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Context and purpose There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. Methods IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5-86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds. Results To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. Conclusions Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose-response relationship and risk characterisation for health outcomes. Trail registration PROSPERO International Prospective Register of Systematic Reviews (Registration Number: CRD42018097260).

BACKGROUND: Vitamin D insufficiency is associated with risk of cardiovascular diseases (CVD) and cancer in observational studies, but evidence for benefits with vitamin D supplementation is limited. OBJECTIVES: To investigate the effects of vitamin D3 supplementation on CVD and cancer incidence. DESIGN: The study was a 5-year randomized placebo-controlled trial among 2495 male participants ≥ 60 years and post-menopausal female participants ≥ 65 years from a general Finnish population who were free of prior CVD or cancer. The study had three arms: placebo, 1600 IU/day or 3200 IU/day vitamin D3. Follow-up was by annual study questionnaires and national registry data. A representative sub-cohort of 551 participants had more detailed in-person investigations. The primary endpoints were incident major CVD and invasive cancer. Secondary endpoints included the individual components of the primary CVD endpoint (myocardial infarction, stroke, and CVD mortality), site-specific cancers and cancer death. RESULTS: During the follow-up, there were 41 (4.9%), 42 (5.0%) and 36 (4.3%) major CVD events in the placebo, 1600 IU/d (vs. placebo: hazard ratio (HR), 0.97;95% CI, 0.63,1.49; P = 0.89), and 3200 IU/d (HR, 0.84;95% CI, 0.54,1.31; P = 0.44) arms, respectively. Invasive cancer was diagnosed in 41 (4.9%), 48 (5.8%) and 40 (4.8%) participants in the placebo, 1600 IU/d (HR, 1.14;95% CI, 0.75,1.72; P = 0.55), and 3200 IU/d (HR, 0.95;95% CI, 0.61,1.47; P = 0.81) arms, respectively. There were no significant differences in the secondary endpoints or total mortality. In the sub-cohort, the mean (standard deviation) baseline serum 25-hydroxyvitamin D concentration was 75 (18) nmol/L. After 12 months, the concentrations were 73 (18) nmol/L, 100 (21) nmol/L and 120 (22) nmol/L in the placebo, 1600 IU/d and 3200 IU/d arms, respectively. CONCLUSIONS: Vitamin D3 supplementation did not lower the incidence of major CVD events or invasive cancer among older adults, possibly due to sufficient vitamin D status in most participants at baseline. Clinical Trial Registry number: ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813. CC BY 4.0Virtanen, Jyrki K.(corresponding author)Published: 04 January 2022This study was supported by funding from the Academy of Finland (#137826), University of Eastern Finland, Juho Vainio Foundation, Medicinska Understödsföreningen Liv och Hälsa, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, and Finnish Cultural Foundation.

The safety considerations of food-based solutions for vitamin D deficiency prevention, such as fortification and supplementation, are critical. On the basis of collective data from 20 randomized controlled trials (RCTs) and 20 national healthy surveys, as well as prospective cohort studies (PCSs) across the ODIN project (“Food-based solutions for optimal vitamin D nutrition and health through the life cycle”, FP7-613977), we analyzed the potential safety issues arising from vitamin D intakes and/or supplementation. These adverse consequences included high serum 25-hydroxyvitamin D (S-25(OH)D) concentrations (>125 nmol/L), high serum calcium concentrations, and vitamin D intakes in excess of the tolerable upper intake levels (ULs). In the RCTs (n = 3353, with vitamin D doses from 5–175 µg/day), there were no reported adverse effects. The prevalence of high S-25(OH)D was 125 nmol/L were rare in the RCTs and PCSs, and no associated adverse effects were observed.

