Two capsules contain: Choline Bitartrate 100 mg • Vitamin B5 (pantothenic acid) 20 mg • Shredz Fat Burning Complex 984 mg: Dendrobium , R-Beta-Methyl Phenylethylamine HCl , Caffeine Anhydrous , Green Tea extract (98% polyphenols), Alpha Lipoic Acid , Theobromine , Acetyl L-Carnitine , Synephrine HCl , Guggulsterone E & Z, Yohimbine HCl , Cayenne Pepper extract. Other Ingredients: Maltodextrin, Magnesium Stearate, Guggul Lipid Extract, Gelatin, Titanium Dioxide, FD&C Yellow #5, FD&C Yellow #6.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
This product has been discontinued by the manufacturer.
This product has been discontinued by the manufacturer.
Below is general information about the effectiveness of the known ingredients contained in the product ShredZ Maximum Strength Fat Burner (Mens formula). 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
There is insufficient reliable information available about the effectiveness of dendrobium for any use.
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 ShredZ Maximum Strength Fat Burner (Mens formula). Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally and appropriately. Acetyl-L-carnitine has been used safely in doses up to 3 grams daily in clinical trials lasting up to 33 months (42,1589,1594,1595,1596,1597,1598,1599,3600,3601) (9105,9791,10076,12743,12745,58375,90755,90756,90759,90761)(90766,90767,90768,95063,95067,111862).
POSSIBLY SAFE ...when used parenterally and appropriately under medical supervision (1591,1592,12743).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Acetyl-L-carnitine has been safely used orally in children for up to 6 weeks (90754).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Alpha-lipoic acid has been used with apparent safety in doses of up to 2 grams daily for 3 months to 2 years. Lower doses of 600 mg daily have been used with apparent safety for up to 4 years (3540,3541,3542,20479,96449,97630,101867,101869,103327,103333)(103335,104651,104660). ...when used topically and appropriately. A cream containing alpha-lipoic acid 5% has been used with apparent safety in clinical trials lasting up to 12 weeks (12021). ...when given intravenously and appropriately. Intravenous alpha-lipoic acid has been used safely in doses of up to 6000 mg weekly in clinical trials lasting up to 3 weeks (3540,3557,10148,12106).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
Alpha-lipoic acid has been used with apparent safety in doses of up to 600 mg daily for 3 months in children aged 10-17 years (103330).
CHILDREN: POSSIBLY UNSAFE
when used orally in amounts over 600 mg daily.
At least five cases of alpha-lipoic acid intoxication have been reported for children aged 14 months to 16 years who consumed alpha-lipoic acid at doses up to 226 mg/kg (approximately 2400 mg). Symptoms of alpha-lipoic acid-induced intoxication included seizures, acidosis, vomiting, and unconsciousness (90444,96227,96234,104653).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term.
Alpha-lipoic acid has been used safely during pregnancy at doses up to 600 mg daily for up to 4 weeks (96222).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY UNSAFE .... ..when used orally. BMPEA is an amphetamine-like compound that has been shown to have stimulant properties and is associated with severe cardiovascular adverse effects (29823,94317).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally.
BMPEA is an amphetamine-like compound that has been shown to have stimulant properties and is associated with severe cardiovascular adverse effects (29823,94317).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Bitter orange has Generally Recognized as Safe (GRAS) status in the US (4912,35751).
POSSIBLY SAFE ...when bitter orange essential oil is used topically or by inhalation as aromatherapy (6972,7107,98331,104186,104187,108642).
POSSIBLY UNSAFE ...when used orally for medicinal purposes. Although single doses of synephrine, or low daily doses used short-term, may be safe in healthy adults (2040,11269,15381,35757,35759,91681,97256,98332), laboratory analyses raise concerns that many marketed bitter orange products contain higher amounts of synephrine and other natural and synthetic amines than on the label, increasing the risk for serious stimulant-related adverse effects (104185). Additionally, there is a lack of agreement regarding a safe daily dose of synephrine. Health Canada has approved 50 mg of p-synephrine daily when used alone, or 40 mg of p-synephrine in combination with up to 320 mg of caffeine daily in healthy adults (91684). The Federal Institute for Risk Assessment in Germany recommends that supplements should provide no more than 6.7 mg of synephrine daily. This recommendation is meant to ensure that patients who frequently consume synephrine in conventional foods will receive no more than 25.7 mg daily (91290). These limits are intended to reduce the risk for serious adverse effects. There have been several case reports of ischemic stroke and cardiotoxicity including tachyarrhythmia, cardiac arrest, syncope, angina, myocardial infarction, ventricular arrhythmia, and death in otherwise healthy patients who have taken bitter orange extract alone or in combination with other stimulants such as caffeine (2040,6979,12030,13039,13067,14326,14342,91680).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in the amounts found in foods.
Bitter orange has Generally Recognized as Safe (GRAS) status in the US (4912).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally for medicinal purposes.
There are case reports of cardiotoxicity including tachyarrhythmia, syncope, and myocardial infarction in otherwise healthy adults who have taken bitter orange extract alone or in combination with other stimulants such as caffeine (2040,6979,12030,13039,13067,14326,14342,91680). The effects of bitter orange during lactation are unknown; avoid use.
LIKELY SAFE ...when used orally, parenterally, or rectally and appropriately. Caffeine has Generally Recognized As Safe (GRAS) status in the US (4912,98806). Caffeine is also an FDA-approved product and a component of several over-the-counter and prescription products (4912,11832). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, doses of caffeine up to 400 mg daily are 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). This amount of caffeine is similar to the amount of caffeine found in approximately 4 cups of coffee. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine from caffeine-containing natural ingredients such as coffee or green tea does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.
POSSIBLY UNSAFE ...when used orally, long-term or in high doses (91063). Chronic use, especially in large amounts, can produce tolerance, habituation, psychological dependence, and other adverse effects (3719). Acute use of high doses, typically above 400 mg daily, has been associated with significant adverse effects such as tachyarrhythmia and sleep disturbances (11832). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine from caffeine-containing natural ingredients such as coffee or green tea 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 used orally in very high doses. The fatal acute oral dose of caffeine is estimated to be 10-14 grams (150-200 mg/kg). Serious toxicity can occur at lower doses depending on variables in caffeine sensitivity such as smoking, age, or prior caffeine use (11832,95700,97454,104573). Caffeine products sold to consumers in highly concentrated or pure formulations are considered to a serious health concern because these products have a risk of being used in very high doses. Concentrated liquid caffeine can contain about 2 grams of caffeine in a half cup. Powdered pure caffeine can contain about 3.2 grams of caffeine in one teaspoon. Powdered pure caffeine can be fatal in adults when used in doses of 2 tablespoons or less. As of 2018, these products are considered by the FDA to be unlawful when sold to consumers in bulk quantities (95700).
CHILDREN: POSSIBLY SAFE
when used orally or intravenously and appropriately in neonates under the guidance of a healthcare professional (6371,38340,38344,91084,91087,97452).
...when used orally in amounts commonly found in foods and beverages in children and adolescents (4912,11833,36555). Daily intake of caffeine in doses of less than 2.5 mg/kg daily are not associated with significant adverse effects in children and adolescents (11733,98806). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine from caffeine-containing natural ingredients such as coffee or green tea does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.
PREGNANCY: POSSIBLY SAFE
when used orally in amounts commonly found in foods.
Intakes of caffeine should be monitored during pregnancy. Caffeine crosses the human placenta, but is not considered a teratogen (38048,38252,91032). Fetal blood and tissue levels are similar to maternal concentrations (4260). The use of caffeine during pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects (2708,2709,2710,2711,9606,16014,16015,98806,108814). In some studies consuming amounts over 200 mg daily is associated with a significantly increased risk of miscarriage (16014,37960). This increased risk seems 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, up to 300 mg daily can be consumed during pregnancy without an increased risk of spontaneous abortion, stillbirth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). However, observational research in a Norwegian cohort found that caffeine consumption is associated with a 16% increased odds of the baby being born small for gestational age when compared with no consumption (100369,103707). The same Norwegian cohort found that low to moderate caffeine consumption during pregnancy is not associated with changes in neurodevelopment in children up to 8 years of age (103699). Advise patients to keep caffeine consumption below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee or tea.
PREGNANCY: POSSIBLY UNSAFE
when used orally in amounts over 300 mg daily.
Caffeine crosses the placenta, producing fetal blood concentrations similar to maternal levels (4260,98806). Consumption of caffeine in amounts over 300 mg daily is associated with a significantly increased risk of miscarriage in some studies (16014,98806). Advise patients to keep caffeine consumption below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee or tea. Additionally, 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 (2709,2711,91033,91048,95949). 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).
LACTATION: POSSIBLY SAFE
when used orally in amounts commonly found in foods.
Caffeine intake should be closely monitored while breast-feeding. During lactation, breast milk concentrations of caffeine are thought to be approximately 50% of serum concentrations and caffeine peaks in breastmilk approximately 1-2 hours after consumption (23590).
LACTATION: POSSIBLY UNSAFE
when used orally in large amounts.
Caffeine is excreted slowly in infants and may accumulate. Caffeine can cause sleep disturbances, irritability, and increased bowel activity in breast-fed infants exposed to caffeine (2708,6026).
LIKELY SAFE ...when used orally in amounts typically found in food. Capsicum has Generally Recognized as Safe (GRAS) status in the US (4912). ...when used topically and appropriately (7038,10650,105345). The active capsicum constituent capsaicin is an FDA-approved ingredient used in certain over-the-counter, topical preparations (272).
POSSIBLY SAFE ...when used orally and appropriately, short-term in medicinal amounts. A specific sustained-release chili extract (Capsifen) has been used safely in doses of up to 200 mg daily, for up to 28 days (105196). ...when used intranasally and appropriately, short-term. Capsicum-containing nasal sprays, suspensions, and swabs seem to be safe when applied multiple times over 24 hours or when applied daily or every other day for up to 14 days. Although no serious side effects have been reported in clinical trials, intranasal application of capsicum-containing products can be very painful (14322,14324,14328,14329,14351,14352,14353,14356,14357) (14358,14359,14360,15016,105204). POSSIBLY UNSAFE when used orally, long-term or in high doses. There is concern that long-term use or use of excessive doses might be linked to hepatic or kidney damage, as well as hypertensive crisis (12404,40569,40606). There is insufficient reliable information available about the safety of capsicum when injected.
CHILDREN: POSSIBLY UNSAFE
when used topically in children under 2 years old (272).
There is insufficient reliable information available about the safety of capsicum when used orally in children.
PREGNANCY: LIKELY SAFE
when used topically and appropriately (272).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term.
Capsicum 5 mg daily has been used for up to 28 days during the latter half of the second trimester and the third trimester (96457).
LACTATION: LIKELY SAFE
when used topically and appropriately (272).
LACTATION: POSSIBLY UNSAFE
when used orally.
Dermatitis can sometimes occur in infants when foods heavily spiced with capsicum peppers are ingested during lactation (739). Also, observational research suggests that intake of raw capsicum peppers during pregnancy is associated with an increased risk of sensitization to inhalant allergens in children by the age of 2 years (41021).
LIKELY SAFE ...when used orally and appropriately. Choline is safe in adults when taken in doses below the tolerable upper intake level (UL) of 3.5 grams daily (3094) ...when used intravenously and appropriately. Intravenous choline 1-4 grams daily for up to 24 weeks has been used with apparent safety (5173,5174).
POSSIBLY UNSAFE ...when used orally in doses above the tolerable upper intake level (UL) of 3. 5 grams daily. Higher doses can increase the risk of adverse effects (3094).
CHILDREN: LIKELY SAFE
when used orally and appropriately (3094).
Choline is safe in children when taken in doses below the tolerable upper intake level (UL), which is 1 gram daily for children 1-8 years of age, 2 grams daily for children 9-13 years of age, and 3 grams daily for children 14-18 years of age (3094).
CHILDREN: POSSIBLY UNSAFE
when used orally in doses above the UL.
