Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO 3 −), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22–79 year of age and weighing 52.1–114.9 kg were studied using a randomized, double‐blind, placebo‐controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO 3 −. Plasma NO 3 − and nitrite (NO 2 −) were measured as indicators of NO bioavailability and maximal knee extensor speed (V max), power (P max), and fatigability were determined via isokinetic dynamometry. On average, dietary NO 3 − increased (P < 0.05) P max by 4.4 ± 8.1%. Individual changes, however, ranged from −9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO 3 − dose per kg), body mass index (surrogate for body composition) or placebo trial V max or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO 2 − concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO 3 −‐induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO 2 − and possibly female sex.

BackgroundMultiple randomized controlled trials of remote ischemic preconditioning (RIPC) prior to cardiac surgery have failed to demonstrate clinical benefit. The aim of this updated meta‐analysis was to evaluate the effect of RIPC on outcomes following cardiac surgery.Methods and ResultsSearches of PubMed, Cochrane, EMBASE, and Web of Science databases were performed for 1970 to December 13, 2015. Randomized controlled trials comparing RIPC with a sham procedure prior to cardiac surgery performed with cardiopulmonary bypass were assessed. All‐cause mortality, acute kidney injury (AKI), and myocardial infarction were the primary outcomes of interest. We identified 21 trials that randomized 5262 patients to RIPC or a sham procedure prior to undergoing cardiac surgery. The majority of patients were men (72.6%) and the mean or median age ranged from 42.3 to 76.3 years. Of the 9 trials that evaluated mortality, 188 deaths occurred out of a total of 4210 randomized patients, with 96 deaths occurring in 2098 patients (4.6%) randomized to RIPC and 92 deaths occurring in 2112 patients (4.4%) randomized to a sham control procedure, demonstrating no significant reduction in all‐cause mortality (risk ratio [RR], 0.987; 95% CI, 0.653–1.492, P=0.95). Twelve studies evaluated AKI in 4209 randomized patients. In these studies, AKI was observed in 516 of 2091 patients (24.7%) undergoing RIPC and in 577 of 2118 patients (27.2%) randomized to a sham procedure. RIPC did not result in a significant reduction in AKI (RR, 0.839; 95% CI, 0.703–1.001 [P=0.052]). In 6 studies consisting of 3799 randomized participants, myocardial infarction occurred in 237 of 1891 patients (12.5%) randomized to RIPC and in 282 of 1908 patients (14.8%) randomized to a sham procedure, resulting in no significant reduction in postoperative myocardial infarction (RR, 0.809; 95% CI, 0.615–1.064 [P=0.13]). A subgroup analysis was performed a priori based on previous studies suggesting that propofol may mitigate the protective benefits of RIPC. Three studies randomized patients undergoing cardiac surgery to RIPC or sham procedure in the absence of propofol anesthesia. Most of these patients were men (60.3%) and the mean or median age ranged from 57.0 to 70.6 years. In this propofol‐free subgroup of 434 randomized patients, 71 of 217 patients (32.7%) who underwent RIPC developed AKI compared with 103 of 217 patients (47.5%) treated with a sham procedure. In this cohort, RIPC resulted in a significant reduction in AKI (RR, 0.700; 95% CI, 0.527–0.930 [P=0.014]). In studies of patients who received propofol anesthesia, 445 of 1874 (23.7%) patients randomized to RIPC developed AKI compared with 474 of 1901 (24.9%) who underwent a sham procedure. The RR for AKI was 0.928 (95% CI, 0.781–1.102; P=0.39) for RIPC versus sham. There was no significant interaction between the two subgroups (P=0.098).ConclusionsRIPC does not reduce morbidity or mortality in patients undergoing cardiac surgery with cardiopulmonary bypass. In the subgroup of studies in which propofol was not...

Acute dietary NO intake increases VOpeak and performance in patients with HFrEF. These data, in conjunction with our recent data demonstrating that dietary NO also improves muscle contractile function, suggest that dietary NO supplementation may be a valuable means of enhancing exercise capacity in this population.

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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.