|Year : 2016 | Volume
| Issue : 1 | Page : 1-5
Is Vitamin D deficiency a cause or result of childhood obesity?
Abdul Hadi H Almazroea
Department of Pediatrics, Taibah University, Tayba, Medina, Saudi Arabia
|Date of Web Publication||23-May-2016|
Abdul Hadi H Almazroea
Department of Pediatrics, Taibah University, Tayba, Medina
Source of Support: None, Conflict of Interest: None
Obesity is increasing worldwide. Obese individuals are at higher risk of Vitamin D deficiency, which is highly prevalent in infants, children, and adolescents. In addition to causing rickets, there is a known association between obesity and Vitamin D status in both adults and children. Serum 25-hydroxy Vitamin D, a Vitamin D biomarker used in clinical diagnostics, is inversely associated with body mass index, waist circumference, and total body fat in both adults and adolescents. This association between low Vitamin D levels and high body weight suggests that Vitamin D deficiency may be causative for obesity; however, the opposite might also be true. Here, we review the relationship between Vitamin D deficiency and obesity, in particular, the genetics and biochemical pathways thought to link the two, with particular reference to the pediatric population. Regardless of etiology, pediatricians must be aware of Vitamin D deficiency in obese children and recommend healthy lifestyle choices.
Keywords: Adolescents, children, obesity, Vitamin D
|How to cite this article:|
Almazroea AH. Is Vitamin D deficiency a cause or result of childhood obesity?. Saudi J Health Sci 2016;5:1-5
| Introduction|| |
Obesity is increasing worldwide: Approximately one-third of the population is now obese. Obesity is defined as a body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) of over 30 kg/m 2 . Although there is a known genetic component to obesity, people generally become obese by consuming more energy from food and drink than needed for their daily activities. Thus, maintaining a healthy diet and exercising regularly can prevent obesity. Obese individuals are at increased risk diabetes, heart disease, and stroke and as a consequence, live shorter lives. They are also at higher risk of Vitamin D deficiency.
Vitamin D deficiency is highly prevalent in infants, children, and adolescents around the world. In Saudi Arabia, the overall prevalence of obesity is about 35.5%.  In addition to causing rickets, there is growing evidence to suggest that Vitamin D deficiency may place individuals at increased risk of serious chronic disease including autoimmunity, cardiovascular disease, and cancer. 
There is a known association between obesity and Vitamin D status in both adults and children. ,,,,, The association between low Vitamin D levels and high body weight has caused speculation that Vitamin D deficiency may be causative for obesity  while other studies have shown that the opposite might be true, i.e., obesity is a potential cause of Vitamin D deficiency.  Serum 25-hydroxy Vitamin D (25(OH)D), a Vitamin D biomarker used in clinical diagnostics, is inversely associated with BMI, waist circumference, and total body fat in both adults and adolescents. ,,, Sequestration of Vitamin D in body fat stores and consequently reduced bioavailability might explain this association. , Here, we review the relationship between Vitamin D deficiency and obesity, in particular, the genetics and biochemical pathways thought to link the two, with particular reference to the pediatric population.
| Vitamin d metabolism|| |
Exposure of the skin to sunlight is the main source of Vitamin D production. , Over 80% of systemic Vitamin D 3 is derived from the epidermis, with the remaining 20% obtained from the diet from animal-derived cholecalciferol (D 3 ), plant-derived ergocalciferol (D 2 ), or drug supplementation. 
Production of Vitamin D 3 in the skin relies on a photochemical process in which epidermal 7-dehydrocholesterol (provitamin D 3 ) is converted to pre-Vitamin D 3 (pre-D 3 ) by ultraviolet radiation.  Pre-D 3 then isomerizes to D 3 via a thermosensitive but noncatalytic process.  This reaction requires specific UVB wavelengths between 290 and 315 nm, which are only emitted during certain parts of the day at specific latitudes and certain seasons. Therefore, the optimal formation of pre-D 3 is multifactorial, being dependent on genetic and environmental factors such as skin pigmentation, clothing, and sunscreen use. 