High doses can increase the risk of adverse effects (3094).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Choline is safe when taken in doses below the tolerable upper intake level (UL), which is 3 grams daily during pregnancy and lactation in those up to 18 years of age and 3.5 grams daily for those 19 years and older (3094,92114). There is insufficient reliable information available about the safety of choline used in higher doses during pregnancy and lactation.
LIKELY SAFE ...when used orally and appropriately (13161,14306,14307,14308,15655,15752,17187,92271,92274,103247)(103250,108898). However, cocoa naturally contains caffeine, and caffeine may be unsafe when used orally in doses of more than 400 mg daily (11733,98806). While most cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), one cup of unsweetened, dry cocoa powder can contain up to 198 mg of caffeine (100515). To be on the safe side, cocoa should be used in amounts that provide less than 400 mg of caffeine daily. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine naturally found in ingredients such as cocoa does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Advise patients to consume cocoa in moderation. ...when used topically. Cocoa butter is used extensively as a base for ointments and suppositories and is generally considered safe (11).
CHILDREN: POSSIBLY UNSAFE
when dark chocolate is used orally.
Cocoa and dark chocolate products worldwide contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Children are at increased risk of adverse effects from intake of lead and/or cadmium. There is insufficient reliable information available about the safety of other chocolate-based products that typically contain smaller quantities of cocoa.
PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts.
However, due to the caffeine content of cocoa preparations, intake should be closely monitored during pregnancy to ensure moderate consumption. Fetal blood concentrations of caffeine approximate maternal concentrations (4260). Some research has 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). While many cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), unsweetened, dry cocoa powder can contain up to 198 mg of caffeine per cup (100515). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, doses of up to 300 mg daily can be consumed during pregnancy without an increased risk of spontaneous abortion, still birth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). To be on the safe side, cocoa should be used in amounts that provide less than 300 mg of caffeine daily. 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 cocoa, 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 found in cocoa 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). Additionally, high intake of caffeine during pregnancy have been associated with premature delivery, low birth weight, and loss of the fetus (6). While many cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), unsweetened, dry cocoa powder can contain up to 198 mg of caffeine per cup (100515). To be on the safe side, cocoa should be used in amounts that provide less than 300 mg of caffeine daily (2708). 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 cocoa, 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. Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Large doses or excessive intake of cocoa should be avoided during pregnancy.
LACTATION: POSSIBLY SAFE
when used in moderate amounts or in amounts commonly found in foods.
Due to the caffeine content of cocoa preparations, intake should be closely monitored while breastfeeding. During lactation, breast milk concentrations of caffeine are thought to be approximately 50% of serum concentrations. Moderate consumption of cocoa would likely result in very small amounts of caffeine exposure to a nursing infant (6). 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 cocoa, 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.
LACTATION: POSSIBLY UNSAFE
when used orally in large amounts.
Consumption of excess chocolate (16 oz per day) may cause irritability and increased bowel activity in the infant (6026). Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Large doses or excessive intake of cocoa should be avoided during lactation.
There is insufficient reliable information available about the safety of dendrobium.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
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 the prepared gum resin is used orally and appropriately. It has been used with apparent safety in clinical trials for up to 24 weeks (3267,3268,10371). There is insufficient reliable information available about the safety of guggul when used topically.
PREGNANCY: LIKELY UNSAFE
when used orally; avoid using.
Guggul gum resin appears to stimulate menstrual flow and the uterus (12).
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. The pantothenic acid derivative calcium pantothenate has a generally recognized as safe (GRAS) status for use in food products (111258). While a tolerable upper intake level (UL) has not been established, pantothenic has been used in doses of 10-20 grams daily with apparent safety (15,6243,111258) ...when applied topically and appropriately, short-term. The Cosmetic Ingredient Review Expert Panel has concluded that pantothenic acid and its derivatives are safe for use in cosmetic products in concentrations up to 5.3% (111258). Gels or ointments containing a derivative of pantothenic acid, dexpanthenol, at concentrations of up to 5%, have been used safely for up to 30 days (67802,67806,67817).
POSSIBLY SAFE ...when applied intranasally and appropriately, short-term. A dexpanthenol nasal spray has been used with apparent safety up to four times daily for 4 weeks (67826). ...when applied in the eyes appropriately, short-term. Dexpanthenol 5% eyedrops have been used with apparent safety for up to 28 days (67783). ...when injected intramuscularly and appropriately, short-term. Intramuscular injections of dexpanthenol 500 mg daily for up to 5 days or 250 mg weekly for up to 6 weeks have been used with apparent safety (67822,111366).
CHILDREN: LIKELY SAFE
when used orally and appropriately (15,6243).
Calcium pantothenate is generally recognized as safe (GRAS) when used as a food additive and in infant formula (111258). However, a tolerable upper intake level (UL) has not been established (15,6243). ...when applied topically and appropriately (67795,105190,111262). Infant products containing pantothenic acid and its derivatives have been used safely in concentrations of up to 5% for infant shampoos and 2.5% for infant lotions and oils. The Cosmetic Ingredient Review Expert Panel has concluded that pantothenic acid and derivatives are safe for use in topical infant products. (111258).
PREGNANCY: LIKELY SAFE
when used orally and appropriately.
The daily adequate intake (AI) during pregnancy is 6 mg (3094).
LACTATION: LIKELY SAFE
when used orally and appropriately.
The daily adequate intake (AI) during lactation is 7 mg (3094).
POSSIBLY UNSAFE ...when used orally. Yohimbine, a constituent of yohimbe, has been associated with serious adverse effects including cardiac arrhythmia, agitation, myocardial infarction, seizure, and others (17465). Some research shows that yohimbine can be safely used under close medical supervision for up to 10 weeks (3305,3307,3311,3313). However, due to safety concerns, yohimbe should not be used without medical supervision.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally.
Yohimbe might have uterine relaxant effects and also cause fetal toxicity (19).
Below is general information about the interactions of the known ingredients contained in the product ShredZ Maximum Strength Fat Burner (Mens formula). Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of acenocoumarol.
 Details
L-carnitine, the parent compound of acetyl-L-carnitine, might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant that is similar to warfarin, but shorter-acting (9878,12165). There are at least two case reports of INR elevation when L-carnitine was taken with acenocoumarol. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product (12165). It is unclear if such an interaction would also occur with acetyl-L-carnitine.
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Theoretically, acetyl-L-carnitine might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders, when taken with serotonergic drugs.
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Animal research shows that acetyl-L-carnitine can increase levels of serotonin in the brain (95065).
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Theoretically, acetyl-L-carnitine might decrease the effectiveness of thyroid hormone replacement.
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L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells (12761). Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism (8047). It is unclear if such an interaction would occur with acetyl-L-carnitine.
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Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of warfarin.
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Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of alkylating agents.
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The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy. Advise patients to consult their oncologist before using alpha-lipoic acid.
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Theoretically, alpha-lipoic acid may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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In vitro, alpha-lipoic acid inhibits platelet aggregation (98682).
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Theoretically, taking alpha-lipoic acid with antidiabetes drugs might increase the risk of hypoglycemia.
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Although some small clinical studies have suggested that alpha-lipoic acid can lower blood glucose levels (3545,3874,3875,3876,20490,20493,104650), larger clinical studies in patients with diabetes have shown no clinically meaningful effect (20494,20495,20496,90443,90445,110118). Additionally, co-administration of single doses of alpha-lipoic acid and glyburide or acarbose did not cause detectable drug interactions in healthy volunteers (3870).
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Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of antitumor antibiotics.
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The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of antitumor antibiotic drugs, which work by generating free radicals (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using alpha-lipoic acid.
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Theoretically, alpha-lipoic acid might decrease the effects of thyroid hormone drugs.
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Animal research suggests that co-administration of thyroxine with alpha-lipoic acid reduces conversion into the active T3 form (8946).
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Theoretically, BMPEA might increase the levels and clinical effects of CYP2D6 substrates.
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In vitro research shows that BMPEA strongly inhibits CYP2D6 (91878).
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Theoretically, BMPEA might increase the levels and clinical effects of CYP3A4 substrates.
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In vitro research shows that BMPEA inhibits CYP3A4 by up to 37% (91878).
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Theoretically, taking BMPEA with other stimulant drugs might increase the risk of adverse cardiovascular effects.
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Theoretically, bitter orange might increase the risk of hypoglycemia when taken with antidiabetes drugs.
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Some clinical research shows that drinking a tea containing bitter orange and Indian snakeroot reduces fasting and postprandial glucose levels in patients with type 2 diabetes who are using antidiabetes drugs (35751). However, it is unclear if these effects are due to bitter orange, Indian snakeroot, or the combination. An animal study also shows that p-synephrine in combination with gliclazide , a sulfonylurea, causes an additional 20% to 44% decrease in glucose levels when compared with gliclazide alone (95658).
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Bitter orange might increase blood pressure and heart rate when taken with caffeine.
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Bitter orange might affect colchicine levels.
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Colchicine is a substrate of P-glycoprotein and cytochrome P450 3A4 (CYP3A4). Bitter orange has been reported to inhibit CYP3A4 and increase levels of CYP3A4 substrates (7029,11362,93470). However, one small clinical study in healthy adults shows that drinking bitter orange juice 240 mL twice daily for 4 days and taking a single dose of colchicine 0.6 mg on the 4th day decreases colchicine peak serum levels by 24%, time to peak serum level by 1 hour, and overall exposure to colchicine by 20% (35762). The clinical significance of this finding is unclear.
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Theoretically, bitter orange might increase levels of drug metabolized by CYP2D6.
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In vitro research shows that octopamine, a constituent of bitter orange, weakly inhibits CYP2D6 enzymes (91878). This effect has not been reported in humans.
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Bitter orange might increase levels of drugs metabolized by CYP3A4.
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Small clinical studies suggest that single or multiple doses of freshly squeezed bitter orange juice 200-240 mL can inhibit CYP3A4 metabolism of drugs (7029,11362,93470), causing increased drug levels and potentially increasing the risk of adverse effects. However, the extent of the effect of bitter orange on CYP3A4-mediated drug interactions is unknown. Some evidence suggests that bitter orange selectively inhibits intestinal CYP3A4, but not hepatic CYP3A4. Its effect on P-glycoprotein, which strongly overlaps with CYP3A4 interactions, is unclear (7029,11269,11270,11362). One small clinical study shows that drinking 8 ounces of freshly squeezed bitter orange juice has no effect on cyclosporine, which seems to be more dependent on hepatic CYP3A4 and P-glycoprotein than intestinal CYP3A4 (11270).
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Bitter orange might increase blood levels of dextromethorphan.
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One small clinical study shows that bitter orange juice increases dextromethorphan levels, likely through cytochrome P450 3A4 (CYP3A4) inhibition (11362). Theoretically, bitter orange might increase the risk for dextromethorphan-related adverse effects.
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Bitter orange might increase blood levels of felodipine.
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One small clinical study shows that bitter orange juice increases felodipine levels, likely through cytochrome P450 3A4 (CYP3A4) inhibition (7029). Theoretically, bitter orange might increase the risk for felodipine-related adverse effects.
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Bitter orange might increase blood levels of indinavir.
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One small clinical study shows that bitter orange juice slightly increases indinavir levels, but this effect is likely to be clinically insignificant. Bitter orange selectively inhibits intestinal cytochrome P450 3A4 (CYP3A4); however, the metabolism of indinavir seems to be more dependent on hepatic CYP3A4 (11269). The effect of bitter orange on other protease inhibitors has not been studied.
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Bitter orange might increase blood levels of midazolam.
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One small clinical study shows that bitter orange juice can increase midazolam levels, likely through inhibition of cytochrome P450 3A4 (CYP3A4) (7029). Theoretically, bitter orange might increase the risk of midazolam-related adverse effects.
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Theoretically, taking MAOIs with synephrine-containing bitter orange preparations might increase the hypertensive effects of synephrine, potentially leading to hypertensive crisis.
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Theoretically, bitter orange might have an additive effect when combined with drugs that prolong the QT interval, potentially increasing the risk of ventricular arrhythmias.
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One case report suggests that taking bitter orange in combination with other stimulants such as caffeine might prolong the QT interval in some patients (13039).
