Table 1.
Effect of inorganic nitrate and nitrite supplementation on select physiological responses to exercise and exercise tolerance in patients with HFpEF and HFrEF
| HF Phenotype and Study | Duration | Design | Participants/Groups | Dose and Administration Route | Exercise Protocol | Main Exercise Outcomes |
|---|---|---|---|---|---|---|
| Heart failure with preserved ejection fraction (HFpEF) | ||||||
| Eggebeen et al. (43) | Acute | Randomized, double-blind, placebo-controlled, crossover | 18 patients with HFpEF (85% female) 69 ± 7 yr | Oral (beetroot juice, 6.1 mmol nitrate, single dose) | Upright submaximal cycling exercise (∼75% WRmax) | ↔V̇o2peak, ↔tlim, ↔BP |
| Chronic | Randomized, double-blind, placebo-controlled | Oral (beetroot juice, 6.1 mmol nitrate/day for 1 wk) | ↔V̇o2peak, ↑tlim, ↔BP | |||
| Shaltout et al. (44)* | Chronic | Randomized, double-blind, placebo-controlled | Placebo and exercise training: 9 patients with HFpEF (89% female) 71 ± 8 yrBeetroot juice and exercise training: 10 HFpEF patients (80% female) 68 ± 6 yr | Oral (beetroot juice, 6.1 mmol nitrate 3× per wk for 4 wks) | Upright maximal and submaximal cycling exercise (∼75% WRmax) | ↔V̇o2peak, ↔WRmax, ↔tlim, ↔BP |
| Borlaug et al. (45)† | Chronic | Multicenter, randomized, double-blind, placebo-controlled, crossover | 105 patients with HFpEF (56% female) 68 yr | Inhaled (nebulized inorganic nitrite, 46 mg 3× per day for 1 wk + 80 mg 3× per day for 3 wks) | Upright maximal cycling exercise | ↔V̇o2peak, ↔tlim |
| Zamani et al. (46) | Chronic | Randomized, double-blind, placebo-controlled | Placebo: 3 patients with HFpEF (67% female) 63 ± 8 yrPotassium nitrate: 9 patients with HFpEF (67% female) 62 ± 5 yr | Oral (potassium nitrate, 6 mmol 2× per day for 1 wk + 6 mmol 3× per day for 1 wk) | Supine maximal cycling exercise | ↔V̇o2peak, ↑WRmax, ↑tlim, ↔BP |
| Zamani et al. (31) | Acute | Randomized, double-blind, placebo-controlled, crossover | 17 patients of HFpEF (12% female) 65 ± 9 yr | Oral (beetroot juice, 12.9 mmol nitrate, single dose) | Supine maximal cycling exercise | ↑V̇o2peak, ↑WRmax, ↑tlim, ↔BP |
| Heart failure with reduced ejection fraction (HFrEF) | ||||||
| Kerley et al. (47) | Acute | Randomized, double-blind, placebo-controlled, crossover | 10 patients with HFrEF (64% male), 56 ± 11 yr | Oral (beetroot juice 12.9 mmol nitrate, single dose) | Incremental shuttle walk test | ↑distance walked, ↔BP |
| Coggan et al. (48)‡ | Acute | Randomized, double-blind, placebo-controlled, crossover | 9 patients with HFrEF (56% male) 57 ± 10 yr | Oral (beetroot juice, 11.2 mmol nitrate, single dose) | 6-min walk test and single leg isokinetic dynamometry | ↔distance walked,↑maximal knee extensor power & velocity, ↔BP |
| Hirai et al. (49) | Chronic | Randomized, double-blind, placebo-controlled, crossover | 10 patients with HFrEF (100% male) 63 ± 5 yr | Oral (beetroot juice, 12.9 mmol nitrate per day for 9 days) | Upright low- and high-intensity cycling exercise | ↔V̇o2peak, ↔tlim, ↔BP |
| Coggan et al. (50) | Acute | Randomized, double-blind, placebo-controlled, crossover | 8 patients with HFrEF (75% male) 52 ± 5 yr | Oral (beetroot juice, 11.2 mmol nitrate, single dose) | Semirecumbent submaximal and maximal cycling exercise | ↑V̇o2peak, ↑tlim, ↔BP |
| Woessner et al. (51) | Chronic | Randomized, double-blind, placebo-controlled, crossover | 16 patients with HFrEF (93.75% male) 63 ± 4 yr | Oral (beetroot juice, 16 mmol nitrate per day for 5 days) | Treadmill maximal exercise | ↔V̇o2peak, ↔tlim, ↔BP |
BP, blood pressure (i.e., mean arterial pressure and/or systolic blood pressure); tlim, time to exhaustion; V̇o2peak, peak oxygen uptake; WRmax, maximal power output.
*
Protocol includes combined exercise training and nitrate intervention.
†
Protocol utilized nebulized nitrite intervention.
‡
Protocol includes resistance strength outcomes.