| Ingredients | Amount Per Serving |
|---|---|
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ISO Lean 1 Proprietary Blend
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1066 mg |
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Metabolic Enhancer | Neuro Focus Blend
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(Garcinia cambogia )
(50%)
(Garcinia cambogia Genus: Garcinia Species: cambogia Note: 50% )
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(45%)
(Green Coffee extract Note: 45% )
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(90%)
(Green Tea extract Note: 90% )
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Lipstatin
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Carb Blocker/Anti Appetite Blend
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(Hoodia )
(20:1)
(Hoodia Extract Genus: Hoodia Note: 20:1 )
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(Cassia nomame )
(8%)
(Cassia nomame Genus: Cassia Species: nomame Note: 8% )
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(Vanadium Citrate)
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Hydro Cut Blend
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(Arctostaphylos uva ursi )
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(Foeniculum vulgare )
(seed)
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(Taraxacum officinale )
(root)
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(Juniperus communis )
(berries)
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Thermogenic Delivery System
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MCT oil
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Gelatin, Dicalcium Phosphate, Magnesium Stearate, Titanium Dioxide, Silica
Below is general information about the effectiveness of the known ingredients contained in the product ISO Lean 1. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
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 ISO Lean 1. 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. In clinical trials, 7-keto-DHEA has been used safely in doses up to 100 mg twice daily for up to 8 weeks (10404).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when consumed in amounts commonly found in foods. Cassia cinnamon has Generally Recognized As Safe (GRAS) status in the US for use as a spice or flavoring agent (4912) ...when used orally and appropriately, short-term. Cassia cinnamon up to 2 grams daily has been used safely for up to 3 months (17011,21914). Cassia cinnamon 3-6 grams daily has been used safely for up to 6 weeks (11347,14344). Cassia cinnamon extract corresponding to 3 grams daily of cassia cinnamon powder has also been used safely for up to 4 months (21916).
POSSIBLY SAFE ...when used topically, short-term. Cassia cinnamon oil 5% cream applied topically to the legs has been used safely in one clinical trial (59580).
POSSIBLY UNSAFE ...when used orally in high doses, long-term. Some cassia cinnamon products contain high levels of coumarin. Coumarin can cause hepatotoxicity in animal models (15299,21920). In humans, very high doses of coumarin from 50-7000 mg daily can result in hepatotoxicity that resolves when coumarin use is discontinued (15302). In most cases, ingestion of cassia cinnamon will not provide a high enough amount of coumarin to cause significant toxicity; however, in especially sensitive people, such as those with liver disease, prolonged ingestion of large amounts of cassia cinnamon might exacerbate the condition.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Cassia cinnamon 1 gram daily has been used safely in adolescents 13-18 years of age for up to 3 months (89648).
PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods (4912).
There is insufficient reliable information available about the safety of cassia cinnamon when used in medicinal amounts during pregnancy and breast-feeding. Stay on the safe side and stick to food amounts.
POSSIBLY SAFE. ..when used orally, short-term. Chitosan has been used with apparent safety in clinical studies at a dose of up to 1.35 grams daily for up to 3 months (1942,9609,9610,10022,10023,10024,10025,11307,13171,14314)(15126,92781,97708). ...when used topically, short-term (1944,1945,4269,4270,97712,106521).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Chromium has been safely used in doses up to 1000 mcg daily for up to 6 months (1934,5039,5040,6858,6859,6860,6861,6862,6867,6868)(7135,7137,10309,13053,14325,14440,17224,90057,90061)(90063,94234,95095,95096,95097,98687); however, most of these studies have used chromium doses in a range of 150-600 mcg. The Food and Drug Administration (FDA) and Institute of Medicine (IOM) evaluations of the safety of chromium suggest that it is safe when used in doses of 200 mcg daily for up to 6 months (13241,13242).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, long-term. Chromium has been safely used in a small number of studies at doses of 200-1000 mcg daily for up to 2 years (7060,7135,42618,42628,42666,110605,110607,110609). However, the Food and Drug Administration (FDA) and Institute of Medicine (IOM) evaluations of the safety of chromium suggest that it is safe when used in doses of 200 mcg daily for up to 6 months (13241,13242).
CHILDREN: LIKELY SAFE
when used orally and appropriately in amounts not exceeding the daily adequate intake (AI) levels by age: 0-6 months, 0.
2 mcg; 7-12 months, 5.5 mcg; 1-3 years, 11 mcg; 4-8 years, 15 mcg; males 9-13 years, 25 mcg; males 14-18 years, 35 mcg; females 9-13 years, 21 mcg; females 14-18 years, 24 mcg (7135). POSSIBLY SAFE...when used orally and appropriately in amounts exceeding AI levels. Chromium 400 mcg daily has been used safely for up to 6 weeks (42680).
PREGNANCY: LIKELY SAFE
when used orally and appropriately in amounts not exceeding adequate intake (AI) levels.
The AI for pregnancy is 28 mcg daily for those 14-18 years of age and 30 mcg daily for those 19-50 years of age (7135).
PREGNANCY: POSSIBLY SAFE
when used orally in amounts exceeding the adequate intake (AI) levels.
There is some evidence that patients with gestational diabetes can safely use chromium in doses of 4-8 mcg/kg (1953); however, patients should not take chromium supplements during pregnancy without medical supervision.
LACTATION: LIKELY SAFE
when used orally and appropriately in amounts not exceeding adequate intake (AI) levels.
The AI for lactation is 44 mcg daily for those 14-18 years of age and 45 mcg daily for those 19-50 years of age (7135). Chromium supplements do not seem to increase normal chromium concentration in human breast milk (1937). There is insufficient reliable information available about the safety of chromium when used in higher amounts while breast-feeding.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Dandelion has Generally Recognized As Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12). There is insufficient reliable information available about the safety of dandelion when used topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those in foods.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Fennel has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when fennel essential oil or extract is used orally and appropriately, short-term. Twenty-five drops (about 1.25 mL) of fennel fruit extract standardized to fennel 2% essential oil has been safely used four times daily for 5 days (49422). Also, two 100 mg capsules each containing fennel 30% essential oil standardized to 71-90 mg of anethole has been safely used daily for 8 weeks (97498). Powdered fennel extract has been used with apparent safety at a dose of 800 mg daily for 2 weeks (104199). ...when creams containing fennel 2% to 5% are applied topically (49429,92509).
CHILDREN: POSSIBLY SAFE
when combination products containing fennel are used to treat colic in infants for up to one week.
Studied products include up to 20 mL of a fennel seed oil emulsion; a specific product (ColiMil) containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg; and up to 450 mL of a specific tea (Calma-Bebi, Bonomelli) containing fennel, chamomile, vervain, licorice, and lemon balm (16735,19715,49428).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Observational research has found that regular use of fennel during pregnancy is associated with shortened gestation (100513).
LACTATION: POSSIBLY UNSAFE
when used orally.
Case reports have linked consumption of an herbal tea containing extracts of fennel, licorice, anise, and goat's rue to neurotoxicity in two breast-feeding infants. The adverse effect was attributed to anethole, a constituent of fennel and anise (16744). However, levels of anethole were not measured in breastmilk, and the herbal tea was not tested for contaminants. Furthermore, other adverse effects related to use of fennel during lactation have not been reported. However, until more is known, avoid using.
There is insufficient reliable information available about the safety of garcinia extract when used orally. However, there is some concern about liver toxicity. There are numerous case reports of elevated liver enzymes and symptoms of liver toxicity in patients who have taken garcinia alone or in combination with other ingredients for as little as one week. In at least two reports, hepatotoxicity occurred in patients who were taking garcinia alone. Most other reports occurred in patients taking multi-ingredient products (13037,53511,93380,93381,93384,93385,93392,93393,93394,96535)(102544,102545,111241).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
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.
There is insufficient reliable information available about the safety of hoodia.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Juniper, juniper berry, and juniper extract have Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used topically on limited areas of skin (12230). ...when the oil is used by inhalation and appropriately as aromatherapy (7107). There is insufficient reliable information available about the safety of juniper when used orally in doses of less than 10 grams of berries or 100 mg of oil daily, short-term. Juniper oil and berry have a long history of traditional use (12,103759).
