Grape Seed Extract 50 mg by Vitamer Laboratories

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Serving Size 1 Tablet(s)

Ingredients	Amount Per Serving
Leucoselect Grape seed extract (including Oligomeric Proanthocyanidins, naturally concentrated in Polyphenols) (Leucoselect Grape seed extract (Form: naturally concentrated in Polyphenols, including Oligomeric Proanthocyanidins (Alt. Name: OPCs)) )	50 mg
Green Tea extract (Camellia sinensis )	50 mg
Lemon Bioflavonoid Complex	50 mg

Other Ingredients

Cellulose, Silica, Glycerin, Magnesium Stearate Note: vegetable source

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Effectiveness view details

Below is general information about the effectiveness of the known ingredients contained in the product Grape Seed Extract 50 mg. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

GRAPE (Leucoselect Grape seed extract)

POSSIBLY EFFECTIVE

Chronic venous insufficiency (CVI). Oral grape leaf extract might improve CVI symptoms. It is unknown if other grape products are beneficial for CVI. Details: Some clinical trials in patients with CVI show that taking a specific grape leaf extract, known as red vine leaf extract (AS 195, Antistax, Boehringer Ingelheim), seems to improve leg edema after 6 weeks of treatment when compared with placebo. Doses of 360 mg and 720 mg daily were both effective, but the higher dose produced a slightly greater effect. Patients also reported decreases in subjective complaints such as tired or heavy legs, tension, and tingling and pain after 2-12 weeks of treatment (2538,52985,53005,53206).

POSSIBLY INEFFECTIVE

Allergic rhinitis (hay fever). Oral grape seed extract does not seem to improve hay fever symptoms. Details: A clinical study in patients with seasonal allergic rhinitis shows that taking grape seed extract 100 mg twice daily for 8 weeks before ragweed pollen season does not seem to decrease seasonal allergic rhinitis symptoms or antihistamine usage when compared with placebo (9182).
Chemotherapy-induced nausea and vomiting (CINV). Drinking grape juice does not seem to improve CINV. Details: Clinical research shows that taking 4 ounces of chilled Concord grape juice 30 minutes prior to meals for a week following each of four cycles of chemotherapy does not seem to reduce CINV when compared with placebo (53175).
Lower urinary tract symptoms (LUTS). Drinking grape juice does not seem to improve LUTS. Details: Clinical research in middle-aged and older men with LUTS shows that drinking 100% Concord grade juice 240 mL daily for 3 months does not improve symptoms when compared with placebo (96190).
Mastalgia. Oral grape seed extract does not seem to improve mastalgia symptoms. Details: Clinical research in patients treated for early breast cancer using high-dose radiotherapy shows that taking the grape seed extract constituent proanthocyanidin 100 mg orally three times daily for 6 months does not reduce breast tissue hardness, pain, or tenderness when compared with placebo (53048).
Obesity. Oral grape products do not seem to improve weight loss. Details: Clinical research in overweight or obese individuals shows that drinking Concord grape juice 480 mL daily for 12 weeks does not improve weight or body composition when compared to baseline (53181). Furthermore, taking grape pomace alone or in combination with schisandra fruit extract daily for 4-10 weeks does not improve body composition, abdominal fat, or body weight when compared with control (96200,99269,99270). Taking grape pomace 7-8 grams daily for 4-6 weeks seems to improve insulin resistance by about 33%, but does not affect blood lipids or blood pressure, when compared with placebo in overweight or obese adults with at least one metabolic syndrome factor (99269,99270).

INSUFFICIENT RELIABLE EVIDENCE to RATE

Aging skin. Oral grape skin extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in adults with signs of aging skin shows that taking a specific combination product (Celergen, Laboratories-Dom) containing grape skin extract 10 mg, marine collagen peptides 570 mg, coenzyme Q10 10 mg, luteolin 10 mg, and selenium 0.05 mg, one capsule with breakfast and dinner for 2 months, might improve skin elasticity when compared with baseline. However, there was no effect on moisture or biological skin age (97930). It is not clear if these effects are due to grape skin extract, the other ingredients, or the combination.
Age-related macular degeneration (AMD). Although there is interest in using oral grape seed for AMD, there is insufficient reliable information about the clinical effects of grape for this condition.
Atherosclerosis. Oral grape seed extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in postmenopausal adults shows that taking a specific combination product (Karinat, INAT-Farma) containing grape seed extract constituent proanthocyanidin 40 mg, garlic 100 mg, hops 160 mg, green tea 115 mg, vitamin C 30 mg, silicon 8 mg, vitamin E 6.6 mg, and beta-carotene 0.5 mg three capsules daily for 12 months might slow the progression of atherosclerosis as measured by mean carotid intima thickness when compared with placebo. However, the combination product does not seem to affect the growth of existing plaques, and it does not seem to improve lipid parameters (97929). It is not clear if these effects are due to grape seed extract, the other ingredients, or the combination.
Athletic performance. It is unclear if oral grape products are beneficial for athletic performance. Details: A small study in elite athletes shows that taking a specific grape extract (Powergrape, Naturex SA) 400 mg daily for one month can increase total power in a jumping task when compared with placebo, but has no effect on initial power and maintenance of power (53310). Another small study in recreationally active young adults shows that drinking juice prepared from 46 grams of a freeze-dried preparation of whole grapes daily for 6 weeks prior to a running exercise test does not improve maximal oxygen uptake or work capacity during exercise when compared with placebo (91540).
Atopic dermatitis (eczema). Topical grape products have only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with atopic dermatitis shows that twice daily application with a cream containing grape polyphenols, vitamin E, and epigallocatechin gallate for 28 days does not improve symptoms or reduce the affected area based on physician assessment when compared with placebo (96196).
Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral grape seed for ADHD, there is insufficient reliable information about the clinical effects of grape for this condition.
Canker sores. Although there is interest in using oral grape seed for canker sores, there is insufficient reliable information about the clinical effects of grape for this condition.
Cardiovascular disease (CVD). It is unclear if oral grape products are beneficial for reducing CVD risk. Details: There is preliminary evidence that taking grape products, such as purple grape juice or red grape juice concentrate, might improve endothelium-dependent vasodilation, prevent low-density lipoprotein (LDL) oxidation, reduce markers of inflammation, and suppress platelet-mediated thrombosis. Theoretically, chronic ingestion of these products might reduce the risk of CVD in various patient populations, including adults with type 2 diabetes or hypercholesterolemia, those undergoing hemodialysis, and children with metabolic syndrome (8745,8746,52954,53030,53062,53106,53155,53174). However, a large meta-analysis shows that although taking grape products, including grape extract, grape juice, raisins, and grape seed extract, reduces levels of blood fats by a small amount in a mixed population of adults, these effects were not present in a subgroup of patients with CVD when compared with placebo. There was a small benefit on total cholesterol and high-density lipoprotein (HDL) cholesterol (102610).
Cognitive function. It is unclear if oral grape products improve cognitive function. Details: Clinical research in healthy adults aged 55-75 years with no cognitive decline shows that taking a specific grape fruit extract (Cognigrape, Bionap srl) 250 mg daily for 12 weeks improves cognitive functioning by 4.5%, and overall neuropsychological status, including attention, language, and recall, by 6%, compared with no change in the placebo group (96198). Also, a preliminary clinical study in middle-aged women under moderate stress shows that drinking Concord grape juice 355 mL daily for 12 weeks improves immediate spacial memory and may improve executive function and verbal recall when compared with placebo (96195).
Cognitive impairment. Small clinical studies suggest that oral grape products may not slow cognitive decline in older patients with cognitive impairment. Details: One very small study in in patients with mild cognitive decline shows that taking a freeze-dried grape powder 36 grams twice daily for 6 months does not improve most measures of cognitive function and memory, including immediate memory, delayed memory, speed of information processing, cognitive ability, or language, when compared with placebo (96199). Another very small study in older adults with signs of memory decline shows that drinking 100% Concord grape juice 6-9 mL/kg daily for 12 weeks does not improve delayed verbal recall or spatial memory when compared with placebo, although it does seem to moderately improve verbal learning (53166).
Colorectal cancer. Oral grape seed extract is has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with colorectal cancer shows that taking a product containing grape seed extract, turmeric extract, fermented soybean extract, green tea extract, spirulina, and Taiwanofungus camphoratus, 1920 mg three times daily for 16 weeks during a chemotherapy regimen might modestly increase the effectiveness of treatment when compared with placebo. No patients in the treatment group experienced disease progression, compared with 15.8% (6 patients) of the placebo group. However, there was no significant effect on overall survival or the best response to treatment (96183).
Constipation. Although there is interest in using oral grape products for constipation, there is insufficient reliable information about the clinical effects of grape for this condition.
Dental caries. Although there is interest in using topical grape seed for dental caries, there is insufficient reliable information about the clinical effects of grape for this purpose.
Diabetes. Oral grape extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study of males with type 2 diabetes mellitus and erectile dysfunction suggests that an oral combination product containing alpha lipoic acid, Gingko biloba, and grape extract (Blunorm Forte, Uriach S.p.A.) taken for 3 months may decrease fasting plasma glucose and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score both alone and when combined with avanafil when compared with baseline and placebo (110707).
Diabetic retinopathy. It is unclear if oral grape seed extract is beneficial in patients with diabetic retinopathy. Details: A preliminary clinical study in patients with non-proliferative diabetic retinopathy shows that taking a specific grape seed proanthocyanidin extract (Entelon, Hanlim Pharm) 50 mg three times daily for 12 months reduces the severity of hard exudates when compared with calcium dobesilate or placebo. Grape seed extract had a treatment success rate 3-fold and 5.5-fold higher than those of calcium dobesilate and placebo, respectively. Treatment success was defined as a 2-grade decrease in hard exudate severity. No significant improvements in retinopathy grade or visual acuity were reported (100954). However, the study may not have been adequately powered to detect a difference in these outcomes.
Erectile Dysfunction (ED). Oral grape extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large study of males with type 2 diabetes mellitus and erectile dysfunction suggests that a specific combination product containing alpha lipoic acid, grape extract, and gingko biloba (Blunorm Forte, Uriach S.p.A.) administered orally for three months with avanafil prior to sexual acts improves International Index of Erectile Function (IIEF) scores when compared with either product alone, placebo, and baseline, and may reduce markers of ED including high sensitivity-c-reactive protein, nitrates/nitrites, and metalloproteinases-2 and -9. These results suggest that an oral combination nutraceutical consisting of alpha lipoic acid, grape extract, and gingko biloba (Blunorm Forte, Uriach S.p.A.) may react synergistically with avanafil to enhance sexual performance in males with type 2 diabetes and erectile dysfunction. It is unclear if this effect is due to the alpha lipoic acid, grape extract, or gingko biloba, but researchers theorize that it may be due to the inhibition of phosphodiesterase-5 enzymes by grape extract (110707).
Hemorrhoids. Although there is interest in using oral grape seed for hemorrhoids, there is insufficient reliable information about the clinical effects of grape for this purpose.
Hypercholesterolemia. Small clinical studies suggest that oral grape products reduce cholesterol levels by a small amount. Details: A large meta-analysis of heterogeneous clinical trials shows that taking grape products, including grape extract, grape juice, raisins, or grape seed extract, for 2-54 weeks reduces levels of total and low-density lipoprotein (LDL) cholesterol, as well as triglycerides, by a small amount when compared with placebo in a mixed population of adults. In a sub-group of patients with any hyperlipidemia, the mean decreases in LDL cholesterol and triglycerides were 11 mg/dL and 14 mg/dL, respectively. There was no effect on levels of high-density lipoprotein (HDL) in the mixed population or in adults with hyperlipidemia (102610). Although some individual studies disagree, the most evidence for benefit is related to use of whole grape extract or grape seed extract. It is not clear if benefit is dependent on dose or duration of use. These results suggest a benefit of grape products in patients with hypercholesterolemia, but any benefit is likely to be small (42585,96816,102610).
Hypertension. Some research suggests that oral grape products may modestly lower blood pressure; however, results are inconsistent. Details: Some clinical trials have shown modest benefit in patients with prehypertension, mild hypertension, or metabolic syndrome (18228,53149,96197), but conflicting results exists (91541,90079). A 2016 meta-analysis including 16 trials of 810 patients shows that when compared with placebo, grape seed extract or polyphenols reduces systolic blood pressure (SBP) and diastolic blood pressure (DBP) by about 6 mmHg and 3 mmHg, respectively, with greatest improvements observed in those with obesity or metabolic syndrome. This meta-analysis suggests that a minimum treatment duration of 8 weeks may be necessary before benefit is seen (96194). However, other research in adults with hypertension shows that taking grape seed polyphenols 1000 mg daily for 6 weeks does not alter blood pressure. Also, when grape seed polyphenols were combined with vitamin C 500 mg daily, some patients experienced an increase in blood pressure and worsening of nighttime and daytime variation in blood pressure (13162,90079). The reason for these conflicting findings is unclear but may due to patient characteristics and comorbidities. A meta-analysis of clinical research in various patient populations shows that taking grape seed extract 150-2100 mg for 2-25 weeks improves DBP and heart rate when compared with control, but does not improve SBP or flow-mediated dilation, regardless of dose, duration, sex, BMI, or health status. Additionally, subgroup analyses suggest that blood pressure effects may be greater in patients who are otherwise healthy, female, overweight, and/or under 50 years of age. Also, the use of lower doses and longer treatment durations may be associated with greater benefit (108090). The validity of these findings is limited by the high heterogeneity of included studies. A clinical study in adults with mildly elevated blood pressure shows that a specific grape seed extract (Enovita; Indena SpA) standardized to provide at least 95% oligomeric proanthocyanins, taken as 150 mg twice daily for 16 weeks, does not reduce SBP or DBP when compared with placebo. However, a subgroup analysis suggests that taking grape seed extract improves blood pressure in males, but not in females, when compared with placebo (108091). Some research has also evaluated the effects of grape juice on blood pressure. Two clinical studies in patients with hypertension show that drinking grape juice can reduce blood pressure when compared to baseline; however, another study shows that drinking grape juice does not reduce blood pressure when compared with placebo in these patients (53018,53156,53199).
Melasma. It is unclear if oral grape seed extract is beneficial in patients with melasma. Details: A very small clinical study in Japanese females with melasma shows that taking grape seed extract (Gravinol, Kikkoman Co) containing 54 mg of proanthocyanidins three times daily for 6-11 months reduces skin hyperpigmentation when compared to pretreatment (53016). The validity of this finding is limited by the lack of a control group.
Menopausal symptoms. It is unclear if oral grape seed extract is beneficial in patients with menopausal symptoms. Details: Preliminary clinical research in adults with at least one menopausal symptom shows that taking grape seed extract (Gravinol, Kikkoman Biochemifa Co) containing proanthocyanidin 200 mg daily for 8 weeks reduces anxiety when compared with placebo. It also reduces hot flashes and other physical symptoms when compared to baseline, but not when compared with placebo. A lower dose of proanthocyanidin 100 mg daily does not appear to improve these outcomes. Neither doses improved insomnia or depression (91542).
Metabolic syndrome. Small studies suggest that various oral grape products might improve lipid levels and blood pressure in patients with metabolic syndrome. Details: A meta-analysis of small clinical studies in adults with type 2 diabetes or metabolic syndrome shows that taking grape products, usually grape seed or grape extract, for 4-48 weeks reduces levels of total and low-density lipoprotein (LDL) cholesterol, as well as triglycerides, by a small amount when compared with placebo. The mean decreases in LDL cholesterol and triglycerides were 2.6 mg/dL and 11 mg/dL, respectively (102610). These findings are limited by significant heterogeneity of the included research. Also, a small clinical study in overweight or obese adults, most with metabolic syndrome, shows that taking grape pomace 8 grams daily for 6 weeks improves insulin resistance by about 33%, but does not affect blood lipids, blood pressure, or fasting glucose, when compared with placebo (99270). Some grape products have also shown benefit for improving blood pressure in patients with metabolic syndrome. One small clinical crossover study in males with metabolic syndrome shows that taking 46 grams daily of a freeze-dried, dehydrated preparation of grape polyphenols (equivalent to about 250 grams of fresh grapes daily) for 30 days seems to modestly lower systolic, but not diastolic, blood pressure, and increase brachial artery flow-mediated dilation (FMD) when compared with placebo (18228). Also, a small clinical study in adolescents with metabolic syndrome suggests that drinking natural grape juice 18 mL/kg daily for one month improves FMD when compared with baseline (53174).The validity of this finding is limited by the lack of a control group. A very small clinical study in patients with metabolic syndrome shows that taking a specific grape seed extract (Meganatural BP, Polyphenolics) 150-300 mg daily for 4 weeks modestly reduces blood pressure when compared with placebo (53149). The validity of this finding is limited due to small study size and because patients in the treatment groups had higher blood pressure at baseline.
Minor bleeding. Topical grape vine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that topically applying 4 mL of a specific product (Ankaferd blood stopper) containing grape vine, alpinia, licorice, thyme, and stinging nettle reduces bleeding, but does not improve the surgical time for episiotomy repair, when compared with saline (31010). It is unclear if this effect is due to grape vine, other ingredients, or the combination.
Muscle soreness. It is unclear if oral grape products improve muscle soreness. Details: One small study in active young adults shows that drinking juice, prepared from 46 grams of freeze-dried whole grapes, daily for 6 weeks prior to an eccentric arm exercise test does not reduce muscle inflammation or pain at 24 or 48 hours post-exercise when compared with placebo (91540).
Night vision. Although there is interest in using oral grape seed extract for improving night vision, there is insufficient reliable information about the clinical effects of grape for purpose.
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral grape seed extract reverses fatty liver in patients with NAFLD. Details: One small clinical study in adults with NAFLD shows that taking grape seed extract 1000 mg twice daily for 3 months improves some, but not all, markers of liver damage and improves the grade of fatty liver change when compared with vitamin C supplementation (53190).
Ocular stress. Although there is interest in using oral grape seed extract for ocular stress, there is insufficient reliable information about the clinical effects of grape for this purpose.
Premenstrual syndrome (PMS). Although there is interest in using oral grape seed extract for PMS, there is insufficient reliable information about the clinical effects of grape for this condition.
Wound healing. Limited research suggests that topical grape seed extract might improve wound healing. Details: A small clinical study in adults undergoing surgical removal of minor skin lesions shows that applying red grape seed extract 2% cream twice daily to the affected areas reduces the time to complete wound healing by about 6 days when compared with a placebo cream (91539). Also, preliminary clinical research in patients recovering from cesarean section shows that applying grape seed extract 5% ointment twice daily to cesarean section wounds for 14 days improves wound healing, as measured by a scoring system assessing redness, edema, ecchymosis, discharge, and wound closure, when compared with a placebo ointment. A 2.5% ointment did not improve wound healing measures when compared with placebo (100955). More evidence is needed to rate grape for these uses.

