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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there has been interest in using oral GABA for anxiety, there is insufficient reliable information about the clinical effects of GABA for this condition.
• Athletic performance. Although there has been interest in using sublingual GABA for athletic performance, there is insufficient reliable information about the clinical effects of GABA for this purpose.
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral GABA for ADHD, there is insufficient reliable information about the clinical effects of GABA for this condition.
• Cerebral palsy. It is unclear if oral GABA is beneficial for cerebral palsy in children. Details: Preliminary clinical research in children with cerebral palsy shows that taking a specific product containing GABA (Gammalon) one to four tablets daily (depending on age) for 2 months, in addition to standard therapy for cerebral palsy, improves mental development, learning, vocabulary, physical function, motor strength and activity, and motor hyperactivity in a greater percentage of children when compared with standard therapy alone (19362). These findings are limited by poor study design.
• Chronic bronchitis. It is unclear if oral GABA is beneficial for chronic bronchitis. Details: Preliminary clinical research in adults with chronic bronchitis shows that taking a specific GABA product (Aminalon) 1.5-3 grams daily for 18-20 days, along with conventional treatment for acute exacerbations of bronchitis, increases the duration of subsequent remission by about 3 months when compared with conventional treatment alone (19361).
• Cushing syndrome. It is unclear if oral GABA is beneficial for Cushing syndrome. Details: Preliminary clinical research shows that taking a specific GABA product (Aminalon) 1-3 grams daily for one month decreases plasma levels of adrenocorticotropic hormone (ACTH) 60 minutes after administration, as well as cortisol and ACTH levels up to 2 days after GABA discontinuation, when compared with baseline (19363). The validity of these findings is limited by the lack of a comparator group.
• Depression. Although there has been interest in using oral GABA for depression, there is insufficient reliable information about the clinical effects of GABA for this condition.
• Epilepsy. It is unclear if oral GABA is beneficial for epilepsy. Details: Preliminary clinical research shows that taking a combination of GABA 2.5-3 grams and phosphatidylserine 500 mg daily for 3-8 months reduces seizure frequency when compared with placebo in patients with absence seizures, but not in those with focal aware or focal impaired awareness seizures (19364). Other preliminary clinical research suggests that taking GABA 3 grams with phosphatidylserine 600-1200 mg daily for 2 days does not affect the seizure photosensitivity range in people with photoconvulsive responses (5113).
• Hypertension. Preliminary clinical research suggests that oral GABA may modestly reduce blood pressure in patients with mild or borderline hypertension. Details: Preliminary clinical research in adults with hypertension shows that drinking 100 mL of fermented milk containing GABA 10-12 mg daily at breakfast for 12 weeks reduces systolic and diastolic blood pressure by about 17 mmHg and 7 mmHg, respectively, when compared with baseline. Compared with patients treated with a placebo milk, these reductions were significant. However, it is unclear if the placebo milk also differed from the fermented milk in other ways (19367). Other preliminary clinical research in patients with borderline hypertension shows that taking a chlorella supplement containing GABA 20 mg twice daily for 12 weeks reduces systolic blood pressure when compared with placebo (19368). However, these findings are limited by poor study design.
• Insomnia. It is unclear if oral GABA is beneficial for insomnia. Details: Two small clinical studies in adults with insomnia show that taking fermented rice germ extract, standardized to provide GABA 75 mg or 300 mg, one hour before bedtime for 4 weeks modestly decreases sleep latency when compared with placebo, but does not improve sleep efficacy or reduce episodes of waking after sleep onset (110134,110135). As these doses were evaluated in separate studies, no direct comparison between GABA 75 mg and 300 mg has been conducted.
• Meningitis. It is unclear if oral GABA is beneficial for meningitis. Details: Preliminary clinical research in children aged 7 months to 16 years with meningitis shows that taking a specific GABA product (Aminalon) 0.5-1.5 grams daily, starting within 2-4 weeks of illness and continuing for one month thereafter, decreases the incidence of residual disease manifestations and prevents the development of cerebrospinal syndrome when compared with control (19369). However, this study was conducted prior to the development of current treatment guidelines for meningitis; it is unclear if GABA is beneficial when used in conjunction with current standard care.
• Menopausal symptoms. Although there has been interest in using oral GABA for menopausal symptoms, there is insufficient reliable information about the clinical effects of GABA for this purpose.
• Motion sickness. It is unclear if oral GABA is beneficial for motion sickness. Details: Preliminary clinical research shows that taking a specific GABA product (Aminalon) 0.5 grams as a single dose 40-50 minutes before induced motion sickness or three times daily for 4 days significantly delays onset of motion sickness when compared with placebo. GABA also decreases the occurrence of motion sickness symptoms including chills, cold sweats, and pallor when compared with placebo (19370).
• Obesity. Although there has been interest in using oral and sublingual GABA for weight loss, there is insufficient reliable information about the clinical effects of GABA for this purpose.
• Pain (acute). Although there has been interest in using oral and sublingual GABA for acute pain, there is insufficient reliable information about the clinical effects of GABA for this purpose.
• Post-traumatic stress disorder (PTSD). Although there has been interest in using oral GABA for PTSD, there is insufficient reliable information about the clinical effects of GABA for this condition.
• Premenstrual syndrome (PMS). Although there has been interest in using oral GABA for PMS, there is insufficient reliable information about the clinical effects of GABA for this condition.
• Psychological well-being. Although there has been interest in using oral and sublingual GABA to improve well-being, there is insufficient reliable information about the clinical effects of GABA for this purpose.
• Stress. It is unclear if oral GABA is beneficial for stress. Details: Preliminary clinical research shows that taking a single dose of GABA 100-200 mg by mouth 10-70 minutes prior to completing a mentally stressful task does not appear to reduce subjective measure of stress when compared with placebo (90568). However, it does attenuate alpha wave reduction and reduces beta wave upsurge on the EEG during testing when compared with placebo (19373,90568). More evidence is needed to rate GABA for these uses.