Background Genetic factors modify serum 25-hydroxyvitamin D [25(OH)D] concentration and can affect the optimal intake of vitamin D. Objectives We aimed to personalize vitamin D supplementation by applying knowledge of genetic factors affecting serum 25(OH)D concentration. Methods We performed a genome-wide association study of serum 25(OH)D concentration in the Finnish Health 2011 cohort (n = 3339) using linear regression and applied the results to develop a population-matched genetic risk score (GRS) for serum 25(OH)D. This GRS was used to tailor vitamin D supplementation for 96 participants of a longitudinal Digital Health Revolution (DHR) Study. The GRS, serum 25(OH)D concentrations, and personalized supplementation and dietary advice were electronically returned to participants. Serum 25(OH)D concentrations were assessed using immunoassays and vitamin D intake using FFQs. In data analyses, cross-sectional and repeated-measures statistical tests and models were applied as described in detail elsewhere. Results GC vitamin D-binding protein and cytochrome P450 family 2 subfamily R polypeptide 1 genes showed genome-wide significant associations with serum 25(OH)D concentration. One single nucleotide polymorphism from each locus (rs4588 and rs10741657) was used to develop the GRS. After returning data to the DHR Study participants, daily vitamin D supplement users increased from 32.6% to 60.2% (P = 6.5 x 10(-6)) and serum 25(OH)D concentration from 64.4 +/- 20.9 nmol/L to 68.5 +/- 19.2 nmol/L (P = 0.006) between August and November. Notably, the difference in serum 25(OH)D concentrations between participants with no risk alleles and those with 3 or 4 risk alleles decreased from 20.7 nmol/L to 8.0 nmol/L (P = 0.0063). Conclusions We developed and applied a population-matched GRS to identify individuals genetically predisposed to low serum 25(OH)D concentration. We show how the electronic return of individual genetic risk, serum 25(OH)D concentrations, and factors affecting vitamin D status can be used to tailor vitamin D supplementation. This model could be applied to other populations and countries.

ObjectiveTo investigate serum 25-hydroxyvitamin D (S-25(OH)D) concentration in a multi-ethnic population of northern Norway and determine predictors of S-25(OH)D, including Sami ethnicity.DesignCross-sectional data from the second survey of the Population-based Study on Health and Living Conditions in Regions with Sami and Norwegian Populations (the SAMINOR 2 Clinical Survey, 2012–2014). S-25(OH)D was measured by the IDS-iSYS 25-Hydroxy Vitamin Dˢ assay. Daily dietary intake was assessed using an FFQ. BMI was calculated using weight and height measurements.SettingTen municipalities of northern Norway (latitude 68°–70°N).ParticipantsMales (n 2041) and females (n 2424) aged 40–69 years.ResultsMean S-25(OH)D in the study sample was 64·0 nmol/l and median vitamin D intake was 10·3 µg/d. The prevalence of S-25(OH)DConclusionsThere were many modifiable risk factors related to S-25(OH)D, however no clear ethnic differences were found. Even in winter, the low prevalence of vitamin D deficiency found among participants with non-Sami, multi-ethnic Sami and Sami self-perceived ethnicity was likely due to adequate vitamin D intake.

Objective:We investigated the determinants of serum 25-hydroxyvitamin D [S-25(OH)D] and dietary vitamin D sources among three immigrant groups in Finland and compared their S-25(OH)D to the general Finnish population.Design:Cross-sectional population-based Migrant Health and Wellbeing Study and the nationally representative Finnish Health 2011 Survey. S-25(OH)D was standardised according to the Vitamin D Standardisation Program. Vitamin D sources were assessed by interview.Setting:Six different municipalities in Finland (60°–63°N).Participants:Immigrants aged 18–64 years (446 Russians, 346 Somalis, 500 Kurds), 798 Finns aged 30–64 years.Results:The mean of S-25(OH)D was 64 (95 % CI 62, 66), 44 (95 % CI 41, 46), 35 (95 % CI 34, 37) and 64 (95 % CI 62, 66) nmol/l for Russians, Somalis, Kurds and Finns, respectively. S-25(OH)D among Somalis and Kurds was lower compared with Finns (P < 0·001). The prevalence of vitamin D deficiency (S-25(OH)D P < 0·001). Vitamin D-rich foods differed between the groups; vitamin D-fortified fat spread consumption was higher among Somalis (91 %) than among Russians (73 %) and Kurds (60 %); fish was less consumed among Kurds (17 %) than among Russians (43 %) and Somalis (38 %); and 57 % Russians, 56 % Kurds and 36 % Somalis consumed vitamin D-fortified dairy daily (P < 0·001 for all). Daily smoking, alcohol consumption and winter blood sampling were determinants of vitamin D insufficiency (P ≤ 0·03). Older age, physical activity, fish and vitamin D-fortified dairy consumption were associated with lower odds of insufficiency (P ≤ 0·04).Conclusions:Vitamin D status differed among immigrant groups and the determinants are, to some degree, associated with learned or existing cultural behaviours.

