I3C and DIM for Breast & Prostate Cancer Prevention

Thursday, October 11, 2012
By: Byron J. Richards,
Board Certified Clinical Nutritionist
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Renewed scientific interest in the cancer preventing properties of cruciferous vegetables has gripped the scientific community in the past few years. When digested, cruciferous vegetables, produce a variety of sulfur rich metabolites. Indole-3-carbinol (I3C) and diindolylmethane (DIM) are especially important. I3C and DIM exhibit great potential for the prevention and part of the treatment for breast and prostate cancer. They may provide specific benefit in risk reduction for these cancers when associated with being overweight, which typically involves the most aggressive forms of breast and prostate cancer. This review brings you up to date on the current state of the science.

Epidemiologic studies, while sometimes inconclusive, support the intake of cruciferous vegetables for the prevention of breast and prostate cancer. U.S. researchers at the Roswell Park Cancer Institute found that intake of cruciferous vegetables in premenopausal women was inversely associated with the risk of breast cancer. The researchers concluded, “cruciferous vegetables may play an important role in decreasing the risk of premenopausal breast cancer.”

Researchers at Yale University found that men with the highest intake of cruciferous vegetables cut their risk for spreading and aggressive prostate cancer in half. These men had two or more servings of cruciferous vegetables per week, mostly broccoli and cauliflower.   

Cruciferous vegetables contain sulfur rich glucosinolates that need to go through an enzymatic reaction before producing the cancer fighting I3C and DIM.  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 actually two I3C molecules connected together during the digestive process.

Unfortunately, various factors may reduce the cancer fighting potency of cruciferous vegetables. Boiling, steaming, and microwaving can reduce the activity of the myrosinase enzyme.  Because glucosinolates are water soluble they are readily leeched into the water when cruciferous vegetables are boiled, reducing their content up to 58 percent. Due to these factors, eating cruciferous vegetables raw or lightly sautéing them will help maximize the amount of I3C and DIM that may be formed.

Fortunately, dietary supplements of I3C and DIM can provide high levels of these potent nutrients in a single and convenient capsule, wherein one capsule contains far more I3C and DIM than a serving of cruciferous vegetables. 

I3C, DIM & Breast Cancer

The buzz about 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 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 prestigious MD Anderson Cancer Center, a place where state-of-the-art gene related cancer research and nutrition takes place. Their scientists 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.”

As explained in the above study by MD Anderson researchers, I3C and DIM have been proven to help protect against the human papilloma virus (HPV), which causes cervical cancer. HPV is a common vaginal infection that is transferable to the mouth of men via oral sex and has been implicated in the dramatic rise in throat cancer in men.

I3C, DIM & Prostate Cancer

The same research group at Berkley also proved 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, as I reviewed in an earlier feature length article, Prostate Cancer & the Androgen Receptor – A Clearer Picture of the Problem.  In 2009 this research group published a detailed review of the science supporting the use of I3C and DIM relating to breast and prostate cancer.

Researchers at Wayne State University School of Medicine have also done extensive research on I3C, DIM, 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.”

Overweight, I3C, DIM & Cancer

As a person gains weight hormonal signaling systems become confused. Insulin does not work properly, which results in insulin resistance. The structure of insulin is very close to the structure of growth hormone. In fact, growth hormone signaling is referred to as insulin-like growth factor-1 (IGF-1). When insulin and insulin-like signaling get confused, bad things can happen. Growth hormone, instead of repairing your body and keeping it young, can actually help cancer grow. Both breast and prostate cancer seek to hijack IGF-1 signaling to fuel their growth. While this is not necessarily the cause for the cancer, it is an important cofactor required for the growth and spread of the cancer.  Hijacking IGF-1 signaling is easier in the already confused metabolism of an overweight person, which is why the more overweight people are, the more at risk they are for aggressive breast or prostate cancer.

Research at the U.S. Department of Agriculture now shows that part of the anti-cancer activity of I3C and DIM is the reduction in inappropriate excess signaling of IGF-1. This finding may have widespread application value for many types of cancer that hijack IGF-1 as part of their spreading process.

A fascinating new area of research is studying the impact of I3C on obesity. Animal studies are showing that I3C has a direct impact on white adipose tissue, boosting adiponectin to reduce insulin resistance while lowering triglycerides and leptin, in turn preventing weight gain from a high fat diet.

A second study by this research group found that I3C could reduce the inflammation associated with a high fat diet while propping up the ability of fat burning genes to work better. This study helped expand the understanding of the multiple beneficial mechanisms I3C contributes toward preventing weight gain or helping weight loss.

Collectively, these studies indicate that I3C and DIM play a protective role against the undesirable metabolic effects of obesity that contribute to breast and prostate cancer risk. Furthermore, they may actually help weight loss. Regardless, they offer protection to an overweight person.

Summary

I3C and DIM now have adequate science to support their use in the prevention of breast and prostate cancer, especially in those who are overweight and have issues with hormone imbalance. In women this means issues of estrogen surplus. In men this means prostate swelling or elevated PSA. Plus, it is a top choice nutrient to help prevent a recurrence for any person who has had breast or prostate cancer.

The wide array of gene signaling influenced by these compounds to reduce inflammation and improve hormonal communication is fascinating. Certainly, everyone should have several servings of cruciferous vegetables as part of their diet each week.

It is certainly nice to know that a simple capsule of I3C and DIM can provide the equivalent of 5-10 servings of cruciferous veggies. If you don’t eat these veggies you could simply take one or two capsules per week.  If you want therapeutic support then women need 400 mg of I3C per day and men need 600 mg.

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