Each tablet contains: Selenium (as sodium selenite) 100 mcg • Fenugreek seed extract 150 mg • Marshmallow root extract 50 mg • Mullein leaf powder (verbascum thapsus) 50 mg • Chinese Skullcap leaf powder 45 mg • Para-Aminobenzoic Acid 25 mg • Watercress leaf powder 25 mg • Garlic bulb powder (allium sativum) 20 mg • Onion powder 20 mg • Pleurisy root 20 mg • Turnip powder 20 mg • Cascara Sagrada root 15 mg • Coltsfoot aerial 5 mg • Pau d'Arco root 5 mg • Thyme aerial 5 mg • Proprietary Blend 102 mg: Licorice root, Alfalfa leaf, Cayenne fruit extract, Bioperene brand Black Pepper fruit extract (95% piperine).
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Respiratory Cleanse & Defense. 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
There is insufficient reliable information available about the effectiveness of coltsfoot.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
There is insufficient reliable information available about the effectiveness of pleurisy root.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
There is insufficient reliable information available about the effectiveness of watercress.
Below is general information about the safety of the known ingredients contained in the product Respiratory Cleanse & Defense. 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 the leaves are used orally and appropriately, short-term (4,6,12).
LIKELY UNSAFE ...when large amounts are used long-term. Chronic ingestion of alfalfa has been associated with drug-induced lupus effects (381,14828,30602).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Alfalfa contains constituents with possible estrogenic activity (4,11,30592).
POSSIBLY SAFE ...when used orally and appropriately, short-term. Oral Baikal skullcap 0.5-3.52 grams daily has been used with apparent safety for up to 8 weeks (92776,101738,101739,110023). However, a high quality assessment of safety has not been conducted. A specific product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been associated with an increased risk for liver and lung injury. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination. There is insufficient reliable information available about the safety of Baikal skullcap when used intravenously or topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Black pepper has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when black pepper oil is applied topically. Black pepper oil is nonirritating to the skin and is generally well tolerated (11). ...when black pepper oil is inhaled through the nose or as a vapor through the mouth, short-term. Black pepper oil as a vapor or as an olfactory stimulant has been used with apparent safety in clinical studies for up to 3 days and 30 days, respectively (29159,29160,29161,90502). There is insufficient reliable information available about the safety of black pepper when used orally in medicinal amounts.
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
CHILDREN: POSSIBLY UNSAFE
when used orally in large amounts.
Fatal cases of pepper aspiration have been reported in some patients (5619,5620). There is insufficient reliable information available about the safety of topical pepper oil when used in children.
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
PREGNANCY: LIKELY UNSAFE
when used orally in large amounts.
Black pepper might have abortifacient effects (11,19); contraindicated. There is insufficient reliable information available about the safety of topical pepper when used during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
There is insufficient reliable information available about the safety of black pepper when used in medicinal amounts during breast-feeding.
LIKELY SAFE ...when used orally in amounts typically found in food. Capsicum has Generally Recognized as Safe (GRAS) status in the US (4912). ...when used topically and appropriately (7038,10650,105345). The active capsicum constituent capsaicin is an FDA-approved ingredient used in certain over-the-counter, topical preparations (272).
POSSIBLY SAFE ...when used orally and appropriately, short-term in medicinal amounts. A specific sustained-release chili extract (Capsifen) has been used safely in doses of up to 200 mg daily, for up to 28 days (105196). ...when used intranasally and appropriately, short-term. Capsicum-containing nasal sprays, suspensions, and swabs seem to be safe when applied multiple times over 24 hours or when applied daily or every other day for up to 14 days. Although no serious side effects have been reported in clinical trials, intranasal application of capsicum-containing products can be very painful (14322,14324,14328,14329,14351,14352,14353,14356,14357) (14358,14359,14360,15016,105204). POSSIBLY UNSAFE when used orally, long-term or in high doses. There is concern that long-term use or use of excessive doses might be linked to hepatic or kidney damage, as well as hypertensive crisis (12404,40569,40606). There is insufficient reliable information available about the safety of capsicum when injected.
CHILDREN: POSSIBLY UNSAFE
when used topically in children under 2 years old (272).
There is insufficient reliable information available about the safety of capsicum when used orally in children.
PREGNANCY: LIKELY SAFE
when used topically and appropriately (272).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term.
Capsicum 5 mg daily has been used for up to 28 days during the latter half of the second trimester and the third trimester (96457).
LACTATION: LIKELY SAFE
when used topically and appropriately (272).
LACTATION: POSSIBLY UNSAFE
when used orally.
Dermatitis can sometimes occur in infants when foods heavily spiced with capsicum peppers are ingested during lactation (739). Also, observational research suggests that intake of raw capsicum peppers during pregnancy is associated with an increased risk of sensitization to inhalant allergens in children by the age of 2 years (41021).
POSSIBLY SAFE ...when used orally and appropriately, short-term. Cascara sagrada seems to be safe when used for less than one week (272,25023,40087). Cascara sagrada was formerly approved by the US Food and Drug Administration (FDA) as a safe and effective over-the-counter (OTC) laxative, but this designation was removed in 2002 due to a lack of supporting evidence (8229).
POSSIBLY UNSAFE ...when used orally, long-term. Using cascara sagrada for more than 1-2 weeks can lead to dependence, electrolyte loss, and hypokalemia (272).
CHILDREN: POSSIBLY UNSAFE
when used orally in children.
Cascara sagrada should be used cautiously in children due to the risk of electrolyte loss and hypokalemia (272).
PREGNANCY:
Insufficient reliable information available; avoid using.
LACTATION: POSSIBLY UNSAFE
when used orally.
Cascara sagrada is excreted into breast milk and might cause diarrhea (272).
LIKELY UNSAFE ...when products containing hepatotoxic pyrrolizidine alkaloid (PA) constituents are used orally. Repeated exposure to low concentrations of hepatotoxic PAs can cause severe veno-occlusive disease. Hepatotoxic PAs might also be carcinogenic and mutagenic (12841,12842). Dietary supplement products sold in the US are not required to include the amount of PAs they may contain; therefore, all preparations used orally containing coltsfoot should be considered potentially unsafe (3484). Tell patients not to use coltsfoot preparations that are not certified and labeled as hepatotoxic PA-free.
PREGNANCY: LIKELY UNSAFE
when products containing hepatotoxic pyrrolizidine alkaloid (PA) constituents are used orally.
Coltsfoot preparations containing hepatotoxic pyrrolizidine alkaloid (PA) constituents might be teratogenic and hepatotoxic (575,12841,12842). There is one case report of fatal hepatic veno-occlusive disease in a neonate associated with regular maternal consumption during pregnancy of an herb tea containing several pyrrolizidine alkaloid herbs, including coltsfoot (575). There is insufficient reliable information available about the safety of using coltsfoot products certified and labeled as hepatotoxic PA-free during pregnancy; avoid using.
LACTATION: LIKELY UNSAFE
when used orally.
Hepatotoxic pyrrolizidine alkaloid (PA) constituents in coltsfoot are excreted in milk (12841,12842). There is insufficient reliable information available about the safety of using coltsfoot products certified and labeled as hepatotoxic PA-free during lactation; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Fenugreek has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when the seed is used orally in medicinal amounts. Fenugreek seed powder 5-10 grams daily has been used with apparent safety for up to 3 years. Fenugreek seed extract 1 gram daily has been used with apparent safety for up to 3 months (7389,9783,18359,18362,49868,90112,90113,90117,93419,93420)(93421,93422,93423,96065,103285,108704).
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (4912).
There is insufficient reliable information available about the safety of fenugreek when used in larger amounts. Unusual body and urine odor has been reported after consumption of fenugreek tea. Although the odor appears to be harmless, it may be misdiagnosed as maple syrup urine disease (9782,96068).
PREGNANCY: LIKELY UNSAFE
when used orally in amounts greater than those found in food.
Fenugreek has potential oxytoxic and uterine stimulant activity (12531). There are case reports of congenital malformations, including hydrocephalus, anencephaly, cleft palate, and spina bifida, after consumption of fenugreek seeds during pregnancy (96068). Consumption of fenugreek immediately prior to delivery may cause the neonate to have unusual body odor. Although this does not appear to cause long-term sequelae, it may be misdiagnosed as maple syrup urine disease (9781,96068).
LACTATION: POSSIBLY SAFE
when used orally to stimulate lactation, short-term.
Although most available clinical studies lack safety testing in the lactating parent or infant (12535,22569,22570), some evidence suggests that taking fenugreek 1725 mg three times daily orally for 21 days does not cause negative side effects in the infant (90115).
LIKELY SAFE ...when used orally and appropriately. Garlic has been used safely in clinical studies lasting up to 7 years without reports of significant toxicity (1873,4782,4783,4784,4785,4786,4787,4789,4790,4797)(4798,6457,6897,14447,96008,96009,96014,102016,102670,103479)(107238,107239,107352,108607,110722,111763,114892).
POSSIBLY SAFE ...when used topically. Garlic-containing gels, lipid-soluble garlic extracts, garlic pastes, and garlic mouthwashes have been safely used in clinical research for up to 3 months (4766,4767,8019,15030,51330,51386). ...when used intravaginally. A vaginal cream containing garlic and thyme has been safely used nightly for 7 nights (88387).
POSSIBLY UNSAFE ...when raw garlic is used topically (585). Raw garlic might cause severe skin irritation when applied topically.
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (3319).
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Garlic is reported to have abortifacient activity (11020). One study also suggests that garlic constituents are distributed to the amniotic fluid after a single dose of garlic (4828). However, there are no published reports of garlic adversely affecting pregnancy. In clinical research, garlic 800 mg daily was used during the third trimester of pregnancy with no reported adverse outcomes (9201,51626). There is insufficient reliable information available about the safety of topical garlic during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (3319).
LACTATION: POSSIBLY UNSAFE
when used orally in amounts greater than those found in foods.
Several small studies suggest that garlic constituents are secreted in breast milk, and that nursing infants of mothers consuming garlic are prone to extended nursing (3319,4829,4830). There is insufficient reliable information available about the safety of topical garlic during lactation.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately for up to 8 weeks.
Garlic extract 300 mg three times daily has been used with apparent safety for up 8 weeks in children ages 8-18 years (4796). There is insufficient reliable information available about the safety of garlic when used over longer durations or in higher doses.
CHILDREN: POSSIBLY UNSAFE
when raw garlic is used topically.
Raw garlic might cause severe skin irritation when applied topically (585,51210).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Licorice has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes. Licorice flavonoid oil 300 mg daily for 16 weeks, and deglycyrrhizinated licorice products in doses of up to 4.5 grams daily for up to 16 weeks, have been used with apparent safety (6196,11312,11313,17727,100984,102960). ...when licorice products containing glycyrrhizin are used orally in low doses, short-term. Licorice extract 272 mg, containing glycyrrhizin 24.3 mg, has been used daily with apparent safety for 6 months (102961). A licorice extract 1000 mg, containing monoammonium glycyrrhizinate 240 mg, has been used daily with apparent safety for 12 weeks (110320). In addition, a syrup providing licorice extract 750 mg has been used twice daily with apparent safety for 5 days (104558). ...when applied topically. A gel containing 2% licorice root extract has been applied to the skin with apparent safety for up to 2 weeks. (59732). A mouth rinse containing 5% licorice extract has been used with apparent safety four times daily for up to one week (104564).