Aims: Nordic countries share fairly similar food culture and geographical location as well as common nutrition recommendations. The aim of this paper was to review the latest data on vitamin D status and intake and to describe the national supplementation and food fortification policies to achieve adequate vitamin D intake in the Nordic countries. Methods: The data are based on results derived from a literature search presented in a workshop held in Helsinki in November 2018 and completed by recent studies. Results: Vitamin D policies and the implementation of the recommendations differ among the Nordic countries. Vitamin D fortification policies can be mandatory or voluntary and widespread, moderate or non-existent. Vitamin D supplementation recommendations differ, ranging from all age groups being advised to take supplements to only infants. In the general adult population of the Nordic countries, vitamin D status and intake are better than in the risk groups that are not consuming vitamin D supplements or foods containing vitamin D. Non-Western immigrant populations in all Nordic countries share the problem of vitamin D insufficiency and deficiency. Conclusions: Despite the common nutrition recommendations, there are differences between the Nordic countries in the implementation of the recommendations and policies to achieve adequate vitamin D intake and status. There is a need for wider Nordic collaboration studies as well as strategies to improve vitamin D status, especially in risk groups.

Insufficient vitamin D status (serum 25-hydroxyvitamin D (S-25(OH)D)3 supplementation, through a 5-month randomised controlled trial, in East African and Finnish women in Southern Finland (60°N) from December 2014 to May 2015. Vitamin D intakes (dietary and supplemental) were also examined. Altogether, 191 subjects were screened and 147 women (East Africans n 72, Finns n 75) aged 21–64 years were randomised to receive placebo or 10 or 20 µg of vitamin D3/d. S-25(OH)D concentrations were assessed by liquid chromatography–tandem MS. At screening, 56 % of East Africans and 9 % of Finns had S-25(OH)Dsd 14·3) v. 15·2 (sd 13·4) µg/d, Psd=16·3) nmol/l) than in East Africans (51·5 (sd 15·4) nmol/l) (P=0·001). In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D), mean S-25(OH)D increased by 8·5 and 10·0 nmol/l with a 10-µg dose and by 10·7 and 17·1 nmol/l with a 20-µg dose for Finns and East Africans, respectively (P>0·05 for differences between ethnic groups). In conclusion, high prevalence of vitamin D insufficiency existed among East African women living in Finland, despite higher vitamin D intake than their Finnish peers. Moderate vitamin D3 supplementation was effective in increasing S-25(OH)D in both groups of women, and no ethnic differences existed in the response to supplementation.

Dear Editor, We read with interest the recently published paper by McClure et al. [1] that reports trends in intake and primary sources of dietary phosphorus in the NHANES data for the period 2001–2014.[...] Non

The Department of Nutrition for Health and Development of the World Health Organization (WHO) in collaboration with the Executive Committee of the 18th Vitamin D Workshop (VDW), organised a joint symposium on the prevention and consequences of vitamin D deficiency in pregnant women and children, convening experts on vitamin D, clinicians and policy-makers. The overall aim was to identify priority areas for research and to discuss the need for global options for policy, with a focus on the prevention of rickets in infants and children and vitamin D deficiency in pregnant women. The scope and purpose were: (i) to present the WHO research strategy for health, addressing vitamin D-related public health problems and the process for the development of evidence-informed guidelines in general and how vitamin D interventions in diverse populations could be prioritised; (ii) to provide an overview of vitamin D status in children and pregnant and lactating women across the world; (iii) to review the health risks associated with vitamin D deficiency in children and in pregnant women and their offspring; (iv) to understand the aetiology of vitamin D deficiency in pregnant women and children; (v) to identify and interpret biomarkers to assess vitamin D status and to consider possible clinical and biochemical screening tools for determining the prevalence of nutritional rickets in at risk groups or communities; and (vi) to provide an overview of policies and recommendations on vitamin D across the world. The format of the symposium was a composite of comprehensive scientific presentations and a panel debate with international experts on WHO guidelines, nutritional rickets, nutritional policy and consequences of vitamin D deficiency during pregnancy. This paper summarizes the content and outcomes of the panel debate. (C) 2015 Elsevier Ltd. All rights reserved.

