| Ingredients | Amount Per Serving |
|---|---|
|
Calories
|
15 Calorie(s) |
|
Total Carbohydrates
|
2 Gram(s) |
|
(Fe)
|
0.6 mg |
|
(Na)
|
10 mg |
|
Proprietary Blend
|
858 mg |
|
(Phosphatidylcholine)
(contains 23% phosphatidylcholine)
|
|
|
(aerial parts)
|
|
|
(root)
|
|
|
(Glycyrrhiza glabra root extract, Glycyrrhizin)
(10% glycyrrhizin)
|
|
|
(fruit)
|
|
|
(Black Pepper Fruit Extract)
(95% piperine)
|
|
|
(leaf)
|
300 mg |
|
(leaf)
|
180 mg |
|
Chlorogenic Acid
(CGA)
(15% chlorogenic acids)
|
27 mg |
|
(Taraxacum officinale Root Extract)
|
150 mg |
|
Vitexin
(3% vitexin)
|
4.5 mg |
|
(seed)
|
150 mg |
|
(80% silymarin)
|
120 mg |
|
(root)
|
120 mg |
|
(95% curcuminoids)
|
114 mg |
|
Barberry Flower Extract
(flower)
(4:1)
|
105 mg |
|
(leaf)
(4:1)
|
105 mg |
|
(herb)
(3:1)
|
90 mg |
|
(root)
|
90 mg |
|
(Phyllanthus amarus )
(aerial parts)
|
66 mg |
|
Bitter Principles
(3% bitter principles)
|
1.98 mg |
|
(Picrorhiza kurrooa root extract)
|
66 mg |
|
Kutkin
(3.5% kutkin)
|
2.31 mg |
|
(Schisandra chinensis fruit extract)
|
66 mg |
|
Schisandrins
(1% schisandrin)
|
0.66 mg |
|
(Taraxacum officinale, Powder)
|
60 mg |
|
(seed)
|
60 mg |
Microcrystalline Cellulose, Silicon Dioxide (Alt. Name: SiO2), Maltodextrin, Croscarmellose Sodium, Hydroxypropyl Cellulose (Alt. Name: HPC), Magnesium Stearate (Alt. Name: Mg Stearate), Stearic Acid, Dextrin, Alginic Acid, Sodium Carboxymethylcellulose, Dextrose, Sodium Citrate (Alt. Name: Na Citrate)
Below is general information about the effectiveness of the known ingredients contained in the product Milk Thistle Liver Cleanse. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
There is insufficient reliable information available about the effectiveness of fringetree.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Milk Thistle Liver Cleanse. 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).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Artichoke has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts. Artichoke extract has been used with apparent safety at doses up to 3200 mg daily for up to 12 weeks (6282,15204,52235,91475,91478,100934). Artichoke leaf powder has been used with apparent safety at a dose of 1000 mg daily for up to 8 weeks (104133). Cynarin, a constituent in artichoke extract, has been used with apparent safety at daily doses of 750 mg daily for up to 3 months or 60 mg daily for up to 7 months (1423,1424,52222,52223,52236).
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of artichoke when used in medicinal amounts during pregnancy or lactation; avoid amounts greater than those found in foods.
LIKELY SAFE ...when used in amounts commonly found in foods.
POSSIBLY SAFE ...when used orally and appropriately for medicinal purposes, short term. Beetroot juice has been safely used in clinical trials in doses of up to 500 mL daily for up to 7 days and a beetroot-based nutritional gel has been used safely in doses of up to 100 grams daily for 8 days (94461,94462,94464,100149,100152,100153).
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of beets used medicinally during pregnancy and breast-feeding.
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 commonly found in foods. Boldo has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
POSSIBLY UNSAFE ...when used orally in medicinal amounts. The volatile oil (2.5% in the leaf) contains the liver toxin ascaridole (4). Boldo has also been linked to a documented case of liver damage (13178). If boldo preparations are taken for medicinal purposes, only ascaridole-free preparations should be used. There is insufficient reliable information available about the safety of boldo when used topically.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in medicinal amounts.
In animals, boldo and the constituent boldine have abortive and teratogenic effects (100302). Also, the ascaridole constituent of boldo is a liver toxin (4).
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 taken orally in doses of up to 3 grams daily for up to 12 months (3924,3928,41180,41186,41224,41287,41294,41318,98846,107946)(114011). There is insufficient reliable information available about the safety of chanca piedra when used topically.
PREGNANCY: POSSIBLY UNSAFE
when used during pregnancy or in those trying to become pregnant.
Animal research shows that chanca piedra, particularly at high doses, may have contraceptive effects or may increase the risk of low birth weight or birth defects (41183,41316,41317); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Dandelion has Generally Recognized As Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12). There is insufficient reliable information available about the safety of dandelion when used topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those in foods.
There is insufficient reliable information available about the safety of fringetree.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY UNSAFE ...when used orally. Greater celandine has been implicated in dozens of cases of liver damage, primarily in European countries including Germany (363,13410,16839,41412,53502,53504,53506,53507,53510). There is insufficient reliable information available about the safety of greater celandine when used topically or when derivatives of greater celandine constituents are used intravenously.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. For people age 14 and older with adequate iron stores, iron supplements are safe when used in doses below the tolerable upper intake level (UL) of 45 mg per day of elemental iron. The UL is not meant to apply to those who receive iron under medical supervision (7135,96621). To treat iron deficiency, most people can safely take up to 300 mg elemental iron per day (15). ...when used intravenously and appropriately. Ferric carboxymaltose 200 mg and iron sucrose 200 mg have been given intravenously for up to 10 doses with no reported serious adverse effects (91179). A meta-analysis of clinical studies of hemodialysis patients shows that administering high-dose intravenous (IV) iron does not increase the risk of hospitalization, infection, cardiovascular events, or death when compared with low-dose IV iron, oral iron, or no iron treatment (102861). A more recent meta-analysis of clinical studies of all patient populations shows that administering IV iron does not increase the risk of hospital length of stay or mortality, although the risk of infection is increased by 16% when compared with oral iron or no iron (110186). Despite these findings, there are rare reports of hypophosphatemia and/or osteomalacia (112603,112608,112609,112610).
LIKELY UNSAFE ...when used orally in excessive doses. Doses of 30 mg/kg are associated with acute toxicity. Long-term use of high doses of iron can cause hemosiderosis and multiple organ damage. The estimated lethal dose of iron is 180-300 mg/kg; however, doses as low as 60 mg/kg have also been lethal (15).
CHILDREN: LIKELY SAFE
when used orally and appropriately (7135,91183,112601).
CHILDREN: LIKELY UNSAFE
when used orally in excessive amounts.
Tell patients who are not iron-deficient not to use doses above the tolerable upper intake level (UL) of 40 mg per day of elemental iron for infants and children. Higher doses frequently cause gastrointestinal side effects such as constipation and nausea (7135,20097). Iron is the most common cause of pediatric poisoning deaths. Doses as low as 60 mg/kg can be fatal (15).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Iron is safe during pregnancy and breast-feeding in patients with adequate iron stores when used in doses below the tolerable upper intake level (UL) of 45 mg daily of elemental iron (7135,96625,110180).
PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally in high doses.
Tell patients who are not iron deficient to avoid exceeding the tolerable upper intake level (UL) of 45 mg daily of elemental iron. Higher doses frequently cause gastrointestinal side effects such as nausea and vomiting (7135) and might increase the risk of preterm labor (100969). High hemoglobin concentrations at the time of delivery are associated with adverse pregnancy outcomes (7135,20109).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Lecithin has Generally Recognized As Safe (GRAS) status in the US (2619,105544). ...when used orally and appropriately in medicinal amounts. Lecithin has been used safely in doses of up to 30 grams daily for up to 6 weeks (5140,5149,5152,5156,14817,14822,14838,19212). ...when used topically (4914).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts.
Lecithin has Generally Recognized As Safe (GRAS) status in the US (105544). There is insufficient reliable information available about the safety of medicinal amounts of lecithin during pregnancy or lactation; avoid using.
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 used orally and appropriately. A specific milk thistle extract standardized to contain 70% to 80% silymarin (Legalon, Madaus GmbH) has been safely used in doses up to 420 mg daily for up to 4 years (2613,2614,2616,7355,63210,63212,63278,63280,63299,63340)(88154,97626,105792). Higher doses of up to 2100 mg daily have been safely used for up to 48 weeks (63251,96107,101150). Another specific milk thistle extract of silymarin (Livergol, Goldaru Pharmaceutical Company) has been safely used at doses of 140 mg daily for up to 6 months and doses of 420 mg daily for up to 6 weeks (95021,95029,102851,102852,105793,105794,105795,113979). Some isolated milk thistle constituents also appear to be safe. Silibinin (Siliphos, Thorne Research) has been used safely in doses up to 320 mg daily for 28 days (63218). Some combination products containing milk thistle and other ingredients also appear to be safe. A silybin-phosphatidylcholine complex (Silipide, Inverni della Beffa Research and Development Laboratories) has been safely used in doses of 480 mg daily for 7 days (7356) and 240 mg daily for 3 months (63320). Tree turmeric and milk thistle capsules (Berberol, PharmExtracta) standardized to contain 60% to 80% silybin have been safely used twice daily for up to 12 months (95019,96140,96141,96142,97624,101158).
POSSIBLY SAFE ...when used topically and appropriately, short-term. A milk thistle extract cream standardized to silymarin 0.25% (Leviaderm, Madaus GmbH) has been used safely throughout a course of radiotherapy (63239). Another milk thistle extract cream containing silymarin 1.4% has been used with apparent safety twice daily for 3 months (105791,110489). A cream containing milk thistle fruit extract 25% has been used with apparent safety twice daily for up to 12 weeks (111175). A milk thistle extract gel containing silymarin 1% has been used with apparent safety twice daily for 9 weeks (95022). There is insufficient reliable information available about the safety of intravenous formulations of milk thistle or its constituents.
