Written by Luc Geeraert and the CAM-Cancer Consortium.
Updated September 30, 2015

Vitamin E during cancer treatment

Abstract and key points

  • Vitamin E is a generic term encompassing different chemical compounds, each having a different metabolism and biological activity.
  • Vitamin E compounds are fat-soluble antioxidants and some of them might have additional presumed anticancer properties.
  • As an adjunct to conventional anticancer therapy, vitamin E might reduce side effects (i.e. oral mucositis, hand-foot-syndrome and peripheral neurotoxicity).
  • No clinical trials describing the use of vitamin E monotherapy as an anticancer treatment have been published.
  • Vitamin E is considered to have a very low toxicity, and is generally well-tolerated in low doses.

Vitamin E is a generic term encompassing natural (alpha-, beta-, gamma-, and delta-tocopherol, and alpha-, beta-, gamma-, and delta-tocotrienol) and synthetic (all-rac-alpha-tocopherol) forms, and the esters thereof. The role of some forms of vitamin E in cancer prevention and therapy has been proposed.

This summary focuses on vitamin E during cancer, i.e. when used as an anticancer agent or to alleviate the adverse events of cancer treatments. Vitamin E in the prevention of cancer is not covered by this summary.

No clinical trials describing the use of vitamin E monotherapy as an anticancer treatment have been published. The available peer-reviewed clinical literature describes the use of alpha-tocopherol, all-rac-alpha-tocopherol, and tocotrienol as components of multivitamin regimens or mixtures of micronutrients, in combination with non-cancer drugs, or as adjuncts to conventional chemotherapy or radiation. In 5 randomized, placebo-controlled studies in adults and children, it was found that topical vitamin E might prevent oral mucositis induced by chemotherapy or radiotherapy. In five randomized, controlled or placebo-controlled clinical studies a decrease of the incidence and severity of peripheral neurotoxicity induced by taxanes or platinum-based chemotherapy by alpha-tocopherol was found, but this finding was not confirmed in two other randomized, placebo-controlled studies.

Vitamin E is considered to have a very low toxicity, and is generally well-tolerated. However, special consideration should be given when high doses of alpha-tocopherol are administered to cardiovascular disease patients or individuals taking anticoagulant therapy (e.g., warfarin), and to those with vitamin-K-related clotting disorders. Non-healthy patients should not take daily doses of 400 IU or higher. Little information is available on the adverse events of other forms of vitamin E.

Citation

Luc Geeraert, CAM-Cancer Consortium. Vitamin E during cancer treatment [online document]. http://www.cam-cancer.org/The-Summaries/Dietary-approaches/Vitamin-E-during-cancer-treatment. September 30, 2015.

Document history

Summary updated in September 2015 by Luc Geeraert.
Summary fully revised and updated in July 2013 by Luc Geeraert.
Summary first published in August 2011, authored by Luc Geeraert.