LIKELY UNSAFE ...when used orally in excessive amounts or long-term. Use of daily doses greater than 10 grams of juniper berries (about 60 berries) or 100 mg of juniper essential oil, or prolonged oral use longer than 4 weeks, have been reported to increase the risk of severe adverse effects such as convulsions or kidney damage (8,19,103759).
PREGNANCY: UNSAFE
when used orally.
Juniper can increase uterine tone, interfere with fertility and implantation, and cause abortion (4,19).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Most research has evaluated a specific Phaseolus vulgaris (white kidney bean) extract (Phase 2, Pharmachem Labs), which appears to be safe in doses of up to 3 grams daily for 2-3 months (12186,15518,26157,29926). Other Phaseolus vulgaris (white kidney bean) extracts also seem to be safe in doses of 0.9-2.4 grams daily when used for up to 3 months (10633,104875).
POSSIBLY UNSAFE ...when large amounts of fresh Phaseolus vulgaris husks are ingested. Raw Phaseolus vulgaris husks contain lectins that can cause gastrointestinal upset. Cooking destroys the lectins (18).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in food amounts. Raspberry ketone has Generally Recognized as Safe (GRAS) status for use as a food additive (102356,102358). There is insufficient reliable information available about the safety of raspberry ketone when used in medicinal amounts. However, raspberry ketone is structurally similar to synephrine, a known stimulant agent. Orally, cases of heart palpitations, tachycardia, elevated blood pressure, coronary vasospasm, sweating, feelings of shakiness, and diarrhea are reported after taking raspberry ketone (17961,112386,112400). In one case report, pulseless electrical activity arrest followed by resistant polymorphic ventricular tachycardia occurred in a patient taking raspberry ketone (112386).
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of raspberry ketone; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Uva ursi has been used with apparent safety in doses of up to 3600 mg daily for 3-5 days (101815).
POSSIBLY UNSAFE ...when used orally long-term or in high doses. There is concern about the safety of long-term or high-dose use because of the hydroquinone content of uva ursi. Hydroquinone is thought to have mutagenic and carcinogenic effects (7). At high doses (around 20 grams of dried herb) it can cause convulsions, cyanosis, delirium, shortness of breath, and collapse. At very high doses (30 grams of dried herb or more) it can be fatal (4).
CHILDREN: POSSIBLY UNSAFE
when used orally by children.
Uva ursi contains hydroquinone and high tannin levels, which can cause severe liver problems in children (4,18); avoid using.
PREGNANCY: LIKELY UNSAFE
when used orally.
Uva ursi can have oxytocic effects, increasing the speed of labor (4,7,19); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. Vanadium is safe when taken in amounts below the tolerable upper intake level (UL) of 1.8 mg daily (7135).
POSSIBLY UNSAFE ...when used orally in high doses. Taking more than the tolerable upper intake level (UL) of 1.8 mg daily can increase the risk of gastrointestinal side effects and theoretically, kidney toxicity (7135). In some cases, patients with diabetes have used very high doses (100 mg daily) safely for up to 4 weeks (3055,3056,3057). However, there is concern that prolonged use of high doses might cause serious side effects including kidney damage (7135). Doses of 22.5 mg daily for five months can cause cramps and diarrhea (3012).
CHILDREN: LIKELY SAFE
when used orally in amounts found in foods (7135).
There is insufficient reliable information available about the safety of vanadium when used in amounts greater than those typically found in foods.
PREGNANCY: LIKELY SAFE
when used orally in amounts found in foods (7135).
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Epidemiological research has found that increased urinary levels of vanadium are associated with an increased risk of both term and preterm premature rupture of membranes (PROM). When comparing tertiles of urinary vanadium levels, patients in the middle tertile had 1.66 times the risk of term PROM when compared with the lowest tertile, and those in the highest tertile had 3.75 times the risk. For preterm PROM (rupture prior to 37 weeks' gestation), those in the highest tertile had an 8.14 times increased risk when compared with those in the lowest tertile (99052). Epidemiological research has also found that higher prenatal serum levels of vanadium are associated with impaired fetal growth, particularly in male newborns. The risk appears greatest with vanadium exposure in the second trimester (102096).
LACTATION: LIKELY SAFE
when used orally in amounts found in foods (7135).
There is insufficient reliable information available about the safety of vanadium when used in amounts greater than those typically found in foods; avoid using.
POSSIBLY SAFE ...when used orally and appropriately for up to 12 months (1784,1788,82041,82074,82089,82091,82120,82121,82151,82152)(82153,82154,82179,82180,82182,82183,104522,106845,110744). ...when used intravenously and appropriately, short-term (82074,82099,82147,82158,82159,82186,110744).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
In June 2019, the US Food and Drug Administration (FDA) issued a statement of warning that those who are pregnant or who could become pregnant should avoid vinpocetine (95751). In rats, vinpocetine has been associated with an increased risk of miscarriage at a dose of 60 mg/kg daily and with reduced fetal weight and increased incidence of birth defects at a dose of 5-20 mg/kg. Based on pharmacokinetic analyses, a daily vinpocetine dose of 10 mg in humans is comparable to a daily dose of 5 mg/kg in rats (99701).
LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product ISO Lean 1. 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, cassia cinnamon may have additive effects with antidiabetes drugs.
 Details
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Theoretically, large doses of cassia cinnamon might cause additive effects when used with hepatotoxic drugs.
Details
There is some concern that ingesting large amounts of cassia cinnamon for an extended duration might cause hepatotoxicity in some people. Cassia cinnamon contains coumarin, which can cause hepatotoxicity in animal models (15299,21920). In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin use is discontinued (15302,97249). Lower amounts might also cause liver problems in sensitive people, such as those with liver disease or those taking potentially hepatotoxic agents.
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Chitosan can reduce the absorption of acyclovir, potentially increasing the risk for treatment failure.
Details
Clinical research in humans shows that taking chitosan along with acyclovir 200 mg reduces acyclovir absorption. Concomitant administration of chitosan 400 mg or 1000 mg reduced the acyclovir area under the curve (AUC) and peak plasma concentration by about 30% and 40%, respectively, compared with control. Concomitant administration with chitosan 1000 mg also increased time to peak concentration from 1 hour to 2 hours (92780). In vitro research suggests that the mechanism for reduced absorption is due to acyclovir entrapment in chitosan-mucus complexes, which reduces intestinal absorption (112352).
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Theoretically, chitosan might increase the risk of bleeding when taken with warfarin.
Details
In a case report, a patient taking warfarin had a significantly increased international normalized ratio (INR) after starting chitosan 1200 mg daily. The INR normalized after chitosan was discontinued and vitamin K was administered. The patient once again started taking chitosan and again had a significant increase in INR. The INR stabilized again once chitosan was discontinued (15909). Researchers theorize that this interaction might occur because chitosan decreases absorption of fat-soluble vitamins, including vitamin K, which could increase the anticoagulant effect of warfarin.
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Theoretically, chromium may have additive effects with antidiabetic agents and increase the risk of hypoglycemia.
Details
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Theoretically, aspirin might increase chromium absorption.
Details
Animal research suggests that aspirin may increase chromium absorption and chromium levels in the blood (21055).
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Theoretically, concomitant use of chromium and insulin might increase the risk of hypoglycemia.
Details
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Chromium might bind levothyroxine in the intestinal tract and decrease levothyroxine absorption.
Details
Clinical research in healthy volunteers shows that taking chromium picolinate 1000 mcg with levothyroxine 1 mg decreases serum levels of levothyroxine by 17% when compared to taking levothyroxine alone (16012). Advise patients to take levothyroxine at least 30 minutes before or 3-4 hours after taking chromium.
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NSAIDs might increase chromium levels in the body.
Details
Drugs that are prostaglandin inhibitors, such as NSAIDs, seem to increase chromium absorption and retention (7135).
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Theoretically, taking dandelion root along with anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.
Details
In vitro research suggests that dandelion root inhibits platelet aggregation (18291).
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Theoretically, dandelion might increase the risk for hypoglycemia when used with antidiabetes drugs.
Details
Laboratory research suggests that dandelion extract may have moderate alpha-glucosidase inhibitor activity and might also increase insulin secretion (13474,90926). Also, in a case report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemia 2 weeks after beginning to eat salads containing dandelion (46960).
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Theoretically, dandelion might increase levels of drugs metabolized by CYP1A2.
