Pediatric Nephrology

, Volume 21, Issue 12, pp 1790–1801 | Cite as

Vitamin E in renal therapeutic regimens



Administration of vitamin E in children with immunoglobulin A (IgA) nephropathy, focal segmental glomerulosclerosis (FSGS) and type I diabetes demonstrated potential towards ameliorating progression. Oral vitamin E therapy reduced endothelial dysfunction, lipid peroxidation and oxidative stress in patients with chronic kidney failure (CKF). Moreover, the use of vitamin E-bonded hemodialyzers reduced atherosclerotic changes, erythropoietin dosage and muscular cramps in patients on hemodialysis (HD). However, several controlled clinical trials failed to document beneficial effects on the study subjects’ cardiovascular and renal outcomes. A recent report of increased all-cause mortality in adult patients receiving high dose vitamin E therapy has caused considerable concern and debate. These issues regarding the efficacy and safety of vitamin E in renal therapeutic regimens will be reviewed in this article.


Vitamin E Alpha-tocopherol Glomerulosclerosis IgA nephropathy Chronic renal insufficiency 


  1. 1.
    Tucker JM, Townsend DM (2005) Alpha-tocopherol: roles in prevention and therapy of human disease. Biomed Pharmacother 59:380–387PubMedGoogle Scholar
  2. 2.
    Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE (2005) Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA 294:56–65PubMedGoogle Scholar
  3. 3.
    Pearson PJ, Lewis SA, Britton J, Fogarty A (2004) Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial. Thorax 59:652–656PubMedGoogle Scholar
  4. 4.
    Granot E, Kohen R (2004) Oxidative stress in abetalipoproteinemia patients receiving long-term vitamin E and vitamin A supplementation. Am J Clin Nutr 79:226–230PubMedGoogle Scholar
  5. 5.
    Vajro P, Mandato C, Franzese A, Ciccimarra E, Lucariello S, Savoia M, Capuano G, Migliaro F (2004) Vitamin E treatment in pediatric obesity-related liver disease: a randomized study. J Pediatr Gastroenterol Nutr 38:48–55PubMedGoogle Scholar
  6. 6.
    Pathak A, Roth P, Piscitelli J, Johnson L (2003) Effects of vitamin E supplementation during erythropoietin treatment of the anaemia of prematurity. Arch Dis Child Fetal Neonatal Ed 88:F324–F328PubMedGoogle Scholar
  7. 7.
    Chan JCM, Mahan JD, Trachtman H, Scheinman J, Flynn JT, Alon US, Lande MB, Weiss RA, Norkus EP (2003) Vitamin E therapy in IgA nephropathy: a double-blind, placebo controlled study. Pediatr Nephrol 18:1015–1019PubMedGoogle Scholar
  8. 8.
    Engler MM, Engler MB, Malloy MJ, Chiu EY, Schloetter MC, Paul SM, Stuehlinger M, Lin KY, Cooke JP, Morrow JD, Ridker PM, Rifai N, Miller E, Witztum JL, Mietus-Snyder M (2003). Antioxidant vitamins C and E improve endothelial function in children with hyperlipidemia: Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial. Circulation 108:1059–1063PubMedGoogle Scholar
  9. 9.
    Tesoriere L, D’Arpa D, Butera D, Allegra M, Renda D, Maggio A, Bongiorno A, Livrea MA (2001) Oral supplements of vitamin E improve measures of oxidative stress in plasma and reduce oxidative damage to LDL and erythrocytes in beta-thalassemia intermedia patients. Free Radical Res 34:529–540Google Scholar
  10. 10.
    Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P (2000) Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342:154–160PubMedGoogle Scholar
  11. 11.
    Skyrme-Jones RA, O’Brien RC, Berry KL, Meredith IT (2000) Vitamin E supplementation improves endothelial function in type I diabetes mellitus: a randomized, placebo-controlled study. J Am Coll Cardiol 36:94–102PubMedGoogle Scholar
  12. 12.
    Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A (2000) Secondary prevention with antioxidants of cardiovascular disease in end stage renal disease (SPACE): randomised placebo-controlled trial. Lancet 356:1213–1218PubMedGoogle Scholar
  13. 13.
    Fryer MJ (2000) Vitamin E as a protective antioxidant in progressive renal failure. Nephrology 5:1–7Google Scholar
  14. 14.
    Brigelius-Flohé R, Traber MG (1999) Vitamin E: function and metabolism. FASEB J 13:1145–1155PubMedGoogle Scholar
  15. 15.
    Singh U, Devaraj S, Jialal I (2005) Vitamin E, oxidative stress, and inflammation. Annu Rev Nutr 25:151–174PubMedGoogle Scholar
  16. 16.
    Singh U, Jialal I (2004) Anti-inflammatory effects of alpha-tocopherol. Ann N Y Acad Sci 1031:195–203PubMedGoogle Scholar
  17. 17.
    Traber MG, Sies H (1996) Vitamin E in humans: demand and delivery. Annu Rev Nutr 16:321–347PubMedGoogle Scholar
  18. 18.
    Schuelke M, Mayatepek E, Inter M, Becker M, Pfeiffer E, Speer A, Hübner C, Finckh B (1999) Treatment of ataxia in isolated vitamin E deficiency caused by α-tocopherol transfer protein deficiency. J Pediatr 134:240–244PubMedGoogle Scholar
  19. 19.
    Gordon N (2001) Hereditary vitamin-E deficiency. Dev Med Child Neurol 43:133–135PubMedGoogle Scholar
  20. 20.
