Each capsule contains Antioxidant Blend 400 mg: CoffeeBerry Forte brand Green Coffee extract, Pomegranate extract, Green Tea extract, Acai berry 4:1, Wolfberry extract, Biovin brand Grape extract. Other Ingredients: Gelatin, Microcrystalline Cellulose, Silicon Dioxide, Magnesium Stearate.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Prograde Longevity. 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
Below is general information about the safety of the known ingredients contained in the product Prograde Longevity. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Acai pulp, in a dose of up to 162.5 grams daily, has been used with apparent safety for up to 3 months in clinical research (17731,99400). There is insufficient reliable information available about the safety of acai when used topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when goji fruit preparations are used orally and appropriately, short-term. Goji berry whole fruit, boiled or steamed, has been used with apparent safety at a dose of 15 grams daily for 16 weeks (105489). Other goji berry products have also been used with apparent safety in clinical research, including a specific goji fruit juice (GoChi, FreeLife International) 120 mL daily for 30 days (52532), a goji fruit polysaccharide 300 mg daily for 3 months (92117), and a specific milk-based formulation of goji berry (Lacto-Wolfberry, Nestlé Research Center) for 3 months (52539). There has been some concern about the atropine content of goji; however, most analyses show that levels of atropine in goji berries from China and Thailand are far below potentially toxic levels (52524,94667). There is insufficient reliable information available about the safety of oral use of other parts of the goji plant.
PREGNANCY AND LACTATION:
Insufficient reliable information available.
Some animal research shows that goji fruit may stimulate the uterus (12). However, this has not been reported in humans. Until more is known, avoid using during pregnancy or lactation.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Grapes and grape skin extracts have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
POSSIBLY SAFE ...when the whole fruit of the grape, or extracts of the fruit, seed, or leaf, are used orally and appropriately in medicinal amounts. Grape seed extracts have been used with apparent safety in doses up to 200 mg daily for up to 11 months (9182,53016) and in doses up to 2000 mg daily for up to 3 months (53149,53190). Specific grape fruit extracts (Stilvid, Actafarma; Cognigrape, Bionap srl) have been used with apparent safety in doses up to 250-350 mg daily for 3-12 months or 700 mg daily for 6 months (53254,53256,96198). A specific grape leaf extract (AS 195, Antistax, Boehringer Ingelheim) has been used with apparent safety in doses up to 720 mg daily for up to 3 months (2538,52985,53005,53206). A preparation of dehydrated whole grapes, equivalent to 250 grams of fresh grapes daily, has also been used with apparent safety for up to 30 days (18228). A specific grape seed extract (Enovita; Indena SpA) 150 mg twice daily, standardized to provide at least 95% oligomeric proanthocyanins, has been used with apparent safety for up to 16 weeks (108091) ...when used topically and appropriately. Creams and ointments containing grape seed extract 2% or 5% have been used topically with apparent safety for up to 3 weeks (91539,100955). There is insufficient reliable information available about the safety of other grape plant parts when used topically.
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods.
Grapes and grape skin extracts have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912). However, whole grapes should be eaten with caution in children aged 5 years and under. Whole grapes can be a choking hazard for young children (96193). To reduce the risk of choking, whole grapes should be cut in half or quartered before being given to children. There is insufficient reliable information available about the safety of grape when used in medicinal amounts in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods.
There is insufficient reliable information available about the safety of medicinal amounts during pregnancy and breast-feeding; avoid using in amounts greater than what is commonly found in foods.
POSSIBLY SAFE ...when used orally and appropriately. Green coffee extracts taken in doses up to 1000 mg daily, providing up to 500 mg chlorogenic acid, have been used with apparent safety for up to 12 weeks in clinical research (17971,17972,103954). A specific green coffee extract (Svetol, Naturex) has been used with apparent safety in doses up to 200 mg five times daily for up to 12 weeks (17981,17982,17983). Green coffee also contains caffeine, although in lower amounts than regular coffee. One cup of green coffee contains about 20-50 mg of caffeine, compared with about 100 mg in one cup of regular coffee. 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). 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 coffee, 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 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 green tea extract cream or ointment is used topically and appropriately, short-term. A green tea extract 3% cream, applied twice daily, has been used with apparent safety for up to 8 weeks, and a specific green tea extract ointment (Veregen, Bradley Pharmaceuticals) providing 15% kunecatechins has been safely used for up to 16 weeks (15067). The safety of treatment for longer durations 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.