Details
Laboratory research suggests that dandelion might inhibit CYP1A2 (12734). So far, this interaction has not been reported in humans. However, until more is known, watch for an increase in the levels of drugs metabolized by CYP1A2 in patients taking dandelion.
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Theoretically, dandelion might increase the clearance of drugs that are UDP-glucuronosyltransferase substrates.
Details
There is some preliminary evidence that dandelion might induce UDP-glucuronosyltransferase, a phase II enzyme (12734).
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Theoretically, through diuretic effects, dandelion might reduce excretion and increase levels of lithium.
Details
Animal research suggests that dandelion has diuretic properties (13475). As diuretics can increase serum lithium levels, the dose of lithium might need to be decreased when taken with dandelion.
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Theoretically, dandelion might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.
Details
Dandelion contains significant amounts of potassium (13465).
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Theoretically, dandelion might lower fluoroquinolone levels.
Details
Animal research shows that dandelion reduces absorption of ciprofloxacin and can lower levels by 73% (13477). However, this effect has not been reported in humans.
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Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
Details
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Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.
Details
Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin (6135). |
Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.
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Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.
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Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.
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Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.
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Some constituents of fennel have estrogenic activity (11), which may interfere with the antiestrogenic activity of tamoxifen. |
Theoretically, hydroxycitric acid (HCA), the main active ingredient in garcinia, might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
Details
HCA inhibits platelet aggregation in vitro. The inhibitory effect seems to be greater in platelets extracted from diabetic subjects than non-diabetic subjects (26862).
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Theoretically, hydroxycitric acid (HCA), the main active ingredient in garcinia, might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia.
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Theoretically, concomitant use with other potentially hepatotoxic drugs might increase the risk of developing liver damage.
Details
There have been reports of acute hepatitis with elevated liver enzymes associated with garcinia, when taken alone or in combination with other ingredients (13037,53511,93380,93381,93384,93392,93393,93394,102544,102545). Case reports collected from the Drug Induced Liver Injury Network suggest this risk may be greater in people who carry the HLA B*35:01 allele (108401).
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Theoretically, combining garcinia with other serotonergic drugs might increase the risk of serotonergic side effects, including serotonin syndrome.
Details
In one report, a patient experienced serotonin syndrome after taking garcinia extract (60% hydroxycitric acid) 1000 mg daily in combination with escitalopram 20 mg, which had been taken for a year. The patient was switched to sertraline 50 mg daily and again experienced serotonin syndrome (23545).
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Theoretically, green coffee might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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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.
Details
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.
Details
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.
Details
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Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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.
Details
Animal research shows that taking green tea in amounts equivalent to about 6 cups daily in humans for 4 weeks prior to receiving a single injection of 5-fluorouracil increases the maximum plasma levels of 5-fluorouracil by about 2.5-fold and the area under the curve by 425% (98424).
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Theoretically, green tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Details
Green tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine doesn't seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests (11770). However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).
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Theoretically, alcohol might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Concomitant use of alcohol and caffeine can increase caffeine serum concentrations and the risk of caffeine adverse effects. Alcohol reduces caffeine metabolism (6370).
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Theoretically, green tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
Conflicting reports exist regarding the effect of green tea on bleeding risk when used with anticoagulant or antiplatelet drugs; however, most evidence suggests that drinking green tea in moderate amounts is unlikely to cause a significant interaction. Green tea contains small amounts of vitamin K, approximately 7 mcg per cup (100524). Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea (1460,1461,1463,4211,6048,8028,20868). However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects. Furthermore, the catechins and caffeine in green tea are reported to have antiplatelet activity (733,8028,8029,12882,100524).
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Theoretically, taking green tea with antidiabetes drugs might interfere with blood glucose control.
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Green tea extract seems to reduce the levels and clinical effects of atorvastatin.
Details
In healthy humans, taking green tea extract 300 mg or 600 mg along with atorvastatin reduces plasma levels of atorvastatin by approximately 24%. The elimination of atorvastatin is not affected (102714). Atorvastatin is a substrate of organic anion-transporting polypeptides (OATPs). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs. Some OATPs are expressed in the small intestine and are responsible for the uptake of drugs and other compounds, which may have resulted in reduced plasma levels of atorvastatin (19079). It is not clear if drinking green tea alters the absorption of atorvastatin.
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Green tea contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists (15).
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Theoretically, green tea might interfere with the effects of bortezomib.
Details
In vitro research shows that green tea polyphenols, such as epigallocatechin gallate (EGCG), interact with bortezomib and block its proteasome inhibitory action. This prevents the induction of cell death in multiple myeloma or glioblastoma cancer cell lines (17212). Advise patients taking bortezomib, not to take green tea.
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Theoretically, green tea might reduce the effects of carbamazepine and increase the risk for convulsions.
Details
Green tea contains caffeine. Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg (23559,23561). Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals (23562).
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Theoretically, green tea might reduce the levels and clinical effects of celiprolol.
Details
In a small human study, taking green tea daily for 4 days appears to decrease blood and urine levels of celiprolol by at least 98% (104607). This interaction is possibly due to the inhibition of organic anion transporting polypeptide (OATP). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is found in the intestine (19079,19080,98461) The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea (98461).
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Theoretically, concomitant use might increase the effects and adverse effects of caffeine in green tea.
Details
Green tea contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42% (11736).
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Theoretically, green tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Details
Animal research suggests that, although green tea extract does not affect the elimination of clozapine, it delays the time to reach peak concentration and reduces the peak plasma levels (90173). Also, concomitant administration of green tea and clozapine might theoretically cause acute exacerbation of psychotic symptoms due to the caffeine in green tea. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine (13741).
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Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in green tea.
Details
Green tea contains caffeine. Oral contraceptives can decrease caffeine clearance by 40% to 65% (8644).
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Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2) (3941,5051,11741,23557,23573,23580,24958,24959,24960,24962), (24964,24965,24967,24968,24969,24971,38081,48603). Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from green tea and increase caffeine levels.
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Green tea is unlikely to produce clinically significant changes in the levels and clinical effects of CYP3A4 substrates.
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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.
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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.
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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.
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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.
Details
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Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Details
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Theoretically, green tea might reduce the effects of phenytoin and increase the risk for convulsions.
Details
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Theoretically, green tea might increase the levels and clinical effects of pioglitazone.
Details
Green tea contains caffeine. Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone (108812). However, the exact mechanism of this interaction is unclear.
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Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
Details
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Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Details
Green tea contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2, and concomitant use might reduce metabolism of one or both agents (11739).
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Theoretically, green tea extract might alter the absorption and distribution of rosuvastatin.
Details
In animal research, giving green tea extract with rosuvastatin increased plasma levels of rosuvastatin. Rosuvastatin is a substrate of organic anion-transporting polypeptide (OATP)1B1, which is expressed in the liver. The increased plasma levels may have been related to inhibition of OATP1B1 (102717). However, in humans, taking EGCG with rosuvastatin reduced plasma levels of rosuvastatin, suggesting an inhibition of intestinal OATP (102730). It is not clear if drinking green tea alters the absorption of rosuvastatin.
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Theoretically, concomitant use might increase stimulant adverse effects.
Details
Green tea contains caffeine. Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects (11832).
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Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).
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Theoretically, green tea might increase the levels and adverse effects of theophylline.
Details
Green tea contains caffeine. Large amounts of caffeine might inhibit theophylline metabolism (11741).
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Theoretically, green tea might increase the levels and adverse effects of tiagabine.
Details
Green tea contains caffeine. Animal research suggests that chronic caffeine administration can increase the serum concentrations of tiagabine. However, concomitant use does not seem to reduce the antiepileptic effects of tiagabine (23561).
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Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.
Details
Green tea contains caffeine. In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.
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Theoretically, green tea might reduce the effects of valproate and increase the risk for convulsions.
Details
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Theoretically, concomitant use might increase the levels and adverse effects of both verapamil and caffeine.
Details
Animal research suggests that the green tea constituent EGCG increases the area under the curve (AUC) values for verapamil by up to 111% and its metabolite norverapamil by up to 87%, likely by inhibiting P-glycoprotein (90138). Also, theoretically, concomitant use of verapamil and caffeinated beverages such as green tea might increase plasma caffeine concentrations and the risk of adverse effects, due to the caffeine contained in green tea. Verapamil increases plasma caffeine concentrations by 25% (11741).
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Theoretically, green tea may increase the risk of bleeding if used with warfarin.
