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The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention

  • Michael F. Holick
Article

Abstract

Vitamin D deficiency and insufficiency is a global health issue that afflicts more than one billion children and adults worldwide. The consequences of vitamin D deficiency cannot be under estimated. There has been an association of vitamin D deficiency with a myriad of acute and chronic illnesses including preeclampsia, childhood dental caries, periodontitis, autoimmune disorders, infectious diseases, cardiovascular disease, deadly cancers, type 2 diabetes and neurological disorders. This review is to put into perspective the controversy surrounding the definition for vitamin D deficiency and insufficiency as well as providing guidance for how to treat and prevent vitamin D deficiency.

Keywords

Vitamin D deficiency Vitamin D insufficiency Sunlight Rickets Vitamin D2 Vitamin D3 25-hydroxyvitamin D Vitamin D toxicity 

Notes

Compliance with ethical standards

This is a review and therefore there are no issues regarding compliance and ethical standards.

Conflict of interest

The author declares that he is a consultant for Quest Diagnostics, Ontometrics Inc. and is on speaker’s Bureau for Sanofi Inc.

References

  1. 1.
    Holick MF. Vitamin D deficiency. New Engl J Med. 2007;357:266–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Chapuy MC, Schott AM, Garnero P, Hans D, Delmas PD, Meunier J, et al. Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. J Clin Endocrinol Metab. 1996;81:1129–33.PubMedGoogle Scholar
  3. 3.
    Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet. 1998;351:805–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Thomas KK, Lloyd-Jones DH, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338:777–83.CrossRefPubMedGoogle Scholar
  5. 5.
    Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA. Chen E and de Papp prevalence of vitamin D inadequacy among postmenopausal north American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005;90(6):3215–24.CrossRefPubMedGoogle Scholar
  6. 6.
    Valcour A, Blocki F, Hawkins DM, Rao SD. Effects of age and serum 25-OH-vitamin D on serum parathyroid hormone levels. J Clin Endocrinol Metab. 2012;97(11):3989–95.CrossRefPubMedGoogle Scholar
  7. 7.
    IOM (Institute of Medicine) Dietary reference intakes for calcium and vitamin D. Committee to Review Dietary Reference Intakes for Calcium and Vitamin D Washington DC: The National Academies Press Institute of Medicine 2011.Google Scholar
  8. 8.
    Priemel M, von Domarus C, Klatte TO, Kessler S, Schlie J, Meier S, Proksch N, Pastor F, Netter C, Streichert T, Puschel K, Amling M. Bone mineralization defects and vitamin D deficiency: Histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res. 2010;25(2):305–12.CrossRefPubMedGoogle Scholar
  9. 9.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30.CrossRefPubMedGoogle Scholar
  10. 10.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Controversy in clinical Endocrinology: guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab. 2012;97:1153–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Murad MH, Elamin KB, AbuElnour NO, Elamin MB, Alkatib AA, Fatourechi MM, Almandoz JP, Mullan RJ, Lane MA, Liu H, Erwin PJ, Hensrud DD, Montori VM. Interventions to raise vitamin D level and functional outcomes: a systematic review and metaanalysis. J Clin Endocrinol Metab. 2011;96(7):1911–30.CrossRefPubMedGoogle Scholar
  12. 12.
    American Geriatrics Society Workgroup on Vitamin D Supplementation for Older Adults. Recommendations abstracted from the American Geriatrics Society Consensus Statement on vitamin D for Prevention of Falls and Their Consequences. J Am Geriatr Soc. 2014;62:147.CrossRefGoogle Scholar
