Vitamin D and obesity: current perspectives and future directions

In recent years, new functional roles of vitamin D beyond its traditional role in calcium homoeostasis and bone metabolism have emerged linking the fat-soluble vitamin to various non-communicable diseases. Vitamin D deficiency (25-hydroxyvitamin D (25(OH)D) < 25–30 nmol/l) and sub-optimal status (25(OH)D < 50–100 nmol/l) are increasingly associated with unfavourable metabolic phenotypes, including insulin resistance, type 2 diabetes and CVD; conditions also commonly linked with overweight and obesity. Early studies reported poor vitamin D status in the morbidly obese. More recently, it has been observed that a graded relationship between vitamin D status and BMI, or specifically adiposity, exists in the general population. A number of hypotheses have been proposed to explain the potential mechanisms whereby alterations in the vitamin D endocrine system occur in the obese state. Plausible explanations include sequestration in adipose tissue, volumetric dilution or negative feedback mechanisms from increased circulating 1,25-dihydroxyvitamin D3. Others hypothesise that heavier individuals may partake in less outdoor activity, may also cover-up and wear more clothing than leaner individuals, thus decreasing sun exposure and limiting endogenous production of cholecalciferol in the skin. Moreover, in some but not all studies, BMI and adiposity have been negatively associated with the change in vitamin D status following vitamin D supplementation. It therefore remains unclear if body size and/or adiposity should be taken into account when determining the dietary requirements for vitamin D. This review will evaluate the current evidence linking vitamin D status and supplementation to overweight and obesity, and discuss the implications for setting dietary requirements.

[1]  Hayden L. Smith,et al.  A Retrospective Evaluation of Response to Vitamin D Supplementation in Obese Versus Nonobese Patients , 2015, Journal of pharmacy practice.

[2]  E. Stokic,et al.  Vitamin D and Dysfunctional Adipose Tissue in Obesity , 2015, Angiology.

[3]  J. Vidal,et al.  Prospective Study of Individualized or High Fixed Doses of Vitamin D Supplementation After Bariatric Surgery , 2015, Obesity Surgery.

[4]  A. Esteghamati,et al.  Differences in vitamin D concentration between metabolically healthy and unhealthy obese adults: associations with inflammatory and cardiometabolic markers in 4391 subjects. , 2014, Diabetes & metabolism.

[5]  R. Rabasa-Lhoret,et al.  Characterization of metabolically healthy but obese individuals: should we add vitamin D to the puzzle? , 2014, Diabetes & metabolism.

[6]  M. Amiot,et al.  Vitamin D protects against diet-induced obesity by enhancing fatty acid oxidation. , 2014, The Journal of nutritional biochemistry.

[7]  K. Tucker,et al.  The longitudinal association of vitamin D serum concentrations & adiposity phenotype , 2014, The Journal of Steroid Biochemistry and Molecular Biology.

[8]  M. Uusitupa,et al.  Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals. , 2014, Molecular nutrition & food research.

[9]  A. Holmäng,et al.  A new approach to measuring vitamin D in human adipose tissue using time-of-flight secondary ion mass spectrometry: a pilot study. , 2014, Journal of photochemistry and photobiology. B, Biology.

[10]  J. Stein,et al.  Review article: the nutritional and pharmacological consequences of obesity surgery , 2014, Alimentary pharmacology & therapeutics.

[11]  F. Guerini,et al.  Vitamin D Receptor Gene Polymorphisms Are Associated with Obesity and Inflammosome Activity , 2014, PloS one.

[12]  Elina Hyppönen,et al.  Vitamin D and adipose tissue—more than storage , 2014, Front. Physiol..

[13]  Yun Zhao,et al.  Vitamin D supplementation and body weight status: a systematic review and meta‐analysis of randomized controlled trials , 2014, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[14]  I. Sergeev,et al.  High vitamin D and calcium intakes reduce diet-induced obesity in mice by increasing adipose tissue apoptosis. , 2014, Molecular nutrition & food research.

[15]  A. McTiernan,et al.  Vitamin D3 supplementation during weight loss: a double-blind randomized controlled trial. , 2014, The American journal of clinical nutrition.

[16]  D. English,et al.  Environmental, personal, and genetic determinants of response to vitamin D supplementation in older adults. , 2014, The Journal of clinical endocrinology and metabolism.

[17]  R. Heaney,et al.  25-Hydroxyvitamin D response to graded vitamin D₃ supplementation among obese adults. , 2013, The Journal of clinical endocrinology and metabolism.

