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Peripheral Deiodination - table link

Discussion in 'Thyroid Dysfunction' started by Iritu1021, Jun 4, 2018.

  1. Iritu1021

    Iritu1021 Breaking Through The Fog

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  2. Iritu1021

    Iritu1021 Breaking Through The Fog

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    I made a typo in my table which I corrected now - flavonoids actually decrease D1, not increase.
     
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  3. pattismith

    pattismith Senior Member

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    great table! You may add that D1 is very important to clear rT3
     
  4. drob31

    drob31 Senior Member

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    Great table. I still want to lower rt3.
     
  5. Iritu1021

    Iritu1021 Breaking Through The Fog

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    @drob31 @pattismith @debored13 @Hip

    I have spoken before about the phenomenon that I consistently observed back when I was using micro-doses of slow release T3 - that they made my TSH go UP rather than down. Today a reader of my blog sent me this diagram which finally suggests an explanation (see image attached).

    So I guess at doses that are too low to suppress TSH, T3 has stimulatory action on serotonin which helps to raise hypothalamic TRH.

    Apart from improving hypothyroid function, TRH in itself has been shown to have a strong immediate anti-depressant effect. I'm personally done with T3 in any shape, dose or form but I thought it was worth sharing. For someone who is too fragile to tolerate lithium and T3, micro-T3 (Blanchard protocol) might might a good starting option. They key is that the dose has too be low enough to only affect serotonin but not to affect TRH.

    I should also note that the evidence about lithium effect on D2 is somewhat conflicting. My personal experience with lithium however suggests that it has three stages:
    a) lowers catecholamines (might be good or bad depending on how adrenergic you are)
    b) causes hyperthyroidism through effect on deiodinases (at this point catecholamine effects go away)
    c) causes T4 deficiency in the long run due to its effect on thyroid
    Capture d’eěcran 2018-10-02 aĚ 18.02.43.png
     
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  6. debored13

    debored13 Senior Member

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    Hmm I tend to think of serotonin as something I am trying to depress, so I will have to mull on this.

    I also have had decent effects from serotonin antagonists. Also thought the "low serotonin" hypothesis of depression was unproven.
     
  7. debored13

    debored13 Senior Member

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    but I did start reading the blanchard book! going to try and convince my parents to read it too
     
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  8. Iritu1021

    Iritu1021 Breaking Through The Fog

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    @debored13 If serotonin was an issue for you, then you wouldn't have felt good on your higher doses of T3. And obviously Ray Peat is not very well versed in neurochemistry if he recommends T3 (which is known to raise serotonin and increase serotonin receptors) but at the same time tells them to avoid serotonin containing food (which by they way can hardly cross the blood brain barrier).

    The serotonin issue is so much more complicated than what most people think it is. There are at least seven serotonin receptors and each one has a different effect, which makes the whole concept of serotonin by itself pretty obsolete. T3 primarily affects 5HT1. A lot of people with CFS seem to have issues with 5HT2A and/or 5HT2C.

    Even this diagram might be an oversimplification. The only thing I know for a fact is that micro-doses of T3 raised my TSH while regular doses lowered it, and I observed the same effect in my husband when we tried it in him.
     
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  9. debored13

    debored13 Senior Member

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    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666469/


    This is just rats, but it does seem complicated. I found a bunch of studies showing T3/t4 decreased prolactin, which is associated with decreased serotonin I think.

    As far as the vegetables and serotonin thing, it does seem crazy; but I do think peripheral action of serotonin is important, not just brain serotonin. Especially in those of us that have predominantly physical, whole body symptoms, and not much depression (I would count myself as one of these people).

    https://www.ncbi.nlm.nih.gov/pubmed/9822800



    https://pdfs.semanticscholar.org/ec2d/5a6aea74538030207b4143de5aee9b270e70.pdf



    I will look into all of this further. I do remember reading up on the history of LSD studies and how it used to be considered a serotonin antagonist due to peripherally inhibiting actions of serotonin, whereas now it's considered a serotonin agonist by most scientists... But it's actions are also very, very different than serotonin releasers like MDMA or all those diet drugs that caused cardiac fibrosis which they pulled off the market in the 90s.


    I respect your point of view and am not interested in getting in an extended argument about serotonin atm; basically I think what Peat says is often polemical and sometimes oversimplified, but this is true perhaps even more so of the dominant viewpoint until recently in psychiatry, that seemed almost wholly pop-science-informed, speculative ideas about low serotonin = depression. There were also some studies of high serotonin in CFS patients, I believe. The trouble with testing these theories in an individual person is that almost all drugs that are serotonin antagonists are very dirty and have lots of other effects



    Anyway at this point I don't think I'll be able to parse much more theory and am more interested in clinical experiences. "Peat's protocol" which I don't think is really peats, but what I would describe as a moderate/small, but not super-small dosing of t3, at around 3 mcg per dose, plus t3/t4 combo, seems to work for a subset of people that are very enthusiastic about it. It might not work as well for CFS patients.