PREGNANCY AND LACTATION:
While research in an animal model shows that taking milk thistle during pregnancy and lactation does not adversely impact infant development (102850), there is insufficient reliable information available about its safety during pregnancy or lactation in humans; avoid using.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
A milk thistle extract 140 mg three times daily has been used with apparent safety for up to 9 months (88154,98452). A specific product containing the milk thistle constituent silybin (Siliphos, Thorne Research Inc.) has been used with apparent safety in doses up to 320 mg daily for up to 4 weeks in children one year of age and older (63218).
POSSIBLY SAFE ...when used orally and appropriately. Picrorhiza seems to be safe when used for up to 1 year (11493,11848,11858).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Schisandra extract up to 1 gram daily has been used for up to 12 weeks with apparent safety (12,96632,105562,105563,112887).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Some evidence suggests schisandra fruit is a uterine stimulant (11).
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. Sodium is safe in amounts that do not exceed the Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams daily (100310). Higher doses can be safely used therapeutically with appropriate medical monitoring (26226,26227).
POSSIBLY UNSAFE ...when used orally in high doses. Tell patients to avoid exceeding the CDRR intake level of 2.3 grams daily (100310). Higher intake can cause hypertension and increase the risk of cardiovascular disease (26229,98176,98177,98178,98181,98183,98184,100310,109395,109396,109398,109399). There is insufficient reliable information available about the safety of sodium when used topically.
CHILDREN: LIKELY SAFE
when used orally and appropriately (26229,100310).
Sodium is safe in amounts that do not exceed the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310).
CHILDREN: POSSIBLY UNSAFE
when used orally in high doses.
Tell patients to avoid prolonged use of doses exceeding the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310). Higher intake can cause hypertension (26229).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Sodium is safe in amounts that do not exceed the CDRR intake level of 2.3 grams daily (100310).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in higher doses.
Higher intake can cause hypertension (100310). Also, both the highest and the lowest pre-pregnancy sodium quintile intakes are associated with an increased risk of hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, and the delivery of small for gestational age (SGA) infants when compared to the middle intake quintile (106264).
LIKELY SAFE ...when used orally and appropriately, short-term. Turmeric products providing up to 8 grams of curcumin have been safely used for up to 2 months (10453,11144,11150,17953,79085,89720,89721,89724,89728,101347)(81036,101349,107110,107116,107117,107118,107121,109278,109283). Turmeric in doses up to 3 grams daily has been used with apparent safety for up to 3 months (102350,104146,104148,113357). ...when used topically and appropriately (11148).
POSSIBLY SAFE ...when used as an enema, short-term. Turmeric extract in water has been used as a daily enema for up to 8 weeks (89729). ...when used topically as a mouthwash, short-term. A mouthwash containing 0.05% turmeric extract and 0.05% eugenol has been used safely twice daily for up to 21 days (89723).
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in food.
PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts; turmeric might stimulate the uterus and increase menstrual flow (12).
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food.
There is insufficient reliable information available about the safety of using turmeric in medicinal amounts during lactation.
Below is general information about the interactions of the known ingredients contained in the product Milk Thistle Liver Cleanse. 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.
 Details
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Theoretically, alfalfa might interfere with the activity of contraceptive drugs.
Details
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Theoretically, alfalfa might interfere with hormone therapy.
Details
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Theoretically, alfalfa might decrease the efficacy of immunosuppressive therapy.
Details
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Theoretically, concomitant use of alfalfa with photosensitizing drugs might have additive effects.
Details
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.
Details
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Theoretically, artichoke leaf extract may increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
A meta-analysis of small clinical studies shows that taking artichoke leaf extract for 8-12 weeks can modestly reduce fasting plasma glucose when compared with placebo (105768).
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Theoretically, artichoke leaf extract may increase the risk of hypotension when taken with antihypertensive drugs.
Details
A meta-analysis of small clinical studies in patients with hypertension shows that taking artichoke can reduce systolic blood pressure by around 3 mmHg and diastolic blood pressure by around 2 mmHg when compared with placebo (105767).
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Theoretically, artichoke might increase serum levels of drugs metabolized by CYP2B6.
Details
In vitro research shows that artichoke leaf extract inhibits CYP2B6 activity (97717). However, this interaction has not been reported in humans.
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Theoretically, artichoke might increase serum levels of drugs metabolized by CYP2C19.
Details
In vitro research shows that artichoke leaf extract inhibits CYP2C19 activity (97717). However, this interaction has not been reported in humans.
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Theoretically, beet might decrease the levels and clinical effects of CYP1A2 substrates.
Details
In vitro research suggests that beet induces CYP1A2 enzymes (111404).
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Theoretically, beet might increase the levels of CYP3A4 substrates.
Details
In vitro research suggests that betanin, the major pigment in beet, competitively inhibits CYP3A4 in a dose-dependent manner similarly to strong CYP3A4 inhibitor ketoconazole (113425).
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Theoretically, black pepper might increase the effects and side effects of amoxicillin.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
Details
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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.
Details
Black pepper is thought to have diuretic properties (11).
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Black pepper might increase blood levels of nevirapine.
Details
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.
Details
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Theoretically, black pepper might increase the sedative effects of pentobarbital.
Details
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.
Details
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.
Details
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.
Details
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Black pepper might increase blood levels of theophylline.
Details
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, taking boldo with anticoagulant/antiplatelet drugs might increase the risk of bleeding.
Details
Animal and in vitro research shows that boldine, a constituent of boldo, has antiplatelet activity (5191,36789). In one case report, an adult taking a combination of boldo and fenugreek with warfarin experienced an increase in international normalized ratio (INR); however, it is unclear if this effect was due to boldo, fenugreek, the combination, or another factor (5191).
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Theoretically, taking boldo with hepatotoxic drugs might increase the risk of hepatic injury and disease.
Details
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Theoretically, taking boldo with lithium might increase the levels and clinical effects of lithium.
Details
Boldo is believed to have diuretic effects (4). Theoretically, these diuretic effects might reduce the excretion of lithium. The dose of lithium might need to be decreased.
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Taking boldo with tacrolimus may decrease the levels and clinical effects of tacrolimus, potentially increasing the risk of transplant rejection.
Details
In one case report, a patient with a long-term history of stable tacrolimus levels developed subtherapeutic levels after taking boldo 300 mg twice daily orally for several weeks. Tacrolimus levels returned to normal after discontinuing boldo. However, the mechanism of this interaction is unclear (92601).
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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.
Details
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.
Details
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.
Details
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.
Details
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Theoretically, chanca piedra might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs.
Details
In vitro research suggests that methyl brevifolincarboxylate, a constituent isolated from chanca piedra, can inhibit platelet aggregation (41234). This effect has not been reported in humans.
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Theoretically, concomitant use with antidiabetes drugs might affect glucose control and increase the risk of hypoglycemia.
Details
Animal research suggests that chanca piedra can have hypoglycemic effects (19,41226,41280,41305,41306,41307). However, a small clinical study in adults with diabetes shows that chanca piedra extract 25 grams orally daily for 1 week does not lower fasting or postprandial blood glucose levels (41186).
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Theoretically, concomitant use of chanca piedra with antihypertensive drugs might have additive blood pressure lowering effects.
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Theoretically, concomitant use of chanca piedra with diuretics might increase diuresis.
Details
Some preliminary clinical research in adults with hypertension shows that chanca piedra has diuretic properties (3928). However, higher quality research in adults with kidney stones shows taking chanca piedra does not increase urine volume when compared with placebo (41202). Until more is known, use cautiously in patients taking diuretic drugs.
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Theoretically, chanca piedra might reduce excretion and increase levels of lithium.
Details
Some preliminary clinical research in adults with hypertension shows that chanca piedra has diuretic properties (3928). However, higher quality research in adults with kidney stones shows that taking chanca piedra does not increase urine volume when compared with placebo (41202). Until more is known, use cautiously in patients taking lithium. The dose of lithium might need to be decreased.
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Theoretically, chanca piedra may reduce the effects of norepinephrine.
Details
Animal research suggests that methyl brevifolincarboxylate, a constituent isolated from chanca piedra, can reverse blood vessel contraction caused by norepinephrine (41215).
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Theoretically, taking dandelion root along with anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.
Details
In vitro research suggests that dandelion root inhibits platelet aggregation (18291).
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Theoretically, dandelion might increase the risk for hypoglycemia when used with antidiabetes drugs.
Details
Laboratory research suggests that dandelion extract may have moderate alpha-glucosidase inhibitor activity and might also increase insulin secretion (13474,90926). Also, in a case report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemia 2 weeks after beginning to eat salads containing dandelion (46960).
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Theoretically, dandelion might increase levels of drugs metabolized by CYP1A2.
Details
Laboratory research suggests that dandelion might inhibit CYP1A2 (12734). So far, this interaction has not been reported in humans. However, until more is known, watch for an increase in the levels of drugs metabolized by CYP1A2 in patients taking dandelion.
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Theoretically, dandelion might increase the clearance of drugs that are UDP-glucuronosyltransferase substrates.
Details
There is some preliminary evidence that dandelion might induce UDP-glucuronosyltransferase, a phase II enzyme (12734).
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Theoretically, through diuretic effects, dandelion might reduce excretion and increase levels of lithium.
Details
Animal research suggests that dandelion has diuretic properties (13475). As diuretics can increase serum lithium levels, the dose of lithium might need to be decreased when taken with dandelion.
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Theoretically, dandelion might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.