Dietary Vitamin D is fat-soluble and therefore transported via the lymphatics in chylomicrons and subsequently into the venous circulation. Although adipose tissue and muscle consume some dietary Vitamin D, the remainder is transported to the liver where it is metabolized by the Vitamin D 25-hydroxylase cytochrome P450 enzymes (CYP2R1 and CYP27A1) to (25(OH)D).  25(OH)D is then converted to the biologically active form of Vitamin D, 1,25(OH) 2 D, in the proximal renal tubules. ,
| Storage, Circulation, and Excretion|| |
25(OH)D is the major stored and circulating form of Vitamin D and is used clinically as a biomarker of Vitamin D status. Circulating 25(OH)D levels are usually high in the plasma, but in reality 25(OH)D is sequestered in adipose tissue and muscle. , Although 25(OH)D's circulating half-life is approximately 10-15 days, , tissue release results in an actual half-life of 2-3 months.  Vitamin D's distribution in humans has been demonstrated by injecting radiolabeled Vitamin D3 and monitoring biological activity and radioactivity in fat tissue. 
In contrast, biologically active 1,25(OH) 2 D circulates at the picomolar range. 1α-hydroxylation is under strict, rate-limiting regulation by serum parathyroid hormone (PTH) and fibroblast growth factor 23 in response to calcium and phosphate levels.
Vitamin D pathway metabolites mainly circulate bound to Vitamin D-binding protein (DBP, 85-90%) and albumin (about 10-15%); only about 1% circulates freely.  DBP and albumin have a similar structure,  DBP circulates at concentrations of 0.6-11 μmol/L,  showing high affinity for 25(OH)D but not Vitamin D or 1,25(OH) 2 D. , Therefore, 1,25(OH) 2 D is not an accurate measure of total Vitamin D due to its tight metabolic regulation and short half-life, with its use limited to altered 1α-hydroxylation states. For instance, it is reduced in chronic kidney disease and increased in granulomatous disease.
Ultimately, 25(OH)D and 1,25(OH) 2 D undergo urinary and biliary excretion after conversion to water-soluble calcitroic acid via a multistep pathway. ,
| Vitamin d and adipose tissue|| |
As noted above, Vitamin D insufficiency may be causally related to obesity, , and Vitamin D receptor (VDR) gene polymorphisms are associated with obesity.  In Saudi Arabia, a high prevalence of Vitamin D deficiency was detected in children in Jeddah: Over 58% of children had relative 25(OH)D deficiency while over 27% had severe deficiency.  Vitamin D deficiency was also highly common in older age groups, for instance, in healthy Saudi medical students in the eastern province of Saudi Arabia  and in individuals in the Madinah Region.  Further afield, two studies in New York and North Texas reported high rates of Vitamin D deficiency in the obese pediatric population. ,
Hyppönen and Boucher recommended that pregnant women should receive daily Vitamin D supplementation because low Vitamin D levels in pregnancy are associated with insulin resistance and muscle loss,  and a high prevalence of Vitamin D deficiency in young pregnant women may increase childhood obesity rates in offspring.  Furthermore, other population studies have found that people with lower levels of Vitamin D are more likely to be obese than those with higher levels of Vitamin D  although the opposite might also be true. 
| Genetic factors related to vitamin d and obesity|| |
Given these epidemiological and biological data, a number of genetic studies have attempted to establish links between Vitamin D and obesity. Vitamin D is immunoregulatory and antiproliferative in disease via the VDR. The VDR is expressed in adipose tissue and may, therefore, mediate Vitamin D's action in fat cells. Calcitriol binds to preadipocyte cells but not mature adipocytes  consistent with the hypothesis that Vitamin D is only likely to play a role in adipose tissue during preadipocyte to adipocyte transition. However, mechanisms of adipogenesis via the VDR vary depending on calcitriol binding. Although the VDR is expressed early in adipogenesis, functional activation of adipocytes results in high but transient VDR expression. ,
A number of in vivo studies support a causative role for Vitamin D signaling in adipose metabolism. The murine Insig-2 promoter contains a functional Vitamin D response element that might mediate preadipocyte differentiation.  VDR-knockout mice show adipose tissue atrophy around the prostate and mammary glands , and overall lower body fat and plasma triglyceride and cholesterol levels compared to wild-type mice. VDR-null mice on high-fat diets grow slower and accumulate less fat than wild-type mice, , and human VDR-overexpressing mice develop obesity due to reduced energy expenditure. 
