 21 patients experienced eosinophilia (92843).

Musculoskeletal ...In a clinical trial of a polysaccharide extract from maitake mushroom, one patient reported joint swelling (61239).

Pulmonary/Respiratory ...There is one case of occupational hypersensitivity pneumonitis (HP) caused by maitake mushroom spores (61228).

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General ...Orally, reishi mushroom is generally well tolerated.
Most Common Adverse Effects:
Orally: Dizziness, dry mouth, itching, nausea, rash, and stomach upset.

Dermatologic ...Orally, reishi mushroom can cause itching, rash, and other skin reactions (12,5479).

Gastrointestinal ...Orally, reishi mushroom can cause dryness of the mouth, throat, or nasal cavity, nausea, stomach upset, and, more rarely, diarrhea (12,70779,91438,108309).

Hematologic ...Orally, reishi mushroom can cause nosebleed and bloody stools (12,91438).

Hepatic ...One case of hepatotoxicity and one case of fatal fulminant hepatitis have been reported in patients who had used reishi mushroom powder for 1-2 months (70766). There is a case report of a 61-year-old male with hypereosinophilia associated with hepatic nodules following the use of reishi mushroom powder for about 2 months. Symptoms resolved after discontinuation of the product. Although these side effects were thought to be associated with the use of reishi mushroom powder, it is unclear if other factors played a role. The patient had been taking tegafur, gimeracil, and oteracil potassium for about 4 months following anterior resection for rectal adenocarcinoma but discontinued these agents and initiated reishi mushroom due to liver injury (108312).

Neurologic/CNS ...Orally, reishi mushroom can cause dizziness (91438). Other rare symptoms include insomnia and headache (70776,70779).

Pulmonary/Respiratory ...Respiratory allergy to reishi spores can occur (12,5479). Sore throat and runny nose have also been reported (70776,91438).

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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.

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General ...Orally, topically, and when inhaled, sage seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, agitation, diarrhea, dizziness, nausea, and vomiting.
Topically: Burning, dermatitis, pain.
Serious Adverse Effects (Rare):
Orally: Generalized tonic-clonic seizures associated with the thujone, camphor, and/or cineol constituents.

Cardiovascular ...By inhalation, sage essential oil has been reported to increase the blood pressure of hypertensive patients (10334).

Dermatologic ...Orally, sage extract has been reported to cause acneiform skin eruptions in one patient in a clinical trial (91970).
Topically, sage leaves can cause contact dermatitis (46902,72661,72710). Sage extract can cause burning and pain (10437).

Gastrointestinal ...Orally, sage can cause nausea, vomiting, abdominal pain, and diarrhea (10810,17177).
Topically, sage extract sprayed into the mouth and throat can cause dryness or mild burning of the throat (72619).

Neurologic/CNS ...Orally, sage can cause dizziness or agitation (10810,17177). Thujone, a constituent of common sage (Salvia officinalis), is a neurotoxin and can cause seizures (10812,12868). Camphor and cineol, constituents of common sage and Spanish sage, can also cause neurotoxicity and seizures in high doses (10334,12868). Generalized tonic-clonic seizures have been reported in adults, children, and infants after ingestion of sage oil (12868,72666).

Pulmonary/Respiratory ...Orally, sage can cause wheezing (10810,17177).
Occupational exposure to sage dust can cause reduction in ventilatory capacity and chronic respiratory impairment (72672,72682,72686).

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General ...Orally, shiitake mushroom is generally well tolerated when cooked and consumed as a food.
Most Common Adverse Effects:
Orally: Abdominal discomfort, bloating, diarrhea, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Consumption of raw shiitake mushroom can cause shiitake dermatitis, a skin eruption resembling whiplash marks which can be accompanied by systemic symptoms. Large pieces that have been inadequately chewed can cause intestinal blockage, occasionally requiring surgery.