    Morimoto H, Nakao K, Fukuoka K, Sarai A, Yano A, Kihara T, Fukuda S, Wada J, Makino H (2005) Long-term use of vitamin E-coated polysulfone membrane reduces oxidative stress markers in haemodialysis patients. Nephrol Dial Transplant 20:2775–2782PubMedGoogle Scholar
  21. 21.
    Vela C, Cristol JP, Ribstein J (2000) Antioxidant supplementation and chronic renal transplant dysfunction. Transplant Proc 32:427–428PubMedGoogle Scholar
  22. 22.
    Tahzib M, Frank R, Gauthier B, Valderrama E, Trachtman H (1999) Vitamin E treatment of focal segmental glomerulosclerosis: results of an open-label study. Pediatr Nephrol 13:649–652PubMedGoogle Scholar
  23. 23.
    Johnson KJ, Rehan A, Ward PA (1987) The role of oxygen radicals in kidney disease and tissue injury. Proc Upjohn Symp:115–121Google Scholar
  24. 24.
    Andreoli S (1991) Reactive oxygen molecules, oxidant injury and kidney disease. Pediatr Nephrol 5:733–742PubMedGoogle Scholar
  25. 25.
    Stratta P, Canavese C, Dogliani M (1991) The role of free radicals in the progression of kidney disease. Am J Kidney Dis 17:33–37PubMedGoogle Scholar
  26. 26.
    Morrison AR, Portilla D (1988) Lipid peroxidation and the kidney. In: Chow CK, Raton B (eds) Cellular antioxidant defense mechanisms. CRC Press, Boca Raton, pp 173–184Google Scholar
  27. 27.
    Miller ER, Pastor-Barriuso R, Dalal D, Riemersna RA, Appel LJ, Guallar E (2005) Meta-analysis: high dose vitamin E supplementation may increase all-cause mortality. Ann Int Med 142:37–46PubMedGoogle Scholar
  28. 28.
    Thakur V, Walker PD, Shah SV (1988) Evidence suggesting a role for hydroxyl radical in puromycin aminonucleoside-induced proteinuria. Kidney Int 34:494–499PubMedGoogle Scholar
  29. 29.
    Shah S (1989) Role of reactive oxygen metabolites in experimental glomerular disease. Kidney Int 35:1093–1106PubMedGoogle Scholar
  30. 30.
    Trachtman H, Schwob N, Maesaka J, Valderrama E (1995) Dietary vitamin E supplementation ameliorates kidney injury in chronic puromycin aminonucleoside nephropathy. J Am Soc Nephr 5:1811–1819Google Scholar
  31. 31.
    Van den Branden C, Verelst R, Vamecq J, Vanden Houte K, Verbeelen D (1997) Effect of vitamin E on antioxidant enzymes, lipid peroxidation products and glomerulosclerosis in the rat remnant kidney. Nephron 76:77–81PubMedGoogle Scholar
  32. 32.
    Hahn S, Krieg RJ Jr, Hisano S, Chan W, Kuemmerle NB, Saborio P, Chan JC (1999) Vitamin E suppresses oxidative stress and glomerulosclerosis in rat remnant kidney. Pediatr Nephrol 13(3):195–198PubMedGoogle Scholar
  33. 33.
    Mune M, Otani H, Yukawa S (2002) Effects of antioxidants on kidney disease. Mech Aging Dev 123:1041–1046PubMedGoogle Scholar
  34. 34.
    Van den Branden C, Deman A, Ceyssens B, Pauwels M, Empsen C, Verbeelen D (2002) Vitamin E protects renal antioxidant enzymes and attenuates glomerulosclerosis in Adriamycin-treated rats. Nephron 91:129–133PubMedGoogle Scholar
  35. 35.
    Trachtman H, Chan JCM, Chan W, Brandt R, Wakely P, Futterweit S, Maesaka J, Ma C (1996) Vitamin E ameliorates kidney injury in an experimental model of immunoglobulin a nephropathy. Pediatr Res 40:620–626PubMedGoogle Scholar
  36. 36.
    Ward KP, Kuemmerle NB, Krieg RJ Jr, Saboria P, Norkus EP, Chan JCM (2000) Indices of progression of IgA nephropathy are modulated by α-tocopherol in rats. Clin Exp Nephrol 4:187–192Google Scholar
  37. 37.
    Kuemmerle NB, Krieg RJ Jr, Chan W, Trachtman H, Norkus EP, Chan JCM (1999) Influence of α-tocopherol over the time course of experimental IgA nephropathy. Pediatr Nephrol 13:108–112PubMedGoogle Scholar
  38. 38.
    Chade AR, Krier JD, Rodriquez-Porcel M, Breen JF, McKusick MA, Lerman A, Lerman LO (2004) Comparison of acute and chronic antioxidant interventions in experimental renovascular disease. Amer J Physiol 286:F1079–F1086Google Scholar
  39. 39.
    Koya D, Hayashi K, Kitada M, Kashiwagi A, Kikkawa R, Haneda M (2003) Effects of antioxidants in diabetes-induced oxidative stress in the glomeruli of diabetic rats. J Am Soc Nephrol 14:S250–S253PubMedGoogle Scholar
  40. 40.
    Koya D, Lee IK, Ishi H, Kanoh H, King GL (1997) Prevention of glomerular dysfunction in diabetic rats by treatment with d-alpha-tocopherol. J Am Soc Nephrol 8:426–435PubMedGoogle Scholar
  41. 41.
