By Jyothirmai Gubili, MS, Jason Hou, PharmD, DiplOM, Lac, and Eugenie Spiguel, MSN, ANP-BC

Reactive oxygen species (ROS), such as hydroxyl and superoxide radicals, singlet oxygen, and hydrogen peroxide, are byproducts of metabolic processes in the body and play an important role in regulating cell physiology and function.

But uncontrolled ROS formation (oxidative stress) can result in DNA, protein, and lipid damage, which has been implicated in several diseases, including cancer. Antioxidants, produced endogenously or in supplemental form, function as ROS scavengers and inhibit oxidative stress. Popular antioxidants include vitamins C and E, selenium, beta carotene, lycopene, resveratrol, flavonoids, anthocyanins, and catechins. They are widely used to prevent cancer and its recurrence.

Current Evidence

Epidemiologic data have associated consumption of vegetables rich in beta carotene with reduction in cancer risk (especially lung cancer) and indicate that certain micronutrients inhibit cancer. But reviews of randomized clinical trials did not find benefits of supplementation with vitamins C, E, or beta carotene for preventing cancer incidence or for affecting cancer mortality; another concluded that beta carotene may actually increase overall mortality. Data from the Women’s Health Study involving 39,876 healthy women showed no overall benefit of 600 IU vitamin E for preventing cancer or major cardiovascular events, and did not affect total mortality.

The large prevention trial SELECT (Selenium and Vitamin E Cancer Prevention Trial) involving 35,533 men also failed to find effectiveness of selenium (200 mcg of selenomethionine) or vitamin E (400 IU of synthetic DL alpha-tocopherol), taken orally alone or combined for a median of 5.5 years, for lowering prostate cancer risk. Furthermore, a cross-sectional analysis of patients with prostate cancer showed that selenium levels may influence the risk of aggressive prostate cancer and supplementation may increase prostate cancer mortality.
According to conclusions of the latest review of 83 studies, clear evidence of selenium’s cancer preventive potential is lacking.

Vitamin C is another popular antioxidant, and high oral doses have been employed as an alternative cancer treatment. But randomized controlled trials of patients with advanced cancer did not find significant benefit of supplementation over placebo. Some findings suggest that IV administration of high-dose vitamin C may improve the quality of life of patients with terminal cancer.

In addition, low-dose antioxidants have been studied to minimize chemotherapy-induced toxicity and improve cancer outcomes.  But systematic reviews found mixed evidence for reducing toxicity with no impact on survival.

A major concern when using antioxidants during cancer treatments is that they can render chemotherapy drugs such as anthracycline and platinum compounds less effective and cause detrimental effects when used with radiation therapy by disarming ROS. Vitamin C has actually been shown to antagonize the efficacy of doxorubicin, cisplatin, vincristine, methotrexate, and imatinib in a model of human hematopoietic cancers.

Noteworthy also is the recommendation from U.S. Preventive Services Task Force against taking beta carotene or vitamin E supplements for preventing cancer or cardiovascular disease.

Nursing Implications

Although antioxidants obtained through diet are considered safe, robust data are lacking to support use of supplemental forms for cancer prevention. Supplementation during treatment is especially controversial: no definitive data show that antioxidant supplements (vitamins, herbs, or herbal compounds) have the ability to protect healthy tissues without compromising the cytotoxicity of chemotherapy drugs. Until concrete evidence becomes available, patients should avoid antioxidant supplements during treatment.

Patients may be frustrated when asked to stop taking their trusted supplements. As patient advocates and educators, oncology nurses are in an excellent position to teach patients about the potential risks of antioxidant supplementation. When patients understand that the supplements may make their treatment less effective, they are more likely to be compliant and avoid them.