Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease

Abstract

Peripheral arterial disease (PAD) results in a failure to adequately supply blood and oxygen (O(2)) to working tissues and presents as claudication pain during walking. Nitric oxide (NO) bioavailability is essential for vascular health and function. Plasma nitrite (NO(2)(-)) is a marker of vascular NO production but may also be a protected circulating "source" that can be converted to NO during hypoxic conditions, possibly aiding perfusion. We hypothesized that dietary supplementation of inorganic nitrate in the form of beetroot (BR) juice would increase plasma NO(2)(-) concentration, increase exercise tolerance, and decrease gastrocnemius fractional O(2) extraction, compared with placebo (PL). This was a randomized, open-label, crossover study. At each visit, subjects (n = 8) underwent resting blood draws, followed by consumption of 500 ml BR or PL and subsequent blood draws prior to, during, and following a maximal cardiopulmonary exercise (CPX) test. Gastrocnemius oxygenation during the CPX was measured by near-infrared spectroscopy. There were no changes from rest for [NO(2)(-)] (152 ± 72 nM) following PL. BR increased plasma [NO(2)(-)] after 3 h (943 ± 826 nM; P ≤ 0.01). Subjects walked 18% longer before the onset of claudication pain (183 ± 84 s vs. 215 ± 99 s; P ≤ 0.01) and had a 17% longer peak walking time (467 ± 223 s vs. 533 ± 233 s; P ≤ 0.05) following BR vs. PL. Gastrocnemius tissue fractional O(2) extraction was lower during exercise following BR (7.3 ± 6.2 vs. 10.4 ± 6.1 arbitrary units; P ≤ 0.01). Diastolic blood pressure was lower in the BR group at rest and during CPX testing (P ≤ 0.05). These findings support the hypothesis that NO(2)(-)-related NO signaling increases peripheral tissue oxygenation in areas of hypoxia and increases exercise tolerance in PAD.

Improvement in blood pressure after short-term inorganic nitrate supplementation is attenuated in cigarette smokers compared to non-smoking controls

“…Increased dietary NO 3 -intake in the form of NO 3 --rich beetroot [11][12][13] or spinach [14,15] supplementation alone has also been shown to lower resting blood pressure. These findings are consistent with the emerging body of evidence to support improved vascular health following dietary NO 3 -supplementation (4-16 mmol·day -1 ) in younger [11][12][13] and older [16,17] normotensive adults, and in individuals with hypertension [18], peripheral artery disease [19] and heart failure [20]. Therefore, enriching the diet with NO 3 -, at a dose that can be readily achieved by a diet high in vegetables [4,7,9], might represent a practical and cost-effective intervention to lower cardiovascular disease morbidity and mortality.…”

Effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes

“…There was no apparent difference in BP lowering effect in the DASH trial when subjects were stratified into obese/non-obese (women were defined as obese if their BMI was ≥ 27.3: men were defined as obese if their BMI was ≥ 27.8). 48 The subjects in the study by Kenjale et al - 44 who had no change in systolic BP -had a BMI of 28.6 ± 5.8 kg/m 2 .…”

“…These medications were continued throughout the study period. Prior to the present study, Kenjale et al's pilot study, 44 in peripheral arterial disease, was the only trial examining the effect of dietary nitrate in subjects already taking vasoactive medications. There was no difference in systolic BP following nitrate supplementation in their study.…”

“…Kenjale et al 44 examined the effect of dietary nitrate on exercise performance in subjects with peripheral artery disease. There was no effect on resting systolic BP in a group with a mean age of 67 ± 13 years following supplementation with 9 mmoles of nitrate, using beetroot juice as a source of nitrate.…”

Nitrate pharmacokinetics: Taking note of the difference

“…Numerous exercise performance studies in disease states such as peripheral arterial disease [29], chronic heart failure [30] and pulmonary diseases [31] are starting to emerge.…”