In some areas of the world, the only such high-dose option available by prescription is vitamin D 2. Thus, intermittent use of high-dose vitamin D treatment is a potentially attractive option. Regardless, poor adherence with daily dosing of medications and supplements is widely appreciated. Nevertheless, these two forms of vitamin D are currently considered equal and interchangeable, as evidenced by the observation that supplements containing equal amounts of “vitamin D” may contain either vitamin D 2 or vitamin D 3. Indeed, a recent report finds similar effects from administering either D 2 or D 3 on circulating 25(OH)D levels ( 8) supporting their equivalence, whereas other publications find vitamin D 2 less “potent” at maintaining serum 25(OH)D than is vitamin D 3 ( 9– 12). Although chemical differences exist between these two forms, it remains controversial whether vitamin D 2 and vitamin D 3 are equally effective at increasing circulating 25-hydroxyvitamin D and/or have equivalent physiological effects. Food and/or supplement intake may provide either vitamin D 2 or D 3. Vitamin D 3 is produced from 7-dehydrocholesterol when human skin is exposed to UV B radiation ( 7). Two chemically distinct forms of vitamin D exist vitamin D 3 (cholecalciferol) is a 27-carbon molecule, whereas vitamin D 2 (ergocalciferol) contains 28 carbons and differs from vitamin D 3 by the presence of an additional methyl group and a double bond between carbons 22 and 23. Therefore, identification of optimal approaches to provide supplementation and correct low vitamin D status is required. Because current indoor lifestyle, clothing choices, and sun avoidance/sunscreen use severely limit sun exposure-dependent vitamin D production, vitamin D supplementation is often necessary. Additionally, low vitamin D status is increasingly associated with increased risk for other nonmusculoskeletal chronic diseases ( 3– 6). Low vitamin D status is extremely common worldwide and adversely affects musculoskeletal health ( 1, 2).
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