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Bitter orange juice might increase blood levels of sildenafil.
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A small clinical study in healthy adult males shows that drinking freshly squeezed bitter orange juice 250 mL daily for 3 days and taking a single dose of sildenafil 50 mg on the 3rd day increases the peak plasma concentration of sildenafil by 18% and the overall exposure to sildenafil by 44%. Theoretically, this may be due to inhibition of cytochrome P450 3A4 by bitter orange (93470).
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Theoretically, bitter orange might increase the risk of hypertension and adverse cardiovascular effects when taken with stimulant drugs.
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Theoretically, caffeine might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
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Some evidence shows that caffeine is a competitive inhibitor of adenosine and can reduce the vasodilatory effects of adenosine in humans (38172). However, other research shows that 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 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).
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Theoretically, concomitant use might increase levels and adverse effects of caffeine.
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Alcohol reduces caffeine metabolism. Concomitant use of alcohol can increase caffeine serum concentrations and the risk of caffeine adverse effects (6370).
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Theoretically, caffeine may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Theoretically, taking caffeine with antidiabetes drugs might interfere with blood glucose control.
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Theoretically, large amounts of caffeine might increase the cardiac inotropic effects of beta-agonists (15).
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Theoretically, caffeine might reduce the effects of carbamazepine and increase the risk for convulsions.
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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).
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Theoretically, cimetidine might increase the levels and adverse effects of caffeine.
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Cimetidine decreases the rate of caffeine clearance by 31% to 42% (11736).
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Caffeine might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
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Caffeine might 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). Although researchers speculate that caffeine might inhibit CYP1A2, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to an interaction between clozapine and caffeine (13741). In one case report, severe, life-threatening clozapine toxicity and multiorgan system failure occurred in a patient with schizophrenia stabilized on clozapine who consumed caffeine 600 mg daily (108817).
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Theoretically, contraceptive drugs might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
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Theoretically, caffeine might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
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Caffeine inhibits 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).
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Theoretically, disulfiram use might increase the levels and adverse effects of caffeine.
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Disulfiram decreases the rate of caffeine clearance (11840).
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Theoretically, using caffeine with diuretic drugs might increase the risk of hypokalemia.
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Theoretically, concomitant use might increase the risk for stimulant adverse effects.
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Use of ephedrine with caffeine can increase the risk of stimulatory adverse effects. 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).
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Theoretically, estrogens might increase the levels and adverse effects of caffeine.
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Theoretically, caffeine might reduce the effects of ethosuximide and increase the risk for convulsions.
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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.
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Theoretically, caffeine might reduce the effects of felbamate and increase the risk for convulsions.
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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.
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Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
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Fluconazole decreases caffeine clearance by approximately 25% (11022).
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Theoretically, caffeine might increase the levels and adverse effects of flutamide.
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In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553). However, this effect has not been reported in humans.
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Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
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Fluvoxamine reduces caffeine metabolism (6370).
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Theoretically, abrupt caffeine withdrawal might increase the levels and adverse effects of lithium.
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Theoretically, metformin might increase the levels and adverse effects of caffeine.
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Animal research suggests that metformin can reduce caffeine metabolism (23571). However, this effect has not been reported in humans.
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Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.
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Methoxsalen reduces caffeine metabolism (23572).
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Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the risk of a hypertensive crisis.
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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.
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Theoretically, concomitant use might increase the risk of hypertension.
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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).
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Theoretically, caffeine might decrease the effects of pentobarbital.
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Caffeine might negate the hypnotic effects of pentobarbital (13742).
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Theoretically, caffeine might reduce the effects of phenobarbital and increase the risk for convulsions.
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Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
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Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
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Theoretically, caffeine might reduce the effects of phenytoin and increase the risk for convulsions.
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Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.
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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.
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Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
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Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce the metabolism of one or both agents (11739).
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Theoretically, concomitant use might increase stimulant adverse effects.
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Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects (11832).
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Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
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Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).
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Theoretically, caffeine might increase the levels and adverse effects of theophylline.
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Large amounts of caffeine might inhibit theophylline metabolism (11741).
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Theoretically, caffeine might increase the levels and adverse effects of tiagabine.
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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).
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Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.
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In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.
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Theoretically, caffeine might reduce the effects of valproate and increase the risk for convulsions.
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Theoretically, verapamil might increase the levels and adverse effects of caffeine.
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Verapamil increases plasma caffeine concentrations by 25% (11741).
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Theoretically, using topical capsaicin may increase the risk of ACE inhibitor-induced cough.
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There is one case report of a topically applied capsaicin cream contributing to the cough reflex in a patient using an ACEI (12414). However, it is unclear if this interaction is clinically significant.
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Theoretically, capsicum may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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In vitro research shows that capsicum might increase the effects of antiplatelet drugs (12406,12407). Also, population research shows that capsicum is associated with an increased risk of self-reported bleeding in patients taking warfarin (12405,20348). However, clinical research shows that taking a single dose of capsaicin (Asian Herbex Ltd.), the active ingredient in capsicum, 400-800 mcg orally in combination with aspirin 500 mg does not decrease platelet aggregation when compared with taking aspirin 500 mg alone. Also, there was no notable effect on measures of platelet aggregation with capsaicin (92990). It is unclear whether capsaicin must be used in more than a single dose to affect platelet aggregation.
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Theoretically, taking capsicum with antidiabetes drugs might increase the risk of hypoglycemia.
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Preliminary clinical research shows that consuming capsicum 5 grams along with a glucose drink attenuates the rise in plasma glucose after 30 minutes by 21%, decreases the 2-hour postprandial area under the curve of plasma glucose by 11%, and increases the 2-hour postprandial area under the curve of plasma insulin by 58% in healthy individuals when compared with placebo (40453,40614). Other clinical research shows that taking capsicum 5 mg daily for 28 days significantly reduces postprandial blood glucose and insulin levels, but not fasting blood glucose and insulin levels, in patients with gestational diabetes (96457).
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Theoretically, taking capsicum with aspirin might reduce the bioavailability of aspirin.
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Animal research shows that acute or chronic intake of capsicum pepper reduces oral aspirin bioavailability (22617). This has not been shown in humans.
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Theoretically, taking capsicum with ciprofloxacin might increase levels and adverse effects of ciprofloxacin.
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Animal research shows that concomitant use of capsaicin, the active constituent of capsicum, and ciprofloxacin increases the bioavailability of ciprofloxacin by up to 70% (22613).
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Theoretically, taking capsicum with theophylline might increase the levels and adverse effects of theophylline.
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Theoretically, choline might decrease the effects of atropine in the brain.
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Animal research shows that administering choline one hour before administering atropine can attenuate atropine-induced decreases in brain levels of acetylcholine (42240). Theoretically, concomitant use of choline and atropine may decrease the effects of atropine.
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Theoretically, taking cocoa with ACEIs might increase the risk of adverse effects.
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Theoretically, cocoa might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Details
Cocoa 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. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. However, methylxanthines appear more likely to interfere with dipyridamole than adenosine-induced stress testing (11771).
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Theoretically, concomitant use might increase levels and adverse effects of caffeine.
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Cocoa contains caffeine. Alcohol reduces caffeine metabolism. Concomitant use of alcohol can increase caffeine serum concentrations and the risk of caffeine adverse effects (6370).
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Theoretically, cocoa may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Clinical research shows that intake of cocoa can inhibit platelet adhesion, aggregation, and activity (6085,17076,41928,41948,41957,41958,41995,42014,42070,42145)(111526) and increase aspirin-induced bleeding time (23800). For patients on dual antiplatelet therapy, cocoa may enhance the inhibitory effect of clopidogrel, but not aspirin, on platelet aggregation (111526).
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Theoretically, taking cocoa with antihypertensive drugs might increase the risk of hypotension.
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Theoretically, large amounts of cocoa might increase the cardiac inotropic effects of beta-agonists.
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Cocoa contains caffeine. Theoretically, large amounts of caffeine might increase cardiac inotropic effects of beta-agonists (15). A case of atrial fibrillation associated with consumption of large quantities of chocolate in a patient with chronic albuterol inhalation abuse has also been reported (42075).
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Theoretically, concomitant use might increase the effects and adverse effects of caffeine in cocoa.
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Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in cocoa.
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Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
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Cocoa 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 cocoa and increase caffeine levels.
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Theoretically, cocoa might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Details
Cocoa contains caffeine. Caffeine may 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 than adenosine-induced stress testing (11771).
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Theoretically, disulfiram might increase the risk of adverse effects from caffeine.
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Cocoa contains caffeine. In human research, disulfiram decreases the rate of caffeine clearance (11840).
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Theoretically, using cocoa with diuretic drugs might increase the risk of hypokalemia.
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Theoretically, concomitant use might increase the risk for stimulant adverse effects.
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Theoretically, estrogens might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Estrogen inhibits caffeine metabolism (2714).
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Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022).
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Theoretically, cocoa might increase the levels and adverse effects of flutamide.
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Cocoa contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553).
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Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Details
Cocoa contains caffeine. Fluvoxamine reduces caffeine metabolism (6370).
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Theoretically, abrupt cocoa withdrawal might increase the levels and adverse effects of lithium.
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Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Methoxsalen can reduce caffeine metabolism (23572).
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Theoretically, metformin might increase the levels and adverse effects of caffeine.
Details
Cocoa contains caffeine. Animal research suggests that metformin can reduce caffeine metabolism (23571).
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Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
Details
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Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Details
Cocoa contains caffeine. Large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15).
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Theoretically, concomitant use might increase the risk of hypertension.
Details
Cocoa 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).
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Theoretically, cocoa might decrease the effects of pentobarbital.
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Cocoa contains caffeine. Caffeine might negate the hypnotic effects of pentobarbital (13742).
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Theoretically, cocoa might reduce the effects of phenobarbital and increase the risk for convulsions.
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Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
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Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Details
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Theoretically, cocoa might reduce the effects of phenytoin and increase the risk for convulsions.
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Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Details
Cocoa contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2, and concomitant use might reduce metabolism of one or both agents (11739).
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Theoretically, concomitant use might increase stimulant adverse effects.
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Cocoa contains caffeine. Concomitant use might increase the risk of stimulant adverse effects (11832).
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Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Terbinafine decreases the rate of caffeine clearance (11740).
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Theoretically, cocoa might increase the levels and adverse effects of theophylline.
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Theoretically, cocoa tea might increase the levels and adverse effects of tiagabine.
Details
Cocoa 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).
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Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.
Details
Cocoa contains caffeine. In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.
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Theoretically, cocoa might reduce the effects of valproate and increase the risk for convulsions.
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Theoretically, verapamil might increase the levels and adverse effects of caffeine.
Details
Cocoa contains caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).
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The dendrobium constituent dendrobine is reported to have convulsant effects (7162). Theoretically, combining dendrobium with anticonvulsant drugs might decrease drug effectiveness and increase the risk of seizure. Some anticonvulsant drugs include phenobarbital, primidone (Mysoline), valproic acid (Depakene), gabapentin (Neurontin), carbamazepine (Tegretol), phenytoin (Dilantin), and others.
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The dendrobium constituent dendrobine is reported to have hypotensive effects (7162). Theoretically, combining dendrobium with antihypertensive drugs might increase the risk of hypotension; use with caution.
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The dendrobium constituent dendrobine is reported to have convulsant effects (7162). Theoretically, combining dendrobium with pro-convulsant drugs might increase the risk of seizure. Some drugs that lower the seizure threshold include anesthetics (propofol, others), antiarrhythmics (mexiletine), antibiotics (amphotericin, penicillin, cephalosporins, imipenem), antidepressants (bupropion, others), antihistamines (cyproheptadine, others), immunosuppressants (cyclosporine), narcotics (fentanyl, others), stimulants (methylphenidate), theophylline, and others.
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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).
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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).
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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).
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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).
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Theoretically, taking green tea with antidiabetes drugs might interfere with blood glucose control.
Details
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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.
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Green tea contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists (15).
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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.
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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).
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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).
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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).
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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).
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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).
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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.
