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

Key points Recent studies have indicated that antioxidant supplementation may blunt adaptations to exercise, such as mitochondrial biogenesis induced by endurance training. However, studies in humans are sparse and results are conflicting. Isolated vitamin C and E supplements are widely used, and unravelling the interference of these vitamins in cellular and physiological adaptations to exercise is of interest to those who exercise for health purposes and to athletes. Our results show that vitamin C and E supplements blunted the endurance training-induced increase of mitochondrial proteins (COX4), which is important for improving muscular endurance. Training-induced increases in V O2 max and running performance were not detectably affected by the supplementation. The present study contributes to understanding of how antioxidants may interfere with adaptations to exercise in humans, and the results indicate that high dosages of vitamins C and E should be used with caution. In this double-blind, randomised, controlled trial, we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000mg of vitamin C and 235mg of vitamin E or a placebo daily for 11weeks. During supplementation, the participants completed an endurance training programme consisting of three to four sessions per week (primarily of running), divided into high-intensity interval sessions [4-6x4-6min; >90% of maximal heart rate (HRmax)] and steady state continuous sessions (30-60min; 70-90% of HRmax). Maximal oxygen uptake (V O2 max ), submaximal running and a 20m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. Participants in the vitamin C and E group increased their V O2 max (mean +/- s.d.: 8 +/- 5%) and performance in the 20m shuttle test (10 +/- 11%) to the same degree as those in the placebo group (mean +/- s.d.: 8 +/- 5% and 14 +/- 17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4) and cytosolic peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha) increased in the m. vastus lateralis in the placebo group by 59 +/- 97% and 19 +/- 51%, respectively, but not in the vitamin C and E group (COX4: -13 +/- 54%; PGC-1 alpha: -13 +/- 29%; P <= 0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group than in the placebo group (P <= 0.05). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in V O2 max and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to the performance tests applied in this study, we advocate caution when considering antioxidant supplementation combined with endurance exercise.