Abstract
Background: Influences of nutrition on acid-base balance have long been recognized, and significant pathophysiological effects of diet-induced metabolic acidosis (DIMA) are now acknowledged, making it a potential target for preventive dietary interventions. Despite biological plausibility, recent cross-sectional and prospective studies have failed to provide consistent evidence supporting an association between DIMA and blood pressure (BP), systemic hypertension, or cardiovascular risk. Objective: To assess associations of validated DIMA indices computed from dietary information with BP, using data from the International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP). Methods: The INTERMAP Study is a cross-sectional epidemiological investigation with standardized quality-controlled methods. It includes 4,680 participants from four countries (China, Japan, UK, and USA) with detailed lifestyle, anthropometric, and dietary information, as well as two 24-hour urine samples. Participants reporting use of BP-lowering medications were excluded. Two indices were investigated: energy-adjusted Potential Renal Acid Load (PRAL, mEq/MJ/day), which quantifies the dietary acid-forming potential only, and Net Endogenous Acid Production (NEAP, mEq/1.73m 2 /day), which assesses the balance between endogenous acid production and PRAL, and thus provides a more accurate measure of DIMA. Analyses were stratified by ethnic group: non-Hispanic Whites (NHWs, N=1,397), Japanese (N=1,273), Chinese (N=804), and African-Americans (N=253). All models were adjusted for known hypertension risk factors. Additional analyses were conducted to investigate associations of DIMA indices with BMI. Results: NEAP was positively associated with BP in NHWs and Japanese. In NHWs, systolic BP: 0.08 (95% confidence interval: 0.03 to 0.13) mmHg higher per mEq/1.73m 2 /day in men, 0.19 (0.12 to 0.26) mmHg higher in women; diastolic BP: 0.06 (0.03 to 0.1) mmHg higher in men, 0.11 (0.06 to 0.16) mmHg higher in women. In Japanese, systolic BP: 0.11 (0.03 to 0.18) mmHg higher in men, 0.15 (0.07 to 0.25) mmHg higher in women; diastolic BP: 0.08 (0.02 to 0.13) mmHg higher in men, 0.11 (0.05 to 0.18) mmHg higher in women. These associations were not significant after controlling for BMI. PRAL was not significantly associated with BP in any model. NEAP was also significantly associated with BMI across ethnic groups, which is consistent with a possible mediating role of BMI in the association between NEAP and BP. Conclusions: Our data indicate ethnicity-specific positive associations of DIMA (as measured by NEAP) with BP, possibly mediated by obesity.
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