Vitamin D (Cholecalciferol)
Description
Vitamin D is a fat soluble vitamin. It includes a variety of molecules that all produce effects similar to the activity of “cholecalciferol”.
Cholecalciferol is naturally synthesized by the body following exposure of the skin to UV rays.
Function
Vitamin D plays a major role in calcium absorption and bone formation, as well as in the regulation of blood calcium levels and prevention of osteoporosis. It also plays a role in the production of insulin, in immune functions.
Deficiency
In children, deficiency may lead to rickets, which is secondary to demineralization of bones; in adults, it leads to a similar condition called osteomalacia.
Sources
Dietary sources include milk (in North America, vitamin D is added to milk), fish (especially cod liver oil, herring, kipper, mackerel, salmon), egg yolks.
Also widely found as a supplement, alone either in the form of tablet or capsule, or as part of a multivitamin preparation.
Toxicity
Excess intake may lead to hypercalcemia (manifested by fatigue, loss of appetite, headache, nausea and vomiting. In more advance cases hypercalcemia may lead to cardiac arrhythmia, hypertension, renal insufficiency, and weight loss.
There are known interaction with some anticonvulsant, cardiac and anti-hypertensive drugs.
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Scientific References
Books
PDR for Nutritional Supplements. Hendler SS, Rorvik DR, eds. Montvale: Medical Economics Company, Inc; 2001.
Sodium, chloride and potassium. Sheng H-W. In: Stipanuk M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Company; 2000:686-710.
Vitamin D. Norman AW. In: Bowman BA, Russell RM, eds. Present Knowledge in Nutrition. 8th ed. Washington, DC: ILSI Press; 2001:146-155.
Vitamin D. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Food and Nutrition Board, Institute of Medicine. Washington, D.C.: National Academies Press; 1999:250-287.
Scientific Articles
Vitamin D Recommended Intake and Insufficiency
Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. Vieth R. J Steroid Biochem Mol Biol. 2004;89-90(1-5):575-579.
[Abstract]
Fortification of orange juice with vitamin D: a novel approach for enhancing vitamin D nutritional health. Tangpricha V, Koutkia P, Rieke SM, Chen TC, Perez AA, Holick MF. Am J Clin Nutr. 2003;77(6):1478-1483.
[Abstract]
Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. Glerup H, Mikkelsen K, Poulsen L, et al. J Intern Med. 2000;247(2):260-268.
[Abstract]
Vitamin D insufficiency and hyperparathyroidism in a low income, multiracial, elderly population. Harris SS, Soteriades E, Coolidge JA, Mudgal S, Dawson-Hughes B. J Clin Endocrinol Metab. 2000;85(11):4125-4130.
[Abstract]
Hypovitaminosis D in older adults. Allain TJ, Dhesi J. Gerontology. 2003;49(5):273-278.
[Abstract]
Hypovitaminosis D and vitamin D deficiency in exclusively breast-feeding infants and their mothers in summer: a justification for vitamin D supplementation of breast-feeding infants. Dawodu A, Agarwal M, Hossain M, Kochiyil J, Zayed R. J Pediatr. 2003;142(2):169-173.
[Abstract]
Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Am J Clin Nutr. 2006;84(1):18-28.
[Abstract]
Long-latency deficiency disease: insights from calcium and vitamin D. Heaney RP. Am J Clin Nutr. 2003;78(5):912-919.
[Abstract]
Vitamin D in preventive medicine: are we ignoring the evidence? Zittermann A. Br J Nutr. 2003;89(5):552-572.
[Abstract]
Rickets. Wharton B, Bishop N. Lancet. 2003;362(9393):1389-1400.
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Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Wagner CL, Greer FR, and the Section on Breastfeeding and Committee on Nutrition. American Academy of Pediatrics. 2008;122(5):1142-1152.
Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Plotnikoff GA, Quigley JM. Mayo Clin Proc. 2003;78(12):1463-1470.
[Abstract]
Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Nesby-O'Dell S, Scanlon KS, Cogswell ME, et al. Am J Clin Nutr. 2002;76(1):187-192.
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Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab. Arunabh S, Pollack S, Yeh J, Aloia JF. 2003;88(1):157-161.
