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Low-dose DHEA Inhibits Aromatase By 35% And Endotoxin Blocks That Effect

Discussion in 'Scientific Studies' started by haidut, Sep 10, 2016.

  1. haidut

    haidut Member

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    I found this study while researching the conversion of DHEA into steroids with immunomodulating effects. As you can see (attached picture), a DHEA concentration of 1µM inhibited aromatase activity by about 35%. This concentration of DHEA can be easily achieved with 3mg - 5mg topical DHEA in DMSO. The aromatase inhibition effect was greatly reduced (or even disappeared) when cells were exposed to endotoxin (LPS). Endotoxin itself is an aromatase activator and this illustrates once again Ray's advice to keep DHEA doses low as in people under severe stress or high endotoxin loads the compound loses much of its androgenic and anti-estrogenic potential.

    http://joe.endocrinology-journals.org/content/164/2/161.full.pdf

    "...Since aromatase is one of the key enzymes for the downstream conversion of DHEA via delta-4 steroids to estrogens, the modulation of the aromatase activity by DHEA and the typical macrophage activator, LPS, were investigated. DHEA (1µM) significantly inhibited aromatase activity (Fig. 7). In the presence of LPS, DHEA was unable to inhibit aromatase activity. Taken together, these results indicate that LPS counteracts the inhibitory action of DHEA on aromatase under these conditions."
     

    Attached Files:

  2. CKA

    CKA Member

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    Better eat my carrots and charcoal before I pull the trigger on some pansterone!
     
  3. OP
    haidut

    haidut Member

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    Or make sure your vitamin D & A levels are optimal. Both of them are TLR4 (endotoxin) antagonists.
     
  4. marikay

    marikay Member

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    Does this mean A and D help with endotoxin once it has been absorbed and is wreaking havoc in the body?
     
  5. OP
    haidut

    haidut Member

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    Anything that blocks the TLR4 receptor will greatly diminish or even eliminate the effects of endotoxin. That is why drugs that are known to block that receptor are in accelerated trials for treatment of sepsis.
     
  6. marikay

    marikay Member

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    Wow. That's good to hear. I have been wondering what (if anything) can fight endotoxin after it has been absorbed. I'll search for more substances that block the TLR4 receptor. Thanks a bunch.
     
  7. mirc12354

    mirc12354 Member

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    Cod liver oil wins again ;)
     
  8. tankasnowgod

    tankasnowgod Member

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    Well, except for those nasty PUFAs. I'd say A, D, Thiamine and Riboflavin win again.
     
  9. CKA

    CKA Member

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    why riboflavin? I thought it's an iron agonist
     
  10. Makrosky

    Makrosky Member

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    Do you mean blocking TLR4 will greatly diminish just the endotoxin symptoms? Or will it make the body believe there's no endotoxin thus sparing the liver and immune system the really hard work they have to do in the pressence of endotoxin?

    It's two different things, right ?
     
  11. OP
    haidut

    haidut Member

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    Both. It seems that the TLR4 receptor is needed for endotoxin to do its damage. Mice without the TLR4 receptor pretty much don't react to endotoxin at all. Ideally, you'd want to start at the top (i.e. not produce endotoxin at all) but if it is there already a TL4 antagonist of a serotonin antagonist is your best bet (especially if it is a serious case like sepsis).
     
  12. bzmazu

    bzmazu Member

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    "Or make sure your vitami.n D & A levels are optimal. Both of them are TLR4 (endotoxin) antagonists."

    What is considered the optimal level of A? Getting my D from subtropical sun and D from liver with once weekly Estroban. No testing available.
     
  13. OP
    haidut

    haidut Member

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    I think the blood test for A is fairly reliable. If it is within range then you are probably OK, and given that you eat liver there is probably no need for supplements other than the once weekly EstroBan. Peat himself takes 2mg - 3mg K2 on the skin once weekly, which is what EstroBan will provide per dose.
     
  14. bzmazu

    bzmazu Member

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    but can't get bld test for A...is there some optimal range?...am only relying on my FitDay nutrient log
     
  15. bzmazu

    bzmazu Member

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    it's OK...I'll figure it out...have more info now than before your comment...thank you!
     
  16. Sheila

    Sheila Member

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    Dear Mr Bzmazu,
    I have read your posts on CLL with interest, and your approach using ARTEMISININ. I am wondering now whether endotoxin release is a 'feature' of CLL at least for some presentations, perhaps others get prostate trouble from their endotoxin load, different people 'break' differently. I hope you will bear with me whilst I write a little more, I would be interested in your opinion if you would care to share it especially as you thrive on research and may have a piece of the puzzle too!

    Adding this to your previous posts on CLL, and seeing a considerable endotoxin load in some of my patients with CLL - now I know how to look at it, my follow on thought regarding artemisinin is whether it works in some way to block endotoxin. Note there have been other posts on using high dose Vit A & K to improve CLL presentations. Again, it would seem their ability to work on the gut barrier is important.

    Now, back to artemisin. The wormwood family have been known for years for their activity against worms and parasites and I wouldn't mind betting that they have significant activity against viruses and bacteria also. If that is the case, maybe they improve the robustness of the gut which reduces blood pathogen load and the body is able to recover from there, just as it did for you taking artemisin for malaria. (Was that the falciparum strain as opposed to vivax?)

