Each 1.5 tsp serving contains: Camellia sinensis 10 mg, providing Polyphenols 5 mg • Inositol 100 mg • L-5-Hydroxytryptophan 25 mg • L-Glutamine 10 mg • L-Theanine 200 mg • Lepidium meyenii 4:1 extract (DHE: 200 mg) 50 mg • Schisandra chinensis 300 mg. Other Ingredients: Methyl 4-Hydroxybenzoate, Oryza Sativa, Propyl P- Hydroxybenzoate, Sodium Benzoate, Purified Water.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
In 2004, Canada began regulating natural medicines as a category of products separate from foods or drugs. These products are officially recognized as "Natural Health Products." These products include vitamins, minerals, herbal preparations, homeopathic products, probiotics, fatty acids, amino acids, and other naturally derived supplements.
In order to be marketed in Canada, natural health products must be licensed. In order to be licensed in Canada, manufacturers must submit applications to Health Canada including information about uses, formulation, dosing, safety, and efficacy.
Products can be licensed based on several criteria. Some products are licensed based on historical or traditional uses. For example, if an herbal product has a history of traditional use, then that product may be acceptable for licensure. In this case, no reliable scientific evidence is required for approval.
For products with non-traditional uses, some level of scientific evidence may be required to support claimed uses. However, a high level of evidence is not necessarily required. Acceptable sources of evidence include at least one well-designed, randomized, controlled trial; well-designed, non-randomized trials; cohort and case control studies; or expert opinion reports.
Finished products licensed by Health Canada must be manufactured according to Good Manufacturing Practices (GMPs) as outlined by Health Canada.
Below is general information about the effectiveness of the known ingredients contained in the product Neurotonik. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Neurotonik. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately. 5-HTP has been used safely in doses up to 400 mg daily for up to one year (913,30007,30130). Doses up to 1.2 grams daily have been used with apparent safety for up to 10 months (914,30018,30125,30164,30165). Doses of 3 grams daily have been used safely for 3 weeks (30138). There is some controversy about the safety of 5-HTP due to concerns for eosinophilia myalgia syndrome (EMS) (902,919,7067,10084,30178). There is speculation that only certain, contaminated 5-HTP products may cause this serious adverse effect (88174). So far, there is not enough evidence to know if EMS is caused by 5-HTP, contaminants, or other unknown factors (919,7067,10084).
POSSIBLY UNSAFE ...when used orally in large doses. Doses of 6-10 grams daily have been associated with severe gastrointestinal effects and hyperkinesis (30139,30183). The risk may be reduced if the dose is increased gradually.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
Doses of 5-HTP up to 5 mg/kg daily have been used safely for up to 3 years in infants and children up to 12 years old (30128,30153,88173).
There is some controversy about the safety of 5-HTP due to concerns for eosinophilia myalgia syndrome (EMS) (902,919,7067,10084,30178). There is speculation that only certain, contaminated 5-HTP products may cause this serious adverse effect (88174). So far, there is not enough evidence to know if EMS is caused by 5-HTP, contaminants, or other unknown factors (919,7067,10084).
LIKELY SAFE ...when consumed orally in moderate amounts (1452,9222,9223,9224,9228,9233,9234,9235,9236,36376)(36426,36434,36436,36581). Black tea contains caffeine. According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, drinking up to 4 cups of black 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).
POSSIBLY UNSAFE ...when consumed orally long term or in high amounts. Black 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 6 cups of black 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 black 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 black 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.
LIKELY UNSAFE ...when consumed orally in very high amounts. 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, prior caffeine use, etc. (11832).
CHILDREN: POSSIBLY SAFE
when used in food and beverage amounts (4912,11833).
PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts.
Due to the caffeine content of black tea, mothers should closely monitor their intake to ensure moderate consumption. Caffeine crosses the human placenta but is not considered a teratogen. 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 (2708,2709,2710,2711,9606,11733,16014,16015,37802,37584). 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 females 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 patients can safely consume doses up to 300 mg daily during pregnancy 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 3 cups of black 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 black 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.
PREGNANCY: POSSIBLY UNSAFE
when used orally in large amounts.
Caffeine from black 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 (16014,98806). Advise keeping caffeine consumption from all sources below 300 mg daily. This is similar to the amount of caffeine in about 3 cups of black tea. High doses of caffeine throughout pregnancy have 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 (2709,2711,24995,24998,37561,37898,38012,38186,38199,38212)(38285,38290). Preliminary evidence from a population study also suggests that increasing consumption of black tea might increase the risk of spina bifida (15112); however, this finding needs to be verified with additional research.
Cohort studies suggest that consuming large amounts of caffeine during pregnancy may reduce the height and weight of the infants born as they grow up. In a cohort of mother/infant pairs with a median maternal plasma caffeine level of 168.5 ng/mL (range 29.5-650.5 ng/mL) during pregnancy, birth weights and lengths were lower in the 4th quartile of caffeine intake compared with the 1st. By age 7, heights and weights were lower by 1.5 cm and 1.1 kg respectively. In another cohort of mother/infant pairs with higher maternal pregnancy plasma caffeine levels, median 625.5 ng/mL (range 86.2 to 1994.7 ng/mL), heights at age 8 were 2.2 cm lower, but there was no difference in weights (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 black 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.
More evidence is needed to determine the safety of using black tea during pregnancy. For now, advise avoidance of large quantities of black tea during pregnancy.
LACTATION: POSSIBLY SAFE
when used orally in moderate amounts.
Due to the caffeine content of black tea, caffeine intake should be closely monitored. Breast milk concentrations of caffeine are thought to be approximately 50% of maternal serum concentrations. Minimal consumption would likely result in limited exposure to a nursing infant (9892).
LACTATION: POSSIBLY UNSAFE
when used orally in large amounts.
Consumption of black tea might cause irritability and increased bowel activity in nursing infants (6026). Black tea might also interfere with iron metabolism and folic acid bioavailability in nursing infants (631,53782). Large doses or excessive intake of black tea should be avoided during lactation.
LIKELY SAFE ...when used orally and appropriately. Glutamine has been safely used in clinical research in doses up to 40 grams per day or 1 gram/kg daily (2334,2337,2338,2365,5029,5462,7233,7288,7293), (52288,52307,52308,52311,52313,52337,52349,52350,96516,97366). A specific glutamine product (Endari) is approved by the US Food and Drug Administration (FDA) (96520). ...when used intravenously. Glutamine has been safely incorporated into parenteral nutrition in doses up to 600 mg/kg daily in clinical trials (2363,2366,5448,5452,5453,5454,5458,7293,52272,52275), (52283,52289,52304,52306,52316,52341), (52359,52360,52371,52377,52381,52284,52385,52408,96637,96507,96516).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Glutamine has been shown to be safe in clinical research when used in amounts that do not exceed 0.7 grams/kg daily in children 1-18 years old (11364,46657,52321,52323,52363,86095,96517). A specific glutamine product (Endari) is approved by the US Food and Drug Administration for certain patients 5 years of age and older (96520). ...when used intravenously. Glutamine has been safely incorporated into parenteral nutrition in doses up to 0.4 grams/kg daily in clinical research (52338,96508). There is insufficient reliable information available about the safety of glutamine when used in larger amounts in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods.
There is insufficient reliable information available about the safety of glutamine when used in larger amounts as medicine during pregnancy or lactation.
