The effect of dietary nitrate deprivation and subsequent supplementation on blood pressure in humans

Abstract

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality globally, accounting for approximately 17.5 million deaths annually. Hypertension is both the strongest predictor and most preventable risk factor of CVD; thus, the prevention of hypertension is central to reducing CVD-associated mortality. Dietary nitrate (NO3-) supplementation has emerged as a potential therapeutic strategy to manage hypertension and prevent CVD. Therefore, it is also possible that dietary NO3- deprivation may cause hypertension. However, research is required to investigate whether dietary NO3- deprivation causes a measurable increase in blood pressure in humans. Furthermore, rodent studies have demonstrated a ‘super compensation’ effect when NO3- supplementation is administered after a period of dietary NO3- deprivation. This phenomenon may have important applications as an anti-hypersensitive intervention. This thesis investigates the effect of dietary NO3- deprivation and subsequent supplementation on blood pressure in humans. Methods: In a repeated measures, crossover design study, thirteen healthy subjects ingested 180 mg.d-1 NO3- for 3 days, followed by a low NO3- diet (< 30 mg.d-1 NO3-) or a standard NO3- diet (180 mg.d-1 NO3- ) for 7 days. Finally subjects ingested > 800 mg.d-1 NO3- for 3 days. Subjects reported to the lab after each diet allocation for blood pressure measurements. Results: No interaction effects were observed following 7 days dietary NO3- deprivation for systolic blood pressure (SBP), diastolic blood pressure (DBP) or mean arterial pressure (MAP) (P > 0.05). However, a significant main effect of time was observed (P < 0.05; η2p= 0.30) in SBP with post-hoc t-test analysis demonstrating a significant decrease after 3 days NO3- supplementation compared to baseline (- 4 ± 3 mmHg; P = 0.001) in the standard condition. There were no significant differences in blood pressure variables following NO3- deprivation (P > 0.05). Additionally, NO3- supplementation following NO3- deprivation did not reduce blood pressure to a greater extent than NO3- supplementation following a standard NO3- diet. Conclusion: 7 days dietary NO3- deprivation does not cause a significant increase in blood pressure within healthy humans. Moreover, 3 days NO3- supplementation reduced SBP following a standard diet. However, supplementation, when administered after a period of deprivation does not accentuate the blood pressure-lowering effects of dietary NO3-. These findings contribute to our understanding of the regulation of blood pressure by dietary NO3-. Specifically, the results suggest that the NOS-dependent pathway performs compensatory NO generation which offsets the decrease in NO generation from the NO3--NO2--NO pathway during a period of dietary NO3- deprivation.