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Vitamin D pp 3-33 | Cite as

Vitamin D and Health: Evolution, Biologic Functions, and Recommended Dietary Intakes for Vitamin D

  • Michael F. Holick
Chapter
Part of the Nutrition and Health book series (NH)

Abstract

Vitamin D deficiency is now being recognized as one of the most common medical conditions worldwide. The consequences of vitamin D deficiency include poor bone development and health as well as increased risk of many chronic diseases including type I diabetes, rheumatoid arthritis, Crohn’s disease, multiple sclerosis, heart disease, stroke, infectious diseases, as well as increased risk of dying of many deadly cancers including colon, prostate, and breast. The major source of vitamin D for most humans is exposure to sunlight. However, avoidance of sun exposure has resulted in an epidemic of vitamin D deficiency. Once vitamin D is made in the skin or ingested from the diet, it requires activation steps in the liver and kidney to form 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D. 25(OH)D is the major circulating form of vitamin D used by clinicians to determine a patient’s vitamin D status. A blood level of 25(OH)D <20 ng/ml is considered to be vitamin D deficiency, whereas a level 21–29 ng/ml is insufficient, and to maximize vitamin D’s effect for health, 25(OH)D should be >30 ng/ml. Vitamin D intoxication will not occur until a blood level of 25(OH)D exceeds 150–200 ng/ml. Both the adequate intake recommendations and safe upper limits for vitamin D are woefully underestimated. For every 100 IU of vitamin D ingested, the blood level of 25(OH)D increases by 1 ng/ml. Thus, children during the first year of life need at a minimum 400 IU of vitamin D/day and 1,000 IU of vitamin D/day may be more beneficial and will not cause toxicity. The same recommendation can be made for children 1 year and older. For adults, a minimum of 1,000 IU of vitamin D/day is necessary and 2,000 IU of vitamin D/day is preferred if there is inadequate sun exposure. The safe upper limit for children can easily be increased to 5,000 IU of vitamin D/day, and for adults, up to 10,000 IU of vitamin D/day has been shown to be safe. The goal of this chapter is to give a broad perspective about vitamin D and to introduce the reader to the vitamin D deficiency pandemic and its insidious consequences on health that will be reviewed in more detail in the ensuing chapters.

Key Words

Vitamin D sunlight 25-hydroxyvitamin D cancer diabetes adequate intake rickets vitamin D deficiency, 1,25-dihydroxyvitamin D, vitamin D receptor 

Notes

Acknowledgments

This work was supported in part by NIH grant UL1RRO 25771 and the UV Foundation.