(Read more about GRAPE)

GREEN TEA (Green Tea extract)

LIKELY EFFECTIVE

Human papillomavirus (HPV). A specific green tea extract ointment (Polyphenon E ointment 15%) is approved by the US Food and Drug Administration (FDA) for treating external genital warts caused by HPV. Details: A specific green tea extract ointment (Veregen, Bradley Pharmaceuticals; Polyphenon E ointment 15%, MediGene AG) providing 150 mg of sinecatechins per gram of ointment, applied three times daily to external warts, completely clears external genital and perianal warts in 24% to 60% of patients after 10-16 weeks of treatment (15067,36438,36442,53777,53907,54018). This green tea extract is an FDA-approved prescription product (15067).

POSSIBLY EFFECTIVE

Cardiovascular disease (CVD). Drinking green tea seems to reduce the risk of CVD and CVD-related mortality. Details: Large-scale population research in Japan suggests that consuming at least 3-5 cups of green tea daily is associated with a reduced risk of cardiovascular mortality when compared with drinking less than 1 cup daily. This association appears to be primarily related to a decrease in risk for cerebral infarction and heart disease. This association appears to be stronger in females than in males (14498,53789,100202). Population research also suggests that drinking green tea is associated with a reduced risk of CVD. One meta-analysis suggests that drinking green tea is associated with a 28% reduced risk of CAD (54017). Another meta-analysis suggests that consuming small to moderate amounts of green tea, 1-5 cups or 300 to 1500 mL daily, is associated with an 8% to 16% reduced risk of coronary heart disease over 5 to 13 years when compared with consuming no green tea (111017). One meta-analysis suggests that a 1 cup increase in green tea consumption is associated with a 5% reduced risk of CVD mortality and a 3% reduced risk of CVD events (102728). When compared with drinking less than 1 cup of green tea daily, epidemiological research in a population at high risk of coronary artery disease (CAD) suggests that drinking more than 3 cups of green tea daily is associated with a 46% reduced odds of having CAD, especially severe CAD, as determined by a coronary angiography (104588). A sub-group analysis suggests that these odds only occurred in individuals consuming fruits more than 4 times weekly and not in individuals consuming fruits less often (104588). However, some population research suggests that any association seems to be greater for males than females (53691). Other population studies suggest that general tea consumption might protect against ischemic heart disease or death from CVD; however, many of the tea drinkers in some of these studies consumed black tea rather than green tea (8119,8120,8121,102728).
Endometrial cancer. Drinking green tea seems to be beneficial for endometrial cancer prevention. Details: Meta-analyses of epidemiological research have found that people who drink green tea often, usually more than once daily, have a 21% to 23% reduced risk of developing endometrial cancer when compared with those who never or rarely drink green tea (53919,92409,102716). One of these meta-analyses also found that increasing green tea intake by one cup per day is associated with an 11% reduced risk of developing endometrial cancer (92409).
Hyperlipidemia. Oral green tea seems to reduce levels of low-density lipoprotein (LDL) cholesterol by a small amount. Details: Clinical research and a meta-analysis of clinical research in people with or without hyperlipidemia shows that consuming green tea or green tea extract containing 150-2500 mg catechins daily for up to 24 weeks reduces total cholesterol by about 5-24 mg/dL and LDL cholesterol by about 2-25 mg/dL when compared with control (11308,54038,54048,90146,90161,97135,104605). There is also preliminary evidence that taking a green tea extract containing catechins 676 mg daily for 12 weeks reduces oxidation of LDL cholesterol when compared with placebo, which might lead to reduced damage to the vascular endothelium and reduced arteriosclerosis (98458). Epidemiological research has found that higher consumption of green tea, especially 10 cups daily or more, is associated with improved serum lipids in males, but not females (6403,97134).
Ovarian cancer. Drinking green tea seems to be beneficial for ovarian cancer prevention. Details: Consuming tea, including green tea or black tea, appears to significantly lower the risk of developing ovarian cancer when compared with never or seldom consuming tea (9228,13208,90144,102716). One meta-analysis of population research suggests that the highest intake of green tea is associated with a 36% reduced risk of ovarian cancer when compared with the lowest intake (102716). Also, one prospective population study found that those who consume 2 or more cups of tea daily have a 46% lower risk of ovarian cancer when compared with those who don't regularly consume tea (13208). There also appears to be a trend that suggests higher consumption of tea or longer duration of use further reduces the risk of ovarian cancer (9228,13208). However, green tea does not appear to prevent ovarian cancer recurrence. Preliminary clinical research shows that drinking 500 mL of double-brewed green tea (DBGT), prepared with 35 grams/L of tea leaves standardized to contain approximately 640 mg/L of EGCG, daily for up to 18 months does not prevent cancer recurrence in adults with a history of advanced stage serous or endometrioid ovarian cancer (90175).

