Vitamin D Supplementation for Steatotic Liver Disease: an Updated Systematic Review and Dose-Response Meta-analysis of Randomized and Nonrandomized Interventional Studies

Metabolic dysfunction-associated steatotic liver disease (MASLD) is among the leading causes of chronic liver disease, with few approved treatment options. Vitamin D supplementation has been proposed as a safe and efficacious supplement intervention for MASLD. The current study aimed to systematically evaluate the effect of vitamin D supplementation in any preparation on hepatic (histological, radiological, and biomarker) and metabolic parameters (glucose regulation, lipid profile, and indices of obesity) in patients diagnosed with steatotic liver disease. These effects were compared with patient baseline and/or placebo response, where available. MEDLINE, Scopus, Web of Science, the Cochrane Library, clinicaltrials.gov, and International Clinical Trials Registry Platform were systematically searched for relevant randomized or nonrandomized studies of intervention. Screening and data extraction were completed by independent pairs of reviewers. Effects were pooled using random-effects meta-analyses. One-stage dose-response analysis was performed for alanine aminotransferase (ALT) and γ-glutamyl transferase. The effect of baseline vitamin D, ALT, body mass index, and vitamin D response on treatment response was explored via metaregression. Treatment efficacy was evaluated in subgroup analyses according to patient and intervention characteristics. A total of 28 studies (21 randomized controlled trials) were analyzed. Statistically significant improvements were noted in FibroScan parameters, liver enzymes, insulin resistance, serum triglyceride, and high-density lipoprotein. However, the magnitude of effect regarding these improvements was smaller than thresholds for clinical benefit, and analyses demonstrated inconsistencies. Subgroup analyses failed to identify a specific subset of patients with MASLD benefiting from supplementation. Vitamin D supplementation was safe and well-tolerated, but no meaningful clinical benefit was identified for hepatic or metabolic parameters of interest in MASLD. This trial was registered at PROSPERO as CRD420251125809.