References

  1. 1.
    Holick MF (1989) Phylogenetic and evolutionary aspects of vitamin D from phytoplankton to humans. In: Pang PKT and Schreibman MP (eds) Verebrate endocrinology: fundamentals and biomedical implications, Vol. 3. Academic Press, Inc. (Harcourt Brace Jovanovich), Orlando, FLGoogle Scholar
  2. 2.
    Holick MF, Garabedian M (2006) Vitamin D: photobiology, metabolism, mechanism of action, and clinical applications. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 6th edn. American Society for Bone and Mineral Research, Washington, DC.Google Scholar
  3. 3.
    Strugnell SA, DeLuca HF (1997) The vitamin D receptor – structure and transcriptional activation. Proc Soc Exp Biol 215:223–228PubMedGoogle Scholar
  4. 4.
    Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281PubMedCrossRefGoogle Scholar
  5. 5.
    Holick MF (2004) Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Robert H. Herman Memorial Award in Clinical Nutrition Lecture, 2003. Am J Clin Nutr 79:362–371PubMedGoogle Scholar
  6. 6.
    Holick MF (1997) The evolution of vitamin D from phytoplankton to man. Norman AW, Bouillon R, Thomasset M (eds) Vitamin D: chemistry, biology and clinical applications of the steroid hormone (Proceedings of the Tenth Workshop on Vitamin D). University of California Press, Riverside, pp 771–776Google Scholar
  7. 7.
    Rajakumar K, Greenspan SL, Thomas SB, Holick MF (2007) Solar ultraviolet radiation and vitamin D: a historical perspective. Am J Public Health 97(10):1746–1754PubMedCrossRefGoogle Scholar
  8. 8.
    Khosla S (2001) The OPG/RANKL/RANK system. Endocrinology 142(12):5050–5055PubMedCrossRefGoogle Scholar
  9. 9.
    Holtrop ME, Cox KA, Cares DL, Holick MF (1986) Effects of serum calcium and phosphorus on skeletal mineralization in vitamin D-deficient rats. Am J Physiol 251:E234–E240PubMedGoogle Scholar
  10. 10.
    Underwood JL, DeLuca HF (1984) Vitamin D is not directly necessary for bone growth an mineralization. Am J Physiol 246:E493–E498PubMedGoogle Scholar
  11. 11.
    Clemens TL, Henderson SL, Adams JS, Holick MF (1982) Increased skin pigment reduces the capacity of skin to synthesis vitamin D3. Lancet 1(8263):74–76PubMedGoogle Scholar
  12. 12.
    Matsuoka LY, Ide L, Wortsman J, MacLaughlin J, Holick MF (1987) Sunscreens suppress cutaneous vitamin D3 synthesis. J Clin Endocrinol Metab 64:1165–1168PubMedCrossRefGoogle Scholar
  13. 13.
    Holick MF, Matsuoka LY, Wortsman J (1989) Age, vitamin D, and solar ultraviolet. Lancet 2:1104–1105PubMedGoogle Scholar
  14. 14.
    Webb AR, Kline L, Holick MF (1988) 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 67:373–378PubMedCrossRefGoogle Scholar
  15. 15.
    Holick MF, Chen TC (2008) Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 87(4):1080S–1086SPubMedGoogle Scholar
  16. 16.
    Tangpricha V, Koutkia P, Rieke SM, Chen TC, Perez AA, Holick MF (2003) Fortification of orange juice with vitamin D: a novel approach to enhance vitamin D nutritional health. Am J Clin Nutr 77:1478–1483PubMedGoogle Scholar
  17. 17.
    Tanner JT, Smith J, Defibaugh P, Angyal G, Villalobos M, Bueno M, McGarrahan E (1988) Survey of vitamin content of fortified milk. J Assoc Off Analyt Chem 71:607–610Google Scholar
  18. 18.
    Holick MF, Shao Q, Liu WW, Chen TC (1992) The vitamin D content of fortified milk and infant formula. N Engl J Med 326:1178–1181PubMedCrossRefGoogle Scholar
  19. 19.
    Chen TC, Heath H, Holick MF (1993) An update on the vitamin D content of fortified milk from the United States and Canada. N Engl J Med 329:1507PubMedCrossRefGoogle Scholar
  20. 20.
    Markestad T, Elzouki Ay (1991) Vitamin D deficiency rickets in northern Europe and Libya. In: Glorieux FH (ed). Rickets nestle nutrition workshop series. Raven, New YorkGoogle Scholar
  21. 21.
    Malabanan A, Veronikis IE, Holick MF (1998) Redefining vitamin D insufficiency. Lancet 351:805–806PubMedCrossRefGoogle Scholar
