Vitamin D

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Vitamin D is a steroid and is vitamin that "includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone."[1]

Vitamin D serves two classes of functions: (a) an endocrine function, in which a form of vitamin D, calcitriol, produced in the kidneys and secreted into the bloodstream, acts on target organs (gastrointestinal tract, bone, parathyroid glands) in such a way as to regulate aspects of calcium and phosphorus metabolism important to bone health and homeostasis of circulating calcium and phosphorus concentrations; and, (b) an autocrine function, in which the cells of numerous organs and tissues in the body (e.g., parts of the immune system, various epithelial tissues) generate calcitriol that functions in the cells that generate it, in intracellular signaling pathways (e.g., facilitation of the expression of specific genes) important to optimal functioning of those cells.[2] The autocrine mechanisms account for the preponderance of vitamin D utilized by body each day, and therefore tends to set the daily requirement for vitamin D.[2]

Biochemistry

Ergocalciferols (vitamin D2) is formed in plants. Ergocalciferols are "derivatives of ergosterol formed by ultraviolet rays breaking of the C9-C10 bond. They differ from cholecalciferol in having a double bond between C22 and C23 and a methyl group at C24."[3]

Cholecalciferol (vitamin D3) is formed in the skin of animals from 7-dehydrocholesterol by sunlight. Cholecalciferol is a "derivative of 7-dehydroxycholesterol formed by ultraviolet rays breaking of the C9-C10 bond. It differs from ergocalciferol in having a single bond between C22 and C23 and lacking a methyl group at C24."[4]

Vitamin D2 and vitamin D3 are of equal potency.[5]

Vitamin D2 and vitamin D3 are hydroxylated in the liver at the 25 position.[5] This leads to calcitriol (1,25-Dihydroxyvitamin D3). Calcitriol is the "physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption."[6]

Deficiency

Recommended serum levels are 20 ng/mL (50 nmol/L) according to the Institute of Medicine[7] and 30 ng/mL (75 nmol/L) according to the International Osteoporosis Foundation and National Osteoporosis Foundation.[8]

Low levels of vitamin D are common in medical inpatients[9] and some populations of patients with widespread musculoskeletal pain like fibromyalgia[10].[11] However, more recent studies make the associated between Vitamin D and non-specific pain doubtful.[12][12]

About a quarter of older adults have levels below 20 ng/mL.[13]

The best test is assay of serum 25-hydroxyvitamin D (25-OHD) and the best treatment may be calciferol (ergocalciferol or colecalciferol).[14]

Administration

In health adults, Vitamin D2 and vitamin D3 are equally effective in maintaining serum 25-hydroxyvitamin D levels.[15]

Clinical uses

Cancer prevention

A secondary analysis of a randomized controlled trial originally designed to study fractures suggests that cholecalciferol (vitamin D3) combined with calcium may reduce risk of cancer.[16] They reported that 1100 IU of vitamin D (cholecalciferol) combined with 1500 mg of calcium per day administered for four years greatly reduced the risk for new cancers compared with placebo controls (p < 0.005). They also noted that the concentrations of serum 25-hydroxy-vitamin D (25[OH]D) levels, both pre-treatment and during treatment independently predicted cancer risk. The treatment group achieved mean concentrations of serum 25-hydroxy-vitamin D (25[OH]D) of 96 nmol/L (38 ng/ml). Natural levels for people who live and work in the sun: ~50-70 ng/ml (~125-175 nmol/L). [17]

A randomized controlled trial found no benefit on cancer prevention.[18]

Cognition

Vitamin D may help cognition.[19]

Diabetes mellitus type 2

Vitamin D supplementation does not appear to prevent diabetes mellitus type 2.[20]

Secondary hyperparathyroidism

Vitamin D can lower levels of parathyroid hormone in patients with secondary hyperparathryoidism from chronic kidney disease.[21]

Vascular disease prevention

Vitamin D may help prevent vascular disease.[22]

