Indole 3 Carbinol I3C by Ray Sahelian, M.D. Health benefit of INdole 3 carbinol supplement

Indole-3-carbinol is found in cabbage, cauliflower, and brussels sprouts. Indole-3-carbinol is converted in the gut to diindolylmethane (DIM). When an indole 3 carbinol supplement is ingested, there is little or no indole 3 carbinol found in the bloodstream. The substance that is found in the bloodstream after taking an indole 3 carbinol supplement is DIM.

Indole-3-Carbinol (I3C), 200 mg ( With Flax Lignans ), 60 Vcaps
Indole-3-Carbinol ( I3C ) is a naturally occurring phytochemical found in cruciferous vegetables such as cabbage, broccoli, and kale. NOW I3C provides powerful antioxidant protection, helping to prevent cellular damage caused by free radicals. In addition I3C can help to maintain healthy hormonal balance for both men and women and therefore may support the health of the breast, prostate, and other reproductive organs. I3C is also known to support the liver's detoxification processes as well as normal cellular reproduction. LinumLife provides the highest level of Flax Lignans available, which are also beneficial in supporting healthy hormonal balance.*

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Indole 3 Carbinol Supplement Facts
Indole-3-Carbinol (I3C) - 200 mg
LinumLife Complex - 200 mg
     (Flax Seed Lignan Extract) (Linum usitatissimum) (Seed Coat) {yields min. 10 mg as SDG (Secoisolariciresinol Diglucoside)} 

Suggested Usage: As a dietary supplement, take 1 indole 3 carbinol Vcap 1 or 2 times daily, preferably with meals.

* Indole 3 Carbinol I3C daily values are not established.

Effect of indole 3 carbinol supplement ingestion
A phase I study of indole-3-carbinol in women: tolerability and effects.
Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8): Reed GA, Peterson KS, Smith HJ, Gray JC, Sullivan DK, Mayo MS, Crowell JA, Hurwitz A. Department of Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS
We completed a phase I trial of indole-3-carbinol (I3C) in 17 women (1 postmenopausal and 16 premenopausal) from a high-risk breast cancer cohort. Subjects ingested 400 mg I3C daily for 4 weeks followed by a 4-week period of 800 mg I3C daily. These chronic doses were tolerated well by all subjects. Hormonal variables were measured near the end of the placebo and dosing periods, including determination of the urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio. Measurements were made during the follicular phase for premenopausal women. Serum estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin showed no significant changes in response to I3C. Comparing the results from the placebo and the 800 mg daily dose period, CYP1A2 was elevated by I3C in 94% of the subjects, with a mean increase of 4.1-fold. Lymphocyte glutathione S-transferase activity was increased in response to I3C. The maximal increase was observed with the 400 mg daily dose of I3C, with no further increase found at 800 mg daily. If the ratio of hydroxylated estrone metabolites is a biomarker for chemoprevention, as suggested, then 400 mg I3C daily will elicit a maximal protective effect.

Indole 3 carbinol is a blood thinner
indole-3-carbinol is a potent antithrombotic agent with antiplatelet activity. It has its blood thinning effect through the inhibition of GP IIb/IIIa receptor and thromboxane B(2) formation.

Indole 3 carbinol benefits vulvar intraepithelial neoplasia
A randomized phase II trial of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia.
Int J Gynecol Cancer. 2006 Mar-April. Northern Gynaecological Oncology Centre; and Department of Haematology, Queen Elizabeth Hospital, Sheriff Hill, Gateshead, United Kingdom.
The aim of this study was to determine the potential therapeutic benefits of indole-3-carbinol (I3C) in the management of vulvar intraepithelial neoplasia. Women with histologically confirmed high-grade VIN were randomized to receive 200 and 400 mg/day of I3C. There was a significant improvement in symptomatology with the introduction of I3C. Lesion size and severity were also significantly reduced. However, tissue biopsy from the worst-affected vulval areas revealed no improvement in grade of VIN during the 6-month period,. There were no significant differences in results between those women taking 200 mg/day of I3C and those on 400 mg/day. This study has shown significant clinical improvement in symptomatology and vulvoscopic appearance of VIN with I3C therapy.

Indole 3 Carbinol I3C and prostate cancer
Indole 3 Carbinol may play a role in prostate cancer. It may also play a role in breast cancer.

