| Ingredients | Amount Per Serving |
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| 20 mg | |
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Proprietary Blend
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1495 mg |
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Glucosamine HCl
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(root)
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(root)
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(Corydalis )
(rhizome)
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(root)
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(root)
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(herb)
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( Black Pepper extract)
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Vegetarian Capsule (Form: Vegetable Cellulose, Water)
Below is general information about the effectiveness of the known ingredients contained in the product H-Force. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product H-Force. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally 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 and appropriately. Chondroitin sulfate has been used safely in doses of up to 2000 mg daily for up to 6 years (1955,2533,13579,17732,22212,42339,42343,42348,42389,42396)(42398,42463,42477,42513,42520,42536,42541,89516,89558,89592)(89596,94360,94381,95788,95792). However, since chondroitin is often derived from bovine cartilage, historically, there was concern about contamination with diseased animal parts (1825). So far, there are no reports of disease transmission to humans due to use of contaminated chondroitin preparations. ...when used topically and appropriately as an ophthalmic viscosurgical device (OVD). Various products containing chondroitin sulfate and sodium hyaluronate have been granted approval by the US Food and Drug Administration (FDA) for use as an adjunct to cataract surgery (89436,89437).
POSSIBLY SAFE ...when used intramuscularly (10149,42397). ...when used topically as eye drops, short-term. Eye drops containing chondroitin sulfate with xanthan gum or glucosamine have been used with apparent safety four times daily for up to 3 months (89591,104443). ...when administered intravesically under the supervision of a physician (42338,42371,42373,42385,42387,42473,42511,42517,42519,109649).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally, short-term. A specific supplement (Motilitone, Dong-A ST) containing Corydalis yanhusuo extract in combination with Pharbitis seed extract has been used with apparent safety in a dose of 90 mg daily for up to 4 weeks in clinical research (97158,97159,97160). There is insufficient reliable information available about the safety of Corydalis yanhusuo when used orally as a single ingredient.
CHILDREN: LIKELY UNSAFE
when used orally in newborns.
The berberine constituent of Corydalis yanhusuo can cause kernicterus in newborns, particularly preterm neonates with hyperbilirubinemia (2589).
PREGNANCY: LIKELY UNSAFE
when used orally.
Corydalis yanhusuo might promote menstrual flow and stimulate uterine contractions (12). The berberine constituent of Corydalis yanhusuo is thought to cross the placenta and may cause harm to the fetus. Kernicterus has developed in newborn infants exposed to berberine (2589).
LACTATION: LIKELY UNSAFE
when used orally.
The berberine constituent of Corydalis yanhusuo and other harmful constituents can be transferred to the infant through breast milk (2589).
POSSIBLY SAFE ...when used orally and appropriately. Dong quai has been used with apparent safety in a dose of 4.5 grams daily for 24 weeks, or in combination with other ingredients in doses of up to 150 mg daily for up to 6 months (19552,35797). ...when used intravenously as a 25% solution, in a dose of 200-250 mL daily for up to 20 days (48438,48442,48443,48483).
POSSIBLY UNSAFE ...when used orally in large amounts, long-term. Theoretically, long-term use of large amounts of dong quai could be harmful. Dong quai contains several constituents such as bergapten, safrole, and isosafrole that are considered carcinogenic (7162). There is insufficient reliable information available about the safety of dong quai when used topically.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Dong quai has uterine stimulant and relaxant effects (8142); theoretically, it could adversely affect pregnancy. Observational research has found that intake of An-Tai-Yin, an herbal combination product containing dong quai and parsley, during the first trimester is associated with an increased risk of congenital malformations of the musculoskeletal system, connective tissue, and eyes (15129).
LACTATION:
Insufficient reliable information available; avoid use.
LIKELY SAFE ...when hemp seed, hemp protein, and hemp seed oil are used orally in food amounts. Hulled hemp seed, hemp seed protein powder, and hemp seed oil are generally recognized as safe (GRAS) in the US (100531).
