24-h urinary sodium and potassium excretions, plasma metabolomic profiles, and cardiometabolic biomarkers in the United States adults: a cross-sectional study

Rikuta Hamaya; Qi Sun; Jun Li; Huan Yun; Fenglei Wang; Gary C Curhan; Tianyi Huang; JoAnn E Manson; Walter C Willett; Eric B Rimm; Clary Clish; Liming Liang; Frank B Hu; Yuan Ma

doi:10.1016/j.ajcnut.2024.05.010

24-h urinary sodium and potassium excretions, plasma metabolomic profiles, and cardiometabolic biomarkers in the United States adults: a cross-sectional study

Am J Clin Nutr. 2024 May 16:S0002-9165(24)00473-8. doi: 10.1016/j.ajcnut.2024.05.010. Online ahead of print.

Authors

Rikuta Hamaya¹, Qi Sun², Jun Li¹, Huan Yun³, Fenglei Wang⁴, Gary C Curhan⁵, Tianyi Huang⁶, JoAnn E Manson⁷, Walter C Willett⁸, Eric B Rimm², Clary Clish⁹, Liming Liang¹⁰, Frank B Hu¹¹, Yuan Ma¹²

Affiliations

¹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
⁴ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
⁶ Division of Women's Health, Department of Medicine, Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
⁷ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Mary Horrigan Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
⁸ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
⁹ Metabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA, United States.
¹⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
¹¹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States. Electronic address: fhu@hsph.harvard.edu.
¹² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States. Electronic address: yuanma@hsph.harvard.edu.

PMID: 38762185
DOI: 10.1016/j.ajcnut.2024.05.010

Abstract

Background: High-sodium and low-potassium intakes are associated with a higher risk of hypertension and cardiovascular disease, but there are limited data on the circulating metabolomics profiles of 24-h urinary sodium and potassium excretions in free-living individuals.

Objectives: We aimed to characterize the metabolomics signatures of a high-sodium and low-potassium diet in a cross-sectional study.

Methods: In 1028 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 to 4 24-h urine samples with plasma metabolites (quantified using liquid chromatography-tandem mass spectrometry) and metabolomic pathways. Our primary exposures were energy-adjusted 24-h urinary sodium excretion, potassium excretion, and sodium-to-potassium ratio, calculated based on energy expenditure derived from the doubly labeled water method. We then 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 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.

Keywords: cardiovascular disease; metabolomics; potassium; prevention; sodium.