The Effects of Ginseng Supplementation on Oxidative Stress Markers (MDA and SOD): A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Context: Oxidative stress, resulting from an imbalance between reactive oxygen species and antioxidant defenses, is a key driver of chronic diseases such as cardiovascular disorders, diabetes, and neurodegenerative conditions. Objectives: This systematic review and meta-analysis aimed to evaluate the dose-dependent effects of ginseng supplementation on superoxide dismutase (SOD) and malondialdehyde (MDA) levels in randomized controlled trials (RCTs), and to explore sources of heterogeneity to guide clinical applications Methods: According to PRISMA guidelines, we searched PubMed/MEDLINE, Scopus, Google Scholar, and trial registries up to July 2025 for RCTs assessing ginseng’s effects on MDA and/or SOD. Nine studies (366 participants) were included after eligibility screening. Data were pooled using a random-effects model and standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity was assessed via Cochran’s Q and I² statistics, and subgroup analyses explored dose effects based on estimated ginsenoside content (approximately 0.5 - 6 mg), derived from reported extract doses. Results: Ginseng supplementation was associated with a statistically significant increase in SOD activity (SMD = 0.220, 95% CI: 0.095-0.344, P = 0.001) and showed a borderline reduction in MDA levels (SMD = -0.291, 95% CI: -0.585-0.004, P = 0.053). Subgroup analysis indicated the strongest SOD effect in studies corresponding to an estimated ginsenoside exposure of approximately 3 mg (SMD = 0.336, P = 0.005), with variable MDA effects. High heterogeneity (I² = 96.7% for MDA, 60.5% for SOD) was associated with differences in ginseng formulations, study durations, and participant demographics. Conclusions: Ginseng supplementation is thought to increase SOD activity and may reduce MDA levels, particularly at a 3 mg dose, suggesting a possible antioxidant role, which should be interpreted with caution given the observed heterogeneity.