An exploratory analysis of comparative plasma metabolomic and lipidomic profiling in salt-sensitive and salt-resistant individuals from The Dietary Approaches to Stop Hypertension Sodium Trial

OBJECTIVE: This study conducted exploratory metabolomic and lipidomic profiling of plasma samples from the DASH (Dietary Approaches to Stop Hypertension) Sodium Trial to identify unique plasma biomarkers to identify salt-sensitive versus salt-resistant participants. METHODS: Utilizing plasma samples from the DASH-Sodium Trial, we conducted untargeted metabolomic and lipidomic profiling on plasma from salt-sensitive and salt-resistant DASH-Sodium Trial participants. Study 1 analyzed plasma from 106 salt-sensitive and 85 salt-resistant participants obtained during screening when participants consumed their regular diet. Study 2 examined paired within-participant plasma samples in 20 salt-sensitive and 20 salt-resistant participants during a high-salt and low-salt dietary intervention. To investigate differences in metabolites or lipidomes that could discriminate between salt-sensitive and salt-resistant participants or the response to a dietary sodium intervention Principal Component Analysis and Orthogonal Partial Least Square Discriminant Analysis was conducted. Differential expression analysis was performed to validate observed variance and to determine the statistical significance. RESULTS: Differential expression analysis between salt-sensitive and salt-resistant participants at screening revealed no difference in plasma metabolites or lipidomes. In contrast, three annotated plasma metabolites, tocopherol alpha, 2-ketoisocaproic acid, and citramalic acid, differed significantly between high-sodium and low-sodium dietary interventions in salt-sensitive participants. CONCLUSION: In DASH-Sodium Trial participants on a regular diet, plasma metabolomic or lipidomic signatures were not different between salt-sensitive and salt-resistant participants. High-sodium intake was associated with changes in specific circulating metabolites in salt-sensitive participants. Further studies are needed to validate the identified metabolites as potential biomarkers that are associated with the salt sensitivity of blood pressure.