Vitamin D

  • Michael F. HolickEmail author
Part of the Nutrition and Health book series (NH)


Vitamin D deficiency is one of the most common medical conditions. This chapter reviews the photobiology, metabolism, biologic actions of vitamin D as well as strategies to treat and prevent vitamin D deficiency. Vitamin D, the sunshine vitamin, is well recognized as being important for the development and maintenance of bone health throughout life. The major source of vitamin D for children and adults is from sun exposure. Solar ultraviolet B radiation converts 7-dehydrocholesterol to previtamin D3 which in turn thermally isomerizes to vitamin D3. Once formed it enters the circulation and along with vitamin D2 and vitamin D3 coming from dietary sources travels to the liver and is converted to the major circulating form 25-hydroxyvitamin D [25(OH)D]. 25(OH)D enters the circulation and travels to the kidneys where it is converted to its active form 1,25-dihydroxyvitamin D [1,25(OH)2D]. 1,25(OH)2D interacts with its vitamin D receptor (VDR) in the intestine resulting in an increase in intestinal calcium absorption. In the skeleton it increases the number of osteoclasts to mobilize calcium from the skeleton when necessary. Vitamin D deficiency, defined as a 25-hydroxyvitamin D <20 ng/mL, is one of the most common medical disorders worldwide. Strategies using sensible sun exposure with the app along with vitamin D supplementation are discussed in detail. Vitamin D insufficiency has been defined as a 25(OH)D of 21–29 ng/mL and sufficiency as >30 ng/mL. Vitamin D toxicity is usually not observed until 25(OH)D levels are >200 ng/mL. Essentially every tissue and cell in the body has a VDR and many cells including macrophages have the ability to convert 25(OH)D to 1,25(OH)2D. Epidemiologic and association studies have suggested that vitamin D deficiency increases risk for many acute and chronic illnesses including autoimmune diseases such as multiple sclerosis and type 1 diabetes, cardiovascular disease, several cancers, type 2 diabetes, infectious diseases and neurocognitive dysfunction. Because vitamin D toxicity is an extremely rare occurrence based on the totality of evidence to date about the many health benefits of vitamin D it is reasonable to encourage sensible sun exposure in combination with vitamin D supplementation. The Endocrine Society's practice guidelines recommends children 1 year and older receive 600–1,000 IU daily and adults 1,500–2,000 IU daily with the caveat that obese people require 2–3 times more.


Vitamin D Sunlight 25-Hydroxyvitamin D 1,25-Dihydroxyvitamin D Rickets Osteoporosis Osteomalacia Cancer Autoimmune diseases Infectious diseases 



This work was supported in part by National Institutes of Health Grants CTSI UL-1-TR 000157.


  1. 1.
    Holick MF. Phylogenetic and evolutionary aspects of vitamin D from phytoplankton to humans. In: Pang PKT, Schreibman MP, editors. Vertebrate endocrinology: fundamentals and biomedical implications, vol. 3. Orlando, FL: Academic; 1989. p. 7–43.Google Scholar
  2. 2.
    Holick MF. Calcium and vitamin D in human health. Ann Nestle 2002;60(3).Google Scholar
  3. 3.
    Holick MF. Vitamin D: a millennium perspective. J Cell Biochem. 2003;88:296–307.PubMedCrossRefGoogle Scholar
  4. 4.
    Cooke NE, David EV. Serum vitamin D-binding protein is a third member of the albumin and alpha fetoprotein gene family. J Clin Invest. 1985;76:2420–4.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    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
  6. 6.
    Holick MF. Evaluation and treatment of disorders in calcium, phosphorus, and magnesium metabolism. In: Noble J, editor. Textbook of primary care medicine. 3rd ed. St. Louis, IL: Mosby; 2001. p. 886–98.Google Scholar
  7. 7.
    Hossein-nezhad A, Holick MF. Optimize dietary intake of vitamin D: an epigenetic perspective. Curr Opin Clin Nutr Metab Care. 2012;15:567–79.PubMedCrossRefGoogle Scholar
  8. 8.
    Nykjaer A, Dragun D, Walther D, et al. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999;96:507–15.PubMedCrossRefGoogle Scholar
  9. 9.
    MacDonald PN. Molecular biology of the vitamin D receptor. In: Holick MF, editor. Vitamin D: physiology. Totowa, NJ: Molecular Biology and Clinical Applications. Humana; 1999. p. 109–28.Google Scholar
  10. 10.
