Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Communication
  • Published:

Does vitamin C supplementation influence the levels of circulating oxidized LDL, sICAM-1, sVCAM-1 and vWF-antigen in healthy male smokers?

European Journal of Clinical Nutrition volume 58, pages 1587–1593 (2004)Cite this article

Abstract

Objective: To examine the effects of vitamin C supplementation on the concentration of oxidation markers, in particular, circulating oxidized LDL (OxLDL) and on endothelial activation markers.

Design: Randomized double-blind, placebo-controlled crossover trial.

Setting: Belgian population of the city of Leuven.

Subjects: A total of 34 healthy male smokers aged 26–73 y.

Intervention: Smokers were randomly assigned to receive either vitamin C (250 mg twice daily) or placebo capsules, each to be taken for 4 weeks. After a 1-week washout period, participants then crossed over to the alternative capsules for further 4 weeks.

Mean outcome measures: Markers of oxidation (bilirubin, uric acid, α-tocopherol, retinol, malondialdehyde, circulating Oxidized LDL (OxLDL)) and markers of endothelial activation (sICAM-1, sVCAM-1, vWF-antigen) were analysed.

Results: Plasma ascorbate concentrations significantly increased from 46.6±17.6 to 70.1±21.2 μmol/l after a 4-week treatment with 500 mg vitamin C per day. The other plasma antioxidants concentrations, including bilirubin, uric acid, α-tocopherol and retinol, were similar in both treatment periods. Vitamin C did not change plasma malondialdehyde and circulating OxLDL compared with placebo (vitamin C 0.73±0.25 mg/dl OxLDL; placebo 0.72±0.21 mg/dl OxLDL). After vitamin C supplementation, neither sICAM-1 and sVCAM-1 levels nor the concentration of vWF-antigen significantly differed from placebo condition.

Conclusions: Oral supplementation of vitamin C is not associated with changes in markers of oxidation or endothelial activation in healthy male smokers.

Sponsorship: The Unilever Chair in Nutritional Epidemiology, University of Leuven, Belgium.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  • Antoniades C, Tousoulis D, Tentolouris C, Toutouza M, Marinou K, Goumas G, Tsioufis C, Toutouzas P & Stefanadis C (2003): Effects of antioxidant vitamins C and E on endothelial function and thrombosis/fibrinolysis system in smokers. Thromb. Haemost. 89, 990–995.

    Article  CAS  Google Scholar 

  • Blann AD, Seigneur M, Steiner M, Miller JP & McCollum CN (1998): Circulating ICAM-1 and VCAM-1 in peripherial artery disease and hypercholesterolaemia: relationship to the location of atherosclerotic disease, smoking, and in the prediction of adverse events. Thromb. Haemost. 79, 1080–1085.

    Article  CAS  Google Scholar 

  • Caye-Vaugien C, Krempf M, Lamarche P, Charbonnel B & Pieri J (1990): Determination of alfa-tocopherol in plasma, platelets and erythrocytes of type I and type II diabetic patients by HPLC. Int. J. Vitamin. Nutr. Res. 60, 324–330.

    CAS  Google Scholar 

  • Celermajer DS, Sorensen KE, Georgakapoulos D, Bull C, Thomas O, Robinson J & Deanfield JE (1993): Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 88, 2149–2155.

    Article  CAS  Google Scholar 

  • Davies KJA (1995): Oxidative stress: the paradox of aerobic life. Biochem. Soc. Symp. 61, 1–31.

    Article  CAS  Google Scholar 

  • Diana JN (1993): Tobacco smoking and nutrition. Ann. NY. Acad. Sci. 686, 1–11.

    Article  CAS  Google Scholar 

  • Diaz MN, Frei B, Vita JA & Keaney JF (1997): Antioxidants and atherosclerotic heart disease. N. Engl. J. Med. 337, 408–417.

    Article  CAS  Google Scholar 

  • Frei B (1991): Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am. J. Clin. Nutr. 54, 1113S–1118S.

    Article  CAS  Google Scholar 

  • Frei B (1994): Reactive oxygen species and antioxidant vitamins: mechanisms of action. Am. J. Med. 97, 5S–13S.

    Article  CAS  Google Scholar 

  • Friedewald WT, Levy RI & Fredrikson DS (1972): Estimation of the concentration of the low-denstity lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 18, 499–502.

    CAS  Google Scholar 

  • Fuller C, Grundy S, Norkus EP & Jialal I (1996): Effect of ascorbate supplementation on low density lipoprotein oxidation in smokers. Atherosclerosis 119, 139–150.

