Detox Pro Lemon and Lime Flavour by Orthoplex

Colorectal cancer. Consumption of cruciferous vegetables, including broccoli, seems to reduce the risk of developing colorectal cancer. Details: Epidemiological research suggests that the highest intakes of cruciferous vegetables, including broccoli, are associated with an 18% to 20% reduced risk of developing colorectal neoplasms when compared with the lowest intakes (14148,96187,96189).

Bladder cancer. It is unclear if consumption of broccoli reduces the risk of developing bladder cancer. Details: Epidemiological research suggests that eating about 1.75 cups daily of cruciferous vegetables, such as broccoli or cabbage, is associated with a 30% reduced risk of developing bladder cancer (14864).
Breast cancer. It is unclear if consumption of broccoli reduces the risk of developing breast cancer. Details: Epidemiological research suggests that consumption of broccoli is associated with a modestly reduced risk of developing breast cancer in premenopausal adults. However, broccoli consumption does not seem to be associated with breast cancer risk in postmenopausal adults (14146).
Fibromyalgia. Broccoli has only been evaluated in combination with ascorbigen; its effect when used alone is unclear. Details: A small clinical study in females with fibromyalgia shows that taking one capsule containing ascorbigen 100 mg and broccoli powder 400 mg once daily for one month improves pain by 18% and reduces physical impairment by 20% when compared to baseline (19605). It is unclear if this effect is due to broccoli, ascorbigen, or the combination. The validity of these findings is limited by the lack of a comparator group.
Gastric cancer. It is unclear if consumption of broccoli reduces the risk of developing gastric cancer. Details: A small epidemiological study suggests that higher consumption of broccoli is associated with a reduced risk of developing gastric cancer when compared with lower consumption (14148).
Helicobacter pylori. It is unclear if consumption of broccoli is beneficial for treating Helicobacter pylori infection. Details: A moderate-sized clinical study in adults with Helicobacter pylori infection shows that taking broccoli seed extract 200 mg, containing 16% glucosinolates, daily before bedtime for 2 months does not improve Helicobacter pylori eradication rate when compared with placebo (112445,112446).
Hypercholesterolemia. Broccoli has only been evaluated in combination with cabbage; its effect when used alone is unclear. Details: A small clinical study in patients with mild to moderate hypercholesterolemia shows that consuming 160 grams of a beverage containing broccoli, cabbage, and fruit twice daily for 12 weeks reduces levels of low-density lipoprotein (LDL) cholesterol by 8.5% when compared to baseline. It is unclear if the improvement from baseline differed when compared with those consuming a similar beverage without broccoli and cabbage (19607). It is unclear if this effect is due to broccoli, other ingredients, or the combination.
Hypertension. It is unclear if consumption of broccoli can prevent hypertension in healthy adults. Details: A meta-analysis of 3 prospective cohort studies in healthy adults suggests that eating 100 grams of broccoli daily is associated with a 12% reduced risk of hypertension. However, 2 other studies in the meta-analysis suggest that broccoli, consumed as part of a larger group of cruciferous vegetables, is associated with an 11% increased risk of hypertension per 100 grams eaten daily (112087).
Prostate cancer. It is unclear if consumption of broccoli reduces the risk of developing prostate cancer; the available research is conflicting. In patients with prostate cancer, broccoli has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some epidemiological research suggests that consumption of Brassica vegetables, such as broccoli, Brussels sprouts, cauliflower, and cabbage, is associated with a reduced risk of developing prostate cancer (14145). However, other epidemiological research has found no association (14147,15172). Clinical research in adults with prostate cancer shows that taking a whole food formulation containing broccoli powder 100 mg, turmeric powder 100 mg, pomegranate whole fruit powder 100 mg, and green tea extract 20 mg three times daily for 6 months prevents an increase in prostate specific antigen (PSA) levels. Mean PSA levels increased by 15% in the whole food formulation group, compared with 79% in the placebo group. Also, 46% of those taking the whole food formulation showed final PSA levels that were the same or lower than initial PSA levels, compared with 14% of those in the placebo group (89730). However, it is not yet known whether the whole food formulation reduces the risk of prostate cancer progression or recurrence. It is unclear if these effects are due to broccoli, other ingredients, or the combination. More evidence is needed to rate broccoli for these uses.

Athletic performance. Taking oral choline before exercise does not improve athletic performance. Details: Clinical research in trained athletes shows that taking oral choline 2.43 grams as a single dose does not delay fatigue during endurance sports when compared with placebo (5164). Other clinical research in untrained adults shows that taking oral choline 8.425 grams or 50 mg/kg once prior to participating in exhaustive, load-carrying exercise does not improve dexterity, upper or lower body strength, grip strength, or run time-to-exhaustion following exercise when compared with placebo (42229,42237).

Age-related cognitive decline. It is unclear if oral choline is beneficial in patients with age-related cognitive decline. Details: Small clinical studies in adults with memory loss shows that taking choline 2 grams four times daily orally for 21 days does not improve memory when compared with placebo (5170). Observational research in adults over 60 years of age has found that intake of choline 187-399.5 mg daily is associated with a 33% to 42% reduced odds of low cognitive function when compared with intake of less than 187 mg daily. Intake of more than 399.5 mg daily was not associated with low cognitive function when compared with less than 187 mg daily (109100).
Allergic rhinitis (hay fever). It is unclear if oral choline is beneficial in patients with allergic rhinitis. Details: Preliminary clinical research shows that taking oral choline, as tricholine citrate, 500 mg three times daily for 8 weeks is less effective than intranasal budesonide 200 mcg twice daily for reducing symptoms of allergic rhinitis (42252).
Alzheimer disease. Although there has been interest in using oral choline for Alzheimer disease, there is insufficient reliable information about the clinical effects of choline for this purpose.
Asthma. Small clinical studies suggest that oral choline may modestly improve symptoms in patients with asthma. Details: Preliminary clinical research shows that taking choline 500-1000 mg orally three times daily for 3-4 months decreases the severity of symptoms, the number of symptomatic days, and the need to use bronchodilators in patients with asthma when compared with placebo (5165,5166). Preliminary data also shows that choline 3 grams daily might be more effective than 1.5 grams daily (5165).
Autism spectrum disorder. Oral choline has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a combination of donepezil 2.5-5 mg daily and choline bitartrate 350 mg daily for 12 weeks improves receptive language skills, but no other outcomes, for up to 6 months after treatment when compared with placebo in children aged 5-10 years with autism spectrum disorder. Also, adolescents aged 11-16 years experienced no benefits, and some experienced an increase in behavioral symptoms, such as irritability (103571). It is unclear if this effect is due to choline, donepezil, or the combination.
Breast Cancer. It is unclear if dietary intake of choline reduces the risk of breast cancer. Details: A meta-analysis of 6 low to moderate-quality observational studies suggests that neither high nor low dietary intake of choline is associated with breast cancer risk. This finding is largely influenced by inclusion of the European Prospective Investigation into Cancer and nutrition (EPIC) cohort study, which analyzed data from over 300,000 subjects. However, subanalysis of 3 case-control studies suggests that high dietary intake of choline may be associated with a decreased risk of breast cancer when compared with low choline intake (111416). The interpretation of these findings is limited by the heterogeneity of the included studies, self-reported data, and a small number of studies.
Bronchitis. Although there has been interest in using oral and inhaled choline for bronchitis, there is insufficient reliable information about the clinical effects of choline for this purpose.
Cancer. It is unclear if dietary choline intake reduces the risk for cancer. Details: A meta-analysis of 11 low-quality population studies has found that high dietary intake of choline is associated with an 18% lower risk of cancer when compared with low choline intake. High dietary intake of both choline and betaine was associated with a 40% lower risk of cancer (97390).
Cardiovascular disease (CVD). It is unclear if dietary choline intake reduces the risk of CVD or improves outcomes in patients with CVD. Details: A meta-analysis of population research has found that high intake of dietary choline is not associated with a lower risk of coronary artery disease, stroke, or mortality when compared with a diet low in choline (97388). A more recent population study has found that energy-adjusted total choline intake is not associated with the incidence of CVD over ten years. However, the highest intake of free choline is associated with a 34% reduced risk of CVD when compared with the lowest intake (109104).
Cerebellar ataxia. It is unclear if oral choline is beneficial in patients with cerebellar ataxia. Details: Despite some anecdotal reports suggesting that taking choline improves motor function, preliminary clinical research shows that taking choline 4-5 grams orally daily for 4 days to 6 weeks does not reduce cerebellar ataxia (5161,5173,23679).
Cognitive function. It is unclear if oral choline is beneficial for improving cognitive function in healthy adults. Details: Preliminary clinical research shows that taking a single dose of choline 50 mg/kg orally prior to participating in an exhaustive, load-carrying task does not improve reaction time, reasoning, memory, or serial addition and subtraction ability following the task when compared with placebo (42237). Also, preliminary clinical research in patients requiring long-term total parenteral nutrition (TPN) shows that adding choline chloride 2 grams daily to TPN for 24 weeks might improve delayed visual memory, but does not improve other measures of cognitive performance, when compared with TPN alone (42232).
Cirrhosis. Although there has been interest in using oral choline for cirrhosis, there is insufficient reliable information about the clinical effects of choline for this purpose.
Complex partial seizures. Although there has been interest in using oral choline for complex partial seizures, there is insufficient reliable information about the clinical effects of choline for this purpose.
Dementia. Although there has been interest in using oral choline for dementia, there is insufficient reliable information about the clinical effects of choline for this purpose.
Depression. It is unclear if oral choline is beneficial for the treatment or prevention of depression. Details: Observational research has found that dietary choline intake of at least 198 mg daily is associated with a 32% to 43% decreased risk of depressive symptoms when compared with intakes of less than 198 mg daily (109106). It is unclear if choline supplementation is beneficial for depression.
Diabetes. It is unclear if oral choline is beneficial for the treatment or prevention of type 2 diabetes; the available research is conflicting. Details: Preliminary clinical research shows that taking oral choline bitartrate 1000 mg daily for 2 months does not affect coagulation parameters or levels of triglycerides, low-density lipoprotein (LDL) cholesterol, or high-density lipoprotein (HDL) cholesterol in patients with type 2 diabetes (103569). Choline has also been evaluated for the prevention of type 2 diabetes. In Finnish males, observational research has found that dietary intake of total choline at levels of more than 482 mg daily, especially as phosphatidylcholine, is associated with a 25% lower risk of developing type 2 diabetes over the following 19.3 years when compared with intakes of less than 382 mg daily (103567). However, in males and females in the US, additional observational research has found no association between dietary choline and risk of type 2 diabetes over a mean of 9 years (103570). In addition, a sub-analysis found that the highest intakes of choline (a median of 487 mg daily) were associated with a 54% higher risk of type 2 diabetes among females, but not males, when compared with the lowest intakes (a median of 175 mg daily) (103570). Population research in patients with diabetes has found that an intake of dietary choline in amounts of at least 279 mg daily is associated with a 2.1-fold increased odds of diabetic retinopathy in females, but not males, when compared with an intake less than 206 mg daily (109102). It is unclear if choline itself is responsible for the increased odds of diabetic retinopathy in this population.
Fetal alcohol spectrum disorders (FASD). It is unclear if oral choline improves cognition in children with fetal alcohol spectrum disorders (FASD). Details: Clinical research in children aged 2.5-5 years with FASD shows that taking oral choline bitartrate, providing choline 500 mg, daily for 9 months does not improve global cognitive development or hippocampal-dependent memory when compared with placebo. However, a subgroup analysis of only children aged 2.5-4 years suggests that choline may improve hippocampal-dependent memory (92112). Follow-up of this study at 7 years shows that choline improves motor speed and suggests a trend towards improved color naming, which are components of executive functioning testing, when compared with placebo (111745). The validity of these findings is limited by the high rate of patient discontinuation which limits statistical power. A small clinical trial in children 5-10 years old with FASD shows that taking oral glycerophosphocholine, providing choline 625 mg, daily for 6 weeks does not improve cognitive function, executive function, attention, or hyperactivity when compared with placebo (97389).
Hepatitis. Although there has been interest in using oral choline for hepatitis, there is insufficient reliable information about the clinical effects of choline for this purpose.
Huntington disease. Although there has been interest in using oral choline for Huntington disease, there is insufficient reliable information about the clinical effects of choline for this purpose.
Hypertension. It is unclear if oral choline is beneficial for the prevention or treatment of hypertension. Details: Population research has found that every 100-mg increase in daily dietary choline intake is associated with a 15% decreased risk of developing hypertension over the next 4.6 to 9.1 years (109098). However, it is unclear if any benefits are specifically related to dietary choline or whether choline supplementation is beneficial.
Infant development. It is unclear if oral choline intake during pregnancy is beneficial for infant development; the available research is conflicting. Details: Two observational studies have found that higher intake of choline during the second and third trimesters of pregnancy is associated with improvement in offspring cognitive development and visual memory at the age of 18 months and 7 years, respectively, when compared with lower choline intake (94654,94657). One of these studies found that each 1 mcmol/L increase in maternal blood levels of choline at 16 weeks' gestation was associated with a 2.23-point increase in cognitive skill score based on the Bayley Scales of Infant Development (BSID-III) at 18 months of age (94657). Also, some observational research has found that higher plasma levels of choline during pregnancy are associated with higher processing speed and decreased social withdrawal at 4 years of age in the offspring (109101). In contrast, 3 observational studies have found that higher intake of choline during pregnancy, as well as higher maternal and cord blood levels of choline, are not associated with improved offspring intelligence at 5 years of age or cognitive performance at 3 or 7 years of age (94654,94655,94656). However, many of these observational studies, including those with positive findings, included populations with a mean intake of choline that was below the recommended adequate intake of 450 mg daily (94654,94656). It's possible that higher intake of choline is needed to observe a benefit; however, research on the effects of choline supplementation is limited. One small clinical trial shows that taking choline 930 mg daily during the third trimester modestly improves sustained attention in the child at 7 years of age when compared with taking 480 mg daily (109105).
Metabolic syndrome. It is unclear if oral choline is beneficial in patients with metabolic syndrome. Details: Preliminary clinical research in adults with metabolic syndrome shows that taking oral choline 400 mg daily for 4 weeks does not decrease body weight, blood pressure, plasma glucose levels, or low-density lipoprotein (LDL) cholesterol levels, or increase high-density lipoprotein (HDL) cholesterol levels, when compared with baseline (105731).
Neural tube birth defects. It is unclear if oral choline intake is beneficial for preventing neural tube defects. Details: Population research has found that females who have a high dietary choline intake around the time of conception have a lower risk of having offspring with a neural tube defect when compared to those with lower intake (13134).
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral choline is beneficial in patients with nonalcoholic fatty liver disease (NAFLD). Details: A cross-sectional analysis of results from observational and clinical research shows that low dietary intake of choline is associated with increased fibrosis in postmenopausal adults with NAFLD, but not in children, males, or premenopausal adults with NAFLD. Dietary choline intake was not associated with steatosis severity in any patient subgroup (92109).
Schizophrenia. Although there has been interest in using oral choline for schizophrenia, there is insufficient reliable information about the clinical effects of choline for this purpose.
Tourette syndrome. Although there has been interest in using oral choline for Tourette syndrome, there is insufficient reliable information about the clinical effects of choline for this purpose.
TPN-associated hepatic steatosis. It is unclear if intravenous choline is beneficial in patients with TPN-associated hepatic steatosis. Details: In patients receiving long-term total parenteral nutrition (TPN), plasma levels of choline can decrease. Small, low-quality clinical studies show that administering intravenous choline 1-4 grams daily for 24 weeks improves some markers of TPN-associated hepatic steatosis when compared with baseline or placebo (5174,42235). More evidence is needed to rate choline for these uses.

