Vitamin D Influence on Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) affects nearly a quarter of adults worldwide and encompasses a continuum from simple hepatic steatosis to steatohepatitis, fibrosis and cirrhosis. Emerging evidence indicates that vitamin D modulates key processes in NAFLD pathogenesis through its anti-inflammatory, anti-fibrotic and metabolic regulatory properties. At the cellular level, the active form of vitamin D binds the vitamin D receptor (VDR) to regulate genes involved in lipid metabolism, insulin sensitivity and immune responses. Hypovitaminosis D is frequently observed in patients with NAFLD and correlates with disease severity. Mechanistic studies suggest that vitamin D restores mitochondrial function, attenuates oxidative stress and modulates the gut–liver axis by reinforcing intestinal barrier integrity and reducing endotoxin-driven inflammation. Despite promising preclinical data, clinical trials of vitamin D supplementation have yielded mixed results, reflecting heterogeneity in dosage, duration and patient selection. Integrating mechanistic insights with well-designed interventional studies remains essential for defining the clinical utility of vitamin D in the prevention and management of NAFLD.

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Vitamin D Influence on Non-Alcoholic Fatty Liver Disease publication trend

The graph below shows the total number of articles in vitamin d influence on non-alcoholic fatty liver disease across all publications each year (not limited to Nature Index journals).

Technical terms

Non-alcoholic fatty liver disease (NAFLD): spectrum of liver conditions characterised by excessive fat accumulation in hepatocytes in the absence of significant alcohol intake.

Hepatic steatosis: early stage of NAFLD marked by lipid droplet deposition in liver cells.

Insulin resistance: reduced responsiveness of tissues to insulin signalling, contributing to lipid accumulation in the liver.

Vitamin D receptor (VDR): nuclear transcription factor activated by 1,25-dihydroxyvitamin D₃ to regulate genes involved in metabolism and inflammation.

Mitochondrial contact site and cristae organising system (MICOS): protein complex essential for maintaining mitochondrial inner membrane structure and bioenergetic function.

References

1. Vitamin D ameliorates age-induced nonalcoholic fatty liver disease by increasing the mitochondrial contact site and cristae organizing system (MICOS) 60 level. Experimental & Molecular Medicine (2024).
2. No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. BMC Medicine (2016).
3. Strong association between non alcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes. BMC Medicine (2011).
4. Vitamin D Supplementation and Non-Alcoholic Fatty Liver Disease: Present and Future. Nutrients (2017).
5. Vitamin D receptor targets hepatocyte nuclear factor 4α and mediates protective effects of vitamin D in nonalcoholic fatty liver disease. Journal of Biological Chemistry (2020).