    Article  CAS  Google Scholar 

  • Gocke N, Keaney J, Frei B, Holbrook M, Olesiak M, Zachariah BJ, Leeuwenburgh C, Heinecke JW & Vita JA (1999): Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 99, 323–3240.

    Google Scholar 

  • Harats D, Ben-Naim M, Dabach Y, Hollander G, Havivi E, Stein O & Stein Y (1990): Effect of vitamin C and E supplementation on susceptibility of plasma lipoproteins to peroxidation induced by acute smoking. Atherosclerosis 85, 47–54.

    Article  CAS  Google Scholar 

  • Harats D, Chevion S, Nahir M, Norman Y, Sagee O & Berry E (1998): Citrus fruit supplementation reduces lipoprotein oxidation in young men ingesting a diet high in saturated fat: presumptive evidence for an interaction between vitamins C and E in vivo. Am. J. Clin. Nutr. 67, 240–245.

    Article  CAS  Google Scholar 

  • Heitzer T, Just H & Munzel T (1996): Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation 94, 6–9.

    Article  CAS  Google Scholar 

  • Holvoet P (1999): Endothelial dysfunction, oxidation of low-density lipoprotein, and cardiovascular disease. Ther. Apher. 3, 287–293.

    Article  CAS  Google Scholar 

  • Holvoet P, Perez G, Bernar H, Brouwens E, Vanloo B, Rosseneu M & Collen D (1994): Stimulation with a monoclonal antibody (mAb4E4) of scavenger receptor-mediated uptake of chemically modified low density lipoproteins by THP-1 derived macrophages enhances foam cell generation. J. Clin. Invest. 93, 89–98.

    Article  CAS  Google Scholar 

  • Holvoet P, Donck J, Landeloos M, Brouwers E, Luijtens K, Arnout J, Lesaffre E, Vanrenterghem Y & Collen D (1996): Correlation between oxidized low density lipoproteins and von Willebrand factor in chronic renal failure. Thromb. Haemost. 76, 663–669.

    Article  CAS  Google Scholar 

  • Holvoet P, Harris TB, Tracy RP, Verhamme P, Newman AB, Rubin SM, Simonsick EM, Colbert LH & Kritchevsky SB (2003): Association of high coronary heart disease risk status with circulating oxidized LDL in the well-functioning elderly: findings from the Health, Aging, and Body Composition study. Arterioscler. Thromb. Vasc. Biol. 23, 1444–1448.

    Article  CAS  Google Scholar 

  • Jialal I, Vega GL & Grundy SM (1990): Physiologic levels of ascorbate inhibit the oxidative modification of low density lipoprotein. Atherosclerosis 82, 185–191.

    Article  CAS  Google Scholar 

  • Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J & Cantilena LR (1996): Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. 93, 3704–3709.

    Article  CAS  Google Scholar 

  • Lykkesfeldt J, Christen S, Wallock LM, Chang HH, Jacob RA & Ames BN (2000): Ascorbate is depleted by smoking and repleted by moderate supplementation: a study in male smokers and nonsmokers with matched dietary antioxidant intakes. Am. J. Clin. Nutr. 71, 530–536.

    Article  CAS  Google Scholar 

  • Mertens A (2002): The Relation between Qualitative Changes in High- and Low-density Lipoproteins and their (Anti)atherogenic Potential in Obesity PhD thesis. Leuven* Belgium: Leuven University* Leuven University Press. ISBN 90 5867 274 3.

    Google Scholar 

  • Mezzitti A, Lapenna D, Pierdomenico SD, Calafiore AM, Costantini F, Riario-Sforza G, Imbastaro T, Neri M & Cuccurullo F (1995): Vitamins E, C and lipid peroxidation in plasma and arterial tissue of smokers and non-smokers. Atherosclerosis 112, 91–99.

    Article  Google Scholar 

  • Minotti G & Aust SD (1992): Redox cycling of iron and lipid peroxidation. Lipids 27, 219–226.

    Article  CAS  Google Scholar 

  • Morabia A & Wynder EL (1990): Dietary habits of smokers, people who never smoked and exsmokers. Am. J. Clin. Nutr. 52, 933–937.

    Article  CAS  Google Scholar 

  • Motoyama T, Kawano H & Kugiyama K (1997): Endothelium-dependent vasodilation in the brachial artery is impaired in smokers: effect of vitamin C. Am. J. Physiol. 273, H1644–H1650.

    CAS  PubMed  Google Scholar 

  • Neuzil J, Thomas SR & Stocker R (1997): Requirement for, promotion, or inhibition by alpha-tocopherol of radical induced initiation of plasma lipoprotein lipid peroxidation. Free. Rad. Biol. Med. 22, 57–71.