GLUTAMINE

EFFECTIVE

Sickle cell disease. A specific oral glutamine powder (Endari, Emmaus Medical, Inc) is approved by the US Food and Drug Administration (FDA) to reduce acute complications of sickle cell disease. Details: Clinical research in adults and children 5 years of age and older shows that taking glutamine 5-15 grams (0.3 grams/kg body weight) orally twice daily for 48 weeks, either with or without hydroxyurea, delays the median time to first crisis by 30 days, and reduces the incidence of acute chest syndrome by 15%, number of hospitalizations by 33%, and the number of hospitalized days by 40%, when compared with placebo (96519,99414).

Burns. Oral glutamine seems to improve healing in patients with severe burns and may also reduce the risk for burn wound infections; however, it is unclear if glutamine improves hospitalization length or mortality. Details: Some clinical research shows that administering enteral nutrition supplemented with glutamine 0.35-0.5 grams/kg daily for 12-14 days, beginning within 24-48 hours of hospitalization for severe burn injury (excluding inhalation injury), decreases the length of hospital stay by 6-9 days and may shorten wound healing when compared to control enteral nutrition (52307,52337). A clinical study in adults with moderate to severe burns (including inhalation injury) shows that administering enteral nutrition supplemented with intravenous alanyl glutamine 0.5 grams/kg daily, beginning within 24 hours of burn injury and continued for 14 days, may improve burn-induced organ damage, particularly intestinal mucosal injury, but does not improve mortality or length of hospitalization, when compared with standard nutritional support (108027). Another study in the same population shows that administering enteral nutrition supplemented with glutamine 4.3 grams every 4 hours, beginning within 24 hours of burn injury, decreases the risk of mortality by 83% and the risk of Pseudomonas wound infections; however, it does not decrease the duration of hospitalization (52311). A meta-analysis of these trials and one additional trial shows that administering glutamine enterally reduces the risk of Gram-negative bacterial wound infections by 73% and reduces the risk of mortality by 87% when compared to a control group. However, there was no difference in length of stay or overall wound infection rate (97363). Results were based on a small number of patients within each outcome evaluation. Intravenous glutamine has also been evaluated. One small clinical study shows that intravenous glutamine 0.57 grams/kg daily decreases the incidence of Gram-negative bacteremia by 35% when compared with control in patients with severe burns. However, it does not appear to decrease the incidence of Gram-positive bacteremia, the need to use antibiotics, or risk of mortality (52272).
Critical illness (trauma). Oral and intravenous glutamine seem to reduce infectious complications in critically ill adults. However, glutamine does not seem to reduce mortality in this population. Details: Some studies show that glutamine reduces the risk of infectious complications in critically ill, multiple-trauma, or postoperative adult patients (5449,5450,7309,7731,8184,52288,52359). However, other studies show no benefit (52308,52360,97362). Meta-analyses of these and other clinical trials suggest that glutamine supplementation reduces the risk of nosocomial infections in critically ill patients by 15% to 18% and the risk of nosocomial infections in surgical patients by 30% to 41%. This benefit was seen only with parenteral glutamine; enteral glutamine does not appear to reduce the risk for nosocomial infection (91355,91358). The role of glutamine for reducing mortality in critically ill adults is conflicting. Some clinical trials suggest that glutamine-enriched enteral and parenteral nutrition reduces mortality in critically ill patients (52283,52289,52408). However, other studies show no benefit (52288,52308,52354,52359,97362). Meta-analyses of results from these and other clinical trials show that, overall, taking glutamine does not reduce the risk of mortality in critically ill patients (91355,91358). However, the dose and dosage form may affect outcomes. One meta-analysis shows that glutamine does not affect the risk of mortality when administered at doses up to 0.5 grams/kg daily, although doses greater than 0.5 grams/kg daily may INCREASE mortality by 18% (91355). Another meta-analysis shows that glutamine decreases short-term mortality in critically ill patients by 25% when administered parenterally, but not enterally (91358). Neither parenteral nor enteral glutamine appears to decrease the risk of long-term mortality in critically ill patients (91358). Research evaluating glutamine in critically ill children is limited. One clinical study in children ages 1-17 admitted to an intensive care unit (ICU) shows that enteral administration of glutamine along with zinc, selenium, and intravenous metoclopramide does not reduce nosocomial infections when compared with whey supplementation (86095).
HIV/AIDS-related wasting. Oral glutamine seems to attenuate weight loss related to HIV/AIDS. Details: Very small clinical studies show that taking glutamine orally seems to enhance intestinal absorption of nutrients, decrease intestinal permeability, and increase weight gain in adults with HIV/AIDS when compared with placebo. Doses of 40 grams daily seem to produce the greatest effect (2337,2702). Lower doses of 14 grams daily might also be effective when used in combination with arginine and hydroxymethylbutyrate (a leucine metabolite) (7310).
Postoperative recovery. Oral or intravenous glutamine seems to reduce the duration of hospitalization and improve postoperative nutritional status in adults. However, it does not seem to reduce postoperative mortality. Details: Although some conflicting evidence exists (52316), most clinical research shows that receiving free glutamine or glutamine-containing dipeptide intravenously decreases the duration of hospitalization after surgery, particularly after major abdominal surgery (2363,5448,7300,7732,52275,52341). A meta-analysis of this research and other studies shows that IV supplementation with glutamine-containing dipeptides reduces the length of hospital stay by 3 days when compared with no supplementation (96507). Other meta-analyses of clinical research also show that glutamine supplementation, as free glutamine or glutamine-containing dipeptides, reduces the risk of hospital-acquired infections by 30% in surgical intensive care unit (ICU) patients and by 41% in elective surgical patients (91355,91358). In cancer patients undergoing abdominal surgery, glutamine-supplemented parenteral nutrition seems to improve nutritional status and gastrointestinal function (100943). Glutamine-containing dipeptides also appear to help to preserve intestinal integrity (7299,7300,7732,52306). One small study has evaluated oral glutamine 10 grams, in combination with arginine 4.5 grams, in patients undergoing surgery for enterocutaneous fistulas. This study shows that taking this combination daily for 7 days prior to surgery reduces recurrence of fistulas by 35%, and also reduces postoperative infections (103837). Although glutamine seems to decrease length of stay and reduce infection rate, it does not appear to reduce the risk of mortality in either surgical ICU or elective surgical patients (91355,91358,96509,103834), including those receiving major abdominal surgery (5448,52316,91355,96507). Additionally, most research shows that glutamine supplementation does not reduce the incidence of infectious complications following abdominal surgery (52306,52316,52341,5448,7300,96507). The effects of glutamine on reducing infection rate might be related to patient population, modes of nutrition, or dose of glutamine. Taking a combination of glutamine 7 grams, arginine 7 grams, and hydroxymethylbutyrate 1.2 grams (Abound, Abbott) orally daily for 3 days before and 7 days after abdominal surgery does not reduce the incidence of wound infections or other complications (99413). Most of the research evaluating glutamine in surgical patients has been conducted in adults. Information in children is limited. Existing clinical research shows that glutamine-fortified parenteral nutrition does not improve intestinal permeability, nitrogen balance, duration of hospitalization, incidence of infectious complications, or risk of mortality in newborns and infants undergoing digestive-tract surgery (52338,96508).

Athletic performance. Oral glutamine does not seem to improve athletic performance. Details: Small studies in trained athletes or healthy adults show that taking glutamine orally does not seem to enhance performance or immune response during intense acute or prolonged exercise when compared with placebo (2341,2342,5455,5456).
Crohn disease. Oral glutamine does not seem to improve symptoms of this condition. Details: Small clinical studies in adults and children with Crohn disease show that taking glutamine 7 grams three times daily or following a glutamine-enriched diet for 4 weeks does not seem to improve intestinal permeability or disease activity, and might even worsen disease activity, when compared with placebo or a low-glutamine diet (2338,6256).
Cystinuria. Oral glutamine does not seem to improve cystinuria. Details: According to case reports, taking glutamine orally does not seem to reduce the excretion of cysteine in the urine in patients with homozygous cystinuria (2339).
Low birth weight. Oral glutamine does not seem to reduce adverse consequences of low birth weight in infants. Details: Most clinical studies show that glutamine supplementation does not improve the time to full enteral feeding, infant growth rate, or length of hospital stay in low birth weight infants (52305,52312,52325,52342,52362,52410). One follow-up study also shows that neonatal glutamine supplementation is not associated with improvements in cognitive function, motor skills, or behavior outcomes by school age when corrected for neonatal infection rate (52342,97365).
Muscular dystrophy. Oral glutamine does not seem to improve symptoms of Duchenne muscular dystrophy. Details: Clinical studies show that taking glutamine 0.5-0.6 grams/kg orally does not significantly improve muscle strength or whole body protein degradation in children with Duchenne muscular dystrophy when compared with placebo or a nonspecific amino acid mixture (46657,52363).
Prematurity. Oral glutamine does not seem to reduce morbidity or mortality associated with prematurity. Details: A meta-analysis of clinical trials in preterm infants, including infants with low to very low birth weight, shows that use of enteral or parenteral glutamine does not reduce the risk of mortality or morbidities, such as necrotizing enterocolitis, when compared with control. However, limited evidence from a sub-group analysis suggests that enteral glutamine might modestly reduce the risk of invasive infection when compared with control (105015). These findings are limited by the selection bias and heterogeneity of the included trials.
Radiation-induced diarrhea. Oral glutamine does not seem to improve diarrhea due to radiation therapy. Details: One meta-analysis of five randomized, controlled trials shows that taking oral glutamine during radiotherapy for pelvic cancers does not prevent or reduce the severity of diarrhea when compared with placebo (97367).

