Indole 3 carbinol and its influence on estrogen and women breast cancer

Indole-3-carbinol is derived from the breakdown (enzymatic hydrolysis) of the glucosinolate glucobrassicin (a compound containing sulfur), which is found in cruciferous vegetables in fairly high levels. Examples of such vegetables include cabbage, cauliflower, broccoli, kale, brussels sprouts and collard greens. Indole-3-carbinol (or I3C) is also found in nutritional enhancements.

I3C is unstable compound and most of it changes to its metabolites in the intestine to indole carbazole (ICZ) and Diindolymethane (DIM). These two compounds and I3C are all absorbed into the bloodstream and any or all three of them could be active, separately or together, in the real world. Actually, there is an increasing amount of research on DIM with some oncologists believing that it possesses by the most potent properties and that it is easier to use as a regulated-dose supplement. It shows a strong antitumor effect by regulating estrogen activity and metabolism. The chemopreventive and antitumor activity of Indole-3-carbinol however depends on the species and type of tissue.

What is Estrogen?

Estrogen is an essential hormone for the usual growth of the breasts and important organs for childbearing in a woman such as uterus and ovaries. It is important in controlling a woman’s menstrual cycles and reproduction. It also helps to maintain healthy bones and the heart. 

Estrogen is, in other words, a family of hormones. One of them is 16 alpha (or estradiol). However, even with these positive responsibilities of estrogen in a woman’s body, lifetime exposure to estrogen can lead to breast cancer. How is this possible? Estrogen, from the way it binds to the estrogen receptor (ER), plays a significant role in growth of breast cancer and tumor development. 16 alpha (or estradiol) is known to attach itself to cellular receptor sites and cause a lot of trouble inside the cell such as dropping oxygen levels, intensifying sodium levels and prompting a grow signal. It is therefore wise to understand how estrogen works in the body, know how chemicals in the surroundings can affect estrogen levels and understand how nutrition and lifestyle affect estrogen exposure over a lifetime. It is also worthy to know the various treatments given to those with breast cancer. One of the treatments that can be adopted is using indole-3-carbinol (I3C).

I3C And its Anticancer effect

I3C and DIM show anti-cancer action by showing anti-estrogenic activity.  They hinder and reverse estrogen-propagated cancers, where estradiol binds itself to cellular receptor sites causing a lot of disorder inside the cells. They also denature the destructive and aggressive form of estrogen (estradiol) and make it into a weaker form. They are also known to regulate a binding protein and adjust estrogen receptor (ER) sites. This prevents estradiol from binding on cell membranes and consequently the inside of the cells is unscathed. This is valid to both female and male cancers such as breast cancer and prostate cancer. I3C helps change 16 alpha to a much less destructive form, 2OHE1 (estrone), which has considerably weaker cellular effects and efficiently stops the estradiol (16 alpha) form from attaching itself to cellular receptor sites. This therefore leaves the inside of the cell unaffected. DIM has been identified to reinstate the p21 gene action and therefore prevents the replication of DNA for new malignant cells. It hence halts cancers from forming or developing. DIM also reduces HIF-1 alpha and stops tumors forming a blood supply.

Study shows that Indole 3 Carbinol hinders the growth of estrogen receptor-positive breast cancer cells by around 90 per cent while it also stops estrogen receptor-negative cells by nearly 50 per cent. Tamoxifen, a prior drug before I3C accrued a 60 per cent score in a similar initial test, but got no score in the second test.  After metabolism of estradiol, the by-product is also a carcinogen and can also trigger growth signals. It has been connected with breast cancer and other types of cancer such as prostate cancer and endometrial cancer. This by-product is particularly produced by some chemicals, including some estrogen imitators. I3C decreases these metabolites and converts them back 2OHE1 which is much safer.

Effects of I3C on Estrogen Metabolism

The endogenous estrogen 17beta -estradiol can be broken down to 16alpha- hydroxyestrone (16OHE1) or 2- hydroxyestrone (2OHE1). While 16OHE1 is very estrogenic and has been established to stimulate the propagation of several estrogen- sensitive cancer cell lines, 2OHE1 is less estrogenic. A theory that shifting the metabolism of 17beta-estradiol away from 16OHE1 and toward 2OHE1 could cut the risk of estrogen-sensitive cancers (an example is breast cancer) has been propagated.

Oral enhancements with 300-400 mg a day of I3C have steadily amplified the levels of urinary 2OHE1 or urinary 2OHE1:16OHE1ratios in women in controlled clinical trials. Supplementation with 108 milligrams a day of DIM also showed an increase in urinary 2OHE1 levels in women past menopause. The relationship between urinary ratios and breast cancer hazard is unclear. Women with breast cancer had lower urinary 2OHE1:16OHE1 ratios in some small case-control studies. Prospective cohort and larger case-control studies have not established noteworthy relations between urinary 2OHE1:16OHE1 ratios and the risk of breast cancer.

Side Effects of I3C

There have been reports of skin rashes in some patients after taking I3C. Intestinal pain, increase in liver enzymes, balance problems, nausea and tremor are other side effects linked with I3C. It should be consumed in amounts relative to one’s diet. Still, the individual should be under medical supervision. Use of I3C for a long time has proved to promote tumor growth in a way in certain cases. A study carried out on male rats showed that they were left with fertility issues. Also, since I3C helps in inactivation of estrogen, it could also lead to osteoporosis in postmenopausal women. I3C could affect the effectiveness of any medicine which is broken down in the liver. Those pregnant, lactating, or those taking contraception ought to consult with their doctors on how to go about I3C.

It is always essential to seek medical advice from a professional doctor before taking supplements.

Written by dr. Simon Nyamu

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