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

**Authors:** Héctor Fuentes-Barría, Raúl Aguilera-Eguía, Miguel Alarcón-Rivera, Lisse Angarita-Davila, Cherie Flores-Fernández

PMC · DOI: 10.3390/ijms27062532 · 2026-03-10

## TL;DR

This paper reviews how vitamin D may help manage liver disease linked to metabolic issues by influencing liver metabolism and inflammation.

## Contribution

The paper provides a comprehensive overview of vitamin D's molecular mechanisms and clinical potential in managing MASLD.

## Key findings

- Vitamin D reduces inflammation and improves insulin sensitivity in liver cells.
- Vitamin D supplementation may improve liver enzymes and lipid parameters in MASLD patients.
- Study inconsistencies highlight the need for standardized approaches in vitamin D research for MASLD.

## Abstract

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.

## Linked entities

- **Proteins:** PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1), MTOR (mechanistic target of rapamycin kinase)
- **Chemicals:** 1,25-dihydroxyvitamin D3 (PubChem CID 5280453)
- **Diseases:** Metabolic Dysfunction-Associated Steatotic Liver Disease (MONDO:0013209), MASLD (MONDO:0013209)

## Full-text entities

- **Genes:** PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 5563] {aka AMPK, AMPK2, AMPKa2, PRKAA}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** insulin resistance (MESH:D007333), MASLD (MESH:D008107), hepatic steatosis (MESH:D005234), inflammation (MESH:D007249)
- **Chemicals:** 1,25-dihydroxyvitamin D3 (MESH:D002117), lipid (MESH:D008055), Vitamin D (MESH:D014807)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13027214/full.md

---
Source: https://tomesphere.com/paper/PMC13027214