Antiretroviral-associated diarrhea. It is unclear if oral glutamine improves diarrhea caused by antiretroviral agents. Details: A small crossover clinical study in HIV patients shows that oral glutamine 30 grams daily for 10 days seems to reduce the severity of nelfinavir-associated diarrhea when compared with placebo (52313).
Alcohol use disorder. Although there is interest in using oral glutamine for alcohol use disorder, there is insufficient reliable information about the clinical effects of glutamine for this condition.
Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral glutamine for ADHD, there is insufficient reliable information about the clinical effects of glutamine for this condition.
Chemotherapy-induced diarrhea. It is unclear if oral glutamine improves diarrhea caused by chemotherapy. Details: Although preliminary clinical studies show that glutamine might reduce the occurrence of chemotherapy-induced diarrhea (7235,7285), a meta-analysis of this research and others shows no difference in the severity of diarrhea (7233,7295,96516). Despite results showing a significant 1-day reduction in the duration of diarrhea, this might not be considered clinically significant (96516).
Chemotherapy-induced lymphocytopenia. It is unclear if oral glutamine reduces lymphocytopenia caused by chemotherapy. Details: One small clinical study in patients with esophageal cancer receiving chemo-radiotherapy shows that taking glutamine 30 grams daily for 28 days seems to prevent a reduction in lymphocytes when compared with placebo (2705). However, another small clinical trial in patients with leukemia or lymphoma receiving intensive chemotherapy shows that adding glutamine 26 grams to total parenteral nutrition (TPN), in place of other amino acids, does not affect duration of neutropenia when compared with receiving an isonitrogenous standard TPN (7295).
Coronavirus disease 2019 (COVID-19). It is unclear if oral glutamine is beneficial in patients hospitalized with COVID-19 pneumonia. Details: A very small, nonblinded, non-randomized evaluation of otherwise healthy patients over 50 years of age who were hospitalized with mild COVID-19 pneumonia shows that taking glutamine 10 grams three times daily orally with meals is associated with a 1-day decrease in hospital stay (from 10 days to 9) when compared with patients not taking glutamine. In the latter group, 4 patients required transfer to the ICU, compared with no patients in the glutamine group (103839). A similar, non-randomized evaluation of adults hospitalized with COVID-19 pneumonia shows that adding the same dose of glutamine to other therapies for 5 days is associated with a 3-day decrease in hospital stay (from 14 days to 11) when compared with patients not taking glutamine. At the end of treatment, 0% of patients in the glutamine group required ICU services, compared with 54% of patients who did not receive glutamine. This study also shows that taking glutamine may increase appetite (108035). The validity of these findings is limited by short duration of treatment and use of non-standardized treatments.
Cystic fibrosis. It is unclear if oral glutamine improves growth and development in children with cystic fibrosis. Details: A small clinical study in undernourished or stunted children with cystic fibrosis shows that taking glutamine 0.7 grams/kg daily orally for 4 weeks with or without recombinant human growth hormone (rhGH) does not promote protein gain when compared with rhGH alone (52321).
Diabetic foot ulcers. Oral glutamine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific nutritional supplement drink containing glutamine 7 grams, arginine 7 grams, and hydroxymethylbutyrate 1.5 grams (Abound, Abbott) twice daily for 16 weeks does not improve total wound closure or reduce the time to complete healing when compared with a control drink in patients with diabetic foot ulcers (96637). It is unclear if this effect is due to glutamine, other ingredients, or the combination.
Diarrhea. It is unclear if oral glutamine improves diarrhea in children and infants. Details: One preliminary clinical study in 6-24 month-old otherwise healthy children with acute diarrhea shows that taking capsules prepared with a specific glutamine powder (Power Glutamine, Champion Nutrition) 0.3 grams/kg daily for 7 days reduces the duration of diarrhea by about one day when compared with placebo (52323). However, other clinical research in male infants 1-12 months old with acute diarrhea and dehydration shows that adding glutamine 90 mmol/L along with the standard World Health Organization oral rehydration salts (ORS) does not decrease the duration of diarrhea, stool output, or the volume of oral rehydration solution required to achieve and maintain hydration when compared with standard ORS alone (7298).
Hematopoietic stem cell transplant (HSCT). It is unclear whether oral glutamine or glutamine added to parenteral nutrition improves morbidity and mortality in patients undergoing HSCT. Some research has suggested that intravenous glutamine may actually worsen outcomes. Details: Some research suggests that patients receiving glutamine-supplemented parenteral nutrition (PN) after HSCT primarily to treat hematologic malignancies have a diminished incidence of clinical infections, lower rates of microbial colonization, and decreased length of hospital stay when compared to control (2366,52381). However, not all patients seem to benefit. Some research shows that oral glutamine or PN with glutamine does not reduce the risk of mortality or infections in patients with hematologic malignancies and/or solid tumors (5451,52385). Also, a small clinical study in patients undergoing HSCT shows that PN with glutamine dipeptide may increase the duration of hospital stay (52292). Furthermore, one small study has found that receiving PN with glutamine was associated with lower disease-free survival and event-free survival over 3 years when compared with standard PN in patients receiving HSCT for hematologic malignancies (52355).
Irritable bowel syndrome (IBS). There is limited evidence on the oral use of glutamine in patients with IBS. Details: A clinical trial in adults with IBS (diarrhea-predominant, constipation-predominant, mixed, or alternating bowel habits) shows that following a low FODMAP diet supplemented with oral glutamine 15 grams three times daily for 6 weeks improves IBS-Severity Scoring System (IBS-SSS) scores, with 88% of patients in the glutamine group reporting a 45% improvement in severity scores, compared with 60% of patients following the low FODMAP diet alone (108037). The validity of this finding is limited by short duration of treatment and lack of follow-up. Preliminary clinical research in patients with postinfectious, diarrhea-predominant IBS shows that taking glutamine 5 grams three times daily for 8 weeks leads to a nearly 14-fold greater likelihood of symptom improvement, defined as a reduction of 50 points or more on the IBS-SSS, and decreases stool frequency by 2.45 stools daily when compared with placebo. Taking glutamine also seems to reduce abdominal pain ratings by 55% and improve quality of life scores by 53% when compared to baseline in these patients (100944). The validity of these findings is limited by the lack of a comparator group.
Lung cancer. It is unclear if oral glutamine improves survival in patients with advanced lung cancer. Details: One small clinical study in patients with advanced non-small cell lung cancer shows that taking glutamine 10 grams three times daily for 12 months along with palliative chemoradiotherapy prevents weight loss, which is an important predictor of survival, but does not increase the likelihood of progression-free survival when compared with palliative chemoradiotherapy alone (100942). It is unclear if this study was adequately powered to detect a difference in survival between groups.
Malnutrition. It is unclear if oral alanyl-glutamine improves height and weight in children at risk for malnutrition. Details: Preliminary clinical research in children aged 2 months to 5 years from a low-income area of Brazil and at risk for malnutrition, shows that taking 3-12 grams of alanyl-glutamine orally daily for 10 days improves gut integrity and is associated with a modest, short-term increase in weight when compared with a glycine placebo (103838).
Exercise-induced muscle damage. It is unclear if oral glutamine is beneficial for exercise-induced muscle damage. Details: A very small clinical crossover trial in professional athletes undergoing rigorous training shows that taking oral glutamine 6 grams daily for 20 days reduces serum levels of creatine kinase and myoglobin when compared with placebo (108031). The validity of these findings is limited due to the small size and short duration of treatment.
Obesity. It is unclear if oral glutamine is beneficial for weight loss. Details: A preliminary clinical study in 36 overweight or obese adults shows that taking glutamine 30 grams daily for 2 weeks reduces waist circumference by 1.8 cm, but does not improve body weight, body mass index, or glycemic indices, when compared to baseline. None of these outcomes were improved over baseline in an alanine control group (100941). Given the small study size and short duration of therapy, the long-term effects of glutamine on anthropometric measures is unclear.
Opioid withdrawal. Oral glutamine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in Chinese patients undergoing detoxification from heroin shows that taking a combination of tyrosine, lecithin, 5-HTP, and glutamine 50 mg/kg orally daily for 6 days might reduce mood-related withdrawal symptoms when compared with placebo (88178). It is unclear if this effect is due to glutamine, other ingredients, or the combination.
Oral mucositis. There is contradictory evidence about the effects of glutamine in patients with, or at risk of developing, oral mucositis from chemotherapy or radiotherapy. Details: Small clinical studies suggest that taking glutamine orally or swishing and swallowing a glutamine solution can decrease the incidence, severity, and duration of oral mucositis in some patients undergoing chemotherapy and/or radiation therapy for cancer or hematopoietic stem cell transplant (HSCT) (2336,2368,2704,5029). Additionally, three meta-analyses of highly heterogeneous clinical trials in patients with cancer receiving chemotherapy and/or radiation therapy suggests that glutamine reduces the incidence of severe (grade ≥3) oral mucositis when compared with control (105014,108028,108036). These analyses are limited for several reasons, including reporting bias, lack of sensitivity analysis, and population heterogeneity. Some small clinical studies included in these meta-analyses suggest that supplementation with glutamine may reduce the need for feeding tubes and opioid analgesics (108028,108036). However, not all research has been positive. Some small clinical studies in patients receiving chemotherapy with 5-fluorouracil for cancer or HSCT suggest that oral or intravenous glutamine does not reduce the incidence of oral mucositis when compared with control (2365,5451,5462,7296,52349,52350). Furthermore, a meta-analysis of 5 clinical trials in patients with head or neck cancers shows that oral glutamine does not reduce the overall incidence or the incidence of moderate to severe radiation-induced oral mucositis when compared with control (103836). The Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology (MASCC/ISOO) cautiously recommends the use of oral glutamine to prevent oral mucositis in patients with head and neck cancer receiving chemoradiotherapy. However, due to some evidence suggesting that intravenous glutamine may actually worsen outcomes in HSCT patients, the MASCC/ISOO recommends against its use for the prevention of oral mucositis in patients receiving high-dose chemotherapy, with or without total body irradiation, for HSCT (105004).
Paclitaxel-induced myalgia and arthralgia. It is unclear if oral glutamine reduces the risk for myalgias and arthralgias due to paclitaxel. Details: One small clinical study shows that taking glutamine 10 grams three times daily for 5 days, starting on the day of chemotherapy and repeated over 2 cycles of chemotherapy, does not reduce the rate or severity of paclitaxel-induced myalgias or arthralgias when compared with placebo (52331).
Pancreatitis. It is unclear if oral glutamine improves outcomes in patients with acute pancreatitis. Details: Two meta-analyses of the available clinical research in patients with pancreatitis show that enteral or parenteral supplementation with glutamine increases albumin, decreases C-reactive protein, and might reduce mortality, multiple organ dysfunction syndrome, hospital length of stay, and infections. Results are difficult to interpret due to the significant heterogeneity of the included trials and limited generalizability of the results (96513,103835).
Peptic ulcers. Although there is interest in using oral glutamine for peptic ulcers, there is insufficient reliable information about the clinical effects of glutamine for this condition.
Postoperative infection. It is unclear if oral or intravenous glutamine is beneficial for the prevention of postoperative infection in patients with colorectal cancer who are recovering from surgery. Details: A meta-analysis of nonblinded clinical research in adults with colorectal or colon cancer who recently underwent radical surgery shows that daily supplementation with glutamine 0.3-1 grams/kg, administered either orally or parenterally, improves the rate of surgical site infections and anastomotic leakage when compared with control (108033). These findings are limited by the high heterogeneity of the included studies and unclear reporting.
Postoperative recovery. It is unclear if oral or intravenous glutamine is beneficial in patients with colorectal cancer who are recovering from surgery. Details: A meta-analysis of nonblinded clinical research in adults with colorectal or colon cancer who recently underwent radical surgery shows that taking either oral or parenteral glutamine 0.3-1 grams/kg daily may reduce the length of hospital stay when compared with control (108033). These findings are limited by the high heterogeneity of the included studies and unclear reporting.
Pressure ulcers. Oral glutamine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in patients with stages II-IV pressure ulcers shows that taking a specific nutritional supplement drink containing glutamine 7 grams, arginine 7 grams, and hydroxymethylbutyrate 1.5 grams per packet (Abound, Abbott Nutrition) as two packets twice daily by mouth for 2 weeks has no effect on wound area or healing scores by the Pressure Ulcer Scale for Healing (PUSH) measurement when compared with standard nutritional care (96506).
Radiation dermatitis. It is unclear if oral glutamine reduces the risk of developing dermatitis from radiation therapy. Details: One small clinical study in patients with head and neck cancers receiving cisplatin shows that taking a specific supplement containing glutamine 7 grams, arginine 7 grams, and hydroxymethylbutyrate 1.5 grams (Abound, Abbott) orally twice daily, starting on day 1 of radiation and continuing until 1 week after radiation therapy, does not reduce the incidence of severe radiation-induced dermatitis when compared with no supplementation (96639). However, another small clinical study in patients with breast cancer who have had both chemotherapy and surgery shows that taking oral glutamine 5 grams three times daily, starting 1 week before radiation and continuing until 1 week after radiation, is associated with a reduction in grade 1 and grade 2 radiation dermatitis when compared with placebo (97366).
Radiation-induced esophagitis. It is unclear if oral glutamine reduces the risk of developing esophagitis from radiation therapy. Details: A small clinical study in patients with advanced non-small cell lung cancer shows that taking glutamine 10 grams three times daily for 12 months along with a palliative dose of chemoradiotherapy (total 30 Gy) results in a 7% incidence of symptomatic (grade 2 or higher) radiation-induced esophagitis, compared with a 53% incidence with palliative chemoradiotherapy alone. The glutamine group also had a 5.8-day delay in the onset of esophagitis (100942). However, a lower dose of glutamine in patients receiving higher doses of radiotherapy might not be beneficial. A small clinical study in patients with advanced thoracic malignancies shows that taking glutamine 4 grams mixed in water twice daily for 4 weeks along with radiotherapy (total dose of at least 45 Gy) to the esophagus, with or without chemotherapy, does not slow the onset of radiation-induced esophagitis or reduce its severity when compared with a glycine placebo (105011).
Short bowel syndrome. It is unclear if oral glutamine improves symptoms of short bowel syndrome. Details: Although small clinical studies suggest that glutamine plus growth hormone can decrease dependence on parenteral nutrition in some patients (2334,2361,2362,2703), it has not shown benefit for improving intestinal absorption of energy in all studies (8185). Additionally, glutamine alone doesn't appear to be beneficial (7730).
Traumatic Brain injury (TBI). It is unclear if intravenous glutamine is beneficial in patients hospitalized with severe TBI. Details: A clinical trial in patients hospitalized for a severe TBI shows that adherence to a hypocaloric, low-protein diet supplemented with daily intravenous glutamine 0.3 g/kg for 7 days does not improve 28-day mortality when compared with standard nutritional support alone. However, it may reduce the length of ventilator use, hospitalization, and duration of intensive care unit stay (108034).
Vincristine-induced neuropathy. It is unclear if oral glutamine reduces the risk of developing neuropathy from treatment with vincristine in children. Details: Preliminary clinical research in children ages 1-21 years receiving vincristine for various cancer types shows that taking glutamine 6 grams/m2 twice daily orally for 21 days reduces sensory neuropathy when compared with placebo. There was a significant improvement in self-reported, but not parent-reported, quality of life scores as measured by the PedsQL scale. However, there was no effect on motor neuropathy with the use of glutamine (96517).
Wound healing. It is unclear if oral glutamine improves wound healing. Details: Preliminary clinical research in trauma patients with wound healing disorders shows that taking glutamine 20 grams orally daily in combination with ascorbic acid 500 mg, vitamin E 166 mg, beta-carotene 3.2 mg, selenium 100 mcg, and zinc 6.6 mg (Glutamine Plus, Fresenius Kabi) for 14 days reduces the time to wound closure by 29 days when compared with placebo. However, there is no difference in length of stay (97364). More evidence is needed to rate glutamine for these uses.

GLYCINE

Schizophrenia. Oral glycine may improve negative, but not positive, symptoms of schizophrenia when used as adjunct to therapy with typical antipsychotics in patients resistant to monotherapy. However, glycine does not seem to provide additional benefit when used with clozapine. Details: Some small clinical trials show that taking glycine 0.4-0.8 grams/kg daily in divided doses along with conventional treatment seems to reduce negative symptoms of schizophrenia in patients that are resistant to monotherapy with typical antipsychotics such as thioridazine, haloperidol, and perphenazine (10250,10251,10252,98591). However, when used with the atypical antipsychotic clozapine, glycine appears to have a negligible effect on or worsen symptoms of schizophrenia (10253,11321). Additionally, glycine does not seem to improve positive symptoms of schizophrenia (10250,10251,10252,98591).

3-phosphoglycerate dehydrogenase (3-PGDH) deficiency. It is unclear if oral glycine is beneficial in patients with 3-PGDH deficiency. Details: A case series describing two patients with 3-PGDH deficiency who did not respond to serine supplementation suggests that taking oral glycine 0.2 grams/kg daily along with serine might reduce seizure frequency. 3-PGDH deficiency is a rare condition in which serine is not synthesized properly (10254).
Aging. Oral glycine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in adults aged 61-80 years with overweight or obesity shows that taking a specific combination product (GlyNAC), providing glycine 100 mg/kg and N-acetyl cysteine 100 mg/kg, daily for 16 weeks improves some markers associated with aging, including glutathione levels, oxidative stress, mitochondrial impairment, genomic damage, inflammation, and endothelial dysfunction, when compared to baseline. Improvements in these measures were lacking in the placebo group (110624). The validity of these findings is limited by a lack of statistical comparison between groups. Also, it is unclear if these effects are due to glycine, N-acetyl cysteine, or the combination.
Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral glycine for ADHD, there is insufficient reliable information about the clinical effects of glycine for this purpose.
Benign prostatic hyperplasia (BPH). Although there has been interest in using oral glycine for BPH, there is insufficient reliable information about the clinical effects of glycine for this purpose.
Cognitive function. Small clinical studies suggest that oral glycine may modestly improve memory and cognitive function in some patients. Details: Two small clinical studies in healthy young adults and adults with psychosis risk syndrome show that taking glycine 0.2-0.4 grams/kg once or twice daily for up to 24 weeks may improve some measures of memory and cognitive performance when compared with baseline or placebo (11322,92321).
Cystic fibrosis. It is unclear if oral glycine is beneficial in patients with cystic fibrosis. Details: A small clinical trial in patients 6-23 years of age with cystic fibrosis shows that taking glycine 0.5 grams/kg daily for 8 weeks modestly improves some measures of lung function and reduces sputum and dyspnea by 15% and 23%, respectively, when compared with placebo. However, taking glycine does not improve appetite or energy (98583).
Gout. Oral glycine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with mild hyperuricemia shows that taking a powder containing glycine 3 grams and L-tryptophan 0.2 grams nightly at bedtime for 6 weeks reduces serum uric acid levels by 0.3 mg/dL when compared with placebo. Improvements also occurred in the subgroup of patients with uric acid levels greater than 7 mg/dL, the point at which symptoms of gout can occur (99883). However, it is unclear if this combination improves gout-related pain. Also, it is not clear if these findings are due to glycine, L-tryptophan, or the combination.
Insomnia. Small clinical studies suggest that oral glycine may modestly improve sleep quality and daytime feelings of fatigue in patients with poor sleep quality or a restricted sleep duration. Details: Two very small studies in patients who have reported a subjective reduction in sleep quality show that taking glycine 3 grams one hour before bedtime for 2-4 days improves overall sleep quality and sleep efficacy when compared with placebo (92318,92320). Another very small clinical study in healthy males shows that taking glycine 3 grams 30 minutes before bedtime for 3 nights, during which time sleep duration is restricted by 25%, modestly reduces feelings of fatigue after the first night, but not after the third night, when compared with placebo (92316). The effects of glycine on sleep measures have also been evaluated in combination with other ingredients. A very small crossover study in healthy adults without documented sleep disorders shows that taking a combination product containing glycine 3000 mg, tryptophan 1000 mg, magnesium 300 mg, tart cherry powder 220 mg, and L-theanine 200 mg before bed for 3 nights reduces sleep onset latency, increases total sleep time, increases sleep efficiency, and reduces morning sleepiness when compared with placebo (111184). It is unclear if these effects are due to glycine, other ingredients, or the combination.
Isovaleric acidemia. Although there has been interest in using oral glycine for isovaleric acidemia, there is insufficient reliable information about the clinical effects of glycine for this purpose.
Metabolic syndrome. Although there has been interest in using oral glycine for metabolic syndrome, there is insufficient reliable information about the clinical effects of glycine for this purpose.
Obesity. Oral glycine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in adults aged 61-80 years with overweight or obesity shows that taking a specific combination product (GlyNAC), providing glycine 100 mg/kg and N-acetyl cysteine 100 mg/kg, daily for 16 weeks reduces waist circumference but does not improve body weight or body mass index (BMI) when compared to baseline. None of these outcomes were improved in individuals taking placebo (110624). The validity of these findings is limited by a lack of statistical comparison between groups. Also, it is unclear if these effects are due to glycine, N-acetyl cysteine, or the combination.
Overactive bladder. It is unclear if oral glycine is beneficial in patients with overactive bladder. Details: One very small, non-randomized, crossover trial in patients with overactive bladder shows that taking glycine 3 grams twice daily for 4 weeks reduces urinary urgency, urinary incontinence, and nighttime urinary frequency and improves quality of life scores when compared with placebo (106497). The validity of these findings is limited by a lack of randomization.
Physical performance. Oral glycine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in adults aged 61-80 years with overweight or obesity shows that taking a specific combination product (GlyNAC), providing glycine 100 mg/kg and N-acetyl cysteine 100 mg/kg, daily for 16 weeks improves upper and lower extremity strength and gait speed, but not walking distance, when compared to baseline. None of these outcomes were improved in individuals taking placebo (110624). The validity of these findings is limited by a lack of statistical comparison between groups. Also, it is unclear if these effects are due to glycine, N-acetyl cysteine, or the combination.
Stroke. It is unclear if sublingual glycine is beneficial in patients with acute ischemic stroke. Details: One small clinical study in patients with acute ischemic stroke in the carotid artery territory shows that taking glycine 1-2 grams sublingually daily for 5 days, starting within 6 hours after the onset of stroke, modestly improves clinical outcomes on the Orgogozo Stroke Scale, the Scandinavian Stroke Scale, and the Barthel index when compared with placebo (11320).
Venous leg ulcers. Topical glycine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that applying a cream containing glycine, L-cysteine, and DL-threonine to leg ulcers reduces pain and modestly improves healing when compared with a placebo cream (10255). It is unclear if these effects are due to glycine, other ingredients, or the combination.
Wound healing. Although there has been interest in using topical glycine for wound healing, there is insufficient reliable information about the clinical effects of glycine for this purpose. More evidence is needed to rate glycine for these uses.

