(2) Estrogenic Channeling Agents Indole-3-Carbinol (I3C) EVIDENCE-BASED EFFICACY
: I have written extensively in various posts on my support of this compound versus its DIM metabolite as well as any other compound in the post-cycle realm from the category of “dietary supplement.” Perhaps the single-most important mechanism of action of I3C is modulating estrogen metabolism. That’s right, tell your friends – ALL ESTROGEN IS NOT CREATED EQUAL. Estrogen receptors are located on the surface of virtually every type of tissue in the human body. Guys, you too, are not off the hook as this applies to you as well.
The body modifies (metabolizes) estrogens through two mutually exclusive pathways, which lead to compounds with dramatically different biological activities. Estradiol is the primary estrogen in circulation (as the example used above in Diversification Model) and one of the most active. It is metabolized to a number of other chemicals, all with some degree of estrogenic activity.
Key here, are the enzymes 2-hydroxylase and 16-alpha-hydroxylase. Several years ago, scientists hypothesized that a preference towards the 2-hydroxylase pathway and the subsequent generation of 2-hydroxyestrone (2-OHE1), results in less toxic metabolites in the circulation, which was subsequently gone on to support a decreased number of breast cancer outcomes if this were the dominant pathway (later, this proved true for prostate cancer as well). It was also around that same time that the hypothesis of greater estrogenic metabolism via the 16-alpha-hydroxylase enzyme would yield greater amounts of the more potent 16-alpha-hydroxyestrone (16alpha-OHE1) and a larger number of estrogen-dependent cancers would likely be the result. Summary of ORDET study of 2000 (always nice fancy acronyms)
Participants: 10,000 Italian women
Duration: > 5 years
Measured Items: Diet, other breast cancer risks
Findings: Increased level 2-OHE1:16alpha-OHE1 at beginning of study associated with less risk of breast cancer development.
This simply set precedent, mind you – although there is a 1% risk for men to develop breast cancer, posting this study is merely the landmark to establish the importance of greater 2-OHE1:16alpha-OHE1 ratios being desired for decreased estrogen-sensitive cancer risk. This is very important information to someone embarking on post-cycle supplementation. Summary of Prostate Cancer Study
Although there was a failure to achieve statistically significant results in this study, elevated 2-OHE1 urinary levels indicated a decreased risk of prostate cancer, whereas an increased 16alpha-OHE1 urinary level showed an increase of prostate cancer 2-times that of men with the highest levels of 2-OHE1.
I3C modulates these pathways shifting the conversion of estradiol metabolism to favor the 2-hydroxylase pathway and the subsequent 2-OHE1:16alpha-OHE1 ratio is INCREASED, which correlates with a decreased risk of various estrogen-sensitive cancers. A potential caveat worth further exploration is the increase in production of yet another estrogen exhibited by some studies (4-hydroxyestrone – this is very potent). These increases were NOT significant, however, and as you will see and have seen in my various posts, are put out by people with vested interest in other products. There are multitudes of studies that actually show a concurrent DECREASE in 4-OHE1, so the mixed results tend to leave me questioning those trying to prove their various products superior. Catch my drift?
In addition, and certainly not something studied, but the data seems to suggest shifts from the more potent (2-OHE1) to less potent (16alpha-OHE1) in a time when there is the potential for increased conversion (and this goes out to all of my aromatase-inhibitor-loving friends) – namely, during the post-cycle period would also contribute to a shift in dose-response curves to the right (and that is for my pharmacologically-inclined friends). We’ll see in the pharmaceutic exploration (parts IV + V) that this is NOT the entire picture – unfortunately, I can only address these items one by one in a certain time allotment. FORMS & DOSAGES
: 200mg to as high as 400mg has been studied and based on available evidence, this is what I would be hard-pressed not to suggest at this time. There is no upper-limit established, but even while in the post-cycle realm, I would beg you to adhere to a max of 400mg per day as this is simply what has been supported to date. POTENTIAL SIDE EFFECTS / INTERACTIONS
: Although it may seem obvious that a substance consumed over 1000s of years by millions worldwide is inherently safe, it has been challenged recently by those with vested interest in its metabolite DIM. I have expressed my concern at the challenges DIM supporters have offered and it is just plain bad science. Numerous cell culture, animal, and human studies have demonstrated I3C’s safety and tolerability, along with its targeted ability to SUPPRESS estrogen-receptor-sensitive (breast, cervical, and important for this discussion – prostate) cancer growth (sorry Dr. Z), and induce programmed cell death in a variety of tumors, including those associated with breast, prostate, endometrial, leukemia, and colon cancers.
As an aside, the cytochrome P450 enzymatic system discussed above in the AT / ATD section within both the liver and intestinal track is actually STRENGTHENED by use of I3C – something that could prove especially beneficial to C17 alkylated users. CAUTION
: Be careful of “research” supporting concurrent use of DIM – usual vested interest is a hand-in-hand with the funding of such studies.