DIM Is A Potent Androgen Antagonist And Estrogen Agonist

haidut

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The question of supplementing DIM often comes up on this forum despite Peat directly advising against it. Aside from its known anti-thyroid functions, we can now add a potent androgen antagonism to its list of "benefits". So, please stop loading up on DIM in the (false) hope that it somehow steers estrogen metabolism towards less potent estrogens. All estrogens are about equally bad and it is really not wise to play with such chemical, which is now also known to be BOTH an AR antagonist (capable of displacing even DHT form its receptor) AND an estrogen receptor agonist.

Plant-derived 3,3'-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. - PubMed - NCBI

"...3,3'-Diindolylmethane (DIM) is a major digestive product of indole-3-carbinol, a potential anticancer component of cruciferous vegetables. Our results indicate that DIM exhibits potent antiproliferative and antiandrogenic properties in androgen-dependent human prostate cancer cells. DIM suppresses cell proliferation of LNCaP cells and inhibits dihydrotestosterone (DHT) stimulation of DNA synthesis. These activities were not produced in androgen-independent PC-3 cells. Moreover, DIM inhibited endogenous PSA transcription and reduced intracellular and secreted PSA protein levels induced by DHT in LNCaP cells. Also, DIM inhibited, in a concentration-dependent manner, the DHT-induced expression of a prostate-specific antigen promoter-regulated reporter gene construct in transiently transfected LNCaP cells. Similar effects of DIM were observed in PC-3 cells only when these cells were co-transfected with a wild-type androgen receptor expression plasmid. Using fluorescence imaging with green fluorescent protein androgen receptor and Western blot analysis, we demonstrated that DIM inhibited androgen-induced androgen receptor (AR) translocation into the nucleus. Results of receptor binding assays indicated further that DIM is a strong competitive inhibitor of DHT binding to the AR. Results of structural modeling studies showed that DIM is remarkably similar in conformational geometry and surface charge distribution to an established synthetic AR antagonist, although the atomic compositions of the two substances are quite different. Taken together with our published reports of the estrogen agonist activities of DIM, the present results establish DIM as a unique bifunctional hormone disrupter. To our knowledge, DIM is the first example of a pure androgen receptor antagonist from plants."
 
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Regina

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The question of supplementing DIM often comes up on this forum despite Peat directly advising against it. Aside from its known anti-thyroid functions, we can now add a potent androgen antagonism to its list of "benefits". So, please stop loading up on DIM in the (false) hope that it somehow steers estrogen metabolism towards less potent estrogens. All estrogens are about equally bad and it is really not wise to play with such chemical, which is now also known to be BOTH an AR antagonist (capable of displacing even DHT form its receptor) AND an estrogen receptor agonist.

Plant-derived 3,3'-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. - PubMed - NCBI

"...3,3'-Diindolylmethane (DIM) is a major digestive product of indole-3-carbinol, a potential anticancer component of cruciferous vegetables. Our results indicate that DIM exhibits potent antiproliferative and antiandrogenic properties in androgen-dependent human prostate cancer cells. DIM suppresses cell proliferation of LNCaP cells and inhibits dihydrotestosterone (DHT) stimulation of DNA synthesis. These activities were not produced in androgen-independent PC-3 cells. Moreover, DIM inhibited endogenous PSA transcription and reduced intracellular and secreted PSA protein levels induced by DHT in LNCaP cells. Also, DIM inhibited, in a concentration-dependent manner, the DHT-induced expression of a prostate-specific antigen promoter-regulated reporter gene construct in transiently transfected LNCaP cells. Similar effects of DIM were observed in PC-3 cells only when these cells were co-transfected with a wild-type androgen receptor expression plasmid. Using fluorescence imaging with green fluorescent protein androgen receptor and Western blot analysis, we demonstrated that DIM inhibited androgen-induced androgen receptor (AR) translocation into the nucleus. Results of receptor binding assays indicated further that DIM is a strong competitive inhibitor of DHT binding to the AR. Results of structural modeling studies showed that DIM is remarkably similar in conformational geometry and surface charge distribution to an established synthetic AR antagonist, although the atomic compositions of the two substances are quite different. Taken together with our published reports of the estrogen agonist activities of DIM, the present results establish DIM as a unique bifunctional hormone disrupter. To our knowledge, DIM is the first example of a pure androgen receptor antagonist from plants."
Wow. I have several friends who pay top fees to their Naturopath Drs who have them on 4 Dim-plus capsules per day for supposedly reducing bad estrogen. :confused
 
