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Xeno/estrogens link to CFS/Fibromyalgia - Success!!

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Gestalt, Jun 9, 2012.

  1. iacyi

    iacyi

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    Aromatase is the enzyme which synthesises oestrogen, and inhibitors act to block it somehow. I think aromatase inhibitor refers to drugs that reduce it, so maybe it isn't technically the same thing.

    I think it could be a good thing. I don't know how it applies to females or humans, since the study talked about male rats, but K2 is supposed to be pretty safe anyway. There's a thread about K2 here.
  2. Hoops

    Hoops

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    Hey Gestalt

    Thanks for the great post, congratulations on a valuable discovery. In your reading on xenoestrgens, I was wondering if you have learned:

    1. If any other common prescription drugs can act as potent xenoestrogens ?
    2. If elevated liver enzymes (AST, ALT) can be a sign of problems metabolising xenoestrogens ?

    Also do you know if 23andme covers the SNP's in the Genova DetoxiGenomic panel ?

    Many thanks ....
  3. globalpilot

    globalpilot Senior Member

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    Just doing a little more research on DIM:



    http://cancerprevres.aacrjournals.org/content/2/3/251.full

    - CYP1A1 and CYP1A2 metabolize E2 to 2-hydroxyestradiol (2-OHE2), a noncarcinogenic compound (1, 3). 2-OHE2 can be further metabolized to 2-methoxyestradiol (2-MeOE2), a beneficial compound that protects against breast tumors in rodents and is being studied as a treatment for human breast cancer (20, 21). CYP1B1 metabolizes E2 to 4-hydroxyestradiol (4-OHE2), a highly genotoxic and carcinogenic metabolite (1, 3).

    - We find that DIM strongly induces all CYP1 mRNAs in a dose-dependent fashion (Table 1). Induction at 30 μmol/L DIM was 310-, 49-, and 11-fold for CYP1A1, CYP1A2, and CYP1B1, respectively.

    - DIM strongly inhibits estrogen receptor-α expression and estrogen signaling,



    http://www.ncbi.nlm.nih.gov/pubmed/9741959

    - Compared with control liver slice microsomes (dimethyl sulphoxide-only treated), DIM induced levels of CYP1A2 but had little effect on levels of CYP3A4.



    So, just to clarify

    - DIM , at least in the 2nd study had no effect on CYP3A4.

    - pathways leading to both 2-hydroxy and 4-hydroxy are upregulated but the 2-hydroxy pathway is much more regulated … does this mean more or less 4-hydroxy will be produced ?

    - the fact that Dim strongly inhibits estrogen receptor expression and estrogen signaling is concerning



    As a person with an upregulated CYP1B1, documented oxidative stress and a person who needs estrogen (we all do!) I’m not sure what to do. I don’t want to downregulate the receptors or reduce estrogen signaling but I may be producing a lot of extra oxidative stress due to the CYP1B1 upregulation.
    cigana and Beyond like this.
  4. Gestalt

    Gestalt Senior Member

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    To Answer your questions..
    1 and 2: No idea

    3. Yes some, and and a few others

    Calico13 made a very good spreadsheet, Click on the bottom 2 tabs, tab 2 & 3 for reference

    Excellent research finds! A very strong induction of CYP1A1 and CYP1A2 will have a net effect of less 4-hydroxy production.

    In regards to inhibition of estrogen receptor-α expression and estrogen signaling...

    (wikipedia)

    ."This activity of DIM relates to a blocking function toward the aryl hydrocarbon receptor which is then resistant to activation by pesticides.74 " Search this site: http://www.dimfaq.com/site/articles.htm for receptor to find more details

    It would seem that DIM is safe in regards to your concerns about inhibition of estrogen receptors and for the most part is a beneficial process. You could e-mail the docs on that site, and perhaps get more specifics if your still concerned.
  5. triffid113

    triffid113 Day of the Square Peg

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    /DIm
    I take I3C/DIM in this product from Life EXtension to ward off cancer. I have done so since before getting on the methylation protocol, however I have always taken supplements supporting methylation, just not ACTIVE ones (and I have 18out of 30 genetic defects in the methylation area (Yasko panel) so the active supplements are highly needed by me (but I never really had startup symptoms due to never being totally without anything...although I had mild (very mild) startup symptoms when I stopped taking a lot of my supplements several times due to too many pills cauing nausea). So I cannot tell you what I3C/DIM does functionally except that it has been proven to make your hormones come out right so I take it to avoid breast cancer. And one of my friends who started bioidentical hormone replacement same time as me has contracted breats cancer while I have not. I am placing my faith in this supplement and hope it is not misguided: http://www.iherb.com/Life-Extension-Triple-Action-Cruciferous-Vegetable-Extract-60-Veggie-Caps/22969
  6. globalpilot

    globalpilot Senior Member

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    Based on what I found above I don't think it is misguided. The 4-hydroxy does result in quinones and the DIM upregulates it's pathway but upregulates the pathway to 2-hydroxy much, much more.

