Silymarin is a complex extracted from the dried seeds and fruits of the plant Silybum marianum (milk thistle). Silymarin contains a mixture of flavonolignans (silybin, isosilibinin, silichristin, and silidianin) and a flavonoid (taxifolin). Silybin is recognized as the primary bioactive component, constituting 50–70% of the extract, and commercial supplements are often standardized based on its content.^[1][2][3][4]

Silymarin has a historical application in treating several liver disorders (e.g., alcoholic liver disease, hepatotoxicity, cirrhosis, viral hepatitis). However, findings from clinical (human) studies are often conflicting.

Supplementation with silymarin may be beneficial for individuals affected by nonalcoholic fatty liver disease (NAFLD). One meta-analysis found that supplementation with silymarin reduced the levels of two liver enzyme biomarkers, alanine transaminase (ALT) and aspartame transaminase (AST), high levels of which can be indicative of liver damage.^[3]

Additionally, positive preliminary results have been observed in individuals with liver cirrhosis and liver disease, showing a decrease in AST levels following supplementation with silymarin.^[5]

Conversely, in individuals with chronic hepatitis C virus (HCV) infection, silymarin did not lead to a decrease in ALT levels compared to placebo, and it did not significantly impact HCV RNA levels (the concentration of HCV in the bloodstream). Although there was an improvement in some symptoms (mean physical functioning and bodily pain), these results suggest that silymarin may not be an effective treatment for chronic HCV infection.^[6]

Silymarin is generally considered a safe and well-tolerated supplement.

Some reported side effects include dry mouth, mild gastrointestinal symptoms (e.g., nausea, irregular stools, dyspepsia, diarrhea), headaches, and allergic reactions. However, the frequency of occurrence of such adverse events remains unclear, and a direct attribution to silymarin has not yet been confirmed.^[7][8][5]

Additionally, in studies on cancer patients, asymptomatic mild liver toxicity has been observed at very high dosages of silymarin (between 10 and 20 grams per day).^[8]

However,the safety of silymarin during pregnancy and breastfeeding has not been established; more research is needed, and its use is therefore not recommended during pregancy and breastfeeding.^[7]

Finally, although in vitro studies have suggested potential interactions between silymarin and medications metabolized by some enzymes in the cytochrome P450 family, particularly CYP3A4 and CYP2C9 (the latter of which is involved in warfarin’s metabolism, for example), clinical trials have not yet confirmed these findings.^[5]

In vitro and animal studies have shown that silymarin’s hepatoprotective effects may be attributed to its antioxidant properties and its ability to inhibit the formation of free radicals, particularly those derived from toxic substances like alcohol. Silymarin acts by binding to free radical species, preventing them from damaging organs and tissues. Silymarin also regulates cell membrane permeability by interfering with lipid peroxidation. Additionally, silymarin may act as an iron chelator (i.e., a substance that binds tightly to iron ions, inactivating them), and it appears to increase the activity of superoxide dismutase, as well as levels of glutathione and glutathione peroxidase, all crucial in reducing oxidative stress.^[8][9]

Furthermore, silymarin interferes with the inflammatory system. It regulates levels of pro-inflammatory cytokines while increasing levels of the anti-inflammatory interleukin 10 (IL-10). Studies have also shown its ability to inhibit the activation of nuclear factor kappa B (NF-kB) and the expression of cyclooxygenase-2 (COX-2), both key components in the inflammatory cascade.^[8][10]

Finally, some studies have shown that silymarin may prevent the deposition of collagen fibers by decreasing the synthesis of platelet-derived growth factor (PDGF) induced DNA in cells. Moreover, silymarin was associated with a reduction in serum TGF-B (TGF-β) levels, which plays an important role in the pathogenesis of liver fibrosis.^[8]