A systematic review and meta-regression analysis of the vitamin D intake-serum 25-hydroxyvitamin D relationship to inform European recommendations

The present study used a systematic review approach to identify relevant randomised control trials (RCT) with vitamin D and then apply meta-regression to explore the most appropriate model of the vitamin D intake-serum 25-hydroxyvitamin D (25(OH) D) relationship to underpin setting reference intake values. Methods included an updated structured search on Ovid MEDLINE; rigorous inclusion/exclusion criteria; data extraction; and meta-regression (using different model constructs). In particular, priority was given to data from winter-based RCT performed at latitudes >49.5 degrees N (n 12). A combined weighted linear model meta-regression analyses of natural log (Ln) total vitamin D intake (i.e. diet and supplemental vitamin D) v. achieved serum 25(OH) D in winter (that used by the North American Dietary Reference Intake Committee) produced a curvilinear relationship (mean (95% lower CI) serum 25(OH) D (nmol/l) 9.2 (8.5) Ln (total vitamin D)). Use of non-transformed total vitamin D intake data (maximum 1400 IU/d; 35 mu g/d) provided for a more linear relationship (mean serum 25(OH) D (nmol/l) 0.044 x (total vitamin D) + 33.035). Although inputting an intake of 600 IU/d (i.e. the RDA) into the 95% lower CI curvilinear and linear models predicted a serum 25(OH) D of 54.4 and 55.2 nmol/l, respectively, the total vitamin D intake that would achieve 50 (and 40) nmol/l serum 25(OH) D was 359 (111) and 480 (260) IU/d, respectively. Inclusion of 95% range in the model to account for inter-individual variability increased the predicted intake of vitamin D needed to maintain serum 25(OH) D >= 50 nmol/l to 930 IU/d. The model used to describe the vitamin D intake-status relationship needs to be considered carefully when setting new reference intake values in the Europe.