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Vitamin D: More than just affecting calcium and bone

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Abstract

Vitamin D is a fat-soluble steroid that is essential for main-taining normal calcium metabolism. In vitamin D deficiency, calcium absorption is insufficient and cannot satisfy the body’s needs. Consequently, parathyroid hormone produc-tion increases and calcium is mobilized from bones and reabsorbed in the kidneys to maintain normal serum calcium levels—a condition defined as secondary hyper-parathyroidism. Most organs, including the gut, brain, heart, pancreas, skin, kidneys, and immune system have receptors for 1,25 (OH)vitamin D. Furthermore, all of these organs have the capacity to synthesize 1,25 (OH)vitamin D from vitamin D. Extensive research suggests that vitamin D deficiency is common and represents a global health prob-lem. Clinical consequences related to low vitamin D levels include not only osteomalacia, osteoporosis, and rickets, but also neuro-muscular dysfunction and fractures. Falls related to neuromuscular dysfunction lead to 40% of all nursing home admissions and are the largest single cause of injury-related deaths in elderly people. About one-third of all persons 65 and older fall at least once a year, resulting in more than 1.5 million emergency room treatments and more than 300,000 hospitalizations. Falls cause more than 11,000 deaths per year, most of them in elderly patients ??????75 years) who suffer hip fractures. It is well established that vitamin D deficiency not only has serious conse-quences for bone health, but also for other organ systems. Previous studies have shown that vitamin D supplementa-tion reduces the number of fractures and directly improves neuromuscular function, thus helping to prevent falls and subsequent fractures. In addition, vitamin D appears to have other important functions as a regulator of cell differ-entiation and cell growth.

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References and Recommended Reading

  1. DeLuca HF, Zierold C: Mechanisms and functions of vitamin D. Nutr Rev 1998, 56:S4–10.

    Article  PubMed  CAS  Google Scholar 

  2. van den Berg H: Bioavailability of vitamin D. Eur J Clin Nutr 1997, 51(Suppl 1):S76-S79.

    PubMed  Google Scholar 

  3. van den Berg H: Vitamin D. Int J Vitam Nutr Res 1993, 63:257–259.

    PubMed  Google Scholar 

  4. Bringhurst FR, Demay MB, Kronenberg HM: Mineral metabo-lism. In Williams Textbook of Endocrinology. Edited by Larson PR, Kronenberg HM, Melmed S, Polonsky KS. Amsterdam: Elsevier; 2003:1317–1320.

    Google Scholar 

  5. Favus MJ, Christakos S: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, edn 3. Philadelphia: Lippincott-Raven; 1996.

    Google Scholar 

  6. Holick MF: Evolution and function of vitamin D. Recent Results Cancer Res 2003, 164:3–28.

    PubMed  CAS  Google Scholar 

  7. Hayes CE, Nashold FE, Spach KM, Pedersen LB: The immuno-logical functions of the vitamin D endocrine system. Cell Mol Biol 2003, 49:277–300.

    PubMed  CAS  Google Scholar 

  8. Holick MF: McCollum Award Lecture, 1994: vitamin D: new horizons for the 21st century. Am J Clin Nutr 1994, 60:619–630.

    PubMed  CAS  Google Scholar 

  9. 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.

    Article  CAS  Google Scholar 

  10. Wharton B, Bishop N: Rickets. Lancet 2003, 362:1389–1400.

    Article  PubMed  CAS  Google Scholar 

  11. Food and Nutrition Board IoM. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. Washington: National Academy Press, 1996.

    Google Scholar 

  12. 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. Vitamin D deficiency plays an important role in increasing the risk for many common and serious diseases, including some common cancers, type 1 diabetes, cardiovascular disease, and osteoporosis. Numerous epidemiologic studies suggest that exposure to sunlight, which enhances the production of vitamin D in the skin, is important in preventing many chronic diseases.

    PubMed  CAS  Google Scholar 

  13. Dhesi JK, Bearne LM, Moniz C, et al.: Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status. J Bone Miner Res 2002, 17:891–897.

    Article  PubMed  CAS  Google Scholar 

  14. Lips P, Chapuy MC, Dawson-Hughes B, et al.: An international comparison of serum 25-hydroxyvitamin D measurements. Osteoporos Int 1999, 9:394–397.

