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J Am Coll Cardiol, 2000; 35:1616-1621
© 2000 by the American College of Cardiology Foundation
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CLINICAL STUDIES

Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect

Olli T. Raitakari, MD, PhD* {ddagger}, Mark R. Adams, MB, BS, PhD, FRACP*, Robyn J. McCredie, BSc*, Kaye A. Griffiths, DMU*, Roland Stocker, PhD{dagger} and David S. Celermajer, MB, BS, PhD, FRACP*

* Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia
{dagger} Heart Research Institute, Sydney, Australia
{ddagger} Department of Clinical Physiology, University of Turku, Turku, Finland

Manuscript received July 2, 1999; revised manuscript received November 30, 1999, accepted January 14, 2000.

Reprint requests and correspondence: Dr. David S. Celermajer, Department of Cardiology, Royal Prince Alfred Hospital, Missenden Road, Camperdown NSW 2050, Sydney, Australia
davidc{at}card.rpa.cs.nsw.gov.au

OBJECTIVES

To test the hypothesis that antioxidant therapy would improve endothelial function in smokers.

BACKGROUND

Several studies have documented a beneficial effect of short-term oral or parenteral vitamin C on endothelial physiology in subjects with early arterial dysfunction. Possible long-term effects of vitamin C on endothelial function, however, are not known.

METHODS

We studied the effects of short- and long-term oral vitamin C therapy on endothelial function in 20 healthy young adult smokers (age 36 ± 6 years, 8 male subjects, 21 ± 10 pack-years). Each subject was studied at baseline, 2 h after a single dose of 2 g vitamin C and 8 weeks after taking 1 g vitamin C daily, and after placebo, in a randomized double-blind crossover study. Blood samples were analyzed for plasma ascorbate levels and endothelial function was measured as flow-mediated dilation of the brachial artery, using high resolution ultrasound. Nitroglycerin-mediated dilation (endothelium-independent) was also measured at each visit.

RESULTS

At baseline, plasma ascorbate level was low in the smokers (42 ± 21 µmol/liter; normal range, 50 to 150 µmol/liter), increased with vitamin C therapy after 2 h to 120 ± 54 µmol/liter (p < 0.001) and remained elevated after eight weeks of supplementation at 92 ± 32 µmol/liter (p < 0.001, compared with placebo). Flow-mediated dilation, however, increased at 2 h (from 2.8 ± 2.0% to 6.3 ± 2.8%, p < 0.001), but there was no sustained beneficial effect after eight weeks (3.9 ± 3.2%, p = 0.26). Nitroglycerin-mediated dilation was unchanged throughout.

CONCLUSION

Oral vitamin C therapy improves endothelial dysfunction in the short term in healthy young smokers, but it has no beneficial long-term effect, despite sustained elevation of plasma ascorbate levels.

Abbreviations and Acronyms
  ANOVA = analysis of variance
  FMD = flow-mediated dilation
  HDL = high-density lipoprotein
  LDL = low-density lipoprotein




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