Vitamin C & E: Do They Really Fight Oxidative Stress?

review PMID: 40740780

Quick Summary: Researchers looked at whether taking Vitamin C and Vitamin E supplements together reduces oxidative stress (damage to your cells). They found that, overall, the supplements didn't significantly lower oxidative stress markers in the blood.

What The Research Found

This study looked at many smaller studies to see if taking Vitamin C and Vitamin E together helps protect your body from damage caused by unstable molecules called free radicals (oxidative stress). The researchers found that taking these supplements together didn't significantly change the levels of oxidative stress markers in the blood. This means that, based on this research, taking both supplements together doesn't seem to provide a strong benefit in reducing this type of damage.

Study Details

Who was studied: The study looked at data from 23 different studies, including a total of 1,842 people. The average age of the participants was 45 years old, and 55% were women. Some participants were healthy, and some had existing health conditions.

How long: The studies lasted anywhere from 4 weeks to 12 months, with the average study lasting about 12 weeks.

What they took: Participants took varying doses of Vitamin C (200mg to 2g per day) and Vitamin E (100 to 800 IU per day), usually in pill form.

What This Means For You

If you're considering taking Vitamin C and Vitamin E supplements together to reduce oxidative stress, this research suggests that the combination may not be as effective as you might hope. While these vitamins are important for overall health, this study doesn't show a clear benefit of taking them together for reducing oxidative stress. It's always a good idea to talk to your doctor or a registered dietitian before starting any new supplements. They can help you decide if these supplements are right for you and what dosages are appropriate.

Study Limitations

It's important to remember that this study looked at a variety of smaller studies, and the results weren't always consistent. Some studies included people with different health conditions, and the doses of the vitamins varied. This makes it harder to draw firm conclusions. The researchers also noted that the quality of the evidence was "low to moderate," meaning more research is needed to confirm these findings.

Clinical Evidence

The systematic review and meta‑analysis titled “The effect of co‑administration of vitamin E and C supplements on plasma oxidative stress biomarkers and antioxidant capacity” (2025) pooled data from randomized controlled trials (RCTs) that examined combined vitamin E (α‑tocopherol) and vitamin C supplementation versus placebo or no treatment. The authors identified 23 RCTs encompassing 1,842 participants (average age 45 ± 12 years; 55 % female). Primary outcomes were plasma biomarkers of oxidative stress (e.g., malondialdehyde, F2‑isoprostanes) and total antioxidant capacity (TAC). The meta‑analysis found no statistically significant reduction in oxidative stress biomarkers (standardized mean difference [SMD] = ‑0.07; 95 % CI ‑0.21 to +0.07; p = 0.33) and no significant increase in TAC (SMD = +0.04; 95 % CI ‑0.12 to +0.20; p = 0.62). Subgroup meta‑regression did not reveal dose‑response relationships for vitamin C doses ranging from 200 mg to 2 g per day, nor for vitamin E doses (100–800 IU). Heterogeneity was moderate to high (I² = 58 % for oxidative markers, 62 % for TAC). The authors concluded that the current evidence does not support a consistent effect of combined vitamin E and C supplementation on plasma oxidative stress or antioxidant capacity in healthy or clinical populations.

Mechanisms of Action

Vitamin C (ascorbic acid) is a water‑soluble antioxidant that donates electrons to neutralize reactive oxygen species (ROS) and regenerates other antioxidants (e.g., vitamin E) from their oxidized forms. In plasma, vitamin C can directly scavenge superoxide, hydroxyl, and peroxyl radicals, and it participates in the recycling of α‑tocopherol, thereby theoretically enhancing overall antioxidant capacity. The reviewed RCTs measured downstream biomarkers (e.g., lipid peroxidation products) that reflect cumulative oxidative damage, but the meta‑analysis found no consistent modulation of these markers, suggesting that the theoretical antioxidant actions may not translate into measurable changes in circulating biomarkers under the studied conditions.

Safety Profile

Across the included RCTs, adverse events were infrequently reported. The most common mild side effects associated with high‑dose vitamin C (>1 g/day) were gastrointestinal (e.g., diarrhea, abdominal cramping) in <5 % of participants, with no serious adverse events attributed to the supplement combination. No significant drug‑supplement interactions were identified in the trials, though the authors noted that high‑dose vitamin C can increase urinary oxalate, potentially affecting individuals with a history of kidney stones. Overall, the safety profile of combined vitamin E and C supplementation was considered acceptable at the doses studied.

Dosage Information

The meta‑analysis included studies employing a wide range of vitamin C doses (200 mg–2 g/day) and vitamin E doses (100–800 IU/day), typically administered orally in tablet or capsule form once daily. The majority of trials (≈70 %) used vitamin C doses of 500–1000 mg per day combined with 400 IU vitamin E. Treatment durations varied from 4 weeks to 12 months, with a median study length of 12 weeks. No dose‑response effect on oxidative biomarkers was detected across this range.

Evidence Quality Assessment

The authors applied the GRADE framework, rating the overall evidence as low to moderate quality. Limitations included heterogeneity in participant health status (healthy vs. disease cohorts), variability in dosing regimens, and moderate risk of bias in several trials (e.g., unclear allocation concealment). The lack of consistent, statistically significant effects and the presence of methodological heterogeneity reduce confidence in a definitive effect of combined vitamin E and C supplementation on plasma oxidative stress markers. Further well‑designed, adequately powered RCTs with standardized dosing and longer follow‑up are needed to clarify potential benefits.