Abstract
BACKGROUND: Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet enhances potassium intake and reduces sodium intake and blood pressure (BP), but the underlying metabolic pathways are unclear. OBJECTIVES: Among free-living populations, we delineated metabolic signatures associated with the DASH diet adherence, 24-hour urinary sodium and potassium excretions, and the potential metabolic pathways involved. METHODS: We used 24-hour urinary metabolic profiling by proton nuclear magnetic resonance spectroscopy to characterize the metabolic signatures associated with the DASH dietary pattern score (DASH score) and 24-hour excretion of sodium and potassium among participants in the United States (n = 2164) and United Kingdom (n = 496) enrolled in the International Study of Macro- and Micronutrients and Blood Pressure (INTERMAP). Multiple linear regression and cross-tabulation analyses were used to investigate the DASH-BP relation and its modulation by sodium and potassium. Potential pathways associated with DASH adherence, sodium and potassium excretion, and BP were identified using mediation analyses and metabolic reaction networks. RESULTS: Adherence to the DASH diet was associated with urinary potassium excretion (correlation coefficient, r = 0.42; P < 0.0001). In multivariable regression analyses, a 5-point higher DASH score (range, 7 to 35) was associated with a lower systolic BP by 1.35 mmHg (95% CI, -1.95 to -0.80 mmHg; P = 1.2 × 10-5); control of the model for potassium but not sodium attenuated the DASH-BP relation. Two common metabolites (hippurate and citrate) mediated the potassium-BP and DASH-BP relationships, while 5 metabolites (succinate, alanine, S-methyl cysteine sulfoxide, 4-hydroxyhippurate, and phenylacetylglutamine) were found to be specific to the DASH-BP relation. CONCLUSIONS: Greater adherence to the DASH diet is associated with lower BP and higher potassium intake across levels of sodium intake. The DASH diet recommends greater intake of fruits, vegetables, and other potassium-rich foods that may replace sodium-rich processed foods and thereby influence BP through overlapping metabolic pathways. Possible DASH-specific pathways are speculated but confirmation requires further study. INTERMAP is registered as NCT00005271 at www.clinicaltrials.gov.