Milk thistle (Milk thistle (Silybum marianum) is a purple-flowered plant. Its sap and seeds contain the active ingredient silymarin, a potent antioxidant and a term often used interchangeably with milk thistle. Silymarin can be further divided into 3 primary flavonoids: silybin, silydianin, and silychristin. Extracts of milk thistle should be standardized to 80 percent silymarin. ) is a purple-flowered plant. Its sap and seeds contain the active ingredient silymarin, a potent antioxidant and a term often used interchangeably with milk thistle. Silymarin can be further divided into 3 primary flavonoids: silybin, silydianin, and silychristin. Extracts of milk thistle should be standardized to 80 percent silymarin.
Claims for Milk ThistleClaims for Milk Thistle
Milk thistle is said to treat cirrhosis and to protect the liver from viral hepatitis, the damaging effects of alcohol, and hepatotoxic drugs (Milk thistle is said to treat cirrhosis and to protect the liver from viral hepatitis, the damaging effects of alcohol, and hepatotoxic drugs (1). Milk thistle may also improve glycemic control in type 2 diabetes (). Milk thistle may also improve glycemic control in type 2 diabetes (2), and individual case reports claim fatality reduction in mushroom poisoning (3).
Evidence for Milk ThistleEvidence for Milk Thistle
A 2007 Cochrane review of 13 randomized clinical trials assessed milk thistle in 915 patients with alcoholic and/or hepatitis B or C virus liver diseases (A 2007 Cochrane review of 13 randomized clinical trials assessed milk thistle in 915 patients with alcoholic and/or hepatitis B or C virus liver diseases (4). Data from this analysis determined that intervention had no significant effect on all-cause mortality, complications of liver disease, or liver histology. When all trials were included in the analysis, liver-related mortality was significantly reduced; however, in an analysis limited to high-quality studies, this reduction was not significant. Milk thistle was not associated with a significant increase in adverse effects. The design of these clinical trials did come into question, and the authors questioned the benefits of milk thistle and suggested the need for more well-designed placebo-controlled studies. ). Data from this analysis determined that intervention had no significant effect on all-cause mortality, complications of liver disease, or liver histology. When all trials were included in the analysis, liver-related mortality was significantly reduced; however, in an analysis limited to high-quality studies, this reduction was not significant. Milk thistle was not associated with a significant increase in adverse effects. The design of these clinical trials did come into question, and the authors questioned the benefits of milk thistle and suggested the need for more well-designed placebo-controlled studies.
A meta-analysis of randomized controlled studies of milk thistle for hepatitis C reported that, although well tolerated, it does not provide overall benefit (A meta-analysis of randomized controlled studies of milk thistle for hepatitis C reported that, although well tolerated, it does not provide overall benefit (5). In vitro, silymarin increases levels of intrahepatic glutathione, an antioxidant important for detoxification (6).
An 8-week trial of milk thistle for metabolic dysfunction–associated steatotic liver disease (MASLD; formerly called nonalcoholic fatty liver disease) in 52 patients with morbid obesity who were awaiting bariatric surgery reported improvements in liver enzymes, although FibroScan staging and Fib-4 scores did not change (An 8-week trial of milk thistle for metabolic dysfunction–associated steatotic liver disease (MASLD; formerly called nonalcoholic fatty liver disease) in 52 patients with morbid obesity who were awaiting bariatric surgery reported improvements in liver enzymes, although FibroScan staging and Fib-4 scores did not change (7).
A meta-analysis of 26 randomized trials including 2375 patients evaluated the impact of milk thistle in patients with nonalcoholic fatty liver disease and reported decreased fatty liver index levels, fatty liver scores, and liver enzymes as well as decreased hepatic steatosis on liver histology (A meta-analysis of 26 randomized trials including 2375 patients evaluated the impact of milk thistle in patients with nonalcoholic fatty liver disease and reported decreased fatty liver index levels, fatty liver scores, and liver enzymes as well as decreased hepatic steatosis on liver histology (8).
Several reviews have shown improvements in glucose and lipid levels attributed to milk thistle. A meta-analysis of 7 studies (370 patients) found that milk thistle significantly decreased fasting glucose by 37.9 mg/dL (2.1 mmol/L) and hemoglobin A1C by 1.4% (Several reviews have shown improvements in glucose and lipid levels attributed to milk thistle. A meta-analysis of 7 studies (370 patients) found that milk thistle significantly decreased fasting glucose by 37.9 mg/dL (2.1 mmol/L) and hemoglobin A1C by 1.4% (2). Another meta-analysis of 16 studies (1358 patients) reported that milk thistle reduced fasting glucose, hemoglobin A1C, total cholesterol, and low-density lipoprotein cholesterol (). Another meta-analysis of 16 studies (1358 patients) reported that milk thistle reduced fasting glucose, hemoglobin A1C, total cholesterol, and low-density lipoprotein cholesterol (9).