[18]  N. Jablonski,et al.  The Human Environment and the Vitamin D Compromise: Scotland as a Case Study in Human Biocultural Adaptation and Disease Susceptibility , 2013, Human biology.

[19]  E. Hyppönen,et al.  DHCR7 mutations linked to higher vitamin D status allowed early human migration to Northern latitudes , 2013, BMC Evolutionary Biology.

[20]  M. Holick,et al.  Vitamin D for health: a global perspective. , 2013, Mayo Clinic proceedings.

[21]  L. Borrell,et al.  The effect of body mass index on optimal vitamin D status in U.S. adults: the National Health and Nutrition Examination Survey 2001-2006. , 2013, Annals of epidemiology.

[22]  Lynette M. Smith,et al.  The effect of vitamin D supplementation on serum 25OHD in thin and obese women , 2013, The Journal of Steroid Biochemistry and Molecular Biology.

[23]  Ahmad Esmaillzadeh,et al.  Serum 25‐hydroxy vitamin D levels in relation to body mass index: a systematic review and meta‐analysis , 2013, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[24]  H. Brenner,et al.  Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study. , 2013, The American journal of clinical nutrition.

[25]  R. Gama,et al.  Vitamin D: a negative acute phase reactant , 2013, Journal of Clinical Pathology.

[26]  S. Vanlint Vitamin D and Obesity , 2013, Nutrients.

[27]  T. Spector,et al.  Causal Relationship between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts , 2013, PLoS medicine.

[28]  J. Whittaker,et al.  Genetic association analysis of vitamin D pathway with obesity traits , 2013, International Journal of Obesity.

[29]  Wei Zhu,et al.  Calcium plus vitamin D3 supplementation facilitated Fat loss in overweight and obese college students with very-low calcium consumption: a randomized controlled trial , 2013, Nutrition Journal.

[30]  M. Holick,et al.  25-Hydroxyvitamin D3 and 1,25-Dihydroxyvitamin D3 Promote the Differentiation of Human Subcutaneous Preadipocytes , 2012, PloS one.

[31]  C. Rock,et al.  Weight Loss Is Associated With Increased Serum 25‐Hydroxyvitamin D in Overweight or Obese Women , 2012, Obesity.

[32]  D. Viswanath,et al.  Dietary Reference Intakes for Calcium and Vitamin D , 2012, Pediatrics.

[33]  Dan Gao,et al.  Vitamin D signalling in adipose tissue , 2012, British Journal of Nutrition.

[34]  R. Heaney,et al.  Volumetric Dilution, Rather Than Sequestration Best Explains the Low Vitamin D Status of Obesity , 2012, Obesity.

[35]  M. Soares,et al.  Mechanistic roles for calcium and vitamin D in the regulation of body weight , 2012, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[36]  M. Soares,et al.  Calcium and vitamin D for obesity: a review of randomized controlled trials , 2011, European Journal of Clinical Nutrition.

[37]  A. McTiernan,et al.  Effects of weight loss on serum vitamin D in postmenopausal women. , 2011, The American journal of clinical nutrition.

[38]  A. Tremblay,et al.  Elevated Serum 25(OH)D Concentrations, Vitamin D, and Calcium Intakes Are Associated With Reduced Adipocyte Size in Women , 2011, Obesity.

[39]  R. Sladek,et al.  Characterizing the profile of obese patients who are metabolically healthy , 2011, International Journal of Obesity.

[40]  M. Kiely,et al.  Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol response to supplementation in healthy young and older Irish adults , 2011, British Journal of Nutrition.

[41]  C. Gordon,et al.  Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. , 2011, The Journal of clinical endocrinology and metabolism.

[42]  T. Tzotzas,et al.  Rising serum 25-hydroxy-vitamin D levels after weight loss in obese women correlate with improvement in insulin resistance. , 2010, The Journal of clinical endocrinology and metabolism.

[43]  G. Steinberg,et al.  Adipose tissue as an endocrine organ , 2010, Molecular and Cellular Endocrinology.

[44]  J. Eisman,et al.  Adequacy of vitamin D replacement in severe deficiency is dependent on body mass index. , 2009, The American journal of medicine.

[45]  R. Koerfer,et al.  Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. , 2009, The American journal of clinical nutrition.

[46]  J. Strain,et al.  Estimation of the dietary requirement for vitamin D in free-living adults >=64 y of age. , 2009, The American journal of clinical nutrition.