References

  1. Kline K, Lawson KA, Yu W, Sanders BG. Vitamin E and cancer. Vitam. Horm. 2007;76:435-461.
  2. Brigelius-Flohé R, Traber MG. Vitamin E: function and metabolism. FASEB J. 1999 Jul;13(10):1145-1155.
  3. Sylvester PW, Shah SJ. Mechanisms mediating the antiproliferative and apoptotic effects of vitamin E in mammary cancer cells. Front. Biosci. 2005 January 1;10:699-709.
  4. Fleshner NE. Vitamin E and prostate cancer. Urol Clin North Am. 2002 February;29(1):107-113.
  5. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000.
  6. Brigelius-Flohé R, Kelly FJ, Salonen JT, Neuzil J, Zingg JM, Azzi A. The European perspective on vitamin E: current knowledge and future research. Am. J. Clin. Nutr. 2002 October;76(4):703-716.
  7. Evans HM, Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science. 1922 December;56(1458):650-651.
  8. Herrera E, Barbas C. Vitamin E: action, metabolism and perspectives. J. Physiol. Biochem. 2001 March;57(2):43-56.
  9. Prasad KN, Kumar B, Yan XD, Hanson AJ, Cole WC. Alpha-tocopheryl succinate, the most effective form of vitamin E for adjuvant cancer treatment: a review. J. Am. Coll. Nutr. 2003 April;22(2):108-117.
  10. Neuzil J. Vitamin E succinate and cancer treatment: a vitamin E prototype for selective antitumour activity. Br. J. Cancer. 2003 November 17;89(10):1822-1826.
  11. Miyazawa T, Shibata A, Sookwong P, Kawakami Y, Eitsuka T, Asai A, Oikawa S, Nakagawa K. Antiangiogenic and anticancer potential of unsaturated vitamin E (tocotrienol). J Nutr Biochem. 2009 February;20(2):79-86.
  12. Das S. Vitamin E in the genesis and prevention of cancer. A review. Acta Oncol. 1994;33(6):615-619.
  13. Kayden HJ, Traber MG. Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J. Lipid Res. 1993 March;34(3):343-358.
  14. Hensley K, Benaksas EJ, Bolli R, Comp P, Grammas P, Hamdheydari L, Mou S, Pye QN, Stoddard MF, Wallis G, Williamson KS, West M, Wechter WJ, Floyd RA. New perspectives on vitamin E: gamma-tocopherol and carboxyelthylhydroxychroman metabolites in biology and medicine. Free Radic. Biol. Med. 2004 Jan 1;36(1):1-15.
  15. Velicer CM, Ulrich CM. Vitamin and mineral supplement use among US adults after cancer diagnosis: a systematic review. J. Clin. Oncol. 2008 February 1;26(4):665-673.
  16. Blanke CD, Stipanov M, Morrow J, Rothenberg M, Chinery R, Shyr Y, Coffey R, Johnson DH, Leach SD, Beauchamp RD. A phase I study of vitamin E, 5-fluorouracil and leucovorin for advanced malignancies. Invest. New Drugs. 2001;19(1):21-27.
  17. Nesaretnam K, Selvaduray KR, Abdul Razak G, Veerasenan SD, Gomez PA. Effectiveness of tocotrienol-rich fraction combined with tamoxifen in the management of women with early breast cancer: a pilot clinical trial. Breast Cancer Res. 2010;12(5):R81. doi: 10.1186/bcr2726. Epub 2010 Oct 8.
  18. Bairati I, Meyer F, Gélinas M, Fortin A, Nabid A, Brochet F, Mercier JP, Têtu B, Harel F, Abdous B, Vigneault E, Vass S, Del Vecchio P, Roy J. Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J. Clin. Oncol. 2005a August 20;23(24):5805-5813.
  19. Bairati I, Meyer F, Gélinas M, Fortin A, Nabid A, Brochet F, Mercier JP, Têtu B, Harel F, Mâsse B, Vigneault E, Vass S, del Vecchio P, Roy J. A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. J. Natl. Cancer Inst. 2005b April 6;97(7):481-488.
  20. Bairati I, Meyer F, Jobin E, Gélinas M, Fortin A, Nabid A, Brochet F, Têtu B. Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int. J. Cancer. 2006 November 1;119(9):2221-2224.
  21. Chitra S, Shyamaladevi CS. Modulatory action of α-tocopherol on erythrocyte membrane adenosine triphosphatase against radiation damage in oral cancer. J Membr Biol. 2011 Mar;240(2):83-8.
  22. Galuppi A, Perrone AM, La Macchia M, Santini D, Medoro S, Maccarini LR, Strada I, Pozzati F, Rossi M, De Iaco P. Local α-tocopherol for acute and short-term vaginal toxicity prevention in patients treated with radiotherapy for gynecologic tumors. Int J Gynecol Cancer. 2011 Dec;21(9):1708-11.
