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Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation

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It has been suggested that part of the failure of antioxidant supplementation to reduce oxidative stress and promote health is that it has been administered in humans with normal levels of antioxidants.


To test this hypothesis, we screened 100 males for vitamin C baseline values in blood. Subsequently, the 10 individuals with the lowest and the 10 with the highest vitamin C values were assigned in two groups. Using a placebo-controlled crossover design, the 20 selected subjects performed aerobic exercise to exhaustion (oxidant stimulus) before and after vitamin C supplementation for 30 days.


The low vitamin C group had lower VO2max values than the high vitamin C group. Vitamin C supplementation in this group marginally increased VO2max. Baseline concentration of F2-isoprostanes and protein carbonyls was higher in the low vitamin C group compared to the high vitamin C group. Vitamin C supplementation decreased the baseline concentration of F2-isoprostanes and protein carbonyls in both groups, yet the decrease was greater in the low vitamin C group. Before vitamin C supplementation, F2-isoprostanes and protein carbonyls were increased to a greater extent after exercise in the high vitamin C group compared to the low vitamin C group. Interestingly, after vitamin C supplementation, this difference was narrowed.


We show for the first time that low vitamin C concentration is linked with decreased physical performance and increased oxidative stress and that vitamin C supplementation decreases oxidative stress and might increase exercise performance only in those with low initial concentration of vitamin C.

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  1. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK, Levine M (2003) Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 22:18–35

    Article  CAS  Google Scholar 

  2. Bjelakovic G, Nikolova D, Gluud C (2014) Antioxidant supplements and mortality. Curr Opin Clin Nutr Metab Care 17:40–44

    CAS  Google Scholar 

  3. Jiang L, Yang KH, Tian JH, Guan QL, Yao N, Cao N, Mi DH, Wu J, Ma B, Yang SH (2010) Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials. Nutr Cancer 62:719–727

    Article  CAS  Google Scholar 

  4. Nikolaidis MG, Kerksick CM, Lamprecht M, McAnulty SR (2012) Does vitamin C and E supplementation impair the favorable adaptations of regular exercise? Oxid Med Cell Longev 2012:707941

    Google Scholar 

  5. Nikolaidis MG, Kyparos A, Spanou C, Paschalis V, Theodorou AA, Vrabas IS (2012) Redox biology of exercise: an integrative and comparative consideration of some overlooked issues. J Exp Biol 215:1615–1625

    Article  CAS  Google Scholar 

  6. Halliwell B (2009) The wanderings of a free radical. Free Radic Biol Med 46:531–542

    Article  CAS  Google Scholar 

  7. Bernard D, Christophe A, Delanghe J, Langlois M, De Buyzere M, Comhaire F (2003) The effect of supplementation with an antioxidant preparation on LDL-oxidation is determined by haptoglobin polymorphism. Redox Rep 8:41–46

    Article  CAS  Google Scholar 

  8. Block G, Jensen CD, Morrow JD, Holland N, Norkus EP, Milne GL, Hudes M, Dalvi TB, Crawford PB, Fung EB, Schumacher L, Harmatz P (2008) The effect of vitamins C and E on biomarkers of oxidative stress depends on baseline level. Free Radic Biol Med 45:377–384

    Article  CAS  Google Scholar 

  9. Braakhuis AJ (2012) Effect of vitamin C supplements on physical performance. Curr Sports Med Rep 11:180–184

    Article  Google Scholar 

  10. Duffield-Lillico AJ, Slate EH, Reid ME, Turnbull BW, Wilkins PA, Combs GF Jr, Park HK, Gross EG, Graham GF, Stratton MS, Marshall JR, Clark LC (2003) Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst 95:1477–1481

    Article  CAS  Google Scholar 

  11. Halliwell B (1999) Establishing the significance and optimal intake of dietary antioxidants: the biomarker concept. Nutr Rev 57:104–113

    Article  CAS  Google Scholar 

  12. Halliwell B (1999) Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radic Res 31:261–272

    Article  CAS  Google Scholar 

  13. Hercberg S (2006) The SU.VI.MAX study, a randomized, placebo-controlled trial on the effects of antioxidant vitamins and minerals on health. Ann Pharm Fr 64:397–401

    Article  CAS  Google Scholar 

  14. Lykkesfeldt J, Poulsen HE (2010) Is vitamin C supplementation beneficial? Lessons learned from randomised controlled trials. Br J Nutr 103:1251–1259

    Article  CAS  Google Scholar 

  15. Steinhubl SR (2008) Why have antioxidants failed in clinical trials? Am J Cardiol 101:14D–19D

    Article  CAS  Google Scholar 

  16. Omaye ST, Turnbull JD, Sauberlich HE (1979) Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol 62:3–11

    Article  CAS  Google Scholar 

  17. Karlsen A, Blomhoff R, Gundersen TE (2005) High-throughput analysis of vitamin C in human plasma with the use of HPLC with monolithic column and UV-detection. J Chromatogr B Analyt Technol Biomed Life Sci 824:132–138

    Article  CAS  Google Scholar 

  18. Lykkesfeldt J (2012) Ascorbate and dehydroascorbic acid as biomarkers of oxidative stress: validity of clinical data depends on vacutainer system used. Nutr Res 32:66–69