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Green tea is unlikely to produce clinically significant changes in the levels and clinical effects of CYP3A4 substrates.
Details
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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).
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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).
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Theoretically, using green tea with diuretic drugs might increase the risk of hypokalemia.
Details
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Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Details
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Theoretically, estrogens might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Estrogen inhibits caffeine metabolism (2714).
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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.
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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.
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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).
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Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022).
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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.
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Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Fluvoxamine reduces caffeine metabolism (6370).
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Theoretically, concomitant use might have additive adverse hepatotoxic effects.
Details
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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.
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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).
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Theoretically, abrupt green tea withdrawal might increase the levels and adverse effects of lithium.
Details
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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.
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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.
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Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Mexiletine can decrease caffeine elimination by 50% (1260).
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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.
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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.
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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).
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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.
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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).
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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).
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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).
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Theoretically, green tea might decrease the effects of pentobarbital.
Details
Green tea contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).
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Theoretically, green tea might reduce the effects of phenobarbital and increase the risk for convulsions.
Details
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Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
Details
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Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Details
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Theoretically, green tea might reduce the effects of phenytoin and increase the risk for convulsions.
Details
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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.
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Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
Details
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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).
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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.
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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).
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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).
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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).
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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).
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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.
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Theoretically, green tea might reduce the effects of valproate and increase the risk for convulsions.
Details
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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).
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Theoretically, green tea may increase the risk of bleeding if used with warfarin.
Details
Conflicting reports exist regarding the potential of green tea to antagonize the effect of warfarin; however, most evidence suggests that drinking green tea in moderation is unlikely to cause a significant interaction. Green tea contains a small amount of vitamin K, approximately 7 mcg per cup (100524). Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea (1460,1461,1463,4211,6048,8028,20868). However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects (1460,1461,1463,8028). Therefore, use of green tea in moderate amounts is unlikely to antagonize the effects of warfarin; however, very large doses should be avoided.
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Theoretically, guggul might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.
Details
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Theoretically, guggul might increase the risk of adverse effects when taken with contraceptive drugs.
Details
In vitro research shows that guggul has estrogen-alpha receptor agonist activity (12444).
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Theoretically, guggul might reduce the effects of CYP3A4 substrates.
Details
In vitro research shows that guggul constituents known as guggulsterones can induce CYP3A4 (12444).
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Guggul might reduce the effects of diltiazem.
Details
A small pharmacokinetic study shows that concomitant use of guggul with diltiazem reduces the bioavailability of diltiazem (383).
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Theoretically, guggul might increase the risk of adverse effects when taken with estrogens.
Details
In vitro research shows that guggul constituents known as guggulsterones have estrogen-alpha receptor agonist activity (12444).
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Guggul might reduce the effects of propranolol.
Details
A small pharmacokinetic study shows that concomitant use of guggul with propranolol reduces the bioavailability of propranolol (383).
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Theoretically, guggul might increase the effects and adverse effects of rosuvastatin.
Details
Animal research shows that guggul increases the bioavailability and hypolipidemic effects of rosuvastatin (109584). The mechanism of this interaction is unclear.
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Theoretically, guggul might interfere with tamoxifen therapy.
Details
In vitro research shows that guggul has estrogen-alpha receptor agonist activity (12444).
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Theoretically, guggul might increase the risk for adverse effects when taken with thyroid hormone therapy.
Details
Animal research suggests that guggul has thyroid-stimulating effects (8153).
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Theoretically, combining yohimbe bark with antiplatelet or anticoagulant drugs might have additive effects; however, this has not been reported in clinical research.
Details
Research in healthy adults shows that taking yohimbine, a constituent of yohimbe bark, in doses of 8 mg or more, seems to inhibit platelet aggregation in vitro by binding to the alpha-2 adrenoceptor (86773,86806,86835,86853). The effects of yohimbe bark itself are unclear; yohimbe bark contains 0.6% to 1.38% yohimbine, but it is unclear how much is absorbed (86862,89263).
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Theoretically, yohimbe might reduce the effects of antihypertensive drugs.
Details
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Theoretically, yohimbe might precipitate clonidine withdrawal.
Details
Chronic clonidine use can downregulate alpha-2 adrenoreceptors. Animal research and one human case report suggest that concomitant administration of yohimbine, an alpha-2 adrenoceptor antagonist, may precipitate clonidine withdrawal and lead to sympathomimetic toxicity, including hypertensive crisis (111406).
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Theoretically, yohimbe might decrease the levels and clinical effects of CYP1A2 substrates.
Details
In vitro research shows that yohimbe extract induces CYP1A2 enzymes (111404).
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Theoretically, CYP2D6 inhibitors might increase the levels and adverse effects of yohimbine, a constituent of yohimbe.
Details
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Theoretically, yohimbe might increase the levels and adverse effects of CYP2D6 substrates.
Details
In vitro research suggests that yohimbine, a constituent of yohimbe bark, inhibits CYP2D6 enzyme activity (23117).
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Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of yohimbine, a constituent of yohimbe bark.
Details
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Theoretically, yohimbe might decrease the levels and clinical effects of CYP3A4 substrates.
Details
In vitro research shows that yohimbe extract induces CYP3A4 enzymes (111404).
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Concomitant use of MAOIs with yohimbe can result in additive effects.
Details
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Theoretically, using yohimbine with phenothiazines might have additive effects.
Details
Yohimbine, a constituent of yohimbe, has alpha-2 adrenergic antagonist effects. Theoretically, combining it with phenothiazines can cause additive alpha-2 adrenergic antagonism (19).
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Theoretically, taking yohimbe with stimulant drugs can have additive effects.
Details
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Theoretically, taking yohimbe with TCAs can increase adverse effects.
Details
A small clinical study in patients taking TCAs for at least 4 weeks shows that receiving doses of intravenous yohimbine 2.5-20 mg daily for up to 7 days precipitates severe anxiety, agitation, and tremor (105881). The effects of yohimbe bark itself are unclear; oral yohimbe bark contains 0.6% to 1.38% yohimbine, but it is unclear how much is absorbed (86862,89263).
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Below is general information about the adverse effects of the known ingredients contained in the product ShredZ Maximum Strength Fat Burner (Mens formula). 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, acetyl-L-carnitine is generally well tolerated.
Most Common Adverse Effects:
Orally: Agitation, dry mouth, headache, insomnia, and reduced appetite. A metabolite of acetyl-L-carnitine has been reported to cause a fishy odor of the urine, breath, and sweat.
Cardiovascular ...Orally, one patient in a pharmacokinetic study reported high blood pressure 8 hoursafter taking acetyl-L-carnitine 500 mg; however, it is unclear if this was due to acetyl-L-carnitine or another factor (95061).
Dermatologic ...Orally, a combination of acetyl-L-carnitine and alpha-lipoic acid may cause rash (90441).
Gastrointestinal ...Orally, acetyl-L-carnitine may cause nausea, vomiting, diarrhea, constipation, hiccups, abdominal distension and gastrointestinal upset or pain. However, gastrointestinal symptoms do not usually occur more often in patients receiving acetyl-L-carnitine than in patients receiving placebo (1596,1599,12743,13007,58922,90755,95063,95067,111889,111894). Acetyl-L-carnitine may also cause dry mouth and anorexia (58342). When taken orally, a combination of acetyl-L-carnitine and alpha-lipoic acid may cause diarrhea, constipation, and dyspepsia (90441).
Neurologic/CNS ...Orally, acetyl-L-carnitine may cause headache and insomnia (90760,90767,95063). In one clinical trial, two patients with antiretroviral toxic neuropathy reported paresthesia, pain, and neuropathy after taking acetyl-L-carnitine 1000 mg daily (58342). A case of mania has been reported for a patient with bipolar I disorder currently in remission. The patient presented with symptoms after taking multiple supplements for the past 4 weeks including acetyl-L-carnitine 1000 mg twice daily. The symptoms appeared 3 days after beginning to take acetyl-L-carnitine and worsened over the next week. The patient had increased speech rate and volume and reported increased energy levels and racing thoughts. The patient's parent reported irritability and an increase in loud behaviors at home, similar to a previous episode of mania. The patient was advised to discontinue acetyl-L-carnitine, and the manic symptoms disappeared 3 days later (95062).
Psychiatric ...Orally, acetyl-L-carnitine may cause agitation (restlessness and motor overactivity) (1596,1599,12743,13007). Side effects reported in people with Alzheimer disease include psychiatric disturbances such as depression, mania, confusion and aggression, but it is not clear whether these are due to acetyl-L-carnitine or the condition itself (1594,1595,1596,1597,1598,1599,9105,10391).
Other ...One of the metabolites of acetyl-L-carnitine can cause the urine, breath, and sweat to have a fishy odor (12756). Also, foul smelling urine has been reported following oral use of a combination of acetyl-L-carnitine and alpha-lipoic acid (90441).
General
...Alpha-lipoic acid appears to be generally well tolerated when used orally, intravenously, or topically.
Most Common Adverse Effects:
Orally: Headache, heartburn, nausea, and vomiting.
Topically: Irritation and rash.
Intravenously: Nausea and vomiting.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about insulin autoimmune syndrome (IAS).
Cardiovascular ...Orally, hypotension has been reported rarely in a clinical trial (104650).
Dermatologic ...Orally, skin rash and itching have been reported after use of alpha-lipoic acid (16391,20490,21674,96233,104650). Topically, alpha-lipoic acid can cause local irritation, including burning, stinging, mild rash, or contact dermatitis (12021,30836,111701). In one case, an 86-year-old female developed allergic contact dermatitis with severe itching and oozing after applying alpha-lipoic acid 5% cream to her lower extremities. The patient had a positive skin patch test for alpha-lipoic acid, confirming the causative agent (111701). In another case, a 47-year-old female developed contact dermatitis characterized by a pruritic rash and labial adhesions hours after applying a 5% vulvar serum containing lipoic acid 0.9 grams, vitamin E, vitamin C, hyaluronic acid, and retinol palmitate to the vulva to treat vulvar lichen sclerosis. Testing confirmed that the causative agent was alpha-lipoic acid (111704). Intravenously, local allergic reactions have occurred at the injection site (1547).
Endocrine ...Orally, at least 50 published cases of insulin autoimmune syndrome (IAS) thought to be associated with use of alpha-lipoic acid have been reported (16392,104656,104657,104658,104659,107893,112941). Most reported cases have been associated with alpha-lipoic acid supplements or enriched foods; IAS has not been reported with intake of alpha-lipoic acid in food. IAS has been linked to compounds, such as alpha-lipoic acid, that contain sulfhydryl groups, but it is unclear if taking alpha-lipoic acid with other drugs known to trigger IAS increases the risk (107893,112941). IAS is characterized by very high serum insulin levels and high titers of autoantibodies against endogenous insulin. Sulfhydryl groups interact with disulfide bonds of insulin, increasing its immunogenicity (112941). Symptoms include severe spontaneous hypoglycemic episodes, as well as hunger and neuroglycopenic symptoms such as blurred vision, weakness, confusion, dizziness, sweating, and palpitations (104656,104657,107893,112941). Time to onset of IAS ranges from 1 week to 4 months (107893). Most cases of IAS have been reported in Japan and have occurred in individuals with the human leucocyte antigen (HLA)-DRB1*04:06 allele (16392,104656,107893). For patients of European decent, cases of IAS have mainly occurred in individuals with the HLA-DRB1*04:03 allele (104656,104658,104659,107893). This suggests that either of these alleles might produce a genetic predisposition to alpha-lipoic acid-associated IAS. Reported doses of alpha-lipoic acid have ranged from 200-800 mg daily, most commonly 600 mg daily (104656,104658,104659,107893). IAS-related hypoglycemic episodes have been treated with oral or intravenous glucose or sucrose, as well as prednisone. Episodes decline following discontinuation of alpha-lipoic acid, and insulin values normalize within 3-9 months (104656,104658,104659,107893).
