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3-Iodothyronamine ( T1AM ) administered to rodents induce a hypometabolic state

frozenborderline

Senior Member
Messages
4,405
@pattismith I never said lithium activates D1. I only know that it can activate D2 (the main dio in the CNS) based on the rodent study I linked earlier.

http://press.endocrine.org/doi/10.1210/endo.141.3.7358

Fourteen days of administration of two different dosages of lithium had opposing effects on 5′D-II activities (Fig. 5, right). The 0.15% lithium diet reduced 5′D-II activity in the cortex, whereas the 0.3% lithium diet enhanced it. T4 levels were significantly elevated after the low dose and significantly reduced after the high dose. Likewise, the serum concentrations of T4and T3 were enhanced after the 0.15% diet and lowered after the 0.3% diet (Table 1). The activities of 5D-III were, however, significantly reduced after administration of both dosages.

It is also possible that lithium inhibits both T3 and T1AM synthesis, therefore if you take T3+lithium, you end up with net gain minus T1AM effect.

I'm more convinced by what I observed personally than from what I've read.

The dose of lithium I took before my TSH levels began to go up was pretty high (I worked up to 20 mg of lithium orotate per day in divided doses). I would not be able to tolerate that dose without some thyroid onboard. I tried lithium before and while it calmed me it always worsened my CFS and gave me "leaden paralysis".

Initially, I took it with low dose levothyroxine, not T3. After a month on that regimen my T4 was borderline high (1.7) - very strange given how low the dose I was taking - but strangely my TSH also went up for the first time. There was a disconnect in the feedback mechanism which I could (Unfortunately, I got those through primary care doctor who failed to order T3. I began to have more energy and motivation and better sensory perception but it gave me severe psychological anxiety and palpitations so I stopped. Before lithium I could not tolerate T4 at all, it made me feel dreadful, so this was still a significant change.

I remember that when I combined lithium and T3 it had a very powerful amplification effect on T3. I pretty much had to discontinue T3 right away.

The other explanation is that lithium has direct effect on modulating TRH release (described here):
https://www.ncbi.nlm.nih.gov/pubmed/12401339
https://www.nature.com/articles/1380514.pdf?origin=ppub

Also, both lithium and carbamazepine decrease deoidonase 3.
https://www.ncbi.nlm.nih.gov/pubmed/8981386

I did look at that SPINA and while I misunderstood initially what TTSI stands for, I'm still trying to figure out why do did my body raised my TSH so much at the same time when it simultaneously more than doubled my thyroid resistance. I'm no longer taking lithium on a regular basis but the TSH trend continues. That makes me think that I'm actually hyperthyroid right now and the markedly increased resistance is a protective mechanism.

The other possible explanation I can think of right now is that there was some hypothalamic level response when I went on lithium because it caused functional iodine deficiency (lithium replace iodine). When I first got off lithium my T3 was naturally at 3.5 which never happened before. I had too much anxiety on that level. I suspect my ideal fT3 is 3.2. Very narrow range. Anything below that affects my mood, energy brain function. Anything above that gives fibromyalgia, anxiety and POTS.

I'm going to test myself for TSH receptor antibodies just to rule the concurrent processes going on that might be making thyroid regulation so tricky. If there are no antibodies then I will lean toward hypothalamic or genomic changes.

By the way I did find cases online about IVIG raising thyroid antibodies in patients, and one woman who had pre-existing Graves but was hypothyroid before IVIG wrote that it caused her to develop hyperthyroidism again.

do you think ivig should be avoided in people with possible thyroid issues but normal blood hormone levels?
 

Iritu1021

Breaking Through The Fog
Messages
586
do you think ivig should be avoided in people with possible thyroid issues but normal blood hormone levels?
I don't really know the answer to this question. I do know that they usually like to pre-medicate people with high dose dexamethasone before IVIG and that can definitely worsen the existing thyroid problem. It may not be necessary with low dose subcutaneous IG, which sounds safer and equally efficacious.
 

frozenborderline

Senior Member
Messages
4,405
I don't really know the answer to this question. I do know that they usually like to pre-medicate people with high dose dexamethasone before IVIG and that can definitely worsen the existing thyroid problem. It may not be necessary with low dose subcutaneous IG, which sounds safer and equally efficacious.
I've heard bad things about corticosteroids, but also occasional doses shouldn't really be that much of a problem, should they?? maybe i'm wrong

high dose dexmethasone certainly sounds iffy, given that my bp sometimes runs a little high (it's probably just anxiety/pots stuff but still...)
they can do SCIG without high dose corticosteroids? i'm gonna bring that up to my doctor
 