  23. Wadleigh RG, Redman RS, Graham ML, Krasnow SH, Anderson A, Cohen MH. Vitamin E in the treatment of chemotherapy-induced mucositis. Am. J. Med. 1992 May;92(5):481-484.
  24. Lopez I, Goudou C, Ribrag V, Sauvage C, Hazebroucq G, Dreyfus F. [Treatment of mucositis with vitamin E during administration of neutropenic antineoplastic agents] Ann. Med. Interne (Paris). 1994;145(6):405-408.
  25. Ferreira PR, Fleck JF, Diehl A, Barletta D, Braga-Filho A, Barletta A, Ilha L. Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: a double-blind randomized trial. Head Neck. 2004 April;26(4):313-321.
  26. El-Housseiny AA, Saleh SM, El-Masry AA, Allam AA. The effectiveness of vitamin "E" in the treatment of oral mucositis in children receiving chemotherapy. J. Clin. Pediatr. Dent. 2007 Spring;31(3):167-170.
  27. Khurana H, Pandey RK, Saksena AK, Kumar A. An evaluation of Vitamin E and Pycnogenol in children suffering from oral mucositis during cancer chemotherapy. Oral Dis. 2013 Jul;19(5):456-64.
  28. Sung L, Tomlinson GA, Greenberg ML, Koren G, Judd P, Ota S, Feldman BM. Serial controlled N-of-1 trials of topical vitamin E as prophylaxis for chemotherapy-induced oral mucositis in paediatric patients. Eur. J. Cancer. 2007 May;43(8):1269-1275.
  29. Delanian S, Porcher R, Balla-Mekias S, Lefaix JL. Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. J. Clin. Oncol. 2003 July 1;21(13):2545-2550.
  30. Ravo V, Calvanese MG, Di Franco R, Crisci V, Murino P, Manzo R, Morra A, Cammarota F, Muto P. Prevention of cutaneous damages induced by radiotherapy in breast cancer: an institutional experience. Tumori. 2011 Nov-Dec;97(6):732-736.
  31. Chitra S, Shyamala Devi CS. Effects of radiation and alpha-tocopherol on saliva flow rate, amylase activity, total protein and electrolyte levels in oral cavity cancer. Indian J Dent Res. 2008 Jul-Sep;19(3):213-8.
  32. Fallahi B, Beiki D, Abedi SM, Saghari M, Fard-Esfahani A, Akhzari F, Mokarami B, Eftekhari M. Does vitamin E protect salivary glands from I-131 radiation damage in patients with thyroid cancer? Nucl Med Commun. 2013 Aug;34(8):777-86.
  33. Pace A, Savarese A, Picardo M, Maresca V, Pacetti U, Del Monte G, Biroccio A, Leonetti C, Jandolo B, Cognetti F, Bove L. Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. J. Clin. Oncol. 2003 Mar 1;21(5):927-931.
  34. Argyriou AA, Chroni E, Koutras A, Ellul J, Papapetropoulos S, Katsoulas G, Iconomou G, Kalofonos HP. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology. 2005 January 11;64(1):26-31.
  35. Argyriou AA, Chroni E, Koutras A, Iconomou G, Papapetropoulos S, Polychronopoulos P, Kalofonos HP. A randomized controlled trial evaluating the efficacy and safety of vitamin E supplementation for protection against cisplatin-induced peripheral neuropathy: final results. Support Care Cancer. 2006a November;14(11):1134-1140.
  36. Argyriou AA, Chroni E, Koutras A, Iconomou G, Papapetropoulos S, Polychronopoulos P, Kalofonos HP. Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation. J. Pain Symptom Manage. 2006b September;32(3):237-244.
  37. Pace A, Giannarelli D, Galiè E, Savarese A, Carpano S, Della Giulia M, Pozzi A, Silvani A, Gaviani P, Scaioli V, Jandolo B, Bove L, Cognetti F. Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial. Neurology. 2010 Mar 2;74(9):762-766.
  38. Kottschade LA, Sloan JA, Mazurczak MA, Johnson DB, Murphy BP, Rowland KM, Smith DA, Berg AR, Stella PJ, Loprinzi CL. The use of vitamin E for the prevention of chemotherapy-induced peripheral neuropathy: results of a randomized phase III clinical trial. Support Care Cancer. 2011 Nov;19(11):1769-1777.
