Obesity and hypovitaminosis D: causality or casualty?

Abstract

Epidemiological studies reported that vitamin D deficiency represents an increasingly widespread phenomenon in various populations. Vitamin D deficiency is considered a clinical syndrome determined by low circulating levels of 25-hydroxyvitamin D (25(OH)D), which is the biologically-inactive intermediate and represents the predominant circulating form. Different mechanisms have been hypothesized to explain the association between hypovitaminosis D and obesity, including lower dietary intake of vitamin D, lesser skin exposure to sunlight, due to less outdoor physical activity, decreased intestinal absorption, impaired hydroxylation in adipose tissue and 25(OH)D accumulation in fat. However, several studies speculated that vitamin D deficiency itself could cause obesity or prevent weight loss. The fat-solubility of vitamin D leads to the hypothesis that a sequestration process occurs in body fat depots, resulting in a lower bioavailability in the obese state. After investigating the clinical aspects of vitamin D deficiency and the proposed mechanisms for low 25(OH)D in obesity, in this manuscript we discuss the possible role of vitamin D replacement treatment, with different formulations, to restore normal levels in individuals affected by obesity, and evaluate potential positive effects on obesity itself and its metabolic consequences. Food-based prevention strategies for enhancement of vitamin D status and, therefore, lowering skeletal and extra-skeletal diseases risk have been widely proposed in the past decades; however pharmacological supplementation, namely cholecalciferol and calcifediol, is required in the treatment of vitamin D insufficiency and its comorbidities. In individuals affected by obesity, high doses of vitamin D are required to normalize serum vitamin D levels, but the different liposolubility of different supplements should be taken into account. Although the results are inconsistent, some studies reported that vitamin D supplementation may have some beneficial effects in people with obesity.

Fig. 1

Model of hypovitaminosis D-induced alterations in obesity. Potential mechanisms in the modulation of skeletal and extra-skeletal modification. Red lines: inhibition pathways. Dotted lines: not well established mechanisms. PHT: parathormone; Ca²⁺: calcium; P: phosphorus; ↓: decreased; ↑: increased