Vitamin C supplementation decreases oxidative DNA damage in mononuclear blood cells of smokers

Eur J Nutr. 2004 Oct;43(5):267-74. doi: 10.1007/s00394-004-0470-6. Epub 2004 Jan 6.

Abstract

Background: Antioxidants, in particular vitamin C, have been suggested to decrease oxidative DNA damage. Such effects have been shown in mononuclear blood cells in the first few hours after ingestion, whereas studies of longer-term effects in well-nourished humans have been mainly negative.

Aim: To investigate the antioxidant effect of vitamin C in terms of oxidative DNA damage measured by the comet assay and DNA repair measured by expression of OGG1 mRNA in blood cells of male smokers given 2 x 250 mg vitamin C daily as plain or slow release tablets combined with plain release vitamin E 2 x 91 mg, or placebo for 4 wk.

Results: This study showed a difference in DNA protective effects between a slow release and a plain release vitamin C formulation. Ingestion of slow release vitamin C formulation was associated with fewer endonuclease III and formamidopyrimidine DNA glycosylase sensitive sites measured by the comet assay in mononuclear blood cells obtained 4 h and 8 h after a single tablet and 4 wk after two tablets a day. Ingestion of the vitamin formulation with plain release only indicated a damage-reducing effect 4 h after intake of a single tablet, and the effect was more apparent on endonuclease III than formamidopyrimidine DNA glycosylase sites. Overall the slow release tablets of vitamin C formulation had a more pronounced and a sustained protective effect on base damage compared with the plain release tablets. Plasma vitamin E was unaltered in the first 12 h after ingestion of a single tablet, suggesting that the antioxidant effect was mediated by vitamin C. Differences in plasma vitamin C levels at steady state could not explain the difference between the two vitamin C formulations, whereas wider amplitudes of plasma vitamin C were seen after ingestion of plain release formulation compared to slow release formulation. Assessment of OGG1 mRNA levels by RT-PCR did not indicate increased expression of this DNA repair gene after 4 wk of vitamin supplementation.

Conclusion: This study suggests that long-term vitamin C supplementation at high dose, i. e. 500 mg together with vitamin E in moderate dose, 182 mg, decreases the steady-state level of oxidative DNA damage in mononuclear blood cells of smokers.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / blood
  • Ascorbic Acid / pharmacology*
  • Comet Assay
  • DNA Damage / drug effects*
  • DNA Glycosylases / genetics
  • DNA Glycosylases / metabolism
  • DNA-Formamidopyrimidine Glycosylase / genetics
  • DNA-Formamidopyrimidine Glycosylase / metabolism
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Endonucleases / genetics
  • Endonucleases / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Oxidative Stress
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smoking / blood
  • Smoking / metabolism*
  • Vitamin E / pharmacology

Substances

  • Antioxidants
  • Delayed-Action Preparations
  • RNA, Messenger
  • Vitamin E
  • Endonucleases
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human
  • DNA-Formamidopyrimidine Glycosylase
  • Ascorbic Acid