Oxidative Stress Mediates Sleep Irregularity-Induced Vascular Dysfunction in Young Individuals with Generalized Anxiety Disorder

Introduction: Generalized anxiety disorder (GAD) is a disabling condition linked to early cardiovascular disease (CVD). Irregular sleep patterns, common in GAD, are also associated with CVD risk. Our laboratory previously found higher oxidative stress and reduced macrovascular function—precursors to CVD—in young individuals with GAD and high total sleep time irregularity (TSTI). However, whether oxidative stress mediates these vascular impairments is unclear. This study aimed to evaluate the role of oxidative stress in macrovascular dysfunction in this population. We hypothesized that TSTI-induced reductions in macrovascular function would be improved with acute antioxidant (AO) supplementation, highlighting oxidative stress as a key modulator of vascular dysfunction in young individuals with GAD. Methods: Twenty-five young participants (24 ± 4 years) with GAD (21 F, 4 M) were separated into either a “low” or “high” TSTI group via a median split of TST standard deviations derived from 7 nights of sleep assessment evaluated through wrist-worn accelerometry. Macrovascular function was assessed via examination of exercise-induced brachial artery dilation. To assess the potential role of oxidative stress as a modulator of macrovascular function in this population, whole blood superoxide production was determined, and an acute AO (1000 milligrams Vitamin C; 800 IU Vitamin E; 600 milligrams Alpha-Lipoic Acid) supplementation was administered. Results: The “high” TSTI group (TST SD ≥ 67.68 minutes/night) displayed significantly higher whole blood superoxide production (“high” TSTI: 29159 ± 10483; “low” TSTI: 18881 ± 9632; p= 0.02) and significantly lower macrovascular function (“high” TSTI: 2.3 ± 3.5; “low” TSTI: 6.4± 2.7%; p < 0.01) when compared to the “low” TSTI group (TST SD < 67.68 minutes/night). The acute AO supplementation significantly lowered whole blood superoxide production (“high” TSTI: 23629 ± 10622; “low” TSTI: 21694 ± 10567; p = 0.67) and increased macrovascular function (“high” TSTI: 6.8 ± 6.1; “low” TSTI: 8.9 ± 7.2%; p = 0.44) in the “high” TSTI group to which the prior significant group differences were negated. No significant groups differences in participant characteristics (age (p = 0.35), body composition (p = 0.24), resting blood pressure/heart rate (p > 0.51 for all)) or self-reported anxiety/depression symptoms (p > 0.37 for all). Conclusions: Individuals with GAD who experience significant fluctuations in day-to-day TSTI may be at higher risk for the development of CVD, made evident by lower macrovascular function. Lower macrovascular function was revealed to be linked to significant oxidative stress in young individuals with GAD reporting high TSTI, as an acute antioxidant supplementation significantly improved macrovascular function. 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.