Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, C104

Oral Communications

Dietary nitrate supplementation reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia

A. Vanhatalo1, J. Fulford2, J. R. Blackwell1, S. J. Bailey1, P. G. Winyard2, A. M. Jones1

1. College of Life and Environmental Sciences, University of Exeter, Exeter, Devon, United Kingdom. 2. Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, Devon, United Kingdom.


For the same metabolic rate, there is a greater muscle metabolic perturbation (e.g., greater fall in [PCr]) during exercise performed in hypoxia compared to normoxia. It has been proposed that plasma nitrite, which can be markedly elevated by dietary nitrate consumption, may be reduced to nitric oxide under hypoxic conditions, thereby enabling a more precise local matching of blood flow to metabolic rate (1). We therefore hypothesised that the reduction in exercise tolerance that is typically observed in hypoxia compared to normoxia would be attenuated when hypoxic exercise is preceded by dietary nitrate intake. Following ethical approval, 9 subjects (2 female; mean±SD age 28±7 years) were studied on three occasions in a double-blind, randomised crossover design. The experimental protocol consisted of a 24 s bout of high-intensity knee-extension exercise for the assessment of [PCr] recovery kinetics (an index of mitochondrial function) and, after 6 min of rest, a bout of continuous severe-intensity exercise performed to the limit of tolerance (Tlim) inside the bore of a 1.5 T superconducting magnet. Subjects completed one trial in normoxia (21% O2; CON) and two trials in hypoxia (15% O2). During 24 h prior to the hypoxic trials, subjects consumed 0.75 L of nitrate-rich beetroot juice (9.3 mmol nitrate; H-BR) or 0.75 L of nitrate-depleted beetroot juice (0.006 mmol nitrate; H-PL). Muscle metabolism was assessed during and after exercise using calibrated 31P-magnetic resonance spectroscopy, and pre-exercise plasma [nitrite] was measured using a modified chemiluminescence technique. Data were analyzed using one-way repeated measures ANOVA with significance accepted at P<0.05. Plasma [nitrite] was elevated (P<0.01) following BR (194±51 nM) compared to PL (129±23 nM) and CON (142±37 nM). Tlim was reduced in H-PL compared to CON (393±169 vs. 471±200 s; P<0.05) but was not different between CON and H-BR (477±200 s). The end-exercise [PCr] was not different between conditions, but the overall rate of decline in [PCr] was greater (P<0.01) in H-PL (63±28 μM.s-1) than in CON (48±24 μM.s-1) and H-BR (48±21 μM.s-1). The PCr recovery rate constant was reduced (P<0.01) in H-PL (2.2 ± 0.4 min-1) compared to CON (2.7 ± 0.6 min-1) and H-BR (2.6 ± 0.5 min-1). Dietary nitrate supplementation reduced muscle metabolic perturbation during severe-intensity exercise in hypoxia and restored exercise tolerance to that observed in normoxia. Nitrate supplementation also abolished the reduction in the rate of PCr recovery which was observed in hypoxia, indicating enhanced muscle oxygenation and a restoration of mitochondrial function. These results suggest that dietary nitrate supplementation may have important therapeutic applications for improving skeletal muscle energetics and functional capacity in conditions where muscle O2 delivery is compromised.

Where applicable, experiments conform with Society ethical requirements