POSSIBLY SAFE ...when hemp seed oil is used orally and appropriately as medicine, short-term. Hemp seed oil in doses of 2-6.3 grams daily has been safely used for 3-6 months (88183,16791,101145). Hemp seed oil in doses of 30 mL (27.6 grams) daily has been used safely for 2 months (101125). There is insufficient reliable evidence available about the safety of hemp oil, flowers, or leaves.
CHILDREN:
There is insufficient reliable information available about the safety of hemp in children.
Adverse effects have been noted in case reports, but details related to specific hemp products are limited (101153,110287).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short term. Total glucosides of peony has been used with apparent safety in doses of up to 1800 mg daily for up to 12 months (92786,97949,97950,98466,100992,110432,112861,112862). Peony root extract has been used with apparent safety at a dose of 2250 mg daily for up to 3 months (97216). There is insufficient reliable information available about the safety of peony when used orally, topically, or rectally, long-term.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Total glucosides of peony has been used with apparent safety in children 1.5-4 years of age at doses up to 180 mg/kg daily or 1.2 grams daily for up to 12 months (92785). Peony root extract 40 mg/kg daily has also been used with apparent safety in children 1-14 years of age for 4 weeks (106851).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Preliminary research suggests that peony can cause uterine contractions (13400). However, other preliminary research suggests a combination of peony and angelica with or without motherwort, banksias rose, and ligustica, might be safe (11015,48433). Until more is known, avoid use.
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Sweet Annie 300 mg daily has been used with apparent safety in studies lasting up to 9 months (11055,94520,94521). Sweet Annie tea, prepared from dried leaves and twigs and consumed in divided doses daily, has been used with apparent safety for up to 7 days (11055,11058). While rare, there is some concern that Sweet Annie might cause liver damage (16895,103254,103255).
POSSIBLY SAFE ...when used sublingually and appropriately, short-term. Sweet Annie up to 2400 biological units daily as sublingual immunotherapy has been used with apparent safety in studies lasting up to 16 months (106441,112392,112393,112394). There is insufficient reliable information available about the safety of Sweet Annie when used topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
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.
LIKELY SAFE ...when used orally in the amounts commonly found in foods. Wormwood extracts are included in bitters, vermouth, absinthe, and other food or drink products (12814,15007). Wormwood products that are thujone-free have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912); however, products containing thujone might not be safe. Wormwood is described in the pharmacopoeia of various European countries. After being banned for a period of time, it is now allowed in European Union countries; however, beverages must not contain thujone in concentrations greater than 35 mg/kg (12814,15007,86551).
POSSIBLY SAFE ...when wormwood products not containing thujone are used orally in medicinal amounts, short-term (93468,93469). A specific product
POSSIBLY UNSAFE ...when wormwood products containing thujone are used orally. Thujone is a neurotoxin that is present in wormwood oil (12617). Seizures, rhabdomyolysis, and acute kidney failure can occur when as little as 10 mL of wormwood oil is ingested (662,12817).
PREGNANCY:
LIKELY UNSAFE .
.when used orally in amounts greater than those found in foods (662,12817). Some wormwood products contain thujone, a neurotoxin. Theoretically, thujone also has potential uterine and menstrual stimulant effects (12617). There is insufficient reliable information available about the safety of wormwood when used topically during pregnancy.
LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product H-Force. 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, 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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Taking chondroitin in combination with glucosamine might increase the anticoagulant effects of warfarin. However, the effect of chondroitin alone is unclear.
Details
There have been multiple reports of increased international normalized ratio (INR) in patients taking warfarin with glucosamine, with or without chondroitin. The lack of reports with chondroitin alone seem to suggest that the interactions occurring in these reports may have been due to glucosamine. In two individual case reports, glucosamine/chondroitin combinations were associated with a significant increase in INR in patients previously stabilized on warfarin (11389,16130). Additionally, 20 voluntary case reports to the US Food & Drug Administration (FDA) have linked glucosamine plus chondroitin with increased INR, bruising, and bleeding in patients who were also taking warfarin (16130). There have also been 20 additional case reports to the World Health Organization (WHO) that link glucosamine alone, without chondroitin, to increased INR in patients taking warfarin (16131).
