Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial
Fifty-four young men and women were randomised to 1000 mg vitamin C plus 235 mg vitamin E, or placebo, daily for 11 weeks while completing three to four endurance sessions a week, mostly running. VO2max and 20 m shuttle-run performance improved to the same degree in both groups.
In the vastus lateralis, however, the mitochondrial marker COX4 and cytosolic PGC-1α rose in the placebo group but not in the vitamin group, and mRNA of CDC42 and MAPK1 was lower with the vitamins. The authors conclude that vitamin C and E hampered cellular adaptations in the exercised muscles and advocate caution with antioxidant supplementation during endurance training.
Participants
n=54 young men and women, randomly allocated to vitamin C and E or placebo.
Protocol
Supplement: 1000 mg vitamin C and 235 mg vitamin E daily, or placebo, for 11 weeks (double-blind).
Training: three to four sessions per week, primarily running:
high-intensity intervals 4-6 × 4-6 min at >90% of HRmax
steady continuous sessions of 30-60 min at 70-90% of HRmax
Tests before and after: VO2max, submaximal running, 20 m shuttle run; blood samples and vastus lateralis biopsies.
Key Results
VO2max: +8 ± 5% with vitamins, +8 ± 5% with placebo.
20 m shuttle test: +10 ± 11% with vitamins, +14 ± 17% with placebo — no clear interaction for performance.
COX4 (mitochondrial marker): +59 ± 97% with placebo vs -13 ± 54% with vitamins.
Cytosolic PGC-1α: +19 ± 51% with placebo vs -13 ± 29% with vitamins (P ≤ 0.03 between groups for both markers).
mRNA of CDC42 and MAPK1 in trained muscle was lower with vitamins than placebo (P ≤ 0.05).
Practical Application
"Should I take vitamin C and E while I train?" In an 11-week double-blind RCT of 54 young adults doing endurance training, 1000 mg vitamin C plus 235 mg vitamin E a day stopped the rise in muscle mitochondrial markers (COX4 +59% on placebo vs -13% on vitamins), even though VO2max rose 8% in both groups. The authors advise caution; there is no performance gain from the pills to set against the blunted adaptation.
Not from this paper; the base's own practice: no routine high-dose antioxidant supplements during build phases; vitamins from food are not what was tested here. The recovery-versus-adaptation reasoning is SYNTH-70.
Inference, not tested here: the performance tests (VO2max, shuttle run) did not show harm over 11 weeks; whether blunted mitochondrial markers cost performance over a longer block is not known from this trial.
Limitations
Mixed-sex, young sample; baseline fitness not stated in the abstract.
Cellular markers were blunted but performance was not; the trial was not powered to show small performance differences.
One combined dose of two vitamins; the separate effect of C or E is not tested.
Written from the abstract and record metadata only (full text not read).
How this entry was checked and changed
Why this level
parallel RCT, n=54
Content correction 2026-09-27
2026-10-01: cross-reference repointed from a merged framework to the one that replaced it (SYNTH-01→31, 05→34, 09→70, 12/15→32, 19→26).
2026-10-01: citation of the superseded pointer SYNTH-09 repointed to SYNTH-70, which carries the cited content.