    But, also, I think the above extracts I posted also imply there will be less estrogen in circulation. I'm not sure that is a good thing.
  7. Gestalt

    Gestalt Senior Member

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    "Inhibition of Estrogen receptor-α expression and estrogen signaling" and "estrogen in circulation" are two very different things that don't necessarily correlate. According to everything I have read DIM does not change actual estrogen levels; It changes how estrogen is metabolized. It is important to make very careful distinctions between wording and phrasing here so you don't jump to the wrong conclusions and misinterpret biochemical nomeclature.
  8. globalpilot

    globalpilot Senior Member

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    I'm basing my concern on the fact that the enzymes are upregulated. I don't know why an upregulation wouldn't result in lower levels of the metabolite in circulation.
  9. Gestalt

    Gestalt Senior Member

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    There is no evidence in any of the medical literature for lower estrogen levels due to an up-regulation in the CYP enzymes. DIM is safe to take for those even on the pill.

    I suggest you read the description section here: http://www.healthsuperstore.com/p-enzymatic-therapy-estrobalance.htm

    Also this site is an incredible resource: http://www.dimfaq.com/site/intro.htm
  10. rocky

    rocky

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    Gestalt interesting post that you make. i am suffering from side effects from propecia which includes a higher than average estradiol level, whcih makes me think some of what you said i may relate to.

    i got the 23andme test and tried to lookup the CYP3A4 gene, but it gave me 57 different SNPs from it. how does that lab your girlfriend purchased choose which SNP to choose because I don't seei t listed there? I'm kind of at a loss here on how to know if I have a similar mutation or not because I have too many SNPs to look at. I've been trying to research each of tehse SNPs, but not come to any conclusions as of yet.

    thanks for any info.
  11. Gestalt

    Gestalt Senior Member

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    rocky

    Most labs choose a SNP to look at based on some kind of genetic cross-reference study with noted effects. You could always call up Genova labs and ask them why they chose that specific SNP and what their sources or reasons are. The other SNPs technically may even be more important but genetic research is in it's infancy.

    You can check the Spreadsheet Calico13 created here:
    https://docs.google.com/spreadsheet/ccc?key=0As5xqg3KuimidDZVRWxKa1gwS0p2a2ZhcnlGSGhPUnc#gid=1

    Click on the bottom tab "Cytochrome P450 SNP's" and then look for CYP3A4 and then cross-reference the rs#.
    rocky likes this.
  12. rocky

    rocky

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    thank you for that spreadsheet, that is very helpful document with this.

    i used it to look up CYP1B1, similar to what your girlfriend have, and I seem to have 2 that are +/- out of 3 (one is -/-). How does that test that she took determine if there is a problem, does it have to be +/+, or because I am +/-, I have part of a problem?

    thanks for any help. btw, i was reading through your journal.. very interesting stuff, you seem to know the specific gene pathways jobs in many different ways. did this take research of your own on specific snps. i saw the heartfix website you linked to and have read much of it, very interesting stuff happenign with this.
  13. Beyond

    Beyond 10% of discount in iHerb!--> PEZ915

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    I got my 23andme a month or so ago and now I am ready to tackle the whole xenoestrogens thingie! It seems I have a good clust of double mutations in the CYP1 genes and some hetero in the COMT. The calico spread sheet link doesnt works aymore :( How can we access to the SNP´s used by genova now? I will investigate globalpilot These are good news for me. With all my CYP1A1, CYP1A2 and CYP1B1 mutations DIM makes sense.
  14. freshveggies

    freshveggies Senior Member

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    go to MTHFRsupport.com and you can upload your 23 and me raw data and get a 19 page report showing a lot of snips, including CYP.
  15. Gestalt

    Gestalt Senior Member

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    Alternatively you can use this site: https://geneticgenie.org/detox-profile/
  16. Beyond

    Beyond 10% of discount in iHerb!--> PEZ915

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    Thanks, guys. Oh have just noticed that the gene I was looking for, CYP3A4, was in genetic genie. Shoot, I did that weeks ago -__- Brainfoggy me!
  17. cigana

    cigana Senior Member

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    I am very interested in this as I have the same 3 mutations as your gf (COMT, CYP3A4 and CYP1B1).
    I have had plenty of cruciferous vegetables and DIM supplements in the past to no avail, though.
  18. Gestalt

    Gestalt Senior Member

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    Try Yerba Santa. Worked like a charm for my gf...
    http://www.gestaltreality.com/2012/07/16/curing-psoriasis-eczema/

    Also Mangosteen extract seems to be helping balance her hormones lately. The compound you are after is "xanthones".
    cigana likes this.
  19. knackers323

    knackers323 Senior Member

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    @Gestalt and @Beyond are these treatments still working for you? What level of functioning are you at?
  20. Gestalt

    Gestalt Senior Member

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    On a good day I am a 9/10 on a bad day 6/10. Not doing these treatments anymore.

    It is my conclusion based off seeing what happened with myself and my gf, the estrogen issue really is a microbial issue. http://www.gestaltreality.com/2013/09/21/metabolic-cholestatic-pruritus/

    It has to do with enterohepatic re-circulation and gut dysbiosis. Fix the gut with the right pre & pro biotics and the hormonal issues and detox issues fix themselves.

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