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Efficacy of indole-3-carbinol

10/25/2003 11:47PM

Question:

Is indole-3-carbinol effective in helping to combat or slow down cancer?

Answer:

Interest in Indole-3-carbinol (I3C) was stimulated by the finding that people eating diets containing higher amounts of fruits and vegetables seemed to have lower cancer rates. I3C is one of a number of plant derived substances that may explain this finding. It is a formed from substances found in the Brassica vegetables, which includes, kale, cabbage, broccoli, brussels sprouts and others. There is some data indicating that I3C may slow the development or prevent the formation of certain types of cancer. Current research is focused on the use of I3C to prevent cancer of the colon, breast, endometrium and cervix. Some of the current research is quite promising, but other research indicates that I3C could actually induce cancer. This is worrisome for obvious reasons. Therefore, the risk versus benefit profile for I3C remains to be determined. The chief effect of I3C seems to be stimulation of the enzymes the body uses for breakdown and detoxification of chemicals. In addition to its stimulatory effects on metabolic enzymes some evidence indicates that I3C may cause cancer cell death and differential cell cycle arrest in cancer cells. I3C has an antioxidant effect that might also provide some benefit. Stimulation of metabolic enzymes can result in reduced levels of some carcinogens. For example, under normal circumstances estrogen is converted into two metabolites. One of the metabolites has a large amount of estrogenic activity and the other is much less active. I3C shifts the metabolism of estrogen to the metabolite with much lower estrogenic activity. This change could result in a beneficial effect against tumors sensitive to estrogen. Many breast, endometrial, and cervical cancers are estrogen sensitive. The effect of I3C is not limited to estrogen sensitive tumors alone and tumor regression has been shown in a number of studies done under laboratory conditions using cell cultures or animals. However, data from studies in humans is limited. Three well-controlled studies in humans have been completed. In a small study of patients with cervical dysplasia or cervical intraepithelial neoplasia (CIN) doses of 200-400 mg per day for 12 weeks resulted in complete regression in about 50 percent of the patients. Similar promising results were reported in a study of patients with a rare condition called recurrent respiratory papillomatosus. The human papilloma virus causes this condition, and is also associated with cervical cancers. Finally, a study of I3C in patients with breast cancer has recently been completed, but to date the results have not been published. I3C must be taken by mouth to be effective. I3C is typically well tolerated at doses up to 400mg daily. Skin rashes and slight increases in liver enzymes have been noted in the available studies. Doses greater than 400 mg per day, may result in vertigo, tremor, and nausea Most individuals consume 20 – 120 mg of I3C per day from various vegetables in their diet. A typical cabbage contains about 1200 mg of I3C. I3C may also be safe when taken at doses used for cancer prevention (200-400 mg daily). However, the long-term risks associated with these higher doses remain unclear. Since I3C stimulates metabolic enzymes, it may reduce the activity of prescription medications. I3C has the potential to interact with tamoxifen (Nolvadex®), clozapine (Clozaril®), cyclobenzaprine (Flexeril®), fluvoxamine (Luvox®), haloperidol (Haldol®), imipramine (Doornail®), mexiletine (Mexitil®), olanzapine (Zyprexa®), pentazocine (Talwin®), propranolol (Inderal®), tacrine (Cognex®), theophylline, Zileuton (Zyflo®), nicotine, and zolmitriptan (Zomig®). I3C may affect the metabolism of other medicines as well. The induction and promotion of cancer is a complicated process. Many factors are involved. The isolated use of (I3C), as opposed to eating a diet high in fruits and vegetables ignores the potential benefit from other components of fruits and vegetables. While most of the information available for I3C indicates it has a beneficial effect, laboratory evidence that I3C promotes some cancers is worrisome. Thus, while it makes sense to eat a diet high in fruits and vegetables, the decision to add I3C in the form of a dietary supplement is something that should be considered in light of the possible risks and benefits. Current information is inadequate to allow easy determination of which patients are likely to benefit or be harmed by the isolated addition of (I3C). This is something that should be determined by a physician. Our current advice - eat your vegetables. 

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Response by:

Cincinnati Children’s Hospital Medical Center Robert James Goetz, PharmD, DABAT
Assistant Professor of Pharmacy Practice
Drug and Poison Information Center
Cincinnati Children’s Hospital Medical Center
University of Cincinnati