IntroductionOur previous study-level (aggregate data) meta-analysis suggested that vitamin D supplements may be beneficial for bone density specifically in children with vitamin D deficiency. However, the misclassification of vitamin D status inherent in study-level data means that the results are not definitive and cannot provide an accurate assessment of the size of any effect. Therefore, we propose to undertake an individual patient data (IPD) meta-analysis to determine whether the effect of vitamin D supplementation on bone density in children differs according to baseline vitamin D status, and to specifically estimate the effect of vitamin D in children who are vitamin D deficient.Methods and analysisThis study has been designed to adhere to the Preferred Reporting Items for Systematic Review and Meta-Analyses of IPD statement. We will include randomised placebo-controlled trials of vitamin D supplementation reporting bone density outcomes at least 6 months after the study commenced in children and adolescents (aged 2and potential publication bias (small-study effects) and availability bias by funnel plots, Egger’s test and Peter’s test.Ethics and disseminationEthics approval will not be required as the data are to be used for the primary purpose for which they were collected and all original individual studies had ethics approval. Results of the IPD meta-analysis will be submitted for publication in a peer-reviewed journal.PROSPERO registration numberCRD42017068772.

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to revise the tolerable upper intake level (UL) for vitamin D for infants (≤ 1 year) set in 2012. From its literature review, the Panel concluded that the available evidence on daily vitamin D intake and the risk of adverse health outcomes (hypercalciuria, hypercalcaemia, nephrocalcinosis and abnormal growth patterns) cannot be used alone for deriving the UL for infants. The Panel conducted a meta‐regression analysis of collected data, to derive a dose–response relationship between daily supplemental intake of vitamin D and mean achieved serum 25(OH)D concentrations. Considering that a serum 25(OH)D concentration of 200 nmol/L or below is unlikely to pose a risk of adverse health outcomes in infants, the Panel estimated the percentage of infants reaching a concentration above this value at different intakes of vitamin D. Based on the overall evidence, the Panel kept the UL of 25 μg/day for infants aged up to 6 months and set a UL of 35 μg/day for infants 6–12 months. The Panel was also asked to advise on the safety of the consumption of infant formulae with an increased maximum vitamin D content of 3 μg/100 kcal (Commission Delegated Regulation (EU) 2016/127 repealing Directive 2006/141/EC in 2020). For infants aged up to 4 months, the intake assessment showed that the use of infant formulae containing vitamin D at 3 μg/100 kcal may lead some infants to receive an intake above the UL of 25 μg/day from formulae alone without considering vitamin D supplemental intake. For infants aged 4–12 months, the 95th percentile of vitamin D intake (high consumers) estimated from formulae and foods fortified or not with vitamin D does not exceed the ULs, without considering vitamin D supplemental intake., This publication is linked to the following EFSA Supporting Publications article: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2018.EN-1456/full

Objective The in utero environment plays an important role in shaping development and later life health of the fetus. It has been shown that maternal genetic factors in the metabolic pathway of vitamin D associate with type 1 diabetes in the child. In this study we analyzed the genetic determinants of serum 25-hydroxyvitamin D (25OHD) concentration during pregnancy in mothers whose children later developed type 1 diabetes and in control mothers. Study design 474 mothers of type 1 diabetic children and 348 mothers of non-diabetic children were included in the study. We previously selected 7 single nucleotide polymorphisms (SNPs) in four genes in the metabolic pathway of vitamin D vitamin based on our previously published data demonstrating an association between genotype and serum 25OHD concentration. In this re-analysis, possible differences in strength in the association between the SNPs and serum 25OHD concentration in mothers of type 1 diabetic and non-diabetic children were investigated. Serum 25OHD concentrations were previously shown to be similar between the mothers of type 1 diabetic and non-diabetic children and vitamin D deficiency prevalent in both groups. Results Associations between serum 25OHD concentration and 2 SNPs, one in the vitamin D receptor (VDR) gene (rs4516035) and one in the group-specific component (GC) gene (rs12512631), were stronger during pregnancy in mothers whose children later developed type 1 diabetes than in mothers whose children did not (p(interaction) = 0.03, 0.02, respectively). Conclusions We show for the first time that there are differences in the strength of genetic determinants of serum 25OHD concentration during pregnancy between the mothers of type 1 diabetic and non-diabetic children. Our results emphasize that the in utero environment including maternal vitamin D metabolism should be important lines of investigation when searching for factors that lead to early programming of type 1 diabetes.