Gastrointestinal ...Orally, heartburn, nausea, and vomiting have been reported after use of alpha-lipoic acid (3557,12106,16391,20475,30844,96225,101868,103327,103328,103333)(103335,104650,104654,104655). Higher doses (1200-1800 mg daily) seem to cause more severe effects than lower doses (600 mg daily) (3557,20475,30844,96225). Alpha-lipoic acid may also cause a burning sensation from the throat to the stomach, abdominal discomfort, or bitter taste when used orally (20478,20490,21664,96225). Intravenously, alpha-lipoic acid can cause gastrointestinal upset, including nausea and vomiting. Adverse effects are more common in patients receiving higher intravenous doses (3557) and may be more common in the elderly (96225).
Genitourinary ...Orally, alpha-lipoic acid may cause urinary disorders (20479). Oral alpha-lipoic acid has also been associated with a change in urine odor (96225,103327).
Neurologic/CNS
...Orally, alpha-lipoic acid may cause headache (21664,103328,104655) or dizziness (104650).
Intravenously, paresthesias have been reported to worsen temporarily at the beginning of therapy. Also, intravenous alpha-lipoic acid can cause headache. Adverse effects are more common in patients receiving higher intravenous doses (3557).
General
...BMPEA is an amphetamine derivative which can cause serious stimulant adverse effects.
Most Common Adverse Effects:
Hypertension and tachycardia.
Serious Adverse Effects (Rare):
Cardiac arrest, stroke.
Cardiovascular ...Hemorrhagic stroke was reported in a healthy 53-year-old female who took a specific supplement (Jacked Power, MM sports) 30 minutes prior to exercise. It was not labeled as containing BMPEA, but testing showed a level of 290 mg per dose (89219). A combination of BMPEA with other stimulants including synephrine, yohimbine, and caffeine has been associated with cardiac arrest and several reports of tachycardia and palpitations (21079).
General
...Orally, bitter orange might be unsafe when used in medicinal amounts.
Topically and when inhaled as aromatherapy, bitter orange seems to be well tolerated.
Most Common Adverse Effects:
Orally: Hypertension and tachycardia, particularly when used in combination with caffeine and/or other stimulant ingredients.
Topically: Skin irritation.
Serious Adverse Effects (Rare):
Orally: Myocardial infarction, QT prolongation, seizures, stroke, syncope, tachyarrhythmia, and ventricular fibrillation have been reported in patients taking bitter orange in combination with other ingredients. It is unclear if these effects are due to bitter orange, other ingredients, or the combination.
Cardiovascular
...Bitter orange, which contains adrenergic agonists synephrine and octopamine, may cause hypertension and cardiovascular toxicity when taken orally (2040,6969,6979).
Studies evaluating the effect of bitter orange on cardiovascular parameters have been mixed. Several studies show that taking bitter orange alone or in combination with caffeine increases blood pressure and heart rate. In one clinical study, bitter orange in combination with caffeine increased systolic and diastolic blood pressure and heart rate in otherwise healthy normotensive adults (13657). In another study, a single dose of bitter orange 900 mg, standardized to 6% synephrine (54 mg), also increased systolic and diastolic blood pressure and heart rate for up to 5 hours in young, healthy adults (13774). Using half that dose of bitter orange and providing half as much synephrine, did not seem to significantly increase blood pressure or QT interval in healthy adults (14311). Increased diastolic, but not systolic, blood pressure or heart rate also occurred in a clinical trial involving a specific supplement containing synephrine 21 mg and caffeine 304 mg (Ripped Fuel Extreme Cut, Twinlab) (35743). Synephrine given intravenously to males increased systolic blood pressure, but lacked an effect on diastolic blood pressure or heart rate (12193).
In clinical research and case reports, tachycardia, tachyarrhythmia, QT prolongation, ischemic stroke, variant angina, and myocardial infarction have occurred with use of bitter orange or synephrine-containing multi-ingredient products (12030,13039,13067,13091,13657,14326,35749,91680). In one case report, a combination product containing bitter orange may have masked bradycardia and hypotension while exacerbating weight loss in a 16 year-old female with an eating disorder taking the product for weight loss (35740). From 1998 to 2004, Health Canada received 16 reports of serious adverse cardiovascular reactions such as tachycardia, cardiac arrest, ventricular fibrillation, blackout, and collapse. In two of these cases, the patient died. In almost all of these cases, bitter orange was combined with another stimulant such as caffeine, ephedrine, or both (14342).
Other research has found no significant effect of bitter orange on blood pressure or heart rate. Several clinical studies have reported that, when taken as a single dose or in divided doses ranging from 20-100 mg for one day, p-synephrine had no significant effect on blood pressure, heart rate, electrocardiogram results or adverse cardiovascular events in healthy adults (35772,91681,91681,95659,101708) Similarly, no difference in blood pressure, heart rate or electrocardiogram results were reported when p-synephrine from bitter orange (Advantra Z/Kinetic; Nutratech/Novel Ingredients Inc.) was taken for 6 weeks in healthy patients (11268). Another clinical study showed no significant effect of bitter orange (Nutratech Inc.), standardized to synephrine 20 mg, on blood pressure or heart rate when taken daily for 8 weeks in healthy males (95656). In other research, changes in blood pressure, heart rate, or QTc interval were lacking when bitter orange was given alone or in combination with caffeine and green tea (14311,35753,35755,35764,35769,35770). In one study of healthy adults, taking a single dose of p-synephrine 103 mg actually reduced mean diastolic blood pressure by 0.4-4 mmHg at 1 and 2 hours after administration when compared with placebo (95659).
A meta-analysis of clinical trials in adults with or without obesity suggests that taking p-synephrine 6-214 mg orally daily does not affect blood pressure or heart rate when used short-term, but modestly increases blood pressure and heart rate when taken for 56-60 days (109950).
The effect of bitter orange on blood pressure, heart rate, and electrocardiogram results in patients with underlying conditions, particularly cardiovascular disease, is unknown and requires further study.
Dermatologic ...Photosensitivity may occur, particularly in fair-skinned people (11909). In a clinical trial, topical application with bitter orange essential oil resulted in irritation (6972).
Endocrine ...Some clinical research shows that taking a specific supplement containing 21 mg of synephrine and 304 mg of caffeine (Ripped Fuel Extreme Cut, Twinlab) increases levels of postprandial glucose (35743). Other preliminary clinical research shows that taking a specific pre-workout supplement (Cellucor C4 Pre-Workout, Nutrabolt) along with a bitter orange extract standardized for synephrine 20 mg (Nutratech Inc.) 30 minutes once before exercise causes a significant 12% increase in glucose (95657); however, there is no difference in blood glucose when compared with placebo when this combination is taken daily for 8 weeks (95656). The effect of bitter orange itself is unclear.
Gastrointestinal ...Bitter orange has been linked to a report of ischemic colitis. In one case, a 52-year-old female developed ischemic colitis after taking a bitter orange-containing supplement (NaturalMax Skinny Fast, Nutraceutical Corporation) for a week. Symptoms resolved within 48 hours after discontinuing the supplement (15186). As this product contains various ingredients, the effect of bitter orange itself is unclear.
Musculoskeletal ...Unsteady gait has been noted in one case report of a patient taking bitter orange (13091). In another case, an otherwise healthy, Black male with sickle cell trait, developed severe rhabdomyolysis following ingestion of a specific weight loss product (Lipo 6, Nutrex Research Inc.), which contained synephrine and caffeine (16054). However, other preliminary clinical research shows that taking a specific pre-workout supplement (Cellucor C4 Pre-Workout, Nutrabolt) along with a bitter orange extract standardized for synephrine 20 mg (Nutratech Inc.), taken 30 minutes once before exercise (95657) or daily for 8 weeks, does not affect creatine kinase or serum creatinine levels when compared with placebo (95656). As these products contain various ingredients, the effect of bitter orange itself is unclear.
Neurologic/CNS ...Dizziness, difficulty in concentrating, memory loss, syncope, seizure, and stroke have been noted in case reports following bitter orange administration (13091,13039). Theoretically, bitter orange may trigger a migraine or cluster headache due to its synephrine and octopamine content (35768). When used as aromatherapy, bitter orange essential oil has also been reported to cause headache in some patients (104187). Sprint athletes taking the bitter orange constituent p-synephrine 3 mg/kg (Synephrine HCL 99%, Nutrition Power) 60 minutes before exercises and sprinting reported more nervousness (mean difference 0.9) when compared with placebo on a Likert scale. Although statistically significant, this difference is not considered clinically significant (95655).
General
...Caffeine in moderate doses is typically well tolerated.
Most Common Adverse Effects:
Orally: Anxiety, dependence with chronic use, diarrhea, diuresis, gastric irritation, headache, insomnia, muscular tremors, nausea, and restlessness.
Serious Adverse Effects (Rare):
Orally: Stroke has been reported rarely.
Cardiovascular
...Caffeine can temporarily increase blood pressure.
Usually, blood pressure increases 30 minutes after ingestion, peaks in 1-2 hours, and remains elevated for over 4 hours (36539,37732,37989,38000,38300).
Although acute administration of caffeine can cause increased blood pressure, regular consumption does not seem to increase either blood pressure or pulse, even in mildly hypertensive patients (1451,1452,2722,38335). However, the form of caffeine may play a role in blood pressure increase after a more sustained caffeine use. In a pooled analysis of clinical trials, coffee intake was not associated with an increase in blood pressure, while ingesting caffeine 410 mg daily for at least 7 days modestly increased blood pressure by an average of 4.16/2.41 mmHg (37657). Another meta-analysis of clinical research shows that taking caffeine increases systolic and diastolic blood pressure by approximately 2 mmHg when compared with control. Preliminary subgroup analyses suggest that caffeine may increase blood pressure more in males or at doses over 400 mg (112738).
When used prior to intensive exercise, caffeine can increase systolic blood pressure by 7-8 mmHg (38308). The blood pressure-raising effects of caffeine are greater during stress (36479,38334) and after caffeine-abstinence of at least 24 hours (38241).
Epidemiological research suggests there is no association of caffeine consumption with incidence of hypertension (38190). Habitual coffee consumption also doesn't seem to be related to hypertension, but habitual consumption of sugared or diet cola is associated with development of hypertension (13739).
Epidemiological research has found that regular caffeine intake of up to 400 mg daily is not associated with increased incidence of atrial fibrillation (38018,38076,91028,91034,97451,97453,103708), atherosclerosis (38033), cardiac ectopy (91127), stroke (37804), ventricular arrhythmia (95948,97453), and cardiovascular disease in general (37805,98806). One clinical trial shows that in adults with diagnosed heart failure, consumption of 500 mg of coffee does not result in an increased risk for arrhythmia during exercise (95950). However, caffeine intake may pose a greater cardiovascular risk to subjects that are not regular users of caffeine. For example, in one population study, caffeinated coffee consumption was associated with an increased risk of ischemic stroke in subjects that don't regularly drink coffee (38102). In a population study in Japanese subjects, caffeine-containing medication use was modestly associated with hemorrhagic stroke in adults that do not consume caffeine regularly (91059).
The most common side effect of caffeine in neonates receiving caffeine for apnea is tachycardia (98807).
Dermatologic ...There are several case reports of urticaria after caffeine ingestion (36546,36448,36475).
Endocrine
...Some evidence shows caffeine is associated with fibrocystic breast disease or breast cancer in females; however, this is controversial since findings are conflicting (8043,108806).
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 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).
Clinical research in healthy adults shows that an increase consumption of caffeine results in increased insulin resistance (91023).
Gastrointestinal ...Gastrointestinal upset, nausea, diarrhea, abdominal pain, and fecal incontinence may occur with caffeine intake (36466,37755,37806,37789,37830,38138,38136,38223,95956,95963). Also, caffeine may cause feeding intolerance and gastrointestinal irritation in infants (6023). Perioperative caffeine during cardiopulmonary bypass surgery seems to increase the rate of postoperative nausea and vomiting (97451). Caffeine and coffee consumption have been associated with an increase in the incidence of heartburn (37545,37575,38251,38259,38267) and gastrointestinal esophageal reflux disease (GERD) (38329,37633,37631,37603).