INSUFFICIENT RELIABLE EVIDENCE to RATE

Acne. Topical green tea might reduce acne lesions by a small amount. It is unclear if oral green tea is beneficial for acne. Details: A meta-analysis of preliminary clinical research shows that topical application of green tea extract reduces the number of inflammatory and non-inflammatory lesions by a small amount (104609). In one small study, applying a solution containing the green tea constituent epigallocathechin-3-gallate (EGCG) 1% or 5% twice daily for 8 weeks was used (54074). However, oral green tea extract had limited or no effect in one study included in a meta-analysis (104609). Higher quality studies are needed to confirm this finding.
Age-related cognitive decline. It is unclear if oral green tea is beneficial for cognitive decline associated with age. Details: In elderly individuals living in the community, clinical research shows that taking matcha green tea powder (Yabukita, Kyoeiseicha Co., Ltd.) 3 grams daily for 12 weeks does not improve overall measures of cognitive function when compared with placebo. However, a sub-group analysis in females found a small improvement in language, but not other measures, including memory, impulsivity, and attention (104602). Other clinical research in middle aged and older adults shows that taking green tea extract (Thea-Flan 90S, ITO EN Ltd.) providing catechins 336.4 mg daily for 12 weeks does not improve most measures of cognitive function, although there was a small effect on one measure of working memory. In addition, a single dose has a small effect on errors during an attention task (104603).
Amyloidosis. It is unclear if oral green tea is beneficial for amyloidosis. Details: Preliminary clinical research in patients with cardiac transthyretin amyloidosis shows that drinking green tea (Green Darjeeling, FTGFOP1, Teekampagne Projektwerkstatt GmbH) 1.5-2 liters standardized to contain epigallocatechin-3-gallate (EGCG) 340 mg/L and/or taking specific capsules (Praevent-loges, Dr. Loges + Co. GmbH) containing 300 mg green tea extract standardized to contain EGCG 75 mg/capsule for 12 months protects against an increase in left ventricular wall thickness and left ventricular myocardial mass (54064).
Anxiety. Although there has been interest in using oral green tea for anxiety, there is insufficient reliable information about the clinical effects of green tea for this condition.
Athletic performance. The evidence on the effects of green tea constituents for athletic performance is conflicting. Details: Some preliminary clinical research shows that taking green tea extract containing up to 572.8 mg of catechins as a beverage does not improve respiration efficiency, maximal oxygen uptake, or time trial performance in individuals undergoing endurance training when compared with beverages without catechins (53987,53991). However, other preliminary research shows that taking specific pills (Teavigo, Healthy Origins) containing epigallocatechin-3-gallate (EGCG) 135 mg/pill, taken three times daily with meals for a total dose of seven pills, improves maximal oxygen uptake but not maximum work rate or respiration efficiency, in healthy adults when compared with placebo (53944). Also, a small study in untrained adults shows that taking a single dose of green tea polyphenols 640 mg, 90 minutes before exercise, increases maximal oxygen uptake. However, the effect on athletic performance was not determined (104606).
Beta-thalassemia. It is unclear if oral green tea is beneficial for reducing iron accumulation in beta-thalassemia. Details: A small clinical trial shows that taking green tea 3 cups daily after meals for 12 months, in addition to usual treatment with blood transfusions and deferasirox, an iron chelator, reduces levels of liver iron and serum ferritin by moderate amounts when compared with usual treatment alone. Hemoglobin values did not differ between groups. Each green tea bag contained 2 grams green tea (Lipton, Unilever Gulf) (104601).
Bladder cancer. It is unclear if drinking green tea is beneficial for bladder cancer prevention. Details: Some epidemiological evidence suggests that drinking green tea is associated with a reduced risk of bladder cancer (1458,1459,90179). However, conflicting evidence exists. A meta-analysis of some epidemiological evidence suggests that drinking green tea is not associated with a reduced risk of bladder cancer (54077,90166,102716).
Breast cancer. Evidence evaluating the association between green tea intake and breast cancer risk is inconsistent; any association may be dependent on genotype and menopausal status. Details: Meta-analyses of cohort and case-control studies have found that green tea intake is not associated with a reduced risk of breast cancer (98460,102716). However, some individual population studies suggests that green tea intake is associated with a reduced odds of developing breast cancer in Asian-American (14427,53866), but not Asian (13189,14426,90181), populations. Any protective effect of green tea on breast cancer risk might depend on patient genotype or menopausal status. Green tea consumption does not seem to lower breast cancer risk in Asian females with low-activity angiotensin-converting enzyme (ACE) genotype, although it does seem to decrease breast cancer risk in Asian females with high-activity ACE genotype (14430). Similarly, Asian-American females who drink green tea seem to have a lower breast cancer risk if they have low-activity catechol-O-methyltransferase (COMT) genotype. However, they do not seem to benefit if they do not have the low-activity COMT genotype (14431). Additionally, some observational research suggests that there is a link between green tea and modestly reduced breast cancer risk in pre-menopausal, but not postmenopausal, females (99788). Some research has evaluated the effect of green tea on breast cancer recurrence. Population research suggests that Asian females who have had stage I or II breast cancer who drink at least 3 cups of green tea daily seem to have reduced risk of breast cancer recurrence (3926,13189,54112). However, drinking green tea does not seem to significantly reduce the risk of recurrence of later-stage breast cancer. In April 2012, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that consuming green tea may reduce the risk of breast cancer, although the FDA has concluded that there is very little scientific evidence to support this claim (102106).
Cervical cancer. It is unclear if oral green tea is beneficial for cervical cancer. Details: Clinical research in adults with persistent high-risk HPV (HR HPV) infection and concomitant low-grade cervical intraepithelial neoplasia shows that taking a specific green tea extract (Polyphenon E), four capsules standardized to contain epigallocatechin-3-gallate (EGCG) 200 mg/capsule, once daily for 4 months does not affect HR HPV-positive status or histological outcomes when compared with placebo (90145).
Cervical dysplasia. It is unclear if topical green tea is beneficial for cervical dysplasia. Details: Preliminary clinical research shows that applying a specific ointment (Polyphenon E ointment 15%, MediGene AG) containing epigallocatechin-3-gallate (EGCG) to human papilloma virus (HPV)-infected cervical lesions twice weekly and/or taking a specific green tea extract (Polyphenon E) 200 mg daily containing EGCG by mouth for 8-12 weeks can improve lesion appearance when compared with control (11310).
Chronic fatigue syndrome (CFS). Although there has been interest in using oral green tea for CFS, there is insufficient reliable information about the clinical effects of green tea for this condition.
Chronic obstructive pulmonary disease (COPD). It is unclear if drinking green tea reduces the risk of COPD. Details: One prospective, observational study in older adults has found that consumption of at least 3 cups daily of tea, including green tea, oolong tea, and black tea, is associated with a 23% reduction in COPD prevalence and a 65% reduced risk of developing COPD in models adjusted for potential confounders when compared with the lowest tea consumption (107201). However, green tea was only consumed by about 19% of the population included in this study and consumption of green tea itself was not associated with a reduced risk of COPD.
Cognitive function. It is unclear if oral green tea improves cognitive function in healthy adults. Details: A small clinical study in adults ages 50-69 years shows that taking matcha powder (Hojin no shiro, Ito En, Ltd.) 9 capsules daily for 12 weeks, providing 170 mg total catechins daily, modestly improves some measures of attention and work performance when compared with taking placebo or caffeine. However, there was no effect on other measures of these outcomes, or on verbal memory tasks, visual information processing, working memory, motor function, or facial expression recognition (107168). Another small clinical study shows that taking a single dose of the green tea constituent, epigallocathechin-3-gallate (EGCG), 135 or 270 mg does not seem to improve mood or cognitive performance in healthy adults (54059).
Cognitive impairment. It is unclear if oral green tea is beneficial for the prevention or treatment of mild cognitive impairment in elderly adults. Details: Some population research in elderly individuals has found that drinking green tea at least once per week is associated with a 53% reduced incidence of dementia or mild cognitive impairment when compared to not consuming green tea (104598). In addition, drinking at least two cups of green tea daily was associated with a 54% lower prevalence of cognitive impairment (104611). Some clinical research shows that taking two capsules of a specific combination product containing green tea extract 360 mg/capsule and L-theanine 60 mg/capsule (LGNC-07, LG Household & Health Care, Ltd) twice daily after meals for 16 weeks improves memory and attention in patients with mild cognitive impairment when compared with placebo (54019).
Colorectal adenoma. It is unclear if oral green tea extract is beneficial for reducing colorectal adenoma recurrence. Details: A large clinical trial in patients with previously removed colorectal adenomas shows that taking green tea extract (Dr. Loges + Co. GmbH) standardized to epigallocatechin gallate (EGCG) 150 mg twice daily for 3 years does not affect the risk of developing new metachronous adenomas when compared with taking placebo (111020). However, a sub-group analysis shows that taking green tea extract results in a 10% absolute reduction in risk of adenoma formation in males, but not females (111020). Also, preliminary clinical research in patients with previously removed colorectal adenomas shows that taking green tea extract 1.5 grams daily for 12 months reduces the incidence of metachronous adenomas when compared with placebo (53816).
Colorectal cancer. It is unclear if oral green tea is beneficial for colorectal cancer prevention. Details: Although evidence from individual population studies is mixed (9222,9223,14498,90176,90178,90181,102718), meta-analyses of population research suggest that a high intake of green tea is associated with a reduced risk of colorectal cancer (36416,102716). The highest intake of green tea is associated with a 16% reduced risk when compared with the lowest; however, the benefit appears to be specific to colon cancer, not rectal cancer (102716). When subdivided according to gender, evidence from case-control research suggests that green tea is associated with a reduced risk of colon and rectal cancer for females (54096).
Common cold. It is unclear if oral green tea is beneficial for the common cold. Details: Preliminary clinical research shows that taking two capsules of a specific formulation (ImmuneGuard, Nutraceutical Holdings LLC) containing L-theanine (Suntheanine, Taiyo International) plus epigallocatechin gallate (Sunphenon, Taiyo International) twice daily for 3 months reduces cold or flu symptoms and duration of symptoms when compared with placebo in healthy adults (53754).
Crohn disease. Although there has been interest in using oral green tea for Crohn disease, there is insufficient reliable information about the clinical effects of green tea for this condition.
Dementia. It is unclear if drinking green tea is beneficial for dementia prevention. Details: A meta-analysis of observational studies in over 20,000 adults suggests that the risk of any cognitive deficit (including mild cognitive impairment and dementia) is associated with a 6% reduction per cup of green tea consumed daily (107829). Some population research in elderly individuals suggests that drinking green tea at least once per week is associated with a 53% reduced incidence of dementia or mild cognitive impairment when compared to not consuming green tea (104598). Other population research in adults ages 40-74 years suggests that drinking at least 600 mL of green tea daily is not associated with a reduced risk of developing dementia when compared with drinking less than 60 mL daily. However, there is a modest reduction in dementia risk specifically in individuals ages 60-69 years (107164). A prospective, observational study suggests that consumption of tea, including both green and black tea, of at least 4 cups, in conjunction with 0.5-1 cups of coffee, daily is associated with a 30% reduced risk of dementia when compared with not drinking tea or coffee. Also, drinking 2-3 cups daily of both tea and coffee is associated with a 28% reduced risk of dementia when compared with not drinking tea and coffee (107204). Any association between drinking green tea specifically and developing dementia cannot be determined from this study.
Dental plaque. It is unclear if oral or topical green tea is beneficial for reducing dental plaque. Details: A meta-analysis of clinical research shows that use of oral or topical products containing green tea modestly reduces dental plaque when compared with control products, including triclosan toothpaste, placebo, and chlorhexidine rinse. However, a sub-group analysis shows that a green tea rinse is no more effective than a chlorhexidine rinse. Green tea products in these studies included mouth rinse, paste, tea, capsules, and strips (107156). Many of these studies are limited by a lack of clear blinding. A more recent clinical study in children ages 10-14 years with plaque and gingivitis shows that using a mouthwash containing green tea extract 5% twice daily, alone or at half strength with ginger extract, for 30 days reduces plaque and gingivitis severity. The mouthwash containing the combination of green tea and ginger extract was most effective, and the green tea extract alone was at least as effective as chlorhexidine (107163).
Depression. It is unclear if drinking green tea is beneficial for depression prevention. Details: Epidemiological research suggests that consuming green tea is associated with a reduced prevalence of depression and depressive symptoms. In Japanese adults, drinking four or more cups of green tea daily is associated with a 44% to 51% lower prevalence of mild to severe depression when compared to consuming one cup or less daily (90160,90163). A meta-analysis suggests that the highest green tea consumption is associated with a 34% reduced risk of depressive symptoms when compared with the lowest (111024). Other research in a general population of Chinese adults suggests that consuming at least 1 cup of green tea daily is associated with a 22% decreased risk of depressive symptoms over 2 years when compared with almost never consuming green tea. However, there is no association between depressive symptoms and less frequent green tea consumption in this population (111023).
Diabetes. It is unclear if drinking green tea or taking green tea extract is beneficial for the prevention of diabetes or the improvement of glycemic control. Details: Epidemiological research has found that Japanese adults who consume 6 or more cups of green tea daily have a 33% lower risk of developing type 2 diabetes when compared to those who consume one cup or less daily. The risk reduction appears to be more pronounced in females when compared with males (14313). Also, epidemiological research has found that Chinese adults who consume at least one cup of green tea per week have a 59% to 77% lower risk of impaired fasting glucose when compared to those who consume less than one cup per week (90149). Other epidemiological research has found that consumption of any amount of green tea daily by Chinese adults is associated with an 8% reduced risk of developing type 2 diabetes when compared with never drinking green tea (107165). In contrast, some epidemiological research in Chinese adults has found that green tea consumption is associated with a 20% increased risk of developing type 2 diabetes when compared with non-green tea drinkers. A dose-response relationship was found for both the amount and duration of tea consumed (107170). Also, clinical research in patients with prediabetes shows that drinking one cup of green tea three times daily for 14 weeks does not improve fasting blood glucose or glycated hemoglobin (HbA1c) when compared to control (90174). There is inconsistent evidence regarding the effects of green tea in patients with type 2 diabetes. Epidemiological research suggests that drinking at least 4 cups of green tea daily is associated with a 40% reduction in mortality risk when compared to not drinking green tea (104589). Other epidemiological research in patients with type 2 diabetes has found that consumption of any amount of green tea daily is associated with a 10% reduction in mortality risk when compared to never drinking green tea. However, there was no association between green tea intake and the incidence of developing macrovascular or microvascular complications (107165). Meta-analyses of clinical research show that green tea extract and green tea catechins reduce fasting blood glucose when compared to control when patients with type 2 diabetes, borderline diabetes, or normal blood glucose status are evaluated together (90154,90187). However, a meta-analysis of up to 15 mainly small clinical trials involving patients with type 2 diabetes shows that taking green tea does not affect fasting blood glucose or insulin or improve insulin resistance or glucose control when compared with placebo. Most included studies used green tea or its extract in doses of 400-10,000 mg daily for 8-16 weeks (104604). Also, clinical research shows that taking green tea extract daily for up to 16 weeks does not improve blood glucose, HbA1c, or insulin when compared with placebo in patients with type 2 diabetes or borderline diabetes (37678,37781,54035). Some research has evaluated the effect of green tea on other outcomes in patients with type 2 diabetes. One meta-analysis shows that taking green tea extract modestly reduces fasting triglyceride levels when compared with control. This benefit was seen with doses of at least 800 mg daily taken for longer than 8 weeks. This dose and duration reduces levels of total cholesterol, but not low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol levels (102715). Another meta-analysis shows that taking green tea modestly reduces body weight, body mass index (BM), and body fat. A sub-analysis shows that these benefits occur in studies lasting more than 8 weeks, using doses of up to 800 mg daily, and in patients who were overweight. There was no effect on waist circumference. Most patients included in the analysis were overweight or had obesity (104610).
Diabetic neuropathy. It is unclear if oral green tea is beneficial for improving diabetic neuropathy symptoms. Details: Clinical research in patients with mild-to-moderate diabetic peripheral neuropathy shows that taking decaffeinated green tea extract 500 mg three times daily for 16 weeks modestly reduces neural pain and dysfunction, as well as overall symptom severity, when compared with placebo (107159).
Down syndrome. It is unclear if oral green tea is able to alter facial morphology in children with Down syndrome.
Down syndrome. There was no effect in children aged 4-18 years (107167). This study is limited by its observational design. The dosage, time of onset, and duration of treatment differed between individuals.
Dry eye. It is unclear if oral green tea is beneficial for improving dry eye symptoms. Details: In patients with mild to moderate dry eye and meibomian gland dysfunction, preliminary clinical research shows that applying green tea extract into the eyes three times daily for one month, in addition to artificial tears three times daily, improves symptoms of dry eye. Symptoms of itching, burning, foreign body sensation, and redness were improved by a moderate amount over artificial tears alone (104612).
Dysmenorrhea. It is unclear if drinking green tea is beneficial for preventing dysmenorrhea symptoms. Details: Population research has found that drinking green tea is associated with a 37% reduced odds of experiencing dysmenorrhea and a 58% reduced odds of having moderate-to-severe dysmenorrhea when compared with not drinking green tea (102729).
Esophageal cancer. It is unclear if drinking green tea is beneficial for preventing esophageal cancer; the available research is conflicting. Details: Although some epidemiological evidence and observational studies have found that drinking green tea is associated with a reduced risk of esophageal cancer, most meta-analyses do not support this finding in a mixed group of adults (1457,36542,90169,90185,90186,102004,102716,107154). Meta-analyses of epidemiological studies suggest that drinking green tea is associated with a 54% reduction in the risk of esophageal cancer, or a 21% reduced odds per cup of green tea consumed daily, only in females (90169,90185,102004,107154). Also, some epidemiological research found that drinking green tea that is very hot is associated with an increased risk of esophageal cancer (53828). In addition, drinking decaffeinated green tea 5 mg daily for 12 months does not seem to be an effective treatment for patients diagnosed with esophageal precancerous lesions (53702).
Fractures. It is unclear if drinking green tea reduces fracture risk. Details: Population research has found that consumption of green tea is associated with a 12% lower risk of any fracture and 20% lower risk of hip fracture when compared with no tea consumption (99800).
Gastric cancer. Evidence evaluating an association between green tea consumption and gastric cancer risk is conflicting. Details: Most meta-analyses of epidemiological studies suggest that green tea consumption is not associated with gastric cancer risk (53767,53813,90181,102716). Although the most recent meta-analysis of epidemiological research suggests that drinking green tea regularly is associated with up to a 9% reduced risk of gastric cancer when compared with non-regular consumption, sub-analyses suggest that there is no association between gastric cancer and intake of specific amounts of green tea up to at least 3 cups daily (111025). Also, other population research suggests that drinking 10 or more cups of green tea daily is associated with a reduced risk of gastric cancer (8903,9222,9225,9226,9227), while consuming less than 10 cups daily is not consistently associated with a reduced risk (7033,9223,54090). The association between drinking green tea and gastric cancer-related mortality has also been investigated, A large-scale population study in Japan suggests that drinking 5 or more cups of green tea daily is not associated with a reduced risk of gastric cancer-related mortality when compared to drinking less than one cup daily (14498). Discrepancies might be related to the temperature of the green tea. The most recent meta-analysis suggests that intake of cold or warm green tea, and not hot green tea, is associated with a modest reduction in gastric cancer risk (111025).
Gingivitis. It is unclear if oral or topical green tea is beneficial for gingivitis. Details: A meta-analysis of clinical research shows that use of oral or topical products containing green tea modestly reduces gingivitis and gingival bleeding when compared with control products, including triclosan toothpaste, placebo, and chlorhexidine rinse. However, a sub-group analysis shows that a green tea rinse is no more effective than a chlorhexidine rinse. Green tea products used in these studies were heterogeneous and included mouth rinse, gel, paste, tea, strips, and capsules (107156). Many of these studies are limited by a lack of clear blinding. A more recent clinical study in children ages 10-14 years with plaque and gingivitis shows that using a mouthwash containing green tea extract 5% twice daily, alone or at half-strength with ginger extract, for 30 days reduces plaque and gingivitis severity. The mouthwash containing the combination of green tea and ginger extract was most effective, and the green tea extract alone was at least as effective as chlorhexidine (107163).
Headache. Although there has been interest in using oral green tea for headache, there is insufficient reliable information about the clinical effects of green tea for this condition.
Hypertension. The evidence is mixed as to whether drinking green tea reduces the risk of hypertension and whether oral green tea lowers blood pressure in patients with hypertension. Details: Some epidemiological research from China shows that drinking 120-599 mL of green tea or oolong tea daily is associated with a 46% lower risk of developing hypertension when compared with non-habitual tea drinkers; drinking more than 600 mL daily is associated with a 65% reduced risk (12518). In contrast, drinking green tea daily is associated with a 38% increased odds of having hypertension when compared with never drinking green tea in elderly Chinese males, but not females (107166). Green tea may help lower blood pressure in patients with or without hypertension; however, the evidence is mixed, and any reductions appear to be small. A meta-analysis of two clinical trials in patients with hypertension shows that drinking green tea for 4-16 weeks reduces systolic, but not diastolic, blood pressure by about 6 mmHg (104583). Meta-analyses in patients with or without hypertension, including overweight or obese adults, suggest that green tea reduces systolic and diastolic blood pressure by 1-3 mmHg (90146,90155,90161,98423,102726,111018). Some studies used green tea, made by boiling a 3 gram tea bag with 150 mL water and then waiting for 5 minutes and consuming three times daily approximately 2 hours after each meal for 4 weeks (90159), or green tea extract up to 1500 mg daily for up to 12 weeks (111018), including a specific product (Olimp Labs) 379 mg, taken daily with the morning meal for 3 months (54068).
Hypotension. It is unclear if oral green tea is beneficial for postprandial hypotension in elderly adults. Details: Some research shows that consuming caffeinated beverages increases blood pressure in elderly people with postprandial hypotension (11834,11835). Also, preliminary clinical research shows that drinking 400 mL of green tea before lunch increases postprandial systolic and diastolic blood pressure by 15 mmHg and 6 mmHg, respectively, in older elderly people with postprandial hypotension (89482).
Infertility. Oral green tea has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in females with a history of problems conceiving shows that taking three capsules daily of a proprietary blend of Vitex agnus-castus extract (standardized to 0.5% agnusides), green tea extract (standardized to 50% phenols), L-arginine, vitamins E, B6, and B12, folate, iron, magnesium, zinc, and selenium (FertilityBlend, The Daily Wellness Company) for three menstrual cycles increases the rate of pregnancy at three months by 61% when compared with placebo (41479).
Influenza. It is unclear if oral green tea is beneficial for preventing the flu. Details: A meta-analysis of five clinical trials in individuals with or without prior influenza vaccination shows that use of green tea catechins, either in capsule form or as a gargled liquid, reduces the rate of influenza infections by 33% when compared with control. Also, a meta-analysis of observational research has found that gargling with or consuming green tea containing catechins is associated with a 48% reduced risk of influenza when compared with not taking green tea catechins. More information is needed to compare the efficacy of the different forms of green tea catechins (107152). Some epidemiological research not included in this meta-analysis has found that drinking at least 5 cups of green tea weekly is associated with a 32% reduced odds of developing confirmed influenza when compared with drinking less than one cup weekly. A sub-group analysis suggests that this association is only evident in individuals who had not received the influenza vaccination (104608). Conversely, other preliminary research shows that gargling with green tea at least three times daily for 90 days does not prevent influenza in high school students when compared with water (90150). Green tea has also been evaluated in combination with theanine. One small study shows that taking a combination of green tea catechins (THEA-FLAN 90S, Ito-en Co) 378 mg standardized to 270 mg of epigallocatechin gallate (EGCG) with theanine 210 mg daily for 5 months reduces the risk of developing clinically defined influenza, but not laboratory-confirmed influenza infection, when compared with placebo (54021). Other preliminary clinical research in healthy adults shows that taking two capsules of a specific formulation (ImmuneGuard, Nutraceutical Holdings LLC) containing L-theanine (Suntheanine, Taiyo International) plus EGCG (Sunphenon, Taiyo International) twice daily for 3 months reduces the number of subjects with cold or flu symptoms and the number of days with symptoms when compared with placebo (53754).
Japanese cedar pollinosis. It is unclear if oral green tea is beneficial for preventing Japanese cedar pollinosis symptoms. Details: In patients with Japanese cedar pollinosis, clinical research shows that drinking Benifuuki green tea drink 350 mL containing O-methylated catechin 34-40 mg daily beginning 6-10 weeks before pollen exposure until the end of pollen season can reduce nasal and ocular symptoms. Clinical research compared the "benifuuki" drink enriched in O-methylated EGCG with that of another green tea "yabukita," containing no O-methylated EGCG (53884,90156).
Kidney stones (nephrolithiasis). It is unclear if drinking green tea prevents kidney stones. Details: Population research suggests that drinking green tea is associated with a reduced risk of having kidney stones. This risk was 22% lower in males and 16% lower in females when compared with never or former green tea drinkers (104613).
