L-Theanine Liquid by NuMedica

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral German chamomile for allergic rhinitis, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Anxiety. It is unclear if inhaled German chamomile essential oil, as aromatherapy, is beneficial in patients with anxiety. Details: A large clinical study in adults in Iran hospitalized with acute coronary syndrome shows that placing 7 drops of German chamomile essential oil 10% on a cotton ball and inhaling for 12 hours nightly for 2 nights modestly lowers anxiety scores when compared with a control group (114528). The validity of this finding is limited by the potential for inadequate blinding and the short study duration. However, a small clinical study in adults with gastrointestinal, neuroendocrine, and skin cancers receiving intravenous infusion therapy shows that inhaling German chamomile essential oil 3 times daily for 7 days does not reduce self-reported anxiety when compared with a control group (111379). German chamomile has also been studied in combination with other ingredients. A small, open-label study in critically ill children in the pediatric intensive care unit shows that aromatherapy massage with an essential oil 1% blend of lavender, German chamomile, and neroli in grapeseed oil reduces distress, anxiety, and heart rate when compared to baseline (111378). However, the validity of these findings is limited by a lack of blinding and control group. It is unclear if these effects are due to German chamomile, other ingredients, or the combination.
• Atopic dermatitis (eczema). It is unclear if topical German chamomile is beneficial in patients with atopic dermatitis. Details: Clinical research in patients with atopic dermatitis shows that applying a specific cream containing a 2% ethanolic extract of German chamomile flowers (Kamillosan, Asta Medica AG) up to three times daily for up to 4 weeks improves pruritus, erythema, and desquamation when compared with placebo or hydrocortisone 0.5% cream (19707).
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral German chamomile for ADHD, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Burning mouth syndrome. German chamomile has only been evaluated as a mouthwash in combination with flaxseed; its effect when used alone is unclear. Details: Preliminary clinical research in female patients with burning mouth syndrome shows that using a mouthwash containing German chamomile and flaxseed 3-4 times daily for 3 months decreases subjective burning and dry mouth symptoms, increases salivary flow rate, and decreases saliva viscosity when compared with baseline (104807). However, the validity of these results is limited by the lack of a control group and product standardization, as the mouthwash was prepared by each patient from ingredients they purchased.
• Cancer-related anorexia. It is unclear if inhaled German chamomile essential oil, as aromatherapy, is beneficial in patients with cancer-related anorexia. Details: A small clinical study in adults with gastrointestinal, neuroendocrine, and skin cancers receiving intravenous infusion therapy shows that inhaling German chamomile essential oil 3 times daily for 7 days does not increase self-reported appetite when compared with a control group (111379).
• Chemotherapy-induced fatigue. It is unclear if inhaled German chamomile essential oil, as aromatherapy, is beneficial in patients with chemotherapy-induced fatigue. Details: A small clinical study in adults with gastrointestinal, neuroendocrine, and skin cancers receiving intravenous infusion therapy shows that inhaling German chamomile essential oil 3 times daily for 7 days does not reduce self-reported fatigue when compared with a control group (111379).
• Chemotherapy-induced nausea and vomiting (CINV). It is unclear if inhaled German chamomile essential oil, as aromatherapy, is beneficial in patients with CINV. Details: A small clinical study in adults treated for gastrointestinal, neuroendocrine, and skin cancers with intravenous infusion therapy shows that inhaling German chamomile essential oil 3 times daily for 7 days does not improve self-reported nausea when compared with a control group. (111379).
• Colic. Oral German chamomile has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical studies in infants with colic show that two multi-ingredient products given orally twice daily for 1-4 weeks reduce crying times when compared with placebo or simethicone 60 mg twice daily. The products studied contained German chamomile 178 mg with fennel and lemon balm (ColiMil, Milte Italia SPA) and German chamomile 9 mg with lemon balm and Lactobacillus acidophilus (ColiMil Plus, Milte Italia SPA) (16735,96278). Other clinical research in infants shows that taking 150 mL of a specific herbal tea preparation (Calma-Bebi, Bonomelli) containing extracts of German chamomile, vervain, licorice, fennel, and lemon balm up to three times daily after each episode of colic for 7 days increases the percentage of infants with relief by 31% when compared with placebo, although there was no effect on the number of night awakenings (19715).
• Common cold. It is unclear if inhaling the steam from a solution of German chamomile in hot water is beneficial in patients with a common cold. Details: Preliminary clinical research shows that inhaling the steam from a solution containing 13-39 mL of German chamomile alcoholic extract (Kneipp Kamillen-Konzentrat, Kneipp Werke) dissolved in 1000 mL of hot water for 10 minutes reduces symptoms when compared to baseline in patients suffering from an uncomplicated common cold (19360).
• Diarrhea. Oral German chamomile has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In children aged 6 months to 6 years with acute diarrhea, using a specific combination product (Diarrhoesan, Dr. Loges + Co. GmbH) containing apple pectin and German chamomile extract for 1-3 days reduces stool frequency and improves symptom relief when compared with placebo (19705).