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Redefining vitamin D insufficiency. Malabanan A, Veronikis IE, Holick MF. Lancet. 1998;351(9105):805-806.
Prevalence of vitamin D insufficiency in an adult normal population. Chapuy MC, Preziosi P, Maamer M, et al. Osteoporos Int. 1997;7(5):439-443.
[Abstract]
Hypovitaminosis D in medical inpatients. Thomas MK, Lloyd-Jones DM, Thadhani RI, et al. N Engl J Med. 1998;338(12):777-783.
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Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. Heaney RP, Dowell MS, Hale CA, Bendich A. J Am Coll Nutr. 2003;22(2):142-146.
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Vitamin D deficiency: what a pain it is. Holick MF. Mayo Clin Proc. 2003; 78(12):1457-1459.
Vitamin D deficiency. Holick MF. N Engl J Med. 2007;357(3):266-281.
[Abstract]
Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Vieth R. Am J Clin Nutr. 1999;69(5):842-856.
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Vitamin D: how much do we need, and how much is too much? Heaney RP. Osteoporos Int. 2000;11(7):553-555.
Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin. Hollis BW. D. J Nutr. 2005;135(2):317-322.
[Abstract]
Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Am J Clin Nutr. 68(4):854-858.
[Abstract]
Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Am J Clin Nutr. 2003;77(1):204-210.
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Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Vieth R, Chan PC, MacFarlane GD. Am J Clin Nutr. 2001;73(2):288-294.
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Vitamin D - General Aspects
Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Holick MF. Am J Clin Nutr. 2004;79(3):362-371.
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Overview of general physiologic features and functions of vitamin D. DeLuca HF. Am J Clin Nutr. 2004;80(6 Suppl):1689S-1696S.
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The pleiotropic actions of vitamin D. Lin R, White JH. Bioessays. 2004;26(1):21-28.
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Vitamin D2 is much less effective than vitamin D3 in humans. Armas LA, Hollis BW, Heaney RP. J Clin Endocrinol Metab. 2004;89(11):5387-5391.
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Vitamin D: A millenium perspective. Holick MF. J Cell Biochem. 2003;88(2):296-307.
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Vitamin D: more than a "bone-a-fide" hormone. Sutton AL, MacDonald PN. Mol Endocrinol. 2003;17(5):777-791.
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Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Holick MF. Curr Opin Endocrinol Diabetes. 2002;9(1):87-98.
Vitamin D and Cardio-Vascular Diseases
Effect of winter oral vitamin D3 supplementation on cardiovascular risk factors in elderly adults. Scragg R, Khaw KT, Murphy S. Eur J Clin Nutr. 1995;49(9):640-646.
[Abstract]
Ultraviolet light may contribute to geographic and racial blood pressure differences. Rostand SG. Hypertension. 1997;30(2 Pt 1):150-156.
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Ultraviolet B and blood pressure. Krause R, Buhring M, Hopfenmuller W, Holick MF, Sharma AM. Lancet. 1998;352(9129):709-710.
Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. Pfeifer M, Begerow B, Minne HW, Nachtigall D, Hansen C. J Clin Endocrinol Metab. 2001;86(4):1633-1637.
[Abstract]
No significant effect of calcium and vitamin D supplementation on blood pressure and calcium metabolism in elderly Chinese. Pan WH, Wang CY, Li LA, Kao LS, Yeh SH. Chin J Physiol. 1993;36(2):85-94.
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Regulation of renin expression and blood pressure by vitamin D(3). Sigmund CD. J Clin Invest. 2002;110(2):155-156.
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1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. J Clin Invest. 2002;110(2):229-238.
[Abstract]
Vitamin D and Cancer
Vitamin D and vitamin D analogs as cancer chemopreventive agents. Guyton KZ, Kensler TW, Posner GH. Nutr Rev. 2003;61(7):227-238.
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Vitamin D and prostate cancer. Blutt SE, Weigel NL. Proc Soc Exp Biol Med. 1999;221(2):89-98.
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Calcium and vitamin D. Their potential roles in colon and breast cancer prevention. Garland CF, Garland FC, Gorham ED. Ann N Y Acad Sci. 1999;889:107-119.
