Effects of silymarin on insulin resistance and sensitivity: A systematic review and meta-analysis of randomized controlled trials.

Objective: This study aims to evaluate the effect of silymarin on insulin resistance and insulin sensitivity through a systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library up to September 2024 for relevant RCTs. The intervention required silymarin supplementation for at least 4 weeks. Primary outcomes were homeostatic model assessment of insulin resistance (HOMA-IR) and fasting insulin (FI), while secondary outcomes included quantitative insulin sensitivity check index (QUICKI). Bias risk was assessed using Cochrane RoB 2. Subgroup analyses were based on disease type, duration, and dosage. Sensitivity and publication bias analyses were conducted using Egger's and Begg's tests. Statistical analysis and meta-analysis were performed using Stata 15.1.

Results: Six studies with 673 participants from Iran, Egypt, and Italy were included. All studies had low risk of bias. Meta-analysis showed that Silybum marianum significantly improved HOMA-IR (WMD = -2.29, 95 % CI: -4.55 to -0.03, p = 0.047) but had no effect on FI (WMD = -2.56, 95 % CI: -7.60 to 2.48, p = 0.862). Subgroup analyses revealed improvements in HOMA-IR for T2DM and diabetics with alcoholic cirrhosis, but no effect in non-alcoholic fatty liver disease (NAFLD) patients. QUICKI did not show significant changes in any group. Only one study reported changes in QUICKI. The results indicated that, compared to the placebo, silymarin improved insulin sensitivity in patients with type 2 diabetes mellitus (T2DM).

Conclusion: In conclusion, the results of this study indicate that there is limited evidence supporting the effectiveness of silymarin in improving HOMA-IR and FI levels in metabolic diseases, and it generally does not appear to significantly improve these parameters. Future studies should aim to increase the number of high-quality RCTs to further validate the efficacy and safety of silymarin, as well as to explore its underlying mechanisms.