In human gene association studies, VDR polymorphisms have been associated with several disease states and also to the risk of Vitamin D deficiency in children and adolescents.  The VDR TaqI allele is associated with obesity, , and VDR BsmI and ApaI polymorphisms are also significantly associated with increased BMI. , These observations suggested that altered VDR function might play a role in obesity.
| Vitamin d status and parathyroid hormone in obesity|| |
It has become increasingly clear that low 25(OH)D and high PTH levels are associated with obesity. This appears to occur as a consequence of PTH stimulating renal hydroxylation of 25(OH)D to 1,25(OH) 2 D and calcium influx into adipocytes. Intracellular calcium enhances lipogenesis by activating fatty acid synthase and inhibiting lipolysis, , the net effect being enhanced lipid storage. 
Vitamin D is also an important cofactor for insulin secretion,  with Vitamin D improving insulin sensitivity and secretion, at least in animal models.  In human studies, Thomas et al. found that fasting PTH levels were increased and 25(OH)D concentrations were decreased in obese children,  with these alterations normalizing after weight reduction, suggesting reversible weight loss.
| The beneficial role of calcium and vitamin d in obesity|| |
As noted above, dietary calcium plays a pivotal role energy metabolism. High calcium diets prevent lipid accumulation in fat cells and weight gain from energy-dense diets and increase lipolysis during calorie restriction, thereby speeding up weight loss.  Lipid metabolism and triglyceride storage in adipocytes are regulated by intracellular calcium, which stimulates lipogenic gene expression and lipogenesis, suppresses lipolysis, and increases adipose tissue. In an indirect pathway, calcitriol released in response to low calcium diets stimulates calcium influx in human adipocytes and promotes adiposity. Calcitriol suppression via increased dietary calcium may, therefore, be an attractive strategy to prevent and manage obesity: In a transgenic mouse model of obesity, low calcium diets caused accelerated weight gain and fat accumulation while high calcium diets markedly inhibited lipogenesis, accelerated lipolysis, and suppressed fat accumulation. In clinical studies, increased dietary calcium is associated with a reduced risk of obesity, with calcium from dairy products exerting a greater anti-obesity effect than supplements.
| Exploiting The Vitamin D-Endocrine Axis for Therapeutic Benefit|| |
The prevalence of being overweight and obese is increasing in both children and adults and is an important public health issue.  The Vitamin D-endocrine system appears to be dysregulated in obese individuals, and Vitamin D deficiency is common in obese patients. Many studies have demonstrated the significant effect of calcitriol and calcium on adipocytes while human and animal genetics studies have provided insights into causative links between Vitamin D and obesity. Although we have focused on the VDR, other signaling pathways such as receptor tyrosine kinase and toll-like receptor signaling may also play a role.
In terms of clinical control of obesity, calcitriol, the active form of the Vitamin D 3 metabolite, is likely to be most beneficial since its receptors are present in adipocytes and it modulates inflammatory cytokine expression, thereby possibly overcoming both genetic and nongenetic pathways.  Calcitriol modulates adipokine expression, inhibits anti-inflammatory cytokine expression, reduces monocyte recruitment by human preadipocytes, and restores glucose uptake in adipocytes. ,, Furthermore, serum monitoring of 25(OH)D after calcitriol intake is unnecessary because calcitriol inhibits 25(OH)D synthesis in the liver. , There is, therefore, compelling evidence that calcitriol is active in obesity. However, it should be noted that some studies have demonstrated little or no effect of Vitamin D on weight, , and cholecalciferol supplementation has been shown to have no effect on inflammatory markers in obese subjects. 