Details
Conflicting reports exist regarding the potential of green tea to antagonize the effect of warfarin; however, most evidence suggests that drinking green tea in moderation is unlikely to cause a significant interaction. Green tea contains a small amount of vitamin K, approximately 7 mcg per cup (100524). Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea (1460,1461,1463,4211,6048,8028,20868). However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects (1460,1461,1463,8028). Therefore, use of green tea in moderate amounts is unlikely to antagonize the effects of warfarin; however, very large doses should be avoided.
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Animal research shows that a steroid glycoside of hoodia, gordonoside F, increases glucose-stimulated insulin secretion by activating GPR119. This effect enhances glucose disposal (91614). Theoretically, concomitant use of hoodia with antidiabetes medications may enhance blood glucose-lowering effects and increase the risk of hypoglycemia. Some antidiabetes medications include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), tolbutamide (Orinase), and others.
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Clinical research shows that hoodia can increase blood pressure (18052). Theoretically, concomitant use of hoodia with antihypertensive drugs might decrease the effectiveness of the antihypertensive drugs and increase the risk of hypertension. Some antihypertensive drugs include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.
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Evidence from in vitro research shows that hoodia may stimulate beta-adrenergic receptors (91607). Also, clinical research shows that hoodia can increase blood pressure and heart rate (18052). Theoretically, using hoodia with beta-blockers might decrease the effects of these medications. Some beta-blocker drugs include atenolol (Tenormin), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), and propranolol (Inderal).
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Animal research shows that a steroid glycoside of hoodia, gordonoside F, increases glucose-stimulated insulin secretion by activating GPR119 (91614). Theoretically, concomitant use of hoodia with insulin may enhance the blood glucose-lowering effects of insulin. Blood glucose levels should be monitored.
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Theoretically, taking juniper berry with antidiabetes medications might cause additive hypoglycemia.
Details
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Theoretically, juniper berry might increase the risk of adverse effects from diuretic drugs.
Details
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Theoretically, juniper berry might reduce lithium excretion and increase serum levels of lithium.
Details
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Theoretically, Phaseolus vulgaris might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
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Theoretically, raspberry ketone might increase the risk of adverse cardiovascular effects with stimulant drugs.
Details
Structurally, raspberry ketone resembles synephrine, a known stimulant agent. Heart palpitations, elevated blood pressure, coronary vasospasm, pulseless electrical activity arrest, and resistant polymorphic ventricular tachycardia have been reported in patients taking raspberry ketone (17961,112386,112400).
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Theoretically, raspberry ketone might increase warfarin dose requirements.
Details
In one case report, a patient taking warfarin 55 mg per week had a decrease in INR over a period of one month while taking raspberry ketone 250 mg daily. A warfarin dose increase to 70 mg per week was necessary to maintain a therapeutic INR while taking raspberry ketone (17962). The mechanism for this potential interaction is not known.
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Theoretically, uva ursi may decrease the metabolism of CYP2C19 substrates.
Details
In vitro, uva ursi appears to inhibit cytochrome CYP2C19 (98550). This effect has not been reported in humans.
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Theoretically, uva ursi may decrease the metabolism of CYP3A4 substrates.
Details
In vitro, uva ursi appears to inhibit CYP3A4 (98550). This effect has not been reported in humans.
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Theoretically, uva ursi may increase levels of drugs metabolized by glucuronidation.
Details
In vitro, uva ursi extract appears to strongly inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1). However, uva ursi extract does not appear to inhibit UGT1A1 in animal models (98549). This effect has not been reported in humans.
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Theoretically, uva ursi may increase lithium levels, necessitating a decrease in dose.
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Uva ursi may have diuretic properties (81637). Diuretics may increase lithium reabsorption with sodium in the proximal tubule of the kidney. Theoretically, uva ursi might reduce excretion and increase levels of lithium.
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Theoretically, uva ursi may alter the levels of drugs transported by P-glycoprotein.
Details
In vitro, uva ursi appears to inhibit the multi-drug transporter protein, P-glycoprotein (98550). This effect has not been reported in humans.
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Effects of uva ursi in the urinary tract may be reduced by urinary acidifying agents.
Details
Uva ursi seems to work best in alkaline urine. Theoretically, taking uva ursi with medications known to acidify the urine may decrease any effects of uva ursi on the urinary tract (19).
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Theoretically, vanadium might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.
Details
In vitro research shows that the sodium orthovanadate form of vanadium prolongs clotting time, likely through inhibition of thrombin and factor Xa (3054).
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Theoretically, vanadium might increase the risk of hypoglycemia when taken with antidiabetes drugs.
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Vinpocetine might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Details
Clinical research shows that vinpocetine decreases red blood cell aggregation, as well as plasma and whole blood viscosity. This effect has been seen with intravenous vinpocetine 1 mg/kg and oral vinpocetine 30 mg daily (82101,82119). Vinpocetine also seems to have antiplatelet effects (1801,10061,82117).
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Theoretically, vinpocetine might increase levels of drugs metabolized by CYP2C9.
Details
In vitro research shows that vinpocetine weakly inhibits CYP2C9 (92933). However, this effect has not been reported in humans.
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Vinpocetine might modestly increase the risk of bleeding when taken with warfarin.
Details
Clinical research shows that the combination of warfarin and vinpocetine leads to slight increases in prothrombin time and the area under the concentration curve for warfarin. However, these increases were small, and researchers suggest that this interaction is not likely to be clinically significant in most patients (10829).
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Below is general information about the adverse effects of the known ingredients contained in the product ISO Lean 1. 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, 7-keto-DHEA seems to be well tolerated when used short-term.
Cardiovascular ...Orally, 7-keto-DHEA may modestly decrease blood pressure in some patients (10404).
Gastrointestinal ...Orally, 7-keto-DHEA has been associated with two reports of nausea in one clinical study (92185).
Hematologic ...A case report describes decreased hemoglobin and hematocrit levels in a man taking 7-keto-DHEA orally, 25 mg twice daily for 7 days (10404). The clinical significance of this is not clear.
Neurologic/CNS ...Orally, 7-keto-DHEA has been associated with one report of vertigo in one clinical study (92185).
General
...Orally, cassia cinnamon appears to be well-tolerated.
Significant side effects have not been reported in most patients.
Most Common Adverse Effects:
Topically: Burning mouth, stomatitis.
Dermatologic
...In one clinical trial, a rash was reported in one patient taking cassia cinnamon 1 gram daily for 90 days (17011).
In one case, a 58-year-old female with a documented allergy to topically applied cinnamic alcohol presented with eyelid dermatitis, which was found to be a manifestation of systemic contact dermatitis to cinnamon in the diet. Symptoms improved in two days and completely cleared five days after discontinuing the addition of cinnamon to food products (95599). In other case reports, two adults presented with allergic contact cheilitis following the ingestion of chai tea with cinnamon and yogurt with cinnamon. Cinnamon components were confirmed as the causative allergic agents with patch tests, and both cases of allergic contact cheilitis completely resolved upon cessation of the cinnamon-containing products (113516,113515).
Topically, allergic skin reactions and stomatitis from toothpaste flavored with cassia cinnamon have been reported (11915,11920). Intraoral allergic reactions with symptoms of tenderness and burning sensations of the oral mucosa have also been reported in patients using breath fresheners, toothpaste, mouthwash, candy, or chewing gum containing cinnamon, cinnamic aldehyde or cinnamic alcohol as flavoring agents. Glossodynia, or burning mouth syndrome, has also been reported in a 62-year-old female who ate apples dipped in cinnamon nightly (95598), and allergic contact dermatitis has been reported in a teenage female using a homemade cinnamon sugar face scrub (95596).
Endocrine ...In one clinical trial, a hypoglycemic seizure was reported in one patient taking cassia cinnamon 1 gram daily for 3 months. The event occurred one day after enrolling in the study (89648). It is unclear if cassia cinnamon caused this event.