In case reports, 2 cases of Amanita mushroom ingestion poisoning (3) showed favorable results after treatment with silybin, which has been proposed to promote hepatocyte growth and inhibit hepatic oxidation.
Adverse Effects of Milk ThistleAdverse Effects of Milk Thistle
No serious adverse effects have been reported, although gastrointestinal upset may occur. Also, people who have allergies to chrysanthemums, marigolds, and daisies may also have allergic reactions to milk thistle.
Women who have hormone-sensitive conditions (eg, breast, uterine, and ovarian cancer; endometriosis; uterine fibroids) should avoid the above-ground parts of milk thistle.Women who have hormone-sensitive conditions (eg, breast, uterine, and ovarian cancer; endometriosis; uterine fibroids) should avoid the above-ground parts of milk thistle.
Drug Interactions with Milk ThistleDrug Interactions with Milk Thistle
Milk thistle may intensify the effects of antihyperglycemic drugs (Milk thistle may intensify the effects of antihyperglycemic drugs (10) and may interfere with protease inhibitors (eg, indinavir, saquinavir) () and may interfere with protease inhibitors (eg, indinavir, saquinavir) (11). Milk thistle may increase international normalized ratio (INR) in patients taking warfarin.). Milk thistle may increase international normalized ratio (INR) in patients taking warfarin.
Milk thistle may also decrease sirolimus clearance in renal transplant patients with hepatic impairment.Milk thistle may also decrease sirolimus clearance in renal transplant patients with hepatic impairment.
(See also table Some Possible Dietary Supplement–Medication Interactions.)
References
1. Abenavoli L, Izzo AA, Milic N, et al. Milk thistle (Silybum marianum): a concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. . Milk thistle (Silybum marianum): a concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases.Phytother Res. 32(11):2202-2213, 2018. doi: 10.1002/ptr.6171
2. Hadi A, Pourmasoumi M, Mohammadi H, et al. The effects of silymarin supplementation on metabolic status and oxidative stress in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of clinical trials. Complement Ther Med. 41:311-319, 2018. doi: 10.1016/j.ctim.2018.08.010
3. Ward J, Kapadia K, Brush E, et al. Amatoxin poisoning: case reports and review of current therapies. J Emerg Med. 44(1):116-121, 2013. doi: 10.1016/j.jemermed.2012.02.020
4. Rambaldi A, Jacobs BP, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. . Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases.Cochrane Database Syst Rev. (4)CD003620, 2007. doi: 10.1002/14651858.CD003620.pub3
5. Yang Z, Zhuang L, Lu Y, et al. Effects and tolerance of silymarin (milk thistle) in chronic hepatitis C virus infection patients: a meta-analysis of randomized controlled trials. . Effects and tolerance of silymarin (milk thistle) in chronic hepatitis C virus infection patients: a meta-analysis of randomized controlled trials.Biomed Res Int. 941085, 2014. doi: 10.1155/2014/941085
6. Valenzuela A, Aspillaga M, Vial S, et al. Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med. 55(5):420-422, 1989. doi: 10.1055/s-2006-962056
7. Mirhashemi SH, Hakakzadeh A, Yeganeh FE, Oshidari B, Rezaee SP. Effect of 8 Weeks milk thistle powder (silymarin extract) supplementation on fatty liver disease in patients candidates for bariatric surgery. . Effect of 8 Weeks milk thistle powder (silymarin extract) supplementation on fatty liver disease in patients candidates for bariatric surgery.Metabol Open. 2022 May 21;14:100190. doi: 10.1016/j.metop.2022.100190
8. Li S, Duan F, Li S, Lu B. Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis. Ann Hepatol. 2024 Mar-Apr;29(2):101174. doi: 10.1016/j.aohep.2023.101174
9. Xiao F, Gao F, Zhou S, et al. The therapeutic effects of silymarin for patients with glucose/lipid metabolic dysfunction: a meta-analysis. Medicine (Baltimore). 99(40):e22249, 2020. doi:10.1097/MD.0000000000022249
10. Wu JW, Lin LC, Tsai TH. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol. 121(2):185-193, 2009. doi: 10.1016/j.jep.2008.10.036
11. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 28(1):4-15, 2017. doi: 10.1177/0956462416671087
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