| Conclusions|| |
Obesity is an emerging health problem of growing importance. Vitamin D deficiency is common in pediatric populations. There is evidence that the Vitamin D-endocrine system is dysregulated in obese subjects. Since Vitamin D deficiency is largely undertreated in children and even adults worldwide, this may be a significant contributor to the obesity epidemic. Furthermore, obese children often consume high-calorie foods that are low in minerals and vitamins, are more likely to be sedentary, and have reduced sunlight exposure, further compounding the problem and setting up a vicious cycle in which higher body fat mass and decreased Vitamin D bioavailability further increase the risk of Vitamin D deficiency in obese children.
As the number of obese children increases, pediatricians must be aware of Vitamin D deficiency in obese children and recommend healthy lifestyle choices. We recommend Vitamin D deficiency screening and treatment of obese and overweight children although further studies are required to determine the sequelae of low levels of Vitamin D, the amount and duration of treatment necessary to avoid complications, and the effects of Vitamin D supplementation on the obese pediatric population.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Al-Nozha MM, Al-Mazrou YY, Al-Maatouq MA, Arafah MR, Khalil MZ, Khan NB, et al.
Obesity in Saudi Arabia. Saudi Med J 2005;26:824-9.
Huh SY, Gordon CM. Vitamin D deficiency in children and adolescents: Epidemiology, impact and treatment. Rev Endocr Metab Disord 2008;9:161-70.
Alemzadeh R, Kichler J, Babar G, Calhoun M. Hypovitaminosis D in obese children and adolescents: Relationship with adiposity, insulin sensitivity, ethnicity, and season. Metabolism 2008;57:183-91.
Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, et al.
Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. Am J Clin Nutr 2009;90:459-67.
Liel Y, Ulmer E, Shary J, Hollis BW, Bell NH. Low circulating vitamin D in obesity. Calcif Tissue Int 1988;43:199-201.
Reis JP, von Mühlen D, Miller ER 3 rd
, Michos ED, Appel LJ. Vitamin D status and cardiometabolic risk factors in the United States adolescent population. Pediatrics 2009;124:e371-9.
Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of Vitamin D in obesity. Am J Clin Nutr 2000;72:690-3.
Yanoff LB, Parikh SJ, Spitalnik A, Denkinger B, Sebring NG, Slaughter P, et al.
The prevalence of hypovitaminosis D and secondary hyperparathyroidism in obese Black Americans. Clin Endocrinol (Oxf) 2006;64:523-9.
Olson ML, Maalouf NM, Oden JD, White PC, Hutchison MR. Vitamin D deficiency in obese children and its relationship to glucose homeostasis. J Clin Endocrinol Metab 2012;97:279-85.
Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, et al.
Causal relationship between obesity and Vitamin D status: Bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med 2013;10:e1001383.
Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL, et al.
Adiposity, cardiometabolic risk, and Vitamin D status: The framingham heart study. Diabetes 2010;59:242-8.
McKinney K, Breitkopf CR, Berenson AB. Association of race, body fat and season with Vitamin D status among young women: A cross-sectional study. Clin Endocrinol (Oxf) 2008;69:535-41.
Rodríguez-Rodríguez E, Navia-Lombán B, López-Sobaler AM, Ortega RM. Associations between abdominal fat and body mass index on Vitamin D status in a group of Spanish schoolchildren. Eur J Clin Nutr 2010;64:461-7.
Vilarrasa N, Maravall J, Estepa A, Sánchez R, Masdevall C, Navarro MA, et al.
Low 25-hydroxyvitamin D concentrations in obese women: Their clinical significance and relationship with anthropometric and body composition variables. J Endocrinol Invest 2007;30:653-8.
Blum M, Dolnikowski G, Seyoum E, Harris SS, Booth SL, Peterson J, et al.