Genitourinary ...Caffeine, a known diuretic, may increase voiding, give a sense of urgency, and irritate the bladder (37874,37961,104580). In men with lower urinary tract symptoms, caffeine intake increased the risk of interstitial cystitis/painful bladder syndrome (38115). Excessive caffeine consumption may worsen premenstrual syndrome. Consumption of up to 10 cups of caffeinated drinks daily was associated with increased severity of premenstrual syndrome (38177). Finally, population research shows that exposure to caffeine was not associated with an increased risk of endometriosis (91035).
Immunologic ...Caffeine can cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).
Musculoskeletal
...Caffeine can induce or exacerbate muscular tremors (38136,37673,38161).
There has also been a report of severe rhabdomyolysis in a healthy 40-year-old patient who consumed an energy drink containing 400 mg of caffeine (4 mg/kg) and then participated in strenuous weightlifting exercise (108818).
Epidemiological evidence regarding the relationship between caffeine use and the risk for osteoporosis is contradictory. Caffeine can release calcium from storage sites and increase its urinary excretion (2669,10202,11317,111489). 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, less than 300 mg daily, does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317). Premature infants treated with intravenous caffeine for apnea of prematurity, have a lower bone mineral content compared with infants who are not treated with caffeine, especially when treatment extends beyond 14 days (111489).
Neurologic/CNS ...Caffeine can cause headaches, anxiety, jitteriness, restlessness, and nervousness (36466,37694,37755,37806,37865,37830,37889,38223,95952). In adolescents, there is an inverse correlation between the consumption of caffeine and various measurements of cognitive function (104579). Insomnia is a frequent adverse effect in children (10755). Caffeine may result in insomnia and sleep disturbances in adults as well (36445,36483,36512,36531,37598,37795,37819,37862,37864,37890)(37968,37971,38091,38242,91022,92952). Additionally, caffeine may exacerbate sleep disturbances in patients with acquired immunodeficiency syndrome (AIDS) (10204). 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). Finally, epidemiological research suggests that consuming more than 190 mg of caffeine daily is associated with an earlier onset of Huntington disease by 3.6 years (91078).
Ocular/Otic
...In individuals with glaucoma, coffee consumption and caffeine intake has been found to increase intraocular pressure (8540,36464,36465,37670).
The magnitude of this effect seems to depend on individual tolerance to caffeine. Some research in healthy young adults shows that caffeine increases intraocular pressure to a greater degree in low-consumers of caffeine (i.e., 1 cup of coffee or less daily) when compared to high-consumers (i.e., those consuming 2 cups of coffee or more daily) (100371). The peak increase of intraocular pressure seems to occur at about 1.5 hours after caffeine ingestion, and there is no notable effect 4 hours after ingestion (36462,100371).
Oncologic ...Most human studies which have examined caffeine or methylxanthine intake have found that they do not play a role in the development of various cancers, including breast, ovarian, brain, colon, rectal, or bladder cancer (37641,37737,37775,37900,38050,38169,38220,91054,91076,108806).
Psychiatric
...Caffeine may lead to habituation and physical dependence (36355,36453,36512,36599), with amounts as low as 100 mg daily (36355,36453).
An estimated 9% to 30% of caffeine consumers could be considered addicted to caffeine (36355). Higher doses of caffeine have caused nervousness, agitation, anxiety, irritability, delirium, depression, sleep disturbances, impaired attention, manic behavior, psychosis and panic attacks (36505,37717,37818,37839,37857,37982,38004,38017,38028,38072)(38079,38138,38306,38325,38331,38332,97464). Similar symptoms have been reported in a caffeine-naïve individual experiencing fatigue and dehydration after a dose of only 200 mg, with resolution of symptoms occurring within 2 hours (95952).
Withdrawal: 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). Headache is the most common symptom, due to cerebral vasodilation and increased blood flow (37769,37991,37998). Other researchers suggest symptoms such as tiredness and fatigue, decreased energy, alertness and attentiveness, drowsiness, decreased contentedness, depressed mood, difficulty concentration, irritability, and lack of clear-headedness are typical of caffeine withdrawal (13738). Withdrawal symptoms typically occur 12-24 hours after the last dose of caffeine and peak around 48 hours (37769,36600). Symptoms may persist for 2-9 days. 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). In a case report, caffeine consumption of 560 mg daily was associated with increased suicidality (91082).
Renal ...Data on the relationship between caffeine intake and kidney stones are conflicting. Some clinical research shows that caffeine consumption may increase the risk of stone formation (37634,111498), while other research shows a reduced risk with increasing caffeine intakes (111498). A meta-analysis of 7 studies found that overall, there is an inverse relationship, with a 32% decrease in the risk of kidney stones between the lowest and highest daily intakes of caffeine (111498).
Other ...People with voice disorders, singers, and other voice professionals are often advised against the use of caffeine; however, this recommendation has been based on anecdotal evidence. One small exploratory study suggests that caffeine ingestion may adversely affect subjective voice quality, although there appears to be significant intra-individual variability. Further study is necessary to confirm these preliminary findings (2724).
General
...Orally, capsicum is generally well tolerated in amounts typically found in food or when the extract is used in doses of up to 200 mg daily.
Topically and intranasally, capsaicin, a constituent of capsicum, is generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, bloating, burning, diarrhea, dyspepsia, gas, headache, mild constipation, nausea, rhinorrhea, skin flushing, and sweating.
Serious Adverse Effects (Rare):
Orally: Cases of myocardial infarction and hypertensive crisis have been reported.
Cardiovascular
...Orally, palpitation was reported in one clinical trial (105196).
One case of myocardial infarction has been reported in a 41-year-old male without cardiovascular risk factors; the event was attributed to the use of an oral capsicum pepper pill that the patient had been taking for weight loss (40768). Another case of coronary vasospasm and acute myocardial infarction has been reported for a healthy 29-year-old male; the event was attributed to the use of a topical capsicum-containing patch that the patient had been applying to the middle of the back for 6 days (40658). Two cases of arterial hypertensive crisis have been reported for individuals who ingested a large amount of peppers and chili peppers the day before. One of the patients also had an acute myocardial infarction, and the other had high levels of thyroid stimulating hormone (40569,40606).
Dermatologic
...Orally, capsicum or its constituent capsaicin may cause urticaria and skin wheals in rare cases (96457,105203).
Topically, capsicum can cause a prickling sensation, itching, pain, burning, edema, stinging, irritation, rash, and erythema. About 1 in 10 patients who use capsaicin topically discontinue treatment because of adverse effects. These effects seem to occur more often with topical formulations containing higher concentrations of capsaicin, the active constituent of capsicum. Side effects tend to diminish with continued use (12401,15260,15261,40358,40439,40483,40547,40676,40682,40719)(40784,40847,92979,92983,92984,96453,105193,105197,105202,111514). In one case, application of a capsaicin 8% patch (Qutenza) for 60 minutes caused a second-degree burn, characterized by burning, erythema, severe pain, and blistering at the administration site. The burn was treated with topical corticosteroids, but 9 months later neuropathic pain persisted, resulting in limited mobility. It is unclear whether the mobility sequalae were caused by topical capsaicin or the patient's pre-existing neurological disorders (111514). Skin contact with fresh capsicum fruit can also cause irritation or contact dermatitis (12408).
Intranasally, capsaicin can cause nasal burning and pain in most patients. It also often causes lacrimation, sneezing, and excessive nasal secretion; however, these side effects appear to diminish with repeat applications (14323,14329,14358). In some cases, the burning sensation disappears after 5-8 applications (14351,14358). In some cases, patients are pretreated with intranasal lidocaine to decrease the pain of intranasal capsaicin treatment. However, even with lidocaine pretreatment, patients seem to experience significant pain (14324).
Gastrointestinal
...Orally, capsicum can cause upper abdominal discomfort, including irritation, fullness, dyspepsia, gas, bloating, nausea, epigastric pain and burning, anal burning, diarrhea, mild constipation, and belching (12403,12410,40338,40427,40456,40503,40560,40584,40605,40665)(40718,40725,40745,40808,40828,96456,96457,105194,105196).
There is a case report of a 3-year-old female who experienced a burning and swollen mouth and lips after touching the arm of a parent that had been treated with a capsaicin patch and then placing the fingers in the mouth (105199). Excessive amounts of capsaicin can lead to gastroenteritis and hepatic necrosis (12404). In a case report, a 40-year-old male with diabetes consumed white wine daily and chewed cayenne which was thought to result in black teeth stains and loss of enamel (40809). Some preliminary research links ingestion of capsaicin with stomach and gallbladder cancer; however the link may be due to contamination of capsaicin products with carcinogens (40771).
Topically, capsaicin can cause diarrhea and vomiting (105202).
Immunologic ...In a case report, a 34-year-old female had anaphylaxis involving difficulty breathing and stupor and also urticaria after consuming a red bell pepper, which is in the capsicum genus. The causal chemical was theorized to be 1,3-beta-glucanase (92978). In another case report, a 33-year-old female experienced angioedema, difficulty breathing and swallowing, and urticaria after ingesting raw green and red peppers (92982).
Neurologic/CNS ...Orally, capsicum can cause sweating and flushing of the head and neck, lacrimation, headache, faintness, and rhinorrhea (7005,12410,105196,105203). Topically, applying capsaicin can cause headache (96450,105202). Injection of capsaicin into the intermetatarsal space has also been associated with headache (96454).
Ocular/Otic
...Topically, capsicum can be extremely irritating to the eyes and mucous membranes.
Capsicum oleoresin, an oily extract in pepper self-defense sprays, causes intense eye pain. It can also cause erythema, blepharospasm, tearing, shortness of breath, and blurred vision. In rare cases, corneal abrasions have occurred (12408,12409,40345,40348,40383,40720,40857).
Inhalation of capsicum can cause eye irritation, and allergic alveolitis (5885). In a case report, a 38-year-old female had acute anterior uveitis that developed about 12 hours after using a specific patch (Isola Capsicum N Plus) that contained capsaicin 1.5 mg per patch and methyl salicylate 132 mg per patch for neck pain. The uveitis was controlled with topical steroids and did not recur (92977).
Oncologic ...Population research suggests that moderate to high intake of capsaicin, the active constituent of capsicum, is associated with an increased risk of gastric cancer, while low intake is associated with a decreased risk. It is not clear from the study what amount of capsaicin is considered high versus low intake (92988). Additionally, some research suggests that any link may be due to contamination of capsaicin products with carcinogens (40771).
Pulmonary/Respiratory
...Orally, difficulty breathing was reported in a clinical trial (105196).
Topically, nasopharyngitis related to the use of a cream containing capsaicin has been reported (105202).
Inhalation of capsicum and exposure to capsicum oleoresin spray can cause cough, dyspnea, pain in the nasal passages, sneezing, rhinitis, and nasal congestion (5885,15016,40522,40546,40647). In rare cases, inhalation of the capsicum oleoresin or pepper spray has caused cyanosis, apnea, respiratory arrest and death in people. Death was caused by asphyxiation probably due to acute laryngeal edema and bronchoconstriction from inhalation of the capsicum oleoresin spray (40546,40672,40837,40879).
In a case report, a 47-year-old female who was exposed to capsaicin gas for more than 20 minutes experienced acute cough, shortness of breath, short-term chest pain, wheezing, and difficulty breathing for months afterwards (92980). In rare cases, exposure to capsicum oleoresin spray resulted in apnea, pulmonary injury, cyanosis, and even respiratory arrest (40383,40546).
General
...Orally, choline is well tolerated when used appropriately.
Adverse effects have been reported with doses exceeding the tolerable upper intake level (UL) of 3.5 grams daily.
Most Common Adverse Effects:
Orally: Fishy body odor. At high doses of at least 9 grams daily, choline has been reported to cause diarrhea, nausea, salivation, sweating, and vomiting.
Cardiovascular ...Orally, doses of choline greater than 7. 5 grams daily may cause low blood pressure (94648).
Gastrointestinal ...Orally, large doses of choline can cause nausea, vomiting, salivation, and anorexia (42275,91231). Gastrointestinal discomfort has reportedly occurred with doses of 9 grams daily, while gastroenteritis has reportedly occurred with doses of 32 grams daily (42291,42310). Doses of lecithin 100 grams standardized to 3.5% choline have reportedly caused diarrhea and fecal incontinence (42312).