Leukemia. It is unclear if drinking green tea is beneficial for leukemia prevention. Details: Although some large epidemiological studies suggest that drinking green tea reduces the risk of leukemia by 51% to 80% (53799,90183,102723), a meta-analysis of generally low-quality population research shows a variable association between green tea intake and risk of leukemia (102716).
Liver cancer. It is unclear if drinking green tea is beneficial for liver cancer prevention. Details: Two meta-analyses of epidemiological research suggest that green tea consumption is associated with a reduced risk of liver cancer (97132,111016). The most recent meta-analysis in approximately 1.5 million adults in Asia, North America, and Europe suggests that the highest intake of green tea is associated with a 20% reduced risk of liver cancer when compared with the lowest. The most benefit was associated with consumption of at least 4 cups daily (111016). Another meta-analysis that included studies conducted in Japan, China, or Singapore suggests that higher green tea consumption is associated with a 12% reduced incidence of liver cancer when compared with the lowest consumption of green tea. However, the benefit appears to be limited to females; green tea consumption was not associated with a reduced risk of liver cancer in males (97132). A large epidemiological study in Chinese females also suggests that green tea consumption is associated with a reduced risk of liver cancer. Consuming a cumulative intake of 30 kg dried green tea leaves is associated with a 46% reduced risk of primary liver cancer over a median of 18 years when compared with never drinking green tea (111030). In contrast, some individual epidemiological studies suggest that green tea consumption is not associated with a reduced risk of liver cancer in Japanese individuals (90181,102716).
Lung cancer. It is unclear if drinking green tea is beneficial for lung cancer prevention. Details: Individual observational studies and meta-analyses of population research have yielded conflicting evidence about the effects of green tea on lung cancer risk (13190,14498,53829,90177,102716). Although one meta-analysis of population research suggests that the highest intake of green tea does not reduce lung cancer risk when compared to the lowest intakes (102716), other analyses suggest that increasing green tea consumption by two cups daily is associated with an 18% decreased risk of lung cancer, and that drinking 7-10 cups of green tea daily is associated with an 18% to 33% reduced risk of lung cancer when compared with drinking less than one cup daily (53829,90177).
Mental alertness. It is unclear if oral green tea is beneficial for mental alertness. Details: Green tea contains caffeine. Consumption of caffeinated beverages seems to prevent a decline in alertness and cognitive capacity when consumed throughout the day (4221,4224). Also, combining caffeine with glucose as an "energy drink" seems to improve mental performance better than placebo or either caffeine or glucose alone (13732). However, there is mixed evidence regarding the effects of green tea on mental alertness.
Metabolic syndrome. It is unclear if oral green tea is beneficial for improving metabolic parameters in people with this condition. Details: Preliminary clinical research shows that taking green tea extract 1000 mg daily or drinking four cups of green tea daily for 8 weeks does not improve metabolic syndrome features, including waist circumference, blood pressure, cholesterol levels, or blood sugar in obese patients with metabolic syndrome when compared to control (53995).
Multiple myeloma. It is unclear if drinking green tea is beneficial for multiple myeloma prevention. Details: Population research suggests that drinking at least 5 cups of green tea each day is not associated with a reduced risk of multiple myeloma when compared with never drinking green tea (102723).
Myocardial infarction (MI). It is unclear if drinking green tea prevents MI or if drinking green tea prevents mortality in patients with a previous MI. Details: When compared with drinking less than one cup of green tea daily, epidemiological research in a population at high risk of coronary artery disease has found that drinking more than three cups of green tea daily is associated with a 49% reduced odds of having a past MI as determined by a coronary angiography. A sub-group analysis found that these odds only occurred in individuals consuming both fruits and vegetables more than four times weekly and not in individuals consuming fruits or vegetables less often (104588). In addition, observational research has found that drinking either 1-3 cups or at least 4 cups of green tea daily is associated with 19% and 32% lower odds of MI, respectively, when compared to drinking less than 1 cup daily (97134). In patients with a previous MI, drinking at least 7 cups of green tea daily is associated with a 53% reduced odds of all-cause mortality over a median of 18.5 years when compared with not drinking green tea (107160).
Nasopharyngeal cancer. It is unclear if drinking green tea is beneficial for nasopharyngeal cancer prevention. Details: A meta-analysis of epidemiological research has found that the highest intake of green tea is associated with a 51% reduced risk of nasopharyngeal cancer when compared with the lowest intake (102716).
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral green tea is beneficial for NAFLD. Details: Clinical research shows that drinking green tea 700 mL containing 1080 mg of catechins daily for 12 weeks does not affect body weight or body mass index (BMI), but does reduce body fat percentage from 34% to 32%, when compared with drinking either green tea 700 mL containing 200 mg of catechins or a control tea. Also, the liver-to-spleen attenuation ratio increased by 11% when compared with baseline (90168). Meta-analyses of four studies in patients with NAFLD show that taking green tea extract 500-1000 mg daily or green tea catechins 600 mg daily improves liver function tests when compared with placebo (98459,102720). One meta-analysis also shows that these doses improve BMI, total cholesterol, and low-density lipoprotein (LDL) cholesterol when compared with placebo (98459).
Non-Hodgkin lymphoma. It is unclear if drinking green tea is beneficial for non-Hodgkin lymphoma prevention. Details: Population research has found that drinking at least 3.5 cups of green tea daily is not associated with a reduced risk of non-Hodgkin lymphoma when compared with never drinking or drinking less than 1 cup of green tea daily (102005,102723).
Obesity. Evidence for the use of green tea products for weight loss is conflicting. The conflicting findings may be related to the caffeine and catechin content of the studied products, as well as the physical activity level of the individual. Details: Many clinical studies show that drinking green tea or taking green tea extract that contains caffeine (about 70-200 mg) and high levels of catechins (about 576-886 mg) daily for 12-24 weeks modestly improves weight loss when compared to control in overweight individuals or patients with obesity (8114,37725,53906,90184). A meta-analysis of 25 randomized clinical trials shows that taking green tea extract containing caffeine results in an additional weight loss of 1.8 kg when compared with a control group not taking green tea extract (102719). In addition, a meta-analysis of clinical trials shows that taking green tea reduces body weight by 0.4 kg in mainly overweight individuals with type 2 diabetes (104610). Some research also shows that drinking green tea or taking green tea extract containing high levels of catechins but no caffeine reduces weight and visceral fat in overweight individuals or patients with obesity when used for up to 12 weeks (53994,54039,90184). In these clinical trials, the following doses have been used: two capsules of green tea extract daily standardized to containing 870 mg of catechins (460 mg EGCG) or 4 cups of green tea daily standardized to contain 928 mg of catechins (440 mg EGCG) for 8 weeks (53994); a specific decaffeinated green tea extract (Sunphenon 90LB, Taiyo Kagaku Ltd.) 530 mg twice daily for 6 weeks (54039); catechin-enriched green tea beverages providing 234-886 mg of catechins once or twice daily for approximately 3 months (37705,53906,90184); a specific green tea extract (AR25, Exolise, Arkopharma), taken as four capsules standardized to contain 375 mg of catechins (epigallocatechin gallate 270 mg) in two divided doses daily for 12 weeks (8114). Some research has also shown weight loss benefits of multi-ingredient products or diets containing green tea. Multi-ingredient products have included an herbal mixture of garcinia extract 650 mg, green tea extract 100 mg, coffee extract 75 mg, and banaba extract 25 mg per tablet (IQP-GC-101, InQpharm Europe Ltd.) 30 minutes before meals twice daily for 12 weeks (90137) and a specific product (Sanavita Industry, Piracicaba) containing powdered green tea (40 mg of caffeine), orange pulp, vitamin C, zinc, and selenium, taken as 20 grams in two divided doses daily for 8 weeks (90134). Drinking green tea has also been used as part of a Mediterranean diet also including Wolffia globose (109888). However, many studies show conflicting results (37715,37753,54035,98419,98420,98422). Reasons for these inconsistent findings are not entirely clear, but may relate to the use of decaffeinated green tea products, the use of green tea products containing low catechin amounts, or the presence and type of concomitant exercise. Some research shows that green tea extract containing a lower catechin amount (491 mg daily) or decaffeinated green tea products do not improve weight loss when compared with placebo in patients with obesity (37753,54035,98419). One meta-analysis of 15 clinical studies including about 1240 patients with obesity shows that using green tea products that are decaffeinated does not improve body weight, body mass index, or waist circumference when compared with control, while green tea products containing catechins 576-714 mg daily and caffeine do improve these outcomes (16892). Taking green tea after weight loss does not seem to improve weight maintenance when compared with control (14428,54076). Other clinical research shows that green tea does not improve weight loss in individuals with obesity who are already participating in exercise, such as walking and interval sprinting (37715,98420). In contrast, another small clinical study shows that taking green tea 500 mg daily for 10 weeks while participating in HIIT improves weight, body fat percentage, triglycerides, and low-density lipoprotein (LDL) cholesterol levels when compared with either green tea or HIIT alone. However, it appears that the majority of these improvements are due to participation in HIIT (100201). There is also some limited research in children. One small clinical trial in obese children ages 6-16 years shows that taking green tea providing 576 mg catechins daily for 24 weeks modestly reduces waist circumference, as well as systolic blood pressure and low-density lipoprotein (LDL) cholesterol, when compared with taking green tea providing 75 mg catechins daily. However, there were no significant difference between groups for other anthropometric measures or cardiovascular risk factors (37743). Another clinical trial in obese females ages 6-10 years who were also given diet and exercise advice shows that taking decaffeinated green tea polyphenols 400 mg daily for 12 weeks modestly reduces fat mass, but does not affect other anthropometric measures, when compared with placebo. Also, taking green tea polyphenols modestly reduces ovary volume, but has no effect on other measures of early puberty, such as breast development, uterine volume, or levels of sex hormones (107162).
Oral cancer. It is unclear if oral green tea is beneficial for oral cancer prevention. Details: Meta-analyses of epidemiological research suggest that the highest intake of green tea is associated with a 20% to 29% reduction in risk of oral cancer when compared with the lowest intake (90180,102716). Also, preliminary clinical research in patients with high-risk oral premalignant lesions shows that taking a green tea extract 500-1000 mg/m2 three times daily after meals for 12 weeks increases the rate of clinical and histological response when compared with placebo (53936).
Oral leukoplakia. It is unclear if drinking green tea and concomitantly applying topical green tea to lesions is beneficial for oral leukoplakia. Details: Preliminary clinical research in patients with oral leukoplakia shows that drinking 3 grams of a mixed tea product containing green tea daily for 6 months, while also topically applying a 10% mixed tea product in the mouth three times daily, reduces oral lesion size by about 38%, compared with a 3% increase in those taking placebo. It is not clear if this effect is due to green tea, the other ingredients, or the combination (4213).
Osteopenia. It is unclear if oral green tea is beneficial for preventing osteopenia. Details: Population research suggests that drinking green tea for 10 years is associated with increased bone mineral density (8116). Other population research suggests that drinking less than one cup of green tea daily is associated with an 81% to 85% increased odds of having osteopenia when compared with drinking green tea 1-3 times daily (111026). Preliminary clinical research in postmenopausal adults with osteopenia shows that taking capsules containing green tea polyphenols 500 mg (233 mg as epigallocatechin-3-gallate or EGCG) daily, possibly while practicing tai chi 60 minutes three times weekly, for 24 weeks improves serum markers of bone turnover and muscle strength when compared to baseline (54040). However, the results from this study are limited by a lack of control group and the fact that diagnostic measures of bone health, such as T-score or Z-score, were not assessed.
Osteoporosis. It is unclear if oral green tea is beneficial for preventing osteoporosis. Details: Population research suggests that drinking green tea for 10 years is associated with increased bone mineral density (8116). Other population research suggests that drinking less than one cup of green tea daily is associated with up to a 91% increased odds of having osteoporosis when compared with drinking green tea 1-3 times daily (111026). More recent clinical research shows that taking decaffeinated green tea extract supplying approximately 1315 mg of catechins (843 mg as EGCG) daily does not improve bone mineral density, T-score, or Z-score in postmenopausal adults (98419).
Overall mortality. Some population research suggests that drinking green tea may reduce the risk of overall mortality by a small amount. Details: A meta-analysis of population research in Japanese adults found that drinking at least 5 cups of green tea daily is associated with reduced risk of all-cause mortality when compared with drinking less than 1 cup daily (102002). Another meta-analysis of population research found that each one cup per day increase in green tea consumption is associated with a 3% reduced risk of all-cause mortality (102728). However, more recent population research has found that although drinking green tea is associated with reduced risk of all-cause mortality in patients with a previous MI and stroke, drinking as much as 7 cups of green tea daily is not associated with a reduced odds of all-cause mortality over a median of 18.5 years in individuals with no history of stroke or MI when compared with not drinking green tea (107160).
Pancreatic cancer. It is unclear if drinking green tea is beneficial for pancreatic cancer prevention. Details: A meta-analysis of population research suggests that the highest intake of green tea is not associated with a reduced risk of pancreatic cancer when compared with the lowest intake (102716). However, one epidemiological study suggests that drinking green tea is associated with a reduced risk of pancreatic cancer (54096).
Parkinson disease. Although consuming caffeinated beverages might reduce the risk of developing Parkinson disease, it is unclear if oral green tea prevents or improves symptoms in people with this condition. Details: There is some evidence from large-scale epidemiological studies that the incidence of Parkinson disease decreases with increased consumption of caffeinated beverages such as coffee, tea, and cola. For men, the effects seem to be dose related. Men consuming a total of 421-2716 mg of caffeine (approximately 5-33 cups of tea) from any source daily seem to have the greatest reduction in risk. However, there seems to be a significant reduction in risk even with consumption of as little as 124-208 mg caffeine daily (approximately one to three cups tea) (6022). In females, the effects do not seem to be dose related. Moderate consumption of approximately 1-4 cups daily seems to provide the most reduction in risk (1238). It is unclear if consuming green tea is more or less effective than other caffeinated beverages for reducing Parkinson disease risk.
Periodontitis. It is unclear if oral or topical green tea is beneficial for improving oral health or improving periodontal disease. Details: Epidemiological research has found that intake of green tea is inversely associated with symptoms of periodontal disease, including probing depth, attachment loss, and bleeding on probing (53844). A small clinical trial shows that taking green tea extract 1.55% by weight in chewable candy for 28 days appears to reduce plaque accumulation and gingival inflammation (7594). A small clinical trial in patients with chronic periodontitis shows that applying a gel containing green tea extract 1 gram/100 mL into the periodontal pocket as an adjunct to scaling improves gingivitis, periodontal disease, and clinical attachment by 7%, 112%, and 116%, respectively, when compared with placebo gel (90135). A meta-analysis of low-quality clinical research also shows that use of oral or topical products containing green tea modestly improve clinical attachment when compared with control products, including triclosan toothpaste and placebo. Green tea products included gel, paste, and tea (107156).
Pneumonia. It is unclear if drinking green tea is beneficial for pneumonia prevention. Details: Epidemiological research in Japanese females has found that consuming green tea is associated with a lower risk of death from pneumonia when compared to those who do not drink green tea (53897). However, other epidemiological research in hospitalized elderly Japanese adults has found that there is no association between green tea consumption during the past month and prevalence of pneumonia at time of hospitalization (107161).
Polycystic ovary syndrome (PCOS). It is unclear if oral green tea is beneficial for PCOS. Details: A meta-analysis of 4 small clinical trials shows that taking green tea modestly reduces weight in patients with PCOS when compared with placebo. However, there was no effect on other endpoints including body mass index (BMI), percent body fat, or waist or hip circumference. Three studies in the meta-analysis used green tea 1000-2000 mg/daily in tablets or capsules; the other study used green tea powder providing epigallocatechin gallate 1620 mg daily (111019). However, the included studies were small and utilized heterogeneous dosing regimens.
Postoperative pain. It is unclear if rinsing the mouth with green tea is beneficial for postoperative pain associated with molar removal. Details: In patients undergoing third molar extraction, a small clinical trial shows that using 15 mL of a mouthwash containing green tea extract 5 grams/100 mL twice daily, beginning the day after surgical removal of impacted molars and continuing for 7 days thereafter, reduces pain by 60% and analgesic use during the first three days when compared with using a mouthwash that does not contain green tea (90141).
Prostate cancer. It is unclear if drinking green tea or taking green tea catechins by mouth is beneficial for prostate cancer treatment or prevention. Details: Green tea catechins have been evaluated for reducing prostate cancer risk in high-risk patients (14127,98421,102716). A meta-analysis of results from three clinical trials shows that taking green tea catechins 400-600 mg daily for 12-30 months reduces the risk of prostate cancer by approximately 62% when compared with placebo in high-risk patients (98421). However, another meta-analysis including two of these studies plus one additional does not show that taking green tea catechins reduces the incidence of prostate cancer in high-risk patients (102716). Most population research has found that drinking higher amounts of green tea is not associated with a reduced risk for prostate cancer when compared with those who never or rarely drink green tea (14128,54036,53741,53753,90153,90181,98421). However, one meta-analysis of population research found that people who drink very high amounts of green tea (7-15 cups daily) have a 19% to 44% reduced risk of prostate cancer (98421). Another population study found that higher green tea intake is associated with a reduced risk of advanced, but not overall, prostate cancer risk (53753). In April 2012, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that consuming green tea may reduce the risk of prostate cancer, although the FDA has concluded that there is very little scientific evidence to support this claim (102106). Additionally, most clinical research shows that drinking large amounts of green tea or taking green tea extract does not reduce disease progression in patients with prostate cancer (11366,53726). Green tea and green tea catechins have also been evaluated for reducing prostate specific antigen (PSA) levels. A meta-analysis of clinical research in patients with or at risk of prostate cancer shows that taking green tea or green tea extract for 3 weeks to 12 months does not modify PSA levels when compared with water or placebo. However, sub-analyses suggest that there is significant heterogeneity with respect to findings between geographical locations, with some evidence of benefit in studies conducted in the US (107155).
Radiation dermatitis. It is unclear if topical green tea is beneficial for preventing radiation dermatitis. Details: Preliminary clinical research in patients undergoing radiotherapy after breast cancer surgery shows that spraying epigallocatechin gallate (EGCG) over the radiation field prevents the development of at least moderate severity radiation dermatitis by 30% when compared with saline as placebo. Also, occurrence of symptoms was delayed by about 2.7 days and symptom severity was reduced. EGCG 660 mcmol/L was sprayed 3 times daily from the first day of radiation until 2 weeks after completion at 0.05 mL per squared cm (111031). The interpretation of these results is limited by the unbalanced treatment groups.
Radiation-induced diarrhea. It is unclear if oral green tea is beneficial for reducing diarrhea associated with radiotherapy. Details: A small clinical trial shows that taking a green tea tablet (Camgreen, Iran Giahessence Pharmacy Co.) 450 mg daily for 5 weeks during pelvic irradiation reduces the frequency of diarrhea in patients undergoing radiotherapy treatment. In the fifth week of treatment, 19% of patients taking green tea had diarrhea, compared with approximately 62% of those taking placebo (104614).
Radiation-induced nausea and vomiting. It is unclear if oral green tea is beneficial for reducing vomiting associated with radiotherapy. Details: A small clinical trial shows that taking a green tea tablet (Camgreen, Iran Giahessence Pharmacy Co.) 450 mg daily for 5 weeks during pelvic irradiation does not reduce the frequency of vomiting when compared with placebo in patients undergoing radiotherapy treatment (104614).
Renal cell carcinoma. It is unclear if oral green tea is beneficial for preventing kidney cancer. Details: Epidemiological research suggests that green tea intake is not associated with risk of kidney cancer over a mean of 19 years in Japanese adults. However, in females, consuming at least 5 cups of green tea daily, but not lesser amounts, is associated with a 55% reduced risk of kidney cancer when compared with rare intake (111022).
Skin cancer. Although there has been interest in using oral or topical green tea for skin cancer, there is insufficient reliable information about the clinical effects of green tea for this condition.
Stress. It is unclear if oral green tea is beneficial for stress reduction. Details: Preliminary clinical research shows that taking a specific brand of green tea extract (Teavigo, DSM) 300 mg orally for 7 days reduces stress and increases calmness when compared with placebo in healthy individuals (54055).
Stroke. It is unclear if consumption of green tea is associated with a reduced risk of stroke or with reduced all-cause mortality in patients with a previous stroke. Details: Large-scale population research in Japanese individuals suggests that consuming at least 3-5 cups of green tea daily is associated with a reduced risk of cerebrovascular mortality when compared with drinking less than 1 cup daily. This association appears to be primarily related to a decrease in risk for cerebral infarction or hemorrhage (14498,54080,102002). Other population research suggests that drinking 1-3 cups of green tea daily is associated with a 36% reduced odds of stroke when compared with drinking less than 1 cup daily, while drinking 4 or more cups daily has no effect. Also, green tea consumption was not associated with reduced incidence of cerebral hemorrhage or infarction in this study (97134). Meta-analyses of population research suggest that an increase of 1 cup per day in green tea consumption is associated with a 6% reduced risk of stroke or cerebral hemorrhage (102728,111021). A prospective, observational study also suggests that higher intake of tea, including green and black tea, of at least 2 cups daily is associated with a 16% reduced risk of stroke when compared with not drinking tea. This study also found that drinking 2-3 cups daily of each tea and coffee is associated with a 38% reduced risk of stroke when compared with not drinking tea and coffee. The combination of 0.5-1 cups of coffee and 2-3 cups of tea daily, but not tea alone, was associated with a 50% reduced risk of post-stroke dementia when compared with not drinking tea and coffee (107204). In patients with a previous stroke, drinking at least 3 cups of green tea daily is associated with a 48% to 62% reduced odds of all-cause mortality over a median of 18.5 years when compared with not drinking green tea (107160).
Sunburn. It is unclear if oral or topical green tea is beneficial for preventing ultraviolet radiation-induced erythema. Details: A meta-analysis of three small clinical trials shows that taking green tea catechins 540-1402 mg daily for 6 to 12 weeks has a small to moderate protective effect against ultraviolet radiation-induced erythema when compared with placebo, especially at lower doses of ultraviolet radiation. A single topical dose of green tea ingredients may also be beneficial, but data is limited (107153).
Systemic lupus erythematosus (SLE). It is unclear if oral green tea is beneficial for SLE. Details: Preliminary clinical research shows that taking green tea extract 500 mg (containing 22% polyphenols) twice daily for 3 months modestly improves disease activity, general health, and vitality when compared with placebo (97136).
Tinea pedis. It is unclear if a topical green tea footbath is beneficial for athlete's foot. Details: In bedridden, elderly patients with cognitive deficiency, use of a footbath containing a 0.1% green tea extract for 15 minutes once daily for 12 weeks does not improve symptoms of athlete's foot, but does improve skin condition, when compared with a footbath not containing green tea. The green tea extract Sunphenon BG-3 (Taiyo Kagaku Co. Ltd., Yokkaichi), prepared by dissolving 5 grams of the Sunphenon BG-3 product in 5 liters of water to create a 0.1% green tea solution, was used (90151).
Ulcerative colitis. It is unclear if oral green tea is beneficial for ulcerative colitis. Details: Preliminary clinical research in patients with mild to moderate ulcerative colitis shows that taking a specific green tea product (Polyphenon E, Mitsui-Norin) 200 mg or 400 mg twice daily for 8 weeks may increase the number of people who respond to therapy and achieve remission when compared with placebo. After treatment, 10 of 15 patients in the green tea extract group responded to therapy and 8 of 15 patients achieved remission, compared with 0 in the placebo group (90140).
Upper respiratory tract infection (URTI). It is unclear if gargling and swallowing green tea is beneficial for reducing URTI symptoms. Details: Preliminary clinical research shows that gargling and swallowing green tea (Morgentau, Ronnefeld KG) 100 mL daily over 4 days is less effective than proprietary labdanum lozenges (CYSTUS052, Dr Pandalis Urheimische Medizin GmbH & Co.) for upper respiratory tract symptoms in patients with URTIs (53867).
Urinary tract infections (UTIs). It is unclear if oral green tea is beneficial for reducing UTI symptoms. Details: A small clinical study in females with acute uncomplicated cystitis shows that adding green tea 2000 mg daily for 3 days to treatment with trimethoprim-sulfamethoxazole reduces symptoms of cystitis when compared with placebo (99799). This study is limited by its small size and the lack of information on antibiotic resistance in each treatment group.
Wrinkled skin. It is unclear if oral or topical green tea is beneficial for wrinkles. Details: Some preliminary clinical research shows that taking green tea catechins 175 mg twice daily for two years does not reduce signs of photo-aging of the skin in females with facial photo-aging when compared with placebo (53873). However, using a combination of topical green tea 10% cream and oral green tea extract 300 mg twice daily for 8 weeks seems to improve skin elasticity in females with moderate photo-aging based on microscopic analysis, although the clinical appearance of the skin does not seem to significantly improve (53731). Other preliminary clinical research shows that consuming one liter of a beverage with green tea polyphenols for 12 weeks improves skin elasticity, roughness, and hydration in middle-aged females when compared with placebo (54030). More evidence is needed to rate green tea for these uses.