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POSSIBLY EFFECTIVE

• 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 glycemic and lipid parameters, as well as ovulation and pregnancy rates, in some patients with PCOS. Details: Inositol has shown modest benefit on metabolic parameters in patients with PCOS. A meta-analysis of clinical research shows that taking inositol (type not specified) modestly reduces fasting blood glucose, fasting insulin, total cholesterol, triglycerides, and testosterone levels when compared to control (98944). In individual clinical studies, taking D-chiro-inositol 1-1.2 grams or myo-inositol 4 grams with folic acid 400 mcg daily for 6 months decreases serum triglyceride and testosterone levels, modestly decreases blood pressure, and improves ovarian function (2028,91552). An unblinded clinical study shows that taking metformin with a combination of myo-inositol 550 mg and D-chiro-inositol 150 mg twice daily is associated with improved lipid parameters and postprandial insulin levels at 6 months when compared with metformin alone (108822). It is unclear if the improvement from baseline differed between groups. Other research shows that taking myo-inositol and D-chiro-inositol together may improve metabolic parameters faster than taking myo-inositol alone (91550). 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 shows that taking myo-inositol 2-4 grams daily, with or without folic acid, for 12-24 weeks does not improve fasting insulin, insulin resistance (HOMA-IR), androgen levels, body mass index (BMI), or waist-hip ratio when compared with metformin 1.5-2.5 grams daily, although it seems to have a lower risk of adverse effects (100705,108823). These analyses are limited due to the small size, methodological issues, and high heterogeneity of the included studies. Other research has evaluated the effects of inositol on ovulation and pregnancy outcomes. Some research suggests that inositol increases ovulation rate in patients with PCOS (98944). 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). 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). 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). It is unclear if the improvement from baseline differed between groups. The validity of these findings is limited by the unblinded nature of the study.
• 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.

POSSIBLY INEFFECTIVE

• 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: 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).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• 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: Preliminary clinical research in children aged 5-12 with bipolar disorder shows that taking a combination of inositol 80 mg/kg (maximum 2 grams) and eicosapentaenoic acid (EPA; Nordic Naturals) 3 grams daily for 12 weeks moderately reduces manic and depressive symptoms as well as symptoms of anxiety and oppositional defiant disorder. This improvement is greater than what is seen when either ingredient is taken alone (95092).
• 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. 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. 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.
• Infertility. It is unclear if oral inositol is beneficial in patients undergoing intracytoplasmic sperm injection (ICSI). 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) by mouth 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).
• 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).
• 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).
• 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.

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POSSIBLY EFFECTIVE

• 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).