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Theoretically, Corydalis yanhusuo might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
Details
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Theoretically, Corydalis yanhusuo may increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
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Theoretically, Corydalis yanhusuo might have additive effects with antihypertensive drugs.
Details
Corydalis yanhusuo contains berberine. Animal research suggests that berberine can have hypotensive effects (33692,34308). Also, a clinical study suggests that taking berberine in combination with amlodipine can lower systolic and diastolic blood pressure when compared with amlodipine alone (91956). Theoretically, Corydalis yanhusuo might also reduce blood pressure.
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Theoretically, Corydalis yanhusuo might increase the sedative effects of CNS depressants.
Details
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Theoretically, Corydalis yanhusuo might increase blood levels of cyclosporine.
Details
Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can reduce metabolism of cyclosporine and increase serum levels, likely through inhibition of cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine (13524). Theoretically, Corydalis yanhusuo might also reduce the metabolism of cyclosporine.
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Theoretically, Corydalis yanhusuo might increase serum levels of drugs metabolized by CYP2C9.
Details
Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can inhibit CYP2C9 (34279). Theoretically, Corydalis yanhusuo might also inhibit CYP2C9.
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Theoretically, Corydalis yanhusuo might increase serum levels of drugs metabolized by CYP2D6.
Details
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Theoretically, Corydalis yanhusuo might increase serum levels of drugs metabolized by CYP3A4.
Details
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Theoretically, Corydalis yanhusuo may increase serum levels of dextromethorphan.
Details
Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 2D6 (CYP2D6) activity and reduce the metabolism of dextromethorphan (34279). Theoretically, Corydalis yanhusuo may also inhibit the metabolism of dextromethorphan.
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Theoretically, Corydalis yanhusuo might reduce the therapeutic effects of losartan by decreasing its conversion to its active form.
Details
Corydalis yanhusuo contains berberine. Preliminary clinical research suggests that berberine can inhibit cytochrome P450 2C9 (CYP2C9) activity and reduce metabolism of losartan (34279). Theoretically, Corydalis yanhusuo might also inhibit the metabolism of losartan.
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Theoretically, Corydalis yanhusuo might increase the therapeutic and adverse effects of metformin.
Details
Corydalis yanhusuo contains berberine. In vitro and animal studies show that berberine can increase the systemic exposure and half-life of metformin, potentially increasing metformin's effects and side effects. This interaction seems to be most apparent when berberine is administered 2 hours prior to metformin. Taking berberine and metformin at the same time does not appear to increase systemic exposure to metformin (103195). It is unclear if Corydalis yanhusuo might have this same effect.
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Theoretically, Corydalis yanhusuo might reduce metabolism of midazolam, which might increase the risk of severe adverse effects.
Details
Corydalis yanhusuo contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 3A4 (CYP3A4) activity and reduce metabolism of midazolam (34279). Theoretically, Corydalis yanhusuo might also inhibit the metabolism of midazolam.
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Theoretically, Corydalis yanhusuo might increase the sedative effect of pentobarbital.
Details
Corydalis yanhusuo contains berberine. Animal research shows that berberine can prolong pentobarbital-induced sleeping time (13519). Theoretically, Corydalis yanhusuo might increase the sedative effects of pentobarbital.
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Theoretically, Corydalis yanhusuo might increase blood levels of tacrolimus.
Details
Corydalis yanhusuo contains berberine. In a 16-year-old patient with idiopathic nephrotic syndrome who was being treated with tacrolimus 6.5 mg twice daily, intake of berberine 200 mg three times daily increased the blood concentration of tacrolimus from 8 to 22 ng/mL. Following a reduction of the tacrolimus dose to 3 mg daily, blood levels of tacrolimus decreased to 12 ng/mL (91954). It is unclear if Corydalis yanhusuo might have this same effect.