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LEMON (Lemon Bioflavonoid Complex)

INSUFFICIENT RELIABLE EVIDENCE to RATE

Allergic rhinitis (hay fever). Lemon has only been evaluated in combination with quince in a nasal spray for hay fever; its effect when used alone is unclear. Details: A small clinical study in patients with grass pollen allergy shows that using a specific nasal spray (Gencydo, Weleda AG) containing lemon and quince three times daily for 7 days does not improve the symptoms of allergic rhinitis when compared with placebo. In this study, using the nasal spray reduced airway resistance during inspiration at 10 and 20 minutes after pollen exposure, and reduced airway resistance during expiration at 20 minutes after pollen exposure (98826).
Anxiety. It is unclear if aromatherapy with lemon essential oil reduces test anxiety. Details: A small clinical study in first year nursing students in Turkey shows that administering aromatherapy with lemon essential oil for 15 minutes prior to an exam reduces test anxiety scores when compared with control students (110779). However, it is unclear whether any improvements are clinically significant or lead to improved test scores.
Halitosis. Lemon essential oil has only been evaluated in combination with other essential oils; its effect when used alone is unclear. Details: Preliminary research in males with dementia in a long-term care facility shows that cleaning the tongue, gums, and teeth with a solution of lemon, peppermint, and tea tree essential oils twice daily for 7 days improves oral condition, measured on the Korean Oral Assessment Guide scale, increases salivary pH into the normal range, and decreases halitosis score when compared with saline control. On a scale of 0 to 5, the essential oil mixture reduced the halitosis score by 1.24 points, compared with 0.2 points for the control (112957).
Hypertension. It is unclear if oral lemon is beneficial in patients with high blood pressure. Details: A small, prospective, population study in middle-aged Japanese women has found that increased lemon intake is associated with a modest reduction in systolic, but not diastolic, blood pressure (93471).
Kidney stones (nephrolithiasis). It is unclear if oral lemon juice is beneficial for recurrent idiopathic calcium oxalate nephrolithiasis. Details: A randomized, controlled trial in patients with recurrent idiopathic calcium oxalate nephrolithiasis shows that taking fresh lemon juice 60 mL orally twice daily for 2 years with a standard diet does not improve the time to stone recurrence when compared with no supplementation. The validity of these findings is limited due to poor patient adherence, which declined from 79% at 6 months, to 68% at 1 year, and 48% at 2 years. When restricted to a 1-year follow-up, stone recurrence occurred in 10% of patients taking lemon juice, compared with 21% of patients in the control group; this difference was statistically significant (107489).
Meniere disease. Although there is interest in using lemon orally for Meniere disease, there is insufficient reliable information about the clinical effects of lemon for this condition.
Myocardial infarction (MI). It is unclear if aromatherapy with lemon essential oil is beneficial in patients with acute MI. Details: A small clinical study in hospitalized patients with acute MI shows that administering aromatherapy with lemon essential oil over 3 days moderately reduces systolic blood pressure, but not diastolic blood pressure, when compared with a paraffin control. Heart rate and anxiety were reduced by a small amount the day following the completion of lemon aromatherapy (103455).
Nausea and vomiting. It is unclear if aromatherapy with lemon oil is beneficial in palliative care patients with nausea and vomiting. Details: A small observational study in hospitalized palliative care patients with advanced cancer has found that administering aromatherapy with lemon oil pads relieves nausea and vomiting in 73% of applications (110778). The interpretation of these findings is limited by the use of a retrospective chart review and the lack of a comparator group.
Obesity. Although there is interest in using lemon orally for obesity, there is insufficient reliable information about the clinical effects of lemon for this condition.
Oral mucositis. Lemon has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A randomized, controlled trial in patients with head and neck cancer receiving external beam radiotherapy 5 days weekly shows that using a 2:1 oral honey-lemon throat spray four to eight times daily, beginning 1 day prior to radiotherapy initiation and continuing for 5 weeks, does not improve severity of mucositis when compared with oral benzydamine hydrochloride throat spray applied four to eight times daily. The actual rate of oral mucositis occurrence is 65% in those receiving the honey-lemon spray, compared with 35% with the benzydamine hydrochloride spray; however, this difference was not statistically significant (107487). This study may have been inadequately powered to detect a difference between groups. Also, the validity of these findings is limited due to the lack of objective outcome measures.
Postoperative nausea and vomiting (PONV). It is unclear if aromatherapy with lemon essential oil is beneficial in patients with PONV. Details: Preliminary research in patients undergoing lower extremity fracture surgery shows that aromatherapy with lemon essential oil started the morning of surgery, then every 2 hours to the end of surgery, in the recovery room, and 16 hours after surgery reduces the frequency, severity, and amount of PONV, and the frequency of anti-emetic drug administration after surgery, when compared with control. The intensity of pain is also reduced, but not the amount of post-operative opioid needed (112956).
Pregnancy-induced nausea and vomiting. It is unclear if aromatherapy with lemon essential oil is beneficial in patients with nausea and vomiting due to pregnancy. Details: A small clinical study in pregnant patients shows that practicing aromatherapy with 2 drops of lemon essential oil placed on a cotton ball as needed modestly reduces pregnancy-induced nausea and vomiting on 2 of 4 days of the study when compared with placebo (93475).
Radiation-induced sialadenitis. Aromatherapy with lemon essential oil has only been evaluated in combination with other essential oils; its effect when used alone is unclear. Details: A small clinical study in patients with thyroid cancer shows that receiving 10-minute aromatherapy baths with lemon and ginger essential oils prior to meals for 2 weeks before treatment with radioactive iodine therapy attenuates damage to the salivary gland when compared with distilled water baths (98129).
Respiratory tract infections. Although there is interest in using lemon orally for respiratory tract infections such as cold and flu, there is insufficient reliable information about the clinical effects of lemon for these conditions. More evidence is needed to rate lemon for these uses.