  13. 13.
    Fischer PR, Thacher TD, Pettifor JM. Pediatric vitamin D and calcium nutrition in developing countries. Rev Endocr Metab Disord. 2008;9(3):181–92.CrossRefPubMedGoogle Scholar
  14. 14.
    Merewood A, Mehta SD, Grossman X, Chen TC, Mathieu JS, Holick MF, et al. Widespread vitamin D deficiency in urban Massachusetts newborns and their mothers. Pediatr. 2010;125:640–7. 416CrossRefGoogle Scholar
  15. 15.
    Zhu Z, Zhan J, Shao J, et al. High prevalence of vitamin D deficiency among children aged 1 month to 16 years in Hangzhou, China. BMC Public Health. 2012;12:126.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Sacheck J, Goodman E, Chui K, et al. Vitamin D deficiency, adiposity, and cardiometabolic risk in urban schoolchildren. J Pediatr. 2011;159:945–50.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Shivane VK, Sarathi V, Bandgar T, et al. High prevalence of hypovitaminosis D in young healthy adults from the western part of India. Postgrad Med J. 2011;87:514–8.CrossRefPubMedGoogle Scholar
  18. 18.
    van Schoor NM, Lips P. Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab. 2011;25(4):671–80.CrossRefPubMedGoogle Scholar
  19. 19.
    Fields J, Trivedi NJ, Horton E, Mechanick JI. Vitamin D in the Persian Gulf: integrative physiology and socioeconomic factors. Curr Osteoporos Rep. 2011;9:243–50.CrossRefPubMedGoogle Scholar
  20. 20.
    Ganji V, Zhang X, Tangpricha V. Serum 25-hydroxyvitamin D concentrations and prevalence estimates of hypovitaminosis D in the U.S. population based on assay adjusted data. J Nutr. 2012;142(3):498–507.CrossRefPubMedGoogle Scholar
  21. 21.
    Zhang R, Naughton DP. Vitamin D in health and disease: current perspectives. Nutr J. 2010;9:65.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Greene-Finestone LS, Berger C, de Groh M, et al. 25-Hydroxyvitamin D in Canadian adults: biological, environmental, and behavioral correlates. Osteoporos Int. 2011;22:1389–99.CrossRefPubMedGoogle Scholar
  23. 23.
    González-Gross M, Valtueña J, Breidenassel C, et al. Vitamin D status among adolescents in Europe: the healthy lifestyle in Europe by nutrition in adolescence study. Br J Nutr. 2012;107(5):755–64.CrossRefPubMedGoogle Scholar
  24. 24.
    Daly RM, Gagnon C, Lu ZX, et al. Prevalence of vitamin D deficiency and its determinants in Australian adults aged 25 years and older: a national, population-based study. Clin Endocrinol. 2012;77:26–35.CrossRefGoogle Scholar
  25. 25.
    Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013;88(7):720–55.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, Shoenfeld Y, Lerchbaum E, Llewellyn DJ, Kienreich K, Soni M. Vitamin D effects on musculoskeletal health, immunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality – a review of recent evidence. Autoimmun Rev. 2013;12:976–89.CrossRefPubMedGoogle Scholar
  27. 27.
    Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third national health and nutrition examination survey, 1988-1994. Am J Clin Nutr. 2002;76:187–92.PubMedGoogle Scholar
  28. 28.
    Lee JM, Smith JR, Philipp BL, Chen TC, Mathieu J, Holick MF. Vitamin D deficiency in a healthy group of mothers and newborn infants. Clin Pediatr. 2007;46:42–4.CrossRefGoogle Scholar
  29. 29.
    Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr. 2007;85(3):788–95.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Merewood A, Mehta SD, Chen TC, Holick MF, Bauchner H. Association between severe vitamin D deficiency and primary caesarean section. J Clin Endocrinol Metab. 2009;94(3):940–5.CrossRefPubMedGoogle Scholar
  31. 31.
