Vitamin D

From Anvita Health Wiki

Contents 1 More Specific Terms 2 Introduction 3 Indications 4 Contraindications 5 Dosage 6 Adverse-effects 7 Laboratory 8 Mechanism-of-action 9 Notes 10 More General Terms 11 Additional Terms 12 References

More Specific Terms

• calcipotriene; calcipotriol (Dovonex, Dovobet)
• cholecalciferol; vitamin D3
• dihydrotachysterol; DHT, (Hytakerol, Dichystrolum, Antitanil)
• doxercalciferol (Hectorol)
• ergocalciferol (vitamin D2, Drisdol)

Introduction

• Recommended daily allowance ( RDA):
• 400 IU (10 ug) infants [40]

• older recommendation of 200 IU (5 ug)/day (infants)* [2]

• 600 IU (15 ug) (children & adults) Institute of Medicine [40]
• 800 IU (20 ug) (elderly)

• 600 IU (15 ug) appears to be adequate for elderly white women [49]

• 800-2000 (20-50 ug) IU (adults) [11,40]
  *Breast milk does NOT contain sufficient vitamin D; supplementation recommended [2]; use children's multivitamin

Indications

• hypocalcemia
• prevention & treatment of osteoporosis

• in combination with Ca+2 supplementation
• diminishes risk of vertebral & hip fractures at dose of 800 IU (20 ug)/day [4,44]

• fall prevention in the elderly [2,14]

• via increased muscle strength
• also increases muscle strength in adolescent girls
• benefit may be restricted to vitamin D deficient elderly women also supplemented with calcium [43]
• doses of > 800 IU (20 ug) /day may be needed for benefit [43]

• risk reduction of multiple sclerosis [7]
• reduction in all cause mortality [23]
• studies on vitamin D, calcium, or both & health outcomes are inconsistent [30,31]

Contraindications

• does not diminish risk of hypertension [10]
• does not improve diffuse musculoskeletal pain [26]
• no effect on wintertime respiratory tract infections [38]
• no clear evidence that vitamin D supplementation prevents cardiovascular disease [44]

• cardiovascular risk reduction ? [23,24,28]

• conflicting findings on whether vitamin D might decrease (or even increase) the risk for cancer [44,]

• lymphoma, prostate cancer?, lung cancer, skin cancer colon cancer (& colorectal adenomatous polyps) [8]
• breast cancer [25]
• relative risk 43% in post- menopausal women with 1100 IU (27.5 ug)/day vitamin D3 [15]
• neither vitamin D nor calcium supplements affect cancer incidence or mortality or overall mortality [45]

Dosage

• hypocalcemia:

• requires weeks to achieve full effect
• 50,000 IU (1250 ug) PO QD (initially)
• 50,000-100,000 (1250-2500 ug) IU PO QD (maintenance)
• dose may be increased at 4-6 week intervals

• osteoporosis, fracture & fall prevention:

• 800 IU (20 ug) QD [2,3,4]
• 2000 IU (50 ug) QD for prevention of hospital re-admission after hip fracture in women with vitamin D deficiency [41]
• 500,000 IU (12.5 mg) PO given to women annually paradoxically increases risk of fracture [33]

• vitamin D deficiency:

• 50,000 IU (1.25 mg) weekly for 6-12 weeks [36]

• toxicity

• risk begins at doses above 4000 IU/day
• doses > 10,000 IU (250 ug)/day associated with kidney damage [40]
• may occur at doses of 50,000 (1.25 mg) IU/day for several months in adults [36]

Adverse-effects

• hypercalcemia

• may take over 2 months to resolve
• symptomatic hypercalcemia due to vitamin D should be treated with prednisone

• corneal opacification

Laboratory

• serum 25-OH vitamin D provides best indicator of total body vitamin D status

Mechanism-of-action

• precursor to calcitriol
• reduces production of renin [6]
• stimulate production of insulin [6]
• vitamin D2 & vitamin D3 equally effective in raising serum levels of 25-OH vitamin D [16]
• upregulates genes to induce Toll-like receptor-2 (TLR-2) on keratinocytes & increases expression of antimicrobial peptides such as cathelicidin; effects may be mediated through activation of SRC3 [27]

Notes

• vitamin D production from exposure to sunlight varies by age, Fitzpatrick skin type, geographic location, season & time of day [35]