Background: Both exercise and vitamin D are recommended means to prevent falls among older adults, but their combined effects on fallinduced injuries are scarcely studied. Methods: A 2-year follow-up of a previous 2-year randomized controlled trial with vitamin D and exercise (Ex) of 409 older home-dwelling women using a factorial 2 x 2 design (D(-)Ex(-), D(+)Ex(-), D(-)Ex(+), D(+)Ex(+)). Besides monthly fall diaries, femoral neck bone mineral density (fn-BMD), and physical functioning were assessed at 1 and 2 years after the intervention. Results: After the intervention, S-25OHD concentrations declined to baseline levels in both supplement groups. The groups did not differ for change in fn-BMD or physical functioning, except for leg extensor muscle strength, which remained about 10% greater in the exercise groups compared with the reference group (D(-)Ex(-)). There were no between-group differences in the rate of all falls, but medically attended injurious falls reduced in D+ Ex-and D(-)Ex(+) groups compared with D(-)Ex(-). However, all former treatment groups had less medically attended injured fallers, HRs (95% CI) being 0.62 (0.39-1.00) for D+ Ex-, 0.46 (0.28-0.76) for D(-)Ex(+), and 0.55 (0.34-0.88) for D(+)Ex(+), compared with D(-)Ex(-). Conclusions: Exercise-induced benefits in physical functioning partly remained 2 years after cessation of supervised training. Although there was no difference in the rate of all falls, former exercise groups continued to have lower rate of medically attended injured fallers compared with referents even 2 years after the intervention. Vitamin D without exercise was associated with less injurious falls with no difference in physical functioning.

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.

Vitamin D and calcium insufficiencies are risk factors for multiple chronic diseases. Data from 46 recent studies from Europe, North America, South-East Asia and the South Pacific area clearly indicate that a low vitamin D status and inadequate calcium nutrition are highly prevalent in the general population (30–80%), affecting both genders. The extent of insufficiencies is particularly high in older populations, and in some geographical areas, also in children and in young women of child-bearing age, in ethnic minorities and immigrants, as well as in people of low socio-economic status. Enrichment of cereal grain products with vitamin D and calcium would be a viable approach to increase consumption and improve health outcomes in the general population worldwide.

Fibroblast growth factor 23 (FGF23), a bone-derived hormone, participates in the hormonal bone–parathyroid–kidney axis, which is modulated by PTH, 1,25-dihydroxyvitamin D, plasma phosphate (Pi), and diet. Inappropriately high serum FGF23, seen in certain genetic and acquired disorders, results in urinary phosphate wasting and impaired bone mineralization. This study investigated the impact of FGF23 gene variation on phosphate homeostasis and bone health. The study included 183 children and adolescents (110 girls) aged 7–19 years (median 13.2years). Urine and blood parameters of calcium and phosphate homeostasis were analyzed. Bone characteristics were quantified by DXA and peripheral quantitative computed tomography (pQCT). Genetic FGF23 variation was assessed by direct sequencing of coding exons and flanking intronic regions. Nine FGF23 polymorphisms were detected; three of them were common: rs3832879 (c.212-37insC), rs7955866 (c.716C>T, p.T239M) and rs11063112 (c.2185A>T). Four different haplotypes and six different diplotypes were observed among these three polymorphisms. The variations in FGF23 significantly associated with plasma PTH and urinary Pi excretion, even after adjusting for relevant covariates. FGF23 variations independently associated with total hip BMD Z-score, but not with other bone outcomes. In instrument analysis, genetic variance in FGF23 was considered a weak instrument as it only induced small variations in circulating FGF23, PTH and Pi concentrations (F statistic less than 10). The observed associations between FGF23 variations and circulating PTH, and Pi excretion and total hip BMD Z-scores suggest that FGF23 polymorphisms may play a role in mineral homeostasis and bone metabolism.

