Vitamin D and Metabolic Dysfunction-Associated Steatotic Liver Disease: Molecular Mechanisms and Clinical Implications—A Narrative Review

Vitamin D has been extensively investigated for its role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a chronic condition characterized by hepatic steatosis, insulin resistance, inflammation, and metabolic dysregulation. This review examines the molecular mechanisms through which vitamin D influences liver metabolism, insulin signaling, lipid accumulation, and inflammatory pathways while evaluating its potential clinical applications in MASLD management. In its active form, 1,25-dihydroxyvitamin D3, vitamin D modulates hepatocyte function by reducing proinflammatory cytokines, enhancing insulin sensitivity, activating AMPK signaling, inhibiting mTOR pathways, and regulating lipid homeostasis. These effects contribute to decreased hepatic fat deposition and improved metabolic profiles, which are key in MASLD progression. Evidence also suggests that vitamin D supplementation may improve liver enzymes, insulin resistance, and lipid parameters in patients with MASLD, although responses vary depending on dosage, baseline vitamin D status, and patient characteristics. Despite promising findings, inconsistencies in study design, measurement methods, and population differences underscore the need for standardized approaches and personalized strategies. In conclusion, vitamin D demonstrates complementary therapeutic potential in MASLD, highlighting research gaps related to optimal dosing, duration, and long-term outcomes. Future studies should integrate mechanistic insights with clinical trials to optimize vitamin D's role in improving liver and metabolic health.