Common Names

  • I3C
  • Indole-3-methanol
  • 3-(Hydroxymethyl)indole
  • 3-Indolylcarbinol
  • Indolylmethanol

For Patients & Caregivers

How It Works

Indole 3-carbinol has cancer-preventive effects, but it has not been shown to treat cancer in humans.

Indole-3-carbinol, also called I3C, is a resulting compound that comes from eating vegetables such as Brussels sprouts, cabbage, cauliflower, broccoli, and kale. It is known to stimulate detoxifying enzymes in the gut and liver. Because diets high in these vegetables slow cancer growth in animals, I3C is thought to be a good candidate for cancer prevention. Laboratory studies show that I3C may have anticancer activities across a variety of tumor types, and may have added benefit with some chemotherapy drugs. However, other animal studies suggest that I3C might also promote tumor growth. Additional studies and human clinical trials are needed to determine the circumstances under which I3C might be suitable for cancer prevention.

Purported Uses

  • To prevent cancer
    Laboratory and animal studies suggest that indole-3-carbinol may prevent a variety of cancers, including estrogen-dependent cancers, but only one clinical trial has been performed. This small study concluded that I3C can reverse cervical intraepithelial neoplasia (CIN), a condition that can lead to cervical cancer, but these findings are too limited to draw definite conclusions. In addition, some animal studies indicate that I3C supplementation might have tumor-promoting effects. More studies including clinical trials are needed.
  • To treat viral infections
    Preliminary studies suggest several benefits to immune function including counteracting the activity of human papiloma virus (HPV), but no studies have been conducted in humans.

Do Not Take If

  • You are taking cytochrome P450 1A2 substrate drugs: I3C may reduce the effectiveness of these drugs.

Side Effects

  • Skin rash
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For Healthcare Professionals

Scientific Name

Indole-3-Methanol, 1H-Indole-3-methanol

Clinical Summary

Indole-3-Carbinol (I3C) is a phytochemical derived from the breakdown of glucosinolates found in cruciferous vegetables including Brussels sprouts, kale, broccoli, cabbage, and cauliflower (26). Epidemiologic studies suggest that a diet high in cruciferous vegetables is associated with a lower risk of cancer and that I3C has anticarcinogenic properties across a wide range of cancers (27).

Various in vitro and in vivo studies suggest antimicrobial (28) (29), anti-inflammatory (30) (31) (32), anti-estrogenic (33) , and antiangiogenic (21) (22) effects. Antiproliferative and anticancer effects have been demonstrated in human breast (34) (35) (36) (37), prostate (38), melanoma (39), endometrial (40) , liver (41) (42), and pancreatic cancer cells (43), as well as animal models of lung (12) (23) (44), laryngeal (45), and nasopharyngeal carcinoma (46). In addition, preliminary experiments suggest I3C may potentiate or have sensitizing effects in combination with bortezomib (25) (47), tamoxifen (48), doxorubicin (49) (50), vemurafenib (51), fludarabine (52), gemcitabine (24) (43), or acetylsalicylic acid (53), and may reverse cytotoxicity with dexamethasone (54) or cardiotoxicity with doxorubicin (50) . However, these effects have not been confirmed in humans. Studies in animal carcinogenesis models suggest that I3C may also promote tumor growth (55) (56) (57) (58) (59) (60) (61). Additional studies are needed to determine under what conditions I3C could be a suitable chemopreventive agent in humans.

Data from early phase clinical trials suggested that I3C is effective against precancerous cervical dysplasia (2) and vulvar intraepithelial neoplasia (3). In premenopausal women, a supplement containing I3C and 7-hydroxymatairesinol, a dietary ingredient, increased the urinary 2:16-hydroxyestrone ratio, a known biomarker for the reduction of breast cancer risk (4).

I3C is generally well tolerated when taken orally, but it is unclear if I3C supplementation can benefit humans due to its mixed effects in preliminary studies and its ability to induce cytochrome P450 enzymes (14) (62), which may cause interactions with several medications.

Food Sources

Broccoli, Brussels sprouts, cabbage, cauliflower, collards, kale, kohlrabi, mustard greens, rapeseed, rutabaga, turnips

Purported Uses

  • Cancer prevention
  • Detoxification
  • Viral infections

Mechanism of Action

Indole-3-carbinol (I3C) is a natural indolecarbinol compound derived from the breakdown of glucobrassicin produced in cruciferous vegetables such as broccoli and Brussels sprouts (39). Some of the health-protective effects of I3C are attributed to epigenetic mechanisms such as the regulation of HDAC and HAT activities and acetylation of histones and non-histone chromatin proteins (63).

Preliminary studies suggest several benefits to immune function. I3C counteracted immune evasion mechanisms of HPV16 by antagonizing E6 repression of E-cadherin (64). It decreased pro-inflammatory cytokine production and T cell activation by acting as histone deacetylase class I (HDAC-I) inhibitors (31). Other anti-inflammatory mechanisms include regulation of TIR-domain-containing adapter-inducing interferon-β (TRIF)-dependent signaling pathways (30).

In cancer cells, I3C at higher doses (>400 μM) induced apoptosis, while lower doses (<200 μM) inihbited cell growth as well as cyclin E and CDK2 expression (27). It is among compounds that exert antiproliferative and/or proapoptotic effects through regulation of one or more microRNAs (miRNAs), short noncoding RNAs that regulate gene expression by messenger RNA (mRNA) degradation or translation repression (65).

