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Breast cancer runs in my family, so I’m looking for preventatives.

Q:Breast cancer runs in my family, so I’m looking for preventatives. I notice that LifeLink sells indole-3-carbinol (I3C) — an anti-cancer nutritional supplement. The Oregon State University website has an interesting page about it, but their pro-and-con discussion leaves me unsure whether to include I3C in my anti-cancer regimen. What is your opinion?

A:In my opinion, I3C has a lot more going for it than the LPI’s review would suggest. I don’t give medical advice in this column, but I will tell you what I know about this supplement.

The website you mentioned — at Oregon State University — is the website of the Linus Pauling Institute (LPI). I was surprised to see how lukewarm LPI’s review of I3C was, in view of the fact that I3C is usually regarded as being among the two or three most exciting and promising anti-cancer substances known today. I think the reviewer at LPI was excessively influenced by several experiments with high-dose I3C in lab animals in which cancers were induced by chemical treatments. These experiments are described below.

What is I3C?

Indole-3-carbinol (I3C) is a substance that results from cooking or crushing a wide variety of plant foods — especially ‘cruciferous vegetables’, which include broccoli, brussels sprouts, and cauliflower. Enzymes in the plants convert certain plant biochemicals into I3C. In the stomach I3C is converted into other compounds (such as ‘DIM’), some of which appear to be responsible for the anti-cancer activity of these vegetables.

Reviews

For general information about I3C, I recommend the reviews by Rogan1, Thorne 2, Stoewsand3, and Broadbent4,5. More specialized reviews are those by Aggarwal6, Shertzer7, and Kim8.

History

Interest in I3C as an anti-cancer agent dates back at least to 19759 when it was shown that I3C stimulates cells to produce enzymes that destroy carcinogens. Ethnic dietary surveys showed that diets high in cruciferous vegetables are correlated with lower rates of breast cancer.10 Although it was already known in 1978 (from rat experiments) that I3C inhibits the formation of breast cancer tumors,11 not a single clinical study was done until the mid-1990s to determine whether this promising substance prevents or treats cancer in the human body. Throughout the 1980s, sporadic efforts were made to understand the biochemical mechanisms through which I3C affects cells. But only when I3C became available as a nutritional supplement, and women began to use it to treat cervical dysplasia, did the medical research community begin to show much interest in it. Even so, 30 years after I3C’s anti-cancer potential was first revealed, there have been no clinical trials aimed at determining directly whether I3C prevents breast cancer or causes existing breast tumors to shrink. Consequently, crucial decisions about treatment must still be based mainly on extrapolations of cell culture experiments, lab animal data, and suggestive biochemical ‘markers’.

Peter Greenwald of the U.S. National Institutes of Health has written a good review covering the history and possible future prospects for clinical trials in cancer prevention10 — a review that unintentionally illustrates the snail’s pace at which the medical research community operates.

Most other potential applications of I3C have been treated with a similar lack of urgency. These other applications include the prevention or treatment of: • prostate cancer • melanoma • non-melanoma skin cancer • lung cancer • colon cancer • recurrent respiratory papillomatosis • herpes simplex • fetal cancer • Alzheimer’s • ovulation. Only in the case of cervical dysplasia did the medical world make a concerted effort to answer the question “Does I3C work in the human body?”, and the answer turned out to be the same one arrived at earlier by supplement users: “Yes”.

Let us take a quick look at what is known about I3C’s effects on these conditions.

Cervical dysplasia, papillomatosis

Cervical dysplasia (CIN) is a precancerous condition caused by infection of the cervix by certain strains of Human Papilloma Virus. A clinical trial of I3C was reported in 2000 to cause complete regression of CIN in 50% of patients who used 200 mg/day of I3C for 12 weeks.12

Recurrent respiratory papillomatosis (RRP) is the repeated growth of papillomas in the larynx and trachea. In a 1998 clinical trial of I3C, one-third of RRP patients saw their papillomas stop growing; another third experienced a reduction in growth rate.13

