The effects of ellagic acid in metabolic dysfunction-associated steatotic liver disease (MASLD) patients: a randomized, add-on, double-blind, controlled trial.

BACKGROUND

With few effective therapies, metabolic dysfunction-associated steatotic liver disease (MASLD) is a rising worldwide health problem. Ellagic acid (EA), a polyphenol with antioxidant and anti-inflammatory properties, may address the multifactorial pathogenesis of MASLD. This trial evaluated the efficacy of EA supplementation combined with a hypocaloric diet in reducing hepatic fat and improving metabolic and liver function markers.

METHODS

In this double-blind, randomized, placebo-controlled study, 60 persons with MASLD participated. Included patients were randomly assigned to consume either 200 mg of EA once a day or a placebo, alongside a hypocaloric diet for 8 weeks. The primary outcome was the absolute mean change in HRI. Secondary outcomes included liver stiffness (LS), liver function tests, metabolic profile, high-sensitivity C-reactive protein (hs-CRP), and anthropometric indices.

RESULTS

EA supplementation significantly reduced HRI compared to the placebo group (mean difference [MD]: -0.23; P < 0.001). Improvements were also observed in LS (MD: - 0.47 kPa; P < 0.001), alanine transaminase (MD: - 27.89 U/L; P < 0.001), aspartate transaminase (MD: - 8.20 U/L; P < 0.001), fasting blood sugar (MD: - 6.78 mg/dL; P < 0.001), triglyceride (MD: - 42.65 mg/dL; P = 0.004), low-density lipoprotein cholesterol (MD: - 14.63 mg/dL; P = 0.026), high-density lipoprotein cholesterol (MD: + 3.38 mg/dL; P = 0.019), and hs-CRP (MD: - 0.81 mg/L; P < 0.001). Anthropometric indices improved significantly by week 8.

CONCLUSIONS

EA supplementation, combined with a hypocaloric diet, effectively reduced hepatic fat and improved metabolic and liver function markers in patients with MASLD. EA represents a promising adjunct therapy for MASLD management, warranting further investigation.

TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (Trial identifier: IRCT20180103038199N16).