LIKELY SAFE ...when pomegranate fruit or fruit juice is used orally and appropriately. Pomegranate juice has been safely used in studies lasting up to 3 years (4912,8310,13022,13023,13690,14137,14388,17329,91693).
POSSIBLY SAFE ...when pomegranate extract is taken orally and appropriately. A specific pomegranate ellagitannin-enriched polyphenol extract (POMx, POM Wonderful) 1-3 grams daily has been safely used for up to 18 months (17729,69261,91686,91695,91697,99100,105269). ...when pomegranate seed oil is used orally and appropriately. Pomegranate seed oil 60 mg daily has been used with apparent safety for up to 12 weeks (91685). ...when a hot water extract of pomegranate seed powder is used orally and appropriately. Pomegranate seed powder 5 grams daily has been used with apparent safety for up to 8 weeks (105270). ...when pomegranate extract is used topically on oral mucosa (13689).
POSSIBLY UNSAFE ...when the pomegranate root, stem, and peel are used orally in large amounts. Bark of the pomegranate root and stem contains the piperidine alkaloids pelletierine, pseudopelletierine, isopelletierine, and methyl isopelletierine. These alkaloids have muscle relaxant properties that have been associated with paralysis and death in animals (13687,13694,13695). Dried pomegranate peel may contain aflatoxin, which is a potent hepatocarcinogen and toxin (92018).
PREGNANCY AND LACTATION: POSSIBLY SAFE
when the fruit or fruit juice is consumed orally and appropriately (13686,105267).
There is insufficient reliable information available regarding the safety of using other forms of pomegranate or other parts of the plant during pregnancy or lactation; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Prograde Longevity. 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, taking acai with antidiabetes drugs might interfere with glycemic control.
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Theoretically, concomitant use of goji fruit polysaccharides or goji root bark with antidiabetes drugs might have additive effects.
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Animal and in vitro research show that goji root bark and fruit polysaccharides might have hypoglycemic effects (7126,92118,94667). However, clinical research has only shown that taking goji fruit polysaccharides with or without antidiabetes drugs modestly reduces postprandial glucose when compared with control, with no reports of hypoglycemia (92117).
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Theoretically, concomitant use of goji root bark, but not goji fruit, with antihypertensive drugs might have additive effects.
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Theoretically, goji berry might inhibit CYP2C19 and reduce metabolism of CYP2C19 substrates.
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In vitro research shows that goji berry tincture and juice inhibit CYP2C19 enzymes (105486). Concomitant use with goji may decrease metabolism and increase levels of CYP2C19 substrates. However, this has not been reported in humans.
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Theoretically, goji berry might inhibit CYP2C9 and reduce metabolism of CYP2C9 substrates.
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In vitro research shows that goji berry tincture and juice inhibit CYP2C9 enzymes (105486). Additionally, multiple case reports suggest that goji berry concentrated tea and juice inhibit the metabolism of warfarin, a CYP2C9 substrate (7158,105462). Concomitant use with goji may decrease metabolism and increase levels of CYP2C9 substrates.
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Theoretically, goji berry might inhibit CYP2D6 and reduce metabolism of CYP2D6 substrates.
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In vitro research shows that goji berry juice inhibits CYP2D6 enzymes (105486). Concomitant use with goji may decrease metabolism and increase levels of CYP2D6 substrates. However, this has not been reported in humans.
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Theoretically, goji berry might inhibit CYP3A4 and reduce metabolism of CYP3A4 substrates.
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In vitro research shows that goji berry juice inhibits CYP3A4 enzymes (105486). Concomitant use with goji may decrease metabolism and increase levels of CYP3A4 substrates. However, this has not been reported in humans.
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Theoretically, goji berry might increase the levels and clinical effects of flecainide.
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In one case report, a 75-year-old patient stable on flecainide and warfarin presented to the emergency room with fainting and pleomorphic arrhythmia caused by flecainide toxicity. Flecainide toxicity was attributed to drinking 1-2 glasses of concentrated goji tea daily for 2 weeks. Theoretically, goji may have inhibited the cytochrome P450 2D6 (CYP2D6) metabolism of flecainide (105462).
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Goji can increase the effects of warfarin and possibly increase the risk of bleeding.
