Adherence to Vitamin D Supplementation Recommendations for Breastfed Infants and Young Children: An Analysis of Canadian Community Health Survey Data Cycles From 2015 to 2018.

BACKGROUND: In Canada, nutrition policy, as outlined in the Nutrition for Healthy Term Infants recommendations, includes a daily vitamin D supplement of 10 µg (400 IU) for breastfed infants and young children to support adequate vitamin D status. OBJECTIVES: This study aimed to report on adherence to vitamin D supplementation recommendations for breastfed infants (≤12 months); and for children breastfed >12 mo. METHODS: Canadian Community Health Survey (paired-cycles 2015/2016 and 2017/2018) maternal experiences data for infants born 2012-2018 who received any breastmilk formed the sample (n = 7079). Whether the infant was given a vitamin D supplement (yes/no) and the frequency (daily/almost every day, 1-2/wk, or <1/wk) were surveyed. Weighted data (95% CI) were summarized according to breastfeeding history (exclusive to 6 mo and continuing; partial to 6 mo and continuing; and stopped ≤6 mo). Correlates of supplement adherence were explored using logistic regression. RESULTS: Overall, 87.1% (95% CI: 85.9%, 88.3%) of participants reported giving their infant (≤12 mo) a vitamin D supplement, and of these, 83.3% (95% CI: 81.9%, 84.7%) did so daily/almost every day, 12.4% (95% CI: 11.1%, 13.7%) did so 1-2/wk, and 4.3% (95% CI: 3.6%, 5.0%) did so <1/wk. Lower adjusted odds of adherence were observed among participants reporting: stopped breastfeeding ≤6 mo, lower education or income, recent immigration, and overweight prepregnancy body mass index; higher odds of adherence were observed in the western provinces. Regarding mothers of children >12 mo and breastfed (n = 2312), 58.0% (95% CI: 54.9%, 61.1%) gave a vitamin D supplement daily/almost every day. CONCLUSIONS: Adherence to providing a vitamin D supplement to breastfed infants is high in Canada. Nonetheless, we estimate that ∼27% of mothers are nonadherent to daily/almost every day administration of a vitamin D supplement and that adherence declines in children breastfed >12 mo. Further promotion to support uptake of the current guidance may be necessary, particularly for parents of recent immigration or lower socioeconomic status.

The Relationship Between Vitamin D Intake and Serum 25-hydroxyvitamin D in Young Children: A Meta-Regression to Inform WHO/FAO Vitamin D Intake Recommendations.

BACKGROUND: This work was commissioned by the World Health Organization and Food and Agriculture Organization to inform their update on the vitamin D requirements for children aged <4 y. OBJECTIVES: The objective of this work was to undertake multilevel and multivariable dose-response modeling of serum 25-hydroxyvitamin D (25OHD) to total vitamin D intake in children aged <4 y with the goal of deriving updated vitamin D requirements for young children. METHODS: Systematically identified randomized controlled trials among healthy children from 2 wk up to 3.9 y of age provided with daily vitamin D supplements or vitamin D-fortified foods were included. Linear and nonlinear random effects multilevel meta-regression models with and without covariates were fitted and compared. Interindividual variability was included by simulating the individual serum 25OHD responses. The percentage of individuals reaching set minimal and maximal serum 25OHD thresholds was calculated and used to derive vitamin D requirements. RESULTS: A total of 31 trials with 186 data points from North America, Europe, Asia, and Australasia/Oceania, with latitudes ranging from 61°N to 38°S, and with participants of likely mostly light or medium skin pigmentation, were included. In 29 studies the children received vitamin D supplements and in 2 studies the children received vitamin D-fortified milk with or without supplements. The dose-response relationship between vitamin D intake and serum 25OHD was best fitted with the unadjusted quadratic model. Adding additional covariates, such as age, did not significantly improve the model. At a vitamin D intake of 10 µg/d, 97.3% of the individuals were predicted to achieve a minimal serum 25OHD threshold of 28 nmol/L. At a vitamin D intake of 35 µg/d, 1.4% of the individuals predicted to reach a maximal serum 25OHD threshold of 200 nmol/L. CONCLUSIONS: In conclusion, this paper details the methodological steps taken to derive vitamin D requirements in children aged <4 y, including the addition of an interindividual variability component.

