Antioxidant Supplementation in Patients with Cancer: Is It Safe and Effective?


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Although it is not yet clear whether or in which specific cases antioxidant consumption may interfere with chemotherapy or radiation treatment, it is advisable to apply the cautionary principle and advise patients to avoid antioxidant dietary supplements during treatment, until further study brings greater clarity.

Antioxidant supplements are widely used by healthy individuals as a preventive measure against cancer and heart disease and by patients with cancer to promote healing and prevent recurrence. Studies suggest that dietary supplements are used by up to 81% of cancer survivors, and that 14% to 32% begin using supplements following diagnosis.1 Increasing one’s intake of antioxidants, which are involved in repairing cellular oxidative damage, theoretically should lower cancer risk, but there is little evidence to suggest that supplementation is efficacious, or even safe.2,3

Although increased consumption of antioxidant-rich fruits and vegetables may reduce the risk of certain cancers, studies of isolated antioxidants in supplement form have not been equally promising. Of particular concern to clinicians and patients is the use of antioxidant supplements during the course of chemotherapy and/or radiation therapy, as antioxidants consumed at doses common in nutritional supplements could potentially interfere with the effectiveness of these treatments.4 Here we provide an overview of relevant findings and existing recommendations on antioxidant supplementation that may be useful to clinicians.

Can Antioxidants Help Prevent Cancer?

Antioxidants comprise a broad class of compounds that counteract free radicals, thus inhibiting oxidative chain reactions that can react with DNA and damage cells. Their chemical structures and particular mechanisms, however, vary widely. While studies have described an inverse relationship between consumption of antioxidant-rich foods and cancer risk, there is no definitive evidence that dietary supplements containing high levels of antioxidants can reduce cancer incidence. Antioxidant supplementation has been studied in randomized clinical trials, most of which found no decrease in cancer risk or, in some cases, an increased risk.

The SELECT trial, for instance, investigated the effects of supplemental selenium and vitamin E on the incidence of prostate cancer in 34,887 healthy men and found that vitamin E supplementation significantly increased cancer risk.5 Similarly, high-dose supplementation with beta-carotene in several clinical trials showed no benefit in preventing lung and other cancers. Two of these studies found that the supplements increased the risk of lung cancer in cigarette smokers.6,7 Studies of vitamin C supplementation have had null results as well; the Physicians’ Health Study II found no significant effect of vitamin C supplementation (500 mg/d) on prostate or total cancer incidence.8

To reduce cancer risk, the American Cancer Society (ACS) recommends that antioxidants be consumed through food sources rather than as dietary supplements. “The best advice,” the ACS guidelines state, “is to consume at least 2.5 cups of a variety of colorful fruits and vegetables each day.”3

Can Antioxidants Interfere with Chemotherapy and/or Radiotherapy?

The safety and efficacy of antioxidant supplements taken during the course of treatment is particularly controversial. Many clinicians are concerned that high-dose antioxidant supplements could decrease the effectiveness of chemotherapy or radiation by protecting cancer cells as well as healthy cells from oxidative damage associated with these treatments. Others argue that antioxidant supplementation could selectively protect healthy cells from such damage, thus minimizing toxicity and adverse side effects of the treatment regimen.4

Although findings vary among existing randomized controlled trials of antioxidant use during cancer treatment, many are of relatively low quality and/or limited statistical power. Moreover, it is difficult to draw conclusions due to variations in malignancy type, antioxidant type and dose, and treatment regimen, among other factors.4 One of the best designed studies involved 540 patients with head and neck cancer undergoing radiation treatment. It found significantly higher mortality among those prescribed 400 IU of daily vitamin E supplementation compared to placebo.9

In the absence of definitive evidence, the American Cancer Society and most other national nutrition guidelines advise caution, suggesting that patients with cancer “obtain antioxidants through food or beverage sources rather than dietary supplements.” The ACS further states that “it is prudent for cancer survivors currently receiving chemotherapy or radiation therapy to limit the usage of supplements to nutrients for which a deficiency has been demonstrated, and avoid dietary supplements exceeding 100% of the Daily Value for antioxidant vitamins.”2

Can Antioxidants Help Prevent Recurrence and/or Reduce Mortality?