Hepatic ...There is some concern about the safety of ingesting large amounts of cassia cinnamon for extended durations due to its coumarin content. Coumarin can cause hepatotoxicity in animal models (15299). In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin is discontinued (15302). In clinical trials, taking cassia cinnamon 360 mg to 12 grams daily for 3 months did not significantly increase levels of aspartate transaminase (AST) or alanine transaminase (ALT) (21918,96280,108259). However, in one case report, acute hepatitis with elevated AST and ALT occurred in a 73-year-old female who started taking a cinnamon supplement (dose unknown) one week prior to admission. The cinnamon supplement was added on to high-dose rosuvastatin, which may have led to additive adverse hepatic effects. After discontinuing both products, liver function returned to normal, and the patient was able to restart rosuvastati without further complications (97249). In most cases, ingestion of cassia cinnamon won't provide a high enough amount of coumarin to cause significant toxicity; however, in especially sensitive people, such as those with liver disease or taking potentially hepatotoxic agents, prolonged ingestion of large amounts of cassia cinnamon might exacerbate the condition.
Immunologic ...An unspecified allergic reaction was reported in one patient taking cassia cinnamon 1 gram daily for 3 months (89648).
General
...Orally and topically, chitosan seems to be well tolerated, short-term.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, flatulence, epigastric discomfort, and nausea.
Dermatologic ...In one clinical trial, a subject with kidney failure reported itching during 12 weeks of oral chitosan treatment (1942). It is not clear if this was related to the underlying renal failure or the use of oral chitosan.
Gastrointestinal ...Orally, chitosan has been reported to cause epigastric discomfort, constipation, flatulence, diarrhea, nausea, and dryness of the throat (1942,3243,9986,11307,14314,41688,92781,100170). Excessive discharge of fat in the feces, also known as steatorrhea, has been reported with chitosan therapy (41724,41726). Theoretically, chitosan may alter the normal intestinal flora via antimicrobial activity, which could interfere with lipid digestibility and bile acid metabolism, leading to the growth of resistant pathogens (41687,41709,41725).
Musculoskeletal ...Orally, chitosan has been reported to cause swollen heels and wrists in two patients (41688).
Neurologic/CNS ...Headaches have been reported in patients taking oral chitosan (41688).
Ocular/Otic ...Topically, an eye drop containing chitosan-N-acetylcysteine has been reported to cause itching and irritation of the eyes (97710).
General
...Orally, chromium is generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal irritation, headaches, insomnia, irritability, mood changes.
Serious Adverse Effects (Rare):
Orally: Rare cases of kidney and liver damage, rhabdomyolysis, and thrombocytopenia have been reported.
Dermatologic
...Orally, chromium-containing supplements may cause acute generalized exanthematous pustulosis (42561), skin rashes (42679), and urticaria (17224).
Also, chromium picolinate or chromium chloride may cause systemic contact dermatitis when taken orally, especially in patients with contact allergy to chromium (6624,90058). In one clinical study, a patient taking chromium nicotinate 50 mcg daily reported itchy palms that improved after the intervention was discontinued. It is unclear of this effect was due to the chromium or another factor (95096).
Topically, hexavalent chromium, which can be present in some cement, leather products, or contaminated soil, may cause allergic contact dermatitis (42645,42789,90060,90064,110606).
A case of lichen planus has been reported for a patient following long-term occupational exposure to chromium (42688).
Endocrine ...Orally, cases of hypoglycemia have been reported for patients taking chromium picolinate 200-1000 mcg daily alone or 200-300 mcg two or three times weekly in combination with insulin (42672,42783). Chromium picolinate has also been associated with weight gain in young females who do not exercise and in those following a weight-lifting program (1938).
Gastrointestinal
...Orally, chromium in the form of chromium picolinate, chromium polynicotinate, chromium-containing brewer's yeast, or chromium-containing milk powder may cause nausea, vomiting, diarrhea, decreased appetite, constipation, flatulence, or gastrointestinal upset (14325,42594,42607,42622,42643,42679).
Long-term exposure to heavy metals, including chromium, has been associated with increased risk of gallbladder disease and cancer (42682,42704).
Genitourinary ...Orally, chromium polynicotinate has been associated with disrupted menstrual cycles in patients taking the supplement to prevent weight gain during smoking cessation (42643).
Hematologic ...Anemia, hemolysis, and thrombocytopenia were reported in a 33 year-old female taking chromium picolinate 1200-2400 mcg daily for 4-5 months (554). The patient received supportive care, blood product transfusions, and hemodialysis and was stabilized and discharged a few days later. Lab values were normal at a one-year follow-up.
Hepatic ...Liver damage has been reported for a 33-year-old female taking chromium picolinate 1200 mcg daily for 4-5 months (554). Also, acute hepatitis has been reported in a patient taking chromium polynicotinate 200 mcg daily for 5 months (9141). Symptoms resolved when the product was discontinued. Two cases of hepatotoxicity have been reported in patients who took a specific combination product (Hydroxycut), which also contained chromium polynicotinate in addition to several herbs (13037).
Musculoskeletal ...Acute rhabdomyolysis has been reported for a previously healthy 24-year-old female who ingested chromium picolinate 1200 mcg over a 48-hour time period (42786). Also, chromium polynicotinate has been associated with leg pain and paresthesia in patients taking the supplement to prevent weight gain during smoking cessation (42643).
Neurologic/CNS ...Orally, chromium picolinate may cause headache, paresthesia, insomnia, dizziness, and vertigo (6860,10309,14325,42594). Vague cognitive symptoms, slowed thought processes, and difficulty driving occurred on three separate occasions in a healthy 35-year-old male after oral intake of chromium picolinate 200-400 mcg (42751). Transient increases in dreaming have been reported in three patients with dysthymia treated with chromium picolinate in combination with sertraline (2659). A specific combination product (Hydroxycut) containing chromium, caffeine, and ephedra has been associated with seizures (10307). But the most likely causative agent in this case is ephedra.
Psychiatric ...Orally, chromium picolinate has been associated with irritability and mood changes in patients taking the supplement to lose weight, while chromium polynicotinate has been associated with agitation and mood changes in patients taking the supplement to prevent weight gain during smoking cessation (6860,42643).
Renal
...Orally, chromium picolinate has been associated with at least one report of chronic interstitial nephritis and two reports of acute tubular necrosis (554,1951,14312).
Laboratory evidence suggests that chromium does not cause kidney tissue damage even after long-term, high-dose exposure (7135); however, patient- or product-specific factors could potentially increase the risk of chromium-related kidney damage. More evidence is needed to determine what role, if any, chromium has in potentially causing kidney damage.
Intravenously, chromium is associated with decreased glomerular filtration rate (GFR) in children who receive long-term chromium-containing total parenteral nutrition - TPN (11787).
Topically, burns caused by chromic acid, a hexavalent form of chromium, have been associated with acute chromium poisoning with acute renal failure (42699). Early excision of affected skin and dialysis are performed to prevent systemic toxicity.
Other ...Another form of chromium, called hexavalent chromium, is unsafe. This type of chromium is a by-product of some manufacturing processes. Chronic exposure can cause liver, kidney, or cardiac failure, pulmonary complications, anemia, and hemolysis (9141,11786,42572,42573,42699). Occupational inhalation of hexavalent chromium can cause ulceration of the nasal mucosa and perforation of the nasal septum, and has been associated with pneumoconiosis, allergic asthma, cough, shortness of breath, wheezing, and increased susceptibility to respiratory tract cancer and even stomach and germ cell cancers (42572,42573,42601,42610,42636,42667,42648,42601,42788,90056,90066). Although rare, cases of interstitial pneumonia associated with chromium inhalation have been reported. Symptoms resolved with corticosteroid treatment (42614).
General
...Orally, dandelion seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, heartburn, and stomach discomfort.
Topically: Dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.
Cardiovascular ...In one report, a 39-year-old obese woman developed palpitations and syncope after taking a weight loss supplement containing a combination of dandelion, bladderwrack, and boldo for 3 weeks. The patient was found to have prolonged QT-interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether dandelion, another ingredient, or the combination of ingredients is responsible for this adverse effect. The product was not analyzed to determine the presence of any potential toxic contaminants.
Dermatologic ...Topically, dandelion can cause contact dermatitis and erythema multiforme in sensitive individuals. Dandelion can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family (13478,13481,42893,46945,46977). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.
Endocrine ...In one report, a 56-year-old man with renal impairment developed hyperoxalaemia and peripheral gangrene after ingesting large amounts of dandelion tea (10 to 15 cups daily for 6 months). The adverse effect was attributed to the high oxalate content of dandelion tea (258 mcmol/L) and reduced renal oxalate clearance caused by renal impairment (90639). In another report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemic symptoms 2 weeks after beginning to eat salads containing dandelion (46960). The hypoglycemic effect was attributed to the potential alpha-glucosidase inhibitory activity of dandelion.
