Associations Between Oral Nitrate Reducing Capacity and Aerobic Fitness in Older Individuals with Heart Failure (HFrEF) and Healthy Controls

BACKGROUND: Nitric oxide (NO) is essential for cardiovascular health and is purported as an exercise ergogenic. Vascular endothelial dysfunction and a reduction in endogenous NO production is a hallmark of heart failure. Low NO bioavailability may also contribute to reduced exercise capacity in these populations. Oral inorganic nitrate supplementation has been shown to increase circulating plasma nitrite (NO2-) and consequently bioavailable NO. This occurs via reduction of nitrate by oral commensal bacteria. Patients with heart failure with reduced ejection fraction (HFrEF) display blunted increases in plasma NO2- and do not increase exercise tolerance following nitrate supplementation. Therefore, the purpose of this pilot study was to examine the associations between the bacterial oral nitrate reducing capacity (ONRC) and markers of exercise capacity [VO2peak and VO2 at ventilatory threshold (VT)] in patients with HFrEF versus age-matched healthy controls. HYPOTHESIS: We hypothesized that individuals with HFrEF would have decreased ONRC compared to healthy, age-matched controls, and that exercise capacity (VO2peak and VO2 at VT) would be positively associated with ONRC. METHODS: 6 individuals with HFrEF (Age: 77.50 ± 6.09yrs, VO2peak: 14.24 ± 4.45ml/kg/min) and 9 healthy controls (Age: 71.89 ± 4.23yrs, VO2peak: 24.25 ± 2.86ml/kg/min) completed a symptom-limited incremental VO2peak test on a cycle ergometer. VO2 at VT was determined as the VO2 just prior to the curvilinear increase in ventilation. ONRC was measured using a 5-min oral rinse of 10mL UltraPure Water containing 8.50mg NaNO3. Saliva samples were analyzed via ozone-based chemiluminescence using a Sievers NOA 280i. Comparisons between HFrEF and healthy controls for ONRC were assessed via a Mann Whitney U Test and differences in VO2peak, and VO2 at VT were examined via independent samples t-tests. Associations between ONRC and VO2 were explored through Spearman’s Rank correlations. RESULTS: ONRC was lower in HFrEF (NO2-: 452.3 ± 210.6µM) vs. controls (NO2-: 737.2 ± 302.9µM) (p = 0.035). ONRC for all participants was moderately to strongly correlated with VO2peak (r = 0.668; p = 0.007) and VO2 at VT (r = 0.775; p = 0.002). In individuals with HFrEF, ONRC was strongly correlated with VO2 at VT (r = 0.900; p = 0.037). CONCLUSIONS: This data is the first to suggest that ONRC may be dysfunctional in HFrEF in comparison to age-matched healthy participants. Furthermore, higher aerobic fitness improves ONRC in both healthy older individuals and those with HFrEF. This work was supported by the University of Virginia School of Education and Human Development and the National Institutes of Health (R01 AG075556). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.