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

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 (alpha = 6.49 x 10(-4)), dietary interventions significantly changed 40 metabolites. Changes of erucate (22:1n9), an omega-9 fatty acid, are positively associated with systolic BP changes (Beta = 1.90, p = 6 center dot 27 x 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 (22:1n9) increases systolic BP. Acylcholine enhances and cheese intake reduces the BP lowering effect of soy protein supplement.