New Systematic Review of Antioxidants and Chemotherapy Provides Some Reason for Hope and Little Reason for Concern   

Author: Steve Austin, N.D.

Reference: Nakyama A, Alladin KP, Igbokwe O, White JD. Systematic review: generating evidence-based guidelines on the concurrent use of dietary antioxidants and chemotherapy or radiotherapy. Cancer Invest 2011;29:655-67.

Design: This review discusses outcomes from 52 clinical trials studying the effects of adding antioxidant nutrients to chemotherapy in the treatment of patients with cancer. Half of these trials used glutathione (GSH), 11 used vitamin E, 5 used N-acetylcysteine (NAC), and 10 trials used vitamin C, coenzyme Z10, zinc, selenium, or a combination of these nutrients.

Key Findings: The GSH trials used varying doses (1.2 to 5 g), mostly administered I.V. and most frequently given to patients who were also given cisplatin-containing chemotherapy combinations. One trial found that GSH reduced nephrotoxicity while improving quality of life and increasing the number of patients capable of withstanding 6 courses of cisplatin. Another trial reported a statistically nonsignificant trend suggesting less cisplatin-induced toxicity in those given GSH. One trial reported a statistically significant reduction in chemotherapy-induced neuropathy on one hand, with no reduction in the effectiveness of the chemotherapy on the other. In a trial with gastric CA patients, those given GSH had more complete remissions, less neuropathy, and higher rates of tumor response to the chemotherapy–effects that were statistically significant. One trial that was included in the review found neither improvement with GSH nor interference with the therapeutic effect of the cisplatin.

In the vitamin E trials, doses varied from essentially 200 IU per day up to 3,200 IU per day. Less chemotherapy-induced mucositis was reported in patients assigned to supplemental vitamin E. In a trial using synthetic vitamin E, higher second primary head and neck cancers and recurrences occurred during the supplementation period, but lower rates of both occurred after vitamin E therapy was discontinued (when compared with outcomes in patients who had not received vitamin E). In those receiving radiation without chemotherapy fewer chemotherapy-induced side effects were reported in patients assigned to vitamin E. Two additional trials, both using natural vitamin E with patients given cisplatin combinations, found reduced neurotoxicity in the vitamin E group compared with the control group.

Reduced chemotherapy-induced neuropathy occurred in those assigned to NAC versus the control groups. Three other NAC trials looked for a therapeutic advantage in the NAC groups, did not find it, but also did not report interference with the efficacy of the chemotherapy.

Apparently, the lack of sufficient evidence regarding the effects of the other antioxidants led to a lack of details regarding those trials that have used supplemental vitamin C, selenium, or other antioxidant nutrients.

Practice Implications: The medical literature continues to include occasional articles that favor providing cancer patients given chemotherapy and/or radiation with antioxidants. This recommendation is often based on evidence showing reduced drug and radiation toxicity, as discussed in the new review.

A more prevalent view also appearing in the literature posits that the providing cancer patients undergoing chemotherapy and/or radiation with antioxidants would be dangerous because doing so should interfere with the actions of the conventional treatments. Though there are a few exceptions, for the most part, this position is supported by mechanistic considerations rather than actual clinical evidence. Yet, presumably for ideological reasons, the lack of supportive clinical evidence continues to not dissuade practitioners (and in some cases researchers) who cling to this weakly-supported position.

How are practitioners to deal with the incomplete information? It’s important to keep in mind that not all antioxidants are the same nor are all chemotherapy drugs. Adding certain antioxidants to chemotherapy and radiation regimens may prove useful in some circumstances but not in others. It even remains possible that under some circumstances, problems could arise by prescribing antioxidants to patients given certain drugs or radiation. That mostly-hypothetical possibility remains unlikely, given the relative strength of those conventional treatments that act by causing oxidative damage, when compared with the significantly less powerful effects of antioxidant nutrients. For now, however, there continues to be little clinical support for the idea that antioxidants need to be avoided when patients are given these toxic treatments in the course of their cancer therapy.