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There are at least 5 case reports of increased international normalized ratio (INR) in patients stabilized on warfarin who began drinking goji juice, concentrated goji tea, or goji wine (7158,16529,23896,105462,105487). Goji may inhibit the metabolism of warfarin by cytochrome P450 2C9 (CYP2C9) (7158).
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Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
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A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water (53177). Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.
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Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
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A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2 (2539).
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It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
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In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes (11094,53011,53089). However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism (11094). The effects of continued grape juice consumption are unclear.
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Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
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In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes (53011). However, this interaction has not been reported in humans.
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Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
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In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes (52949). However, this interaction has not been reported in humans.
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It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
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Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
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Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination (53011).
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Grape juice might decrease phenacetin absorption.
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A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2) (2539).
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Theoretically, green coffee might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
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Green coffee can contain caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products, be stopped 24 hours prior to pharmacological stress tests (11770). However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).
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Theoretically, alcohol might increase the levels and adverse effects of caffeine.
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Theoretically, green coffee may decrease the levels and effects of alendronate.
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In human research, drinking coffee with alendronate reduces the bioavailability of alendronate by 60% (11735). Whether green coffee reduces the bioavailability of alendronate has not been investigated. Separate green coffee ingestion and alendronate administration by two hours.
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Theoretically, green coffee may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Green coffee can contain caffeine. Caffeine is reported to have antiplatelet activity (8028,8029). Theoretically, caffeine in green coffee might increase the risk of bleeding when used concomitantly with these agents. However, this interaction has not been reported in humans. There is some evidence that caffeinated coffee might increase the fibrinolytic activity in blood (8030).
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Theoretically, taking green coffee and antidiabetes drugs might interfere with blood glucose control.
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Theoretically, taking green coffee with antihypertensive drugs might increase the risk of hypotension.
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Theoretically, concomitant use of large amounts of green coffee might increase cardiac inotropic effects of beta-agonists.
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Green coffee can contain caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists (15).
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Theoretically, cimetidine might increase the effects and adverse effects of caffeine in green coffee.
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Theoretically, green coffee might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
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Green coffee can contain caffeine. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to an 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 coffee.
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Theoretically, green coffee might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
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Green coffee can contain caffeine. Caffeine is a methylxanthine that may inhibit dipyridamole-induced vasodilation (11770,11772,24974,37985,53795). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products such as green coffee, 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 levels and adverse effects of caffeine.
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Green coffee can contain caffeine. In human research, disulfiram decreases the clearance and increases the half-life of caffeine (11840).
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Theoretically, concomitant use might increase the risk of hypokalemia.
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Theoretically, concomitant use might increase the risk of stimulant adverse effects.
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Green coffee can contain caffeine. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death (1275,6486,9740,10307). Tell patients to avoid taking caffeine with ephedrine and other stimulants.
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Theoretically, estrogens might increase the levels and adverse effects of caffeine.
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Green coffee can contain 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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Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
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Theoretically, abrupt green coffee withdrawal might increase the levels and adverse effects of lithium.
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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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Theoretically, concomitant use might increase the risk of hypertension.
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Green coffee can contain 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, green coffee might reduce the effects of pentobarbital.
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Green coffee can contain caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).
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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 increase the levels and clinical effects of pioglitazone.
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Green coffee 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.
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Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
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Green coffee can contain caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), 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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Green coffee can contain 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.
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Green coffee can contain caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).
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Theoretically, green coffee might increase the levels and adverse effects of theophylline.
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Green coffee can contain caffeine. Large amounts of caffeine might inhibit theophylline metabolism (11741).
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Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
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Green coffee can contain caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).
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Theoretically, high doses of green tea might increase the effects and side effects of 5-fluorouracil.
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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.
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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.
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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.
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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.
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Green tea extract seems to reduce the levels and clinical effects of atorvastatin.
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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.
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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.
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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.
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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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Green tea might increase the levels and adverse effects of P-glycoprotein (P-gp) substrates.
Details
In vitro research and case reports suggest that green tea inhibits drug efflux by P-gp, potentially increasing serum levels of P-gp substrates. Case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking green tea and certain P-gp substrates (111644).
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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.
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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.
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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, taking pomegranate with ACEIs might increase the risk of adverse effects.
Details
Pomegranate juice is thought to have ACE inhibitor-like effects (8310).
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Theoretically, taking pomegranate with antihypertensive drugs might increase the risk of hypotension.