L

lollipop

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Wow. I have several friends who pay top fees to their Naturopath Drs who have them on 4 Dim-plus capsules per day for supposedly reducing bad estrogen. :confused
I see this as well @Regina in my circle. Sooooo frustrating convincing them otherwise. They simply do not listen and "experts" and internet articles support that distorted view.
 

TubZy

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Never a fan of DIM despite how much it's praised on other forums. I would also assume too much cruciferous veggies could be bad too.
 

Tarmander

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I tried DIM several times when I worked at a healthfood store years ago. I would become almost inconsolably angry, so much rage. I thought erroneously at the time that I was "detoxing estrogen." Or that the anger was from too much male hormone. Oh how we learn. Thank you for posting this haidut.
 

Blossom

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I took it too prior to peating. :arghh: My old doctor had me on DIM, estrogen, paleo and a bunch of other stuff that I'm purposely trying not to remember. No wonder I felt terrible. If I didn't know better I would think she was trying to kill me and from a peat perspective that's not too much of an exaggeration! I'm still grateful everyday that I found Peat, this forum and learned how to help myself heal.
 

Regina

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I took it too prior to peating. :arghh: My old doctor had me on DIM, estrogen, paleo and a bunch of other stuff that I'm purposely trying not to remember. No wonder I felt terrible. If I didn't know better I would think she was trying to kill me and from a peat perspective that's not too much of an exaggeration! I'm still grateful everyday that I found Peat, this forum and learned how to help myself heal.
:dancers: we're glad you're here.
 

< Rain

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The question of supplementing DIM often comes up on this forum despite Peat directly advising against it. Aside from its known anti-thyroid functions, we can now add a potent androgen antagonism to its list of "benefits". So, please stop loading up on DIM in the (false) hope that it somehow steers estrogen metabolism towards less potent estrogens. All estrogens are about equally bad and it is really not wise to play with such chemical, which is now also known to be BOTH an AR antagonist (capable of displacing even DHT form its receptor) AND an estrogen receptor agonist.

Plant-derived 3,3'-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. - PubMed - NCBI

"...3,3'-Diindolylmethane (DIM) is a major digestive product of indole-3-carbinol, a potential anticancer component of cruciferous vegetables. Our results indicate that DIM exhibits potent antiproliferative and antiandrogenic properties in androgen-dependent human prostate cancer cells. DIM suppresses cell proliferation of LNCaP cells and inhibits dihydrotestosterone (DHT) stimulation of DNA synthesis. These activities were not produced in androgen-independent PC-3 cells. Moreover, DIM inhibited endogenous PSA transcription and reduced intracellular and secreted PSA protein levels induced by DHT in LNCaP cells. Also, DIM inhibited, in a concentration-dependent manner, the DHT-induced expression of a prostate-specific antigen promoter-regulated reporter gene construct in transiently transfected LNCaP cells. Similar effects of DIM were observed in PC-3 cells only when these cells were co-transfected with a wild-type androgen receptor expression plasmid. Using fluorescence imaging with green fluorescent protein androgen receptor and Western blot analysis, we demonstrated that DIM inhibited androgen-induced androgen receptor (AR) translocation into the nucleus. Results of receptor binding assays indicated further that DIM is a strong competitive inhibitor of DHT binding to the AR. Results of structural modeling studies showed that DIM is remarkably similar in conformational geometry and surface charge distribution to an established synthetic AR antagonist, although the atomic compositions of the two substances are quite different. Taken together with our published reports of the estrogen agonist activities of DIM, the present results establish DIM as a unique bifunctional hormone disrupter. To our knowledge, DIM is the first example of a pure androgen receptor antagonist from plants."
Thank You, I always appreciate your input - it is being marketed the other way around. On Examine.com the note that dosages above 100 md daily become estrogen. I do not want to find out as I am lowering estro now do to varicose veins/itching in legs. I did order the androsterone and will mix w/ DHEA and Vit E. Blessings.
 

