Indole-3-Carbinol

Indole-3-carbinol or I3C is a breakdown product of glucosinolate glucobrassicin which is primarily found in cruciferous vegetables. Cruciferous vegetables include cabbage, broccoli, brussel sprouts, cauliflower, bok choy and kale. When cruciferous vegetables are macerated (cell walls broken), an enzyme called myrosinase is released. Myrosinase produces I3C from the glucosinolates in the vegetables. I3C is converted to diindolymethane (DIM), indole (3,2,b) carbazole (ICZ) and other compounds by stomach acid. DIM and ICZ are absorbed from the gastrointestinal tract. The most recent research attributes DIM as the primary anti-cancer compound. Research indicates that Indole-3-carbinol and its derivatives may modulate estrogen metabolism and have anti-carcinogenic, antioxidant and anti-atherogenic properties.

Indole-3 Carbinol and Herpes Viruses

Research has shown that I3C is a "cell cycle G1 antagonist" and that herpes simplex virus (HSV) requires cell cycle factors to replicate. Subsequently, an in vitro study investigated the effect of I3C on monkey kidney and human lung cells infected with HSV-1 and HSV-2 viruses. The replication of all HSV types tested was inhibited by at least 99.9% by the I3C but the test cells required pretreatment with I3C for at least 12 to 36 hours prior to infection. The observed inhibition was not due to direct viral inactivation by I3C or drug induced cytoxicity. Rather, inhibition was the apparent result of disrupting cell cycle factors required by HSV for replication. I3C may also be useful in inhibiting the formation of papillomatosis cysts caused by the human papilloma virus (HPV).

This study suggests that I3C may be helpful in preventing outbreaks of herpes family viruses if consumed daily, but may not be very helpful in treating an outbreak that is already in progress. Human trials to test this hypothesis have not been performed. Given the questions regarding I3C safety in above food source amounts, it may be advisable to use other alternatives for preventing herpes outbreaks until further research is done on this application of this supplement.

Cancer, Indole-3 Carbinol and DIM (diindolymethane

Historically, the Roman statesman, Cato the Elder (234-149 BC) wrote: "If a cancerous ulcer appears upon the breasts, apply a crushed cabbage leaf and it will make it well." Crushing a cabbage leaf would convert indole-3-glucosinolate to I3C, among other reactions. Recent research indicates that I3C and several of its derivatives, DIM in particular, modulate estrogen metabolism. Specifically, DIM increases the ratio of 2-hydroxyestrone to 16 alpha-hydroxyestrone and also inhibits the 4-hydroxylation of estradiol. This is important because 16 alpha-hydroxyestrone has been demonstrated to be carcinogenic while 2-hydroxylation has been demonstrated to have anti-cancer properties. Indole-3-carbinol has also been shown to increase apoptosis (cell death) in some cancer cell lines. I3C and DIM have demonstrated anti-cancer properties with endometrium, lung, tongue, colon, liver, breast, uterine and prostate cancers. DIM is also being investigated as a treatment for cervical dysplasia.

Estrogen modulation is very important because:

Many pesticides, plastics and other synthetic chemicals in the environment mimic estrogen when introduced into the human body.
Increased estrogenic pollutants may play a role in infertility, pre-mature births, cancer, obesity and male impotence.
Increased estrogen levels from birth control pills can have undesirable health effects.
Estrogen / Testosterone imbalance associated with aging can contribute to age related weight gain and obesity.
Imbalances in estrogen metabolites can increase the risk of certain cancers.

Many of the studies on I3C and its derivatives have been performed with animals or cell cultures in a laboratory. Some epidemological studies involving humans have been done. In one study polish women were observed to have approximately four times the rate of breast cancer after emigrating to the United States. The increase in breast cancer was correlated with a reduction in the consumption of cruciferous vegetables, especially cabbage sauerkraut.

More recently, human trials are being done, primarily with DIM because DIM appears to be safe while I3C safety in large doses has been questioned.