    Article  PubMed  CAS  Google Scholar 

  15. Dhesi J, Allain TJ, Moniz C: Vitamin D deficiency in the elderly. CPD Clin Biochem 2001, 3:9–13.

    Google Scholar 

  16. Dawson-Hughes B, Heaney RP, Holick MF, et al.: Vitamin D roundtable. In Nutritional Aspects of Osteoporosis, edn 2. Edited by Burckhardt P, Dawson-Hughes B, Heaney RP. San Diego: Elsevier, Inc.; 2004:263–270.

    Google Scholar 

  17. Vieth R: Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999, 69:842–856.

    PubMed  CAS  Google Scholar 

  18. Heaney RP, Davies KM, Chen TC, et al.: Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003, 77:204–210.

    PubMed  CAS  Google Scholar 

  19. Heaney RP: Functional indices of vitamin D status and rami-fications of vitamin D deficiency. Am J Clin Nutr 2004, 80:1706S-1709S. Serum 25-hydroxyvitamin D [25(OH)D] concentrations are currently recognized as the functional status indicator for vitamin D. Serum concentrations of less than 80 nmol/L are associated with reduced calcium absorption, osteoporosis, and increased fracture risk. For typical older individuals, supplemental oral intakes of similar to 300 IU/d are required to reach the lower end of the optimal range.

    PubMed  CAS  Google Scholar 

  20. Vieth R: Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol 2004, 89-90:575–579.

    Article  PubMed  CAS  Google Scholar 

  21. Chapuy MC, Pamphile R, Paris E, et al.: Combined calcium and vitamin D3 supplementation in elderly women: confir-mation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study. Osteoporos Int 2002, 13:257–264.

    Article  PubMed  CAS  Google Scholar 

  22. Chapuy MC, Arlot ME, Duboeuf F, et al.: Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992, 327:1637–1642.

    Article  PubMed  CAS  Google Scholar 

  23. Bischoff-Ferrari HA, Willett WC, Wong JB, et al.: Fracture pre-vention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005, 293:2257–2264. Several randomized controlled trials have shown that oral vitamin D supplementation between 700 to 800 IU/d appears to reduce the risk for hip and any nonvertebral fractures in ambulatory or institutional-ized elderly persons. An oral vitamin D dose of 400 IU/d is not sufficient for fracture prevention.

    Article  PubMed  CAS  Google Scholar 

  24. Stein MS, Wark JD, Scherer SC, et al.: Falls relate to vitamin D and parathyroid hormone in an australian nursing home and hostel. J Am Geriatr Soc 1999, 47:1195–1201.

    PubMed  CAS  Google Scholar 

  25. Janssen HC, Samson MM, Verhaar HJ: Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr 2002, 75:611–615.

    PubMed  CAS  Google Scholar 

  26. Pfeifer M, Begerow B, Minne HW, et al.: Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 2000, 15:1113–1118.

    Article  PubMed  CAS  Google Scholar 

  27. Gallagher JC: The effects of calcitriol on falls and fractures and physical performance tests. J Steroid Biochem Mol Biol 2004, 89-90:497–501.

    Article  PubMed  CAS  Google Scholar 

  28. Bischoff HA, Stahelin HB, Urscheler N, et al.: Muscle strength in the elderly: its relation to vitamin D metabolites. Arch Phys Med Rehabil 1999, 80:54–58.

    Article  PubMed  CAS  Google Scholar 

  29. Geusens P, Vandevyver C, Vanhoof J, et al.: Quadriceps and grip strength are related to vitamin D receptor genotype in elderly nonobese women. J Bone Miner Res 1997, 12:2082–2088.

    Article  PubMed  CAS  Google Scholar 

  30. Verhaar HJ, Samson MM, Jansen PA, et al.: Muscle strength, functional mobility and vitamin D in older women. Aging (Milano) 2000, 12:455–460.

    CAS  Google Scholar 

  31. Geusens P, Vanhoof J, Declerck K, Bruckers L: Effect of vitamin D supplements on bone density and muscle strength in elderly women. A double-blind, placebocontrolled study. 26th European Symposiumon Calcified Tissues, Maastricht 1999, 1–29.

  32. Gloth FM, III, Smith CE, Hollis BW, Tobin JD: Functional improvement with vitamin D replenishment in a cohort of frail, vitamin D-deficient older people. J Am Geriatr Soc 1995, 43:1269–1271.

