My (Not So Good) Experience With TMG

[DavidZ]

About 2 months ago, I tried TMG based upon comments in this forum. After about 3 days, I stopped taking it because I was getting high E2 symptoms.

I suspected back then that TMG somehow interferes with the action of Indolplex/DIM. Phil's experience confirms my observation.

[pmgamer18]

Originally Posted by DavidZ

About 2 months ago, I tried TMG based upon comments in this forum. After about 3 days, I stopped taking it because I was getting high E2 symptoms.

I suspected back then that TMG somehow interferes with the action of Indolplex/DIM. Phil's experience confirms my observation.

Thank God you posted this now I am not so worried. Most don't understand how I can tell if I am high or low but you do. I am getting back to normal I can feel it to day. Yet it did make my Total E go down but my DHT went way up over 2000. Not sure why.

[SWALE]

A couple of studies have shown that taking DIM without also taking TMG may elevate the dangerously genotoxic, mutagenic and procarcinogenic 4-OHE metabolite.

[pmgamer18]

Originally Posted by SWALE

I couple of studies have shown that taking DIM without also taking TMG may elevate the dangerously genotoxic, mutagenic and procarcinogenic 4-OHE metabolite.

But there is DIM and then there is Indolplex/DIM guys taking reg. DIM are finding that if they take it with oil it works better. Indolplex/DIM is different and the stomach does not effect the power of the DIM none of it is killed in the stomach. We are thinking the Indolplex in the DIM we are taking dose not work good with TMG.
http://www.ritecare.com/prodsheets/PHY-15336.html
Both David and I take this and adding TMG caused problems with higher E2. Yet my Total E came down my E2 went up and I am taking .5 mg of Arimidex a day to keep it down. Also my DHT went up over 2000.

[DavidZ]

A simple Medline search will yield numerous articles about the anti-cancer powers of diindolylmethane (DIM). The claim that DIM is pro-cancer flies against all of the literature on the topic.

One example of many is shown below.

***********************************************

Br J Cancer. 2004 Oct 4;91(7):1358-63.

Induction of apoptosis in human prostate cancer cell line, PC3, by 3,3'-diindolylmethane through the mitochondrial pathway.

Nachshon-Kedmi M, Yannai S, Fares FA.

Faculty of Food Engineering and Biotechnology, Technion-Israel Institute of Technology, Haifa 32000, Israel.

Prostate cancer is the most common malignancy and the second leading cause of male death in Western countries. Prostate cancer mortality results from metastases to the bones and lymph nodes and progression from androgen-dependent to androgen-independent disease. Although androgen ablation was found to be effective in treating androgen-dependent prostate cancer, no effective life-prolonging therapy is available for androgen-independent cancer. Epidemiological studies have shown a strong correlation between consumption of cruciferous vegetables and a lower risk of prostate cancer. These vegetables contain glucosinolates, which during metabolism give rise to several breakdown products, mainly indole-3-carbinol (I3C), which may be condensed to polymeric products, especially 3,3'-diindolylmethane (DIM). It was previously shown that these indole derivatives have significant inhibitory effects in several human cancer cell lines, which are exerted through induction of apoptosis. We have previously reported that I3C and DIM induce apoptosis in prostate cancer cell lines through p53-, bax-, bcl-2- and fasL-independent pathways. The objective of this study was examination of the apoptotic pathways that may be involved in the effect of DIM in the androgen-independent prostate cancer cell line, PC3, in vitro. Our results suggest that DIM induces apoptosis in PC3 cells, through the mitochondrial pathway, which involves the translocation of cytochrome c from the mitochondria to the cytosol and the activation of initiator caspase, 9, and effector caspases, 3 and 6, leading to poly ADP-ribose polymerase (PARP) cleavage and induction of apoptosis. Our findings may lead to the development of new therapeutic strategies for the treatment of androgen-independent prostate cancer.

PMID: 15328526 [PubMed - indexed for MEDLINE]

[cpeil2]

Originally Posted by DavidZ

A simple Medline search will yield numerous articles about the anti-cancer powers of diindolylmethane (DIM). The claim that DIM is pro-cancer flies against all of the literature on the topic.

