Cork Centre for Vitamin D and Nutrition Research - Journal Articles

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    Vitamin D biomarkers for Dietary Reference Intake development in children: A systematic review and meta-analysis
    (Oxford University Press, 2021-10-23) Cashman, Kevin D.; Ritz, Christian; Carlin, Aoife; Kennedy, Mairead
    Background: Circulating 25-hydroxyvitamin D [25(OH)D] has been the accepted vitamin D exposure/intake biomarker of choice within recent DRI exercises, but use of other vitamin D–related biomarkers as well as functional markers has been suggested. These may be of value in future vitamin D DRI exercises, such as the FAO/WHO's one for young children. Objectives: To systematically review the usefulness of circulating 25(OH)D, parathyroid hormone (PTH), free and bioavailable 25(OH)D, C3-epimer of 25(OH)D, vitamin D3, 24,25-dihydroxyvitamin D [24,25(OH)2D], and bone turnover markers and calcium absorption as vitamin D biomarkers for DRI development in children. Methods: Methods included structured searches of published articles, full-text reviews, data extraction, quality assessment, meta-analysis, and random-effects meta-regression. Results: Fifty-nine vitamin D supplementation randomized controlled trials (RCTs) were included (39 in infants/children as the priority group and the remainder in adults since pediatric studies were absent/limited). Vitamin D supplementation significantly raised circulating 25(OH)D in infants and children, but the response was highly heterogeneous [weighted mean difference (WMD): 27.7 nmol/L; 95% CI: 22.9, 32.5; 27 RCTs; I2 = 93%]. Meta-regression suggested an increase by 1.7 nmol/L (95% CI: 0.7, 2.6) in serum 25(OH)D per each 100-IU increment in vitamin D intake (P = 0.0005). Vitamin D supplementation had a significant effect on circulating 24,25(OH)2D (WMD: 3.4 nmol/L; 95% CI: 2.4, 4.5; 13 RCTs; I2 = 95%), with a dose–response relation (+0.15 nmol/L per 100 IU; 95% CI: –0.01, 0.29). With circulating PTH, although there was a significant effect of vitamin D on WMD (P = 0.05), there was no significant dose–response relation (P = 0.32). Pediatric data were too limited in relation to the usefulness of the other biomarkers. Conclusions: Circulating 25(OH)D may be a useful biomarker of vitamin D exposure/intake for DRI development in infants and children. Circulating 24,25(OH)2D also showed some promise, but further data are needed, especially in infants and children.
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    Food-based solutions for vitamin D deficiency: putting policy into practice and the key role for research
    (Cambridge University Press on behalf of The Nutrition Society, 2016-10-25) Hayes, Aoife; Cashman, Kevin D.; Department of Health and Social Care; Department of Agriculture, Food and the Marine, Ireland; Seventh Framework Programme
    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.
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    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
    (Elsevier B.V., 2017-03-23) Dowling, Kirsten G.; Hull, George; Sundvall, Jouko; Lamberg-Allardt, Christel; Cashman, Kevin D.; Seventh Framework Programme; Terveyden ja hyvinvoinnin laitos
    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 μL 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.
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    Implementation strategies for improving vitamin D status and increasing vitamin D intake in the UK: Current controversies and future perspectives. Proceedings of the 2nd Rank Prize Funds Forum on Vitamin D
    (Cambridge University Press, 2021-07-21) Buttriss, J. L.; Lanham-New, S. A.; Steenson, S.; Levy, L.; Swan, G. E.; Darling, A. L.; Cashman, Kevin D.; Allen, R. E.; Durrant, L. R.; Smith, C. P.; Magee, P.; Hill, T. R.; Uday, S.; Kiely, M.; Delamare, G.; Hoyland, A. E.; Larsen, L.; Street, L. N.; Mathers, J. C.; Prentice, A.; Rank Prize, United Kingdom
    A multi-disciplinary expert group met to discuss vitamin D deficiency in the UK, and strategies for improving population intakes and status. Changes to UK Government advice since the 1st Rank Forum on Vitamin D (2009) were discussed, including rationale for setting a RNI (10µg/day;400IU/day) for adults and children (4+ years). Current UK data show inadequate intakes among all age groups, and high prevalence of low vitamin D status among specific groups (e.g. pregnant women and adolescent males/females). Evidence of widespread deficiency within some minority ethnic groups, resulting in nutritional rickets (particularly among Black and South Asian infants), raised particular concern. It is too early to establish whether population vitamin D status has altered since Government recommendations changed in 2016. Vitamin D food fortification was discussed as a potential strategy to increase population intakes. Data from dose-response and dietary modelling studies indicate dairy products, bread, hens' eggs and some meats as potential fortification vehicles. Vitamin D3 appears more effective than vitamin D2 for raising serum 25-hydroxyvitamin D concentration, which has implications for choice of fortificant. Other considerations for successful fortification strategies include: i) need for 'real-world' cost information for use in modelling work; ii) supportive food legislation; iii) improved consumer and health professional understanding of vitamin D's importance; iv) clinical consequences of inadequate vitamin D status; v) consistent communication of Government advice across health/social care professions, and via the food industry. These areas urgently require further research to enable universal improvement in vitamin D intakes and status in the UK population.
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    Iron, iodine and vitamin D deficiencies during pregnancy - epidemiology, risk factors and developmental impacts
    (Cambridge University Press, 2021-05-14) Kiely, Mairead E.; McCarthy, Elaine K.; Hennessy, Áine; Science Foundation Ireland; Health Research Board
    Micronutrient deficiency persists throughout the world, and while the burden is higher in low resource settings, it is also prevalent in wealthy countries, a phenomenon termed â hidden hungerâ . Due to their high requirements for vitamins and minerals relative to their energy intake, young women and children are particularly vulnerable to hidden hunger. As they share several risk factors and impact on overlapping outcomes, we consider how deficiency of iron, iodine and vitamin D can have profound impacts on perinatal health and infant development. We review the epidemiology of these micronutrient deficiencies during pregnancy, including social, environmental and dietary risk factors. We identify the main challenges in defining nutritional status of these nutrients using validated diagnostic criteria linked with meaningful clinical outcomes. Public health strategies are urgently required to improve the overall health and nutritional status of women of reproductive age. Obesity prevention and early detection of malnutrition with standardised screening methods would detect pregnant women at increased risk of iron deficiency. Development of sensitive, individual biomarkers of iodine status are required to protect maternal health and fetal/infant brain development. Risk assessments of vitamin D requirements during pregnancy need to be revisited from the perspective of fetal and neonatal requirements. International consensus on standardised approaches to micronutrient assessment, analysis and reporting as well as sensitive, clinically-validated infant and child neuro-behavioural outcomes will enable progression of useful observational and intervention studies.