Effect of vitamin D supplementation alone or with calcium on adiposity measures: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT The independent or interactive effects of vitamin D and calcium on adiposity remain inconclusive. OBJECTIVE The objective of this systematic review and meta-analysis was to assess whether vitamin D and calcium supplements cause changes in adiposity. DATA SOURCES MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials databases were searched for literature published from 1966 to March 2014. STUDY SELECTION A systematic search was conducted for randomized clinical trials with ≥ 50 participants aged ≥ 18 years at baseline who had received at least 12 weeks of treatment. Among the inclusion criteria were supplementation with vitamin D with or without calcium and measurement of adiposity (weight, body mass index [BMI], and/or fat mass). DATA EXTRACTION The primary endpoints assessed were changes in weight, BMI, or fat mass. DATA SYNTHESIS Of 953 trials identified, 26 randomized clinical trials (n = 12, vitamin D alone; n = 10, vitamin D plus calcium versus calcium control; n = 4, vitamin D plus calcium versus placebo) with a total of 42,430 participants (median duration, 12 months) met the inclusion criteria. When compared with placebo, vitamin D supplementation had no significant effect on BMI (weighted mean difference [WMD], -0.06 kg/m(2); 95% confidence interval [95%CI], -0.14 to 0.03), weight (WMD, -0.05 kg; 95%CI, -0.32 to 0.23), or fat mass (WMD, -0.43 kg; 95%CI, -1.69 to 0.84). Likewise, no significant reduction in BMI (WMD, 0.02 kg/m(2); 95%CI, -0.11 to 0.14), weight (WMD, 0.12 kg; 95%CI, -0.24 to 0.49), or fat mass (WMD, 0.12 kg; 95%CI, -0.22 to 0.45) was observed in participants who received vitamin D plus calcium compared with those who received calcium control. CONCLUSIONS Supplementation with vitamin D showed no effect on adiposity measures in adults.

[1]  A. Frey,et al.  Comparison of skinfold thickness models with DEXA: impact of visceral adipose tissue. , 2016, Journal of Sports Medicine and Physical Fitness.

[2]  Christine L. Taylor,et al.  Dietary Reference Intakes for Calcium and Vitamin D , 2016, Pediatric Clinical Practice Guidelines & Policies.

[3]  J. Johnston,et al.  Measurement of muscle and fat in postmenopausal women: precision of previously reported pQCT imaging methods. , 2015, Bone.

[4]  Jose Lara,et al.  Age-related changes in resting energy expenditure in normal weight, overweight and obese men and women. , 2015, Maturitas.

[5]  J. Manson,et al.  VITAL-Bone Health: rationale and design of two ancillary studies evaluating the effects of vitamin D and/or omega-3 fatty acid supplements on incident fractures and bone health outcomes in the VITamin D and OmegA-3 TriaL (VITAL). , 2015, Contemporary clinical trials.

[6]  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.

[7]  M. Sarzynski,et al.  Commonality versus specificity among adiposity traits in normal-weight and moderately overweight adults , 2014, International Journal of Obesity.

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

[9]  J. Manson,et al.  Impact of Vitamin D Supplementation on Inflammatory Markers in African Americans: Results of a Four-Arm, Randomized, Placebo-Controlled Trial , 2013, Cancer Prevention Research.

[10]  L. Rejnmark,et al.  Effects of vitamin D supplementation on body fat accumulation, inflammation, and metabolic risk factors in obese adults with low vitamin D levels - results from a randomized trial. , 2013, European journal of internal medicine.

[11]  A. Tjønneland,et al.  Mediterranean diet and colorectal cancer risk: results from a European cohort , 2013, European Journal of Epidemiology.

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

[13]  Martin L. Lee,et al.  High-Dose Vitamin D Supplementation in People With Prediabetes and Hypovitaminosis D , 2013, Diabetes Care.

[14]  F. Shidfar,et al.  A 12-week double-blind randomized clinical trial of vitamin D3 supplementation on body fat mass in healthy overweight and obese women , 2012, Nutrition Journal.

[15]  D. Reid,et al.  Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. , 2012, The Journal of clinical endocrinology and metabolism.

[16]  J. Svartberg,et al.  Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial. , 2012, The British journal of psychiatry : the journal of mental science.

