Revised August 2009

In 2004/5 the Pharmaceutical company, Hoechst, started to patent a number of close relatives and synthetic versions of Indole 3 Carbinol. What’s the fuss, especially given that most people reading this piece have hardly heard of this compound anyway? Well, Hoechst claimed that eventually these new compounds (Indole drugs) will be used to treat all manner of illnesses from arthritis to MS to cancer, and even replace Tamoxifen with a far better alternative.

 Great for patients – not so good for Tamoxifen profitsIn Cancer Watch (icon 2006 issue 4), we covered research that showed women on tamoxifen needed less of the drug if they supplemented with Indole 3 Carbinol, deriving the same benefits whilst reducing side effects. (Great for patients – not so good for Tamoxifen profits.) Surprisingly, as I discovered when I looked into this further, this has apparently been consistently noted in a number of studies. I wonder how many doctors use this fact?

It is often stated that Indole 3 Carbinol is found in cruciferous vegetables (the cabbage family). This, strictly speaking, is not true. Actually it is Indole 3 glucosinolate (I3G), which is found in good concentrations in broccoli, kale, cabbage, bok choi, brussels sprouts, cauliflower and even turnip. I3G has minimal anti-cancer activity but upon cutting, mastication or light cooking an enzyme (called myrosinase) is released in the vegetables and this converts indole 3 glucosinolate to Indole 3 carbinol. Research indicates that the latter has significant anti-cancer properties.

So. Indole 3 Carbinol (I3C) is a member of the glucosinolates family. This group of compounds contains other indoles and also isothiocyanates, such as sulphoraphane. These are known antioxidants and natural detoxifying enzymes.

The first recorded use of I3C was the recommendation of Cato the Elder, a Roman Statesman around 200 BC, who wrote that, “If a cancerous ulcer appears on the breast, apply a crushed cabbage leaf and it will make it well”.

Between 1990 and the current time, there have been over 60 peer-reviewed scientific studies on Indole 3 Carbinol with cancers such as breast cancer, prostate cancer, cervical cancer and even respiratory tract cancers. For example in one – albeit small – double blind study on women with cervical cancer, supplementation of 200mgs to 400 mgs of Indole 3 Carbinol reversed the early stages in 8 of the 17 women. I3C is potent stuff.

So what does it actually do?

This is a really complex issue, especially as I3C seems to work at a number of levels. Indeed, it may not even be I3C that is working as your stomach acids convert it to two other substances – Diindolymethane (DIM) and indole carbazole (ICZ). I3C, DIM and ICZ are all absorbed into the bloodstream and any or all could be active, separately or in conjunction, in the real world.

What is known so far is that I3C can act in several ways on cells and tissues.

Antioxidant:

Indoles and isothiocyanates are known antioxidants and can naturally neutralise free radicals. For example, research has shown that they can inhibit free radicals which cause the oxidation of fats, for example, in the oxidation of low-density lipoprotein.

Anti-artherogenic activity:

A by-product of I3C in the body inhibits smooth muscle proliferation and would therefore inhibit some heart and artery wall problems.

Anti-cancer activity:

At the preliminary level, I3C has been shown to inhibit the action of some aflatoxins in research with cancers in fish. It also prevents aflatoxin-induced liver cancer, leukaemia and colon cancer.

seeming ability to reduce, even reverse, oestrogen-driven tumour growth In cell cultures, I3C inhibits human papilloma virus (HPV) proliferation, and the development of cysts and pre-cancerous lesions. There is some evidence that I3C may help prevent recurrences of respiratory papillomatosis.

Further research indicates that I3C may well protect your liver, but the most interesting aspect of I3C is its seeming ability to reduce, even reverse, oestrogen-driven tumour growth. The Roman was right!

I3C seems to act in five ways:

• By partially blocking oestrogen receptor sites on cell membranes.
• By returning alpha and beta receptor site expression to normal levels
• By converting highly active oestrogen forms, and their by-products, to much safer compounds
• By blocking other cancer enhancing receptor sites
• By directly killing cancer cells.

The Tamoxifen rival

Without getting too complicated, forms of ‘oestrogen’ such as the molecules 16 alpha-hydroxyoestrone and 4-hydroxyoestrone are known carcinogens and have been shown at work in a number of cancers such as breast and prostate; however, the 2-hydroxy form is actually protective. And I3C helps raise the level of 2 whilst decreasing 16 and 4.

To put this in layman’s terms, oestrogen is a ‘family of hormones’. One, 16 alpha - by the common name of oestradiol - is known to attach to cellular receptor sites and cause havoc inside the cell (lowering oxygen levels, increasing sodium levels, and prompting a ‘grow’ signal, as with a foetus). In 1991 Researchers from the Institute for Hormone Research in New York showed that I3C helps convert it to a far less aggressive form, 2OHE, commonly called oestrone, which has much weaker cellular effects and effectively blocks the oestradiol 16 form from attaching to cellular receptor sites and passing harm messages to the inside of the cell. In one study, I3C was given to 25 women for two months. Levels of 16 AH oestradiol declined, while levels of 2OHE oestrone increased. At the same time levels of a metabolite directly associated with both breast and endometrial cancer fell.

Now, a lot is known about these cellular oestrogen receptor sites, but we do not know completely about the message transfer systems into the cell. We do know that Tamoxifen aims to sit on these same receptor sites and thus block any similar action by oestradiol. However we do not know fully the action of Tamoxifen or how/whether it transfers messages. And we know it has some less desirable side effects. For this reason some US experts dub I3C (whose simple action mechanism in converting aggressive oestrogen to the safer variety is quite clear), the ‘Safer, Natural, Tamoxifen’.

