Deepak P. Thomas

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure A Double-Blind, Placebo-Controlled, Randomized Trial

Background—Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3−) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction. Methods and Results—Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3− in 9 patients with heart failure. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol of NO3−. Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3− increased (P<0.05–0.001) breath NO by 35% to 50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the 2 highest movement velocities tested (ie, 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (ie, 4.74±0.41 versus 4.20±0.33 W/kg; P<0.05) after dietary NO3− intake. Calculated maximal velocity of knee extension was also higher after NO3− ingestion (ie, 12.48±0.95 versus 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. Conclusions—In this pilot study, acute dietary NO3− intake was well tolerated and enhanced NO bioavailability and muscle power in patients with systolic heart failure. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart FailureCLINICAL PERSPECTIVE

Background—Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3−) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction. Methods and Results—Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3− in 9 patients with heart failure. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol of NO3−. Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3− increased (P<0.05–0.001) breath NO by 35% to 50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the 2 highest movement velocities tested (ie, 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (ie, 4.74±0.41 versus 4.20±0.33 W/kg; P<0.05) after dietary NO3− intake. Calculated maximal velocity of knee extension was also higher after NO3− ingestion (ie, 12.48±0.95 versus 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. Conclusions—In this pilot study, acute dietary NO3− intake was well tolerated and enhanced NO bioavailability and muscle power in patients with systolic heart failure. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.

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.

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.

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart FailureCLINICAL PERSPECTIVE: A Double-Blind, Placebo-Controlled, Randomized Trial

Background—Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3−) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction. Methods and Results—Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3− in 9 patients with heart failure. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol of NO3−. Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3− increased (P<0.05–0.001) breath NO by 35% to 50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the 2 highest movement velocities tested (ie, 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (ie, 4.74±0.41 versus 4.20±0.33 W/kg; P<0.05) after dietary NO3− intake. Calculated maximal velocity of knee extension was also higher after NO3− ingestion (ie, 12.48±0.95 versus 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. Conclusions—In this pilot study, acute dietary NO3− intake was well tolerated and enhanced NO bioavailability and muscle power in patients with systolic heart failure. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.