Effects of Genetic and Nongenetic Factors on Total and Bioavailable 25(OH)D Responses to Vitamin D Supplementation

Context: Little is known about how genetic and nongenetic factors modify responses of vitamin D supplementation in nonwhite populations. Objective: To investigate factorsmodifying 25-hydroxyvitaminD[25(OH) D] and bioavailable 25(OH)D [25(OH)D-Bio] responses after vitamin D3 supplementation. Design, Setting, Participants, and Intervention: In this 20-week, randomized, double-blinded, placebo-controlled trial, 448 Chinese with vitamin D deficiency received 2000 IU/d vitamin D-3 or placebo. Main Outcome Measures: Serum 25(OH) D, vitamin D-binding protein (VDBP), parathyroid hormone (PTH) and calcium were measured, and 25(OH)D-Bio was calculated based on VDBP levels. Six common polymorphisms in vitamin D metabolism genes were genotyped. Results: Between-armnet changeswere + 30.6 +/- 1.7 nmol/L for 25(OH)D, + 2.7 +/- 0.2 nmol/L for 25(OH) D-Bio, and -5.2 +/- 1.2 pg/mL for PTH, corresponding to 70% [95% confidence interval (CI), 62.8% to 77.2%] net reversion rate for vitamin D deficiency atweek 20 (P < 0.001). Only 25(OH) DBio changewas positively associated with calcium change (P < 0.001). Genetic factors (GC-rs4588/GC-rs7041, VDR-rs2228570, and CYP2R1-rs10741657; P # 0.04) showed stronger influences on 25(OH)D or 25(OH)D-Bio responses than nongenetic factors, including baseline value, body mass index, and sex. An inverse association of PTH-25(OH) Dwas demonstrated only at 25(OH)D of, 50.8 (95% CI, 43.6 to 59.0) nmol/L. Conclusions: Supplemented 2000 IU/d vitamin D3 raised 25(OH)D and 25(OH)D-Bio but was unable to correct deficiency in 25% of Chinese participants, which might be partially attributed to the effect of geneticmodification. More studies are needed to elucidate appropriate vitaminDrecommendations for Asians and the potential clinical implications of 25(OH)D-Bio.