Comprehensive Guide to Indole-3-Carbinol

Indole-3-CarbinolDr. James Meschino DC, MS, ND
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General Features
Indole-3-Carbinol has been shown to be one of the major anti-cancer substances found in cruciferous vegetables. Frequent consumption of these vegetables (broccoli, cauliflower, cabbage, Brussels sprouts, kale and bok choy) is associated with reduced risk of cancer in many human and animal studies.1-8 Indole -3-Carbinol is a member of the class of sulfur-containing chemicals called glucosinolates (previously called thioglucosides).9 It is formed by the action of myrosinase enzyme acting on the parent compound glucosinolates, whenever cruciferous vegetables are crushed (e.g., chewing) or cooked.10,11 Indole-3-Carbinol and other glucosinolates (e.g., other indoles and isothiocyanates such as sulforphane) are antioxidants and potent stimulators of Phase I and Phase II detoxification enzymes in the liver and intestinal epithelial cells.12,13,14 In this capacity it helps the body more easily eliminate toxic compounds, including many carcinogens.15,16,17 Indole-3-Carbinol also acts as a phytoestrogen (plant-based estrogens) and, in this capacity, can bind to estrogen receptors in the body, reducing the ability of stronger estrogens from over stimulating reproductive tissues such as the breast, cervix, uterus, and in males, the prostate gland. In this regard, the ingestion of Indole-3-Carbinol is highly associated with the prevention of reproductive organ cancers in women and men.3,4,8 It also promotes the metabolism of certain endogenous estrogens (estrone) into a safer, less cancer-promoting form (2-OH-estrone), further helping to reduce risk of reproductive organ cancers, according to modern wisdom.18,19,20 Thus far, human studies have used a dose of 300-400 mg per day to demonstrate this outcome
Clinical Application and Mechanism of Action
1. Prevention of Female Reproductive Cancers
In experimental animal testing with mice and rats, Indole-3-Carbinol and brussels sprouts, respectively, have demonstrated an ability to reduce mammary cancer incidence in animals exposed to carcinogens that are known to promote mammary cancer in these species.21,22 In human studies, the ingestion of Indole-3-Carbinol has been shown to increase the metabolism of estrone hormone to 2-hydroxyestrone rather than the16-alpha-hydroxyestrone metabolite. Studies indicate that 16-alpha-hydroxyestrone is associated with an increased risk of breast cancer in women and, conversely, 2-hydroxyestrone is associated with a reduction in breast cancer risk. Thus, Indole-3-Carbinol influences the body’s enzyme systems in a fashion that favorably influences the 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio, helping to reduce risk of breast cancer.20,21,23,24 A large prospective study involving 5,000 Italian women and a second study of patients with either benign or malignant breast lesions highlighted the ability of a higher 2/16 hydroxyestrone ratio to predict which women were less prone to breast cancer development.
a. Breast Cancer: Epidemiological studies and experimental evidence strongly suggests that Indole-3-Carbinol may reduce breast cancer risk through the above-cited mechanisms.25,26,27,28 To date there are no human intervention trials that have tested Indole-3-Carbinol as a preventive or therapeutic agent against breast cancer.
b. Cervical Cancer: In a 12-week double-blind study, 8 of 17 patients with early-stage cervical cancer given 200 or 400 mg of Indole-3-Carbinol per day experienced a complete reversal of their condition.29 Animal studies have also shown that indole-3-carbinol can help prevent cervical cancer in the presence of various carcinogens.30,31
2. Respiratory Tract Papillomas
Indole-3-Carbinol supplementation reduced or halted the formation of papillomas (precancerous lesions) in 12 out of 18 patients with recurrent respiratory tract papillomas in a small trial.
3. Prostate Cancer
In animal studies, the ingestion of Indole-3-Carbinol has been shown to inhibit the growth of PC-3-type human prostate cancer cells by arresting their cell division cycle and by promoting apoptosis (programmed cell death).8 A Seattle study of men living in that city indicated that men consuming three or more servings per week of cruciferous vegetables had a risk of prostate cancer that was 50% lower than men consuming fewer servings of these vegetables, after controlling for other confounding variables.33 To date there no human intervention trials have tested Indole-3-Carbinol as a preventive or therapeutic agent against prostate cancer.
Dosage and Standardized Grade
1. General Health Maintenance: 25-100 mg per day
2. Therapeutic Applications: 300-400 mg per day
Adverse Side Effects, Toxicity and Contraindications
At doses of 800 mg per day, Indole-3-Carbinol has caused dizziness and unsteady gait (signs of nervous system toxicity) in humans and in animal studies. As well, Indole-3-Carbinol is a powerful stimulator of phase I detoxification enzymes, and as such, it may speed up the detoxification of certain medications, changing their required dosage. However, one challenge study of this kind revealed that Indole-3-Carbinol intake did not interfere with oral contraceptive medications.33 Nevertheless, health practitioners and patients should monitor their response to Indole-3-Carbinol supplementation, if taken at therapeutic doses concurrently with other drugs. According to animal studies, this appears to be especially true in regards to the following medications:
testosterone replacement therapy
oral contraceptives
hormone replacement therapy
anti-seizure medications
immune-suppressant and anti-viral drugs
Drug-Nutrient Interactions
1. Antacids and Heartburn medications (H-2 antagonist drugs ): By reducing stomach acidity these drugs reduce the absorption of indole-3-carbinol. Therefore, they should not be taken at the same time of day or at the same meal.33
2. More Rapid Detoxification Of Other Drugs: As stated above, Indole-3-Carbinol may speed up the detoxification of any number of drugs due to its stimulation affect on phase I detoxification centers. Thus, patient monitoring is required with Indole-3-Carbinol supplementation at the therapeutic doses mentioned previously (300-400 mg per day).
Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the developing fetus and there is generally insufficient evidence at this time to determine an absolute level of safety for most dietary supplements other than a prenatal supplement. Any supplementation practices beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium and the treatment of preeclampsia.)

References: Pregnancy and Lactation
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3. The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.
4. Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine. Institute of Applied Complementary Medicine Inc. 1997.
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