Vitamin D(3) in fat tissue. Endocrine 2008;33:90-4.
Holick MF, MacLaughlin JA, Doppelt SH. Regulation of cutaneous previtamin D3 photosynthesis in man: Skin pigment is not an essential regulator. Science 1981;211:590-3.
Hanwell HE, Vieth R, Cole DE, Scillitani A, Modoni S, Frusciante V, et al.
Sun exposure questionnaire predicts circulating 25-hydroxyvitamin D concentrations in Caucasian Hospital workers in southern Italy. J Steroid Biochem Mol Biol 2010;121:334-7.
Fraser WD, Milan AM. Vitamin D assays: Past and present debates, difficulties, and developments. Calcif Tissue Int 2013;92:118-27.
Holick MF. Sunlight, UV-radiation, Vitamin D and skin cancer: How much sunlight do we need? Adv Exp Med Biol 2008;624:1-15.
Holick MF. The cutaneous photosynthesis of previtamin D3: A unique photoendocrine system. J Invest Dermatol 1981;77:51-8.
Slominski AT, Kim TK, Li W, Yi AK, Postlethwaite A, Tuckey RC. The role of CYP11A1 in the production of Vitamin D metabolites and their role in the regulation of epidermal functions. J Steroid Biochem Mol Biol 2014;144 Pt A: 28-39.
St-Arnaud R, Glorieux FH. 24, 25-Dihydroxyvitamin D - Active metabolite or inactive catabolite? Endocrinology 1998;139:3371-4.
Clemens TL, Zhou XY, Myles M, Endres D, Lindsay R. Serum Vitamin D2 and Vitamin D3 metabolite concentrations and absorption of Vitamin D2 in elderly subjects. J Clin Endocrinol Metab 1986;63:656-60.
Lumb GA, Mawer EB, Stanbury SW. The apparent Vitamin D resistance of chronic renal failure: A study of the physiology of Vitamin D in man. Am J Med 1971;50:421-44.
Slominski A, Zjawiony J, Wortsman J, Semak I, Stewart J, Pisarchik A, et al.
A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin. Eur J Biochem 2004;271:4178-88.
Gray RW, Caldas AE, Wilz DR, Lemann J Jr., Smith GA, DeLuca HF. Metabolism and excretion of 3H-1, 25-(OH) 2-Vitamin D3 in healthy adults. J Clin Endocrinol Metab 1978;46:756-65.
Jones G. Pharmacokinetics of Vitamin D toxicity. Am J Clin Nutr 2008;88:582S-6S.
Mawer EB, Backhouse J, Holman CA, Lumb GA, Stanbury SW. The distribution and storage of Vitamin D and its metabolites in human tissues. Clin Sci 1972;43:413-31.
Turner AG, Anderson PH, Morris HA. Vitamin D and bone health. Scand J Clin Lab Invest Suppl 2012;243:65-72.
Aloia JF, Dhaliwal R, Shieh A, Mikhail M, Fazzari M, Ragolia L, et al.
Vitamin D supplementation increases calcium absorption without a threshold effect. Am J Clin Nutr 2014;99:624-31.
Haussler MR, Whitfield GK, Kaneko I, Haussler CA, Hsieh D, Hsieh JC, et al.
Molecular mechanisms of Vitamin D action. Calcif Tissue Int 2013;92:77-98.
Turner RT, Puzas JE, Forte MD, Lester GE, Gray TK, Howard GA, et al. In vitro
synthesis of 1 alpha, 25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol by isolated calvarial cells. Proc Natl Acad Sci 1980;77:5720-4.
Anderson PH, Atkins GJ. The skeleton as an intracrine organ for Vitamin D metabolism. Mol Aspects Med 2008;29:397-406.
Turner AG, Hanrath MA, Morris HA, Atkins GJ, Anderson PH. The local production of 1,25(OH)2D3 promotes osteoblast and osteocyte maturation. J Steroid Biochem Mol Biol 2014;144:114-8.