POSSIBLY UNSAFE ...when licorice products containing glycyrrhizin are used orally in large amounts for several weeks, or in smaller amounts for longer periods of time. The European Scientific Committee on Food recommends that a safe average daily intake of glycyrrhizin should not exceed 10 mg (108577). In otherwise healthy people, consuming glycyrrhizin daily for several weeks or longer can cause severe adverse effects including pseudohyperaldosteronism, hypertensive crisis, hypokalemia, cardiac arrhythmias, and cardiac arrest. Doses of 20 grams or more of licorice products, containing at least 400 mg glycyrrhizin, are more likely to cause these effects; however, smaller amounts have also caused hypokalemia and associated symptoms when taken for months to years (781,3252,15590,15592,15594,15596,15597,15599,15600,16058)(59731,59740,59752,59785,59786,59787,59792,59795,59805,59811)(59816,59818,59820,59822,59826,59828,59849,59850,59851,59867)(59882,59885,59888,59889,59895,59900,59906,97213,110305). In patients with hypertension, cardiovascular or kidney conditions, or a high salt intake, as little as 5 grams of licorice product or 100 mg glycyrrhizin daily can cause severe adverse effects (15589,15593,15598,15600,59726).
PREGNANCY: UNSAFE
when used orally.
Licorice has abortifacient, estrogenic, and steroid effects. It can also cause uterine stimulation. Heavy consumption of licorice, equivalent to 500 mg of glycyrrhizin per week (about 250 grams of licorice per week), during pregnancy seems to increase the risk of delivery before gestational age of 38 weeks (7619,10618). Furthermore, high intake of glycyrrhizin, at least 500 mg per week, during pregnancy is associated with increased salivary cortisol levels in the child by the age of 8 years. This suggests that high intake of licorice during pregnancy may increase hypothalamic-pituitary-adrenocortical axis activity in the child (26434); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when marshmallow root and leaf are used in amounts commonly found in foods. Marshmallow root has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
POSSIBLY SAFE ...when marshmallow root and leaf are used orally in medicinal amounts (4,12). ...when used topically (4,62020). There is insufficient reliable information available about the safety of marshmallow flower.
PREGNANCY AND LACTATION:
Insufficient reliable information available.
LIKELY SAFE ...when consumed in amounts commonly found in foods. Onion has Generally Recognized as Safe (GRAS) status in the US (4912). ...when onion extract is used topically (66742,66883,66895,66903,67089,95151,95154,95156).
POSSIBLY SAFE ...when onion extract is used orally and appropriately (2). Onion extract has been used safely in doses of 300 mg three times daily for up to 12 weeks (95149,101747).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using in amounts greater than used in foods.
LIKELY SAFE ...when used topically and appropriately. PABA is FDA approved for topical use and there have not been reports of significant toxicity (266,272).
POSSIBLY SAFE ...when used orally and appropriately (10). PABA is an FDA-approved drug, but some potentially serious side effects have been reported (10).
POSSIBLY UNSAFE ...when used orally in high doses. Doses greater than 12 grams per day have been associated with leukopenia (1061).
CHILDREN: LIKELY SAFE
when used topically and appropriately (266,272).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately (10).
PABA is an FDA-approved drug for use in children, but serious side effects have been reported (10).
CHILDREN: POSSIBLY UNSAFE
when used orally in high doses.
Doses greater than 220 mg/kg/day have been associated with fatal toxic effects (1061).
PREGNANCY AND LACTATION: LIKELY SAFE
when used topically and appropriately (266,272).
There is insufficient reliable information available about the safety of the oral use of PABA during pregnancy and breast-feeding; avoid using.
POSSIBLY UNSAFE ...when used orally. The safety of pau d'arco in typical doses is unclear. Serious toxicities have been found with high doses of the lapachol constituent (91939). In patients with cancer, doses of lapachol above 1.5 grams daily were associated with significant gastrointestinal toxicities and an increased risk of bleeding (91939). However, in patients with dysmenorrhea, doses of pau d'arco 1050 mg plus rutin 75 mg daily for up to 8 weeks did not lead to serious adverse effects (114012). There is insufficient reliable information available about the safety of pau d'arco when used topically.
PREGNANCY: POSSIBLY UNSAFE
when used orally in typical doses.
Animal studies have found that lapachol, a constituent of pau d'arco, has teratogenic and abortifacient effects (68314,68315); avoid using. There is insufficient reliable information available about the safety of pau d'arco when used topically in pregnancy; avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY UNSAFE ...when used orally. Pleurisy root contains digitalis-like cardenolide glycosides (4). When taken in large doses, it can cause digitalis-like poisoning symptoms (18). Canadian regulations do not allow pleurisy root as an ingredient in oral products (12).
PREGNANCY: UNSAFE
when used orally (12).
Pleurisy root might have uterine stimulant and estrogenic activity (19).
LACTATION: POSSIBLY UNSAFE
when used orally (12); avoid using.
LIKELY SAFE ...when used orally and appropriately. Selenium appears to be safe when taken short-term in amounts below the tolerable upper intake level (UL) of 400 mcg daily (4844,7830,7831,7836,7841,9724,9797,14447,17510,17511)(17512,17513,17515,17516,97087,97943,109085); however, there is concern that taking selenium long-term might not be safe. Some evidence shows that consuming a diet containing more than the recommended dietary allowance (RDA) of selenium, which is 55 mcg daily for most adults, is associated with an increased risk for developing type 2 diabetes (99661). Some evidence also shows that taking a selenium supplement 200 mcg daily for an average of 3-8 years increases the risk of developing type 2 diabetes (97091,99661). Higher serum levels of selenium are also associated with an increased risk of developing diabetes and increased mortality (16710,99661). ...when used intravenously. Selenium, as selenious acid, is an FDA-approved drug. Sodium selenite intravenous infusions up to 1000 mcg daily have been safely used for up to 28 days (90347,92910).
POSSIBLY UNSAFE ...when used orally in high doses or long-term. Doses above 400 mcg daily can increase the risk of developing selenium toxicity (4844,7825). Additionally, some evidence shows that consuming a diet containing more than the recommended dietary allowance (RDA) of selenium, which is 55 mcg daily for most adults, is associated with an increased risk for developing type 2 diabetes (99661). There is also concern that taking a selenium supplement 200 mcg daily long-term, for an average of 3-8 years, increases the risk of developing type 2 diabetes (99661). Higher serum levels of selenium are also associated with an increased risk of developing diabetes and increased mortality (16710,99661).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
Selenium seems to be safe when used short-term in doses below the tolerable upper intake level (UL) of 45 mcg daily for infants up to age 6 months, 60 mcg daily for infants 7 to 12 months, 40-90 mcg daily for children 1 to 3 years, 100-150 mcg daily for children 4 to 8 years, 200-280 mcg daily for children 9 to 13 years, and 400 mcg daily for children age 14 years and older (4844,86095); however, there is some concern that long-term use might not be safe. ...when used via a nasogastric tube in premature infants (7835,9764).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately.
Selenium appears to be safe when used short-term in amounts that do not exceed the tolerable upper intake level (UL) of 400 mcg daily (4844,17507,74419,74481,74391); however, there is concern that long-term use might not be safe.
PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive doses.
Doses above 400 mcg daily may cause significant toxicity (4844).
LACTATION: POSSIBLY SAFE
when used orally and appropriately.
Selenium appears to be safe when used short-term in amounts that do not exceed the tolerable upper intake level (UL) of 400 mcg daily when taken short-term (4844,74467); however, there is concern that long-term use might not be safe.
LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
Doses above 400 mcg daily may cause significant toxicity (4844,7838). ...when used orally in HIV-positive women. Selenium supplementation in HIV-positive women not taking highly active antiretroviral therapy may increase HIV-1 levels in breast milk (90358).
LIKELY SAFE ...when used in amounts commonly found in foods. Thyme has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when thyme is used orally and appropriately in supplemental amounts. Orally, thyme, in combination with other herbs, has been used safely for up to 23 days (13557,49219,49223,78133). ...when diluted thyme oil is used topically, short-term. Diluted thyme oil has been used with apparent safety for up to 7 months (5177). There is insufficient reliable information available about the safety of thyme oil when used orally or when inhaled.
CHILDREN: LIKELY SAFE
when used in amounts commonly found in foods.
Thyme has Generally Recognized as Safe (GRAS) status in the US (4912).
CHILDREN: POSSIBLY SAFE
when thyme is used orally in medicinal amounts in combination with English ivy.
Thyme has been used with apparent safety in combination with English ivy for up to 10 days (78181).
There is insufficient reliable information available about the safety of thyme oil when used orally or topically in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when used in amounts commonly found in foods.
Thyme has Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of thyme when used in medicinal amounts during pregnancy and breast-feeding; avoid using.
LIKELY SAFE ...when consumed in amounts commonly found in foods.
POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. Watercress extract 750 mg/kg daily has been used with apparent safety for up to 5 weeks (103891).
POSSIBLY UNSAFE ...when used orally in excessive amounts or long-term (8,12,19). Watercress can cause gastric mucosal irritation (8,12,85599) or damage (19).
CHILDREN: LIKELY UNSAFE
when used orally in medicinal amounts; avoid using in children younger than 4 years old (12,19).
PREGNANCY: LIKELY UNSAFE
when used in medicinal amounts.
Watercress might stimulate menstruation or have abortifacient effects (19).
LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Respiratory Cleanse & Defense. 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, alfalfa might increase the risk of hypoglycemia when taken with antidiabetes drugs.
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Theoretically, alfalfa might interfere with the activity of contraceptive drugs.
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Theoretically, alfalfa might interfere with hormone therapy.
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Theoretically, alfalfa might decrease the efficacy of immunosuppressive therapy.
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Theoretically, concomitant use of alfalfa with photosensitizing drugs might have additive effects.
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Animal research suggests that excessive doses of alfalfa may increase photosensitivity, possibly due to its chlorophyll content (106043). It is unclear if this effect would be clinically relevant in humans.
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Theoretically, alfalfa might reduce the anticoagulant activity of warfarin.
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Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol.
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In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.
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Theoretically, Baikal skullcap might increase the risk of bleeding when used concomitantly with anticoagulant and antiplatelet drugs.
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Preliminary clinical research suggests that taking capsules containing a combination of astragalus, goldthread, and Baikal skullcap daily for 4 weeks inhibits platelet aggregation; the effect seems to be similar to that of aspirin 50 mg daily (33075). It is unclear if this effect is due to Baikal skullcap, other ingredients, or the combination.
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Theoretically, concomitant use of Baikal skullcap with antidiabetes drugs might enhance blood glucose lowering effects.
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Baicalein, a constituent of Baikal skullcap, has alpha-glucosidase inhibitory activity in vitro (6292). Animal research also suggests that Baikal skullcap enhances the antidiabetic effects of metformin (33408). However, in a small human study, taking Baikal skullcap extract did not enhance the antidiabetic effects of metformin, although it did modestly lower glucose levels during an oral glucose tolerance test (OGTT) (101738). Until more is known, use cautiously.
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Theoretically, concomitant use of Baikal skullcap with antihypertensive drugs might have additive effects and increase the risk of hypotension.
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Animal research suggests that baicalein, a constituent of Baikal skullcap, might lower blood pressure (33374).
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Theoretically, concomitant use of Baikal skullcap and antithyroid drugs may result in additive activity and increase the risk of hypothyroidism.
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In an animal hyperthyroid model, Baikal skullcap improved levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) (101736). The clinical significance of this effect is unclear.
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Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties.
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In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.
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Theoretically, Baikal skullcap may increase levels of drugs metabolized by CYP1A2 enzymes.
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Theoretically, Baikal skullcap might increase levels of drugs metabolized by CYP2C19 enzymes.
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In vitro evidence suggest that wogonin, a constituent of Baikal skullcap, modestly inhibits the activity of CYP2C19 enzymes (33484). This effect has not been reported in humans.