DesertRat

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I took it prior to Peating, and it really shifted by N-telopeptides into a good range -- or what was considered good in the non-Peat world, which correlates with bone resorption. It's interesting that I tried it a few months ago, on the persuasive advice of my doctor, but stopped after 1-2 days because it aggravated my psoriasis.
What I don't understand is why an AR antagonist would be bad for older women who start to get symptoms resembling androgen excess. I do take a lot of progesterone to try to offset them, but so far the hair keeps growing on my chin.
 

Blossom

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What I don't understand is why an AR antagonist would be bad for older women who start to get symptoms resembling androgen excess. I do take a lot of progesterone to try to offset them, but so far the hair keeps growing on my chin.
That's a good point. I wish I understood this more myself. For something so common it would seem like there would be widely known ways of preventing unwanted facial hair in women besides just cosmetic treatments. Obviously progesterone isn't always enough. Pregnenolone has been mentioned as helpful before by Peat. I've been wondering if aromatase inhibitors (simple dietary and supplemental ones not the strong drugs) might make a difference? My mom has a full beard and I know it bothers her to have to deal with it!
 

ilovethesea

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This is good information, thank you!

Any thoughts on why people like this blogger have so much success with DIM and Estroblock for acne?
How I Cured my Adult Female Hormonal Acne

I know Ray has said that estrogen causes oil glands to atrophy so they don't support bacterial growth as well. So would that be the reason? (Same mechanism as the birth control pill which also clears acne for most women?)
 

sladerunner69

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Never a fan of DIM despite how much it's praised on other forums. I would also assume too much cruciferous veggies could be bad too.

Yep I remember loading up on cruciferous veggies after reading about how they could flush out bad estrogen. I remember eating tons of broccoli and brussel sprouts one day, like a pound at each meal. That was a few months after my pfs crash and I never felt worse.
 

Texon

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If you all have a moment Google 'DIM is a neurotoxin'. I somehow came across the quote string after reading about the subject of adrenochrome being discussed by Dr. Hoffer. I took some of the stuff one time as recommended by my endocrinologist and had a very nasty anxiety reaction.
 

TubZy

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Yep I remember loading up on cruciferous veggies after reading about how they could flush out bad estrogen. I remember eating tons of broccoli and brussel sprouts one day, like a pound at each meal. That was a few months after my pfs crash and I never felt worse.

I feel so much better cutting out vegetables in excess. I mainly just eat mushrooms fried in coconut oil if I do.
 

sladerunner69

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I feel so much better cutting out vegetables in excess. I mainly just eat mushrooms fried in coconut oil if I do.

Yeah I try to eat mushrooms once a day. Danny Roddy recommends boiling them to remove some chemical that could build up if eatenf ried everyday. But I do prefer the taste of fried and then stuffed in a pasture egg omlette with cheddar cheese.

As far as green veggie go I will eat the occasional couple leaves of spinach from my school cafetria or one stem of broccoli if im having family dinner but generally I avoid raw greens. Ancient man probably would have avoided eating leaves as well, unless in a survival situation.
 