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Safety view details

Below is general information about the safety of the known ingredients contained in the product Grape Seed Extract 50 mg. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

GRAPE (Leucoselect Grape seed extract)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Grapes and grape skin extracts have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).

POSSIBLY SAFE ...when the whole fruit of the grape, or extracts of the fruit, seed, or leaf, are used orally and appropriately in medicinal amounts. Grape seed extracts have been used with apparent safety in doses up to 200 mg daily for up to 11 months (9182,53016) and in doses up to 2000 mg daily for up to 3 months (53149,53190). Specific grape fruit extracts (Stilvid, Actafarma; Cognigrape, Bionap srl) have been used with apparent safety in doses up to 250-350 mg daily for 3-12 months or 700 mg daily for 6 months (53254,53256,96198). A specific grape leaf extract (AS 195, Antistax, Boehringer Ingelheim) has been used with apparent safety in doses up to 720 mg daily for up to 3 months (2538,52985,53005,53206). A preparation of dehydrated whole grapes, equivalent to 250 grams of fresh grapes daily, has also been used with apparent safety for up to 30 days (18228). A specific grape seed extract (Enovita; Indena SpA) 150 mg twice daily, standardized to provide at least 95% oligomeric proanthocyanins, has been used with apparent safety for up to 16 weeks (108091) ...when used topically and appropriately. Creams and ointments containing grape seed extract 2% or 5% have been used topically with apparent safety for up to 3 weeks (91539,100955). There is insufficient reliable information available about the safety of other grape plant parts when used topically.

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods. Grapes and grape skin extracts have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912). However, whole grapes should be eaten with caution in children aged 5 years and under. Whole grapes can be a choking hazard for young children (96193). To reduce the risk of choking, whole grapes should be cut in half or quartered before being given to children. There is insufficient reliable information available about the safety of grape when used in medicinal amounts in children.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods. There is insufficient reliable information available about the safety of medicinal amounts during pregnancy and breast-feeding; avoid using in amounts greater than what is commonly found in foods.

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GREEN TEA (Green Tea extract)

LIKELY SAFE ...when green tea is consumed as a beverage in moderate amounts (733,6031,9222,9223,9225,9226,9227,9228,14136,90156)(90159,90168,90174,90184,95696). Green tea contains caffeine. According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, drinking up to 8 cups of green tea daily, or approximately 400 mg of caffeine, is not associated with significant adverse cardiovascular, bone, behavioral, or reproductive effects in healthy adults (11733,98806). The US Dietary Guidelines Advisory Committee states that there is strong and consistent evidence that consumption of caffeine 400 mg daily is not associated with increased risk of major chronic diseases, such as cardiovascular disease or cancer, in healthy adults (98806). ...when a specific green tea extract ointment is used topically and appropriately, short-term. The specific green tea extract ointment (Veregen, Bradley Pharmaceuticals) providing 15% kunecatechins is an FDA-approved prescription product. It has been safely used in trials lasting up to 16 weeks (15067). The safety of treatment beyond 16 weeks or multiple treatment courses is not known.

POSSIBLY SAFE ...when green tea extract is used orally. Green tea extract containing 7% to 12% caffeine has been used safely for up to 2 years (8117,37725). Also decaffeinated green tea extract up to 1.3 grams daily enriched in EGCG has been used safely for up to 12 months (90158,97131). In addition, green tea extract has been safely used as part of an herbal mixture also containing garcinia, coffee, and banaba extracts for 12 weeks (90137). ...when used topically and appropriately as a cream or mouthwash (6065,11310,90141,90150,90151).

POSSIBLY UNSAFE ...when consumed as a beverage in large quantities. Green tea contains a significant amount of caffeine. Chronic use, especially in large amounts, can produce tolerance, habituation, psychological dependence, and other significant adverse effects. Doses of caffeine greater than 600 mg per day, or approximately 12 cups of green tea, have been associated with significant adverse effects such as tachyarrhythmias and sleep disturbances (11832). These effects would not be expected to occur with the consumption of decaffeinated green tea. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as green tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. There is also some speculation that green tea products containing higher amounts of the catechin epigallocatechin gallate (EGCG) might have increased risk of adverse events. Some research has found that taking green tea products containing EGCG levels greater than 200 mg is associated with increased risk of mild adverse effects such as constipation, increased blood pressure, and rash (90161). Other research has found that doses of EGCG equal to or above 800 mg daily may be associated with increased risk of liver injury in humans (95440,95696,97131).

LIKELY UNSAFE ...when used orally in very high doses. The fatal acute oral dose of caffeine is estimated to be 10-14 grams (150-200 mg per kilogram). Serious toxicity can occur at lower doses depending on variables in caffeine sensitivity such as smoking, age, and prior caffeine use (11832).

CHILDREN: POSSIBLY SAFE
when used orally by children and adolescents in amounts commonly found in foods and beverages (4912,11833). Intake of caffeine in doses of less than 2.5 mg/kg daily is not associated with significant adverse effects in children and adolescents (11733,98806). ...when used for gargling three times daily for up to 90 days (90150). There is insufficient reliable information available about the safety of green tea extract when used orally in children. However, taking green tea extract orally has been associated with potentially serious, albeit uncommon and unpredictable cases, of hepatotoxicity in adults. Therefore, some experts recommend that children under the age of 18 years of age do not use products containing green tea extract (94897).

PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts. Due to the caffeine content of green tea, pregnant patients should closely monitor their intake to ensure moderate consumption. Fetal blood concentrations of caffeine approximate maternal concentrations (4260). The use of caffeine during pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects (2708,2709,2710,2711,9606,11733,16014,16015,98806). In some studies consuming amounts over 200 mg daily is associated with a significantly increased risk of miscarriage (16014). This increased risk may be most likely to occur in those with genotypes that confer a slow rate of caffeine metabolism (98806). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, most healthy pregnant patients can safely consume doses up to 300 mg daily without an increased risk of spontaneous abortion, stillbirth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). Advise keeping caffeine consumption below 300 mg daily. This is similar to the amount of caffeine in about 6 cups of green tea. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as green tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. Based on animal models, green tea extract catechins are also transferred to the fetus, but in amounts 50-100 times less than maternal concentrations (15010). The potential impact of these catechins on the human fetus is not known, but animal models suggest that the catechins are not teratogenic (15011).

PREGNANCY: POSSIBLY UNSAFE
when used orally in amounts providing more than 300 mg caffeine daily. Caffeine from green tea crosses the placenta, producing fetal blood concentrations similar to maternal levels (4260). Consumption of caffeine in amounts over 300 mg daily is associated with a significantly increased risk of miscarriage in some studies (16014,98806). Advise keeping caffeine consumption from all sources below 300 mg daily. This is similar to the amount of caffeine in about 6 cups of green tea. High maternal doses of caffeine throughout pregnancy have also resulted in symptoms of caffeine withdrawal in newborn infants (9891). High doses of caffeine have also been associated with spontaneous abortion, premature delivery, and low birth weight (2709,2711). However, some research has also found that intrauterine exposure to even modest amounts of caffeine, based on maternal blood levels during the first trimester, is associated with a shorter stature in children ages 4-8 years (109846). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as green tea, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. There is also concern that consuming large amounts of green tea might have antifolate activity and potentially increase the risk of folic acid deficiency-related birth defects. Catechins in green tea inhibit the enzyme dihydrofolate reductase in vitro (15012). This enzyme is responsible for converting folic acid to its active form. Preliminary evidence suggests that increasing maternal green tea consumption is associated with increased risk of spina bifida (15068). Also, evidence from epidemiological research suggests that serum folate levels in pregnant patients with high green tea intake (57.3 mL per 1000 kcal) are decreased compared to participants who consume moderate or low amounts of green tea (90171). More evidence is needed to determine the safety of using green tea during pregnancy. For now, advise pregnant patients to avoid consuming large quantities of green tea.

LACTATION: POSSIBLY SAFE
when used orally in moderate amounts. Due to the caffeine content of green tea, nursing parents should closely monitor caffeine intake. Breast milk concentrations of caffeine are thought to be approximately 50% of maternal serum concentrations (9892).

LACTATION: POSSIBLY UNSAFE
when used orally in large amounts. Consumption of green tea might cause irritability and increased bowel activity in nursing infants (6026). There is insufficient reliable information available about the safety of green tea extracts when applied topically during breast-feeding.

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LEMON (Lemon Bioflavonoid Complex)

LIKELY SAFE ...when used in amounts commonly found in foods. Lemon has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when inhaled in amounts used for aromatherapy, short-term. Lemon essential oil has been used with apparent safety as aromatherapy for up to 2 weeks in clinical research (93475,98128,98129). There is insufficient reliable information available about the safety of lemon when used topically, or when used orally or intranasally in medicinal amounts.

PREGNANCY AND LACTATION:
Insufficient reliable information available. Avoid using in amounts greater than those typically found in foods.

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Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product Grape Seed Extract 50 mg. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

GRAPE (Leucoselect Grape seed extract)

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Details

In vitro evidence suggests that grape extracts might decrease platelet aggregation (53017,53087).

CYCLOSPORINE (Neoral, Sandimmune)

Interaction Rating = Moderate Be cautious with this combination.

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

Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.

Details

A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water (53177). Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.

Details

A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2 (2539).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

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

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.

Details

In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes (11094,53011,53089). However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism (11094). The effects of continued grape juice consumption are unclear.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.

Details

In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes (53011). However, this interaction has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.

Details

In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes (52949). However, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.

Details

In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes (53089). However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver (53011). So far, these interactions have not been reported in humans.

MIDAZOLAM (Versed)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.

Details

Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination (53011).

PHENACETIN

Interaction Rating = Moderate Be cautious with this combination.

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

Grape juice might decrease phenacetin absorption.

Details

A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2) (2539).

(Read more about GRAPE)

GREEN TEA (Green Tea extract)

5-FLUOROURACIL

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, high doses of green tea might increase the effects and side effects of 5-fluorouracil.

Details

Animal research shows that taking green tea in amounts equivalent to about 6 cups daily in humans for 4 weeks prior to receiving a single injection of 5-fluorouracil increases the maximum plasma levels of 5-fluorouracil by about 2.5-fold and the area under the curve by 425% (98424).

ADENOSINE (Adenocard)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.

Details

Green tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine doesn't seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests (11770). However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).

ALCOHOL (Ethanol)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, alcohol might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Concomitant use of alcohol and caffeine can increase caffeine serum concentrations and the risk of caffeine adverse effects. Alcohol reduces caffeine metabolism (6370).

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Details

Conflicting reports exist regarding the effect of green tea on bleeding risk when used with anticoagulant or antiplatelet drugs; however, most evidence suggests that drinking green tea in moderate amounts is unlikely to cause a significant interaction. Green tea contains small amounts of vitamin K, approximately 7 mcg per cup (100524). Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea (1460,1461,1463,4211,6048,8028,20868). However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects. Furthermore, the catechins and caffeine in green tea are reported to have antiplatelet activity (733,8028,8029,12882,100524).

ANTIDIABETES DRUGS

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, taking green tea with antidiabetes drugs might interfere with blood glucose control.

Details

Concomitant use of green tea and antidiabetes drugs might interfere with blood glucose control. The data are conflicting. Reports claim that green tea and/or caffeine, a constituent of green tea, might increase or decrease blood sugar (6024,8646,54011,54035,54068,90154).

ATORVASTATIN (Lipitor)

Interaction Rating = Major Do not take this combination.

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

Green tea extract seems to reduce the levels and clinical effects of atorvastatin.

Details

In healthy humans, taking green tea extract 300 mg or 600 mg along with atorvastatin reduces plasma levels of atorvastatin by approximately 24%. The elimination of atorvastatin is not affected (102714). Atorvastatin is a substrate of organic anion-transporting polypeptides (OATPs). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs. Some OATPs are expressed in the small intestine and are responsible for the uptake of drugs and other compounds, which may have resulted in reduced plasma levels of atorvastatin (19079). It is not clear if drinking green tea alters the absorption of atorvastatin.

BETA-ADRENERGIC AGONISTS

Interaction Rating = Moderate Be cautious with this combination.

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

Green tea contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists (15).

BORTEZOMIB (Velcade)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might interfere with the effects of bortezomib.

Details

In vitro research shows that green tea polyphenols, such as epigallocatechin gallate (EGCG), interact with bortezomib and block its proteasome inhibitory action. This prevents the induction of cell death in multiple myeloma or glioblastoma cancer cell lines (17212). Advise patients taking bortezomib, not to take green tea.

CARBAMAZEPINE (Tegretol)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might reduce the effects of carbamazepine and increase the risk for convulsions.

Details

Green tea contains caffeine. Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg (23559,23561). Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals (23562).

