Outcomes After Anticancer Treatment

A multicenter, double-blind trial randomly assigned 540 patients with stage I or II head and neck cancer to receive alpha-tocopherol (400 IU per day) and beta-Carotene (30 mg/day) or placebo on their first day of radiation and continued for 3 years.17 beta-Carotene was discontinued, however, because of ethical concerns.

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Vitamin E supplementation increased the risk of second primary cancers (HR, 2.88; 95% CI, 1.56-5.31) and recurrence/second primary cancer (HR, 1.86, 95% CI, 1.27-2.72) compared with placebo during the intervention period, but trended toward a decreased risk after supplementation was discontinued (HR, 0.41; 95% CI, 0.16-1.03 and HR, 0.71; 95% CI, 0.33-1.53, respectively).

An analysis of the ATBC trial, however, found improved survival among patients with prostate cancer who had high serum levels of alpha-tocopherol at baseline (HR, 0.67; 95% CI, 0.45-1.00) and who received alpha-tocopherol supplementation and also had high baseline (HR, 0.51; 95% CI, 0.20-0.90) or 3-year (HR, 0.26; 95% CI, 0.09-0.71) serum levels.18

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Prevention of Treatment-related Toxicities

Multiple trials have evaluated the effect of vitamin E supplementation on reducing toxicities associated with anticancer treatments.

Several randomized, controlled trials demonstrated that vitamin E supplementation improved paclitaxel- or cisplatin-associated neurotoxicity compared with placebo.19-23 Another study found that vitamin E supplementation improved hand-foot syndrome caused by sorafenib among patients with hepatocellular carcinoma.24

Vitamin E did not, however, improve chemotherapy-induced peripheral sensory neuropathy.25,26

Vitamin E supplementation also improved radiation-induced toxicities. In one trial, vitamin E reduced severe acute adverse effects during radiation (odds ratio [OR], 0.72; 95% CI, 0.52-1.02), which was significant when vitamin E was combined with beta-Carotene (OR, 0.38; 95% CI, 0.21-0.71), though there was no improvement in quality of life.27 Local recurrence was, however, numerically higher with supplementation compared with placebo (HR, 1.37; 95% CI, 0.93-2.02).

Topically applied vitamin E supplementation improved radiation-induced vaginal toxicity and pain associated with radiotherapy for the treatment of gynecologic tumors.28 Oral vitamin E improved radiation-induced mucositis, salivary gland dysfunction, and xerostomia.29-31


The available evidence suggests that vitamin E supplementation does not prevent cancer, though one large study found a small increased risk of prostate cancer.

Vitamin E supplementation appears to reduce the risk of chemotherapy-induced neurotoxicity and several radiation-induced toxicities, though one study found increased recurrence rates with its use.


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  14. Kristal AR, Arnold KB, Neuhouser ML, et al. Diet, supplement use, and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Am J Epidemiol. 2010;172:566-77. doi: 10.1093/aje/kwq148
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  16. Kelly K, Kittelson J, Franklin WA, et al. A randomized phase II chemoprevention trial of 13-CIS retinoic acid with or without α tocopherol or observation in subjects at high risk for lung cancer. Cancer Prev Res (Phila). 2009;2:440-9. doi: 10.1158/1940-6207.CAPR-08-0136
  17. Bairati I, Meyer F, Gelinas M, et al. A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. J Natl Cancer Inst. 2005;97:481-8. doi: 10.1093/jnci/dji095
  18. Watters JL, Gail MH, Weinstein SJ, Virtamo J, Albanes D. Associations between α-tocopherol, β-carotene, and retinol and prostate cancer survival. Cancer Res. 2009;69:3833-41. doi: 10.1158/0008-5472.CAN-08-4640
  19. Pace A, Savarese A, Picardo M, et al. Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. J Clin Oncol. 2003;21:927-31.
  20. Pace A, Giannarelli D, Galie E, et al. Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial. Neurology. 2010;74:762-6. doi: 10.1212/WNL.0b013e3181d5279e
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  22. Argyriou AA, Chroni E, Koutras A, et al. Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation. J Pain Symptom Manage. 2006;32:237-44. doi:10.1016/j.jpainsymman.2006.03.013
  23. Argyriou AA, Chroni E, Koutras A, et al. 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. 2006;14:1134-40.
  24. 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;16:759-64.
  25. Kottschade LA, Sloan JA, Mazurczak MA, et al. 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;19:1769-77. doi:10.1007/s00520-010-1018-3.
  26. de Afonseca SO, Cruz FM, Cubero DIG, et al. Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: a pilot randomized clinical trial. Sao Paulo Med J. 2013;131:35-38.
  27. Bairati I, Meyer F, Gelinas M, et al. Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J Clin Oncol. 2005;23:5805-13. doi: 10.1200/JCO.2005.05.514
  28. Galuppi A, Perrone AM, La Macchia M, et al. Local α-tocopherol for acute and short-term vaginal toxicity prevention in patients treated with radiotherapy for gynecologic tumors. Int J Gynecol Cancer. 2011;21:1708-11. doi: 10.1097/IGC.0b013e318223659d
  29. Ferreira PR, Fleck JF, Diehl A, et al. Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: a double-blind randomized trial. Head Neck. 2004;26:313-21.
  30. Fallahi B, Beiki D, Abedi SM, et al. Does vitamin E protect salivary glands from I-131 radiation damage in patients with thyroid cancer? Nucl Med Commun. 2013;34:777-86. doi: 10.1097/MNM.0b013e328362b1f2
  31. Chung MK, Kim do H, Ahn YC, Choi JY, Kim EH, Son YI. Randomized trial of vitamin C/E complex for prevention of radiation-induced xerostomia in patients with head and neck cancer. Otolaryngol Head Neck Surg. 2016;155:423-30. doi: 10.1177/0194599816642418.