Biochemical and metabolomic phenotyping in the identification of a vitamin D responsive metabotype for markers of the metabolic syndrome

Scope: Metabolic phenotyping promises to be a useful tool in human intervention studies. This study examined whether metabolic phenotyping could identify responders to vitamin D supplementation in terms of the metabolic syndrome. Methods and results: In a double-blind, randomised placebo-controlled dietary intervention subjects were assigned to receive 15 mu g vitamin D-3 or placebo daily. Serum 25-hydroxyvitamin D (25(OH)D) and biochemical markers of the metabolic syndrome were measured at baseline and following the 4-wk intervention. k-means clustering and H-1-NMR metabolomic analysis were used to explore responsive phenotypes. Vitamin D supplementation significantly increased serum 25(OH) D to an endpoint concentration of 78.1 +/- 20.0 nmol/L (p < 0.001). There was no effect of supplementation on the measured markers of the metabolic syndrome. k-means cluster analysis based on 13 biochemical markers of the metabolic syndrome and 25(OH)D concentrations revealed five discrete biomarker clusters. One of these clusters, characterised by lower serum 25(OH) D and higher levels of adipokines, showed significant responses in insulin (15% decrease), homestatic model assessment scores (19% decrease) and c-reactive protein (54% decrease). Metabolomic analysis revealed further changes and the extent of change in serum vitamin D correlated negatively with changes in glucose. Conclusion: Overall, metabolic phenotyping revealed a phenotype that was responsive to vitamin D supplementation.