    Cojocel C, Al-Maghrebi M, Thomson MS, Rawoot P, Raghupathy R (2005) Modulation of the transforming growth factor beta1 by vitamin E in early nephropathy. Med Princ Pract 14(6):422–429PubMedGoogle Scholar
  42. 42.
    Montero A, Munger KA, Khan RZ, Valdivielso JM, Morrow JD, Guasch A, Ziyadeh FN, Badr KF (2000) F(2)-isoprostanes mediate high glucose-induced TGF-beta synthesis and glomerular proteinuria in experimental type I diabetes. Kidney Int 58:1963–1972PubMedGoogle Scholar
  43. 43.
    Stulak JM, Lerman A, Porcel MR, Caccitolo JA, Romero JC, Schaff HV, Napoli C, Lerman LO (2001) Renal vascular function in hypercholesterolemia is preserved by chronic antioxidant supplementation. J Am Soc Nephrol 12:1882–1891PubMedGoogle Scholar
  44. 44.
    Traber MG (1999) Vitamin E. In: Shils M, Olson JA, Shike M, Ross AC (eds) Nutrition in health and disease, 9 edn. Williams & Wilkins, Baltimore, pp 347–362Google Scholar
  45. 45.
    Islam KN, O’Byrne D, Devaraj S, Palmer B, Grundy SM, Jialal I (2000) Alpha-tocopherol supplementation decreases the oxidative susceptibility of LDL in renal failure patients on dialysis therapy. Atherosclerosis 150:217–224PubMedGoogle Scholar
  46. 46.
    Roob JM, Khoschsorur G, Tiran A, Horina JH, Holzer H, Winklhofer-Roob BM (2000) Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis. J Am Soc Nephrol 11:539–549PubMedGoogle Scholar
  47. 47.
    Maccarrone M, Meloni C, Manca-di-Villahermosa S, Cococcetta N, Casciani CU, Finazzi-Agro A, Taccone-Gallucci M (2001) Vitamin E suppresses 5-lipoxygenase-mediated oxidative stress in peripheral blood mononuclear cells of hemodialysis patients regardless of administration route. Am J Kidney Dis 37:964–969PubMedGoogle Scholar
  48. 48.
    Cristol JP, Bosc JY, Badiou S, Leblanc M, Lorrho R, Descomps B, Canaud B (1997) Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation. Nephrol Dial Transplant 12:2312–2317PubMedGoogle Scholar
  49. 49.
    Ono K (1985) Effects of large dose vitamin E supplementation on anemia in hemodialysis patients. Nephron 40:440–445PubMedGoogle Scholar
  50. 50.
    Ono K (1985) Reduction of osmotic haemolysis and anaemia by high dose vitamin E supplementation in regular haemodialysis patients. Proc Eur Dial Transplant Assoc Eur Ren Assoc 21:296–299PubMedGoogle Scholar
  51. 51.
    Diepeveen SH, Verhoeven GW, Van Der Palen J, Dikkeschel LD, Van Tits LJ, Kolsters G, Offferman JJ, Bilo HJ, Stalenhoef AF (2005) Effects of atorvastatin and vitamin E on lipoproteins and oxidative stress in dialysis patients: a randomized-controlled trial. J Int Med 257:438–445Google Scholar
  52. 52.
    Wang X, Quinn PJ (1999) Vitamin E and its function in membranes. Prog Lipid Res 38:309–336PubMedGoogle Scholar
  53. 53.
    Erin AN, Spirin MM, Tabidze IV, Kagan VE (1984) Formation of α-tocopherol complexes with fatty acids. A hypothetical mechanism of stabilization of biomembranes by vitamin E. Biochim Biophys Acta 774:96–102PubMedGoogle Scholar
  54. 54.
    Forrest VJ, Kang Y, McClain DE, Robinson DH, Ramakrishnan N (1994) Oxidative stress-induced apoptosis prevented by Trolox. Free Radical Biol Med 16:675–684Google Scholar
  55. 55.
    Huang N, Lineberg B, Stner M (1988) Alpha-tocopherol, a potent modulator of endothelial cell function. Thromb Res 50:547–557PubMedGoogle Scholar
  56. 56.
    Cachia O, Léger CL, Descomps B (1998) Monocyte superoxide production is highly sensitive and inversely related to normal changes of low density lipoprotein in α -tocopherol. Atherosclerosis 138:263–269PubMedGoogle Scholar
  57. 57.
    Luostarinen R, Siegbahn A, Saldeen T (1991) Effects of dietary supplementation with vitamin E on human neutrophil chemotaxis and generation of LTB4. Upsala J Med Sci 96:103–111PubMedCrossRefGoogle Scholar
  58. 58.
    Freedman JE, Farhat JH, Loscalzo J, Keaney JFJ (1996) Alpha-tocopherol inhibits aggregation of human platelets by a protein kinase C-dependent mechanism. Circulation 94:2434–2440PubMedGoogle Scholar
  59. 59.
    US Renal Data System (2003) USRDS 2003 Annual Data Report. The National Institutes of Health, National Institute of Diabetes and Digestive Diseases, Bethesda, MDGoogle Scholar
  60. 60.
    North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) (2003) Annual report: renal transplantation, dialysis, chronic renal insufficiency. EMMES, Rockville, MDGoogle Scholar
  61. 61.