• fair-skin persons produce more vitamin D than dark-skin persons
• exposure to 1 hour of bright sunlight can generate production of 20,000 IU (500 ug) of vitamin D in a fair-skin person at southern lattitudes &/or summer months
• north of the sun-belt, it is difficult to obtain sufficient sunlight exposure during the winter to produce the RDA of vitamin D [35]

• vitamin D should be obtained through foods, beverages, & supplements, not through unprotected exposure to sunlight [18]
• most Americans get enough vitamin S [40]
• medications that adversely affect vitamin D status include phenobarbital, phenytoin, carbamazepine, rifampicin, & antiretroviral
• activated macrophages in granulomatous diseases in the setting of renal failure can cause extrarenal metabolism of vitamin D, resulting in hypercalcemia
• higher serum 25-hydroxyvitamin D levels associated with better cognitive function in adults

• this does not seem to be apparent in adolescents [47]
• low serum 25-hydroxyvitamin D is associated with cognitive decline [37]
• low serum 25-hydroxyvitamin D is associated increased risk of Parkinson's disease [48]

More General Terms

• vitamin
• sterol
• endocrine agent

Additional Terms

• 25-hydroxyvitamin D2/D3 (calcidiol/calcifediol) in serum
• calcifediol; 25-OH cholcalciferol; 25-OH vitamin D3 (Calderol)
• calcitriol; 1,25-dihydroxycholcalciferol; 1,25-dihydroxyvitamin D3
• hypervitaminosis D
• vitamin D deficiency

