Effect of Dietary Sodium Restriction on Human Urinary Metabolomic Profiles

Abstract

Background and objectives Metabolomics is a relatively new field of "-omics" research, focusing on highthroughput identification of small molecular weight metabolites. Diet has both acute and chronic effects on metabolic profiles; however, alterations in response to dietary sodium restriction (DSR) are completely unknown. The goal of this study was to explore changes in urine metabolites in response to DSR, as well as their association with previously reported improvements in vascular function with DSR.Design, setting, participants, & measurements Using stored urine samples from a 10-week randomized placebo-controlled crossover study of DSR in 17 middle-aged/older adults (six men and 11 women; mean age 6268 years) who had moderately elevated systolic BP (130-159 mmHg) and were otherwise healthy, a liquid chromatography/mass spectrometry-based analysis of 289 metabolites was performed. This study identified metabolites that were significantly altered between the typical (153629 mmol/d) and low (70629 mmol/d) sodium conditions, as well as their baseline (typical sodium) association with responsiveness to previously reported improvements in vascular endothelial function (brachial artery flow-mediated dilation) and large elastic artery stiffness (aortic pulse wave velocity).Results Of the 289 metabolites surveyed, 10 were significantly altered (nine were upregulated and one was downregulated) during the low sodium condition, and eight of these exceeded our prespecified clinically significant threshold of a .40% change. These metabolites were involved in biologic pathways broadly related to cardiovascular risk, nitric oxide production, oxidative stress, osmotic regulation, and metabolism. One metabolite, serine, was independently (positively) associated with previously reported improvements in the primary vascular outcome of brachial artery flow-mediated dilation.Conclusions This proof-of-concept study provides the first evidence that DSR is a stimulus that induces significant changes in urinary metabolomic profiles. Moreover, serine was independently associated with corresponding changes in vascular endothelial function after DSR. Larger follow-up studies will be required to confirm and further elucidate the metabolic pathways that are altered in response to DSR.

Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)–Sodium Feeding Study

“…Metabolites were measured in 24-h urine samples collected at the end of each intervention. Sodium restriction was associated with increases in succinate, methionine sulfoxide, S-adenosylhomocysteine, D-gluconate, and asparagine (40). Our study of plasma metabolites replicated the increases in succinate, gluconate, and asparagine, but we did not observe the same direction of associations for succinate or methionine sulfoxide.…”

An Overview of Metabolic Phenotyping in Blood Pressure Research

“…Several pathways have been suggested in relation to blood pressure including the possible role of the gut microflora [ 55 ••, 56 ••, 57 ], inflammatory [ 68 ••], oxidative stress [ 65 , 70 ], and lipid pathways [ 63 ••, 66 , 83 ]. Metabolic changes have also been identified associated with blood pressure lowering effects of diets high in fruits and vegetables and low in meat intake [ 51 , 52 , 56 ••]. However, the current body of literature on metabolic profiling and blood pressure is still in its infancy, not fully consistent and requires careful interpretation.…”

“…Metabolic phenotyping in relation to dietary sodium reduction has also been studied. The response of dietary sodium reduction (DSR) was studied in a 10-week crossover RCT study among 17 adults with elevated systolic blood pressure (130–159 mmHg) [ 51 ]. Ten (of 289) measured urinary metabolites were significantly altered (nine upregulated and one downregulated) during low-sodium diet.…”

Low-Salt Diet and Circadian Dysfunction Synergize to Induce Angiotensin II–Dependent Hypertension in Mice

“…47 Aside from the effect on volume depletion, reduction of sodium in diet can also induce an array of changes as demonstrated in the human urinary metabolome, affecting pathways related to cardiovascular risk, nitric oxide production, oxidative stress, osmotic regulation, and metabolism. 48 Studies exploring the effect of sodium restriction and its effect on rhythmic blood pressure are limited 49–51 and little is known with regard to how low salt diets influence blood pressure during human circadian dysfunction and circadian decline, as in sleep disorders, 2, 52–54 shift work, 55 and aging, 1 given the prevalence of hypertension in these conditions.…”