One example of many is shown below.

***********************************************

Br J Cancer. 2004 Oct 4;91(7):1358-63.

Induction of apoptosis in human prostate cancer cell line, PC3, by 3,3'-diindolylmethane through the mitochondrial pathway.

Nachshon-Kedmi M, Yannai S, Fares FA.

Faculty of Food Engineering and Biotechnology, Technion-Israel Institute of Technology, Haifa 32000, Israel.

Prostate cancer is the most common malignancy and the second leading cause of male death in Western countries. Prostate cancer mortality results from metastases to the bones and lymph nodes and progression from androgen-dependent to androgen-independent disease. Although androgen ablation was found to be effective in treating androgen-dependent prostate cancer, no effective life-prolonging therapy is available for androgen-independent cancer. Epidemiological studies have shown a strong correlation between consumption of cruciferous vegetables and a lower risk of prostate cancer. These vegetables contain glucosinolates, which during metabolism give rise to several breakdown products, mainly indole-3-carbinol (I3C), which may be condensed to polymeric products, especially 3,3'-diindolylmethane (DIM). It was previously shown that these indole derivatives have significant inhibitory effects in several human cancer cell lines, which are exerted through induction of apoptosis. We have previously reported that I3C and DIM induce apoptosis in prostate cancer cell lines through p53-, bax-, bcl-2- and fasL-independent pathways. The objective of this study was examination of the apoptotic pathways that may be involved in the effect of DIM in the androgen-independent prostate cancer cell line, PC3, in vitro. Our results suggest that DIM induces apoptosis in PC3 cells, through the mitochondrial pathway, which involves the translocation of cytochrome c from the mitochondria to the cytosol and the activation of initiator caspase, 9, and effector caspases, 3 and 6, leading to poly ADP-ribose polymerase (PARP) cleavage and induction of apoptosis. Our findings may lead to the development of new therapeutic strategies for the treatment of androgen-independent prostate cancer.

PMID: 15328526 [PubMed - indexed for MEDLINE]

But this doesn't seem to have anything to do with estrogen metabolites.

[ciobl]

Originally Posted by cpeil2

But this doesn't seem to have anything to do with estrogen metabolites.

apoptosis :a genetically determined process of cell self-destruction that is marked by the fragmentation of nuclear DNA, is activated either by the presence of a stimulus or by the removal of a stimulus or suppressing agent, is a normal physiological process eliminating DNA-damaged, superfluous, or unwanted cells (as immune cells targeted against the self in the development of self-tolerance or larval cells in amphibians undergoing metamorphosis), and when halted (as by genetic mutation) may result in uncontrolled cell growth and tumor formationcalled also programmed cell death.

a type of cell death in which the cell uses specialized cellular machinery to kill itself; a cell suicide mechanism that enables metazoans to control cell number and eliminate cells that threaten the animal's survival

Disintegration of cells into membrane-bound particles that are then eliminated by phagocytosis or by shedding.

[cpeil2]

Originally Posted by ciobl

apoptosis :a genetically determined process of cell self-destruction that is marked by the fragmentation of nuclear DNA, is activated either by the presence of a stimulus or by the removal of a stimulus or suppressing agent, is a normal physiological process eliminating DNA-damaged, superfluous, or unwanted cells (as immune cells targeted against the self in the development of self-tolerance or larval cells in amphibians undergoing metamorphosis), and when halted (as by genetic mutation) may result in uncontrolled cell growth and tumor formationcalled also programmed cell death.

a type of cell death in which the cell uses specialized cellular machinery to kill itself; a cell suicide mechanism that enables metazoans to control cell number and eliminate cells that threaten the animal's survival

Disintegration of cells into membrane-bound particles that are then eliminated by phagocytosis or by shedding.

Thanks Ciobl. As I said before, the reference doesn't seem to have anything to do with estrogen metabolites.

[cpeil2]

There seems to be plenty of literature on DIM's beneficial effect on the ratio of 2-hydroxy- to 16-alpha hydroxy estrogen metabolites. But I can't find anything that talks about DIM's effect on the 4-hydroxy metabolites.