    Article  CAS  Google Scholar 

  • Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR & Grandjean P (1997): Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin. Chem. 43, 1209–1214.

    CAS  Google Scholar 

  • Niki E (1991): Action of ascorbic acid as a scavenger of active and stable oxygen radicals. Am. J. Clin. Nutr. 54, 1119S–1124S.

    Article  CAS  Google Scholar 

  • Penn MS & Chisolm GM (1994): Oxidized lipoproteins, altered cell function and atherosclerosis. Atherosclerosis 108, S21–S29.

    Article  Google Scholar 

  • Pyror WA & Stone K (1993): Oxidants in cigarette smoking: radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite. Ann. NY. Acad. Sci. 28, 12–28.

    Article  Google Scholar 

  • Rayment SJ, Shaw J, Woollard KJ, Lunec J & Griffiths HR (2003): Vitamin C supplementation in normal subjects reduces constitutive ICAM-1 expression. Biochem. Biophys. Res. Commun. 308, 339–345.

    Article  CAS  Google Scholar 

  • Retsky KL, Freeman MW & Frei B (1993): Ascorbic acid oxidation product(s) protect human low density lipoprotein against atherogenic modification. J Biol. Chem. 268, 1304–1309.

    CAS  PubMed  Google Scholar 

  • Schectman G, Byrd JC & Gruchow HW (1989): The influence of smoking on vitamin C status in adults. Am. J. Public. Health. 79, 158–162.

    Article  CAS  Google Scholar 

  • Tousoulis D, Antoniades C, Tentolouris C, Tsioufis C, Toutouza M, Toutouzas P & Stefanadis C (2003): Effects of combined administration of vitamins C and E on reactive hyperemia and inflammatory process in chronic smokers. Atherosclerosis 170, 261–267.

    Article  CAS  Google Scholar 

  • Van Hoydonck PGA, Schouten EG & Temme EHM (2003): Reproducibility of blood markers of oxidative status and endothelial function in healthy individuals. Clin. Chem. 49, 936–965.

    Article  Google Scholar 

  • Walmsley CM, Bates CJ, Prentice A & Cole TJ (1999): Relationship between cigarette smoking and nutrient intake and blood status indices of older people living in the UK: further analysis of data from the National Diet and Nutrition Survey of people aged 65 years and over, 1994/95. Public. Health. Nutr. 2, 199–208.

    Article  CAS  Google Scholar 

  • Washko PW, Welch KR, Dhariwal KR, Wang Y & Levine M (1992): Ascorbic acid and dehydroascorbic acid analyses in biological samples. Anal. Biochem. 204, 1–14.

    Article  CAS  Google Scholar 

  • Weber C, Erl W, Weber K & Weber P (1996): Increased adhesiveness of isolated monocytes is prevented by vitamin C intake in smokers. Circulation 93, 1488–1492.

    Article  CAS  Google Scholar 

  • Zeiher AM, Schachinger V & Minners J (1995): Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation 92, 1094–1100.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the volunteers for their participation in the study. We thank the personnel of the division of Youth Health Care (University of Leuven) for taking the blood samples, Centre of Experimental Surgery and Anaesthesiology (University of Leuven) for assisting with OxLDL, sICAM-1 and sVCAM-1 determinations and Metabolic Research Unit (University of Antwerp) for performing the analysis of plasma ascorbate, α-tocopherol, retinol and malondialdehyde.

Author information

Authors and Affiliations

  1. Department of Public Health, Division of Nutritional Epidemiology, University of Leuven, Leuven, Belgium

    P G A Van Hoydonck & E H M Temme

  2. Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen, The Netherlands

    E G Schouten

  3. Metabolic Research Unit, University of Antwerp, Antwerp, Belgium

    B Manuel-y-Keenoy & A van Campenhout

  4. Department of Public Health, Division of Youth Health Care, University of Leuven, Leuven, Belgium

    K P M Hoppenbrouwers

Authors
  1. P G A Van Hoydonck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E G Schouten
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B Manuel-y-Keenoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A van Campenhout
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K P M Hoppenbrouwers
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E H M Temme
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E H M Temme.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Van Hoydonck, P., Schouten, E., Manuel-y-Keenoy, B. et al. Does vitamin C supplementation influence the levels of circulating oxidized LDL, sICAM-1, sVCAM-1 and vWF-antigen in healthy male smokers?. Eur J Clin Nutr 58, 1587–1593 (2004). https://doi.org/10.1038/sj.ejcn.1601990

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601990

Keywords

This article is cited by

Search

Advanced search

Quick links