  22. 22.
    Thomas KK, Lloyd-Jones DH, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JSL (1988) Hypovitaminosis D in medical inpatients. N Engl J Med 338: 777–783Google Scholar
  23. 23.
    Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA, Chen E, de Papp AE (2005) Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 90:3215–3224PubMedGoogle Scholar
  24. 24.
    Heaney RP, Dowell MS, Hale CA, Bendich A (2003) Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 22(2):142–146PubMedGoogle Scholar
  25. 25.
    Moan J, Porojnicu AC, Dahlback A, Setlow RB (2008) Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure. Proc Natl Acad Sci USA 105(2):668–673PubMedCrossRefGoogle Scholar
  26. 26.
    Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28PubMedGoogle Scholar
  27. 27.
    Grant WB, Holick MF (2005) Benefits and requirements of vitamin D for optimal health: a review. Alter Med Rev 10:94–111Google Scholar
  28. 28.
    Holick MF (2006) High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 81(3):353–373PubMedCrossRefGoogle Scholar
  29. 29.
    Sedrani SH (1984) Low 25-hydroxyvitamin D and normal serum calcium concentrations in Saudi Arabia: Riyadh region. Ann Nutr Metab 28:181–185PubMedCrossRefGoogle Scholar
  30. 30.
    Chapuy MC, Preziosi P, Maaner M, Arnaud S, Galan P, Hercberg S, Meunier PJ (1997) Prevalence of vitamin D insufficiency in an adult normal population. Osteopor Int 7:439–443CrossRefGoogle Scholar
  31. 31.
    Boonen S, Bischoff-Ferrari A, Cooper C, Lips P, Ljunggren O, Meunier PJ, Reginster JY (2006) Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence. Calcif Tissue Int 78(5):257–270PubMedCrossRefGoogle Scholar
  32. 32.
    Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477–501PubMedCrossRefGoogle Scholar
  33. 33.
    Bakhtiyarova S, Lesnyak O, Kyznesova N, Blankenstein MA, Lips P (2006) Vitamin D status among patients with hip fracture and elderly control subjects in Yekaterinburg, Russia. Osteoporos Int 17(3):441–446PubMedCrossRefGoogle Scholar
  34. 34.
    McKenna MJ (1992) Differences in vitamin D status between countries in young adults and the elderly. Am J Med 93:69–77PubMedCrossRefGoogle Scholar
  35. 35.
    Larsen ER, Mosekilde L, Foldspang A (2004) Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. J Bone Miner Res 19:370–378PubMedGoogle Scholar
  36. 36.
    Lips P, Hosking D, Lippuner K et al (2006) The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med 260:245–254PubMedCrossRefGoogle Scholar
  37. 37.
    Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ (2003) Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77:204–210PubMedGoogle Scholar
  38. 38.
    Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, Reitz R, Salameh W, Ameri A, Tannenbaum AD (2008) Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab 93(3):677–681PubMedGoogle Scholar
  39. 39.
    Lee JM, Smith JR, Philipp BL, Chen TC, Mathieu J, Holick MF (2007) Vitamin D deficiency in a healthy group of mothers and newborn infants. Clin Pediatr 46:42–44CrossRefGoogle Scholar
  40. 40.
    Bodnar LM, Simhan HN, Powers RW, Frank MP, Cooperstein E, Roberts JM (2007) High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. J Nutr 137:447–452PubMedGoogle Scholar
  41. 41.
    Hollis BW, Wagner CL (2004) Assessment of dietary vitamin D requirements during pregnancy and lactation. Am J Clin Nut 79:717–726Google Scholar
  42. 42.
    Specker BL, Valanis B, Hertzberg V, Edwards N, Tsang RC (1985) Cyclical serum 25-hydroxyvitamin D concentrations paralleling sunshine exposure in exclusively breast-fed infants. J Pediatr 110:744–747Google Scholar
  43. 43.
    Specker BL, Valanis B, Hertzberg V, Edwards N, Tsang RC (1985) Sunshine exposure and serum 25-hydroxyvitamin D. J Pediatr 107:372–376PubMedGoogle Scholar
  44. 44.
    Food and Nutrition Board Institurte of Medicine (1997) Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and Fluoride. IOM National Academy Press, Washington, DC, pp 7–30Google Scholar