CELIPROLOL (Celicard)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might reduce the levels and clinical effects of celiprolol.

Details

In a small human study, taking green tea daily for 4 days appears to decrease blood and urine levels of celiprolol by at least 98% (104607). This interaction is possibly due to the inhibition of organic anion transporting polypeptide (OATP). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is found in the intestine (19079,19080,98461) The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea (98461).

CIMETIDINE (Tagamet)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concomitant use might increase the effects and adverse effects of caffeine in green tea.

Details

Green tea contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42% (11736).

CLOZAPINE (Clozaril)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.

Details

Animal research suggests that, although green tea extract does not affect the elimination of clozapine, it delays the time to reach peak concentration and reduces the peak plasma levels (90173). Also, concomitant administration of green tea and clozapine might theoretically cause acute exacerbation of psychotic symptoms due to the caffeine in green tea. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine (13741).

CONTRACEPTIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in green tea.

Details

Green tea contains caffeine. Oral contraceptives can decrease caffeine clearance by 40% to 65% (8644).

CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concomitant use might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2) (3941,5051,11741,23557,23573,23580,24958,24959,24960,24962), (24964,24965,24967,24968,24969,24971,38081,48603). Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from green tea and increase caffeine levels.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

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

Green tea is unlikely to produce clinically significant changes in the levels and clinical effects of CYP3A4 substrates.

Details

In vitro and in vivo research suggests that green tea can inhibit intestinal CYP3A and induce hepatic CYP3A4 enzymes (20896,53747,53835,90170). However, this effect is unlikely to be clinically significant, as green tea does not appear to affect CYP3A4 activity in humans (14429,90170).

DIPYRIDAMOLE (Persantine)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.

Details

Green tea contains caffeine. Caffeine might inhibit dipyridamole-induced vasodilation (11770,11772). It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).

DISULFIRAM (Antabuse)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, disulfiram might increase the risk of adverse effects from caffeine.

Details

In human research, disulfiram decreases the clearance and increases the half-life of caffeine (11840).

DIURETIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, using green tea with diuretic drugs might increase the risk of hypokalemia.

Details

Green tea contains caffeine. In excessive amounts, caffeine can reduce potassium levels due to stimulation of the sodium-potassium pump (23579,37905,37953,38003,38034). Diuretics can also cause lower potassium levels.

EPHEDRINE

Interaction Rating = Major Do not take this combination.

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

Theoretically, concomitant use might increase the risk for stimulant adverse effects.

Details

Green tea contains caffeine. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death (6486,10307).

ESTROGENS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, estrogens might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Estrogen inhibits caffeine metabolism (2714).

ETHOSUXIMIDE (Zarontin)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might reduce the effects of ethosuximide and increase the risk for convulsions.

Details

Green tea contains caffeine. Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide (23560). However, this effect has not been reported in humans.

FELBAMATE (Felbatol)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might reduce the effects of felbamate and increase the risk for convulsions.

Details

Green tea contains caffeine. Animal research suggests that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate (23563). However, this effect has not been reported in humans.

FEXOFENADINE (Allegra)

Interaction Rating = Moderate Be cautious with this combination.

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

Green tea can decrease blood levels of fexofenadine.

Details

Clinical research shows that green tea can significantly decrease blood levels and excretion of fexofenadine. Taking green tea extract with a dose of fexofenadine decreased bioavailability of fexofenadine by about 30%. In vitro, green tea inhibits the cellular accumulation of fexofenadine by inhibiting the organic anion transporting polypeptide (OATP) drug transporter (111029). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs, specifically OATP1A2, OATP1B1, and OATP2B1. In addition, green tea has been shown to reduce the absorption of some drugs that are OATP substrates (19079,102714,102730).

FLUCONAZOLE (Diflucan)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, fluconazole might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022).

FLUTAMIDE (Eulexin)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might increase the levels and adverse effects of flutamide.

Details

Green tea contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553). Theoretically, concomitant use of caffeine and flutamide might increase serum concentrations of flutamide and increase the risk adverse effects.

FLUVOXAMINE (Luvox)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Fluvoxamine reduces caffeine metabolism (6370).

HEPATOTOXIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concomitant use might have additive adverse hepatotoxic effects.

Details

Green tea extract supplements have been linked to several cases of hepatotoxicity (14136,14310,53740,53742,53746,53752,53775,54016,15026,54027)(93256,102722).

IMATINIB (Gleevec)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might reduce the levels and clinical effects of imatinib.

Details

In animal research, a single dose of green tea extract reduces the area under the curve (AUC) of imatinib by up to approximately 64% and its main metabolite N-desmethyl imatinib by up to approximately 81% (104600). This interaction has not been shown in humans. The mechanism of action is unclear but may involve multiple pathways.

LISINOPRIL

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might reduce the levels and clinical effects of lisinopril.

Details

Preliminary clinical research shows that a single dose of green tea extract reduces plasma concentrations of lisinopril. Compared to a control group, peak levels and area under the curve (AUC) of lisinopril were reduced by approximately 71% and 66%, respectively (104599). This may be due to inhibition of organic anion transporting polypeptides (OATP) by green tea catechins (19079,19080,98461) The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea (98461).

LITHIUM

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, abrupt green tea withdrawal might increase the levels and adverse effects of lithium.

Details

Green tea contains caffeine. Abrupt caffeine withdrawal can increase serum lithium levels (609). Two cases of lithium tremor that worsened with abrupt coffee withdrawal have been reported (610).

METFORMIN (Glucophage)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, metformin might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Animal research suggests that metformin can reduce caffeine metabolism (23571). Theoretically, concomitant use can increase caffeine serum concentrations and the risk of caffeine adverse effects.

METHOXSALEN (Oxsoralen)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Methoxsalen can reduce caffeine metabolism (23572). Concomitant use can increase caffeine serum concentrations and the risk of caffeine adverse effects.

MEXILETINE (Mexitil)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, mexiletine might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Mexiletine can decrease caffeine elimination by 50% (1260).

MIDAZOLAM (Versed)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, green tea might increase the levels and adverse effects of midazolam.

Details

Animal research suggests that green tea extract can increase the maximum plasma concentration, but not the half-life, of oral midazolam. This effect has been attributed to the inhibition of intestinal cytochrome P450 3A4 (CYP3A4) and induction of hepatic CYP3A4 enzymes by green tea constituents (20896). However, it is unlikely that this effect is clinically significant, as the dose used in animals was 50 times greater than what is commonly ingested by humans.

MONOAMINE OXIDASE INHIBITORS (MAOIs)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concomitant use might increase the risk of a hypertensive crisis.

Details

Green tea contains caffeine. Caffeine has been shown to inhibit monoamine oxidase (MAO) A and B in laboratory studies (37724,37877,37912,38108). Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15). In a case report, a patient that consumed 10-12 cups of caffeinated coffee and took the MAOI tranylcypromine presented with severe hypertension (91086). Hypertension was resolved after the patient switched to drinking decaffeinated coffee.

NADOLOL (Corgard)

Interaction Rating = Major Do not take this combination.

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

Green tea seems to reduce the levels and clinical effects of nadolol.

Details

Preliminary clinical research shows that green tea consumption reduces plasma concentrations of nadolol. Compared to a control group, both peak levels and total drug exposure (AUC) of nadolol were reduced by approximately 85% in subjects who drank green tea daily for two weeks. Drinking green tea with nadolol also significantly reduced nadolol's systolic blood pressure lowering effect (19071). Other clinical research shows that a single dose of green tea can affect plasma nadolol levels for at least one hour (102721). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is involved in the uptake of nadolol in the intestine (19071,19079,19080,98461) The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea (98461).

NICARDIPINE (Cardene)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, green tea might increase the levels and adverse effects of nicardipine.

Details

Green tea contains EGCG. Animal research shows that EGCG increases the area under the curve (AUC) and absolute oral bioavailability of nicardipine. The mechanism of action is thought to involve inhibition of both intestinal P-glycoprotein and hepatic cytochrome P450 3A (90136). The effect of green tea itself on nicardipine is unclear.

NICOTINE

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concomitant use might increase the risk of hypertension.

Details

Green tea contains caffeine. Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly (36549).

NINTEDANIB (Ofev)

Interaction Rating = Moderate Be cautious with this combination.

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

Green tea seems to reduce the levels of nintedanib.

Details

Clinical research shows that green tea can significantly decrease blood levels of nintedanib. Taking green tea extract twice daily for 7 days 30 minutes prior to a meal along with nintedanib with the meal decreased the 12-hour area under the curve (AUC) values for nintedanib by 21%. There was no effect on the maximum concentration of nintedanib (111028).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might reduce the absorption of organic anion-transporting polypeptide (OATP) substrates.

Details

OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds. Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs, specifically OATP1A2, OATP1B1, and OATP2B1. In addition, green tea has been shown to reduce the absorption of some drugs that are OATP substrates, including lisinopril and celiprolol (19079,102714,102730).

PENTOBARBITAL (Nembutal)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might decrease the effects of pentobarbital.

Details

Green tea contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).

PHENOBARBITAL (Luminal)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might reduce the effects of phenobarbital and increase the risk for convulsions.

Details

Green tea contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital (23558,23559,23561). The exact mechanism of this interaction is unclear.

PHENOTHIAZINES

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Phenothiazines can reduce the metabolism of caffeine by inhibiting cytochrome P450 1A2 (CYP1A2) (23573,23574).

PHENYLPROPANOLAMINE

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure (11738). Phenylpropanolamine also seems to increase caffeine serum levels (13743).

PHENYTOIN (Dilantin)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might reduce the effects of phenytoin and increase the risk for convulsions.

Details

Green tea contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenytoin (23559,23561). The effect does not seem to be related to the seizure threshold-lowering effects of caffeine. However, the exact mechanism of this interaction is unclear.

PIOGLITAZONE (Actos)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might increase the levels and clinical effects of pioglitazone.

Details

Green tea contains caffeine. Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone (108812). However, the exact mechanism of this interaction is unclear.

QUINOLONE ANTIBIOTICS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Quinolones (also called fluoroquinolones) can decrease caffeine clearance by inhibiting cytochrome P450 1A2 (CYP1A2) enzyme (606,607,608,23554,23555,23556).

RILUZOLE (Rilutek)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.

Details

Green tea contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2, and concomitant use might reduce metabolism of one or both agents (11739).

ROSUVASTATIN (Crestor)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea extract might alter the absorption and distribution of rosuvastatin.

Details

In animal research, giving green tea extract with rosuvastatin increased plasma levels of rosuvastatin. Rosuvastatin is a substrate of organic anion-transporting polypeptide (OATP)1B1, which is expressed in the liver. The increased plasma levels may have been related to inhibition of OATP1B1 (102717). However, in humans, taking EGCG with rosuvastatin reduced plasma levels of rosuvastatin, suggesting an inhibition of intestinal OATP (102730). It is not clear if drinking green tea alters the absorption of rosuvastatin.

STIMULANT DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concomitant use might increase stimulant adverse effects.

Details

Green tea contains caffeine. Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects (11832).

TERBINAFINE (Lamisil)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, terbinafine might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).

THEOPHYLLINE

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might increase the levels and adverse effects of theophylline.

Details

Green tea contains caffeine. Large amounts of caffeine might inhibit theophylline metabolism (11741).

TIAGABINE (Gabitril)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, green tea might increase the levels and adverse effects of tiagabine.

Details

Green tea contains caffeine. Animal research suggests that chronic caffeine administration can increase the serum concentrations of tiagabine. However, concomitant use does not seem to reduce the antiepileptic effects of tiagabine (23561).

TICLOPIDINE (Ticlid)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.

Details

Green tea contains caffeine. In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.

VALPROATE

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea might reduce the effects of valproate and increase the risk for convulsions.

Details

Green tea contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of valproate (23558,23559,23561,37882). However, the exact mechanism of this interaction is unclear.

VERAPAMIL (Calan, others)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concomitant use might increase the levels and adverse effects of both verapamil and caffeine.

Details

Animal research suggests that the green tea constituent EGCG increases the area under the curve (AUC) values for verapamil by up to 111% and its metabolite norverapamil by up to 87%, likely by inhibiting P-glycoprotein (90138). Also, theoretically, concomitant use of verapamil and caffeinated beverages such as green tea might increase plasma caffeine concentrations and the risk of adverse effects, due to the caffeine contained in green tea. Verapamil increases plasma caffeine concentrations by 25% (11741).

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, green tea may increase the risk of bleeding if used with warfarin.

Details

Conflicting reports exist regarding the potential of green tea to antagonize the effect of warfarin; however, most evidence suggests that drinking green tea in moderation is unlikely to cause a significant interaction. Green tea contains a small amount of vitamin K, approximately 7 mcg per cup (100524). Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea (1460,1461,1463,4211,6048,8028,20868). However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects (1460,1461,1463,8028). Therefore, use of green tea in moderate amounts is unlikely to antagonize the effects of warfarin; however, very large doses should be avoided.

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LEMON (Lemon Bioflavonoid Complex)

ITRACONAZOLE (Sporanox)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, taking itraconazole capsules or tablets with a beverage containing lemon might increase the levels and clinical effects of itraconazole.

Details

In one case report, dissolving itraconazole tablets in a small amount of specific beverages containing lemon prior to administration increased the level of itraconazole in a lung transplant patient. In this case, the increased bioavailability was desirable and was likely due to improved tablet dissolution in the acidic beverage (110781).

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Adverse Effects view details

Report an Adverse Reaction to Grape Seed Extract 50 mg

Below is general information about the adverse effects of the known ingredients contained in the product Grape Seed Extract 50 mg. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

GRAPE (Leucoselect Grape seed extract)

General ...Orally, the whole fruit, as well as the seed, fruit, and leaf extracts, seem to be well tolerated. Topically, grape seed extracts seem to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, dry mouth, dyspepsia, headache, joint pain, and nausea.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis to grape skin has been reported.

Dermatologic ...Orally, mild hair thinning has been reported in a patient taking a specific grape leaf extract AS195 KG) (2538). Urticaria (hives) has also been reported with this same extract (53206). Cases of contact dermatitis have been reported in grape workers, including those working in California vineyards (53270,53272,53275).

Gastrointestinal ...Orally, abdominal pain and nausea have been reported with use of grape seed extract, but these effects typically occur at rates similar to placebo (9182,13162). In a case report of a 57-year-old man, intermittent nausea, vomiting, and diarrhea occurred over a 10-day period and improved once grape seed extract was stopped (96764). Gastrointestinal adverse effects have also been reported with use of a different grape seed extract (Entelon, Hanlim Pharm). However, the specific types of gastrointestinal effects were not described (100954). A specific grape leaf extract AS195 (Antistax, Boehringer Ingelheim Pharma GmbH & Co. KG) has reportedly caused flatulence, mild constipation, gastrointestinal discomfort, diarrhea, dyspepsia, dry mouth, and retching (2538,52985,53206). Diarrhea, gastrointestinal distress, indigestion, and aversion to taste have been reported with use of Concord grape juice (52972,53166,53175,53181,53199). Loose stools have been reported in a clinical trial of grape pomace (99270). Bowel obstruction caused by intact grapes and grape seeds has been described in case reports (53241,53284,53278). Excessive consumption of grapes, dried grapes, raisins, or sultanas might cause diarrhea due to laxative effects (4201).

Hematologic ...Orally, one case of leg hematoma following a minor trauma was reported in a person using grape leaf extract (2538). Also, one case of bruising was reported in a person drinking Concord grape juice daily for 2 weeks (52972).