    Hossein-nezhad A, Spira A, Holick MF. Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial. PLoS One. 2013;8(3):e58725. doi: 10.1371/journal.pone.0058725.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Freedman LP. Multimeric coactivator complexes for steroid/nuclear receptors. Trends Endocrinol Metab. 1999;10:403–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Raval-Pandya M, Porta AR, Christakos S. Mechanism of action of 1,25-dihydroxyvitamin D3 on intestinal calcium absorption and renal calcium transport. In: Holick MF, editor. Vitamin D: physiology. Totowa, NJ: Molecular Biology and Clinical Applications. Humana; 1999. p. 163–73.Google Scholar
  13. 13.
    Khosla S. The OPG/RANKL/RANK system. Endocrinology. 2001;142:5050–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Jimi E, Nakamura I, Amano H, et al. Osteoclast function is activated by osteoblastic cells through a mechanism involving cell-to-cell contact. Endocrinology. 1996;137:2187–90.Google Scholar
  15. 15.
    Holick MF. Vitamin D deficiency. New Engl J Med. 2007;357:266–81.PubMedCrossRefGoogle Scholar
  16. 16.
    Zerwekh JE, Sakhaee K, Pak CYC. Short-term 1,25-dihydroxyvitamin D3 administration raises serum osteocalcin in patients with postmenopausal osteoporosis. J Clin Endocrinol Metab. 1985;60:615–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Holick MF. Evolution, biologic functions, and recommended dietary allowances for vitamin D. In: Holick MF, editor. Vitamin D: physiology, molecular biology, and clinical applications. Totowa, NJ: Humana; 1999. p. 1–16.CrossRefGoogle Scholar
  18. 18.
    Underwood JL, DeLuca HF. Vitamin D is not directly necessary for bone growth and mineralization. Am J Physiol. 1984;246:E493–8.PubMedGoogle Scholar
  19. 19.
    Holtrop ME, Cox KA, Carnes DL, Holick MF. Effects of serum calcium and phosphorus on skeletal mineralization in vitamin D-deficient rats. Am J Physiol. 1986;251(2 pt 1):E234–40.PubMedGoogle Scholar
  20. 20.
    Balsan S, Garabedian M, Larchet M, et al. Long-term nocturnal calcium infusions can cure rickets and promote normal mineralization in hereditary resistance to 1,25-dihydroxyvitamin D. J Clin Invest. 1986;77:1661–7.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Steenbock H. The induction of growth-prompting and calcifying properties in a ration exposed to light. Science. 1924;60:224–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Holick MF. Vitamin D: importance for bone health, cellular health and cancer prevention. In: Holick MF, editor. Biologic effects of light. Boston, MA: Kluwer; 2001. p. 155–73.Google Scholar
  23. 23.
    Oppé TE. Infantile hypercalcemia, nutritional rickets, and infantile survey in Great Britain. Br Med J. 1964;1:1659–61.CrossRefGoogle Scholar
  24. 24.
    Tangpricha V, Koutkia P, Rieke SM, Chen TC, Perez AA, Holick MF. Fortification of orange juice with vitamin D: a novel approach to enhance vitamin D nutritional health. Am J Clin Nutr. 2003;77:1478–83.PubMedGoogle Scholar
  25. 25.
    MacLaughlin JA, Anderson RR, Holick MF. Spectral character of sunlight modulates the photosynthesis of previtamin D3 and its photo isomers in human skin. Science. 1982;1001–1003.Google Scholar
  26. 26.
    Holick MF, Tian XQ, Allen M. Evolutionary importance for the membrane enhancement of the production of vitamin D3 in the skin of poikilothermic animals. Proc Natl Acad Sci U S A. 1995;92(8):3124–6.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Tian XQ, Chen TC, Matsuoka LY, Wortsman J, Holick MF. Kinetic and thermodynamic studies of the conversion of previtamin D3 to vitamin D3 in human skin. J Biol Chem. 1993;268(20):14888–92.PubMedGoogle Scholar
  28. 28.
    Haddad JG, Matsuoka LY, Hollis BW, Hu YZ, Wortsman J. Human plasma transport of vitamin D after its endogenous synthesis. J Clin Invest. 1993;91:2552–5.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Clemens TL, Henderson SL, Adams JS, Holick MF. Increased skin pigment reduces the capacity of skin to synthesize vitamin D3. Lancet. 1982;74–76.Google Scholar
  30. 30.