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.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Inositol has been used with apparent safety in doses up to 18 grams daily for up to 6 weeks or 6 grams daily for 10 weeks (2184,2185,2187,95089). Myo-inositol 4 grams daily has also been used with apparent safety for 6 months (95085). There is insufficient reliable information available about the safety of inositol when used topically.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
Inositol 80 mg/kg (maximum 2 grams) has been taken daily for up to 12 weeks in children aged 5-12 years (95092). ...when used enterally or intravenously and appropriately in premature infants for treating acute respiratory distress syndrome for up to 10 days (2191,2192,91546,91551).
CHILDREN: POSSIBLY UNSAFE
when used enterally or intravenously for extended durations in premature infants.
A large clinical study in infants born at less than 28 weeks' gestation found that myo-inositol 40 mg/kg, given intravenously and then enterally every 12 hours for up to 10 weeks, was associated with a small increased risk of death (98946). Long-term follow-up until 24 months corrected age confirms that the initial increase in mortality rate in the myo-inositol group remained stable; however, there was no difference in a composite outcome of death or survival with moderate or severe neurodevelopmental impairment, as well as no difference in the risk of retinopathy of prematurity, between those who received myo-inositol or control (108819).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term.
Myo-inositol has been used with apparent safety in amounts up to 4000 mg daily during pregnancy (91548,95082,104688).
LACTATION:
Insufficient reliable information available; avoid using.
Breast milk is rich in endogenous inositol (2138); however, the effects of exogenously administered inositol are not known.
LIKELY SAFE ...when maca is consumed in food amounts (9926).
POSSIBLY SAFE ...when used orally and appropriately, short term. Maca appears to be safe in doses up to 3 grams daily for 4 months (9928,10218,18289,90278,108603).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when consumed as a beverage in moderate amounts (12518,104785). Oolong tea contains caffeine. According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, drinking up to 4 cups of 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).
POSSIBLY UNSAFE ...when consumed as a beverage in large quantities. Oolong 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 4 cups of 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 oolong tea.
CHILDREN: POSSIBLY SAFE
when used in amounts commonly found in foods and beverages (11833).
PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts.
Due to the caffeine content of oolong tea, mothers should closely monitor their intake to ensure moderate consumption. Fetal blood concentrations of caffeine approximate maternal concentrations (4260). Use of caffeine in pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects (2708,2709,2710,2711,9606,16014).
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 adults can safely consume doses up to 300 mg daily during pregnancy 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 during pregnancy. This is similar to the amount of caffeine found in about 3 cups of tea. There is also some evidence to suggest that a component found in oolong tea may inhibit folate metabolism and decrease folic acid concentrations during pregnancy. Folic acid levels should be monitored closely (94078).
PREGNANCY: POSSIBLY UNSAFE
when used orally in large amounts.
Caffeine from oolong tea crosses the placenta, producing fetal blood concentrations similar to maternal levels (4260). In a cohort of mother/infant pairs with a median maternal plasma caffeine level of 168.5 ng/mL (range 29.5-650.5 ng/mL) during pregnancy, birth weights and lengths were lower in the 4th quartile of caffeine intake compared with the 1st. By age 7, heights and weights were lower by 1.5 cm and 1.1 kg respectively. In another cohort of mother/infant pairs with higher maternal pregnancy plasma caffeine levels, median 625.5 ng/mL (range 86.2 to 1994.7 ng/mL), heights at age 8 were 2.2 cm lower, but there was no difference in weights (109846).
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 during pregnancy. This is similar to the amount of caffeine in about 3 cups of tea. High maternal doses of caffeine throughout pregnancy have 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).
LACTATION: POSSIBLY SAFE
when used orally in moderate amounts.
Due to the caffeine content of oolong tea, caffeine intake should be closely monitored. Breast milk concentrations of caffeine are thought to be approximately 50% of maternal serum concentrations.
LACTATION: POSSIBLY UNSAFE
when used orally in large amounts.
Consumption of oolong tea might cause irritability and increased bowel activity in nursing infants (6026). Large doses or excessive intake of oolong tea should be avoided during lactation.
POSSIBLY SAFE ...when used orally in moderate amounts. Pu-erh tea has not been associated with significant adverse effects (15465). Pu-erh tea extract has been used with apparent safety in doses of up to 1 gram daily for 12 weeks (102759). Pu-erh tea contains caffeine. According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, drinking up to 4 cups of 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).
POSSIBLY UNSAFE ...when consumed as a beverage in large quantities. Pu-erh 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 daily, or approximately 6 cups of 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 pu-erh tea.
CHILDREN: POSSIBLY SAFE
when used orally in amounts commonly found in foods and beverages in children and adolescents (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).
PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts.
Due to the caffeine content of pu-erh tea, intake should be closely monitored during pregnancy to ensure moderate consumption. Fetal blood concentrations of caffeine approximate maternal concentrations (4260). Use of caffeine in pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects (2708,2709,2710,2711,9606,98806). In some studies, consuming caffeine in amounts over 200 mg daily is associated with a significantly increased risk of miscarriage (16014,37960). 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 adults can safely consume caffeine 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 during pregnancy. This is similar to the amount of caffeine found in about 3 cups of tea (2708).
PREGNANCY: POSSIBLY UNSAFE
when used orally in large amounts.
Caffeine from pu-erh 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 during pregnancy. This is similar to the amount of caffeine in about 3 cups of tea. High intake of caffeine throughout pregnancy has 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). In a study that included 2 large cohorts of mother/infant pairs, the first cohort with a median maternal plasma caffeine level of 168.5 ng/mL (range 29.5-650.5 ng/mL) during pregnancy, suggests birth weights and lengths were lower in the 4th quartile of caffeine intake compared with the 1st. By age 7, heights and weights were lower by 1.5 cm and 1.1 kg respectively. In the second cohort of mother/infant pairs with higher maternal pregnancy plasma caffeine levels, median 625.5 ng/mL (range 86.2 to 1994.7 ng/mL), heights at age 8 were 2.2 cm lower, but there was no difference in weights (109846).
LACTATION: POSSIBLY SAFE
when used orally in moderate amounts.
Due to the caffeine content of pu-erh tea, caffeine intake should be closely monitored. Breast milk concentrations of caffeine are thought to be approximately 50% of maternal serum concentrations and caffeine peaks in milk approximately 1-2 hours after consumption (23590).
POSSIBLY UNSAFE...when used orally in large amounts. Consumption of pu-erh tea might cause irritability and increased bowel activity in nursing infants (6026). Large doses or excessive intake of pu-erh tea should be avoided during lactation.
POSSIBLY SAFE ...when used orally and appropriately. Schisandra extract up to 1 gram daily has been used for up to 12 weeks with apparent safety (12,96632,105562,105563,112887).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Some evidence suggests schisandra fruit is a uterine stimulant (11).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. L-theanine has been used safely in clinical research in doses of up to 900 mg daily for 8 weeks (12188,36439,96331,96332,96334,96341,97923,101986,104976). There is insufficient reliable information available about the safety of L-theanine when used long-term.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
A specific L-theanine product (Suntheanine, Taiyo Kagaku) 200 mg twice daily has been used safely in males aged 8-12 years for up to 6 weeks (91744).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Neurotonik. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Combining 5-HTP and carbidopa can increase the risk of serotonergic side effects.