Immunologic ...Orally, there is one report of an anaphylactic reaction to oral grape skin extract, which included urticaria and angioedema (4073).

Musculoskeletal ...Orally, musculoskeletal disorders, including back pain, have been reported with use of a specific grape leaf extract AS195 KG) (2538,53206). Joint pain and lumbago have been reported with use of grape seed extract, but these effects occur at rates similar to placebo (91541).

Neurologic/CNS ...Orally, headache has been reported with use of grape seed extract, but this effect occurs at rates similar to placebo (9182,91541). A specific grape leaf extract AS195 (Antistax, Boehringer Ingelheim Pharma GmbH & Co. KG) has reportedly caused dizziness, tiredness, headache, and sleep problems (2538,53206). As a class, nervous system adverse effects have been reported with use of a specific grape seed extract (Entelon, Hanlim Pharm). However, the specific types of adverse neurologic effects were not described (100954).

Ocular/Otic ...Orally, ocular adverse effects have been reported with use of a specific grape seed extract (Entelon, Hanlim Pharm). However, the specific types of ocular adverse effects were not described (100954).

Pulmonary/Respiratory ...Orally, nasopharyngitis and oropharyngeal pain have been reported with use of a specific grape leaf extract AS195 KG) (53206). Sore throat, cough, allergic rhinitis, and nasopharyngitis have been reported with use of grape seed extract, but these effects occur at rates similar to placebo (9182,91541). One case report describes a 16-year-old female who developed increased levels of immunoglobulin E (IgE) following skin-prick exposure to grape vine pollen, as well as positive test responses following bronchial and conjunctival provocation (53301). Reduced forced vital capacity has been described in California grape workers (53080,53081). Occupational eosinophilic lung was diagnosed in a grape grower with a history of asthma. Respiratory exposure to sulfites in grape was implicated as the cause of the adverse reaction (53285).

Other ...Orally, grape products can cause adverse effects due to contamination with pesticides or mycotoxins. Some evidence has shown that pesticides used in vineyards may remain on grape surfaces post-harvesting. For example, the fungicide folpet sprayed on grapevines has been shown to remain on the grape surface. Although there was minimal penetration of the epicuticular wax, it showed high resistance to washing (52935). Carbaryl has been identified in over 58% of juice samples collected in Canada. This pesticide reportedly occurred more frequently in grape than in other juices. However, estimates of short-term intake were below proposed acute reference doses (53003).
Ochratoxin A is a mycotoxin that is suspected to be nephrotoxic, teratogenic, hepatotoxic and carcinogenic and has been identified in grape juice, frozen grape pulps, and red and white wine sold in Rio de Janeiro, Brazil. However, the highest levels identified in grape products were lower than the established virtually safe dose of 5 ng/kg of body weight daily (53010,53004). Ochratoxin A has also been identified in red, but not white, grape juice marketed in Switzerland, Canada, and the U.S. (53292,53020).

(Read more about GRAPE)

GREEN TEA (Green Tea extract)

General ...Orally, green tea is generally well tolerated when consumed as a beverage in moderate amounts. Green tea extract also seems to be well tolerated when used for up to 12 months.
Most Common Adverse Effects:
Orally: Bloating, constipation, diarrhea, dyspepsia, flatulence, and nausea.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity, hypokalemia, and thrombotic thrombocytopenic purpura have been reported rarely.

Cardiovascular ...Acute or short-term oral administration of green tea may cause hypertension (53719,54014,54065,54076,102716). The risk may be greater for green tea products containing more than 200 mg epigallocatechin gallate (EGCG) (90161). However, consumption of brewed green tea does not seem to increase blood pressure or pulse, even in mildly hypertensive patients (1451,1452). In fact, some evidence suggests that habitual tea consumption is associated with a reduced risk of developing hypertension (12518). Also, epidemiological research suggests there is no association of caffeine consumption with incidence of hypertension or with cardiovascular disease mortality in patients with hypertension (13739,111027). Rarely, green tea consumption may cause hypotension (53867).
Epidemiological research suggests that regular caffeine intake of up to 400 mg per day, or approximately 8 cups of green tea, is not associated with an increased incidence of atrial fibrillation (38018,38076,91028,91034,97451,97453), atherosclerosis (38033), cardiac ectopy (91127), stroke (37804), ventricular arrhythmia (95948,97453), and cardiovascular disease in general (37805,98806).
Combining ephedra with caffeine can increase the risk of adverse effects. Jitteriness, hypertension, seizures, and temporary loss of consciousness has been associated with the combined use of ephedra and caffeine (2729). There is also a report of ischemic stroke in an athlete who consumed ephedra 40-60 mg, creatine monohydrate 6 grams, caffeine 400-600 mg, and a variety of other supplements daily for 6 weeks (1275). In theory, combining caffeinated green tea with ephedra would have similar effects.
In a case report, the EGCG component of a specific weight loss supplement (Hydroxycut) was thought to be responsible for atrial fibrillation (54028). The patient was given two doses of intravenous diltiazem and was loaded with intravenous digoxin. Thirty-six hours after the last product dose, she spontaneously converted to normal sinus rhythm. The authors suggested that the block of the atrial-specific KCNA5 potassium channel likely played a role in this response.
A case of thrombotic thrombocytopenic purpura has been reported for a patient who consumed a weight loss product containing green tea (53978). She presented at the emergency department with a one-week history of malaise, fatigue, and petechiae of the skin. Twelve procedures of plasmapheresis were performed, and corticosteroid treatment was initiated. She was discharged after 20 days.

Dermatologic ...Orally, green tea may cause skin rashes or skin irritation (53731,54038,90161,90187,102716). Topically, green tea may cause local skin reactions or skin irritation, erythema, burning, itching, edema, and erosion (53731,54018,97136,104609,111031). A green tea extract ointment applied to the cervix can cause cervical and vaginal inflammation, vaginal irritation, and vulval burning (11310,36442,36438). When applied to external genital or perianal warts, a specific green tea extract ointment (Veregen, Bradley Pharmaceuticals) providing 15% kunecatechins can cause erythema, pruritus, local pain, discomfort and burning, ulceration, induration, edema, and vesicular rash (15067,53907).

Endocrine ...There is some concern that, due to its caffeine content, green tea may be associated with an increased risk of fibrocystic breast disease, breast cancer, and endometriosis. However, this is controversial since findings are conflicting (8043). Restricting caffeine in females with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996).
A population analysis of the Women's Health Initiative observational study has found no association between consumption of caffeine-containing beverages, such as green tea, and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors (108806). Also, a dose-response analysis of 2 low-quality observational studies has found that high consumption of caffeine is not associated with an increased risk of breast cancer (108807).
A case of hypoglycemia has been reported for a clinical trial participant with type 2 diabetes who used green tea in combination with prescribed antidiabetes medication (54035).

Gastrointestinal ...Orally, green tea beverage or supplements can cause nausea, vomiting, abdominal bloating and pain, constipation, dyspepsia, reflux, morning anorexia, increased thirst, flatulence, and diarrhea. These effects are more common with higher doses of green tea or green tea extract, equivalent to 5-6 liters of tea per day (8117,11366,36398,53719,53867,53936,54038,54076,90139,90140)(90161,90175,90187,97131,97136,102716).

Hepatic ...There is concern that some green tea products, especially green tea extracts, can cause hepatotoxicity in some patients. In 2017, the regulatory agency Health Canada re-issued a warning to consumers about this concern. The updated warning advises patients taking green tea extracts, especially those with liver disease, to watch for signs of liver toxicity. It also urges children to avoid taking products containing green tea extracts (94897). In 2020, the United States Pharmacopeia (USP) determined that any products bearing its seal of verification must include a specific warning on the label stating "Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes)" (102722).
Numerous case reports of hepatotoxicity, primarily linked to green tea extract products taken in pill form, have been published. A minimum of 29 cases have been deemed at least probably related to green tea and 38 have been deemed possibly related. In addition, elevated liver enzymes have been reported in clinical research (14136,15026,53740,53746,53775,53859,54027,90139,90162,90164)(93256,94898,94899,102716,102720,102722,107158,111020). Most cases of toxicity have had an acute hepatitis-like presentation with a hepatocellular-elevation of liver enzymes and some cholestasis. Onset of hepatotoxic symptoms usually occurs within 3 months after initiation of the green tea extract supplement, and symptoms can persist from 10 days to 1 year (95439,94897,94898,107158). Some reports of hepatotoxicity have been associated with consumption of green tea-containing beverages as well (15026,53742,54016,90125,90143).
In most cases, liver function returned to normal after discontinuation of the green tea product (14136,15026,53859,93256,107158). In one case, use of a specific ethanolic green tea extract (Exolise, Arkopharma) resulted in hepatotoxicity requiring a liver transplant. Due to concerns about hepatotoxicity, this specific extract was removed from the market by the manufacturer (14310). Since then, at least 5 cases of liver toxicity necessitating liver transplantation have been reported for patients who used green tea extracts (94898,107158). In another case, use of green tea (Applied Nutrition Green Tea Fat Burner) in combination with whey protein, a nutritional supplement (GNC Mega Men Sport), and prickly pear cactus resulted in acute liver failure (90162).
Despite the numerous reports of hepatotoxicity associated with the use of green tea products, the actual number of hepatotoxicity cases is low when the prevalence of green tea use is considered. From 2006 to 2016, liver injury from green tea products was estimated have occurred in only 1 out of 2.7 million patients who used green tea products (94897,95440).
In addition to the fact that green tea hepatotoxicity is uncommon, it is also not clear which patients are most likely to experience liver injury (94897,95440). The hepatotoxicity does not appear to be an allergic reaction or an autoimmune reaction (94897). It is possible that certain extraction processes, for example, ethanolic extracts, produce hepatotoxic constituents. However, in most cases, the presence of contaminants in green tea products has not been confirmed in laboratory analyses (90162).
Although results from one analysis of 4 small clinical studies disagrees (94899), most analyses of clinical data, including one conducted by the European Food Safety Association, found that hepatotoxicity from green tea products is associated with the dose of EGCG in the green tea product. Results show that daily intake of EGCG in amounts greater than or equal to 800 mg per day is associated with a higher incidence of elevated liver enzymes such as alanine transaminase (ALT) (95440,95696,97131). However, it is still unclear what maximum daily dose of EGCG will not increase liver enzyme levels or what minimum daily dose of EGCG begins to cause liver injury. In many cases of liver injury, the dose of green tea extract and/or EGCG is not known. Therefore, a minimum level of green tea extract or EGCG that would cause liver injury in humans cannot be determined (102722). Keep in mind that daily intake of green tea infusions provides only 90-300 mg of EGCG daily. So for a majority of people, green tea infusions are likely safe and unlikely to cause liver injury (95696). Also, plasma levels of EGCG are increased when green tea catechins are taken in the fasting state, suggesting that green tea extract should be taken with food (102722).
Until more is known, advise patients that green tea products, especially those containing green tea extract, might cause liver damage. However, let them know that the risk is uncommon, and it is not clear which products are most likely to cause the adverse effect or which patients are most likely to be affected. Advise patients with liver disease to consult their healthcare provider before taking products with green tea extract and to notify their healthcare provider if they experience symptoms of liver damage, including jaundice, dark urine, sweating, or abdominal pain (102722).

Immunologic ...Orally, matcha tea has resulted in at least one case of anaphylaxis related to green tea proteins. A 9-year-old male experienced systemic redness and hives, nausea, and anaphylaxis 60 minutes after consuming matcha tea-flavored ice cream (107169). The caffeine found in green tea can also cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).

Musculoskeletal ...Orally, the ingestion of the green tea constituent epigallocatechin gallate (EGCG) or a decaffeinated green tea polyphenol mixture may cause mild muscle pain (36398).
There is some concern regarding the association between caffeinated green tea products and osteoporosis. Epidemiological evidence regarding the relationship between caffeinated beverages such as green tea and the risk for osteoporosis is contradictory. Caffeine can increase urinary excretion of calcium (2669,10202,11317). Females with a genetic variant of the vitamin D receptor appear to be at an increased risk for the detrimental effect of caffeine on bone mass (2669). However, moderate caffeine intake of less than 400 mg per day, or about 8 cups of green tea, doesn't seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317).

Neurologic/CNS ...Orally, green tea can cause central nervous system stimulation and adverse effects such as headache, anxiety, dizziness, insomnia, fatigue, agitation, tremors, restlessness, and confusion. These effects are more common with higher doses of green tea or green tea extract, equivalent to 5-6 liters of tea per day (8117,11366,53719,90139,102716). The green tea constituent epigallocatechin gallate (EGCG) or decaffeinated green tea may also cause mild dizziness and headache (36398).
Combining ephedra with caffeine can increase the risk of adverse effects. Jitteriness, hypertension, seizures, temporary loss of consciousness, and hospitalization requiring life support has been associated with the combined use of ephedra and caffeine (2729). Topically, green tea extract (Polyphenon E ointment) may cause headache when applied to the genital area (36442).

Psychiatric ...Green tea contains a significant amount of caffeine. Chronic use, especially in large amounts, can produce tolerance, habituation, and psychological dependence (11832). The existence or clinical importance of caffeine withdrawal is controversial. Some researchers think that if it exists, it appears to be of little clinical significance (11839). Other researchers suggest symptoms such as headache; tiredness and fatigue; decreased energy, alertness, and attentiveness; drowsiness; decreased contentedness; depressed mood; difficulty concentrating; irritability; and lack of clear-headedness are typical of caffeine withdrawal (13738). Withdrawal symptoms such as delirium, nausea, vomiting, rhinorrhea, nervousness, restlessness, anxiety, muscle tension, muscle pains, and flushed face have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).

Pulmonary/Respiratory ...A case of granulomatous alveolitis with lymph follicles has been reported for a 67-year-old female who used green tea infusions to wash her nasal cavities for 15 years (54088). Her symptoms disappeared 2 months after stopping this practice and following an undetermined course of corticosteroids. In a case report, hypersensitivity pneumonitis was associated with inhalation of catechin-rich green tea extracts (54025). Occupational exposure to green tea dust can cause sensitization, which may include nasal and asthmatic symptoms (11365).

Renal ...There are two cases of hypokalemia associated with drinking approximately 8 cups daily of green tea in an elderly couple of Asian descent. The hypokalemia improved after reducing their intake by 50%. It is possible that this was related to the caffeine in the green tea (98418).

Other ...Orally, intake of a specific green tea extract product (Polyphenon E) may cause weight gain (90139).

(Read more about GREEN TEA)

LEMON (Lemon Bioflavonoid Complex)

General ...Orally, lemon is well tolerated in amounts commonly found in foods. A thorough evaluation of safety outcomes has not been conducted on the use of larger amounts.
Most Common Adverse Effects:
Orally: Epigastralgia and heartburn with the regular consumption of fresh lemon juice.

Dermatologic ...Topically, the application of lemon oil might cause photosensitivity, due to furocoumarin derivative content. This occurs most often in fair-skinned people (11019).

Gastrointestinal ...Orally, fresh lemon juice, taken as 60 mL twice daily, has been reported to cause gastrointestinal disturbances in 37% of patients in one clinical trial, compared with 8% of patients in the placebo group. Specifically, of the patients consuming lemon juice, 21% experienced heartburn and 8% experienced epigastralgia, compared to 1% and 3%, respectively, in the placebo group (107489).

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Report an Adverse Reaction to Grape Seed Extract 50 mg

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