    PubMed  CAS  Google Scholar 

  33. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al.: Effect of vitamin D on falls: a meta-analysis. JAMA 2004, 291:1999–2006. Vitamin D supplementation appears to reduce the risk for falls among ambulatory or institutionalized older individuals with stable health by more than 20%.

    Article  PubMed  CAS  Google Scholar 

  34. Reid IR: The roles of calcium and vitamin D in the prevention of osteoporosis. Endocrinol Metab Clin North Am 1998, 27:389–398.

    Article  PubMed  CAS  Google Scholar 

  35. Heaney RP: Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr 2003, 78:912–919.

    PubMed  CAS  Google Scholar 

  36. Parfitt AM: Osteomalacia and related disorders. In Metabolic bone disease and clinically related disorders, edn 3. Edited by Avioli LV, Krane SM. San Diego: Academic Press; 1998:329–387.

    Google Scholar 

  37. LeBoff MS, Kohlmeier L, Hurwitz S, et al.: Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA 1999, 281:1505–1511.

    Article  PubMed  CAS  Google Scholar 

  38. Dawson-Hughes B, Harris SS, Krall EA, et al.: Rates of bone loss in postmenopausal women randomly assigned to one of two dosages of vitamin D. Am J Clin Nutr 1995, 61:1140–1145.

    PubMed  CAS  Google Scholar 

  39. Reid IR: Therapy of osteoporosis: calcium, vitamin D, and exercise. Am J Med Sci 1996, 312:278–286.

    Article  PubMed  CAS  Google Scholar 

  40. de Sevaux RG, Hoitsma AJ, Corstens FH, Wetzels JF: Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study. J Am Soc Nephrol 2002, 13:1608–1614.

    Article  PubMed  CAS  Google Scholar 

  41. Lukert BP, Raisz LG: Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med 1990, 112:352–364.

    PubMed  CAS  Google Scholar 

  42. Johnson JA, Grande JP, Windebank AJ, Kumar R: 1,25-Dihydroxy-vitamin D(3) receptors in developing dorsal root ganglia of fetal rats. Brain Res Dev Brain Res 1996, 92:120–124.

    Article  PubMed  CAS  Google Scholar 

  43. Demay M: Muscle: a nontraditional 1,25-dihydroxyvitamin D target tissue exhibiting classic hormone-dependent vitamin D receptor actions. Endocrinology 2003, 144:5135–5137.

    Article  PubMed  CAS  Google Scholar 

  44. Posner GH: Low-calcemic vitamin D analogs (deltanoids) for human cancer prevention. J Nutr 2002, 132:3802S-3803S.

    PubMed  Google Scholar 

  45. Grant WB, Garland CF: Reviews: a critical review of studies on vitamin D in relation to colorectal cancer. Nutr Cancer 2004, 48:115–123.

    Article  PubMed  CAS  Google Scholar 

  46. Garland CF, Garland FC, Gorham ED: Calcium and vitamin D. Their potential roles in colon and breast cancer prevention. Ann N Y Acad Sci 1999, 889:107–119.

    Article  PubMed  CAS  Google Scholar 

  47. Cross HS, Kallay E, Farhan H, et al.: Regulation of extrarenal vitamin D metabolism as a tool for colon and prostate cancer prevention. Recent Results Cancer Res 2003, 164:413–425.

    PubMed  CAS  Google Scholar 

  48. Lieberman DA, Prindiville S, Weiss DG, Willett W: Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals. JAMA 2003, 290:2959–2967.

    Article  PubMed  Google Scholar 

  49. McCullough ML, Robertson AS, Rodriguez C, et al.: Calcium, vitamin D, dairy products, and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States). Cancer Causes Control 2003, 14:1–12.

    Article  PubMed  Google Scholar 

  50. Grant WB, Garland CF: Evidence supporting the role of vitamin D in reducing the risk of cancer. J Intern Med 2002, 252:178–179.

    Article  PubMed  Google Scholar 

  51. Grant WB: An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Cancer 2002, 94:272–281.

    Article  PubMed  Google Scholar 

  52. John EM, Schwartz GG, Dreon DM, Koo J: Vitamin D and breast cancer risk: the NHANES I Epidemiologic follow-up study, 1971–1975 to 1992. National Health and Nutrition Examination Survey. Cancer Epidemiol Biomarkers Prev 1999, 8:399–406.