 Details
Carbidopa is sometimes used with 5-HTP to minimize peripheral 5-HTP metabolism and boost the amount that reaches the brain. However, this combination might also increase the risk of some side effects including hypomania, restlessness, rapid speech, anxiety, insomnia, and aggressiveness (30076,30132,30158). Combining carbidopa and 5-HTP might also increase the risk of scleroderma-like skin changes due to elevated serotonin levels (1403).
|
Theoretically, concomitant use of 5-HTP with medications that cause sedation might have additive effects.
Details
|
Combining serotonergic drugs with 5-HTP might cause additive serotonergic effects.
Details
5-HTP can increase serotonin levels and cause serotonergic effects (901). Theoretically, combining serotonergic drugs with 5-HTP might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders (8056). However, serotonin syndrome with 5-HTP has not yet been reported in humans (104941). Monitor patients for signs of serotonin syndrome and other serotonergic side effects if using 5-HTP with serotonergic drugs.
|
Theoretically, black tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Details
Black tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level (38172). However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines such as caffeine, as well as 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).
|
Theoretically, alcohol might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, black tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
|
Theoretically, taking black tea with antidiabetes drugs might interfere with blood glucose control.
Details
|
Theoretically, concomitant use of large amounts of black tea might increase cardiac inotropic effects of beta-agonists.
Details
Black tea contains caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists (15).
|
Theoretically, black tea might reduce the effects of carbamazepine and increase the risk for convulsion.
Details
Black tea contains caffeine. Animal research suggests that 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).
|
Theoretically, concomitant use might increase the effects and adverse effects of caffeine in black tea.
Details
|
Theoretically, black tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Details
Concomitant administration of black tea and clozapine might theoretically cause acute exacerbation of psychotic symptoms due to the caffeine in black 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).
|
Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in black tea.
Details
|
Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Details
Black tea contains caffeine. Caffeine is metabolized by 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 black tea and increase caffeine levels.
|
Theoretically, black tea might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Details
Black tea contains caffeine. Caffeine is a methylxanthine that may inhibit dipyridamole-induced vasodilation (11770,11772,24974,37985,53795). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products such as black tea, 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).
|
Theoretically, disulfiram might increase the risk of adverse effects from caffeine.
Details
Black tea contains caffeine. In human research, disulfiram decreases the clearance and increases the half-life of caffeine (11840).
|
Theoretically, using black tea with diuretic drugs might increase the risk of hypokalemia.
Details
|
Theoretically, concomitant use might increase the risk for simulant adverse effects.
Details
Black 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 (6486,9740,10307). Tell patients to avoid taking caffeine with ephedrine and other stimulants.
|
Theoretically, estrogens might increase the levels and adverse effects of caffeine.
Details
Black tea contains caffeine. Estrogen inhibits caffeine metabolism (2714).
|
Theoretically, black tea might reduce the effects of ethosuximide and increase the risk for convulsions.
Details
Black 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 observed in humans.
|
Theoretically, black tea might reduce the effects of felbamate and increase the risk for convulsions.
Details
Black tea contains caffeine. Animal research suggests that a high dose of caffeine 161.7 mg/kg can decrease the anticonvulsant activity of felbamate (23563). However, this effect has not been observed in humans.
|
Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, black tea might decrease the metabolism of flurbiprofen.
Details
In vitro research shows that black tea decreases the metabolism of flurbiprofen, a cytochrome P450 2C9 (CYP2C9) substrate, by about 10%. However, clinical research suggests that drinking black tea does not significantly affect flurbiprofen plasma levels, metabolism, or elimination (11094).
|
Theoretically, black tea might increase the levels and adverse effects of flutamide.
Details
Black 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 of adverse effects.
|
Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, abrupt black tea withdrawal might increase the levels and adverse effects of lithium.
Details
|
Theoretically, metformin might increase the levels and adverse effects of caffeine.
Details
Black 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.
|
Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.
Details
Black tea contains caffeine. Methoxsalen can reduce caffeine metabolism (23572). Concomitant use can increase caffeine serum concentrations and the risk of caffeine adverse effects.
|
Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Details
Black 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 caffeinate coffee and took the MAOI tranylcypromine presented with severe hypertension (91086). Hypertension was resolved after the patients switched to drinking decaffeinated coffee.
|
Theoretically, concomitant use might increase the risk of hypertension.
Details
Black 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).
|
Theoretically, black tea might reduce the absorption of organic anion-transporting polypeptide (OATP) substrates.
Details
In vitro, black tea extract inhibits organic anion-transporting polypeptide (OATP)2B1. OATP2B1 is expressed in the small intestine and liver and is responsible for the uptake of drugs and other compounds. In an animal model, black tea extract was found to inhibit the absorption of rosuvastatin, a substrate of OATP2B1 (104584). However, this effect has not been reported in humans.
|
Theoretically, black tea might decrease the effects of pentobarbital.
Details
Black tea contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).
|
Theoretically, black tea might reduce the effects of phenobarbital and increase the risk for convulsions.
Details
|
Theoretically, phenothiazines might increase the levels and adverse effects of caffeine. Also, black tea may bind to phenothiazines and reduce their absorption.
Details
|
Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Details
|
Theoretically, black tea might reduce the effects of phenytoin and increase the risk for convulsions.
Details
|
Theoretically, black tea might increase the levels and clinical effects of pioglitazone.
Details
|
Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Details
Black tea contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce metabolism of one or both agents (11739).
|
Theoretically, concomitant use might decrease the levels and clinical effects of rosuvastatin.
Details
In animals, taking black tea extract along with rosuvastatin reduces plasma levels of rosuvastatin by approximately 48%. In vitro, black tea extract was found to inhibit organic anion-transporting polypeptide (OATP)2B1, a protein expressed in the small intestine that is responsible for the uptake of rosuvastatin and other compounds (104584). This effect has not been reported in humans.
|
Theoretically, concomitant use might increase stimulant adverse effects.
Details
Black 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).
|
Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
Details
Black tea contains caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).
|
Theoretically, black tea might increase the levels and adverse effects of theophylline.
Details
|
Theoretically, black tea might increase the levels and adverse effects of tiagabine.
Details
Black 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).
|
Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.
Details
Black tea contains caffeine. In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.
|
Theoretically, TCAs might bind with black tea constituents when taken at the same time.
Details
|
Theoretically, black tea might reduce the effects of valproate and increase the risk for convulsions.
Details
|
Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Details
Black tea contains caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).
|
Consuming large amounts of black tea might decrease the effects of warfarin.
Details
In one case, a 67-year-old female who took warfarin and who regularly consumed large amounts of black tea had a stable international normalized ratio (INR) of 1.7 to 2.7. However, the INR increased to 5 when tea consumption was discontinued. It is thought that the vitamin K content of black tea may have reduced the effects of warfarin (16902). Monitor patients carefully who start or discontinue drinking black tea while taking warfarin.
|
Theoretically, glutamine might antagonize the effects of anticonvulsant medications.
Details
|
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).
|
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).
|
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).
|
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).
|
Theoretically, taking green tea with antidiabetes drugs might interfere with blood glucose control.
Details
|
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.
|
Green tea contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists (15).
|
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.
|
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).
|
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).
|
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).
|
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).
|
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).
|
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.
|
Green tea is unlikely to produce clinically significant changes in the levels and clinical effects of CYP3A4 substrates.
Details
|
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).
|
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).
|
Theoretically, using green tea with diuretic drugs might increase the risk of hypokalemia.
