Nonalcoholic Fatty Liver Disease and Reduced Serum Vitamin D3 Levels

Nonalcoholic fatty liver disease (NAFLD) and vitamin D-3 deficiency are two highly prevalent pathologic conditions worldwide that share several cardiometabolic risk factors. In addition to its traditional calcium-related effects on the skeleton, vitamin D-3 deficiency has now been recognized to exert nonskeletal adverse effects on several other organ systems. Accumulating epidemiological evidence suggests that low levels of serum 25-hydroxyvitamin D-3 are associated with the presence and severity of NAFLD, independently of several potential confounders, including features of the metabolic syndrome. The molecular mechanisms of this association remain incompletely understood. A variety of biologically plausible mechanisms may mediate a hepato-protective role for the active metabolite of vitamin D-3. 1 alpha,25-dihydroxyvitamin D-3 modulates the insulin signaling pathway/insulin resistance, suppresses fibroblast proliferation and collagen production, exerts anticoagulant and profibrinolytic effects, and modulates macrophage activity and inflammatory cytokine generation. Overall, the high prevalence of vitamin D-3 deficiency and the plausible biological mechanisms linking this to NAFLD suggest that treatment of vitamin D-3 deficiency to prevent and/or treat NAFLD is a promising field to explore. Large placebo-controlled randomized clinical trials are urgently needed to determine whether vitamin D-3 supplementation could have any potential benefit in reducing the development and progression of NAFLD.