Agent207

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The Anti-Carcinogenic Effect of Indole-3-Carbinol and 3, 3'-Diindolylmethane and their Mechanism of Action

These studies prove evidence that the diet-derived indole derivated, I3C and DIM, exert anticancer effects mediated through the regulation of cell cycle, induction of apoptosis, transcription, cell signal transduction, inhibiting angiogenesis and suppressing cell invasion (Figure 3). The activation of the mitochondrial pathway through releasing of cytochrome C and activation of caspases, together with inactivation of hormonal, PI3K/Akt, MAPK, Bcl-2 and NF-kB pathways may represent the possible molecular mechanism of indole-derivatives in their anticancer activity.

The anti-cancer activity of I3C and DIM was detected in various target organs including breast, prostate, colon, liver, cervix, endometrium, melanoma and lung using human cancer cell lines or various animal models. Furthermore, these derivatives were evaluated in clinical trials phase I and phase II as a potential chemopreventive agents against breast, ovary and colon cancers. Preliminary findings of these studies showed a significant clinical improvement. In addition, the use of indole derivatives was found to be safe without any indicated side effects.



Multiple therapeutic and preventive effects of 3,3′-diindolylmethane on cancers including prostate cancer and high grade prostatic intraepithelial neoplasia

Epidemiological studies in vitro and in vivo animal models have shown that DIM has anticancer properties in treating multiple cancers including prostate cancer[47]-[49],[84]-[89]. Using prostate cancer cells including LNCaP, PC-3, DU145 and C4-2B, studies have shown that DIM has anti-prostate cancer properties involving apoptosis[24],[31]-[34],[90], anti-proliferation[28]-[34], anti-angiogenesis[36]-[38], cell cycle arrest[24],[28]-[30], or anti-inflammatory activity[39],[44],[78].



Chemopreventive properties of 3,3'-diindolylmethane in breast cancer: evidence from experimental and human studies. - PubMed - NCBI

Research of the cancer-preventive activity of DIM has yielded basic mechanistic, animal, and human trial data. Further, this body of evidence is largely supported by observational studies. Bioactive DIM has demonstrated chemopreventive activity in all stages of breast cancer carcinogenesis. This review describes current evidence related to the metabolism and mechanisms of DIM involved in the prevention of breast cancer. Importantly, this review also focuses on current evidence from human observational and intervention trials that have contributed to a greater understanding of exposure estimates that will inform recommendations for DIM intake.


All estrogens are about equally bad
I understand it won't be your purpose here to educate people on physiology which statements as such.

Meanwhile you can keep posting the undoubtful real-world applicable evidence from in-vitro studies or others about the fascinating c. elegans world.
 
Last edited:

haidut

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The Anti-Carcinogenic Effect of Indole-3-Carbinol and 3, 3'-Diindolylmethane and their Mechanism of Action

These studies prove evidence that the diet-derived indole derivated, I3C and DIM, exert anticancer effects mediated through the regulation of cell cycle, induction of apoptosis, transcription, cell signal transduction, inhibiting angiogenesis and suppressing cell invasion (Figure 3). The activation of the mitochondrial pathway through releasing of cytochrome C and activation of caspases, together with inactivation of hormonal, PI3K/Akt, MAPK, Bcl-2 and NF-kB pathways may represent the possible molecular mechanism of indole-derivatives in their anticancer activity.

The anti-cancer activity of I3C and DIM was detected in various target organs including breast, prostate, colon, liver, cervix, endometrium, melanoma and lung using human cancer cell lines or various animal models. Furthermore, these derivatives were evaluated in clinical trials phase I and phase II as a potential chemopreventive agents against breast, ovary and colon cancers. Preliminary findings of these studies showed a significant clinical improvement. In addition, the use of indole derivatives was found to be safe without any indicated side effects.



Multiple therapeutic and preventive effects of 3,3′-diindolylmethane on cancers including prostate cancer and high grade prostatic intraepithelial neoplasia

Epidemiological studies in vitro and in vivo animal models have shown that DIM has anticancer properties in treating multiple cancers including prostate cancer[47]-[49],[84]-[89]. Using prostate cancer cells including LNCaP, PC-3, DU145 and C4-2B, studies have shown that DIM has anti-prostate cancer properties involving apoptosis[24],[31]-[34],[90], anti-proliferation[28]-[34], anti-angiogenesis[36]-[38], cell cycle arrest[24],[28]-[30], or anti-inflammatory activity[39],[44],[78].