Indole-3 Carbinol and Heart and Vascular Healt

; Indole-3-carbinol induces the synthesis of 2-hydroxyestrone which inhibits the oxidation of low-density lipoprotein (LDL). 2-hydroxyestrone also appears to inhibit smooth muscle proliferation. Inhibition of smooth muscle proliferation and inhibition of the oxidation of LDL could account for the possible anti-atherogenic activity of indole-3-carbinol.

I3C Drug Interactions

The conversion of indole-3-carbinol to DIM and ICZ requires stomach acid. Therefore, antacids and stomach acid reducing medications may inhibit the effectiveness of I3C.

Indole-3-carbinol and DIM may be synergistic with tamoxifen in protecting against breast cancer.

Indole-3 Carbinol from Food

The enzyme myrosinase is the key to obtaining maximum I3C and DIM from cruciferous vegetables. Enzymes are destroyed by cooking. Therefore, cruciferous vegetables provide the most I3C when consumed raw. The enzyme is released and activated by breaking the cell walls. Therefore, bruising, macerating, crushing, blending or otherwise mechanically disrupting as many cell walls as possible will yield the most I3C. There are two ways to meet this requirement. One is eating the vegetables raw and chewing them well. The other is making fermented vegetables. Traditional fermented Sauerkraut uses exactly this process. Cabbage (or other cruciferous vegetables) is shredded and pounded, then a small amount of salt is added to draw out the juice and provide an anaerobic environment for fermentation. The lactic acid produced by the fermentation facilitates conversion of I3C to DIM. Cruciferous vegetables are believed to have some goitrogenic properties which may be deactivated by fermentation as well.

The amount of raw cruciferous vegetables needed to provide a maximum protective benefit has been estimated to be a minimum of two pounds per day. Consuming this much is impractical and may not be healthy.

Research has indicated that individuals who consume a high amount of cruciferous vegetables in pre-teen and adolescent years retain a protective effect later in life even if they no longer consume large amounts. Consumption later in life also provided a protective effect.

Indole-3 Carbinol Safety

Indole-3-Carbinol activates many cellular enzymes and itself forms many derivative products. Some of these derivative products have been tested and produced mixed results with regards to benefits and safety. Given that epidemological data shows that consumption of cruciferous vegetables is associated with health benefits, it would appear that I3C in reasonable nutritional quantities is not particularly hazardous. Taking high doses of I3C as a supplement may be another matter. The chemistry of I3C is quite complex. In brief, several derivative products are formed in the presence of stomach acid. Their acronyms are ICZ, LTR, CTR, ASG, and DIM. All of these except DIM have some beneficial and some harmful properties. They are chemically similar to dioxin and affect the same receptor sites as dioxin. There is some research investigating the use of these substances as a substitute for dioxin in cancer therapy. It is hoped that some of them may exhibit some of the same anti-cancer properties as dioxin with less toxic effects.

Only DIM exerts its control over cancer cell growth without activating the dioxin receptor or inducing unwanted enzymes. Direct control over cancer cell growth by DIM has now been shown in breast, uterine, cervical, ovarian, and colon cancer cells. It is believed that much of the anti-cancer activity attributed to I3C may be attributable to DIM that forms from the I3C.

DIM has, so far, a firmly established safety record and most current research with humans is focusing on DIM.

DIM Dosage

The use of absorbable DIM has been shown effective in amounts close to that obtainable from our diet (0.3 mg/kg/day of DIM). That corresponds to 22 mg. per day for a 160 pound individual. I3C requires about 15 times more than this (4.5 mg/kg/day), and is associated with side effects. This corresponds to 327 mg. per day for a 160 pound individual.

I3C Indole-3-carbinol and Diindolymethane (DIM) Supplements

Here are some recommended I3C Indole-3-carbinol and Diindolymethane (DIM) Supplementss.

Triple Action Cruciferous Vegetable Extract

Breast Health Formula

Triple Action Cruciferous Vegetable Extract with Resveratrol

Indole-3-Carbinol with DIM

DIM

I3C References

Click to Expand References

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