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Theoretically, concomitant use of large amounts of Baikal skullcap might interfere with hormone replacement therapy, due to competition for estrogen receptors.
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In vitro evidence suggests that Baikal skullcap has estrogenic activity (16061).
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Theoretically, Baikal skullcap might reduce lithium excretion and increase serum levels of lithium.
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Baikal skullcap is thought to have diuretic properties, which may reduce lithium excretion (5541). The dose of lithium might need to be decreased.
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Theoretically, Baikal skullcap might alter the levels and clinical effects of OATP substrates.
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Some pharmacokinetic research shows that baicalin, a constituent of Baikal skullcap, can decrease plasma levels of rosuvastatin. The mechanism is thought to involve stimulation of the activity of the organic anion-transporting polypeptide 1B1 (OATP1B1), which transports rosuvastatin into the liver. This decreases plasma levels of the drug, but increases levels at the site of action in the liver. The degree to which rosuvastatin levels are affected depends on the OATP1B1 haplotype of the individual (16395). Baikal skullcap might also affect other OATP1B1 substrates (16396,16397,16398).
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Theoretically, Baikal skullcap might increase levels of drugs transported by P-glycoprotein.
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Theoretically, black pepper might increase the effects and side effects of amoxicillin.
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Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin (29269). This has not been reported in humans.
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Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.
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In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation (29206). This has not been reported in humans.
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Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
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Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels (29225). Monitor blood glucose levels closely. Dose adjustments might be necessary.
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Theoretically, black pepper might increase blood levels of atorvastatin.
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Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold (104188). This has not been reported in humans.
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Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.
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One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects (16833). In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner (103819).
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Theoretically, black pepper might increase the effects and side effects of cyclosporine.
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In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine (29282). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP1A1.
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In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP1A1 (29213). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP2B1.
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In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP2B1 (29332). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
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Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.
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Black pepper is thought to have diuretic properties (11).
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Black pepper might increase blood levels of nevirapine.
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Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study (29209).
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Theoretically, black pepper might increase levels of P-glycoprotein substrates.
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Theoretically, black pepper might increase the sedative effects of pentobarbital.
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Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time (29214).
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Black pepper might increase blood levels of phenytoin.
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Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin (537,14442). Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin (14375). Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper (14442).
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Black pepper might increase blood levels of propranolol.
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Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol (538).
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Black pepper might increase blood levels of rifampin.
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Black pepper might increase blood levels of theophylline.
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Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline (538).
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Theoretically, using topical capsaicin may increase the risk of ACE inhibitor-induced cough.
Details
There is one case report of a topically applied capsaicin cream contributing to the cough reflex in a patient using an ACEI (12414). However, it is unclear if this interaction is clinically significant.
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Theoretically, capsicum may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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In vitro research shows that capsicum might increase the effects of antiplatelet drugs (12406,12407). Also, population research shows that capsicum is associated with an increased risk of self-reported bleeding in patients taking warfarin (12405,20348). However, clinical research shows that taking a single dose of capsaicin (Asian Herbex Ltd.), the active ingredient in capsicum, 400-800 mcg orally in combination with aspirin 500 mg does not decrease platelet aggregation when compared with taking aspirin 500 mg alone. Also, there was no notable effect on measures of platelet aggregation with capsaicin (92990). It is unclear whether capsaicin must be used in more than a single dose to affect platelet aggregation.
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Theoretically, taking capsicum with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Preliminary clinical research shows that consuming capsicum 5 grams along with a glucose drink attenuates the rise in plasma glucose after 30 minutes by 21%, decreases the 2-hour postprandial area under the curve of plasma glucose by 11%, and increases the 2-hour postprandial area under the curve of plasma insulin by 58% in healthy individuals when compared with placebo (40453,40614). Other clinical research shows that taking capsicum 5 mg daily for 28 days significantly reduces postprandial blood glucose and insulin levels, but not fasting blood glucose and insulin levels, in patients with gestational diabetes (96457).
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Theoretically, taking capsicum with aspirin might reduce the bioavailability of aspirin.
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Animal research shows that acute or chronic intake of capsicum pepper reduces oral aspirin bioavailability (22617). This has not been shown in humans.
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Theoretically, taking capsicum with ciprofloxacin might increase levels and adverse effects of ciprofloxacin.
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Animal research shows that concomitant use of capsaicin, the active constituent of capsicum, and ciprofloxacin increases the bioavailability of ciprofloxacin by up to 70% (22613).
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Theoretically, taking capsicum with theophylline might increase the levels and adverse effects of theophylline.
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Theoretically, cascara sagrada might increase the risk of hypokalemia when taken with corticosteroids.
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Theoretically, cascara sagrada might decrease the effects of CYP3A4 substrates.
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In vitro research suggests that cascara sagrada can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer (110704).
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Theoretically, cascara sagrada might cause hypokalemia, potentially increasing the risk of digoxin toxicity.
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Theoretically, cascara sagrada might increase the risk of hypokalemia when taken with diuretic drugs.
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Theoretically, cascara sagrada might have additive adverse effects when taken with stimulant laxatives.
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Cascara sagrada has stimulant laxative effects and might compound fluid and electrolyte losses when taken with stimulant laxatives (19).
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Theoretically, cascara sagrada might increase the risk of bleeding when taken with warfarin.
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Cascara sagrada has stimulant laxative effects (19). In some people, cascara sagrada can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding.
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Concomitant use might increase the risk of bleeding due to decreased platelet aggregation. Coltsfoot has been reported to inhibit platelet aggregation (12864); avoid concomitant use. Some of these drugs include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), warfarin (Coumadin), and others.
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Theoretically, excessive doses of coltsfoot may interfere with antihypertensive or cardiovascular therapy (12858).
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Hepatotoxic pyrrolizidine alkaloids (PA) are substrates of cytochrome P450 3A4 (CYP3A4) (12841,12860). Theoretically, drugs that induce CYP3A4 might increase the conversion of PAs to toxic metabolites. Some drugs that induce CYP3A4 include carbamazepine (Tegretol), phenobarbital, phenytoin (Dilantin), rifampin, rifabutin (Mycobutin), and others.
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Theoretically, fenugreek might have additive effects when used with anticoagulant or antiplatelet drugs.
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Some of the constituents in fenugreek have antiplatelet effects in animal and in vitro research. However, common fenugreek products might not contain sufficient concentrations of these constituents for clinical effects. A clinical study in patients with coronary artery disease or diabetes shows that taking fenugreek seed powder 2.5 grams twice daily for 3 months does not affect platelet aggregation, fibrinolytic activity, or fibrinogen levels (5191,7389,49643).
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Theoretically, fenugreek seed might have additive hypoglycemic effects when used with antidiabetes drugs.
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Theoretically, fenugreek seed might alter the clinical effects of clopidogrel by inhibiting its conversion to the active form.
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Animal research shows that fenugreek seed 200 mg/kg daily for 14 days increases the maximum serum concentration of clopidogrel by 21%. It is unclear how this affects the pharmacokinetics of the active metabolite of clopidogrel; however, this study found that concomitant use of fenugreek seed and clopidogrel prolonged bleeding time by an additional 11% (108701).
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Theoretically, fenugreek seed might have additive hypotensive effects when used with metoprolol.
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Animal research shows that fenugreek seed 300 mg/kg daily for 2 weeks decreases systolic and diastolic blood pressure by 9% and 11%, respectively, when administered alone, and by 15% and 22%, respectively, when given with metoprolol 10 mg/kg (108703).
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Theoretically, fenugreek might decrease plasma levels of phenytoin.
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Animal research shows that taking fenugreek seeds for 1 week decreases maximum concentrations and the area under the curve of a single dose of phenytoin by 44% and 72%, respectively. This seems to be related to increased clearance (110905). So far, this interaction has not been reported in humans.
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Theoretically, concurrent use of sildenafil and fenugreek might reduce levels and therapeutic effects of sildenafil.
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Animal research shows that taking fenugreek seeds for 1 week reduces maximum concentrations and the area under the curve of a single dose of sildenafil by 27% and 48%, respectively (110898). So far, this interaction has not been reported in humans.
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Theoretically, fenugreek may reduce the levels and clinical effects of theophylline.
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Animal research shows that fenugreek 50 grams daily for 7 days reduces the maximum serum concentration (Cmax) of theophylline by 28% and the area under the plasma drug concentration-time curve (AUC) by 22% (90118).
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Theoretically, fenugreek might have additive effects with warfarin and increase the international normalized ratio (INR).
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Garlic may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Theoretically, taking garlic with antidiabetes drugs might increase the risk of hypoglycemia.
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Theoretically, taking garlic with antihypertensive drugs might increase the risk of hypotension.
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Theoretically, garlic might decrease levels and effects of atazanavir.
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In a case report, a patient consuming six stir-fried garlic cloves three times weekly developed suboptimal atazanavir levels and increases in HIV viral load. While the exact cause of this interaction is unclear, there is speculation that garlic might decrease the intestinal absorption of atazanavir or increase its metabolism by inducing cytochrome P450 3A4 (CYP3A4) (88388). Until more is known, advise patients not to consume large amounts of garlic while taking atazanavir.
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Garlic might increase levels of drugs metabolized by CYP2E1.
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Clinical research suggests garlic oil can inhibit the activity of CYP2E1 by 39% (10847). Use garlic oil cautiously in patients taking drugs metabolized by these enzymes.
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Theoretically, garlic products containing allicin might induce intestinal CYP3A4 and inhibit hepatic CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
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Some human research suggests that garlic may induce INTESTINAL CYP3A4, reducing levels of drugs metabolized by this enzyme. This is primarily based on a study showing that taking a specific allicin-containing garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induced CYP3A4 in the gut mucosa (7027,93578). Another study shows that giving docetaxel intravenously, bypassing the CYP3A4 enzymes in the gut mucosa, along with the same specific garlic product for 12 consecutive days, does not affect docetaxel levels (17221). Conversely, there is concern that garlic may inhibit HEPATIC CYP3A4. In a single case report, increased tacrolimus levels and liver injury occurred in a liver transplant patient after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days (96010). Several other studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506).
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Theoretically, garlic might decrease levels of isoniazid.
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Animal research suggests that an aqueous extract of garlic reduces isoniazid levels by about 65%. Garlic reduced the maximum concentration (Cmax) and area under the curve (AUC), but not the half-life, of isoniazid. This suggests that garlic extract might inhibit isoniazid absorption across the intestinal mucosa (15031); however, the exact mechanism of this potential interaction is not known.
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Theoretically, garlic products containing allicin might decrease levels of PIs.
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Protease inhibitors are metabolized by cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4, reducing plasma levels of protease inhibitors. This is primarily based on a study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces levels of saquinavir, a PI, by approximately 50%. It is speculated that the allicin constituent induce CYP3A4 in the gut mucosa (7027,93578). Several studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506).
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Theoretically, garlic containing allicin might decrease levels of saquinavir.
Details
Saquinavir is a substrate of cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4 and cause subtherapeutic levels of saquinavir. This is primarily based on a pharmacokinetic study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induces CYP3A4 in the gut mucosa (7027,93578). Several pharmacokinetic studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506). Until more is known about this potential interaction, use garlic containing allicin cautiously in patients taking saquinavir.
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Theoretically, taking garlic with sofosbuvir might decrease its effectiveness.
Details
Animal research in rats shows that giving aged garlic extract 120 mg/kg orally daily for 14 days decreases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 36%, increases the clearance by 63%, and decreases the plasma concentrations at 1 and 8 hours by 35% and 58%, respectively. This interaction is hypothesized to be due to induction of intestinal P-glycoprotein expression by garlic (109524).
