Abstract
Dietary Reference Values (DRVs) for vitamin D have a key role in the prevention of vitamin D deficiency. However, despite adopting similar risk assessment protocols, estimates from authoritative agencies over the last 6 years have been diverse. This may have arisen from diverse approaches to data analysis. Modelling strategies for pooling of individual subject data from cognate vitamin D randomized controlled trials (RCTs) are likely to provide the most appropriate DRV estimates. Thus, the objective of the present work was to undertake the first-ever individual participant data (IPD)-level meta-regression, which is increasingly recognized as best practice, from seven winter-based RCTs (with 882 participants ranging in age from 4 to 90 years) of the vitamin D intake–serum 25-hydroxyvitamin D (25(OH)D) dose-response. Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of 25(OH)D concentrations >25, 30, and 50 nmol/L across the population are 10, 13, and 26 µg/day, respectively. In contrast, standard meta-regression analyses with aggregate data (as used by several agencies in recent years) from the same RCTs estimated that a vitamin D intake requirement of 14 µg/day would maintain 97.5% of 25(OH)D >50 nmol/L. These first IPD-derived estimates offer improved dietary recommendations for vitamin D because the underpinning modeling captures the between-person variability in response of serum 25(OH)D to vitamin D intake.
Highlights
Using the threshold for vitamin D deficiency of a serum 25-hydroxyvitamin D (25(OH)D)concentration 55,000 individuals, reported that one in eight European residents has vitamin D deficiency [4]
These randomized controlled trials (RCTs) were conducted in: 4–8 year-old children [17], 11 year-old girls [18], 14–18 year-old adolescents [19], adults aged 20–40 years [20], 50+ years [21,22], and 65+ years [23], and were all implemented using the same study design, analytical platform for serum 25(OH)D, and dietary assessment method. Most of these RCTs were among the 44 used collectively in the Institute of Medicine (IOM), NORDEN, and European Food Safety Authority (EFSA) exercises for deriving dietary reference values (DRVs) [1,10,11]. These seven RCTs all fulfill or exceed the previously defined RCT selection criteria established by the IOM as part of their process [1], and five of the seven [18,20,21,22,23] have been used in the recent DRV
The present analysis clearly illustrates that the vitamin D DRV estimates arising from an individual participant data (IPD) approach, increasingly recognized as best practice [15,16], were considerably higher than those derived from the standard meta-regression approach based on aggregate data
Summary
Using the threshold for vitamin D deficiency of a serum 25-hydroxyvitamin D (25(OH)D)concentration 55,000 individuals, reported that one in eight European residents has vitamin D deficiency [4]. Using the threshold for vitamin D deficiency of a serum 25-hydroxyvitamin D (25(OH)D). Many investigators in the vitamin D field concur with the Endocrine Society’s 25(OH)D threshold of
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