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Theoretically, dong quai may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs; however, research is conflicting.
Details
Animal studies suggest that dong quai has antithrombin activity and inhibits platelet aggregation due to its coumarin components (6048,10057,96137). Additionally, some case reports in humans suggest that dong quai can increase the anticoagulant effects of warfarin (3526,6048,23310,48439). However, clinical research in healthy adults shows that taking 1 gram of dong quai root daily for 3 weeks does not significantly inhibit platelet aggregation or cause bleeding (96137). Until more is known, use dong quai with caution in patients taking antiplatelet/anticoagulant drugs.
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Theoretically, dong quai may reduce the effects of estrogens.
Details
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Dong quai may increase the risk of bleeding when used with warfarin.
Details
Case reports suggest that concomitant use of dong quai with warfarin can increase the anticoagulant effects of warfarin and increase the risk of bleeding (3526,6048,23310,48439). In one case, after 4 weeks of taking dong quai 565 mg once or twice daily, the international normalized ratio (INR) increased to 4.9. The INR normalized 4 weeks after discontinuation of dong quai (3526).
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Theoretically, consuming hemp seed protein isolate with ACE inhibitors might have additive effects and increase the risk of hypotension.
Details
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Theoretically, hemp seed might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs.
Details
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Theoretically, hemp seed protein may have additive effects with antihypertensive drugs.
Details
In a hypertensive animal model, hemp seed protein hydrolysate reduced systolic blood pressure by a mechanism possibly involving the inhibition of renin and angiotensin converting enzyme (ACE) activities. However, there was no effect of hemp seed protein on blood pressure in normotensive animals (101136). Furthermore, hempseed oil consumption does not seem to reduce blood pressure in humans (101144).
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Theoretically, hemp might interfere with hormone therapy due to its estrogenic effects.
Details
In an ovariectomized animal model, a diet containing hemp seed 1%, 2%, or 10% resulted in normalized plasma levels of 17-beta-estradiol (101132). The mechanism of action for this effect is unclear.
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Theoretically, combining peony with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
Details
In vitro research suggests that peony might have antiplatelet, anticoagulant, and antithrombotic effects (92787).
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Theoretically, peony might increase the levels and clinical effects of clozapine.
Details
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on cytochromes P450 (CYP) 1A2 and CYP3A4 (92790). This effect has not been reported in humans.
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Theoretically, peony might interfere with contraceptive drugs due to competition for estrogen receptors.
Details
In vitro and animal research shows that peony extract has estrogenic activity (100990). Concomitant use might also increase the risk for estrogen-related adverse effects.
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Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.
Details
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect has not been reported in humans.
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Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP3A4.
Details
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect has not been reported in humans.
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Theoretically, concomitant use of large amounts of peony might interfere with hormone replacement therapy and/or increase the risk for estrogen-related adverse effects.
Details
In vitro and animal research shows that peony extract has estrogenic activity (100990). Theoretically, peony might compete for estrogen receptors and/or cause additive estrogenic effects.
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Theoretically, peony might reduce the levels and clinical effects of phenytoin.
Details
Animal research shows that taking peony root reduces levels of phenytoin (8657). Some researchers suggest that peony root might affect cytochrome P450 (CYP) 2C9, which metabolizes phenytoin. However, preliminary research in humans shows that peony root does not alter levels of losartan (Cozaar), which is also metabolized by CYP2C9 (11480).
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Sweet Annie may alter plasma levels and clinical effects of drugs metabolized by CYP2B6.
Details
In vitro research shows that the Sweet Annie constituent artemisinin induces CYP2B6, possibly increasing CYP2B6 activity by 1.6-fold (92501,109316). However, Sweet Annie extract seems to inhibit the activity of CYP2B6 in vitro, suggesting that other constituents of Sweet Annie play a role in its effects on the overall activity of this enzyme (109316). More information is needed to determine whether taking Sweet Annie extract affects the metabolism of CYP2B6 substrates.