• Dysmenorrhea. Although there has been interest in using oral German chamomile for dysmenorrhea, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Dyspepsia. Oral German chamomile has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Two specific combination products containing German chamomile (Iberogast, Steigerwald Arzneimittelwerk GmbH; STW-5-S, Steigerwald Arzneimittelwerk GmbH), 1 mL three times daily for 4 weeks, seem to improve symptoms of dyspepsia. The combinations include German chamomile plus milk thistle, peppermint leaf, licorice, caraway, celandine, angelica, and lemon balm, with (Iberogast) or without (STW-5-S) clown's mustard plant (19532). A meta-analysis of studies using Iberogast product suggests that taking 1 mL orally three times daily for 4 weeks reduces severity of acid reflux, epigastric pain, cramping, nausea, and vomiting when compared with placebo (13089). Also, using a preparation containing clown's mustard plant, German chamomile, peppermint, caraway, licorice, and lemon balm (STW 5-II, Steigerwald Arzneimittelwerk GmbH), 1 mL three times daily for up to 12 weeks, improves symptoms in 40% more patients than placebo (12724).
• Fibromyalgia. Although there has been interest in using oral German chamomile for fibromyalgia, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Flatulence. It is unclear if oral German chamomile is beneficial in adults with flatulence post-laparoscopic cholecystectomy. Details: A moderate-sized clinical study in adults undergoing laparoscopic cholecystectomy conducted in Iran shows that German chamomile extract 20 drops given once orally 1 hour before surgery mitigates the severity and incidence of flatulence 2 hours postoperatively when compared with placebo (112364). The interpretation of these findings is limited by the use of self-reported outcomes. In addition, providers had influence on who received German chamomile, raising concerns about selection bias.
• Generalized anxiety disorder (GAD). It is unclear if oral German chamomile is beneficial in adults with GAD. Details: Small clinical studies in adults with GAD show that taking German chamomile extract 220-1500 mg daily for 8-26 weeks improves anxiety rating scores but does not reduce the risk of relapse when compared with placebo (19377,111380). Clinical practice guidelines from the World Federation of Societies of Biological Psychiatry and the Canadian Network for Mood and Anxiety Treatments do not currently recommend German chamomile as monotherapy or adjunctive therapy in patients with GAD (110318).
• Gingivitis. Topical German chamomile has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in people with gingivitis shows that using a toothpaste containing German chamomile, sage, myrrh, eucalyptus, calcium carbonate, and sodium monofluorophosphate twice daily for 30 days reduces gingivitis scores when compared with baseline, but not when compared with standard toothpaste (19702).
• Hemorrhoids. Topical German chamomile might improve symptoms after anal surgery for hemorrhoids. Details: Preliminary clinical research in patients with hemorrhoids shows that German chamomile ointment (Kamillosan, Asta Medica AG) applied twice daily for 6 weeks, in combination with band ligation plus anal dilation surgery, improves anal bleeding, itching, burning, and oozing when compared with surgery alone (19714).
• Hyperprolactinemia. Oral German chamomile might lower prolactin levels, but is not likely to work as well as conventional medications. Details: Preliminary clinical research in female patients with idiopathic hyperprolactinemia shows that taking a syrup containing 10% of a German chamomile dried flower extract 5 mL twice daily for 4 weeks produces a significant decline in serum prolactin levels when compared with baseline. However, the decrease is less than that associated with taking cabergoline 0.25 mg twice weekly for 4 weeks. Serum prolactin levels normalized in 96% of patients taking cabergoline, and 72% of patients taking German chamomile (104806).
• Inflammatory bowel disease (IBD). Although there has been interest in using oral German chamomile for IBD, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Insomnia. Oral German chamomile does not seem to be beneficial in patients with primary insomnia. Details: Preliminary clinical research in patients with primary insomnia shows that taking German chamomile 270 mg twice daily for 28 days does not improve total sleep time, sleep efficiency, sleep latency, sleep quality, waking after sleep onset, or number of awakenings when compared with placebo (19716).
• Leukemia. It is unclear if oral German chamomile is beneficial in children with leukemia. Details: One small clinical study in children aged 2-18 years with acute lymphoblastic leukemia suggests that taking German chamomile flower extract 125 mg in 2.5 mL syrup daily for 30 days during induction chemotherapy is associated with a more rapid recovery in absolute neutrophil counts, but not white blood cell counts, when compared with placebo (103180). However, statistical methods used are unclear, and it is not known if German chamomile altered the effectiveness of chemotherapy.
• Mastalgia. Preliminary research suggests that German chamomile might be effective for reducing the pain of premenstrual mastalgia. Details: Preliminary clinical research in patients with cyclic (premenstrual) mastalgia shows that taking 5 drops of German chamomile extract orally three times daily for 2 months reduces the severity of mastalgia when compared with placebo (104811).