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

[18]  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.

[19]  V. Mootha,et al.  Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation , 2012, Science.

[20]  Lynette M. Smith,et al.  Dose Response to Vitamin D Supplementation in Postmenopausal Women , 2012, Annals of Internal Medicine.

[21]  P. Glendenning,et al.  Effects of three‐monthly oral 150,000 IU cholecalciferol supplementation on falls, mobility, and muscle strength in older postmenopausal women: A randomized controlled trial , 2012, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[22]  R. Jorde,et al.  Vitamin D, Insulin Secretion, Sensitivity, and Lipids , 2011, Diabetes.

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

[24]  A. Renzaho,et al.  Vitamin D, obesity, and obesity-related chronic disease among ethnic minorities: a systematic review. , 2011, Nutrition.

[25]  P. Lips,et al.  Worldwide vitamin D status. , 2011, Best practice & research. Clinical endocrinology & metabolism.

[26]  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.

[27]  Daniel Keeton,et al.  Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African-American adults. , 2011, American journal of hypertension.

[28]  C. Rosen.  Clinical practice. Vitamin D insufficiency. , 2011, The New England journal of medicine.

[29]  Alison Avenell,et al.  Behavioural Interventions for Obese Adults with Additional Risk Factors for Morbidity: Systematic Review of Effects on Behaviour, Weight and Disease Risk Factors , 2010, Obesity Facts.

[30]  JoAnn E. Manson,et al.  The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know , 2010, The Journal of clinical endocrinology and metabolism.

[31]  L. Blizzard,et al.  Not a simple fat‐soluble vitamin: changes in serum 25‐(OH)D levels are predicted by adiposity and adipocytokines in older adults , 2010, Journal of internal medicine.

[32]  Qin Zhang,et al.  The effect of calcium and vitamin D supplementation on obesity in postmenopausal women: secondary analysis for a large-scale, placebo controlled, double-blind, 4-year longitudinal clinical trial , 2010, Nutrition & metabolism.

[33]  C. Gadegbeku,et al.  Relationship of vitamin D and parathyroid hormone with obesity and body composition in African Americans , 2010, Clinical endocrinology.

[34]  R. Jorde,et al.  No improvement in cardiovascular risk factors in overweight and obese subjects after supplementation with vitamin D3 for 1 year , 2010, Journal of internal medicine.

[35]  T. Wren,et al.  Vitamin D status and its relation to muscle mass and muscle fat in young women. , 2010, The Journal of clinical endocrinology and metabolism.

[36]  F. Finelli,et al.  Postoperative metabolic and nutritional complications of bariatric surgery. , 2010, Gastroenterology clinics of North America.

[37]  O. Franco,et al.  Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. , 2010, Maturitas.

[38]  Fritz Schick,et al.  Correlation of Fat Distribution in Whole Body MRI With Generally Used Anthropometric Data , 2009, Investigative radiology.

[39]  J. Coad,et al.  Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient – a randomised, placebo-controlled trial , 2009, British Journal of Nutrition.

[40]  J. Norris,et al.  Association of plasma vitamin D levels with adiposity in Hispanic and African Americans. , 2009, The Journal of clinical endocrinology and metabolism.

[41]  J. Alvarez,et al.  Role of Vitamin D in Insulin Secretion and Insulin Sensitivity for Glucose Homeostasis , 2009, International journal of endocrinology.

[42]  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.

[43]  L. Lind,et al.  Treatment with one-alpha-hydroxycholecalciferol in middle-aged men with impaired glucose tolerance--a prospective randomized double-blind study. , 2009, Acta medica Scandinavica.

[44]  R. Jorde,et al.  Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels , 2009, European journal of nutrition.

[45]  X. J. Sun,et al.  Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins. , 2009, American journal of physiology. Endocrinology and metabolism.

[46]  J. Nagpal,et al.  A double‐blind, randomized, placebo‐controlled trial of the short‐term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle‐aged, centrally obese men , 2009, Diabetic medicine : a journal of the British Diabetic Association.

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

[48]  A. Więcek,et al.  Influence of Calcium and Vitamin D Supplementation on Weight and Fat Loss in Obese Women , 2008, Obesity Facts.

[49]  A. LaCroix,et al.  Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures , 2008, Annals of Internal Medicine.