Adherence to vitamin D supplementation guidelines in children under five years of age: a systematic literature review.

PURPOSE: Despite the presence of guidelines on vitamin D supplementation in infants and young children, little is known about parental adherence to their recommendations. This review aims to summarise the evidence from observational studies investigating adherence to vitamin D supplementation guidelines in children under five years of age. METHODS: Databases of PubMed, Scopus, Web of Science, and CINAHL were searched from January 2000 until July 2022. Qualitative data synthesis was used to summarise evidence on supplementation adherence. The adherence rate was categorised as low, moderate, and high if it was ≤ 50%, between 50 and 70%, and ≥ 70%, respectively. RESULTS: Eleven studies investigating adherence to eight different vitamin D supplementation guidelines from European countries, USA and Canada were included. The majority of studies were cross-sectional and conducted among infants. Overall, the adherence rate ranged between 14.29% and 95.6%. Low, moderate, and high adherence to supplementation guidelines were reported in six, three, and two studies, respectively. CONCLUSION: There is generally poor adherence to vitamin D supplementation guidelines in children under five years of age. Nevertheless, the evidence comes from a limited number of studies, mainly conducted in infants, with high methodological heterogeneity in terms of the vitamin D supplementation guideline assessed and the definition of supplementation adherence in the study population. Further research is warranted to identify effective health promotion interventions to increase supplementation adherence and reduce the risk of vitamin D deficiency at this critical life stage.

Increased Serum Total and Free 25-Hydroxyvitamin D with Daily Intake of Cholecalciferol-Fortified Skim Milk: A Randomized Controlled Trial in Colombian Adolescents.

BACKGROUND: The efficacy of cholecalciferol (vitamin D3) food fortification in low- and middle-income countries near the Equator is unknown. OBJECTIVES: We examined the effects of providing cholecalciferol-fortified skim milk to adolescents and their mothers on serum total 25(OH)D, free 25(OH)D, and vitamin D-binding protein (DBP) concentrations in a randomized controlled trial. METHODS: We randomly assigned 80 Colombian families each with a child aged 12-14.5 y and their mother 1 L of skim milk daily, either fortified with 2400 IU (60 µg) cholecalciferol or unfortified, for 6 wk. We prescribed 500 mL of milk daily to adolescents; mothers consumed the remainder ad libitum. We estimated intent-to-treat effects as the between-arm difference in the change in serum total and free 25(OH)D and DBP concentrations from baseline to the end of follow-up. Secondary analyses included stratification by baseline characteristics and per-protocol comparisons. RESULTS: Among adolescents, fortification effects (95% CI) on serum total 25(OH)D, free 25(OH)D, and DBP concentrations were 5.4 nmol/L (2.1, 8.8 nmol/L), 0.6 pmol/L (-0.2, 1.4 pmol/L), and -416 nmol/L (-944, 112 nmol/L), respectively. Effects on total 25(OH)D were stronger in adolescents with lower DBP concentrations, darker skin, less sunlight exposure, and higher compliance than in their respective counterparts. Fortification increased free 25(OH)D concentrations in high compliers. Among mothers, the effects (95% CI) on total 25(OH)D and DBP concentrations were 4.0 nmol/L (0.6, 7.5 nmol/L) and -128 nmol/L (-637, 381 nmol/L), respectively. There were no adverse events. CONCLUSIONS: Provision of cholecalciferol-fortified skim milk increases serum total 25(OH)D concentrations in Colombian adolescents and adult women.

Vitamin D, testosterone and depression in middle-aged and elderly men: a systematic review.