Details
|
Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Details
|
Theoretically, estrogens might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Estrogen inhibits caffeine metabolism (2714).
|
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.
|
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.
|
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).
|
Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022).
|
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.
|
Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Fluvoxamine reduces caffeine metabolism (6370).
|
Theoretically, concomitant use might have additive adverse hepatotoxic effects.
Details
|
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.
|
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).
|
Theoretically, abrupt green tea withdrawal might increase the levels and adverse effects of lithium.
Details
|
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.
|
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.
|
Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Mexiletine can decrease caffeine elimination by 50% (1260).
|
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.
|
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.
|
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).
|
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.
|
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).
|
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).
|
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).
|
Theoretically, green tea might decrease the effects of pentobarbital.
Details
Green tea contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).
|
Theoretically, green tea might reduce the effects of phenobarbital and increase the risk for convulsions.
Details
|
Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Details
|
Theoretically, green tea might reduce the effects of phenytoin and increase the risk for convulsions.
Details
|
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.
|
Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
Details
|
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).
|
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.
|
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).
|
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).
|
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).
|
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).
|
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.
|
Theoretically, green tea might reduce the effects of valproate and increase the risk for convulsions.
Details
|
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).
|
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.
|
Theoretically, taking inositol with antidiabetes drugs might increase the risk of hypoglycemia.
Details
|
Theoretically, oolong tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Details
Oolong tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines such as caffeine, as well as 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).
|
Theoretically, alcohol might increase the levels and adverse effects of caffeine in oolong tea.
Details
Oolong 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).
|
Theoretically, oolong tea might increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
|
Theoretically, taking oolong tea with antidiabetes drugs might interfere with blood glucose control.
Details
|
Theoretically, large amounts of oolong tea might increase the cardiac inotropic effects of beta-agonists.
Details
Oolong tea contains caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists (15).
|
Theoretically, concomitant use might increase the effects and adverse effects of caffeine in oolong tea.
Details
Oolong tea contains caffeine. Cimetidine can reduce the rate of caffeine clearance by 30% to 50% (11736).
|
Theoretically, oolong tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Details
Oolong tea contains caffeine. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg per day 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).
|
Theoretically, concomitant use might increase the effects and adverse effects of caffeine in oolong tea.
Details
|
Theoretically, concomitant use might increase the levels and adverse effects of the caffeine in oolong tea.
Details
Oolong 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 oolong tea and increase caffeine levels.
|
Theoretically, oolong tea might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Details
Oolong tea contains caffeine. Caffeine is a methylxanthine that may inhibit dipyridamole-induced vasodilation (11770,11772). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products such as oolong tea, be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole than adenosine-induced stress testing (11771).
|
Theoretically, disulfiram might increase the risk of adverse effects from caffeine in oolong tea.
Details
Oolong tea contains caffeine. Disulfiram decreases the clearance and increases the half-life of caffeine (15).
|
Theoretically, using oolong tea with diuretic drugs might increase the risk of hypokalemia.
Details
|
Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Details
Oolong 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 (1275,6486,10307). Tell patients to avoid taking caffeine with ephedrine and other stimulants.
|
Theoretically, estrogens might increase the levels and adverse effects of caffeine in oolong tea.
Details
Oolong tea contains caffeine. Estrogen inhibits caffeine metabolism (2714).
|
Theoretically, fluconazole might increase the levels and adverse effects of caffeine in oolong tea.
Details
Oolong tea contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022).
|
Theoretically, oolong tea might increase the levels and adverse effects of flutamide.
Details
Oolong tea contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553).
|
Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine in oolong tea.
Details
Oolong tea contains caffeine. Fluvoxamine reduces caffeine metabolism (6370).
|
Theoretically, abrupt oolong tea withdrawal might increase the levels and adverse effects of lithium.
Details
|
Theoretically, methoxsalen might increase the levels and adverse effects of caffeine in oolong tea.
Details
Oolong tea contains caffeine. Methoxsalen can reduce caffeine metabolism (23572).
|
Theoretically, mexiletine might increase the levels and adverse effects of caffeine in oolong tea.
Details
|
Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Details
|
Theoretically, concomitant use might increase the risk of hypertension.
Details
Oolong 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).
|
Theoretically, caffeine in oolong tea might decrease the effects of pentobarbital.
Details
Oolong tea contains caffeine. The caffeine in oolong tea might negate the hypnotic effects of pentobarbital (13742).
|
Theoretically, oolong tea might reduce the effects of phenobarbital and increase the risk for convulsions.
Details
|
Theoretically, phenothiazines might increase the levels and adverse effects of caffeine in oolong tea.
Details
|
Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine in oolong tea.
Details
|
Theoretically, oolong tea might reduce the effects of phenytoin and increase the risk for convulsions.
Details
|
Theoretically, oolong tea might increase the levels and clinical effects of pioglitazone.
Details
Oolong 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.
|
Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine in oolong tea.
Details
|
Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Details
Oolong tea contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce metabolism of one or both agents (11739).
|
Theoretically, concomitant use might increase stimulant adverse effects.
Details
|
Theoretically, terbinafine might increase the levels and adverse effects of caffeine in oolong tea.
Details
Oolong tea contains caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).
|
Theoretically, oolong tea might increase the levels and adverse effects of theophylline.
Details
Oolong tea contains caffeine. Caffeine decreases theophylline clearance 23% to 29% (11741).
|
Theoretically, oolong tea might increase the levels and adverse effects of tiagabine.
Details
Oolong 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).
|
Theoretically, ticlopidine might increase the levels and adverse effects of caffeine in oolong tea.
Details
Oolong tea contains caffeine. In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.
|
Theoretically, oolong tea might reduce the effects of valproate and increase the risk for convulsions.
Details
|
Theoretically, concomitant use might increase the levels and adverse effects of caffeine in oolong tea.
Details
Oolong tea contains caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).
|
Theoretically, pu-erh tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Details
Pu-erh tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level (38172). However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines, such as caffeine, 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).
|
Theoretically, alcohol might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, pu-erh tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
|
Theoretically, taking pu-erh tea with antidiabetes drugs might interfere with blood glucose control.
Details
|
Theoretically, concomitant use of large amounts of pu-erh tea might increase cardiac inotropic effects of beta-agonists.
Details
Pu-erh tea contains caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists (15).
|
Theoretically, pu-erh tea might reduce the effects of carbamazepine and increase the risk for convulsions.
Details
Pu-erh 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 (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).
|
Theoretically, concomitant use might increase the effects and adverse effects of caffeine in pu-erh tea.
Details
|
Theoretically, pu-erh tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Details
Pu-erh tea contains caffeine. 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).
|
Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in pu-erh tea.
Details
|
Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Details
Pu-erh tea contains caffeine. Caffeine is metabolized by 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 pu-erh tea and increase caffeine levels.
|
Theoretically, pu-erh tea might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Details
Pu-erh tea contains caffeine. Caffeine is a methylxanthine that may inhibit dipyridamole-induced vasodilation (11770,11772,24974,37985,53795). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products such as pu-erh tea, 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).
|
Theoretically, disulfiram might increase the risk of adverse effects from caffeine.
Details
Pu-erh tea contains caffeine. In human research, disulfiram decreases the clearance and increases the half-life of caffeine (11840).
|
Theoretically, using pu-erh tea with diuretic drugs might increase the risk of hypokalemia.
Details
|
Theoretically, concomitant use might increase the risk for simulant adverse effects.
Details
|
Theoretically, estrogens might increase the levels and adverse effects of caffeine.