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Dietary calcium and vitamin D intake and risk of colorectal cancer: a prospective cohort study in women. Terry P, Baron JA, Bergkvist L, Holmberg L, Wolk A. Nutr Cancer. 2002;43(1):39-46.
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Calcium, vitamin D, and the occurrence of colorectal cancer among women. Martinez ME, Giovannucci EL, Colditz GA, et al. J Natl Cancer Inst. 1996;88(19):1375-1382.
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Calcium, vitamin D, and dairy foods and the occurrence of colon cancer in men. Kearney J, Giovannucci E, Rimm EB, et al. Am J Epidemiol. 1996;143(9):907-917.
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Relation of calcium, vitamin D, and dairy food intake to incidence of colon cancer among older women. The Iowa Women's Health Study. Bostick RM, Potter JD, Sellers TA, McKenzie DR, Kushi LH, Folsom AR. Am J Epidemiol. 1993;137(12):1302-1317.
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Calcium, vitamin D, dairy products, and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States). McCullough ML, Robertson AS, Rodriguez C, et al. Cancer Causes Control. 2003;14(1):1-12.
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Vitamin D, calcium, and vitamin D receptor polymorphism in colorectal adenomas. Peters U, McGlynn KA, Chatterjee N, et al. Cancer Epidemiol Biomarkers Prev. 2001;10(12):1267-1274.
[Abstract]
Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D. Holt PR, Arber N, Halmos B, et al. Cancer Epidemiol Biomarkers Prev. 2002;11(1):113-119.
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Plasma vitamin D metabolites and risk of colorectal cancer in women. Feskanich D, Ma J, Fuchs CS, et al. Cancer Epidemiol Biomarkers Prev. 2004;13(9):1502-1508.
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Calcium plus vitamin D supplementation and the risk of colorectal cancer. Wactawski-Wende J, Kotchen JM, Anderson GL, et al. N Engl J Med. 2006;354(7):684-696.
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Calcium plus vitamin D and the risk of colorectal cancer. Holick MF. N Engl J Med. 2006;354(21):2287-2288; author reply 2287-2288.
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Vitamin D and prevention of colorectal cancer. Gorham ED, Garland CF, Garland FC, et al. J Steroid Biochem Mol Biol. 2005;97(1-2):179-194.
[Abstract]
An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Grant WB. Cancer. 2002;94(1):272-281.
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Vitamin D and breast cancer risk: the NHANES I Epidemiologic follow-up study, 1971-1975 to 1992. National Health and Nutrition Examination Survey. John EM, Schwartz GG, Dreon DM, Koo J. Cancer Epidemiol Biomarkers Prev. 1999;8(5):399-406.
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Intake of dairy products, calcium, and vitamin d and risk of breast cancer. Shin MH, Holmes MD, Hankinson SE, Wu K, Colditz GA, Willett WC. J Natl Cancer Inst. 2002;94(17):1301-1311.
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Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. Lowe LC, Guy M, Mansi JL, et al. Eur J Cancer. 2005;41(8):1164-1169.
[Abstract]
Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Bertone-Johnson ER, Chen WY, Holick MF, et al. Cancer Epidemiol Biomarkers Prev. 2005;14(8):1991-1997.
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Vitamin D and prevention of breast cancer: pooled analysis. Garland CF, Gorham ED, Mohr SB, et al. J Steroid Biochem Mol Biol. 2007;103(3-5):708-711.
[Abstract]
The prostate 25-hydroxyvitamin D-1{alpha}-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D. Young MV, Schwartz GG, Wang L, et al. Carcinogenesis. 2004;25(6):967-71
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Vitamin D and prostate cancer: a prediagnostic study with stored sera. Corder EH, Guess HA, Hulka BS, et al. Cancer Epidemiol Biomarkers Prev. 1993;2(5):467-472.
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Prostate cancer and prediagnostic levels of serum vitamin D metabolites (Maryland, United States). Braun MM, Helzlsouer KJ, Hollis BW, Comstock GW. Cancer Causes Control. 1995;6(3):235-239.
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Serum vitamin D metabolite levels and the subsequent development of prostate cancer (Hawaii, United States). Nomura AM, Stemmermann GN, Lee J, et al. Cancer Causes Control. 1998;9(4):425-432.