Depression is one of the common psychiatric disorders during elderly. This systematic review aims to present the relationship between vitamin D deficiency, depression and testosterone serum concentration in the middle-aged and elderly men. We performed a comprehensive search in the Google Scholar, PubMed, ProQuest, Web of Science, Cochrane, Science Direct, and Scopus databases to collect any relevant published studies. The data of the articles that had been investigated the relationship between depression and 25-hydroxy vitamin D (25[OH]D) serum concentration (nine studies), or testosterone and 25[OH]D (six studies), as the primary outcomes, were included in our review. The results of the cohort and cross-sectional studies have shown that vitamin-D deficiency is associated with the incidence of depression in older men. In addition, documents have reported the positive association between vitamin D and testosterone, and previous studies have shown that testosterone can involve in the mood. We have proposed scientific mechanisms that have shown vitamin D may also play a protective role in depression through its effect on the testosterone. Therefore, it is a low risk and safe recommendation for the middle-aged and elderly men to use the vitamin D supplement or exposure to the sunlight to prevent depression.

The future is bright: Biofortification of common foods can improve vitamin D status.

Vitamin D deficiency is a global concern, linked to suboptimal musculoskeletal health and immune function, with status inadequacies owing to variations in UV dependent cutaneous synthesis and limited natural dietary sources. Endogenous biofortification, alongside traditional fortification and supplement usage is urgently needed to address this deficit. Evidence reviewed in the current article clearly demonstrates that feed modification and UV radiation, either independently or used in combination, effectively increases vitamin D content of primary produce or ingredients, albeit in the limited range of food vehicles tested to date (beef/pork/chicken/eggs/fish/bread/mushrooms). Fewer human trials have confirmed that consumption of these biofortified foods can increase circulating 25-hydroxyvitamin D [25(OH)D] concentrations (n = 10), which is of particular importance to avoid vitamin D status declining to nadir during wintertime. Meat is an unexplored yet plausible food vehicle for vitamin D biofortification, owing, at least in part, to its ubiquitous consumption pattern. Consumption of PUFA-enriched meat in human trials demonstrates efficacy (n = 4), lighting the way for exploration of vitamin D-biofortified meats to enhance consumer vitamin D status. Response to vitamin D-biofortified foods varies by food matrix, with vitamin D3-enriched animal-based foods observing the greatest effect in maintaining or elevating 25(OH)D concentrations. Generally, the efficacy of biofortification appears to vary dependent upon vitamer selected for animal feed supplementation (vitamin D2 or D3, or 25(OH)D), baseline participant status and the bioaccessibility from the food matrix. Further research in the form of robust human clinical trials are required to explore the contribution of biofortified foods to vitamin D status.

Vitamin D in pregnancy (GRAVITD) - a randomised controlled trial identifying associations and mechanisms linking maternal Vitamin D deficiency to placental dysfunction and adverse pregnancy outcomes - study protocol.

