Paulsen · The Journal of physiology 2014 · double-blind randomized controlled trial · n=54

Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial.

Cited 324 times in the scientific literature.

Level 2 - randomized trial

Double-blind randomized controlled trial in humans

PubMed 24492839 · doi:10.1113/jphysiol.2013.267419 · record verified 2026-08-26

What was done

Fifty-four young men and women were randomly allocated in a double-blind design to receive daily supplementation of either vitamins C (1000 mg) and E (235 mg) or a placebo for 11 weeks. Participants engaged in an endurance training program (3–4 sessions per week of running, consisting of high-intensity intervals at >90% HRmax and steady-state sessions at 70–90% HRmax). Maximal oxygen uptake (VO2 max), submaximal running, and a 20 m shuttle run test were evaluated, alongside blood samples and vastus lateralis muscle biopsies before and after the training period.

What was found

Both groups achieved similar gains in VO2 max (8 ± 5% in the antioxidant group vs. 8 ± 5% in placebo) and 20 m shuttle run performance (10 ± 11% vs. 14 ± 17%). However, vastus lateralis mitochondrial marker cytochrome c oxidase subunit IV (COX4) increased by 59 ± 97% in the placebo group but fell by -13 ± 54% in the antioxidant group (P ≤ 0.03 between groups). Cytosolic PGC-1α increased by 19 ± 51% in placebo versus -13 ± 29% with antioxidants (P ≤ 0.03). Messenger RNA levels of CDC42 and MAPK1 were also significantly lower in the trained muscle of the vitamin C and E group compared to placebo (P ≤ 0.05).

Why it matters

High-dose antioxidant supplementation can actively blunt exercise-induced signaling pathways essential for mitochondrial biogenesis in skeletal muscle, suggesting caution when using antioxidants during endurance training.

Limits

The study was limited to a small sample (n = 54) of young healthy individuals over an 11-week period, which may not capture longer-term performance consequences. Inter-individual variance in molecular markers was wide, and dietary antioxidant intake outside the intervention was not reported in the abstract.

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