Pure Tranquility Liquid [Discontinued] by Pure Encapsulations

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.
• Prediabetes. It is unclear if oral GABA is beneficial for prediabetes. Details: A small clinical study in adults with prediabetes and overweight or obesity shows that taking GABA 500 mg (GABA, Swanson Health) 3 times daily for 95 days does not improve postprandial glucose response to oral glucose tolerance testing, fasting glucose, glycated hemoglobin (HbA1c), or glycemic variability when compared with placebo (112830).
• 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.

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

POSSIBLY EFFECTIVE

• 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).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• 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.

(Read more about GLYCINE)

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 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. Another small clinical study in adults with MDD shows that taking L-theanine 200 mg daily with sertraline for 6 weeks reduces depression symptoms and increases remission rates but does not improve treatment response rates when compared with sertraline and placebo (112278). The validity of these effects is limited by the small sample size and short study duration. Additionally, it is unclear if the reduction in depressive symptoms is clinically significant.
• 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. It is unclear if oral L-theanine is beneficial for insomnia. Details: A very small clinical study in young healthy adults with sleep quality worsened by caffeine intake shows that taking L-theanine 50 mg (Suntheanine, Taiyo Kagaku Co. Ltd) once 10 minutes before bedtime suppresses caffeine-induced elevations in wake after sleep onset time but does not improve parameters of sleep quality including sleep onset latency, sleep time, or number of times waking after sleep onset when compared with placebo (112275). L-theanine has also been studied in combination with other ingredients. 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 (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.
• Obsessive-compulsive disorder (OCD). It is unclear if oral L-theanine is beneficial for OCD. Details: A small clinical study in adults with OCD shows that taking L-theanine 100 mg twice daily for 10 weeks with fluvoxamine reduces OCD symptoms, particularly obsessive symptoms, and increases the proportion of patients with a complete response to treatment but does not improve compulsive symptoms, partial response rates, or remission rates when compared with placebo and fluvoxamine (112276).
• 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 small 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). In contrast, two small clinical studies show that taking L-theanine 400 mg (Suntheanine, BioSynergy Health Alternatives) with antipsychotics and with or without pregnenolone 50 mg daily for 8 weeks reduces 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, extrapyramidal side effects, or symptoms of depression (97923,112277). 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.

(Read more about THEANINE)

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. 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.

(Read more about GLYCINE)

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).

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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.

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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, headache, or tiredness (5115,19364,112830). 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 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).

(Read more about GLYCINE)

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).

(Read more about THEANINE)