I3C may act as a chemopreventive agent for breast cancer through its estrogen receptor (ER) modulating effect (15) or upregulation of apoptotic enzyme activities (48). It disrupted ER alpha-mediated transcription within IGF1 cascade cell signaling components (34), downregulated expression of estrogen-responsive genes pS2 and cathepsin-D, and upregulated BRAC1 (17). Other inhibitory mechanisms include suppressing epithelial-to-mesenchymal transition (EMT), blocking extracellular signal-regulated kinase (ERK)/Sp1-mediated gene transcription, reducing matrix metalloproteinase (MMP)-2 and MMP-9 activities, and decreasing aromatase expression (16) (36) (37). One randomized clinical trial suggests that the decreased risk of ER-sensitive breast and cervical cancers with I3C may be due to an increase in the 2-OH-estrone:estriol metabolite ratio (18).

In HepG2 cells, I3C induced phase II and antioxidant enzymes (41). Other hepatoprotective mechanisms include immunomodulation and inhibition of pro-inflammatory cytokines and chemokines (66). Acute hepatic inflammation was suppressed via decreased miR-31 expression and subsequent caspase-2-dependent apoptosis in T cells (32). In human lung carcinoma A549 cells, I3C significantly reduced cell proliferation and induced apoptosis and cell cycle arrest at the G0/G1 phase (12). In murine models, chemopreventive effects against lung tumors occurred via reductions in levels of proinflammatory and procarcinogenic proteins (44). In melanoma cells, I3C induced G1-phase cell-cycle arrest and apoptosis by stabilization of PTEN that express wild-type PTEN (39). In prostate cancer cells, I3C inhibits androgen-dependent pathways and appeared to block the inflammatory microenvironment (38), and caused apoptosis by inhibiting Akt activation (8).

I3C coadministration with doxorubicin potentiated cytotoxic effects compared with either agent alone in pre-B acute lymphoblastic leukemia cells (49). Chemosensitive effects were produced in gemcitabine-resistant pancreatic cancer cells via microRNA-21 downregulation (43). I3C also lowered the LD50 of gemcitabine and decreased growth of pancreatic cancer cells, possibly through reactivation of the tumor suppressor gene p16INK4a (19). I3C with genistein produced synergy of apotosis and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in endometrial cancer cells (40). It reversed dexamethasone cytotoxicity via ROS inhibition and enhanced nuclear factor erythroid 2–related factor 2 (Nrf2) expression (54).

Some animal studies suggest that I3C is both an inhibitor and promoter of carcinogenesis with strong induction of placental glutathione S-transferase foci in the liver (57), and modulatory activity that included apoptotic inhibition in colon tumors (55). In addition, I3C may promote endometrial adenocarcinoma through hepatic CYP1 induction and estrogen metabolism modulation (56).

Adverse Reactions

Skin rash (5) (15)

Herb-Drug Interactions

  • Cytochrome P450 1A2 substrates: I3C induces CYP 1A2 and can reduce serum concentrations of medications metabolized by this enzyme (14) (62).

Herb Lab Interactions

In rare cases, small increases in ALT have occurred (5) (15).

Dosage (OneMSK Only)


  1. Bell MC, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol 2000;78:123-9.

  2. 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.

  3. Indole-3-Carinol(I3C). National Toxicology Program. NIEHS. Accessed November 6, 2012.

  4. 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.

  5. 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.

  6. Wong GY, et al. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl 1997;28-29:111-6.

  7. 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.

  8. 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.

  9. 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.

  10. Wang ML, Shih CK, Chang HP, Chen YH. Antiangiogenic activity of indole-3-carbinol in endothelial cells stimulated with activated macrophages. Food Chem. 2012 Sep 15;134(2):811-20.

  11. Taylor-Harding B, Agadjanian H, Nassanian H, et al. Indole-3-carbinol synergistically sensitises ovarian cancer cells to bortezomib treatment. Br J Cancer. 2012 Jan 17;106(2):333-43.

  12. Caruso JA, Campana R, Wei C, et al. Indole-3-carbinol and its N-alkoxy derivatives preferentially target ERalpha-positive breast cancer cells. Cell Cycle. 2014;13(16):2587-2599.

  13. Parajuli B, Shin SJ, Kwon SH, et al. The synergistic apoptotic interaction of Indole-3-Carbinol and Genistein with TRAIL on endometrial cancer cells. J Korean Med Sci. Apr 2013;28(4):527-533.

  14. Wang YQ, Chen C, Chen Z, et al. Indole-3-carbinol inhibits cell proliferation and induces apoptosis in Hep-2 laryngeal cancer cells. Oncol Rep. Jul 2013;30(1):227-233.

  15. Taylor-Harding B, Agadjanian H, Nassanian H, et al. Indole-3-carbinol synergistically sensitises ovarian cancer cells to bortezomib treatment. Br J Cancer. Jan 17 2012;106(2):333-343.

  16. Malejka-Giganti D, Parkin DR, Bennett KK, et al. Suppression of mammary gland carcinogenesis by post-initiation treatment of rats with tamoxifen or indole-3-carbinol or their combination. Eur J Cancer Prev. Apr 2007;16(2):130-141.

  17. Adwas AA, Elkhoely AA, Kabel AM, et al. Anti-cancer and cardioprotective effects of indol-3-carbinol in doxorubicin-treated mice. J Infect Chemother. Jan 2016;22(1):36-43.

  18. Stoner G, Casto B, Ralston S, et al. Development of a multi-organ rat model for evaluating chemopreventive agents: efficacy of indole-3-carbinol. Carcinogenesis. Feb 2002;23(2):265-272.

  19. Vahid F, Zand H, Nosrat-Mirshekarlou E, et al. The role dietary of bioactive compounds on the regulation of histone acetylases and deacetylases: a review. Gene. May 10 2015;562(1):8-15.

  20. D’Costa ZJ, Leong CM, Shields J, et al. Screening of drugs to counteract human papillomavirus 16 E6 repression of E-cadherin expression. Invest New Drugs. Dec 2012;30(6):2236-2251.

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