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.

Disclosure statement

This letter was written independently; no company or institution supported this financially. NK has given talks, attended conferences and participated in trials sponsored by Amgen, Angelini, Astra Zeneca, Boehringer Ingelheim, MSD, Novartis, Novo Nordisk and Sanofi. AS has nothing to declare. MB: speaker bureau: Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, KRKA, MSD, Sanofi-Aventis; consultant to Abbott Vascular, Amgen, Daichii Sankyo, Esperion, Lilly, MSD, Resverlogix and Sanofi-Aventis.

Niki Katsiki
Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece
Amirhossein Sahebkar
Biotechnology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
Maciej Banach
Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland
Healthy Aging Research Centre (HARC), Medical University of Lodz, Lodz, Poland
[email protected]