Dietary Nitrate (NO3−)‐Induced Increases in Skeletal Muscle Contractile Function: High vs. Low Responders
Authors: Coggan Andrew R. , Mikhalvkova Deana , Mahmood Kiran , Bole Indra , Leibowitz Joshua , Kadkhodayan Ana , Park Soo , Thomas Deepak , Thies Dakkota , Peterson Linda R. 
Published: November 2023

We have recently reported that acute ingestion of dietary NO3−, an important source of nitric oxide (NO) via the enterosalivary pathway, increases the maximal speed and power of skeletal muscle in healthy individuals, in athletes, and in patients with systolic heart failure. This ergogenic effect is hypothesized to be the result of NO‐mediated stimulation of soluble guanyl cyclase and hence production of cyclic GMP. However, consistent with studies of the effects of dietary NO3− on blood pressure or aerobic exercise performance, not all of the subjects we studied previously demonstrated comparable improvements in muscle speed and/or power. In the present investigation we sought to identify factors contributing to this interindividual variability. Eighteen healthy subjects (12 men and 6 women) ranging in age from 22 to 79 (mean 48±20) y were studied used a randomized, double‐blind, placebo‐controlled, crossover design. On one occasion, subjects were tested 2 h after ingesting a concentrated beetroot juice (BRJ) supplement containing 11.2 mmol NO3−. On another, they were tested 2 h after ingesting BRJ depleted of NO3− (placebo). Breath NO was measured periodically as an indicator of NO bioavailability, and muscle contractility was assessed using isokinetic dynamometry. For all subjects combined, dietary NO3− increased (P<0.05) peak knee extensor torque, and hence power, at 6.28 rad/s (~½maximal velocity; Vmax) from 6.38±2.16 to 6.53±2.33 W/kg, or by 2.4%. Individual changes, however, ranged from −21.5 to +26.8%, with 14 of 18 subjects being positive “responders”. This interindividual variability was not significantly correlated with age (i.e., r=−0.19; P=0.45), with in vivo indicators of muscle fiber type distribution, i.e., baseline Vmax (i.e., r=0.10; P=0.68) or fatigability (i.e., r=−0.14; P=0.58), or with the increase in breath NO in either absolute (i.e., r=−0.21; P=0.41) or relative (i.e., r=−0.18; P=0.46) terms. In contrast, significant positive correlations were observed between the magnitude of the dietary nitrate NO3− ‐induced increase in power and female sex (i.e., r=0.53; P=0.02) and dose of NO3−/kg of body mass (i.e., r=0.47; P=0.05). However, the latter correlation appears to have simply been the result of the women being lighter on average, as there was no correlation between the relative improvement in muscle power and dose of NO3−/kg of body mass when the men (i.e., r=0.14; P=0.66) or women (i.e., r=0.26; P=0.62) were analyzed separately. We conclude that the magnitude of the dietary NO3− ‐induced increase in muscle power is independent of age, baseline muscle function, or increase in whole‐body NO bioavailability, but that women generally benefit more than men. The effect of NO3− dose on muscle speed and power, on the other hand, awaits further study.Support or Funding InformationResearch reported in this publication was supported by the Barnes‐Jewish Hospital Foundation, the Washington University Mentors in Medicine and C‐STAR programs, and Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.