StLouis, Erik

Abstract Introduction Poor sleep quality is bidirectionally associated with cardiovascular and neurocognitive disorders. Preclinical data implicate nitric oxide (NO) in the onset, and maintenance, of sleep. Acute inorganic nitrate supplementation increases NO bioavailability via serial reduction for >12hrs. We tested if objective (Aim 1) or subjective (Aim 2) sleep quality was better following acute, pre-sleep nitrate supplementation relative to a placebo. Methods Seven non-shift working adults (4F/3M, 40±8yrs, 25.8±1.6kg/m2) with no history of sleep, cardiovascular, or neurocognitive disorders completed three overnight polysomnography (PSG) visits with time in bed standardized to 2200-0600hrs. Visit 1 was for acclimation and screening for sleep-disordered breathing. On Visits 2 and 3, participants consumed beetroot juice containing (6.45mmol) or devoid of (0mmol) inorganic nitrate at 2200 using a randomized, cross-over study design. PSG-derived outcomes included slow-wave (SWS) and rapid eye-movement (REM) sleep, sleep efficiency, and wake after sleep onset (WASO). Subjective sleep quality assessments were administered in-laboratory including a 0-10 scale, the Stanford Sleepiness Scale (SSS), and performance with mental arithmetic shortly after awakening. Results No participant demonstrated evidence for sleep-disordered breathing (apnea-hypopnea index = 1.7±0.9events/hr). Total sleep time (TST, 434±17 vs. 412±19min), sleep efficiency (89±3 vs. 85±4%), as well as SWS duration (75±10 vs. 66±9min) and percent of TST (17±2 vs. 16±2%) were higher after nitrate relative to the placebo (p< 0.05 for all). WASO (47±16 vs. 62±19min, p< 0.05) was lower after nitrate versus placebo and no differences were seen in REM sleep duration (131±23 vs. 117±12min, p=0.45) nor percent of TST (30±5 vs. 29±3%, p=0.80). Neither the 0-10 scale (6.7±0.5 vs. 6.8±0.6units, p=0.84), SSS (2.6±0.4 vs. 2.5±0.3units, p=0.68), or arithmetic performance (82±3 vs. 81±5% correct, p=0.85) differed post-nitrate compared to post-placebo. Conclusion These data suggest that acutely increasing nocturnal NO levels via pre-sleep inorganic nitrate supplementation improves objective indices of sleep quality in healthy adults. However, greater amounts of nitrate or prolonged supplementation (weeks) may be needed to improve perceived sleep quality. Support (if any) The National Institutes of Health (K12 AR084222 to JMB, R01s HL160619 and HL65176 to VKS), Sleep Research Society Foundation (CDA 038-JP-23 to JMB), and the American Heart Association (24POST1241616 to IMG).