Details
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Theoretically, taking pomegranate with carbamazepine might increase the risk of adverse effects, although research suggests this interaction is unlikely to be clinically significant.
Details
Animal research shows that pomegranate juice may inhibit cytochrome P450 3A4 (CYP3A4) metabolism of carbamazepine and increase levels of carbamazepine by 1.5 times without prolonging the elimination half-life. This suggests that pomegranate juice inhibits intestinal CYP3A4, but might not inhibit hepatic CYP3A4 (13188). However, some human research suggests that pomegranate does not significantly inhibit CYP3A4 drug metabolism in humans (16711,16712,17326).
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Theoretically, pomegranate might increase levels of drugs metabolized by CYP2C9.
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Theoretically, pomegranate might increase levels of drugs metabolized by CYP2D6.
Details
In vitro, pomegranate juice inhibits CYP2D6 (13703). However, the clinical significance of this potential interaction in humans is not known.
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Theoretically, pomegranate might increase levels of drugs metabolized by CYP3A4, but most research suggests this interaction is unlikely to be clinically significant.
Details
Pomegranate contains several polyphenols that have individually been shown to inhibit CYP3A4. However, there is contradictory evidence about the effect of whole pomegranate juice on CYP3A4 activity. In vitro, pomegranate juice significantly inhibits the CYP3A4 enzyme, with comparable inhibition to grapefruit juice (13188,16711,17326). In an animal model, pomegranate juice inhibits CYP3A4 metabolism of carbamazepine and increases levels of carbamazepine by 1.5 times (13188); however, in human volunteers, drinking a single glass of pomegranate juice 240 mL or taking 200 mL daily for 2 weeks does not significantly affect levels of the CYP3A4 substrate midazolam after oral or intravenous administration (16711,17730). Another study in healthy volunteers shows that consuming pomegranate juice 300 mL three times daily for three days also does not significantly affect levels of simvastatin, a CYP3A4 substrate (16712,91696) This suggests that pomegranate is unlikely to significantly affect levels of CYP3A4 substrates in humans (17326).
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Theoretically, taking pomegranate with rosuvastatin might increase the risk of adverse effects.
Details
In one case, a patient taking rosuvastatin 5 mg every other day in combination with ezetimibe 10 mg daily developed rhabdomyolysis after drinking pomegranate juice 200 mL twice weekly for 3 weeks. This patient had a history of elevated creatine kinase levels while not receiving any statin treatment. This suggests a possible underlying myopathy and predisposition to rhabdomyolysis (14465).
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Theoretically, pomegranate might increase levels of tolbutamide, although research suggests this interaction is unlikely to be clinically significant.
Details
Animal research shows that pomegranate juice inhibits the cytochrome P450 2C9 (CYP2C9) metabolism of tolbutamide. Pomegranate juice increased tolbutamide levels by 1.2 times without prolonging the elimination half-life. This suggests that pomegranate juice inhibits intestinal CYP2C9, but might not inhibit hepatic CYP2C9 (17327). Despite this evidence, clinical research shows that neither pomegranate juice nor pomegranate extract have a significant effect on CYP2C9 activity in humans (91694). This interaction does not appear to be clinically significant in humans.
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Theoretically, pomegranate might increase warfarin levels and increase the risk of bleeding. Also, discontinuing regular consumption of pomegranate juice might decrease warfarin levels.
Details
In one case report, a patient had a stable, therapeutic bleeding time, as measured by international normalized ratio (INR), while taking warfarin in combination with pomegranate juice 2-3 times per week. The patient became subtherapeutic within about 10 days after discontinuing pomegranate juice, which required a warfarin dose increase (17328). In another case report, a patient with a stable INR for over one year presented with an INR of 14. The patient noted no changes to medications or diet but did report consuming around 3 liters of pomegranate juice over the previous week. The patient's INR stabilized upon moderation of pomegranate juice consumption (24273). The mechanism of this potential interaction is unclear.
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Below is general information about the adverse effects of the known ingredients contained in the product Prograde Longevity. 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, acai seems to be well tolerated.
Other ...Raw acai fruit and juice can be contaminated with a parasitic protozoan called Trypanosoma cruzi, which causes American trypanosomiasis or Chagas Disease. A Brazilian outbreak of this disease in 2006 was linked to consumption of acai juice (17194,30245).
General
...Orally, goji fruit seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Allergic reactions including anaphylaxis.
