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October 1999

Continued from :
I3C Indole 3 carbinol The Tamoxifen Substitute Cancer Prevention For Thinking People.

And more. . .

In 1997, researchers at Strang Cancer Research Laboratory at Rockefeller University discovered that when I3C changes "strong" estrogen to "weak," it stops human cancer cells from growing (54-61%) and provokes the cells to self-destruct (apoptosis). Subsequent studies done at the University of California at Berkeley, show that I3C inhibits MCF7 human breast cancer cells from growing by as much as 90% in culture. Growth arrest does not depend on estrogen receptors.

I3C does more than just turn strong estrogen to weak. 16alpha-hydroxyestrone (16OHE) is an estrogen metabolite that is biologically active-i.e., like estradiol, it can send "grow" signals. In breast cancer, the bad 16OHE is elevated, and the good 2OHE is decreased. Cancer-causing chemicals change the metabolism of estrogen so that 16OHE is elevated. I3C changes them back so that 2OHE is increased.

In an experiment at New York University, researchers gave African-American women I3C, 400 mg for five days. Most of them experienced an increase in the "good" 2OHE and a decrease of the "bad" 16OHE. However, some did not. It turns out that those who did not have a mutation in a gene that helps metabolize estrogen to the 2OHE version. Those women have an eight times higher risk of breast cancer.

The I3C receptor

A startling discovery shows that I3C controls estrogen metabolism through the same receptor that allows dioxin into the cell-the "Ah" receptor (aryl hydrocarbon). Ah is similar to the estrogen receptor in that it can induce cellular growth. Unlike the estrogen receptor, however, scientists haven't found the body's natural "Ah" that fits into the Ah receptor. The only substances known to activate Ah are certain phytochemicals, including I3C-and the proven cancer promoter, dioxin. Dioxin is a chemical made from chlorine. It's so toxic that scientists measure it in trillionths of a gram. It's used in all kinds of things-from Saran Wrap(r) to pesticides to wood preservative. It has been detected in McDonald's Big Macs(r), Haagen-Daz(r) ice cream and Kentucky Fried Chicken(r). Meat, dairy products and fish are the most concentrated sources. When paper is bleached or plastic is burned, dioxin is released into the environment. Because it lodges in fat, it's almost impossible to remove from the human body. Losing weight simply causes it to hunker down in the remaining fat.

A study on people who worked in a dioxin plant shows that women exposed to the chemical have more than twice the risk of breast cancer, but some studies don't show any association at all. Part of the problem with dioxin studies is that there are hundreds of similar chemicals, with hundreds of different metabolites that may interact in ways we don't currently understand.

Dioxin, like I3C, affects estrogen metabolism. For this reason, it has been called an estrogen blocker (like tamoxifen). But it esn't work through the estrogen receptor. Dioxin and I3C both affect estrogen metabolism through the Ah receptor. But just as tamoxifen sends a different signal that genuine estrogen when it gets in the estrogen receptor, so does dioxin send a different signal than I3C in the Ah receptor. In addition to changing the metabolism of estrogen, dioxin also disrupts other important growth regulatory factors. Among those factors are insulin, IGF-1 (insulin-like growth factor), and tumor necrosis factor (TNF). It also activates cancer genes and suppresses tumor suppressor genes.

I3C, on the other hand, fits into the Ah receptor, but instead of sending signals that help cancer grow, it sends signals that stop it. I3C uses the Ah receptor to indirectly affect estrogen metabolism also, but in a beneficial way. Not only does it positively affect estrogen, it can also keep dioxin out of cells. When researchers at Texas A & M University treated breast cancer cells with I3C and dioxin at the same time, dioxin's adverse effects were reduced 90% by I3C.

I3C prevents chemically-induced breast cancer in rodents by 70-96%. It also prevents other types of cancer, including aflatoxin-induced liver cancer, leukemia and colon cancer. Studies show that I3C inhibits free radicals, particularly those that cause the oxidation of fat.

I3C stops cancer cells from growing

I3C not only weakens estrogen and keeps chemicals out of cells, it also goes after cancer in ways similar to tamoxifen. It, like tamoxifen, interrupts the cell cycle. In studies from the University of California mentioned above, I3C inhibited the growth of estrogen receptor-positive breast cancer cells by 90% compared to tamoxifen's 60% by stopping the cell cycle. (Adding tamoxifen to I3C gave a 5% boost.) In estrogen receptor-negative cells I3C stopped the synthesis of DNA for new cells by about 50% whereas tamoxifen had no significant effect. I3C also restores p21 and other tumor suppressors that act as check points during synthesis of a new cell. Tamoxifen, by contrast, has no effect on p21. I3C also inhibits cancers caused by other chemicals, in addition to dioxin. If animals are fed I3C before exposure to certain other cancer-causing chemicals, DNA damage and cancer will be virtually eliminated. A study on rodents shows that damaged DNA in breast cells is reduced 91% by I3C. Similar results happen in the liver. And in a study from New York University Medical Center, female smokers taking 400 mg of I3C significantly reduced their levels of a major lung carcinogen. Chemicals in cigarrettes are known to affect estrogen metabolism.

While there is no proven breast cancer preventive, the best and most comprehensive scientific evidence so far stands behind phytochemicals such as I3C. I3C beat out more than 80 other substances, including tamoxifen, for anti-cancer potential in an assay done at the National Cancer Institute.

Recently, researchers at the Hoechst Marrion Roussel drug company staked patent claims to dozens of indole-3 look-alikes. They claim that the indoles, which down-regulate estrogen receptors, can be used to treat and prevent cancer and autoimmune diseases such as multiple sclerosis, arthritis and lupus. They hope to replace all the chemically-altered estrogen drugs such as tamoxifen with a new generation of chemically-altered indole drugs that fit in the Ah receptor, and regulate estrogen indirectly. Will the fake indoles create cancer in other organs as tamoxifen does? Will they lead to chemical tumor dependency as tamoxifen does?

Time will tell if the constant stream of chemical lookalikes will continue to stop/feed cancer. In the meantime, those wishing to get off the chemical merry-go-round, and get serious cancer prevention without the side effects have a terrific option: I3C.

Inhibition of growth in estrogen
receptor-positive breast cancer cells

Note: we cannot say that I3C will absolutely prevent breast cancer. The studies that would allow us to give you the absolute proof haven't been done.

Currently there are two government-sponsored trials underway involving estrogen metabolism and vegetables. One is going to assess the "interactive effects of dietary fat and fruits and vegetables on the levels of oxidative DNA damage and cholesterol oxides in women at high risk for breast cancer." This study is enrolling a grand total of 160 women in the next two and a half years. The other plans to look at how fiber affects estrogen metabolism in postmenopausal women. This study is enrolling a phenomenal 40 women over four years. Should the government ever get serious about preventing breast cancer, and spend $100 million of your tax dollars on testing I3C as they have on testing tamoxifen, we would be able to give you the proof. For now, we can only give you the best evidence and let you decide.

Recommended Dosage/Precautions:

Note that while a little is good, a lot is not necessarily better. As with certain antioxidants that can actually promote oxidation at high levels, too much I3C can have the opposite effect of what you want. Therefore, don't exceed the dosage. The effective dose established in human studies is 6-7 mg per kg of weight per day. For a 120 lb. woman, this is just under 400 mg/day.

Also note that pregnant women should not take I3C, due to its modulation of estrogen. The reported aversion to cruciferous vegetables by pregnant women may be associated with their ability to change estrogen metabolism.

Product Information


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