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Vitamin D is essential for the maintenance of calcium homeostasis and bone mineralization. Overt deficiency of vitamin D causes rickets in children and osteomalacia in adults. Vitamin D deficiency is an important public health problem worldwide. This review examines the available published data from all peer-reviewed original research articles of community and hospital-based research carried out on vitamin D status in different population groups in Bangladesh. Baseline data of intervention trials are also included. The available selected articles were in English and retrieved from 2002 to January 2022. The paper concentrates on underlying factors for increased prevalence of vitamin D deficiency in Bangladesh. Studies uniformly report very high prevalences of hypovitaminosis D among different population groups. Age and sex-specific comparisons indicate that prevalence is higher for the elderly and women. Hypovitaminosis D ranged from 21 to 75 % for infants, children, and adolescents, 38 to 100 percent for premenopausal women, 66 to 94.2 % for pregnant women, 6 to 91.3 % for adult men and 82 to 95.8 % for postmenopausal women. Important underlying factors related to this silent epidemic include dark skin colour, homebound and sedentariness, insufficient sunlight exposure, atmospheric pollution, clothing style, obesity, use of sunscreen and no supplementation. A comprehensive strategy to alleviate and control the health consequences of vitamin D deficiency is needed. This would include the creation of public awareness, refrain in sunscreen usage, exposure to sunlight, regular exercise, food fortification, and supplementation with vitamin D (bearing in mind potential differences between them and food-based sources).

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.

Objective: To assess whether supplementation with long chain n-3 fatty acids during pregnancy, lactation, or infancy reduces the risk of developing asthma or atopic disease during childhood. Methods: Searches were performed in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus up to 2021-09-20, for randomized controlled trials (RCTs) that investigated the effect of supplemental long chain n-3 fatty acids during pregnancy, lactation, or infancy for the prevention of childhood asthma or allergy. Article selection, data extraction, and risk of bias assessment (Cochrane’s Risk of Bias 2.0) were independently conducted by two assessors. The evidence was synthesized qualitatively according to the criteria of the World Cancer Research Fund and meta-analyzed. Results: A total of nine RCTs met inclusion criteria; six were conducted during pregnancy, two during infancy, and one during both pregnancy and infancy. Meta-analysis showed that long chain n-3 fatty acid supplementation during pregnancy significantly reduced the risk of asthma/wheeze in the child (RR 0.62 [95% confidence interval 0.34–0.91], P = 0.005, I2 = 67.4%), but not other outcomes. Supplementation during lactation of infancy showed no effects on any outcome. The strength of evidence that long chain n-3 fatty acid supplementation during pregnancy reduces risk of asthma/wheeze in the offspring was considered limited – suggestive. No conclusion could be made for the effects of long chain n-3 fatty acid supplementation during pregnancy for other atopic diseases, or for supplementation during lactation or infancy for any outcome. Conclusion: The intake of long chain n-3 fatty acid supplements during pregnancy may reduce the risk of asthma and/or wheeze in the offspring, but the strength of evidence is low. There is inconclusive evidence for the effects of long chain n-3 fatty acid supplements during pregnancy for other outcomes, as well as for supplementation during lactation or infancy. publishedVersion

Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) 10% of Europeans. The European Calcified Tissue Society (ECTS) advises that the measurement of serum 25(OH)D be standardized, for example, by the Vitamin D Standardization Program. Risk groups include young children, adolescents, pregnant women, older people (especially the institutionalized) and non-Western immigrants. Consequences of vitamin D deficiency include mineralization defects and lower bone mineral density causing fractures. Extra-skeletal consequences may be muscle weakness, falls and acute respiratory infection, and are the subject of large ongoing clinical trials. The ECTS advises to improve vitamin D status by food fortification and the use of vitamin D supplements in risk groups. Fortification of foods by adding vitamin D to dairy products, bread and cereals can improve the vitamin D status of the whole population, but quality assurance monitoring is needed to prevent intoxication. Specific risk groups such as infants and children up to 3 years, pregnant women, older persons and non-Western immigrants should routinely receive vitamin D supplements. Future research should include genetic studies to better define individual vulnerability for vitamin D deficiency, and Mendelian randomization studies to address the effect of vitamin D deficiency on long-term non-skeletal outcomes such as cancer.