Dermatologic ...A case of photosensitivity secondary to consumption of goji berries has been reported. The patient presented with a pruriginous eruption that had lasted for 2 weeks. The patient had been taking goji berries for 5 months and cat's claw for 3 months. Upon testing, it was revealed that the patient tested positive to goji berries in a photoprovocation test, but not to cat's claw (40263).
Hepatic ...Orally, consumption of goji berries has been associated with a single case report of autoimmune hepatitis (52541). A case of acute hepatitis has also been reported in a female who consumed 2 ounces of a specific combination product (Euforia, Nuverus International) containing goji berry, pomegranate, curcumin, green tea, noni, acai berry, aloe vera, blueberry, resveratrol, mangosteen, and black seed, daily for one month. It is unclear whether the liver injury was caused by goji berry, other ingredients, or the combination (90125).
Immunologic ...Several cases of allergic reactions secondary to consumption of goji berries have been reported. Symptoms included facial angioedema with dyspnea, pharyngeal itching, itching in the mouth, ears, and axilla, labial angioedema, and perioral skin rash (92116). Anaphylaxis has also been reported (52538).
General
...Orally, the whole fruit, as well as the seed, fruit, and leaf extracts, seem to be well tolerated.
Topically, grape seed extracts seem to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, dry mouth, dyspepsia, headache, joint pain, and nausea.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis to grape skin has been reported.
Dermatologic ...Orally, mild hair thinning has been reported in a patient taking a specific grape leaf extract AS195 KG) (2538). Urticaria (hives) has also been reported with this same extract (53206). Cases of contact dermatitis have been reported in grape workers, including those working in California vineyards (53270,53272,53275).
Gastrointestinal ...Orally, abdominal pain and nausea have been reported with use of grape seed extract, but these effects typically occur at rates similar to placebo (9182,13162). In a case report of a 57-year-old man, intermittent nausea, vomiting, and diarrhea occurred over a 10-day period and improved once grape seed extract was stopped (96764). Gastrointestinal adverse effects have also been reported with use of a different grape seed extract (Entelon, Hanlim Pharm). However, the specific types of gastrointestinal effects were not described (100954). A specific grape leaf extract AS195 (Antistax, Boehringer Ingelheim Pharma GmbH & Co. KG) has reportedly caused flatulence, mild constipation, gastrointestinal discomfort, diarrhea, dyspepsia, dry mouth, and retching (2538,52985,53206). Diarrhea, gastrointestinal distress, indigestion, and aversion to taste have been reported with use of Concord grape juice (52972,53166,53175,53181,53199). Loose stools have been reported in a clinical trial of grape pomace (99270). Bowel obstruction caused by intact grapes and grape seeds has been described in case reports (53241,53284,53278). Excessive consumption of grapes, dried grapes, raisins, or sultanas might cause diarrhea due to laxative effects (4201).
Hematologic ...Orally, one case of leg hematoma following a minor trauma was reported in a person using grape leaf extract (2538). Also, one case of bruising was reported in a person drinking Concord grape juice daily for 2 weeks (52972).
Immunologic ...Orally, there is one report of an anaphylactic reaction to oral grape skin extract, which included urticaria and angioedema (4073).
Musculoskeletal ...Orally, musculoskeletal disorders, including back pain, have been reported with use of a specific grape leaf extract AS195 KG) (2538,53206). Joint pain and lumbago have been reported with use of grape seed extract, but these effects occur at rates similar to placebo (91541).
Neurologic/CNS ...Orally, headache has been reported with use of grape seed extract, but this effect occurs at rates similar to placebo (9182,91541). A specific grape leaf extract AS195 (Antistax, Boehringer Ingelheim Pharma GmbH & Co. KG) has reportedly caused dizziness, tiredness, headache, and sleep problems (2538,53206). As a class, nervous system adverse effects have been reported with use of a specific grape seed extract (Entelon, Hanlim Pharm). However, the specific types of adverse neurologic effects were not described (100954).
Ocular/Otic ...Orally, ocular adverse effects have been reported with use of a specific grape seed extract (Entelon, Hanlim Pharm). However, the specific types of ocular adverse effects were not described (100954).
