How It Works
Bottom Line: The only cancer that indole-3-carbinol has been shown to prevent is cervical cancer, and only in women with pre-cancerous cervical growths.
Indole-3-carbinol, also called I3C, is a natural compound found in vegetables such as broccoli, brussel sprouts, cabbage, cauliflower, and kale. It is known to stimulate detoxifying enzymes in the gut and liver, but it has come under more study lately for its potential anti-cancer properties. Animals that are fed a diet rich in I3C have a slower growth of their cancers. Laboratory studies show that it blocks estrogen activity by interfering with the estrogen receptor. This suggests that I3C might be useful in preventing or treating estrogen-sensitive cancers (such as breast and cervical cancers), possibly in addition to tamoxifen, but not enough studies have been done in humans to determine this. In addition, I3C can cause cell death in prostate cancer cells in the laboratory. One source of worry is a few experiments in animals that showed that I3C increased the cancer-causing potential of certain environmental carcinogens, but this has not been confirmed in humans.
Purported Uses
To prevent cancer
Laboratory and animal studies suggest that indole-3-carbinol may prevent estrogen-dependent cancers, but only one clinical trial has been performed, which showed that indole-3-carbinol can cause regression of cervical intraepithelial neoplasia (CIN), a condition that can lead to cervical cancer.
To detoxify the body
Indole-3-carbinol stimulates detoxifying enzymes in the gut and liver, but this use has not been tested in clinical trials.
To treat viral infections
No scientific evidence supports this use.
Research Evidence
Cervical cancer prevention:
A clinical trial was performed to study the ability of indole-3-carbinol (I3C) to treat cervical intraepithelial neoplasia (CIN), a pre-cancerous growth that can lead to cervical cancer. Thirty women enrolled in the study. They were randomly assigned to take (1) a placebo pill, (2) 200 mg/day of I3C, or (3) 400 mg/day of I3C for 12 weeks. At the end of the study, almost half of the women taking I3C had complete regression of their CIN, compared to none of the women who took placebo. Usually, CIN is surgically removed, so I3C may be a non-surgical option for women with this condition. More clinical trials will help establish this.
Warnings
A few experiments in animals suggested that I3C might promote tumor growth in animals exposed to carcinogens, rather than fight it. This effect has not been confirmed in humans.
Because I3C affects the liver enzyme cytochrome P450 1A2, which metabolizes many common medications for removal from the body, you should check with your doctor to see if I3C will interfere with your medication(s).
This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
Side Effects
Skin rash
Scientific Name
Indole-3-Methanol
Common Name
I3C, 1H-Indole-3-methanol, indole-3-methanol, 3-(Hydroxymethyl)indole, 3-indolylcarbinol, indolylmethanol
Brand Name
I3C Plus (Health Products Distributors)
Clinical Summary
Indole-3-Carbinol (I3C) is a specific compound found in cruciferous vegetables including broccoli, cabbage and cauliflower. Because diets high in these vegetables retard cancer growth in animals, I3C is thought to be a good candidate for cancer prevention. I3C is known to stimulate detoxification enzymes in the gut and liver
(6). Several studies demonstrate that it can cause cell cycle arrest
(3) (8) and apoptosis
(4) (13) (14) (15)in cancer cell lines. Data from clinical trials show that I3C is effective in treatment of precancerous cervical dysplasia
(2)and vulvar intraepithelial neoplasia
(16).
I3C is generally well tolerated when taken orally. Certain studies suggest I3C may promote tumor growth in animals that have been exposed to carcinogens
(5), but the potential risk has never been documented in humans. Because it may induce cytochrome P450s
(17), I3C may interact with several medications.
Food Sources
Broccoli, brussel sprouts, cabbage, cauliflower, collards, kale, kohlrabi, mustard greens, rapeseed, rutabaga, turnip
Purported uses
Cancer prevention
Detoxification
Viral infections
Mechanism of Action
I3C is a naturally occurring compound found in cruciferous vegetables that is known to stimulate detoxifying enzymes in the gut and liver (6). Many studies indicate its potential value as a chemopreventive agent for breast cancer through its estrogen receptor (ER) modulating effect (7). I3C also down-regulates the expression of the estrogen-responsive genes pS2 and cathepsin-D and up-regulates BRAC1 (12). Other in vitro studies show that I3C inhibits the expression of cycline-dependent kinase-6 and induces a G1 cell cycle arrest independent of ER signaling (8). Diidolylmethane (DIM), a metabolite of I3C, can induce apoptosis by modulating the expression of the Bax/Bcl-2. (14) There is evidence to support the fact that I3C has a different mechanism of action than tamoxifen and that these two substances can be used synergistically (3). One randomized clinical trial suggests that I3C can increase the 2-OH-estrone:estriol metabolite ratio (10). This is thought to decrease the risk of ER-sensitive breast cancer and cervical cancer. I3C can cause apoptosis of prostate cancer cells in vitro by inhibition of Akt activation (4). It also holds promise in preventing cancer with a papillomavirus component (11). I3C induces cytochrome P450 1 family, which may lead to potential drug interactions (17). There is some evidence from animal studies that increases in cytochrome P450 1A1 activity also metabolizes some environmental procarcinogens to their carcinogenic form, but this has not been confirmed in humans.