    McDonald SP, Craig JC (2004) Long-term survival of children with end-stage renal disease. N Engl J Med 350:2654–2662PubMedGoogle Scholar
  62. 62.
    Chavers BM, Li S, Collins AJ, Herzog CA (2002) Cardiovascular disease in pediatric chronic dialysis patients. Kidney Int 62:648–653PubMedGoogle Scholar
  63. 63.
    Groothoff JW, Gruppen MP, Offringa M, Hutten J, Lilien MR, Van De Kar NJ, Wolff ED, Davin JC, Heymans HS (2002) Mortality and causes of death of end-stage renal disease in children: a Dutch cohort study. Kidney Int 61:621–629PubMedGoogle Scholar
  64. 64.
    Parekh RS, Carroll CE, Wolfe RA, Port FK (2002) Cardiovascular mortality in children and young adults with end-stage kidney disease. J Pediatr 141:191–197PubMedGoogle Scholar
  65. 65.
    Mitsnefes MM, Kimball TR, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2003) Left ventricular mass and systolic performance in pediatric patients with chronic renal failure. Circulation 107:864–868PubMedGoogle Scholar
  66. 66.
    Silverstein DM, Palmer J, Polinsky MS, Braas C, Conley SB, Baluarte HJ (2000) Risk factors for hyperlipidemia in long-term pediatric renal transplant recipients. Pediatr Nephrol 14:105–110PubMedGoogle Scholar
  67. 67.
    Mann JF, Lonn EM, Yi Q, Gerstein HC, Hoogwerf BJ, Pogue J, Bosch J, Dagenais GR, Yusuf S, HOPE Investigators (2004) Effects of vitamin E on cardiovascular outcomes in people with mild-to-moderate renal insufficiency: results of the HOPE study. Kidney Int 65:1375–1380PubMedGoogle Scholar
  68. 68.
    Ghiadoni L, Cupisti A, Huang Y, Mattei P, Cardinal H, Favilla S, Rindi P, Barsotti G, Taddei S, Salvetti A (2004) Endothelial dysfunction and oxidative stress in chronic renal failure. J Nephrol 17:512–519PubMedGoogle Scholar
  69. 69.
    Yilmaz MI, Saglam M, Caglar K, Cakir E, Sonmez A, Ozgurtas T, Aydin A, Eyileten T, Ozcan O, Acikel C, Tasar M, Genctoy G, Erbil K, Vural A, Zoccali C (2006) The determinants of endothelial dysfunction in CKD: oxidative stress and asymmetric dimethylarginine. Am J Kidney Dis 47:42–50PubMedGoogle Scholar
  70. 70.
    Usberti M, Gerardi GM, Gazzotti RM, Benedini S, Archetti S, Sugherini L, Valentini M, Tira P, Bufano G, Albertini A, Di Lorenzo D (2002) Oxidative stress and cardiovascular disease in dialyzed patients. Nephron 91:25–33PubMedGoogle Scholar
  71. 71.
    Bochev P, Tzvetkov N, Alexandrova M, Magrisso M, Bechev B, Monovich O, Markova V (1997) Development of oxidative stress in chronic kidney insufficiency following the progression of disease. Nephron 77:244–245PubMedGoogle Scholar
  72. 72.
    Zwolinska D, Grzeszczak W, Szczepanska M, Kilis-Pstrusinska K, Szprynger K (2006) Vitamins A, E and C as non-enzymatic antioxidants and their relation to lipid peroxidation in children with chronic renal failure. Nephron Clinical Practice 103:c12–c18PubMedGoogle Scholar
  73. 73.
    Kari JA, Donald AE, Vallace DT, Bruckdorfer KR, Leone A, Mullen MJ, Bunce T, Dorado B, Deanfield JE, Rees L (1997) Physiology and biochemistry of endothelial function in children with chronic renal failure. Kidney Int 52:468–472PubMedGoogle Scholar
  74. 74.
    Annuk M, Lind L, Linde T, Fellström B (2001) Impaired endothelium-dependent vasodilatation in renal failure in humans. Nephrol Dial Transplant 16:302–306PubMedGoogle Scholar
  75. 75.
    Saran R, Novak JE, Desai A, Abdulhayoglu E, Warren JS, Bustami R, Handelman GJ, Barbato D, Weitzel W, D’Alecy LG, Rajagopalan S (2003) Impact of vitamin E on plasma asymmetric dimethylarginine (ADMA) in chronic kidney disease (CKD): a pilot study. Nephrol Dial Transplant 18:2415–2420PubMedGoogle Scholar
  76. 76.
    Kobayashi S, Moriya H, Aso K, Ohtake T (2003) Vitamin E-bonded hemodialyzer improves atherosclerosis associated with a rheological improvement of circulating red blood cells. Kidney Int 63:1881–1887PubMedGoogle Scholar
  77. 77.
    Panel on Dietary Antioxidants and Related Compounds, Food and Nutrition Board, Institute of Medicine, National Academy of Sciences (2000) Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. National Academy Press, Washington DC, 249–259Google Scholar
  78. 78.
    Himmelfarb J, Kane J, McMonagle E (2003) Alpha and gamma tocopherol metabolism in healthy subjects and patients with end-stage renal disease. Kidney Int 64:978–991PubMedGoogle Scholar
  79. 79.
    Galli F, Floridi AG, Floridi A, Buoncristiani U (2004) Accumulation of vitamin E metabolites in the blood of renal failure patients. Clin Nutr 23:205–212PubMedGoogle Scholar
  80. 80.
