Examination of Serum Metabolome Altered by Dietary Carbohydrate, Milk Protein, and Soy Protein Interventions Identified Novel Metabolites Associated with Blood Pressure: The ProBP Trial.

ABSTRACT

SCOPE This study aims to discover metabolites of dietary carbohydrate, soy and milk protein supplements and evaluate their roles in blood pressure (BP) regulation in the protein and blood pressure (ProBP), a cross-over trial. METHODS AND RESULTS: Plasma metabolites are profiled at pre-trial baseline and after 8 weeks of supplementation with carbohydrate, soy protein, and milk protein, respectively, among 80 ProBP participants. After Bonferroni correction (α = 6.49 × 10-4 ), dietary interventions significantly changed 40 metabolites. Changes of erucate (221n9), an omega-9 fatty acid, are positively associated with systolic BP changes (Beta = 1.90, p = 6·27 × 10-4 ). This metabolite is also associated with higher odds of hypertension among 1261 participants of an independent cohort (odds ratio per unit increase = 1.34; 95% confidence interval 1.07-1.68). High levels of acylcholines dihomo-linolenoyl-choline (p = 4.71E-04) and oleoylcholine (p = 3.48E-04) at baseline predicted larger BP lowering effects of soy protein. Increasing cheese intake during the trial, as reflected by isobutyrylglycine and isovalerylglycine, reduces the BP lowering effect of soy protein. CONCLUSIONS: The study identifies molecular signatures of dietary interventions. Erucate (221n9) increases systolic BP. Acylcholine enhances and cheese intake reduces the BP lowering effect of soy protein supplement.