    Ullah MI, Koch CA, Tamanna S, Rouf S. Shamsuddin. Vitamin D deficiency and the risk of preeclampsia and eclampsia in Bangladesh. Horm Metab Res. 2013;45(9):682–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Kumar J, Muntner P, Kaskel FJ, Hailpern SM. Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001-2004. Pediatrics. 2009;124(3):e362–70.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Looker AC, Johnson CL, Lachner DA, Pfeiffer CM, Schleicher RL, Sempos CT. Vitamin D status: United States, 2001-2006. NCHS Data Brief. 2011;56Google Scholar
  34. 34.
    Wacker M, Holick MF. Sunlight and vitamin D: a global perspective for health. Dermato-Endocrinol. 2013;5(1):51–108.CrossRefGoogle Scholar
  35. 35.
    Holick MF. Biologic effects of sunlight, ultraviolet radiation, visible light, infrared, and vitamin D for health. Anticancer. 2016;36:1345–56.Google Scholar
  36. 36.
    Heaney R, Armas LAG, French C. All-sources: basal vitamin D inputs are greater than previously thought and cutaneous inputs are smaller. J Nutr. 2013;143:571–5.CrossRefPubMedGoogle Scholar
  37. 37.
    Crowe FL, Steur M, Allen NE, Appleby PN, Travis RC, Key TJ. Plasma concentrations of 25-hydroxyvitamin D in meat eaters, fish eaters, vegetarians and vegans: results from the EPIC-Oxford study. Public Health Nutr. 2011;14(2):340–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Manicourt DH, Devogelaer JP. Urban tropospheric ozone increases the prevalence of vitamin D deficiency among Belgian postmenopausal women with outdoor activities during summer. J Clin Endocrinol Metab. 2008;93(10):3893–9.CrossRefPubMedGoogle Scholar
  39. 39.
    Moan J, Dahlback A, Porojnicu AC. At what time should one go out in the sun? Adv Exp Med Biol. 2008;624:86–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Seckmeyer G, Glandorf M, Wichers C, McKenzie R, Henriques D, Carvalho F, Webb A, Siani AM, Bais A, Kjeldstad B, Brogniez C, Werle P, Koskela T, Lakkala K, Gröbner J, Slaper H, denOuter P, Feister U. Europe's darker atmosphere in the UV-B. Photochem Photobiol Sci 2008, 7(8):925–30.Google Scholar
  41. 41.
    Brogniez C, Werle P, Koskela T, Lakkala K, Gröbner J, Slaper H, denOuter P, Feister U. Europe's darker atmosphere in the UV-B. Photochem Photobiol Sci. 2008;7(8):925–30.CrossRefPubMedGoogle Scholar
  42. 42.
    Brinkmann RT, Green AE, Barth CA. Atmospheric scattering of the solar flux in the middle ultraviolet. Appl Opt. 1967;6(3):373–83. doi: 10.1364/AO.6.000373.CrossRefPubMedGoogle Scholar
  43. 43.
    Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab. 1988;67:373–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Clemens TL, Henderson SL, Adams JS, Holick MF. Increased skin pigment reduces the capacity of skin to synthesis vitamin D3. Lancet. 1982;1(8263):74–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Matsuoka LY, Ide L, Wortsman J, MacLaughlin JA, Holick MF. Sunscreens suppress cutaneous vitamin D3 synthesis. J Clin Endocrinol Metab. 1987;64:1165–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Matsuoka LY, Wortsman J, Hanifan N, Holick MF. Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D. A preliminary study. Arch Dermatol. 1988;124:1802–4.CrossRefPubMedGoogle Scholar
  47. 47.
    Godar DE, Pope SJ, Grant WB, Holick MF. Solar UV doses of adult and vitamin D3 production. Dermato-Endocrinol. 2011;3(4):1–8. 437CrossRefGoogle Scholar
  48. 48.
    Keegan RJ, Lu Z, Bogusz JM, Williams JE, Holick MF. Photobiology of vitamin D in mushrooms and its bioavailability in humans. Dermato-Endocrinol. 2013;5(1):165–76.CrossRefGoogle Scholar
  49. 49.
    Tang HM, Cole DEC, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998;68:854–8.Google Scholar
  50. 50.
