Benefits
Liver enzyme levels (ALT and AST)
In people with fatty liver disease, a meta-analysis of 26 randomized trials found silymarin lowered ALT and AST liver enzymes and improved liver fat on biopsy. Larger single trials did not meet their main goals: in two 48-week fatty liver trials the liver activity score did not improve more than with placebo (one saw less scarring, the other did not), and in a 24-week hepatitis C trial ALT fell no more than with placebo.
Antioxidant enzyme activity in the blood
In a 45-day triple-blind trial in 40 adults with type 2 diabetes, 420 mg a day of silymarin raised the antioxidant enzymes superoxide dismutase and glutathione peroxidase and total antioxidant capacity compared with placebo. This is one small trial in people with diabetes, and it did not test whether these blood markers change health outcomes.
Blood sugar and insulin markers
In the same 45-day trial in 40 adults with type 2 diabetes on stable medication, silymarin lowered fasting blood sugar, insulin and triglycerides and raised HDL cholesterol compared with placebo. In the fatty liver meta-analysis fasting insulin fell, but HOMA-IR insulin resistance did not change significantly. Anyone on diabetes medication should talk with a doctor first.
Lower hs-CRP, a blood marker of inflammation
In the same 40-person diabetes trial, hs-CRP fell by about 27 percent with silymarin compared with placebo. Lab research describes anti-inflammatory effects, but no cited trial tested whether this changes symptoms or how people feel.
Mechanism of action
Liver protection
In animal studies, silymarin protected the liver against a range of liver-damaging substances. How, or whether, this carries over to people is not established.
Antioxidant activity
Silymarin acts as an antioxidant in lab studies, and in one small human trial it raised blood levels of the antioxidant enzymes superoxide dismutase and glutathione peroxidase.
Anti-inflammatory and antifibrotic effects
Lab research describes anti-inflammatory and anti-scarring (antifibrotic) effects. In people, one 48-week trial in inflammatory fatty liver disease found less fibrosis on biopsy with silymarin, a finding the authors say needs confirmation, while a second 48-week trial saw fibrosis improve most in the placebo group (not significant).
Clinical trials
Multicenter double-blind placebo-controlled trial at 4 US medical centers: silymarin 420 mg or 700 mg, or placebo, three times daily for 24 weeks. Primary outcome: serum ALT in the normal range or a large decline. Funded by the NIH; the maker of the Legalon product (Rottapharm|Madaus) donated the silymarin and placebo, had no role in design, conduct or data analysis, and gave nonbinding comments on a draft; several authors reported research grants from the maker. (Fried et al. 2012, JAMA)
154 adults with chronic hepatitis C and raised ALT whose interferon treatment had not worked.
Null primary outcome: only 2 people in each group reached the ALT target. Mean ALT decline, viral load and quality of life did not differ significantly from placebo. Side effects were similar to placebo.
Double-blind placebo-controlled trial in Kuala Lumpur, Malaysia: silymarin 700 mg or placebo three times daily for 48 weeks, with repeat liver biopsy. Primary outcome: a 30% or greater fall in NAFLD activity score. (Wah Kheong et al. 2017, Clin Gastroenterol Hepatol)
99 adults with biopsy-proven NASH.
Null primary outcome: 32.7% on silymarin vs 26.0% on placebo reached the target (not significant). More people on silymarin had less fibrosis on biopsy (22.4% vs 6.0%) and on liver stiffness scans (24.2% vs 2.3%). Adverse events did not differ.
Exploratory double-blind placebo-controlled trial at 5 US centers: Legalon 420 mg or 700 mg, or placebo, three times daily for 48 weeks. Primary outcome: at least a 2-point improvement in NAFLD activity score. The trial began with NIH funding; from May 2009 it was funded by the product's maker, Rottapharm|Madaus, as an investigator-initiated study, and one author was a company employee. (Navarro et al. 2019, PLoS One)
78 adults with NASH without cirrhosis.
Null primary outcome: 15% (700 mg), 19% (420 mg) and 12% (placebo) reached it (p = 0.79). Fibrosis improved most in the placebo group, though not significantly. Many participants did not meet entry criteria on central review. Adverse events did not differ significantly between groups.
Double-blind randomized trial of silymarin 140 mg three times daily vs placebo, with a mean observation period of 41 months. (Ferenci et al. 1989, J Hepatol)
170 adults with cirrhosis (91 alcohol-related, 79 other causes).
Four-year survival was 58% with silymarin vs 39% with placebo (P = 0.036), with subgroup effects in alcohol-related cirrhosis and Child A patients. No side effects were observed. A later Cochrane review of 18 trials found no significant effect of milk thistle on overall mortality.
Randomized double-blind placebo-controlled multicenter pilot of oral Siliphos (a 1:2 mix of silibinin and soy phosphatidylcholine), dosed by body weight at 80 to 320 mg of silibinin a day for 28 days, in children on maintenance chemotherapy. Funded by the American Institute for Cancer Research, the Tamarind Foundation and the National Cancer Institute; Thorne Research donated the product and placebo. (Ladas et al. 2010, Cancer)
50 children with acute lymphoblastic leukemia and chemotherapy-related liver toxicity.
No significant change in ALT, AST or bilirubin at day 28. At day 56 AST was lower with milk thistle (P = .05) and ALT showed a trend (P = .07). Side effects did not differ, and cell tests showed no antagonism of two chemotherapy drugs (vincristine and L-asparaginase). Any supplement during cancer care needs the oncology team's approval.
Triple-blind randomized placebo-controlled trial of silymarin 140 mg three times daily for 45 days in adults on stable medication. Antioxidant enzyme and hs-CRP results come from a companion report of the same trial (Ebrahimpour Koujan et al. 2015, Phytomedicine). (Ebrahimpour-Koujan et al. 2018, Phytomedicine)
40 adults aged 25 to 50 with type 2 diabetes.
Compared with placebo, silymarin lowered fasting blood sugar by 11%, insulin by 14%, HOMA-IR by 26% and triglycerides by 24%, and raised HDL cholesterol by 7%. A companion report from the same trial found higher antioxidant enzyme activity and 27% lower hs-CRP. One small trial; it needs confirmation.
Cochrane systematic review and meta-analysis of randomized trials of milk thistle vs placebo or no intervention, searched to July 2007. (Rambaldi et al. 2007, Cochrane Database Syst Rev)
18 trials with 1,088 people with alcohol-related liver disease and/or hepatitis B or C.
No significant effect on overall mortality, complications of liver disease or liver histology. Liver-related deaths were lower across all trials but not in high-quality trials. Trial quality was low overall. Adverse events were not increased.