Pulmonary/Respiratory ...Orally, nasopharyngitis and oropharyngeal pain have been reported with use of a specific grape leaf extract AS195 KG) (53206). Sore throat, cough, allergic rhinitis, and nasopharyngitis have been reported with use of grape seed extract, but these effects occur at rates similar to placebo (9182,91541). One case report describes a 16-year-old female who developed increased levels of immunoglobulin E (IgE) following skin-prick exposure to grape vine pollen, as well as positive test responses following bronchial and conjunctival provocation (53301). Reduced forced vital capacity has been described in California grape workers (53080,53081). Occupational eosinophilic lung was diagnosed in a grape grower with a history of asthma. Respiratory exposure to sulfites in grape was implicated as the cause of the adverse reaction (53285).
Other
...Orally, grape products can cause adverse effects due to contamination with pesticides or mycotoxins.
Some evidence has shown that pesticides used in vineyards may remain on grape surfaces post-harvesting. For example, the fungicide folpet sprayed on grapevines has been shown to remain on the grape surface. Although there was minimal penetration of the epicuticular wax, it showed high resistance to washing (52935). Carbaryl has been identified in over 58% of juice samples collected in Canada. This pesticide reportedly occurred more frequently in grape than in other juices. However, estimates of short-term intake were below proposed acute reference doses (53003).
Ochratoxin A is a mycotoxin that is suspected to be nephrotoxic, teratogenic, hepatotoxic and carcinogenic and has been identified in grape juice, frozen grape pulps, and red and white wine sold in Rio de Janeiro, Brazil. However, the highest levels identified in grape products were lower than the established virtually safe dose of 5 ng/kg of body weight daily (53010,53004). Ochratoxin A has also been identified in red, but not white, grape juice marketed in Switzerland, Canada, and the U.S. (53292,53020).
General ...Orally, green coffee appears to be well-tolerated. Although green coffee contains caffeine, it is present in small quantities which are less likely to cause adverse effects. Green coffee contains about 20-50 mg caffeine per cup, compared with about 100 mg caffeine per cup of brewed coffee.
Cardiovascular
...Although acute administration of caffeine, a constituent of green coffee, can cause increased blood pressure, regular consumption does not seem to increase either blood pressure or pulse, even in mildly hypertensive patients (1451,1452,2722,13739).
Drinking one or more cups daily of caffeinated coffee, such as green coffee, also doesn't seem to increase the risk of developing hypertension in habitual coffee drinkers (8033,13739).
Chlorogenic acids found in green coffee extracts may adversely affect plasma homocysteine levels. In one randomized controlled trial, 2 grams of chlorogenic acids (the amount found in about 1.5 L of strong coffee) daily for one week resulted in a 12% increase in plasma homocysteine levels (8035). However, in another trial of green coffee extract in a dose equivalent to 140 mg of chlorogenic acids daily for 4 months, there was a slight decrease in plasma homocysteine levels from baseline, but this did not differ significantly from placebo treatment (17970).
The diterpenes cafestol and kahweol found in green coffee beans have been implicated in the hypercholesterolemic effects of unfiltered coffee (19336,53599). However, these compounds are removed from some green coffee extracts. For instance, Svetol (Naturex, South Hackensack, NJ) is reported to contain less than 4 ppm of cafestol and kahweol (88171).
Dermatologic ...Positive skin tests and symptoms of contact allergy have been reported in workers exposed to green coffee bean dust (53568,53653).
Endocrine
...Some evidence shows that caffeine, a constituent of green coffee, is associated with fibrocystic breast disease, breast cancer, and endometriosis in females; 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 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 increased consumption of caffeine results in increased insulin resistance (91023).
Gastrointestinal ...Orally, stomach irritation was reported by one person in a clinical trial of green coffee extract (104831).
Musculoskeletal ...Epidemiological evidence regarding the relationship between caffeine, which is found in green coffee, and the risk of osteoporosis is contradictory. Caffeine can increase urinary excretion of calcium (2669,10202,11317). Females identified with a genetic variant of the vitamin D receptor appear to be at an increased risk of the detrimental effect of caffeine on bone mass (2669). However, moderate caffeine intake, less than 300 mg per day, does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317).
Neurologic/CNS ...Orally, dizziness was reported by one person in a clinical trial of green coffee extract (104831).
Ocular/Otic ...Conjunctivitis caused by green coffee bean dust in coffee workers has been described in case reports (53657,53589).