Genitourinary ...Orally, large doses of choline greater than 9 grams daily have been reported to cause urinary incontinence (42291).
Neurologic/CNS ...Orally, high intake of choline may cause sweating due to peripheral cholinergic effects (42275).
Oncologic ...In one population study, consuming large amounts of choline was associated with an increased risk of colorectal cancer in females, even after adjusting for red meat intake (14845). However, more research is needed to confirm this finding.
Psychiatric ...Orally, large doses of choline (9 grams daily) have been associated with onset of depression in patients taking neuroleptics. Further research is needed to clarify this finding (42270).
Other ...Orally, choline intake may cause a fishy body odor due to intestinal metabolism of choline to trimethylamine (42285,42275,42310,92111,92112).
General
...Orally and topically, cocoa is generally well tolerated.
Most Common Adverse Effects:
Orally: Borborygmi, constipation, diuresis, gastrointestinal discomfort, headaches, and nausea.
Serious Adverse Effects (Rare):
Orally: Tachycardia.
Cardiovascular ...Some cases of increased heart rate have been reported with oral cocoa use (13161,42132).
Dermatologic ...In some cases, when taken orally, cocoa can cause allergic skin reactions (13161). Topically, cocoa butter has occasionally caused a rash. In animals, it has been shown to block pores and cause acne; however, this has not been found in humans (11).
Gastrointestinal ...In human trials, chocolate consumption was associated with a higher incidence of flatulence, irritable bowel syndrome, upset stomach, gastric upset, borborygmi (a gurgling noise made by fluid or gas in the intestines), bloating, nausea, vomiting, and constipation or obstipation (41986,42221,41921,1374,42220,1373,42099,42097,42156,42123,18229,42169,42111). Chocolate consumption has been implicated as a provoking factor in gastroesophageal reflux disease (GERD) (41974,42005,41946,1374). Unpalatability has been reported (42079,42169). Consumption of chocolate and other sweet foods may lead to increased dental caries (42129,42030).
Genitourinary ...In some cases, when taken orally, cocoa can cause increased urination (13161).
Neurologic/CNS ...In some cases, when taken orally, cocoa can cause shakiness and might trigger migraine and other headaches (13161,42169,92271).
Other ...Due to the high sugar and caloric content of chocolate, there is concern about weight gain in people who consume large amounts of chocolate (17187).
General ...Orally, a thorough evaluation of safety outcomes has not been conducted. The only reports of adverse effects, including jitteriness, upset stomach, and insomnia, are related to the use of a combination product that was found to contain amphetamine-like ingredients (90320,100517). It is unclear whether any of these effects can be attributed to dendrobium.
Gastrointestinal ...Orally, upset stomach has been reported in patients taking a specific pre-workout supplement (Craze, Driven Sports) purportedly containing dendrobium extract plus creatine, betaine anhydrous, and other ingredients (doses unknown) daily for 6 weeks (90320). It's unclear whether this was due to dendrobium, other ingredients, or the combination. It should be noted that this product has been identified and formally documented by the US Food and Drug Administration (FDA) as being adulterated with amphetamine-like ingredients (100517).
Neurologic/CNS ...Orally, jitteriness and transient difficulty sleeping have been reported in patients taking a specific pre-workout supplement (Craze, Driven Sports) purportedly containing dendrobium extract plus creatine, betaine anhydrous, and other ingredients (doses unknown) daily for 6 weeks (90320). It's unclear whether these were due to dendrobium, other ingredients, or the combination. It should be noted that this product has been identified and formally documented by the US Food and Drug Administration (FDA) as being adulterated with amphetamine-like ingredients (100517).
General
...Orally, green tea is generally well tolerated when consumed as a beverage in moderate amounts.
Green tea extract also seems to be well tolerated when used for up to 12 months.
Most Common Adverse Effects:
Orally: Bloating, constipation, diarrhea, dyspepsia, flatulence, and nausea.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity, hypokalemia, and thrombotic thrombocytopenic purpura have been reported rarely.
Cardiovascular
...Acute or short-term oral administration of green tea may cause hypertension (53719,54014,54065,54076,102716).
The risk may be greater for green tea products containing more than 200 mg epigallocatechin gallate (EGCG) (90161). However, consumption of brewed green tea does not seem to increase blood pressure or pulse, even in mildly hypertensive patients (1451,1452). In fact, some evidence suggests that habitual tea consumption is associated with a reduced risk of developing hypertension (12518). Also, epidemiological research suggests there is no association of caffeine consumption with incidence of hypertension or with cardiovascular disease mortality in patients with hypertension (13739,111027). Rarely, green tea consumption may cause hypotension (53867).
Epidemiological research suggests that regular caffeine intake of up to 400 mg per day, or approximately 8 cups of green tea, is not associated with an increased incidence of atrial fibrillation (38018,38076,91028,91034,97451,97453), atherosclerosis (38033), cardiac ectopy (91127), stroke (37804), ventricular arrhythmia (95948,97453), and cardiovascular disease in general (37805,98806).
Combining ephedra with caffeine can increase the risk of adverse effects. Jitteriness, hypertension, seizures, and temporary loss of consciousness has been associated with the combined use of ephedra and caffeine (2729). There is also a report of ischemic stroke in an athlete who consumed ephedra 40-60 mg, creatine monohydrate 6 grams, caffeine 400-600 mg, and a variety of other supplements daily for 6 weeks (1275). In theory, combining caffeinated green tea with ephedra would have similar effects.
In a case report, the EGCG component of a specific weight loss supplement (Hydroxycut) was thought to be responsible for atrial fibrillation (54028). The patient was given two doses of intravenous diltiazem and was loaded with intravenous digoxin. Thirty-six hours after the last product dose, she spontaneously converted to normal sinus rhythm. The authors suggested that the block of the atrial-specific KCNA5 potassium channel likely played a role in this response.
A case of thrombotic thrombocytopenic purpura has been reported for a patient who consumed a weight loss product containing green tea (53978). She presented at the emergency department with a one-week history of malaise, fatigue, and petechiae of the skin. Twelve procedures of plasmapheresis were performed, and corticosteroid treatment was initiated. She was discharged after 20 days.
Dermatologic ...Orally, green tea may cause skin rashes or skin irritation (53731,54038,90161,90187,102716). Topically, green tea may cause local skin reactions or skin irritation, erythema, burning, itching, edema, and erosion (53731,54018,97136,104609,111031). A green tea extract ointment applied to the cervix can cause cervical and vaginal inflammation, vaginal irritation, and vulval burning (11310,36442,36438). When applied to external genital or perianal warts, a specific green tea extract ointment (Veregen, Bradley Pharmaceuticals) providing 15% kunecatechins can cause erythema, pruritus, local pain, discomfort and burning, ulceration, induration, edema, and vesicular rash (15067,53907).
Endocrine
...There is some concern that, due to its caffeine content, green tea may be associated with an increased risk of fibrocystic breast disease, breast cancer, and endometriosis.
However, this is controversial since findings are conflicting (8043). Restricting caffeine in females with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996).
A population analysis of the Women's Health Initiative observational study has found no association between consumption of caffeine-containing beverages, such as green tea, and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors (108806). Also, a dose-response analysis of 2 low-quality observational studies has found that high consumption of caffeine is not associated with an increased risk of breast cancer (108807).
A case of hypoglycemia has been reported for a clinical trial participant with type 2 diabetes who used green tea in combination with prescribed antidiabetes medication (54035).
Gastrointestinal ...Orally, green tea beverage or supplements can cause nausea, vomiting, abdominal bloating and pain, constipation, dyspepsia, reflux, morning anorexia, increased thirst, flatulence, and diarrhea. These effects are more common with higher doses of green tea or green tea extract, equivalent to 5-6 liters of tea per day (8117,11366,36398,53719,53867,53936,54038,54076,90139,90140)(90161,90175,90187,97131,97136,102716).
Hepatic
...There is concern that some green tea products, especially green tea extracts, can cause hepatotoxicity in some patients.
In 2017, the regulatory agency Health Canada re-issued a warning to consumers about this concern. The updated warning advises patients taking green tea extracts, especially those with liver disease, to watch for signs of liver toxicity. It also urges children to avoid taking products containing green tea extracts (94897). In 2020, the United States Pharmacopeia (USP) determined that any products bearing its seal of verification must include a specific warning on the label stating "Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes)" (102722).
Numerous case reports of hepatotoxicity, primarily linked to green tea extract products taken in pill form, have been published. A minimum of 29 cases have been deemed at least probably related to green tea and 38 have been deemed possibly related. In addition, elevated liver enzymes have been reported in clinical research (14136,15026,53740,53746,53775,53859,54027,90139,90162,90164)(93256,94898,94899,102716,102720,102722,107158,111020). Most cases of toxicity have had an acute hepatitis-like presentation with a hepatocellular-elevation of liver enzymes and some cholestasis. Onset of hepatotoxic symptoms usually occurs within 3 months after initiation of the green tea extract supplement, and symptoms can persist from 10 days to 1 year (95439,94897,94898,107158). Some reports of hepatotoxicity have been associated with consumption of green tea-containing beverages as well (15026,53742,54016,90125,90143).
In most cases, liver function returned to normal after discontinuation of the green tea product (14136,15026,53859,93256,107158). In one case, use of a specific ethanolic green tea extract (Exolise, Arkopharma) resulted in hepatotoxicity requiring a liver transplant. Due to concerns about hepatotoxicity, this specific extract was removed from the market by the manufacturer (14310). Since then, at least 5 cases of liver toxicity necessitating liver transplantation have been reported for patients who used green tea extracts (94898,107158). In another case, use of green tea (Applied Nutrition Green Tea Fat Burner) in combination with whey protein, a nutritional supplement (GNC Mega Men Sport), and prickly pear cactus resulted in acute liver failure (90162).
Despite the numerous reports of hepatotoxicity associated with the use of green tea products, the actual number of hepatotoxicity cases is low when the prevalence of green tea use is considered. From 2006 to 2016, liver injury from green tea products was estimated have occurred in only 1 out of 2.7 million patients who used green tea products (94897,95440).
In addition to the fact that green tea hepatotoxicity is uncommon, it is also not clear which patients are most likely to experience liver injury (94897,95440). The hepatotoxicity does not appear to be an allergic reaction or an autoimmune reaction (94897). It is possible that certain extraction processes, for example, ethanolic extracts, produce hepatotoxic constituents. However, in most cases, the presence of contaminants in green tea products has not been confirmed in laboratory analyses (90162).
Although results from one analysis of 4 small clinical studies disagrees (94899), most analyses of clinical data, including one conducted by the European Food Safety Association, found that hepatotoxicity from green tea products is associated with the dose of EGCG in the green tea product. Results show that daily intake of EGCG in amounts greater than or equal to 800 mg per day is associated with a higher incidence of elevated liver enzymes such as alanine transaminase (ALT) (95440,95696,97131). However, it is still unclear what maximum daily dose of EGCG will not increase liver enzyme levels or what minimum daily dose of EGCG begins to cause liver injury. In many cases of liver injury, the dose of green tea extract and/or EGCG is not known. Therefore, a minimum level of green tea extract or EGCG that would cause liver injury in humans cannot be determined (102722). Keep in mind that daily intake of green tea infusions provides only 90-300 mg of EGCG daily. So for a majority of people, green tea infusions are likely safe and unlikely to cause liver injury (95696). Also, plasma levels of EGCG are increased when green tea catechins are taken in the fasting state, suggesting that green tea extract should be taken with food (102722).
Until more is known, advise patients that green tea products, especially those containing green tea extract, might cause liver damage. However, let them know that the risk is uncommon, and it is not clear which products are most likely to cause the adverse effect or which patients are most likely to be affected. Advise patients with liver disease to consult their healthcare provider before taking products with green tea extract and to notify their healthcare provider if they experience symptoms of liver damage, including jaundice, dark urine, sweating, or abdominal pain (102722).