    Matsuoka LY, Ide L, Wortsman J, MacLaughlin J, Holick MF. Sunscreens suppress cutaneous vitamin D3 synthesis. J Clin Endocrinol Metab. 1987;64:1165–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Matsuoka LY, Wortsman J, Dannenberg MJ, Hollis BW, Lu Z, Holick MF. Clothing prevents ultraviolet-B radiation-dependent photosynthesis of vitamin D3. J Clin Endocrinol Metab. 1992;75(4):1099–103.PubMedGoogle Scholar
  32. 32.
    Taha SA, Dost SM, Sedrani SH. 25-Hydroxyvitamin D and total calcium: extraordinarily low plasma concentrations in Saudi mothers and their neonates. Pediatr Res. 1984;18:739–41.PubMedCrossRefGoogle Scholar
  33. 33.
    Glerup H, Mikkelsen K, Poulsen L, et al. Hypovitaminosis D myopathy without osteomalacic bone involvement. Calcif Tissue Int. 2000;66(6):419–24.PubMedCrossRefGoogle Scholar
  34. 34.
    Holick MF. McCollum award lecture, 1994: vitamin D: new horizons for the 21st century. Am J Clin Nutr. 1994;60:619–30.PubMedGoogle Scholar
  35. 35.
    Chen TC. Photobiology of vitamin D. In: Holick MF, editor. Vitamin D: physiology, molecular biology, and clinical applications. Totowa, NJ: Humana; 1999. p. 17–37.Google Scholar
  36. 36.
    Brown EM, Pollak M, Seidman CE, et al. Calcium-ion-sensing cell-surface receptors. N Engl J Med. 1995;333:234–40.PubMedCrossRefGoogle Scholar
  37. 37.
    Juppner H, Brown EM, Kronenberg HM. Parathyroid hormone. In: Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. 4th ed. Philadelphia: Lippincott-Raven; 1999. p. 80–7.Google Scholar
  38. 38.
    Hordon LD, Peacock M. Osteomalacia and osteoporosis in femoral neck fracture. Bone Miner. 1990;11:247–59.PubMedCrossRefGoogle Scholar
  39. 39.
    Chapuy MC, Arlot M, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med. 1992;327:1627–42.CrossRefGoogle Scholar
  40. 40.
    Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997;337:670–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Schnitzler CM, Solomon L. Osteomalacia in elderly white South African women with fractures of the femoral neck. S Afr Med J. 1983;64:527–30.PubMedGoogle Scholar
  42. 42.
    Al-Ali H, Fuleihan GEH. Nutritional osteomalacia: substantial clinial improvement and gain in bone density post-therapy. J Clin Densitom. 2000;3:97–101.PubMedCrossRefGoogle Scholar
  43. 43.
    Malabanan AO, Turner AK, Holick MF. Severe generalized bone pain and osteoporosis in a premenopausal black female: effect of vitamin D replacement. J Clin Densitom. 1998;1:201–4.CrossRefGoogle Scholar
  44. 44.
    Holick MF. Sunlight and vitamin D, both good for cardiovascular health (editorial). J Gen Intern Med. 2002;17:733–5.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Rimaniol J, Authier F, Chariot P. Muscle weakness in intensive care patients: initial manifestation of vitamin D deficiency. Intensive Care Med. 1994;20:591–2.PubMedCrossRefGoogle Scholar
  46. 46.
    Bischoff HA, Stahelin HB, Dick W, et al. Effect of vitamin D and calcium supplementation on falls: a randomized controlled study. J Bone Miner Res. 2003;18(2):343–51.PubMedCrossRefGoogle Scholar
  47. 47.
    Gloth FM, Gundberg CM, Hollis BW, Haddad HG, Tobin JD. Vitamin D deficiency in homebound elderly persons. JAMA. 1995;274:1683–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet. 1998;351:805–6.PubMedCrossRefGoogle Scholar
  49. 49.
    Lips P. Vitamin D, deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev. 2001;22(4):477–501.PubMedCrossRefGoogle Scholar
  50. 50.
    Chapuy MC, Preziosi P, Maaner M, et al. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporosis Int. 1997;7:439–43.CrossRefGoogle Scholar
  51. 51.
    Tangpricha V, Pearce EN, Chen TC, Holick MF. Vitamin D insufficiency among free-living healthy young adults. Am J Med. 2002;112:659–62.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005;135:317–22.PubMedGoogle Scholar
  53. 53.
    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; 2011.Google Scholar
  54. 54.
    Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest. 2006;116(8):2062–72.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Thomas MK, Lloyd-Jones DM, Thadhani RI, et al. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338:777–83.PubMedCrossRefGoogle Scholar
  56. 56.
    Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013;88(7):720–55.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Lo CW, Paris PW, Clemens TL, Nolan J, Holick MF. Vitamin D absorption in healthy subjects and in patients with intestinal malabsorption syndromes. Am J Clin Nutr. 1985;42:644–9.PubMedGoogle Scholar
  58. 58.
    Shane E, Silverberg SJ, Donovan D, et al. Osteoporosis in lung transplantation candidates with end-stage pulmonary disease. Am J Med. 1996;101:262–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Shike M, Harrison J, Sturtridge C, et al. Metabolic bone disease in patients receiving long-term parenteral nutrition. Ann Intern Med. 1994;92:343–50.CrossRefGoogle Scholar
  60. 60.
    Shike M, Shils ME, Heller A, et al. Bone disease in prolonged parenteral nutrition: osteopenia without mineralization defect. Am J Clin Nutr. 1986;44:89–98.PubMedGoogle Scholar
  61. 61.
    Chel VGM, Ooms ME, Popp-Snijders C, et al. Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly. J Bone Miner Res. 1998;13:1238–42.PubMedCrossRefGoogle Scholar
  62. 62.
    Chuck A, Todd J, Diffey B. Subliminal ultraviolet-B irradiation for the prevention of vitamin D deficiency in the elderly: a feasibility study. Photochem Photoimmun Photomed. 2001;17(4):168–71.CrossRefGoogle Scholar
  63. 63.
    Lund B, Sorensen OH. Measurement of 25-hydroxyvitamin D in serum and its relation to sunshine, age and Vitamin D intake in the Danish population. Scand J Clin Lab Invest. 1979;39:23–30.PubMedCrossRefGoogle Scholar
  64. 64.
    Bell NH, Epstein S, Greene A, Shary J, Oexmann MJ, Shaw S. Evidence for alteration of the vitamin D-endocrine system in obese subjects. J Clin Invest. 1985;76:370–3.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment & prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30.PubMedCrossRefGoogle Scholar
  66. 66.
    Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level1-3. Am J Clin Nutr. 2001;73:288–94.PubMedGoogle Scholar
  67. 67.
    Barger-Lux MJ, Heaney RP, Dowell S, Chen TC, Holick MF. Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteopor Int. 1998;8:222–30.CrossRefGoogle Scholar
  68. 68.
    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
  69. 69.
    Chapuy MC, Schott AM, Garnero P, 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
  70. 70.
    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.PubMedCrossRefGoogle Scholar
  71. 71.
    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.PubMedCrossRefGoogle Scholar
  72. 72.
    Bauer JM, Freyberg RH. Vitamin D intoxication and metastatic calcification. JAMA. 1946;1208–1215.Google Scholar
  73. 73.
    Adams JS, Lee G. Gains in bone mineral density with resolution of vitamin D intoxication. Ann Intern Med. 1997;127:203–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Jacobus CH, Holick MF, Shao Q, et al. Hypervitaminosis D associated with drinking milk. N Engl J Med. 1992;326:1173–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Pietras SM, Obayan BK, Cai MH, Holick MF. Research letter: vitamin D2 treatment for vitamin D deficiency and insufficiency for up to 6 years. Arch Intern Med. 2009;169(19):1806–8.PubMedCrossRefGoogle Scholar
  76. 76.
    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 Pract. 2012;18(3):399–402.PubMedCrossRefGoogle Scholar
  77. 77.
    Heikinheimo RJ, Ubjivaaram JA, Jantti PO, Maki-Jokela PL, Rajala SA, Sievanen H. Intermittant parenteral vitamin D supplementation in the elderly in nutritional aspects of osteoporosis. In: Burckhard P, Heaney RP, editors. Challenges of modern medicine. Geneva, Switzerland: Ares-Serono; 1994. p. 335–40.Google Scholar
  78. 78.
    Wacker M, Holick MF. Sunlight and vitamin D: a global perspective for health. DermatoEndocrinology. 2013;5(1):51–108.CrossRefGoogle Scholar
  79. 79.
    Koutkia P, Lu Z, Chen TC, Holick MF. Treatment of vitamin D deficiency due to Crohn’s disease with tanning bed ultraviolet B radiation. Gastroenterology. 2001;121(6):1485–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Apperly FL. The relation of solar radiation to cancer mortality in North America. Cancer Res. 1941;1:191–5.Google Scholar
  81. 81.
    Garland CF, Garland FC, Shaw EK, Comstock GW, Helsing KJ, Gorham ED. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet. 1989;18:1176–8.CrossRefGoogle Scholar
  82. 82.