    Article  CAS  Google Scholar 

  19. Jacob RA (1990) Assessment of human vitamin C status. J Nutr 120(Suppl 11):1480–1485

    CAS  Google Scholar 

  20. Nikolaidis MG, Margaritelis NV, Paschalis V, Theodorou AA, Kyparos A, Vrabas IS (2014) Common questions and tentative answers on how to assess oxidative stress after antioxidant supplementation and exercise. CRC Press, New York

    Book  Google Scholar 

  21. Close GL, Ashton T, Cable T, Doran D, Holloway C, McArdle F, MacLaren DP (2006) Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process. Br J Nutr 95:976–981

    Article  CAS  Google Scholar 

  22. Moller P, Viscovich M, Lykkesfeldt J, Loft S, Jensen A, Poulsen HE (2004) Vitamin C supplementation decreases oxidative DNA damage in mononuclear blood cells of smokers. Eur J Nutr 43:267–274

    Article  CAS  Google Scholar 

  23. Elhaimeur F, Courderot-Masuyer C, Nicod L, Guyon C, Richert L, Berthelot A (2002) Dietary vitamin C supplementation decreases blood pressure in DOCA-salt hypertensive male Sprague-Dawley rats and this is associated with increased liver oxidative stress. Mol Cell Biochem 237:77–83

    Article  CAS  Google Scholar 

  24. Premkumar K, Bowlus CL (2004) Ascorbic acid does not increase the oxidative stress induced by dietary iron in C3H mice. J Nutr 134:435–438

    CAS  Google Scholar 

  25. Kelly RP, Poo Yeo K, Isaac HB, Lee CY, Huang SH, Teng L, Halliwell B, Wise SD (2008) Lack of effect of acute oral ingestion of vitamin C on oxidative stress, arterial stiffness or blood pressure in healthy subjects. Free Radic Res 42:514–522

    Article  CAS  Google Scholar 

  26. Theodorou AA, Nikolaidis MG, Paschalis V, Koutsias S, Panayiotou G, Fatouros IG, Koutedakis Y, Jamurtas AZ (2011) No effect of antioxidant supplementation on muscle performance and blood redox status adaptations to eccentric training. Am J Clin Nutr 93:1373–1383

    Article  CAS  Google Scholar 

  27. Rossman MJ, Garten RS, Groot HJ, Reese V, Zhao J, Amann M, Richardson RS (2013) Ascorbate infusion increases skeletal muscle fatigue resistance in patients with chronic obstructive pulmonary disease. Am J Physiol Regul Integr Comp Physiol 305:R1163–R1170

    Article  CAS  Google Scholar 

  28. Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, Vina J (2008) Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr 87:142–149

    CAS  Google Scholar 

  29. Marshall RJ, Scott KC, Hill RC, Lewis DD, Sundstrom D, Jones GL, Harper J (2002) Supplemental vitamin C appears to slow racing greyhounds. J Nutr 132:1616S–1621S

    CAS  Google Scholar 

  30. Roberts LA, Beattie K, Close GL, Morton JP (2011) Vitamin C consumption does not impair training-induced improvements in exercise performance. Int J Sports Physiol Perform 6:58–69

    Google Scholar 

  31. Margaritelis NV, Kyparos A, Paschalis V, Theodorou AA, Panayiotou G, Zafeiridis A, Dipla K, Nikolaidis MG, Vrabas IS (2014) Reductive stress after exercise: the issue of redox individuality. Redox Biol 2:520–528

    Article  CAS  Google Scholar 

  32. Higashida K, Kim SH, Higuchi M, Holloszy JO, Han DH (2011) Normal adaptations to exercise despite protection against oxidative stress. Am J Physiol Endocrinol Metab 301:E779–E784

    Article  CAS  Google Scholar 

  33. Paulsen G, Cumming KT, Holden G, Hallen J, Ronnestad BR, Sveen O, Skaug A, Paur I, Bastani NE, Ostgaard HN, Buer C, Midttun M, Freuchen F, Wiig H, Ulseth ET, Garthe I, Blomhoff R, Benestad HB, Raastad T (2014) Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial. J Physiol 592:1887–1901

    Article  CAS  Google Scholar 

  34. Ristow M, Zarse K, Oberbach A, Kloting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Bluher M (2009) Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci USA 106:8665–8670

    Article  CAS  Google Scholar 

  35. Yfanti C, Akerstrom T, Nielsen S, Nielsen AR, Mounier R, Mortensen OH, Lykkesfeldt J, Rose AJ, Fischer CP, Pedersen BK (2010) Antioxidant supplementation does not alter endurance training adaptation. Med Sci Sports Exerc 42:1388–1395

    Article  CAS  Google Scholar 

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This work was partially funded by research Grant awarded to AAT and to GP by the European University Cyprus as well as to ISV (No. 89778) by the Research Dissemination Center of the Aristotle University of Thessaloniki, Greece.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

An informed written consent was obtained for all participants, after they were informed of all risks, discomforts, and benefits involved in the study. The procedures were in accordance with the Helsinki declaration of 1975, as revised in 2000, and approval was received from the Ethics Committee of the local university.

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Correspondence to Michalis G. Nikolaidis.

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Paschalis, V., Theodorou, A.A., Kyparos, A. et al. Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation. Eur J Nutr 55, 45–53 (2016).

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