Indole-3-Carbinol (I3C) as part of PCT? - AnabolicMinds.com

Indole-3-Carbinol (I3C) as part of PCT?

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    Thumbs up Indole-3-Carbinol (I3C) as part of PCT?


    This discussion branched off another thread about Chrysin. I'm re-starting it here for people who might have avoided the other thread due to its Chrysin title:

    In short, there seems to be some strong indications that Indole-3-Carbinol (I3C) - a chemical derived from cruciferous vegetables - causes the rapid excretion of estrogen from the body - specifically the "stronger" estrogens with the highest estrogen receptor activity. This would seem a natural compliment to PCT possibly allowing for lower doses of the tried-and-true PCT chemicals. Has anyone with the training to actually understand this researched this line of thinking? Citations follow:

    Scientists found that Indole-3-Carbinol (I3C) causes the body to metabolize estrogen via the 2-hydroxylation pathway. By funneling estrogen into this tumor suppressor pathway, I3C stimulates the rate at which the body expels estrogen, essentially vacuuming away the estrogen. These scientists found that 400 mg of I3C given daily resulted in a 50 percent increase of 2-hydroxylation - Michnoviez JJ, Bradlow HL. Induction of estradiol metabolism by dietary indole-3-carbinol in humans. J Natl Cancer Inst, 1990; 82(11): 947-949. AND Michnoviez JJ, Bradlow HL. Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer, 1991;16 (1): 59-66.

    J Natl Cancer Inst. 1997 May 21;89(10):718-23.
    Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans.

    Michnovicz JJ, Adlercreutz H, Bradlow HL.

    Rockefeller University Hospital and The Institute for Hormone Research, New York, NY 10016, USA.

    BACKGROUND: The oxidative metabolism of estrogens in humans is mediated primarily by cytochrome P450, many isoenzymes of which are inducible by dietary and pharmacologic agents. One major pathway, 2-hydroxylation, is induced by dietary indole-3-carbinol (I3C), which is present in cruciferous vegetables (e.g., cabbage and broccoli). PURPOSE: Because the pool of available estrogen substrates for all pathways is limited, we hypothesized that increased 2-hydroxylation of estrogens would lead to decreased activity in competing metabolic pathways. METHODS: Urine samples were collected from subjects before and after oral ingestion of I3C (6-7 mg/kg per day). In the first study, seven men received I3C for 1 week; in the second study, 10 women received I3C for 2 months. A profile of 13 estrogens was measured in each sample by gas chromatography-mass spectrometry. RESULTS: In both men and women, I3C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol, and 16alpha-hydroxyestrone, were lower after I3C treatment. CONCLUSIONS: These findings support the hypothesis that I3C-induced estrogen 2-hydroxylation results in decreased concentrations of several metabolites known to activate the estrogen receptor. This effect may lower estrogenic stimulation in women. IMPLICATIONS: I3C may have chemopreventive activity against breast cancer in humans, although the long-term effects of higher catechol estrogen levels in women require further investigation.


    Eur J Cancer Prev. 2002 Aug;11 Suppl 2:S86-93.
    Multiple molecular targets of indole-3-carbinol, a chemopreventive anti-estrogen in breast cancer.

    Ashok BT, Chen YG, Liu X, Garikapaty VP, Seplowitz R, Tschorn J, Roy K, Mittelman A, Tiwari RK.

    Department of Microbiology, Immunology and Medicine, New York Medical College, Valhalla, NY 10595, USA.

    The mechanism of action of the anti-estrogen indole-3-carbinol (I3C), present in cruciferous vegetables, is being examined in our laboratory with a view to promote the use of this naturally occurring chemopreventive as an alternative to synthetic anti-estrogens in human breast cancer. Our previous results clearly demonstrated that despite its low affinity for the estrogen receptor (ER), I3C abrogated estradiol-mediated cellular and biochemical effects in estradiol-responsive cells and tissues. In an earlier report, we identified ER phosphorylation as one of the targets of I3C, and in this communication we describe the consequence of inhibition of ER phosphorylation. Estradiol-induced DNA-binding proteins that bound to several DNA-responsive elements were inhibited by I3C and this effect was not at the level of DNA-protein physical interaction as inclusion of I3C in vitro in the reaction mix did not affect the binding. We analyzed the spectrum of genes induced by estradiol and modulated and/or intercepted by I3C. Our results conclude that although estradiol-mediated functions are affected by I3C, its biochemical targets are multiple and some of these may be modulated by the oligomeric products of I3C.