Details
Dandelion contains significant amounts of potassium (13465).
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Theoretically, dandelion might lower fluoroquinolone levels.
Details
Animal research shows that dandelion reduces absorption of ciprofloxacin and can lower levels by 73% (13477). However, this effect has not been reported in humans.
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Research in vitro shows that chelidonine, a constituent of greater celandine, inhibits cytochrome P450 2D6 (CYP2D6) enzyme activity (99455). Theoretically, greater celandine might increase levels of drugs metabolized by CYP2D6.
Details
Some drugs metabolized by CYP2D6 include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide (Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone (Dolophine), metoprolol (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), and many others.
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There is some concern that greater celandine can adversely affect the liver. Greater celandine has been linked to many cases of hepatotoxicity (363,13410,16839,41412,53502,53504,53506,53507,53510). Theoretically, concomitant use with other potentially hepatotoxic drugs might increase the risk of developing liver damage. Some of these drugs include acarbose (Precose, Prandase), amiodarone (Cordarone), atorvastatin (Lipitor), azathioprine (Imuran), carbamazepine (Tegretol), cerivastatin (Baycol), diclofenac (Voltaren), felbamate (Felbatol), fenofibrate (TriCor), fluvastatin (Lescol), gemfibrozil (Lopid), isoniazid, itraconazole, (Sporanox), ketoconazole (Nizoral), leflunomide (Arava), lovastatin (Mevacor), methotrexate (Rheumatrex), nevirapine (Viramune), niacin, nitrofurantoin (Macrodantin), pioglitazone (Actos), pravastatin (Pravachol), pyrazinamide, rifampin (Rifadin), ritonavir (Norvir), rosiglitazone (Avandia), simvastatin (Zocor), tacrine (Cognex), tamoxifen, terbinafine (Lamisil), valproic acid, and zileuton (Zyflo).
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Preliminary clinical research suggests that taking a specific semi-synthetic derivative of the greater celandine constituent chelidonine (Ukrain; not available in North America) might stimulate immune responses in cancer patients (53473,53497). Theoretically, taking greater celandine might decrease the effects of immunosuppressive therapy. Immunosuppressant drugs include azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), daclizumab (Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), and other corticosteroids (glucocorticoids).
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Theoretically taking monoamine oxidase inhibitors (MAOIs) with greater celandine might increase the risk of serotonergic side effects including serotonin syndrome. In vitro research shows that chelerythrine, an isoquinoline alkaloid in greater celandine, strongly, selectively, and reversibly inhibits an isoform of recombinant human monoamine oxidase-A (MAO-A). It was also a weak but selective inhibitor of monoamine oxidase-B (MAO-B) (99454). Some MAOIs include phenelzine (Nardil), tranylcypromine (Parnate), and others.
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Iron reduces the absorption of bisphosphonates.
Details
Advise patients that doses of bisphosphonates should be separated by at least two hours from doses of all other medications, including supplements such as iron. Divalent cations, including iron, can decrease absorption of bisphosphonates by forming insoluble complexes in the gastrointestinal tract (15).
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Theoretically, taking chloramphenicol with iron might reduce the response to iron therapy in iron deficiency anemia.
Details
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Iron might decrease dolutegravir levels by reducing its absorption.
Details
Advise patients to take dolutegravir at least 2 hours before or 6 hours after taking iron. Pharmacokinetic research shows that iron can decrease the absorption of dolutegravir from the gastrointestinal tract through chelation (93578). When taken under fasting conditions, a single dose of ferrous fumarate 324 mg orally along with dolutegravir 50 mg reduces overall exposure to dolutegravir by 54% (94190).
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Theoretically, taking iron along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Details
Iron is a divalent cation. There is concern that iron may decrease the absorption of integrase inhibitors from the gastrointestinal tract through chelation (93578). One pharmacokinetic study shows that iron can decrease blood levels of the specific integrase inhibitor dolutegravir through chelation (94190). Also, other pharmacokinetic research shows that other divalent cations such as calcium can decrease the absorption and levels of some integrase inhibitors through chelation (93578,93579).
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Iron might decrease levodopa levels by reducing its absorption.
Details
Advise patients to separate doses of levodopa and iron as much as possible. There is some evidence in healthy people that iron forms chelates with levodopa, reducing the amount of levodopa absorbed by around 50% (9567). The clinical significance of this hasn't been determined.
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Iron might decrease levothyroxine levels by reducing its absorption.
Details
Advise patients to separate levothyroxine and iron doses by at least 2 hours. Iron can decrease the absorption and efficacy of levothyroxine by forming insoluble complexes in the gastrointestinal tract (9568).
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Iron might decrease methyldopa levels by reducing its absorption.
Details
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Theoretically, iron might decrease mycophenolate mofetil levels by reducing its absorption.
Details
Advise patients to take iron 4-6 hours before, or 2 hours after, mycophenolate mofetil. It has been suggested that a decrease of absorption is possible, probably by forming nonabsorbable chelates. However, mycophenolate pharmacokinetics are not affected by iron supplementation in available clinical research (3046,20152,20153,20154,20155).
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Iron might decrease penicillamine levels by reducing its absorption.
Details
Advise patients to separate penicillamine and iron doses by at least 2 hours. Oral iron supplements can reduce absorption of penicillamine by 30% to 70%, probably due to chelate formation. In people with Wilson's disease, this interaction has led to reduced efficacy of penicillamine (3046,3072,20156).
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Iron might decrease levels of quinolone antibiotics by reducing their absorption.
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Iron might decrease levels of tetracycline antibiotics by reducing their absorption.
Details
Advise patients to take iron at least 2 hours before or 4 hours after tetracycline antibiotics. Concomitant use can decrease absorption of tetracycline antibiotics from the gastrointestinal tract by 50% to 90% (15).
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Theoretically, licorice might reduce the effects of antihypertensive drugs.
Details
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Theoretically, licorice might reduce the effects of cisplatin.
Details
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 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.
Details
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.
Details
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.
Details
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.
Details
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.
Details
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Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.
Details
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.
Details
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.
Details
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.
Details
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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Taking milk thistle with antidiabetes drugs may increase the risk of hypoglycemia.
Details
Clinical research shows that milk thistle extract, alone or along with tree turmeric extract, can lower blood glucose levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, including those already taking antidiabetes drugs (15102,63190,63314,63318,95019,96140,96141,97624,97626,113987).
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Theoretically, milk thistle might inhibit CYP2B6.
Details
An in vitro study shows that silybin, a constituent of milk thistle, binds to and noncompetitively inhibits CYP2B6. Additionally, silybin might downregulate the expression of CYP2B6 by decreasing mRNA and protein levels (112229).
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It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
Details
In vitro research suggests that milk thistle might inhibit CYP2C9 (7089,17973,17976). Additionally, 3 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP2C9 substrates, including imatinib and capecitabine (111644). However, contradictory clinical research shows that milk thistle extract does not inhibit CYP2C9 or significantly affect levels of the CYP2C9 substrate tolbutamide (13712,95026). Differences in results could be due to differences in dosages or formulations utilized (95026).
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It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Details
While laboratory research shows conflicting results (7318,17973,17975,17976), pharmacokinetic research shows that taking milk thistle extract 420-1350 mg daily does not significantly affect the metabolism of the CYP3A4 substrates irinotecan, midazolam, or indinavir (8234,17974,93578,95026). However, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP3A4 substrates, including gefitinib, sorafenib, doxorubicin, and vincristine (111644).
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Theoretically, milk thistle might interfere with estrogen therapy through competition for estrogen receptors.
Details
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Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
Details
Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation (7318,17973). Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase (7354), although the significance of this effect is unclear.
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Theoretically, milk thistle might interfere with statin therapy by decreasing the activity of organic anion transporting polypeptide 1B1 (OATB1B1) and inhibiting breast cancer resistance protein (BCRP).
Details
Preliminary evidence suggests that a milk thistle extract of silymarin can decrease the activity of the OATP1B1, which transports HMG-CoA reductase inhibitors into the liver to their site of action, and animal research shows this increases the maximum plasma concentration of pitavastatin and pravastatin (113975). The silibinin component also inhibits BCRP, which transports statins from the liver into the bile for excretion. However, in a preliminary study in healthy males, silymarin 140 mg three times daily had no effect on the pharmacokinetics of a single 10 mg dose of rosuvastatin (16408).
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Theoretically, milk thistle may induce cytochrome P450 3A4 (CYP3A4) enzymes and increase the metabolism of indinavir; however, results are conflicting.
Details
One pharmacokinetic study shows that taking milk thistle (Standardized Milk Thistle, General Nutrition Corp.) 175 mg three times daily in combination with multiple doses of indinavir 800 mg every 8 hours decreases the mean trough levels of indinavir by 25% (8234). However, results from the same pharmacokinetic study show that milk thistle does not affect the overall exposure to indinavir (8234). Furthermore, two other pharmacokinetic studies show that taking specific milk thistle extract (Legalon, Rottapharm Madaus; Thisilyn, Nature's Way) 160-450 mg every 8 hours in combination with multiple doses of indinavir 800 mg every 8 hours does not reduce levels of indinavir (93578).
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Theoretically, milk thistle might increase the levels and clinical effects of ledipasvir.
Details
Animal research in rats shows that milk thistle increases the area under the curve (AUC) for ledipasvir and slows its elimination (109505).
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Theoretically, concomitant use of milk thistle with morphine might affect serum levels of morphine and either increase or decrease its effects.
Details
Animal research shows that milk thistle reduces serum levels of morphine by up to 66% (101161). In contrast, laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation (7318,17973). Theoretically, this could decrease the clearance and increase morphine levels. The effect of taking milk thistle on morphine metabolism in humans is not known.