Details
Pu-erh tea contains caffeine. Estrogen inhibits caffeine metabolism (2714).
|
Theoretically, pu-erh tea might reduce the effects of ethosuximide and increase the risk for convulsions.
Details
Pu-erh 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 observed in humans.
|
Theoretically, pu-erh tea might reduce the effects of felbamate and increase the risk for convulsions.
Details
Pu-erh tea contains caffeine. Animal research suggests that a high dose of caffeine 161.7 mg/kg can decrease the anticonvulsant activity of felbamate (23563). However, this effect has not been observed in humans.
|
Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, pu-erh tea might increase the levels and adverse effects of flutamide.
Details
Pu-erh 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 of adverse effects.
|
Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, abrupt pu-erh tea withdrawal might increase the levels and adverse effects of lithium.
Details
|
Theoretically, metformin might increase the levels and adverse effects of caffeine.
Details
Pu-erh 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.
|
Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.
Details
Pu-erh tea contains caffeine. Methoxsalen can reduce caffeine metabolism (23572). Concomitant use can increase caffeine serum concentrations and the risk of caffeine adverse effects.
|
Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Details
Pu-erh 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 patients switched to drinking decaffeinated coffee.
|
Theoretically, concomitant use might increase the risk of CNS effects or hypertension.
Details
Pu-erh tea contains caffeine. Concomitant use of caffeine and nicotine has been shown to have additive CNS effects or cardiovascular effects, including increased heart rate and blood pressure (2719,36549). In one study, blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly (36549).
|
Theoretically, pu-erh tea might decrease the effects of pentobarbital.
Details
Pu-erh tea contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).
|
Theoretically, pu-erh tea might reduce the effects of phenobarbital and increase the risk for convulsions.
Details
|
Theoretically, phenothiazines might increase the levels and adverse effects of caffeine. Also, pu-erh tea may bind to phenothiazines and reduce their absorption.
Details
|
Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Details
|
Theoretically, pu-erh tea might reduce the effects of phenytoin and increase the risk for convulsions.
Details
|
Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.
Details
Pu-erh 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.
|
Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
Details
|
Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Details
Pu-erh tea contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce metabolism of one or both agents (11739).
|
Theoretically, concomitant use might increase stimulant adverse effects.
Details
Pu-erh 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).
|
Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
Details
Pu-erh tea contains caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).
|
Theoretically, pu-erh tea might increase the levels and adverse effects of theophylline.
Details
|
Theoretically, pu-erh tea might increase the levels and adverse effects of tiagabine.
Details
Pu-erh 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).
|
Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.
Details
Pu-erh tea contains caffeine. In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.
|
Theoretically, TCAs might bind with pu-erh tea constituents when taken at the same time.
Details
|
Theoretically, pu-erh tea might reduce the effects of valproate and increase the risk for convulsions.
Details
|
Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Details
Pu-erh tea contains caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).
|
Theoretically, schisandra might increase the levels and clinical effects of cyclophosphamide.
Details
In vitro research shows that schisandra increases the concentration of cyclophosphamide, likely through inhibition of cytochrome P450 3A4. After multiple doses of the schisandra constituents schisandrin A and schisantherin A, the maximum concentration of cyclophosphamide was increased by 7% and 75%, respectively, while the overall exposure to cyclophosphamide was increased by 29% and 301%, respectively (109636).
|
Schisandra can increase the levels and clinical effects of cyclosporine.
Details
A small observational study in children with aplastic anemia found that taking schisandra with cyclosporine increased cyclosporine trough levels by 93% without increasing the risk of adverse events. However, the dose of cyclosporine was reduced in 9% of children to maintain appropriate cyclosporine blood concentrations (109637).
|
Theoretically, schisandra might increase the levels and clinical effects of CYP2C19 substrates.
Details
In vitro research shows that schisandra inhibits CYP2C19, and animal research shows that schisandra increases the concentration of voriconazole, a CYP2C19 substrate (105566). Theoretically, schisandra may also inhibit the metabolism of other CYP2C19 substrates. This effect has not been reported in humans.
|
Theoretically, schisandra might decrease the levels and clinical effects of CYP2C9 substrates.
Details
In vitro and animal research suggests that schisandra induces CYP2C9 enzymes (14441). This effect has not been reported in humans.
|
Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.
Details
Most clinical and laboratory research shows that schisandra, administered either as a single dose or up to twice daily for 14 days, inhibits CYP3A4 and increases the concentration of CYP3A4 substrates such as cyclophosphamide, midazolam, tacrolimus, and talinolol (13220,17414,23717,91386,91388,91387,96631,105564,109636,109638,109639,109640,109641). Although one in vitro and animal study shows that schisandra may induce CYP3A4 metabolism (14441), this effect appears to be overpowered by schisandra's CYP3A4 inhibitory activity and has not been reported in humans.
|
Schisandra can increase the levels and clinical effects of midazolam.
Details
A small pharmacokinetic study in healthy adults shows that taking schisandra extract (Hezheng Pharmaceutical Co.) containing deoxyschizandrin 33.75 mg twice daily for 8 days and a single dose of midazolam 15 mg on day 8 increases the overall exposure to midazolam by about 119%, increases the peak plasma level of midazolam by 86%, and decreases midazolam clearance by about 52%. This effect has been attributed to inhibition of CYP3A4 by schisandra (91388).
|
Schisandra might increase the levels and clinical effects of P-glycoprotein substrates.
Details
In vitro research shows that schisandra extracts and constituents such as schisandrin B inhibit P-glycoprotein mediated efflux in intestinal cells and in P-glycoprotein over-expressing cell lines (17414,105643,105644). Additionally, a small clinical study shows that schisandra increases the peak concentration and overall exposure to talinolol, a P-glycoprotein probe substrate (91386). Theoretically, schisandra might inhibit the efflux of other P-glycoprotein substrates.
|
Schisandra can increase the levels and clinical effects of sirolimus.
Details
A small pharmacokinetic study in healthy volunteers shows that taking 3 capsules of schisandra (Hezheng Pharmaceutical Company) containing a total of 33.75 mg deoxyschizandrin twice daily for 13 days and then taking a single dose of sirolimus 2 mg increases the overall exposure and peak level of sirolimus by two-fold. This effect is thought to be due to inhibition of cytochrome P450 3A4 by schisandra, as well as possible inhibition of the P-glycoprotein drug transporter (105643).
|
Schisandra can increase the levels and clinical effects of tacrolimus.
Details
Clinical research in healthy children and adults, transplant patients, and patients with nephrotic syndrome and various rheumatic immunologic disorders shows that taking schisandra with tacrolimus increases tacrolimus peak levels by 183% to 268%, prolongs or delays time to peak tacrolimus concentrations, increases overall exposure to tacrolimus by 126% to 343%, and decreases tacrolimus clearance by 19% to 73% (17414,91387,15570,96631,105623,109638,109639,109640,109641,112889)(112890,112972,112973,112974). This effect is thought to be due to inhibition of P-glycoprotein drug transporter and CYP3A4 and CYP3A5 by schisandra (17414,96631,105623,105643,105644,112974). Some clinical and observational studies suggest that schisandra increases tacrolimus levels similarly in both expressors and non-expressors of CYP3A5, while other studies suggest it does so to a greater degree in CYP3A5 expressors than non-expressors (105623,109638,109639,109640,112889,112890,112973,112974). Animal research suggests that the greatest increase in tacrolimus levels occurs when schisandra is taken either concomitantly or up to 2 hours before tacrolimus (105564), and clinical and observational research in humans suggests that schisandra may increase whole blood levels of tacrolimus and decrease clearance of tacrolimus in a dose-dependent manner (109639,109640,112972).
|
Schisandra can increase the levels and clinical effects of talinolol.
