Acute Mountain Sickness (AMS) is a frequent condition triggered by exposure to hypobaric hypoxia at high altitude. Its pathophysiology involves endothelial dysfunction and oxidative stress, with elevated oxidative molecules identified as key contributors to its development. Antioxidant therapies such as vitamins C/E, α-lipoic acid, and Ginkgo biloba have been proposed, though results across studies remain inconsistent. Objective This study aims to evaluate the effects of antioxidant treatments in subjects with AMS induced by high-altitude exposure, examining their impact on clinical outcomes and oxidative stress markers. Methods A systematic review and meta-analysis were performed according to PRISMA2020 guidelines. Searches were conducted in PubMed, Scopus, and Web of Science through November 2025, supplemented by snowball methods, focusing on studies investigating antioxidant treatments in humans exposed to hypobaric or high-altitude hypoxia. Inclusion criteria were original research in English with full-text availability, human exposure to hypobaric hypoxia, AMS assessment using the Lake Louise Score (LLS), and explicit antioxidant interventions compared with placebo or control. A random-effects meta-analysis using the REML estimator was applied to calculate relative risk (RR), including continuity corrections for zero-event studies. Data extraction was performed in duplicate, and risk of bias was evaluated using the Cochrane tool. Results The search yielded 727 records; nineteen studies were included in the qualitative synthesis, and four trials provided comparable dichotomous data for quantitative analysis. Pooled estimates showed a non-significant trend toward reduced AMS incidence with antioxidant treatment (RR ≈ 0.73; 95% CI: 0.47–1.11; p = 0.14). Moderate heterogeneity was detected (I 2 = 52%, Q p = 0.048). Although not statistically significant, all studies showed a direction of effect favoring antioxidants. Nevertheless, interpretation is limited using pre-2018 LLS diagnostic criteria, absence of studies under chronic intermittent hypobaric hypoxia, and methodological variability. Conclusion Current evidence does not demonstrate a statistically significant protective effect of antioxidant therapy against AMS; however, findings remain inconclusive due to few available trials, small sample sizes, pharmacokinetics and pharmacodynamics analysis, and methodological heterogeneity. Larger, well-designed trials with standardized ascent profiles and redox biomarkers are required to determine clinical efficacy. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261331390 , identifier CRD420261331390.
Pena et al. (Mon,) studied this question.