Effectiveness of intermittent hypoxia on muscle recovery in rats: A systematic review

The objective of this review was to synthesize evidence from animal models on the effects of intermittent hypobaric hypoxia (IHH), cold exposure, and their combinations, with or without exercise, on skeletal muscle recovery after fatigue or injury. The review systematically examined controlled animal studies evaluating hypoxia- or cold-based interventions for muscle recovery. The data sources PubMed, SPORTDiscus, Web of Science, and Scopus were searched up to July 2025 following PRISMA guidelines (PROSPERO CRD420251013029). Studies deemed eligible for inclusion were interventional animal studies assessing IHH, cold exposure, or combined protocols and reporting functional, physiological, or mechanistic outcomes. Risk of bias was evaluated using RoB 2. Five studies met inclusion criteria. IHH protocols simulated ~4000-4500 m for several hours per day, while cold exposure used ~4°C; some studies added low-intensity treadmill exercise. IHH alone enhanced muscle regeneration, reduced fibrosis, and improved contractile force compared with passive recovery. Combined with aerobic exercise, IHH maintained oxidative capacity and increased PGC-1α and VEGF expression, supporting angiogenesis. Cold exposure elevated mitochondrial complex expression but increased oxidative stress, whereas IHH improved redox balance. IHH plus light exercise also raised circulating CD34⁺ and endothelial progenitor cells, suggesting improved repair capacity. Overall risk of bias was rated as "some concerns," mainly due to limited reporting of randomization. Our conclusion is that IHH shows potential to enhance muscle regeneration and redox balance in animal models. Its application in athletic recovery is promising, but standardized protocols and human trials are required before translation.