Details
A small pharmacokinetic study in healthy volunteers shows that taking schisandra extract 300 mg twice daily for 14 days with a single dose of talinolol 100 mg on day 14 increases the peak talinolol level by 51% and the overall exposure to talinolol by 47%. This effect is thought to be due to the possible inhibition of cytochrome P450 3A4 and P-glycoprotein by schisandra (91386).
tly.
|
Theoretically, schisandra might increase the levels and clinical effects of voriconazole.
Details
Animal research shows that oral schisandra given daily for 1 or 14 days increases levels of intravenously administered voriconazole, a cytochrome P450 (CYP) 2C19 substrate. This effect is thought to be due to inhibition of CYP2C19 by schisandra (105566). However, this interaction has not been reported in humans.
|
Theoretically, schisandra might decrease the levels and clinical effects of warfarin.
Details
Animal research suggests that oral schisandra extract, given daily for 6 days, reduces levels of intravenously administered warfarin. This effect might be due to the induction of cytochrome P450 (CYP) 2C9 metabolism by schisandra (14441). However, this interaction has not been reported in humans.
|
Theanine might lower blood pressure, potentiating the effects of antihypertensive drugs.
Details
|
Theoretically, theanine might have additive sedative effects when used in conjunction with CNS depressants. However, it is unclear if this concern is clinically relevant.
Details
|
Below is general information about the adverse effects of the known ingredients contained in the product Neurotonik. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, 5-HTP is generally well tolerated, short-term.
Most Common Adverse Effects:
Orally: Abdominal pain, anorexia, dizziness, diarrhea, drowsiness, fatigue, headache, insomnia, nausea, and vomiting. Severity appears to be dose-dependent.
Serious Adverse Effects (Rare):
Orally: Aggression, hallucinations, mania, severe gastrointestinal complaints.
Cardiovascular ...Orally, palpitations have been reported with 5-HTP (30076,30130,30167). Conversely, bradycardia has been reported in patients taking 5-HTP 0.4-2 grams daily in combination with carbidopa 100-300 mg daily (30132). In patients with schizophrenia, a combination of 5-HTP in doses up to 6 grams daily and carbidopa 150 mg daily was associated with diaphoresis and mild diastolic hypotension, especially when doses were increased at a rate faster than 200 mg per day (30183).
Dermatologic ...Orally, 5-HTP has been reported to cause urticaria, other allergic-type skin reactions, and flushing (2204,30000,30140). A scleroderma-like illness was reported in a 70-year-old man who had been taking 5-HTP 1400 mg daily and carbidopa 150 mg daily for 20 months. Elevated serotonin levels may be linked to this condition (1403).
Gastrointestinal ...Orally, 5-HTP has been reported to cause gastrointestinal side effects such as nausea, vomiting, abdominal or epigastric pain, heartburn, constipation, diarrhea, flatulence, anorexia, and taste alteration at any dose (2203,2204,30000,30112,30114,30125,30132,30139,30140)(30165,30183,104250). Severity may be dose-dependent and also related to how quickly doses are increased (30183). Some data suggests that these effects may diminish or disappear with continued use of 5-HTP (30132).
Hematologic ...Symptoms suggestive of eosinophilia myalgia syndrome (EMS) have been reported in some patients using 5-HTP (902,10084,30178,88174,90927). In one case, a woman was exposed to 5-HTP, tetrahydrobiopterin, carbidopa, and levodopa while administering them to her children for 2 years (90927). Her diagnosis was not confirmed, and the validity of the tests performed on the 5-HTP product has been questioned (88174). Other cases of eosinophilia or EMS in patients taking 5-HTP have been attributed to impurities that resemble previously identified contaminants found in L-tryptophan products (902,919,7067,10084). The L-tryptophan contaminants associated with EMS were linked to a specific manufacturer's production method that is not used in the preparation of 5-HTP (88174). Although 5-HTP supplements have been associated with EMS, it seems that this adverse effect is likely due to the presence of contaminants in the 5-HTP products, not 5-HTP itself.
Musculoskeletal ...Orally, rhabdomyolysis was noted in one patient with progressive myoclonus epilepsy who was treated with 5-HTP 300 mg daily for 21 days (30162).
Neurologic/CNS ...Orally, 5-HTP has been reported to cause drowsiness, dizziness, insomnia, fatigue, and headache (30076,30112,30132).
Psychiatric ...Orally, 5-HTP has been associated with euphoria, hypomania and mania, anxiety, insomnia, and aggressiveness (30076,30132,30158,88179). In patients with schizophrenia, a combination of high-dose 5-HTP, up to 6 grams daily, and carbidopa 150 mg daily was associated with transient increases in hallucinations, delusions, marked confusion, looseness of associations, flight of ideas, and a hyperkinetic syndrome consisting of restlessness, hand wringing, pacing, and an inability to sit quietly in a chair (30183).
General
...Orally, black tea is well tolerated when consumed as a beverage in moderate amounts.
Most Common Adverse Effects:
Orally: Many of the adverse effects of black tea can be attributed to its caffeine content, such as diuresis, gastric irritation, insomnia, nausea, nervousness, restlessness, tachycardia, tachypnea, tremors, and vomiting.
Serious Adverse Effects (Rare):
Orally: Many of the adverse effects of black tea can be attributed to its caffeine content, such as arrhythmia, chest pain, convulsions, delirium, premature heartbeat, and respiratory alkalosis. Large doses of caffeine can cause massive catecholamine release and subsequent sinus tachycardia, metabolic acidosis, hyperglycemia, and ketosis.
Cardiovascular
...Orally, black tea can cause some cardiovascular-related adverse events.
Some of these effects may be due to the caffeine content of black tea. Acute administration of black tea can cause increased blood pressure. However, regular consumption does not seem to increase blood pressure or pulse, even in patients with mild hypertension (1451,1452,2722). Also, epidemiological research suggests that there is no association of caffeine consumption with incidence of hypertension (13739).
Black tea, which contains caffeine, may cause other adverse cardiovascular effects when used orally. These effects include tachycardia, tachypnea, chest pain, premature heartbeat, arrhythmia, and hypertension (2729,11832,11838,13735). Large doses of caffeine can also cause massive catecholamine release and subsequent sinus tachycardia (13734).
There is evidence that daily consumption of strong black tea (2 liters) or black tea solids (4 grams) can raise plasma homocysteine levels. It is unclear if lower doses have this effect (8035). Some epidemiological research has linked tea consumption with ischemic heart disease and total mortality (220,36339). Combining caffeinated beverages such as black tea with ephedra may theoretically increase the risk of adverse cardiovascular events. There is 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).
Dental ...Orally, black tea may cause tooth surface loss and teeth staining (36370).
Endocrine
...Black tea contains caffeine.
Large doses of caffeine can cause massive catecholamine release and subsequent metabolic acidosis, hyperglycemia, and ketosis (13734).
Some evidence shows caffeine is associated with fibrocystic breast disease, breast cancer, and endometriosis. However, other research has not supported this finding (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 found no association between consumption of caffeine-containing beverages such as black tea and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors (108806). Also, a dose-response analysis of two low-quality observational studies found that high consumption of caffeine is not associated with an increased risk of breast cancer (108807).