    Muller C, Eisenbrand G, Gradinger M, Rath T, Albert FW, Vienken J, Singh R, Farmer PB, Stockis JP, Janzowski C (2004) Effects of hemodialysis, dialyzer type and iron infusion on oxidative stress in uremic patients. Free Radical Res 38:1093–1100Google Scholar
  81. 81.
    Ward RA, McLeish KR (2003) Oxidant stress in hemodialysis patients: what are the determining factors? Artif Organs 27:230–236PubMedGoogle Scholar
  82. 82.
    Khajehdehi P, Mojerlou M, Behzadi S, Rais-Jalali GA (2001) A randomized, double-blind, placebo-controlled trial of supplementary vitamins E, C and their combination for treatment of haemodialysis cramps. Nephrol Dial Transplant 16:1448–1451PubMedGoogle Scholar
  83. 83.
    Mydlik M, Derzstova K, Racz O, Sipulova A, Boldizsar J, Lovasova E, Hribikova M (2002) Vitamin E as an antioxidant agent in CAPD patients. Int J Artif Organs 25:373–378PubMedGoogle Scholar
  84. 84.
    Yang CC, Hsu SP, Wu MS, Hsu SM, Chien CT (2006) Effects of vitamin C infusion and vitamin E-coated membrane on hemodialysis-induced oxidative stress. Kidney Int 69:706–714PubMedGoogle Scholar
  85. 85.
    Clermont G, Lecour S, Cabanne JF, Motte G, Guilland JC, Chevet D, Rochette L (2001) Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients. Free Radical Biol Med 31:233–241Google Scholar
  86. 86.
    Satoh M, Yamasaki Y, Nagake Y, Kasahara J, Hashimoto M, Nakanishi N, Makino H (2001) Oxidative stress is reduced by the long-term use of vitamin E-coated dialysis filters. Kidney Int 59:1943–1950PubMedGoogle Scholar
  87. 87.
    Miyazaki H, Matsuoka H, Itabe H, Usui M, Ueda S, Okuda S, Imaizumi T (2000) Hemodialysis impairs endothelial function via oxidative stress: effects of vitamin E-coated dialyzer. Circulation 101:1002–1006PubMedGoogle Scholar
  88. 88.
    Girndt M, Lengler S, Kaul H, Sester U, Sester M, Kohler H (2000) Prospective crossover trial of the influence of vitamin E-coated dialyzer membranes on T-cell activation and cytokine induction. Am J Kidney Dis 35:95–104PubMedGoogle Scholar
  89. 89.
    Nakamura T, Kawagoe Y, Matsuda T, Takahashi Y, Sekizuka K, Ebihara I, Koide H (2003) Effects of LDL apheresis and vitamin E-modified membrane on carotid atherosclerosis in hemodialyzed patients with arteriosclerosis obliterans. Kidney Blood Press Res 26:185–191PubMedGoogle Scholar
  90. 90.
    Zoccali C, Bode-Boger S, Mallamaci F, Benedetto F, Tripepi G, Malatino L, Cataliotti A, Bellanuova I, Fermo I, Frolich J, Boger R (2001) Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet 358:2113–2117PubMedGoogle Scholar
  91. 91.
    Maccarrone M, Taccone-Gallucci M, Finazzi-Agro A (2003) 5-Lipoxygenase-mediated mitochondrial damage and apoptosis of mononuclear cells in ESRD patients. Kidney Int Suppl 84:S33–S36PubMedGoogle Scholar
  92. 92.
    Al-Jondeby MS, Cabaguing IT, Pajarillo AA, Hawas FA, Mousa DH, Al-Sulaiman MM, Shaheen FA, Al-Khader AA (2003) Comparative crossover controlled study using polysulphone and vitamin E coated dialyzers. Saudi Med J 24:265–268PubMedGoogle Scholar
  93. 93.
    Bonnefont-Rousselot D, Lehmann E, Jaudon MC, Delattre J, Perrone B, Rechke JP (2000) Blood oxidative stress and lipoprotein oxidizability in haemodialysis patients: effect of the use of a vitamin E-coated dialysis membrane. Nephrol Dial Transplant 15:2020–2028PubMedGoogle Scholar
  94. 94.
    Galli F, Rovidati S, Chiarantini L, Campus G, Canestrari F, Buoncristiani U (1998) Bioreactivity and biocompatibility of a vitamin E-modified multilayer hemodialysis filter. Kidney Int 54:580–589PubMedGoogle Scholar
  95. 95.
    Morena M, Cristol JP, Descomps B, Canaud B (1999) Does vitamin E bound on dialysis membrane improve the LDL susceptibility to oxidation? Lessons from an in vitro model. In: Ronco C, La Greca G (eds) Vitamin E-bonded membrane: a further step in dialysis optimization. Contrib Nephrol Karger Basel 127:128–138Google Scholar
  96. 96.
    Mune M, Yukawa S, Kishino M, Otani H, Kimura K, Nishikawa O, Takhashi T, Kodama N, Saika Y, Yamada Y (1999) Effect of vitamin E on lipid metabolism and atherosclerosis in ESRD patients. Kidney Int 56(Suppl 71):S126–S129Google Scholar
  97. 97.
    Smith KS, Lee CL, Ridlington JW, Leonard SW, Devaraj S, Traber MG (2003) Vitamin E supplementation increases circulating vitamin E metabolites tenfold in end-stage renal disease patients. Lipids 38:813–819PubMedGoogle Scholar
  98. 98.