    PMID: 12570340 [PubMed - indexed for MEDLINE]

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    IMO DIM is better at least 600 mgs, very pricey at that dosage. ALso check muscle gurus they have a thread about it in which PA discusses in detail.

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    Quote Originally Posted by Apowerz6
    IMO DIM is better at least 600 mgs, very pricey at that dosage. ALso check muscle gurus they have a thread about it in which PA discusses in detail.
    Have any citations for DIM you could gesture towards?

    •   
       

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    Not PCT, but related.

    This guy, posting as David Zolt and David Z, on the now Google newsgroups posted his experiences with varying doseages and timings with bloodtest results on DIM as HRT.

    Here's a cut and paste of one of his postings on Chrysin and DIM.


    David Zolt
    Jan 1 2002, 10:35 am
    Newsgroups: alt.support.impotence
    From: "David Zolt" <davidz...@ameritech.net> - Find messages by this author
    Date: Tue, 1 Jan 2002 1027 -0500
    Local: Tues, Jan 1 2002 10:35 am
    Subject: A Primer on Estrogen Management - Chrysin, DIM and Arimidex


    Men convert a small amount of their testosterone (T) to estrogen (E) by the action of the aromatase enzyme. As men age, they experience both decreasing levels of T and increasing levels of E. When the T/E ratio begins to tip downwards, a number of negative health effects occur.

    Men who are on T replacement therapy (TRT) often experience elevated Eas a side effect of boosting their T back to normal.

    Whether you are on TRT or not, putting the T/E ratio back into proper balance generally restores a man's vigor including improved erectilefunction. The remainder of this primer discusses three remedies that are used in estrogen management - (1) Chrysin, (2) Diindolylmethane
    (DIM) and (3) Arimidex.

    (1) Chrysin is a bioflaviniod that, according to scientific studies,
    acts as an anti-aromatase. It has virtually no effect when taken orally because it's digested before it gets to the blood. Therefore, the only effective way to take Chrysin is topically (via gel or cream). Many men have reported a very significant increase in erectile function andlibido in the first few weeks on topical Chrysin, but the effect soonfades. The residual effect is still generally positive, but disappointing compared with the initial surge experience.

    My blood tests indicate that Chrysin gel has no impact on lowering Estradiol (the most potent estrogen). However, it has a remarkablypositive effect on improving insulin sensitivity (I'm T2 diabetic). So,I continue to apply Chrysin gel at 90 mg/day.

    (2) Diindolylmethane (DIM) is a naturally occurring substance foundprimarily in cruciferous vegetables (e.g., cabbage, broccoli,
    cauliflower, Brussels sprouts, etc.) that helps the liver
    digest/metabolize Estradiol into more benign/healthy estrogens. DIM isalso not very bioavailable when taken orally; however, Indolplex(a.k.a.,Di-indolin) is a proprietary formulation that increases DIM'soral bioavailability.

    I experienced a tremendous surge in erectile function during the first 2or 3 months on a very low dosage of Indoplex (25 to 50 mg/day).Unlike the fade that occurred after 2 or 3 weeks on Chrysin gel, theeffect of Indoplex remains at about 80% of the surge effect level at about 6 months after starting.

    The recommended dosage for Indolplex is about 300 mg/day. This dosageis way too much for me, but I'm highly responsive to it. I would suggest starting at 100 mg/day at dinner for 2 or 3 weeks and see how it goes.
    Depending upon your response, adjust your dosage from there. I prefer the tablets to the capsules because they break easily in half or smallerquantities so I can adjust my dosage more precisely. This is important because the window of optimal dosage is small.

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    Quote Originally Posted by Rogue Drone
    Not PCT, but related.

    This guy, posting as David Zolt and David Z, on the now Google newsgroups posted his experiences with varying doseages and timings with bloodtest results on DIM as HRT.
    Excellent post. Thanks!