• Nocturnal enuresis. Topical German chamomile has only been evaluated in combination with almond oil; its effect when used alone is unclear. Details: Preliminary clinical research in children with enuresis shows that applying 6 drops of almond oil infused with German chamomile flower to the perineal and suprapubic areas nightly for 6 weeks reduces the frequency of enuresis by about 3 episodes per week when compared with placebo (98621).
• Oral mucositis. Small clinical studies suggest that oral rinses containing German chamomile might help to prevent or treat oral mucositis associated with radiation therapy, chemotherapy, or hematopoietic stem cell transplantation (HSCT). Details: Clinical research shows that using an oral rinse containing German chamomile extract (Kamillosan Liquidum, Asta Media AG) three times daily might help prevent or treat mucositis associated with radiation therapy and several chemotherapy drugs, but not 5-fluorouracil (6655,6656). Other clinical research in patients undergoing HSCT shows that using German chamomile 1% oral rinse twice daily along with standard care reduces the risk of oral mucositis by 67% when compared with standard care alone. However, 0.5% and 2% rinses did not decrease the risk, suggesting that the study may have been underpowered to detect differences (99853). German chamomile has also been studied in combination with other herbal ingredients. One clinical study shows that using an oral rinse containing 1% peppermint oil and 1% German chamomile extract, diluted in water, three times daily starting 1 week before HSCT might help to reduce the severity and duration of oral mucositis induced by high-dose pre-HSCT chemotherapy when compared with placebo. However, the oral rinse does not prevent oral mucositis or reduce the duration of hospitalization when compared with placebo (95622). Another small clinical study in adults with head and neck cancer receiving radiotherapy shows that rinsing with 5 mL of a mouthwash containing German chamomile, peppermint oil, aloe vera, and honey 3 times daily for 60 seconds for 6 weeks starting on the first day of radiotherapy reduces oral mucositis incidence, severity, and pain compared with chlorhexidine and placebo (111291). It is unclear if these findings are due to German chamomile, other ingredients, or the combination.
• Peptic ulcers. Although there has been interest in using oral German chamomile for peptic ulcers, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Periodontitis. German chamomile 1% mouthwash may be similarly effective to chlorhexidine 0.12% mouthwash. Details: Preliminary clinical research shows that using 15 mL of a 1% German chamomile flower mouthwash twice daily for 30 days reduces symptoms and severity of periodontitis by a similar amount when compared with chlorhexidine 0.12% mouthwash (104808).
• Pressure ulcers. Although there has been interest in using oral German chamomile for pressure ulcers, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Radiation dermatitis. It is unclear if topical German chamomile is beneficial for preventing dermatitis caused by radiotherapy. Details: A small clinical study in adults with head and neck cancer undergoing radiotherapy who developed dry desquamation shows that applying a German chamomile 2.5% compress, 20 minutes 3 times daily, results in complete or partial regression of the dry desquamation in 65% and 35% of patients, respectively, and delays the development of moist desquamation by 5-10 days (111376). The validity of these findings is limited by a lack of a comparator group. Another small clinical study in females with breast cancer shows that using a lotion containing a microencapsulated German chamomile extract 0.2%, applied daily after radiation therapy, starting on the first day and continued until the end of treatment, does not improve the incidence or time to onset of any grade of radiation dermatitis on day 35, although it may delay the time to onset of grades 2 or greater, when compared with an identical lotion vehicle control. German chamomile may modestly improve the rate of skin recovery in those with more severe dermatitis over the 15 days following therapy completion (108993). However, due to the small size of the study and short follow-up duration, the validity of these findings is unclear.
• Rhinosinusitis. Using German chamomile nose drops might improve symptoms of rhinosinusitis. Details: Preliminary clinical research in patients with rhinosinusitis shows that using 3 drops of an ethanolic German chamomile extract in each nostril three times daily for 3 weeks reduces symptom scores and improves quality of life when compared with a sesame seed oil placebo (104810).
• Sexual dysfunction. A 5% German chamomile vaginal gel may have similar efficacy to conjugated estrogen vaginal cream in postmenopausal patients. Details: Preliminary clinical research in postmenopausal patients with sexual dysfunction shows that using a 5% German chamomile vaginal gel, 1 gram nightly for 2 weeks then twice weekly for 10 weeks, decreases dyspareunia and increases sexual satisfaction to a similar extent as conjugated estrogen vaginal cream used in the same dosage (104809).
• Vaginitis. Although there has been interest in using oral German chamomile for vaginitis, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Venous leg ulcers. Although there has been interest in using oral German chamomile for venous leg ulcers, there is insufficient reliable information about the clinical effects of German chamomile for this purpose.
• Wound healing. It is unclear if topical German chamomile is beneficial for wound healing. Details: Preliminary clinical research in adults undergoing abrasive tattoo removal shows that applying a topical German chamomile product (Kamille Spitzner, W. Spitzner Arzneimittelfabrik GmbH) three times daily for 14 days reduces wound size by day 4 of treatment when compared with placebo (19718). However, no significant differences in wound healing were observed after 18 days. More information is needed to rate German chamomile for these uses.

