Pharmacological regulation of different hyperplastic diseases requires a long-term drug therapy; therefore the adverse effects are always a problem. With this in mind, extensive trials were performed with indole-3-carbinol on tissue cultures, laboratory animals and in clinical studies. Almost every week new data is presented or another specialized study extending the basis of knowledge on the effects of the indole-3-carbinol.

Studies of Firestone et al.
The results of the research show that indole-3-carbinol is effective in prostatic cancer as well. In 1999, Firestone from the University of California conducted an interesting laboratory study on rats, demonstrating that the indole-3-carbinol is capable of blocking the cell cycle at the G1 receptor of cancer cells with higher efficacy than tamoxifen. In 2003 this study was repeated and confirmed on the human prostate cancer cells. Indole-3-carbinol induced the blockage of the cell cycle at the G1 receptor, inhibiting the synthesis of the prostate specific antigen PSA, which is synthesized in the LNCaP prostate cancer cells, by inhibition of CKD (cyclin dependent kinase) and by stimulation of the p16 CDK inhibitor. The author concluded the study by stating: “The results demonstrate that indole-3-carbinol has a potential antiproliferative effect in human prostate cancer cells. These findings prove that this dietary indole acts as a potential chemotherapeutic agent controlling the growth of the human prostate cancer cells.

In May of 2002 the indole-3-carbinol research demonstrated for the first time that the effects of this substance may reach beyond the affections of the female genital organs and prostate and may include the colon cancer. By observing the proliferation of the colon cancer cells, it has been shown that indole-3-carbinol (I3C) significantly reduced the cell proliferation in these tumors.

Studies of Bradlow et al.
The initial study conducted by Bradlow in 1994 focused on determination of the capability of the indole-3-carbinol to stimulate the synthesis of 2α-hydroxyestron (2-OHE1). Experimental tests involved two groups of women. One was test group and the second control group, with 20 female subjects in each group. The subjects in the first group received 400 mg of indole-3-carbinol every day over 3 months, whereas the control group received placebo. Standard blood chemistry and assessment of the 2-OHE1/16a-OHE1 ratio were performed every 30 days. The study results demonstrated that the biochemical parameters were identical in both groups – test as well as control. In 17 of 20 subjects in the test group, a visible shift towards the estradiol 2-OHE1 and the change was observed for another 3 months of wash-out period.

In another placebo-controlled clinical study a statistically significant improvement was observed in patients with cervical dysplasia CIN II and CIN III compared to the control group. The subjects received 200-400 mg of indole-3-carbinol daily over the period of 12 weeks. Full regression was observed in 48% subjects in the test group, while no regression was observed in the placebo control group.

This has leaded the authors to conclude that indole-3-carbinol is capable of affecting the estrogen metabolism.

Studies of the Preventive Cancer Research Fund
In 1997 similar clinical trials were conducted in the U.S.A under the sponsorship of the Preventive Cancer Research Fund. 60 women were included in the clinical trial. They were divided in three groups: control (placebo) group, group receiving low dose of indole-3 carbinol (50, 100 and 200 mg per day) and high dose indole-3-carbinol group (300 and 400 mg per day). Indole-3-carbinol was administered on a daily basis over a period of 4 weeks. The 2-OHE1/16a-OHE1 index was measured in all subjects as the biological marker of the pharmaceutical efficacy of the preparation. The results of the study can be summarized as follows:
  • Adverse effects were not present in 100% of all subjects
  • Minimum daily dose capable of shifting the 2-OHE1/16a-OHE1 index was 300 mg. Recommended preventive dose was 300-400 mg.

Another clinical study of the efficacy of the indole-3-carbinol was also conducted under sponsorship of the Preventive Cancer Research Fund in 1998. In this study female volunteer subjects aged 35-47, used 400 mg of indole-3-carbinol daily over a period of 2 months. Significantly increased levels of 2α-hydroxyestron (2-OHE1) in blood confirmed the high clinical efficacy of the indole-3-carbinol. Stable, more than two-fold increase of the 2α-hydroxyestron levels compared to 16α-hydroxyestron (OHE1) was an evidence of adequate regulation of the estrogen metabolism and proved the positive effect of the indole-3-carbinol.

These effects of the indole-3-carbinol with respect to mastopathy, uterine myomatosis and cervical dysplasia were clinically tested in order to confirm the numerous experimental reports on the high therapeutic effects of indole-3-carbinol in the pharmacological regulation of various hyperplastic conditions.

Trials performed by MiraxPharma Moscow
Researchers from MiraxPharma from Russia focused on the general toxicological properties of the indole-3-carbinol with respect to the compliance with the regulations specified in the Manual for experimental (pre-clinical) testing of new pharmacological substances.

The following parameters were researched:

* The effect of the indole-3-carbinol on the general condition of the experimental animals with special effect on the dynamics of body mass and weighting indexes of individual body organs.
* The effect of the indole-3-carbinol on urinary excretion, CNS, cardiovascular system, blood parameters, clotting parameters, blood biochemistry and pathological and morphological changes of individual organs.
* Special series of tests was devoted to the study of local irritant effects of the indole-3-carbinol on the skin and mucous membranes and on the allergic and embryotoxic properties.

The results of these studies have confirmed an absolute non-presence of the adverse effects of the indole-3-carbinol and confirmed its high efficiency in clinical applications.

Another line of research focused on clarification of the capability of the indole-3-carbinol to affect the estrogen metabolism. The estradiol metabolites ratio, 2-OHE1/16a-OHE1, is considered a reliable indicator of malignant transformation, including breast cancer. Indole-3-carbinol demonstrates high affinity to estrogen-specific receptors AhR, subsequently the complex enters the cellular nucleus and initiates transcription of cytochrome P450 (an iso-form of CYP1A), which hydroxylates the estron at position 2, resulting in 2α-hydroxyestron (2-OHE1). This metabolite has an antiproliferative and antiestrogen effect, therefore its increased levels – compared to the 16a-OHE1 with strong carcinogenic effects – are considered to be very beneficial for human organism.