[50]  G. Major,et al.  Calcium plus vitamin D supplementation and fat mass loss in female very low-calcium consumers: potential link with a calcium-specific appetite control. , 2008, The British journal of nutrition.

[51]  J. Glowacki,et al.  Vitamin D-deficiency and post-fracture changes in lower extremity function and falls in women with hip fractures , 2008, Osteoporosis International.

[52]  K. Zhu,et al.  Effects of calcium and vitamin D supplementation on hip bone mineral density and calcium-related analytes in elderly ambulatory Australian women: a five-year randomized controlled trial. , 2008, The Journal of clinical endocrinology and metabolism.

[53]  Sandro Giannini,et al.  Limb fat-free mass and fat mass reference values by dual-energy X-ray absorptiometry (DEXA) in a 20-80 year-old Italian population. , 2008, Clinical nutrition.

[54]  K. Zhu,et al.  Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. , 2008, Archives of internal medicine.

[55]  C. Pieper,et al.  Distribution and correlates of serum 25-hydroxyvitamin D levels in a sample of patients with hip fracture. , 2007, The American journal of geriatric pharmacotherapy.

[56]  S. Weisnagel,et al.  Measuring insulin sensitivity in postmenopausal women covering a range of glucose tolerance: comparison of indices derived from the oral glucose tolerance test with the euglycemic-hyperinsulinemic clamp. , 2007, Metabolism: clinical and experimental.

[57]  Udo Hoffmann,et al.  Abdominal Visceral and Subcutaneous Adipose Tissue Compartments: Association With Metabolic Risk Factors in the Framingham Heart Study , 2007, Circulation.

[58]  A. Mitrakou,et al.  The Effects of Calcium and Vitamin D Supplementation on Blood Glucose and Markers of Inflammation in Nondiabetic Adults , 2007, Diabetes Care.

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

[60]  B. Dawson-Hughes,et al.  The Effects of Calcium and Vitamin D Supplementation on Blood Glucose and Markers of Inflammation in Nondiabetic Adults , 2007, Diabetes Care.

[61]  Y. Manios,et al.  Skeletal site-dependent response of bone mineral density and quantitative ultrasound parameters following a 12-month dietary intervention using dairy products fortified with calcium and vitamin D: the Postmenopausal Health Study , 2006, British Journal of Nutrition.

[62]  M. Holick.  High prevalence of vitamin D inadequacy and implications for health. , 2006, Mayo Clinic proceedings.

[63]  J. Aloia,et al.  A randomized controlled trial of vitamin D3 supplementation in African American women. , 2005, Archives of internal medicine.

[64]  M. Visser,et al.  Adiposity in relation to vitamin D status and parathyroid hormone levels: a population-based study in older men and women. , 2005, The Journal of clinical endocrinology and metabolism.

[65]  B. Boucher,et al.  Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. , 2004, The American journal of clinical nutrition.

[66]  M. Saad,et al.  Hypovitaminosis D is associated with insulin resistance and β cell dysfunction , 2004 .

[67]  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.

[68]  R. Heaney,et al.  Long-latency deficiency disease: insights from calcium and vitamin D. , 2003, The American journal of clinical nutrition.

[69]  D. Lau,et al.  Long‐term pharmacotherapy for obesity and overweight , 2003 .

[70]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[71]  S. Kritchevsky,et al.  One- and two-year change in body composition as measured by DXA in a population-based cohort of older men and women. , 2003, Journal of applied physiology.

[72]  M. Schlichting,et al.  Combined Calcium and Vitamin D3 Supplementation in Elderly Women: Confirmation of Reversal of Secondary Hyperparathyroidism and Hip Fracture Risk: The Decalyos II Study , 2002, Osteoporosis International.

[73]  M. Zemel.  Regulation of Adiposity and Obesity Risk By Dietary Calcium: Mechanisms and Implications , 2002, Journal of the American College of Nutrition.

[74]  Robert P. Heaney,et al.  Calcium and Weight: Clinical Studies , 2002, Journal of the American College of Nutrition.

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

[76]  O. Johnell,et al.  Changes in Bone Mineral, Lean Body Mass and Fat Content as Measured by Dual Energy X-ray Absorptiometry: A Longitudinal Study , 2000, Calcified Tissue International.