Pharmacokinetics
No published data regarding the pharmacokinetics of I3C in humans currently exists. Animal studies shows that I3C itself is not active. Gastric acid converts I3C to active metabolites diindoylmethane and indolylcarbazole, which are further metabolized in the liver. Most metabolites are excreted through the feces.
(6)
Warnings
Preliminary evidence suggests that I3C might promote tumor growth in animals exposed to carcinogens.
(5)
Adverse Reactions
I3C is usually well tolerated when taken orally.
Reported: Some patients can experience skin rash.
(6) (7)
Herb-Drug Interactions
Theoretically, I3C induces cytochrome P450 1 family and reduces serum concentration of medications metabolized by this enzyme.
Lab Interactions
In rare cases, small increases in ALT have been known to occur.
(6) (7)
Literature Summary and Critique
Bell MC, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol 2000;78:123-9.A double-blind placebo-controlled study of indole-3-Carbinol. Thirty women with biopsy-proven cervical intraepithelial neoplasia (CIN) received placebo, 200 or 400 mg/day of I3C for 12 weeks. None of the patients in the placebo arm had complete regression of CIN, whereas 4 of 8 (p=0.023) from the 200 mg/day arm and 4 of 9 (p=0.032) from the 400 mg/day arm had complete regression after 12 weeks. The ratio of 2-hydroxyestrone to 16-alpha-hydroxyestrone changed in a dose-dependent fashion. The results of this study show promise for the use of I3C as a nonsurgical option for the treatment of CIN, although the data needs to be confirmed in a large multicenter trial.
References
- Wattenberg LW, Loub WD. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res 1978;38:1410-3.
- Bell MC, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol 2000;78:123-9.
- Cover CM, et al. Indole-3-carbinol and Tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells. Cancer Res 1999; 59:1244-51.
- Chinni SR, Sarkar FH. Akt inactivation is a key event in indole-3-carbinol-induced apoptosis in PC-3 cells. Clin Cancer Res 2002;8:1228-36.
- Dashwood RH. Indole-3-carbinol: anticarcinogen or tumor promoter in brassica vegetables? Chem Biol Interact 1998;110:1-5.
- Indole-3-Carinol(I3C) Background Information. National Toxicology Program. NIEHS.
- Wong GY, et al. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl 1997;28-29:111-6.
- Cover CM, et al. Indole-3-carbinol inhibits the expression of cyclin-dependent kinase-6 and induces a G1 cell cycle arrest of human breast cancer cells independent of estrogen receptor signaling. J Biol Chem 1998;273:3838-47.
- Rosen CA, et al. Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg 1998;118:810-5.
- Bradlow HL, et al. Long-term responses of women to indole-3-carbinol or a high fiber diet. Cancer Epidemiol Biomarkers Prev 1994;3:591-5.
- Jin L, et al. Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Cancer Res 1999;59:3991-7.
- Meng Q, et al. Indole-3-carbinol is a negative regulator of estrogen receptor-alpha signaling in human tumor cells. J Nutr 2000;130:2927-31.
- Chen DZ, et al. Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium. J Nutr 2001;131:3294-302.
- Hong C, et al. Bcl-2 family-mediated apoptotic effects of 3,3'-diindolylmethane (DIM) in human breast cancer cells. Biochem Pharmacol 2002 Mar 15;63(6):1085-97.
- Nachshon-Kedmi M, et al. Indole-3-carbinol and 3,3'-diindolylmethane induce apoptosis in human prostate cancer cells. Food Chem Toxicol 2003 Jun;41(6):745-52.
- Naik R, Nixon S, Lopes A, et al. A randomized phase II trials of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia. Int J Gynecol Cancer 2006;16(2):786-90.
- Yoshida M, Katashima S, Ando J, et al. Dietary indole-3-carbinol promotes endometrial adenocarcinoma development in rats initiated with N-ethyl-N'-nitro-N-nitrosoguanidine, with induction of cytochrome P450s in the liver and consequent modulation of estrogen metabolism. Carcinogenesis. 2004 Nov;25(11):2257-64.