Gastrointestinal ...Orally, caffeine in black tea can cause gastric irritation, nausea, and vomiting (11832,11838,13735). Some believe that long-term use of caffeine can cause withdrawal symptoms following discontinuation of use. However, the existence of caffeine withdrawal is controversial. Some researchers think that if it exists, it appears to be of little clinical significance (11839). Gastrointestinal withdrawal symptoms such as nausea and vomiting have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects. Clinically significant gastrointestinal symptoms caused by caffeine withdrawal may be uncommon (2723,11839).
Hematologic ...Orally, caffeine in black tea can cause hypokalemia (11832,11838,13735). In infants, black tea can cause microcytic anemia (631).
Immunologic ...Orally, caffeine in black tea can cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).
Musculoskeletal
...Some epidemiological research suggests that caffeine, which is found in black tea, may be associated with an increased risk of osteoporosis, but conflicting evidence exists.
Caffeine can increase urinary excretion of calcium (2669,10202,11317). Females identified 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, less than 300 mg per day, does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317).
Some researchers believe that stopping regular use of caffeine may cause withdrawal symptoms such as muscle tension and muscle pains. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839).
Neurologic/CNS
...Orally, caffeine in black tea can cause insomnia, nervousness, headache, anxiety, agitation, jitteriness, restlessness, ringing in the ears, tremors, delirium, and convulsions (11832,11838,13735).
Caffeine may also exacerbate sleep disturbances in patients with acquired immunodeficiency syndrome (AIDS) (10204).
There is some concern that stopping regular use of caffeine may cause withdrawal 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). Other symptoms such as delirium, nervousness, restlessness, and anxiety have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839).
Oncologic ...There is some evidence that consumption of black tea (greater than 1 cup per day) may increase the risk of colon and rectal cancers (8041,36482). Drinking 3 or more cups daily has been shown to increase the risk of pancreatic cancer (36507). In addition, drinking black tea more than once a day, drinking strong black tea, or using more than 300 grams of tea leaves per month is associated with an approximately 2-fold increased risk of esophageal cancer when compared with drinking black tea up to once daily, drinking mild to moderate black tea, or using up to 300 grams of tea leaves per month (102756). Some evidence also shows caffeine, which is found in black tea, is associated with breast cancer in females. However, this is controversial since findings are conflicting (8043).
Pulmonary/Respiratory ...Orally, caffeine in black tea may cause tachypnea-induced respiratory alkalosis (11832,11838,13735). Some researchers think that stopping regular use of caffeine may cause withdrawal symptoms such as runny nose. However, this symptom may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839).
Renal ...Orally, caffeine in black tea may cause diuresis (11832,11838,13735).
General
...Orally and intravenously, glutamine is generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, bloating, constipation, cough, diarrhea, flatulence, gastrointestinal pain, headache, musculoskeletal pain, nausea, and vomiting.
Endocrine ...One case of hot flashes has been reported in a patient taking glutamine 5-15 grams orally twice daily for up to 1 year (96520).
Gastrointestinal ...Orally, glutamine has been associated with belching, bloating, constipation, flatulence, nausea, vomiting, diarrhea, and gastrointestinal (GI) pain. Nausea, vomiting, constipation, diarrhea, and GI pain have been reported in clinical trials using high-dose glutamine 10-30 grams (0.3 grams/kg) in two divided doses daily to treat sickle cell disease (99414). One case of dyspepsia and one case of abdominal pain have been reported in patients taking glutamine 5-15 grams twice daily orally for up to 1 year (96520). In a small trial of healthy males, taking a single dose of about 60 grams (0.9 grams/kg of fat free body mass [FFM]) was associated with a 50% to 79% incidence of GI discomfort, nausea, and belching, compared with a 7% to 28% incidence with a lower dose of about 20 grams (0.3 gram/kg FFM). Flatulence, bloating, lower GI pain, and urge to regurgitate occurred at similar rates regardless of dose, and there were no cases of heartburn, vomiting, or diarrhea/constipation (105013). It is possible that certain GI side effects occur only after multiple doses of glutamine.
Musculoskeletal ...Orally, glutamine 30 grams daily has been associated with cases of musculoskeletal pain and non-cardiac chest pain in clinical trials for patients with sickle cell disease (99414).
Neurologic/CNS ...Orally, glutamine has been associated with dizziness and headache. A single case of dizziness has been reported in a patient treated with oral glutamine 0.5 grams/kg. However, the symptom resolved after reducing the dose to 0.25 grams/kg (91356). Mania and hypomania have been reported in 2 patients with bipolar disorder taking commercially purchased glutamine up to 4 grams daily (7291). Glutamine is metabolized to glutamate and ammonia, both of which might have neurological effects in people with neurological and psychiatric diseases or in people predisposed to hepatic encephalopathy (7293).
Oncologic ...There is some concern that glutamine might be used by rapidly growing tumors and possibly stimulate tumor growth. Although tumors may utilize glutamine and other amino acids, preliminary research shows that glutamine supplementation does not increase tumor growth (5469,7233,7738). In fact, there is preliminary evidence that glutamine might actually reduce tumor growth (5469).
Other ...Orally, glutamine has been associated with cough when a powdered formulation is used. It is unclear if this was due to accidental inhalation. One case of a burning sensation and one case of hypersplenism has been reported in a patient taking glutamine 5-15 grams twice daily orally for up to 1 year (96520).
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) formed an expert panel to review concerns of green tea extract-related hepatotoxicity. Based on their findings, USP determined that any products claiming compliance with USP quality standards for green tea extract 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).
General
...Orally and intravenously, inositol seems to be well tolerated.
Topically, no adverse effects have been reported, although a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Diarrhea, gas, and nausea.
Gastrointestinal ...Orally, inositol may cause nausea, diarrhea, gas, and gastrointestinal discomfort (10387,11972,91547,91549,95089,95090,95092).
Immunologic ...Orally, inositol in combination with omega-3 fatty acids has been associated with reports of cold and allergy symptoms in children in clinical research (95092).
Musculoskeletal ...Orally, inositol in combination with omega-3 fatty acids has been associated with reports of tics and other musculoskeletal side effects in children in clinical research (95092).
Neurologic/CNS ...Orally, inositol may cause dizziness, tiredness, insomnia, agitation, and headache (10387,11972,95089,95092). In combination with omega-3 fatty acids, inositol has been associated with reports of feelings of thirst in children in clinical research (95092).
Psychiatric ...In one case report, a 36-year-old male with adequately controlled bipolar disorder was hospitalized with symptoms of mania after consuming several cans of an energy drink containing inositol, caffeine, taurine, and other ingredients (Red Bull Energy Drink) over a period of 4 days (14302). It is not known if this is related to inositol, caffeine, taurine, a different ingredient, or a combination of the ingredients.
General ...Orally, no adverse effects have been reported with the medicinal use of maca. However, a thorough evaluation of safety outcomes has not been conducted.
Gastrointestinal ...Consumption of fresh, uncooked maca may cause stomach pain (40231).
General
...Orally, oolong tea is well tolerated when consumed as a beverage in moderate amounts.
Most Common Adverse Effects:
Orally: Many of the adverse effects of oolong tea can be attributed to its caffeine content, such as insomnia, nervousness, restlessness, tachycardia, tachypnea, and tremors.