References

1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 472, 495-496
2. Prescriber's Letter 10(5):29 2003 Journal Watch 24(11):87, 2004 Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB. Effect of Vitamin D on falls: a meta-analysis. JAMA. 2004 Apr 28;291(16):1999-2006. Review. PMID: [1]
3. Prescriber's Letter 11(7):32 2004 Detail-Document#: [2] (subscription needed) [3]
4. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005 May 11;293(18):2257-64. Review. PMID: [4]
5. Netscape News cites: (05/22/05) Giovannucci E Department of Nutrition, Harvard School of Public Health, Boston, Mass 02115 at the American Association for Cancer Research meeting in Anaheim, Calif.
6. Netscape News cites: (12/24/05) Michael F. Holick, PhD, MD, Vitamin D, Skin, and Bone Research Laboratory, Boston University School of Medicine.
7. VanAmerongen BM, Dijkstra CD, Lips P, Polman CH. Multiple sclerosis and vitamin D: an update. Eur J Clin Nutr. 2004 Aug;58(8):1095-109. Review. PMID: [5]
   - Munger KL, Zhang SM, O'Reilly E, Hernan MA, Olek MJ, Willett WC, Ascherio A. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004 Jan 13;62(1):60-5. PMID: [6]
8. Hartman TJ, Albert PS, Snyder K, Slattery ML, Caan B, Paskett E, Iber F, Kikendall JW, Marshall J, Shike M, Weissfeld J, Brewer B, Schatzkin A, Lanza E; Polyp Prevention Study Group. The association of calcium and vitamin D with risk of colorectal adenomas. J Nutr. 2005 Feb;135(2):252-9. PMID: [7]
   - Harris DM, Go VL. Vitamin D and colon carcinogenesis. J Nutr. 2004 Dec;134(12 Suppl):3463S-3471S. Review. PMID: [8]
9. Holick MF. Vitamin D: important for prevention of osteoporosis, cardiovascular heart disease, type 1 diabetes, autoimmune diseases, and some cancers. South Med J. 2005 Oct;98(10):1024-7. Review. PMID: [9]
10. Forman JP, Bischoff-Ferrari HA, Willett WC, Stampfer MJ, Curhan GC. Vitamin D intake and risk of incident hypertension: results from three large prospective cohort studies. Hypertension. 2005 Oct;46(4):676-82. Epub 2005 Sep 6. PMID: [10]
11. Internal Medicine World Report Dec 2005 cites Willet W, Chairman, Department of Nutrition, Harvard School of Public Health, at the annual meeting of the American Society of Nephrology
12. Gorham ED, Garland CF, Garland FC, Grant WB, Mohr SB, Lipkin M, Newmark HL, Giovannucci E, Wei M, Holick MF. Vitamin D and prevention of colorectal cancer. J Steroid Biochem Mol Biol. 2005 Oct;97(1-2):179-94. Epub 2005 Oct 19. PMID: [11]
    - Giovannucci E. The epidemiology of vitamin D and colorectal cancer: recent findings. Curr Opin Gastroenterol. 2006 Jan;22(1):24-9. Review. PMID: [12]
13. Prescriber's Letter 14(3): 2007 Calcium and Vitamin D Supplementation: Who Needs It? Detail-Document#: [13] (subscription needed) [14]
14. Wicherts IS et al, Vitamin D status predicts physical performance and its decline in older persons. J Clin Endocrinol Metabol 2007, 92:2058 PMID: [15]
15. Prescriber's Letter 14(7): 2007 Vitamin D and Calcium: Not Just for Bones Anymore Detail-Document#: [16] (subscription needed) [17]
    - Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R, Felsenfeld A, Levine B, Mehrotra R, Norris K. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2007 Jun 11;167(11):1159-65. PMID: [18]
    - Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007 Jun;85(6):1586-91. PMID: [19]
16. Holick MF et al, Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab 2008, 93:667 PMID: [20]
17. Prescriber's Letter 15(11): 2008 New Guidelines for Vitamin D Intake in Infants and Children Detail-Document#: [21] (subscription needed) [22]
    - Wagner CL et al, Prevention of rickets and vitamin d deficiency in infants, children, and adolescents. Pediatrics. 2008 Nov;122(5):1142-52. PMID: [23]
18. Ward KA et al Vitamin D status and muscle function in post-menarchal adolescent girls. J Clin Endocrinol Metab 2009 Feb; 94:559. PMID: [24]
19. American Academy of Dermatology Position statement on vitamin D, 11/01/2008 [25]
20. Prescriber's Letter 16(5): 2009 Vitamin D Dosing Detail-Document#: [26] (subscription needed) [27]
21. Orwoll E et al. Vitamin D deficiency in older men. J Clin Endocrinol Metab 2009 Apr; 94:1214. PMID: [28]
22. Jacobs ET et al. Vitamin D insufficiency in southern Arizona. Am J Clin Nutr 2008 Mar; 87:608. PMID: [29]
23. Dobnig H et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med 2008 Jun 23; 168:1340. PMID: [30]
24. Giovannucci E et 25-Hydroxyvitamin D and Risk of Myocardial Infarction in Men. A Prospective Study. Arch Intern Med. 2008;168(11):1174-1180. PMID: [31]
25. Blackmore KM et al. Vitamin D from dietary intake and sunlight exposure and the risk of hormone-receptor-defined breast cancer. Am J Epidemiol 2008 Oct 15; 168:915. PMID: [32]
26. Hicks GE et al Associations between vitamin D status and pain in older adults: The Invecchiare in Chianti Study. J Am Geriatr Soc 2008 May; 56:785 PMID: [33]
    - Warner AE and Arnspiger SA. Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D. J Clin Rheumatol 2008 Feb; 14:12. PMID: [34]