  45. 45.
    Nakao H (1998) Nutritional significance of human milk vitamin D in neonatal period. Kobe J Med Sci 34:21–128Google Scholar
  46. 46.
    Feliciano ES, Ho ML, Specker BL, Falciglia G et al (1994) Seasonal and geographical variations in the growth rate of infants in China receiving increasing dosages of vitamin D supplements. J Trop Pediatr 40:162–165PubMedGoogle Scholar
  47. 47.
    Foman SJ, Younoszai K, Thomas L (1966) Influence of vitamin D on linear growth of normal full-term infants. J Nutr 88:345–350Google Scholar
  48. 48.
    Specker B, Ho M, Oestreich A, Yin T et al (1992) Prospective study of vitamin D supplementation and rickets I China. J Pediatr 120:733–739PubMedGoogle Scholar
  49. 49.
    Jeans PC (1950) Vitamin D. JAMA 1243:177–181Google Scholar
  50. 50.
    Wagner CL, Greer FR and the Section on Breast Feeding and Committee on Nutrition (2008) Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 122:1142–1152PubMedCrossRefGoogle Scholar
  51. 51.
    Hypponen E, Laara E, Jarvelin M-R (2001) Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 358:1500–1503PubMedCrossRefGoogle Scholar
  52. 52.
    Pettifor JM, Ross FP, Moodley G, Wang J et al (1978) Serum calcium, magnesium, phosphorus, alkaline, phosphatase and 25-hydroxyvitamin D concentrations in children. S Afr Med J 53:751–754PubMedGoogle Scholar
  53. 53.
    Maalouf J, Nabulsi M, Vieth R, Kimball S, El-Rassi R, Mahfoud Z, Fuleihan GE (2008) Short term and long term safety of weekly high dose of vitamin D3 supplementation in school children. J Clin Endocrin Metab First published ahead of print April 29, 2008 as doi: 10.1210/jc.2007–2530Google Scholar
  54. 54.
    Gordon CM, Feldman HA, Sinclair L, Williams AL, Kleinman PK, Perez-Rossello J, Cox JE (2008) Prevalence of vitamin D deficiency among healthy infants and toddlers. Arch Pediatr Adolesc Med 162(6):505–512PubMedCrossRefGoogle Scholar
  55. 55.
    Gordon CM, Williams AL, Feldman HA, May J, Sinclair L, Vasquez A, Cox JE (2008) Treatment of hypovitaminosis D in infants and toddlers. J Clin Endocrinol Metab 93(7):2716–2721PubMedCrossRefGoogle Scholar
  56. 56.
    Rajakumar K, Fernstrom JD, Holick MF, Janosky JE, Greenspan SL (2008) Vitamin D status and response to vitamin D3 in obese vs. non-obese African American children. Obesity 16:90–95PubMedCrossRefGoogle Scholar
  57. 57.
    Aksnes L, Aarskog D (1982) Plasma concentrations of vitamin D metabolites in puberty: effect of sexual maturation and implications for growth. J Clin Endocrinol Metab 55:94–101PubMedCrossRefGoogle Scholar
  58. 58.
    Gultekin A, Ozalp I, Hasanoglu A, Unal A (1987) Serum-25-hydroxycholecalciferol levels in children and adolescents. Turk J Pediatr 29:155–162PubMedGoogle Scholar
  59. 59.
    Meier DE, Luckey MM, Wallenstein S, Clements TL et al (1991) Calcium, vitamin D, and parathyroid hormone status in young white and black women: association with racial differences in bone mass. J Clin Endocrinol Metab 72:703–710PubMedCrossRefGoogle Scholar
  60. 60.
    Kinyamu HK, Gallagher JC, Galhorn KE, Petranick KM, Rafferty KA (1997) Serum vitamin D metabolites and calcium absorption in normal young and elderly free-living women and in women living in nursing homes. Am J Clin Nutr 65:790–797PubMedGoogle Scholar
  61. 61.
    Holick MF (1986) Vitamin D requirements for the elderly. Clin Nutr 5:121–129Google Scholar
  62. 62.
    Clemens TL, Zhou X, Myles M, Endres D, Lindsay R (1986) Serum vitamin D2 and vitamin D3 metabolite concentrations and absorption of vitamin D2 in elderly subjects. J Clin Endocrinol Metab 63:656–660PubMedCrossRefGoogle Scholar
  63. 63.
    Krall EA, Dawson-Hughes B (1991) Relation of fractional 47Ca retention to season and rates of bone loss in healthy postmenopausal women. J Bone Miner Res 6:1323–1329PubMedGoogle Scholar
  64. 64.
