Milk Thistle (Silymarin)

Wang et al. (Cochrane Database Syst Rev, 2025; PMID 40552569): 17 randomized trials, 2,069 adults with metabolic dysfunction-associated steatotic liver disease; silymarin lowered ALT against placebo at very low certainty because of bias, small trials and heterogeneity, with no benefit against other treatments, no mortality or quality-of-life data, and silymarin complexes with vitamin E or phosphatidylcholine no better than placebo on ALT. Navarro et al. (PLoS One, 2019; PMID 31536511): NIH-funded multicenter phase II trial, 78 patients with biopsy-proven NASH, 420 or 700 mg three times daily for 48 weeks; the histologic primary endpoint was met by 15 to 19 percent on silymarin and 12 percent on placebo (p=0.79), no benefit. Wah Kheong et al. (Clin Gastroenterol Hepatol, 2017; PMID 28419855): 99 patients with biopsy-proven NASH, 700 mg three times daily for 48 weeks; the primary endpoint, a 30 percent fall in NAFLD activity score, was not met (32.7 against 26.0 percent, p=0.467); fibrosis improved as a secondary outcome. Li et al. (Annals of Hepatology, 2024; PMID 38579127): 26 trials pooled, enzymes and lipids lower; it pools silybin complexes and combination products with plain silymarin, its histology claim conflicts with the two placebo-controlled biopsy trials, and its ALT and AST effects are labeled standardized mean differences at values (-12.39, -10.97) that are implausible for that statistic, so its pooled numbers are read with caution. Zhong et al. (Medicine (Baltimore), 2017; PMID 29245314): 8 trials, 587 patients, AST and ALT lower by 6 to 9 units. Grade C: randomized evidence on a surrogate, very low certainty, with the best-designed trials null on their primary endpoints.