BACKGROUND: The prevalence of vitamin D deficiency is high among pregnant women. Vitamin D deficiency in pregnancy is associated with increased risk of adverse pregnancy outcomes especially complications related to placental dysfunction and insulin resistance. The objective of this study is to investigate if a higher dose of vitamin D supplementation in pregnancy reduces the prevalence of vitamin D deficiency and prevents adverse pregnancy outcome with special emphasize on preeclampsia, foetal growth restriction and gestational diabetes. METHODS: GRAVITD is a double-blinded randomised trial with parallel groups where all pregnant women attending the free of charge national nuchal translucency scan programme in gestational week 10-14 at Randers Regional Hospital are invited to participate. Enrolment started in June 2020. Participants are randomised in a two armed randomization with a 1:1 allocation ratio into 1) control group - receives 10 µg of vitamin D or 2) intervention group - receives 90 µg of vitamin D. A total of 2000 pregnant women will be included. Maternal blood samples and questionnaires describing life-style habits are collected upon enrolment. For half of the participants blood samples and questionnaires will be repeated again in 3rd trimester. Blood samples will be analysed for 25-hydroxy-vitamin D using high-performance liquid chromatography coupled with tandem mass spectrometry. Upon delivery, placental tissue and umbilicalcord blood will be collected and information on maternal and fetal outcomes will be exstracted from medical records. The primary outcomes are serum levels of 25-hydroxy-vitamin D ≥ 75 nmol/L and the rate of preeclampsia, foetal growth restriction and gestational diabetes. Secondary outcome includes identification and impact on placental functions related to vitamin D. A tertiary outcome is to initiate a cohort of children born from mothers in the trial for future follow-up of the effects of vitamin D on childhood health. DISCUSSION: Provided that this trial finds beneficial effects of a higher dose of vitamin D supplementation in pregnancies, official recommendations can be adjusted accordingly. This will provide a low-cost and easily implementable adjustment of prenatal care which can improve health for both mother and child during pregnancy and beyond. TRIAL REGISTRATION: ClinicalTrial.gov: NCT04291313 . Registered February 17, 2020.

How effective is public health policy in Scotland on vitamin D deficiency during pregnancy?

OBJECTIVE: To evaluate the uptake of universal vitamin D supplementation during pregnancy, its effectiveness in preventing vitamin D deficiency and the factors associated with these. DESIGN: The regional public health organisation in Ayrshire, Scotland has a policy of universal provision of vitamin D supplements (10 µg/d) to all pregnant women for the duration of their pregnancy. Pregnant women in this area were recruited at their 12-week antenatal appointment. Blood samples were collected at the 12-week and 34-week appointments. To account for the seasonal variation, women were recruited in two cohorts: summer and winter. Telephone interviews were conducted at 34 weeks to assess the uptake of vitamin D supplements during pregnancy. Other variables were obtained from medical records. SETTING: The study was conducted in the NHS Ayrshire and Arran Health Board in Scotland. PARTICIPANTS: 612 pregnant women (aged 15-44 years) living in Ayrshire (latitude 55°), Scotland. RESULTS: Sixty-six percentage took supplementation as recommended. Consumption of supplementation was significantly associated with a higher median serum 25-hydroxyvitamin D concentrations at 34 weeks. Despite this at 34 weeks, 33 % of the summer cohort had insufficient or deficient vitamin D status, while 15 % of the winter cohort had insufficient or deficient status. In multivariable analysis, only adherence and season were independent predictors of vitamin D status. CONCLUSIONS: While supplementation improved and maintained vitamin D status during pregnancy, it was not adequate to ensure all those insufficient at 12 weeks achieved sufficient status at the end of pregnancy.

Evidence of low vitamin D intakes in the Australian population points to a need for data-driven nutrition policy for improving population vitamin D status.

BACKGROUND: Nearly one in four Australian adults is vitamin D deficient (serum 25-hydroxyvitamin D concentrations [25(OH)D] < 50 nmol L-1 ) and current vitamin D intakes in the Australian population are unknown. Internationally, vitamin D intakes are commonly below recommendations, although estimates generally rely on food composition data that do not include 25(OH)D. We aimed to estimate usual vitamin D intakes in the Australian population. METHODS: Nationally representative food consumption data were collected for Australians aged ≥ 2 years (n = 12,153) as part of the cross-sectional 2011-2013 Australian Health Survey (AHS). New analytical vitamin D food composition data for vitamin D3 , 25(OH)D3 , vitamin D2 and 25(OH)D2 were mapped to foods and beverages that were commonly consumed by AHS participants. Usual vitamin D intakes (µg day-1 ) by sex and age group were estimated using the National Cancer Institute method. RESULTS: Assuming a 25(OH)D bioactivity factor of 1, mean daily intakes of vitamin D ranged between 1.84 and 3.25 µg day-1 . Compared to the estimated average requirement of 10 µg day-1 recommended by the Institute of Medicine, more than 95% of people had inadequate vitamin D intakes. We estimated that no participant exceeded the Institute of Medicine's Upper Level of Intake (63-100 µg day-1 , depending on age group). CONCLUSIONS: Usual vitamin D intakes in Australia are low. This evidence, paired with the high prevalence of vitamin D deficiency in Australia, suggests that data-driven nutrition policy is required to safely increase dietary intakes of vitamin D and improve vitamin D status at the population level.