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.

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.

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives dietary reference values (DRVs) for vitamin K. In this Opinion, the Panel considers vitamin K to comprise both phylloquinone and menaquinones. The Panel considers that none of the biomarkers of vitamin K intake or status is suitable by itself to derive DRVs for vitamin K. Several health outcomes possibly associated with vitamin K intake were also considered but data could not be used to establish DRVs. The Panel considers that average requirements and population reference intakes for vitamin K cannot be derived for adults, infants and children, and therefore sets adequate intakes (AIs). The Panel considers that available evidence on occurrence, absorption, function and content in the body or organs of menaquinones is insufficient, and, therefore, sets AIs for phylloquinone only. Having assessed additional evidence available since 1993 in particular related to biomarkers, intake data and the factorial approach, which all are associated with considerable uncertainties, the Panel maintains the reference value proposed by the Scientific Committee for Food (SCF) in 1993. An AI of 1 μg phylloquinone/kg body weight per day is set for all age and sex population groups. Considering the respective reference body weights, AIs for phylloquinone are set at 70 μg/day for all adults including pregnant and lactating women, at 10 μg/day for infants aged 7–11 months, and between 12 μg/day for children aged 1–3 years and 65 μg/day for children aged 15–17 years., This publication is linked to the following EFSA Supporting Publications article: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2017.EN-1220/full

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.

BACKGROUND Plant-based diets may reduce the risk of chronic diseases, but can also lead to low calcium and vitamin D intakes, posing a risk for bone health. OBJECTIVES We investigated whether partial replacement of animal proteins with plant-based proteins using a whole-diet approach affects bone and mineral metabolism in healthy adults in 3 groups fed diets differing in protein composition. METHODS This 12-week clinical trial was comprised of 107 women and 29 men (20-69 years old; BMI mean ± SD, 24.8 ± 3.9) randomly assigned to consume 1 of 3 diets designed to provide 17 energy percent (E%) protein: "animal" (70% animal protein, 30% plant protein of total protein intake), "50/50" (50% animal, 50% plant), and "plant" (30% animal, 70% plant) diets. We examined differences in bone formation [serum intact procollagen type I amino-terminal propeptide (S-iPINP)], bone resorption [serum collagen type 1 cross-linked C-terminal telopeptide (S-CTX)], mineral metabolism markers (primary outcomes), and nutrient intakes (secondary outcomes) by ANOVA/ANCOVA. RESULTS S-CTX was significantly higher in the plant group (mean ± SEM, 0.44 ± 0.02 ng/mL) than in the other groups (P values

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.

In Finland the recommendation for the use of vitamin D supplement is a daily supplement throughout the year for all children. It is also recommended that fluid milk products and fat spreads are fortified with vitamin D. The purpose of this study was to provide up-to-date data on children's dietary and supplemental intake of vitamin D. We also examined educational level differences in the intake and sources of vitamin D.A cross-sectional study on the diet in Finnish 3–6-year-old preschool children (the DAGIS Study) was carried out in 2015–2016. Children were recruited in preschools in Southern Finland and in the Southern Ostrobothnia Region (n = 864). The parents reported child's supplement use (brand name, dose, frequency of use) during the last month and their own education level. The highest parental education level (PEL) was used in analysis. Parents and preschool personnel also filled in a 3-day food record for the child. A part of the families also kept an additional 2-day food record, which we sent to capture seasonal variation in the diet. In this analysis we included children (n = 794) with data for supplement use and at least 1-day food record. We calculated dietary intake based on the Fineli food composition database and created a dietary supplement database. We used Kruskal-Wallis test for statistical analysis.Most of the children in all PELs used vitamin D supplements (low 77%, medium 85%, high 85%). Dietary supplements covered almost half of the total intake in all groups (low 42%, medium 48%, high 47%, p = 0,087). The main dietary sources of vitamin D were fortified fluid milk products, fortified fat spreads and fish dishes. A higher proportion of vitamin D was obtained from fish dishes in families with higher PEL (low 4.3%, medium 4.5%, high 6.1%, p = 0.005), but otherwise there were no differences in the proportions of the main sources. The vitamin D intake from diet and supplements was lowest in families with low PEL but the total intake of vitamin D was adequate in all groups (low 18.3, medium 20.7, high 20.7 μg/day, p = 0.001).The use of vitamin D fortified fluid milk products and fat spreads and the vitamin D supplementation seem to ensure adequate vitamin D intake in all children, regardless the level of parental education.