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Milk thistle may inhibit one form of OATP, OATP-B1, which could reduce the bioavailability and clinical effects of OATP-B1 substrates.
Details
In vitro research shows that milk thistle inhibits OATP-B1. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are OATP substrates, including sorafenib and methotrexate (111644). OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.
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Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.
Details
In vitro research shows that milk thistle can inhibit P-glycoprotein activity (95019,111644) and 1 case report from the World Health Organization (WHO) adverse drug reaction database describes increased abdominal pain in a patient taking milk thistle and the cancer medication vincristine, a P-glycoprotein substrate, though this patient was also taking methotrexate (111644). However, a small pharmacokinetic study in healthy volunteers shows that taking milk thistle (Enzymatic Therapy Inc.) 900 mg, standardized to 80% silymarin, in 3 divided doses daily for 14 days does not affect absorption of digoxin, a P-glycoprotein substrate (35825).
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Theoretically, milk thistle might decrease the clearance and increase levels of raloxifene.
Details
Laboratory research suggests that the milk thistle constituents silibinin and silymarin inhibit the glucuronidation of raloxifene in the intestines (93024).
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Milk thistle might decrease the clearance of sirolimus.
Details
Pharmacokinetic research shows that a milk thistle extract of silymarin decreases the apparent clearance of sirolimus in hepatically impaired renal transplant patients (19876). It is unclear if this interaction occurs in patients without hepatic impairment.
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Theoretically, milk thistle might decrease the levels and clinical effects of sofosbuvir.
Details
Animal research in rats shows that milk thistle reduces the metabolism of sofosbuvir, as well as the hepatic uptake of its active metabolite (109505).
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Theoretically, the milk thistle constituent silibinin might increase tamoxifen levels and interfere with its conversion to an active metabolite.
Details
Animal research suggests that the milk thistle constituent silibinin might increase plasma levels of tamoxifen and alter its conversion to an active metabolite. The mechanism appears to involve inhibition of pre-systemic metabolism of tamoxifen by cytochrome P450 (CYP) 2C9 and CYP3A4, and inhibition of P-glycoprotein-mediated efflux of tamoxifen into the intestine for excretion (17101). Whether this interaction occurs in humans is not known.
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Theoretically, milk thistle might increase the effects of warfarin.
Details
In one case report, a man stabilized on warfarin experienced an increase in INR from 2.64 to 4.12 after taking a combination product containing milk thistle 200 mg daily, as well as dandelion, wild yam, niacinamide, and vitamin B12. Levels returned to normal after stopping the supplement (101159). Although a direct correlation between milk thistle and the change in INR cannot be confirmed, some in vitro research suggests that milk thistle might inhibit cytochrome P450 2C9 (CYP2C9), an enzyme involved in the metabolism of various drugs, including warfarin (7089,17973,17976).
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Evidence from animal research suggests that an extract of picrorhiza can reduce fasting and non-fasting blood sugar levels (57220). Theoretically, picrorhiza might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia. Monitor blood glucose levels closely. Dose adjustments might be necessary. Some antidiabetes drugs include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), and others.
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Picrorhiza seems to have immunostimulating activity (11492,11853). Theoretically, picrorhiza may interfere with immunosuppressant therapy. Immunosuppressant drugs include azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), daclizumab (Zenapax), muromonab-CD3 (OKT3, Orthoclone OKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), and other corticosteroids (glucocorticoids).
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Theoretically, schisandra might increase the levels and clinical effects of cyclophosphamide.
Details
In vitro research shows that schisandra increases the concentration of cyclophosphamide, likely through inhibition of cytochrome P450 3A4. After multiple doses of the schisandra constituents schisandrin A and schisantherin A, the maximum concentration of cyclophosphamide was increased by 7% and 75%, respectively, while the overall exposure to cyclophosphamide was increased by 29% and 301%, respectively (109636).
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Schisandra can increase the levels and clinical effects of cyclosporine.
Details
A small observational study in children with aplastic anemia found that taking schisandra with cyclosporine increased cyclosporine trough levels by 93% without increasing the risk of adverse events. However, the dose of cyclosporine was reduced in 9% of children to maintain appropriate cyclosporine blood concentrations (109637).
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Theoretically, schisandra might increase the levels and clinical effects of CYP2C19 substrates.
Details
In vitro research shows that schisandra inhibits CYP2C19, and animal research shows that schisandra increases the concentration of voriconazole, a CYP2C19 substrate (105566). Theoretically, schisandra may also inhibit the metabolism of other CYP2C19 substrates. This effect has not been reported in humans.
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Theoretically, schisandra might decrease the levels and clinical effects of CYP2C9 substrates.
Details
In vitro and animal research suggests that schisandra induces CYP2C9 enzymes (14441). This effect has not been reported in humans.
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Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.
Details
Most clinical and laboratory research shows that schisandra, administered either as a single dose or up to twice daily for 14 days, inhibits CYP3A4 and increases the concentration of CYP3A4 substrates such as cyclophosphamide, midazolam, tacrolimus, and talinolol (13220,17414,23717,91386,91388,91387,96631,105564,109636,109638,109639,109640,109641). Although one in vitro and animal study shows that schisandra may induce CYP3A4 metabolism (14441), this effect appears to be overpowered by schisandra's CYP3A4 inhibitory activity and has not been reported in humans.
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Schisandra can increase the levels and clinical effects of midazolam.
Details
A small pharmacokinetic study in healthy adults shows that taking schisandra extract (Hezheng Pharmaceutical Co.) containing deoxyschizandrin 33.75 mg twice daily for 8 days and a single dose of midazolam 15 mg on day 8 increases the overall exposure to midazolam by about 119%, increases the peak plasma level of midazolam by 86%, and decreases midazolam clearance by about 52%. This effect has been attributed to inhibition of CYP3A4 by schisandra (91388).
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Schisandra might increase the levels and clinical effects of P-glycoprotein substrates.
Details
In vitro research shows that schisandra extracts and constituents such as schisandrin B inhibit P-glycoprotein mediated efflux in intestinal cells and in P-glycoprotein over-expressing cell lines (17414,105643,105644). Additionally, a small clinical study shows that schisandra increases the peak concentration and overall exposure to talinolol, a P-glycoprotein probe substrate (91386). Theoretically, schisandra might inhibit the efflux of other P-glycoprotein substrates.
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Schisandra can increase the levels and clinical effects of sirolimus.
Details
A small pharmacokinetic study in healthy volunteers shows that taking 3 capsules of schisandra (Hezheng Pharmaceutical Company) containing a total of 33.75 mg deoxyschizandrin twice daily for 13 days and then taking a single dose of sirolimus 2 mg increases the overall exposure and peak level of sirolimus by two-fold. This effect is thought to be due to inhibition of cytochrome P450 3A4 by schisandra, as well as possible inhibition of the P-glycoprotein drug transporter (105643).
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Schisandra can increase the levels and clinical effects of tacrolimus.
Details
Clinical research in healthy children and adults, transplant patients, and patients with nephrotic syndrome and various rheumatic immunologic disorders shows that taking schisandra with tacrolimus increases tacrolimus peak levels by 183% to 268%, prolongs or delays time to peak tacrolimus concentrations, increases overall exposure to tacrolimus by 126% to 343%, and decreases tacrolimus clearance by 19% to 73% (17414,91387,15570,96631,105623,109638,109639,109640,109641,112889)(112890,112972,112973,112974). This effect is thought to be due to inhibition of P-glycoprotein drug transporter and CYP3A4 and CYP3A5 by schisandra (17414,96631,105623,105643,105644,112974). Some clinical and observational studies suggest that schisandra increases tacrolimus levels similarly in both expressors and non-expressors of CYP3A5, while other studies suggest it does so to a greater degree in CYP3A5 expressors than non-expressors (105623,109638,109639,109640,112889,112890,112973,112974). Animal research suggests that the greatest increase in tacrolimus levels occurs when schisandra is taken either concomitantly or up to 2 hours before tacrolimus (105564), and clinical and observational research in humans suggests that schisandra may increase whole blood levels of tacrolimus and decrease clearance of tacrolimus in a dose-dependent manner (109639,109640,112972).
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Schisandra can increase the levels and clinical effects of talinolol.
Details
A small pharmacokinetic study in healthy volunteers shows that taking schisandra extract 300 mg twice daily for 14 days with a single dose of talinolol 100 mg on day 14 increases the peak talinolol level by 51% and the overall exposure to talinolol by 47%. This effect is thought to be due to the possible inhibition of cytochrome P450 3A4 and P-glycoprotein by schisandra (91386).
tly.
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Theoretically, schisandra might increase the levels and clinical effects of voriconazole.
Details
Animal research shows that oral schisandra given daily for 1 or 14 days increases levels of intravenously administered voriconazole, a cytochrome P450 (CYP) 2C19 substrate. This effect is thought to be due to inhibition of CYP2C19 by schisandra (105566). However, this interaction has not been reported in humans.
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Theoretically, schisandra might decrease the levels and clinical effects of warfarin.
Details
Animal research suggests that oral schisandra extract, given daily for 6 days, reduces levels of intravenously administered warfarin. This effect might be due to the induction of cytochrome P450 (CYP) 2C9 metabolism by schisandra (14441). However, this interaction has not been reported in humans.
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Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.
Details
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Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.
Details
Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone (4425).
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Altering dietary intake of sodium might alter the levels and clinical effects of lithium.
Details
High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion (26225). Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate (26224,26225). Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L (112909). Patients taking lithium should avoid significant alterations in their dietary intake of sodium.
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Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.
Details
The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population (100310). Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.
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Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.
Details
Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia (29406). Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.