    PubMed  CAS  Google Scholar 

  53. Shin MH, Holmes MD, Hankinson SE, et al.: Intake of dairy products, calcium, and vitamin d and risk of breast cancer. J Natl Cancer Inst 2002, 94:1301–1311.

    PubMed  CAS  Google Scholar 

  54. Blutt SE, Weigel NL: Vitamin D and prostate cancer. Proc Soc Exp Biol Med 1999, 221:89–98.

    Article  PubMed  CAS  Google Scholar 

  55. Young MV, Schwartz GG, Wang L, et al.: The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D. Carcinogenesis 2004, 25:967–971.

    Article  PubMed  CAS  Google Scholar 

  56. Gann PH, Ma J, Hennekens CH, et al.: Circulating vitamin D metabolites in relation to subsequent development of pros-tate cancer. Cancer Epidemiol Biomarkers Prev 1996, 5:121–126.

    PubMed  CAS  Google Scholar 

  57. Glerup H, Mikkelsen K, Poulsen L, et al.: Commonly recom-mended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Int Med 2000, 247:260–268.

    Article  CAS  Google Scholar 

  58. Plotnikoff GA, Quigley JM: Prevalence of severe hypovitamin-osis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc 2003, 78:1463–1470. In this cross-sectional study, 150 patients presented with persistent, nonspecific musculoskeletal pain to the Community University Health Care Center. Of the black, East African, Hispanic, and American Indian patients, 100% had deficient levels of vitamin D ????20 ng/mL). Of all patients, 93% had deficient levels of vitamin D. All patients with persistent, nonspecific musculoskeletal pain are at high risk for the consequences of unrecognized and untreated severe hypovitaminosis D.

    Article  PubMed  Google Scholar 

  59. Garcion E, Sindji L, Nataf S, et al.: Treatment of experimental autoimmune encephalomyelitis in rat by 1,25-dihydroxyvita-min D3 leads to early effects within the central nervous system. Acta Neuropathol (Berl) 2003, 105:438–448.

    CAS  Google Scholar 

  60. Garcion E, Wion-Barbot N, Montero-Menei CN, et al.: New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 2002, 13:100–105.

    Article  PubMed  CAS  Google Scholar 

  61. Ibi M, Sawada H, Nakanishi M, et al.: Protective effects of 1 alpha,25-(OH)(2)D(3) against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture. Neuropharmacology 2001, 40:761–771.

    Article  PubMed  CAS  Google Scholar 

  62. DeLuca HF, Cantorna MT: Vitamin D: its role and uses in immunology. FASEB J 2001, 15:2579–2585.

    Article  PubMed  CAS  Google Scholar 

  63. Hypponen E, Laara E, Reunanen A, et al.: Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001, 358:1500–1503.

    Article  PubMed  CAS  Google Scholar 

  64. Munger KL, Zhang SM, O’Reilly E, et al.: Vitamin D intake and incidence of multiple sclerosis. Neurology 2004, 62:60–65.

    PubMed  CAS  Google Scholar 

  65. Merlino LA, Curtis J, Mikuls TR, et al.: Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum 2004, 50:72–77.

    Article  PubMed  CAS  Google Scholar 

  66. Vieth R, Chan PC, MacFarlane GD: Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr 2001, 73:288–294.

    PubMed  CAS  Google Scholar 

  67. 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, 337:670–676.

    Article  PubMed  CAS  Google Scholar 

  68. Trivedi DP, Doll R, Khaw KT: Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortal-ity in men and women living in the community: randomised double blind controlled trial. BMJ 2003, 326:469.

    Article  PubMed  CAS  Google Scholar 

  69. Lips P, Graafmans WC, Ooms ME, et al.: Vitamin D supple-mentation and fracture incidence in elderly persons. A ran-domized, placebo-controlled clinical trial. Ann Intern Med 1996, 124:400–406.

    PubMed  CAS  Google Scholar 

  70. Gartner LM, Greer FR: Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. Pediatrics 2003, 111:908–910.

    Article  PubMed  Google Scholar 

  71. Holick MF, Matsuoka LY, Wortsman J: Age, vitamin D, and solar ultraviolet. Lancet 1989, 2:1104–1105.

    Article  PubMed  CAS  Google Scholar 

  72. van der Wielen RP, Lowik MR, van den Berg H, et al.: Serum vitamin D concentrations among elderly people in Europe. Lancet 1995, 346:207–210.

