Abstract 14096: Examination of the Serum Metabolome After Dietary Carbohydrate, Milk Protein, and Soy Protein Interventions Identified Novel Metabolites for Blood Pressure: The ProBP Trial

Abstract

Introduction: In the Protein and Blood Pressure (ProBP) trial, milk and soy protein supplements reduced blood pressure (BP) compared to carbohydrate intervention. We investigated the underlying mechanisms influencing the effects. Methods: Serum metabolites were profiled at pre-trial baseline and after supplementation with carbohydrate, soy protein, and milk protein, respectively, among 80 ProBP participants. We tested the mediating and modifying effects of metabolites on BP-lowering effects of soy and milk protein interventions. Results: Dietary interventions significantly ( P <6.49х10 -4 ) changed 40 metabolites, of which 29 had reduced levels. Two clusters of metabolites mediated 45.5% and 100% of the effects of soy and milk protein interventions, respectively. Within the clusters, lipid 4-cholesten-3-one had the largest effect and mediated 12.7% ( P =0.03) and 16.3% ( P =0.045) of the effects of soy and milk protein interventions, respectively. At baseline, amino acids 5-oxoproline and taurine, lysophospholipid 1-arachidonoyl-GPA(20:4) , and acylcholines oleoylcholine , dihomo-linolenoyl-choline , and arachidonoylcholine predicted BP increase during carbohydrate intervention; while lipids N-stearoyl-sphinganine(d18:0/18:0) and isoursodeoxycholate and peptide gamma-glutamylserine predicted less reduction of BP during soy protein and milk protein supplements ( P <6.49х10 -4 ). Finally, effects of soy and milk protein interventions on systolic and diastolic BP were influenced by changes of isobutyrylglycine ( P for interaction=0.02 and 9.12х10 -5 , respectively). In the bottom tertile of isobutyrylglycine changes, soy and milk protein reduced 5.10 ( P =0.03) and 4.43 ( P =0.01) mmHg systolic BP and 3.22 ( P =0.03) and 3.12 ( P =0.04) mmHg diastolic BP, respectively; while in the top tertile, the two interventions had no or increasing effects on systolic (β soy protein =-0.04, P =0.98; β milk protein =-2.34, P =0.25) and diastolic BP (β soy protein =3.19, P =0.02; β milk protein =1.08, P =0.43). Conclusions: We documented serum metabolites altered by dietary carbohydrate, milk protein, and soy protein interventions, and identified important metabolites mediating or modifying the BP-lowering effect of milk and soy protein interventions.