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      Improved Dietary Guidelines for Vitamin D: Application of Individual Participant Data (IPD)-Level Meta-Regression Analyses

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          Abstract

          Dietary Reference Values (DRVs) for vitamin D have a key role in the prevention of vitamin D deficiency. However, despite adopting similar risk assessment protocols, estimates from authoritative agencies over the last 6 years have been diverse. This may have arisen from diverse approaches to data analysis. Modelling strategies for pooling of individual subject data from cognate vitamin D randomized controlled trials (RCTs) are likely to provide the most appropriate DRV estimates. Thus, the objective of the present work was to undertake the first-ever individual participant data (IPD)-level meta-regression, which is increasingly recognized as best practice, from seven winter-based RCTs (with 882 participants ranging in age from 4 to 90 years) of the vitamin D intake–serum 25-hydroxyvitamin D (25(OH)D) dose-response. Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of 25(OH)D concentrations >25, 30, and 50 nmol/L across the population are 10, 13, and 26 µg/day, respectively. In contrast, standard meta-regression analyses with aggregate data (as used by several agencies in recent years) from the same RCTs estimated that a vitamin D intake requirement of 14 µg/day would maintain 97.5% of 25(OH)D >50 nmol/L. These first IPD-derived estimates offer improved dietary recommendations for vitamin D because the underpinning modeling captures the between-person variability in response of serum 25(OH)D to vitamin D intake.

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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

          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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            Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization.

            Endemic hypovitaminosis D contributes to osteoporosis development. However, variation in 25-hydroxyvitamin D (25OHD) measurement is reported and confounds the diagnosis of vitamin D insufficiency/deficiency. This report emphasizes the marked variability observed in serum 25OHD measurements between laboratories.Initially, postmenopausal women had serum 25OHD determinations: 42 in laboratory A, 20 in laboratory B. Their mean (sem) serum 25OHD concentrations were 46 (2.1) and 21 (2.3) ng/ml in laboratories A and B, respectively. Furthermore, there was little overlap in serum 25OHD among these clinically similar individuals. Specifically, 17% of those measured in laboratory A but 90% in laboratory B were below an arbitrary threshold value of 32 ng/ml.Subsequently, serum was obtained from 10 healthy adults. Two aliquots from each individual, one of which was spiked with 20 ng/ml 25OHD, were sent to six laboratories. Substantial variability was noted between these six laboratories. The mean serum 25OHD concentration ranged from 17.1-35.6 ng/ml. Similarly, the mean increase produced by spiking with 20 ng/ml ranged from 7.7-18.0 ng/ml.In conclusion, 25OHD assays yield markedly differing results; whether an individual is found to have low or normal vitamin D status is a function of the laboratory used. If the medical community is to make progress in correcting widespread hypovitaminosis D, 25OHD measurement must be standardized.
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              Assessing the prevalence of nutrient inadequacy.

              To describe an approach for assessing the prevalence of nutrient inadequacy in a group, using daily intake data and the new Estimated Average Requirement (EAR). Observing the proportion of individuals in a group whose usual intake of a nutrient is below their requirement for the nutrient is not possible in general. We argue that this proportion can be well approximated in many cases by counting, instead, the number of individuals in the group whose intakes are below the EAR for the nutrient. This is a methodological paper, and thus emphasis is not on analysing specific data sets. For illustration of one of the statistical methods presented herein, we have used the 1989-91 Continuing Survey on Food Intakes by Individuals. We show that the EAR and a reliable estimate of the usual intake distribution in the group of interest can be used to assess the proportion of individuals in the group whose usual intakes are not meeting their requirements. This approach, while simple, does not perform well in every case. For example, it cannot be used on energy, since intakes and requirements for energy are highly correlated. Similarly, iron in menstruating women presents some difficulties, due to the fact that the distribution of iron requirements in this group is known to be skewed. The apparently intractable problem of assessing the proportion of individuals in a group whose usual intakes of a nutrient are not meeting their requirements can be solved by comparing usual intakes to the EAR for the nutrient, as long as some conditions are met. These are: (1) intakes and requirements for the nutrient must be independent, (2) the distribution of requirements must be approximately symmetric around its mean, the EAR, and (3) the variance of the distribution of requirements should be smaller than the variance of the usual intake distribution.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                08 May 2017
                May 2017
                : 9
                : 5
                : 469
                Affiliations
                [1 ]Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Cork T12 Y337, Ireland
                [2 ]Department of Medicine, University College Cork, Cork T12 DFK4, Ireland
                [3 ]Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg C DK-1958, Denmark; ritz@ 123456nexs.ku.dk
                [4 ]Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork T12 DFK4, Ireland; m.kiely@ 123456ucc.ie
                Author notes
                [* ]Correspondence: k.cashman@ 123456ucc.ie ; Tel.: +353-21-4901317
                Article
                nutrients-09-00469
                10.3390/nu9050469
                5452199
                28481259
                f26f335e-a1c1-4404-9b42-b8acfce69e24
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 March 2017
                : 02 May 2017
                Categories
                Article

                Nutrition & Dietetics
                vitamin d recommendations,drv,rda,ear,individual participant data-level meta-regression analyses

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