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Sweet Annie may alter plasma levels and clinical effects of drugs metabolized by CYP3A4.
Details
In vitro research shows that the Sweet Annie constituent artemisinin induces CYP3A4, possibly increasing CYP3A4 activity by 1.9-fold (92501). However, Sweet Annie extract seems to inhibit the activity of CYP3A4 in vitro, suggesting that other constituents of Sweet Annie play a role in its effects on the overall activity of this enzyme (109316). More information is needed to determine whether taking Sweet Annie extract affects the metabolism of CYP3A4 substrates.
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Theoretically, concomitant use might have additive adverse hepatotoxic effects.
Details
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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.
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Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.
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Turmeric might increase levels of drugs metabolized by CYP3A4.
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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.
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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.
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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.
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Theoretically, turmeric might increase the effects of losartan.
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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.
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Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.
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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.
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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.
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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.
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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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Theoretically, taking wormwood might interfere with the effects of anticonvulsant drugs.
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Thujone, a constituent of wormwood, has convulsant effects (12816).
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Below is general information about the adverse effects of the known ingredients contained in the product H-Force. 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, 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 and topically, chondroitin sulfate is generally well tolerated.
Intramuscular and ophthalmic use also seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, constipation, diarrhea, heartburn, nausea.
Serious Adverse Effects (Rare):
Orally: There have been rare reports of hepatotoxicity.
Cardiovascular ...One case of congestive heart failure and another case of myocardial infarction has been possibly attributed to use of glucosamine hydrochloride and chondroitin sulfate (13579,42477). Also, a case of mesenteric occlusion in one patient was considered possibly related to treatment with chondroitin sulfate and glucosamine (89520).
Dermatologic ...Orally, chondroitin sulfate has been associated with skin symptoms, such as eyelid edema, lower limb edema, alopecia, and skin rash (42513). Combinations of chondroitin sulfate along with glucosamine hydrochloride may also be associated with rash, water retention around eyes and scars, and hives on face, chest, torso, and legs when taken orally (42436,110628). A case of photosensitization that was reproducible with rechallenge has been reported following treatment with oral glucosamine-chondroitin products. However, it is not clear if this effect was due to glucosamine, chondroitin sulfate, or contaminants in the product (10408). A case of rash following treatment with intravesical chondroitin sulfate has been reported to be possibly related to the product (42385).
Gastrointestinal ...Orally, chondroitin might cause nausea, bloating, abdominal pain, diarrhea, constipation, vomiting, dyspepsia, and epigastric burning (42396,42436,42541,89561,110628,111647).
Genitourinary ...Intravesical chondroitin sulfate has been associated with cases of vulvar burning, vaginitis, urinary tract infection (UTI), dysuria, pelvic pain, and other bladder symptoms, such as increased frequency, urgency, or incontinence. However, these effects might be due to catheterization rather than chondroitin sulfate (42385,42387,42473).
Hematologic ...Concern has been expressed about possible anticoagulant activity of oral chondroitin sulfate. However, hematological changes have not occurred in patients taking chondroitin sulfate in clinical trials (760).
Hepatic ...Although relatively uncommon, combinations of glucosamine and chondroitin sulfate have been associated with acute liver injury that mimics autoimmune hepatitis. Two cases of elevated aminotransferase levels have been reported for patients taking glucosamine (form unspecified) and chondroitin sulfate at recommended doses. Aminotransferase levels, which were increased by four- to seven-fold, returned to normal following discontinuation of treatment (89515). Another case of abdominal pain, jaundice, fatigue, and elevated liver enzymes has been reported for a patient who used chondroitin sulfate (Condrosulf) for 2 years followed by a combination of glucosamine sulfate and chondroitin sulfate (Vita Mobility Complex) for 8 weeks. The patient required maintenance treatment with azathioprine to remain in remission (89518). A case of acute cholestatic hepatitis due to Glucosamine Forte, which contains glucosamine hydrochloride, chondroitin sulfate, Devil's claw, and shark cartilage, has been reported (89522). It is unclear whether these adverse events were related to chondroitin sulfate, other ingredients, or the combination.
