Identification of Dietary Supplements Associated with Blood Metabolites in the Hispanic Community Health Study/Study of Latinos Cohort Study

Background: Metabolomics approaches have been widely used to define the consumption of foods but have less often been used to study exposure to dietary supplements. Objectives: This study aimed to identify dietary supplements associated with metabolite levels and to examine whether these metabolites predicted incident diabetes risk. Methods: We studied 3972 participants from a prospective cohort study of 18–74-y-old Hispanic/Latino adults. At a baseline examination, we ascertained use of dietary supplements using recall methods and concurrently, a serum metabolomic panel. After adjustment for potential confounders, we identified dietary supplements associated with metabolites. We then examined the association of these metabolites with incident diabetes at the 6-y study examination. Results: We observed a total of 110 dietary supplement–metabolite associations that met the criteria for statistical significance adjusted for age, sex, field center, Hispanic/Latino background, body mass index, diet, smoking, physical activity, and number of medications (adjusted P < 0.05). This included 13 metabolites uniquely associated with only one dietary supplement ingredient. Vitamin C had the most associated metabolites (n = 15), including positive associations with oxalate, tartronate, threonate, and isocitrate, which were each in turn protective for the risk of incident diabetes. Vitamin C was also associated with higher N-acetylvaline level, which was an unfavorable diabetes risk factor. Other findings related to branched chain amino acid related compounds including α-hydroxyisovalerate and 2-hydroxy-3-methylvalerate, which were inversely associated with thiamine or riboflavin intake and also predicted higher diabetes risk. Vitamin B12 had an inverse association with γ-glutamylvaline, levels of which were positively associated with the risk of diabetes. Conclusions: Our data point to potential metabolite changes associated with vitamin C and B vitamins, which may have favorable metabolic effects. Knowledge of blood metabolites that can be modified by dietary supplement intake may aid understanding the health effects of dietary supplements and identify potential biological mediators.