INOSITOL

Metabolic syndrome. Oral inositol seems to modestly improve lipid parameters, blood pressure, and insulin resistance in patients with metabolic syndrome. Details: Some clinical research in postmenopausal adults with metabolic syndrome following a low-calorie diet shows that taking myo-inositol 2 grams twice daily for one year reduces total cholesterol by 29 mg/dL, triglycerides by 64 mg/dL, systolic and diastolic blood pressure by 9 mmHg and 6 mmHg, respectively, increases high-density lipoprotein (HDL) cholesterol by 6 mg/dL, and improves insulin resistance when compared with placebo. It did not reduce body mass index or waist circumference in these patients (91554). A meta-analysis of clinical studies in a mixed population shows similar effects on blood pressure, especially among postmenopausal adults with metabolic syndrome, at durations exceeding 8 weeks, and at doses of at least 4 grams (108820). Another clinical study in postmenopausal adults with metabolic syndrome and at risk for breast cancer shows that taking a combination of inositol and alpha-lipoic acid daily for 6 months, in combination with a low-calorie diet, reduces insulin resistance (HOMA-IR) by at least 20% when compared with a low-calorie diet alone. Also, taking inositol and alpha-lipoic acid seems to increase HDL cholesterol by about 6% and reduce triglycerides by 5% when compared to baseline (91543). It is unclear if these effects are due to inositol, alpha-lipoic acid, or the combination.
Polycystic ovary syndrome (PCOS). Oral inositol, often in combination with folic acid, seems to improve some glycemic, lipid, metabolic, hormonal, and reproductive parameters in patients with PCOS. However, research is conflicting. Details: Oral inositol, most frequently in the forms of myo-inositol or D-chiro-inositol, has been evaluated for efficacy in a wide range of outcomes associated with PCOS including reproductive and pregnancy outcomes, metabolic parameters, and anthropomorphic measures. Often, inositol is taken in combination with folic acid or metformin. Inositol has been investigated for its effect on metabolic parameters that are often altered in PCOS. A meta-analysis of 9 studies in patients with PCOS shows that taking myo-inositol or D-chiro-inositol with or without folic acid marginally decreases body mass index (BMI) by about 0.5 kg/m2 when compared with placebo (111670). Inositol has also been evaluated for its effect on glucose metabolism in adults with PCOS. Meta-analyses of about 10 studies show that taking myo-inositol or D-chiro-inositol with or without folic acid reduces fasting plasma glucose by 1-4 mg/dL (98944,111670). However, evidence is conflicting on the effect of inositol on insulin levels and measures of insulin resistance (98944,111670). Additionally, most studies show that inositol does not improve measures of glucose metabolism more than metformin. The effect of inositol on lipid profiles has also been studied. A meta-analysis of 2 clinical studies and other small clinical studies show that taking inositol as D-chiro-inositol with or without folic acid modestly reduces total cholesterol and triglycerides when compared with control (2028,98944,91552). Some studies have also investigated the effect of inositol on hormone levels. Meta-analyses show that inositol modulates androgen levels as shown by reduced total and free testosterone, androstenedione, and increased sex-hormone binding globulin when compared with placebo. (2028,91552,98944,111670). The validity of these effects is limited by high heterogeneity in terms of inclusion and exclusion criteria, dose, and treatment duration within the included studies. Myo-inositol has also been compared with metformin in some clinical research, with some evidence of benefit (95085,95086). Meta-analyses of small clinical studies show that taking myo-inositol 2-4 grams daily, with or without folic acid, for 12-24 weeks does not improve fasting blood glucose, fasting insulin, insulin resistance (HOMA-IR), BMI, waist-hip circumference, or androgen levels when compared with metformin 1.5-2.5 grams daily (100705,108823,111670,111670). However, inositol seems to have a lower risk of adverse effects than metformin. These analyses are limited due to the small size, methodological issues, and high heterogeneity of the included studies. In combination with metformin, small clinical studies show that taking metformin, myo-inositol 550 mg, and D-chiro-inositol 150 mg twice daily is associated with improved lipid parameters and postprandial insulin levels when compared with metformin alone (108822). Meta-analyses and clinical studies have investigated the effect of inositol on ovulation, reproduction, and pregnancy outcomes. Some research suggests that inositol increases ovulation rate, promotes cycle normalization, and improves ovarian function in patients with PCOS (2028,91552,98944,111670). A small clinical study shows that taking myo-inositol 4 grams and folic acid 400 mcg (Inofolic, Lo.Li.Pharma) daily for three spontaneous cycles induces ovulation in about 62% of individuals with anovulatory PCOS and insulin resistance. Adding clomiphene citrate with myo-inositol induces ovulation in about 72% of the patients who remain anovulatory after treatment with myo-inositol alone (91547). Another clinical study shows that taking a combination of inositol 2 grams, folic acid 200 mcg, and N-acetyl cysteine 600 mg (Ovaric HP, Just Pharma) twice daily for 12 months improves ovulation rates in PCOS patients with oligomenorrhea, regardless of insulin sensitivity at baseline (91553). Despite evidence that inositol improves ovulation rates, it does not appear to impact pregnancy rates (111670). Some research has also investigated the effects of taking both isomers of inositol concomitantly. Taking myo-inositol 550 mg plus D-chiro-inositol 13.8 mg (Inofolic Combi, Lo.Li.Pharma) twice daily, beginning 12 weeks before ovarian hyperstimulation and continuing throughout pregnancy, improves oocyte quality when compared to treatment with D-chiro-inositol alone. The combination appears to increase fertilization rate in patients aged 35 years or younger, but not those older than 35 years (91544). Other clinical research shows that taking myo-inositol 550 mg and D-chiro-inositol 150 mg twice daily for 12 weeks improves pregnancy rates and live birth rates by an additional 10% and 11%, respectively, when compared with myo-inositol 550 mg plus D-chiro-inositol 13.8 mg. The higher-dose combination also resulted in a 15% lower rate of ovarian hyperstimulation syndrome when compared with those taking the lower dose of D-chiro-inositol (102317). Lastly, other research shows that taking myo-inositol and D-chiro-inositol together may improve metabolic parameters faster than taking myo-inositol alone (91550). Research has also evaluated the effects of inositol on other pertinent clinical outcomes in PCOS. Several small clinical studies show that taking the combination of myo-inositol and D-chiro-inositol, alone or in combination with metformin, improves menstrual cycle irregularity when compared with metformin alone, but not as much as a taking a combined hormonal contraceptive (108822,108824). The validity of these findings is limited by the unblinded nature of the studies. Also, a small clinical study shows that taking metformin with myo-inositol 550 mg and D-chiro-inositol 150 mg twice daily is associated with improved acne, but not hirsutism, at 6 months, when compared with metformin alone (108822). The validity of these findings is limited by the unblinded nature of the study. More research is needed to clarify the effect of inositol on anthropometric, metabolic, and endocrine outcomes in patients with PCOS.
Preterm labor. Oral inositol in combination with folic acid seems to prevent preterm labor in individuals at risk for gestational diabetes. Details: A meta-analysis of five clinical trials in individuals at risk for gestational diabetes shows that taking myo-inositol plus folic acid daily, beginning during the first trimester and continuing throughout pregnancy, decreases the risk of preterm delivery by 64% when compared with folic acid alone. Patients in all but one study included in this analysis took myo-inositol 2 grams plus folic acid 200 mcg twice daily, while patients in the other study took myo-inositol 1100 mg plus D-chiro-inositol 27.6 mg and folic acid 400 mcg daily (100706). It's unclear if these results are generalizable to individuals with a low risk for gestational diabetes.

Acute respiratory distress syndrome (ARDS). Oral or intravenous inositol does not seem to prevent ARDS in preterm infants and may be associated with worsened outcomes. Details: Historically, small clinical trials in infants with or at risk for ARDS have suggested that myo-inositol, given parenterally and enterally for 5-10 days, might improve survival and reduce the risk of death and serious complications (2191,2192,91546). However, a large, high-quality clinical study in infants born at less than 28 weeks' gestation at risk for ARDS shows that myo-inositol 40 mg/kg given intravenously and then enterally every 12 hours for up to 70 days does not reduce the risk of death or retinopathy of prematurity (ROP). In fact, the rate of death or type 1 ROP increased by 7% in the myo-inositol group when compared to the control group, and a higher incidence of adverse events in the myo-inositol group, including poor perfusion, hypotension, and infections, led to early trial discontinuation (98946). Long-term follow-up until 24 months corrected age confirms that the initial increase in mortality rate in the myo-inositol group remained stable; however, there was no difference in a composite outcome of death or survival with moderate or severe neurodevelopmental impairment, as well as no difference in the risk of ROP, between the treatment and control groups (108819). The most recent meta-analysis, which incorporates this large clinical study, concludes that inositol supplementation does not reduce the risk of death in infants at risk for ARDS (102319).
Anxiety. Oral inositol does not seem to be beneficial for patients with anxiety. Details: A meta-analysis of four clinical trials shows that taking inositol orally does not improve anxiety severity in patients with anxiety disorders, including obsessive-compulsive disorder, panic disorder, or post-traumatic stress disorder, when compared with placebo (91549).
Depression. Oral inositol does not seem to be beneficial for patients with depression. Details: Guidelines from the World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that inositol in doses up to 12 grams daily is not currently recommended as monotherapy or adjunctive use for major depressive disorder due to a lack of evidence for efficacy (110318). Additionally, a meta-analysis of seven clinical trials shows that inositol does not significantly improve symptoms of depression in patients with bipolar depression, major depressive disorder, or premenstrual dysphoric disorder (PMDD) (91549). While limited research shows that patients receiving inositol for 4 weeks may improve, patients initially responding to inositol seem to relapse rapidly upon discontinuation of treatment (2026,2185). Additionally, taking inositol with a selective serotonin reuptake inhibitor (SSRI) doesn't appear to improve the effectiveness of SSRI therapy or improve depression in SSRI treatment failures (2025,10851).
Diabetic neuropathy. Oral inositol does not seem to be beneficial for patients with diabetic neuropathy. Details: Most preliminary clinical research shows that taking inositol orally doesn't improve the symptoms of diabetic neuropathy (2193,2194,2195).
Retinopathy of prematurity. Oral or intravenous inositol does not seem to prevent retinopathy of prematurity (ROP) in preterm infants. Details: A meta-analysis of six clinical trials shows that myo-inositol, given parenterally and/or enterally, does not seem to reduce the risk of ROP when compared with placebo in preterm infants (100704). A large, high-quality clinical study included in this meta-analysis shows that myo-inositol 40 mg/kg given intravenously and then enterally every 12 hours for up to 70 days does not reduce the risk of death or ROP in infants born at less than 28 weeks' gestation. In fact, the rate of death or type 1 ROP increased by 7% in the myo-inositol group when compared with placebo and a higher incidence of adverse events in the myo-inositol group, including poor perfusion, hypotension, and infections, led to early trial discontinuation (98946). Long-term follow-up until 24 months corrected age confirms that the initial increase in mortality rate in the myo-inositol group remained stable; however, there was no difference in a composite outcome of death or survival with moderate or severe neurodevelopmental impairment, as well as no difference in the risk of ROP, between the treatment and control groups (108819).