  39. de Afonseca SO, Cruz FM, de Iracema Gomes Cubero D, Lera AT, Schindler F, Okawara M, Souza LF, Rodrigues NP, del Giglio A. Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: a pilot randomized clinical trial. Sao Paulo Med J. 2013;131(1):35-8.
  40. Whittaker JA, Al-Ismail SA. Effect of digoxin and vitamin E in preventing cardiac damage caused by doxorubicin in acute myeloid leukaemia. Br. Med. J. (Clin. Res. Ed.). 1984 January;288(6413):283-284.
  41. Legha SS, Wang YM, Mackay B, Ewer M, Hortobagyi GN, Benjamin RS, Ali MK. Clinical and pharmacologic investigation of the effects of alpha-tocopherol on adriamycin cardiotoxicity. Ann. N. Y. Acad. Sci. 1982;393:411-418.
  42. Kara IO, Sahin B, Erkisi M. Palmar-plantar erythrodysesthesia due to docetaxel-capecitabine therapy is treated with vitamin E without dose reduction. Breast. 2006 Jun;15(3):414-24.
  43. Yamamoto D, Yamamoto C, Iwase S, Kuroda Y, Odagiri H, Nagumo Y. Efficacy of Vitamin E Treatment for Hand-Foot Syndrome in Patients Receiving Capecitabine. Breast Care (Basel). 2010;5(6):415-416.
  44. Bozkurt Duman B, Kara B, Oguz Kara I, Demiryurek H, Aksungur E. Hand-foot syndrome due to sorafenib in hepatocellular carcinoma treated with vitamin E without dose modification; a preliminary clinical study. J BUON. 2011 Oct-Dec;16(4):759-64.
  45. Wood LA. Possible prevention of adriamycin-induced alopecia by tocopherol. N. Engl. J. Med. 1985 April 18;312(16):1060.
  46. Martin-Jimenez M, Diaz-Rubio E, Gonzalez Larriba JL, Sangro B. Failure of high-dose tocopherol to prevent alopecia induced by doxorubicin. N. Engl. J. Med. 1986 October 2;315(14):894-895.
  47. Perez JE, Macchiavelli M, Leone BA, Romero A, Rabinovich MG, Goldar D, Vallejo C. High-dose alpha-tocopherol as a preventive of doxorubicin-induced alopecia. Cancer Treat. Rep. 1986 October;70(10):1213-1214.
  48. Kappus H, Diplock AT. Tolerance and safety of vitamin E: a toxicological position report. Free Radic. Biol. Med. 1992;13(1):55-74.
  49. Steiner M. Influence of vitamin E on platelet function in humans. J. Am. Coll. Nutr. 1991 October;10(5):466-473.
  50. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med. 1994 Apr 14;330(15):1029-1035.
  51. Booth SL, Golly I, Sacheck JM, Roubenoff R, Dallal GE, Hamada K, Blumberg JB. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr. 2004 Jul;80(1):143-8.
  52. Hayden KM, Welsh-Bohmer KA, Wengreen HJ, Zandi PP, Lyketsos CG, Breitner JC; Cache County Investigators. Risk of mortality with vitamin E supplements: the Cache County study. Am J Med. 2007 Feb;120(2):180-4.
  53. Miller ER 3rd, 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 January;142(1):37-46.
  54. Seifried HE, McDonald SS, Anderson DE, Greenwald P, Milner JA. The antioxidant conundrum in cancer. Cancer Res. 2003 Aug 1;63(15):4295-8.
  55. Lamson DW, Brignall MS. Antioxidants in cancer therapy; their actions and interactions with oncologic therapies. Altern. Med. Rev. 1999 October;4(5):304-329.
  56. D'Incalci M, Steward WP, Gescher AJ. Modulation of response to cancer chemotherapeutic agents by diet constituents: is the available evidence sufficiently robust for rational advice for patients? Cancer Treat. Rev. 2007 May;33(3):223-229.
  57. Sylvester PW, Vikram BW, Sunitha VB, Amit BS, Nehad MA, Mohamed RA. Tocotrienol combination therapy results in synergistic anticancer response. Frontiers in Bioscience 2011;17:3183-3195.
  58. Pédeboscq S, Rey C, Petit M, Harpey C, De Giorgi F, Ichas F, Lartigue L. Non-antioxidant properties of α-tocopherol reduce the anticancer activity of several protein kinase inhibitors in vitro. PLoS One. 2012;7(5):e36811.
  59. Moss RW. Do antioxidants interfere with radiation therapy for cancer? Integr. Cancer Ther. 2007 September;6(3):281-292.
  60. Sung L, Greenberg ML, Koren G, Tomlinson GA, Tong A, Malkin D, Feldman BM. Vitamin E: the evidence for multiple roles in cancer. Nutr. Cancer. 2003;46(1):1-14.