Vitamin D biomarkers for Dietary Reference Intake development in children: a systematic review and meta-analysis

Background Circulating 25-hydroxyvitamin D [25(OH)D] has been the accepted vitamin D exposure/intake biomarker of choice within recent DRI exercises, but use of other vitamin D-related biomarkers as well as functional markers has been suggested. These may be of value in future vitamin D DRI exercises, such as the FAO/WHO's one for young children. Objectives To systematically review the usefulness of circulating 25(OH)D, parathyroid hormone (PTH), free and bioavailable 25(OH)D, C3-epimer of 25(OH)D, vitamin D-3, 24,25-dihydroxyvitamin D [24,25(OH)(2)D], and bone turnover markers and calcium absorption as vitamin D biomarkers for DRI development in children. Methods Methods included structured searches of published articles, full-text reviews, data extraction, quality assessment, meta-analysis, and random-effects meta-regression. Results Fifty-nine vitamin D supplementation randomized controlled trials (RCTs) were included (39 in infants/children as the priority group and the remainder in adults since pediatric studies were absent/limited). Vitamin D supplementation significantly raised circulating 25(OH)D in infants and children, but the response was highly heterogeneous [weighted mean difference (WMD): 27.7 nmol/L; 95% CI: 22.9, 32.5; 27 RCTs; I-2 = 93%]. Meta-regression suggested an increase by 1.7 nmol/L (95% CI: 0.7, 2.6) in serum 25(OH)D per each 100-IU increment in vitamin D intake (P = 0.0005). Vitamin D supplementation had a significant effect on circulating 24,25(OH)(2)D (WMD: 3.4 nmol/L; 95% CI: 2.4, 4.5; 13 RCTs; I-2 = 95%), with a dose-response relation (+0.15 nmol/L per 100 IU; 95% CI: -0.01, 0.29). With circulating PTH, although there was a significant effect of vitamin D on WMD (P = 0.05), there was no significant dose-response relation (P = 0.32). Pediatric data were too limited in relation to the usefulness of the other biomarkers. Conclusions Circulating 25(OH)D may be a useful biomarker of vitamin D exposure/intake for DRI development in infants and children. Circulating 24,25(OH)(2)D also showed some promise, but further data are needed, especially in infants and children.