    Article  PubMed  Google Scholar 

  73. Chapuy MC, Schott AM, Garnero P, et al.: Healthy elderly French women living at home have secondary hyperparathy-roidism and high bone turnover in winter. EPIDOS Study Group. J Clin Endocrinol Metab 1996, 81:1129–1133.

    Article  PubMed  CAS  Google Scholar 

  74. Perry HM, III, Miller DK, Morley JE, et al.: A preliminary report of vitamin D and calcium metabolism in older African Americans. J Am Geriatr Soc 1993, 41:612–616.

    PubMed  Google Scholar 

  75. Allain TJ, Dhesi J: Hypovitaminosis D in older adults. Gerontology 2003, 49:273–278.

    Article  PubMed  CAS  Google Scholar 

  76. Sato Y, Asoh T, Oizumi K: High prevalence of vitamin D deficiency and reduced bone mass in elderly women with Alzheimer’s disease. Bone 1998, 23:555–557.

    Article  PubMed  CAS  Google Scholar 

  77. Sato Y, Kikuyama M, Oizumi K: High prevalence of vitamin D deficiency and reduced bone mass in Parkinson’s disease. Neurology 1997, 49:1273–1278.

    PubMed  CAS  Google Scholar 

  78. Dhesi JK, Moniz C, Close JC, et al.: A rationale for vitamin D prescribing in a falls clinic population. Ageing 2002, 31:267–271.

    Article  Google Scholar 

  79. Inderjeeth CA, Nicklason F, Al-Lahham Y, et al.: Vitamin D deficiency and secondary hyperparathyroidism: clinical and biochemical associations in older non-institutionalised Southern Tasmanians. Aust N Z J Med 2000, 30:209–214.

    PubMed  CAS  Google Scholar 

  80. Webb AR, Pilbeam C, Hanafin N, Holick MF: An evaluation of the relative contributions of exposure to sunlight and of diet to the circulating concentrations of 25-hydroxyvitamin D in an elderly nursing home population in Boston. Am J Clin Nutr 1990, 51:1075–1081.

    PubMed  CAS  Google Scholar 

  81. Nesby-O’Dell S, Scanlon KS, Cogswell ME, et al.: Hypovitamino-sis 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, 76:187–192.

    PubMed  CAS  Google Scholar 

  82. Lo CW, Paris PW, Clemens TL, et al.: Vitamin D absorption in healthy subjects and in patients with intestinal malabsorp-tion syndromes. Am J Clin Nutr 1985, 42:644–649.

    PubMed  CAS  Google Scholar 

  83. Holick MF: Vitamin D. In Modern Nutrition in Health and Disease, edn 9. Edited by Shils M, Olson J, Shike M, Ross AC. Baltimore: Williams and Wilkins; 1999.

    Google Scholar 

  84. Zittermann A: Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr 2003, 89:552–572.

    Article  PubMed  CAS  Google Scholar 

  85. Malabanan A, Veronikis IE, Holick MF: Redefining vitamin D insufficiency. Lancet 1998, 351:805–806.

    Article  PubMed  CAS  Google Scholar 

  86. Chapuy MC, Preziosi P, Maamer M, et al.: Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 1997, 7:439–443.

    Article  PubMed  CAS  Google Scholar 

  87. Thomas MK, Lloyd-Jones DM, Thadhani RI, et al.: Hypovita-minosis D in medical inpatients. N Engl J Med 1998, 338:777–783.

    Article  PubMed  CAS  Google Scholar 

  88. Heaney RP, Dowell MS, Hale CA, Bendich A: Calcium absorp-tion varies within the reference range for serum 25-hydroxy-vitamin D. J Am Coll Nutr 2003, 22:142–146.

    PubMed  CAS  Google Scholar 

  89. Tangpricha V, Koutkia P, Rieke SM, et al.: Fortification of orange juice with vitamin D: a novel approach for enhanc-ing vitamin D nutritional health. Am J Clin Nutr 2003, 77:1478–1483.

    PubMed  CAS  Google Scholar 

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Staud, R. Vitamin D: More than just affecting calcium and bone. Curr Rheumatol Rep 7, 356–364 (2005). https://doi.org/10.1007/s11926-005-0020-0

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