Risk perception of sun exposure and knowledge of vitamin D among the healthcare providers in a high-risk country: a cross-sectional study.

BACKGROUND: High levels of vitamin D deficiency are commonly reported even in regions with abundant sunshine. This necessitates a comprehensive understanding of the determinants that influence sun exposure practices. As the primary source of health-related knowledge for the general public, the attitude of the healthcare professionals towards sunlight and their awareness related to vitamin D deficiency can be critical in this regard. METHODS: A cross-sectional survey was conducted among 2,242 physicians, intern doctors, and senior medical students in Bangladesh from October 2019 to February 2020. A pre-tested structured questionnaire (containing twelve close-ended questions) was used. The perceptions of health risks due to sun exposure, and basic knowledge of the physiological and epidemiological aspects of vitamin D deficiency were tested. RESULTS: An overall negative attitude towards sunlight in the context of Bangladesh was highlighted - 68% participants thought regular sun exposure would be harmful or very harmful; 26% thought the level of UV radiation was very high; 44% recommended using sunscreen always; skin burns, heat stroke, and cancer were selected as potential consequences of regular sun exposure by 45%, 21%, and 30% respondents respectively. Overall knowledge regarding vitamin D deficiency appeared to be biased towards bone health; other symptoms and associated illnesses not having obvious link to Calcium-metabolism were identified much lesser frequently. Furthermore, 'sunrise to 10 am' was identified as the best time to get vitamin D by 69% participants; 60% believed < 30 min of weekly sun exposure would be sufficient for the Bangladeshi population; an only 33% identified that prevalence of vitamin D insufficiency in Bangladesh would be 50% or more. Taking vitamin D-rich food was suggested by more respondents over regular sun exposure (43% vs. 33%) as more effective remedial strategy to curb vitamin D deficiency in Bangladesh. CONCLUSION: In addition to highlighting some crucial knowledge gaps, results from this study provides a comprehensive baseline dataset for knowledge and attitude regarding the public health aspects of vitamin D deficiency among the healthcare providers in Bangladesh, which would be generalizable to other countries with similar socio-demographic context, and will facilitate taking more effective policies worldwide.

Pregnancy, Breastfeeding, and Vitamin D.

Exclusive breastfeeding is considered the ideal food in the first six months of life; however, paradoxically, vitamin D content in human breast milk is clearly low and insufficient to obtain the recommended intake of 400 IU daily. This article summarizes the extraordinary metabolism of vitamin D during pregnancy and its content in human breast milk. The prevalence of hypovitaminosis D in pregnant women and/or nursing mothers and its potential maternal-fetal consequences are analyzed. The current guidelines for vitamin D supplementation in pregnant women, nursing mothers, and infants to prevent hypovitaminosis D in breastfed infants are detailed. Low vitamin D content in human breast milk is probably related to active changes in human lifestyle habits (reduced sunlight exposure).

Vitamin D deficiency rickets in a toddler.

ABSTRACT: Nutritional rickets is the failure of normal bone formation in children, caused by vitamin D deficiency, low calcium intake, or a combination of both. In the United States, prolonged breastfeeding without vitamin D supplementation is a major risk factor. Increasing awareness of the rationale for and importance of vitamin D supplements for all breastfed infants and children should reduce the incidence of vitamin D deficiency rickets and prevent bone deformity.

Yeast as a biological platform for vitamin D production: A promising alternative to help reduce vitamin D deficiency in humans.