Indole-3-carbinol (I3C) exhibits inhibitory and preventive effects on prostate tumors in mice.
Food Chem Toxicol. 2007 Oct 30. Faculty of Biotechnology and Food Engineering, Technion – Israel Institute of Technology, Haifa 32000, Israel.
This study was designed to investigate the effect of indole-3-carbinol (I3C) in cell lines and on prostate cancer tumor growth in mice when given as a therapeutic and as a preventive treatment. I3C, injected intraperitonially significantly inhibited the tumor growth and affected the angiogenesis process by decreasing the microvessel density and complexity. I3C has a significant inhibitory effect on prostate cancer cells in vitro and in vivo, and offers a potential usage as both preventive and therapeutic agent for humans.

Indole-3-carbinol and prostate cancer.
J Nutr. 2004 Dec;134(12 Suppl):3493S-3498S. Sarkar FH, Li Y.
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI
Epidemiological and dietary studies have revealed an association between high dietary intake of cruciferous vegetables and decreased prostate cancer risk. Our studies have shown that indole-3-carbinol, a common phytochemical in cruciferous vegetables, and its in vivo dimeric product 3,3'-diindolylmethane (DIM) upregulate the expression of phase I and phase II enzymes, suggesting increased capacity for detoxification and inhibition of carcinogens. Indole-3-carbinol can induce G1 cell-cycle arrest and apoptosis in prostate cancer cells. Indole-3-carbinol and DIM regulate many genes that are important for the control of cell cycle, cell proliferation, signal transduction, and other cellular processes, suggesting the pleiotropic effects of indole-3-carbinol and DIM on prostate cancer cells. We recently found that indole 3 carbinol functions as an inhibitor of Akt and nuclear factor kappaB (NF-kappaB), which play important roles in cell survival and which are believed to be potential targets in cancer therapy. Studies have already shown that the inactivation of Akt and NF-kappaB is responsible for chemosensitization of chemoresistant cancer cells. Because there is no effective treatment strategy for hormone-dependent and, most importantly, hormone-independent and metastatic prostate cancer, our strategies to sensitize prostate cancer cells to a chemotherapeutic agent by indole-3-carbinol and DIM is a novel breakthrough that could be used for devising novel therapies for prostate cancer.

Indole-3-Carbinol and breast cancer
Vegetables such as broccoli contain a compound called I3C. The repair protein, regulated by genes called BRCA1 and BRCA2, is important for preventing damaged genetic information being passed on to the next generation of cells. If people have a faulty BRCA gene they are at a higher risk of developing some forms of cancer, including breast, ovarian and prostate cancer. Low amounts of the BRCA proteins are seen in cancer cells, so the scientists propose higher levels might prevent cancer developing. Researchers suggest the ability of indole-3-carbinol to boost the amount of BRCA proteins could explain its protective effects.

Indole-3-carbinol is a negative regulator of estrogen.
J Nutr. 2003 Jul;133(7 Suppl):2470S-2475S. Auborn KJ, Fan S, Rosen EM, Goodwin L, Chandraskaren A, Williams DE, Chen D, Carter TH. North Shore-Long Island Jewish Research Institute, Manhasset, NY
Dietary indole-3-carbinol prevents the development of estrogen-enhanced cancers including breast, endometrial and cervical cancers. Epidemiological, laboratory, animal and translational studies support the efficacy of indole-3-carbinol. Whereas estrogen increases the growth and survival of tumors, indole-3-carbinol causes growth arrest and increased apoptosis and ameliorates the effects of estrogen. Our long-range goal is to best use indole-3-carbinol together with other nutrients to achieve maximum benefits for cancer prevention. This study examines the possibility that induction of growth arrest in response to DNA damage (GADD) in genes by diindolylmethane (DIM), which is the acid-catalyzed condensation product of indole-3-carbinol, promotes metabolically stressed cancer cells to undergo apoptosis. We evaluated whether genistein, which is the major isoflavonoid in soy, would alter the ability of indole-3-carbinol/DIM to cause apoptosis and decrease expression driven by the estrogen receptor (ER)-alpha. Expression of GADD was evaluated by real-time reverse transcription-polymerase chain reaction. We show a synergistic effect of indole-3-carbinol and genistein for induction of GADD expression, thus increasing apoptosis, and for decrease of expression driven by ER-alpha. Because of the synergistic effect of indole-3-carbinol and genistein, the potential exists for prophylactic or therapeutic efficacy of lower concentrations of each phytochemical when used in combination.