[47]  J. Blum,et al.  Supplements of 20 microg/d cholecalciferol optimized serum 25-hydroxyvitamin D concentrations in 80% of premenopausal women in winter. , 2009, The Journal of nutrition.

[48]  Y. J. Foss Vitamin D deficiency is the cause of common obesity. , 2009, Medical hypotheses.

[49]  J. Moan,et al.  Seasonal variation of 1,25-dihydroxyvitamin D and its association with body mass index and age , 2009, The Journal of Steroid Biochemistry and Molecular Biology.

[50]  Michelle Chan,et al.  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. , 2009, Endocrinology.

[51]  J. Wallace,et al.  Obesity and inflammation: the effects of weight loss , 2008, Nutrition Research Reviews.

[52]  R. Jorde,et al.  Supplementation with cholecalciferol does not result in weight reduction in overweight and obese subjects. , 2008, European journal of endocrinology.

[53]  J. Strain,et al.  Estimation of the dietary requirement for vitamin D in healthy adults. , 2008, The American journal of clinical nutrition.

[54]  A. Karelis,et al.  Metabolically healthy but obese individuals , 2008, The Lancet.

[55]  Elizabeth A Yetley,et al.  Overview of the conference "Vitamin D and Health in the 21st Century: an Update". , 2008, The American journal of clinical nutrition.

[56]  M. Holick,et al.  Prolapsed intervertebral disc , 2008, British medical journal.

[57]  B. Dawson-Hughes,et al.  Body Size and Serum 25 Hydroxy Vitamin D Response to Oral Supplements in Healthy Older Adults , 2008, Journal of the American College of Nutrition.

[58]  A. Karelis,et al.  Inclusion of C-reactive protein in the identification of metabolically healthy but obese (MHO) individuals. , 2008, Diabetes & metabolism.

[59]  S. Booth,et al.  Vitamin D3 in fat tissue , 2008, Endocrine.

[60]  B. Person,et al.  Nutritional Deficiencies in Morbidly Obese Patients: A New Form of Malnutrition? , 2008, Obesity surgery.

[61]  R. Jorde,et al.  Serum 1,25-dihydroxy vitamin D is inversely associated with body mass index , 2008, European journal of nutrition.

[62]  A. Looker Do body fat and exercise modulate vitamin D status? , 2007, Nutrition reviews.

[63]  A. LaCroix,et al.  Calcium plus vitamin D supplementation and the risk of postmenopausal weight gain. , 2007, Archives of internal medicine.

[64]  N. Paynter,et al.  The effect of weight loss on C-reactive protein: a systematic review. , 2007, Archives of internal medicine.

[65]  Bradford W Hesse,et al.  Identifying sedentary subgroups: the National Cancer Institute's Health Information National Trends Survey. , 2006, American journal of preventive medicine.

[66]  S. Kasim-Karakas,et al.  The effect of weight loss and dietary fatty acids on inflammation , 2006, Current atherosclerosis reports.

[67]  E. Hyppönen,et al.  Vitamin D Status and Glucose Homeostasis in the 1958 British Birth Cohort , 2006, Diabetes Care.

[68]  Herbert Tilg,et al.  Adipocytokines: mediators linking adipose tissue, inflammation and immunity , 2006, Nature Reviews Immunology.

[69]  E. Mannarino,et al.  The endocrine function of adipose tissue: an update , 2006, Clinical endocrinology.

[70]  Wilfried De Backer,et al.  Body surface area in normal-weight, overweight, and obese adults. A comparison study. , 2006, Metabolism: clinical and experimental.

[71]  A. Greenberg,et al.  Obesity and the role of adipose tissue in inflammation and metabolism. , 2006, The American journal of clinical nutrition.

[72]  M. Ferry Strategies for ensuring good hydration in the elderly. , 2005, Nutrition reviews.

[73]  K. Frayn Obesity and metabolic disease: is adipose tissue the culprit? , 2005, The Proceedings of the Nutrition Society.

[74]  I. S. Wood,et al.  Adipokines: inflammation and the pleiotropic role of white adipose tissue , 2004, British Journal of Nutrition.

[75]  T. Suda Vitamin D and bone , 2004, Proceedings of the Japan Academy. Series B, Physical and Biological Sciences.

[76]  J. Yanovski,et al.  The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. , 2004, The Journal of clinical endocrinology and metabolism.

[77]  L. Tartaglia,et al.  Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. , 2003, The Journal of clinical investigation.

[78]  M. Desai,et al.  Obesity is associated with macrophage accumulation in adipose tissue. , 2003, The Journal of clinical investigation.