Vitamin D is an important human hormone, known primarily to be involved in the intestinal absorption of calcium and phosphate, but it is also involved in various nonskeletal processes (molecular, cellular, immune, and neuronal). One of the main health problems nowadays is the vitamin D deficiency of the human population due to lack of sun exposure, with estimates of one billion people worldwide with vitamin D deficiency, and the consequent need for clinical intervention (i.e., prescription of pharmacological vitamin D supplements). An alternative to reduce vitamin D deficiency is to produce good dietary sources of it, a scenario in which the yeast Saccharomyces cerevisiae seems to be a promising alternative. This review focuses on the potential use of yeast as a biological platform to produce vitamin D, summarizing both the biological aspects of vitamin D (synthesis, ecology and evolution, metabolism, and bioequivalence) and the work done to produce it in yeast (both for vitamin D2 and for vitamin D3 ), highlighting existing challenges and potential solutions.

Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude.

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).

Vitamin D supplementation and increased dairy protein intake do not affect muscle strength or physical function in healthy 6-8-year-old children: the D-pro randomized trial.

PURPOSE: To investigate separate and combined effects of vitamin D supplementation during the extended winter and increased dairy protein intake on muscle strength and physical function in children, and furthermore to explore potential sex differences. METHODS: In a 2 × 2-factorial, randomized winter trial, 183 healthy, 6-8-year-old children received blinded tablets with 20 µg/day vitamin D3 or placebo, and substituted 260 g/day dairy with yogurts with high (HP, 10 g protein/100 g) or normal protein content (NP, 3.5 g protein/100 g) for 24 weeks during winter at 55° N. We measured maximal isometric handgrip and leg press strength, and physical function by jump tests and a 30 s sit-to-stand test. Physical activity was measured by 7-day accelerometry. RESULTS: Baseline (mean ± SD) serum 25-hydroxyvitamin D was 80.8 ± 17.2 nmol/L, which increased to 88.7 ± 17.6 nmol/L with vitamin D supplementation and decreased to 48.4 ± 19.2 nmol/L with placebo. Baseline protein intake was 15.5 ± 2.4 E%, which increased to 18.4 ± 3.4 E% with HP and was unchanged with NP. We found no separate or combined effects of vitamin D supplementation and/or increased dairy protein intake on muscle strength or physical function (all P > 0.20). There was an interaction on the sit-to-stand test (Pvitamin×yogurt = 0.02), which however disappeared after adjusting for physical activity (P = 0.16). Further, vitamin D supplementation increased leg press strength relatively more in girls compared to boys (mean [95% CI] 158 [17, 299] N; Pvitamin×sex = 0.047). CONCLUSION: Overall, vitamin D and dairy protein supplementation during the extended winter did not affect muscle strength or physical function in healthy children. Potential sex differences of vitamin D supplementation should be investigated further. REGISTERED AT CLINICALTRIALS.GOV: NCT0395673.

How Much Does Serum 25(OH)D Improve by Vitamin D Supplement and Fortified Food in Children? A Systematic Review and Meta-Analysis.

OBJECTIVES: This study was conducted to respond certain important questions regarding the efficacy of vitamin D fortification and supplementation in children using a meta-analytical approach. METHODS: MEDLINE, PubMed, Embase, Cochrane Library, and Google Scholar were searched, and 2341 studies were found in a preliminary search. After screening of titles and abstracts, 31 studies were selected. RESULTS: Significant raises in circulating 25-hydroxy vitamin D (25(OH)D) concentrations were observed in both groups that took vitamin D supplement (mean difference [MD] 28.7, 95% confidence interval [CI] 22.5-34.9) and vitamin D-fortified foods (MD 20.29, 95% CI 13.3-27.2). The meta-regression revealed a significant association between age of participants (B -1.4, 95% CI -2.8, -0.02, P = 0.047) and dose of vitamin D (B 0.007, 95% CI 0.003, 0.01, P < 0.001), with the effect on serum 25(OH)D concentrations. The analysis showed that serum 25(OH)D concentration increases by 0.7 nmol/L for every 100 IU of vitamin D intake after adjustment for age, baseline serum 25(OH)D and latitude which is far less than the reported amount in adults. CONCLUSIONS: Altogether, these findings indicate that in a mass vitamin D fortification program, circulating 25(OH)D concentration response in children may be lower in children than in adults and vitamin D supplementation may still be needed in this subpopulation.