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Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
Details
In vitro research suggests that curcumin, a constituent of turmeric, inhibits mechlorethamine-induced apoptosis of breast cancer cells by up to 70%. Also, animal research shows that curcumin inhibits cyclophosphamide-induced tumor regression (96126). However, some in vitro research shows that curcumin does not affect the apoptosis capacity of etoposide. Also, other laboratory research suggests that curcumin might augment the cytotoxic effects of alkylating agents. Reasons for the discrepancies may relate to the dose of curcumin and the specific chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have on alkylating agents.
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Taking turmeric with amlodipine may increase levels of amlodipine.
Details
Animal research shows that giving amlodipine 1 mg/kg as a single dose following the use of turmeric extract 200 mg/kg daily for 2 weeks increases the maximum concentration and area under the curve by 53% and 56%, respectively, when compared with amlodipine alone (107113). Additional animal research shows that taking amlodipine 1 mg/kg with a curcumin 2 mg/kg pretreatment for 10 days increases the maximum concentration and area under the curve by about 2-fold when compared with amlodipine alone (103099).
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Turmeric may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Details
Curcumin, a constituent of turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271). Furthermore, two case reports have found that taking turmeric along with warfarin or fluindione was associated with an increased international normalized ratio (INR) (89718,100906). However, one clinical study in healthy volunteers shows that taking curcumin 500 mg daily for 3 weeks, alone or with aspirin 100 mg, does not increase antiplatelet effects or bleeding risk (96137). It is possible that the dose of turmeric used in this study was too low to produce a notable effect.
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Theoretically, taking turmeric with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Animal research and case reports suggest that curcumin, a turmeric constituent, can reduce blood glucose levels in patients with diabetes (79692,79984,80155,80313,80315,80476,80553,81048,81219). Furthermore, clinical research in adults with type 2 diabetes shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg decreased postprandial glucose levels for up to 24 hours when compared with glyburide alone, despite the lack of a significant pharmacokinetic interaction (96133). Another clinical study in patients with diabetes on hemodialysis shows that taking curcumin 80 mg daily for 12 weeks can reduce blood glucose levels when compared with placebo (104149).
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Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
Details
In vitro and animal research shows that curcumin, a constituent of turmeric, inhibits doxorubicin-induced apoptosis of breast cancer cells by up to 65% (96126). However, curcumin does not seem to affect the apoptosis capacity of daunorubicin. In fact, some research shows that curcumin might augment the cytotoxic effects of antitumor antibiotics, increasing their effectiveness. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effects, if any, antioxidants such as turmeric have on antitumor antibiotics.
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Theoretically, turmeric might increase or decrease levels of drugs metabolized by CYP1A1. However, research is conflicting.
Details
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Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.
Details
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Turmeric might increase levels of drugs metabolized by CYP3A4.
Details
In vitro and animal research show that turmeric and its constituents curcumin and curcuminoids inhibit CYP3A4 (21497,21498,21499). Also, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking turmeric and cancer medications that are CYP3A4 substrates, including everolimus, ruxolitinib, ibrutinib, and palbociclib, and bortezomib (111644). In another case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels after consuming turmeric powder at a dose of 15 or more spoonfuls daily for ten days prior. It was thought that turmeric increased levels of tacrolimus due to CYP3A4 inhibition (93544).
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Theoretically, turmeric might increase blood levels of oral docetaxel.
Details
Animal research suggests that the turmeric constituent, curcumin, enhances the oral bioavailability of docetaxel (80999). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.
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Theoretically, large amounts of turmeric might interfere with hormone replacement therapy through competition for estrogen receptors.
Details
In vitro research shows that curcumin, a constituent of turmeric, displaces the binding of estrogen to its receptors (21486).
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Theoretically, taking turmeric and glyburide in combination might increase the risk of hypoglycemia.
Details
Clinical research shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 diabetes. While maximal blood concentrations of glyburide were not affected, turmeric modestly decreased postprandial glucose levels for up to 24 hours when compared to glyburide alone, possibly due to the hypoglycemic effect of turmeric demonstrated in animal research (96133).
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Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs.
Details
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Theoretically, turmeric might increase the effects of losartan.
Details
Research in hypertensive rats shows that taking turmeric can increase the hypotensive effects of losartan (110897).
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Theoretically, turmeric might have additive effects when used with hepatotoxic drugs such as methotrexate.
Details
In one case report, a 39-year-old female taking methotrexate, turmeric, and linseed oil developed hepatotoxicity (111644).
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Theoretically, turmeric might increase the effects and adverse effects of norfloxacin.
Details
Animal research shows that taking curcumin, a turmeric constituent, can increase blood levels of orally administered norfloxacin (80863).
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Theoretically, turmeric might increase blood levels of OATP4C1 substrates.
Details
In vitro research shows that the turmeric constituent curcumin competitively inhibits OATP4C1 transport. This transporter is expressed in the kidney and facilitates the renal excretion of certain drugs (113337). Theoretically, taking turmeric might decrease renal excretion of OATP substrates.
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Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.
Details
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Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.
Details
Clinical research in adults with breast cancer receiving intravenous paclitaxel suggests that taking turmeric may modestly alter paclitaxel pharmacokinetics. Patients received paclitaxel on day 1, followed by either no treatment or turmeric 2 grams daily from days 2-22. Pharmacokinetic modeling suggests that turmeric reduces the maximum concentration and area under the curve of paclitaxel by 12.1% and 7.7%, respectively. However, these changes are not likely to be considered clinically relevant (108876). Conversely, animal research suggests that curcumin, a constituent of turmeric, enhances the oral bioavailability of paclitaxel (22005). However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.
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Turmeric might increase the effects and adverse effects of sulfasalazine.
Details
Clinical research shows that taking the turmeric constituent, curcumin, can increase blood levels of sulfasalazine by 3.2-fold (81131).
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Turmeric might increase the effects and adverse effects of tacrolimus.
Details
In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting at the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to cytochrome P450 3A4 (CYP3A4) inhibition (93544). In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4 (21497,21498,21499).
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Turmeric may reduce the absorption of talinolol in some situations.
Details
Clinical research shows that taking curcumin for 6 days decreases the bioavailability of talinolol when taken together on the seventh day (80079). The clinical significance of this effect is unclear.
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Theoretically, turmeric might reduce the levels and clinical effects of tamoxifen.
Details
In a small clinical trial in patients with breast cancer taking tamoxifen 20-30 mg daily, adding curcumin 1200 mg plus piperine 10 mg three times daily reduces the 24-hour area under the curve of tamoxifen and the active metabolite endoxifen by 12.8% and 12.4%, respectively, as well as the maximum concentrations of tamoxifen, when compared with tamoxifen alone. However, in the absence of piperine, the area under the curve for endoxifen and the maximum concentration of tamoxifen were not significantly reduced. Effects were most pronounced in patients who were extensive cytochrome P450 (CYP) 2D6 metabolizers (107123).
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Turmeric has antioxidant effects. There is some concern that this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
Details
In vitro research shows that curcumin, a constituent of turmeric, inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71% (96126). However, other in vitro research shows that curcumin augments the cytotoxic effects of camptothecin. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agents. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects (96125). More evidence is needed to determine what effect, if any, turmeric might have.
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Turmeric might increase the risk of bleeding with warfarin.
Details
One case of increased international normalized ratio (INR) has been reported for a patient taking warfarin who began taking turmeric. Prior to taking turmeric, the patient had stable INR measurements. Within a few weeks of starting turmeric supplementation, the patient's INR increased to 10 (100906). Additionally, curcumin, the active constituent in turmeric, has demonstrated antiplatelet effects in vitro (11143,81204,81271), which may produce additive effects when taken with warfarin.
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Below is general information about the adverse effects of the known ingredients contained in the product Milk Thistle Liver Cleanse. 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, artichoke extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, flatulence, hunger, and nausea.
Topically: Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis to artichoke inulin has been reported in individuals sensitive to inulin.
Topically: Chest tightness, cough, and dyspnea after occupational exposure in sensitive individuals.
Dermatologic
...Artichoke can cause an allergic reaction in some patients.
Patients sensitive to the Asteraceae/Compositae family may be at the greatest risk. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. Topically, allergic contact dermatitis can occur with the use of artichoke. This has been attributed to the constituent cynaropicrin (11,52206,52226,52230). Redness in the face (11774) and sweating (91475) have been reported rarely following oral use of artichoke extract.
Occupational or airborne exposure to artichoke may also cause allergic reactions. In one case, a 52-year-old male presented with severe spongiotic dermatitis in exposed areas that was recurrent over the past 8 years. A patch test confirmed allergies to artichokes and sesquiterpene lactones, a group of allergens from the Compositae family, and the patient confirmed occupational and airborne exposure to artichokes during the time of his symptoms. The patient improved considerably after treatment with dupilumab (111565).
Gastrointestinal
...Orally, artichoke extract might increase abdominal discomfort, flatulence, diarrhea, hunger, and nausea in some patients (2562,52238,91475).
Abdominal pain and a bitter taste in the mouth were reported by a single person following oral use of a dietary supplement containing artichoke extract, as well as red yeast rice, pine bark extract, and garlic extract (89452). It is not clear if this adverse effect was due to artichoke, other ingredients, or the combination.
In one case report, the autopsy of an 84-year-old female revealed a colonic bezoar comprised of artichoke fiber and fragments. This bezoar caused complete intestinal obstruction, leading to fatal acute peritonitis. Although rare, patients who lack adequate teeth and/or who have a history of gastric surgery are at increased risk for fibrous bezoar formation (97716).
Pulmonary/Respiratory
...Following occupational exposure, allergic symptoms including dyspnea, cough, chest tightness, and asthma symptoms or exacerbation have been reported.
