15 N-labeled dietary nitrate supplementation increases human skeletal muscle nitrate concentration and improves muscle torque production.

Aim: Dietary nitrate (NO ₃ ^- ) supplementation increases nitric oxide bioavailability and can enhance exercise performance. We investigated the distribution and metabolic fate of ingested NO ₃ ^- at rest and during exercise with a focus on skeletal muscle.
Methods: In a randomized, crossover study, 10 healthy volunteers consumed 12.8 mmol ¹⁵ N-labeled potassium nitrate (K ¹⁵ NO ₃ ; NIT) or potassium chloride placebo (PLA). Muscle biopsies were taken at baseline, at 1- and 3-h post-supplement ingestion, and immediately following the completion of 60 maximal intermittent contractions of the knee extensors. Muscle, plasma, saliva, and urine samples were analyzed using chemiluminescence to determine absolute [NO ₃ ^- ] and [NO ₂ ^- ], and by mass spectrometry to determine the proportion of NO ₃ ^- and NO ₂ ^- that was ¹⁵ N-labeled.
Results: Neither muscle [NO ₃ ^- ] nor [NO ₂ ^- ] were altered by PLA. Following NIT, muscle [NO ₃ ^- ] (but not [NO ₂ ^- ]) was elevated at 1-h (from ~35 to 147 nmol/g, p < 0.001) and 3-h, with almost all of the increase being ¹⁵ N-labeled. There was a significant reduction in ¹⁵ N-labeled muscle [NO ₃ ^- ] from pre- to post-exercise. Relative to PLA, mean muscle torque production was ~7% greater during the first 18 contractions following NIT. This improvement in torque was correlated with the pre-exercise ¹⁵ N-labeled muscle [NO ₃ ^- ] and the magnitude of decline in ¹⁵ N-labeled muscle [NO ₃ ^- ] during exercise (r = 0.66 and r = 0.62, respectively; p < 0.01).
Conclusion: This study shows, for the first time, that skeletal muscle rapidly takes up dietary NO ₃ ^- , the elevated muscle [NO ₃ ^- ] following NO ₃ ^- ingestion declines during exercise, and muscle NO ₃ ^- dynamics are associated with enhanced torque production during maximal intermittent muscle contractions.
(© 2023 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)