Vitamin D Supplementation in the Age of Lost Innocence
Authors: Eliseo Guallar
Journal: Annals of Internal Medicine (2010)

Editorials2 March 2010Vitamin D Supplementation in the Age of Lost InnocenceEliseo Guallar, MD, DrPH, Edgar R. Miller III, MD, PhD, Jose M. Ordovas, PhD, and Saverio Stranges, MD, PhDEliseo Guallar, MD, DrPHFrom Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; National Center for Cardiovascular Research, Madrid 28029, Spain; Friedman School of Nutrition Science and Policy at Tufts University, Boston, MA 02111; and Health Sciences Research Institute, University of Warwick Medical School, Coventry CV4 7AL, United Kingdom., Edgar R. Miller III, MD, PhDFrom Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; National Center for Cardiovascular Research, Madrid 28029, Spain; Friedman School of Nutrition Science and Policy at Tufts University, Boston, MA 02111; and Health Sciences Research Institute, University of Warwick Medical School, Coventry CV4 7AL, United Kingdom., Jose M. Ordovas, PhDFrom Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; National Center for Cardiovascular Research, Madrid 28029, Spain; Friedman School of Nutrition Science and Policy at Tufts University, Boston, MA 02111; and Health Sciences Research Institute, University of Warwick Medical School, Coventry CV4 7AL, United Kingdom., and Saverio Stranges, MD, PhDFrom Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; National Center for Cardiovascular Research, Madrid 28029, Spain; Friedman School of Nutrition Science and Policy at Tufts University, Boston, MA 02111; and Health Sciences Research Institute, University of Warwick Medical School, Coventry CV4 7AL, United Kingdom.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-5-201003020-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Recently, we have witnessed an explosion of scientific and media attention to the health effects of vitamin D status and vitamin D supplementation (1). Vitamin D3 (cholecalciferol), the most powerful form of vitamin D, is synthesized in the skin from 7-dehydrocholesterol by action of sunlight (ultraviolet B radiation) (2). Vitamin D is biologically inert and must be converted to the active hormone 1,25-dihydroxy vitamin D [1,25(OH)2D] (calcitriol). Vitamin D's pivotal role in regulating calcium homeostasis and bone metabolism has been long recognized (2–4); however, mounting evidence suggests that vitamin D may also influence various nonskeletal medical conditions, including cardiovascular disease, ...References1. Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr. 2008;88:491S-499S. [PMID: 18689389] CrossrefMedlineGoogle Scholar2. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academies Pr; 1997. Google Scholar3. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293:2257-64. [PMID: 15886381] CrossrefMedlineGoogle Scholar4. Abrahamsen B, Masud T, Avenell A, Anderson F, Meyer HE, Cooper C, et al; DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ. 2010;340:b5463. [PMID: 20068257] CrossrefMedlineGoogle Scholar5. Raiten DJ, Picciano MF. Vitamin D and health in the 21st century: bone and beyond. Executive summary. Am J Clin Nutr. 2004;80:1673S-7S. [PMID: 15585787] CrossrefMedlineGoogle Scholar6. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79:362-71. [PMID: 14985208] CrossrefMedlineGoogle Scholar7. Teegarden D, Donkin SS. Vitamin D: emerging new roles in insulin sensitivity. Nutr Res Rev. 2009;22:82-92. [PMID: 19555519] CrossrefMedlineGoogle Scholar8. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167:1730-7. [PMID: 17846391] CrossrefMedlineGoogle Scholar9. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-81. [PMID: 17634462] CrossrefMedlineGoogle Scholar10. Vieth R, Bischoff-Ferrari H, Boucher BJ, Dawson-Hughes B, Garland CF, Heaney RP, et al. The urgent need to recommend an intake of vitamin D that is effective [Editorial]. Am J Clin Nutr. 2007;85:649-50. [PMID: 17344484] CrossrefMedlineGoogle Scholar11. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297:842-57. [PMID: 17327526] CrossrefMedlineGoogle Scholar12. Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006;296:2720-6. [PMID: 17164458] CrossrefMedlineGoogle Scholar13. Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009;301:39-51. [PMID: 19066370] CrossrefMedlineGoogle Scholar14. Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37-46. [PMID: 15537682] LinkGoogle Scholar15. Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, et al. Systematic review: vitamin D and cardiometabolic outcomes. Ann Intern Med. 2010;152:307-14. LinkGoogle Scholar16. Wang L, Manson JE, Song Y, Sesso HD. Systematic review: vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med. 2010;152:315-23. LinkGoogle Scholar17. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326:469. [PMID: 12609940] CrossrefMedlineGoogle Scholar18. Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, et al; Women's Health Initiative Investigators. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115:846-54. [PMID: 17309935] CrossrefMedlineGoogle Scholar19. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al; Women's Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354:669-83. [PMID: 16481635] CrossrefMedlineGoogle Scholar20. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. 2009;339:b3692. [PMID: 19797342] CrossrefMedlineGoogle Scholar21. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006;84:18-28. [PMID: 16825677] CrossrefMedlineGoogle Scholar22. Guallar E, Hanley DF, Miller ER. An editorial update: annus horribilis for vitamin E [Editorial]. Ann Intern Med. 2005;143:143-5. [PMID: 16027457] LinkGoogle Scholar23. Miller ER 3rd, Guallar E. Vitamin E supplementation: what's the harm in that? Clin Trials. 2009;6:47-9; discussion 50-1. [PMID: 19254933] Google Scholar Author, Article, and Disclosure InformationAuthors: Eliseo Guallar, MD, DrPH; Edgar R. MillerIII, MD, PhD; Jose M. Ordovas, PhD; Saverio Stranges, MD, PhDAffiliations: From Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; National Center for Cardiovascular Research, Madrid 28029, Spain; Friedman School of Nutrition Science and Policy at Tufts University, Boston, MA 02111; and Health Sciences Research Institute, University of Warwick Medical School, Coventry CV4 7AL, United Kingdom.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-0183.Corresponding Author: Eliseo Guallar, MD, DrPH, Welch Center for Prevention, Epidemiology, and Clinical Research, 2024 East Monument Street, Room 2-639, Baltimore, MD 21205; e-mail, eguallar@jhsph.edu.Current Author Addresses: Drs. Guallar and Miller: Welch Center for Prevention, Epidemiology, and Clinical Research, 2024 East Monument Street, Baltimore, MD 21205.Dr. Ordovas: Tufts University, 711 Washington Street, Boston, MA 02111.Dr. Stranges: Health Sciences Research Institute, Gibbet Hill Campus, Medical School Building, Room A105, Coventry CV4 7AL, United Kingdom. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSystematic Review: Vitamin D and Cardiometabolic Outcomes Anastassios G. Pittas , Mei Chung , Thomas Trikalinos , Joanna Mitri , Michael Brendel , Kamal Patel , Alice H. Lichtenstein , Joseph Lau , and Ethan M. Balk Systematic Review: Vitamin D and Calcium Supplementation in Prevention of Cardiovascular Events Lu Wang , JoAnn E. Manson , Yiqing Song , and Howard D. Sesso Does Inconclusive Evidence for Vitamin D Supplementation to Reduce Risk for Cardiovascular Disease Warrant Pessimism? Gregory A. Plotnikoff Does Inconclusive Evidence for Vitamin D Supplementation to Reduce Risk for Cardiovascular Disease Warrant Pessimism? Robert P. Heaney Does Inconclusive Evidence for Vitamin D Supplementation to Reduce Risk for Cardiovascular Disease Warrant Pessimism? William B. Grant Does Inconclusive Evidence for Vitamin D Supplementation to Reduce Risk for Cardiovascular Disease Warrant Pessimism? Eliseo Guallar , Edgar R. Miller III , Jose M. Ordovas , and Saverio Stranges Metrics Cited byVitamin D supplementation for chronic liver diseases in adultsEffect of vitamin D supplementation during pregnancy on mid-to-late gestational blood pressure in a randomized controlled trial in BangladeshGlobal prevalence and disease burden of vitamin D deficiency: a roadmap for action in low‐ and middle‐income countriesVitamin D supplementation for chronic liver diseases in adultsVitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic EffectsRationale and Design of the Vitamin D and Type 2 Diabetes (D2d) Study: A Diabetes Prevention TrialVitamin D supplementation for prevention of cancer in adultsEffect of a Single, Oral, High-dose Vitamin D Supplementation on Endothelial Function in Patients with Peripheral Arterial Disease: A Randomised Controlled Pilot StudyPlasma 25-Hydroxyvitamin D and Risk of Pancreatic CancerVitamin D With or Without Calcium Supplementation for Prevention of Cancer and Fractures: An Updated Meta-analysis for the U.S. Preventive Services Task ForceMei Chung, PhD, MPH, Jounghee Lee, PhD, Teruhiko Terasawa, MD, PhD, Joseph Lau, MD, and Thomas A. Trikalinos, MD, PhDCase Studies and Enrichment ReferencesDoes Inconclusive Evidence for Vitamin D Supplementation to Reduce Risk for Cardiovascular Disease Warrant Pessimism?Gregory A. Plotnikoff, MD, MTSDoes Inconclusive Evidence for Vitamin D Supplementation to Reduce Risk for Cardiovascular Disease Warrant Pessimism?Robert P. Heaney, MDDoes Inconclusive Evidence for Vitamin D Supplementation to Reduce Risk for Cardiovascular Disease Warrant Pessimism?William B. Grant, PhDVitamin D and the prevention of falls: has the time come?The role of vitamin D and SLCO1B1 gene polymorphism in statin-associated myalgias 2 March 2010Volume 152, Issue 5Page: 327-329KeywordsAttentionCalciumCardiovascular diseasesClinical epidemiologyHazard ratioHypertensionMortalityObservational studiesRandomized trialsVitamin D ePublished: 2 March 2010 Issue Published: 2 March 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...