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    Quote Originally Posted by Rogue Drone
    Not PCT, but related.

    This guy, posting as David Zolt and David Z, on the now Google newsgroups posted his experiences with varying doseages and timings with bloodtest results on DIM as HRT.

    Here's a cut and paste of one of his postings on Chrysin and DIM.


    David Zolt
    Jan 1 2002, 10:35 am
    Newsgroups: alt.support.impotence
    From: "David Zolt" <davidz...@ameritech.net> - Find messages by this author
    Date: Tue, 1 Jan 2002 1027 -0500
    Local: Tues, Jan 1 2002 10:35 am
    Subject: A Primer on Estrogen Management - Chrysin, DIM and Arimidex


    Men convert a small amount of their testosterone (T) to estrogen (E) by the action of the aromatase enzyme. As men age, they experience both decreasing levels of T and increasing levels of E. When the T/E ratio begins to tip downwards, a number of negative health effects occur.

    Men who are on T replacement therapy (TRT) often experience elevated Eas a side effect of boosting their T back to normal.

    Whether you are on TRT or not, putting the T/E ratio back into proper balance generally restores a man's vigor including improved erectilefunction. The remainder of this primer discusses three remedies that are used in estrogen management - (1) Chrysin, (2) Diindolylmethane
    (DIM) and (3) Arimidex.

    (1) Chrysin is a bioflaviniod that, according to scientific studies,
    acts as an anti-aromatase. It has virtually no effect when taken orally because it's digested before it gets to the blood. Therefore, the only effective way to take Chrysin is topically (via gel or cream). Many men have reported a very significant increase in erectile function andlibido in the first few weeks on topical Chrysin, but the effect soonfades. The residual effect is still generally positive, but disappointing compared with the initial surge experience.

    My blood tests indicate that Chrysin gel has no impact on lowering Estradiol (the most potent estrogen). However, it has a remarkablypositive effect on improving insulin sensitivity (I'm T2 diabetic). So,I continue to apply Chrysin gel at 90 mg/day.

    (2) Diindolylmethane (DIM) is a naturally occurring substance foundprimarily in cruciferous vegetables (e.g., cabbage, broccoli,
    cauliflower, Brussels sprouts, etc.) that helps the liver
    digest/metabolize Estradiol into more benign/healthy estrogens. DIM isalso not very bioavailable when taken orally; however, Indolplex(a.k.a.,Di-indolin) is a proprietary formulation that increases DIM'soral bioavailability.

    I experienced a tremendous surge in erectile function during the first 2or 3 months on a very low dosage of Indoplex (25 to 50 mg/day).Unlike the fade that occurred after 2 or 3 weeks on Chrysin gel, theeffect of Indoplex remains at about 80% of the surge effect level at about 6 months after starting.

    The recommended dosage for Indolplex is about 300 mg/day. This dosageis way too much for me, but I'm highly responsive to it. I would suggest starting at 100 mg/day at dinner for 2 or 3 weeks and see how it goes.
    Depending upon your response, adjust your dosage from there. I prefer the tablets to the capsules because they break easily in half or smallerquantities so I can adjust my dosage more precisely. This is important because the window of optimal dosage is small.

    Thanks Rogue Drone, although I do not have the links... Dr. Serrano, from Infinity Fitness also suggests DIM, he was interviewed in Dec. Muscle Mag (i know I know, I work at vitamin world, and they don't have MD, so i needed something to read!!!) Anyhow he was talking about natural test boosters and that was one he mentioned along with 6-oxo, both he confirmed with blood tests. Dr. Serrano is pretty interesting, ALRI has interviewed him in the CORE mag also...

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    Anyone have any ideas on where to get this?

    Am I searching for "Indolplex"

    Thanks!


    EDIT: Found a place that says it was renamed Phytosorb-DIM ?

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    Quote Originally Posted by JonesersRX7
    Looks interesting....thanks for the link!

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    Quote Originally Posted by yeahright
    Looks interesting....thanks for the link!
    No problem at all -- thanks for starting the topic!