    Heaney RP, Recker RR, Grote J, Horst RL, Armas LAG. Vitamin D3 is more potent than vitamin D2 in humans. J Clin Endocrinol Metab. 2011;152(2):741.Google Scholar
  51. 51.
    Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89(11):5387–91.CrossRefPubMedGoogle Scholar
  52. 52.
    Heaney RP, Recker RR, Grote J, Horst RL, Armas LA. Vitamin D(3) is more potent than vitamin D(2) in humans. J Clin Endocrinol Metab. 2011;96(3):E447–52.CrossRefPubMedGoogle Scholar
  53. 53.
    Oliveri B, Mastaglia SR, Brito GM, Seijo M, Keller GA, Somoza J, Diez RA, Di Girolamo G. Vitamin D3 seems more appropriate than D2 to sustain adequate levels of 25OHD: a pharmacokinetic approach. Eur J Clin Nutr. 2015;69(6):697–702.CrossRefPubMedGoogle Scholar
  54. 54.
    Biancuzzo RM, Cai MH, Winter MR, Klein EK, Ameri A, Reitz R, Salameh W, Young A, Bibuld D, Chen TC, Holick MF. Fortification of orange juice with vitamin D2 or vitamin D3 is as effective as an oral supplement in maintaining vitamin D status in adults. Am J Clin Nutr. 2010;91:1621–6.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Biancuzzo RM, Clarke N, Reitz RE, Travison TG, Holick MF. Serum concentrations of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin D3 supplementation. J Clin Endocrinol Metab. 2013;98(3):973–9.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Pietras SM, Obayan BK, Cai MH, Holick MF. Vitamin D2 treatment for vitamin D deficiency and insufficiency for up to 6 years. Arch Intern Med. 2009;169:1806–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC, Khan H, Baena CP, Prabhakaran D, Hoshen MB, Feldman BS, Pan A, Johnson L, Crowe F, Hu FB, Franco OH. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Chun RF, Hernandez I, Pereira R, Swinkles L, Huijs T, Zhou R, Liu NQ, Shieh A, Guemes M, Mallya SM, Adams JS, Hewison M. Differential responses to vitamin D2 and vitamin D3 are associated with variations in free 25-hydroxyvitamin D. Endocrinology. 2016;157:3420–30.CrossRefPubMedGoogle Scholar
  59. 59.
    Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87(4):1080S–6S.PubMedGoogle Scholar
  60. 60.
    Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77:204–10.PubMedGoogle Scholar
  61. 61.
    Demetriou ETW, Travison TG, Holick MF. Treatment with 50,000 IU vitamin D2 every other week and effect on Serum 25-hydroxyvitamin D2, 25-hydroxyvitamin D3 and total 25-hydroxyvitamin D in a clinical setting. Endocr Prac. 2012;18(3):399–402.CrossRefGoogle Scholar
  62. 62.
    Ekwaru JP, Zwicker JD, Holick MF, Giovannucci E, Veugelers PJ. The importance of body weight for the dose response relationship of oral vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers. PLoS One. 2014; doi: 10.1371/journal.pone.0111265. 520.
  63. 63.
    Hollis BW, Johnson D, Hulsey TC, Ebeling M. Wagner. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011;26(10):2341–57. doi: 10.1002/jbmr.463.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    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.PubMedGoogle Scholar
  65. 65.
    Boonchaya-anant P, Holick MF, Apovian CM. Serum 25-hydroxyvitamin D levels and metabolic health status in extremely obese individuals. Obes J. 2014;22(12):2539–43. doi: 10.1002/oby.20877. 516.Google Scholar
  66. 66.
    Dabai NS, Pramyothin P, Holick MF. The effect of ultraviolet radiation from a novel portable flourescent lamp on serum 25-hydroxyvitamin D3 Levels in healthy adults with Fitzpatrick skin types II and III. Photodermatol Photoimmunol Photomed. 2012;28(6):307–11. 474CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Koutkia P, Lu Z, Chen TC, Holick MF. Treatment of vitamin D deficiency due to Crohn's disease with tanning bed ultraviolet B radiation. Gastroenterol. 2001;121:1485–8.CrossRefGoogle Scholar