POSSIBLY INEFFECTIVE

• 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).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• 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.
• 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: 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 seven 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 and recreationally active males show that taking taurine 50 mg/kg 1.5-2 hours prior to a cycling test increases the time to exhaustion when compared with placebo (101475,103211). 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). 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 1.5 grams twice daily for 4 months does not affect blood glucose, HbA1c, lipids, or insulin in patients with type 2 diabetes when compared with placebo (77074). The reasons for these discrepant findings are unclear; however, both 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.
• 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).
• 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.

(Read more about TAURINE)

POSSIBLY EFFECTIVE

• Cognitive function. Oral L-theanine may improve some aspects of cognitive function. It is unclear if using L-theanine in conjunction with caffeine can enhance the effects of either ingredient. Details: A single dose of L-theanine 100 mg seems to improve vigilant attention, reducing error rates in cognitive tests when compared with placebo (91747). However, taking L-theanine (Suntheanine, Taiyo Kagaku) 200 mg daily for 4 weeks does not improve verbal fluency, memory, motor speed, or executive function in an adult population, although it may moderately improve verbal fluency in a subgroup of people with lower cognitive function at baseline (101986). When L-theanine is combined with caffeine, a meta-analysis and multiple individual clinical studies show that the combination improves alertness, as well as accuracy during a test that requires switching attention between different tasks, but does not improve reaction time (38116,91750,96335,96336). Some research also shows that L-theanine plus caffeine improves cognitive performance and reduces task-induced fatigue when compared with baseline and placebo. However, it is unclear if this is due to the individual ingredients or the combination (38116,96335,96336). Some research suggests that the combination is no better than either individual ingredient alone (91747,96335,96336).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral L-theanine, taken continuously or as a single dose, improves cognition in older adults. Details: A small clinical study in healthy, Japanese adults aged 50-69 years shows that taking a specific product (Suntheanine; Taiyo International.) containing L-theanine 101 mg daily after breakfast for 12 weeks does not improve mini-mental state exam (MMSE) scores when compared with placebo. However, a single-dose analysis from this study shows that administration of L-theanine 101 mg may improve the quality of working memory and reaction times during a cognitive function test when compared with placebo (108553). Patients were permitted to consume polyphenol-rich beverages during the study period; however, consumption was not documented, limiting the validity of this finding.
• Alzheimer disease. Although there is interest in using oral theanine for Alzheimer disease, there is insufficient reliable information about the clinical effects of theanine for this condition.
• Anxiety. It is unclear if oral L-theanine is beneficial in patients with anxiety. Results of clinical research are conflicting. Details: A preliminary clinical study shows that taking a single dose of a specific L-theanine product (Suntheanine, Taiyo Kagaku) 200 mg does not reduce experimentally-induced anticipatory anxiety when compared with placebo (12188). However, another preliminary clinical study in healthy adults with stress-related anxiety shows that taking L-theanine 200 mg daily for 4 weeks reduces anxiety scale scores and sleep disturbance when compared with placebo (101986).
• Attention. It is unclear if oral theanine improves attention. Details: A small clinical study in healthy males shows that taking a single dose of L-theanine 200 mg improves selective attention similar to a single dose of caffeine 160 mg (96337). However, other small clinical studies in adults show that taking L-theanine 100-400 mg does not improve most measures of attention, especially sustained attention or attention in executive control tasks, but doses of 100-200 mg may improve performance in simple attentional tasks when compared with placebo (96338,111396). Some of these studies suggest that taking L-theanine with caffeine appears to provide more benefit than either individual ingredient alone (96337,96338).
