Nitrate supplementation alters the oxygen re-saturation response following hypoxia in patients with obstructive sleep apnea

Jack Shelley; Joshua Bock; Darren Casey

doi:10.1152/physiol.2025.40.S1.2003

Abstract only Obstructive sleep apnea (OSA), a sleep disorder that is associated with exposure to repeated bouts of hypoxia overnight. Evidence suggests that the oxyhemoglobin dissociation curve (ODC) may be shifted rightward with OSA. Nitric oxide (NO) functions as an allosteric regulator of hemoglobin oxygen-binding properties, possibly shifting the ODC curve leftward. Nitrate/nitrite supplementation increases NO bioavailability and attenuates the physiological responses to hypoxia which may be due to changes in the ODC. Therefore, we explored the hypothesis that dietary nitrate supplementation improves oxygen re-saturation following inspiratory hypoxia in subjects with OSA. Fourteen subjects with untreated mild-moderate OSA (53 ± 10yr, 8M/6F; Apnea-hypopnea Index, 17.8 ± 8.1 events) completed two separate study visits. Each visit consisted of two hypoxic bouts separated by ~2 hours and the consumption of one of two beetroot juice beverages (Placebo [BR P ] containing 5-10 mg nitrate, no detectable nitrite, or Active [BR A ] containing 500mg nitrate and 40mg nitrite). For each hypoxia bout, subjects’ pulse oxygen saturation (%SpO 2 ) was titrated to ≤80% over 3-5min by blending a 10% FiO2 gas cylinder with room air. Once ≤80% SpO 2 was achieved, subjects inhaled normoxic room air (~21% FiO2) and oxygen saturation was monitored until SpO 2 returned to baseline (recovery). During recovery, SpO 2 was averaged into 5 sec bins from the end of hypoxia (nadir) up to +15 SpO 2 % above nadir. The ‘hypoxic load’ during recovery was calculated as ( i =1 ∑ n ∣Value i −nadir+15∣) and reflects a total sum of each 5 sec bin ( n ). BR A increased plasma nitrite (248 ± 155 to 738 ± 427nM, P < 0.05), whereas there was no change following BR P (266 ± 153 to 277 ± 164nM, P = 0.87). The level of desaturation (SpO 2 nadir) at the end of hypoxia did not differ within or between trials (BR A : Pre 78 ± 2 vs. 78 ± 3; BR P : Pre 78 ± 2 vs. 78 ± 2, condition x time interaction P = 0.21). Hypoxia load increased following BR P (162.7 ± 36.6 vs. 231.8 ± 65.7, P < 0.001), but was unchanged following BR A (174.3 ± 54.2 vs. 191.2 ± 52, P = 0.32). In summary, our study suggests that acute nitrate supplementation may cause a leftward shift in the ODC in patients with untreated OSA. This is supported by a reduced hypoxic load following a repeat bout of inspiratory hypoxia. These findings may have implications for the health of patients with OSA. Foundation for the National Institutes of Health, K12 AR084222 (Joshua Bock) 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.

Nitrate supplementation alters the oxygen re-saturation response following hypoxia in patients with obstructive sleep apnea

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