  68. 68.
    Chandra P, Wolfenden LL, Ziegler TR, Tian J, Luo M, Stecenkoo AA, Chen TC, Holick MF, Tangpricha V. Treatment of vitamin D deficiency with UV light in patients with malabsorption syndromes: a case series. Phtodermatol Photoimunol Photmed. 2007;23(5):179–85.CrossRefGoogle Scholar
  69. 69.
    Hollis BW, Wagner CL, Howard CR, Ebeling M, Shary JR, Smith PG, Taylor SN, Morella K, Lawrence RA, Hulsey TC. Maternal versus infant vitamin D supplementation during lactation: a randomized controlled trial. Pediatrics. 2015;136:625–34.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Gordon CM, Williams AL, Feldman HA, May J, Sinclair L, Vasquez A, Cox JE. Treatment of hypovitaminosis D in infants and toddlers. J Clin Endocrinol Metab. 2008;93(7):2716–21.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Holick MF. Case 3-2009: a 9-month-old boy with seizures. New Eng J Med CPC. 2009;360(4):398–407.CrossRefGoogle Scholar
  72. 72.
    Holick MF. Vitamin D is not as toxic as was once thought: A historical and an up-to-date perspective. 2015 May. Mayo Clin Proc. 90(5):561–4. 530Google Scholar
  73. 73.
    Araki T, Holick MF, Alfonso BD, Charlap E, Romero CM, Rizk D, Newman LG. Vitamin D intoxication with severe hypercalcemia due to manufacturing and labelling errors for two dietary supplements made in the United States. J Clin Endocrinol Metab. 2011;96(12):3603–8. 451CrossRefPubMedGoogle Scholar
  74. 74.
    Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med. 2001;345(1):66–7.CrossRefPubMedGoogle Scholar
  75. 75.
    Jacobus, C.H., Holick, M.F., Shao, Q., Chen, T.C., Holm I.A., Kolodny, J.M., El-Hajj Fuleihan, G. and Seely, E. Hypervitaminosis D associated with drinking milk. N Engl J Med. 1992. 326(18):1173–1177. 120.Google Scholar
  76. 76.
    Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999, 69(5):842–856.Google Scholar
  77. 77.
    Melamed ML, Michos ED, Post W, Astor B. 25-Hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168(15):1629–37.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Grant WB, Karras SN, Bischoff-Ferrari HA, Annweiler C, Boucher BJ, Juzeniene A, Garland CF, Holick MF. Do studies reporting 'U'-shaped serum 25-hydroxyvitamin D-health outcome relationships reflect adverse effects? Dermato-Endocrinology. 2016;8(1):e1187349.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Kroll MH, Bi C, Garber CC, et al. Temporal relationship between vitamin D status and parathyroid hormone in the United States. PLoS One. 2015;10(3):e 0118108. doi: 10.1371/journal.pone.0118108.eCollection 2015.CrossRefGoogle Scholar
  80. 80.
    Rosen CJ, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Manson JE, Mayne ST, Ross AC, Shapses SA, Taylor CL. IOM Committee members respond to Endocrine Society vitamin D guideline. J Clin Endocrinol Metab. 2012;97(4):1146–52.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Płudowski P, Karczmarewicz E, Bayer M, Carter G, Chlebna-Sokół D, Czech-Kowalska J, Dębski R, Decsi T, Dobrzańska A, Franek E, Głuszko P, Grant WP, Holick MF, Yankovskaya L, Konstantynowicz J, Książyk JB, Księżopolska-Orłowska K, Lewiński A, Litwin M, Lohner S, Lorenc RS, Łukaszkiewicz J, Marcinowska-Suchowierska E, Milewicz A, Misiorowski W, Nowicki M, Povoroznyuk V, Rozentryt P, Rudenka E, Shoenfeld Y, Socha P, Solnica B, Szalecki M, Tałałaj M, Varbiro S, Żmijewski MA. Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe – recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency. Endokrynol Pol. 2013;64(4):319–27. 502CrossRefPubMedGoogle Scholar
  82. 82.
