Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise

Free Radic Biol Med. 2001 Sep 15;31(6):745-53. doi: 10.1016/s0891-5849(01)00640-2.


There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / adverse effects*
  • Adult
  • Antioxidants / analysis
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / adverse effects*
  • Bleomycin
  • Creatine Kinase / blood
  • Dinoprost* / analogs & derivatives*
  • Double-Blind Method
  • Exercise*
  • F2-Isoprostanes / blood
  • Glutathione Peroxidase / blood
  • Humans
  • Interleukin-6 / blood
  • Iron / blood
  • L-Lactate Dehydrogenase / blood
  • Lipid Peroxidation
  • Lipid Peroxides / blood
  • Male
  • Muscle, Skeletal / injuries*
  • Muscle, Skeletal / pathology
  • Myoglobin / blood
  • Myositis / etiology
  • Myositis / metabolism*
  • Myositis / pathology
  • Oxidative Stress*
  • Pain
  • Peroxidase / blood
  • Placebos
  • Superoxide Dismutase / blood


  • Antioxidants
  • F2-Isoprostanes
  • Interleukin-6
  • Lipid Peroxides
  • Myoglobin
  • Placebos
  • Bleomycin
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • Iron
  • L-Lactate Dehydrogenase
  • Peroxidase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Creatine Kinase
  • Ascorbic Acid
  • Acetylcysteine