The effect of dietary nitrate on exercise capacity in chronic kidney disease: a randomized controlled pilot study

Abstract

Background: Chronic Kidney Disease (CKD) patients exhibit a reduced exercise capacity that impacts quality of life. Dietary nitrate supplementation has been shown to have favorable effects on exercise capacity in disease populations by reducing the oxygen cost of exercise. This study investigated whether dietary nitrates would acutely improve exercise capacity in CKD patients.

Methods and results: In this randomized, double-blinded crossover study, 12 Stage 3-4 CKD patients (Mean ± SEM: Age, 60 ± 5yrs; eGFR, 50.3 ± 4.6 ml/min/1.73 m²) received an acute dose of 12.6 mmol of dietary nitrate in the form of concentrated beetroot juice (BRJ) and a nitrate depleted placebo (PLA). Skeletal muscle mitochondrial oxidative function was assessed using near-infrared spectroscopy. Cardiopulmonary exercise testing was performed on a cycle ergometer, with intensity increased by 25 W every 3 min until volitional fatigue. Plasma nitric oxide (NO) metabolites (NOm; nitrate, nitrite, low molecular weight S-nitrosothiols, and metal bound NO) were determined by gas-phase chemiluminescence. Plasma NOm values were significantly increased following BRJ (BRJ vs. PLA: 1074.4 ± 120.4 μM vs. 28.4 ± 6.6 μM, p < 0.001). Total work performed (44.4 ± 10.6 vs 39.6 ± 9.9 kJ, p = 0.03) and total exercise time (674 ± 85 vs 627 ± 86s, p = 0.04) were significantly greater following BRJ. Oxygen consumption at the ventilatory threshold was also improved by BRJ (0.90 ± 0.08 vs. 0.74 ± 0.06 L/min, p = 0.04). These changes occurred in the absence of improved skeletal muscle mitochondrial oxidative capacity (p = 0.52) and VO_2peak (p = 0.35).

Conclusions: Our findings demonstrate that inorganic nitrate can acutely improve exercise capacity in CKD patients. The effects of chronic nitrate supplementation on CKD related exercise intolerance should be investigated in future studies.

Keywords: Chronic; Exercise tolerance; Mitochondria; Muscle; Nitrates; Renal insufficiency.

Figure 1.

(A) VO_2Peak and (B) Total Exercise Time after PLA and BRJ treatments. PLA, placebo; BRJ, beetroot juice.

Figure 2.

(A) Ventilatory threshold and (B) Work performed after placebo and beetroot juice. PLA, placebo; BRJ, beetroot juice; kJ kilojoules. *p<0.05.

Figure 3.

(A) Oxygen uptake during the final 30 seconds of each stage of exercise and (B) Time constant (τ) corresponding to phosphocreatine recovery kinetics measured by NIRS. W, watts, PLA, placebo, BRJ, beetroot juice.