The effects were attributed to sensitization to artichoke. Subsequent nasal challenge with artichoke extract caused reduced nasal patency in these patients (52210,52230).
Orally, severe anaphylactic shock in response to artichoke inulin as an ingredient in commercially available products has been reported (52217). Individuals with a noted sensitivity to artichokes should consume inulin with caution. While rare, individuals with a known inulin allergy should avoid artichoke and artichoke extract.
General
...Orally, beet seems to be well tolerated when used for medicinal purposes, short term.
Most Common Adverse Effects:
Orally: Red stools and red urine.
Serious Adverse Effects (Rare):
Orally: Hypocalcemia and kidney damage when ingested in large amounts.
Endocrine ...Theoretically, ingestion of large quantities of beets could lead to hypocalcemia because of the oxaluric acid content (18).
Gastrointestinal
...Orally, beet juice may cause red stools (94470,97726,100142,100145,105762).
This red coloring of the stools is not harmful. Additionally, beet supplementation has been reported to cause black stools. In one case, a 79-year-old male on apixaban and clopidogrel presented with black stools, nausea, and vomiting after taking beet pills 2-3 days prior. The likelihood of upper gastrointestinal bleed was determined to be low based on factors such as normal vital signs and lack of severe anemia. The patient was diagnosed with beet-induced pseudo-hematochezia which was successfully treated with fluids and discontinuation of the beet supplement (113426).
Other less common gastrointestinal side effects include loose stools, constipation, and nausea (100149).
Genitourinary ...Orally, beet is known to produce red or pink urine (beeturia) in some people (32569,34134,94464,94470,97725,97726,100142,100145,100152,105762,113422). However, this red coloring of the urine is not harmful and dissipates after about 12 hours (113422).
Neurologic/CNS ...Orally, vivid dreams and worsening headaches have each occurred in one person in a clinical trial, although it is not clear if this is due to beet (97723).
Renal ...Theoretically, ingestion of large quantities of beets could lead to kidney damage due to its oxaluric acid content (18).
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, boldo is generally well tolerated when used in amounts commonly found in foods.
However, when used in medicinal amounts, boldo can cause significant adverse effects such as hepatotoxicity. There is currently a limited amount of information on the adverse effects of topical boldo; however, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Abdominal pain, nausea, vomiting.
Topically: Dermatitis.
Severe Adverse Effects (Rare):
Orally: Hepatotoxicity, jaundice.
Cardiovascular ...In one report, a 39-year-old obese female developed palpitations and syncope after taking a weight loss supplement containing a combination of boldo, dandelion, and bladderwrack for 3 weeks. The patient was found to have prolonged QT-interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether boldo, another ingredient, or the combination of ingredients is responsible for this adverse effect. The product was not analyzed to determine the presence of any potential toxic contaminants.
Dermatologic ...Topically, boldo can be irritating when applied to the skin (4). In one case report, a healthy 64-year-old patient experienced allergic contact dermatitis in an airborne pattern on the face, arms, and dorsum of both hands following airborne exposure to boldo. After exposure to boldo was avoided, the dermatitis resolved (106433).
Gastrointestinal ...In one case report, a manufacturer of an herbal laxative reformulated their product to contain boldo. Within 5 months of switching to this reformulated product, an 82-year-old male developed abdominal discomfort with gastrointestinal upset including heartburn (13178). In another case, a 72-year-old female reported nausea, vomiting, and anorexia, which were thought to be associated with hepatotoxic effects of a boldo infusion (100304).
Hepatic ...Orally, boldo is thought to potentially cause hepatotoxicity. The volatile oil from the boldo leaf contains the liver toxin, ascaridole. In one case report, a manufacturer of an herbal laxative reformulated their product to contain boldo. Within 5 months of switching to this reformulated product, an 82-year-old male with mild hepatic steatosis and very small gallbladder stones developed elevated liver transaminase levels. Levels normalized following discontinuation of the herbal product (13178). Several other cases of hepatotoxicity have been reported in elderly patients who received infusions of boldo leaves. These patients presented with elevated liver transaminase and bilirubin levels, sometimes up to 200 times the upper limit of normal, as well as nausea, vomiting, anorexia, asthenia, and jaundice. Lab tests and symptoms normalized a few days after stopping boldo (100304,106431).
Immunologic ...Boldo intake has been linked to one case of IgE-mediated anaphylactic allergic reaction (13185).
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, chanca piedra seems to be well tolerated.
However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Abdominal pain, nausea, vomiting.
Gastrointestinal ...Orally, use of chanca piedra can cause abdominal pain, nausea, and vomiting (99849,107946).
Ocular/Otic ...Orally, chanca piedra was associated with cases of visual impairment in one clinical trial (107946).
Other ...Orally, chanca piedra was associated with cases of fatigue in one clinical trial (107946).
General
...Orally, dandelion seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, heartburn, and stomach discomfort.
Topically: Dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.
Cardiovascular ...In one report, a 39-year-old obese woman developed palpitations and syncope after taking a weight loss supplement containing a combination of dandelion, bladderwrack, and boldo for 3 weeks. The patient was found to have prolonged QT-interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether dandelion, another ingredient, or the combination of ingredients is responsible for this adverse effect. The product was not analyzed to determine the presence of any potential toxic contaminants.
Dermatologic ...Topically, dandelion can cause contact dermatitis and erythema multiforme in sensitive individuals. Dandelion can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family (13478,13481,42893,46945,46977). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.
Endocrine ...In one report, a 56-year-old man with renal impairment developed hyperoxalaemia and peripheral gangrene after ingesting large amounts of dandelion tea (10 to 15 cups daily for 6 months). The adverse effect was attributed to the high oxalate content of dandelion tea (258 mcmol/L) and reduced renal oxalate clearance caused by renal impairment (90639). In another report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemic symptoms 2 weeks after beginning to eat salads containing dandelion (46960). The hypoglycemic effect was attributed to the potential alpha-glucosidase inhibitory activity of dandelion.
Gastrointestinal ...Gastrointestinal symptoms, including stomach discomfort, diarrhea, and heartburn, have been reported following oral use of dandelion (19146,36931). A case of intestinal blockage has been reported for a patient who ingested a large amount of dandelion greens three weeks after undergoing a stomach operation (46981). Also, a case of hemorrhagic cystitis has been reported for a 33-year-old woman who took a specific herbal product (Slim-Kombu, Balestra and Mech, Vicenza, Italy) containing 20 herbal extracts, including dandelion extract. Symptoms resolved after the patient discontinued using the product, and symptoms resumed when the patient began taking the supplement again four months later. While various ingredients in the supplement may have contributed to the symptoms, it is possible that dandelion extract may have contributed to the effect due to its diuretic, laxative, cholagogue, and antirheumatic properties (46959).
Other ...Orally, products containing dandelion pollen can cause allergic reactions, including anaphylaxis (13479,13480). Also, rhinoconjunctivitis and asthma have been reported after handling products such as bird feed containing dandelion and other herbs, with reported positive skin tests for dandelion hypersensitivity (46948). Dandelion pollen may cause pollinosis, such as allergic rhinitis and conjunctivitis (18065,46951,46964,46966,46972).
General ...Orally, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
General
...Orally, greater celandine has been implicated in dozens of cases of liver damage (363,13410,16839,41412,53502,53504,53506,53507,53510).
Greater celandine can also cause rash (13410). Greater celandine extract has caused a single case of hemolytic anemia (53508).
Topically, greater celandine can cause contact dermatitis (13411).
Intravenously, a derivative of the greater celandine constituent chelidonine (Ukrain) can cause gastrointestinal symptoms, increased body temperature, general burning sensations, and bleeding (13409,53460).
Dermatologic ...Orally, greater celandine can cause rash (13410). Topically, greater celandine can cause contact dermatitis (13411).
Gastrointestinal ...Intravenously, a derivative of the greater celandine constituent chelidonine (Ukrain) can cause gastrointestinal symptoms, including obstipation, nausea, and diarrhea (13409,53460).
Hematologic
...Orally, greater celandine extract has caused a single case of hemolytic anemia.
This resulted in thrombocytopenia, destruction of liver cells, and kidney failure, requiring treatment (53508).
Intravenously, a derivative of the greater celandine constituent chelidonine (Ukrain) can cause bleeding (13409,53460).
Hepatic ...Orally, greater celandine has been implicated in dozens of cases of liver damage (363,13410,16839,41412,53502,53504,53506,53507,53510). The cause is unknown, but appears to be idiopathic. It seems to be independent of dose, and the amount of time before development of liver disease is generally long and variable (363,53506). The main symptom is usually jaundice (53506). Liver enzymes are elevated at least two-fold in all cases where measurements were completed (53506). Although other causes of liver toxicity cannot be ruled out in some cases, many reported cases of hepatotoxicity are probably or likely associated with the use of greater celandine. Recurrence of hepatitis with unintentional re-exposure has also been reported (53506,94282). Discontinuation of greater celandine usually results in a fairly rapid recovery although liver enzymes need months to return to normal (53506,94282). Death has occurred in one patient with hepatitis due to bleeding associated with colonic diverticulitis. Causality was described as possible, not probable, in this case (53506).
Neurologic/CNS ...Intravenously, a derivative of the greater celandine constituent chelidonine (Ukrain) can cause increased body temperature and general burning sensations (13409).
General
...Orally or intravenously, iron is generally well tolerated when used appropriately.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, gastrointestinal irritation, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about oral or gastric ulcerations.
Intravenously: Case reports have raised concerns about hypophosphatemia and osteomalacia.
Cardiovascular
...There is debate regarding the association between coronary heart disease (CHD) or myocardial infarction (MI) and high iron intake or high body iron stores.
