Diet-derived fruit and vegetable metabolites suggest sex-specific mechanisms conferring protection against osteoporosis in humans

Abstract

The impact of nutrition on the metabolic profile of osteoporosis is incompletely characterized. The objective of this cross-sectional study was to detangle the association of fruit and vegetable (FV) intakes with osteoporosis prevalence. Dietary, anthropometric and blood plasma metabolite data were examined from the Boston Puerto Rican Osteoporosis Study, a cohort of 600 individuals (age 46-79yr). High FV intake was protective against osteoporosis prevalence (Odds Ratio=0.73; 95% CI = 0.57, 0.94; P=0.013). Associations of 525 plasma metabolites were assessed with fruit and vegetable intake, and separately with osteoporosis status. Several biological processes affiliated with the FV-associating metabolites, including caffeine metabolism, carnitines and fatty acids, and glycerophospholipids. For osteoporosis-associated metabolites, important processes were steroid hormone biosynthesis in women, and branched-chain amino acid metabolism in men. In all instances, the metabolite patterns differed greatly between sexes, arguing for a stratified nutrition approach in recommending FV intakes to improve bone health. Factors derived from principal components analysis of the FV intakes were correlated with the osteoporosis-associated metabolites, with high intake of dark leafy greens and berries/melons appearing protective in both sexes. These data warrant investigation into whether increasing intakes of dark leafy greens, berries and melons causally affect bone turnover and BMD among adults at risk for osteoporosis via sex-specific metabolic pathways, and how gene-diet interactions alter these sex-specific metabolomic-osteoporosis links.