Effect of Vitamin D Supplementation on Vitamin D Level and Bone Mineral Density in Patients With Cirrhosis: A Randomized Clinical Trial.

INTRODUCTION: In patients with cirrhosis, highly prevalent vitamin D deficiency and low bone mineral density (BMD) increase the burden of disease, and role of vitamin D supplementation is not clear. So, our aim was to determine the effect of vitamin D supplementation on vitamin D level and BMD in patients with cirrhosis. METHODS: Patients with cirrhosis (18-60 years) of any etiology were enrolled. We measured serum 25(OH)D, parathyroid hormone, thyroid-stimulating hormone, free T4, bone-specific alkaline phosphatase, insulin-like growth factor (IGF)-1, and health-related quality of life at entry and at 1 year; however, serum calcium was measured at 3-month interval. BMD was measured by dual-energy x-ray absorptiometry at lumbar spine and left hip neck at entry and after 1 year. Statistical analysis was performed according to intention-to-treat analysis. RESULTS: Of 390 screened patients with cirrhosis, 164 participants (82 in each group) were randomized. There was significant increase in 25(OH)D levels in intervention group after 1 year (33.7 [24.3-45.7] ng/mL vs 23.1 [17-28.2] ng/mL; P < 0.001) when compared with placebo. The mean difference in BMD at lumbar spine and left hip neck was not significantly changed after 1 year of intervention with vitamin D between both groups. There was no significant change in both the groups in levels of calcium, thyroid-stimulating hormone, parathyroid hormone, free T4, IGF-1, and bone-specific alkaline phosphatase and quality of life. DISCUSSION: Supplementation with vitamin D for 1 year improves vitamin D levels but did not result in improvement in BMD at lumbar spine and left hip neck in patients with cirrhosis.

Vitamin D requirements in infancy: an updated systematic review.

PURPOSE OF REVIEW: Systematic review looking for new evidence for recommendations for vitamin D supplementation in healthy infants based upon the most recent (4 years) available literature. RECENT FINDINGS: Randomized controlled trials published since 1 January 2017 that related to vitamin D doses in infancy were reviewed. They do not provide any additional evidence that larger, more generous amounts of daily vitamin D beyond the customary recommended 400 international units (IU) daily dose, affect any significant outcome. Larger amounts may lead to serum 25-hydroxyvitamin D [25(OH)D] concentrations that have been reported to be potentially associated with adverse effects, and a daily dose of 1200 IU may even harm in terms of increasing the risks of allergic sensitization. SUMMARY: There are still many unanswered questions left, in particular, whether or not more 'generous' amounts of vitamin D in infancy may improve long-term health outcomes such as prevention of adult osteoporosis, allergies, or cancer.

Vitamin D Supplementation and Sunlight Exposure on Serum Vitamin D Concentrations in 2 Parallel, Double-Blind, Randomized, Placebo-Controlled Trials.

