About Herbs, Botanicals & Other Products

Scientific Name
Indole-3-Methanol
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Common Name

I3C, 1H-Indole-3-methanol, indole-3-methanol, 3-(Hydroxymethyl)indole, 3-indolylcarbinol, indolylmethanol

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Brand Name

I3C Plus (Health Products Distributors)

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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 (1). Data from clinical trials show that I3C is effective in treatment of precancerous cervical dysplasia (2) and vulvar intraepithelial neoplasia (3). In premenopausal women, a supplement containing I3C and 7-hydroxymatairesinol significantly increased the urinary 2:16-hydroxyestrone ratio, a known biomarker for the reduction of breast cancer risk (4). I3C also stimulates detoxification enzymes in the gut and liver (5). Several in vitro studies demonstrate that it can cause cell cycle arrest (6) (7) and apoptosis (8) (9) (10) (11) (12) in cancer cell lines. I3C is generally well tolerated when taken orally. I3C may promote tumor growth in animals that have been exposed to carcinogens (13). Because it may induce cytochrome P450 enzymes (14), I3C may interact with several medications.

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Food Sources

Broccoli, brussel sprouts, cabbage, cauliflower, collards, kale, kohlrabi, mustard greens, rapeseed, rutabaga, turnip

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Purported Uses
  • Cancer prevention
  • Detoxification
  • Viral infections
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Mechanism of Action

Studies indicate that I3C has potential value as a chemopreventive agent for breast cancer through its estrogen receptor (ER) modulating effect (15). There is also evidence to support the fact that I3C has a different mechanism of action than tamoxifen and that these two substances can be used synergistically (6). An in vitro study also found that I3C reduces breast cancer cell migration and invasion by inhibiting matrix metalloproteinase (MMP)-2 expression and blocking extracellular signal-regulated kinase (ERK)/Sp1-mediated gene transcription (16). I3C also down-regulates the expression of the estrogen-responsive genes pS2 and cathepsin-D and up-regulates BRAC1 (17). 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 (7). One randomized clinical trial suggests that I3C can increase the 2-OH-estrone to -estriol metabolite ratio (18). This is thought to decrease the risk of ER-sensitive breast cancer and cervical cancer. In human lung carcinoma A549 cells, I3C significantly reduced cell proliferation and induced apoptosis and cell cycle arrest at the G0/G1 phase (12). I3C also lowered the LD50 of gemcitabine (Gemzar) and decrease the growth of pancreatic cancer cells, possibly through reactivation of the tumor suppressor gene p16INK4a (19). Diidolylmethane (DIM), a metabolite of I3C, can induce apoptosis by modulating the expression of the Bax/Bcl-2 (10). I3C can cause apoptosis of prostate cancer cells in vitro by inhibition of Akt, activation (8). It also holds promise in preventing cancer with a papillomavirus component (20) (21). I3C induces cytochrome P450 1 family, which may lead to potential drug interactions (14). 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.

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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)

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Adverse Reactions

I3C is usually well tolerated when taken orally.
Reported: Some patients can experience skin rash.
(5) (15)

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Herb-Drug Interactions

Theoretically, I3C induces cytochrome P450 1 family and reduces serum concentration of medications metabolized by this enzyme.

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Herb Lab Interactions

In rare cases, small increases in ALT have been known to occur.
(5) (15)

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Literature Summary and Critique

Laidlaw M, Cockerline CA, Sepkovic DW. Effects of a breast-health herbal formula supplement on estrogen metabolism in pre- and post-menopausal women not taking hormonal contraceptives or supplements: a randomized controlled trial. Breast Cancer. 2010 Dec 16;4:85-95.
This randomized, double-blind, placebo-controlled, parallel group study enrolled pre- (n=47) and post-menopausal (n=49) women who were not on contraceptives or hormone replacement therapy. Subjects were randomized to receive either treatment or placebo. A supplement containing 7-hydroxymatairesinol (HMR lignan) and indole-3 carbinol (I3C), along with other minor herbal constituents, was given to the treatment group. The placebo group received capsules containing microcrystalline cellulose. At baseline and study end (day 28), blood samples were analyzed for serum enterolactone concentrations, and morning urine samples were evaluated for estrogen metabolites. Pre-menopausal women receiving the HMR lignan/I3C upplement had a significant increase (p=0.003) in urinary 2-hydroxyestrone (2-OHE) concentrations and in 2:16á-OHE ratio (p=0.016). Post-menopausal women receiving the supplement had a significant increase in urinary 2-OHE concentrations (p=0.035). In the pre- and post-menopausal groups combined, a significant increase in urinary 2-OHE concentrations (p=0.001) and a trend (p=0.074) toward increased 2:16-OHE ratio were observed. The authors concluded that HMR lignan/I3C supplementation significantly increased estrogen C-2 hydroxylation, which may reduce the risk for breast and other estrogen-related cancers.

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.

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References
  1. Wattenberg LW, Loub WD. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res 1978;38:1410-3.
  2. Bell MC, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol 2000;78:123-9.
  3. 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.
  4. Laidlaw M, Cockerline CA, Sepkovic DW. Effects of a breast-health herbal formula supplement on estrogen metabolism in pre- and post-menopausal women not taking hormonal contraceptives or supplements: a randomized controlled trial. Breast Cancer. 2010 Dec 16;4:85-95.
  5. Indole-3-Carinol(I3C) Background Information. National Toxicology Program. NIEHS.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. Choi HS, Cho MC, Lee HG, et al. Indole-3-carbinol induces apoptosis through p53 and activation of caspase-8 pathway in lung cancer A549 cells. Food Chem Toxicol. 2010 Mar;48(3):883-90.
  13. Dashwood RH. Indole-3-carbinol: anticarcinogen or tumor promoter in brassica vegetables? Chem Biol Interact 1998;110:1-5.
  14. 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.
  15. Wong GY, et al. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl 1997;28-29:111-6.
  16. Hung WC, Chang HC. Indole-3-carbinol inhibits Sp1-induced matrix metalloproteinase-2 expression to attenuate migration and invasion of breast cancer cells. J Agric Food Chem. 2009 Jan 14;57(1):76-82.
  17. 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.
  18. 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.
  19. Lyn-Cook BD, Mohammed SI, Davis C, et al. Gender differences in gemcitabine (Gemzar) efficacy in cancer cells: effect of indole-3-carbinol. Anticancer Res. 2010 Dec;30(12):4907-13.
  20. 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.
  21. 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.
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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.

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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.
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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.

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Patient 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).
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Side Effects
  • Skin rash
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Dosage (Inside MSKCC Only)
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Last updated: May 4, 2011