Oral nitrate-reducing capacity and aerobic fitness are impaired in older individuals with heart failure with reduced ejection fraction

Macy E. Stahl, Emily E. Grammer, Arthur Weltman, Mia C. Burleigh, Cassandra C. Derella, Antonio Abbate, Martin Denicolai, Jason D. Allen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Nitric oxide (NO) is essential for cardiovascular health and is purported as an ergogenic aid. Endothelial dysfunction and reduced endogenous NO production are hallmarks of heart failure (HF), which may contribute to impaired exercise capacity. Oral inorganic nitrate supplementation offers an exogenous route to increase bioavailable NO via reduction of nitrate by oral commensal bacteria. However, individuals with HF with reduced ejection fraction (HFrEF) display blunted increases in plasma nitrite and inconsistent improvements in exercise tolerance following supplementation. Thus, the purpose of this study was to examine whether bacterial oral nitrate-reducing capacity (ONRC) and markers of exercise capacity are impaired in patients with HFrEF compared with age-matched, healthy controls. Nine individuals with HFrEF [age: 74.89 ± 7.40 yr, peak oxygen consumption (V̇o2peak): 15.17 ± 4.23 mL/kg/min; and 5 females and 4 males] and 9 healthy controls (CON) (age: 71.89 ± 4.23 yr, V̇o2peak: 24.25 ± 2.86 mL/kg/min; and 4 females and 5 males) completed a V̇o2peak test, ONRC assessment, and measures of salivary and plasma N-oxides. ONRC and saliva nitrite were lower in HFrEF (P = 0.010 and P = 0.018, respectively). ONRC for all participants was correlated with V̇o2peak (ρ = 0.68; P = 0.002) and oxygen consumption (V̇o2) at ventilatory threshold (ρ = 0.81; P < 0.001), though this relationship was not significant within groups. These data are first to suggest that ONRC may be impaired in HFrEF compared with age-matched, healthy adults. Future research in a larger sample is needed to determine if ONRC is associated with functional capacity in HFrEF.

NEW & NOTEWORTHY Although the link between cardiovascular disease and oral health has been established, the mechanisms underlying this relationship are not fully understood. These data are the first to suggest that the nitrate-reducing capacity of oral microbiota is lower in individuals with heart failure with reduced ejection fraction compared with healthy individuals, indicating that strategies to positively modulate the oral microbiome may improve the therapeutic potential of oral inorganic nitrate supplementation in heart failure.
Original languageEnglish
Pages (from-to)H952-H958
Number of pages7
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume329
Issue number4
DOIs
Publication statusPublished - 1 Oct 2025

Keywords

  • cardiovascular disease
  • nitrate
  • nitrite
  • oral microbiome

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