    Garland C, Shekelle RB, Barrett-Connor E, Criqui MH, Rossof AH, Oglesby P. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet. 1985;9:307–9.CrossRefGoogle Scholar
  83. 83.
    Garland CF, Garland FC, Gorham ED, Raffa J. Sunlight, vitamin D, and mortality from breast and colorectal cancer in Italy. In: Holick MF, Kligman A, editors. Biologic effects of light. Walter de Gruyter: New York; 1992. p. 39–43.Google Scholar
  84. 84.
    Garland FC, Garland CF, Gorham ED, Young JF. Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prevent Med. 1990;19:614–22.CrossRefGoogle Scholar
  85. 85.
    Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer mortality. Cancer. 1992;70:2861–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P. Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control. 2000;11:847–52.PubMedCrossRefGoogle Scholar
  87. 87.
    Grant WB. An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Am Cancer Soc. 2002;94:272–81.Google Scholar
  88. 88.
    Rostand SG. Ultraviolet light may contribute to geographic and racial blood pressure differences. Hypertension. 1979;30:150–6.CrossRefGoogle Scholar
  89. 89.
    Hernan MA, Olek MJ, Ascherio A. Geographic variation of MS incidence in two prospective studies of US women. Neurology. 1999;51:1711–8.CrossRefGoogle Scholar
  90. 90.
    Holick MF. Clinical efficacy of 1,25-dihydroxyvitamin D3 and its analogues in the treatment of psoriasis. Retinoids. 1998;14(1):12–7.Google Scholar
  91. 91.
    Mathieu C, Waer M, Laureys J, Rutgeerts O, Bouillon R. Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3. Diabetologia. 1994;37:552–8.PubMedCrossRefGoogle Scholar
  92. 92.
    Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik S, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zugel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Sciencexpress. 2006;3:1770–3.Google Scholar
  93. 93.
    Hypponen E, Laara E, Jarvelin M-R, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001;358:1500–3.PubMedCrossRefGoogle Scholar
  94. 94.
    Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002;110:229–38.PubMedCentralPubMedCrossRefGoogle Scholar
  95. 95.
    Scragg R, Jackson R, Holdaway IM, Lim T, Beaglehole R. Myocaardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. Int J Epidemiol. 1990;19:559–63.PubMedCrossRefGoogle Scholar
  96. 96.
    Zitterman A, Schulze Schleithoff S, Tenderich C, Berthold H, Koefer R, Stehle P. Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol. 2003;41(1):105–12.CrossRefGoogle Scholar
  97. 97.
    Krause R, Buhring M, Hopfenmuller W, Holick MF, Sharma AM. Ultraviolet B and blood pressure. Lancet. 1998;352(9129):709–10.PubMedCrossRefGoogle Scholar
  98. 98.
    Scragg R. Seasonality of cardiovascular disease mortality and the possible protective effect of utlra-violet radiation. Int J Epidemiol. 1981;10:337–41.PubMedCrossRefGoogle Scholar
  99. 99.
    Schwartz GG, Whitlatch LW, Chen TC, Lokeshwar BL, Holick MF. Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. Cancer Epidemiol Biomarkers Prev. 1998;7(5):391–5.PubMedGoogle Scholar
  100. 100.
    Bikle DD, Nemanic MK, Gee E, Elias P. 1,25-Dihydroxyvitamin D3 production by human keratinocytes: kinetics and regulation. J Clin Invest. 1986;78:557–66.PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Lehmann B, Knuschke P, Meurer M. UVB-induced conversion of 7-dehydrocholesterol to 1α,25-dihydroxyvitamin D3 (calcitriol) in the human keratinocyte line HaCaT. Photochem Photobiol. 2000;72(6):803–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Cross HS, Bareis P, Hofer H, Bischof MG, Bajna E, Kriwanek S. 25-Hydroxyvitamin D3-1α-hydroxylase and vitamin D receptor gene expression in human colonic mucosa is elevated during early cancerogenesis. Steroids. 2001;66:287–92.PubMedCrossRefGoogle Scholar
  103. 103.
    Tangpricha V, Flanagan JN, Whitlatch LW, et al. 25-Hydroxyvitamin D-1a-hydroxylase in normal and malignant colon tissue. Lancet. 2001;357(9269):1673–4.PubMedCrossRefGoogle Scholar
  104. 104.
    Holick MF. Sunlight D-lemma: risk of skin cancer or bone disease and muscle weakness. Lancet. 2001;357:4–6.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Medicine and Endocrine/Vitamin D LabBoston University School of MedicineBostonUSA

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