Gastrointestinal ...Gastrointestinal symptoms, including stomach discomfort, diarrhea, and heartburn, have been reported following oral use of dandelion (19146,36931). A case of intestinal blockage has been reported for a patient who ingested a large amount of dandelion greens three weeks after undergoing a stomach operation (46981). Also, a case of hemorrhagic cystitis has been reported for a 33-year-old woman who took a specific herbal product (Slim-Kombu, Balestra and Mech, Vicenza, Italy) containing 20 herbal extracts, including dandelion extract. Symptoms resolved after the patient discontinued using the product, and symptoms resumed when the patient began taking the supplement again four months later. While various ingredients in the supplement may have contributed to the symptoms, it is possible that dandelion extract may have contributed to the effect due to its diuretic, laxative, cholagogue, and antirheumatic properties (46959).
Other ...Orally, products containing dandelion pollen can cause allergic reactions, including anaphylaxis (13479,13480). Also, rhinoconjunctivitis and asthma have been reported after handling products such as bird feed containing dandelion and other herbs, with reported positive skin tests for dandelion hypersensitivity (46948). Dandelion pollen may cause pollinosis, such as allergic rhinitis and conjunctivitis (18065,46951,46964,46966,46972).
General
...Orally and topically, fennel seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, photosensitivity, and allergic reactions in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Seizures.
Dermatologic ...Advise patients to avoid excessive sunlight or ultraviolet light exposure while using fennel (19). Allergic reactions affecting the skin such as atopic dermatitis and photosensitivity may occur in patients who consume fennel (6178,49507).
Gastrointestinal ...Orally, fennel may cause gastrointestinal complaints, including nausea and vomiting (19146,104196).
Hematologic ...Methemoglobinemia has been reported in four infants following intoxication related to ingestion of a homemade fennel puree that may have been made from improperly stored fennel (49444).
Immunologic ...A case report describes an 11-year-old male who developed an allergy to fennel-containing toothpaste. Immediately after using the toothpaste, the patient experienced sneezing, coughing, itchy mouth, rhinorrhea, nasal congestion, wheezing, difficulty breathing, and palpitations, which resolved within 10 minutes of spitting out the toothpaste and rinsing the mouth. In challenge tests, the patient reacted to chewing fresh fennel root, but not ground fennel seeds (103822).
Neurologic/CNS ...Orally, fennel oil has been associated with tonic clonic and generalized seizures (12868). New-onset cluster headaches are reported in a 24-year-old female while using a toothpaste containing fennel and camphor for 3 months. The headaches resolved upon stopping the toothpaste (112368). It is unclear if this adverse effect can be attributed to fennel, camphor, or the combination.
Pulmonary/Respiratory ...Orally, fennel and fennel seed have been reported to cause bronchial asthma (49478).
General
...Orally, garcinia and its constituent, hydroxycitric acid (HCA), seem to be generally well tolerated in clinical research.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal discomfort, headache, and nausea.
Serious Adverse Effects (Rare):
Orally: Garcinia has been linked with cases of hepatotoxicity and liver failure. There have also been rare cases of mania and pancreatitis.
Cardiovascular
...There is a case report of a 48-year-old female who developed acute necrotizing eosinophilic myocarditis (ANEM) after using a garcinia supplement orally for 2.
5 weeks. On admission to hospital, she was hypotensive and had an elevated serum troponin level, progressing to fulminant heart failure, acute kidney failure, and sustained ventricular arrhythmias. She recovered after treatment with extra-corporeal membrane oxygenation (ECMO) and high-dose corticosteroids (88160). Although the patient had no prior medical history and was not taking any medications, this cannot conclusively be attributed to garcinia.
When taken orally, a specific formulation of the multi-ingredient product Hydroxycut (Iovate Health Sciences Inc.), which was available until 2009, has been associated with malignant hypertension and hypertensive retinopathy. Hydroxycut contains caffeine, garcinia, gymnema, green tea, glucomannan, guarana extract, and willow bark. The suspected causal agent is caffeine, which is dosed at 600 mg daily if Hydroxycut is taken as recommended; however, the responsibility of the other ingredients cannot be ruled out (16527).
Endocrine ...In one case report, a 56-year-old female with pre-existing diabetes, hepatitis C, and hypertension developed diabetic ketoacidosis (DKA) and pancreatitis after taking an unknown amount of garcinia and African mango for one month. Upon admission, she presented with altered mental status, elevated serum glucose and lipase, and high anion gap metabolic acidosis. After 3 days of intensive supportive care, the DKA and pancreatitis resolved. The suspected probable causal agent was garcinia; however, African mango cannot be ruled out (97341). There have been at least 3 other cases of acute pancreatitis associated with use of garcinia (unknown dose) for 2 weeks and up to 7 months in adults ages 36-82 years (105056,105058,105071).
Gastrointestinal ...Orally, garcinia and its active constituent hydroxycitric acid (HCA) have caused mild and infrequent nausea, diarrhea, and other gastrointestinal symptoms (728,11977,19153,88158,88159).
Hepatic
...Orally, garcinia and its constituent hydroxycitric acid (HCA) might cause liver toxicity.
Several cases of acute liver toxicity have been reported in patients taking garcinia supplements (93392,93393,93394,95573,102544,102545,104431,111241). Reported doses of garcinia extract range from 480-1800 mg daily, providing up to 900 mg HCA daily (93392,93394,95573,102544,104431). However, not all experts agree that HCA plays a causal role in the hepatotoxicity associated with garcinia supplements; some suggest other mechanisms may be in play, such as immune-mediated processes (95576,108401). In most cases, patients presented with a hepatocellular pattern of toxicity and symptoms of abdominal pain, coagulopathy, jaundice, and elevated transaminases after taking garcinia for several weeks to several months (93393,93394,95573,102544,102545,104431,108401,111241). In most of these cases, there was no evidence of other natural causes of liver disease, such as viral hepatitis. Some of these patients used acetaminophen at recommended doses for limited durations, suggesting that a potential synergistic effect may occur when multiple hepatotoxic agents are used concomitantly.
The Drug-Induced Liver Injury Network has identified 22 cases (11 moderate; 7 severe) of liver injury from garcinia, with 5 cases occurring with garcinia alone, 16 cases occurring in combination with green tea, and 1 case occurring in combination with ashwagandha. Clinical presentations of liver injury related to garcinia closely resemble green tea-related liver injury. Most patients (82%) presented with a hepatocellular pattern of enzyme elevations. The median age of these case reports was 35 years, 41% identified as Hispanic, and most patients were overweight but not obese. In case reports involving garcinia alone, the carrier frequency on HLAB*35:01 was 60%, which is higher than the carrier frequency found in reports of liver injury due to other supplements (19%) and in population controls (11%). Within 3 months of injury onset, 1 patient required liver transplantation and 1 patient died from liver injury (108401).
There have been at least four cases of liver failure requiring transplantation associated with garcinia supplements (93392,95573,98425,104431). In one case related specifically to garcinia, a 52-year-old female had been taking a combination product (USA Nutra Labs) providing garcinia 1000 mg daily, standardized to 60% HCA. The supplement also provided calcium 50 mg, chromium 200 mcg, and potassium 50 mg. Symptoms started within a few weeks of initiation of the product (93392). In another case, a 34-year-old Hispanic male experienced acute liver failure requiring transplant after taking a specific garcinia product (Garcinia Cambogia 5:1 Extract, Swanson Vitamins) 160 mg three times daily before meals for 5 months (95573). In other reports, one 26-year-old male and one female presented to the emergency room with liver failure after 2-7 months of taking a supplement containing garcinia and green tea, with or without whey protein, Veldt raisin, and coffea arabica (98425,104431).
There have also been numerous cases of acute liver toxicity associated with combination products containing garcinia, such as Hydroxycut (Iovate Health Sciences Inc) (13037,53511,93380,93381,93384,93385,96535,98425,104431). Available until 2009, Hydroxycut contained garcinia, green tea, chromium, caffeine, calcium, potassium, and gymnema. A currently available garcinia-containing combination product called Seryburn Day Triple has also been associated with supplement-induced liver injury. (13037,93380,93381,95570,95572,95575,111241). In most of these cases, patients had elevated levels of liver enzymes without evidence of chronic liver disease. Patients usually developed symptoms within 1-12 weeks of taking the product. The clinical pattern of liver damage was often hepatocellular. Most cases reported altered liver enzyme values including ALT, AST, bilirubin, alkaline phosphatase, and international normalized ratio. In most cases, symptoms resolved with near normalization of enzyme levels once the garcinia-containing combination product was discontinued (13037,53511,93380,93381,93384,95567,95572,95575,111241).