    Túri S, Nemeth I, Varga I, Matkovics B (1999) Erythropoietin and oxidative stress in haemodialysis: beneficial effects of vitamin E supplementation. Nephrol Dial Transpl 14:252–253Google Scholar
  99. 99.
    Nemeth I, Turi S, Haszon I, Bereczki C (2000) Vitamin E alleviates the oxidative stress of erythropoietin in uremic children on hemodialysis. Pediatr Nephrol 14:13–17PubMedGoogle Scholar
  100. 100.
    Usberti M, Gerardi G, Micheli A, Tira P, Bufano G, Gaggia P, Moville E, Cancarini GC, DeMarinis S, D’Avolio G, Broccolli R, Manganoni A, Albertini A, DiLorenzo D (2002) Effects of a vitamin bonded membrane and of glutathione on anemia and erythropoietin requirements in hemodialysis patients. J Nephrol 15:558–564PubMedGoogle Scholar
  101. 101.
    Triolo L, Malaguti M, Ansali F, Comunian MC, Arcangeloni O, Coppolino F, Marrocco F, Sicoli R, Biagini M (2003) Vitamin E-bonded cellulose membrane, lipoperoxidation, and anemia in hemodialysis patients. Artif Cells Blood Substit Immobil Biotech 31:185–191Google Scholar
  102. 102.
    Ha H, Kim KH (1999) Pathogenesis of diabetic nephropathy: the role of oxidative stress and protein kinase C. Diabetes Res Clin Pract 45:147–151PubMedGoogle Scholar
  103. 103.
    Baynes J, Thorpe S (1999) The role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48:1–9PubMedGoogle Scholar
  104. 104.
    Guigliano DA, Ceriello A, Paolisso G (1996) Oxidative stress and diabetic vascular complications. Diabetes Care 19:257–267Google Scholar
  105. 105.
    Jialal I, Devaraj S, Venugopal SK (2002) Oxidative stress, inflammation, and diabetic vasculopathies: the role of alpha tocopherol therapy. Free Radical Res 36:1331–1336Google Scholar
  106. 106.
    Rosen P, Toeller M (1999) Vitamin E in diabetes: increased oxidative stress and its prevention as a strategy to prevent vascular complications? Int J Vitam Nutr Res 69:206–212PubMedGoogle Scholar
  107. 107.
    Pinkney JH, Downs L, Hopton M, Mackness MI, Bolton CH (1999) Endothelial dysfunction in Type 1 diabetes mellitus: relationship with LDL oxidation and the effects of vitamin E. Diabet Med 16:993–999PubMedGoogle Scholar
  108. 108.
    Upritchard JE, Sutherland WH, Mann JI (2000) Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes. Diabetes Care 23:733–738PubMedGoogle Scholar
  109. 109.
    Devaraj S, Jialal I (2000) Alpha tocopherol supplementation decreases CRP and Mo IL-6 from DM-2. Free Radical Biol Med 29:790–792Google Scholar
  110. 110.
    Devaraj S, Chan AV Jr, Jialal I (2002) Alpha tocopherol supplementation decreases plasminogen activator inhibitor-1 and P-selectin levels in type 2 diabetic patients. Diabetes Care 25:524–529PubMedGoogle Scholar
  111. 111.
    Gerstein HC, Bosch J, Pogue J, Taylor DW, Zinman B, Yusuf S (1996) Rationale and design of a large study to evaluate the renal and cardiovascular effects of an ACE inhibitor and vitamin E in high-risk patients with diabetes. The MICRO-HOPE Study. Microalbuminuria, Cardiovascular, and Renal Outcomes. Heart Outcomes Prevention Evaluation. Diabetes Care 19:1225–1228PubMedGoogle Scholar
  112. 112.
    Bursell SE, Clermont AC, Aiello LP, Aiello LM, Schlossman DK, Feener EP, Laffel L, King GL (1999) High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Diabetes Care 22:1245–1251PubMedGoogle Scholar
  113. 113.
    Crino A, Schiaffini R, Manfrini S, Mesturino C, Visalli N, Beretta Anguissola G, Suraci C, Pitocco D, Spera S, Corbi S, Matteoli MC, Patera IP, Manca Bitti ML, Bizzarri C, Pozzilli P, IMDIAB group (2004) A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX). Eur J Endocrinol 150:719–724PubMedGoogle Scholar
  114. 114.
    The Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group (2002) Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 287:2563–2569Google Scholar
  115. 115.
    Gaede P, Poulsen HE, Parving HH, Pedersen O (2001) Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in type 2 diabetic patients. Diabet Med 18:756–760PubMedGoogle Scholar
  116. 116.
    Farvid MS, Jalali M, Siassi F, Hosseini M (2005) Comparison of the effects of vitamins and/or mineral supplementation on glomerular and tubular dysfunction in type 2 diabetes. Diabetes Care 28:2458–2464PubMedGoogle Scholar
  117. 117.
    Aakhus S, Dahl K, Wideroe TE (1999) Cardiovascular morbidity and risk factors in renal transplant patients. Nephrol Dial Transplant 14:648–654PubMedGoogle Scholar
  118. 118.
    Kim YH, Mun KC, Lee SS, Seo SH, Kwak CS, Park SB, Kim HC (2000) Oxidative damage in renal transplant patients. Transplant Proc 32:1777–1778PubMedGoogle Scholar
  119. 119.
    Rabl H, Khoschsorur G, Colombo T (1993) A multivitamin infusion prevents lipid peroxidation and improves transplantation performance. Kidney Int 43:912–917PubMedGoogle Scholar
  120. 120.
