Abstract
Polyphenols, known for their potent antioxidant and anti-inflammatory properties, have emerged as promising, natural, and safe complementary treatment options for metabolic-associated steatotic liver disease (MASLD). Among these, curcumin, resveratrol, and silymarin are the most extensively studied; however, their differential effects on MASLD outcomes remain inconclusive. This systematic review and meta-analysis of RCTs aimed to evaluate the efficacy of curcumin, resveratrol, and silymarin in patients with MASLD. A comprehensive search of seven databases was conducted up to September 2024. Odds ratios (OR), mean differences (MD), and standardized MD (SMD) with 95% confidence intervals (CI) were used to assess treatment effects. Primary outcomes included improvement in hepatic steatosis and ALT activity, while secondary outcomes included changes in AST activity, blood lipids, glucose, BMI, blood pressure, and TNF-α. Twenty-seven studies involving 1691 participants were included. Curcumin significantly improved hepatic steatosis compared to placebo (OR: 4.39, 95% CI: 1.45 to 13.27, p = 0.009), followed by resveratrol (OR: 3.18, 95% CI: 1.20 to 8.42, p = 0.02). Silymarin exhibited the strongest effect in reducing ALT levels (MD: -6.44 U/L, 95% CI: -10.03 to -2.85, p = 0.0004), with curcumin (MD: -5.88 U/L, 95% CI: -9.05 to -2.72, p = 0.0003) also showing significant reductions. A marked reduction in AST was observed with silymarin (MD: -6.99 U/L, 95% CI: -8.56 to -5.42, p < 0.00001), followed by curcumin (MD: -3.36 U/L, 95% CI: -5.35 to -1.36, p = 0.001). Furthermore, curcumin intake significantly improved metabolic indicators (TG, FBG, HOMA-IR, and BMI). Resveratrol reduced FBG and DBP. Curcumin had the strongest effect on hepatic steatosis and improved both transaminase levels and metabolic markers. Silymarin demonstrated the greatest reduction in transaminase levels, while resveratrol showed modest benefits in steatosis and metabolic improvements. The three polyphenols appear as promising therapeutics for the treatment of MASLD.