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]
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]