Hypoxic Pre-acclimatization Strategies Before Rapid Ascent for Preventing Acute Mountain Sickness: A Systematic Review and Network Meta-analysis

BACKGROUND: Acute mountain sickness (AMS) commonly affects unacclimatized lowlanders traveling above 2500 m. Hypoxic pre-acclimatization may reduce AMS risk, but its effectiveness before rapid ascent and the relative merits of different protocols remain uncertain. Therefore, this study compared hypoxic pre-acclimatization strategies for AMS incidence, AMS severity, and peripheral oxygen saturation after rapid ascent. METHODS: PubMed, Embase, Cochrane Library, SPORTDiscus, and Web of Science were searched from inception to December 2, 2025. The review followed PRISMA-NMA guidance. We included randomized controlled trials enrolling healthy adults without prior high-altitude acclimatization that evaluated hypoxic pre-acclimatization and reported AMS incidence or severity after rapid ascent. Two reviewers independently extracted data. Primary outcomes were AMS incidence and severity; peripheral oxygen saturation was the secondary outcome. Bayesian random-effects network meta-analyses estimated odds ratio (OR), standardized mean difference (SMD), and mean difference (MD) with 95% credible interval (CrI). Interventions were ranked using surface under the cumulative ranking curve (SUCRA) values. RESULTS: Thirteen randomized controlled trials involving 576 participants were included. Point estimates for primary outcomes generally favored hypoxic pre-acclimatization over control. Among statistically significant findings, staging at 4300 m showed the most favorable estimate for AMS incidence (OR, 0.02; 95% CrI, 0.001 to 0.33), and staging at 3500 m showed the most favorable estimate for AMS severity (SMD, -1.22; 95% CrI, -2.40 to -0.04). Several interventions increased post-ascent peripheral oxygen saturation. No consistent significant differences were observed between staging and intermittent hypoxic exposure or among intermittent hypoxic exposure modalities. Certainty of evidence for primary outcomes ranged from very low to moderate. CONCLUSIONS: Hypoxic pre-acclimatization may prevent AMS and reduce its severity after rapid ascent. Staging effects may vary by implementation altitude, and intermittent hypoxic exposure modalities showed generally consistent protective directions. The choice between IHE and staging should be guided by preparation time, individual tolerance, and risk preferences.