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

Abstract

Context and purposeThere 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 D 3 -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 SystematicReviews (Registration Number: CRD42018097260)

Clinical Practice in the Prevention, Diagnosis and Treatment of Vitamin D Deficiency: A Central and Eastern European Expert Consensus Statement

“…In detail, we recommend a vitamin D supplementation dose of 800 to 2000 IU per day for adults who want to ensure a sufficient vitamin D status, with up to 4000 IU per day for certain groups, particularly for patients with obesity and malabsorption syndromes, as well as for individuals with a dark skin pigmentation (see Table 5 ). The relatively wide dose ranges for vitamin D account for various differences in the dose-response relationship for a given supplemental vitamin D dose and the achieved 25(OH)D concentration with higher dose requirements with increasing body weight and vice versa [ 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. If a clinician is asked by a random individual which vitamin D dose is safe and very likely avoids vitamin D deficiency, a dose of 800 to 1000 IU per day should fulfill these criteria for the vast majority, even if individual characteristics, including the 25(OH)D status, is unknown.…”

Critical Appraisal of Large Vitamin D Randomized Controlled Trials

“…Individual participant baseline and achieved 25(OH)D concentrations should therefore be considered for the design and analysis of RCTs. Potential ethnic differences should also be accounted for [95]. Accurate and standardized measurements of vitamin D status are also crucial for future vitamin D trials, and additional measurements of vitamin D metabolites and the consideration of bioavailable fractions are also worth considering [96].…”

Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections—Sepsis and COVID-19

“…Despite vitamin D supplements being widely available and economical to use and the availability of sunlight worldwide, vitamin D inadequacy is highly prevalent. Chronic vitamin D deficiency significantly increases ill-health, reduces productivity, and escalates healthcare costs [ 1 , 2 ].…”

“…Sometime during the year, over half of the world’s population is subjected to vitamin D deficiency, thus increasing their vulnerability to infections, and worsening chronic diseases [ 2 ]. Because hypovitaminosis is D-associated adverse effects affecting multiple systems, we estimated that it contributes to a fourth of the overall healthcare costs.…”

“…Moreover, the non-transcriptional actions are not affected by inhibitors of transcription or protein synthesis [ 2 ]. These explain the non-involvement of the genomic mechanisms of the rapid action of lipid-soluble steroid hormones [ 3 ].…”