(Read more about GERMAN CHAMOMILE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. It is unclear if oral stevia is beneficial in patients with diabetes; the available research is conflicting. Details: A small single-dose study shows that taking stevia leaf extract 1000 mg, standardized to contain 91% stevioside, along with a meal reduces postprandial glucose levels by 18% in adults with type 2 diabetes when compared with a starch control (11812). However, clinical research in patients with type 1 or type 2 diabetes shows that taking stevioside 250 mg three times daily for 3 months does not affect blood glucose levels or glycated hemoglobin (HbA1C) when compared with baseline (16705). Also, a small clinical study in patients with diabetes shows that drinking 200 mL of black tea, sweetened with stevia extract 2%, three times daily for 8 weeks does not affect glycemic indices when compared with drinking tea sweetened with sucralose (103695).
• Hypertension. It is unclear if oral stevia is beneficial in patients with hypertension; the available research is conflicting. Details: Some clinical research in patients with mild to moderate hypertension shows that taking stevioside, a constituent of stevia, 750-1500 mg in three divided doses daily reduces systolic blood pressure by 10-14 mmHg and diastolic blood pressure by 6-14 mmHg within one week to three months of treatment initiation and continuing for up to 2 years (11809,11810). However, other clinical research in patients with mild hypertension shows that taking stevioside in doses up to 15 mg/kg daily does not significantly reduce blood pressure (16706).
• Obesity. It is unclear if oral stevia is beneficial in patients with obesity; the available research is conflicting. Details: Although a small clinical study in healthy adults shows that drinking water with stevia (Truvia) 245 ppm as a single dose reduces appetite and energy intake when compared with drinking water alone (103697), other small, single-dose studies have shown no effect of stevia 15.3 mg or 1 gram as a single dose on satiety, energy intake, or fullness when compared with either water alone or a non-nutritive sweetener (103696,110124). A small clinical study in healthy adults shows that taking an aqueous stevia leaf extract (SweetLeaf) twice daily for 12 weeks does not affect body weight, compared with an increase in weight in the control group. This suggests that stevia extract may have attenuated weight gain in this study (106458). More evidence is needed to rate stevia for these uses.