Further UCLA research shows that I3C inhibits the growth of oestrogen receptor-positive breast cancer cells by 90 per cent whilst Tamoxifen only ‘scored’ 60 per cent. The added benefit is that in oestrogen receptor-negative cells I3C stopped the growth of new cells by almost 50 per cent whilst, of course, Tamoxifen had no significant effect.

But this is only a part of I3C’s action. A by-product of the metabolism of oestradiol is also a carcinogen and can also send grow signals, having been linked to prostate, breast and endometrial cancers. This by-product is especially produced by some toxins and chemicals, including some oestrogen mimics. Strang Cancer Research Institute have shown that I3C reduces the levels of these metabolites, changing them back to safer 2OHE. Again Tamoxifen has no particular effect.

The cure for modern day pollution?

If you are thinking of buying indole 3 carbinol you might like to look at the Natural Selection Product of Choice. You can do this by  clicking here.In a separate study at New York University, researchers gave 400mgs of I3C to a number of women only to find that, whilst in most cases the ‘bad’ oestrogen was converted to the ‘safer’ version, in some women nothing happened. It turned out that this latter group had a genetic mutation, preventing I3C action. This group of women have an eight-fold increased risk of breast cancer.

Studies at UCLA, Berkeley show that I3C inhibits MCF7 human breast cancer cells from growing by as much as 90% in vitro. But this action did not depend on action on oestrogen receptor sites. Instead the action involved another, completely different receptor, the ah (Aryl Hydrocarbon) receptor. As yet no one knows what normally acts on this receptor, but we do know it can be hit by chemical dioxins. What are these? Formed from chlorine, they are probably the most lethal everyday chemicals and cancer promoters that surround us. Dioxins stimulate cancer by stimulating oestradiol, IGF-1 (insulin-like growth factor) and insulin itself, and tumour necrosis factor, all known cancer promoters. Dioxins are found in everything from cheap compressed wood products to bleached paper and fast foods. Most commonly they are produced by the action of chlorinated water with other chemicals – for example Triclosan, which is found in some toothpastes. Dioxins are so dangerous their ‘safe’ levels are measured in trillionths of a gramme. They activate cancer genes and suppress tumour suppressor genes.

So, I3C manages to block a receptor site that would otherwise be prone to chemical attack, subsequently causing serious problems inside the cell. And this is really important in this modern era. Researchers at Texas University treated breast cancer cells with I3C and dioxin simultaneously and found that I3C reduced dioxin's negative effects by 90%. Several parallel studies on rats and mice showed I3C prevents chemically-induced breast cancer by as much as 70 to 96 per cent.

The natural cancer combatant.

I3C can also alter the activity of a number of enzymes involved in the cancer process (e.g. glutathione S-transference); it alters the chemical metabolism of carcinogens such as aflatoxin and it has even been shown to increase the death of cancer cells (apoptosis). Researchers at Strang Cancer Research Institute (Rockefeller University) showed in 1997/8 that it stops human cancer cells from growing and can provoke cancer cell death, in vitro.

I3C also restores the activity of the p21 and other tumour suppressors that act as controlling influences, preventing the synthesis of the DNA for new cancer cells.

Dosage

Research usually uses levels of 200-400mgs, although several studies have indicated the higher level to be more appropriate. Apparently the average Japanese diet consumption is over 120 mgs per day. And how much cruciferous vegetable matter are you consuming daily?

Supplementationis thus sensible as a top up, or certainly if you have an oestrogen-driven cancer or if you wish to prevent, say, breast cancer.
Precautions
Some people are actually sensitive to this naturally occurring substance. Since it is an oestrogen modulator, it is inadvisable for use if you are pregnant or nursing.
Not surprisingly, it can affect the use of certain oestrogen drugs including, for example, those prescribed to women who have osteoporosis (Ed: As we repeatedly tell you for osteoporosis, come off the drugs and avoid dairy whilst you increase your magnesium levels. Eat more greens – but that’s a different story!)
In summary
Eat lots of cruciferous vegetables. But also take probiotics or your body will be unable to fully release the goodness if you have been taking drugs, antibiotics or had recent surgery.            At Last - the definitive, research based book on how to build a diet to help beat cancer. Click here to read about it.

Of course, you could always use a top quality natural supplement.

If you are thinking of buying indole 3 carbinol as a supplement, you might like to look at the Natural Selection ‘Product of Choice’ in the online shop; click here.

OTHER ARTICLES OF INTEREST

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SOME REFERENCES:

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Shertzer et al. Biochem Pharmacol 1988; 37. 333-8

Bradlow,  Ann. N Y Acad Science 1999; 889. 204-13
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Grubbs CJ, et al. 1995. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res 15:709-16.Guillot C, et al. 1996. Alteration of p53 damage response by tamoxifen treatment. Clin Cancer Res 2:1439-44.
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Telang NT, et al. 1997. Inhibition of proliferation and modulation of estradiol metabolism: novel mechanisms for breast cancer prevention by the phytochemical I3C. Proc Soc Exp Biol Med 216:246-52.
Thangaraju M, et al. 1994. Effect of tamoxifen on lipid peroxide and antioxidative system in postmenopausal women with breast cancer. Cancer 74:78-82.

Verhagen H, et al. 1995. Reduction of oxidative DNA-damage in humans by brussels sprouts. Carcinogenesis 16:969-70.
Wattenberg LW, et al. 1978. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res 38:1410-13.
Yang JH, et al. 1999. A malignant transformation of human cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin exhibits altered expression of growth regulatory factors. Carcinogenesis 20:13-18.

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