I3C and cancer

In the body, I3C and its metabolites regulate certain hormonal and cell-signalling pathways, particularly those involving estrogens. Some of these pathways are involved in the development of tumors from precancerous cells.6 By disrupting the biochemistry of precancerous cells, I3C causes them to die before they can form tumors — and it does this without harming normal cells.14 I3C-sensitive cancers include those of the breast,15,11,3916,17,18,19 cervix,20 endometrium,21 colon,22 ovaries,3 lung,23 white blood cells (leukemia),6 and skin (melanoma24, and UV-induced non-melanoma skin cancer25). prostate,

It was reported in 2001 that I3C inhibits the basic processes used by cancer cells to form new tumors by metastasis.27

Evidence from tissue culture experiments suggests that genistein (a nutritional supplement extracted from soybeans) works synergistically with I3C to kill cancer cells.21

An often-overlooked cancer risk is that caused by carcinogenic substances in the diet or environment during pregnancy. The fetus can be exposed and develop cancer many years later. Recent experiments in rats have shown that I3C, taken during pregnancy, provides substantial protection against such malignancies.28

Does I3C shrink existing tumors? Until recently it was thought that the anti-tumor potential of I3C supplementation would be limited to prevention. Several experiments with fish and with rats even led some researchers to believe that if I3C supplementation were started after a tumor had already developed, the growth of that tumor might actually be accelerated by I3C.34,35,36,37,38 This idea was largely speculative, however, since no clinical studies had been done (and still haven’t been done) on real tumors in humans. Furthermore, the dosages used in the fish and rats corresponded to higher doses than those used in humans. This issue has not yet been entirely settled. Available evidence suggests that already-existing breast and cervical tumors can be inhibited by I3C, liver tumors can be enlarged by I3C, while the data for colon, prostate, and other tumors is equivocal or nonexistent.14,26,37.

Thus, the latest evidence suggests that when a precancerous condition is detected, the use of an I3C supplement may eliminate the precancerous cells and prevent progression to cancer. I3C supplementation may also inhibit the spread of existing tumors to other parts of the body. It may shrink existing tumors in certain tissues, but it might accelerate the growth of existing tumors in other tissues, especially the liver.

I3C and Herpes simplex (lip and genital herpes)

In 2003 it was reported that in a tissue culture experiment I3C caused a 100% inhibition of the Herpes simplex29,2 Nothing further has been reported on this subject, and apparently no clinical trials have been organized to test I3C as a treatment for herpes. virus.

I3C prevents ovulation

I3C also has anti-ovulatory properties, as was shown in rats in 2002.30 While it would be unwise to rely on I3C as one’s sole birth-control method, regular I3C supplementation might lower the risk of pregnancy due to forgetting to use one’s regular method.

Protection against toxic substances

The body produces many enzymes that inactivate substances that would be toxic if their concentrations became too high. I3C induces the production of such enzymes.31

I3C and Alzheimer’s Disease

A hallmark of Alzheimer’s Disease is the formation of protein tangles called ‘amyloid fibrils’ in nerve cells of the brain. These tangles disrupt the structure of the nerve cells and also collect metal ions which, in turn, promote the production of free radicals that damage and kill nerve cells. Recent Alzheimer’s research has identified I3C as a substance that inhibits the formation of amyloid fibrils.32

Dosage

Most clinical work with I3C uses dosages from 200 mg/day to 400 mg/day.2 The optimum dosage for affecting breast cancer is thought to be 400 mg/day.33

Why take I3C as a supplement when you could instead just eat lots of broccoli or other cruciferous vegetables? There are two reasons: first, the vegetables contain many alkaloidal substances, some of them harmful; second, you have no way of knowing whether a given serving of a vegetable has a lot or only a little of the I3C-related substances you are trying to consume. Supplement capsules solve both of these problems.

Conclusion

If cancer ran in my family (which it doesn’t) — cancer of the breast, prostate, colon, skin, or reproductive organs — then I would definitely be using I3C myself. I would also use it if I knew I already had one of these cancers. But I would avoid using I3C if I had been diagnosed with liver cancer.

References


Disclaimer: The information provided in this “Ask Dr. Zarkov” article contains no medical advice whatsoever — it contains biological information. Nothing in the article constitutes an effort to persuade readers to use, or not to use, this biological information as a basis for action.


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