Indole-3-carbinol
Indole-3-carbinol, also called I3C, is a resulting compound that comes from eating cruciferous vegetables ( Brassica plants), such as cabbage, broccoli, brussels sprouts, cauliflower, kale, kohlrabi, and turnips - see a list. A typical Japanese diet provides the equivalent of about 112 mg of I3C daily; intake in Western diets is lower. Population studies have shown that people who eat a lot of broccoli and other cruciferous vegetables have lower rates of cancer than those who don’t.
Cruciferous vegetables contain sulfur rich glucosinolates that need to go through an enzymatic reaction before producing the cancer fighting I3C and DIM (Diindolylmethane). The enzyme that does this is called myrosinase, which is actually part of cruciferous vegetables. When you cut or chew a cruciferous vegetable the enzyme comes in contact with the glucosinolates, starting the formation process of I3C and DIM. DIM is two I3C molecules connected together during the digestive process.
Unfortunately, we don’t yet exactly know what constituents of these vegetables are responsible for the protective effect. It may be I3C, the carotenoid pigments, vitamin C, or sulforaphane, a compound thought to suppress tumors. Or the cancer-protective effects may be due to two or more of these components acting together.
I3C is known to stimulate detoxifying enzymes in the gut and liver. Because diets high in these vegetables slow cancer growth in animals, I3C is thought to be a good candidate for cancer prevention. Laboratory studies show that I3C may have anticancer activities across a variety of tumor types, and may have added benefit with some chemotherapy drugs.
Indole-3-carbinol appears to work in several ways:
- Facilitating the conversion of estrogen to a less cancer-promoting form
- Partially blocking the effects of estrogen on cells
- Directly killing or inhibiting cancer cells
- Reducing levels of free radicals, which can promote cancer by damaging DNA
Prostate Cancer
Researchers at the University of California, Berkley showed that I3C has powerful prostate cancer killing ability. In 2003 they demonstrated that I3C could directly interact with prostate cancer cells and kill them. They also showed that I3C lowered the production of prostate specific antigen (PSA). In 2005 they proved that I3C directly interacts with the androgen receptor to reduce spreading of prostate cancer. A finding of this nature is quite important. In 2009 this research group published a detailed review of the science supporting the use of I3C relating to breast and prostate cancer.
Researchers at Wayne State University School of Medicine have also done extensive research on I3C, and prostate cancer. This is what they had to say, “The results from our laboratory and from others provide ample evidence for the benefit of I3C and DIM for the prevention and the treatment of prostate cancer.”
I3C & Breast Cancer
Interest in I3C and DIM got started a number of years ago when it was found that they directly influenced estrogen metabolism so as to make estrogen less problematic in terms of breast cancer risk. Estradiol can be metabolized to 16alpha--hydroxyestrone (16αOHE) or 2-hydroxyestrone (2OHE). If too much estrogen goes down the 16aOHE pathway it is considered “bad” because it can stimulate the growth of breast cancer. Balancing this potential issue is the 2OHE estrogen pathway, which is called “good” because it offers protection against breast cancer. Women with breast cancer are known to have higher levels of the “bad” 16aOHE. The ratio of good to bad is a primary indicator of breast cancer risk, a relationship that has also been demonstrated in postmenopausal women.
Researchers demonstrated in women at risk for breast cancer that a dose of 300 mg – 400 mg per day of I3C can significantly change the ratio of estrogen metabolism, reducing the bad and boosting the good. Doses of 200 mg or less were not effective. Other researchers using similar doses confirmed that I3C boosted 2OHE production while lowering 16aOHE as well as lowering estradiol and estrone. A recent human trial has again documented the ability of I3C to favorably impact estrogen metabolism in both pre- and postmenopausal women.
Not all women have imbalanced “good” and “bad” estrogen metabolism. Too much bad estrogen metabolism can be predicted by high estrogenic menstrual cycles (heavier blood flow, cramps, headaches) as well as cyst formation or endometriosis. Postmenopausal women with a prior history like this are also likely to have imbalanced estrogen metabolism. Any woman with an at-risk breast cancer profile, including family history, will want to minimize the likelihood that estrogen metabolism can go awry. And remember that all of these risk factors are increased if a woman is overweight.
The cancer fighting potential of I3C and DIM is not limited to estrogen imbalance. The scientific case that these compounds can inhibit breast cancer directly via multiple mechanisms as mentioned above has been building for more than a decade.
In 1998 University of California, Berkley researchers injected I3C directly into breast cancer cells. I3C halted the cancer cell division by blocking cancer cell DNA duplication. This lead to another study by the same researchers to see if the I3C was as effective as Tamoxifen, which carries numerous undesirable side effects. They injected the first group of human breast cancer cells with I3C, a second with Tamoxifen, and a third with I3C and Tamoxifen. The cells injected with Tamoxifen alone experienced a 60 percent inhibition in DNA synthesis, the cells injected with I3C had a 90 percent inhibition, and the combination had a 95 percent reduction. These studies support the use of I3C for the prevention of a recurrence of breast cancer.
Numerous human, animal, and cell studies followed and continue to this day, showing that I3C and DIM are potent nutrients to protect female health. This body of science was reviewed by the researchers at MD Anderson Cancer Center, where they concluded, “Numerous studies have indicated that I3C also has a strong hepatoprotective activity against various carcinogens. Initial clinical trials in women have shown that I3C is a promising agent against breast and cervical cancers.”
Dosage
A 4-week, double-blind, placebo-controlled trial of 57 women found that a minimum dose of 300 mg of I3C daily may be necessary to reduce risk of estrogen-promoted cancers. Another study found benefits with 400 mg of I3C per day.
Safety
Human trials have found no significant side effects with I3C.