Musculoskeletal ...Orally, chondroitin has been associated with musculoskeletal and connective-tissue events and disorders (13579,42520,95516).
Neurologic/CNS
...Rare cases of headache have been reported following treatment with products containing a combination of oral chondroitin sulfate and glucosamine hydrochloride or glucosamine sulfate (42436,89561).
It is unclear if this effect was due to chondroitin, glucosamine, or the combination.
Patients should adhere to product directions when using chondroitin sulfate products that contain manganese. When taken at doses slightly higher than the recommended dose, these products can sometimes supply greater than the tolerable upper limit (UL) for manganese of 11 mg per day. Ingestion of more than 11 mg per day of manganese might cause significant central nervous system toxicity (7135).
Ocular/Otic ...A case of bilateral pinna chondritis (inflammation of the cartilage of the external ear) has been reported for a patient who received supplements containing glucosamine and chondroitin sulfate (42503).
Pulmonary/Respiratory ...A case of asthma exacerbation has been reported occurred following use of an oral glucosamine and chondroitin sulfate combination product (10002).
General
...Orally, Corydalis yanhusuo is generally well tolerated.
Serious Adverse Effects (Rare):
Orally: Clonic spasms and muscle tremors with high doses.
Musculoskeletal ...Orally, clonic spasms and muscle tremors may occur with overdoses of Corydalis yanhusuo (18).
General
...Orally, dong quai is generally well-tolerated.
Most Common Adverse Effects:
Orally: Burping and flatulence.
Intravenously: Headache.
Cardiovascular ...Orally, dong quai might cause hypertension; according to one case report, a parent and breastfed infant experienced hypertension (195/85 mmHg and 115/69 mmHg, respectively) after the parent consumed a soup containing dong quai root (48428).
Dermatologic ...Dong quai contains psoralens that may cause photosensitivity and photodermatitis (10054,10057,48461).
Endocrine ...In a case report, a male developed gynecomastia after ingesting dong quai tablets (48504).
Gastrointestinal ...Orally, burping and gas may occur with dong quai (738).
Hematologic ...In one case report, a 55-year-old female with protein S deficiency and systemic lupus erythematosus (SLE) had temporary vision loss in the left eye from hemiretinal vein thrombosis three days after taking a phytoestrogen preparation containing dong quai 100 mg, black cohosh 250 mg, wild Mexican yam 276 mg, and red clover 250 mg (13155). It is unclear if dong quai contributed to this event.
Neurologic/CNS ...Dong quai given orally or by injection may be associated with headache (738,48438).
Oncologic ...Dong quai contains constituents that are carcinogenic; however, whether these constituents are present in concentrations large enough to cause cancer with long-term or high-dose use is unknown (7162).
Pulmonary/Respiratory ...A pharmacist experienced allergic asthma and rhinitis after occupational exposure to dong quai and other herbs (48435).
General
...Orally, hemp products are generally well tolerated in food amounts.
In larger amounts, hemp seed oil seems to be well tolerated.
Serious Adverse Effects (Rare):
Orally: Rare cases of anaphylaxis have been reported. Long QT syndrome, torsades de pointes, and syncope have also been reported rarely.
Cardiovascular ...Acquired long QT syndrome, torsades de pointes, and syncope have been reported in a 56-year-old woman following the intake of supplements containing hemp oil. The hemp supplements provided cannabidiol (CBD), and possibly cannabigerol (CBG). Although the exact dose is unknown, up to six times the recommended dose had been used for approximately 6 weeks, in combination with a supplement containing berberine. While hospitalized, intravenous magnesium and saline were used to stabilize heart rhythm. It is unknown whether this adverse effect was related to the hemp oil, berberine, or their interaction (110104).
Hepatic ...Orally, there is a case report of elevated liver enzymes and hepatitis in a two-year-old boy given hemp extract 2. 5 mL, providing 125 mg phytocannabinoid, five to eight times daily for infantile spasms and refractory seizures. The total dose of phytocannabinoids was approximately 60-100 mg/kg daily (110287).
