Vitamin D deficiency and metabolic syndrome: any link with statin intolerance and adipokines dysregulation?

We read with interest the Miñambres et al. review on hypovitaminosis D and the metabolic syndrome (MetS).[1] The authors describe evidence linking vitamin D (vit D) deficiency with MetS or its components, whereas inconsistent results have been reported with regard to vit D supplementation effects on metabolic parameters. The authors suggested that further research is needed to establish whether improving MetS components can increase vit D levels and vice versa. Vit D deficiency has been associated with statin-induced adverse effects.[reviewed in 2,3] In this context, a recent meta-analysis found that low vit D concentrations were related to myalgia in statin-treated patients.[4] Vit D supplementation has also been proposed as an option to manage statin intolerance in patients with vit D deficiency.[5] As MetS patients are at a high cardiovascular (CV) risk, they are often treated with statins.[6] Based on the link between MetS and vit D hypovitaminosis, it follows that measuring vit D levels may be clinically useful in MetS patients to either prevent or treat statin intolerance. In this context, it is also worth noting that statins can interfere with vit D metabolism through CYP3A4,[7] and also increase the availability of cholesterol biosynthesis precursors such as 7-dehydrocholesterol that mediate vitamin D production.[8] These interactions could confound the association between vit D status and MetS and should be considered before interpreting any observational data. On another issue, MetS has been associated with decreased adiponectin and increased leptin levels.[9] These adipokine abnormalities may further increase CV risk in MetS patients.[9] Vit D metabolism has been reported to influence the expression of leptin and adiponectin in adipose tissue.[10] In this context, there are data linking vit D positively with adiponectin and negatively with leptin levels.[11–13] However, a recent meta-analysis did not find any effect of vit D intake on leptin and adiponectin concentrations.[14] Further research is needed to elucidate such associations.