Dietary nitrate supplementation and exercise tolerance in patients with heart failure with reduced ejection fraction.
What this study found
Plasma nitrite concentration increased with nitrate-rich supplementation to about 240 ± 48 nM vs 56 ± 8 nM with placebo (P ≤ 0.05). Time to exercise intolerance did not differ significantly (placebo 495 ± 53 s vs nitrate 489 ± 58 s; P > 0.05). No significant differences were observed in arterial blood pressure, central hemodynamics (stroke volume, heart rate, cardiac output), pulmonary O2 uptake kinetics, skeletal muscle oxygenation, or blood lactate during rest-to-low- and rest-to-high-intensity transitions. Dietary nitrate via beetroot juice did not improve cardiorespiratory function or…
- Study & population
- Double-blind, randomized crossover design.
- Intervention
- Beetroot juice regimen: two 70-ml bottles daily for 9 consecutive days; nitrate-rich juice contained approximately 6.45 mmol nitrate per bottle; morning bottle consumed ~2 hours before testing and the afternoon bottle later in the day; placebo beverage was nitrate-depleted beetroot juice; bottles identical in…
- Key limitation
- Small, all-male sample (n=10) at a single center; short duration per arm (9 days); crossover design with potential carryover despite washout; limited generalizability to women or more severe disease; results may not apply to HF with preserved ejection fraction or non-ischemic etiologies.
Original abstract
Endothelial dysfunction and reduced nitric oxide (NO) signaling are key abnormalities leading to skeletal muscle oxygen delivery-utilization mismatch and poor physical capacity in patients with heart failure with reduced ejection fraction (HFrEF). Oral inorganic nitrate supplementation provides an exogenous source of NO that may enhance locomotor muscle function and oxygenation with consequent improvement in exercise tolerance in HFrEF. Thirteen patients (left ventricular ejection fraction ≤40%) were enrolled in a double-blind, randomized crossover study to receive concentrated nitrate-rich (nitrate) or nitrate-depleted (placebo) beetroot juice for 9 days. Low- and high-intensity constant-load cardiopulmonary exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary oxygen uptake, quadriceps muscle oxygenation (near-infrared spectroscopy), and blood lactate concentration. Ten patients completed the study with no adverse clinical effects. Nitrate-rich supplementation resulted in significantly higher plasma nitrite concentration compared with placebo (240 ± 48 vs. 56 ± 8 nM, respectively; P < 0.05). There was no significant difference in the primary outcome of time to exercise intolerance between nitrate and placebo (495 ± 53 vs. 489 ± 58 s, respectively; P > 0.05). Similarly, there were no significant differences in central hemodynamics, arterial blood pressure, pulmonary oxygen uptake kinetics, skeletal muscle oxygenation, or blood lactate concentration from rest to low- or high-intensity exercise between conditions. Oral inorganic nitrate supplementation with concentrated beetroot juice did not present with beneficial effects on central or peripheral components of the oxygen transport pathway thereby failing to improve exercise tolerance in patients with moderate HFrEF.