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.

Aims: We evaluated the consumption of healthy foods among Russian, Somali and Kurdish immigrants in Finland, and examined the relationship between socio-demographic factors and food consumption. Methods: We used data from the Migrant Health and Wellbeing Study (Maamu), a population-based health interview and examination survey in six different municipalities in Finland between 2010 and 2012. Altogether, 635 men and 737 women, aged 18–64 years, of Russian ( n = 527), Somali ( n = 337) and Kurdish ( n = 508) origin were included. The important socio-demographic determinants of healthy food consumption – sex, age, education, place of residence and household size – were assessed by logistic regression. Results: Based on the consumption frequencies of recommended healthy foods – fruits, berries, vegetables, fish and rye bread – immigrants of Russian origin had higher consumption of healthy foods than their peers of Kurdish and Somali origin. Low consumption of fresh vegetables, fruits and berries was found among Somali immigrants. Sex and age were the most important determinants of healthy food consumption, as women and older age groups had diets closer to the national nutrition recommendations. High educational level was also positively associated with healthy food consumption. Conclusions: We found ethnic differences in the consumption of healthy foods among the immigrant groups of Russian, Somali and Kurdish origin in Finland. Socio-demographic factors, especially age, sex and education, seem to also play an important role in immigrants’ food consumption. Further studies examining the consumption of fruits, berries and fresh vegetables among Somali immigrants in Finland are needed.

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 human leukocyte antigen (HLA) gene region associates with the risk for several autoimmune diseases, including type 1 diabetes. An association between vitamin D deficiency and several autoimmune diseases has been suggested. We tested the association between serum 25-hydroxyvitamin D (25OHD) concentrations and HLA alleles in pregnant Finnish women.HLA-B (n=395), HLA-DRB1 (n=501) and HLA-DQB1 (n=475) alleles were genotyped in pregnant women (mothers of children who later developed type 1 diabetes and mothers of non-diabetic children). HLA-B alleles were divided into supertypes that share similar peptide-binding specificity. Serum 25OHD concentration had been previously measured in these women from sera collected during the first trimester of pregnancy. Multiple testing was controlled for using the false discovery rate method.An association was found between 25OHD concentration and HLA-B44 supertype (P=0.009); women with HLA-B44 supertype (B*18, B*37, B*40 and B*44 alleles) had lower 25OHD concentrations. No association was found between HLA-DRB1 or -DQB1 alleles and 25OHD concentration.In this study we found for the first time an association between HLA genetic polymorphisms and 25OHD concentration. In future studies, the mechanistic background of this association and the role of vitamin D in the regulation of HLA gene expression should be investigated.