Iritu1021

Breaking Through The Fog
Messages
586
Dexamethasone suppresses TSH and inhibits peripheral conversion. I remember years ago - before I even knew I was sick - I had Restylane fillers done and the plastic surgeon gave me a boost of steroids to prevent swelling. He said he does it to all his patients as a favor and "they all love it". I ended up totally crashing fro it and it took me weeks to recover.
I'm no expert on IVIG but in my own research I came across a number of CFS expert opinions who all seem to recommend subcutaneous over IV form as a safer and easier option that patients can do at home. But you'd need to ask one of them if they prescribe steroids with it or not. I believe Teitelbaum is one of those who does it, you can ask on their website. It would probably be easier to get approved for too as it's cheaper.
 

frozenborderline

Senior Member
Messages
4,405
Dexamethasone suppresses TSH and inhibits peripheral conversion. I remember years ago - before I even knew I was sick - I had Restylane fillers done and the plastic surgeon gave me a boost of steroids to prevent swelling. He said he does it to all his patients as a favor and "they all love it". I ended up totally crashing fro it and it took me weeks to recover.
I'm no expert on IVIG but in my own research I came across a number of CFS expert opinions who all seem to recommend subcutaneous over IV form as a safer and easier option that patients can do at home. But you'd need to ask one of them if they prescribe steroids with it or not. I think Teitelbaum is the one who does it, you an ask on their website. It would probably be easier to get approved for too as it's cheaper.
I don't understand why one would require steroids and the other wouldn't, though. Don't both share the same problem of introducing someone elses immunoglobulin into your body, thus possibly causing an allergic reaction or inflammation that would need to be suppressed?
 

frozenborderline

Senior Member
Messages
4,405
Dexamethasone suppresses TSH and inhibits peripheral conversion. I remember years ago - before I even knew I was sick - I had Restylane fillers done and the plastic surgeon gave me a boost of steroids to prevent swelling. He said he does it to all his patients as a favor and "they all love it". I ended up totally crashing fro it and it took me weeks to recover.
I'm no expert on IVIG but in my own research I came across a number of CFS expert opinions who all seem to recommend subcutaneous over IV form as a safer and easier option that patients can do at home. But you'd need to ask one of them if they prescribe steroids with it or not. I believe Teitelbaum is one of those who does it, you can ask on their website. It would probably be easier to get approved for too as it's cheaper.
odd, because dexmethasone apparently helps with post treatment lyme disease syndrome, which is what i originally got diagnosed with
 

Iritu1021

Breaking Through The Fog
Messages
586
It's not an absolute pre-requisite to have steroids. I think they just use it to help prevent adverse effects such as aseptic meningitis.

From Wikipedia page:

Although immunoglobulin is frequently used for long periods of time and is generally considered safe, immunoglobulin therapy can have severe adverse effects, both localized and systemic. Subcutaneous administration of immunoglobulin is associated with a lower risk of both systemic and localized risk when compare to intravenous administration (hyaluronidase-assisted subcutaneous administration is associated with a greater frequency of adverse effects than traditional subcutaneous administration but still a lower frequency of adverse effects when compared to intravenous administration ). Patients who take immunoglobulin are often recommended to take acetaminophen and diphenhydramine before their infusions to reduce the rate of adverse effects, as well as sometimes (especially when first getting accustomed to a new dosage ), prednisone or another oral steroid.

you might want to start a new thread on this subject and ask others for their experiences.
 

Iritu1021

Breaking Through The Fog
Messages
586
odd, because dexmethasone apparently helps with post treatment lyme disease syndrome, which is what i originally got diagnosed with
Dexamethasone helps with many diseases. I can only speak for my own CFS case as someone who is hypothyroid with hypothalamic dysfunction. A lot of people with ME/CFS seem to react poorly to steroids even when they test positive for adrenal fatigue.
 

frozenborderline

Senior Member
Messages
4,405
It's not an absolute pre-requisite to have steroids. I think they just use it to help prevent adverse effects such as aseptic meningitis.

From Wikipedia page:

Although immunoglobulin is frequently used for long periods of time and is generally considered safe, immunoglobulin therapy can have severe adverse effects, both localized and systemic. Subcutaneous administration of immunoglobulin is associated with a lower risk of both systemic and localized risk when compare to intravenous administration (hyaluronidase-assisted subcutaneous administration is associated with a greater frequency of adverse effects than traditional subcutaneous administration but still a lower frequency of adverse effects when compared to intravenous administration ). Patients who take immunoglobulin are often recommended to take acetaminophen and diphenhydramine before their infusions to reduce the rate of adverse effects, as well as sometimes (especially when first getting accustomed to a new dosage ), prednisone or another oral steroid.

you might want to start a new thread on this subject and ask others for their experiences.