Young KA, Engelman CD, Langefeld CD, Hairston KG, Haffner SM, Bryer-Ash M, et al.
Association of plasma Vitamin D levels with adiposity in Hispanic and African Americans. J Clin Endocrinol Metab 2009;94:3306-13.
Gilbert-Diamond D, Baylin A, Mora-Plazas M, Marin C, Arsenault JE, Hughes MD, et al.
Vitamin D deficiency and anthropometric indicators of adiposity in school-age children: A prospective study. Am J Clin Nutr 2010;92:1446-51.
Ochs-Balcom HM, Chennamaneni R, Millen AE, Shields PG, Marian C, Trevisan M, et al.
Vitamin D receptor gene polymorphisms are associated with adiposity phenotypes. Am J Clin Nutr 2011;93:5-10.
Mansour MM, Alhadidi KM. Vitamin D deficiency in children living in Jeddah, Saudi Arabia. Indian J Endocrinol Metab 2012;16:263-9.
Al-Elq AH. The status of Vitamin D in medical students in the preclerkship years of a Saudi medical school. J Family Community Med 2012;19:100-4.
Eman N, Mahmoud AA. Screening of Vitamin D in females in Medina region, KSA. Egypt J Hosp Med 2012;49:891-5.
Smotkin-Tangorra M, Purushothaman R, Gupta A, Nejati G, Anhalt H, Ten S. Prevalence of Vitamin D insufficiency in obese children and adolescents. J Pediatr Endocrinol Metab 2007;20:817-23.
Hyppönen E, Boucher BJ. Avoidance of Vitamin D deficiency in pregnancy in the United Kingdom: The case for a unified approach in National policy. Br J Nutr 2010;104:309-14.
Sarah RC, Nicholas CH, Hazel MI, Keith MG, Cyrus C, Sian MR. Maternal Vitamin D status in pregnancy is associated with adiposity in the offspring. Am J Clin Nutr 2012;96:57-63.
Soares MJ, Chan She Ping-Delfos W, Ghanbari MH. Calcium and Vitamin D for obesity: A review of randomized controlled trials. Eur J Clin Nutr 2011;65:994-1004.
Micah LO, Naim MM, Jon DO, Perrin CW, Michele RH. Vitamin D deficiency in obese children and its relationship to glucose homeostasis. J Clin Endocrinol Metab 2012;97:279-85.
Lýõng KV, Nguyễn LT. Vitamin D and obesity. Med Chem 2012;2:1.
Blumberg JM, Tzameli I, Astapova I, Lam FS, Flier JS, Hollenberg AN. Complex role of the Vitamin D receptor and its ligand in adipogenesis in 3T3-L1 cells. J Biol Chem 2006;281:11205-13.
Fu M, Sun T, Bookout AL, Downes M, Yu RT, Evans RM, et al.
A nuclear receptor atlas: 3T3-L1 adipogenesis. Mol Endocrinol 2005;19:2437-50.
Imagawa M, Tsuchiya T, Nishihara T. Identification of inducible genes at the early stage of adipocyte differentiation of 3T3-L1 cells. Biochem Biophys Res Commun 1999;254:299-305.
Lee S, Lee DK, Choi E, Lee JW. Identification of a functional Vitamin D response element in the murine Insig-2 promoter and its potential role in the differentiation of 3T3-L1 preadipocytes. Mol Endocrinol 2005;19:399-408.
Guzey M, Jukic D, Arlotti J, Acquafondata M, Dhir R, Getzenberg RH. Increased apoptosis of periprostatic adipose tissue in VDR null mice. J Cell Biochem 2004;93:133-41.
Zinser GM, Welsh J. Vitamin D receptor status alters mammary gland morphology and tumorigenesis in MMTV-neu mice. Carcinogenesis 2004;25:2361-72.
Wong KE, Szeto FL, Zhang W, Ye H, Kong J, Zhang Z, et al.
Involvement of the vitamin D receptor in energy metabolism: Regulation of uncoupling proteins. Am J Physiol Endocrinol Metab 2009;296:E820-8.
