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

Abstract

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. In a double-blind, randomised placebo-controlled dietary intervention subjects were assigned to receive 15 μg 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 (1) H-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. Overall, metabolic phenotyping revealed a phenotype that was responsive to vitamin D supplementation.