(Read more about STEVIA)

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. German chamomile has Generally Recognized as Safe (GRAS) status in the US (4912,110318).

POSSIBLY SAFE ...when used orally, for medicinal purposes, short-term. German chamomile has been used with apparent safety at doses of up to 1500 mg daily for up to 26 weeks (6655,12724,12729,13089,19377,19716,104806,111380). ...when applied topically. A lotion containing 0.2% microencapsulated German chamomile extract has been applied to the skin with apparent safety for up to 35 days (108993). ...when used topically as an oral rinse (99853).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Preliminary clinical research suggests that several multi-ingredient products containing German chamomile are safe in infants when used for up to 4 weeks (16735,19705,19715,96278). ...when used topically and appropriately, short-term. Six drops of oil infused with German chamomile flower has been applied nightly with apparent safety for up to 6 weeks in children 6-18 years old (98621).

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

(Read more about GERMAN CHAMOMILE)

LIKELY SAFE ...when certain stevia constituents, including stevioside and rebaudiosides A, D, and M, are used orally as sweeteners in foods. These constituents have generally recognized as safe (GRAS) status in the US for this purpose (16699,16700,16702,16705,16706,108049). The stevia constituent stevioside has been safely used in doses of up to 1500 mg daily for 2 years (11809,11810,11811). There is insufficient reliable information available about the safety of whole stevia or stevia extracts when used orally. The European Food Safety Authority (EFSA) has determined that the acceptable intake of steviol glycosides is 4 mg/kg daily (106456); however, it is unclear how this relates to the use of whole stevia or stevia extract.

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

(Read more about STEVIA)

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)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, German chamomile might have additive effects when used with CNS depressants.  Details German chamomile has mild sedative effects. Theoretically, concomitant use with drugs with sedative properties can cause additive effects and side effects (9765,12725,19719).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, large amounts of German chamomile might reduce the effectiveness of oral contraceptives.  Details In vitro, German chamomile has demonstrated antiestrogenic activity (12728). Theoretically, concomitant use of large amounts of German chamomile might interfere with contraceptive drugs through competition for estrogen receptors.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, German chamomile might inhibit CYP1A2 and increase levels of drugs metabolized by these enzymes.  Details In vitro and animal research shows that German chamomile might inhibit CYP1A2 (12734,19720). So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP1A2 in patients taking German chamomile.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, German chamomile might inhibit CYP2C9 and increase levels of drugs metabolized by these enzymes.  Details In vitro evidence shows that German chamomile might inhibit CYP2C9 (19720). So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2C9 in patients taking German chamomile.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, German chamomile might inhibit CYP2D6 and increase levels of drugs metabolized by these enzymes.  Details In vitro evidence shows that German chamomile might inhibit CYP2D6 (19720). So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2D6 in patients taking German chamomile.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, German chamomile might inhibit CYP3A4 and increase levels of drugs metabolized by these enzymes.  Details In vitro evidence shows that German chamomile might inhibit CYP3A4 (6450,19720). So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP3A4 in patients taking German chamomile.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, large amounts of German chamomile might reduce the effectiveness of estrogens.  Details In vitro, German chamomile has demonstrated antiestrogenic activity (12728). Theoretically, large amounts of German chamomile might interfere with hormone replacement therapy through competition for estrogen receptors.