Increased vitamin D fortification of dairy products has increased the supply of vitamin D-containing products with different vitamin D contents on the market in Finland. The authors developed a ninety-eight-item FFQ with eight food groups and with a question on supplementation to assess dietary and supplemental vitamin D and Ca intakes in Finnish women (60ºN). The FFQ was validated in subgroups with different habitual vitamin D supplement use (0–57·5 µg/d) against the biomarker serum 25-hydroxyvitamin D (S-25(OH)D) and against 3-d food records (FR) (n29–67). Median total vitamin D intake among participants was 9·4 (range 1·6–30·5) µg/d. Spearman’s correlations for vitamin D and Ca ranged from 0·28 (P0·146, FFQv. S-25(OH)D, persons not using supplements) to 0·75 (Pv. FR, supplement use included). The correlations between the FFQ and S-25(OH)D concentrations improved within increasing supplement intake. The Bland–Altman analysis showed wide limits of agreement between FFQ and FR: for vitamin D between −7·8 and 8·8 µg/d and for Ca between −938 and 934 mg/d, with mean differences being 0·5 µg/d and 2 mg/d, respectively. The triads method was used to calculate the validity coefficients of the FFQ for vitamin D, resulting in a mean of 1·00 (95 % CI 0·59, 1·00) and a range from 0·33 to 1·00. The perceived variation in the estimates could have been avoided with a longer FR period and larger number of participants. The results are comparable with earlier studies, and the FFQ provides a reasonable estimation of vitamin D and Ca intakes.

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.

Current vitamin D recommendations have been established based on an assumption that there are no differences between Caucasian and other ethnic/racial groups in terms of vitamin D requirements. This assumption, largely made due to the absence of data, is a key knowledge gap identified by a number of authorities. To test whether the distribution of dietary requirements for maintaining winter serum 25-hydroxyvitamin D [25(OH)D] concentrations ≥ 30 nmol/L (a priority threshold linked to vitamin D deficiency prevention) differ between Caucasian and Somali women living at northerly latitude. We used data from a 5-month, winter-based, vitamin D3 dose-related randomized, placebo-controlled trial in Somali (n 47) and Causcian women (n 69), aged 21–64-year old, living in Southern Finland (60°N), to model the vitamin D intake–serum 25(OH)D dose–response relationship. Regression analyses were used to predict the vitamin D intake required to maintain 97.5% (as well as 50, 90, and 95%) of women in both ethnic groups above serum 25(OH)D thresholds of 30, 40 and 50 nmol/L. Using a model which adjusted for baseline 25(OH)D, age, and BMI, the estimated vitamin D intake that maintained serum 25(OH)D ≥ 30 nmol/L in 97.5% of Caucasian and Somali women was 8 and 18 µg/day, respectively. Ethnic differences were also evident at 40 and 50 nmol/L serum 25(OH)D thresholds. The present study adds further evidence that ethnic differences in the dietary requirement for vitamin D do exist and that dose–response vitamin D intervention studies are required in at-risk target populations specified by ethnicity.

Three hundred eighty-seven home-dwelling older women were divided into quartiles based on mean serum 25-hydroxyvitamin D (S-25(OH)D) levels. The rates of falls and fallers were about 40% lower in the highest S-25(OH)D quartile compared to the lowest despite no differences in physical functioning, suggesting that S-25(OH)D levels may modulate individual fall risk. Vitamin D supplementation of 800 IU did not reduce falls in our previous 2-year vitamin D and exercise RCT in 70–80 year old women. Given large individual variation in individual responses, we assessed here effects of S-25(OH)D levels on fall incidence. Irrespective of original group allocation, data from 387 women were explored in quartiles by mean S-25(OH)D levels over 6–24 months; means (SD) were 59.3 (7.2), 74.5 (3.3), 85.7 (3.5), and 105.3 (10.9) nmol/L. Falls were recorded monthly with diaries. Physical functioning and bone density were assessed annually. Negative binomial regression was used to assess incidence rate ratios (IRRs) for falls and Cox-regression to assess hazard ratios (HR) for fallers. Generalized linear models were used to test between-quartile differences in physical functioning and bone density with the lowest quartile as reference. There were 37% fewer falls in the highest quartile, while the two middle quartiles did not differ from reference. The respective IRRs (95% CI) for falls were 0.63 (0.44 to 0.90), 0.78 (0.55 to 1.10), and 0.87 (0.62 to 1.22), indicating lower falls incidence with increasing mean S-25(OH)D levels. There were 42% fewer fallers (HR 0.58; 040 to 0.83) in the highest quartile compared to reference. Physical functioning did not differ between quartiles. Falls and faller rates were about 40% lower in the highest S-25(OH)D quartile despite similar physical functioning in all quartiles. Prevalent S-25(OH)D levels may influence individual fall risk. Individual responses to vitamin D treatment should be considered in falls prevention.