I will start another thread when I get a little more energy, haha... maybe after i take some T3... or coffee

interesting, I wonder if you can take aspirin instead of acetaminophen, and cyproheptadine instead of benadryl


If SCIG has lower risks but equal efficacy I don't know why on earth I wouldn't do it. i had been under the assumption that IVIG has higher efficacy.
 

frozenborderline

Senior Member
Messages
4,405
I don't know if anyone has mentioned that, but could T1am be the unknown "thing" in the blood that caused the CFS cells to be sick, the thing that Ron Davis mentioned in his video update on research?

@Iritu1021 If nobody has mentioned, you might want to tell Janet Dafoe about this, she is on the forum and could pass it along to Ron. If he could identify the molecule that could be big! seems unlikely, but hey, sometimes "citizen science" works
 

Iritu1021

Breaking Through The Fog
Messages
586
I don't know if anyone has mentioned that, but could T1am be the unknown "thing" in the blood that caused the CFS cells to be sick, the thing that Ron Davis mentioned in his video update on research?

@Iritu1021 If nobody has mentioned, you might want to tell Janet Dafoe about this, she is on the forum and could pass it along to Ron. If he could identify the molecule that could be big! seems unlikely, but hey, sometimes "citizen science" works
Well, I don't mind telling people, even if it's low yield. I already contacted Robert Naviaux who did metabolomics study that described CFS as "dauer state" and he said they'd add it to "their list of target molecules" but I never heard anything since that.
 

frozenborderline

Senior Member
Messages
4,405
Well, I don't mind telling people, even if it's low yield. I already contacted Robert Naviaux who did metabolomics study that described CFS as "dauer state" and he said they'd add it to "their list of target molecules" but I never heard anything since that.
@Janet Dafoe (Rose49)
I know this might be a long shot but if Ron hasn't identified the specific large molecule that he discusses being in ME/CFS blood in this video:
, maybe it's worth seeing if it's this!

Janet, this particular thyroid hormone metabolite puts rats into a "hibernation-like state," that might be akin to dauer, I'm wondering if Ron has looked at this! sorry to bother you but this might be promising!
 

Iritu1021

Breaking Through The Fog
Messages
586
@Janet Dafoe (Rose49)
I know this might be a long shot but if Ron hasn't identified the specific large molecule that he discusses being in ME/CFS blood in this video:
, maybe it's worth seeing if it's this!

Janet, this particular thyroid hormone metabolite puts rats into a "hibernation-like state," that might be akin to dauer, I'm wondering if Ron has looked at this! sorry to bother you but this might be promising!
@Janet Dafoe (Rose49) @debored13
In addition to inducing the acute state of hibernation or torpor, T1AM also:
-- presumed to be synthesized from T4 in the gut which could explain gut microbiome connection
-- opposes the action of T3 which could explain hypometabolic state response to thyroid hormone despite normal serum values
-- affects heart, blood vessels and, glutamatergic, adrenergic and histaminergic transmission
-- regulates fat and glucose metabolism
-- related to TAAR1 receptor that was found abnormal in recent fibromyalgia genomic study

I have a more detailed summary on my blog www.chronicfatiguediagnosis.com
 

pattismith

Senior Member
Messages
3,931
odd, because dexmethasone apparently helps with post treatment lyme disease syndrome, which is what i originally got diagnosed with

Dexamethasone seems to be more suppressive on TSH than Prednisone/prednisolone, but if you take thyroid hormons at the same time, it doesn't really matters. (TH themselves will be suppressive on TSH)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784889/
(DRUGS THAT SUPPRESS TSH OR CAUSE CENTRAL HYPOTHYROIDISM)

Glucocorticoids anyway can regulate deiodinases activity in tissus, so they may impact TH activity even if you take T3 sup.
 

Hip

Senior Member
Messages
17,824
I have a more detailed summary on my blog www.chronicfatiguediagnosis.com

I've just been looking at your article: Trace Iodothyronamine Hypothesis of ME/CFS and PR blog article: Ten Reasons Why TAAR (Trace-Amine Associated Receptor) is the Primary Suspect in ME/CFS and POTS.

Very interesting.

I know nothing about 3-iodothyronamine and its receptor TAAR1, but saw on the TAAR1 Wikipedia page that the main endogenous ligands of TAAR1 in order of potency are: tyramine > phenethylamine (PEA) > dopamine.

So I am wondering whether taking tyramine (found in cheeses like cheddar) or phenethylamine (found in chocolate or available as a pure powder) and observing the effects on ME/CFS symptoms might be a way to probe your theories.