Age-related testosterone deficiency. It is unclear if oral D-chiro-inositol is beneficial in patients with age-related testosterone deficiency. Details: A very small clinical study in males aged 65-75 years with low-normal morning testosterone levels and signs and symptoms of androgen deficiency shows that taking D-chiro-inositol 600 mg twice daily for 30 days improves sexual function and physical strength when compared with baseline (108821). The validity of these findings is limited by the lack of a comparator group.
Bipolar disorder. It is unclear if oral inositol is beneficial in patients with bipolar disorder. Details: Evidence is conflicting on whether inositol helps treat bipolar disorder in children. One very small preliminary study in children aged 5-12 years with bipolar disorder not on concomitant mood-stabilizing medications shows that taking inositol 80 mg/kg (maximum 2 grams) daily for 12 weeks reduces manic symptoms when compared to baseline. Additionally, taking a combination of inositol 80 mg/kg and high eicosapentaenoic acid omega-3 fatty acid capsules (EPA; Nordic Naturals) 1650-3000 mg daily for 12 weeks reduces manic and depressive symptoms when compared to baseline (95092). However, another more recent study with the same intervention and protocol shows that the combination of inositol and high eicosapentaenoic acid omega-3 fatty acid reduces symptoms of depression, but does not improve manic symptoms, when compared with either ingredient taken alone (111676).
Chemotherapy-induced leukopenia. Oral inositol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults undergoing breast cancer surgery and adjuvant chemotherapy shows that taking inositol orally 390 mg twice daily and applying IP-6 gel 4% twice daily to the surgical site, starting 2 weeks before adjuvant chemotherapy and stopping 2 weeks after the last cycle, attenuates reductions in white and red blood cell counts when compared with no intervention. Using inositol and IP-6 also improves breast and arm symptom scores and some quality of life scores; however, these improvements were not consistent over time.
Diabetes. It is unclear if oral inositol is beneficial for the treatment of type 1 diabetes or the prevention of gestational diabetes. Details: Preliminary clinical research in patients with type 1 diabetes and a body mass index of at least 25 kg/m2 shows that taking a specific combination product containing D-chiro-inositol and folic acid (Chirofol 500, LJ Pharma) daily for 6 months, along with insulin therapy, decreases glycated hemoglobin (HbA1c) by approximately 0.5% when compared to taking folic acid alone with insulin therapy. However, there was no difference between groups with respect to insulin resistance or body mass index (95088). Most research shows that taking inositol during pregnancy prevents gestational diabetes. However, most studies conducted to date are of low quality and it is unclear if the results are generalizable. Meta-analyses of 4-7 clinical studies in pregnant adults, some with overweight and obesity, shows that taking myo-inositol 200-4000 mg daily may reduce the risk of gestational diabetes and gestational hypertension, improve 1- and 2-hour glucose tolerance test results, and reduce insulin requirements. Inositol may also be associated with improved infant outcomes such as increased gestational age at birth and reduced preterm delivery but does not seem to influence birth weight, NICU admission rate, neonatal hypoglycemia, the incidence of shoulder dystocia, macrosomia or cesarian delivery when compared with control (111664,111667,111671,111677). The validity of these effects is limited by significant heterogeneity within the included studies, concerns about blinding, and overall low-quality evidence. Most clinical research shows that taking myo-inositol 2 grams plus folic acid 200 mcg twice daily (usually as Inofolic, Lo.Li. Pharma International), beginning during the first trimester and continuing throughout pregnancy, decreases the incidence of gestational diabetes by 57% to 92% when compared with folic acid alone in patients at risk for gestational diabetes. Myo-inositol seems to be more effective than D-chiro-inositol (91545,91548,95083,95084,100706,103750,104688). However, supplementation with lower doses of inositol, mimicking natural inositol occurring in the body, may not be effective. Other evidence is conflicting about whether inositol prevents gestational diabetes. One clinical study shows that taking a combination of myo-inositol 1.1 grams, D-chiro-inositol 27.6 mg, and folic acid 400 mcg (Inofolic Combi, Lo.Li. Pharma International) daily during pregnancy does not decrease the incidence of gestational diabetes when compared with folic acid alone in patients with a family history of diabetes (95082,103750). In patients eventually diagnosed with gestational diabetes, one small clinical study shows that taking myo-inositol 2 grams reduces the number of patients requiring insulin by at least 50% (104688), although another small clinical study shows that adding D-chiro-inositol, myo-inositol, or both to folic acid does not affect insulin resistance when compared with placebo (98945).
Dyslipidemia. Although there has been interest in using oral inositol for hypercholesterolemia and hypertriglyceridemia, there is insufficient reliable information about the clinical effects of inositol for these conditions.
Hypertension. Although there has been interest in using oral inositol for hypertension, there is insufficient reliable information about the clinical effects of inositol for this condition.
Hypothyroidism. It is unclear if oral inositol is beneficial for subclinical hypothyroidism. Details: Clinical research in females aged 18 to 50 years with or at risk for subclinical hypothyroidism in Slovakia shows that taking myo-inositol 600 mg and selenium 83 mcg daily for 6 months modestly reduces thyroid stimulating hormone (TSH) and thyroid auto-antibody titers when compared to baseline. Myo-inositol and selenium supplementation also reduces patient-reported hypothyroid symptoms including fatigue, menstrual cycle irregularity, and intolerance to heat or cold (110591). The interpretation of these results is limited by the lack of a control group. In addition, it is unclear if these effects are due to myo-inositol, selenium, or the combination.
Infertility. It is unclear if oral inositol is beneficial in patients undergoing intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF). Details: Several small studies in patients undergoing ICSI show that taking a specific combination product containing myo-inositol 4 grams and folic acid 400 mcg (Inofolic, Lo.Li. Pharma International S.r.l) daily, starting 1-3 months before ICSI and continuing until ovulation, improves fertilization rate, but does not improve implantation or pregnancy rates, when compared with taking folic acid alone (103752,108825). However, another moderate-sized clinical study in adults with infertility undergoing ICSI and IVF shows that taking the same combination of myo-inositol 4000 mg and folic acid 400 mcg daily for 2 months starting on the third day of the cycle improves mean number of oocytes, meiosis II oocytes, 2 pronuclear embryos, and clinical pregnancy and live birth rates when compared with taking folic acid alone (111672). The effects of inositol on fertility have been studied in patients with specific comorbidities. A case-control study in long-term survivors of lymphoma suggests that taking myo-inositol 400 mg and D-chiro-inositol 45 mg (Ovofert Fast, CRL Pharma) three times daily for 12 months is associated with reductions in follicle stimulating hormone (FSH), luteinizing hormone (LH), dyspareunia, and dysmenorrhea and a modest increase in antral follicle count of the right ovary when compared with control (111673). The validity of these effects is limited by a lack of blinding. Inositol has also been evaluated in females with polycystic ovary syndrome (PCOS). A meta-analysis of clinical studies in adults with PCOS undergoing IVF or ICSI shows that inositol does not improve pregnancy rates when compared to no treatment. However, inositol may increase clinical pregnancy rates when compared with metformin (111675). Inositol has also been evaluated in combination with other ingredients. A large clinical study in females planning to conceive shows that taking a combination product containing myo-inositol 4 grams, vitamin D, riboflavin, vitamin B6, vitamin B12, zinc, and probiotics does not improve time-to-conception, clinical pregnancy rates, or live birth rates when compared with a standard micronutrient supplement. However, the supplement shortens time-to-conception in adults with overweight to durations equivalent to patients who are not overweight, but lengthens time to conception in adults with obesity when compared with placebo (111665). It is unclear whether these effects are due to inositol, other ingredients, or the combination.
Insomnia. It is unclear if oral inositol is beneficial for improving sleep during pregnancy. Details: Clinical research shows that taking myo-inositol 2 grams plus folic acid 200 mcg (Inofolic, Lo.Li. Pharma International) before bed for 10 weeks, starting at 14 weeks gestation, improves overall measures of sleep quality by a small amount when compared with folic acid alone. However, this improvement was not maintained until 37-38 weeks' gestation. Also, the study was not limited to patients with poor sleep quality during pregnancy, but to any healthy pregnant individual (104687).
Lithium-induced side effects. It is unclear if oral inositol is beneficial for reducing lithium-induced side effects. Details: A small clinical study suggests that taking inositol 6 grams daily for 10 weeks may improve psoriasis associated with lithium therapy when compared with baseline (11972). However, taking inositol orally does not seem to improve other lithium-induced adverse effects, such as tremor, thirst, and changes in thyroid and adrenal function (2027).
Lung cancer. It is unclear if oral inositol is beneficial for slowing the rate of bronchial dysplasia. Details: Preliminary clinical research in smokers with bronchial dysplasia considered at high risk for lung cancer shows that taking myo-inositol (Tsuno Food Industries Co., Ltd.) 9 grams orally once daily for 2 weeks then twice daily for 6 months, does not increase the rate of complete or partial response when compared with placebo (95090).
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral inositol is beneficial for NAFLD. Details: A small clinical study in adults with NAFLD and obesity shows that taking myo-inositol powder 4 grams daily for 8 weeks does not improve liver health markers, such as liver function test levels or liver steatosis, but does improve some components of lipid profiles, glycemic indices, and anthropometric measures when compared to baseline (111304) However, this study may have been inadequately powered to detect differences in some of the outcomes.
Obesity. It is unclear if oral inositol is beneficial in patients with overweight or obesity. Details: A meta-analysis of 15 clinical studies in adults shows that taking inositol 600-4450 mg daily for 6-48 weeks decreases body mass index (BMI) by about 0.4 kg/m2. Subgroup analysis suggests that myo-inositol may be beneficial at a dosage less than 1000 mg for less than 12 weeks, especially in patients with polycystic ovary syndrome (PCOS) and overweight or obesity, with higher baseline BMI, and above 40 years of age (111666). However, the validity of this finding is limited by significant heterogeneity in the included studies.
Obsessive-compulsive disorder (OCD). It is unclear if oral inositol is beneficial in patients with OCD. Details: One preliminary clinical study in adults with OCD shows that taking inositol 18 grams daily for 6 weeks improves Yale-Brown Obsessive Compulsive Scale scores when compared with placebo (2186). However, taking inositol does not seem to improve the severity or type of OCD symptoms in patients already taking a selective serotonin reuptake inhibitor (91556). Both of these studies were small, and treatment was administered for only 6 weeks.
Panic disorder. Oral inositol seems to improve symptoms of panic disorder. Details: A very small clinical study shows that taking inositol 12 grams daily reduces the severity and rate of panic attacks and the severity of agoraphobia over 4 weeks of treatment when compared with placebo (2184). Another very small clinical study shows that taking inositol 18 grams daily for one month may be as effective as fluvoxamine 150 mg daily for treatment of panic disorder (10387). However, the one-month duration may not have provided adequate time to see the full effects of fluvoxamine.
Post-traumatic stress disorder (PTSD). It is unclear if oral inositol is beneficial in patients with PTSD. Details: Preliminary clinical research shows that taking inositol 12 grams daily for 4 weeks does not improve distress when compared with placebo in patients with PTSD (91557).
Pregnancy-induced hypertension. It is unclear if oral inositol is beneficial for preventing hypertension during pregnancy. Details: In patients with a body mass index (BMI) between 25-29.9 kg/m2, preliminary clinical research shows that taking myo-inositol 2 grams plus folic acid 200 mcg (Inofolic, Lo.Li. Pharma International) twice daily, beginning during the first trimester and continuing throughout pregnancy, decreases the incidence of pregnancy-induced hypertension by 66% when compared with folic acid alone (104688).
Psoriasis. It is unclear if oral or topical inositol is beneficial for improving symptoms of psoriasis. Details: One small clinical study shows that taking inositol 6 grams daily for 10 weeks does not improve symptoms of psoriasis in a small group of patients when compared to baseline. However, taking this dose of inositol has a moderate effect on overall symptoms in patients with psoriasis related to lithium use (11972). Preliminary clinical research also shows that topical use of D-chiro-inositol is unlikely to be beneficial for reducing overall symptoms of psoriasis. Topical application of inositol 0.25% or 1% for 6 weeks improves overall symptoms when compared with baseline. However, the inositol-containing creams were no more effective than the control cream (104686). Inositol has also been evaluated in combination with other ingredients. A small prospective observational study in adults with mild plaque psoriasis suggests that applying amino-inositol and urea 40% cream (Inosit U40, Biogena) 1-2 times daily for 4 weeks is associated with reductions in the severity and extent of psoriasis symptoms and improvements in quality of life measures when compared to baseline (111668). The validity of these effects is limited by a small sample size, a lack of a comparator group, insufficient blinding, and the observational study design.
Trichotillomania. It is unclear if oral inositol is beneficial for reducing hair pulling. Details: Preliminary clinical research shows that taking inositol in doses ranging from 6-18 grams daily over a period of 10 weeks is no more effective than placebo in reducing subjective or clinician-documented symptoms of hair pulling in patients with trichotillomania (95089). More evidence is needed to rate inositol for these uses.

Cancer. Although there is interest in using oral L-cysteine for prevention of cancers of the upper gastrointestinal tract, there is insufficient reliable information about the clinical effects of L-cysteine for this purpose.
Diabetes. Although there is interest in using oral L-cysteine for diabetes, there is insufficient reliable information about the clinical effects of L-cysteine for this condition.
Erythropoietic protoporphyria (EPP). Although there is interest in using oral L-cysteine for EPP, there is insufficient reliable information about the clinical effects of L-cysteine for this condition.
Hangover. Oral L-cysteine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial shows that an immediate release product (Catapult Cat L-cysteine vitamin tablet) providing L-cysteine 1200 mg in combination with other ingredients, taken six times between 7 pm and midnight in conjunction with alcohol 1.5 grams/kg over 3 hours, modestly reduces symptoms of hangover, including nausea, headache, stress, and anxiety, when compared with placebo. Each L-cysteine tablet also contained thiamine 50 mg, riboflavin 1.4 mg, niacin 16 mg, vitamin B6 1.4 mg, biotin 50 mcg, folic acid 200 mcg, vitamin B12 2.5 mcg, and vitamin C 80 mg (109709). Other researchers have questioned the validity of the statistical methods used in this study and suggest that not all of the noted outcomes were statistically significant (109716).
Photoreactive keratectomy. It is unclear if oral L-cysteine is beneficial for promoting wound healing after photoreactive keratectomy. Details: Preliminary clinical research shows that taking L-cysteine 100 mg twice daily for 14 days starting one week before photoreactive keratectomy reduces complete corneal healing time by about 2 days when compared with taking placebo (109727).
Venous leg ulcers. Topical L-cysteine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial shows that topical application of a cream containing L-cysteine 2 mg/gram, glycine 10 mg/gram, and D,L-threonine 1 mg/gram for 12 weeks modestly increases healing and decreases pain when compared with placebo. However, there was no difference in exudate, offensive smell, or granulation. The cream was used as part of a treatment regimen involving cleaning and bandaging, two to five days each week (10255).
Smoking cessation. It is unclear if oral L-cysteine is beneficial for promoting smoking cessation. Details: Preliminary clinical research shows that use of a slow-release lozenge containing L-cysteine 3 mg (Acetiumlozenge; Biohit Oyj) with each cigarette for 6 months does not increase the odds of smoking cessation when compared with placebo (109714). However, this study may have been inadequately powered to detect a difference between groups. An adequately powered study by the same research group shows that using this lozenge increases the odds of smoking cessation by about 51% when compared with placebo (109710).
Stroke. Although there is interest in using oral L-cysteine for stroke prevention, there is insufficient reliable information about the clinical effects of L-cysteine for this purpose. More evidence is needed to rate L-cysteine for these uses.

METHIONINE

Neural tube birth defects. High dietary intake of methionine during pregnancy seems to reduce the risk of neural tube birth defects. Details: Population research has found that higher dietary intake of methionine during pregnancy is associated with a reduced risk of neural tube defects when compared with lower dietary intake (63117,63135).

