Metabolon Elucidates Molecular Signatures That Explain the Benefits of Reducing Sodium Intake

The Challenge: Exploring the Molecular Outcomes of Dietary Sodium Reduction in Hypertensive Patients

Hypertension, also known as high blood pressure (BP), is a medical condition where the force of blood circulating in the arteries is consistently too high. This condition makes it harder for the heart to pump blood. If left untreated, hypertension can lead to serious health complications, including cardiovascular disease (CVD), kidney disease, and vision loss.
High sodium intake is recognized as one of the main risk factors for hypertension. Previous studies have shown that dietary sodium reduction lowers BP, CVD, and mortality.¹ Despite this well-established relationship, the underlying mechanism of action (MoA) is not well understood. The present study analyzed serum samples from a randomized, double-blind, placebo-controlled cross-over clinical trial (Unique identifier: NCT00152074) of dietary sodium reduction in hypertensive patients. Comparisons were made based on race and sex.

Metabolon Insight: Metabolon Helps Profile the Metabolic Profiles of Hypertensive Patients

This group utilized the Metabolon Global Discovery Panel to profile the serum samples of Black patients with hypertension (n = 64) on a reduced sodium diet.² The research group also used Metabolon’s Short Chain Fatty Acids Targeted Panel to profile serum samples from 145 patients with hypertension (42% Black, 19% Asian, and 34% female) on a low sodium diet.³ Metabolon offered this group the most comprehensive solution to analyze the metabolic profiles of hypertensive patients. The goal was to elucidate metabolic signatures associated with reduced sodium intake in hypertensive patients, providing mechanistic insights that explain the cardiovascular health benefits of a reduced sodium diet.

The Solution: Metabolomics Reveals Molecular Signatures of a Low Sodium Intake Diet

Untargeted metabolomics demonstrated that dietary sodium reduction significantly increased the plasma levels of β-hydroxyisovalerate and methionine sulfone. These changes were associated with changes in cardiovascular phenotypes. For example, increased β-hydroxyisovalerate was associated with reduced systolic BP (SBP) and pulse pressure (PP).  Methionine sulfone was associated with reduced diastolic BP (DBP) and improved skin capillary density (microcirculation).
Targeted metabolomics showed that reduced sodium intake significantly increased the levels of many short-chain fatty acids (SCFAs). The levels of 2-methylbutyric acid (2-methylbutyrate) increased in both males and females, while increases in butyric acid (butyrate), caproic acid (hexanoate), isobutyric acid (isobutyrate), isovaleric acid (isovalerate), and valeric acid (valerate) were significant in females only. Changes in SCFAs were associated with changes in cardiovascular phenotypes. Increased circulating isovaleric acid was associated with reduced BP. Increased isobutyric acid was associated with reduced PP and BP. Finally, increased valeric acid was associated with decreased carotid-femoral pulse wave velocity (cfPWV).

The Outcome: Metabolomics Unravels the Mechanisms That Explain the Benefits of Reducing Sodium Intake

Untargeted and targeted metabolomics reveal a probable MoA that explains the benefits of reducing sodium consumption in hypertensive patients. This study shows that dietary sodium reduction alters the metabolome and that there is a sex difference in SCFA response to sodium reduction. These findings suggest that changes in circulating SCFAs may underlie the BP responses to dietary sodium reduction in females but not males. Metabolomic profiling can detect small molecule metabolic products in response to environmental changes, which could serve as biomarkers or underlying mechanisms for biological response to dietary intervention.