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, large amounts of German chamomile might interfere with the activity of tamoxifen.  Details In vitro, German chamomile has demonstrated antiestrogenic activity (12728).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D German chamomile might increase the effects of warfarin and increase the risk of bleeding.  Details In one case, a 70-year-old female taking warfarin developed retroperitoneal hematoma and bilateral recti muscle bleeding along with an INR of 7.9 following ingestion of German chamomile tea 4-5 cups daily and use of a topical chamomile-based lotion applied 4-5 times daily (14309).

(Read more about GERMAN CHAMOMILE)

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, stevia might increase the risk for hypoglycemia when combined with antidiabetes drugs.  Details Preliminary clinical research in patients with type 2 diabetes suggests that taking a single dose of stevia extract 1000 mg reduces postprandial blood glucose levels when taken with a meal (11812). However, other clinical research in patients with type 1 or type 2 diabetes suggests that taking stevioside 250 mg three times daily does not significantly affect blood glucose levels or glycated hemoglobin (HbA1C) after three months of treatment (16705).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining stevia or stevia constituents with antihypertensive agents might increase the risk of hypotension.  Details Stevia extract and stevioside might lower blood pressure in patients with hypertension (3745,3747,5031,11809,11810). However, other clinical research suggests that stevioside does not significantly lower blood pressure in patients with hypertension (16706).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, stevia might decrease clearance and increase levels of lithium.  Details Animal research suggests that stevia extracts might have diuretic activity (3746,3747). Theoretically, increased reabsorption of lithium along with sodium might reduce excretion and increase levels of lithium.

(Read more about STEVIA)

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).

(Read more about THEANINE)

General ...Orally and topically, German chamomile is well tolerated.
Most Common Adverse Effects:
Orally and topically: Allergic reactions and irritation.

Dermatologic ...Topically, German chamomile may cause allergic dermatitis and eczema (9766,9768,10377,110318).

Gastrointestinal ...When used topically as an oral rinse, German chamomile has been reported to cause nausea and burning in the mouth in some patients (99853).

Immunologic ...Orally, German chamomile tea can cause allergic reactions including severe hypersensitivity reactions and anaphylaxis in some patients (567). In one case report, a 47-year-old female who tolerated drinking chamomile tea, reported sneezing, nasal and ocular itching, red and watery eyes, and severe rhinorrhea after 10 years of occupational exposure to German chamomile dust (90542).

Ocular/Otic ...If used near the eyes, German chamomile can cause irritation (10377).

(Read more about GERMAN CHAMOMILE)

General ...Orally, stevia and steviol glycosides appear to be well tolerated. Most minor adverse effects seem to resolve after the first week of use.
Most Common Adverse Effects:
Abdominal bloating, dizziness, headache, myalgia, nausea, and numbness.
Serious Adverse Effects (Rare):
Allergic reactions.

Gastrointestinal ...Orally, stevia and steviol glycosides such as stevioside, can cause gastrointestinal adverse effects such as abdominal fullness and nausea. However, these generally resolve after the first week of use (11809,11810).

Immunologic ...Theoretically, stevia might cause allergic reactions in individuals sensitive to plants in the Asteraceae/Compositae family (11811). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Musculoskeletal ...Orally, stevia and steviol glycosides may cause myalgia, but this generally resolves after the first week of use (11809,11810).

Neurologic/CNS ...Orally, stevia and steviol glycosides may cause headache, dizziness, and numbness (11809,11810).

(Read more about STEVIA)

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)