    The Blanchard protocol seems to work very well for people who have normal blood tests but are symptomatic, which might be a big crossover with CFS for obvious reasons (it's a diagnosis of exclusion, so any competent doctor would at least exclude thyroid dysfunction thru blood tests).

    I wonder if this is just different subsets of patients, because I do know people who do great on the t3/t4 amounts that peat recommends, for years, but these people probably didn't have CFS per se. It could probably take me years to parse the theory on this so I'm just going to look at anecdotal evidence and get my t3 compounded and start experimenting with low doses.
     
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  10. drob31

    drob31 Senior Member

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    I know that it seems that I have bad results with tryptophan and good results with BH4. I also have good results with melatonin which skips the serotonin step. I know that melatonin is also very good for mitochondria.
     
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  11. Iritu1021

    Iritu1021 Breaking Through The Fog

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    @debored13 I tend to think that how people respond to T3 probably depends on where they fall on the "mood spectrum" (see pscycheducation.org for definition on that) and on the specific profile of their deiodinases and neuroreceptors abnormalities.

    How one responds to T3 or T4 is basically the same crapshoot as everything else when it comes both to psychiatry and CFS. But I agree with you that Blanchard's population seems to be the closest to our case since a lot of his patients failed to improve on regular T3 protocols or got worse on them.

    The peripheral effects of serotonin are well represented by carcinoid tumors and do not show much correlation with CFS. However, if one is regularly taking T3 to treat their CNS problems then I can see that one might want to limit dietary serotonin. You have to keep in mind that Peat's conclusions were mostly based on his self observations. So we don't know if he was sensitive to serotonin before or after he started using T3. But I'll shut up now since you stated you don't want to get into an argument :)

    Anyway, I'm really interested in what your experience will be with slow release micro T3 because to me it felt like a completely different drug.
     
  12. Iritu1021

    Iritu1021 Breaking Through The Fog

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    [QUOTE="debored13, post: 1003261, member:

    https://pdfs.semanticscholar.org/ec2d/5a6aea74538030207b4143de5aee9b270e70.pdf

    [/QUOTE]

    I've read this article before and it made me wonder if my initial improvement from T3 might have had something to do with effect on 5HT1 receptors while the decompensation came from the sensitization of 5HT2 that came later on.

    Maybe using 5HT2 antagonist could have prevented this to some degree but as you said there are no clean antagonists.
     
  13. Iritu1021

    Iritu1021 Breaking Through The Fog

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    @drob31 Did you feel different effect from regular T3 and micro slow release T3? And from Armour? To me they all had a very different "flavor" to them. Not completely different but kind of like beer/wine/whiskey different.

    I guess your micro T3 experience might be different too since you already were on T4 when you tried it.
     
  14. drob31

    drob31 Senior Member

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    I had tried SR T3 previously with the same results (at an obviously higher dose).

    To me it seems like anything that trys to force the metabolism faster than it wants to go triggers a negative feedback loop in the form of (decreased TSH/TRH/Adrenal hormones??). This happened with iodine, and higher doses of t3, and the lower doses I guess trigger the same thing somehow? That's just a very general observation.
     
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  15. debored13

    debored13 Senior Member

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    This (the bolded part) is interesting as far as possible comorbidity but I'm trying to treat more profound physical fatigue and lactic acidosis which isn't or wasn't comorbid with depression or any mood disorders, although it did cause some small changes in mood once starting it. I'm skeptical of framing CFS at all as being centrally mediated or solely neurological, because I don't think the fatigue is neurological, I think it's real fatigue caused by reductive stress/hypometabolism. Obviously problems of metabolism can correlate with mood disorders too; but in my case, before starting thyroid, my primary problems were not mood disorders, I was not diagnosed with mood disorders, and despite the difficulty in distinguishing between mood symptoms caused by CFS and genuine mood disorders (with self-reported depression scales using so many fatigue-related behaviors), I don't think I was/am depressed.
     
  16. Learner1

    Learner1 Forum Support Assistant

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    What BH4 product are you taking? Kuvan?
     
  17. debored13

    debored13 Senior Member

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    I continue to have much better results with cynoplus than cynomel, even tho the cynoplus dose has an equal amount of t3 as the cynomel , and it’s not slow release. You would think that even with t4, the t3 would spike , but I don’t get this effect Sometimes it even lowers my heart rate but I feel warmer and less stressed, which is also something I used to get pre-illness from the right dose of ritalin
     
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  18. debored13

    debored13 Senior Member

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    How Long did it take to get to the second stage you describe with lithium?
     
  19. drob31

    drob31 Senior Member

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    I got pure BH4 from another site. I can give you the name if you want, forget off the top of my head. I took 5mg bh4. Seemed like really smooth energy.
     
  20. aquariusgirl

    aquariusgirl Senior Member

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    @drob31

    Yes pls PM me your source tnx
     

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