Individual participant data (IPD)-level meta-analysis of randomised controlled trials among dark-skinned populations to estimate the dietary requirement for vitamin D

Estimation of the dietary requirements for vitamin D is crucial from a public health perspective in providing a framework for the prevention of vitamin D deficiency. It has been shown that pooling individual participant-level data (IPD) from selected randomised controlled trials (RCTs) of white children and adults facilitated the generation of more accurate estimates of the vitamin D requirement. Recent RCT data suggest the vitamin D requirement of dark-skinned, particularly black, individuals, an at-risk group of vitamin D deficiency, is greater than those of white counterparts. Thus, we wished to develop a study protocol for the conduct of an IPD-level meta-analysis of vitamin D requirements using data from appropriate vitamin D RCTs in dark-skinned population subgroups

The effect of high-dose vitamin D supplementation on muscular function and quality of life in postmenopausal women—A randomized controlled trial

Objective: Observational studies have suggested positive associations between serum 25-hydroxyvitamin D (25(OH)D) levels and muscular strength, balance and quality of life. Our aim was to examine whether high-dose vitamin D supplementation would improve these measures as compared to standard-dose vitamin D, as well as the possible muscular effects of single nucleotide polymorphisms (SNPs) in genes encoding vitamin D-related enzymes. Design: A 12-month randomized, double-blind, controlled trial where the participants received daily elemental calcium (1000 mg) plus vitamin D3 (800 IU). In addition, the participants were randomized to receive either capsules with vitamin D3 (20 000 IU) or matching placebos to be taken twice a week. Patients: A total of 297 postmenopausal women with osteopenia or osteoporosis. Measurements: Muscle strength (handgrip and knee extensor strength), balance (tandem test) and quality of life (EQ-5D) were measured at baseline and after 12 months. The subjects were genotyped for SNPs related to vitamin D metabolism. Results: Of the 297 included women, 275 completed the study. Mean serum 25(OH)D levels dramatically increased in the high-dose group (from 64.7 to 164.1 nmol/L; P<.01), while a more moderate increased was observed in the standard-dose group (from 64.1 to 81.8 nmol/L; P<.01). There was no significant difference between the groups in change in muscular strength, balance or quality of life over the intervention period. Polymorphisms in rs3829251 (located in the 7-dehydrocholesterol reductase gene) were associated with muscle strength and treatment effects. Conclusion: One-year treatment with high-dose vitamin D had no effect on muscular strength, balance or quality of life in postmenopausal women with osteopenia or osteoporosis as compared to standard dose. The association between rs3829251 and muscle strength needs confirmation in other populations

Food-based solutions for vitamin D deficiency: putting policy into practice and the key role for research

Recent re-evaluations of dietary reference values (DRV) for vitamin D have established intake requirements between 10 and 20 µg/d. National nutrition surveys indicate that habitual mean intakes of vitamin D in the population are typically in the range 3–7 µg/d. As vitamin D supplementation will not be effective at a population level because the uptake is generally low, creative food-based solutions are needed to bridge the gap between current intakes and these new requirement values. The overarching aim of this review is to highlight how food-based solutions can have an important role in bridging this gap and counteracting vitamin D inadequacy in Europe and elsewhere. The present review initially briefly overviews very recent new European DRV for vitamin D and, while not in agreement on requirement estimates, how they point very clearly to the need for food-based solutions. The review discusses the need for traditional fortification of foods in the dairy and other sectors, and finally overviews recent advances in the area of biofortification of food with vitamin D. In conclusion, increasing vitamin D intakes across the population distribution is important from a public health perspective to reduce the high degree of inadequacy of vitamin D intake in Europe. Fortification, including biofortification, of a wider range of foods, which accommodate diversity, is likely to have the potential to increase vitamin D intakes across the population distribution. Research has had, and will continue to have, a key role in terms of developing food-based solutions and tackling vitamin D deficiency

Improved dietary guidelines for vitamin D: application of individual participant data (IPD)-level meta-regression analyses

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

A systematic review and meta-regression analysis of the vitamin D intake-serum 25-hydroxyvitamin D relationship to inform European recommendations

