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The effect of co-administration of vitamin E and C supplements on plasma oxidative stress biomarkers and antioxidant capacity: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials with meta-regression.

  • 2025-07-16
  • Frontiers in immunology 16
    • Mahdi Moabedi
    • Alireza Milajerdi

Study Design

Type
Meta-Analysis
Sample size
n = 965
Population
17 trials with a total sample size of 965
Methods
Systematic search in online databases; meta-analysis of randomized controlled trials investigating effect of vitamins E and C simultaneously compared with control

Background

There is no conclusion on the effect of vitamins E and C on plasma biomarkers of oxidative stress and antioxidant status. We conducted this meta-analysis to gain a clearer view of this area.

Methods

We performed a systematic search in online databases using the relevant keyword combination. Randomized controlled trials that investigated the effect of vitamins E and C simultaneously, compared with control, on oxidative stress and antioxidant status biomarkers were included in the analyses.

Results

A total of 17 trials were included in the meta-analysis, building a total sample size of 965. The dosage of vitamin E and C supplements varied from 54 to 536 and 250 to 1000 mg/d, respectively, across included studies. We found significant results for MDA [WMD: -0.38, 95% CI: -0.48, -0.28 µg/L, P <0.001], LP [WMD: -1.01, 95% CI: -1.49, -0.54 µg/L, P <0.001], TAC [WMD: 0.09, 95% CI: 0.05, 0.13 mmol/L, P <0.001], and GPx [WMD: 1251.74, 95% CI: 258.92, 2244.56 U/L, P = 0.013], but not for SOD [WMD: 16.69, 95% CI: -29.40, 62.78 U/L, P = 0.278]. Regarding subgroup analysis, only studies on unhealthy participants showed a significant effect on MDA [WMD: -1.62, 95% CI: -2.08, -1.15 µg/L, P <0.001] and TAC [WMD: 0.08, 95% CI: 0.03, 0.14 mmol/L, P <0.001], unlike LP, where significance was only observed in healthy adults [WMD: -0.41, 95% CI: -0.45, -0.37 µg/L, P <0.001]. Moreover, only studies in which a placebo was administered, supplementation of vitamins showed significant effects on MDA [WMD: -0.47, 95% CI: -0.58, -0.35 µg/L, P <0.001], LP [WMD: -1.28, 95% CI: -1.85, -0.72 µg/L, P <0.001], and TAC [WMD: 0.10, 95% CI: 0.05, 0.15 mmol/L, P <0.001].

Conclusion

Our review and analyses revealed that a combination of vitamin C and E has a beneficial effect on oxidative stress biomarkers and antioxidant status.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024590197, identifier CRD42024590197.

Research Insights

  • Vitamin C→Increased Antioxidant Capacity

    TAC [WMD: 0.09, 95% CI: 0.05, 0.13 mmol/L, P <0.001]

    Effect
    Beneficial
    Effect size
    Small
    Dose
    250 to 1000 mg/d
  • Vitamin C→Reduced Lipid Peroxidation

    We found significant results for MDA [WMD: -0.38, 95% CI: -0.48, -0.28 µg/L, P <0.001], LP [WMD: -1.01, 95% CI: -1.49, -0.54 µg/L, P <0.001]

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    250 to 1000 mg/d
  • Vitamin E→Increased Antioxidant Capacity

    TAC [WMD: 0.09, 95% CI: 0.05, 0.13 mmol/L, P <0.001]

    Effect
    Beneficial
    Effect size
    Small
    Dose
    54 to 536 mg/d
  • Vitamin E→Reduced Lipid Peroxidation

    We found significant results for MDA [WMD: -0.38, 95% CI: -0.48, -0.28 µg/L, P <0.001], LP [WMD: -1.01, 95% CI: -1.49, -0.54 µg/L, P <0.001]

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    54 to 536 mg/d
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