    Williams MJ, Sutherland WH, McCormick MP, de Jong SA, McDonald JR, Walker RJ (2001) Vitamin C improves endothelial dysfunction in renal allograft recipients. Nephrol Dial Transplant 16:1251–1255PubMedGoogle Scholar
  121. 121.
    Hussein O, Rosenblat M, Refael G, Aviram M (1997) Dietary selenium increases cellular glutathione peroxidase activity and reduces the enhanced susceptibility to lipid peroxidation of plasma and low-density lipoprotein in kidney transplant recipients. Transplantation 63:679–685PubMedGoogle Scholar
  122. 122.
    Blackhall ML, Coombes JS, Fassett R (2004) The relationship between antioxidant supplements and oxidative stress in renal transplant recipients: a review. ASAIO J 50:451–457PubMedGoogle Scholar
  123. 123.
    Sutherland WH, Walker RJ, De-Jong SA, Upritchard JE (1999) Supplementation with tomato juice increases plasma lycopene but does not alter susceptibility to oxidation of low-density lipoproteins from renal transplant recipients. Clin Nephrol 52:30–36PubMedGoogle Scholar
  124. 124.
    Bandyopadhyay D, Chattopadhyay A, Ghosh G, Datta AG (2004) Oxidative stress-induced ischemic heart disease: protection by antioxidants. Curr Med Chem 11:369–387PubMedGoogle Scholar
  125. 125.
    Coombes JS, Powers SK, Demirel HA, Jessup J, Vincent HK, Hamilton KL, Naito H, Shanley RA, Sen CK, Packer L, Ji LL (2000) Effect of combined supplementation with vitamin E and alpha-lipoic acid on myocardial performance during in vivo ischemia-reperfusion. Acta Physiol Scand 169:261–269PubMedGoogle Scholar
  126. 126.
    Blackhall MR, Fassett RG, Sharman JE, Geraghty DP, Coombes JS (2005) Effects of antioxidant supplementation on blood cyclosporin A and glomerular filtration rate in renal transplant recipients. Nephrol Dial Transplant 20:1970–1975PubMedGoogle Scholar
  127. 127.
    Kashem A, Masayuki E, Nomoto Y (1994) FcαR expression on polymorphonuclear leukocyte and superoxide generation in IgA nephropathy. Kidney Int 45:868–875PubMedGoogle Scholar
  128. 128.
    Chen A, Chen WP, Sheu LF, Lin CY (1994) Pathogenesis of IgA nephropathy: in-vitro activation of human mesangial cells by IgA immuno complex leads to cytokine secretion. J Path 173:119–126PubMedGoogle Scholar
  129. 129.
    Diamond JR (1991) Analogous pathobiologic mechanisms in glomerulosclerosis and atherosclerosis. Kidney Int Suppl 31:S29–S34PubMedGoogle Scholar
  130. 130.
    Parra T, de-Arriba G, Arribas I, Perez de Lema G, Rodriguez-Puyol D, Rodriguez-Puyol M (1998) Cyclosporine A nephrotoxicity: role of thromboxane and reactive oxygen species. J Lab Clin Med 131:63–70PubMedGoogle Scholar
  131. 131.
    Parra T, Conejo GJR, Carballo AF, de-Arriba G (2003) Antioxidant nutrients protect against cyclosporine A nephrotoxicity. Toxicology 189:99–111Google Scholar
  132. 132.
    Wang C, Salahudeen AK (1995) Lipid peroxidation accompanies cyclosporine nephrotoxicity: effects of vitamin E. Kidney Int 47:927–934PubMedGoogle Scholar
  133. 133.
    Jenkins JK, Huang H, Ndebele K, Salahudeen AK (2001) Vitamin E inhibits renal mRNA expression of COX II, HO I, TGFbeta, and osteopontin in the rat model of cyclosporine nephrotoxicity. Transplantation 71:331–334PubMedGoogle Scholar
  134. 134.
    Barany P, Sstenvinkel P, Ottosson-Seeberger A, Alvestrand A, Morrow J, Roberts JJ, Salahudeen AK (2001) Effect of 6 weeks of vitamin E administration on renal haemodynamic alterations following a single dose of neural in healthy volunteers. Nephrol Dialysis Transpl 16:580–584Google Scholar
  135. 135.
    McQueen MJ, Lonn E, Gerstein HC, Bosch J, Yusuf S (2005) The HOPE (Heart Outcomes Prevention Evaluation) Study and its consequences. Scand J Clin Lab Invest Supp 240:140–156Google Scholar
  136. 136.
    GISSI-Prevenzione Investigators (1999) 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 354:447–455Google Scholar
  137. 137.
    Heart Protection Study Collaborative Group (2002) MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:23–33Google Scholar
  138. 138.
    Stampfer M, Hennekens C, Manson J, Colditz G, Rosner B, Willett W (1993) Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 328:1444–1449PubMedGoogle Scholar
  139. 139.
    Rimm, ER, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC (1993) Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 328:1450–1456PubMedGoogle Scholar
  140. 140.
    Devaraj S, Jialal I (2005) Failure of vitamin E in clinical trials: is gamma-tocopherol the answer? Nutr Rev 63:290–293PubMedGoogle Scholar
  141. 141.
    Jiang Q, Elson-Schwab I, Courtemance C, Ames BN (2000) Gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc Natl Acad Sci USA 97:11494–11499PubMedGoogle Scholar
  142. 142.
