Dietary nitrate-induced increases in human muscle power: High versus low responders

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 (NO3- ), 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 NO3- . Plasma NO3- and nitrite (NO2- ) were measured as indicators of NO bioavailability and maximal knee extensor speed (Vmax ), power (Pmax ), and fatigability were determined via isokinetic dynamometry. On average, dietary NO3- increased (P < 0.05) Pmax 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 NO3- dose per kg), body mass index (surrogate for body composition) or placebo trial Vmax 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 NO2- 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 NO3- -induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO2- and possibly female sex

Dietary Nitrate Increases VO2peak and Performance but Does Not Alter Ventilation or Efficiency in Patients With Heart Failure With Reduced Ejection Fraction

Background Patients with heart failure with reduced ejection fraction (HFrEF) exhibit lower efficiency, dyspnea, and diminished peak oxygen uptake (VO2peak) during exercise. Dietary nitrate (NO3−), a source of nitric oxide (NO), has improved these measures in some studies of other populations. We determined the effects of acute NO3− ingestion on exercise responses in 8 patients with HFrEF using a randomized, double-blind, placebo-controlled, crossover design. Methods and Results Plasma NO3−, nitrite (NO2−), and breath NO were measured at multiple time points and respiratory gas exchange was determined during exercise after ingestion of beetroot juice containing or devoid of 11.2 mmol of NO3−. NO3− intake increased (P < .05–0.001) plasma NO3− and NO2− and breath NO by 1469 ± 245%, 105 ± 34%, and 60 ± 18%, respectively. Efficiency and ventilation during exercise were unchanged. However, NO3− ingestion increased (P < .05) VO2peak by 8 ± 2% (ie, from 21.4 ± 2.1 to 23.0 ± 2.3 mL.min−1.kg−1). Time to fatigue improved (P < .05) by 7 ± 3 % (ie, from 582 ± 84 to 612 ± 81 seconds). Conclusions Acute dietary NO3− intake increases VO2peak and performance in patients with HFrEF. These data, in conjunction with our recent data demonstrating that dietary NO3− also improves muscle contractile function, suggest that dietary NO3− supplementation may be a valuable means of enhancing exercise capacity in this population

Sex Affects Myocardial Blood Flow and Fatty Acid Substrate Metabolism in Humans with Nonischemic Heart Failure

In animal models of heart failure (HF), myocardial metabolism shifts from the normal preference for high-energy fatty acid (FA) metabolism towards the more efficient fuel, glucose. However, FA (vs. glucose) metabolism generates more ATP/mole; thus FA metabolism may be especially advantageous in HF. Sex modulates myocardial blood flow (MBF) and substrate metabolism in normal humans. Whether sex affects MBF and metabolism in patients with HF is unknown. We studied 19 well-matched men and women with nonischemic HF with similar ejection fractions (all ≤ 35%). MBF and myocardial substrate metabolism were quantified using positron emission tomography. Women had higher MBF (mL/g/min), FA uptake (mL/g/min), utilization (nmol/g/min) (P<0.005, <0.005, <0.05, respectively) and trended towards higher FA oxidation than men (P=0.09). These findings were independent of age, obesity, and insulin resistance. There were no sex-related differences in fasting myocardial glucose uptake or metabolism. In an exploratory analysis of the longitudinal follow-up of these subjects (mean 7 y), we found that 4 men had a major cardiovascular event, while one woman died of non-cardiac causes. Higher MBF related to improved event-free survival (HR=0.31, P=0.02). In sum, in nonischemic HF, women have higher MBF and FA uptake and metabolism than men, and these changes are not due to differences in other variables that can affect myocardial metabolism (e.g., age, obesity, or insulin resistance). Moreover, higher MBF portends a better prognosis. These sex-related differences should be taken into account in the development and targeting of novel agents aimed at modulating in MBF and metabolism in HF

A Paradox between LV Mass Regression and Hemodynamic Improvement after Surgical and Transcatheter Aortic Valve Replacement

<p><b>Background:</b> Surgical aortic valve replacement (SAVR) results in higher AV gradients than transcatheter AVR (TAVR), yet calculated left ventricular (LV) mass regresses faster and greater after SAVR vs. TAVR. We examined why LV mass regression is greater after SAVR.</p> <p><b>Methods:</b> Serial echocardiographic studies of high-risk patients with severe aortic stenosis (AS) randomized to SAVR vs. TAVR with the CoreValve bioprosthesis were analyzed by an echocardiographic core laboratory blinded to treatment and outcomes. Measurements followed established guidelines and LV mass was calculated using the formula of Devereux and colleagues.</p> <p><b>Results:</b> Echo data were available in 389 TAVR and 353 SAVR patients, whose baseline LVEDD, PWT, SWT, LV mass, and stroke volume (SV) as well as AS severity were similar. At discharge after SAVR, LV mass reduction was significant (227.45 ± 65.02 to 215.08 ± 59.02 g [<i>p</i> = 0.002]) due to decreased LVEDD (5.01 ± 0.64 to 4.81 ± 0.65 cm [<i>p</i> < 0.001]) associated with reduced SV (72.6 ± 27.0 mL to 58.9 ± 21.1 mL (<i>p</i> = 0.015]). PWT and SWT were unchanged. However, after TAVR, all these variables remained similar. At 1 year, LV mass, SV and LVEDD remained smaller following SAVR vs. TAVR. There was a trend toward higher 30-day mortality in patients with greater LV mass reduction in SAVR (4.7% vs. 0.8 %; <i>p</i> = 0.058) which was not observed after TAVR.</p> <p><b>Conclusion:</b> The greater reduction in LV mass calculated after SAVR vs. TAVR is due to a smaller postoperative LVEDD and is associated with significantly reduced SV. There was a tendency for increased 30-day mortality associated with greater reduction in calculated LV mass after SAVR.</p