The aim was to describe vitamin D status and its association with changes in PF during 12 months in Finnish community-dwelling elderly (≥65 years).Baseline serum 25-hydroxyvitamin D (25OHD) concentration was measured by enzymeimmunoassay, and participants (n=518) were divided according to 25OHD to three groups (I50 nmol/l, II 50-74.9 nmol/l, and III ≥75 nmol/l). PF (maximal isometric extension strength of right and left knee, and time in five-repetition sit-to-stand test (5STS) and 10-m walking test) was measured at baseline and after 12 months. 25OHD deficiency (50 nmol/l) was found in 20.5% of the participants. During a 12-month follow-up, differences in changes in knee extensor strength of right (p=0.044) and left (p=0.010) lower extremity and in 10-m walking test (p=.040) between the groups were significant. According to further pairwise comparisons these differences were between groups I and III (right knee, p=0.036; left knee, p=0.009; 10-m walk, p=0.044), with the exception of left knee extensor strength in which there were also significant difference between groups I and II (p=0.039). All significant differences in changes were in favour of group II or III. Significant differences in changes in knee extensor strengths maintained after adjustments for group (intervention/control), parathyroid hormone, and baseline level of knee extensor strength.Prospective analyses showed low 25OHD concentrations (50 nmol/l) to be associated with deterioration in PF during 12 months compared with high 25OHD concentrations (≥75 nmol/l).

Background Falls are the leading cause of unintentional injury and injury-related death among older people. In addition to physical activity, vitamin D also may affect balance and neuromuscular function. Low serum 25-hydroksivitamin D level increases the risk of bone loss, falls and fractures. Thus, an appropriate exercise program and sufficient vitamin D intake may significantly improve not only functional balance, but also balance confidence. Balance represents a complex motor skill determined by reaction time, muscle strength, and speed and coordination of movement. Methods/Design A 2-year randomized double-blind placebo-controlled vitamin D and open exercise trial of 409 home-dwelling women 70 to 80 years of age comprising four study arms: 1) exercise + vitamin D (800 IU/d), 2) exercise + placebo, 3) no exercise + vitamin D (800 IU/d), 4) no exercise + placebo. In addition to monthly fall diaries, general health status, life style, bone health, physical functioning, and vitamin D metabolism will be assessed. The primary outcomes are the rate of falls and fall-related injuries. Secondary outcomes include changes in neuromuscular functioning (e.g. body balance, muscle strength), ADL- and mobility functions, bone density and structure, cardiovascular risk factors, quality of life and fear of falling. Discussion The successful completion of this trial will provide evidence on the effectiveness of exercise and vitamin D for falls reduction. Trial Registration ClinicalTrial.gov -register (NCT00986466).

Vitamin D binding protein (DBP)/group-specific component (Gc), correlates positively with serum vitamin D metabolites, and phenotype influences serum 25-hydroxyvitamin D (S-25(OH)D) concentration. The protein isoform has been associated with decreased bone mineral density (BMD) and increased fracture risk. We examined the role of GC genotypes in S-25(OH)D status and BMD in 231 Finnish children and adolescents aged 7-19 yr. BMD was measured with DXA from lumbar spine (LS), total hip, and whole body, and for 175 subjects, radial volumetric BMD was measured with pQCT. Background characteristic and total dietary intakes of vitamin D and calcium were collected. The concentrations of 25(OH)D, parathyroid hormone (PTH), calcium and other markers of calcium homeostasis were determined from blood and urine. Genotyping was based on single-nucleotide polymorphism (rs4588) in the GC gene. The genotype distribution was: GC 1/1 68%, GC 1/2 26% and GC 2/2 6%. A significant difference emerged in 25(OH)D and PTH concentrations between the genotypes, (p = 0.001 and 0.028 respectively, ANCOVA). There was also a linear trend in: Gc 2/2 had the lowest 25(OH) D and PTH concentrations (p = 0.025 and 0.012, respectively). Total hip bone mineral content was associated with GC genotype (BMC) (p = 0.05, ANCOVA) in boys. In regression analysis, after adjusting for relevant covariates, GC genotype was associated with LS BMC and strength and strain index (SSI) Z-score in both genders, and LS BMD in boys. In conclusion, the present study demonstrates the association between GC genotypes and S-25(OH)D and PTH concentrations. The results show the influence of DBP genetic variation on bone mass accrual in adolescence.

