24-hour urinary sodium and potassium excretions, plasma metabolomic profiles, and cardiometabolic biomarkers in US adults: A cross-sectional study

Background High sodium and low potassium intakes are associated with a higher risk of hypertension and cardiovascular disease (CVD), but there are limited data on the circulating metabolomics profiles of 24-hour urinary sodium and potassium excretions in free-living individuals. Objectives To characterize metabolomics signatures of a high-sodium and low-potassium diet in a cross-sectional study. Methods In 1,028 healthy older adults from the Women’s and Men’s Lifestyle Validation Studies, we investigated the association of habitual sodium and potassium intakes measured by 2-4 24-hour urine samples with plasma metabolites (quantified using liquid chromatography-tandem mass spectrometry) and metabolomic pathways. Our primary exposures were energy-adjusted 24-hour urinary sodium excretion, potassium excretion, and sodium-to-potassium ratio, calculated based on energy expenditure derived from the Doubly Labelled Water method. Then we assessed the partial correlations of their metabolomics scores, derived from elastic net regressions, with cardiometabolic biomarkers. Results Higher sodium excretion was associated with 38 metabolites including higher piperine, phosphatidylethanolamine, and C5:1 carnitine. In pathway analysis, higher sodium excretion was associated with enhanced biotin and propanoate metabolism, and enhanced degradation of lysine and branched-chain amino acids (BCAAs). Metabolites associated with higher potassium and lower sodium-to-potassium ratio included quinic acid and proline-betaine. After adjusting for confounding factors, the metabolomics score for sodium-to-potassium ratio positively correlated with fasting insulin (Spearman's rank correlation coefficient ρ=0.27), C-peptide (ρ=0.30), and triglyceride (ρ=0.46), and negatively with adiponectin (ρ=-0.40), and high-density lipoprotein (HDL) cholesterol (ρ=-0.42). Conclusions We discovered metabolites and metabolomics pathways associated with a high-sodium diet, including metabolites related to biotin, propanoate, lysine, and BCAA pathways. The metabolomics signature for a higher sodium-low potassium diet is associated with multiple components of elevated cardiometabolic risk.