Dermatologic ...Orally, shiitake mushrooms can cause shiitake dermatitis, a skin eruption that resembles whiplash marks, usually found on the trunk and limbs. This dermatitis is thought to be a toxic response to lentinan or other compounds found normally in uncooked or inadequately cooked shiitake mushroom. The rash can be made worse by scratching. Symptom onset is usually within hours to days and can persist for 3-4 weeks before resolving on its own. There is some evidence that treatment with steroids alone or with antihistamines might reduce the duration of the rash by a small amount in some people (1148,1152,74782,74806,94236,94237,94238,94240,94241,94243) (94244,94246,94247,94248,94249,94252,94253,94254,94255,94256)(94257,94259,94261,94262,108302,111909,111912,111913). The dermatitis may include small purple spots from broken capillaries, skin plaques, burning, blanching, and pustules (94256,108302). Rarely the rash may look like measles rather than whiplash (94256). Histologically, there may be evidence of dermal and epidermal edema, lymphocyte infiltration, and skin thickening (94256,94257). Other symptoms associated with the dermatitis include fever, aching, malaise, eosinophilia, diarrhea, prickling in the hands, trouble swallowing, conjunctivitis, and pustules with small ulcers in the mouth (94240,94246,94247,94249,94256,94257,108302). It is likely that the dermatitis and other symptoms are due to a delayed type hypersensitivity reaction (94244,94255). Cooking shiitake mushroom generally prevents shiitake dermatitis, although some cases have occurred in people who have consumed cooked sources (94242,94244). It appears that to inactivate lentinan, cooking temperatures of at least 130°C are needed (94243).
Less common is a photosensitivity reaction associated with oral ingestion, which involves rash and pruritus after sun exposure (1148,94241).
Orally, the shiitake mushroom extract AHCC has been reported to cause mild itching (30375).

Gastrointestinal ...Orally, shiitake mushrooms can cause abdominal discomfort, including bloating, nausea, pain, vomiting, and diarrhea (1149,30365,30375,30419,94241). Gastrointestinal symptoms, such as diarrhea, problems swallowing, or mouth ulcers have been associated with shiitake dermatitis (94241,94256). Consumption of large pieces of shiitake mushroom with inadequate chewing can cause abdominal obstruction that has resulted in death in one case and surgical intervention in two others. In another case, parenteral nutrition was used exclusively until the shiitake mushroom pieces were passed (1147,94260,103160,108303,108304).
Topically, an oral rinse containing shiitake mushroom extract has been associated with teeth sensitivity, teeth staining, and burning in the mouth (94250).

Hematologic ...Ingestion of shiitake mushroom powder 4 grams daily for 10 weeks caused eosinophilia in 5 of 10 healthy humans (1149). Eosinophilia, and leukocytosis or leukopenia have been reported with shiitake dermatitis (94254,94256,94257).

Immunologic ...Allergic contact dermatitis can occur by contact with shiitake hyphae (filaments) (1153,74785,111913). It appears to be more common in growers or others that handle shiitake mushrooms extensively (94241,94259). Contact or inhalation also results in other symptoms of allergy, such as asthma, rhinitis, conjunctivitis, and pneumonia (94241,94249,94258,94259).

Musculoskeletal ...Orally, the shiitake mushroom extract AHCC has been reported to cause foot cramps and difficulty moving hand joints (30365,30416).

Neurologic/CNS ...In patients experiencing shiitake dermatitis, other symptoms may include prickling in the hands (94256). Malaise has also been reported following oral intake or contact (1151,94240).
Orally, the shiitake mushroom extract AHCC has been reported to cause mild and transient headache (30365).

Ocular/Otic ...Conjunctivitis has been reported rarely in mushroom growers and handlers, or following oral intake in patients with shiitake dermatitis (94241,94256,94259).