Background : Calcium (Ca) is an essential nutrient for the human body. Despite lively research, there is uncertainty about Ca requirements in terms of desirable health outcomes including an upper intake level above which the potential for harm increases. Objectives : The aim was to conduct a review to update requirements and desirable or harmful health effects of Ca on the current scientific evidence. Methods :We searched Medline and Swemed from January 2000 to December 2011 and included all systematic reviews that reported Ca supplementation or usual Ca intake on health outcomes. Meta-analyses, randomized clinical trials and cohort studies were included in the second search between May 2009 and March 2011 and an additional search covering studies till the end of 2011. This review concentrated on studies reporting independent effects of Ca, although a few recent trials report sole effects of Ca on health outcomes, most trials use Ca in combination with vitamin D vs. placebo. Results : In total, we reviewed 38 studies addressing the effects of Ca on bone, pregnancy-related outcomes, cancers, cardiovascular outcomes, obesity, and mortality. There was a lot of heterogeneity in the study protocols, which made it difficult to draw any strong conclusions. According to the literature, high Ca intake seems to have a small positive effect on bone mineral content (BMC) or bone mineral density (BMD) in children and postmenopausal women. We did not find any consistent evidence on the effects of Ca on bone health in premenopausal women or men. Also, the evidence that Ca supplementation reduces fracture incidence is scarce and inconsistent. Maternal diet may influence the peak bone mass of offspring but more studies are required. There was no overall effect of Ca intake on cancers. Ca was associated with a decreased risk of breast cancer and a slightly increased risk of prostate cancer in two of the three studies. No associations were found with other cancers. We found no consistent association between cardiovascular outcomes and Ca intake except for blood pressure. A small decrease of 2-4 mmHg in systolic blood pressure was found in pregnant and in hypertensive subjects with Ca supplementation. Reviewed studies did not show consistent evidence relating Ca intake to either mortality or obesity. Conclusion : Based on this evidence, there is no need to change the Nordic recommendations for Ca intake. However, due to heterogeneity in the studies it is difficult to interpret the results and provide single summary statement. Keywords : Calcium intake; calcium requirements; disease prevention; osteoporosis; bone mineral density; health maintenance; health outcomes (Published: 16 May 2013) Citation: Food & Nutrition Research 2013. 57 : 21082 - http://dx.doi.org/10.3402/fnr.v57i0.21082 Special Issue: This paper is part of the Nordic Nutrition Recommendations - The NNR5 project . More papers from this issue can be found at http://www.foodandnutritionresearch.net

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations>75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.

As background information, the reader should appreciate that at he 13th Vitamin DWorkshop in 2006 it was agreed that about half f elderly North Americans and Western Europeans and probably lso two thirds of the rest of the world are vitamin D deficient as udgedby their inability tomaintain a healthy bonedensity [1–3]. It as also generally agreed that the serum concentration of 25(OH)D n normal subjects is the best indicator for judging the vitamin D tatus in patients with vitamin D-related disease states [4]. The14thWorkshoponVitaminD,held inBrugge, Belgium,Octoer 4–8, 2009wasattendedby419 scientists from35countrieswho ere privileged to listen and participate in a Vitamin D Roundtable hat was held in order to allow presentation and broad discusion of two distinct views of and approaches to worldwide vitamin nutritional status. One Roundtable position is that an absolute inimum 25(OH)D level of 20ng/ml (50nmol/l) is necessary in all ndividuals in order to support and maintain all the classic actions f vitamin D on bone andmineral health and that, according to this riterion, a large proportion of the world’s population is vitamin D eficient. Thosewhohold this position further believe that thehuge ffort needed to ameliorate this deficiency must be undertaken as oon and actively as possible and that the target 25(OH)D levels of 20ng/ml should be obtained in the majority of the target populaion. The second Roundtable position is that newer data showing ssociations between vitamin D status and prevalence of several iseases such as cardiovascular disease, hypertension, colon and reast cancer, multiple sclerosis as well as the involvement of vitain D in muscle strength and immune functions [5], indicates that arget levels of 25(OH)D should be 30–40ng/ml (75–100nmol/l) t the minimum. As a basis for policy decision making, these two ositions are incompatible with one another. However, through onsideration of the aspects of vitamin D nutrition upon which the roponents of the two views agree, as well as acknowledging diferences in opinion, consensus on how to proceed in the near term an emerge. This was the goal of the Vitamin D Roundtable. TheRoundtable, chaired byAnthonyNorman (USA) andChristoher Gallagher (USA), began with 15-min presentations from obert Heaney (USA) and Reinhold Vieth (Canada), both propoents of 25(OH)D>40ng/ml, followed by presentations by Roger ouillon (Belgium) and Paul Lips (Netherlands),who advocateminmum25(OH)D levels of 20ng/ml. A selected group of experts from round theworld, Bess Dawson-Hughes (USA), John Pettifor (South frica), Peter Ebeling (Australia), and Christine Lamberg-Allardt