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    Quote Originally Posted by yeahright
    This discussion branched off another thread about Chrysin. I'm re-starting it here for people who might have avoided the other thread due to its Chrysin title:

    Good thinking, I skipped it because of the Chrysin title.

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    Quote Originally Posted by D_town
    Good thinking, I skipped it because of the Chrysin title.
    Yep, that's what I was afraid would happen. So far emerging from this thread are two othe rinteresting facts:

    1) Ester Vitamin C apparently has some anti-estrogenic effects above 2 grams a day;
    2) DIM (when processed to be made better bioavailable) is effective and maybe more effective than I3C.

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    Does it have to be Ester C?

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    Quote Originally Posted by JonesersRX7
    Does it have to be Ester C?
    I have no idea. I'm just quoting from BIOMAN's post where he quotes Dr. D. Here it is:

    "Dr D had mentioned that Vitamin C has some natural AI properties. I took this to mean it was very weak otherwise we'd be hearing a lot more about it. I tried Ester C on a whim prior to my current cycle and I noted a increase in libido. I didn't really think much of it nor did I seriously attribute it to the Ester C.

    Well, my perception of it is changing now that I'm on a cycle of 4AD/19Nor/1 Test dermal. Last time I ran this stack I had puffy nipples and a lot of bloating. This resulted in the beginings of gyno which, forturnately, went away with aggressive Nolva and Ultra Hotter treatment during PCT.

    At 4-5 weeks into this cycle I am having very little nipple puffiness, no signs of gyno and less bloat than last cycle. The main difference is that I am taking 2-4 grams of Ester C per day along with the addition of 2 tablespoons of colloidal gold. I doubt that the CG is responsible for the AI-like effect.

    I am NOT saying that Ester C is a replacement for a proper AI, SERM or PCT protocol but I am encouraging people to give it a try during cycle and PCT just to see if I'm being crazy or not, lol. Can't hurt."

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    Quote Originally Posted by Apowerz6
    Thanks Rogue Drone, although I do not have the links
    Google took over the old usenet newsgroups a few years ago, they have then archived back to the 80's. I came across David Zolt's DIM expermentation a few years in alt. oldguys. limpdick a few years ago, do a search for him.

    The thing that comes across in his postings is how specifically he had to dose in order to get his E2 levels, and maybe his test, don't remember, where he wanted them. DIM comes across as a pretty tricky substance to properly administer.

    My concern with using DIM would be the specific dosing issue, and the article I read that stated it bound to the AR and blocked test and DHT in skeletal muscle. At the time, the article read as credible to me in source and citation, but I don't know where it is.

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    DIM study:


    Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer.

    Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF.

    Department of Molecular and Cell Biology, University of California, Berkeley, 94720-3200, USA.

    Dietary indoles, present in Brassica plants such as cabbage, broccoli, and Brussels sprouts, have been shown to provide potential protection against hormone-dependent cancers. 3,3'-Diindolylmethane (DIM) is under study as one of the main protective indole metabolites. Postmenopausal women aged 50-70 yr from Marin County, California, with a history of early-stage breast cancer, were screened for interest and eligibility in this pilot study on the effect of absorbable DIM (BioResponse-DIM) supplements on urinary hormone metabolites. The treatment group received daily DIM (108 mg DIM/day) supplements for 30 days, and the control group received a placebo capsule daily for 30 days. Urinary metabolite analysis included 2-hydroxyestrone (2-OHE1), 16-alpha hydroxyestrone (16alpha-OHE1), DIM, estrone (El), estradiol(E2), estriol (E3), 6beta-hydroxycortisol (6beta-OHC), and cortisol in the first morning urine sample before intervention and 31 days after intervention. Nineteen women completed the study,for a total of 10 in the treatment group and 9 in the placebo group. DIM-treated subjects, relative to placebo, showed a significant increase in levels of2-OHE1 (P=0. 020), DIM (P =0. 045), and cortisol (P = 0.039), and a nonsignificant increase of 47% in the 2-OHE1/16alpha-OHE1 ratio from 1.46 to 2.14 (P=0.059). In this pilot study, DIM increased the 2-hydroxylation of estrogen urinary metabolites.

