Each caplet contains: Milk Thistle powdered seed extract (silybum marianum, provided by 60 mg 1:35 extract) 2100 mg • Burdock root powder (juglans cineraria) 155 mg • Dandelion root powder (taraxacum officinale) 155 mg • Licorice root powder (glycyrrhiza glabra) 40 mg • Wild Yam root powder (dioscorea villosa) 60 mg.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Milk Thistle Extract Formula. 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
Below is general information about the safety of the known ingredients contained in the product Milk Thistle Extract Formula. 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 in amounts commonly found in foods (12659,12660). Burdock root is commonly eaten as a vegetable (37422,92153,92154)
POSSIBLY SAFE ...when used topically, short-term. An emulsion containing burdock fruit extract 1.2% has been safely applied to the face twice daily for 4 weeks (37420). There is insufficient reliable information available about the safety of burdock when used orally in supplemental doses.
PREGNANCY AND 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).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those in foods.
LIKELY SAFE ...when used orally in amounts commonly found in foods. 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). 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. A dose of 50 mg (containing 8 mg diosgenin) has been used with apparent safety for 12 weeks (12,96724). ...when used topically. A wild yam cream has been used with apparent safety for 3 months (10989).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Milk Thistle Extract Formula. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, taking burdock with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
 Details
In vitro research shows that lignans from burdock reduce rabbit platelet aggregation by inhibiting platelet activating factor (12619). This interaction has not been reported in humans. |
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.
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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.
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Animal research shows that dandelion reduces absorption of ciprofloxacin and can lower levels by 73% (13477). However, this effect has not been reported in humans.
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Theoretically, licorice might reduce the effects of antihypertensive drugs.
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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.
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Overuse or misuse of licorice with cardiac glycoside therapy might increase the risk of cardiac toxicity due to potassium loss (10393).
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Theoretically, concomitant use of licorice with diuretic drugs might increase the risk of hypokalemia.
Details
Overuse of licorice might compound diuretic-induced potassium loss (10393,20045,20046,59812). In one case report, a 72-year-old male with a past medical history of hypertension, type 2 diabetes, hyperlipidemia, arrhythmia, stroke, and hepatic dysfunction was hospitalized with severe hypokalemia and uncontrolled hypertension due to pseudohyperaldosteronism. This was thought to be provoked by concomitant daily consumption of a product containing 225 mg of glycyrrhizin, a constituent of licorice, and hydrochlorothiazide 12.5 mg for 1 month (108577).
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Theoretically, licorice might increase or decrease the effects of estrogen therapy.
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Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.
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Theoretically, loop diuretics might enhance the mineralocorticoid effects of licorice by inhibiting the enzyme that converts cortisol to cortisone; however, bumetanide (Bumex) does not appear to have this effect (3255).
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Theoretically, licorice might increase levels of methotrexate.
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.
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Multiple doses of licorice taken concomitantly with paclitaxel might reduce the effectiveness of paclitaxel. Animal research shows that licorice 3 grams/kg given orally for 14 days before intravenous administration of paclitaxel decreases the exposure to paclitaxel and increases its clearance. Theoretically, this occurs because licorice induces cytochrome P450 3A4 enzymes, which metabolize paclitaxel. Notably, a single dose of licorice did not affect exposure or clearance of paclitaxel (102959).
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Theoretically, licorice might decrease plasma levels and clinical effects of warfarin.
Details
Licorice seems to increase metabolism and decrease levels of warfarin in animal models. This is likely due to induction of cytochrome P450 2C9 (CYP2C9) metabolism by licorice (14441). Advise patients taking warfarin to avoid taking licorice.
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Taking milk thistle with antidiabetes drugs may increase the risk of hypoglycemia.
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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). 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.
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Theoretically, milk thistle might interfere with estrogen therapy through competition for estrogen receptors.
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Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
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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. 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.
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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.
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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.
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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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Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.
Details
Although in vitro research shows that milk thistle can inhibit P-glycoprotein activity (95019), clinical research does not agree. 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 probe 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.
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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.
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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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Theoretically, wild yam might increase or decrease the effects of estrogen.
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Below is general information about the adverse effects of the known ingredients contained in the product Milk Thistle Extract Formula. 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, burdock is well tolerated when consumed as a food.
Although a thorough evaluation of safety outcomes is lacking, there has been long-standing historical use of burdock with few noted adverse effects.
Serious Adverse Effects (Rare):
All ROAs: Allergic reactions, including contact dermatitis and anaphylaxis.
Dermatologic ...Contact dermatitis has been reported secondary to burdock, especially after prolonged use of the root oil (37422). There are cases of allergic dermatitis secondary to using burdock plasters. Two males and a 14 year-old female developed erythematous and vesicular, pruritic, and exudative reactions in areas corresponding to the application of burdock root plasters (12667). Reactions occurred up to 7 days after initial use. Patch testing was positive for burdock sensitivity in all three patients and was nonreactive in matched controls.
Hematologic ...In one case report, a 38-year-old female developed immune-mediated thrombocytopenia after consuming a "cleansing" tea containing unknown amounts of burdock and yellow dock. The patient presented with bruising, mild weakness, and fatigue, which started 2-3 days after consuming the tea, and was found to have a platelet count of 5,000 per mcL. Symptoms resolved after platelet transfusion and treatment with oral dexamethasone (108971). It is unclear if these effects were caused by burdock, yellow dock, the combination, or other contributing factors.
Hepatic ...A case of idiosyncratic drug-induced liver disease (DILI) is reported in a 36-year-old female who presented with abdominal pain after 1 month of taking an herbal liver detox tea containing burdock and other ingredients. Remarkable laboratory values included elevated liver enzymes, alkaline phosphatase, and total bilirubin. The patient received a loading dose of N-acetylcysteine and was hospitalized for 12 days (112178). However, it is unclear if the adverse effect was due to burdock, other ingredients, or the combination.
Immunologic ...There is one case of anaphylactic shock secondary to eating boiled burdock. One hour after eating boiled burdock the patient presented with redness over the entire body and dyspnea. He was found to have low blood pressure and was treated with subcutaneous epinephrine 1 mg and intravenous lactated ringer's solution containing hydrocortisone 100 mg and dexamethasone 8 mg. The cause of anaphylactic shock was attributed to allergenicity to burdock based on positive skin prick test results. Previously, the patient had experienced urticaria after eating boiled burdock (12660).
Neurologic/CNS ...Anticholinergic reactions including dry mouth, dizziness, blurred vision, weakness, dilated pupils, inability to urinate, and bradycardia have been reported following the consumption of burdock products (12662,37421,37431,37434,37435). However, these anticholinergic reactions are believed result from contamination of burdock with belladonna alkaloids. Burdock itself does not contain atropine or other constituents that would be responsible for these reactions.
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 diurectic, 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, 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, wild yam is generally well tolerated.
Most Common Adverse Effects:
Orally: Fever, headache, upset stomach, and vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.
Gastrointestinal ...Orally, wild yam can cause upset stomach and vomiting, especially at higher doses (12,86450).
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 3 days after taking a combination phytoestrogen product containing wild yam 276 mg, dong quai 100 mg, red clover 250 mg, and black cohosh 250 mg (13155). It is unclear if wild yam contributed to this event.
Immunologic ...There are three case reports of anaphylaxis after ingestion of cooked wild yam (96722).
Neurologic/CNS ...Orally, wild yam can cause headache and fever, especially at higher doses (86450).
