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Vitamin D in an ecological context. Björn LO, Wang T. Int J Circumpolar Health. 2000 Jan;59(1):26-32. PMID: 10850004

Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, Reitz R, Salameh W, Ameri A, Tannenbaum AD. J Clin Endocrinol Metab. 2008 Mar;93(3):677-81. Epub 2007 Dec 18. PMID: 18089691 Conclusion: A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.

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. 1998 Oct;68(4):854-8. PMID: 9771862 Although the 1.7-times greater efficacy for vitamin D3 shown here may seem small, it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitamin D3 dose. The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered.

Serum vitamin D level after an annual intramuscular injection of ergocalciferol. Heikinheimo RJ, Haavisto MV, Harju EJ, Inkovaara JA, Kaarela RH, Kolho LA, Rajala SA. Calcif Tissue Int. 1991;49 Suppl:S87. PMID: 1933611 An annual intramuscular injection of ergocalciferol (150,000 IU) normalized low serum (25(OH)D concentrations in elderly people for 1 year. The treatment had a slight effect on serum 24,25(OH)2D levels but no effect on 1,25(OH)2D levels.

Annual injection of vitamin D and fractures of aged bones. Heikinheimo RJ, Inkovaara JA, Harju EJ, Haavisto MV, Kaarela RH, Kataja JM, Kokko AM, Kolho LA, Rajala SA. Calcif Tissue Int. 1992 Aug;51(2):105-10. PMID: 1422948

Vitamin D supplementation. Eveleigh B. Can Fam Physician. 2007 Sep;53(9):1435; author reply 1435. PMID: 17872869 My concern regarding vitamin D2 is that it is a synthetic analogue and might interact with the vitamin D receptor differently in various cell systems. It has been reported that vitamin D3 might improve glycemic control.7 Vitamin D2 has been reported to cause worsening of glycemic control in people of East Indian descent.8 Is this because of vitamin D receptor polymorphism, or because of enhanced 24-hydroxylase enzyme activation, or is it due to how vitamin D2 interacts with the receptor? Until this has been sorted out, I feel safest using vitamin D3. There are about 2000 synthetic analogues of vitamin D. The search is on for one that can cross the blood-brain barrier to treat certain types of brain cancers without causing hypercalcemia.9 But then again, what other effects would this compound have? There are still so many unknowns

Why would vitamin D be prescribed when vitamin D3 is available over-the-counter? Let's review the known differences between vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol): --D3 is the human form; D2 is the non-human form found in plants. --Dose for dose, D3 is more effective at raising blood levels of 25-hydroxy vitamin D than D2. It requires roughly twice to 250% of the dose of D2 to match that of D3 (Trang H et al 1998). --D2 blood levels don't yield long-term sustained levels of 25-hydroxy vitamin D as does D3. When examined as a 28-day area under the curve (AUC--a superior measure of biologic exposure), D3 yields better than a 300% increased potency compared to D2. This means that it requires around 50,000 units D2 to match the effects of 15,000 units D3 (Armas LA et al 2004). --D2 has lower binding affinity for vitamin D-binding protein, compared to D3 --Mitochondrial vitamin D 25-hydroxylase converts D3 to the 25-hydroxylated form five times more rapidly than D2. --As we age, the ability to metabolize D2 is dramatically reduced, while D3 is not subject to this phenomenon

Together, the earlier data and the data of Heaney et al indicate that an oral dose of vitamin D2 or vitamin D3 would lead to a comparable increase in circulating 25(OH)D concentrations in children and adults when the initial 25(OH)D3 concentrations in the groups are similar and when equivalent oral vitamin D doses expressed per kilogram body weight/d are given. Serum 25-hydroxyvitamin D response to oral vitamin D intake in children. Zittermann A. Am J Clin Nutr. 2003 Sep;78(3):496-7. PMID: 12936937

Vitamin D2 is much less effective than vitamin D3 in humans. Armas LA, Hollis BW, Heaney RP. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. PMID: 15531486 Vitamin D2 potency is less than one third that of vitamin D3. Physicians resorting to use of vitamin D2 should be aware of its markedly lower potency and shorter duration of action relative to vitamin D3.

Unusually prolonged vitamin D intoxication after discontinuation of vitamin D: possible role of primary hyperparathyroidism. Taskapan H, Vieth R, Oreopoulos DG. Int Urol Nephrol. 2008;40(3):801-5. Epub 2008 Jun 5. PMID: 18528779 DOI: 10.1007/s11255-008-9404-1

Vitamin D is a group of fat-soluble prohormones, the two major forms of which are vitamin D2 (or ergocalciferol) and vitamin D3 (or cholecalciferol).[1] The term vitamin D also refers to metabolites and other analogues of these substances. Vitamin D3 is produced in skin exposed to sunlight, specifically ultraviolet B radiation.\nVitamin D plays an important role in the maintenance of organ systems

Decreased bioavailability of vitamin D in obesity. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Am J Clin Nutr. 2000 Sep;72(3):690-3. Erratum in: Am J Clin Nutr. 2003 May;77(5):1342. PMID: 10966885 Conclusions: Obesity-associated vitamin D insufficiency is likely due to the decreased bioavailability of vitamin D3 from cutaneous and dietary sources because of its deposition in body fat compartments.

Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, Vasikaran SD, Taranto M, Musk AA, Fraser WD. Bone. 2009 Nov;45(5):870-5. Epub 2009 Jul 23. PMID: 19631774 doi:10.1016/j.bone.2009.07.015 Cholecalciferol supplementation resulted in a 31% greater increase in total HPLC-measured 25OHD (p=0.010) and 52% greater rise in RIA-measured 25OHD (p0.05). In vitamin D-insufficient hip fracture patients, supplementation with cholecalciferol 1000 IU/day for three months was more effective in increasing serum 25OHD than an equivalent dose of ergocalciferol. However, the lack of difference in PTH lowering between calciferol treatments raises questions about the biological importance of this observation.

"Ergocalciferol (Deltalin, Eli Lilly and Company) is a form of vitamin D, also called vitamin D2. It has the systematic name "(3β,5Z,7E,22E)-9,10-secoergosta-5,7,10(19),22-tetraen-3-ol". It is created from viosterol, which in turn is created when ultraviolet light activates ergosterol."

The effect of vitamin D2 and vitamin D3 on intestinal calcium absorption in Nigerian children with rickets. Thacher TD, Obadofin MO, O'Brien KO, Abrams SA. J Clin Endocrinol Metab. 2009 Sep;94(9):3314-21. Epub 2009 Jun 30. PMID: 19567516 Conclusions: Despite similar increases in 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with vitamin D2 or vitamin D3, fractional calcium absorption did not increase, indicating that rickets in Nigerian children is not primarily due to vitamin D-deficient calcium malabsorption