Recent cross-sectional data suggest that better vitamin K status in young girls (aged 3–16 years) is associated with decreased bone turnover, even though it is not associated with bone mineral content (BMC). The objective of the present study was to investigate the relationship between serum percentage of undercarboxylated osteocalcin (%ucOC), as an index of vitamin K status, and BMC and biochemical indices of bone turnover in peri-pubertal Danish girls. This peri-pubertal stage is a dynamic period of bone development, and as such, may represent an important window of opportunity for vitamin K status to modulate childhood bone health. Serum %ucOC and serum 25-hydroxyvitamin D (25 (OH) D) were measured at baseline in a study of 223 healthy girls aged 11–12 years. Urinary pyridinium crosslinks of collagen and serum total osteocalcin as markers of bone resorption and formation, respectively, as well as BMC (total body and lumbar spine) were also measured. Serum %ucOC (median 21·9 %) was not associated with markers of bone resorption or with total osteocalcin. Serum %ucOC was inversely correlated with serum 25 (OH) D (r− 0·143;P P P

Summary In this prospective study, 87 children were followed up from birth to 14 months with data on maternal vitamin D status during the pregnancy. Postnatal vitamin D supplementation improved vitamin D status but only partly eliminated the differences in bone variables induced by maternal vitamin D status during the fetal period. Introduction Intrauterine nutritional deficits may have permanent consequences despite improved nutritional status postnatally. We evaluated the role of prenatal and postnatal vitamin D status on bone parameters in early infancy. Methods Eighty-seven children were followed from birth to 14 months. Background data were collected with a questionnaire and a 3-day food record. At 14 months bone variables were measured with peripheral computed tomography (pQCT) from the left tibia. Serum 25-OHD and bone turnover markers were determined. Findings were compared with maternal vitamin D status during pregnancy. Results The children were divided into two groups based on vitamin D status during pregnancy. Despite discrepant S-25-OHD at baseline (median 36.3 vs. 52.5 nmol/l, p

Background Dietary phosphorus (P) intake in Western countries is 2- to 3-fold higher than recommended, and phosphate is widely used as a food additive in eg. cola beverages and processed meat products. Elevated serum phosphate concentrations have been associated with cardiovascular disease (CVD) risk factors and CVD itself in several studies in patients with renal dysfunction and in a few studies in the general population. Carotid intima-media thickness (IMT) is a CVD risk factor, thus the aim of the study was to determine if an association between dietary P, especially food additive phosphate (FAP), intake, and IMT exists. Methods Associations among total phosphorus (TP) and FAP intake and carotid IMT were investigated in a cross-sectional study of 37- to 47-year-old females (n = 370) and males (n = 176) in Finland. Associations among TP intake, FAP intake, and IMT were tested by analysis of covariance (ANCOVA) in quintiles (TP) and sextiles (FAP) using sex, age, low-density/high-density lipoprotein cholesterol ratio, smoking status, and IMT sonographer as covariates. Results No significant associations were present between TP or FAP intake and IMT (p > 0.05, ANCOVA), but in between-group comparisons some differences were found indicating higher IMT among subjects with higher P intake. When testing for a significant linear trend with contrast analysis, a positive trend was observed between energy-adjusted TP intake and IMT among all subjects (p = 0.039), and among females a tendency for a trend existed (p = 0.067). Among all subjects, a significant positive linear trend was also present between FAP intake and IMT (p = 0.022); this trend was also seen in females (p = 0.045). In males, no significant associations or trends were noted between TP or FAP intake and IMT (p > 0.05). Conclusions Our results indicate that a significant linear trend exists between energy-adjusted TP intake and FAP intake, and IMT among all subjects. Based on these results, high dietary P intake should be further investigated due to its potential association with adverse cardiovascular health effects in the general population.