• Attention deficit-hyperactivity disorder (ADHD). Oral L-theanine seems to improve some aspects of ADHD, including cognition and sleep. Details: Some preliminary clinical research in children with ADHD shows that taking a one-time dose of L-theanine 2.5 mg/kg increases cognition scores, but does not improve results on sustained attention or inhibitory control tests, when compared with placebo. Taking L-theanine with caffeine 2 mg/kg also increases cognition scores and improves performance on a sustained attention test, but does not improve inhibitory control, when compared with placebo (104141). Other preliminary clinical research in males aged 8-12 years with ADHD shows that taking a specific L-theanine product (Suntheanine, Taiyo Kagaku) 200 mg orally twice daily for 6 weeks increases the percent of time spent in restful sleep by about 5% and decreases the number of bouts of nocturnal activity by about 6 when compared with placebo (91744).
• Cancer. Although there is interest in using oral theanine for cancer, there is insufficient reliable information about the clinical effects of theanine for this condition.
• Chemotherapy-induced diarrhea. Oral L-theanine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with colon cancer shows that taking L-cystine 700 mg and L-theanine 280 mg (Ajinomoto Co. Inc.) orally once daily, starting one week before chemotherapy with TS-1 (Taiho Pharmaceutical) and continuing for 28 days, increases the rate of therapy completion by 49%, reduces the incidence of diarrhea by 37%, reduces appetite loss by 33%, and improves the reported tolerability of chemotherapy when compared with chemotherapy alone (96334). However, this combination does not appear to be beneficial in patients with gastric cancer, or in those with colorectal cancer receiving 4 courses of capecitabine-based adjuvant chemotherapy. (96334,101985).
• Cognitive impairment. Oral L-theanine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One very small clinical study in adults with mild cognitive impairment shows that taking a product containing L-theanine 120 mg and green tea extract 720 mg (LGNC-07, LG Household & Health Care, Ltd) orally twice daily after meals for 16 weeks modestly improves memory and attention when compared with baseline. However, taking this product does not appear to improve memory and attention when patients with self-reported memory problems, but without mild cognitive impairment, are also considered (96339).
• Depression. It is unclear if oral L-theanine is beneficial in patients with depression. Details: A small clinical study shows that taking a specific L-theanine product (Suntheanine, Taiyo Kagaku Co. Ltd.) 250 mg orally at bedtime for 8 weeks reduces symptoms and improves sleep quality when compared to baseline in individuals with mild major depressive disorder (MDD) (96331). The validity of these findings is limited by the lack of a comparator group.
• Erythema. Oral L-theanine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy females with self-perceived skin sensitivity shows that taking a specific supplement containing L-theanine, ashwagandha, and saffron (InnerCalm, Arbonne) daily for 8 weeks reduces facial pigmentation when compared to baseline (111399). The validity of this finding is limited by a lack of a placebo group. It is unclear if these effects are due to L-theanine, other ingredients, or the combination.
• Generalized anxiety disorder (GAD). It is unclear if oral L-theanine is beneficial for reducing anxiety in people with GAD. Details: One small clinical study in adults with GAD shows that taking L-theanine 225 mg twice daily for 4 weeks, then 450 mg twice daily for 4 weeks, in conjunction with prescribed antidepressants, does not reduce anxiety scores when compared with antidepressants and placebo (104976).
• Hypertension. Although there is interest in using oral theanine for hypertension, there is insufficient reliable information about the clinical effects of theanine for this condition.
• Influenza. Oral L-theanine 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 of green tea catechins (THEA-FLAN 90S, Ito-en Co.) 378 mg, standardized to contain epigallocatechin gallate 270 mg and L-theanine (Suntheanine, Taiyo Kagaku) 210 mg daily for 5 months reduces the risk of developing clinically diagnosed influenza when compared with placebo. However, the combination does not seem to prevent laboratory-confirmed influenza infection (54021).
• Insomnia. Oral L-theanine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with insomnia or disturbed sleep patterns shows that a specific product (RLX2; LiveLife Biosciences AG) containing L-theanine 50 mg and a specific casein peptide, alpha-s1-casein tryptic hydrolysate, 150 mg, taken one hour before bedtime for 4 weeks, increases sleep duration by 45 minutes and improves habitual sleep efficiency and daytime dysfunction when compared with baseline. However, it does not affect blood pressure, heart rate, or cortisol levels (108556). Another very small clinical study in healthy adults shows that taking a combination product containing tryptophan, glycine, magnesium, tart cherry powder, and L-theanine 2 hours before bedtime decreases sleep onset latency and increases total sleep duration, leading to better sleep efficiency and reduced morning sleepiness, when compared with placebo (111184). Another combination product containing L-theanine, ashwagandha, and saffron (InnerCalm, Arbonne), taken daily for 8 weeks, seems to improve sleep quality when compared to baseline (111399). However, the validity of this finding is limited by a lack of a control group. It is unclear if the effects described above are due to L-theanine, other ingredients, or the combination.
