Effect of inorganic nitrate on exercise capacity, mitochondria respiration, and vascular function in heart failure with reduced ejection fraction

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Heart failure with reduced ejection fraction (HFrEF) (n=16). Intervention: Inorganic nitrate (beetroot juice) vs. Nitrate-depleted placebo. Primary outcome: VO2peak (p=0.13).

Mary N. Woessner; Christopher Neil; Nicholas J. Saner; Craig A. Goodman; Luke C. McIlvenna; Joaquin Ortiz de Zevallos; Andrew Garnham; Itamar Levinger; Jason D. Allen

doi:10.1152/japplphysiol.00850.2019

April 2, 2020Journal of Applied PhysiologyOpen Access

Effect of inorganic nitrate on exercise capacity, mitochondria respiration, and vascular function in heart failure with reduced ejection fraction

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Key result

Inorganic nitrate supplementation did not significantly improve peak oxygen consumption (VO2peak) compared to placebo in patients with heart failure with reduced ejection fraction (18.5 vs 19.3 ml/kg/min, p=0.13).

Why the study?

The study was conducted to examine the effects of inorganic nitrate supplementation on exercise capacity, vascular function, and mitochondrial respiration in patients with HFrEF.

Does oral inorganic nitrate supplementation improve VO2peak in patients with HFrEF?

Key Points

To evaluate whether inorganic nitrate supplementation enhances exercise capacity, vascular function, and mitochondrial respiration in patients with heart failure with reduced ejection fraction (HFrEF).
Administered daily inorganic nitrate supplementation to patients with heart failure with reduced ejection fraction.
Assessed changes in circulating plasma nitrite concentrations alongside measures of exercise capacity, vascular function, and mitochondrial respiration.
Daily inorganic nitrate supplementation successfully increased circulating plasma nitrite levels.

Study Design

Type

RCT (n=16)

Blinding

Double-blind

Randomization

Randomized

Multicenter

No

Structured PICO

Does oral inorganic nitrate supplementation improve VO2peak in patients with HFrEF?

P

Population

16 patients (mean age 63 years, 6% female) with heart failure with reduced ejection fraction (EF <40%) on stable medications.

I

Intervention

Oral inorganic nitrate supplementation (nitrate-rich beetroot juice, 16 mmol nitrate/day) for at least 5 days (average 7-15 days).

C

Comparator

Nitrate-depleted placebo (<0.1 mmol nitrate/day) matched for duration.

O

Outcome

VO2peak during treadmill exercisesurrogate

Main Result

Absolute Event Rate: 18.5% vs 19.3%

p-value: p=0.13

Inorganic nitrate supplementation as a standalone treatment is ineffective at improving exercise capacity, vascular function, or mitochondrial respiration in patients with HFrEF.

Limitations

Small sample size
Only one female participant included
Potential poor conversion of nitrate to nitrite in HFrEF patients due to oral microbiome differences
Primarily male cohort
Diet not specifically controlled
Plasma nitrate/nitrite only assessed during CPX visit
NIRS and muscle biopsy performed in different tissues

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Answers are grounded in this paper and cite their sources.

Implication

Does not support inorganic nitrate supplementation in HFrEF; challenges smaller prior trials and extends null findings to vascular and mitochondrial outcomes.

Abstract

This is the largest study to date to examine the effects of inorganic nitrate supplementation in patients with heart failure with reduced ejection fraction (HFrEF) and the first to include measures of vascular function and mitochondrial respiration. Although daily supplementation increased plasma nitrite, our data indicate that supplementation with inorganic nitrate as a standalone treatment is ineffective at improving exercise capacity, vascular function, or mitochondrial respiration in patients with HFrEF.

Discussion

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Cite This Study

Woessner et al. (2020) conducted an RCT in Heart failure with reduced ejection fraction (HFrEF) (n=16). Inorganic nitrate (beetroot juice) vs. Nitrate-depleted placebo was evaluated on VO2peak (p=0.13). Inorganic nitrate supplementation did not significantly improve peak oxygen consumption (VO2peak) compared to placebo in patients with heart failure with reduced ejection fraction (18.5 vs 19.3 ml/kg/min, p=0.13).

synapsesocial.com/papers/6a86c606a131ca67071545c5 https://doi.org/10.1152/japplphysiol.00850.2019

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Effect of inorganic nitrate on exercise capacity, mitochondria respiration, and vascular function in heart failure with reduced ejection fraction

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Effect of inorganic nitrate on exercise capacity, mitochondria respiration, and vascular function in heart failure with reduced ejection fraction

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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