Cancer survivors are at an increased risk of secondary cancers, and the ACS advises that such patients “should be encouraged to consume a variety of … antioxidant-rich foods each day.”2 Clinical studies, however, suggest that consumption of antioxidant supplements after diagnosis is not likely to improve prognosis or long-term survival in patients with cancer.

A 2006 systematic review of randomized controlled trials in patients with cancer or preinvasive lesions found no relationship between antioxidant supplementation and all-cause mortality.10 Another study followed 77,719 residents of Washington State over 10 years and found no association between supplementation with vitamin E or C and cancer mortality.11 Additionally, a randomized trial found that beta-carotene supplements raised the risk of recurrence in colorectal adenoma patients who smoke and/or consume alcohol (but decreased it in nonsmokers/nondrinkers).12

Concluding Thoughts

Based on existing evidence, patients with cancer should minimize supplement use, especially in doses higher than the recommended daily value, except to meet nutritional needs or as evidence-based therapy for a chronic condition such as osteoporosis.2,3 Very few antioxidant dietary supplements have been studied for their safety and effectiveness, and results from many clinical studies conducted to date have not shown benefits—and in some cases have suggested harm.

Although it is not yet clear whether or in which specific cases antioxidant consumption may interfere with chemotherapy or radiation treatment, it is advisable to apply the cautionary principle and advise patients to avoid antioxidant dietary supplements during treatment, until further study brings greater clarity. Moderate consumption of antioxidant-containing foods such as vegetables and fruits, however, may be beneficial in reducing cancer risk and in maintaining health postdiagnosis. Vitamin pills in no way compensate for consumption of healthful foods. ■

Disclosure: Dr. Cassileth and Mr. Yarett reported no potential conflicts of interest.

References

1. Velicer CM, Ulrich CM: Vitamin and mineral supplement use among US adults after cancer diagnosis: A systematic review. J Clin Oncol 26:665-673, 2008.

2. Rock CL, Doyle C, Demark-Wahnefried W, et al: Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 62:243-274, 2012.

3. Kushi LH, Doyle C, McCullough M, et al: American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: Reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin 62:30-67, 2012.

4. Lawenda BD, Kelly KM, Ladas EJ, et al: Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst 100:773-783, 2008.

5. Klein EA, Thompson IM, Jr., Tangen CM, et al: Vitamin E and the risk of prostate cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306:1549-1556, 2011.

6. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 330:1029-1035, 1994.

7. Omenn GS, Goodman GE, Thornquist MD, et al: Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334:1150-1155, 1996.

8. Gaziano JM, Glynn RJ, Christen WG, et al: Vitamins E and C in the prevention of prostate and total cancer in men: The Physicians’ Health Study II randomized controlled trial. JAMA 301:52-62, 2009.

9. Bairati I, Meyer F, Jobin E, et al: Antioxidant vitamins supplementation and mortality: A randomized trial in head and neck cancer patients. Int J Cancer 119:2221-2224, 2006.

10. Davies AA, Davey Smith G, Harbord R, et al: Nutritional interventions and outcome in patients with cancer or preinvasive lesions: systematic review. J Natl Cancer Inst 98:961-973, 2006.

11. Pocobelli G, Peters U, Kristal AR, et al: Use of supplements of multivitamins, vitamin C, and vitamin E in relation to mortality. Am J Epidemiol 170:472-483, 2009.

12. Baron JA, Cole BF, Mott L, et al: Neoplastic and antineoplastic effects of beta-carotene on colorectal adenoma recurrence: Results of a randomized trial. J Natl Cancer Inst 95:717-722, 2003.



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