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Doxorubicin

Also indexed as: Adriamycin®, Rubex®

Doxorubicin is a chemotherapy drug used primarily to treat people with cancer.

Interactions with Dietary Supplements

Carnitine
Animal research suggests carnitine may prevent doxorubicin’s toxicity.1

Coenzyme Q10
Pretreating people with the antioxidant coenzyme Q10 before administration of doxorubicin has reduced cardiac toxicity2 —an action also reported in animals.3 Some doctors recommend 100 mg per day.

Melatonin
Melatonin supplementation (20 mg per day) has decreased toxicity and improved effectiveness of chemotherapy with doxorubicin.4

N-acetyl cysteine (NAC)
The antioxidant supplement N-acetyl cysteine (NAC) has protected animals from the cardiotoxicity of doxorubicin,5 although human research has not been able to confirm these results.6 Most doctors do not yet suggest NAC for people taking doxorubicin.

Riboflavin
Animal research suggests doxorubicin may deplete riboflavin and that riboflavin deficiency promotes doxorubicin toxicity.7

Vitamin C
The antioxidant vitamin C has protected against cardiotoxicity (damage to the heart) of doxorubicin in an animal study.8 In this trial, vitamin C significantly increased the life expectancy of mice and guinea pigs without interfering with anticancer action of the drug. Despite the lack of human data, some doctors recommend that patients taking doxorubicin supplement at least 1 gram of vitamin C per day.

Vitamin E
Animal studies show that the antioxidant activity of vitamin E protects against doxorubicin-induced cardiotoxicity.9 10 Test tube evidence suggests that vitamin E might also enhance the anticancer action of the drug.11 Human trials exploring the cardioprotective action of vitamin E in people taking doxorubicin remain inconclusive; however, some evidence suggests that vitamin E may allow for higher drug doses without increasing toxicity.12

Anecdotal reports indicate that very high (1,600 IU) amounts of vitamin E may reduce the amount of hair loss accompanying use of doxorubicin.13 However, while protection against hair loss was confirmed in a rabbit study, human research has not found this to be true.14

Summary of Interactions for Doxorubicin

Depletion or interference Riboflavin*
Adverse interaction None known
Side effect reduction/prevention Carnitine*
Coenzyme Q10
Melatonin
Vitamin C*
Vitamin E*
Supportive interaction Melatonin
Reduced drug absorption/bioavailability None known
Other (see text) N-acetyl cysteine (NAC)

For the convenience of the reader, the information in the summary is categorized as follows: “Depletion or interference” indicates the drug may deplete or interfere with the absorption or function of the supplement or herb. “Adverse interaction” indicates that the supplement or herb used together with the drug may result in undesirable effects. “Side effect reduction/prevention” indicates the supplement or herb may reduce the likelihood and/or severity of a potential side effect caused by the drug. “Supportive interaction” indicates the supplement or herb may support or aid the function of the drug. “Reduced drug absorption/bioavailability” indicates that the supplement or herb may decrease the absorption and/or activity of the drug in the body. An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

References:

1. Alberts DS, Peng Y-M, Moon TE, Bressler R. Carnitine prevention of adriamycin toxicity in mice. Biomedicine 1978;29:265–8.

2. Judy WV, Hall JH, Dugan W, et al. Coenzyme Q10 reduction of Adriamycin® cardiotoxicity. In Biomedical and Clinical Aspects of Coenzyme Q, vol. 4, ed. K Folkers, Y Yamamura. Amsterdam: Elsevier/North Holland Biomedical Press, 1984, 231–41.

3. Ogura R, Toyama H, Shimada T, Murakami M. The role of ubiquinone (coenzyme Q10) in preventing Adriamycin®-induced mitochondrial disorders in rat heart. J Appl Biochem 1979;1:325.

4. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.

5. Doroshow JH, Locker GY, Ifrim I, et al. Prevention of doxorubicin cardiac toxicity in the mouse by N-acetylcysteine. J Clin Invest 1981;68:1053–64.

6. Meyers C, Bonow R, Palmeri S, et al. A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by N-acetylcysteine. Semin Oncol 1983;10:53–5.

7. Pinto J, Raiczyk GB, Huang YP, Rivlin RS. New approaches to the possible prevention of side effects of chemotherapy by nutrition. Cancer 1986;58:1911–4.

8. Fujita K, Shinpo K, Yamada K, et al. Reduction of Adriamycin® toxicity by ascorbate in mice and guinea pigs. Cancer Res 1982;42:309–16.

9. Myers C, McQuire W, Young R. Adriamycin® amelioration of toxicity by alpha-tocopherol. Cancer Treat Rep 1976;60:961–2.

10. Sonneveld P. Effect of alpha-tocopherol on the cardiotoxicity of Adriamycin® in the rat. Cancer 1978;62:1033–6.

11. Ripoll EAP, Rama BN, Webber MM. Vitamin E enhances the chemotherapeutic effects of Adriamycin® on human prostatic carcinoma cells in vitro. J Urol 1986;136:529–31.

12. Weijl NI, Cleton FJ, Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treatment Rev 1997;23:209–40 [review].

13. Wood LA. Possible prevention of Adriamycin®-induced allopecia by tocopherol. N Engl J Med 1985;312:1060 [letter].

14. Weijl NI, Cleton FJ, Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treatment Rev 1997;23:209–40 [review].