Pulmonary/Respiratory ...In mushroom workers, hypersensitivity pneumonitis due to shiitake spore inhalation has occurred. Symptoms include difficulty breathing, chest pain, a dry cough, asthma, and rhinitis (1150,1151,74776,74813,94239,94241,94258,94259).

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General ...Orally, turkey tail mushroom and its PSK component are generally well tolerated. There have been reports of gastrointestinal side effects, hematological abnormalities, liver dysfunction, and palpitations, but these are in patients who received PSK in addition to standard chemotherapy. It is not known if these are due to PSK, the chemotherapy, or both.

Cardiovascular ...Palpitations have occurred when PSK is taken with standard chemotherapy for cancer (1657). It is not clear if this is due to PSK, the chemotherapy, or both.

Dermatologic ...Pigmentation of the nails and erythema have occurred when PSK is taken with standard chemotherapy (1657,1660,70175,94076). It is not clear if this is due to PSK, the chemotherapy, or both.
Intravaginally, a specific gel (Papilocare, Procare Health) containing turkey tail mushroom with neem, carboxymethyl-beta-glucan, hyaluronic acid, gotu kola, aloe, and alpha-glucan oligosaccharide has been reported to cause vulvovaginal stinging, burning, itching, and candidiasis (108305,111904). The specific role of turkey tail mushroom is unclear.

Gastrointestinal ...Nausea, vomiting, appetite loss, stomach discomfort, diarrhea, constipation, and gastric ulcer have occurred when PSK is taken with standard chemotherapy for cancer (1651,1657,70175,70201,94076). However, one study reported a decreased incidence of gastrointestinal side effects when PSK was taken with chemotherapy (70188,70197).

Hematologic ...Leukopenia, thrombocytopenia, and albuminuria have occurred when PSK is taken with standard chemotherapy (1651,1657,70175,70201,94076). It is not clear if this is due to PSK, the chemotherapy, or both.

Hepatic ...Elevated liver enzymes, liver function impairment, and hepatotoxicity have occurred when PSK is taken with standard chemotherapy (1651,1657,70175,70201,94076). It is not clear if this is due to PSK, the chemotherapy, or both.

Musculoskeletal ...Malaise and fatigue have occurred when PSK is taken with standard chemotherapy (1657,1660,70175,94076). It is not clear if this is due to PSK, the chemotherapy, or both.

Pulmonary/Respiratory ...Coughing has occurred when PSK is taken with standard chemotherapy (1657,1660,70175,94076). It is not clear if this is due to PSK, the chemotherapy, or both.

(Read more about TURKEY TAIL MUSHROOM)

General ...Orally, vitex agnus-castus is generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, fatigue, headache, insomnia, irregular menstruation, nausea, skin irritation, stomach pain, vomiting.

Dermatologic ...Orally, skin conditions such as itching, irritation, urticaria, rash, acne, eczema, and hair loss have been reported (7055,7076,7078,7079,12207,13393,15065,90617,90619,101981).

Gastrointestinal ...Orally, gastrointestinal upset or pain, diarrhea, and nausea and vomiting, have been reported (7079,12207,13393,15065,90620,101981,101982). In one clinical trial, a single patient reported persistent gastroenteritis while taking vitex agnus-castus (7076). Orally, development of a bezoar resulting in colonic obstruction is described in a 63-year-old male who consumed an unknown amount of vitex agnus-castus seeds (111752).

Genitourinary ...Orally, irregular or prolonged menstrual bleeding has been reported (7055,7079,12207,13393,15065,41489,41490,95326).

Hematologic ...Orally, nosebleed has been reported in a single patient in a clinical trial (7079).

Immunologic ...Orally, multiple abscesses have been reported in a single patient (7055).

Neurologic/CNS ...Orally, headache, fatigue, and insomnia (7076,7078,12207,13393,13395,15065), confusion (90617), and vertigo (7079) have been reported.

Other ...Orally, weight gain has been reported (12207,13393,15065).

(Read more about VITEX AGNUS-CASTUS)