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    YIKES! It appears that I3C and DIM both effect the excretion of estrogen through urine, their other effects are different. In this study, it appears that (in rats) combining I3C and Taxomifen cause the creation of a "genotoxic metabolite" whereas DIM doesn't have this effect:


    Differences in the hepatic P450-dependent metabolism of estrogen and tamoxifen in response to treatment of rats with 3,3'-diindolylmethane and its parent compound indole-3-carbinol.

    Parkin DR, Malejka-Giganti D.

    Veterans Affairs Medical Center, Minneapolis, MN 55417, USA.

    Indole-3-carbinol (I3C), present in cruciferous vegetables, and its major in vivo product 3,3'-diindolylmethane (DIM), have been reported to suppress estrogen-responsive cancers. This effect may be mediated through the modification of cytochrome P450 (CYP) complement and activities leading to estrogen detoxification. We examined the effects of a 4-day treatment of female Sprague-Dawley rats with DIM at 8.4 and 42 mg/kg body weight (bwt), on the hepatic CYP protein level, CYP1A1, 1A2, 2B1/2 and 3A1/2 probe activities and CYP-dependent metabolism of 17beta-estradiol (E2) and estrone (E1). At 42 mg/kg bwt, DIM effected a small increase (2.8-fold) in CYP1A1 activity, and at both dose levels it reduced CYP3A1/2 activity by approximately 40%. At the higher dose level, DIM decreased the rates of oxidation of E2 to 4-OH-E2, 4-OH-E1, 6alpha-OH-E2 and 6(alpha+beta)-OH-E1 by 39, 44, 71 and 60%, respectively, and E1 to 6(alpha+beta)-OH-E1 by 39%. These effects were considerably different from those of I3C reported by us previously. We also examined the effects of DIM and I3C on the hepatic microsomal metabolism of tamoxifen (TAM). Whereas metabolism of TAM was unaffected by DIM, formation of N-desmethyl-TAM (and its presumed derivative) was increased approximately 3-fold by I3C at 250 mg/kg bwt. Since N-desmethyl-TAM is transformed to a genotoxic metabolite, dietary exposure to I3C may enhance hepatic carcinogenicity of TAM in the rat. The differences between I3C and DIM in CYP-mediated activities and metabolism indicate that DIM is not a proximate intermediate in the mechanism of action of I3C.

    PMID: 15041081 [PubMed - indexed for MEDLINE]

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    Carcinogenesis. 1998 Sep;19(9):1631-9.
    Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane.

    Chen I, McDougal A, Wang F, Safe S.

    Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466, USA.

    Phytochemicals such as indole-3-carbinol (I3C) and sulforaphane are components of cruciferous vegetables which exhibit antitumorigenic activity associated with altered carcinogen metabolism and detoxification. Diindolylmethane (DIM) is a major acid-catalyzed metabolite of I3C formed in the gut that binds to the aryl hydrocarbon receptor (AhR) and treatment of MCF-7 human breast cancer cells with 10-50 microM DIM resulted in rapid formation of the nuclear AhR complex and induction of CYP1A1 gene expression was observed at concentrations >50 microM. Previous studies have demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a high affinity AhR ligand, inhibits 17beta-estradiol (E2)-induced responses in MCF-7 cells and growth of E2-dependent 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats. Results of this study show that like TCDD, DIM inhibits E2-induced proliferation of MCF-7 cells, reporter gene activity in cells transiently transfected with an E2-responsive plasmid (containing a frog vitellogenin A2 gene promoter insert) and down-regulates the nuclear estrogen receptor. Moreover, DIM (5 mg/kg every other day) also inhibits DMBA-induced mammary tumor growth in Sprague-Dawley rats and this was not accompanied by induction of hepatic CYP1A1-dependent activity. Thus, DIM represents a new class of relatively non-toxic AhR-based antiestrogens that inhibit E2-dependent tumor growth in rodents and current studies are focused on development of analogs for clinical treatment of breast cancer.