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Theoretically, garlic might increase levels of tacrolimus.
Details
In one case report, a liver transplant patient taking tacrolimus experienced increased tacrolimus levels and liver injury after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days. It is speculated that garlic inhibited hepatic cytochrome P450 3A4 (CYP3A4), which increased plasma levels of tacrolimus (96010).
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Theoretically, garlic might increase the risk of bleeding with warfarin.
Details
Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time (586,616,1874,3234,4366,4802,4803,51397). In addition, there is a report of two patients who experienced an increase in a previously stabilized international normalized ratio (INR) with concomitant garlic and warfarin use (51228,51631). However, this report has been subsequently debated due to limited clinical information. Other clinical studies have not identified an effect of garlic on INR, warfarin pharmacokinetics, or bleeding risk (15032,16416). More evidence is needed to determine the safety of using garlic with warfarin.
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Theoretically, licorice might reduce the effects of antihypertensive drugs.
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Theoretically, licorice might reduce the effects of cisplatin.
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In animal research, licorice diminished the therapeutic efficacy of cisplatin (59763).
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Theoretically, concomitant use of licorice and corticosteroids might increase the side effects of corticosteroids.
Details
Case reports suggest that concomitant use of licorice and oral corticosteroids, such as hydrocortisone, can potentiate the duration of activity and increase blood levels of corticosteroids (3252,12672,20040,20042,48429,59756). Additionally, in one case report, a patient with neurogenic orthostatic hypertension stabilized on fludrocortisone 0.1 mg twice daily developed pseudohyperaldosteronism after recent consumption of large amounts of black licorice (108568).
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Theoretically, licorice might decrease the levels and clinical effects of CYP1A2 substrates.
Details
In vitro research shows that licorice induces CYP1A2 enzymes (111404).
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Theoretically, licorice might increase levels of drugs metabolized by CYP2B6.
Details
In vitro research shows that licorice extract and glabridin, a licorice constituent, inhibit CYP2B6 isoenzymes (10300,94822). Licorice extract from the species G. uralensis seems to inhibit CYP2B6 isoenzymes to a greater degree than G. glabra extract in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2B6; however, these interactions have not yet been reported in humans.
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Theoretically, licorice might increase levels of drugs metabolized by CYP2C19.
Details
In vitro, licorice extracts from the species G. glabra and G. uralensis inhibit CYP2C19 isoenzymes in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C19; however, this interaction has not yet been reported in humans.
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Theoretically, licorice might increase levels of drugs metabolized by CYP2C8.
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In vitro, licorice extract from the species G. glabra and G. uralensis inhibits CYP2C8 isoenzymes (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C8; however, this interaction has not yet been reported in humans.
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Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP2C9.
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There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes (10300,94822). However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity (14441). Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.
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Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
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Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity (59808). Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity (14441). However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species (10300,94822). Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.
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Theoretically, concomitant use of licorice with digoxin might increase the risk of cardiac toxicity.
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Overuse or misuse of licorice with cardiac glycoside therapy might increase the risk of cardiac toxicity due to potassium loss (10393).
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Theoretically, concomitant use of licorice with diuretic drugs might increase the risk of hypokalemia.
Details
Overuse of licorice might compound diuretic-induced potassium loss (10393,20045,20046,59812). In one case report, a 72-year-old male with a past medical history of hypertension, type 2 diabetes, hyperlipidemia, arrhythmia, stroke, and hepatic dysfunction was hospitalized with severe hypokalemia and uncontrolled hypertension due to pseudohyperaldosteronism. This was thought to be provoked by concomitant daily consumption of a product containing 225 mg of glycyrrhizin, a constituent of licorice, and hydrochlorothiazide 12.5 mg for 1 month (108577).
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Theoretically, licorice might increase or decrease the effects of estrogen therapy.
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Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.
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Theoretically, loop diuretics might enhance the mineralocorticoid effects of licorice by inhibiting the enzyme that converts cortisol to cortisone; however, bumetanide (Bumex) does not appear to have this effect (3255).
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Theoretically, licorice might increase levels of methotrexate.
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Animal research suggests that intravenous administration of glycyrrhizin, a licorice constituent, and high-dose methotrexate may delay methotrexate excretion and increase systemic exposure, leading to transient elevations in liver enzymes and total bilirubin (108570). This interaction has not yet been reported in humans.
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Theoretically, licorice might decrease levels of midazolam.
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In humans, the licorice constituent glycyrrhizin appears to moderately induce the metabolism of midazolam (59808). This is likely due to induction of cytochrome P450 3A4 by licorice. Until more is known, licorice should be used cautiously in people taking midazolam.
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Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.
Details
In vitro research shows that licorice can increase P-glycoprotein activity (104561).
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Theoretically, licorice might decrease plasma levels and clinical effects of paclitaxel.
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Multiple doses of licorice taken concomitantly with paclitaxel might reduce the effectiveness of paclitaxel. Animal research shows that licorice 3 grams/kg given orally for 14 days before intravenous administration of paclitaxel decreases the exposure to paclitaxel and increases its clearance. Theoretically, this occurs because licorice induces cytochrome P450 3A4 enzymes, which metabolize paclitaxel. Notably, a single dose of licorice did not affect exposure or clearance of paclitaxel (102959).
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Theoretically, licorice might decrease plasma levels and clinical effects of warfarin.
Details
Licorice seems to increase metabolism and decrease levels of warfarin in animal models. This is likely due to induction of cytochrome P450 2C9 (CYP2C9) metabolism by licorice (14441). Advise patients taking warfarin to avoid taking licorice.
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Theoretically, marshmallow flower might have antiplatelet effects.
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Animal research suggests that marshmallow flower extract has antiplatelet effects (92846). However, the root and leaf of marshmallow, not the flower, are the plant parts most commonly found in dietary supplements. Theoretically, use of marshmallow flower with anticoagulant/antiplatelet drugs can have additive effects, and might increase the risk for bleeding in some patients.
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Theoretically, due to potential diuretic effects, marshmallow might reduce excretion and increase levels of lithium.
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Marshmallow is thought to have diuretic properties. To avoid lithium toxicity, the dose of lithium might need to be decreased when used with marshmallow.
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Theoretically, mucilage in marshmallow might impair absorption of oral drugs.
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Theoretically, concomitant use of anticoagulant or antiplatelet drugs with onion might increase the risk of bleeding.
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Concomitant use of antidiabetes drugs with onion may increase the risk of hypoglycemia.
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Concomitant use of aspirin with onion may worsen onion allergy.
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In one case report, a patient with a mild onion allergy reported worsening allergy, including swelling and severe urticaria, after taking aspirin (5054).
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Theoretically, taking onion might increase the levels and clinical effects of drugs metabolized by CYP2E1.
Details
Animal research shows that taking onion powder inhibits CYP2E1 (19653). However, this interaction has not been reported in humans.
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Theoretically, concomitant use of PABA and cortisone may increase the effects of cortisone.
Details
Preliminary clinical research shows that PABA decreases the metabolism of cortisone (4488). Dose adjustments of cortisone may be necessary.
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Theoretically, concomitant use of PABA and dapsone may decrease the effects of dapsone.
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Theoretically, concomitant use of PABA and sulfonamide antibiotics inhibits the antibacterial effects of sulfonamide.
Details
Sulfonamide antibiotics competitively inhibit folic acid synthesis from PABA. Excess PABA may overcome the folate depleting effect of the sulfonamides (10). Avoid concurrent use.
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Theoretically, pau d'arco might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
Details
In vitro research shows that pau d'arco reduces platelet aggregation and may interfere with vitamin K (18057,68319). One clinical study shows that taking the lapachol constituent of pau d'arco in doses above 1.5 grams daily increases the risk of bleeding (91939). The effects of whole pau d'arco or pau d'arco extract in humans are unclear.
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Pleurisy root contains digitalis-like cardenolide glycosides. Taking pleurisy root in combination with digoxin could increase the risk of adverse effects and toxicity (19).
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Theoretically, concomitant use of potassium-depleting diuretics and pleurisy root can increase the risk of cardiac glycoside toxicity due to potassium depletion (19). Some diuretics that can deplete potassium include chlorothiazide (Diuril), chlorthalidone (Thalitone), furosemide (Lasix), hydrochlorothiazide (HCTZ, Hydrodiuril, Microzide), and others.
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Theoretically, excessive amounts of pleurisy root might interfere with hormone drug therapy (4).
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Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity (14540). Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation (74406).
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Theoretically, selenium might prolong the sedating effects of barbiturates.
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Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.
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Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels (14544,14545,14546,101343). It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium (14545).
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Gold salts might interfere with selenium activity in tissues.
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Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy.
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Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) levels.
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A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease (7388,11537). It is not known whether this adverse effect is due to a single antioxidant such as selenium, or to the combination. It also is not known whether it will occur in other patient populations.
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Theoretically, selenium might interfere with warfarin activity.
Details
Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors (14541). Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity (14540).
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Theoretically, concurrent use of anticholinergic drugs and thyme essential oil might reduce the effects of anticholinergic drugs.
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In vitro evidence suggests that thyme essential oil and specific essential oil constituents like thymohydroquinone and carvacrol can inhibit acetylcholinesterase (AChE) (78155). However, this effect has not been observed in humans.
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Theoretically, thyme leaf extract might have additive effects with anticoagulant or antiplatelet drugs.
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Theoretically, concurrent use of cholinergic drugs and thyme essential oil might cause additive cholinergic effects.
Details
In vitro evidence suggests that thyme essential oil and specific essential oil constituents like thymohydroquinone and carvacrol can inhibit acetylcholinesterase (AChE) (78155). However, this effect has not been observed in humans.
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Theoretically, thyme might competitively inhibit the effects of estrogen replacement therapy.
Details
In vitro research shows that thyme has estrogen receptor-binding activity and phytoestrogen content (3701). However, this effect has not been observed in humans.
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Watercress might reduce the metabolism of chlorzoxazone and increase its effects and side effects. Clinical research in healthy volunteers shows that a single ingestion of watercress 50 grams increases the chlorzoxazone plasma concentration-time curve by about 56% and increases its half-life by about 53% (4018).
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Watercress is thought to have diuretic properties (18). Theoretically, due to these potential diuretic effects, watercress might reduce excretion and increase levels of lithium.
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Watercress contains vitamin K. Consuming large amounts of watercress might antagonize the anticoagulant effects of warfarin (11285).
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Below is general information about the adverse effects of the known ingredients contained in the product Respiratory Cleanse & Defense. 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, alfalfa leaf seems to be well tolerated.
However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Abdominal discomfort, diarrhea, and flatulence.
Serious Adverse Effects (Rare):
Orally: Lupus-like syndrome after chronic ingestion of alfalfa.
Dermatologic ...Dermatitis associated with alfalfa use has been reported. In a 1954 publication, dermatitis was noted in a 61-year-old female consuming 4-6 cups of tea made with two tablespoonfuls of alfalfa seeds for approximately two months prior to onset. Examination revealed diffuse, confluent edema and erythema on the face, eyelids, ears, hands, forearms, and distal humeral regions. The dermatitis improved with treatment; re-exposure to alfalfa resulted in a similar reaction (30609).
Endocrine
...Alfalfa contains constituents, including coumestrol, with reported estrogenic activity (30586,30592,4753).
Effects in humans are not known.
One case report documents hypokalemia in a female who had been drinking a "cleansing tea" containing alfalfa, licorice, and stinging nettle. The potassium level returned to normal after discontinuing the tea and initiating potassium supplementation. The specific cause of the hypokalemia is not clear. Notably, both stinging nettle and licorice have been associated with hypokalemia and may have been responsible for this effect (30562).