    The old herbalists used to look for a 'septic foci' in chronic diseases which would now be considered to have an 'AI component' such as rheumatoid arthritis etc. , where there was overproduction of tissue/or over activity as a defence mechansism, unfortunately destructive long term (a bit like cancer too I suppose). Examples of septic foci were considered to be: a rotten tooth, unresolved point source infection/wound, foreign body issues, that sort of thing - effectively something that annoys the body and continuously stimulates the immune system in a lower grade and exhausting manner. I have looked high and low in other CLL presentations for this 'trigger' and a couple of them have high viral load, CFS-like on/off, go/no go pictures, but one in particular has been fit as a horse, with the exception of benign prostatic swelling. I am wondering now whether in this case endotoxic load has been the trigger for CLL rather than some unresolved point source infection/irritation. If so, charcoal would be useful, artemisin would be an obvious choice - if tolerated - and basically all Peat-based endotoxin-reduction ideas, including the suggestions in this post.

    I am not sure what question I am asking you specifically perhaps it's just whether any of this makes sense!

    And finally, suggesting that cancer is more active at night fits well with cortisol cycles and in all the presentations of CLL I have seen, cortisol is involved in their pictures, there are no slackers amongst these people!

    So just some thoughts, sincerely
    Sheila
     
  17. bzmazu

    bzmazu Member

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    Sheila, what a co-incidence!...It just recently also occurred to me, this possible connection to endotoxin...because I'm reading here about endotoxin and prostate problems and I have been a little concerned of late about my prostate again. When I was dealing w CLL...I also had prostate issues...they are gone now and I didn't know wether it was the ART. or the Nettle I started taking...and I'm considering taking it again for a short while...want to do some tests first...I believe some sort of maintenance protocol would be helpful. Anyway this is all very interesting and I think there is something to it. At the time of taking ART. I knew nothing of endotoxin but had stumbled across Dr. PEAT in my research and am so happy I did. I will give this some thought...my post stroke brainfog slows all thought process down...but when I'm on to something I don't give up...my intuition and common sense have not let me down yet. I think Artemisinin is an incredible find...for many diseases.
     
  18. Sheila

    Sheila Member

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    Dear Mr Bzmazu
    Thank you for your prompt reply...yes it does sound possible doesn't it? So it might be interesting then if you return to the ART to see if that improves your prostate. I have never seen nettle root be quite so convincing in BPH but I am happy to be wrong.
    Indeed, I do not wish to interfere, so fwiw, I have found that low dose charcoal seems to improve some brain fog in some and, where it does, it is my suspicion, this may be due to brain fog generated by endotoxin. I can't prove this, but that is my current feeling. For some grated carrot also performs this bonus and it would make sense. Higher doses might be needed in some, but bowel frequency should be maintained somehow!
    My last wondering for today is whether those who stimulate metabolism can fall foul of low blood sugar accidentally and that of course increases endotoxin's potential effects. So that is maybe a pitfall to be wary of. High dose charcoal, ditto grated carrot can induce hypoglycaemia if people aren't careful or at least that has been what I have seen/experienced.
    Please do tell me/us how you get on.
    Best to you
    Sheila
     
  19. bzmazu

    bzmazu Member

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    Felt from the beginning it was the nettle that dramatically improved my symptoms...don't remember the timeline on all this...might be on some notes/logs?...could have been both. My PSA was in range for my age (71) and it dropped after my intervention. This week will do some labs, first time in 6 months...prior to hernia operation, brought on by a mistake in my Peat experiment. I had some slight pain in prostate region recently...could have been from hernia and bad leg/walking from stroke...got paranoid...pain now gone.

    Regarding endotoxin...never heard of it until Peat, but am seeing the importance and so I added some precautions to my daily regimen...do eat a carrot 3-4 times week and sporadically do the charcoal. I have the feeling that I have a pretty healthy gut...but who knows?

    You said: "My last wondering for today is whether those who stimulate metabolism can fall foul of low blood sugar accidentally and that of course increases endotoxin's potential effects. So that is maybe a pitfall to be wary of."....could you explain this a little further?...

    Thanks Sheila,
    John
     
  20. Sheila

    Sheila Member

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    Hello John
    Thank you for your reply and confirmation that nettle root was beneficial for you. Good to know.

    Did you find that 'doing carrot' and charcoal improved your brain fog? I have seen marked improvement with both when consistently applied in a range of people, including myself. I think, and who knows as you say, removal or reduction of brain fog with g/carrot and/or charcoal is indicative of endotoxic load. I have also seen reduction in ear ringing in a few where mechanical damage was not causative.

    It has been my experience that use of g/carrot and/or charcoal can reduce blood sugar as the system adapts (begins to work more efficiently?) and if the person doesn't keep their fuel uptake matching their needs closely then the resultant hypoglycaemia and stress response might lower the gut/blood stream barrier enough for the remaining endotoxin or undigested particles (or whatever can cause an inflammatory response) can continue to cause problems. Admittedly one has reduced the endotoxic load from before, but things are still not optimal. Not sure, just a feeling looking for a better explanation!

    Best regards
    Sheila
     
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