MAO-A and MAO-B enzymes will rapidly break down oral tyramine and phenethylamine; however, it should be possible to take an MAO-A and/or an MAO-B inhibitor to prevent this (obviously you'd have to be very careful, as consuming tyramine foods or lots of chocolate with MAO inhibitors is known to be dangerous, leading to serious spikes in blood pressure requiring emergency treatment).

I performed some experiments a few years ago taking a combination of phenethylamine powder 200 mg and selegiline 5 mg, an MAO-B inhibitor. The selegiline slows the breakdown of the phenethylamine, which allows the latter to have stronger effects. One person here used this combination to successfully achieve a stimulant and euphoric effect from phenethylamine. I was interested in seeing if phenethylamine could raise endorphin levels, which are known to be low in ME/CFS.

But I did not notice much from this phenethylamine + selegiline combo.
 

Iritu1021

Breaking Through The Fog
Messages
586
I've just been looking at your article: Trace Iodothyronamine Hypothesis of ME/CFS and PR blog article: Ten Reasons Why TAAR (Trace-Amine Associated Receptor) is the Primary Suspect in ME/CFS and POTS.

Very interesting.

I know nothing about 3-iodothyronamine and its receptor TAAR1, but saw on the TAAR1 Wikipedia page that the main endogenous ligands of TAAR1 in order of potency are: tyramine > phenethylamine (PEA) > dopamine.

So I am wondering whether taking tyramine (found in cheeses like cheddar) or phenethylamine (found in chocolate or available as a pure powder) and observing the effects on ME/CFS symptoms might be a way to probe your theories.

MAO-A and MAO-B enzymes will rapidly break down oral tyramine and phenethylamine; however, it should be possible to take an MAO-A and/or an MAO-B inhibitor to prevent this (obviously you'd have to be very careful, as consuming tyramine foods or lots of chocolate with MAO inhibitors is known to be dangerous, leading to serious spikes in blood pressure requiring emergency treatment).

I performed some experiments a few years ago taking a combination of phenethylamine powder 200 mg and selegiline 5 mg, an MAO-B inhibitor. The selegiline slows the breakdown of the phenethylamine, which allows the latter to have stronger effects. One person here used this combination to successfully achieve a stimulant and euphoric effect from phenethylamine. I was interested in seeing if phenethylamine could raise endorphin levels, which are known to be low in ME/CFS.

But I did not notice much from this phenethylamine + selegiline combo.
hi @Hip, thanks for reading. I have too tried to experiment with PEA but to be honest I was a little scared as I have found some reports in nootropic forums from people who used it in combo with MAO inhibitors and ended up extremely addicted and claimed that coming off from high doses of PEA was harder than coming off from meth.

The selegiline on its own gave me too much overstimulation but that was back when I was sensitive to almost everything. I have COMT Met/Met and some unfavorable MAO alleles so I might not have much room for MAO-inhibition.

I always feel better when I eat cheese or chocolate, there is no denying that. I also experimented with another TAAR agonist called synephrine which comes as bitter orange extract. From what I remember it gave me a slight pleasant stimulation.
 

Hip

Senior Member
Messages
17,824
Taking phenylalanine should also in theory raise PEA levels.

I've tried DL-phenylalanine at doses around 4000 mg, but again did not notice much, except perhaps a very mild mood boost (I was hoping it would have a useful antidepressant effect, since depression is one of the comorbidities I have with my ME/CFS).

I don't think I ever tried phenylalanine with selegiline though.

But my brain may not be the best one for testing out selegiline: I used selegiline on and off for 20 years as an effective mood booster and smart drug (before I developed ME/CFS from a viral infection). But after I was hit with a nasty episode of chronic organophosphate pesticide poisoning, just prior to getting ME/CFS, I noticed that selegiline was never again able to boost my mood. So selegiline seemed to permanently lose its antidepressant effect after my organophosphate exposure. I have not been able to figure out why.
 

Helen

Senior Member
Messages
2,243
MAO-A and MAO-B enzymes will rapidly break down oral tyramine and phenethylamine; however, it should be possible to take an MAO-A and/or an MAO-B inhibitor to prevent this (obviously you'd have to be very careful,
MAO SNP´s have been studied and found more frequent among PWME according to Rich Van Konynenburg, page 13 in the link below. On page 12 there are references and there are more in an article he wrote beside at that time.
http://iaomt.media.fnf.nu/networks/iaomt/IAOMT_talks_Rich_Van_K._2011__Part_1R.pdf

If I recall right, it was evident at the time when people posted their results from 23andme tests on PR. Having enzyme defects, or not, should affect the outcome of trying substances that are broken down by MAO enzymes. Just a thought.
 
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