• Postoperative recovery. Oral theanine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study of adults with esophageal cancer undergoing esophagectomy shows that taking theanine 280 mg and cystine 700 mg daily, staring 4 days before surgery and continued for 13 days after surgery, does not improve measures of physical activity but does improve exercise tolerance and some measures of quality of life when compared with placebo (111400). It is unclear if these findings are due to theanine, cystine, or the combination.
• Schizophrenia. It is unclear if oral L-theanine is beneficial in patients with schizophrenia; the available evidence is limited and conflicting. Details: One preliminary clinical study in adults with schizophrenia or schizoaffective disorder shows that taking L-theanine (Biosynergy) 200 mg orally twice daily for 8 weeks along with antipsychotic medications improves positive symptoms, anxiety, and general psychopathology symptoms, such as poor impulse control and disorientation, when compared with placebo. However, theanine does not improve general disease severity, negative symptoms, depression, cognitive function, extrapyramidal side effects, or quality of life (96341). Another small clinical study shows that taking L-theanine 400 mg (Suntheanine, BioSynergy Health Alternatives) with pregnenolone 50 mg daily for 8 weeks, in addition to antipsychotic medications, improves negative symptoms, general psychopathology symptoms, and anxiety when compared with placebo in patients with schizophrenia or schizoaffective disorder. However, there were no improvements in positive schizophrenia symptoms or extrapyramidal side effects (97923). The inconsistency of results might be due to the small study sizes and the subjectivity of the outcomes measured.
• Stress. It is unclear if oral L-theanine is beneficial in patients with stress. Details: One very small clinical study shows that taking L-theanine 200 mg prior to a stress-inducing exam reduces tension-anxiety and may prevent blood pressure increases caused by psychological stress when compared with placebo (91746). Other preliminary clinical research in pharmacy students shows that taking theanine 200 mg twice daily for one week prior, and then for the first 10 days of a pharmacy practice period, decreases subjective stress scores when compared with placebo (91745). Another small clinical study in healthy young adults shows that drinking a beverage containing L-theanine 200 mg alone or combined with L-arginine 50 mg after a psychological stressor reduces stress, as measured by salivary alpha-amylase activity, when compared with placebo. The combination of L-arginine and L-theanine did not differ from L-theanine alone, suggesting that the combination does not act synergistically to reduce markers of stress (110393). However, not all research has been positive. A small clinical study shows that taking a specific L-theanine product (Suntheanine, Taiyo Kagaku) 200 mg induces subjective feelings of tranquility in relaxed people, but not those with experimentally-induced anticipatory anxiety, when compared with placebo (12188). Also, a small, clinical crossover study in healthy, moderately stressed adults shows that taking a single dose of a specific product (Alphawave; Ethical Naturals) containing L-theanine 200 mg prior to a stress-inducing exam does not improve anxiety at any time point when compared with placebo (108554). Due to the single-dose nature of this study, the effects of continued administration of this product are unclear. L-theanine has also been evaluated in combination with other ingredients. A small clinical study in adults with stress shows that taking a specific combination product (Mg-Teadiola, Sanofi-Aventis Group), containing green tea extract 125 mg (providing 50 mg L-theanine), magnesium 150 mg, vitamin B6 0.2 mg, vitamin B9 0.1 mg, vitamin B12 1.25 mcg, and rhodiola 222 mg, orally once daily for 28 days modestly improves stress and anxiety scores when compared with placebo. Improvements in stress scores, but not anxiety scores, appear to persist at 28 days after treatment completion (108672). It is unclear if any effects are due to L-theanine, other ingredients, or the combination.
• Tourette syndrome. It is unclear if oral L-theanine is beneficial in children with Tourette syndrome. Details: A small, nonblinded clinical study in children aged 4-17 years with untreated Tourette syndrome or with chronic tic disorder and associated symptoms of anxiety shows that taking a liquid nutritional supplement providing L-theanine 200 mg and vitamin B6 2.8 mg daily for 2 months improves scores on the Yale Global Tic Severity Scale, but does not reduce anxiety, when compared with patients receiving psychoeducation (108555). This study may have been inadequately powered to detect a difference between groups. More evidence is needed to rate theanine for these uses.