Chemopreventive properties of 3,3'-diindolylmethane in breast cancer: evidence from experimental and human studies. - PubMed - NCBI

Research of the cancer-preventive activity of DIM has yielded basic mechanistic, animal, and human trial data. Further, this body of evidence is largely supported by observational studies. Bioactive DIM has demonstrated chemopreventive activity in all stages of breast cancer carcinogenesis. This review describes current evidence related to the metabolism and mechanisms of DIM involved in the prevention of breast cancer. Importantly, this review also focuses on current evidence from human observational and intervention trials that have contributed to a greater understanding of exposure estimates that will inform recommendations for DIM intake.



I understand it won't be your purpose here to educate people on physiology which statements as such.

Meanwhile you can keep posting the undoubtful real-world applicable evidence from in-vitro studies or others about the fascinating c. elegans world.

The human trials with DIM also did not find much benefit. Here is one.
http://www.nature.com/bjc/journal/v106/n1/full/bjc2011496a.html

No need to get sarcastic, there are many chemicals that have some anti-estrogenic activity but are not beneficial overall. Tamoxifen, clomiphene, RU486, etc are some that come to mind. Finally, I3C/DIM are known goitrogens that promote liver, thyroid, uterine, and colon cancer. All of these cancers are strongly tied to estrogen. Even the goitrogenic property alone should be enough to give somebody a pause.
Indole-3-Carbinol
"...However, a number of studies have found that I3C actually promoted or enhanced the development of cancer when administered chronically after the carcinogen (post-initiation). The cancer-promoting effects of I3C were first reported in a trout model of liver cancer (60, 61). However, I3C has also been found to promote cancer of the liver (62-64), thyroid (64), colon (65, 66), and uterus (67) in rats."

So, while I3C/DIM may shift the metabolism of estrogen towards less "active" metabolites, we do not know what are it actual effects on estrogen "receptor". There is some evidence that it acts like estrogen agonist there, similar to the soy isovlafone genistein.
 

Agent207

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It was just a bit of humor, no offence intended. But man, that statement was a bit too much to my sight.

Even without counting on phytoestrogens, within the human ones, theres a vast difference in action between 17b-estradiol and estriol.

There is favorable outcomes from mild estrogenic compounds from pomegranates.
 

haidut

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It was just a bit of humor, no offence intended. But man, that statement was a bit too much to my sight.

Even without counting on phytoestrogens, within the human ones, theres a vast difference in action between 17b-estradiol and estriol.

There is favorable outcomes from mild estrogenic compounds from pomegranates.

Pomegranate actually has the most potent known natural carbonic anhydrase inhibitors (aside from thiamine). So, the benefits could be from the higher CO2.
Punicalin - Wikipedia
"...Punicalin is an ellagitannin. It can be found in Punica granatum (pomegranate)[1] or in the leaves of Terminalia catappa, a plant used to treat dermatitis and hepatitis.[2][3] It is also reported in Combretum glutinosum, all three species being Myrtales, the two last being Combretaceae. It is a highly active carbonic anhydrase inhibitor."
 

Agent207

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Pomegranate actually has the most potent known natural carbonic anhydrase inhibitors (aside from thiamine). So, the benefits could be from the higher CO2.
Punicalin - Wikipedia
"...Punicalin is an ellagitannin. It can be found in Punica granatum (pomegranate)[1] or in the leaves of Terminalia catappa, a plant used to treat dermatitis and hepatitis.[2][3] It is also reported in Combretum glutinosum, all three species being Myrtales, the two last being Combretaceae. It is a highly active carbonic anhydrase inhibitor."

Interesting, had not idea about that, thanks for sharing.

Now its pomegranate season here, I use to juice them and mix it with orange juice half and half. Cool taste and so refreshing.
 
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