The present study used a systematic review approach to identify relevant randomised control trials (RCT) with vitamin D and then apply meta-regression to explore the most appropriate model of the vitamin D intake–serum 25-hydroxyvitamin D (25(OH)D) relationship to underpin setting reference intake values. Methods included an updated structured search on Ovid MEDLINE; rigorous inclusion/exclusion criteria; data extraction; and meta-regression (using different model constructs). In particular, priority was given to data from winter-based RCT performed at latitudes >49•58°N (n 12). A combined weighted linear model meta-regression analyses of natural log (Ln) total vitamin D intake (i.e. diet and supplemental vitamin D) versus achieved serum 25(OH)D in winter (that used by the North American Dietary Reference Intake Committee) produced a curvilinear relationship (mean (95% lower CI) serum 25(OH)D (nmol/l) = 9•2 (8•5) Ln (total vitamin D)). Use of non-transformed total vitamin D intake data (maximum 1400 IU/d; 35µg/d) provided for a more linear relationship (mean serum 25(OH)D (nmol/l) = 0•044 × (total vitamin D) + 33•035). Although inputting an intake of 600 IU/d (i.e. the RDA) into the 95% lower CI curvilinear and linear models predicted a serum 25(OH)D of 54•4 and 55•2 nmol/l, respectively, the total vitamin D intake that would achieve 50 (and 40) nmol/l serum 25(OH)D was 359 (111) and 480 (260) IU/d, respectively. Inclusion of 95% range in the model to account for inter-individual variability increased the predicted intake of vitamin D needed to maintain serum 25(OH)D ≥50 nmol/l to 930 IU/d. The model used to describe the vitamin D intake–status relationship needs to be considered carefully when setting new reference intake values in Europe

Dietary vitamin D2 - a potentially underestimated contributor to vitamin D nutritional status of adults?

It has been suggested that vitamin D2 is not very prevalent in the human food chain. However, data from a number of recent intervention studies suggest that the majority of subjects had measurable serum 25-hydroxyvitamin D2 (25(OH)D2) concentrations. Serum 25(OH)D2, unlike 25(OH)D3, is not directly influenced by exposure of skin to sun and thus has dietary origins; however, quantifying dietary vitamin D2 is difficult due to the limitations of food composition data. Therefore, the present study aimed to characterise serum 25(OH)D2 concentrations in the participants of the National Adult Nutrition Survey (NANS) in Ireland, and to use these serum concentrations to estimate the intake of vitamin D2 using a mathematical modelling approach. Serum 25(OH)D2 concentration was measured by a liquid chromatography–tandem MS method, and information on diet as well as subject characteristics was obtained from the NANS. Of these participants, 78·7 % (n 884) had serum 25(OH)D2 concentrations above the limit of quantification, and the mean, maximum, 10th, 50th (median) and 90th percentile values of serum 25(OH)D2 concentrations were 3·69, 27·6, 1·71, 2·96 and 6·36 nmol/l, respectively. To approximate the intake of vitamin D2 from these serum 25(OH)D2 concentrations, we used recently published data on the relationship between vitamin D intake and the responses of serum 25(OH)D concentrations. The projected 5th to 95th percentile intakes of vitamin D2 for adults were in the range of 0·9–1·2 and 5–6 μg/d, respectively, and the median intake ranged from 1·7 to 2·3 μg/d. In conclusion, the present data demonstrate that 25(OH)D2 concentrations are present in the sera of adults from this nationally representative sample. Vitamin D2 may have an impact on nutritional adequacy at a population level and thus warrants further investigation

The role of meat in the European diet: current state of knowledge on dietary recommendations, intakes and contribution to energy and nutrient intakes and status