    PMID: 9771935 [PubMed - indexed for MEDLINE]

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    Just began researching I3C a little and found this, just wondering your opinion:

    "Two cruciferous indoles -- Diindolylmethane (DIM) and its precursor, Indole-3-carbinol (I3C) -- are increasingly popular as dietary supplements. Researchers have been studying the role of these substances in promoting healthier estrogen metabolism and for potential use in estrogen-related conditions, including cancer. Regarding women's health, use of cruciferous vegetable indoles has importance for breast cancer prevention and for the control of cervical dysplasia. Both DIM and I3C show real promise in these areas, yet studies have also uncovered sharp contrasts between them in one critical area -- consumer safety.

    Anyone advocating the benefits of I3C over DIM is ignoring the published scientific facts. A careful review of the research reveals serious questions concerning the safety of I3C. For example, the National Institute of Health (NIH) in its Chemoprevention Branch Report on I3C safety issues says: "Subchronic, preclinical toxicology studies in dogs have identified significant toxicities associated with oral administration of I3C... The possible enhancing effects of I3C on chemical carcinogenesis and toxicity should be investigated, especially in light of the wide variety of enzymes induced... The fact that the I3C condensation product ICZ has both antiestrogenic and estrogenic activities also may have safety implications... Additional genetic toxicity testing may be required." (1)

    This statement and the published evidence are clear -- I3C, and in particular its reaction product ICZ, are associated with a number of unwanted activities that are not compatible with safe, long-term use. Misinformation raised about DIM and the purported superiority of I3C are simply not supported by the facts."


    "In year-long animal tests, independent university-based scientists found evidence of I3C's lack of safety that justified concern -- I3C was found to be highly enzyme-inducing, but DIM was not. In a second test performed by an independent government laboratory, confirming results again showed unwanted enzyme induction by I3C but not DIM.

    Unwanted enzyme-inducing effects from I3C have also been shown in recent animal studies (5). This work clearly demonstrates that oral I3C can increase production of dangerous estrogen metabolites at the same time it increases the beneficial 2-hydroxy metabolites. In effect, this cancels out benefits for estrogen metabolism. Consistent with this, I3C has been shown to be ineffective in controlling the growth of experimental breast cancer (6, 7), while DIM succeeds (8, 9)."

    "Briefly, the reaction products from I3C can be described as follows.

    Indolocarbazole (ICZ) - ICZ resembles dioxin in structure and function (14). Also, like dioxin, ICZ is a powerful inhibitor of estrogen action. Though toxic in many other ways, dioxin has been shown to prevent and treat breast cancer in animals. ICZ is being explored as a possibly less toxic form of dioxin to treat breast cancer. But like dioxin, ICZ does not block the dioxin receptor. It activates it as aggressively as dioxin does (15).

    Though a down-regulator of the estrogen receptor system, ICZ is itself estrogenic and is responsible for promoting enzymes which produce 4-hydroxy estrogen, a metabolite associated with uterine tumors (16) Though more quickly metabolized, ICZ shares many of dioxin's toxicities. Like dioxin, ICZ has been shown to be damaging to the thymus gland and immune system (17), and to damage DNA (18).

    Importantly, the reaction products arising from I3C have been shown to negatively impact the immune system, resulting in lower natural killer cell activity in animals (19). Like dioxin, I3C and its reaction products have also been associated with reproductive toxicity in animals (20, 25). Unlike I3C, DIM cannot be converted into ICZ in vivo.

    Ascorbigen (ASG) - ASG is the most plentifully produced reaction product from I3C, arising from the combination of I3C with vitamin C. ASG occurs following consumption of cruciferous vegetables which contain abundant viatamin C. ASG arises from I3C supplements only when the I3C is taken along with other supplements or foods rich in Vitamin C.

    Once produced in the stomach, a portion of ASG is then converted into ICZ in the lower intestine (21). This makes ASG a source for much of the unwanted enzyme promotion attributed to ICZ. This was demonstrated when ASG was fed as a pure compound to animals and measurements of estrogen metabolism showed increased production of unwanted 4-hydroxy estrogen (22).

    4-hydroxy estrogen is a carcinogenic estrogen metabolite, increased after activation of the dioxin receptor. While some preliminary work demonstrates anti-cancer activity by ASG in animals, further testing reveals that ASG's natural breakdown results in the release of formaldehyde (23). This makes ASG a highly undesirable I3C product during human use. Other undesirable reactions involving ASG have been described resulting in the formation of DNA damaging mutagens (24).