Immunologic
...Orally, there are case reports of allergy to hemp seed, although this is uncommon (101140,101154).
A 44-year-old male developed hives during a meal of hemp seed-crusted seafoods. Later, he developed facial swelling, shortness of breath, and problems speaking. Evaluation revealed allergy to a specific protein in hemp seed. He did not react to smoked cannabis (101140). In other cases, anaphylaxis, facial swelling, and worsening asthma have been reported in association with a first exposure to hemp seed, although some had smoked cannabis previously (101154).
Topically, a case of patch-test confirmed allergic contact dermatitis to hemp seed oil has been reported in a 22-year-old woman. The initial rash started at the application point on her back and spread to her arms, hands, and neck (110288).
Airborne exposure to hemp pollen is a relatively common cause of allergic respiratory symptoms in some locations (101155).
Neurologic/CNS ...Orally, cases of acute cannabinoid toxicity with neurological symptoms in children and adults have been associated with intake of hemp seed oil. There is a case report of decreased alertness, stupor, bloodshot eyes, and fixed gaze in a 2-year-old male probably related to the intake of one teaspoon hemp seed oil (CANAH) containing 0.06% delta-9-tetrahydrocannabinol (THC) twice daily for 3 weeks. After stopping the oil, irritability was reported over the next few days (101153).
General
...Orally, peony seems to be well tolerated when used alone and as part of Chinese herbal formulas.
Most Common Adverse Effects:
Orally: Abdominal distension, anorexia, diarrhea, gastrointestinal discomfort, nausea.
Topically: Dermatitis.
Dermatologic ...Topically, peony has been reported to cause contact dermatitis (13555).
Endocrine ...Orally, a specific traditional Chinese medicine preparation called DDT has been reported to lower follicle-stimulating hormone (FSH) levels and increase estradiol levels. It is not known if this effect is due to peony or the other ingredients (48404). Another specific traditional Chinese medicine preparation, Toki-shakuyaku-san, has been reported to increase plasma progesterone levels in some patients. It is not known if this effect is due to peony or the other ingredients (15294).
Gastrointestinal ...Orally, peony and total glucosides of peony (TGP) have been reported to cause gastrointestinal discomfort, including abdominal distension, anorexia, diarrhea, and nausea, in some patients (13538,92785,97949,98466,100992). In one clinical study, diarrhea was reported in 5% of patients taking TGP 600 mg three times daily for 24 weeks versus 1% of patients taking placebo (100992).
Hematologic ...Orally, there is one case report of easy gum bleeding, epistaxis, and skin bruising with an international normalized ratio (INR) above 6 in a 61-year-old male who was previously stable on warfarin therapy. This patient had switched from one brand of quilinggao, a popular Chinese herbal product, to another brand 5 days prior. This product contained Fritillaria spp. (beimu), Paeonia rubra, Chinese peony (chishao), Lonicera japonica (jinyinhua), and Poncirus trifoliata (jishi). The patient's INR decreased to 1.9 after temporary withdrawal of warfarin therapy. Upon re-initiation of quilinggao, his INR increased to 5.2. It is not known if the increased INR is due to peony or the other ingredients (68343).
General
...Orally, Sweet Annie is generally well-tolerated.
Most Common Adverse Effects:
Orally: Nausea and vomiting.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity.
Gastrointestinal ...Orally, Sweet Annie might cause gastrointestinal upset including nausea and vomiting in some patients (11058,112393).
Hepatic
...Orally, Sweet Annie might cause hepatic adverse effects (16895,103254,103255).