Acetaminophen poisoning. It is unclear if oral methionine is beneficial in patients with acute acetaminophen poisoning. Details: Observational research has found that taking methionine 2.5 grams every 4 hours for a total of four doses, starting within 10 hours of acetaminophen overdose, may have similar efficacy to acetylcysteine for preventing liver damage and death (2413).
Allergic rhinitis (hay fever). Although there has been interest in using oral methionine for seasonal allergies, there is insufficient reliable information about the clinical effects of methionine for this purpose.
Asthma. Although there has been interest in using oral methionine for asthma, there is insufficient reliable information about the clinical effects of methionine for this purpose.
Breast cancer. It is unclear if high dietary intake of methionine reduces the risk of breast cancer. Details: A meta-analysis of observational studies suggests that higher dietary intake of methionine is associated with a 6% lower risk of breast cancer, especially for postmenopausal adults, when compared with lower intake. Increasing dietary intake of methionine by 1 gram daily may be associated with a 4% reduction in the risk of breast cancer. These results appear to be more prominent in postmenopausal adults when compared with premenopausal adults; however, this could have been by chance due to the small number of studies that assessed premenopausal adults (94093). A more recent meta-analysis, including 4 additional observational studies, suggests that there is no significant association between methionine intake and breast cancer risk. This finding is largely influenced by inclusion of the European Prospective Investigation into Cancer and nutrition (EPIC) cohort study, which analyzed data from over 300,000 subjects and found no relationship between methionine intake and breast cancer risk (111416).
Cisplatin-associated ototoxicity. It is unclear if oral D-methionine prevents cisplatin-associated ototoxicity. Details: A small clinical study in adults with cancer receiving cisplatin shows that taking D-methionine 100 mg/kg one hour prior to chemotherapy for up to 5 cycles prevents shifts in the hearing threshold at all four tested frequencies, compared with shifts occurring at three of the four tested frequencies in those receiving placebo (108039). The validity of these findings is limited by the lack of statistical comparison between groups.
Colorectal cancer. It is unclear if high dietary intake of methionine reduces the risk of colorectal cancer. Details: A meta-analysis of observational research has found that higher dietary intake of methionine is associated with an 11% lower risk of colorectal cancer, a 23% lower risk of colon cancer, and a 12% lower risk of rectal cancer, when compared with lower intake of methionine. Increasing dietary intake of methionine by 1 gram daily is associated with a 11% reduction in the risk of colorectal cancer. Subgroup analyses have shown a significant inverse relationship between risk of colorectal cancer and dietary methionine intake in patients followed for at least 13.3 years, in Western populations, and in males (94094). There is some evidence that high dietary intake of methionine and folate might have a synergistic effect in decreasing the risk of colon cancer, especially in those with a family history of colon cancer and in those who consume large amounts of alcohol (9325,9326).
Genital herpes. Oral L-methionine has only been evaluated in combination with other ingredients; its effects when used alone is unclear. Details: A small clinical study in patients with genital warts caused by herpes simplex virus (HSV) shows that taking acyclovir 200 mg five times daily for 5 days followed by 4 capsules of a combination product providing a total daily dose of L-methionine 200 mg, coenzyme Q10 50 mg, vitamin E 50 mg, and selenium 50 mcg for 90 days increases the rate of skin reepithelization by approximately 2 days and decreases the incidence of relapse when compared with acyclovir alone. Patients receiving combination therapy had a relapse rate of 13%, compared with a rate of 43% with acyclovir alone (94091).
Herpes zoster (shingles). Oral L-methionine has only been evaluated in combination with other ingredients; its effects when used alone is unclear. Details: A small clinical study in patients with herpes zoster shows that taking acyclovir 800 mg five times daily for 10 days followed by 4 capsules of a combination product providing a total daily dose of L-methionine 200 mg, coenzyme Q10 50 mg, vitamin E 50 mg, and selenium 50 mcg for 90 days increases the rate of skin reepithelization by approximately 2 days, decreases the incidence of relapse, and decreases postherpetic neuralgia pain when compared with acyclovir alone. Patients receiving combination therapy had a relapse rate of 7%, compared with a rate of 44% with acyclovir alone (94091).
Human papillomavirus (HPV). It is unclear if oral methionine is beneficial for the treatment of HPV lesions or for reducing the incidence of relapse. Details: A clinical study in patients aged 14 years or older with cutaneous warts caused by HPV shows that receiving conventional therapy in combination with one capsule of a product containing methionine, echinacea, inulin, taurine, vitamin A, vitamin C, coenzyme Q10, vitamin B3, zinc gluconate, and probiotics (Immuno Skin Plus tablets, Morgan Pharma S.r.l) daily for 20 days each month for 4 months reduces the number of warts at 6 months by about 5, with complete remission achieved in 86% of patients. The group receiving conventional therapy alone had a reduction in the number of warts by about 3, with complete remission achieved in 55% of patients. Conventional therapy consisted of either liquid nitrogen cryotherapy or topical therapy with salicylic acid 15% and lactic acid 15%. These findings are limited by the fact that patients in the combination therapy group had more warts at baseline when compared with those receiving conventional therapy alone (94092). Another small clinical study in patients with skin warts caused by HPV shows that cryotherapy followed by taking 4 capsules of a product containing a total dose of L-methionine 200 mg, coenzyme Q10 50 mg, vitamin E 50 mg, and selenium 50 mcg daily for 180 days increases the rate of complete recovery and decreases the incidence of relapse when compared with cryotherapy followed by placebo. At 180 days, 56% of patients in the active group experienced complete recovery, compared with 44% in the placebo group, and 30% of patients in the active group experienced a relapse, compared with 41% in the placebo group (94091). It is unclear if these effects are due to methionine, other ingredients, or the combination.
Menopausal symptoms. It is unclear if oral L-methionine is beneficial for reducing hot flashes. Details: Preliminary clinical research in postmenopausal adults experiencing at least 5 hot flashes daily for the prior two months shows that taking L-methionine 1 gram twice daily for 12 weeks, then 2 grams twice daily for 8 weeks, does not improve hot flashes when compared with placebo (94090).
Pancreatitis. Oral methionine has only been evaluated in combination with other ingredients; its effects when used alone is unclear. Details: A meta-analysis of eight randomized and nonrandomized clinical studies in patients with chronic or recurrent acute pancreatitis shows that taking a combination of methionine, selenium, vitamin E, vitamin C, and beta-carotene reduces pain when compared with placebo. However, when the two nonrandomized studies were excluded, the significant reduction in pain was lost. Daily doses of individual components studied included methionine 1.6-2.88 grams, selenium 300-600 mcg, vitamin E 188-280 mg, vitamin C 540-720 mg, and beta-carotene 12-54 mg. The study durations ranged from 10 weeks to 12 months (94095). The validity of these findings is limited by the heterogeneity of the included studies.
Parkinson disease. Although there has been interest in using oral methionine for Parkinson disease, there is insufficient reliable information about the clinical effects of methionine for this purpose.
Urinary tract infections (UTI). Oral methionine has only been evaluated in combination with other ingredients; its effects when used alone is unclear. Details: A low-quality observational study in patients with symptomatic UTI and culture-confirmed bacteriuria during pregnancy has found that taking a specific combination of methionine 800 mg, Hibiscus sabdariffa extract 200 mg, and Boswellia serrata 200 mg (Acidif Plus, Biohealth S.r.l) daily for one week increases the rate of negative urine cultures to 70% and symptom resolution to 63%, compared with 43% and 46%, respectively, in patients who increased fluid intake but did not take the combination product (97263). The validity of these findings is limited by the fact that the study groups were not comparable at baseline.
Wound healing. Although there has been interest in using oral methionine for wound healing, there is insufficient reliable information about the clinical effects of methionine for this purpose. More evidence is needed to rate methionine for these uses.

Biliary disorders. Although there has been interest in using oral radish for biliary disorders, there is insufficient reliable information about the clinical effects of radish for this purpose.
Diabetes. Although there has been interest in using oral radish for diabetes, there is insufficient reliable information about the clinical effects of radish for this purpose. More evidence is needed to rate radish for these uses.

TAURINE

Congestive heart failure (CHF). Oral taurine may improve left ventricular function, heart failure-related symptoms, and exercise capacity in patients with CHF. Details: Taking taurine 2-6 grams in two or three divided doses daily for 6-8 weeks seems to improve left ventricular function (5248,5271,8221) and symptoms of heart failure (5271,5306,8221) when compared with placebo or coenzyme Q10 in patients with New York Heart Association (NYHA) functional class II to IV. Also, taking taurine 500 mg three times daily for 2 weeks seems to improve exercise capacity when compared with placebo in patients with heart failure (77176). Some patients with severe heart failure rapidly improve from NYHA class IV to II after 4-8 weeks of treatment. Improvement seems to continue for as long as taurine treatment is continued, up to one year (5306,8217,8218,8221).
Hepatitis. Oral taurine may improve liver function in patients with acute or chronic hepatitis. Details: Several small clinical trials show that taking taurine 1.5-4 grams daily for up to 3 months improves liver function in patients with acute and chronic hepatitis when compared with placebo (10454,77114,77147).

Obesity. Oral taurine does not appear to improve body weight in adults who are obese or overweight. Details: A meta-analysis of 12 small clinical trials shows that taurine supplementation does not reduce body weight or body mass index (BMI) when compared with placebo. The studies included in this analysis evaluated taurine doses of 0.5-6 grams daily for 15 days to 6 months. Most of the patient populations evaluated in the included studies had liver or metabolic disorders; three studies specifically evaluated overweight or obese adults (104166). Additionally, a more recent clinical trial in a small group of females with obesity shows that taking taurine 1 gram three times daily along with a calorie-restricted diet for 8 weeks does not reduce body weight, BMI, or waist circumference when compared with calorie restriction alone (104167). In contrast, a very small study in adults with type 2 diabetes on antidiabetes medication shows that taking taurine 500 mg twice daily for 8 weeks reduces body mass, BMI, and body fat percentage when compared with control (112271). The validity of these effects is limited by the small sample size.

Academic performance. It is unclear if oral taurine is beneficial to improve academic performance. Details: A very small clinical study in college entrance examinees over age 19 shows that taking a jelly containing taurine 3 grams daily for 14 days does not improve academic achievement when compared with baseline or placebo (110579). Due to its small size, this study may have been inadequately powered to detect a difference between groups.
Age-related macular degeneration (AMD). Although there has been interest in using oral taurine for AMD, there is insufficient reliable information about the clinical effects of taurine for this purpose.
Androgenic alopecia. Oral taurine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with androgenic alopecia or telogen effluvium shows that taking a combination product containing taurine, cysteine, methionine, iron, selenium, and hydrolyzed collagen (GFM Oral, Cantabria Labs) along with conventional therapy, consisting primarily of finasteride or minoxidil, daily for 12 weeks improves hair loss when compared with conventional therapy alone (111636). It is unclear if this effect is due to taurine, other ingredients, or the combination.
Athletic performance. Research on the use of taurine for improving endurance or power output is limited and conflicting; however, it may improve performance by a small amount in some athletes. Details: Research is conflicting on the effects of taurine on athletic performance. Several clinical studies in trained and untrained athletes show that taking taurine 1-6 grams as a single dose before endurance exercise, or 3 grams daily for 8 weeks after endurance exercise, does not improve endurance or aerobic capacity when compared with placebo (77159,77203,95613,98334). However, a meta-analysis of 7 small clinical trials shows that taking taurine 1-6 grams daily for up to 2 weeks slightly improves endurance when compared with control. Also, preliminary studies in male cyclists, recreationally active males, Olympic-level athletes, and female athletes habituated to caffeine show that taking taurine 50 mg/kg or 1-6 grams one time 1.5-2 hours prior to a cycling test increases the time to exhaustion and peak, mean, and minimum power output but does not improve perceived exertion, fatigue index, heart rate, or anaerobic capacity when compared with placebo (101475,103211,112265,112269). The reasons for these discrepancies are unclear; the meta-analysis did not identify a dose or duration-related benefit. One small clinical trial shows that taking taurine 40 mg/kg improves muscle power in caffeine-deprived athletes who regularly use caffeine, but actually seems to worsen muscle power in athletes who do not regularly use caffeine (98335). Overall, it is not clear which population is most likely to benefit from taurine use (98337,98338). Study results are mixed when taurine has been evaluated in combination with other ingredients. One small study shows that taking a specific product containing taurine and caffeine (AdvoCare Spark) does not improve sprint performance in college athletes when compared with placebo (77195). However, other small studies of cyclists and boxers suggest that taking taurine in combination with a variety of other ingredients including B vitamins, caffeine, and glucuronolactone (Red Bull Energy Drink) or ginseng, kudzu, and soybean, may improve measures such as endurance, power, balance, or agility (37815,57945,110577,112269). It is unclear if the benefits seen in these studies are due to taurine, other ingredients, or the combinations.
Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral taurine for ADHD, there is insufficient reliable information about the clinical effects of taurine for this purpose.
Autism spectrum disorder. Although there has been interest in using oral taurine for autism spectrum disorder, there is insufficient reliable information about the clinical effects of taurine for this purpose.
Chemotherapy-induced nausea and vomiting (CINV). It is unclear if oral taurine is beneficial in patients with CINV. Details: One small clinical trial in patients with acute lymphoblastic leukemia receiving 6 months of chemotherapy shows that taking taurine (pure powder, Aviforme) 1000 mg twice daily, starting 6 hours after receiving chemotherapeutic agents, significantly improves CINV in 87.5% of patients. Other symptoms, such as reduced appetite and smell and taste impairment, are also improved in some patients (91512).
Chemotherapy-induced nephrotoxicity. It is unclear if oral taurine is beneficial for preventing or treating chemotherapy-induced nephrotoxicity. Details: One small clinical trial in patients with acute lymphoblastic leukemia receiving 6 months of chemotherapy shows that taking taurine (pure powder, Aviforme) 1000 mg twice daily reduces plasma creatinine, urea, bilirubin, and liver enzymes after 4 months when compared with placebo. This suggests a protective effect against chemotherapy-induced nephrotoxicity and hepatotoxicity. A reduction in overall fatigue is also observed (95616).
Cirrhosis. It is unclear if oral taurine is beneficial in patients with cirrhosis. Details: One small, uncontrolled clinical study in patients with cirrhosis shows that taking taurine 1 gram three times daily for 4 weeks reduces the severity and frequency of muscle cramps when compared to baseline (104165). Another small clinical trial in patients with cirrhosis shows that taking taurine 6 grams daily for 4 weeks reduces portal hypertension by 12%, compared with a 2% increase in the placebo group (98336). However, it is unclear if this is associated with a reduced risk for complications such as variceal bleeding and ascites.
Cognitive function. It is unclear if oral taurine is beneficial for improving cognitive function; however, taking an energy drink (Red Bull Energy Drink) containing taurine and other ingredients may modestly improve some measures of cognitive function. Details: Levels of taurine decrease with age, but supplementation does not seem to have neuroprotective effects or cognitive benefits in the elderly (101471,110574,110578). In one small crossover study, taurine alone did not reduce errors in sleep-deprived individuals when compared with placebo (38154). However, taurine taken as part of an energy drink formulation containing taurine, caffeine, glucuronolactone, and B vitamins (Red Bull Energy Drink) improves focused and sustained attention, wakefulness, verbal reasoning, driving ability and quality, and reaction speed when compared with placebo (9899,38117,77088,77202). Preliminary clinical research in young adults also shows that consuming the Red Bull Energy Drink might improve attention and verbal reasoning, but does not seem to improve memory, when compared with placebo (9899,77088).
Cystic fibrosis. Oral taurine may reduce steatorrhea in children with cystic fibrosis, but it does not seem to improve other measures of nutritional status. Details: Some small clinical studies in children with cystic fibrosis show that taking taurine 30-40 mg/kg daily for 7 days to 6 months might be useful as adjunctive therapy to reduce steatorrhea when compared with baseline or placebo (10455,77227,77231). However, it does not seem to improve growth, lung function, muscle protein breakdown, or other symptoms of cystic fibrosis (77224,77228). Also, adding taurine 500-1500 mg daily to treatment with ursodeoxycholic acid for up to one year does not improve liver function tests, fat absorption, or nutritional status in patients with cystic fibrosis and associated liver disease when compared with ursodeoxycholic acid alone (77246,77256).
Delirium. It is unclear if oral taurine prevents delirium in patients in the intensive care unit. Details: A large clinical study of hospitalized adults in Iran who underwent liver transplantation shows that taking a specific taurine powder product (100% Taurine Amino Acid, MyProtein) 2 grams daily for 30 days post-transplant reduces the risk of delirium by 73% when compared with placebo. These results also suggest that for every four patients treated with taurine over placebo, one additional case of delirium is prevented. Patients who took taurine also had less time on the ventilator and shorter intensive care and hospital stays (110575). However, it is unclear if these effects are due to taurine or other factors since ventilator time and intensive care length of stay are risk factors for delirium.
Diabetes. It is unclear if oral taurine is beneficial in patients with diabetes. Details: Plasma levels of taurine are reported to be lower in patients with diabetes than in healthy controls (101473). However, clinical research evaluating taurine for glycemic control is mixed (77074,103212). One small clinical trial in patients with type 2 diabetes shows that taking taurine 1 gram three times daily for 8 weeks reduces blood glucose, insulin resistance, total cholesterol, and low-density lipoprotein (LDL) cholesterol when compared with placebo (103212). Although there was no improvement in glycated hemoglobin (HbA1c), the study was not long enough to detect a meaningful reduction in HbA1c. Other preliminary clinical research shows that taking taurine 1-1.5 grams twice daily for 2-4 months does not affect fasting blood glucose, HbA1c, or insulin but may improve measures of insulin resistance in patients with type 2 diabetes when compared with placebo (77074,112271). However, taking taurine while following an exercise program 3 times weekly does appear to reduce fasting blood sugar and HbA1c when compared with exercise plus placebo (112271). The reasons for these discrepant findings are unclear; however, all the included studies were small and potentially inadequately powered to detect a difference in outcomes.
Epilepsy. Although there has been interest in using oral taurine for epilepsy, there is insufficient reliable information about the clinical effects of taurine for this condition.
Exercise-induced muscle soreness. Small clinical studies suggest that oral taurine may modestly improve exercise-induced muscle soreness. Details: One small clinical trial in healthy, untrained adults shows that taking taurine 2 grams in combination with branched chain amino acids (BCAAs) three times daily for 2 weeks reduces subjective muscle soreness by 37% when compared with placebo (77212). Another small clinical trial in young, untrained males shows that taking taurine (Taisho Pharmaceutical Co., LTD.) 2 grams three times daily after meals before exercise, and continuing for three days after exercise, reduces delayed onset muscle soreness (DOMS), but not creatine kinase levels, when compared with placebo (91513).
Fatigue. It is unclear if oral taurine is beneficial for improving fatigue. Details: One small clinical trial shows that taurine seems to reduce fatigue when taken alone, but increases fatigue when taken in combination with caffeine (77202). However, an observational study in young adults has found that subjective scores for physical and mental fatigue do not seem to correlate with dietary taurine intake (101472). One small clinical trial shows that drinking 500 mL of an energy drink providing taurine 1 gram plus other ingredients including caffeine and B vitamins decreases measures of driving-related fatigue in a driving simulation when compared with placebo (91075).
Helicobacter pylori. It is unclear if oral taurine can aid in the eradication of helicobacter pylori (H. pylori). Details: One clinical trial shows that taking taurine 500 mg twice daily in combination with conventional treatment for 6 weeks increases H. pylori eradication and shortens duodenal ulcer scarring time in patients with confirmed H. pylori infection when compared with conventional treatment alone (77145).
Hyperlipidemia. It is unclear if oral taurine is beneficial for lowering lipid levels. Details: A meta-analysis of 12 small clinical trials in adults with various liver or metabolic disorders, but without a specific diagnosis of hyperlipidemia, shows that taurine supplementation reduces total cholesterol by 11 mg/dL and triglycerides by 13 mg/dL, but does not seem to improve low-density lipoprotein (LDL) cholesterol or high-density lipoprotein (HDL) cholesterol levels, when compared with placebo. The studies included in this analysis evaluated doses of 0.5-6 grams daily for 15 days to 6 months (104166). The benefits of taurine in adults with hyperlipidemia are unclear. The effect of taurine has also been investigated in combination with exercise. A very small study in adults with type 2 diabetes on antidiabetes medication shows that taking taurine 500 mg twice daily while participating in an exercise program 3 times weekly for 8 weeks reduces triglycerides, total cholesterol, and LDL cholesterol and increases HDL cholesterol when compared with exercise plus placebo (112271).
Hypertension. Oral taurine may modestly reduce blood pressure in patients with hypertension; however, the long-term antihypertensive effects of taurine are unclear. Details: One clinical study in patients with elevated blood pressure or stage 1 hypertension shows that taking taurine 1.6 grams daily for 12 weeks reduces systolic blood pressure (SBP) by 5 mmHg and diastolic blood pressure (DBP) by 3 mmHg when compared with placebo. The benefit is seen after 8 weeks of continued supplementation (95614). A small clinical trial in patients with stage 2 hypertension (previously classified as borderline hypertension) shows that taking taurine 6 grams daily for 7 days reduces both SBP and DBP when compared to baseline (77229). The long-term effects of taurine on blood pressure are unclear. A meta-analysis of 12 small clinical trials in adults with various liver or metabolic disorders, but without a specific hypertension diagnosis, shows that taurine supplementation reduces SBP by 5 mmHg and DBP by 3 mmHg when compared with placebo. The studies included in this analysis evaluated doses of 0.5-6 grams daily for 15 days to 6 months (104166). Taurine is commonly found in energy drinks, and its effect on blood pressure when used in combination with other ingredients in the form of an energy drink has been evaluated. A small observational study in young adults suggests that drinking a specific combination product containing taurine 100 mg, caffeine, and group B vitamins (Redbull Energy Drink) reduces heart rate but does not change SBP or DBP when compared to baseline (112266). However, another small observational study in young healthy adults suggests that drinking a specific combination product containing taurine 2000 mg, caffeine, ginseng, glucuronolactone, inositol, guarana, L-carnitine, and B vitamins (Monster Energy Drink) increases both SBP and DBP by about 16 mmHg and raises heart rate by 17 beats per minute 15 minutes after consumption when compared to baseline. However, 90 minutes after consumption only DBP and heart rate remain elevated (112268). In both studies, the validity of the effects is limited by a lack of a comparator group. Additionally, it is unclear if the effects are due to taurine, other ingredients, or the combination.
Infant development. Higher maternal intake of taurine from the diet may be linked to increased newborn length and weight; however, feeding taurine-containing formula to newborns does not appear to improve infant development. Details: One observational study has found a positive correlation between maternal dietary taurine intake and newborn length. In pregnant patients with high taurine intake (>120 mg/day), neonatal birth weight and length were significantly higher when compared with groups with lower taurine intake (101474). However, clinical research shows that administering infant formula containing taurine 45 mg/L for up to 12 weeks does not affect weight, length, head circumference, or behavior in preterm and full-term infants when compared with formula without taurine (77119,77216,77218,77239,77260).
Iron deficiency anemia. It is unclear if oral taurine is beneficial in patients with iron deficiency anemia. Details: One small clinical trial in females with iron deficiency anemia shows that taking taurine 1000 mg plus ferrous sulfate 325 mg daily for 20 weeks improves hemoglobin concentrations, red blood cell counts, and serum ferritin levels when compared with ferrous sulfate plus placebo (77070).
Muscular dystrophy. It is unclear if oral taurine is beneficial in patients with muscular dystrophy. Details: One very small crossover trial in patients with muscular dystrophy shows that taking taurine 100-150 mg/kg for 6 months improves the ability to relax muscles after voluntary use when compared with placebo (77235).
Physical performance. It is unclear if oral taurine improves physical performance in older adults. Details: A small study in elderly females living in a care facility shows that taking taurine powder 1.5 grams daily for 14 weeks in addition to standardized exercise training may modestly improve some measures of physical fitness (i.e. agility, endurance) when compared to baseline. These measures were not improved in patients who took taurine but did not participate in exercise training or who participated in exercise training but did not take taurine (110574). The validity of these findings is limited by lack of randomization, blinding, and statistical comparison between groups.
Postoperative recovery. It is unclear if oral taurine is beneficial for improving postoperative recovery. Details: One small clinical trial in patients recovering from surgery after a hip fracture shows that taking taurine 6 grams daily for 7 days after surgery does not improve morbidity and mortality outcomes after 1 year when compared with placebo (95615).
Psychosis. It is unclear if oral taurine is beneficial in patients with psychosis. Details: One small clinical trial in adults up to 25 years of age with first-episode psychosis shows that taking taurine 4 grams daily for 12 weeks in combination with prescribed antipsychotics reduces positive psychotic symptoms, but not negative or cognitive symptoms, when compared with placebo (95612).
Sleep deprivation. Oral taurine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination product containing taurine, caffeine, glucuronolactone, and B vitamins (Red Bull Energy Drink) reduces lane drifting and sleepiness and improves driving quality and reaction time during a car-driving simulator exercise in sleep-deprived individuals when compared with placebo (38117,77066). Other preliminary clinical research in sleep-deprived surgical trainees shows that taking taurine 2 grams in addition to caffeine 150 mg improves reaction time during performance of simulated laparoscopic surgery when compared with placebo, although error-making is not reduced (38154).
Tourette syndrome. Oral taurine may improve tic severity in children with Tourette syndrome who are taking tiapride at a dose of 300 mg or less. Taurine may not be effective in children taking higher doses of tiapride. Details: One clinical trial in children 6-16 years of age with Tourette syndrome or other tic disorders shows that taking taurine along with tiapride reduces the severity of tics when compared with tiapride alone. For every 6 children taking taurine, one additional child saw a 60% or greater reduction in tic severity as measured on the Yale Global Tic Severity Scale when compared with placebo. However, taurine did not improve tic severity in children taking tiapride at a dose greater than 300 mg daily (103210). Taurine was taken in age-dependent doses of 2.4 grams daily in those 6-8 years, 3.6 grams daily in those 9-13 years, and 4.8 grams daily in those 14-16 years.
Traumatic brain injury (TBI). It is unclear if oral taurine is beneficial in patients with a TBI. Details: A small clinical study of adults in Iran receiving treatment in the intensive care unit (ICU) following TBI shows that adding a specific taurine powder product (Nutricost) 30 mg/kg/day up to 3 grams daily to enteral nutrition for 14 days may modestly improve disease severity scores, but does not reduce days on the ventilator, ICU length of stay, or mortality at 30 days when compared with usual enteral nutrition (110573). Due to its small size, this study may have been underpowered to detect differences between groups. More evidence is needed to rate taurine for these uses.