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LIKELY SAFE ...when used orally in amounts commonly found in foods.

POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. GABA has been used with apparent safety in doses of 75 mg to 1.5 grams daily for up to one month in small clinical studies (19361,19363,19369,110134,110135). There is insufficient reliable information available about the safety of GABA when used orally for longer than one month or when used sublingually or intravenously.

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

(Read more about GAMMA-AMINOBUTYRIC ACID (GABA))

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.

(Read more about INOSITOL)

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.

(Read more about TAURINE)

POSSIBLY SAFE ...when used orally and appropriately, short-term. L-theanine has been used safely in clinical research in doses of up to 900 mg daily for 8 weeks (12188,36439,96331,96332,96334,96341,97923,101986,104976). There is insufficient reliable information available about the safety of L-theanine when used long-term.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. A specific L-theanine product (Suntheanine, Taiyo Kagaku) 200 mg twice daily has been used safely in males aged 8-12 years for up to 6 weeks (91744).

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

(Read more about THEANINE)

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking GABA with antihypertensive drugs might increase the risk of hypotension.  Details Some clinical research shows that GABA can decrease blood pressure in patients with hypertension (19367).

CNS DEPRESSANTS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, GABA might have additive sedative effects when used in conjunction with CNS depressants. However, it is unclear if this concern is clinically relevant.  Details Endogenous GABA has well-established relaxant effects (51152) and GABA(A) receptors have an established physiological role in sleep (51143). However, the effects of GABA supplements are unclear, as it is unknown whether exogenous GABA crosses the blood-brain barrier (51120,51153,90570). Although there have been limited reports of drowsiness or tiredness with GABA supplements (5115,19364), these effects have not been widely reported in clinical studies. Additionally, intravenous GABA 0.1-1 mg/kg has been shown to induce anxiety in a dose-dependent manner (5116).

(Read more about GAMMA-AMINOBUTYRIC ACID (GABA))

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).

(Read more about INOSITOL)

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.

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ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theanine might lower blood pressure, potentiating the effects of antihypertensive drugs.  Details Animal research shows that theanine can lower blood pressure in spontaneously hypertensive animals (7687,77354). Theoretically, concomitant use of theanine and antihypertensive drugs might potentiate the antihypertensive activity.

CNS DEPRESSANTS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, theanine might have additive sedative effects when used in conjunction with CNS depressants. However, it is unclear if this concern is clinically relevant.  Details Theoretically, theanine may compete with glutamate and/or increase plasma gamma-aminobutyric acid (GABA) levels, which could cause CNS depression (96334). In one clinical study, some subjects taking oral theanine reported drowsiness (96331).

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General ...Orally, GABA seems to be generally well tolerated. Sublingually, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Drowsiness, gastric upset, minor throat burning, muscle weakness, and nausea.

Cardiovascular ...Intravenously, GABA can cause dose-related increases in blood pressure and pulse (5116).

Gastrointestinal ...Orally, minor throat burning has been associated with GABA in one study (5115). In another study in which GABA was administered with phosphatidylserine, one patient experienced severe gastric distress, two patients reported moderate nausea, and one reported constipation (19364). Children with cerebral palsy taking GABA experienced nausea and decreased appetite (19362).

Genitourinary ...In one study, one patient treated with oral GABA and phosphatidylserine reported transient amenorrhea (19364).

Musculoskeletal ...Orally, minor adverse effects associated with GABA included muscle weakness (5115).

Neurologic/CNS ...Orally, GABA may cause drowsiness or tiredness (5115,19364). Four children with cerebral palsy taking GABA had convulsions, and an unspecified number experienced motor restlessness. However, causality of these adverse effects was not clear, and the dose of GABA was not specified (19362). Intravenously, GABA 50 mg has been associated with a "lack of alertness" in healthy female volunteers (51159).

Psychiatric ...Intravenously, GABA 0. 1-1.0 mg/kg has been shown to induce anxiety, dysphoria, and mood disturbances in a dose-dependent manner (5116).

Other ...In one study, patients taking GABA experienced a slight warming of the body (19370).

(Read more about GAMMA-AMINOBUTYRIC ACID (GABA))

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.

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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 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 ...Decreased 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). A case of cardiac arrest following strenuous exercise and an excessive intake of energy drinks containing caffeine and taurine has been reported (77136).

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).

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General ...Orally, L-theanine seems to be well tolerated.
Most Common Adverse Effects:
Orally: Drowsiness, headaches.

Neurologic/CNS ...Orally, L-theanine may cause headaches (36439). Patients have also reported drowsiness, increased duration of sleep, and increased dream activity after oral L-theanine use (96331).
A case of subtle facial tic starting within 4 days of taking L-theanine 400 mg daily has been reported for a pediatric patient. Although the tics reportedly ceased once theanine was discontinued, the child had exhibited tics in the past. Therefore, the adverse effect was not thought to be related to L-theanine (91744).

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