    Dawson-Hughes B, Harris SS, Krall EA, Dallal GE, Falconer G, Green CL (1995) Rates of bone loss in postmenopausal women randomly assigned to one of two dosages fo vitamin D. Am J Clin Nutr 61:1140–1145PubMedGoogle Scholar
  65. 65.
    Dawson-Hughes B, Dallal GE, Krall EA, Harris S, Sokoll LJ, Falconer G (1991) Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Ann Intern Med 115:505–512PubMedGoogle Scholar
  66. 66.
    Krall WE, Sahyoun N, Tannenbaum S, Dallal G, Dawson-Hughes B (1989) Effect of vitamin D intake on seasonal variations in parathyroid hormone secretion in postmenopausal women. N Engl J Med 321:1777–1783PubMedCrossRefGoogle Scholar
  67. 67.
    Tangpricha V, Pearce EN, Chen TC, Holick MF (2002) Vitamin D insufficiency among free-living healthy young adults. Am J Med 112(8):659–662PubMedCrossRefGoogle Scholar
  68. 68.
    Lips P, Wiersinga A, van Ginkel FC et al (1988) The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. J Clin Endocrinol Metab 67:644–650PubMedCrossRefGoogle Scholar
  69. 69.
    Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ (1992) Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 327(23): 1637–1642PubMedCrossRefGoogle Scholar
  70. 70.
    Dawson-Hughes B, Harris SS, Krall EA, Dallal GE (1997) Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 337:670–676PubMedCrossRefGoogle Scholar
  71. 71.
    Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM (2007) Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab 92(9):3517–3522PubMedGoogle Scholar
  72. 72.
    Merewood A, Mehta SD, Chen TC, Holick MF, Bauchner H (2009) Association between severe vitamin D deficiency and primary caesarean section. J Clin Endo Metab 94(3):940–945Google Scholar
  73. 73.
    Vieth R, Garland C, Heaney R et al (2007) The urgent need to reconsider recommendations for vitamin D nutrition intake. Am J Clin Nutr 85:649–650PubMedGoogle Scholar
  74. 74.
    Grey A, Lucas J, Horne A, Gamble G, Davidson JS, Reid IR (2005) Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency. J Clin Endocrinol Metab 90:2122–2126PubMedCrossRefGoogle Scholar
  75. 75.
    Jackson RD, LaCroix AZ, Gass M et al (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354(7):669–683PubMedCrossRefGoogle Scholar
  76. 76.
    K/DOQI (2003) Clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42(Suppl 3):S1-S201CrossRefGoogle Scholar
  77. 77.
    Dusso AS, Sato T, Arcidiacono MV et al (2006) Pathogenic mechanisms for parathyroid hyperplasia. Kidney Int 70:S8–S11CrossRefGoogle Scholar
  78. 78.
    Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, Yetley EA (2008) Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004. Am J Clin Nutr 88(6):1519–1527PubMedCrossRefGoogle Scholar
  79. 79.
    Pietras SM, Obayan BK, Cai MH, Holick MF (2009) Vitamin D2 treatment for vitamin D deficiency and insufficiency for up to 6 years. Arch Int Med 169: 1806–1807Google Scholar
  80. 80.
    Brot C, Vestergaard P, Kolthoff N, Gram J, Hermann AP, Sorensen OH (2001) Vitamin D status and its adequacy in healthy Danish perimenopausal women: relationships to dietary intake, sun exposure and serum parathyroid hormone. Br J Nutr 86(1):S97–S103PubMedCrossRefGoogle Scholar
  81. 81.
    Maeda SS, Kunii IS, Hayashi L, Lazaretti-Castro M (2007) The effect of sun exposure on 25-hydroxyvitamin D concentrations in young healthy subjects living in the city of Sao Paulo, Brazil. Braz J Med Biol Res 40(12):1653–1659PubMedCrossRefGoogle Scholar
  82. 82.
    Hollis BW (2005) Circulating 25-hydroxyvitaminD levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr 135:317–322PubMedGoogle Scholar
  83. 83.

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Michael F. Holick
    • 1
  1. 1.Vitamin D, Skin and Bone Research Laboratory, Section of Endocrinology, Nutrition, and Diabetes, Department of MedicineBoston University School of MedicineBostonUSA

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