Safety view details

Below is general information about the safety of the known ingredients contained in the product Detox Pro Lemon and Lime Flavour. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

BROCCOLI (Brassica oleracea var. italica, Dry, Powder)

LIKELY SAFE ...when used orally in food amounts (14145). There is insufficient reliable information available about the safety of broccoli when used in medicinal amounts.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts (14145). There is insufficient reliable information available about the safety of broccoli when used in medicinal amounts during pregnancy and lactation; avoid using.

LIKELY SAFE ...when used orally and appropriately. Choline is safe in adults when taken in doses below the tolerable upper intake level (UL) of 3.5 grams daily (3094) ...when used intravenously and appropriately. Intravenous choline 1-4 grams daily for up to 24 weeks has been used with apparent safety (5173,5174).

POSSIBLY UNSAFE ...when used orally in doses above the tolerable upper intake level (UL) of 3. 5 grams daily. Higher doses can increase the risk of adverse effects (3094).

CHILDREN: LIKELY SAFE
when used orally and appropriately (3094). Choline is safe in children when taken in doses below the tolerable upper intake level (UL), which is 1 gram daily for children 1-8 years of age, 2 grams daily for children 9-13 years of age, and 3 grams daily for children 14-18 years of age (3094).

CHILDREN: POSSIBLY UNSAFE
when used orally in doses above the UL. High doses can increase the risk of adverse effects (3094).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Choline is safe when taken in doses below the tolerable upper intake level (UL), which is 3 grams daily during pregnancy and lactation in those up to 18 years of age and 3.5 grams daily for those 19 years and older (3094,92114). There is insufficient reliable information available about the safety of choline used in higher doses during pregnancy and lactation.

GLUTAMINE

LIKELY SAFE ...when used orally and appropriately. Glutamine has been safely used in clinical research in doses up to 40 grams per day or 1 gram/kg daily (2334,2337,2338,2365,5029,5462,7233,7288,7293), (52288,52307,52308,52311,52313,52337,52349,52350,96516,97366). A specific glutamine product (Endari) is approved by the US Food and Drug Administration (FDA) (96520). ...when used intravenously. Glutamine has been safely incorporated into parenteral nutrition in doses up to 600 mg/kg daily in clinical trials (2363,2366,5448,5452,5453,5454,5458,7293,52272,52275), (52283,52289,52304,52306,52316,52341), (52359,52360,52371,52377,52381,52284,52385,52408,96637,96507,96516).

CHILDREN: LIKELY SAFE
when used orally and appropriately. Glutamine has been shown to be safe in clinical research when used in amounts that do not exceed 0.7 grams/kg daily in children 1-18 years old (11364,46657,52321,52323,52363,86095,96517). A specific glutamine product (Endari) is approved by the US Food and Drug Administration for certain patients 5 years of age and older (96520). ...when used intravenously. Glutamine has been safely incorporated into parenteral nutrition in doses up to 0.4 grams/kg daily in clinical research (52338,96508). There is insufficient reliable information available about the safety of glutamine when used in larger amounts in children.

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods. There is insufficient reliable information available about the safety of glutamine when used in larger amounts as medicine during pregnancy or lactation.

GLYCINE

POSSIBLY SAFE ...when used orally and appropriately. Glycine has been used safely at doses up to 6 grams daily for 4 weeks (106497) and doses up to 9 grams daily for 3 days (10250,10251,10252,92319). There is insufficient reliable information available about the safety of glycine when used topically.

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

INOSITOL

POSSIBLY SAFE ...when used orally and appropriately, short-term. Inositol has been used with apparent safety in doses up to 18 grams daily for up to 6 weeks or 6 grams daily for 10 weeks (2184,2185,2187,95089). Myo-inositol 4 grams daily has also been used with apparent safety for 6 months (95085). There is insufficient reliable information available about the safety of inositol when used topically.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. Inositol 80 mg/kg (maximum 2 grams) has been taken daily for up to 12 weeks in children aged 5-12 years (95092). ...when used enterally or intravenously and appropriately in premature infants for treating acute respiratory distress syndrome for up to 10 days (2191,2192,91546,91551).

CHILDREN: POSSIBLY UNSAFE
when used enterally or intravenously for extended durations in premature infants. A large clinical study in infants born at less than 28 weeks' gestation found that myo-inositol 40 mg/kg, given intravenously and then enterally every 12 hours for up to 10 weeks, was associated with a small increased risk of death (98946). Long-term follow-up until 24 months corrected age confirms that the initial increase in mortality rate in the myo-inositol group remained stable; however, there was no difference in a composite outcome of death or survival with moderate or severe neurodevelopmental impairment, as well as no difference in the risk of retinopathy of prematurity, between those who received myo-inositol or control (108819).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term. Myo-inositol has been used with apparent safety in amounts up to 4000 mg daily during pregnancy (91548,95082,104688).

LACTATION:
Insufficient reliable information available; avoid using. Breast milk is rich in endogenous inositol (2138); however, the effects of exogenously administered inositol are not known.

LIKELY SAFE ...when used orally in amounts found in foods. There is insufficient reliable information available about the safety of L-cysteine when used orally in amounts greater than those found in foods or when used topically.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts found in foods. There is insufficient reliable information available about the safety of amounts greater than those found in foods; avoid use. Some research suggests that taking L-cysteine during lactation increases levels of free L-cysteine in breastmilk. However, these levels are lower than those found in some commercial hydrolyzed protein infant formulas (109718).

METHIONINE

LIKELY SAFE ...when used orally in amounts commonly found in food (94500).

POSSIBLY SAFE ...when used orally or intravenously and appropriately in medicinal amounts under the supervision of a healthcare professional (2410,2411,2413).

POSSIBLY UNSAFE ...when used orally or intravenously in excessive doses. Doses larger than 100 mg/kg should be avoided to prevent severe and potentially lethal cerebral effects (9339).

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (94500).

CHILDREN: POSSIBLY SAFE
when used intravenously and appropriately (9338).

CHILDREN: POSSIBLY UNSAFE
when used intravenously in infants receiving parenteral nutrition. In infants, blood methionine concentration can increase due to lower enzyme activity and inability to metabolize methionine. High levels of methionine can cause liver toxicity (9338).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food (94500). There is insufficient reliable information available about the safety of methionine in medical doses during pregnancy and lactation; avoid using.

LIKELY SAFE ...when used orally in moderate amounts (18). Large amounts may lead to gastrointestinal irritation (18).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid very large doses.

TAURINE

LIKELY SAFE ...when used in amounts found in foods. Typical daily intakes for adults range from 40-400 mg (101471).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Taurine 2-4 grams daily in two or three divided doses has been used safely in studies lasting up to 3 months (5248,5271,8217,8221,10454,77147,95612,98337,104165,104167). Higher doses of taurine 6 grams daily have been used safely in studies lasting up to 4 weeks (98336,98337). A risk assessment of orally administered taurine has identified an Observed Safe Level (OSL) of up to 3 grams daily for healthy adults (31996).

CHILDREN: LIKELY SAFE
when used in amounts found in foods.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in medicinal amounts. Taurine 2.4-4.8 grams daily in three divided doses has been safely used in children 6-16 years of age for up to 12 weeks (103210).

PREGNANCY AND LACTATION: LIKELY SAFE
when used in amounts found in foods. There is insufficient reliable information available about the safety of taurine when used in medicinal amounts during pregnancy and lactation; avoid using.

Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product Detox Pro Lemon and Lime Flavour. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

BROCCOLI (Brassica oleracea var. italica, Dry, Powder)

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, broccoli might reduce the levels and effects of drugs metabolized by CYP1A2.

Details

Pharmacokinetic research in humans shows that eating 500 grams of fresh broccoli daily for 6-12 days can increase CYP1A2 activity by 10% to 200% (19608,95722). Induction of CYP1A2 activity by broccoli is attributed to its glucosinolate constituents (19608).

CYTOCHROME P450 2A6 (CYP2A6) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, broccoli might reduce the levels and effects of drugs metabolized by CYP2A6.

Details

Pharmacokinetic research in humans shows that eating 500 grams of broccoli daily for 6 days increases CYP2A6 activity by 135% to 550%. Induction of CYP2A6 activity is attributed to its glucosinolate constituents (19608).

ATROPINE

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, choline might decrease the effects of atropine in the brain.

Details

Animal research shows that administering choline one hour before administering atropine can attenuate atropine-induced decreases in brain levels of acetylcholine (42240). Theoretically, concomitant use of choline and atropine may decrease the effects of atropine.