Immunologic ...Orally, matcha tea has resulted in at least one case of anaphylaxis related to green tea proteins. A 9-year-old male experienced systemic redness and hives, nausea, and anaphylaxis 60 minutes after consuming matcha tea-flavored ice cream (107169). The caffeine found in green tea can also cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).
Musculoskeletal
...Orally, the ingestion of the green tea constituent epigallocatechin gallate (EGCG) or a decaffeinated green tea polyphenol mixture may cause mild muscle pain (36398).
There is some concern regarding the association between caffeinated green tea products and osteoporosis. Epidemiological evidence regarding the relationship between caffeinated beverages such as green tea and the risk for osteoporosis is contradictory. Caffeine can increase urinary excretion of calcium (2669,10202,11317). Females with a genetic variant of the vitamin D receptor appear to be at an increased risk for the detrimental effect of caffeine on bone mass (2669). However, moderate caffeine intake of less than 400 mg per day, or about 8 cups of green tea, doesn't seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317).
Neurologic/CNS
...Orally, green tea can cause central nervous system stimulation and adverse effects such as headache, anxiety, dizziness, insomnia, fatigue, agitation, tremors, restlessness, and confusion.
These effects are more common with higher doses of green tea or green tea extract, equivalent to 5-6 liters of tea per day (8117,11366,53719,90139,102716). The green tea constituent epigallocatechin gallate (EGCG) or decaffeinated green tea may also cause mild dizziness and headache (36398).
Combining ephedra with caffeine can increase the risk of adverse effects. Jitteriness, hypertension, seizures, temporary loss of consciousness, and hospitalization requiring life support has been associated with the combined use of ephedra and caffeine (2729).
Topically, green tea extract (Polyphenon E ointment) may cause headache when applied to the genital area (36442).
Psychiatric ...Green tea contains a significant amount of caffeine. Chronic use, especially in large amounts, can produce tolerance, habituation, and psychological dependence (11832). The existence or clinical importance of caffeine withdrawal is controversial. Some researchers think that if it exists, it appears to be of little clinical significance (11839). Other researchers suggest symptoms such as headache; tiredness and fatigue; decreased energy, alertness, and attentiveness; drowsiness; decreased contentedness; depressed mood; difficulty concentrating; irritability; and lack of clear-headedness are typical of caffeine withdrawal (13738). Withdrawal symptoms such as delirium, nausea, vomiting, rhinorrhea, nervousness, restlessness, anxiety, muscle tension, muscle pains, and flushed face have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).
Pulmonary/Respiratory ...A case of granulomatous alveolitis with lymph follicles has been reported for a 67-year-old female who used green tea infusions to wash her nasal cavities for 15 years (54088). Her symptoms disappeared 2 months after stopping this practice and following an undetermined course of corticosteroids. In a case report, hypersensitivity pneumonitis was associated with inhalation of catechin-rich green tea extracts (54025). Occupational exposure to green tea dust can cause sensitization, which may include nasal and asthmatic symptoms (11365).
Renal ...There are two cases of hypokalemia associated with drinking approximately 8 cups daily of green tea in an elderly couple of Asian descent. The hypokalemia improved after reducing their intake by 50%. It is possible that this was related to the caffeine in the green tea (98418).
Other ...Orally, intake of a specific green tea extract product (Polyphenon E) may cause weight gain (90139).
General
...Orally, guggul seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, bloating, diarrhea, headache, nausea, unpleasant taste, and vomiting. Allergic and non-allergic skin reactions.
Topically: Allergic contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Rhabdomyolysis.
Dermatologic
...Orally, guggul can cause hypersensitivity reactions including rash and pruritus (10371,54457).
Guggul can also cause nonallergic adverse skin reactions. The risk of skin reactions appears to be dose-dependent. In one study, the incidence of skin reactions was 3% with a dosage of 1000 mg three times daily, compared with 15% with a dosage of 2000 mg three times daily. The severity of the reactions ranged from pruritus to swelling and erythema of the face to bullous lesion on the lower legs associated with headaches, myalgias, and pruritus (13662).
Topically, guggul can cause allergic contact dermatitis (54464,54467). Also, in a small clinical study, one patient using a cream containing aqueous extracts of guggul and Allium ampeloprasum as well as sesame oil complained of rash at the application site (105751). It is unclear if this reaction was due to guggul, other ingredients, or other factors.
Gastrointestinal ...Orally, guggul can cause nausea, vomiting, loose stools, diarrhea, belching, bloating, hiccups, and mild gastrointestinal discomfort (3267,8155,8158,10371,52033,54492).
Hepatic ...A case of severe hypertransaminasemia has been reported for a 63-year-old female who took a specific product (Equisterol) containing guggulsterone and red yeast rice extract daily for 6 months. Liver function normalized after discontinuing the supplement. It is unclear if the adverse effect was due to guggulsterone, red yeast, or the combination. However, the patient had previously developed hepatotoxicity while taking lovastatin, and red yeast contains monacolin K, which is identical to lovastatin (54477). Also, a case of acute liver failure requiring liver transplantation has been reported for a previously healthy young female who used a mixed-ingredient dietary supplement containing extracts of green tea, guggul, and usnic acid. It is unclear if the hepatotoxicity was due to guggul or other ingredients; green tea has been associated with hepatotoxicity (54027).
Immunologic
...Orally, guggul can cause hypersensitivity reactions including rash and pruritus (10371,54457).
In a small clinical study, two adults with hyperlipidemia developed a hypersensitivity rash, one with facial edema, within minutes of oral administration of a methanolic extract of guggul, together with Terminalia extract (105741). It is unclear if this reaction was due to guggul, Terminalia, or other factors.
Topically, guggul can cause allergic contact dermatitis (54464,54467).
Musculoskeletal ...There is one case of rhabdomyolysis reported in a patient who took guggul 300 mg three times daily. The patient developed hemoglobinuria within 2 weeks of starting guggul in addition to increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase, creatine kinase, and myoglobinemia. The patient did not have any muscular symptoms. The patient's condition improved when guggul was discontinued. The patient had a history of developing elevated creatine kinase levels after taking simvastatin; however, the patient was not taking a statin at the time of this episode of rhabdomyolysis (13029).
Neurologic/CNS ...Orally, guggul can cause headaches (3267,8155,8158,10371,42692,49583). Less commonly, guggul may cause restlessness and apprehension (49583,54492).
General
...Orally, pantothenic acid is generally well tolerated.
Topically and intramuscularly, dexpanthenol, a synthetic form of pantothenic acid, seems to be well tolerated.
Most Common Adverse Effects:
Topically: Burning, contact dermatitis, eczema, irritation, and itching related to dexpanthenol.
Cardiovascular ...There is one case of eosinophilic pleuropericardial effusion in a patient taking pantothenic acid 300 mg per day in combination with biotin 10 mg per day for 2 months (3914).
Dermatologic ...Topically, dexpanthenol has been associated with itching, burning, skin irritation, contact dermatitis, and eczema (67779,67781,67788,111258,111262). Three cases of allergic contact dermatitis have been reported (111260,111261).
Gastrointestinal ...Orally, pantothenic acid has been associated with diarrhea (67822,111258).
General
...Orally, there is limited information available about the adverse effects of yohimbe.
Yohimbine, a constituent of yohimbe, might be unsafe; most reported adverse effects are dose-related.
Most Common Adverse Effects:
Orally: Yohimbine, a constituent of yohimbe, has been associated with anxiety, agitation, diaphoresis, diarrhea, flushing, headache, hypertension, increased urination, nausea, tachycardia, tremors, vertigo, and vomiting.
Serious Adverse Effects (Rare):
Orally: Yohimbine, a constituent of yohimbe, has been associated with atrial fibrillation, hypertensive crisis, myocardial infarction, and QT interval prolongation.
Cardiovascular ...Orally, yohimbine, a constituent of yohimbe, has been associated with hypertension, especially at higher doses (3312,17465,86801,86802,86804,86811,86820,86822,86834,86856)(86786,86896). A case of hypertensive crisis was reported in a 63-year-old male taking a yohimbine-containing herbal product once daily for one month. The patient was successfully managed with intravenous nitroprusside followed by clonidine (91521). Tachycardia, fluid retention, palpitations, and chest discomfort have also been reported (3312,17465,86786,86793,86801,86802,86804,86822,86843,86854)(86856,86866,86867,86869,86871,86874,86875). Conduction abnormalities have also been reported (86856,86786). There have been some reports of myocardial infarction, atrial fibrillation, and QT interval prolongation (17465). In theory, these effects may also occur with the use of yohimbe bark extract.
Dermatologic ...Orally, yohimbine, a constituent of yohimbe, may cause rash, erythrodermic skin eruption, and exanthema (3312,3971,86804,86896,86878).
Gastrointestinal ...Orally, yohimbine, a constituent of yohimbe, may cause nausea, vomiting, increased salivation, diarrhea, and gastrointestinal distress (3970,17465,49902,86780,86781,86786,86801,86804,86824,86827)(86828,86829,86863,86878,86882,86896).
Genitourinary ...Orally, yohimbine may cause dartos contraction or decreased libido in some patients (86786,86882). A case of severe intractable priapism has been reported for a 42-year-old male who took a supplement containing yohimbe extract the previous day for sexual enhancement. Treatment with phenylephrine 400 mcg was unsuccessful at resolving the priapism, so surgical insertion of a proximal cavernosal spongiosum shunt was needed (86804).
Hematologic ...A case of drug-induced agranulocytosis has been reported following prolonged use of oral yohimbine, a constituent of yohimbe (86877).
Immunologic ...There is one report of a hypersensitivity reaction including fever; chills; malaise; itchy, scaly skin; progressive renal failure; and lupus-like syndrome associated with ingestion of a one-day dose of yohimbine, a constituent of yohimbe (6169).
Musculoskeletal ...Orally, yohimbine, a constituent of yohimbe, may cause muscle aches (86850).
Neurologic/CNS ...Orally, yohimbine, a constituent of yohimbe, has been associated with reports of general central nervous system (CNS) and autonomic excitation, tremulousness, head twitching, seizure threshold changes, enhanced brain norepinephrine release, decreased energy, dizziness, vertigo, and headache (3312,3971,86774,86779,86786,86804,86827,86857,86870,86882)(86883). Cold feet and chills have also been reported with yohimbine (86827,86896). Other adverse reactions include flushing and diaphoresis (17465). Excessive doses of yohimbine can also cause paralysis (11,18). A case of acute neurotoxicity characterized by malaise, vomiting, loss of consciousness, and seizures has been reported for a 37-year-old bodybuilder who ingested a single dose of yohimbine 5 grams. Improvement was seen within 12 hours following treatment with furosemide, labetalol, clonidine, urapidil, and gastrointestinal decontamination (86801).
Psychiatric ...Orally, yohimbine, a constituent of yohimbe, may increase malaise, fatigue, insomnia, restlessness, agitation, and anxiety (3312,3970,3971,17465,86786,86801,86804,86822,86827,86834)(86868,86878,86882,86896). In a clinical study of healthy subjects, administration of yohimbine increased impulsivity, with larger doses increasing impulsivity more than 50% (86784,86810).
Pulmonary/Respiratory ...Orally, yohimbine, a constituent of yohimbe, may cause bronchospasm, tachypnea, cough, and rhinorrhea (17465,86825,86850). A case of sinusitis characterized by pain and discomfort above both eyes has been reported for a 59-year-old male taking yohimbine 5.4 mg three times daily to treat erectile dysfunction. Symptoms resolved within 24 hours of discontinuing yohimbine. The effect was attributed to the alpha-2 adrenergic antagonist effects of yohimbine (94112). Excessive doses of yohimbine can cause respiratory depression (1118).
Renal ...Orally, yohimbine, a constituent of yohimbe, may increase urinary frequency (3312,3970,3971,17465,86804,86827,86850,86861,86882). A case of acute renal failure has been reported for a 42-year-old male taking yohimbine. Normalization of renal function was achieved following 2 weeks of treatment with corticosteroids. The renal dysfunction was attributed to yohimbine-induced systemic lupus erythematosus (6169).