[77]  R. Siervogel,et al.  Aging, body composition, and lifestyle: the Fels Longitudinal Study. , 1999, The American journal of clinical nutrition.

[78]  D. Allison,et al.  Relation between body fat and age in 4 ethnic groups. , 1999, The American journal of clinical nutrition.

[79]  J. Glowacki,et al.  Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. , 1999, JAMA.

[80]  L. Niskanen,et al.  Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy. , 1997, European journal of endocrinology.

[81]  G E Dallal,et al.  Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. , 1997, The New England journal of medicine.

[82]  A R Jadad,et al.  Assessing the quality of reports of randomized clinical trials: is blinding necessary? , 1996, Controlled clinical trials.

[83]  K. Khaw,et al.  Effect of winter oral vitamin D3 supplementation on cardiovascular risk factors in elderly adults. , 1995, European journal of clinical nutrition.

[84]  S. Going,et al.  Aging and Body Composition: Biological Changes and Methodological Issues , 1995, Exercise and sport sciences reviews.

[85]  T. Ziegler,et al.  Anabolic Therapy with Growth Hormone Accelerates Protein Gain in Surgical Patients Requiring Nutritional Rehabilitation , 1993, Annals of surgery.

[86]  T. Wadden,et al.  Treatment of Obesity by Moderate and Severe Caloric Restriction: Results of Clinical Research Trials , 1993, Annals of Internal Medicine.

[87]  E. Mason.  Methods for Voluntary Weight Loss and Control A National Institutes of Health Technology Assessment Conference, 30 March-1 April 1992, Bethesda, Maryland, USA , 1992 .

[88]  L. Sokoll,et al.  Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. , 1991, Annals of internal medicine.

[89]  C. Christiansen,et al.  Validation of body composition by dual energy X-ray absorptiometry (DEXA). , 1991, Clinical physiology.

[90]  H. Pijl,et al.  Very low calorie diets and recently developed anti-obesity drugs for treating overweight in non-insulin dependent diabetics. , 1990, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

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

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

[93]  S B Cohen,et al.  A modified approach to small area estimation. , 1979, NIDA research monograph.

[94]  J. Wildberger,et al.  Proton magnetic resonance spectroscopy reveals increased hepatic lipid content after a single high-fat meal with no additional modulation by added protein. , 2015, The American journal of clinical nutrition.

[95]  B. Clarke,et al.  Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures , 2009 .

[96]  S. Giannini,et al.  Fat-free mass and fat mass reference values by dual-energy X-ray absorptiometry (DEXA) in a 20-80 year-old Italian population. , 2008, Clinical nutrition.

[97]  G. Major,et al.  Supplementation with calcium + vitamin D enhances the beneficial effect of weight loss on plasma lipid and lipoprotein concentrations. , 2007, The American journal of clinical nutrition.

[98]  B. Caballero.  The global epidemic of obesity: an overview. , 2007, Epidemiologic reviews.

[99]  J. Aloia,et al.  A randomized controlled trial of vitamin D3 supplementation in African American women. , 2005, Archives of internal medicine.

[100]  M. Macoritto,et al.  Vitamin D treatment of senescence accelerated mice (SAM-P/6) induces several regulators of stromal cell plasticity , 2004, Biogerontology.

[101]  M K Campbell,et al.  Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement. , 2004, Health technology assessment.

[102]  J. Aloia,et al.  Body fat content and 25-hydroxyvitamin D levels in healthy women. , 2003, The Journal of clinical endocrinology and metabolism.

[103]  L. DiPietro,et al.  Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study , 1999, Diabetologia.

[104]  A. Simon,et al.  Predictive value of waist-to-hip ratio on cardiovascular risk events , 1999, International Journal of Obesity.

[105]  Mason.  Methods for Voluntary Weight Loss and Control , 1993, Annals of Internal Medicine.

[106]  A. Astrup,et al.  Dexfenfluramine as adjuvant to a low-calorie formula diet in the treatment of obesity: a randomized clinical trial. , 1992, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[107]  M. Chapuy,et al.  VITAMINE D3 AND CALCIUM TO PREVENT HIP FRACTURE S IN ELDERLY WOMEN , 1992 .

[108]  K. Dickersin,et al.  Meta-analysis: state-of-the-science. , 1992, Epidemiologic reviews.