However, there is one report of transplant related to Hydroxycut use (93381). As the suspected causal agents, garcinia and green tea were removed from the product during reformulation in 2009 (13037,53511,93380,93381,93384). Hepatotoxicity has been reported in at least one new formulation of Hydroxycut not containing garcinia (93394). Consequently, some experts believe that there is not enough information to attribute hepatotoxicity from this product to garcinia or HCA (95576). Also, in some cases, causality of hepatotoxicity was less clear because patients were taking many other supplements and drugs (95570).There is also a report of fatal liver failure in an obese female taking montelukast while also taking two dietary supplements containing multiple ingredients, including garcinia, gymnema, chromium, bitter orange, and many others. The authors speculated that the combination of montelukast with one or more ingredients in these dietary supplements may have resulted in liver failure (93385).
Musculoskeletal ...Orally, garcinia-containing products have been associated with rhabdomyolysis. There is a case report of a patient who developed rhabdomyolysis 3 hours after ingestion of an herbal product containing ephedra, guarana, chitosan, gymnema, garcinia, and chromium (19154). Since there were multiple ingredients, the effect cannot be conclusively attributed to garcinia. Another case of rhabdomyolysis has been reported for a patient taking an undetermined formulation of Hydroxycut at a dose of 4 caplets daily, naproxen sodium 220 mg as needed for pain, dextroamphetamine daily for 5 days, and hydrocodone-acetaminophen and cyclobenzaprine for pain. Two weeks later, after stopping Hydroxycut and receiving supportive care, the rhabdomyolysis resolved. Hydroxycut was determined to be possibly associated with the rhabdomyolysis (95566). Since Hydroxycut contains multiple ingredients and garcinia content was possible but not confirmed, a causal relationship with garcinia could not be determined.
Neurologic/CNS ...Orally, garcinia and its active constituent hydroxycitric acid (HCA) may cause headache and dizziness (11977). A 35-year-old female reported ocular complications, headache, dizziness, and nausea after taking garcinia extract, providing more than 500 mg of HCA, three times daily for one week. The patient's neurologic symptoms resolved one day after discontinuing the garcinia extract (102546). It is unclear if these neurologic adverse effects were separate from or related to the patient's visual disturbances.
Ocular/Otic ...In one case, a 35-year-old female presented with ocular pain in both eyes, decreased vision in the left eye, headache, dizziness, and nausea after taking garcinia extract orally for one week. Ophthalmologic testing was consistent with adverse ocular effects, showing myopic shift with anterior chamber shallowing and swelling of retinal nerve fiber and macula. The patient reported taking a garcinia product containing hydroxycitric acid 500 mg three times daily, which was more than double the recommended dose per the product label. Symptoms resolved upon discontinuation of the garcinia extract and treatment with oral and topical steroids (102546).
Psychiatric ...Orally, garcinia supplements have been linked to several cases of mania. Typically, symptoms develop 1-8 weeks after starting garcinia. In a report of three patients, symptoms included reduced need for sleep, increased activities and spending, delusions of grandiosity, pressured speech, and agitation. Two of the patients were previously diagnosed with bipolar disorder, and use of garcinia was believed to precipitate episodes during stable phases of the disease. The third patient had no history of bipolar disorder, and use of garcinia was thought to possibly have unmasked previously undiagnosed primary bipolar disorder. In all three cases, recovery included discontinuation of garcinia (95568). In a separate case report, a 23-year-old male taking a specific combination product containing garcinia (Hydroxycut) 1-2 capsules daily for 1 month presented to the emergency room with mania. The patient had no history of bipolar disorder. Although the patient was started on risperidone and clonazepam, symptoms resolved following discontinuation of the supplement. Treatment was discontinued within 4 days of initiation, and the patient remained asymptomatic (95574). A 22-year-old female with no history of bipolar disorder developed mania and psychosis, presenting 10 days after starting Garcinia Cambogia Plus (Apex Vitality Health) 500-1500 mg daily, and Cleanse and Detox (Apex Vitality Health). The latter supplement contains raspberry ketones, licorice root, pumpkin seed, buckthorn root, Cascara sagrada, Irvingia gabonensis, rhubarb, pectin, Lactobacillus acidophilus, and aloe. Symptoms improved upon stopping the supplements and starting lithium and quetiapine (99421).
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, hoodia has been reported to cause minor adverse effects including disturbances of skin sensation, headache, dizziness, giddiness, and nausea (18052). There is also concern that hoodia may increase blood pressure and heart rate (18052).
Cardiovascular ...Orally, hoodia might increase blood pressure and heart rate. Clinical research in healthy women shows that intake of purified hoodia extract containing steroid glycosides increases systolic blood pressure by 5.9 to 15.9 mmHg, diastolic blood pressure by 4.6 to 11.5 mmHg, and heart rate by 4.8 to 12.4 beats per minute (18052).
Dermatologic ...Orally, hoodia extract has been reported to cause disturbances of skin sensation (18052).
Gastrointestinal ...Orally, hoodia extract has been reported to cause nausea (18052).
Neurologic/CNS ...Orally, hoodia extract has been reported to cause headache, dizziness, and giddiness (18052).
General
...Orally and topically, juniper seems to be generally well tolerated when used short-term in low doses.
However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Topically: Allergies, skin irritation.
Dermatologic ...Topically, juniper can cause skin irritation. Signs of topical poisoning include burning, erythema, inflammation with blisters, and edema (4). Repeated exposure to the juniper pollen can cause occupational allergies that affect the skin (6). In a case report, a 62-year-old woman developed burn-like blistering lesions after carrying juniper in close contact to her skin. Concurrent sun exposure was thought to worsen the skin irritation caused by juniper (103756).
Genitourinary ...Orally, large amounts of the juniper berry can cause purplish urine (4).
Pulmonary/Respiratory ...Repeated exposure to the juniper pollen can cause occupational allergies that affect the respiratory tract (6).
General
...Orally, Phaseolus vulgaris extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, flatulence, nausea, stomach pain, and vomiting.
Serious Adverse Effects (Rare):
Orally: Hypersensitivity reactions, including anaphylaxis, in sensitive individuals.
Dermatologic ...Topically, Phaseolus vulgaris may cause contact dermatitis in sensitive individuals. A case of occupational contact dermatitis characterized by pruritus, erythema, eczema, and dyspnea has been reported for a 41-year-old farmer who handled the green parts of Phaseolus vulgaris (29920).
Gastrointestinal ...Orally, an extract of the Phaseolus vulgaris variety white kidney bean, as well as alpha-amylase inhibitors isolated from Phaseolus vulgaris, might cause nausea, vomiting, diarrhea, flatulence, constipation, satiety, and stomach pains (11265,18223,29925,104874). Also, white kidney bean extract, taken orally along with carob gum, may cause constipation, flatulence, soft stools, and reduced levels of vitamin B12 and folic acid (10633). Consuming large amounts of raw or undercooked Phaseolus vulgaris beans or extract can cause nausea, vomiting, diarrhea, and gastroenteritis due to the content of phytohaemagglutinin, a plant protein lectin (18223,29916,93082). Cooking usually destroys lectins (18).
Immunologic ...Orally, Phaseolus vulgaris may cause hypersensitivity reactions, including anaphylaxis, in sensitive individuals. A case of severe anaphylactic shock requiring epinephrine and steroid treatment has been reported for a 23-year-old following ingestion of cooked kidney beans, a variety of Phaseolus vulgaris. The causative agents were reported to be phaseolin (vicilin) and phytohaemagglutinin (29918). Also, a case of angioedema resulting from type I hypersensitivity has been reported for a one-year-old child following inhalation of vapors from or ingestion of cooked white beans, another variety of Phaseolus vulgaris (29919).
General
...Orally, a thorough evaluation of safety outcomes for raspberry ketone has not been conducted.
Structurally, raspberry ketone resembles synephrine, a known stimulant agent.