Gastrointestinal ...Orally, flatulence and bulkier feces were reported during the first week of a case series of three subjects ingesting alfalfa (30598). In a case series of 15 patients ingesting alfalfa, increased fecal volume and increased stool frequency was reported. Additional adverse effects included abdominal discomfort in two patients, diarrhea in two patients, loose stools in six patients, and intestinal gas in 13 patients (5816).
Hematologic ...Pancytopenia and splenomegaly were reported in a 59-year-old male who had been taking 80-160 grams of ground alfalfa seeds for up to six weeks at a time, for a five month period. Hematologic values and spleen size returned to normal when alfalfa was discontinued (381).
Other
...Alfalfa products, including sprouts, seeds, and tablets, have been found to be contaminated with Escherichia coli, Salmonella, and Listeria monocytogenes, which have caused documented infections (5600,30566,30568,30572,30569,30564,30604,30610,30563,30607) (30566,30564,30604,30610,30563,30607,30576).
Orally, alfalfa has been associated with the development of a lupus-like syndrome in animals and humans (30594,14828,14830,30602), as well as with possible exacerbations of lupus in patients with known systemic lupus erythematosus (SLE). These reactions may be associated with the amino acid L-canavanine (30594), which appears to be present in alfalfa seeds and sprouts, but not leaves, and therefore should not be present in alfalfa tablets manufactured from the leaves (30601). However, case reports have included individuals ingesting tablets. A lupus-like syndrome was described in four patients taking 12-24 alfalfa tablets per day. Symptoms included arthralgias, myalgias, and rash; positive antinuclear antibodies (ANA) arose anywhere from three weeks to seven months after initiating alfalfa therapy. Upon discontinuation of alfalfa tablets, all four patients became asymptomatic. In two patients, ANA levels normalized (14828). Two additional reports have documented possible exacerbation or induction of SLE associated with alfalfa use. One case involved a female with a 26-year history of SLE, who had been taking 15 tablets of alfalfa daily for nine months prior to an exacerbation. Because of the delay in onset of the exacerbation from the initiation of alfalfa therapy, causation cannot be clearly established (30575). In a different report, SLE and arthritis were found in multiple family members who had been taking a combination of vitamin E and alfalfa tablets for seven years (30602). It is not known what other environmental or genetic factors may have affected these individuals, and the association with alfalfa is unclear.
General
...Orally, Baikal skullcap seems to be well-tolerated.
There is currently a limited amount of information on the adverse effects of intravenous and topical Baikal skullcap.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, erythema, nausea, pruritus, and vomiting.
Intravenously: Skin reactions.
Topically: Dermatitis.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity and hypersensitivity pneumonitis have been reported with a specific combination product (Limbrel, Primus Pharmaceuticals) containing extracts of Baikal skullcap and catechu.
Cardiovascular ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, elevated triglyceride levels occurred in 1 of 10 patients who received 400 mg every 8 hours and 2 of 10 patients treated with 600 mg every 8 hours, compared with 0 of 10 patients who received 200 mg every 8 hours and 0 of 6 patients who received placebo. Triglyceride elevations were considered mild and resolved after discontinuation (110023).
Dermatologic
...Orally, taking Baikal skullcap may cause erythema and pruritus (105867).
Intravenously, Baikal skullcap as part of a Tanreqing injection has been associated with reports of skin reactions in some pediatric patients (96281).
Topically, several cases of allergic contact dermatitis have been reported after applying sunscreen containing Baikal skullcap extract (105869,105870). Allergic contact dermatitis has also been reported after applying a facial cream (Resveratrol BE, Skinceuticals) containing Baikal skullcap root extract 0.5% and resveratrol 1%. Patch testing identified a positive reaction to both ingredients (110024). Baikal skullcap-induced dermatitis appears to respond to treatment with a topical corticosteroid and calcineurin inhibitor (105870).
Gastrointestinal ...Orally, use of Baikal skullcap has been associated with epigastric pain, abdominal pain, constipation, diarrhea, nausea, and vomiting (101738,105867).
Hepatic
...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of acute liver damage.
There have been at least five published reports of liver damage associated with this product. In all cases, the patients were females aged 54-68 years taking doses of 250-500 mg twice daily for 1-3 months. Signs and symptoms included jaundice, pruritus, abdominal pain, fever, rash, and elevated serum bilirubin and liver transaminase levels. All patients fully recovered and levels normalized within 3 months after discontinuation (18009,96282). In addition to these published case reports, approximately 30 liver-related adverse events have been reported to the manufacturer of this product (18009). The mechanism of hepatotoxicity is unclear (18009,18010); it is estimated that the incidence of hepatotoxicity with this product is around 1 in 10,000, although the actual incidence is unknown (18010). In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.
Hepatotoxicity has also been reported in two patients taking a specific dietary supplement (Move Free Advanced, Reckitt Benckiser) containing Baikal skullcap, black catechu, glucosamine, chondroitin, and hyaluronic acid (33460) and in a patient taking Baikal skullcap, elderflower, horseradish, and white willow (101737). The investigators determined that the hepatotoxicity was likely caused by Baikal skullcap in these cases (33460,101737). Additionally, cases of liver injury are reported in 4 of 37 patients taking various Kampo formulations containing Baikal skullcap and other herbs daily. Patients presented with elevated liver function tests 7 to 38 days after consumption (112179). It is unclear if this adverse effect is from Baikal skullcap, other ingredients, or the combination.
In a small study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, liver transaminase elevations occurred in 2 of 10 patients who received 400 mg every 8 hours for 6 days, compared with 0 of 6 patients who received placebo. No patients receiving either 200 mg or 600 mg every 8 hours experienced liver transaminase elevations. The elevations were considered mild and resolved after discontinuation (110023).
Pulmonary/Respiratory ...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of hypersensitivity pneumonitis. Symptoms include fever, chills, headache, cough, chronic bronchitis, shortness of breath, weight loss, and fatigue. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.
Renal ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, proteinuria of undefined severity occurred in 1 of 10 patients who received 200 mg every 8 hours for 6 days, 3 of 10 patients who received 400 mg every 8 hours for 6 days, and 5 of 10 patients who received 600 mg every 8 hours for 6 days, compared with 1 of 6 patients who received placebo. The proteinuria was considered mild and resolved after discontinuation (110023).
General
...Orally, black pepper seems to be well tolerated when used in the amounts found in food or when taken as a medicine as a single dose.
Topically and as aromatherapy, black pepper oil seems to be well tolerated.
Most Common Adverse Effects:
Orally: Burning aftertaste, dyspepsia, and reduced taste perception.
Inhalation: Cough.
Serious Adverse Effects (Rare):
Orally: Allergic reaction in sensitive individuals.
Gastrointestinal ...Orally, black pepper can cause a burning aftertaste (5619) and dyspepsia (38061). Single and repeated application of piperine, the active constituent in black pepper, to the tongue and oral cavity can decrease taste perception (29267). By intragastric route, black pepper 1.5 grams has been reported to cause gastrointestinal microbleeds (29164). It is not clear if such an effect would occur with oral administration.
Immunologic ...In one case report, a 17-month-old male developed hives, red eyes, facial swelling, and a severe cough following consumption of a sauce containing multiple ingredients. Allergen skin tests were positive to both black pepper and cayenne, which were found in the sauce (93947).
Ocular/Otic ...Topically, ground black pepper can cause redness of the eyes and swelling of the eyelids (5619).
Pulmonary/Respiratory ...When inhaled through the nose as an olfactory stimulant, black pepper oil has been reported to cause cough in one clinical trial (29162).
General
...Orally, capsicum is generally well tolerated in amounts typically found in food or when the extract is used in doses of up to 200 mg daily.
Topically and intranasally, capsaicin, a constituent of capsicum, is generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, bloating, burning, diarrhea, dyspepsia, gas, headache, mild constipation, nausea, rhinorrhea, skin flushing, and sweating.
Serious Adverse Effects (Rare):
Orally: Cases of myocardial infarction and hypertensive crisis have been reported.
Cardiovascular
...Orally, palpitation was reported in one clinical trial (105196).
One case of myocardial infarction has been reported in a 41-year-old male without cardiovascular risk factors; the event was attributed to the use of an oral capsicum pepper pill that the patient had been taking for weight loss (40768). Another case of coronary vasospasm and acute myocardial infarction has been reported for a healthy 29-year-old male; the event was attributed to the use of a topical capsicum-containing patch that the patient had been applying to the middle of the back for 6 days (40658). Two cases of arterial hypertensive crisis have been reported for individuals who ingested a large amount of peppers and chili peppers the day before. One of the patients also had an acute myocardial infarction, and the other had high levels of thyroid stimulating hormone (40569,40606).
Dermatologic
...Orally, capsicum or its constituent capsaicin may cause urticaria and skin wheals in rare cases (96457,105203).
Topically, capsicum can cause a prickling sensation, itching, pain, burning, edema, stinging, irritation, rash, and erythema. About 1 in 10 patients who use capsaicin topically discontinue treatment because of adverse effects. These effects seem to occur more often with topical formulations containing higher concentrations of capsaicin, the active constituent of capsicum. Side effects tend to diminish with continued use (12401,15260,15261,40358,40439,40483,40547,40676,40682,40719)(40784,40847,92979,92983,92984,96453,105193,105197,105202,111514). In one case, application of a capsaicin 8% patch (Qutenza) for 60 minutes caused a second-degree burn, characterized by burning, erythema, severe pain, and blistering at the administration site. The burn was treated with topical corticosteroids, but 9 months later neuropathic pain persisted, resulting in limited mobility. It is unclear whether the mobility sequalae were caused by topical capsaicin or the patient's pre-existing neurological disorders (111514). Skin contact with fresh capsicum fruit can also cause irritation or contact dermatitis (12408).
Intranasally, capsaicin can cause nasal burning and pain in most patients. It also often causes lacrimation, sneezing, and excessive nasal secretion; however, these side effects appear to diminish with repeat applications (14323,14329,14358). In some cases, the burning sensation disappears after 5-8 applications (14351,14358). In some cases, patients are pretreated with intranasal lidocaine to decrease the pain of intranasal capsaicin treatment. However, even with lidocaine pretreatment, patients seem to experience significant pain (14324).
Gastrointestinal
...Orally, capsicum can cause upper abdominal discomfort, including irritation, fullness, dyspepsia, gas, bloating, nausea, epigastric pain and burning, anal burning, diarrhea, mild constipation, and belching (12403,12410,40338,40427,40456,40503,40560,40584,40605,40665)(40718,40725,40745,40808,40828,96456,96457,105194,105196).
There is a case report of a 3-year-old female who experienced a burning and swollen mouth and lips after touching the arm of a parent that had been treated with a capsaicin patch and then placing the fingers in the mouth (105199). Excessive amounts of capsaicin can lead to gastroenteritis and hepatic necrosis (12404). In a case report, a 40-year-old male with diabetes consumed white wine daily and chewed cayenne which was thought to result in black teeth stains and loss of enamel (40809). Some preliminary research links ingestion of capsaicin with stomach and gallbladder cancer; however the link may be due to contamination of capsaicin products with carcinogens (40771).
Topically, capsaicin can cause diarrhea and vomiting (105202).
Immunologic ...In a case report, a 34-year-old female had anaphylaxis involving difficulty breathing and stupor and also urticaria after consuming a red bell pepper, which is in the capsicum genus. The causal chemical was theorized to be 1,3-beta-glucanase (92978). In another case report, a 33-year-old female experienced angioedema, difficulty breathing and swallowing, and urticaria after ingesting raw green and red peppers (92982).