    Linear Trimer (LTR) - LTR is an anti-estrogen, but clearly another activator of the dioxin receptor. This was recently proven by feeding I3C to pregnant rats and studying the livers of the mothers and their offspring (25). LTR was found in both mother and offspring. Most importantly, the induction of the enzyme source for 4-hydroxy estrogen, CYP 1B1, was also found together with measurable LTR in the rat pup livers. This is evidence that LTR crosses the placenta and activates the dioxin receptor in an analogous way to ICZ in both mother and developing fetus.

    Cyclic Trimer (CTR) - CTR is produced in stomach acid by the condensation of three I3C molecules into a ring structure. CTR is a direct acting estrogenic compound, occupying and activating the estrogen receptor. CTR powerfully stimulates the growth of growth of breast cancer cells, in the presence or absence of estrogen (26).

    Indole-3-acetonitrile (IAN) also arises from I3C in the acidic milieu of the stomach. Though shown to be protective in an animal model of stomach cancer, IAN has also been shown to be mutagenic (47) and give rise to DNA-damaging reaction products (27). This occurs when I3C is ingested in the presence of nitrates commonly present in foods (47).

    More importantly, IAN is disruptive of cell membranes, activating the arachadonic fatty acid cascade leading to the production of LTB4, a reactive leukotrine (28). Leukotrines are closely related to Lipoxins, which like ICZ, may contribute to further activation of the of the dioxin receptor (29)."

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    hmmm... pros and cons... like so many compounds... good thread gentlemen.

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    DIM is in Diesel Test. It's purported to raise "good estrogens" while lowering E2.

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    Wedgylx, thanks for the research. Yes, it appears that I3C appears to have many unwanted effects. Of special concern to anyone using this as part of PCT would be this study:

    While I3C and DIM both effect the excretion of estrogen through urine, their other effects are different. In this study, it appears that (in rats) combining I3C and Taxomifen cause the creation of a "genotoxic metabolite" whereas DIM doesn't have this effect:


    Differences in the hepatic P450-dependent metabolism of estrogen and tamoxifen in response to treatment of rats with 3,3'-diindolylmethane and its parent compound indole-3-carbinol.

    Parkin DR, Malejka-Giganti D.

    Veterans Affairs Medical Center, Minneapolis, MN 55417, USA.

    Indole-3-carbinol (I3C), present in cruciferous vegetables, and its major in vivo product 3,3'-diindolylmethane (DIM), have been reported to suppress estrogen-responsive cancers. This effect may be mediated through the modification of cytochrome P450 (CYP) complement and activities leading to estrogen detoxification. We examined the effects of a 4-day treatment of female Sprague-Dawley rats with DIM at 8.4 and 42 mg/kg body weight (bwt), on the hepatic CYP protein level, CYP1A1, 1A2, 2B1/2 and 3A1/2 probe activities and CYP-dependent metabolism of 17beta-estradiol (E2) and estrone (E1). At 42 mg/kg bwt, DIM effected a small increase (2.8-fold) in CYP1A1 activity, and at both dose levels it reduced CYP3A1/2 activity by approximately 40%. At the higher dose level, DIM decreased the rates of oxidation of E2 to 4-OH-E2, 4-OH-E1, 6alpha-OH-E2 and 6(alpha+beta)-OH-E1 by 39, 44, 71 and 60%, respectively, and E1 to 6(alpha+beta)-OH-E1 by 39%. These effects were considerably different from those of I3C reported by us previously. We also examined the effects of DIM and I3C on the hepatic microsomal metabolism of tamoxifen (TAM). Whereas metabolism of TAM was unaffected by DIM, formation of N-desmethyl-TAM (and its presumed derivative) was increased approximately 3-fold by I3C at 250 mg/kg bwt. Since N-desmethyl-TAM is transformed to a genotoxic metabolite, dietary exposure to I3C may enhance hepatic carcinogenicity of TAM in the rat. The differences between I3C and DIM in CYP-mediated activities and metabolism indicate that DIM is not a proximate intermediate in the mechanism of action of I3C.

    PMID: 15041081 [PubMed - indexed for MEDLINE]

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    dinoiii says this about DIM & i3c...