Narvaez CJ, Matthews D, Broun E, Chan M, Welsh J. Lean phenotype and resistance to diet-induced obesity in Vitamin D receptor knockout mice correlates with induction of uncoupling protein-1 in white adipose tissue. Endocrinology 2009;150:651-61.
Weber K, Erben RG. Differences in triglyceride and cholesterol metabolism and resistance to obesity in male and female Vitamin D receptor knockout mice. J Anim Physiol Anim Nutr (Berl) 2013;97:675-83.
Wong KE, Kong J, Zhang W, Szeto FL, Ye H, Deb DK, et al.
Targeted expression of human Vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice. J Biol Chem 2011;286:33804-10.
Santos BR, Mascarenhas LP, Satler F, Boguszewski MC, Spritzer PM. Vitamin D deficiency in girls from South Brazil: A cross-sectional study on prevalence and association with Vitamin D receptor gene variants. BMC Pediatr 2012;12:62.
Ye WZ, Reis AF, Dubois-Laforgue D, Bellanné-Chantelot C, Timsit J, Velho G. Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset. Eur J Endocrinol 2001;145:181-6.
Vasilopoulos Y, Sarafidou T, Kotsa K, Papadimitriou M, Goutzelas Y, Stamatis C, et al.
VDR TaqI is associated with obesity in the Greek population. Gene 2013;512:237-9.
McCarty MF, Thomas CA. PTH excess may promote weight gain by impeding catecholamine-induced lipolysis-implications for the impact of calcium, Vitamin D, and alcohol on body weight. Med Hypotheses 2003;61:535-42.
Thomas R, Gideon S, Ute A, Kersting M, Wener A. Vitamin D status and parathyroid hormone in obese children before and after weight loss. Eur J Endocrinol 157:225-32.
Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 2004;79:820-5.
Cade C, Norman AW. Vitamin D3 improves impaired glucose tolerance and insulin secretion in the Vitamin D-deficient rat in vivo
. Endocrinology 1986;119:84-90.
Zemel MB. Regulation of adiposity and obesity risk by dietary calcium: Mechanisms and implications. J Am Coll Nutr 2002;21:146S-51S.
Vinh QL, Nguyen LT. The beneficial role of Vitamin D in obesity: Possible genetic and cell signaling mechanisms. Nutr J 2013;12:89.
Sun X, Zemel MB. Calcium and 1,25-dihydroxyvitamin D3 regulation of adipokine expression. Obesity (Silver Spring) 2007;15:340-8.
Gao D, Trayhurn P, Bing C. 1,25-Dihydroxyvitamin D3 inhibits the cytokine-induced secretion of MCP-1 and reduces monocyte recruitment by human preadipocytes. Int J Obes (Lond) 2013;37:357-65.
Marcotorchino J, Gouranton E, Romier B, Tourniaire F, Astier J, Malezet C, et al.
Vitamin D reduces the inflammatory response and restores glucose uptake in adipocytes. Mol Nutr Food Res 2012;56:1771-82.
Bell NH, Shaw S, Turner RT. Evidence that calcium modulates circulating 25-hydroxyvitamin D in man. J Bone Miner Res 1987;2:211-4.
Luong KV, Nguyen LT. Coexisting hyperthyroidism and primary hyperparathyroidism with Vitamin D-deficient osteomalacia in a Vietnamese immigrant. Endocr Pract 1996;2:250-4.
Zittermann A, Frisch S, Berthold HK, Götting C, Kuhn J, Kleesiek K, et al.
Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr 2009;89:1321-7.
Jorde R, Sneve M, Torjesen P, Figenschau Y. No improvement in cardiovascular risk factors in overweight and obese subjects after supplementation with Vitamin D3 for 1 year. J Intern Med 2010;267:462-72.
Jorde R, Sneve M, Torjesen PA, Figenschau Y, Gøransson LG, Omdal R. No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects. Cytokine 2010;50:175-80.