Review Article

Vitamin D: Important for Prevention of Osteoporosis, Cardiovascular Heart Disease, Type 1 Diabetes, Autoimmune Diseases, and Some Cancers

Authors: Michael F. Holick, MD, PHD

Abstract

Vitamin D is very important for overall health and well-being. A major source of vitamin D comes from exposure to sunlight. Measurement of 25-hydroxyvitamin D in the blood and not 1,25-dihydroxyvitamin D is used to determine vitamin D status. A blood level of 25-hydroxyvitamin D of at least 20 ng/mL is considered to be vitamin D sufficient. Vitamin D deficiency increases the risk of many common cancers, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and type I diabetes.


Key Points


* Ninety percent or more of our vitamin D requirement comes from exposure to sunlight. Without sun exposure, 1,000 IU of vitamin D per day is required.


* 25-hydroxyvitamin D is the major circulating form that is used to determine vitamin D status.


* 1,25-dihydroxyvitamin controls cell growth, regulates renin production, and modulates immune function.


* Season, latitude, sunscreen use, skin pigmentation, and aging can markedly affect vitamin D synthesis in the skin.

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References

1. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 2004;79:362–371.
 
2. Khosla S. The OPG/RANKL/RANK system. Endocrinology 2001;142:5050–5055.
 
3. Holick MF. Vitamin D: photobiology, metabolism, mechanism of action, and clinical applications. In Favus M (ed). Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Fifth Edition. Chapter 20. Washington, DC, American Society for Bone and Mineral Research, 2003, pp 129–137.
 
4. Brown EM, Pollak M, Seidman CE, et al. Calcium-ion-sensing cell-surface receptors. N Engl J Med1995;333:234–240.
 
5. Holick MF. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes 2002;9:87–98.
 
6. Gloth FM III, Lindsay JM, Zelesnick LB, et al. Can vitamin D deficiency produce an unusual pain syndrome? Arch Intern Med 1991;151:1662–1664.
 
7. Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc 2003;78:1463–1470.
 
8. Glerup H, Mikkelsen K, Poulsen L et al. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med 2000;247:260–268.
 
9. Holick MF. Vitamin D deficiency: what a pain it is. Mayo Clin Proc 2003;78:1457–1459.
 
10. Malabanan AO, Turner AK, Holick MF. Severe generalized bone pain and osteoporosis in a premenopausal black female: effect of vitamin D replacement. J Clin Densitometr 1998;1:201–204.
 
11. Glerup H, Middelsen K, Poulsen L, et al. Hypovitaminosis D myopathy without biochemical signs of osteomalacia bone involvement. Calcif Tissue Int 2000;66:419–424.
 
12. Bischoff HA, Stahelin HN, Dick W, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Min Res 2003;18:343.
 
13. Stumpf WE, Sar M, Reid FA, et al. Target cells for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. Science 1979;206:1188–1190.
 
14. Tanaka H, Abe E, Miyaura C, et al. 1,25-Dihydroxycholeciferol and human myeloid leukemia cell line (HL-60): the presence of cytosol receptor and induction of differentiation. Biochem J 1982;204:713–719.
 
15. Chen TC, Holick MF. Vitamin D and prostate cancer prevention and treatment. Trends Endocrinol Metabol 2003;14:423–430.
 
16. Tsoukas CD, Provvedine DM, Manolagas SC. 1,25-Dihydroxyvitamin D3, a novel immuno-regulatory hormone. Science 1984;221:1438–1440.
 
17. Mathieu C, Adorini L. The coming of age of 1,25-dihydroxyvitamin D3 analogs as immunomodulatory agents. Trends Mol Med 2002;8:174–179.
 
18. Li Y, Kong J, Wei M, et al. 1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002;110:229–238.
 
19. Garland CF, Garland FC, Shaw EK, et al. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet 1989;18:1176–1178.
 
20. Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer mortality. Cancer1992;70:2861–2869.
 
21. Grant WB. An estimate of premature cancer mortality in the US due to inadequate doses of solar ultraviolet-B radiation. Cancer 2002;70:2861–2869.
 
22. Hypponen E, Laara E, Jarvelin M-R, et al. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001;358:1500–1503.
 
23. Rostand SG. Ultraviolet light may contribute to geographic and racial blood pressure differences.Hypertension 1979;30:150–156.
 
24. Krause R, Buhring M, Hopfenmuller W, et al. Ultraviolet B and blood pressure. Lancet1998;352:709–710.
 
25. Zittermann A, Schleithoff SS, Tenderich G, et al. Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 2003;41:105–112.
 
26. McGrath J, Selten JP, Chant D. Long-term trends in sunshine duration and its association with schizophrenia birth rates and age at first registration: data from Australia and the Netherlands.Schizophr Res 2002;54:199–212
 
27. Ponsonby A-L, McMichael A, van der Mei I. Ultraviolet radiation and autoimmune disease: insights from epidemiological research. Toxicology 2002;181–182:71–78
 
28. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet 1998;351:805–806.
 
29. Souberbielle J, Lawson-Body E, Hammadi B, et al. The use in clinical practice of parathyroid hormone normative values established in vitamin D-sufficient subjects. J Clin Endocrinol Metab2003;88:3501–3504.
 
30. Holick MF. Editorial: the parathyroid hormone D-Lema. J Clin Endocrinol Metab 2003;88:3499–3500.
 
31. Heaney RP, Dowell MS, Hale CA, et al. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 2003;22:142–146.
 
32. Tangpricha V, Koutkia P, Rieke SM, et al. Fortification of orange juice with vitamin D: a novel approach to enhance vitamin D nutritional health. Am J Clin Nutr 2003;77:1478–1483.
 
33. Tangpricha V, Pearce EN, Chen TC, et al. Vitamin D insufficiency among free-living healthy young adults. Am J Med 2002;112:659–662.
 
34. Gordon CM, DePeter KC, Estherann G, et al. Prevalence of vitamin D deficiency among healthy adolescents. Endo2003, Endocrine Society Meeting (abstract) OR21–2, p 87, 2003.
 
35. Sullivan SS, Rosen CJ, Chen TC, et al. Seasonal changes in serum 25(OH)D in adolescent girls in Maine. ASBMR Annual Meeting (abstract) M470, p S407, 2003.
 
36. Jones G, Dwyer T. Bone mass in prepubertal children: gender differences and the role of physical activity and sunlight exposure. J Clin Endocrinol Metab 1998;83:4274–4279.
 
37. Matsuoka LY, Ide L, Wortsman J, et al. Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D: a preliminary study. Arch Dermatol 1988;124:1802–1804.
 
38. Holick MF. The UV Advantage. New York, NY, ibooks, 2004.