27. Schauber J et al. Histone acetylation in keratinocytes enables control of the expression of cathelicidin and CD14 by 1,25-dihydroxyvitamin D3. J Invest Dermatol 2008 Apr; 128:816 PMID: [35]
    - Segaert S. Vitamin D regulation of cathelicidin in the skin: Toward a renaissance of vitamin D in dermatology? J Invest Dermatol 2008 Apr; 128:773. PMID: [36]
28. Wang TJ et al Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008 Jan 29;117(4):503-11. Epub 2008 Jan 7. <PubMed> PMID: [37] <Internet> [38]
    - Wang L et al. Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med 2010 Mar 2; 152:315. PMID: [39]
    - Guallar E et al. Vitamin D supplementation in the age of lost innocence. Ann Intern Med 2010 Mar 2; 152:327 PMID: [40]
29. Ginde AA et al Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med 2009 Mar 23; 169:626. PMID: [41]
30. AHRQ: Agency for Healthcare Research and Quality Vitamin D and Calcium: Systematic Review of Health Outcomes [42]
31. Annweiler C et al Vitamin D-Related Changes in Physical Performance: A Systematic Review. J Nutr Health Aging. 2009;13(10):893-898. PMID: [43]
32. Prescriber's Letter 17(1): 2010 Vitamin D in the Pediatric Population COMMENTARY: Vitamin D in the Pediatric Population GUIDELINES: AAP Guidelines on Prevention of Rickets and Vitamin D Deficiency GUIDELINES: CPS Guidelines for Vitamin D Supplementation: Recommendations for Canadian Mothers and Infants Detail-Document#: [44] (subscription needed) [45]
33. Medical Knowledge Self Assessment Program (MKSAP) 15, American College of Physicians, Philadelphia 2009
34. Sanders KM et al. Annual high-dose oral vitamin D and falls and fractures in older women: A randomized controlled trial. JAMA 2010 May 12; 303:1815. PMID: [46]
35. Terushkin V et al. Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes. J Am Acad Dermatol 2010 Jun; 62:929.e1. PMID: [47]
    - Tsiaras WG and Weinstock MA. Ultraviolet irradiation and oral ingestion as sources of optimal vitamin D. J Am Acad Dermatol 2010 Jun; 62:935. PMID: [48]
36. Prescriber's Letter 17(7): 2010 Vitamin D Dosing: An Update Detail-Document#: [49] (subscription needed) [50]
37. Llewellyn DJ et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med 2010 Jul 12; 170:1135. PMID: [51]
    - Grey A et al. A place in the sun? Arch Intern Med 2010 Jul 12; 170:1099. PMID: [52]
38. Laaksi I et al. Vitamin D supplementation for the prevention of acute respiratory tract infection: A randomized, double-blinded trial among young Finnish men. J Infect Dis 2010 Sep 1; 202:809. PMID: [53]
39. Cawthon PM et al. Serum 25-hydroxyvitamin D, parathyroid hormone, and mortality in older men. J Clin Endocrinol Metab 2010 Oct; 95:4625 PMID: [54]
40. Institute of Medicine, 11/30/2010 Dietary Reference Intakes for Calcium and Vitamin D [55]
    - Prescriber's Letter 18(1): 2011 COMMENTARY: Calcium and Vitamin D Supplementation: Who Needs It? COMMENTARY: Vitamin D Dosing: An Update PATIENT HANDOUT: Calcium and Vitamin D GUIDELINES: Dietary Reference Intakes for Calcium and Vitamin D Detail-Document#: [56] (subscription needed) [57]
41. Bischoff-Ferrari HA, Dawson-Hughes B, Platz A, et al. Effect of high-dosage cholecalciferol and extended physiotherapy on complications after hip fracture: A randomized controlled trial. Arch Intern Med 2010; 170(9):813-820 PMID: [58]
42. Tsiaras WG and Weinstock MA. Factors influencing vitamin D status. Acta Derm Venereol 2011 Mar; 91:115. PMID: [59]
43. Murad MH et al. The effect of vitamin D on falls: A systematic review and meta-analysis. J Clin Endocrinol Metab 2011 Oct; 96:2997. PMID: [60]
44. Chung M et al Vitamin D With or Without Calcium Supplementation for Prevention of Cancer and Fractures: An Updated Meta-analysis for the U.S. Preventive Services Task Force Annals of Internal Medicine, Dec 20, 2011 155(12)827-838 <PubMed> PMID: [61] <Internet> [62]
    - McGreevy C and Williams D New Insights About Vitamin D and Cardiovascular Disease A Narrative Review Annals of Internal Medicine, Dec 20, 2011 155(12)820-826 <PubMed> PMID: [63] <Internet> [64]
45. Avenell A et al. Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D3 and/or calcium (RECORD Trial). J Clin Endocrinol Metab 2012 Feb; 97:614. PMID: [65]
46. Wikipedia: Vitamin D [66]
47. Tolppanen AM et al Association of serum 25-hydroxyvitamin D3 and D2 with academic performance in childhood: findings from a prospective birth cohort J Epidemiol Community Health doi:10.1136/jech-2011-200114 <PubMed> PMID: [67] <Internet> [68]
48. Knekt P et al Serum Vitamin D and the Risk of Parkinson Disease Arch Neurol. 2010;67(7):808-811 <PubMed> PMID: [69] <Internet> [70]
49. Gallagher JC et al. Dose response to vitamin D supplementation in postmenopausal women: A randomized trial. Ann Intern Med 2012 Mar 20; 156:425 PMID: [71]
50. National Guideline Clearinghouse Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. American Academy of Pediatrics ngc-guideline: [72]

vitamin D