Vitamin D deficiency as a public health issue: using vitamin D2or vitamin D3in future fortification strategies

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Abstract

The role of vitamin D in supporting the growth and maintenance of the skeleton is robust; with recent research also suggesting a beneficial link between vitamin D and other non-skeletal health outcomes, including immune function, cardiovascular health and cancer. Despite this, vitamin D deficiency remains a global public health issue, with a renewed focus in the UK following the publication of Public Health England's new Dietary Vitamin D Requirements. Natural sources of vitamin D (dietary and UVB exposure) are limited, and thus mechanisms are needed to allow individuals to achieve the new dietary recommendations. Mandatory or voluntary vitamin D food fortification may be one of the mechanisms to increase dietary vitamin D intakes and subsequently improve vitamin D status. However, for the food industry and public to make informed decisions, clarity is needed as to whether vitamins D ₂and D ₃are equally effective at raising total 25-hydroxyvitamin D (25(OH)D) concentrations as the evidence thus far is inconsistent. This review summarises the evidence to date behind the comparative efficacy of vitamins D ₂and D ₃at raising 25(OH)D concentrations, and the potential role of vitamin D food fortification as a public health policy to support attainment of dietary recommendations in the UK. The comparative efficacy of vitamins D ₂and D ₃has been investigated in several intervention trials, with most indicating that vitamin D ₃is more effective at raising 25(OH)D concentrations. However, flaws in study designs (predominantly under powering) mean there remains a need for a large, robust randomised-controlled trial to provide conclusive evidence, which the future publication of the D ₂–D ₃Study should provide (BBSRC DRINC funded: BB/I006192/1). This review also highlights outstanding questions and gaps in the research that need to be addressed to ensure the most efficacious and safe vitamin D food fortification practices are put in place. This further research, alongside cost, availability and ethical considerations (vitamin D ₃is not suitable for vegans), will be instrumental in supporting government, decision-makers, industry and consumers in making informed choices about potential future vitamin D policy and practice.

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From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health.

Anthony W Norman (2008)

New knowledge of the biological and clinical importance of the steroid hormone 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] and its receptor, the vitamin D receptor (VDR), has resulted in significant contributions to good bone health. However, worldwide reports have highlighted a variety of vitamin D insufficiency and deficiency diseases. Despite many publications and scientific meetings reporting advances in vitamin D science, a disturbing realization is growing that the newer scientific and clinical knowledge is not being translated into better human health. Over the past several decades, the biological sphere of influence of vitamin D(3), as defined by the tissue distribution of the VDR, has broadened at least 9-fold from the target organs required for calcium homeostasis (intestine, bone, kidney, and parathyroid). Now, research has shown that the pluripotent steroid hormone 1alpha,25(OH)(2)D(3) initiates the physiologic responses of >/=36 cell types that possess the VDR. In addition to the kidney's endocrine production of circulating 1alpha,25(OH)(2)D(3,) researchers have found a paracrine production of this steroid hormone in >/=10 extrarenal organs. This article identifies the fundamentals of the vitamin D endocrine system, including its potential for contributions to good health in 5 physiologic arenas in which investigators have clearly documented new biological actions of 1alpha,25(OH)(2)D(3) through the VDR. As a consequence, the nutritional guidelines for vitamin D(3) intake (defined by serum hydroxyvitamin D(3) concentrations) should be reevaluated, taking into account the contributions to good health that all 36 VDR target organs can provide.

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Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis123

Laura Tripkovic, Helen Lambert, Kathryn Hart … (2012)

Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.

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Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2.

H M Trang, D Cole, L Rubin … (1998)

In all species tested, except humans, biological differences between vitamins D2 and D3 are accepted as fact. To test the presumption of equivalence in humans, we compared the ability of equal molar quantities of vitamin D2 or D3 to increase serum 25-hydroxyvitamin D [25(OH)D], the measure of vitamin D nutrition. Subjects took 260 nmol (approximately 4000 IU) vitamin D2 (n=17) or vitamin D3 (n=55) daily for 14 d. 25(OH)D was assayed with a method that detects both the vitamin D2 and D3 forms. With vitamin D3, mean (+/-SD) serum 25(OH)D increased from 41.3+/-17.7 nmol/L before to 64.6+/-17.2 nmol/L after treatment. With vitamin D2, the 25(OH)D concentration went from 43.7+/-17.7 nmol/L before to 57.4+/-13.0 nmol/L after. The increase in 25(OH)D with vitamin D3 was 23.3+/-15.7 nmol/L, or 1.7 times the increase obtained with vitamin D2 (13.7+/-11.4 nmol/L; P=0.03). There was an inverse relation between the increase in 25(OH)D and the initial 25(OH)D concentration. The lowest 2 tertiles for basal 25(OH)D showed larger increases in 25(OH)D: 30.6 and 25.5 nmol/L, respectively, for the first and second tertiles. In the highest tertile [25(OH)D >49 nmol/L] the mean increase in 25(OH)D was 13.3 nmol/L (P < 0.03 for comparison with each lower tertile). 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.