[DavidZ]

Originally Posted by cpeil2

But this doesn't seem to have anything to do with estrogen metabolites.

True. But it has everything to do with the proven anti-cancer effects of DIM and, therefore, gives some perspective to the discussion.

To add even more perspective, a lot of researchers believe that elevated E2 is extremely harmful to the prostate and may even be the primary culprit in the development of prostate cancer.

The bottom line question is -- how do we best control E2?

[ciobl]

Originally Posted by cpeil2

Thanks Ciobl. As I said before, the reference doesn't seem to have anything to do with estrogen metabolites.

cpeil, I understand your observation bro, but we are running in circles here

he came up with that article from Medline after Dr Crisler comments about the numerous estrogens and chemicals inducing cancer.

2-hydroxyestrone and 2-hydroxyestradiol offer protection against 16-hydroxyestrone .

the cyp1a1 enzyme that catalyzes 2-hydroxyestrone formation is inducible by indole-2-carbinol or diindolylmethane as well as omega -3 fatty acids.

thanks bro

[frankwhardy]

Originally Posted by cpeil2

There seems to be plenty of literature on DIM's beneficial effect on the ratio of 2-hydroxy- to 16-alpha hydroxy estrogen metabolites. But I can't find anything that talks about DIM's effect on the 4-hydroxy metabolites.

I also couldn't find anything when I researched this issue previously. See this thread entitled "Is TMG really necessary when using DIM?":

Is TMG really necessary when using DIM?

[SWALE]

Making the statement that what I wrote "flies in the face of all we know" is unwarranted. We have not seen "all the studies" on the subject here, or anywhere. Maybe someone can find them. I have seen two such studies which showed that DIM stimulated not only the CYP1A1 enzyme, thus increasing 2-OHE, but also the CYP1B1, which is why 4-OHE concentrations rise as well. TMG, or its child, DMG, provides methyl groups, thus helping wash the 4-OHE downstream. IF (and it's a big IF) this is true, in vivo, DIM should not be taken without a methyl donor, and would be especially dangerous in someone with a COMT enzyme deficiency.

The answer to the question "how do we best control estrogen" is an easy one. First, to decrease its overall concentration through an aromatase inhibitor. Then, by controlling its metabolites thorugh these various OTC products.

What exactly is "Indolplex"?

[SPE]

Maybe this has some significance. Three months ago I had the battery of tests done while on the following:

1) .5ml 10% compounded t cream
2) 525iu hcg
3) 35mg zinc
4) 25mg dhea
5) Indoplex DIM with TMG
6) 1 Grain Armour


Results were as follows:

Total T: 616 (range 241-827)
Free T: 18 (Don't know, but 20something being upper limit)
E2: 35 (10-54)
TSH: .03 (.35-5.5)

Last Wednesday I was tested again, only I was on:

1) 1ml 10% compounded test cream
2) 455iu hcg
3) 65mg zinc
4) 50mg dhea
5) 1/2 grain armour and 25mcg synthroid

Results were as follows and same ranges apply:

Total T: 1689
Free T: 43.2
E2: 31
TSH: .004

My T/E ratio went from less than 20:1 to 54:1 and the only thing I changed was zinc, DHEA and HCG. Obviously I need to lower my total T, free T, and thyroid dosages but I thought my T/E ratio was interesting. Still waiting for DHT but since I went to 1ml I've been on 1mg proscar eod. Interesting that my total and free t went up that much while being on proscar. Sex drive still there as well

[cpeil2]

Originally Posted by ciobl

cpeil, I understand your observation bro, but we are running in circles here

he came up with that article from Medline after Dr Crisler comments about the numerous estrogens and chemicals inducing cancer.

2-hydroxyestrone and 2-hydroxyestradiol offer protection against 16-hydroxyestrone .

the cyp1a1 enzyme that catalyzes 2-hydroxyestrone formation is inducible by indole-2-carbinol or diindolylmethane as well as omega -3 fatty acids.

thanks bro

That's the bridge I was looking for. Thanks. I'm lazy. If possible, I like to let others deconstruct biochemical pathways.