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Circulating vitamin D metabolites in relation to subsequent development of prostate cancer. Gann PH, Ma J, Hennekens CH, Hollis BW, Haddad JG, Stampfer MJ. Cancer Epidemiol Biomarkers Prev. 1996;5(2):121-126.
[Abstract]
Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels. (Finland). Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P. Cancer Causes Control. 2000;11(9):847-852.
[Abstract]
Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Tuohimaa P, Tenkanen L, Ahonen M, et al. Int J Cancer. 2004;108(1):104-108.
[Abstract]
Vitamin D and Diabetes
The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R. Int J Clin Pract. 2003;57(4):258-261.
[Abstract]
Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus. Orwoll E, Riddle M, Prince M. Am J Clin Nutr. 1994;59(5):1083-1087.
[Abstract]
Effect of 1 alpha (OH)-vitamin D3 on insulin secretion in diabetes mellitus. Inomata S, Kadowaki S, Yamatani T, Fukase M, Fujita T. Bone Miner. 1986;1(3):187-192.
[Abstract]
Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Lancet. 2001;358(9292):1500-1503.
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Vitamin D and the Immune System
Vitamin D: its role and uses in immunology. Deluca HF, Cantorna MT. FASEB J. 2001;15(14):2579-2585.
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Vitamin D and its analogs as regulators of immune activation and antigen presentation. Griffin MD, Xing N, Kumar R. Annu Rev Nutr. 2003;23:117-145.
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The immunological functions of the vitamin D endocrine system. Hayes CE, Nashold FE, Spach KM, Pedersen LB. Cell Mol Biol. 2003;49(2):277-300.
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Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study. Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG. Arthritis Rheum. 2004;50(1):72-77.
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Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. Zeitz U, Weber K, Soegiarto DW, Wolf E, Balling R, Erben RG. FASEB J. 2003;17(3):509-511.
[Abstract]
Vitamin D and Multiple Sclerosis
Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. JAMA. 2006;296(23):2832-2838.
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Vitamin D intake and incidence of multiple sclerosis. Munger KL, Zhang SM, O'Reilly E, et al. Neurology. 2004;62(1):60-65.
[Abstract]
Vitamin D and Risk of Fractures
Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. JAMA. 2005;293(18):2257-2264.
[Abstract]
Calcium plus vitamin D supplementation and the risk of fractures. Jackson RD, LaCroix AZ, Gass M, et al. N Engl J Med. 2006;354(7):669-683.
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Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. Bischoff HA, Stahelin HB, Dick W, et al. J Bone Miner Res. 2003;18(2):343-351.
[Abstract]
A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. J Am Geriatr Soc. 2007;55(2):234-239.
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Vitamin D status, parathyroid hormone and bone mineral density in patients with inflammatory bowel disease. Jahnsen J, Falch JA, Mowinckel P, Aadland E. Scand J Gastroenterol. 2002;37(2):192-199.
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The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. Lips P, Hosking D, Lippuner K, et al. J Intern Med. 2006;260(3):245-254.
[Abstract]
Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Lips P. Endocr Rev. 2001;22(4):477-501.
[Abstract]
Calcium, vitamin D, milk consumption, and hip fractures: a prospective study among postmenopausal women. Feskanich D, Willett WC, Colditz GA. Am J Clin Nutr. 2003;77(2):504-511.
[Abstract]
Rates of bone loss in postmenopausal women randomly assigned to one of two dosages of vitamin D. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE, Falconer G, Green CL. Am J Clin Nutr. 1995;61(5):1140-1145.
[Abstract]
Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. N Engl J Med. 1997;337(10):670-676.
[Abstract]
Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Am J Clin Nutr. 2000;72(3):745-750.
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Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. Chapuy MC, Arlot ME, Delmas PD, Meunier PJ. BMJ. 1994;308(6936):1081-1082.
Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. Trivedi DP, Doll R, Khaw KT. Effect BMJ. 2003;326(7387):469-474.
[Abstract]
Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM. Ann Intern Med. 1996;124(4):400-406.
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Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Grant AM, Avenell A, Campbell MK, et al. Lancet. 2005;365(9471):1621-1628.
[Abstract]