Serious Adverse Effects (Rare):
Orally: Many of the serious adverse effects of oolong tea can be attributed to its caffeine content, such as arrhythmia, chest pain, convulsions, delirium, premature heartbeat, and respiratory alkalosis.
Cardiovascular
...Orally, oolong tea can cause some cardiovascular-related adverse effects.
Some of these effects may be due to the caffeine content of oolong tea. Acute oral administration of caffeine can cause increased blood pressure, but regular consumption does not seem to increase either blood pressure or pulse, even in mildly hypertensive patients (1451,1452,2722). Also, epidemiological research suggests that there is no association of caffeine consumption with incidence of hypertension (13739). Epidemiological research also suggests that regular caffeine intake of up to 400 mg per day, or approximately 4 cups of 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), or cardiovascular disease in general (37805,98806).
However, due to its caffeine content, oolong tea may cause other adverse cardiovascular effects when used orally. These effects include tachycardia, tachypnea, chest pain, premature heartbeat, arrhythmia, and hypertension (11832,11838,13735). Large doses of caffeine can cause massive catecholamine release and subsequent sinus tachycardia (13734).
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). 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 six weeks (1275).
Endocrine
...Oolong tea contains caffeine.
Large doses of caffeine can cause massive catecholamine release and subsequent metabolic acidosis, hyperglycemia, and ketosis (13734).
Some evidence has found that caffeine is associated with fibrocystic breast disease, breast cancer, and endometriosis in women (8043). However, a population analysis of the Women's Health Initiative observational study suggests that there is no association between consumption of caffeine-containing beverages 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 suggests that high consumption of caffeine is not associated with an increased risk of breast cancer (108807). Restricting caffeine in women with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996). In infants, tea may cause microcytic anemia (631).
Gastrointestinal ...The caffeine in oolong tea may cause feeding intolerance and gastrointestinal irritation in infants (6023).
Immunologic ...Oolong tea contains caffeine. Caffeine can cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).
Musculoskeletal
...Oolong tea contains caffeine.
Some epidemiological research has found that caffeine may be associated with an increased risk of osteoporosis, but conflicting evidence exists. Caffeine can increase urinary excretion of calcium (2669,10202,11317). Women identified 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 4 cups of tea, does not seem to significantly increase osteoporosis risk in most postmenopausal women with normal calcium intake (2669,6025,10202,11317,98806).
Some researchers believe that stopping regular use of caffeine may cause withdrawal symptoms such as muscle tension and muscle pains. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839).
Neurologic/CNS
...Oolong tea contains caffeine.
Orally, caffeine can cause insomnia, nervousness, headache, anxiety, agitation, jitteriness, restlessness, ringing in the ears, tremors, delirium, and convulsions (10755,11832,11838,13735). Caffeine may also exacerbate sleep disturbances in patients with acquired immunodeficiency syndrome (AIDS) (10204).
There is some concern that stopping regular use of caffeine may cause withdrawal symptoms such as headache, tiredness and fatigue, drowsiness, depressed mood, difficulty concentrating, irritability, and decreased energy, alertness, and attentiveness(13738). Other symptoms such as delirium, nervousness, restlessness, and anxiety have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839).
Pulmonary/Respiratory ...Oolong tea contains caffeine. Caffeine may cause tachypnea-induced respiratory alkalosis (11832,11838,13735). Some researchers think that stopping regular use of caffeine may cause withdrawal symptoms such as runny nose. However, this symptom may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839)
General
...Orally, pu-erh tea is well tolerated when consumed as a beverage in moderate amounts.
Most Common Adverse Effects:
Orally: Many of the adverse effects of pu-erh tea can be attributed to its caffeine content, such as diuresis, gastric irritation, insomnia, nausea, nervousness, restlessness, tachycardia, tachypnea, tremors, and vomiting.
Serious Adverse Effects (Rare):
Orally: Many of the severe adverse effects of pu-erh tea can be attributed to its caffeine content, such as arrhythmia, chest pain, convulsions, delirium, premature heartbeat, and respiratory alkalosis. Large doses of caffeine can cause massive catecholamine release and subsequent sinus tachycardia, metabolic acidosis, hyperglycemia, and ketosis.
Cardiovascular
...Pu-erh tea contains caffeine.
Although acute consumption of caffeine can cause increased blood pressure, regular consumption does not seem to increase either blood pressure or pulse, even in mildly hypertensive patients (1451,1452,2722). Epidemiological research suggests there is no association of caffeine consumption with incidence of hypertension. Some evidence suggests chronic consumption of pu-erh tea may reduce the risk of hypertension (12518).
Epidemiological research has found that regular caffeine intake of up to 400 mg daily, or approximately 4 cups of 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).
Endocrine
...Pu-erh tea contains caffeine.
Some evidence has found that caffeine is associated with fibrocystic breast disease, breast cancer, and endometriosis; however, this is controversial since findings are conflicting (8043). Restricting caffeine in those 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 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).
In infants, tea may cause microcytic anemia (631).
Gastrointestinal ...The caffeine in pu-erh tea may cause feeding intolerance and gastrointestinal irritation in infants (6023).
Immunologic ...Pu-erh tea contains caffeine. Caffeine can cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).
Musculoskeletal
...Pu-erh tea contains caffeine.
Some epidemiological research has found that caffeine may be associated with an increased risk of osteoporosis, but conflicting evidence exists. 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 daily, or about 4 cups of tea, does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317,98806).
Some researchers believe that stopping regular use of caffeine may cause withdrawal symptoms such as muscle tension and muscle pains. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839).
Neurologic/CNS
...Pu-erh tea contains caffeine.
Orally, caffeine can cause insomnia, nervousness, headache, anxiety, agitation, jitteriness, restlessness, ringing in the ears, tremors, delirium, and convulsions (10755,11832,11838,13735). Caffeine may also exacerbate sleep disturbances in patients with acquired immunodeficiency syndrome (AIDS) (10204).
There is some concern that stopping regular use of caffeine may cause withdrawal symptoms such as headache, tiredness and fatigue, decreased energy, alertness, and attentiveness, drowsiness, depressed mood, difficulty concentrating, and irritability (13738). Other symptoms such as delirium, nervousness, restlessness, and anxiety have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839).
Pulmonary/Respiratory ...Pu-erh tea contains caffeine. Caffeine may cause tachypnea-induced respiratory alkalosis (11832,11838,13735). Some researchers think that stopping regular use of caffeine may cause withdrawal symptoms such as runny nose. However, this symptom may be from nonpharmacological factors related to knowledge and expectation of effects (2723,11839).
General
...Orally, schisandra seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Decreased appetite, heartburn, stomach upset, and urticaria.
Dermatologic ...Orally, schisandra can cause urticaria in some patients (11).
Gastrointestinal ...Orally, schisandra can cause heartburn, decreased appetite, and stomach upset (11).
General
...Orally, L-theanine seems to be well tolerated.
Most Common Adverse Effects:
Orally: Drowsiness, headaches.
Neurologic/CNS
...Orally, L-theanine may cause headaches (36439).
Patients have also reported drowsiness, increased duration of sleep, and increased dream activity after oral L-theanine use (96331).
A case of subtle facial tic starting within 4 days of taking L-theanine 400 mg daily has been reported for a pediatric patient. Although the tics reportedly ceased once theanine was discontinued, the child had exhibited tics in the past. Therefore, the adverse effect was not thought to be related to L-theanine (91744).