Some observational studies have reported that high body iron stores are associated with increased risk of MI and CHD (1492,9542,9544,9545,15175). Some observational studies reported that only high heme iron intake from dietary sources such as red meat are associated with increased risk of MI and CHD (1492,9546,15174,15205,15206,91180). However, the majority of research has found no association between serum iron levels and cardiovascular disease (1097,1099,9543,9547,9548,9549,9550,56469,56683).
There is one case of Kounis syndrome, also referred to as allergic angina or allergic myocardial infarction, in a 39-year-old female patient without previous coronary artery disease given intravenous ferric carboxymaltose. The patient experienced anaphylactic symptoms, including headache, abdominal pain, and breathing difficulties, 3 minutes after starting the infusion. She was further diagnosed with non-ST-elevation myocardial infarction (112607).
Dermatologic ...Cutaneous hemosiderosis, or skin staining, has been reported following intravenous iron infusion in various case reports. Most of these cases are due to extravasation following iron infusion (112605,112611). In one case, extravasation has occurred following iron derisomaltose infusion in a 41-year-old female with chronic kidney disease (112605). Rarely, diffuse cutaneous hermosiderosis has occurred. In one case, a 31-year-old female with excessive sweating developed cutaneous hemosiderosis in the armpits following an intravenous iron polymaltose infusion (112611).
Endocrine ...Population research in females shows that higher ferritin levels are associated with an approximately 1. 5-fold higher odds of developing gestational diabetes. Increased dietary intake of heme-iron, but not non-heme iron, is also associated with an increased risk for gestational diabetes. The effects of iron supplementation could not be determined from the evaluated research (96618). However, in a sub-analysis of a large clinical trial in pregnant adults, daily supplementation with iron 100 mg from 14 weeks gestation until delivery did not affect the frequency or severity of glucose intolerance or gestational weight gain (96619).
Gastrointestinal
...Orally, iron can cause dry mouth, gastrointestinal irritation, heartburn, abdominal pain, constipation, diarrhea, nausea, or vomiting (96621,102864,104680,104684,110179,110185,110188,110189,110192).
These adverse effects are uncommon at doses below the tolerable upper intake level (UL) of 45 mg per day of elemental iron in adults with normal iron stores (7135). Higher doses can be taken safely in adults with iron deficiency, but gastrointestinal side effects may occur (1095,20118,20119,56698,102864). Taking iron supplements with food seems to reduce gastrointestinal side effects (7135). However, food can also significantly reduce iron absorption. Iron should be taken on an empty stomach, unless it cannot be tolerated.
There are several formulations of iron products such as ferrous sulfate, ferrous gluconate, ferrous fumarate, and others. Manufacturers of some formulations, such as polysaccharide-iron complex products (Niferex-150, etc), claim to be better tolerated than other formulations; however, there is no reliable evidence to support this claim. Gastrointestinal tolerability relates mostly to the elemental iron dose rather than the formulation (17500).
Enteric-coated or controlled-release iron formulations might reduce nausea for some patients, however, these products also have lower absorption rates (17500).
Liquid oral preparations can blacken and stain teeth (20118).
Iron can also cause oral ulcerations and ulcerations of the gastric mucosa (56684,91182,96622,110179). In one case report, an 87-year-old female with Alzheimer disease experienced a mucosal ulceration, possibly due to holding a crushed ferrous sulfate 80 mg tablet in the mouth for too long prior to swallowing (91182). The ulceration was resolved after discontinuing iron supplementation. In another case report, a 76-year old male suffered gastric mucosal injury after taking a ferrous sulfate tablet daily for 4 years (56684). In a third case report, a 14-year-old female developed gastritis involving symptoms of upper digestive hemorrhage, nausea, melena, and stomach pain. The hemorrhage was attributed to supplementation with ferrous sulfate 2 hours after meals for the prior 2 weeks (96622). In one case report, a 43-year old female developed atrophic gastritis with non-bleeding ulcerations five days after starting oral ferrous sulfate 325 mg twice daily (110179).
Intravenously, iron can cause gastrointestinal symptoms sch as nausea (104684,110192).
Immunologic
...Although there is some clinical research associating iron supplementation with an increased rate of malaria infection (56796,95432), the strongest evidence to date does not support this association, at least for areas where antimalarial treatment is available (95433,96623).
In an analysis of 14 trials, iron supplementation was not associated with an increased risk of malaria (96623). In a sub-analysis of 7 preliminary clinical studies, the effect of iron supplementation was dependent upon the access to services for antimalarial treatment. In areas where anemia is common and services are available, iron supplementation is associated with a 9% reduced risk of clinical malaria. In an area where services are unavailable, iron supplementation was associated with a 16% increased risk in malaria incidence (96623). The difference in these findings is likely associated with the use of malaria prevention methods.
A meta-analysis of clinical studies of all patient populations shows that administering IV iron, usually iron sucrose and ferric carboxymaltose, increases the risk of infection by 16% when compared with oral iron or no iron. However, sub-analyses suggest this increased risk is limited to patients with inflammatory bowel disease (IBD) (110186).
Intravenously, iron has rarely resulted in allergic reactions, including anaphylactoid reactions (110185,110192,112606,112607). There is one case of Kounis syndrome, also referred to as allergic angina or allergic myocardial infarction, in a 39-year-old female patient without previous coronary artery disease given intravenous ferric carboxymaltose. The patient experienced anaphylactic symptoms, including headache, abdominal pain, and breathing difficulties, 3 minutes after starting the infusion. She was further diagnosed with non-ST-elevation myocardial infarction (112607).
Musculoskeletal ...Intravenously, iron rarely results in osteomalacia related to hypophosphatemia (112609). At least 2 cases exist of hypophosphatemic osteomalacia. In one case, a 70-year-old male with a genetic hemorrhagic disorder infused with ferric carboxymaltose developed lower limb pain with hypophosphatemia and diffuse bone demineralization in the feet (112609). In a second case, a 61-year-old male developed femoral neck insufficiency fractures following repeated ferric carboxymaltose transfusions for anemia related to vascular malformation in the bowel (112603). Severe hypophosphatemia requiring intravenous phosphate in the absence of osteomalacia has also occurred following intravenous ferric carboxymaltose (112608,112610).
Oncologic
...There is a debate regarding the association between high levels of iron stores and cancer.
Data are conflicting and inconclusive (1098,1099,1100,1102). Epidemiological studies suggest that increased body iron stores may increase the risk of cancer or general mortality (56703).
Occupational exposure to iron may be carcinogenic (56691). Oral exposure to iron may also be carcinogenic. Pooled analyses of population studies suggest that increasing the intake of heme iron increases the risk of colorectal cancer. For example, increasing heme iron intake by 1 mg/day is associated with an 11% increase in risk (56699,91185).
Other ...Intravenously, sodium ferric gluconate complex (SFGC) caused drug intolerance reactions in 0. 4% of hemodialysis patients including 2 patients with pruritus and one patient each with anaphylactoid reaction, hypotension, chills, back pain, dyspnea/chest pain, facial flushing, rash and cutaneous symptoms of porphyria (56527).
General
...Orally, lecithin is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, fullness, and nausea.
Dermatologic ...Orally, lecithin can cause allergic skin reactions in people with egg or soy allergies (15705).
Gastrointestinal ...Orally, lecithin may cause abdominal pain, diarrhea, fullness, and nausea (5140,6243,14817,14822,14838,19204,59281).
Neurologic/CNS ...Orally, lecithin caused CNS complaints and agitation in one patient in a clinical trial (59261).
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, milk thistle is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal bloating, diarrhea, dyspepsia, flatulence, and nausea. However, these adverse effects do not typically occur at a greater frequency than with placebo.
Serious Adverse Effects (Rare):
Orally: Allergic reactions, including anaphylaxis, have been reported.
Dermatologic ...Orally, milk thistle may cause allergic reactions including urticaria, eczema, skin rash, and anaphylaxis in some people (6879,7355,8956,63210,63212,63238,63251,63315,63325,95029). Allergic reactions may be more likely to occur in patients sensitive to the Asteraceae/Compositae family (6879,8956). A case report describes a 49-year-old female who developed clinical, serologic, and immunopathologic features of bullous pemphigoid after taking milk thistle orally for 6 weeks. Symptoms resolved after treatment with prednisone and methotrexate (107376). Topically, milk thistle can cause erythema (110489).
Gastrointestinal ...Mild gastrointestinal symptoms have been reported, including nausea, vomiting, bloating, diarrhea, epigastric pain, abdominal colic or discomfort, dyspepsia, dysgeusia, flatulence, constipation, and loss of appetite (2616,6879,8956,13170,63140,63146,63160,63210,63218,63219)(63221,63244,63247,63250,63251,63320,63321,63323,63324,63325)(63327,63328,95024,95029,107374). There is one report of a 57-year-old female with sweating, nausea, colicky abdominal pain, diarrhea, vomiting, weakness, and collapse after ingesting milk thistle; symptoms subsided after 24-48 hours without medical treatment and recurred with re-challenge (63329).
Musculoskeletal ...In one clinical study three patients taking milk thistle 200 mg orally three times daily experienced tremor; the incidence of this adverse effect was similar for patients treated with fluoxetine 10 mg three times daily (63219).
General ...Orally, picrorhiza may cause vomiting, rash, anorexia, diarrhea, itching, and giddiness (11858).
Dermatologic ...Orally, picrorhiza may cause rash and itching (11858).
Gastrointestinal ...Orally, picrorhiza may cause vomiting, anorexia, and diarrhea (11858).
Neurologic/CNS ...Orally, picrorhiza may cause giddiness (11858).
General
...Orally, schisandra seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Decreased appetite, heartburn, stomach upset, and urticaria.
Dermatologic ...Orally, schisandra can cause urticaria in some patients (11).
