Serum carotenoids and vitamins in relation to markers of endothelial function and inflammation


Background: Endothelial cell dysfunction may be related to an increase in cellular oxidative stress. Carotenoids and vitamins could have an antioxidant-mediated tempering influence on endothelial function and inflammation, thereby reducing the risk of atherosclerosis. Methods: We measured serum carotenoids, α$-tocopherol and Vitamin C concentrations in 379 subjects sampled from the general population. High-sensitive C-reactive protein (CRP), fibrinogen (Fbg) and leukocytes were measured as markers of inflammation. Furthermore, soluble intercellular adhesion molecule-1 (sICAM-1) and flow-mediated vasodilation (FMD; n=165) were measured as markers of endothelial function. Relationships between serum carotenoids and vitamins and markers of endothelial function and inflammation were analysed after adjustment for confounding. Results: In the total study group, lutein and lycopene were inversely related to sICAM-1 with regression-coefficients of −0.38 $±$ 0.19 (p=0.04) and −0.16 $±$ 0.08 (p=0.04) per 1 μmol/l, respectively. $β$-Carotene was inverse related to leukocytes (−0.23 $±$ 0.07; p=0.007) and CRP (−1.09 ± 0.30; p=0.0003) per 1 $μ$mol/l. Vitamin C was inverse related to CRP (−0.01 $±$ 0.005; p=0.04) per 1 $μ$mol/l, whereas $α$-tocopherol was positively related to CRP (0.03 $±$ 0.01; p=0.02) per 1 $μ$/l. Zeaxanthin was inversely related to FMD (31.2 $±$ 15.3; p=0.04) per 1 $μ$mol/l. Conclusion: The inverse relations between carotenoids, Vitamin C and sICAM-1, CRP and leukocytes may help to explain the possible protective effect of carotenoids and Vitamin C on atherosclerosis through an influence on inflammatory processes and endothelial function.

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  1. 1.

    Brown AA, Hu FB. Dietary modulation of endothelial function: Implications for cardiovascular disease. Am J Clin Nutr 2001; 73: 673–686.

    PubMed  CAS  Google Scholar 

  2. 2.

    Hennig B, Toborek M. Nutrition and endothelial cell function: Implications in atherosclerosis. Nutr Res 2001; 21: 279–293.

    Article  CAS  Google Scholar 

  3. 3.

    Navab M, Imes SS, Hama SY, et al. Monocyte trans-migration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein. J Clin Invest 1991; 88: 2039–2046.

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Marui N, Offermann MK, Swerlick R, et al. Vascular cell adhesion molecule-1 (VCAM-1)gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest 1993; 92: 1866–1874.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Berliner JA, Navab M, Fogelman AM, et al. Athero-sclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation 1995; 91: 2488–2496.

    PubMed  CAS  Google Scholar 

  6. 6.

    Ross R. Atherosclerosis–an in. inflammatory disease. N Engl J Med 1999; 340: 115–126.

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Gey KF, Sta ¨helin HB, Eichholzer M. Poor plasma status of carotene and Vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basal prospective study. Clin Invest 1993; 71: 3–6.

    Article  CAS  Google Scholar 

  8. 8.

    Kardinaal AF, Kok FJ, Ringstad J, et al. Antioxidants in adipose tissue and risk of myocardial infarction: The EURAMIC study. Lancet 1993; 342: 1379–1384.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Street DA, Comstock GW, Salkeld RM, Schüep W, Klag MJ. Serum antioxidants and myocardial infarc-tion: Are low levels of carotenoids and a tocopherol risk factors for myocardial infarction? Circulation 1994; 90: 1154–1161.

    PubMed  CAS  Google Scholar 

  10. 10.

    Curran FJ, Sattar N, Talwar D, Baxter JN, Imrie CW. Relationship of carotenoid and Vitamins A and E with the acute inflatammatory response in acute pancreatitis. Br J Surg 2000; 87: 301–305.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Erlinger TP, Guallar E, Miller ER, Stolzenberg-Solo-mon R, Appel LJ. Relationship between systemic markers of inflatammation and serum beta-carotene levels. Arch Int Med 2001; 161: 1903–1908.

    Article  CAS  Google Scholar 

  12. 12.

    Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol 1994, 24: 1468–1474.

    PubMed  CAS  Article  Google Scholar 

  13. 13.

    Demerath E, Towne B, Blangero J, Siervogel RM. The relationship of soluble ICAM-1, VCAM-1, P-selectin and E-selectin to cardiovascular disease risk factors in healthy men and women. Ann Hum Biol 2001; 28: 664–678.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Ridker PM, Hennekes CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836–843.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Blankenberg S, Rupprecht HJ, Bickel C, et al. Circu-lating cell adhesion molecules and death in patients with coronary artery disease. Circulation 2001; 104: 1336–1342.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Danesh J, Collins R, Appleby P, Peto R. Association of brinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: Meta-analyses of prospective studies. JAMA 1998; 279: 1477–1482.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Tracy RP. Epidemiological evidence for inflammation in cardiovascular disease. Thromb Haemost 1999; 82: 826–831.

    PubMed  CAS  Google Scholar 

  18. 18.