Neurologic/CNS ...Orally, capsicum can cause sweating and flushing of the head and neck, lacrimation, headache, faintness, and rhinorrhea (7005,12410,105196,105203). Topically, applying capsaicin can cause headache (96450,105202). Injection of capsaicin into the intermetatarsal space has also been associated with headache (96454).
Ocular/Otic
...Topically, capsicum can be extremely irritating to the eyes and mucous membranes.
Capsicum oleoresin, an oily extract in pepper self-defense sprays, causes intense eye pain. It can also cause erythema, blepharospasm, tearing, shortness of breath, and blurred vision. In rare cases, corneal abrasions have occurred (12408,12409,40345,40348,40383,40720,40857).
Inhalation of capsicum can cause eye irritation, and allergic alveolitis (5885). In a case report, a 38-year-old female had acute anterior uveitis that developed about 12 hours after using a specific patch (Isola Capsicum N Plus) that contained capsaicin 1.5 mg per patch and methyl salicylate 132 mg per patch for neck pain. The uveitis was controlled with topical steroids and did not recur (92977).
Oncologic ...Population research suggests that moderate to high intake of capsaicin, the active constituent of capsicum, is associated with an increased risk of gastric cancer, while low intake is associated with a decreased risk. It is not clear from the study what amount of capsaicin is considered high versus low intake (92988). Additionally, some research suggests that any link may be due to contamination of capsaicin products with carcinogens (40771).
Pulmonary/Respiratory
...Orally, difficulty breathing was reported in a clinical trial (105196).
Topically, nasopharyngitis related to the use of a cream containing capsaicin has been reported (105202).
Inhalation of capsicum and exposure to capsicum oleoresin spray can cause cough, dyspnea, pain in the nasal passages, sneezing, rhinitis, and nasal congestion (5885,15016,40522,40546,40647). In rare cases, inhalation of the capsicum oleoresin or pepper spray has caused cyanosis, apnea, respiratory arrest and death in people. Death was caused by asphyxiation probably due to acute laryngeal edema and bronchoconstriction from inhalation of the capsicum oleoresin spray (40546,40672,40837,40879).
In a case report, a 47-year-old female who was exposed to capsaicin gas for more than 20 minutes experienced acute cough, shortness of breath, short-term chest pain, wheezing, and difficulty breathing for months afterwards (92980). In rare cases, exposure to capsicum oleoresin spray resulted in apnea, pulmonary injury, cyanosis, and even respiratory arrest (40383,40546).
General
...Orally, cascara sagrada seem to be well tolerated when used appropriately, short-term.
Most Common Adverse Effects:
Orally: Mild abdominal discomfort and cramps.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity. Fresh or improperly aged cascara sagrada bark can cause severe vomiting.
Endocrine ...Orally, long-term use of cascara sagrada can lead to potassium depletion (4).
Gastrointestinal
...Orally, cascara sagrada can commonly cause mild abdominal discomfort, colic, and cramps (4).
In some cases, chronic use can cause pseudomelanosis coli. Pseudomelanosis coli (pigment spots in intestinal mucosa) is believed to be harmless, usually reverses with discontinuation, and is not directly associated with an increased risk of developing colorectal adenoma or carcinoma (6138).
Fresh or improperly aged cascara sagrada bark can cause severe vomiting due to the presence of free anthrone constituents (2,92307).
Genitourinary ...Orally, long-term use of cascara sagrada can lead to albuminuria and hematuria (4).
Hepatic ...There is some concern about potential liver problems with cascara sagrada. In some cases, cascara sagrada bark 750-1275 mg (containing approximately 21 mg cascaroside) daily in divided doses for three days resulted in cholestatic hepatitis, ascites, and portal hypertension. Symptoms resolved following discontinuation of cascara sagrada (6895,92306).
Musculoskeletal ...Orally, long-term use of cascara sagrada can lead to muscle weakness and finger clubbing (4).
Other ...Orally, long-term use of cascara sagrada can lead to cachexia (4).
General ...Orally, the major concern with coltsfoot use is its pyrrolizidine alkaloid (PA) content. These alkaloids can cause liver and lung injury (12841,12842). Chronic exposure to other plants containing hepatotoxic PA constituents has been associated with hepatic veno-occlusive disease (4021). Sub-acute veno-occlusive disease can cause vague symptoms, including colicky pains, vomiting, diarrhea, and ascites within several days; persistent liver enlargement occurs within a few weeks (4021,12842). Deep vein thrombosis (DVT) and pulmonary embolus (PE) thought to be associated with coltsfoot have been reported (18242). Coltsfoot products containing PAs should be avoided. There is currently a limited amount of information available about the adverse effects of PA-free coltsfoot.
Cardiovascular ...Orally, a single case report associates coltsfoot and its PA content with deep vein thrombosis (DVT) and pulmonary embolus (PE). A 27-year-old man with no history of coagulation disorders developed a DVT and several PE after consuming unknown quantities of coltsfoot and several other herbs. However, he also had other risk factors for thrombosis, including smoking and recent bed rest (18242).
Hepatic ...Orally, coltsfoot might cause liver damage. Coltsfoot contains hepatotoxic pyrrolizidine alkaloids (PAs) (12841,12842). Chronic exposure to other plants containing hepatotoxic PAs is associated with veno-occlusive disease (4021). Sub-acute veno-occlusive disease can cause vague symptoms, including colicky pains, vomiting, diarrhea, and ascites within several days; persistent liver enlargement occurs within a few weeks (4021,12842).
Pulmonary/Respiratory ...Orally, coltsfoot might cause lung damage. The major concern with coltsfoot use is its pyrrolizidine alkaloid (PA) content. These constituents can cause lung damage with pulmonary-arterial hypertension (12841,12842).
General
...Orally, fenugreek seed is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, diarrhea, dyspepsia, flatulence, hypoglycemia, and nausea.
Serious Adverse Effects (Rare):
All ROA: Severe allergic reactions including angioedema, bronchospasm, and shock.
Endocrine ...Orally, large doses of fenugreek seed, 100 grams daily of defatted powder, have caused hypoglycemia (164,96068).
Gastrointestinal ...Orally, fenugreek seed can cause mild gastrointestinal symptoms, such as diarrhea, dyspepsia, abdominal distention and pain, nausea, and flatulence, especially when taken on an empty stomach (622,12534,18349,93421,96065,96068,105016).
Immunologic ...Fenugreek can cause allergic reactions when used orally and topically, and when the powder is inhaled (719,96068). Orally, fenugreek has caused bronchospasm, diarrhea, and itching, and skin reactions severe enough to require intravenous human immunoglobulin (96068). Topically, fenugreek paste has resulted in facial swelling, wheezing, and numbness around the head (719,96068). When used both orally and topically by a single individual, asthma and rhinitis occurred (96068). Inhalation of fenugreek powder has resulted in fainting, sneezing, runny nose, and eye tearing (719,96068).
Neurologic/CNS ...Orally, loss of consciousness has occurred in a 5 week-old infant drinking tea made from fenugreek (9782). Dizziness and headaches have been reported in clinical research of fenugreek extract (49551,93419). However, these events are rare.
Renal ...Orally, fenugreek aqueous see extract may increase the frequency of micturition, although this even appears to be rare (49551).
Other
...Consumption of fenugreek during pregnancy, immediately prior to delivery, may cause the neonate to have an unusual body odor, which may be confused with maple syrup urine disease.
It does not appear to cause long-term sequelae (9781). This unusual body odor may also occur in children drinking fenugreek tea. A case of a specific urine and sweat smell following oral fenugreek extract use has been reported for a patient in one clinical trial (18349).
In 2011, outbreaks of enteroaggregative hemorrhagic Escherichia coli (EATEC) O104:H4 infection occurred in Germany and Spain. Epidemiological studies linked the outbreaks to fenugreek seeds that had been imported from Africa. However, laboratory analyses were unable to isolate the causative strain of bacteria from fenugreek seed samples (49776,49777,49781,90114).
General
...Orally, garlic is generally well tolerated.
Topically, garlic seems to be well tolerated. Intravenously, there is insufficient reliable information available about adverse effects.
Most Common Adverse Effects:
Orally: Abdominal pain, body odor, flatulence, malodorous breath, and nausea. Allergic reactions in sensitive individuals.
Topically: Burns and dermatitis with fresh garlic.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about increased risk of bleeding with garlic.
Dermatologic
...Orally, garlic may cause pruritus (51316,51474,107239), flushing, and acne (107239).
Oral intake of a specific garlic product containing allicin (Allimax) has been associated with a case of pruritic rash (51474). Enteric-coated garlic tablets standardized to 1.5% allicin have also been associated with a case of pruritus (51316). Garlic has also been associated with a case of superficial pemphigus in a 49-year-old male with type 2 diabetes (51564). Garlic-induced oral ulcers have also been reported (51467).
Topically, garlic may cause contact dermatitis and urticaria (4833,5004,12635,51258,51265,51375,51403,51412,51459,51483)(51511,51512,51530,51616,51617,51618,111769), as well as contact cheilitis (51384). Fresh garlic may be more likely to elicit a reaction than garlic extract. Most reactions have resolved following withdrawal of garlic therapy. In one case report, applying crushed garlic on the neck to help ease a sore throat resulted in an itchy, burning, erythematous lesion in a young female patient. The lesion healed after one week of treatment with topical antibiotics, steroids, and antihistamine ointments (88390). Cases of occupational eczema or dermatitis have been reported in cooks (51303,51210), food handlers (51292), and caterers (51304). According to one case report, dermatitis appeared in chefs exposed to garlic (15033). Treatment with acitretin 25 mg daily or topical psoralen-ultraviolet A (PUVA) for 12 weeks proved effective in mitigating the symptoms. A 34-year-old female with a history of hand dermatitis and paronychia had a worsening of these conditions after peeling raw garlic. She had a positive skin patch test to fresh, raw garlic but not to any other tested allergens, and the conditions resolved when she avoided contact with garlic (105528). Topically, garlic may also cause chemical burns, usually within 12 hours of application. Second- and third-degree chemical burns have been reported in adults, children, and infants exposed to topical garlic, often as an unintended consequence of using garlic medicinally on the skin (585,4832,51226,51230,51252,51281,51377,51418,51468,51495,51536)(51558,51576,51577,88409,96006). A case of painful blisters on the soles of the feet of a 23-year-old Chinese female has been attributed to chemical burns caused by applying crushed raw garlic for 3 hours (51440). Topically, garlic may also cause hyperpigmentation, ulcers, necrotic lesions, facial flushing, and local irritation (4832,15030,51268,51269,108606). In one case report, applying crushed raw garlic to the palatal mucosa for several minutes to relieve mouth pain resulted in a chemical burn that produced a 3 cm necrotic ulcer in an adult female with trigeminal neuralgia (108606).
Gastrointestinal
...Orally, dehydrated garlic preparations or raw garlic may cause malodorous breath (51438,51444), body odor (732,1873,4784,4793,4795,4798,9201,10787,42692,49769)(51269,51316,51467,51602), abdominal pain or fullness, anorexia, diarrhea, constipation, flatulence, belching, heartburn, nausea, unpleasant taste, reflux, and bowel obstruction (1884,6457,6897,9201,49769,51269,51343,51380,51438,51442)(51450,51457,51466,51471,51474,51520,51593,51602,51623,88398)(88405,111766,114892).
Large quantities of garlic may damage the gastrointestinal tract. In one case report, a patient taking garlic for hypertension reported odynophagia and retrosternal pain after taking garlic without any water the previous day. An esophageal lesion 3 cm in length was detected upon endoscopy. The symptoms resolved 3 days after starting a liquid diet and taking lansoprazole 30 mg twice daily and sucralfate four times daily (88389). One case of bowel obstruction was reported in a 66-year-old male who ingested an entire garlic bulb (51525). Esophageal perforation has been reported in at least 17 individuals who consumed entire garlic cloves. In one case the perforation led to mediastinitis and death (102672).