    Cooney RV, Franke AA, Harwood PJ, Hatch-Pigott V, Custer LJ, Mordan LJ (1993) Gamma-tocopherol detoxification of nitrogen dioxide: superiority to alpha-tocopherol. Proc Natl Acad Sci USA 90:1771–1775PubMedGoogle Scholar
  143. 143.
    Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ (1996) Randomized controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347:781–786PubMedGoogle Scholar
  144. 144.
    Kontush A, Finckh B, Karten B, Kohlschütter A, Beisiegel U (1996) Antioxidant and pro-oxidant activity of α-tocopherol in human plasma and low density lipoprotein. J Lipid Res 37:1436–1448PubMedGoogle Scholar
  145. 145.
    Shekelle PG, Morton SC, Jungvig LK, Udani J, Spar M, Tu W (2004) Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease. J Gen Intern Med 19:380–389PubMedGoogle Scholar
  146. 146.
    Eidelman RS, Hollar D, Hebert PR, Lamas GA, Hennekens CH (2004) Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med 164:1552–1556PubMedGoogle Scholar
  147. 147.
    Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ (2003) Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 361:2017–2023PubMedGoogle Scholar
  148. 148.
    Marras C, McDermott MP, Rochon PA, Tanner CM, Naglie G, Rudolph A (2005) Survival in Parkinson disease: thirteen-year follow-up of the DATATOP cohort. Neurology 64:87–93PubMedGoogle Scholar
  149. 149.
    Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med 336:1216–1222PubMedGoogle Scholar
  150. 150.
    de Gaetano G, Collaborative Group of the Primary Prevention Project (2001) Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomized trial in general practice. Collaborative Group of the Primary Prevention Project. Lancet 357:89–95PubMedGoogle Scholar
  151. 151.
    Taylor HR, Tikellis G, Robman LD, McCarty CA, McNeil J (2002) Vitamin E supplementation and macular degeneration: randomized controlled trial. BMJ 325:11PubMedGoogle Scholar
  152. 152.
    Hathcock JN (1997) Vitamins and minerals: efficacy and safety. Am J Clin Nutr 66:427–423Google Scholar
  153. 153.
    Brigelius-Flohe R, Kelly FJ, Salonen JT, Neuzil J, Zingg JM, Azzi A (2002) The European perspective on vitamin E: current knowledge and future research. Am J Clin Nutr 76:703–716PubMedGoogle Scholar
  154. 154.
    Feranchak AP, Sontag MK, Wagener JS, Hammond KB, Accurso FJ, Sokol RJ (1999) Prospective, long-term study of fat-soluble vitamin status in children with cystic fibrosis identified by newborn screen. J Pediatr 135:601–610PubMedGoogle Scholar
  155. 155.
    Roongpraiwan R, Suthutvoravut U, Feungpean B, Phuapradit P (2002) Effect of oral vitamin E supplementation in children with cholestasis. J Med Assoc Thai 85(Suppl 4):S1199–S1205PubMedGoogle Scholar
  156. 156.
    Sokol RJ, Guggenheim M, Iannaccone ST, Barkhaus PE, Miller C, Silverman A, Balistreri WF, Heubi JE (1985) Improved neurologic function after long-term correction of vitamin E deficiency in children with chronic cholestasis. N Engl J Med 313:1580–1586PubMedCrossRefGoogle Scholar
  157. 157.
    Sokol RJ, Heubi JE, Butler-Simon N, McClung HJ, Lilly JR, Silverman A (1987) Treatment of vitamin E deficiency during chronic childhood cholestasis with oral d-alpha-tocopheryl polyethylene glycol-1000 succinate. Gastroenterology 93:975–985PubMedGoogle Scholar
  158. 158.
    Muller DP, Lloyd JK, Bird AC (1977) Long-term management of abetalipoproteinaemia. Possible role for vitamin E. Arch Dis Child 52:209–214PubMedCrossRefGoogle Scholar
  159. 159.
    Runge P, Muller DP, McAllister J, Calver D, Lloyd JK, Taylor D (1986) Oral vitamin E supplements can prevent the retinopathy of abetalipoproteinaemia. Br J Ophthalmol 70:166–173PubMedGoogle Scholar
  160. 160.
    Doria-Lamba L, De Grandis E, Cristiani E, Fiocchi I, Montaldi L, Grosso P, Gellera C (2006) Efficacious vitamin E treatment in a child with ataxia with isolated vitamin E deficiency. Eur J Pediatr 165:494–495PubMedGoogle Scholar
  161. 161.
    Aparicio JM, Belanger-Quintana A, Suàrez L, Mayo D, Benìtez J, Dìaz M, Escobar H (2001) Ataxia with isolated Vitamin E deficiency: case report and review of the Literature. J Pediatr Gastroenterol Nutr 33:206–210PubMedGoogle Scholar
  162. 162.
    Acuff RV, Thedford SS, Hidiroglou NN, Papas AM, Odom TAJ (1994) Relative bioavailability of RRR- and all-rac-alpha-tocopheryl acetate in humans: studies using deuterated compounds. Am J Clin Nutr 60:397–402PubMedGoogle Scholar

Copyright information

© IPNA 2006

Authors and Affiliations

  1. 1.University of AlexandriaAlexandriaEgypt
  2. 2.The Barbara Bush Children’s HospitalMaine Medical CenterPortlandUSA
  3. 3.University of VermontBurlingtonUSA

Personalised recommendations