Cardiovascular ...Structurally, raspberry ketone resembles synephrine, a known stimulant agent. Although not well studied in humans, stimulant-related side effects are possible. Orally, cases of heart palpitations, tachycardia, elevated blood pressure, coronary vasospasm are reported after taking raspberry ketone (17961,112386,112400). In one case report, pulseless electrical activity arrest followed by resistant polymorphic ventricular tachycardia occurred in a patient taking raspberry ketone. The arrhythmia resolved after numerous defibrillation shocks and placement of a temporary transvenous pacemaker with overdrive pacing (112386). In another case report, 5 episodes of ST elevation occurred over 2 days following ingestion of raspberry ketone (112400).
Neurologic/CNS ...Structurally, raspberry ketone resembles synephrine, a known stimulant agent. Although not well studied in humans, stimulant-related side effects are possible. Two case reports describe symptoms of sweating, diarrhea, and feelings of shakiness after oral use of raspberry ketone (17961,112400).
General
...Uva ursi is generally well tolerated in low doses, short-term.
Most Common Adverse Effects:
Orally: Diarrhea, nausea, stomach upset, and vomiting.
Serious Adverse Effects (Rare):
Orally: At high doses (20 grams of dried herb), uva ursi has been reported to cause collapse, convulsions, cyanosis, delirium, shortness of breath, and tinnitus. Very high doses of 30 grams or more may be fatal.
Gastrointestinal ...Orally, uva ursi may cause nausea, vomiting, diarrhea, and stomach upset (92148). It can also irritate the gastrointestinal tract (19).
Genitourinary ...Orally, uva ursi may cause the urine to be greenish-brown. It may also cause irritation and inflammation of the urinary tract mucous membranes (18).
Hepatic ...Uva ursi may be hepatotoxic. Theoretically, chronic use, especially in children, can cause liver impairment due its hydroquinone and high tannin content (4,18).
Neurologic/CNS ...Orally, around 20 grams of uva ursi is reported to supply up to one gram of hydroquinone, which can theoretically cause convulsions and delirium (4).
Ocular/Otic
...Orally, uva ursi may potentially cause retinal toxicity due to its hydroquinone content, which reduces melanin synthesis.
A 56-year-old female developed bilateral bull's-eye maculopathy, paracentral scotomas, and retinal thinning after 3 years of uva ursi tea ingestion (16900).
Taking around 20 grams of uva ursi orally is reported to supply up to one gram of hydroquinone, which can theoretically cause tinnitus (4).
Pulmonary/Respiratory ...Orally, around 20 grams of uva ursi is reported to supply up to one gram of hydroquinone, which can theoretically cause shortness of breath and cyanosis (4).
General
...Orally, vanadium is well tolerated when taken in amounts below the tolerable upper intake level (UL) of 1.
8 mg daily. Higher doses may cause adverse effects.
Most Common Adverse Effects:
Orally: Gastrointestinal adverse effects, including abdominal discomfort, diarrhea, flatulence, and nausea, when taken at doses above the UL.
Serious Adverse Effects (Rare):
Orally: Kidney damage, when taken long-term at high doses.
Topically: Contact dermatitis and other allergic reactions in sensitive individuals.
Cardiovascular ...Higher levels of vanadium in the body have been associated with a greater risk for hypertension (107923). However, it is unclear if oral supplementation with vanadium causes elevated blood pressure.
Dermatologic ...Allergic reactions to vanadium metal have been reported (99051,102095). A 68-year-old female developed an itchy, erythematous rash, ocular pruritus, and a positive skin test to vanadium after implantation of a vanadium-containing knee prosthesis (99051). Contact dermatitis, presenting as pruritic eczema of the hand, and a positive skin patch test to vanadium was reported in a 39-year-old male who worked with vanadium-containing tools (102095).
Endocrine ...In some cases, patients with diabetes have used very high doses (100 mg daily) safely for up to 4 weeks (3055,3056,3057). However, high body levels of vanadium have been associated with an increased incidence malnutrition-related diabetes mellitus (3020).
Gastrointestinal ...Orally, vanadium most commonly causes mild gastrointestinal upset (7135). There is concern that taking doses exceeding the tolerable upper intake level (UL) of 1.8 mg per day can increase the risk of gastrointestinal side effects and possibly lead to more severe toxicity. At higher doses, vanadium frequently causes gastrointestinal effects including abdominal discomfort, diarrhea, nausea, and flatulence (3012,3055,3056,3057,12557,12558). Doses of 22.5 mg daily can also cause cramps (3012). Vanadium has also been associated with green discoloration of the tongue, which is unrelated to dose (7135).
Immunologic
...Allergic reactions to vanadium metal have been reported (99051,102095).
A 68-year-old female developed an itchy, erythematous rash, ocular pruritus, and a positive skin test to vanadium after implantation of a vanadium-containing knee prosthesis (99051). Contact dermatitis, presenting as pruritic eczema of the hand, and a positive skin patch test to vanadium was reported in a 39-year-old male who worked with vanadium-containing tools (102095).
Higher levels of vanadium in the body have been associated with a weakened immune system in children, as measured by reductions in CD3+ and CD4+ cell counts (107924). However, it is unclear if oral supplementation with vanadium causes a weakened immune system or increases the risk of infection.
Neurologic/CNS ...Orally, vanadium has been rarely associated with fatigue, lethargy, and focal neurological lesions, which are unrelated to dose (7135).
Pulmonary/Respiratory ...Severe and chronic respiratory tract disorders have been reported from occupational exposure to vanadium dusts (17).
Renal ...In some cases, patients with diabetes have used very high doses (100 mg daily) of vanadium safely for up to 4 weeks (3055,3056,3057). However, there is concern based on animal research that prolonged use of high doses might cause serious side effects including kidney damage (7135). High body levels of vanadium have also been associated with an increased incidence of kidney stones, distal renal tubular acidosis, hypokalemic periodic paralysis, and sudden unexplained nocturnal death (3020).
General
...Orally and intravenously, vinpocetine seems to be well tolerated.
Most Common Adverse Effects:
Orally: Anxiety, dizziness, headache, flushing, gastric discomfort, sleep disturbances, and urticaria.
Serious Adverse Effects (Rare):
Orally: Agranulocytosis, arrhythmias, and seizures.
Intravenously: Arrhythmias.
Cardiovascular ...Orally, tachycardia, multifocal extra systoles, transient hypotension and hypertension, and palpitations have been reported with vinpocetine in clinical trials (1789,82118,82152,92936). One case of severe hypotension has been reported with oral vinpocetine (106845). Vinpocetine has also been reported to cause atrial fibrillation and ventricular arrhythmias, with the highest incidence occurring after intravenous or intramuscular administration (1789,82128,68753,82123).
Dermatologic ...Orally, vinpocetine has been reported to cause flushing, skin rash, and urticaria (82118,82120,82153,106845). Intravenously, vinpocetine has been associated with one report of allergic dermatitis (98226).
Gastrointestinal ...Orally, gastric discomfort, upper abdominal pain, nausea, diarrhea, constipation, vomiting, heartburn, difficulty swallowing, and dry mouth have been reported with vinpocetine (1787,1789,10061,10221,82120,82154,82155,92936,106845). Intravenously, diarrhea has been reported with vinpocetine (98226).
Hematologic ...Orally, vinpocetine has been associated with one case report of agranulocytosis (82156) and one case report of ecchymoma of the eyelid in a 60-year-old male 12 hours after a botulinum toxin injection. The patient had been taking vinpocetine 30 mg daily and aspirin 100 mg daily (112878).
Neurologic/CNS ...Orally, anxiety, drowsiness, headache, sleep disturbance, nervousness, excitation, hyperirritability, epileptiform convulsion, and vertigo have been reported with vinpocetine (1787,10221,68772,82118,82120,82151,82152,82154,92936,106845). Intravenously, dizziness has been reported with vinpocetine (98226).
Ocular/Otic ...Orally, vinpocetine has been associated with one case of eyelid edema (106845). Also, one case reports ecchymoma of the eyelid in a 60-year-old male 12 hours after a botulinum toxin injection. The patient had been taking vinpocetine 30 mg daily and aspirin 100 mg daily (112878).
Pulmonary/Respiratory ...Orally, vinpocetine has been associated with one case of severe dyspnea (106845).
