The effect of vitamin D supplementation on the liver function in non-alcoholic fatty liver disease patients: a systematic review and meta-analysis of randomized controlled trials

Abstract

BACKGROUND: Empirical studies examining the impact of vitamin D supplementation on the liver function in non-alcoholic fatty liver (NAFLD) disease patients have yielded incongruous outcomes. In this systematic review and meta-analysis of randomized controlled trials (RCTs), we investigated the effect of vitamin D supplementation on liver enzymes (alanine transaminase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP)) in NAFLD patients. METHODS: A systematic literature search was conducted using scientific databases including PubMed/Medline, Embase, Web of Science, Cochrane library and Scopus, through May 2026. The search strategy included terms for the interventions (vitamin D, cholecalciferol, calcitriol) and outcomes (ALT, AST, ALP, and GGT) in NAFLD patients. Weighted/standardized mean differences (WMD, SMD) and 95 CI were analyzed utilizing a random-effects model. RESULTS: Overall, 16 RCTs met our inclusion criteria. The current meta-analysis demonstrates a significant reduction in ALT (SMD: -0.45; 95 CI: - 0.87 to -0.04; P = 0.032), and ALP (WMD: -12.91 IU/L; 95 CI: - 18.75 to -7.08; P < 0.001). However, analysis of studies indicated a non-significant effect on AST, GGT. Subgroup analysis showed that the effect of vitamin D on AST is more pronounced in studies with a dose </= 3500 IU/day, duration > 12 weeks and using cholecalciferol (as opposed to calcitriol). CONCLUSION: The findings of this study indicate that vitamin D supplementation may be associated with improvements in ALT and ALP levels, while no significant effects were observed for AST and GGT. These results suggest a possible beneficial role of vitamin D in supporting liver function among patients with NAFLD; however, the evidence remains inconclusive. Future studies are needed to investigate the effect of vitamin D on health status in in NAFLD patients. PROSPERO CODE: CRD42024545499.