Heart Failure Reviews

, Volume 11, Issue 1, pp 13–17 | Cite as

Selenium and antioxidant defenses as major mediators in the development of chronic heart failure



Increased oxidative stress is involved in the pathogenesis of chronic heart failure (CHF), the common end result of most cardiac diseases. Selenium is an “essential” trace element, which means that it must be supplied by our daily diet and that its blood and tissue concentrations are extremely low. Selenium has a variety of functions. It is a key component of several functional selenoproteins required for normal health. The best known of these are the antioxidant glutathione peroxidase (GPx) enzymes, which remove hydrogen peroxide and the harmful lipid hydroperoxides generated in vivo by oxygen-derived species. GPx deficiency exacerbates endothelial dysfunction, a major contributing factor in the severity of CHF symptoms, in various conditions such as hyperhomocysteinemia. This suggests that homocysteine may be involved in the CHF associated endothelial dysfunction through a peroxide-dependent oxidative mechanism. Selenium also plays a role in the control of thyroid hormone metabolism and in protection against organic and inorganic mercury. One possible additional mechanism by which low selenium may compromise cardiovascular condition may be through the effect of selenium on the synthesis and activity of deiodinases, enzymes converting thyroxin into the biologically active triiodothyronine. Selenium and iodine actually interact in cardiovascular physiology, and further studies are needed to examine their role, in isolation and in association, in the development of CHF. Thus, selenium (through its role in selenoenzymes, thyroid hormones, and interactions with homocysteine and endothelial function) appears to be a major mediator in several pathways potentially contributing to CHF development.


