Skip to main content
SpringerLink
Log in

Antioxidants and CVD in diabetes: Where do we stand now?

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Diabetes is an oxidative stress disorder as a result of both hyperglycemia and increased levels of free fatty acids. Oxidative stress has been implicated in the pathogenesis of diabetes-related complications, and treatment with antioxidants seemed to be a promising therapeutic option. Although animal studies and preliminary human studies were initially encouraging, subsequent human studies have failed to show a clear benefit of antioxidants, whereas some studies have even suggested that they can be potentially harmful. Therefore, treatment with antioxidants cannot be currently recommended as a therapeutic option.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. King GL, Loeken MR: Hyperglycemia-induced oxidative stress in diabetic complications. Histochem Cell Biol 2004, 122:333–338.

    Article  PubMed  CAS  Google Scholar 

  2. Nishikawa T, Edelstein D, Du XL, et al.: Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000, 404:787–790.

    Article  PubMed  CAS  Google Scholar 

  3. Creager MA, Luscher TF, Cosentino F, Beckman JA: Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: Part I. Circulation 2003, 108:1527–1532.

    Article  PubMed  Google Scholar 

  4. Goldin A, Beckman JA, Schmidt AM, Creager MA: Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006, 114:597–605.

    Article  PubMed  CAS  Google Scholar 

  5. Hofmann MA, Drury S, Fu C, et al.: RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 1999, 97:889–901.

    Article  PubMed  CAS  Google Scholar 

  6. Brownlee M: Biochemistry and molecular cell biology of diabetic complications. Nature 2001, 414:813–820.

    Article  PubMed  CAS  Google Scholar 

  7. Craven PA, Studer RK, DeRubertis FR: Impaired nitric oxide-dependent cyclic guanosine monophosphate generation in glomeruli from diabetic rats. Evidence for protein kinase C-mediated suppression of the cholinergic response. J Clin Invest 1994, 93:311–320.

    PubMed  CAS  Google Scholar 

  8. Kolm-Litty V, Sauer U, Nerlich A, et al.: High glucose-induced transforming growth factor beta1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J Clin Invest 1998, 101:160–169.

    PubMed  CAS  Google Scholar 

  9. Du XL, Edelstein D, Dimmeler S, et al.: Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Invest 2001, 108:1341–1348.

    Article  PubMed  CAS  Google Scholar 

  10. Pacher P, Szabo C: Role of peroxynitrite in the pathogenesis of cardiovascular complications of diabetes. Curr Opin Pharmacol 2006, 6:136–141.

    Article  PubMed  CAS  Google Scholar 

  11. Johansen JS, Harris AK, Rychly DJ, Ergul A: Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol 2005, 4:5.

    Article  PubMed  CAS  Google Scholar 

  12. Maritim AC, Sanders RA, Watkins JB 3rd: Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003, 17:24–38.

    Article  PubMed  CAS  Google Scholar 

  13. Stewart-Lee AL, Forster LA, Nourooz-Zadeh J, et al.: Vitamin E protects against impairment of endothelium-mediated relaxations in cholesterol-fed rabbits. Arterioscler Thromb 1994, 14:494–499.

    PubMed  CAS  Google Scholar 

  14. Cinar MG, Ulker S, Alper G, Evinc A: Effect of dietary vitamin E supplementation on vascular reactivity of thoracic aorta in streptozotocin-diabetic rats. Pharmacology 2001, 62:56–64.

    Article  PubMed  CAS  Google Scholar 

  15. Palmer AM, Thomas CR, Gopaul N, et al.: Dietary antioxidant supplementation reduces lipid peroxidation but impairs vascular function in small mesenteric arteries of the streptozotocin-diabetic rat. Diabetologia 1998, 41:148–156.

    Article  PubMed  CAS  Google Scholar 

  16. Alper G, Olukman M, Irer S, et al.: Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat. Diabetes Metab Res Rev 2006, 22:190–197.

    Article  PubMed  CAS  Google Scholar 

  17. Gorbunov NV, Osipov AN, Sweetland MA, et al.: NO-redox paradox: direct oxidation of alpha-tocopherol and alpha-tocopherol-mediated oxidation of ascorbate. Biochem Biophys Res Commun 1996, 219:835–841.

    Article  PubMed  CAS  Google Scholar 

  18. Moens AL, Kass DA: Tetrahydrobiopterin and cardiovascular Disease. Arterioscler Thromb Vasc Biol 2006, 26:2439–2444.

    Article  PubMed  CAS  Google Scholar 

  19. Akamine EH, Kawamoto EM, Scavone C, et al.: Correction of endothelial dysfunction in diabetic female rats by tetrahydrobiopterin and chronic insulin. J Vasc Res 2006, 43:309–320.

    Article  PubMed  CAS  Google Scholar 

  20. Meininger CJ, Marinos RS, Hatakeyama K, et al.: Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency. Biochem J 2000, 349:353–356.

    Article  PubMed  CAS  Google Scholar 

  21. d’Uscio LV, Katusic ZS: Increased vascular biosynthesis of tetrahydrobiopterin in apolipoprotein E-deficient mice. Am J Physiol Heart Circ Physiol 2006, 290:H2466–H2471.

    Article  PubMed  CAS  Google Scholar 

  22. Hammes HP, Du X, Edelstein D, et al.: Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 2003, 9:294–299.

    Article  PubMed  CAS  Google Scholar 

  23. Marchetti V, Menghini R, Rizza S, et al.: Benfotiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/FoxO signaling. Diabetes 2006, 55:2231–2237.

    Article  PubMed  CAS  Google Scholar 

  24. Beckman JA, Goldfine AB, Gordon MB, Creager MA: Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans. Circulation 2001, 103:1618–1623.

