Risk of Recurrence

A double-blind trial conducted in Italy randomly assigned 411 patients with colorectal cancer to receive a multivitamin consisting of vitamin A (2 mg), selenium (200 μg), zinc (30 mg), vitamin C (180 mg), and vitamin E (30 mg) or placebo for 5 years.5 A follow-up colonoscopy was available for 330 patients. There was a significant decrease in the 15-year cumulative incidence of recurrence with the multivitamin compared with the placebo (48.3% vs 64.5%; hazard ratio, 0.59; log-rank P = .009), which was similar for small tubular and advanced adenomas.

Continue Reading

An earlier study also randomly assigned 65 patients with bladder cancer to receive a  multivitamin at the recommended daily allowance (RDA) or a multivitamin at the RDA plus another multivitamin consisting of megadoses of vitamin A (40,000 U), vitamin B6 (100 mg), vitamin C (2000 mg), vitamin E (400 U), and zinc (90 mg).6 All patients also received intravesical bacillus Calmette-Guerin (BCG). Recurrence was significantly decreased with the megadose vitamins, with 5-year estimates of 41% with megadose vitamins compared with 91% with RDA vitamins (P = .0014).

Similar results were demonstrated among patients with stage I non–small cell lung cancer. This study randomly assigned 307 patients to receive vitamin A (retinol palmitate 300,000 IU daily) or no supplementation for 1 year. Recurrence or new primary tumors occurred in 37% of patients who received vitamin A compared with 48% in the control arm after 46 months of follow up, but differences in the disease-free interval were not significant (P = .054).7

The randomized EUROSCAN trial, however, found no significant difference in OS or event-free survival among 2592 patients with head and neck cancer or lung cancer who received vitamin A supplementation (retinyl palmitate 300,000 IU daily for first year, then 150,000 IU daily) with or without N-acetylcysteine (600 mg daily) compared with no supplementation for 2 years.8

A smaller study randomly assigned 106 patients with head and neck cancer who achieved complete regression with radiotherapy and/or surgery to receive vitamin A (retinyl palmitate 200,000 IU per week) or placebo for 1 year. Locoregional recurrence occurred in 19.6% and 10% of patients in the vitamin A and placebo arms, respectively. There was a trend toward higher recurrence rates among patients who had stage I disease with vitamin A compared with placebo.9


The available evidence suggests that vitamin A supplementation may be harmful as a chemopreventative for lung cancer among high-risk populations.

Treatment outcomes, including mortality and risk of recurrence, may be improved with vitamin A supplementation, though the data are mixed. Vitamin A supplementation likely does not reduce chemotherapy efficacy, and for many patients, is unlikely to cause harm.


  1. Vitamin A. National Institutes of Health website. https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/. Accessed August 7, 2017.
  2. Fortmann SP, Burda BU, Senger CA, et al. Vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer: a systematic evidence review for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality; 2013.
  3. Meyskens FL Jr, Kopecky KJ, Appelbaum FR, Balcerzak SP, Samlowski W, Hynes H. Effects of vitamin A on survival in patients with chronic myelogenous leukemia: a SWOG randomized trial. Leuk Res. 1995;19:605-12.
  4. Block KI, Koch AC, Mean MN, Tothy PK, Newman RA, Gyllenhaal C. Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials. Cancer Treat Rev. 2007;33:407-18.
  5. Bonelli L, Puntoni M, Gatteschi B, et al. Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial. J Gastroenterol. 2013;48:698-705. doi: 10.1007/s00535-012-0691-z
  6. Lamm DL, Riggs DR, Shriver JS, van Gilder PF, Rach JF, DeHaven JI. Megadose vitamins in bladder cancer: a double-blind clinical trial. J Urol. 1994;151:21-6.
  7. Pastorino U, Infante M, Maioli M, et al. Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J Clin Oncol. 1993;11:1216-22.
  8. van Zandwijk N, Dalesio O, Pastorino U, de Vries N, van Tinteren H. EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the European Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups. J Natl Cancer Inst. 2000;92:977-86.
  9. Jyothirmayi R, Ramadas K, Varghese C, Jacob R, Nair MK, Sankaranarayanan R. Efficacy of vitamin A in the prevention of loco-regional recurrence and second primaries in head and neck cancer. Eur J Cancer B Oral Oncol. 1996;32B:373-6.