The role of meat in the diet has come under scrutiny recently due to an increased public emphasis on providing healthy diets from sustainable food systems and due to health concerns relating to the consumption of red and processed meat. The present review aimed to summarise dietary guidelines relating to meat, actual meat intakes and the contribution of meat to energy and nutrient intakes of children, teenagers and adults in Europe. The available literature has shown that food-based dietary guidelines for most countries recommend consuming lean meat in moderation and many recommend limiting red and processed meat consumption. Mean intakes of total meat in Europe range from 40 to 160 g/d in children and teenagers and from 75 to 233 g/d in adults. Meat contributes to important nutrients such as protein, PUFA, B vitamins, vitamin D and essential minerals such as Fe and Zn; however, processed meat contributes to significant proportions of saturated fat and Na across population groups. While few data are available on diaggregated intakes of red and processed meat, where data are available, mean intakes in adults are higher than the upper limits recommended by the UK Scientific Advisory Committee on Nutrition (70 g/d) and the World Cancer Research Fund (500 g/week). While there are no recommendations for red and processed meat consumption in children and teenagers, intakes currently range from 30 to 76 g/d. The present review provides a comprehensive overview of the role of meat in the European diet which may be of use to stakeholders including researchers, policy makers and the agri-food sector

Poor bioavailability of vitamin D2 from ultraviolet-irradiated D2-rich yeast in rats

Ultraviolet-irradiated yeast (Saccharomyces cerevisiae) can be used to biofortify bakery products with vitamin D, but in bread, it was not effective in increasing serum 25-hydroxyvitamin D [25(OH)D] in humans, possibly because of the low digestibility of the yeast matrix. We investigated the effects of vitamin D-2-rich intact yeast cells and their separated fraction, yeast cell walls, which we hypothesized to provide vitamin D-2 in a more bioavailable form, on serum 25(OH)D and its metabolites in growing female Sprague-Dawley rats (n = 54) compared to vitamin D-2 and D-3 supplements (8 treatment groups: 300 or 600 IU vitamin D/d, and a control group, 8-week intervention). The D-3 supplement groups had the highest 25(OH)D concentrations, and the vitamin D-2 supplement at the 600-IU dose increased 25(OH)D better than any yeast form (P .05). Serum 24,25-dihydroxyvitamin D (a vitamin D catabolite) concentrations and the trend in the differences between the groups were in line with 25 (OH)D (P .05). These findings do not support the hypothesis: the ability of the different ultraviolet-treated vitamin D-2-containing yeast forms to increase 25(OH)D did not differ, and the poor bioavailability of vitamin D-2 in the yeasts compared D-3 or D-2 supplements could not be explained by the increased vitamin D catabolism in the yeast-treated groups. (C) 2018 Elsevier Inc. All rights reserved.Peer reviewe

Improved accuracy of an tandem liquid chromatography–mass spectrometry method measuring 24R,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D metabolites in serum using unspiked controls and its application to determining cross-reactivity of a chemiluminescent microparticle immunoassay

Measurement of serum 25-hydroxyvitamin D [25(OH)D] is considered the best indicator of vitamin D status. Two minor vitamin D metabolites are common interferences encountered in 25(OH)D assays. The first is 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3], which if not chromatographically resolved from 25-hydroxyvitamin D3 [25(OH)D3], can overestimate 25(OH)D concentrations. The second is 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], which can cross-react with the antibodies in 25(OH)D immunoassays. Our aim was to develop an LCâ MS/MS method capable of detecting both 3-epi-25(OH)D3 and 24R,25(OH)2D3 in serum without the use of a derivatization agent. We report an isotope dilution LCâ MS/MS method, with electrospray ionization in the positive mode, that can simultaneously detect 24R,25(OH)2D3, 25(OH)D3, 3-epi-25(OH)D3, and 25-hydroxyvitamin D2. The method employs a cost-effective liquidâ liquid extraction using only 150 &#956;L of sera and a total run time of 10 min. Method performance was assessed by using quality controls made from pooled sera as an alternative to sera spiked with analytes. Biobanked samples, originally analyzed by chemiluminescent microparticle immunoassay (CMIA), were re-analyzed with this method to determine the contribution of 24R,25(OH)2D3 cross-reactivity to 25(OH)D measurement bias. The CMIA over-estimation of 25(OH)D measurements relative to LCâ MS/MS was found to depend on both 25(OH)D and 24R,25(OH)2D3 concentrations