Prevention and treatment of cancer with indole-3-carbinol.
Altern Med Rev. 2001 Dec;6(6):580-9. Brignall MS.
Seattle Cancer Treatment and Wellness Center, Kirkland, WA
Indole-3-carbinol is a naturally occurring constituent of many plant foods. Oral administration of indole-3-carbinol has been shown to manipulate estrogen metabolism in humans in a possibly beneficial manner. indole-3-carbinol increases the 2/16-hydroxyestrone ratio, a ratio found to be predictive of breast cancer risk in some prospective studies. Animal and in vitro studies have identified a number of other possibly beneficial effects of indole-3-carbinol and its metabolites, including inhibition of estrogen binding and modulation of oncogene expression. A chemopreventive effect of indole-3-carbinol has been demonstrated in a number of animal models. Some chemical carcinogenesis models have found a tumor promoting effect of indole-3-carbinol, however. Epidemiological studies support the hypothesis that high intakes of indole-3-carbinol may have broad chemopreventive effect. Preliminary human trials have demonstrated that indole-3-carbinol is well tolerated and has a sustained estrogen modifying effect. indole-3-carbinol is a good candidate for clinical trial in women at increased risk of developing breast cancer.

The micronutrient indole-3-carbinol: implications for disease and chemoprevention.
Drug Metabol Drug Interact. 2000;17(1-4):159-88. Shertzer HG, Senft AP.
Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati College of Medicine, OH
This review provides a historical perspective for the development of indole-3-carbinol as a chemopreventive or therapeutic agent. Early experiments in animal models clearly showed that feeding cruciferous vegetables reduced the incidence of chemical carcinogenesis. Excitement was generated by the finding that these vegetables contained a high content of indole-containing compounds, and indole 3 carbinol could by itself inhibit neoplasia. The mechanism of action was linked primarily to the ability of indole 3 carbinol and derived substances to induce mixed-function oxidases and phase II antioxidant enzymes by binding and activating the aryl hydrocarbon receptor. Most of the literature on chemoprotection by dietary indole compounds relates to this mechanism of action. Other mechanisms, however, are notable for this class of compounds, including their ability to act as radical and electrophile scavengers; the various ascorbate conjugates of indole 3 carbinol (ascorbigens) may be important in this regard. Exciting recent findings have demonstrated that indole 3 carbinol and its reaction products can affect cellular signaling pathways, regulate the cell cycle, and decrease tumor cell properties related to metastasis. It does not appear that indole 3 carbinol per se is the primary active compound in chemoprotection or chemoprevention. Rather, indole 3 carbinol and ascorbate provide the parent compounds for the formation of a myriad of nonenzymatic reaction products that have strong biological potency.

indole 3 carbinol I3C questions
Q. I've been receiving many health letters and testimonials regarding Indole 3 Carbinol. They state this is the new remedy for BPH, claiming it actually shrinks the prostate. It recommends taking Indole 3 Carbinol with Lycopene. What is your comments on this possible revelation?
   A. I have not seen any studies testing the relation of Indole 3 Carbinol and enlarged prostate. There are a number of herbs that have an influence on prostate tissue, and I prefer using a combination as opposed to one or two.

Q. I have read on your site and various others that there is great promise in Indole 3 Carbinol / DIM in terms of
breast cancer prevention. Would you consider the use of this supplement as effective for preventing a recurrence
of breast cancer, for example, DCIS? Further, if DCIS were removed with clear margins in a wide local excision, do
you think that this supplement could possibly replace the standard follow up treatment of radiation or mastectomy?
Or would it just complement such conventional treatments?
   Q. DCIS, ductal carcinoma In situ, is not an invasive breast cancer. It stays inside the milk duct of the breast in which it started. I could not find human research with indole 3 carbinol in relation to DCIS to know the answers to these questions. It is possible that I3C could complement traditional breast cancer chemotherapy but I have no solid evidence to base this on.

This indole 3 carbinol page was last updated in January 2008.