    PubMed  CAS  Google Scholar 

  25. Timimi FK, Ting HH, Haley EA, et al.: Vitamin C improves endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol 1998, 31:552–557.

    Article  PubMed  CAS  Google Scholar 

  26. Ting HH, Timimi FK, Boles KS, et al.: Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1996, 97:22–28.

    Article  PubMed  CAS  Google Scholar 

  27. Schneider MP, Delles C, Schmidt BM, et al.: Superoxide scavenging effects of N-acetylcysteine and vitamin C in subjects with essential hypertension. Am J Hypertens 2005, 18:1111–1117.

    Article  PubMed  CAS  Google Scholar 

  28. Beckman JA, Goldfine AB, Gordon MB, et al.: Oral antioxidant therapy improves endothelial function in type 1 but not type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol 2003, 285:H2392–H2398.

    PubMed  CAS  Google Scholar 

  29. Chen H, Karne RJ, Hall G, et al.: High-dose oral vitamin C partially replenishes vitamin C levels in patients with type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance. Am J Physiol Heart Circ Physiol 2006, 290:H137–H145.

    Article  PubMed  CAS  Google Scholar 

  30. Jackson TS, Xu A, Vita JA, Keaney JF Jr: Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations. Circ Res 1998, 83:916–922.

    PubMed  CAS  Google Scholar 

  31. Economides PA, Khaodhiar L, Caselli A, et al.: The effect of vitamin E on endothelial function of micro-and macro-circulation and left ventricular function in type 1 and type 2 diabetic patients. Diabetes 2005, 54:204–211.

    Article  PubMed  CAS  Google Scholar 

  32. Stephens NG, Parsons A, Schofield PM, et al.: Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996, 347:781–786.

    Article  PubMed  CAS  Google Scholar 

  33. 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 [no authors listed]. Lancet 1999, 354:447–455.

  34. Yusuf S, Dagenais G, Pogue J, et al.: Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000, 342:154–160.

    Article  PubMed  CAS  Google Scholar 

  35. Lonn E, Bosch J, Yusuf S, et al.: Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005, 293:1338–1347.

    Article  PubMed  Google Scholar 

  36. Eidelman RS, Hollar D, Hebert PR, et al.: Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med 2004, 164:1552–1556.

    Article  PubMed  CAS  Google Scholar 

  37. Shekelle PG, Morton SC, Jungvig LK, et al.: Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease. J Gen Intern Med 2004, 19:380–389.

    Article  PubMed  Google Scholar 

  38. Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al.: Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005, 142:37–46.

    PubMed  CAS  Google Scholar 

  39. Ihlemann N, Rask-Madsen C, Perner A, et al.: Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects. Am J Physiol Heart Circ Physiol 2003, 285:H875–H882.

    PubMed  CAS  Google Scholar 

  40. Heitzer T, Krohn K, Albers S, Meinertz T: Tetrahydrobiopterin improves endothelium-dependent vasodilation by increasing nitric oxide activity in patients with type II diabetes mellitus. Diabetologia 2000, 43:1435–1438.

    Article  PubMed  CAS  Google Scholar 

  41. Stirban A, Negrean M, Stratmann B, et al.: Benfotiamine prevents macro-and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care 2006, 29:2064–2071.

    Article  PubMed  CAS  Google Scholar 

  42. Haupt E, Ledermann H, Kopcke W: Benfotiamine in the treatment of diabetic polyneuropathy—a three-week randomized, controlled pilot study (BEDIP study). Int J Clin Pharmacol Ther 2005, 43:71–77.

    PubMed  CAS  Google Scholar 

  43. Kushi LH, Folsom AR, Prineas RJ, et al.: Dietary antioxidant vitamins and death from coronary heart disease in post-menopausal women. N Engl J Med 1996, 334:1156–1162.

    Article  PubMed  CAS  Google Scholar 

  44. Kris-Etherton P, Eckel RH, Howard BV, et al.: Lyon Diet Heart Study: benefits of a Mediterranean-style, National Cholesterol Education Program/American Heart Association step I dietary pattern on cardiovascular disease. Circulation 2001, 103:1823–1825.

    PubMed  CAS  Google Scholar 

  45. Perez-Jimenez F, Alvarez de Cienfuegos G, Badimon L, et al.: International conference on the healthy effect of virgin olive oil. Eur J Clin Invest 2005, 35:421–424.

    Article  PubMed  CAS  Google Scholar 

  46. Esposito K, Marfella R, Ciotola M, et al.: Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 2004, 292:1440–1446.

    Article  PubMed  CAS  Google Scholar 

  47. van Dam RM, Hu FB: Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA 2005, 294:97–104.

    Article  PubMed  Google Scholar 

  48. Pereira MA, Parker ED, Folsom AR: Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28 812 postmenopausal women. Arch Intern Med 2006, 166:1311–1316.

    Article  PubMed  Google Scholar 

  49. Kuriyama S, Shimazu T, Ohmori K, et al.: Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. JAMA 2006, 296:1255–1265.

    Article  PubMed  CAS  Google Scholar 

  50. Iso H, Date C, Wakai K, et al.: The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med 2006, 144:554–562.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Microcirculation Laboratory, Palmer 321A, Beth Israel Deaconess Medical Center, West Campus, One Deaconess Road, Boston, MA, 02215, USA

    Aristidis Veves MD

Authors
  1. Susie Yim MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Atul Malhotra MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aristidis Veves MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aristidis Veves MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yim, S., Malhotra, A. & Veves, A. Antioxidants and CVD in diabetes: Where do we stand now?. Curr Diab Rep 7, 8–13 (2007). https://doi.org/10.1007/s11892-007-0003-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-007-0003-9

Keywords

Search

Navigation