Garlic has also been associated with eosinophilic infiltration of the gastrointestinal tract. In one case report a 42-year-old female presented with symptoms of eosinophilic gastroenteritis, which included pollinosis, asthma, diarrhea, heart burn, peripheral eosinophilia, and urticaria. After stopping use of garlic and sesame, the patient improved (51441). In a case report of eosinophilic esophagitis, garlic was determined to be the causative agent in a patient with long-standing gastrointestinal symptoms. The patient had attempted to treat upper gastrointestinal symptoms as gastrointestinal reflux disease without success for many years. Skin prick testing showed a positive reaction to garlic, of which the patient noted frequent consumption. Marked symptom improvement was noted within 3 weeks of garlic avoidance (88393).
Intravenously, garlic 1 mg/kg of body weight daily diluted into 500 mL saline and administered over 4 hours has been reported to cause abdominal discomfort, vomiting, diarrhea, nausea, anorexia, flatulence, weight loss, and garlicky body odor (51462).
Clinical research suggests that patients with metabolic syndrome taking 1600 mg of powdered garlic by mouth daily for 3 months may experience improved intestinal transit time when compared with placebo, suggesting that garlic powder may reduce symptoms of constipation (110722).
Genitourinary ...Orally, garlic might cause dysuria, hematuria, or polyuria (51438,51450,51467,113618). In one case, an older male with high dietary and supplemental garlic intake at doses of 300-5400 mg daily for 3-4 years developed severe hematuria with clots after undergoing a minimally invasive prostate procedure (113618).
Hematologic
...Oral use of dietary garlic or supplements containing garlic has caused platelet dysfunction, increased fibrinolytic activity, prolonged bleeding time, retrobulbar hemorrhage (bleeding behind the eye) postoperative bleeding, and spinal epidural hematoma (586,587,4801,4802,11325,51397,51473,51491,51532,51534)(51570,51584,51593,51594,113618).
Also, a case of kidney hematoma following extracorporeal shock-wave lithotripsy (SWL) has been reported in a patient with nephrolithiasis who took aged garlic (51630). A case of increased bleeding time that complicated epistaxis management has been reported in a patient taking garlic, aspirin, and milk thistle (51426).
Intravenously, garlic has been associated with the development of thrombophlebitis at the injection site (51462).
Immunologic
...There is a case report of an immediate sensitivity reaction to oral raw garlic, resulting in wheals, in a 31-year-old female.
The patient did not react to cooked garlic, and skin prick tests showed allergy only to raw garlic (96015). Researchers note that at least some allergens in raw garlic are heat labile (88392,96012,96015). This suggests that consuming cooked rather than raw garlic may help avoid this reaction in patients allergic to raw garlic. However, different people react to different allergens in garlic. At least some of these allergens are heat stable (96012). While rare, garlic-induced anaphylaxis has been reported (88392,96012).
Topically, allergic contact dermatitis has been reported in case reports (51406,51498,51510,51519,51560).
Musculoskeletal ...Orally, garlic has been associated with individual cases of gout and low back pain (51474,51467), but it is not clear if these adverse events can be attributed to garlic.
Neurologic/CNS ...Orally, dizziness, insomnia, headaches, diaphoresis, fever, chills, somnolence, increased appetite, euphoria, and weight loss have been reported with garlic (15032,42692,51316,51467,51471,51520). In one case, the smell of garlic was identified as a trigger for migraines in a 32-year-old female. The subject reported fortification spectra along with visual spots for a few seconds followed by instantaneous biparietal, crushing level (10/10) headaches upon exposure to the scent of garlic or onion (88404).
Pulmonary/Respiratory ...Garlic exposure, most notably in occupational settings, may cause asthma and other symptoms such as sneezing, nasal obstruction, rhinorrhea, and sinusitis (40661,51218). A case of minor hemoptysis has been reported for one patient with cystic fibrosis following intake of garlic capsules orally once daily for 8 weeks (51438). A 77-year-old female developed pneumonia related to the intake of one whole black garlic clove daily. The cloves were prepared by heating a whole garlic bulb in a pot for one month. Symptoms included dyspnea and coughing, and test results were positive for lymphocyte-induced stimulation by black garlic and raw garlic. The patient required treatment with oral steroids and was told to avoid garlic (96011).
General
...Orally, licorice is generally well tolerated when used in amounts commonly found in foods.
It seems to be well tolerated when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes or when used topically, short-term.
Most Common Adverse Effects:
Orally: Headache, nausea, and vomiting.
Topically: Contact dermatitis.
Intravenously: Diarrhea, itching, nausea, and rash.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about acute renal failure, cardiac arrest, cardiac arrhythmias, hypertension, hypokalemia, muscle weakness, paralysis, pseudohyperaldosteronism, and seizure associated with long-term use or large amounts of licorice containing glycyrrhizin.
Cardiovascular
...Orally, excessive licorice ingestion can lead to pseudohyperaldosteronism, which can precipitate cardiovascular complications such as hypertension and hypertensive crisis, ventricular fibrillation or tachycardia, sinus pause, and cardiac arrest.
These effects are due to the licorice constituent glycyrrhizin and usually occur when 20-30 grams or more of licorice product is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,97213) (104563,108574,108576,110305,112234). In one case report, an 89-year-old female taking an herbal medicine containing licorice experienced a fatal arrhythmia secondary to licorice-induced hypokalemia. The patient presented to the hospital with recurrent syncope, weakness, and fatigue for 5 days after taking an herbal medicine containing licorice for 2 months. Upon admission to the hospital, the patient developed seizures, QT prolongation, and ventricular arrhythmia requiring multiple defibrillations. Laboratory tests confirmed hypokalemia and pseudohyperaldosteronism (112234).
However, people with cardiovascular or kidney conditions may be more sensitive, so these adverse events may occur with doses as low as 5 grams of licorice product or glycyrrhizin 100 mg daily (15589,15593,15598,15600,59726). A case report in a 54-year-old male suggests that malnutrition might increase the risk of severe adverse effects with excessive licorice consumption. This patient presented to the emergency room with cardiac arrest and ventricular fibrillation after excessive daily consumption of licorice for about 3 weeks. This caused pseudohyperaldosteronism and then hypokalemia, leading to cardiovascular manifestations. In spite of resuscitative treatment, the patient progressed to kidney failure, refused dialysis, and died shortly thereafter (103791).
Dermatologic
...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912).
There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578). Burning sensation, itching, redness, and scaling were reported rarely in patients applying a combination of licorice, calendula, and snail secretion filtrate to the face. The specific role of licorice is unclear (110322).
In rare cases, the glycyrrhizin constituent of licorice has caused rash and itching when administered intravenously (59712).
Endocrine
...Orally, excessive licorice ingestion can cause a syndrome of apparent mineralocorticoid excess, or pseudohyperaldosteronism, with sodium and water retention, increased urinary potassium loss, hypokalemia, and metabolic alkalosis due to its glycyrrhizin content (781,10619,15591,15592,15593,15594,15595,15596,15597,15598)(15600,16057,16835,25659,25660,25673,25719,26439,59818,59822)(59832,59864,91722,104563,108568,108574,110305,112234).
These metabolic abnormalities can lead to hypertension, edema, EKG changes, fatigue, syncope, arrhythmias, cardiac arrest, headache, lethargy, muscle weakness, dropped head syndrome (DHS), rhabdomyolysis, myoglobinuria, paralysis, encephalopathy, respiratory impairment, hyperparathyroidism, and acute kidney failure (10393,10619,15589,15590,15593,15594,15596,15597,15599)(15600,16057,16835,25660,25673,25719,26439,31562,59709,59716)(59720,59740,59787,59820,59826,59882,59889,59900,91722,97214,100522) (104563,108576,108577). These effects are most likely to occur when 20-30 grams of licorice products containing glycyrrhizin 400 mg or more is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,108574). However, some people may be more sensitive, especially those with hypertension, diabetes, heart problems, or kidney problems (15589,15593,15598,15600,59726,108576,108577) and even low or moderate consumption of licorice may cause hypertensive crisis or hypertension in normotensive individuals (1372,97213). The use of certain medications with licorice may also increase the risk of these adverse effects (108568,108577). One case report determined that the use of large doses of licorice in an elderly female stabilized on fludrocortisone precipitated hypokalemia and hypertension, requiring inpatient treatment (108568). Another case report describes severe hypokalemia necessitating intensive care treatment due to co-ingestion of an oral glycyrrhizin-specific product and hydrochlorothiazide for 1 month (108577). Glycyrrhetinic acid has a long half-life, a large volume of distribution, and extensive enterohepatic recirculation. Therefore, it may take 1-2 weeks before hypokalemia resolves (781,15595,15596,15597,15600). Normalization of the renin-aldosterone axis and blood pressure can take up to several months (781,15595,108568). Treatment typically includes the discontinuation of licorice, oral and intravenous potassium supplementation, and short-term use of aldosterone antagonists, such as spironolactone (108574,108577).
Chewing tobacco flavored with licorice has also been associated with toxicity. Chewing licorice-flavored tobacco, drinking licorice tea, or ingesting large amounts of black licorice flavored jelly beans or lozenges has been associated with hypertension and suppressed renin and aldosterone levels (12671,12837,97214,97215,97217,108574). One case report suggests that taking a combination product containing about 100 mg of licorice and other ingredients (Jintan, Morishita Jintan Co.) for many decades may be associated with hypoaldosteronism, even up to 5 months after discontinuation of the product (100522). In another case report, licorice ingestion led to hyperprolactinemia in a female (59901). Licorice-associated hypercalcemia has also been noted in a case report (59766).
Gastrointestinal ...Nausea and vomiting have been reported rarely following oral use of deglycyrrhizinated licorice (25694,59871). Intravenously, the glycyrrhizin constituent of licorice has rarely caused gastric discomfort, diarrhea, or nausea (59712,59915).
Immunologic ...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912). There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578).
Musculoskeletal ...In a case report, excessive glycyrrhizin-containing licorice consumption led to water retention and was thought to trigger neuropathy and carpal tunnel syndrome (59791).
Neurologic/CNS ...Orally, licorice containing larger amounts of glycyrrhizin may cause headaches. A healthy woman taking glycyrrhizin 380 mg daily for 2 weeks experienced a headache (59892). Intravenously, the glycyrrhizin constituent of licorice has rarely caused headaches or fatigue (59721). In a case report, licorice candy ingestion was associated with posterior reversible encephalopathy syndrome accompanied by a tonic-clonic seizure (97218).
Ocular/Otic ...Orally, consuming glycyrrhizin-containing licorice 114-909 grams has been associated with transient visual loss (59714).
Pulmonary/Respiratory ...Orally, large amounts of licorice might lead to pulmonary edema. In one case report, a 64-year old male consumed 1020 grams of black licorice (Hershey Twizzlers) containing glycyrrhizin 3.6 grams over 3 days, which resulted in pulmonary edema secondary to pseudohyperaldosteronism (31561). Intravenously, the glycyrrhizin constituent of licorice has caused cold or flu-like symptoms, although these events are not common (59712,59721).
General ...Orally and topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
General ...Information regarding the adverse effects of mullein is limited. A thorough evaluation of safety outcomes has not been conducted.
Dermatologic ...Two case reports have described dermatitis, with positive patch tests, after topical exposure to the whole plant, or by occupational inhalation of plant dust (92839,97316). In the case of topical exposure, the patient also had positive patch tests to other plants.