In one case, a 52-year-old patient developed hepatitis after taking the Sweet Annie constituent artemisinin 200 mg three times daily for 10 days. The patient developed abdominal pain and dark urine and was found to have elevated liver enzymes consistent with hepatitis. Symptoms resolved within 2 weeks of discontinuing use. Although it is possible this supplement caused liver disease in this patient, it is not certain. In clinical trials evaluating artemisinin, elevated liver enzymes have only been reported in around 0.9% of patients. However, the dose of artemisinin in this case was substantially higher than a typical dose (16895). A case of severe acute cholestatic hepatitis has also been reported in a 51-year-old male who drank Sweet Annie tea daily, prepared using 1.25 grams of Sweet Annie powder, for malaria prophylaxis during a 4-week trip to Ethiopia. Three weeks after his return, he presented with malaise, abdominal discomfort, jaundice, elevated liver enzymes, and markers of cholestasis. The patient was treated with corticosteroids and ursodeoxycholic acid and ultimately recovered (103255).
A series of cases linking the use of a supercritical carbon dioxide extract of Sweet Annie to hepatoxicity has also been reported. Of the 29 reports of adverse hepatic reactions to this extract, 19 patients noted symptoms within 12 weeks of starting the extract, 16 patients experienced jaundice, and 9 patients required hospitalization. Other common symptoms of hepatotoxicity included abdominal pain, vomiting, nausea, fever, headache, anorexia, malaise, fatigue, and lethargy. All but one case involved doses below or up to the extract's recommended dose of 300 mg daily. Upon discontinuation, symptoms resolved completely or were improved in nearly all cases (103254).
Immunologic ...One case of a mild allergic reaction to Sweet Annie tea has been reported. The reaction was characterized by a rash and cough that resolved quickly and did not require treatment (11059). When low doses are taken sublingually by individuals allergic to Sweet Annie, numbness of the tongue and throat itching have been reported (109315,112392,112393,112394).
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).
General
...Wormwood contains thujone, a neurotoxin.
When products containing thujone are used orally in medicinal amounts, wormwood may be unsafe.
Most Common Adverse Effects:
Orally: The oil from wormwood leaves can cause diffuse muscle aches, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: The oil from wormwood leaves can cause acute kidney toxicity, rhabdomyolysis, and seizures.
Dermatologic ...Topically, a single case report describes a sensitivity or first degree chemical burn reaction, with facial pain and erythema, after a 50-year-old adult applied a homemade poultice containing wormwood to the face for an unreported length of time (93466).
Gastrointestinal ...Orally, the oil from wormwood leaves can cause nausea and vomiting (662). Use of a home-prepared wormwood extract has been associated with vomiting and severe diarrhea in an infant (93467).
Hematologic ...Orally, use of a home-prepared wormwood extract has been associated with severe metabolic acidosis in an infant (93467).
Immunologic ...Theoretically, wormwood might cause an allergic reaction in people sensitive to the Asteraceae/Compositae family (12815). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.
Musculoskeletal ...Orally, the oil from wormwood leaves can cause diffuse muscle aches and rhabdomyolysis (662).
Neurologic/CNS ...Orally, the oil from wormwood leaves can cause seizures (662).
Renal ...Orally, the oil from wormwood leaves can cause acute kidney toxicity and acute kidney failure (662).
Other ...Chronic ingestion of absinthe, an alcoholic beverage that contains wormwood extract, has been linked to absinthism. Absinthism was first described in the 1800s when absinthe was at its peak levels of consumption. It has been characterized by addiction, gastrointestinal adverse effects, insomnia, auditory and visual hallucinations, tremors, paralysis, epilepsy, and brain damage. There is also increased risk of psychiatric disease and suicide (662,12814,15008). Increasing thujone concentrations of absinthe increases anxiety and decreases attention in healthy individuals (86541). A case of bradyarrhythmias associated with absinthe intoxication has also been reported (86543). However, there is speculation that some of the symptoms of absinthism originally described might be attributed to adulteration with metals or toxic plants such as calamus and tansy, rather than the ingredients usually used in absinthe drinks (15007). Some researchers also suggest that absinthism is not a unique condition and is indistinguishable from alcohol use disorder. In fact, some evidence suggests that the thujone concentrations in the absinthe formulations from the 1800s were too low to cause significant thujone-related toxicities (15008,15009).