Psychiatric ...Chronic use of caffeine, especially in large amounts, may produce tolerance, habituation, and psychological dependence (3719). Abrupt discontinuation of caffeine may result in physical withdrawal symptoms, including headache, fatigue, drowsiness, decreased physical energy, difficulty concentrating, depression, anxiety, irritability, and reduced alertness (13738). Certain populations such as children and the elderly may be more susceptible to the adverse effects of caffeine (13736).
Pulmonary/Respiratory ...Occupational exposure to green coffee beans has been documented to cause numerous adverse respiratory reactions, including bronchial reactivity, asthma, and rhinitis (53589,53641,53644,53648,53650,53665). Healthy subjects exposed experimentally to green coffee dust displayed acute decreases in expiratory flow rates (53653). In one study, green coffee workers displayed numerous acute respiratory symptoms when exposed to dust; these included coughing, increased sputum, sneezing, difficulty in breathing, running nose, and wheezing; these symptoms resolved after leaving work (53647).
General
...Orally, green tea is generally well tolerated when consumed as a beverage in moderate amounts.
Green tea extract also seems to be well tolerated when used for up to 12 months.
Most Common Adverse Effects:
Orally: Bloating, constipation, diarrhea, dyspepsia, flatulence, and nausea.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity, hypokalemia, and thrombotic thrombocytopenic purpura have been reported rarely.
Cardiovascular
...Acute or short-term oral administration of green tea may cause hypertension (53719,54014,54065,54076,102716).
The risk may be greater for green tea products containing more than 200 mg epigallocatechin gallate (EGCG) (90161). However, consumption of brewed green tea does not seem to increase blood pressure or pulse, even in mildly hypertensive patients (1451,1452). In fact, some evidence suggests that habitual tea consumption is associated with a reduced risk of developing hypertension (12518). Also, epidemiological research suggests there is no association of caffeine consumption with incidence of hypertension or with cardiovascular disease mortality in patients with hypertension (13739,111027). Rarely, green tea consumption may cause hypotension (53867).
Epidemiological research suggests that regular caffeine intake of up to 400 mg per day, or approximately 8 cups of green tea, is not associated with an increased incidence of atrial fibrillation (38018,38076,91028,91034,97451,97453), atherosclerosis (38033), cardiac ectopy (91127), stroke (37804), ventricular arrhythmia (95948,97453), and cardiovascular disease in general (37805,98806).
Combining ephedra with caffeine can increase the risk of adverse effects. Jitteriness, hypertension, seizures, and temporary loss of consciousness has been associated with the combined use of ephedra and caffeine (2729). There is also a report of ischemic stroke in an athlete who consumed ephedra 40-60 mg, creatine monohydrate 6 grams, caffeine 400-600 mg, and a variety of other supplements daily for 6 weeks (1275). In theory, combining caffeinated green tea with ephedra would have similar effects.
In a case report, the EGCG component of a specific weight loss supplement (Hydroxycut) was thought to be responsible for atrial fibrillation (54028). The patient was given two doses of intravenous diltiazem and was loaded with intravenous digoxin. Thirty-six hours after the last product dose, she spontaneously converted to normal sinus rhythm. The authors suggested that the block of the atrial-specific KCNA5 potassium channel likely played a role in this response.
A case of thrombotic thrombocytopenic purpura has been reported for a patient who consumed a weight loss product containing green tea (53978). She presented at the emergency department with a one-week history of malaise, fatigue, and petechiae of the skin. Twelve procedures of plasmapheresis were performed, and corticosteroid treatment was initiated. She was discharged after 20 days.
Dermatologic ...Orally, green tea may cause skin rashes or skin irritation (53731,54038,90161,90187,102716). Topically, green tea may cause local skin reactions or skin irritation, erythema, burning, itching, edema, and erosion (53731,54018,97136,104609,111031). A green tea extract ointment applied to the cervix can cause cervical and vaginal inflammation, vaginal irritation, and vulval burning (11310,36442,36438). When applied to external genital or perianal warts, a specific green tea extract ointment (Veregen, Bradley Pharmaceuticals) providing 15% kunecatechins can cause erythema, pruritus, local pain, discomfort and burning, ulceration, induration, edema, and vesicular rash (15067,53907).
Endocrine
...There is some concern that, due to its caffeine content, green tea may be associated with an increased risk of fibrocystic breast disease, breast cancer, and endometriosis.
However, this is controversial since findings are conflicting (8043). Restricting caffeine in females with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996).