    Luxwolda MF, Kuipers RS, Kema IP, Dijck-Brouwer DA, Muskiet FA. Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l. Br J Nutr. 2012;108(9):1557–61.CrossRefPubMedGoogle Scholar
  83. 83.
    El-Hajj Fuleihan G, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H, Choucair M, Arabi A, Vieth R. Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. J Clin Endocrinol Metab. 2006;91:405–12.CrossRefPubMedGoogle Scholar
  84. 84.
    Donneyong MM, Taylor KC, Kerber RA, Hornung CA, Scragg R. Is outdoor recreational activity an independent predictor of cardiovascular disease mortality - NHANES III? Nutr Metab Cardiovasc Dis. 2016;26(8):735–42.CrossRefPubMedGoogle Scholar
  85. 85.
    Lindqvist PG, Epstein E, Nielsen K, Landin-Olsson M, Ingvar C, Olsson H. Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the melanoma in southern Sweden cohort. J Intern Med. 2016;280(4):375–87.CrossRefPubMedGoogle Scholar
  86. 86.
    Wolpowitz D, Gilchrest BA. The vitamin D questions: how much do you need and how should you get it? J Am Acad Dermatol. 2006;54:301–17.CrossRefPubMedGoogle Scholar
  87. 87.
    Karimi K, Lindgren TH, Koch CA, Brodell RT. Obesity as a risk factor for malignant melanoma and non-melanoma skin cancer. Rev Endocr Metab Disord. 2016;17(3):389–403.94.CrossRefPubMedGoogle Scholar
  88. 88.
    Kennedy C, Bajdik CD, Willemze R, de Gruijl FR, Bavinck JN. The influence of painful sunburns and lifetime of sun exposure on the risk of actinic keratoses, seborrheic warts, melanocytic nevi, atypical nevi and skin cancer. J Invest Dermatol. 2003;120(6):1087–93.CrossRefPubMedGoogle Scholar
  89. 89.
    Moan J, Porojnicu AC, Dahlback A, Setlow RB. Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure. Proc Natl Acad Sci U S A. 2008;105(2):668–73.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Felton SJ, Cooke MS, Kift R, et al. Concurrent beneficial (vitamin D production) and hazardous (cutaneous DNA damage) impact of repeated low-level summer sunlight exposures. Br J Dermatol. 2016;175:1320–8.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Holick MF. Can you have your cake and eat it too? The sunlight D-lema. Br J Dermatol. 2016;175:1129–31.CrossRefPubMedGoogle Scholar
  92. 92.
    Brot C, Vestergaard P, Kolthoff N, Gram J, Hermann AP, Sorensen OH. Vitamin D status and its adequacy in health Danish perimenopausal women: relationships to dietary intake, sun exposure and serum parathyroid hormone. Brit J Nutr. 2001;86:S97–103.CrossRefPubMedGoogle Scholar
  93. 93.
    Baggerly C, Cuom R, French C, Garland C, Gorham E, Grant W, Heaney R, Holick M. Sunlight and vitamin D: necessary for public health. J Am Coll Nutr. 2015;34(4):359–65.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Osmancevic A, Gillstedt M, Landin-Wilhelmsen K, Wennberg Larko AM, Larko O, Holick M, Krogstad AL. Size of the exposed body surface area, skin erythema and body mass index predict skin production of vitamin D. 2015 June. J Photochem Photobiol B Biol. 2015;149:224–9.CrossRefGoogle Scholar
  95. 95.
    Vieth R. The Pharmacology of Vitamin D, including fortification strategies. Chapter 61 in Vitamin D, 2 Edition. D Feldman, JW Pike, FH Glorieux eds. Elsevier Acad. Press 30 Corporate Dr., Suite 400, Burlington, MA 01803. 2005. pp 995–1015.Google Scholar
  96. 96.
    Rich-Edwards JW, Davaasambuu G, Kleinman K, Sumberzul N, Holick MF, Lkhagvasuren T, Dulguun B, Burke A, Frazier AL. Randomized trial of fortified milk and supplements to raise 25-hydroxyvitamin D concentrations in schoolchildren in Mongolia. Am J Clin Nutr. 2011;94:578–84. 449CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Endocrinology, Nutrition and Diabetes, Department of MedicineBoston University Medical CenterBostonUSA

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