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FATTY LIVER DISEASE: On the undisputed benefits of vitamin D

Fatty liver disease Nonalcoholic fatty liver disease (NAFLD) is an emerging global health problem, recognized as a leading cause of chronic liver disease. Its global prevalence reaches 32%, with higher rates in men (nearly 40%) than in women (26%). The disease is characterized by abnormal lipid accumulation in hepatocytes and elevated levels of liver enzymes. Its progression can lead to nonalcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Recently, NAFLD has been redefined as hepatic steatosis associated with metabolic dysfunction, reflecting its association with metabolic disorders.

Vitamin Dan essential fat-soluble vitamin, plays an important role in calcium homeostasis and bone health. Beyond these better-known roles, vitamin D is involved in a variety of non-skeletal health domains, including anti-inflammatory, antioxidant, and antifibrotic effects. The liver is integral to vitamin D metabolism, converting it to its active form, calcitriol, which exerts these many biological effects.

The authors from the Medical College and Hospital in Faridabad (India) describe here

a real one “molecular crosstalk between vitamin D and non-alcoholic fatty liver disease”,

suggesting that vitamin D opposes at the molecular level each step of the progression from NAFLD to liver cancer. Scientists are deciphering the pathogenesis of NAFLD and showing that it involves multiple molecular pathways. Key aspects of the role of vitamin D in NAFLD include:

  • anti-inflammatory effects: Vitamin D modulates immune responses by downregulating pro-inflammatory cytokines such as TNF-α and IL-6, while upregulating anti-inflammatory cytokines such as IL-10. This modulation helps reduce liver inflammation, a major factor in NAFLD progression;
  • antioxidant effects: Vitamin D enhances the expression of antioxidant enzymes, thereby reducing oxidative stress in hepatocytes. Since oxidative stress is a key factor in liver damage, this antioxidant effect is therefore particularly “valuable”;
  • on lipid metabolism: Vitamin D influences lipid metabolism by regulating the expression of genes involved in the synthesis and oxidation of fatty acids. By promoting lipid oxidation and reducing their synthesis, vitamin D prevents and reduces lipid accumulation in the liver;
  • antifibrotic effects: Vitamin D inhibits the activation of hepatic stellate cells, which are involved in the development of liver fibrosis. This inhibition occurs through different signaling pathways, with vitamin D intervening in these pathways and therefore helping to prevent liver fibrosis.

The inverse relationship between vitamin D levels and NAFLD is already well established: Observational studies have shown the inverse correlation between serum vitamin D levels and the severity of NAFLD. Randomized controlled trials have also suggested that vitamin D supplementation can provide significant improvements in liver enzyme levels, reduction in liver fat content, and improvement in the histological features of NAFLD.

Therapeutic potential of vitamin D in the management of NAFLD is therefore well documented, with its multiple roles in liver health. However, the optimal dosage, duration of treatment and long-term effects of vitamin D supplementation remain to be defined, as well as the possible interaction between vitamin D and other treatments for liver disease.

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