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Clinical Cardiovascular Disease Trials: The Vitamin E Case

  • Joshua B. Wiener
  • Elliot M. Berinstein
  • Andrew P. LevyEmail author
Chapter
Part of the Nutrition and Health book series (NH)

Abstract

Vitamin E is a naturally occurring fat-soluble vitamin. Its antioxidant properties have made it a popular candidate to combat oxidative stress and diseases that are caused by it. It has been widely studied as a potential treatment for both primary and secondary protection of cardiovascular disease because of its well-understood mechanism, its ability to naturally recycle itself, and its promising epidemiological evidence. After numerous prospective and retrospective clinical studies, there has been a lack of consistent evidence supporting the notion that vitamin E should be used for the primary and secondary prevention of cardiovascular disease (CVD). This chapter outlines various clinical trials that have assessed the potential clinical benefit of vitamin E to prevent CVD.

Keywords

Vitamin E Oxidative stress Cardiovascular disease Stroke Myocardial infarction Haptoglobin Diabetes 

References

  1. 1.
    Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320(14):915–24.  https://doi.org/10.1056/NEJM198904063201407.CrossRefPubMedGoogle Scholar
  2. 2.
    Navab M, Anantharamaiah GM, Reddy ST, Van Lenten BJ, Ansell BJ, Fogelman AM. Mechanisms of disease: proatherogenic HDL – an evolving field. Nat Clin Pract Endocrinol Metab. 2006;2(9):504–11.  https://doi.org/10.1038/ncpendmet0245.CrossRefPubMedGoogle Scholar
  3. 3.
    Wolf G. The discovery of the antioxidant function of vitamin E: the contribution of Henry A. Mattill. J Nutr. 2005;135(3):363–6.CrossRefGoogle Scholar
  4. 4.
    Burton GW, Cheng SC, Webb A, Ingold KU. Vitamin E in young and old human red blood cells. Biochim Biophys Acta. 1986;860(1):84–90.CrossRefGoogle Scholar
  5. 5.
    Fahrenholtz SR, Doleiden FH, Trozzolo AM, Lamola AA. On the quenching of singlet oxygen by alpha-tocopherol. Photochem Photobiol. 1974;20(6):505–9.CrossRefGoogle Scholar
  6. 6.
    Kagan VE, Serbinova EA, Forte T, Scita G, Packer L. Recycling of vitamin E in human low density lipoproteins. J Lipid Res. 1992;33(3):385–97.PubMedGoogle Scholar
  7. 7.
    Carr AC, McCall MR, Frei B. Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and antioxidant protection. Arterioscler Thromb Vasc Biol. 2000;20(7):1716–23.CrossRefGoogle Scholar
  8. 8.
    Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993;328(20):1450–6.  https://doi.org/10.1056/NEJM199305203282004.CrossRefPubMedGoogle Scholar
  9. 9.
    Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993;328(20):1444–9.  https://doi.org/10.1056/NEJM199305203282003.CrossRefPubMedGoogle Scholar
  10. 10.
    Virtamo J, Rapola JM, Ripatti S, Heinonen OP, Taylor PR, Albanes D, et al. Effect of vitamin E and beta carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease. Arch Intern Med. 1998;158(6):668–75.CrossRefGoogle Scholar
  11. 11.
    de Gaetano G, Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet. 2001;357(9250):89–95.CrossRefGoogle Scholar
  12. 12.
    Sacco M, Pellegrini F, Roncaglioni MC, Avanzini F, Tognoni G, Nicolucci A, et al. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the primary prevention project (PPP) trial. Diabetes Care. 2003;26(12):3264–72.CrossRefGoogle Scholar
  13. 13.
    Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s health study: a randomized controlled trial. JAMA. 2005;294(1):56–65.  https://doi.org/10.1001/jama.294.1.56.CrossRefPubMedGoogle Scholar
  14. 14.
    Chae CU, Albert CM, Moorthy MV, Lee IM, Buring JE. Vitamin E supplementation and the risk of heart failure in women. Circ Heart Fail. 2012;5(2):176–82.  https://doi.org/10.1161/CIRCHEARTFAILURE.111.963793.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ health study II randomized controlled trial. JAMA. 2008;300(18):2123–33.  https://doi.org/10.1001/jama.2008.600.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Arad Y, Spadaro LA, Roth M, Newstein D, Guerci AD. Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized clinical trial. J Am Coll Cardiol. 2005;46(1):166–72.  https://doi.org/10.1016/j.jacc.2005.02.089.CrossRefGoogle Scholar
  17. 17.
    Kianoush S, Mirbolouk M, Makam RC, Nasir K, Blaha MJ. Coronary artery calcium scoring in current clinical practice: how to define its value? Curr Treat Options Cardiovasc Med. 2017;19(11):85.  https://doi.org/10.1007/s11936-017-0582-y.CrossRefPubMedGoogle Scholar
  18. 18.
    Hodis HN, Mack WJ, LaBree L, Mahrer PR, Sevanian A, Liu CR, et al. Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the vitamin E atherosclerosis prevention study (VEAPS). Circulation. 2002;106(12):1453–9.CrossRefGoogle Scholar
  19. 19.
