Possible Interactions Between Dietary Antioxidants and Chemotherapy

Possible Interactions Between Dietary Antioxidants and Chemotherapy

The use of alternative therapies among cancer patients has increased dramatically since the 1970s. A recent review of published surveys found that anywhere from 7% to 64% of adult cancer patients were using such therapies.[1] Preliminary analysis of a study of children with cancer in New York revealed that 74% were taking some form of alternative therapy and that up to 23% were taking antioxidants.[2]

As patients ask their physicians more questions about these therapies, it has become more important for practicing oncologists to become familiar with the risks and benefits of alternative modalities. The article by Drs. Labriola and Livingston provides several useful strategies for counseling patients interested in antioxidant supplementation. However, it is also useful to review the current limited status of information in this field and to explore why no definitive recommendations about supplements can be made.

Antioxidants and Cancer: What We Do and Do Not Know

The initiation, promotion, and progression of cancer, as well as the side effects of chemotherapy and radiation therapy, are related to an imbalance between reactive oxygen species and the antioxidant defense system.[3] The cancer-protective effects of a healthy diet are most often associated with dietary intake of fruits and vegetables.[4] This is likely related to the role of fruits and vegetables as important sources of antioxidant micronutrients, such as vitamins C and E, carotenoids, coenzyme Q10, phytoestrogens, glutathione, polyphenols, and other bioflavonoids.

The World Cancer Research Fund and the American Institute of Cancer Research panel supported the role of increased fruit and vegetable consumption, but not antioxidant supplementation, in the prevention of cancer.[5] Several large intervention trials have found no evidence that beta-carotene protects against cancer, and there are data to suggest that it may be harmful. Both the Beta-Carotene and Retinol Efficacy Trial (CARET)[6] and the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBCCPS)[7] revealed an increased relative risk for lung cancer among high-risk individuals receiving beta-carotene supplementation. However, a trial from Linxian, China, showed a reduction in mortality from all cancers among patients taking selenium, beta-carotene, and alpha-tocopherol supplements.[8]

There is still limited information about whether levels of antioxidants are reduced in patients with cancer. Studies measuring antioxidant levels in cancer patients have made the following observations: (1) retinol and alpha-tocopherol levels decrease during treatment with doxorubicin[9]; (2) vitamin E and selenium levels return to normal after chemotherapy for cervical cancer[10]; and levels of vitamins E and C and selenium decrease during chemotherapy for breast cancer.[11] Plasma and leukocyte vitamin C levels were shown to be significantly lower in children with acute lymphoblastic leukemia than in healthy controls, even when corrected for intake.[12] In another study, lower levels of the antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase were observed in children with acute lymphoblastic leukemia.[13] However, the benefits of normalizing antioxidant levels in patients with cancer have not been adequately demonstrated.

Although many advocates of alternative therapies encourage the use of antioxidant supplements during chemotherapy, in fact, little is known about their effects. Only a few trials of antioxidant supplementation have been completed in patients with breast, lung, and squamous cell cancer.[14-16] Although increases in survival have been reported, all of these studies had a limited number of patients, and survival data were based on comparisons with historical controls. Therefore, no conclusions about the benefits of supplementation can be drawn from these studies.

What to Tell Patients About Supplements

Until further research on the risks and benefits of antioxidant supplementation is undertaken, recommendations for supplementation must be made with caution. Patients need to clearly understand that by taking antioxidants they may be sacrificing long-term cure for short-term improvements in tolerance to treatment.

Maintaining an open dialogue with patients is paramount. Surveys have demonstrated that approximately 50% of patients do not inform their physicians that they are using alternative therapies, primarily because they were never asked specifically about such therapies or were afraid to discuss them for fear of incurring the physician’s disapproval.[2] However, as alternative therapies have become more widely discussed in the media, patients have shown a greater willingness to discuss their use of such therapies. As there are limited data on the interactions of antioxidants and chemotherapy, patients should still be counseled to defer antioxidant supplementation until after the completion of chemotherapy, to minimize the risk of adversely affecting its efficacy.