A population analysis of the Women's Health Initiative observational study has found no association between consumption of caffeine-containing beverages, such as green tea, and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors (108806). Also, a dose-response analysis of 2 low-quality observational studies has found that high consumption of caffeine is not associated with an increased risk of breast cancer (108807).
A case of hypoglycemia has been reported for a clinical trial participant with type 2 diabetes who used green tea in combination with prescribed antidiabetes medication (54035).
Gastrointestinal ...Orally, green tea beverage or supplements can cause nausea, vomiting, abdominal bloating and pain, constipation, dyspepsia, reflux, morning anorexia, increased thirst, flatulence, and diarrhea. These effects are more common with higher doses of green tea or green tea extract, equivalent to 5-6 liters of tea per day (8117,11366,36398,53719,53867,53936,54038,54076,90139,90140)(90161,90175,90187,97131,97136,102716).
Hepatic
...There is concern that some green tea products, especially green tea extracts, can cause hepatotoxicity in some patients.
In 2017, the regulatory agency Health Canada re-issued a warning to consumers about this concern. The updated warning advises patients taking green tea extracts, especially those with liver disease, to watch for signs of liver toxicity. It also urges children to avoid taking products containing green tea extracts (94897). In 2020, the United States Pharmacopeia (USP) formed an expert panel to review concerns of green tea extract-related hepatotoxicity. Based on their findings, USP determined that any products claiming compliance with USP quality standards for green tea extract must include a specific warning on the label stating "Do not take on an empty stomach. Take with food. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes)" (102722).
Numerous case reports of hepatotoxicity, primarily linked to green tea extract products taken in pill form, have been published. A minimum of 29 cases have been deemed at least probably related to green tea and 38 have been deemed possibly related. In addition, elevated liver enzymes have been reported in clinical research (14136,15026,53740,53746,53775,53859,54027,90139,90162,90164)(93256,94898,94899,102716,102720,102722,107158,111020,111644). 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, pomegranate fruit juice is generally well tolerated.
Pomegranate fruit extract and seed oil seem to be well tolerated. Pomegranate root, stem, and peel should not be used orally in large amounts. Topically, pomegranate fruit extract seems to be well tolerated.
Most Common Adverse Effects:
Oral: Diarrhea, flatulence.
Cardiovascular ...In one clinical trial, 2% of patients experienced hyperlipidemia and hypertension after consumption of pomegranate juice (69175). However, most clinical research shows that pomegranate does not increase cholesterol or blood pressure and may actually improve these parameters in some patients (8310,13022,13023,69168,69373,69374).
Dermatologic ...Topically, pomegranate may cause urticaria (hives) in some patients (8445).
Gastrointestinal ...Orally, pomegranate may cause mild gastrointestinal adverse effects. In one clinical study, drinking pomegranate juice 8 ounces daily caused diarrhea and flatulence in 2% of patients (69175). In another clinical study, taking pomegranate extract (POMx, POM Wonderful LLC) 3000 mg daily caused diarrhea in 10% of patients. This dose of pomegranate extract also caused nausea, abdominal pain, constipation, gastrointestinal upset, and vomiting in a small number of patients (91695).
Immunologic
...Orally, pomegranate fruit or seeds may cause allergic reactions.
These allergic reactions occur more commonly in people who are allergic to other plants (7674). In rare cases, pomegranate fruit can cause angioedema. Angioedema seems to occur without warning and in people who have eaten pomegranate for many years. Patients should be told to stop eating pomegranate if swelling of the tongue or face develops (7673). In one report, a patient experienced pomegranate-dependent, exercise-induced anaphylaxis. The patient developed widespread urticaria (hives) and lip edema after eating pomegranate seeds and then exercising (17331). In another report, an atopic patient experienced an allergic reaction to pomegranate fruit. Symptoms included urticaria (hives), facial angioedema, and hypotension (91692).
Topically, pomegranate may cause contact hypersensitivity characterized by urticaria (hives), angioedema, rhinorrhea, red itchy eyes, and dyspnea arising within a few minutes of exposure (8445).
Pulmonary/Respiratory ...Orally, pomegranate juice may cause nasal congestion, but this event is rare. In one clinical study, pomegranate juice was associated with nasal congestion in 2% of patients (69175). There is also one case report of a 7-year-old asthmatic child who developed bronchospasm moments after ingesting several pomegranate seeds (69149).