    Nanayakkara PW, van Guldener C, ter Wee PM, Scheffer PG, van Ittersum FJ, Twisk JW, et al. Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on carotid intima-media thickness, endothelial function, and renal function in patients with mild to moderate chronic kidney disease: results from the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study. Arch Intern Med. 2007;167(12):1262–70.  https://doi.org/10.1001/archinte.167.12.1262.CrossRefPubMedGoogle Scholar
  20. 20.
    Alves Luzia L, Mendes Aldrighi J, Teixeira Damasceno NR, Rodrigues Sampaio G, Aparecida Manolio Soares R, Tande Silva I, et al. Fish oil and vitamin E change lipid profiles and anti-Ldl-antibodies in two different ethnic groups of women transitioning through menopause. Nutr Hosp. 2015;32(1):165–74.  https://doi.org/10.3305/nh.2015.32.1.9079.CrossRefPubMedGoogle Scholar
  21. 21.
    Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol. 1990;186:407–21.CrossRefGoogle Scholar
  22. 22.
    DeMaio SJ, King SB 3rd, Lembo NJ, Roubin GS, Hearn JA, Bhagavan HN, et al. Vitamin E supplementation, plasma lipids and incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA). J Am Coll Nutr. 1992;11(1):68–73.CrossRefGoogle Scholar
  23. 23.
    Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996;347(9004):781–6.CrossRefGoogle Scholar
  24. 24.
    Investigators G-P. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999;354(9177):447–55.CrossRefGoogle Scholar
  25. 25.
    Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P. Vitamin E supplementation and cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators. N Engl J Med. 2000;342(3):154–60.  https://doi.org/10.1056/NEJM200001203420302.CrossRefPubMedGoogle Scholar
  26. 26.
    Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005;293(11):1338–47.  https://doi.org/10.1001/jama.293.11.1338.CrossRefPubMedGoogle Scholar
  27. 27.
    Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA. 2002;288(19):2432–40.CrossRefGoogle Scholar
  28. 28.
    Heart Protection Study Collaborative G. MRC/BHF heart protection study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):23–33.  https://doi.org/10.1016/S0140-6736(02)09328-5.CrossRefGoogle Scholar
  29. 29.
    Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet. 2000;356(9237):1213–8.CrossRefGoogle Scholar
  30. 30.
    Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 1999;55(5):1899–911.  https://doi.org/10.1046/j.1523-1755.1999.00422.x.CrossRefPubMedGoogle Scholar
  31. 31.
    Galli F, Rovidati S, Chiarantini L, Campus G, Canestrari F, Buoncristiani U. Bioreactivity and biocompatibility of a vitamin E-modified multi-layer hemodialysis filter. Kidney Int. 1998;54(2):580–9.  https://doi.org/10.1046/j.1523-1755.1998.00021.x.CrossRefPubMedGoogle Scholar
  32. 32.
    Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37–46.CrossRefGoogle Scholar
  33. 33.
    Levy AP, Hochberg I, Jablonski K, Resnick HE, Lee ET, Best L, et al. Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: the strong heart study. J Am Coll Cardiol. 2002;40(11):1984–90.CrossRefGoogle Scholar
  34. 34.
    Roguin A, Koch W, Kastrati A, Aronson D, Schomig A, Levy AP. Haptoglobin genotype is predictive of major adverse cardiac events in the 1-year period after percutaneous transluminal coronary angioplasty in individuals with diabetes. Diabetes Care. 2003;26(9):2628–31.CrossRefGoogle Scholar
  35. 35.
    Suleiman M, Aronson D, Asleh R, Kapeliovich MR, Roguin A, Meisel SR, et al. Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction. Diabetes. 2005;54(9):2802–6.CrossRefGoogle Scholar
  36. 36.
    Blum S, Vardi M, Levy NS, Miller-Lotan R, Levy AP. The effect of vitamin E supplementation on cardiovascular risk in diabetic individuals with different haptoglobin phenotypes. Atherosclerosis. 2010;211(1):25–7.  https://doi.org/10.1016/j.atherosclerosis.2010.02.018.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Levy AP, Gerstein HC, Miller-Lotan R, Ratner R, McQueen M, Lonn E, et al. The effect of vitamin E supplementation on cardiovascular risk in diabetic individuals with different haptoglobin phenotypes. Diabetes Care. 2004;27(11):2767.CrossRefGoogle Scholar
  38. 38.
    Milman U, Blum S, Shapira C, Aronson D, Miller-Lotan R, Anbinder Y, et al. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: a prospective double-blinded clinical trial. Arterioscler Thromb Vasc Biol. 2008;28(2):341–7.  https://doi.org/10.1161/ATVBAHA.107.153965.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Hochberg I, Berinstein EM, Milman U, Shapira C, Levy AP. Interaction between the haptoglobin genotype and vitamin E on cardiovascular disease in diabetes. Curr Diab Rep. 2017;17(6):42.  https://doi.org/10.1007/s11892-017-0868-1.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Joshua B. Wiener
    • 1
  • Elliot M. Berinstein
    • 1
  • Andrew P. Levy
    • 1
    Email author
  1. 1.The Ruth and Bruce Rappaport Faculty of MedicineTechnion Israel Institute of TechnologyHaifaIsrael

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