[79]  R. Ahima,et al.  Adipose Tissue as an Endocrine Organ , 2006, Obesity.

[80]  M. Holick,et al.  Decreased bioavailability of vitamin D in obesity. , 2000, The American journal of clinical nutrition.

[81]  N. Jablonski,et al.  The evolution of human skin coloration. , 2000, Journal of human evolution.

[82]  T Nakamura,et al.  Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. , 1999, Biochemical and biophysical research communications.

[83]  S. Coppack,et al.  C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[84]  S. Coppack,et al.  Adipose tissue as an endocrine and paracrine organ , 1998, International Journal of Obesity.

[85]  Philipp E. Scherer,et al.  A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes (*) , 1995, The Journal of Biological Chemistry.

[86]  B. Spiegelman,et al.  Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. , 1995, The Journal of clinical investigation.

[87]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1994, Nature.

[88]  C. Buffington,et al.  Vitamin D Deficiency in the Morbidly Obese , 1993, Obesity surgery.

[89]  B. Hollis,et al.  Low circulating vitamin D in obesity , 1988, Calcified Tissue International.

[90]  D. Lawson,et al.  Estimation of vitamin D3 and 25-hydroxyvitamin D3 in muscle and adipose tissue of rats and man. , 1986, Clinica chimica acta; international journal of clinical chemistry.

[91]  S. Epstein,et al.  Evidence for alteration of the vitamin D-endocrine system in obese subjects. , 1985, The Journal of clinical investigation.

[92]  C. Christiansen,et al.  Impairment of vitamin D metabolism and bone mineral content after intestinal bypass for obesity. A longitudinal study. , 1984, Scandinavian journal of gastroenterology.

[93]  R. Anderson,et al.  Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin. , 1982, Science.

[94]  J. Compston,et al.  Vitamin D status and bone histomorphometry in gross obesity. , 1981, The American journal of clinical nutrition.

[95]  T. Oppé,et al.  Vitamin D deficiency. , 1979, British medical journal.

[96]  S. Teitelbaum,et al.  Abnormalities of circulating 25-OH vitamin D after jejunal-lleal bypass for obesity: evidence of an adaptive response. , 1977, Annals of internal medicine.

[97]  E. Mawer,et al.  The distribution and storage of vitamin D and its metabolites in human tissues. , 1972, Clinical science.

[98]  C. Rich,et al.  Deposition in and release of vitamin D3 from body fat: evidence for a storage site in the rat. , 1971, The Journal of clinical investigation.

[99]  D. Talwar,et al.  The effect of the systemic inflammatory response on plasma vitamin 25 (OH) D concentrations adjusted for albumin. , 2014, PLoS ONE.

[100]  J. Aloia,et al.  The vitamin d dose response in obesity. , 2014, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[101]  J. Gummert,et al.  Vitamin D supplementation, body weight and human serum 25-hydroxyvitamin D response: a systematic review , 2013, European Journal of Nutrition.

[102]  J. Moan,et al.  Serum 25-hydroxyvitamin D is a predictor of serum 1,25-dihydroxyvitamin D in overweight and obese patients. , 2011, The Journal of nutrition.

[103]  N. Jablonski,et al.  Vitamin D: in the evolution of human skin colour. , 2010, Medical hypotheses.

[104]  I. Kunii,et al.  Body fat and cholecalciferol supplementation in elderly homebound individuals. , 2006, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[105]  John N Fain,et al.  Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. , 2006, Vitamins and hormones.

[106]  I. Jialal,et al.  The effect of weight loss on a stable biomarker of inflammation, C-reactive protein. , 2005, Nutrition reviews.

[107]  L. Petersen,et al.  Longitudinal study of the long-term relation between physical activity and obesity in adults , 2004, International Journal of Obesity.

[108]  R. Heaney,et al.  Vitamin D and its Major Metabolites: Serum Levels after Graded Oral Dosing in Healthy Men , 1998, Osteoporosis International.

[109]  M. Maffei,et al.  Positional cloning of the mouse obese gene and its human homologue , 1995, Nature.

[110]  C. Schorah Blood vitamin concentrations during the acute-phase response. , 1993, Critical care medicine.

[111]  M. Holick,et al.  The role of sunlight in the cutaneous production of vitamin D3. , 1988, Annual review of nutrition.

[112]  O. H. Sørensen,et al.  Vitamin D deficiency in obese patients and changes in circulating vitamin D metabolites following jejunoileal bypass. , 1982, International journal of obesity.