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

Abstract

Background: High sodium intake is known to increase blood pressure and is difficult to measure in epidemiologic studies. Objective: We examined the effect of sodium intake on metabolites within the DASH (Dietary Approaches to Stop Hypertension Trial)-Sodium Trial to further our understanding of the biological effects of sodium intake beyond blood pressure. Design: The DASH-Sodium Trial randomly assigned individuals to either the DASH diet (low in fat and high in protein, low-fat dairy, and fruits and vegetables) or a control diet for 12 wk. Participants within each diet arm received, in random order, diets containing high (150 nmol or 3450 mg), medium (100 nmol or 2300 mg), and low (50 nmol or 1150 mg) amounts of sodium for 30 d (crossover design). Fasting blood samples were collected at the end of each sodium intervention. We measured 531 identified plasma metabolites in 73 participants at the end of their high-and low-sodium interventions and in 46 participants at the end of their high-and medium-sodium interventions (N = 119). We used linear mixed-effects regression to model the relation between each log-transformed metabolite and sodium intake. We also combined the resulting P values with Fisher's method to estimate the association between sodium intake and 38 metabolic pathways or groups. Results: Six pathways were associated with sodium intake at a Bonferroni-corrected threshold of 0.0013 (e.g., fatty acid, food component or plant, benzoate, g-glutamyl amino acid, methionine, and tryptophan). Although 82 metabolites were associated with sodium intake at a false discovery rate #0.10, only 4-ethylphenylsufate, a xenobiotic related to benzoate metabolism, was significant at a Bonferroni-corrected threshold (P , 10 25 ). Adjustment for coinciding change in blood pressure did not substantively alter the association for the top-ranked metabolites. Conclusion: Sodium intake is associated with changes in circulating metabolites, including gut microbial, tryptophan, plant component, and g-glutamyl amino acid-related metabolites. This trial was registered at clinicaltrials.gov as NCT00000608.

Calcium Oxalate Nephrolithiasis and Gut Microbiota: Not just a Gut-Kidney Axis. A Nutritional Perspective

“…However, the effects of salt intake on gut microbiota have been investigated only in very recent times. In the Dietary Approaches to Stop Hypertension (DASH)-Sodium Feeding Study, Derkach and colleagues showed that in 119 patients at high risk for hypertension, different levels of salt intake were associated with different urinary levels of several metabolites, including some of gut microbial origin [65]. Namely, high-salt intake was associated with decreased urinary levels of compounds related to fatty acid, benzoate, indole, isovalerate, methionine, and tryptophan metabolism and of the microbial metabolites 4-ethylphenylsulfate and 4-hydroxyphenylpiruvate [65].…”

An Overview of Metabolic Phenotyping in Blood Pressure Research

“…The response of blood pressure regulation to dietary interventions has been investigated through metabolic phenotyping approaches in several studies, where different dietary patterns were adopted including the DASH Diet [ 50 – 52 ], Optimal Macronutrient Intake Trial for Heart Health (OmniHeart) Diets [ 56 ••], and Mediterranean Diet [ 61 ].…”

Reduced 24-h Sodium Excretion Is Associated With a Disturbed Plasma Acylcarnitine Profile in Vasovagal Syncope Children: A Pilot Study

“…The mechanisms by which low sodium loading results in a disturbed acylcarnitine profile have not been explored. Derkach et al also found a phenomenon in a DASH-sodium trial among participants with high blood pressure, that plasma metabolites of acylcarnitines (butyrylcarnitine and valerylcarnitine) were increased with sodium reduction (14). On the other hand, some studies showed a significant increase in renin-angiotensinaldosterone system activity with low sodium intake (12).…”

“…As a result, supplementation of fluid and sodium is a rationally efficient method to treat VVS (13). A possible relationship between the metabolism of carnitine and acylcarnitines and the reducing intake of sodium was mentioned among adults with hypertension (14). However, it is unclear whether low sodium intake in patients with VVS leads to abnormal changes in carnitine and acylcarnitines, which mediates the occurrence of syncope.…”