Gastrointestinal ...Orally, schisandra can cause heartburn, decreased appetite, and stomach upset (11).
General
...Orally, sodium is well tolerated when used in moderation at intakes up to the Chronic Disease Risk Reduction (CDRR) intake level.
Topically, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Worsened cardiovascular disease, hypertension, kidney disease.
Cardiovascular
...Orally, intake of sodium above the CDRR intake level can exacerbate hypertension and hypertension-related cardiovascular disease (CVD) (26229,98176,100310,106263).
A meta-analysis of observational research has found a linear association between increased sodium intake and increased hypertension risk (109398). Observational research has also found an association between increased sodium salt intake and increased risk of CVD, mortality, and cardiovascular mortality (98177,98178,98181,98183,98184,109395,109396,109399). However, the existing research is unable to confirm a causal relationship between sodium intake and increased cardiovascular morbidity and mortality; high-quality, prospective research is needed to clarify this relationship (100312). As there is no known benefit with increased salt intake that would outweigh the potential increased risk of CVD, advise patients to limit salt intake to no more than the CDRR intake level (100310).
A reduction in sodium intake can lower systolic blood pressure by a small amount in most individuals, and diastolic blood pressure in patients with hypertension (100310,100311,106261). However, post hoc analysis of a small crossover clinical study in White patients suggests that 24-hour blood pressure variability is not affected by high-salt intake compared with low-salt intake (112910). Additionally, the available research is insufficient to confirm that a further reduction in sodium intake below the CDRR intake level will lower the risk for chronic disease (100310,100311). A meta-analysis of clinical research shows that reducing sodium intake increases levels of total cholesterol and triglycerides, but not low-density lipoprotein (LDL) cholesterol, by a small amount (106261).
It is unclear whether there are safety concerns when sodium is consumed in amounts lower than the adequate intake (AI) levels. Some observational research has found that the lowest levels of sodium intake might be associated with increased risk of death and cardiovascular events (98181,98183). However, this finding has been criticized because some of the studies used inaccurate measures of sodium intake, such as the Kawasaki formula (98177,98178,101259). Some observational research has found that sodium intake based on a single 24-hour urinary measurement is inversely correlated with all-cause mortality (106260). The National Academies Consensus Study Report states that there is insufficient evidence from observational studies to conclude that there are harmful effects from low sodium intake (100310).
Endocrine ...Orally, a meta-analysis of observational research has found that higher sodium intake is associated with an average increase in body mass index (BMI) of 1. 24 kg/m2 and an approximate 5 cm increase in waist circumference (98182). It has been hypothesized that the increase in BMI is related to an increased thirst, resulting in an increased intake of sugary beverages and/or consumption of foods that are high in salt and also high in fat and energy (98182). One large observational study has found that the highest sodium intake is not associated with overweight or obesity when compared to the lowest intake in adolescents aged 12-19 years when intake of energy and sugar-sweetened beverages are considered (106265). However, in children aged 6-11 years, usual sodium intake is positively associated with increased weight and central obesity independently of the intake of energy and/or sugar-sweetened beverages (106265).
Gastrointestinal ...In one case report, severe gastritis and a deep antral ulcer occurred in a patient who consumed 16 grams of sodium chloride in one sitting (25759). Chronic use of high to moderately high amounts of sodium chloride has been associated with an increased risk of gastric cancer (29405).
Musculoskeletal
...Observational research has found that low sodium levels can increase the risk for osteoporosis.
One study has found that low plasma sodium levels are associated with an increased risk for osteoporosis. Low levels, which are typically caused by certain disease states or chronic medications, are associated with a more than 2-fold increased odds for osteoporosis and bone fractures (101260).
Conversely, in healthy males on forced bed rest, a high intake of sodium chloride (7.7 mEq/kg daily) seems to exacerbate disuse-induced bone and muscle loss (25760,25761).
Oncologic ...Population research has found that high or moderately high intake of sodium chloride is associated with an increased risk of gastric cancer when compared with low sodium chloride intake (29405). Other population research in patients with gastric cancer has found that a high intake of sodium is associated with an approximate 65% increased risk of gastric cancer mortality when compared with a low intake. When zinc intake is taken into consideration, the increased risk of mortality only occurred in those with low zinc intake, but the risk was increased to approximately 2-fold in this sub-population (109400).
Pulmonary/Respiratory ...In patients with hypertension, population research has found that sodium excretion is modestly and positively associated with having moderate or severe obstructive sleep apnea. This association was not found in normotensive patients (106262).
Renal ...Increased sodium intake has been associated with impaired kidney function in healthy adults. This effect seems to be independent of blood pressure. Observational research has found that a high salt intake over approximately 5 years is associated with a 29% increased risk of developing impaired kidney function when compared with a lower salt intake. In this study, high salt intake was about 2-fold higher than low salt intake (101261).
General
...Orally and topically, turmeric is generally well tolerated.
Most Common Adverse Effects:
Orally: Constipation, dyspepsia, diarrhea, distension, gastroesophageal reflux, nausea, and vomiting.
Topically: Curcumin, a constituent of turmeric, can cause contact urticaria and pruritus.
Cardiovascular ...Orally, a higher dose of turmeric in combination with other ingredients has been linked to atrioventricular heart block in one case report. It is unclear if turmeric caused this adverse event or if other ingredients or a contaminant were the cause. The patient had taken a combination supplement containing turmeric 1500-2250 mg, black soybean 600-900 mg, mulberry leaves, garlic, and arrowroot each about 300-450 mg, twice daily for one month before experiencing atrioventricular heart block. Heart rhythm normalized three days after discontinuation of the product. Re-administration of the product resulted in the same adverse effect (17720).
Dermatologic ...Following occupational and/or topical exposure, turmeric or its constituents curcumin, tetrahydrocurcumin, or turmeric oil, can cause allergic contact dermatitis (11146,79270,79470,79934,81410,81195). Topically, curcumin can also cause rash or contact urticaria (79985,97432,112117). In one case, a 60-year-old female, with no prior reactivity to regular oral consumption of turmeric products, developed urticaria after topical application of turmeric massage oil (97432). A case of pruritus has been reported following topical application of curcumin ointment to the scalp for the treatment of melanoma (11148). Yellow discoloration of the skin has been reported rarely in clinical research (113356). Orally, curcumin may cause pruritus, but this appears to be relatively uncommon (81163,97427,104148). Pitting edema may also occur following oral intake of turmeric extract, but the frequency of this adverse event is less common with turmeric than with ibuprofen (89720). A combination of curcumin plus fluoxetine may cause photosensitivity (89728).
Gastrointestinal ...Orally, turmeric can cause gastrointestinal adverse effects (107110,107112,112118), including constipation (81149,81163,96135,113355), flatulence and yellow, hard stools (81106,96135), nausea and vomiting (10453,17952,89720,89728,96127,96131,96135,97430,112117,112118), diarrhea or loose stool (10453,17952,18204,89720,96135,110223,112117,112118), dyspepsia (17952,89720,89721,96161,112118), gastritis (89728), distension and gastroesophageal reflux disease (18204,89720), abdominal fullness and pain (81036,89720,96161,97430), epigastric burning (81444), and tongue staining (89723).
Hepatic
...Orally, turmeric has been associated with liver damage, including non-infectious hepatitis, cholestasis, and hepatocellular liver injury.
There have been at least 70 reports of liver damage associated with taking turmeric supplements for at least 2 weeks and for up to 14 months. Most cases of liver damage resolved upon discontinuation of the turmeric supplement. Sometimes, turmeric was used concomitantly with other supplements and medications (99304,102346,103094,103631,103633,103634,107122,109288,110221). The Drug-Induced Liver Injury Network (DILIN) has identified 10 cases of liver injury which were considered to be either definitely, highly likely, or probably associated with turmeric; none of these cases were associated with the use of turmeric in combination with other potentially hepatotoxic supplements. Most patients (90%) presented with hepatocellular pattern of liver injury. The median age of these case reports was 56 years and 90% identified as White. In these case reports, the carrier frequency on HLAB*35:01 was 70%, which is higher than the carrier frequency found in the general population. Of the ten patients, 5 were hospitalized and 1 died from liver injury (109288).
It is not clear if concomitant use with other supplements or medications contributes to the risk for liver damage. Many case reports did not report turmeric formulation, dosing, or duration of use (99304,103094,103631,103634,109288). However, at least 10 cases involved high doses of curcumin (250-1812.5 mg daily) and the use of highly bioavailable formulations such as phytosomal curcumin and formulations containing piperine (102346,103633,107122,109288,110221).
Neurologic/CNS ...Orally, the turmeric constituent curcumin can cause vertigo, but this effect seems to be uncommon (81163).
Psychiatric ...Orally, the turmeric constituent curcumin or a combination of curcumin and fluoxetine can cause giddiness, although this event seems to be uncommon (81206,89728).
Renal ...Orally, turmeric has been linked to one report of kidney failure, although the role of turmeric in this case is unclear. A 69-year-old male developed kidney failure related to calcium oxalate deposits in the renal tubules following supplementation with turmeric 2 grams daily for 2 years as an anti-inflammatory for pelvic pain. While turmeric is a source of dietary oxalates, pre-existing health conditions and/or chronic use of antibiotics may have contributed to the course of disease (113343).
Other ...There is a single case report of death associated with intravenous use of turmeric. However, analysis of the treatment vial suggests that the vial contained only 0.023% of the amount of curcumin listed on the label. Also, the vial had been diluted in a solution of ungraded polyethylene glycol (PEG) 40 castor oil that was contaminated with 1.25% diethylene glycol. Therefore the cause of death is unknown but is unlikely to be related to the turmeric (96136).
