Systematic review and meta-analysis of antioxidant treatment in patients with acute mountain sickness induced by high altitude exposure

source extracted confidence: high 2026-04-09

Systematic review and meta-analysis of antioxidant treatment in patients with acute mountain sickness induced by high altitude exposure

Pena et al., 2026 | Front Physiol | Systematic Review

Citation

Pena Eduardo, Del Río Alexandra, Flores Sergio. Systematic review and meta-analysis of antioxidant treatment in patients with acute mountain sickness induced by high altitude exposure. Front Physiol. 2026;17:1779008. doi:10.3389/fphys.2026.1779008

Abstract

UNLABELLED: 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 (I2 = 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.

Key Findings

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 (I2 = 52%, Q p = 0.048). Although not statistically significant, all studies showed a direction of effect favoring antioxidants. Nevertheless, in

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population ams induced by high
Sample Size See abstract
Age Range See abstract
Condition stress

MeSH Terms

  • No MeSH terms indexed

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review
  • Vertical: ginkgo

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09