    Broekmans WMR, Klopping-Ketelaars IAA, West-strate JA, et al. Decreased carotenoid concentrations due to dietary sucrose polyesters do not affect possible markers of disease risk in humans. J Nutr 2003; 133: 720–726.

    PubMed  CAS  Google Scholar 

  19. 19.

    Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cho-lesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

    PubMed  CAS  Google Scholar 

  20. 20.

    Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haemat 1957; 17: 237–246.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    De Maat MP, De Bart AC, Hennis BC, et al. Interin-dividual and intraindividual variability in plasma brinogen, TPA antigen, PAI activity, and CRP in healthy, young volunteers and patients with angina pectoris. Arterioscler Thromb Vasc Biol 1996; 16: 1156–1162.

    PubMed  CAS  Google Scholar 

  22. 22.

    Gearing AJ, Hemingway I, Pigott R, Hughes J, Rees AJ, Cashman SJ. Soluble forms of vascular adhesion molecules, E-selectin, ICAM-1, and VCAM-1: Pathological signi cance. Ann NY Acad Sci 1992; 667: 324–331.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    De Roos NM, Bots ML, Katan MB. Replacement of dietary saturated fatty acids by trans fatty acids lowers serum HDL cholesterol and impairs endothelial func-tion in healthy men and women. Arterioscler Thromb Vasc Biol 2001; 21: 1233–1237.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Rothman KJ, Greenland S. Precision and validity of epidemiological studies. In: Rothman KJ, Greenland S (eds), Modern epidemiology, Philadelphia, USA: Lippincott-Raven, 1998; 115–134.

    Google Scholar 

  25. 25.

    Martin KR, Wu D, Meydani M. The effect of carote-noids on the expression of cell surface adhesion mole-cules and binding of monocytes to human aortic endothelial cells. Atherosclerosis 2000; 150: 265–274.

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Wu D, Koga T, Martin KR, Meydani M. Effect of Vitamin E on human aortic endothelial cell production of chemokines and adhesion to monocytes. Athero-sclerosis 1999; 147: 297–307.

    CAS  Google Scholar 

  27. 27.

    Rissanen TH, Voutilainen S, Nyyssonen K, et al. Low serum lycopene concentration is associated with an excess incidence of acute coronary events and stroke: The Kuopio ischaemic heart disease risk factor study. Br J Nutr 2001; 85: 749–754.

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Kohlmeier L, Kark JD, Gomez-Gracia E, et al. Lyco-pene and myocardial infarction risk in the EURAMIC study. Am J Epidemiol 1997; 146: 618–626.

    PubMed  CAS  Google Scholar 

  29. 29.

    Rissanen T, Voutilainen S, Nyyssonen K, Salonen R, Salonen JT. Low plasma lycopene concentration is associated with increased intima-media thickness of the carotid artery wall. Arterioscler Thromb Vasc Biol 2000; 20: 2677–2681.

    PubMed  CAS  Google Scholar 

  30. 30.

    Dwyer JH, Navab M, Dwyer KM, et al. Oxygenated carotenoid lutein and progression of early atheroscle-rosis: The Los Angeles atherosclerosis study. Circula-tion 2001; 103: 2922–2927.

    CAS  Google Scholar 

  31. 31.

    Ridker PM, Hennekens CH, Roitman-Johnson B, Stampfer M, Allen J. Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet 1998; 351: 88–92.

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Malik I, Danesh J, Whincup P, et al. Soluble adhesion molecules and prediction of coronary heart disease: A prospective study and meta-analysis. Lancet 2001; 358: 971–976.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Ridker PM. Role of inflammatory biomarkers in pre-diction of coronary heart disease. Lancet 2001; 358: 946–948.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    De Maat MP, Pijl H, Kluft C, Princen HM. Con-sumption of black and green tea had no effect on inflammation, haemostatis and endothelial markers in smoking healthy individuals. Eur J Clin Nutr 2000; 54: 757–763.

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Kritchevsky SB, Bush AJ, Pahor M, Gross MD. Serum carotenoids and markers of inflammation in non-smokers. Am J Epidemiol 2000; 152: 1065–1071.

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Kritchevsky SB. b Carotene, carotenoids and the prevention of coronary heart disease. J Nutr 1999; 129: 5–8.

    PubMed  CAS  Google Scholar 

  37. 37.

    Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH. b Carotene supplementation and incidence of cancer and cardiovascular disease: The women 's health study. J Natl Cancer Inst 1999; 91: 2102–2106.

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Omenn GS, Goodman GE, Thronquist MD, et al. Effects of a combination of b carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996; 664: 1150–1155.

    Article  Google Scholar 

  39. 39.

    Heart Protection Study Collaborative Group. MRC/ BHF heart protection study of antioxidant vitamin supplementation in 20, 536 high-risk individuals: A randomised placebo-controlled trial. Lancet 2002; 360: 23–33.

    Article  Google Scholar 

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van Herpen-broekmans, W., Klöpping-ketelaars, I., Michiel, B. et al. Serum carotenoids and vitamins in relation to markers of endothelial function and inflammation. Eur J Epidemiol 19, 915–921 (2004).

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  • Carotenoids
  • Endothelial function
  • Humans
  • Inflammation
  • Vitamins