    "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."

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    Quote Originally Posted by yeahright View Post
    Wedgylx, thanks for the research. Yes, it appears that I3C appears to have many unwanted effects. Of special concern to anyone using this as part of PCT would be this study:

    While I3C and DIM both effect the excretion of estrogen through urine, their other effects are different. In this study, it appears that (in rats) combining I3C and Taxomifen cause the creation of a "genotoxic metabolite" whereas DIM doesn't have this effect:


    Differences in the hepatic P450-dependent metabolism of estrogen and tamoxifen in response to treatment of rats with 3,3'-diindolylmethane and its parent compound indole-3-carbinol.

    Parkin DR, Malejka-Giganti D.

    Veterans Affairs Medical Center, Minneapolis, MN 55417, USA.

    Indole-3-carbinol (I3C), present in cruciferous vegetables, and its major in vivo product 3,3'-diindolylmethane (DIM), have been reported to suppress estrogen-responsive cancers. This effect may be mediated through the modification of cytochrome P450 (CYP) complement and activities leading to estrogen detoxification. We examined the effects of a 4-day treatment of female Sprague-Dawley rats with DIM at 8.4 and 42 mg/kg body weight (bwt), on the hepatic CYP protein level, CYP1A1, 1A2, 2B1/2 and 3A1/2 probe activities and CYP-dependent metabolism of 17beta-estradiol (E2) and estrone (E1). At 42 mg/kg bwt, DIM effected a small increase (2.8-fold) in CYP1A1 activity, and at both dose levels it reduced CYP3A1/2 activity by approximately 40%. At the higher dose level, DIM decreased the rates of oxidation of E2 to 4-OH-E2, 4-OH-E1, 6alpha-OH-E2 and 6(alpha+beta)-OH-E1 by 39, 44, 71 and 60%, respectively, and E1 to 6(alpha+beta)-OH-E1 by 39%. These effects were considerably different from those of I3C reported by us previously. We also examined the effects of DIM and I3C on the hepatic microsomal metabolism of tamoxifen (TAM). Whereas metabolism of TAM was unaffected by DIM, formation of N-desmethyl-TAM (and its presumed derivative) was increased approximately 3-fold by I3C at 250 mg/kg bwt. Since N-desmethyl-TAM is transformed to a genotoxic metabolite, dietary exposure to I3C may enhance hepatic carcinogenicity of TAM in the rat. The differences between I3C and DIM in CYP-mediated activities and metabolism indicate that DIM is not a proximate intermediate in the mechanism of action of I3C.

    PMID: 15041081 [PubMed - indexed for MEDLINE]
    This study had rats ingest DIM at 42 mgs/kg of bwt. and I3C at 250 mgs/kg bwt. These are excessive amounts. At the DIM dosage I would be taking almost 4 grams/day. If I were to ingest the amounts of I3C purported in this study it would be almost 27 grams/day. THe usual dose is 300-400 mgs/day for a month.

    Moreover, if you don't use research chems then the toxicity goes away. For all the study's i have seen to date the levels of ingestion of the compounds are excessive and like anything else, taking an excessive amount of something will cause toxicity ...

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    Quote Originally Posted by dmangiarelli View Post
    This study had rats ingest DIM at 42 mgs/kg of bwt. and I3C at 250 mgs/kg bwt. These are excessive amounts. At the DIM dosage I would be taking almost 4 grams/day. If I were to ingest the amounts of I3C purported in this study it would be almost 27 grams/day. THe usual dose is 300-400 mgs/day for a month.

    Moreover, if you don't use research chems then the toxicity goes away. For all the study's i have seen to date the levels of ingestion of the compounds are excessive and like anything else, taking an excessive amount of something will cause toxicity ...

    GOOD JOB...keep all the haters quiet...science never loses...great thread and great post...

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    Aside of the I3C and DIM, I read that
    Chaste berry: keeps prolactin secretion in check.

    Daidzein: also has weak pro-estrogen and anti-estrogen.

    Vitex Agnus-Castus: vitex is effective in regulating pituitary gland function and in normalizing the balance of progesterone to estrogen levels

    Nice thread.

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