BACKGROUND: Vitamin D concentrations are a function of sunlight exposure and dietary intake. However, current dietary vitamin D recommendations do not consider differences in country-specific sunlight availability or spontaneous individual exposure. OBJECTIVES: We aimed to investigate the effects of vitamin D supplementation and sunlight exposure on vitamin D concentrations in Brazilian women living in high compared with low latitudes. METHODS: In 2 parallel, double-blind, randomized placebo-controlled trials, Brazilian women living in England (51°N) composed "without ultraviolet B (UVB) exposure" groups and those living in Brazil (16°S) composed the "with UVB exposure" groups (mean age, 31.39 ± 8.7 years). Participants received 15 µg cholecalciferol or placebo daily for 12 weeks during wintertime. Serum 25-hydroxyvitamin D [25(OH)D] concentrations, the primary outcome, were assessed by HPLC-MS/MS, vitamin D intakes were assessed by 4-day diet diaries, and sunlight exposure was assessed by UVB dosimeters. The effects of supplementation and UVB exposure were tested by the intention to treat with a linear mixed model. RESULTS: The 25(OH)D concentrations increased in both supplemented groups [from 75.1 ± 22.0 to 84.8 ± 21.0 nmol/L (P = 0.004) in the group with UVB exposure; from 38.1 ± 15.9 to 55.1 ± 12.2 nmol/L (P < 0.001) in the group without UVB exposure], with no significant changes in either placebo group. Concentrations in both supplemented groups were higher than those in the placebo group without UVB exposure (P = 0.0002 in the group with UVB exposure; P = 0.0035 in the group without UVB exposure). Postintervention 25(OH)D concentrations were significantly affected by serum 25(OH)D concentrations at baseline (P < 0.0001) and by intervention (placebo or supplement; P > 0.0001), with a large effect size (Cohen's D = 0.768), but were not affected by UVB exposure (with or without; P = 0.1386), nor by the interaction between the intervention (placebo or supplement) and UVB exposure (with or without; P = 0.9845). CONCLUSIONS: Moderate supplementation of 15 ug/d cholecalciferol, in accordance with current recommendations, supports an adequate vitamin D status in adult women, irrespective of latitude, and might concomitantly prevent an increase in parathyroid hormone. The Interaction Between Vitamin D Supplementation and Sunlight Exposure in Women Living in Opposite Latitudes (D-SOL) study was registered at clinicaltrials.gov as NCT03318029.

Vitamin D Food Fortification and Biofortification Increases Serum 25-Hydroxyvitamin D Concentrations in Adults and Children: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Low vitamin D status is a global public health issue that vitamin D food fortification and biofortification may help to alleviate. OBJECTIVES: We investigated the effect of vitamin D food fortification and biofortification on circulating 25-hydroxyvitamin D (25(OH)D) concentrations. We expanded the scope of earlier reviews to include adults and children, to evaluate effects by vitamin D vitamer, and investigate linear and nonlinear dose-response relations. METHODS: We conducted a systematic review and meta-analysis. We searched CINAHL, MEDLINE, PubMed, Embase, the Cochrane Library, and gray and unpublished literature sites for randomized controlled trials, including people of all ages, with the criteria: absence of illness affecting vitamin D absorption, duration ≥4 wk, equivalent placebo food control, dose quantification, dose ≥5 µg/d, baseline and endpoint or absolute change in 25(OH)D concentrations reported, random allocation, and participant blinding. Quality was assessed using the Jadad Scale. RESULTS: Data from 34 publications (2398 adults: 1345 intervention, 1053 controls; 1532 children: 970 intervention, 562 controls) were included. Random-effects meta-analysis of all studies combined (mean dose 16.2 µg/d) indicated a pooled treatment effect of 21.2 nmol/L (95% CI: 16.2, 26.2), with a greater effect for studies using cholecalciferol than ergocalciferol. Heterogeneity was high (I2  > 75%). Metaregression analyses for all studies combined suggested positive effect differences for baseline circulating 25(OH)D concentrations <50 nmol/L, dose ≥10 µg/d and a negative effect difference when the intervention arm included a calcium dose ≥500 mg/d greater than the control arm. Dose-response rates were found to be nonlinear (Wald test for nonlinearity P < 0.001). For all studies combined, a threshold occurred at ∼26 nmol/L for a dose of ∼21 µg/d. CONCLUSIONS: These results support use of vitamin D food fortification to improve circulating 25(OH)D circulations in populations. This work was registered with PROSPERO as CRD42020145497.