Resynchronisation of the Biological Clock Using Exposure to Low Oxygen Levels in Humans: An Exploratory Study

Exposure to reduced oxygen levels occurs in several real-world contexts, such as during air travel or altitude exposure, and emerging evidence suggests that hypoxia may interact with molecular pathways involved in circadian regulation. This exploratory study investigated the effects of normobaric hypoxia on circadian phase shifting in humans, compared to luminotherapy combined with exogenous melatonin. Using a randomised crossover design, 11 healthy adults (6 men, 5 women; mean age 23.3 ± 1.9 years) completed one baseline and two 48-h experimental conditions. The baseline established individual circadian markers. Both experimental conditions simulated a 4-h phase advance. In the hypoxia condition, participants were exposed to reduced oxygen levels (inspired oxygen fraction of 12%) for 2 h, beginning 2 h after habitual wake time. In the luminotherapy and melatonin condition, participants received three-hour morning light therapy (500 nm, 506 lx) at the same time point, combined with 5 mg melatonin administered 6 h before bedtime. Salivary melatonin was collected across conditions to determine dim-light melatonin onset (DLMO). Both conditions produced earlier melatonin onset compared to baseline. The luminotherapy and melatonin condition resulted in a significant phase advance of approximately 78 min. The hypoxia condition produced an average phase advance of approximately 35 min, which was not statistically significant. The present findings do not allow us to determine whether hypoxia can induce circadian phase shifts, while light and melatonin remain an effective intervention. Further research is needed to clarify mechanisms and evaluate hypoxia as a tool for circadian modulation.