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.

Phosphorus (P) intake in Western countries exceeds the nutritional recommendations two- to three-fold, and the increased use of food additive phosphates by the food industry has augmented total P intake with an estimated 10% to 50% of the total P intake coming from additives. Moreover, in food composition databases, P contents of the recipe-based foodstuffs are calculated based on nutrient content of raw materials and not on chemically analyzed values of the finished food product. Thus, the amount of phosphate from additives may not have been taken into account when estimating the total P content. The chemical composition of a foodstuff affects the bioavailability of P. Both human (in vivo) and in vitro studies have shown that bioavailability of P differs between the foodstuffs. Bioavailability of P is higher in processed, phosphate additive–containing foods, such as in processed meats, baking powder–containing bakery products, processed cheeses, and cola drinks. In contrast, P bioavailability of plant-based products is low, especially in legumes and seeds. In cereals, P bioavailability increases during processing when, for example, the bread is fermented and P from phytate is released as absorbable, inorganic P through the action of microbial phytase. Phosphorus bioavailability from animal-based products is generally high, with the exception of cottage cheese. Thus, effects of P on health may depend on the source from which it is ingested. However, there is a growing need to develop research methods by which P bioavailability can be taken into account. Data on the use of food additive phosphates by the food industry and updated information on P content in foodstuffs are also needed.

BACKGROUND: Vitamin D binding protein (DBP) binds vitamin D and its plasma metabolites, including 25-hydroxyvitamin D (25(OH)D), in the circulation. Only a small fraction circulates free (free 25(OH)D). Genetic variation of the GC gene, encoding DBP, has been associated with 25(OH)D concentrations. The roles of DBP and free 25(OH)D concentrations in the biological actions of vitamin D remain unclear. METHODS: We assessed the relationship between GC gene variants rs4588, rs7041, and rs705124, and serum total 25(OH)D, free and bioavailable 25(OH)D, and serum DBP and parathyroid hormone (PTH) concentrations in 622 Caucasian females (421) and males (201) aged 37–47 years. Concentrations of 25(OH)D, DBP, and PTH were measured from fasting blood samples. Dietary intakes of vitamin D and Ca were evaluated using 1-month food use frequency data, which were collected by a validated Food Frequency Questionnaire on vitamin D and calcium intakes. The subjects filled in the questionnaire covering overall health, medications, use of vitamin D and calcium supplements, and holidays in sunny locations. Three SNPs in the GC gene were genotyped: rs4588, rs7041, and rs705124. The SNPs rs4588 and rs7041 combine to form six common diplotypes. Free and bioavailable 25(OH)D were calculated by using specific binding coefficients. Differences among the diplo- and haplotypes of the GC gene in measures of 25(OH)D, DBP, and PTH were tested by analysis of covariance (ANCOVA) using appropriate covariates. RESULTS: We found significant variation among the SNPs rs4588 and rs7041 variants in DBP, total, free, and bioavailable 25(OH)D, and PTH. DBP concentration was lowest in genotype GC2/2 in both diplotypes and haplotypes (p = 0.039 and 0.039, respectively). The lowest 25(OH)D concentrations were found in diplotype variants GC1S/2, GC1S/F,and GC2/2 (p = 0.033), but free and bioavailable 25(OH)D concentrations were highest in the GC2/2 variant after corrected with a genotype-specific binding coefficient (p