References

  1. ↑ Anonymous (2024), Vitamin D (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. ↑ 2.0 2.1 Heaney RP. (2008) 10.2215/CJN.01160308 Vitamin D in Health and Disease. Clin. J. Am. Soc. Nephrol. (first published online June 4, 2008)
  3. ↑ Anonymous (2024), Ergocalciferols (English). Medical Subject Headings. U.S. National Library of Medicine.
  4. ↑ Anonymous (2024), Cholecalciferol (English). Medical Subject Headings. U.S. National Library of Medicine.
  5. ↑ 5.0 5.1 Harper, Harold W.; Murray, Robert F. (2000). “Structure and Function of the Lipid-Soluble Vitamins”, Harper's Biochemistry. Norwalk, CT: Appleton & Lange, 645. ISBN 0-8385-3684-0. 
  6. ↑ Anonymous (2024), Calcitriol (English). Medical Subject Headings. U.S. National Library of Medicine.
  7. ↑ Committee to Review Dietary References Intakes for Vitamin D and Calcium. Ross AC et al., editors. (2010) Dietary References Intakes for Calcium and Vitamin D. Institute of Medicine.
  8. ↑ Dawson-Hughes B, Mithal A, Bonjour JP, Boonen S, Burckhardt P, Fuleihan GE et al. (2010). "IOF position statement: vitamin D recommendations for older adults.". Osteoporos Int 21 (7): 1151-4. DOI:10.1007/s00198-010-1285-3. PMID 20422154. Research Blogging.
  9. ↑ Thomas MK, Lloyd-Jones DM, Thadhani RI, et al (1998). "Hypovitaminosis D in medical inpatients". N. Engl. J. Med. 338 (12): 777–83. PMID 9504937. [e]
  10. ↑ Plotnikoff GA, Quigley JM (2003). "Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain". Mayo Clin. Proc. 78 (12): 1463–70. PMID 14661675. [e]
  11. ↑ Hicks GE, Shardell M, Miller RR, et al (May 2008). "Associations between vitamin D status and pain in older adults: the Invecchiare in Chianti study". J Am Geriatr Soc 56 (5): 785–91. DOI:10.1111/j.1532-5415.2008.01644.x. PMID 18331295. Research Blogging.
  12. ↑ 12.0 12.1 Warner AE, Arnspiger SA (February 2008). "Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D". J Clin Rheumatol 14 (1): 12–6. DOI:10.1097/RHU.0b013e31816356a9. PMID 18431091. Research Blogging.
  13. ↑ Orwoll E, Nielson CM, Marshall LM, et al (April 2009). "Vitamin D deficiency in older men". J. Clin. Endocrinol. Metab. 94 (4): 1214–22. DOI:10.1210/jc.2008-1784. PMID 19174492. Research Blogging.
  14. ↑ Pearce SH, Cheetham TD (2010). "Diagnosis and management of vitamin D deficiency.". BMJ 340: b5664. DOI:10.1136/bmj.b5664. PMID 20064851. Research Blogging.
  15. ↑ Holick MF, Biancuzzo RM, Chen TC, et al (2008). "Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D". J. Clin. Endocrinol. Metab. 93 (3): 677-81. DOI:10.1210/jc.2007-2308. PMID 18089691. Research Blogging.
  16. ↑ Lappe,J.M.; Travers-Gustafson,D.; Davies,K.M.; Recker,R.R.; Heaney,R.P. (2007) Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J. Clin Nutr. 85(6):1586-1591. Full Text.
  17. ↑ Vieth R. (2006) What is the optimal vitamin D status for health? Prog. Biophys. Mol. Biol. 92(1):26-32. Full Text
  18. ↑ Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O'Sullivan MJ et al. (2006). "Calcium plus vitamin D supplementation and the risk of colorectal cancer.". N Engl J Med 354 (7): 684-96. DOI:10.1056/NEJMoa055222. PMID 16481636. Research Blogging. Review in: Evid Based Nurs. 2006 Oct;9(4):114 Review in: ACP J Club. 2006 Jul-Aug;145(1):4-5
  19. ↑ Miller JW (2010). "Vitamin D and cognitive function in older adults: are we concerned about vitamin D-mentia?". Neurology 74 (1): 13-5. DOI:10.1212/WNL.0b013e3181c719a2. PMID 19940269. Research Blogging.
  20. ↑ Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K et al. (2010). "Systematic review: Vitamin D and cardiometabolic outcomes.". Ann Intern Med 152 (5): 307-14. DOI:10.1059/0003-4819-152-5-201003020-00009. PMID 20194237. Research Blogging.
  21. ↑ Palmer SC, McGregor DO, Craig JC, Elder G, Macaskill P, Strippoli GF (2009). "Vitamin D compounds for people with chronic kidney disease not requiring dialysis.". Cochrane Database Syst Rev (4): CD008175. DOI:10.1002/14651858.CD008175. PMID 19821446. Research Blogging. Review in: Ann Intern Med. 2010 Apr 20;152(8):JC4-12
  22. ↑ Wang L, Manson JE, Song Y, Sesso HD (2010). "Systematic review: vitamin d and calcium supplementation in prevention of cardiovascular events.". Ann Intern Med 152 (5): 315-23. DOI:10.1059/0003-4819-152-5-201003020-00010. PMID 20194238. Research Blogging.
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