GLUTAMINE

ANTICONVULSANTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, glutamine might antagonize the effects of anticonvulsant medications.

Details

Glutamine is metabolized to the excitatory neurotransmitter glutamate. Glutamate might have antagonistic effects with anticonvulsant drugs (7292,7293,7294). However, this interaction has not yet been reported in humans.

GLYCINE

CLOZAPINE (Clozaril)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Theoretically, glycine might decrease the effectiveness of clozapine.

Details

One small clinical study in patients with schizophrenia shows that adding glycine to clozapine therapy worsens symptoms of schizophrenia when compared with clozapine alone (10253). The mechanism of this interaction is unclear.

INOSITOL

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = A

Theoretically, taking inositol with antidiabetes drugs might increase the risk of hypoglycemia.

Details

Clinical research shows that inositol lowers blood glucose levels and glycated hemoglobin (HbA1c) levels in patients with diabetes (95083,95084,95088).

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, taking L-cysteine supplements with antidiabetes drugs might increase the risk of hypoglycemia.

Details

Animal research suggests that L-cysteine can have hypoglycemic effects (109722).

METHIONINE

None known.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, radish might increase the risk of hypoglycemia when taken with antidiabetes drugs.

Details

Animal research shows that radish extract, juice, and sprouts can reduce glucose levels (96960). Animal research also shows that radish root juice 300 mg/kg reduces fasting and postprandial blood glucose in a rat model of diabetes, with effects similar to glibenclamide (98051).

TAURINE

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = D

Theoretically, taurine might increase the risk of hypotension when taken with antihypertensive drugs.

Details

Some clinical evidence suggests that taurine can reduce both systolic and diastolic blood pressure (77229,95614,104166).

LITHIUM

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = D

Theoretically, taurine might reduce excretion and increase plasma levels of lithium.

Details

Taurine is thought to have diuretic properties (3647), which might reduce the excretion of lithium.

Report an Adverse Reaction to Detox Pro Lemon and Lime Flavour

Adverse Effects view details

Below is general information about the adverse effects of the known ingredients contained in the product Detox Pro Lemon and Lime Flavour. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

BROCCOLI (Brassica oleracea var. italica, Dry, Powder)

General ...Broccoli is well tolerated when consumed as food. A thorough evaluation of safety outcomes when broccoli is taken as medicine has not been conducted.

Dermatologic ...Topically, allergic reactions to broccoli have caused contact dermatitis (14158).

Gastrointestinal ...Orally, loose stools, diarrhea, abdominal pain, and abdominal cramping have been reported following intake of broccoli seed and sprout extracts, particularly at high doses (114753).

Hepatic ...In one case report, a 56-year-old adult developed elevated transaminases, with alanine aminotransferase (ALT) 5. 8 times above normal, aspartate aminotransferase (AST) 2.4 times above normal, and gamma-glutamyl transpeptidase (GGT) 5.1 times above normal. This was thought to be related to the consumption of 800 mL of broccoli juice daily over a 4-week period. Values returned to normal 15 days after cessation of juice consumption (96191).

Immunologic ...Topically, allergic reactions to broccoli have caused contact dermatitis (14158).

General ...Orally, choline is well tolerated when used appropriately. Adverse effects have been reported with doses exceeding the tolerable upper intake level (UL) of 3.5 grams daily.
Most Common Adverse Effects:
Orally: Fishy body odor. At high doses of at least 9 grams daily, choline has been reported to cause diarrhea, nausea, salivation, sweating, and vomiting.

Cardiovascular ...Orally, doses of choline greater than 7. 5 grams daily may cause low blood pressure (94648).

Gastrointestinal ...Orally, large doses of choline can cause nausea, vomiting, salivation, and anorexia (42275,91231). Gastrointestinal discomfort has reportedly occurred with doses of 9 grams daily, while gastroenteritis has reportedly occurred with doses of 32 grams daily (42291,42310). Doses of lecithin 100 grams standardized to 3.5% choline have reportedly caused diarrhea and fecal incontinence (42312).

Genitourinary ...Orally, large doses of choline greater than 9 grams daily have been reported to cause urinary incontinence (42291).

Neurologic/CNS ...Orally, high intake of choline may cause sweating due to peripheral cholinergic effects (42275).

Oncologic ...In one population study, consuming large amounts of choline was associated with an increased risk of colorectal cancer in females, even after adjusting for red meat intake (14845). However, more research is needed to confirm this finding.

Psychiatric ...Orally, large doses of choline (9 grams daily) have been associated with onset of depression in patients taking neuroleptics. Further research is needed to clarify this finding (42270).

Other ...Orally, choline intake may cause a fishy body odor due to intestinal metabolism of choline to trimethylamine (42285,42275,42310,92111,92112).

GLUTAMINE

General ...Orally and intravenously, glutamine is generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, bloating, constipation, cough, diarrhea, flatulence, gastrointestinal pain, headache, musculoskeletal pain, nausea, and vomiting.

Endocrine ...One case of hot flashes has been reported in a patient taking glutamine 5-15 grams orally twice daily for up to 1 year (96520).

Gastrointestinal ...Orally, glutamine has been associated with belching, bloating, constipation, flatulence, nausea, vomiting, diarrhea, and gastrointestinal (GI) pain. Nausea, vomiting, constipation, diarrhea, and GI pain have been reported in clinical trials using high-dose glutamine 10-30 grams (0.3 grams/kg) in two divided doses daily to treat sickle cell disease (99414). One case of dyspepsia and one case of abdominal pain have been reported in patients taking glutamine 5-15 grams twice daily orally for up to 1 year (96520). In a small trial of healthy males, taking a single dose of about 60 grams (0.9 grams/kg of fat free body mass [FFM]) was associated with a 50% to 79% incidence of GI discomfort, nausea, and belching, compared with a 7% to 28% incidence with a lower dose of about 20 grams (0.3 gram/kg FFM). Flatulence, bloating, lower GI pain, and urge to regurgitate occurred at similar rates regardless of dose, and there were no cases of heartburn, vomiting, or diarrhea/constipation (105013). It is possible that certain GI side effects occur only after multiple doses of glutamine.

Musculoskeletal ...Orally, glutamine 30 grams daily has been associated with cases of musculoskeletal pain and non-cardiac chest pain in clinical trials for patients with sickle cell disease (99414).

Neurologic/CNS ...Orally, glutamine has been associated with dizziness and headache. A single case of dizziness has been reported in a patient treated with oral glutamine 0.5 grams/kg. However, the symptom resolved after reducing the dose to 0.25 grams/kg (91356). Mania and hypomania have been reported in 2 patients with bipolar disorder taking commercially purchased glutamine up to 4 grams daily (7291). Glutamine is metabolized to glutamate and ammonia, both of which might have neurological effects in people with neurological and psychiatric diseases or in people predisposed to hepatic encephalopathy (7293).

Oncologic ...There is some concern that glutamine might be used by rapidly growing tumors and possibly stimulate tumor growth. Although tumors may utilize glutamine and other amino acids, preliminary research shows that glutamine supplementation does not increase tumor growth (5469,7233,7738). In fact, there is preliminary evidence that glutamine might actually reduce tumor growth (5469).

Other ...Orally, glutamine has been associated with cough when a powdered formulation is used. It is unclear if this was due to accidental inhalation. One case of a burning sensation and one case of hypersplenism has been reported in a patient taking glutamine 5-15 grams twice daily orally for up to 1 year (96520).

GLYCINE

General ...Orally and topically, glycine seems to be well tolerated.

Gastrointestinal ...Soft stools, nausea, vomiting, and upper gastrointestinal (GI) tract discomfort have occurred rarely with oral use of glycine. These symptoms resolve rapidly with discontinuation of glycine (10252,11320,92319). Dry mouth has also been reported but any association to glycine is unclear (92321).

Neurologic/CNS ...Mild sedation has occurred rarely with oral use of glycine. Symptoms resolve rapidly with discontinuation of glycine (10252,11320,92321). Irritability, insomnia, fatigue, memory impairment, headache, and sensory impairment have been reported, but any association with glycine is unclear (92321).

INOSITOL

General ...Orally and intravenously, inositol seems to be well tolerated. Topically, no adverse effects have been reported, although a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Diarrhea, gas, and nausea.

Gastrointestinal ...Orally, inositol may cause nausea, diarrhea, gas, and gastrointestinal discomfort (10387,11972,91547,91549,95089,95090,95092).

Immunologic ...Orally, inositol in combination with omega-3 fatty acids has been associated with reports of cold and allergy symptoms in children in clinical research (95092).

Musculoskeletal ...Orally, inositol in combination with omega-3 fatty acids has been associated with reports of tics and other musculoskeletal side effects in children in clinical research (95092).

Neurologic/CNS ...Orally, inositol may cause dizziness, tiredness, insomnia, agitation, and headache (10387,11972,95089,95092). In combination with omega-3 fatty acids, inositol has been associated with reports of feelings of thirst in children in clinical research (95092).

Psychiatric ...In one case report, a 36-year-old male with adequately controlled bipolar disorder was hospitalized with symptoms of mania after consuming several cans of an energy drink containing inositol, caffeine, taurine, and other ingredients (Red Bull Energy Drink) over a period of 4 days (14302). It is not known if this is related to inositol, caffeine, taurine, a different ingredient, or a combination of the ingredients.

General ...Orally, L-cysteine is well tolerated in amounts found in foods. When used in higher doses or when applied topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.

METHIONINE

General ...Orally, methionine is well tolerated when used in amounts commonly found in foods. Intravenously, methionine is generally well tolerated.
Most Common Adverse Effects:
All ROAs: Dizziness, drowsiness, hypotension, irritability, and vomiting. Methionine may also cause headache, increased homocysteine levels, increased urinary calcium excretion, and leukocytosis.
Serious Adverse Effects (Rare):
All ROAs: Cerebral edema, hepatic encephalopathy. In infants, intravenous methionine has been linked to liver toxicity.

Cardiovascular ...Orally or intravenously, methionine can cause hypotension (9339,9340). High-dose methionine (75-100 mg/kg daily) may increase plasma concentrations of homocysteine, which is a risk factor for vascular disease (63112,63114,63115). However, a study of patients with type 2 diabetes and a history of cardiovascular disease (CVD) showed that methionine loading did not increase homocysteine concentrations, and that a cause-effect relationship between increased intake of methionine and endothelial dysfunction has not been clearly established (63110).

Gastrointestinal ...Orally or intravenously, methionine can cause vomiting (9339,9340).

Genitourinary ...Orally or intravenously, methionine may increase urinary calcium excretion (9340,63112,94095).

Hematologic ...Orally or intravenously, methionine may cause leukocytosis when used at a dose of 8-13. 9 grams daily for 4-5 days (9340).

Hepatic ...A single dose of 8 grams of methionine has reportedly caused hepatic encephalopathy in patients with cirrhosis (9340). Long-term use of methionine-containing parenteral nutrition solution has been linked to liver toxicity in infants (9338).

Neurologic/CNS ...Orally or intravenously, methionine can cause dizziness, drowsiness, headache, and irritability (9339,9340,94095).
A case of cerebral edema ultimately leading to death has been reported in a patient receiving methionine 100 mg/kg orally. The post-load plasma concentrations of methionine were substantially higher in this patient than those previously reported in humans receiving this usual oral loading dose, leading the authors to postulate that an overdose of methionine may have been administered erroneously. This can occur when plasma methionine levels rise above 3000 mcmol/L (9339). Another case of progressive cerebral edema associated with high methionine levels and betaine (N,N,N-trimethylglycine) therapy in a patient with cystathionine beta-synthase (CBS) deficiency has been reported (63119). The authors stated that the cerebral edema was most likely precipitated by the betaine therapy, but that the exact mechanism is uncertain.

Oncologic ...Although one case-control study of incident, histologically-confirmed gastric cancer has indicated that a diet rich in methionine, salt, and nitrite is associated with an increased risk of gastric cancer (2409), a large observational study that adjusted for multiple factors, including sodium intake, has found no association between high dietary intake of methionine and gastric cancer (108041).

General ...Orally, radish seems to be well tolerated when used in moderate amounts.

Gastrointestinal ...Large amounts of radish may cause irritation of the gastrointestinal mucus membrane (18). Mild indigestion has also been associated with use of a specific product containing radish, camu camu, acerola, honey, and tapioca in clinical research. However, it is unclear if this adverse event is due to radish, other ingredients in the product, or the combination (94290).

Immunologic ...A case of allergy to oral intake of radish has been reported. Symptoms included throat tightness and generalized urticaria (94289).

TAURINE

General ...Orally, taurine is generally well-tolerated when used in typical doses for up to one year.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, and dyspepsia.
Serious Adverse Effects (Rare):
Orally: Hypersensitivity reactions in sensitive individuals. Case reports raise concerns for serious cardiovascular adverse effects, but these reports have involved energy drinks containing taurine and other ingredients. It is unclear if these adverse effects are due to taurine, other ingredients, or the combination.

Cardiovascular ...Changes in heart rate and increased blood pressure have been reported following the co-administration of taurine and caffeine, although the effects of taurine alone are unclear (77088). In healthy individuals, consumption of energy drinks containing taurine increased platelet aggregation and decreased endothelial function (77151,112268,112741). A case of cardiac arrest following strenuous exercise and an excessive intake of energy drinks containing caffeine and taurine has been reported (77136). In another case report, a 28-year-old male without cardiovascular risk factors presented to the hospital with radiating chest pain, shortness of breath, and diaphoresis after excessive intake of an energy drink containing taurine, caffeine, sugar, and glucuronolactone. Electrocardiogram findings confirmed myocardial infarction, and subsequent catheterization confirmed thrombotic occlusion (112741).

Endocrine ...Orally, taurine has been reported to cause hypoglycemia (77153).

Gastrointestinal ...Orally, constipation has been reported following the administration of taurine (77231). Dyspepsia has also been reported after oral taurine use (104165).

Hematologic ...In clinical research, taurine reduced platelet aggregation (77245). A case of massive intravascular hemolysis, presenting with confusion, dark urine, dyspnea, emesis, and fever, has been reported following the administration of a naturopathic vitamin infusion containing taurine, free amino acids, magnesium, and a vitamin B and D complex (77177). However, the effects of taurine alone are unclear.

Immunologic ...A case report describes a hypersensitivity reaction in a female patient with a history of allergies to sulfonamides, sulfites, and various foods, after ingestion of taurine and other sulfur-containing supplements. The amount of taurine in the products ranged from 50-500 mg per dose. The allergic reaction recurred upon rechallenge with taurine 250-300 mg (91514).

Neurologic/CNS ...In a case study, encephalopathy occurred in a body-builder who took approximately 14 grams of taurine in combination with insulin and anabolic steroids. It is not known if this was due to the taurine or the other drugs taken (15536).
Cases of seizures following the consumption of energy drinks containing taurine have been reported (77105,77196). In clinical research, taurine has been reported to cause drowsiness and ataxia in epileptic children (77241).

Psychiatric ...In a case report, a 36-year-old male with adequately controlled bipolar disorder was hospitalized with symptoms of mania after consuming several cans of an energy drink containing taurine, caffeine, glucuronolactone, B vitamins, and other ingredients (Red Bull Energy Drink) over a period of four days (14302). It is unknown if this effect was related to taurine.

Pulmonary/Respiratory ...In human research, an exacerbation of pulmonary symptoms of cystic fibrosis has been associated with taurine supplementation, although this could also be caused by progression of the disease (77231).

Renal ...A case of acute kidney failure has been reported following the concomitant intake of 1 liter of vodka and 3 liters of an energy drink providing taurine 4. 6 grams, caffeine 780 mg, and alcohol 380 grams (77185).

Report an Adverse Reaction to Detox Pro Lemon and Lime Flavour