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Obesity and Weight Management Hypovitaminosis D and Obesity – Coincidence or Consequence? Fernanda Reis de Azevedo 1 and Bruno Caramelli 2 1. PhD Student; 2. Associate Professor of Medicine, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil Abstract Vitamin D has attracted much scientific interest in recent years, mostly due to its newly described roles in metabolism regulation and cell proliferation. Along with hypovitaminosis D, the incidence of obesity has risen and has become a public health concern. The association between these two conditions is not merely coincidence and is being deeply investigated regarding its prevalence, mechanism, and even a possible causal relation. The data are still inconclusive but there is important evidence indicating that vitamin D is involved with fat accumulation, the responsible mechanism however still the principal question. The three main hypotheses are: adipose tissue sequestration, genetic modulation, such as polymorphism of the vitamin D receptor (VDR), or an organism evolutionary adaptation to cold weather. In conclusion, more evidence is needed to determine what the correct direction of this connection is and the possible therapeutic strategies of vitamin D replenishment and obesity control. Keywords Obesity, vitamin D, cholecalciferol, hypovitaminosis D, parathyroid hormone, polymorphism, adipocytes, supplementation Disclosure: The authors have no conflicts of interest to declare. Received: 5 April 2013 Accepted: 16 April 2013 Citation: European Endocrinology, 2013;9(2):128–31 Correspondence: Fernanda Reis de Azevedo, Heart Institute (InCor), Av. Dr. Enéas de Carvalho Aguiar, 44, Cerqueira Cesar, São Paulo, Brazil, CEP 05403-000. E: freis@usp.br Hypovitaminosis D and Obesity – Coincidence or Consequence? Nowadays the number of studies involving vitamin D and its interaction with metabolism have grown and gained great exposure in the scientific literature. The main reason for this is the high incidence of its deficiency in different populations worldwide and the rising evidence of its role in the aetiology of an extensive range of diseases. 1 Physiological Actions of Vitamin D Apart from its well-established role in the regulation of calcium metabolism and skeletal development, vitamin D has many functions throughout the body. Important pathways were recently described based on the discovery of vitamin D receptors (VDRs) in most tissues and cells in our body and also the ability of most of them to convert it primary circulating form (25-hydroxyvitamin D) into the active form (1,25-dihydroxyvitamin). Thus, vitamin D should be considered essential for overall health and wellbeing, especially since there is growing evidence suggesting that it has multiple functions in the regulation of cellular proliferation, differentiation, apoptosis and angiogenesis and modulation of immune responses. 2,3 Vitamin D Sources There are two ways by which individuals can fulfil their need of this nutrient: skin production, almost 90  % of total requirement, or diet intake. The synthesis of cholecalciferol (vitamin D3) by the skin is dependent on ultraviolet (UV) radiation from the sun, which is absorbed by the skin leading the transformation of 7-dehydrocholesterol into this form of the nutrient. 4 The amount of UV rays absorbed by the skin, and consequently of vitamin D3 produced, will depend on season, latitude, time of day, skin pigmentation, ageing and even 128 sunscreen or clothes used. 5 Dietary sources of vitamin D are few, being represented mainly by fortified dairy products, oily fish (salmon, mackerel and sardines) and fish oil. 6 Once formed or ingested, vitamin D3 is metabolised in the liver to 25-hydroxyvitamin D3 (25(OH)D) and then in the kidney to its biologically active form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D). 4 Vitamin D Deficiency Vitamin D deficiency is considered a clinical syndrome determined by low circulating levels of 25(OH)D: its primary and major circulating form. However, the actual levels in the blood that can define this syndrome remain unclear. Most studies considered vitamin deficiency when 25(OH)D levels are below 20 ng/ml, insufficiency as 21–29 ng/ml and sufficiency levels between 30–100  ng/ml. 7 Measures of 1,25(OH)2D are not good indicators of vitamin D status since it has a very short half-life, approximately 4 hours, and its blood levels are tightly regulated by serum levels of parathyroid hormone (PTH), calcium and phosphate. It also does not reflect vitamin D reserves, as it is frequently elevated in individuals presenting with hypovitaminosis D due to secondary hyperparathyroidism. 7 Vitamin D and Obesity Association Along with the increase incidence of vitamin D deficiency, the prevalence and severity of obesity has risen and has become a public health concern around the world. Associated with that, several studies have demonstrated evidence of an association between low plasma concentrations of 25-hydroxyvitamin and obesity. The first study to notice a possible association between obesity and vitamin D was performed by Bell and colleagues in 1985. The author was intrigued by the fact that most obese individuals had higher values of serum immunoreactive PTH, which has an inverse association with © Touch ME d ica l ME d ia 2013