As Drs. Labriola and Livingston point out, despite their physician’s advice to the contrary, a substantial number of patients still choose to continue antioxidant supplementation. If so, an approach like the one recommended by the authors could be used. However, I would strongly recommend that the pharmacokinetics of both the chemotherapeutic agents and the supplements be used to determine the optimal schedule. This would require the involvement of an experienced pharmacologist or other qualified consultant who can help guide the complicated pharmacokinetic analysis. Such an approach would be amenable to computer modeling.

An important consideration, however, is that for herbs with antioxidant properties, the lack of standardization of products from manufacturer to manufacturer, or even lot to lot, can prohibit such an analysis. For supplements such as vitamin C or coenzyme Q10, the concentration of a particular product can be ascertained more easily.

More Information Needed

More information is needed on the levels of antioxidants in different types of cancers and in the setting of different chemotherapy regimens. A transgenic mouse model to evaluate the interactions of chemotherapy and antioxidants in childhood leukemia is currently being developed. Other studies are assessing the levels of antioxidants and oxidative stress in patients receiving chemotherapy. Eventually, randomized trials of supplementation will be conducted to critically evaluate the risks and benefits of antioxidant supplementation during chemotherapy.


1. Ernst E, Cassileth BR: The prevalence of complementary/alternative medicine in cancer. Cancer 83:777-782, 1998.

2. Kelly KM, Jacobson JS, Kennedy DD, et al: Use of complementary therapies among pediatric oncology patients at an urban medical center (abstract). Proc Am Soc Clin Oncol 17:543a, 1998.

3. Ames BN, Gold LS, Willett WC: The causes and prevention of cancer. Proc Natl Acad Sci USA 92:5258-5265, 1995.

4. Willett WC: Diet, nutrition, and avoidable cancer. Environ Health Perspect 103:165-170, 1995.

5. World Cancer Research Fund: Food, nutrition and the prevention of cancer: a global perspective. World Research Fund/American Institute for Cancer Research, Washington, DC, 1997.

6. Omenn GS, Goodman GE, Thornquist MD, et al: Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst 88:1550-1559, 1996.

7. Albanes D, Heinonen OP, Taylor PR, et al: Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: Effects of baseline characteristics and study compliance. J Natl Cancer Inst 88:1560-1570, 1996.

8. Blot WJ, Li JY, Taylor PR, et al: Nutrition intervention trials in Linxian, China: Supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 85:1483-1492, 1993.

9. Faure H, Coudray C, Mousseau M, et al: 5-Hydroxymethyluracil excretion, plasma t-bars and plasma antioxidant vitamins in Adriamycin-treated patients. Free Radic Biol Med 20:979-983, 1996.

10. Bhuvarahamurthy V, Balasubramanian V, Govindasamy S: Effect of radiotherapy and chemoradiotherapy on the circulating antioxidant system of human uterine cervical carcinoma. Mol Cell Biochem 158:17-23, 1996.

11. Subramaniam S, Shyama S, Jagadeesan M, et al: Oxidant and antioxidant levels in the erythrocytes of breast cancer patients treated with CMF. Med Sci Res 21:79-80, 1993.

12. Kakar S, Wilson C, Bell J: Plasma and leucocyte ascorbic acid concentrations in acute lymphoblastic leukemia. Ir J Med Sci 144:227-232, 1975.

13. Senturker S, Karahalil B, Inal M, et al: Oxidative DNA base damage and antioxidant enzyme levels in childhood acute lymphoblastic leukemia. FEBS Lett 416:286-290, 1997.

14. Jaakkola K, Lahteenmaki P, Laakso J, et al: Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small-cell lung cancer. Anticancer Res 12:599-606, 1992.

15. Rogereau A, Sallerin T, Chapet J, et al: Traitement adjuvant de sujets atteints de lesions neoplasiques par l’association d’un complexe vitaminique et d’un acide amine. Ann Gastroenterol Hepatol 29:99-102, 1993.

16. Folkers K, Brown R, Judy W, et al: Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Comm 192:241-245, 1993.

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