For Patients & Caregivers
Bottom Line: 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 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.
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.
- 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.
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.
For Healthcare Professionals
Indole-3-Carbinol (I3C) is a 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).
Severa studies demonstrate that it can cause cell cycle arrest (6)(7) and apoptosis (8)(9)(10)(11)(12) in cancer cell lines, has antiangiogenic activity (22)and inhibits tobacco smoke-induced lung adenocarcinoma in mice (23). Studies also indicate that I3C enhances efficacy of gemcitabine (24) and acts synergistically with bortezomib (25) in vitro.
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).
I3C is generally well tolerated when taken orally. But it may promote tumor growth in animals that have been exposed to carcinogens (13). Because it induces cytochrome P450 enzymes (14), I3C may interact with several medications.
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 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 cyclin-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). Diindolylmethane (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).
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 diindolylmethane and indolylcarbazole, which are further metabolized in the liver. Most metabolites are excreted through the feces.
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.