General
...Orally, onion is well tolerated.
Topically, onion is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, heartburn.
Topically: Eczema, irritation.
Serious Adverse Effects (Rare):
All ROAs: Anaphylaxis in sensitive individuals.
Dermatologic ...Topically, frequent contact with onions can result in hand eczema, pemphigus, sensitization, and irritation (18,5004,51303,67066,67093).
Gastrointestinal ...The consumption of large quantities of onions or onion powder can cause stomach distress or heartburn (18,95155,104772). Stomach distress from onion powder appears to be transient (104772). In one case report, consumption of raw onions led to esophageal spasm (66841).
Immunologic ...Allergy to onion is rare, although there are reports of symptoms to both oral and topical exposure (41752,101743). In one case, oral exposure or the aroma of onions caused the sensation of throat closing in an allergic woman (88404). In a 35-year-old man, cooked onion ingestion triggered anaphylaxis (101742). In another case, the smell of onion was identified as a trigger for migraines in a 32-year-old female. Because the patient had a positive allergy skin test for onion, allergenic or immunogenic mechanisms were considered to be the origin of the migraines (88404).
Ocular/Otic ...Exposure to onion aroma can cause excessive tearing (67049).
General
...Orally and topically, PABA is generally well tolerated.
Most Common Adverse Effects:
Orally: Anorexia, dyspepsia, fever, nausea, rash, vomiting.
Topically: Dermatitis, paradoxical photosensitivity.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity.
Dermatologic ...Topically, PABA can cause contact dermatitis and sometimes paradoxical photosensitivity (272).
Gastrointestinal ...Orally, the most commonly reported side effects of PABA are diarrhea, nausea, vomiting, anorexia, dyspepsia, fever, and rash (1074). PABA should be discontinued if adverse effects prevent the patient from eating (10). In one report, up to 25% of patients discontinued PABA due to intolerance of side effects (1074).
Hematologic ...High dose PABA (up to 48 grams per day) can cause decreased white blood count below 4000 mm3 in approximately 30% of patients (1061).
Hepatic ...Liver toxicity, including fatal hepatitis has been reported in patients taking PABA in high doses (12-48 grams per day) (1061,1094). In one case, 12 grams per day for 2 months caused liver toxicity (1094). Increased liver function tests from PABA have also been noted (1084), and jaundice was reported in one case of treatment with PABA (68049). Despite these reports, a study reviewing the charts of 274 patients with scleroderma who were taking the potassium salt form of PABA as treatment found no evidence of hepatotoxicity (1065).
Immunologic ...Orally, PABA can cause allergic reactions including fever and skin rash (1074).
Neurologic/CNS ...Orally, PABA may cause headaches, which resolve upon discontinuation of treatment (1074).
Other ...Death has been reported in 3 children treated with 24 grams of PABA per day for rheumatic fever or arthritis. At autopsy, all had fatty changes in the liver, kidney, and myocardium (1061). Topical PABA and its derivatives have a tendency to discolor clothing due to a photo-oxidative reaction (68025).
General ...A thorough evaluation of safety outcomes with pau d'arco has not been conducted. However, taking the lapachol constituent of pau d'arco in doses above 1.5 grams daily is regarded as unsafe.
Gastrointestinal ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause severe nausea, vomiting, and diarrhea (91939).
Hematologic ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause anemia and increased risk of bleeding (91939).
Immunologic ...Occupational exposure to sawdust from the pau d'arco tree and related species may cause asthma and dermatitis. The fresh sawdust can produce erythema and papules which progress to a severe weeping and crusting dermatitis (92184).
Neurologic/CNS ...Orally, the lapachol constituent of pau d'arco, taken in doses above 1. 5 grams daily, may cause dizziness (91939).
General
...Orally, pleurisy root can cause gastrointestinal irritation, nausea, and vomiting (19).
When consumed in large quantities, pleurisy root may cause digitalis-like poisoning symptoms (18). Acute digitalis poisoning symptoms include gastrointestinal upset, contracted pupils, blurred vision, strong slow pulse, nausea, vomiting, dizziness, excessive urination, fatigue, muscle weakness and tremors, stupor, confusion, convulsions, atrial arrhythmias, bradycardia, AV block, cardiovascular shock, and death (6,159,501).
Topically, pleurisy root may cause dermatitis (19).
Cardiovascular ...Orally, consuming large quantities of pleurisy root may cause digitalis-like poisoning symptoms (18). Acute digitalis poisoning symptoms include strong slow pulse, atrial arrhythmias, bradycardia, AV block, cardiovascular shock, and death (6,159,501).
Dermatologic ...Topically, pleurisy root may cause dermatitis (19).
Gastrointestinal ...Orally, pleurisy root can cause gastrointestinal irritation, nausea, and vomiting (19). When consumed in large quantities, pleurisy root may cause digitalis-like poisoning symptoms (18). Acute digitalis poisoning symptoms include nausea, vomiting, and gastrointestinal upset (6,159,501).
Neurologic/CNS ...Orally, consuming large quantities of pleurisy root may cause digitalis-like poisoning symptoms (18). Acute digitalis poisoning symptoms include dizziness, stupor, confusion, convulsions, and fatigue (6,159,501).
Ocular/Otic ...Orally, consuming large quantities of pleurisy root may cause digitalis-like poisoning symptoms (18). Acute digitalis poisoning symptoms include contracted pupils and blurred vision (6,159,501).
Renal ...Orally, consuming large quantities of pleurisy root may cause digitalis-like poisoning symptoms (18). Acute digitalis poisoning symptoms include excessive urination (6,159,501).
General
...Orally, selenium is generally well-tolerated when used in doses that do not exceed the tolerable upper intake level (UL) of 400 mcg daily.
Intravenously, selenium is generally well-tolerated.
Most Common Adverse Effects:
Orally: Gastric discomfort, headache, and rash. Excessive amounts can cause alopecia, dermatitis, fatigue, nail changes, nausea and vomiting, and weight loss.
Serious Adverse Effects (Rare):
Orally: Excessive ingestion has led to cases of multi-organ failure and death.
Dermatologic ...Excess selenium can produce selenosis in humans, affecting liver, skin, nails, and hair (74304,74326,74397,74495,90360,113660) as well as dermatitis (74304). Results from the Nutritional Prevention of Cancer Trial conducted among individuals at high risk of nonmelanoma skin cancer demonstrate that selenium supplementation is ineffective at preventing basal cell carcinoma and that it increases the risk of squamous cell carcinoma and total nonmelanoma skin cancer (10687). Mild skin rash has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months (97943).
Endocrine
...Multiple clinical studies have found an association between increased intake of selenium, either in the diet or as a supplement, and the risk for type 2 diabetes (97091,99661).
One meta-analysis shows that a selenium plasma level of 90 mcg/L or 140 mcg/L is associated with a 50% or 260% increased risk for developing type 2 diabetes, respectively, when compared with plasma levels below 90 mcg/L. Additionally, consuming selenium in amounts exceeding the recommended dietary allowance (RDA) is associated with an increased risk of developing diabetes when compared with consuming less than the RDA daily. Also, taking selenium 200 mcg daily as a supplement is associated with an 11% increased risk for diabetes when compared with a placebo supplement (99661).
Hypothyroidism, secondary to iodine deficiency, has been reported as a result of selenium intravenous administration (14563,14565). One large human clinical trial suggested a possible increased risk of type 2 diabetes mellitus in the selenium group (16707).
Gastrointestinal ...In human research, nausea, vomiting, and liver dysfunction has been reported as a result of high selenium exposure (74439,74376,113660). Mild gastric discomfort has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months (97943).
Genitourinary ...The effect of selenium supplementation on semen parameters is unclear. In human research, selenium supplementation may reduce sperm motility (9729); however, follow-up research reported no effect on sperm motility or any other semen quality parameter (74441).
Musculoskeletal ...Chronic selenium exposure of 30 mg daily for up to 24 weeks may cause arthralgia, myalgia, and muscle spasms (113660).
Neurologic/CNS ...Chronic exposure to organic and inorganic selenium may cause neurotoxicity, particularly motor neuron degeneration, leading to an increased risk of amyotrophic lateral sclerosis (ALS) (74304). Headache has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months and in patients taking sodium selenate 30 mg daily for up to 24 weeks (97943,113660).
General
...Orally, thyme is well tolerated when used in food and seems to be well tolerated when used medicinally.
Topically, thyme seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Allergic reactions, diarrhea, dizziness, headache, heartburn, nausea, or vomiting.
Topically: Contact dermatitis and skin irritation.
Dermatologic ...Topically, thyme, thyme oil, or the constituent thymol can cause contact dermatitis and skin irritation (13463,78252,78362,78384,77982,78154,78310,78313,78384). In one study of 100 patients with contact allergies, 5% were attributed to thyme oil as an allergen contained in wound dressings (78362). Toothpastes containing thymol have been associated with cheilitis and glossitis (13463).
Gastrointestinal
...Orally, thyme and thyme oil may cause heartburn, nausea, vomiting, stomach upset, or diarrhea (13557,94033).
In a clinical study, two patients using extracts of thyme herb and ivy leaves experienced temporary stomach ache and mild nausea (78181).
Intravaginally, cream containing thyme and garlic has been associated with reports of nausea and vomiting in one clinical study (88387). It is not clear if these adverse effects were associated with thyme, garlic, or the combination.
Genitourinary ...Intravaginally, cream containing thyme and garlic has been associated with reports of vaginal dryness and vaginal irritation in one clinical study (88387). It is not clear if these adverse effects were associated with thyme, garlic, or the combination.
Immunologic ...Orally, thyme can cause allergic reactions; however, this is uncommon (13463). Allergic reactions to thyme might be more common in people who are also allergic to oregano and other Lamiaceae species (3808).
Neurologic/CNS ...Orally, thyme may case headache or dizziness (94033).
Pulmonary/Respiratory ...By inhalation, occupational exposure to thyme dust can cause acute airway obstruction (783,13463,13464,77982,78098).
General
...Orally, watercress is well-tolerated when consumed in food amounts.
There is limited reliable information available about the adverse effects of watercress when used in medicinal amounts. When excessive doses are used, watercress can cause gastrointestinal irritation (85599). Consuming raw watercress has been associated with the development of fascioliasis, a parasitic fluke disease of the liver (85575,85574,85573,85567,85564,85582,85563,85562,85580,85561,85560)(85554,85558,85596,85579,85571,85569,85583,85586,85584,85588)(85585,85590,85592,85591).
Topically, watercress can cause contact dermatitis (85594,85587).
Dermatologic ...Topically, watercress can cause contact dermatitis, resulting in hives, rash, itching, or swollen skin (85594,85587).
Gastrointestinal ...Orally, large quantities of watercress may cause gastrointestinal irritation (85599).
Hepatic ...Raw, wild watercress can be contaminated with parasitic flukes which, when ingested, cause the liver disease fascioliasis. Symptoms include abdominal pain, fever, vomiting, diarrhea, urticaria, eosinophilia, and hepatomegaly (85575,85574,85573,85567,85564,85582,85563,85562,85580,85561)(85560,85554,85558,85596,85579,85571,85569,85583,85586,85584)(85588,85585,85590,85592,85591). Clinical research shows that taking a standardized extract of watercress orally 750 mg/kg daily for 5 weeks is not associated with increases in liver function enzymes (109666).
Renal ...Orally, excessive or prolonged use of watercress may theoretically cause kidney damage (85598). However, in overweight adults with physical disabilities, taking a watercress extract 750 mg/kg daily for 5 weeks does not cause any change in levels of creatinine or urea (109666).
