Are alterations needed in Silybum marianum (Silymarin) administration practices? A novel outlook and meta-analysis on randomized trials targeting liver injury

It is widely believed that Silybum marianum (Silymarin) alleviates liver injury arising from various etiologies with different degrees of damage through its anti-inflammatory and antioxidant activities. This meta-analysis investigated the effects of silymarin administration on serum levels of liver enzymes including AST, ALT and ALP. From inception to November, 2023, a comprehensive literature search was conducted. Inclusion criteria for this study were randomized trials that provided sufficient data for each group at the beginning and end of the follow-up period. Ultimately, 55 studies with a total of 3545 patients were included. Comprehensive Meta-Analysis (CMA) V4 software was used for meta-analysis. Begg's funnel plot symmetry status, Begg's rank correlation, and Egger's weighted regression tests were used to examine potential publication bias. According to the findings of this meta-analysis silymarin administration showed a significant reduction in AST (SMD [95% CI]: - 0.670 [- 0.931, - 0.408], p-value = 0.000), and ALT (SMD [95% CI]: - 0.912 [- 1.177, - 0.646], p-value = 0.000) levels. While it had no statistically significant effect on ALP level (SMD [95% CI]: - 0.236 [- 1.929, 1.458], p-value = 0.159). Meta-regression analysis showed that there is no significant association between dose, age, BMI, treatment duration and hepatoprotective effects of silymarin. In subgroup analysis, a greater reduction in liver enzymes levels was observed in patients under 50 years old. The subgroup analysis was also showed significant decrease in AST and ALT levels for patients with BMI less than 30, while silymarin treatment had no significant effects on AST and ALT levels in patients with BMI ≥ 30. Silymarin at a dose of less than 400 mg and treatment duration ≤ 2 months showed greater decreasing effects on AST and ALT levels compared to its high doses and longer treatment duration. AST and ALT levels significantly decreased in patients with NAFLD and viral hepatitis, while it had no significant hepatoprotective effects in patients with drugs induced liver injury and alcohol-related liver disease. Modifying the dose and treatment duration with silymarin is recommended in patients with various causes of liver damage.