Efficacy for Reducing Toxicities
Though the systematic review found no significant difference in the rates of grade 3 to 4 AEs with vitamin C treatment, some reduction has been observed in observational studies and case reports.1
A phase 1/2a pilot trial randomly assigned 27 patients with newly diagnosed stage III or IV ovarian cancer to receive cisplatin plus paclitaxel with or without intravenous vitamin C. The vitamin C infusions were initiated at 15 g and were titrated to 75 or 100 g per infusion given twice weekly in conjunction with chemotherapy for 6 months; the vitamin C was continued for an additional 6 months after chemotherapy completion.
There was no increase in grade 3 or 4 AEs with vitamin C, but the frequency of grade 1 and 2 AEs decreased. Though not powered to detect statistical significance for efficacy, the median time to disease progression was prolonged by 8.75 months with vitamin C compared with chemotherapy alone.5
A double-blind trial not included in the systematic review evaluated the effect of antioxidant supplementation on cisplatin-induced toxicity. Forty-eight patients to be treated with cisplatin-based chemotherapy were randomly assigned to receive a twice daily vanilla-flavored beverage containing 1000 mg vitamin C (L-ascorbic acid), 400 mg vitamin E, and 100 μg of selenium, or placebo. Patients ingested the beverage beginning 7 days prior to the start of chemotherapy and continuing until 3 weeks after chemotherapy completion.
Patients in the antioxidant arm demonstrated greater levels of plasma antioxidant levels compared with the control arm. Overall, there was no significant difference in nephrotoxicity or ototoxicity between the 2 groups. Patients with the highest plasma levels of antioxidants, however, experienced significantly less high-tone hearing loss.6
Though some studies reported improvements in clinical outcomes and quality of life with vitamin C treatment, these findings have not been replicated in randomized controlled studies. There is no evidence, however, that vitamin C therapy decreases response to chemotherapy.
More well-designed, modern randomized controlled studies are needed to provide definitive recommendations regarding the efficacy of vitamin C as an anticancer treatment or for protection against chemotherapy-induced toxicities.
- Jacobs C, Hutton B, Ng T, Shorr R, Clemons M. Is there a role for oral or intravenous ascorbate (vitamin C) in treating patients with cancer? A systematic review. Oncologist. 2015;210-23. doi: 10.1634/theoncologist.2014-0381
- Creagan ET, Moertel CG, O’Fallon JR, et al. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med. 1979;301:687-90.
- Moertel CG, Fleming TR, Creagan ET, Rubin J, O’Connell MJ, Ames MM. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl J Med. 1985;312;137-41.
- Hoenjet KM, Dagnelie PC, Delaere KP, Wijckmans NE, Zambon JV, Oosterhof GO. Effect of a nutritional supplement containing vitamin E, selenium, vitamin C and coenzyme Q10 on serum PSA in patients with hormonally untreated carcinoma of the prostate: a randomised placebo-controlled study. Eur Urol. 2005;47:433-40.
- Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. 2014;6:222ra18. doi: 10.1126/scitranslmed.3007154
- Weijl NI, Elsendoorn TJ, Lentjes EG, et al. Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatin-based chemotherapy: a randomised, double-blind, placebo-controlled study. Eur J Cancer. 2004;40:1713-23.