Chronic heart failure Iodine Selenium Glutathione peroxidase Vascular endothelium Thyroid hormones Homocysteine 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Rayman MP. Dietary selenium: time to act. BMJ 1997;314:387–8.PubMedGoogle Scholar
  2. 2.
    Köhrle J, Jakob F, Contempré B, Dumont JE. Selenium, the thyroid, and the endocrine system. Endocrine Reviews 2005;26:944–84.PubMedCrossRefGoogle Scholar
  3. 3.
    Goyer RA. Toxic and essential metal interactions. Ann Rev Nutr 1997;17:35–50.Google Scholar
  4. 4.
    de Lorgeril M, Salen P, Accominotti M, et al. Dietary and blood antioxidants in patients with chronic heart failure. Insights into the potential importance of selenium in heart failure. Eur J Heart Failure 2001;3:661–9.CrossRefGoogle Scholar
  5. 5.
    Cowie MR, Mostred A, Wood DA, et al. The epidemiology of heart failure. Eur Heart J 1997;18:208–25.PubMedGoogle Scholar
  6. 6.
    Keith M, Geranmayegan A, Sole MJ, et al. Increased oxidative stress in patients with congestive heart failure. J Am Coll Cardiol 1998;31:1352–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Sawyer DB, Colucci WS. Oxidative stress in heart failure. In Antioxidants and cardiovascular diseases. In: Bourassa MG and Tardif JC editors. Springer 2nd edn 2006, chapter 18: 437–50.Google Scholar
  8. 8.
    Neve J. Selenium as a risk factor for cardiovascular diseases. J Cardiovasc Risk 1996;3:42–7.PubMedGoogle Scholar
  9. 9.
    Huttunen JK. Selenium and cardiovascular diseases. An update. Biomed Environ Sci 1997;10:220–6.Google Scholar
  10. 10.
    Chariot P, Perchet H, Monnet I. Dilated cardiomyopathy in HIV-infected patients. N Engl J Med 1999;340:732.PubMedCrossRefGoogle Scholar
  11. 11.
    Ge K, Yang G. The epidemiology of selenium deficiency in the etiological study of endemic diseases in China. Am J Clin Nutr 1993;57 Suppl 2:259S–63S.Google Scholar
  12. 12.
    Takahashi K, Newburger PE, Cohen HJ. Glutathione peroxidase protein. Absence in selenium deficiency states and correlation with enzymatic activity. J Clin Invest 1986;77:1402–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Burk RF, Hill KE. Selenoprotein P. A selenium-rich extracellular glycoprotein. J Nutr 1994;124:1891–7.PubMedGoogle Scholar
  14. 14.
    May JM, Mendiratta S, Hill KE, Burk RF. Reduction of dehydroascorbate to ascorbate by the selenoenzyme thioredoxin reductase. J Biol Chem 1997;272:22607–10.PubMedCrossRefGoogle Scholar
  15. 15.
    Meister A. Glutathione-ascorbic acid antioxidant system in animals. J Biol Chem 1994;269:9397–400.PubMedGoogle Scholar
  16. 16.
    Coats AJ. Origins of symptoms in heart failure. Cardiovasc Drugs Ther 1997;11 Suppl 1:265–72.Google Scholar
  17. 17.
    Zelis R, Flaim SF. Alterations in vasomotor tone in chronic heart failure. Prog Cardiovasc Dis 1982;24:437–59.PubMedCrossRefGoogle Scholar
  18. 18.
    Okita K, Yonezawa K, Nishijima H, et al. Skeletal muscle metabolism limits exercise capacity in patients with chronic heart failure. Circulation 1998;98:1886–91.PubMedGoogle Scholar
  19. 19.
    Drexler H. Endothelium as a therapeutic target in heart failure. Circulation 1998;98:2652–5.PubMedGoogle Scholar
  20. 20.
    Hambrecht R, Fiehn E, Weigl C, et al. Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 1998;98:2709–15.PubMedGoogle Scholar
  21. 21.
    Upchurch GR, Welch GN, Fabian AJ, et al. Homocysteine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem 1997;272:17012–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Kennedy RH, Owings R, Shekhawat N, et al. Acute negative inotropic effects of homocysteine are mediated via the endothelium. Am J Physiol Heart Circ Physiol 2004;287:H812–H817.PubMedCrossRefGoogle Scholar
  23. 23.
    Dayal S, Brown KL, Weydert CJ, et al. Deficiency of glutathione peroxidase-1 sensitizes mice to endothelial dysfunction. Arterioscl Thromb Vasc Biol 2002;22:1996–2002.PubMedCrossRefGoogle Scholar
  24. 24.
    Weiss N, Zhang YY, Heydrick S, et al. Overexpression of cellular glutathione peroxidase rescues homocysteine-induced endothelial dysfunction. Proc Natl Acad Sci USA 2001;98:12503–8.PubMedCrossRefGoogle Scholar
  25. 25.
    de Lorgeril M, Salen P, Defaye P. Importance of nutrition in chronic heart failure patients. Eur Heart J 2005;26:2215–17.PubMedCrossRefGoogle Scholar
  26. 26.
    Witte KA, Nikitin NP, Parker AC, et al. The effect of micronutrient supplementation on quality of life and left ventricular function in elderly patients with chronic heart failure. Eur Heart J 2005;26:2238–44.PubMedCrossRefGoogle Scholar
  27. 27.
    Recommended Dietary Allowances, 1989. Food and Nutrition Board, National Research council, 10ed. National Acad Press.Google Scholar
  28. 28.
    Yang GQ, Xia YM. Studies on human dietary requirements and safe range of dietary intakes of selenium in China and their application in the prevention of related endemic diseases. Biomed Environ Sci 1995;8:187–201.PubMedGoogle Scholar
  29. 29.
    Akbaraly NT, Arnaud J, Hininger-favier I, et al. Selenium and mortality in the elderly: results from the EVA Study. Clin Chem 2005;51:2117–23.PubMedCrossRefGoogle Scholar
  30. 30.
    Ray AL, Semba RD, Walston J, et al. Low selenium serum and total carotenoids predict mortality among older women living in the community: the Women’s Health And Aging Study. J Nutr 2006;136:172–6.PubMedGoogle Scholar
  31. 31.
    Blankenberg S, Rupprecht HJ, Bickel C, et al. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med 2003;349:1605–13.PubMedCrossRefGoogle Scholar
  32. 32.
    Schnabel R, lackner KJ, Rupprecht HJ, et al. Glutathione peroxidase 1 activity and homocysteine for cardiovascular risk prediction. Results from the AtheroGene Study. J Am Coll Cardiol 2005;45:1631–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Wu HY, Xia YM, Ha PC, Chen XS. Changes in myocardial thyroid hormone metabolism and alpha-glycerophosphate activity in rats deficient in iodine and selenium. Br J Nutr 1997;78:671–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Tanguy S, Toufektsian MC, Besse S, et al. Dietary selenium intake affects cardiac susceptibility to ischemia/reperfusion in male senescent rats. Age and Ageing 2003;32:273–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Kazmierczak P, Polak A, Mussur M. Influence of preischemic short-term triiodothyronine administration on hemodynamic function and metabolism of reperfused isolated rat heart. Med Sci Monit 2004;10:381–7.Google Scholar
  36. 36.
    Tang YD, Kuzman JA, Said S, et al. Low thyroid function leads to cardiac atrophy with chamber dilatation, impaired myocardial blood flow, loss of arterioles, and severe systolic dysfunction. Circulation 2005;112:3122–30.PubMedCrossRefGoogle Scholar
  37. 37.
    Parle JV, Maisonneuve P, Sheppard MC, et al. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet 2001;358:861–5.PubMedCrossRefGoogle Scholar
  38. 38.
    Walsh JP, Bremner AP, Bulsara MK, et al. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med 2005;165:2467–72.PubMedCrossRefGoogle Scholar
  39. 39.
    Napoli R, Biondi B, Guardasole V, et al. Impact of hyperthyroidism and its correction on vascular reactivity in humans. Circulation 2001;104:3076–80.PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  1. 1.Laboratoire Nutrition, Vieillissement et Maladies Cardiovasculaires (NVMCV), Faculté de MédecineUniversité Joseph FourierGrenobleFrance

Personalised recommendations