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.Peer reviewe

Influence of awareness and availability of medical alternatives on parents seeking paediatric emergency care

Aims: Direct seeking of care at paediatric emergency departments may result from an inadequate awareness or a short supply of medical alternatives. We therefore evaluated the care-seeking patterns, availability of medical options and initial medical assessments – with overall reference to socioeconomic status – of parents at an urban paediatric emergency department in a Scandinavian country providing free paediatric healthcare. Methods: The parents of children assessed by paediatric emergency department physicians at a Swedish university hospital over a 25-day winter period completed a questionnaire on recent medical contacts and their reasons for attendance. Additional information was obtained from ledgers, patient records and population demographics. Results: In total, 657 of 713 eligible patients (92%) were included. Seventy-nine per cent of their parents either failed to or managed to establish medical contact before the emergency department visit, whereas 21% sought care with no attempt at recent medical contact. Visits with a failed telephone or primary care contact (18%) were more common outside office hours (p=0.014) and were scored as less urgent (p=0.014). A perceived emergency was the main reason for no attempt at medical contact before the visit. Direct emergency department care-seeking was more common from the city district with the lowest socioeconomic status (p=0.027). Conclusions: Although most parents in this Swedish study tried to seek medical advice before attending a paediatric emergency department, perceived emergency, a short supply of telephone health line or primary care facilities and lower socioeconomic status contributed to direct care-seeking by almost 40% of parents. Pre-hospital awareness and the availability of medical alternatives with an emphasis on major differences in socioeconomic status should therefore be considered to further optimize care-seeking in paediatric emergency departments

Effectiveness of vitamin D supplementation in Swedish children may be negatively impacted by BMI and serum fructose

In regions where sunlight exposure is limited, dietary vitamin D intake becomes important for maintaining status. However, Swedish children have been shown to have deficient or marginal status during the winter months even if the recommended dietary intake is met. Since low vitamin D status has been associated with several disease states, this study investigated the metabolic changes associated with improved vitamin D status due to supplementation. During the 3 winter months, 5–7-year-old children (n=170) in northern (Umeå, 63° N) and southern (Malmö, 55° N) Sweden were supplemented daily with 2 (placebo), 10 or 25 μg of vitamin D. BMI-for-age z-scores (BAZ), S-25(OH)D concentrations, insulin concentrations and the serum metabolome were assessed at baseline and follow-up. S-25(OH)D concentrations increased significantly in both supplementation groups (P<.001). Only arginine and isopropanol concentrations exhibited significant associations with improvements in S-25(OH)D. Furthermore, the extent to which S-25(OH)D increased was correlated with a combination of baseline BAZ and the change in serum fructose concentrations from baseline to follow up (P=.012). In particular, the change in S-25(OH)D concentrations was negatively correlated (P=.030) with the change in fructose concentrations for subjects with BAZ ≥0 and consuming at least 20 μg vitamin D daily. These results suggest that although the metabolic changes associated with improved vitamin D status are small, the effectiveness of dietary supplementation may be influenced by serum fructose concentrations

Individual participant data (IPD)-level meta-analysis of randomised controlled trials with vitamin D-fortified foods to estimate Dietary Reference Values for vitamin D

Context and purpose: Individual participant data-level meta-regression (IPD) analysis is superior to meta-regression based on aggregate data in determining Dietary Reference Values (DRV) for vitamin D. Using data from randomized controlled trials (RCTs) with vitamin D3-fortified foods, we undertook an IPD analysis of the response of winter serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among children and adults and derived DRV for vitamin D. Methods: IPD analysis using data from 1429 participants (ages 2–89 years) in 11 RCTs with vitamin D-fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D DRV estimates across a range of serum 25(OH)D thresholds using unadjusted and adjusted models. Results: Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25 and ≥ 30 nmol/L are 6 and 12 µg/day, respectively (unadjusted model). The intake estimates to maintain 90%, 95% and 97.5% of concentrations ≥ 50 nmol/L are 33.4, 57.5 and 92.3 µg/day, respectively (unadjusted) and 17.0, 28.1 and 43.6 µg/day, respectively (adjusted for mean values for baseline serum 25(OH)D, age and BMI). Conclusions: IPD-derived vitamin D intakes required to maintain 90%, 95% and 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L are much higher than those derived from standard meta-regression based on aggregate data, due to the inability of the latter to capture between person-variability. Our IPD provides further evidence that using food-based approaches to achieve an intake of 12 µg/day could prevent vitamin D deficiency (i.e., serum 25(OH)D < 30 nmol/L) in the general population