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

Abstract

Aim Dietary nitrate (NO3−) supplementation increases nitric oxide bioavailability and can enhance exercise performance. We investigated the distribution and metabolic fate of ingested NO3− at rest and during exercise with a focus on skeletal muscle. Methods In a randomized, crossover study, 10 healthy volunteers consumed 12.8 mmol 15N‐labeled potassium nitrate (K15NO3; 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 [NO3−] and [NO2−], and by mass spectrometry to determine the proportion of NO3− and NO2− that was 15N‐labeled. Results Neither muscle [NO3−] nor [NO2−] were altered by PLA. Following NIT, muscle [NO3−] (but not [NO2−]) was elevated at 1‐h (from ~35 to 147 nmol/g, p < 0.001) and 3‐h, with almost all of the increase being 15N‐labeled. There was a significant reduction in 15N‐labeled muscle [NO3−] 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 15N‐labeled muscle [NO3−] and the magnitude of decline in 15N‐labeled muscle [NO3−] 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 NO3−, the elevated muscle [NO3−] following NO3− ingestion declines during exercise, and muscle NO3− dynamics are associated with enhanced torque production during maximal intermittent muscle contractions.

The influence of acute dietary nitrate supplementation on skeletal muscle fatigue and recovery in older women

“…In contrast, Kadach et al [2023] recently found that NO3supplementation increased muscle torque throughout the first 90 s of a 300 s bout of repeated maximal isometric knee extensions (3 s contraction, 2 s rest). Notably, however, numerous other investigations have failed to demonstrate any effect of dietary NO3on maximal isometric torque [Esen et al 2022], making the study by Kadach et al [2023] an exception. Regardless, based on the present as well as our previous results, it seems clear that although acute ingestion of NO3enhances maximal muscle speed and hence power in older individuals [Coggan et al 2020a;Gallardo et al 2021], it does not alter fatigability during intense contractile activity in older persons.…”

“…In contrast, Kadach et al [2023] recently found that NO3supplementation increased muscle torque throughout the first 90 s of a 300 s bout of repeated maximal isometric knee extensions (3 s contraction, 2 s rest). Notably, however, numerous other investigations have failed to demonstrate any effect of dietary NO3on maximal isometric torque [Esen et al 2022], making the study by Kadach et al [2023] an exception.…”

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

“…The most consistent effects found in the studies performed are enhancements of skeletal muscle contractile function with increased muscle power and capacity for sprint performance and an increase in muscular energetic efficiency as mentioned above 2,3 . These studies constitute the background of the paper by Kadach et al 4 in this issue of Acta Physiologica, where the authors present the use of isotope labeled nitrate to track the fate of dietary nitrate and its utilization by contracting muscles. In a randomized, crossover study, 10 healthy volunteers consumed 12.8 mmol 15 N‐labeled potassium nitrate (K 15 NO 3 ) or potassium chloride placebo.…”

Nutritional health

“…While for many commercially available supplements meaningful data are, at best, incomplete, examples of promising preventive approaches by nutrient supplementation may potentially be assumed for antioxidants, 17,18 bioactive collagen peptides, 19 and nitrates. 20 In summary, the intricate interplay between nutrition and physiology underscores the critical importance of dietary choices in maintaining optimal health. By understanding the biochemical mechanisms through which nutrients interact with our bodies, we gain insight into the foundation of physiological wellbeing.…”

“…The global dietary supplement markets are growing at almost obscene rates with an increased consumer demand for preventive healthcare and aging populations in developed countries able to afford these products. While for many commercially available supplements meaningful data are, at best, incomplete, examples of promising preventive approaches by nutrient supplementation may potentially be assumed for antioxidants, 17,18 bioactive collagen peptides, 19 and nitrates 20 …”