Bianco and co workers have developed a T3 derivative that has much better retention and pharmacokinetics than T3 alone. That is, it doesn't "spike" as much after giving it, and lasts longer. The study is in rats as it has to be at first, but it looks as if it might be possible to produce a T3 compound that is less likely to harm and better for intake and use in humans.
Thyroid
DOI: 10.1089/thy.2018.0205
METAL COORDINATED POLY-ZINC-LIOTHYRONINE PROVIDES STABLE
CIRCULATING T3 LEVELS IN HYPOTHYROID RATS
l
Rodrigo R. Da Conceição 1,*, Gustavo W. Fernandes2,*, Tatiana L. Fonseca, Antonio Bianco2
The paper is available to download until the end of October
Written by
diogenes
Remembering
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Gosh some relevant research on the efficiency of thyroid hormones in the body .............. And regarding the infamous T3. This sounds like a real possible breakthrough. When, how much and I'm desperate to know the source of research funding? Thanks diogenes!
I got the impression at the BTA conference in May from Bianco and others that until they could prescribe a T3 that was slow release they would not be happy prescribing T3. Let's hope it's as effective as T3 for this of us who do not do well on T4. I wonder how many years we'll have to wait. Hopefully by then they'll also have more clues as to which subset of patients to use it on. Zinc doesn't sound too unpalatable!
Mr Bianco and co wouldn’t be happy prescribing T3 until a slow release version is available. So in the meantime hypothyroid patients that don’t do well on T4 are meant to do what exactly? Shut up and suffer? Mr Bianco was part of the 2015 study on rats which found that on T4 alone the brain remains hypothyroid but he’d rather a hypothyroid patient is left to suffer than be given a hormone replacement which might just give them their life back. Right now the T3 tablet isn’t perfect but it’s all we have and for those who need it, it works. I won’t hold my breath waiting for this new pill, I’ll probably be dead long before it appears.
I completely agree and I told Bianco and others at the conference I get no ‘hit’ whatsoever from taking my 40 mcg a day in one dose. But apparently physiologically I deliver a T3 spike (that my body shows no outward signs of) that is not natural and therefore can’t be good for me. These developments almost put the fear of dread into me because if T3 works for me now I don’t want anyone to say I have to use something else that may not work. At least Bianco acknowledges and explores why patients don’t respond and thrive on T4 and is looking for a safer solution for those patients instead of pretending ‘it’s a fault with the patient/T4 is perfect/it must be another problem’ which is 99.99% of my experience with GPs and endos in the uk.
I have been on T3 only for over 8 years now and have not had any problems taking 60mcg a day. This is great news. However, we don't want to fall into the same trap of thinking even a new med will suit all.
The debate between Professor Tony Weetman and Professor Colin Dayan is on YouTube. Weetman says he wouldn't prescribe T3 because patients don't take it properly!! he also said that manufacturers don't produce it in smaller tablets so patients take too much at once. They have super-arrogance. He must never had heard of pill cutters. Weetman said something on the lines of he wouldnt prescribe T3 until a slow release version is available. What tosh. We are capable of making our own decisions, using pill cutters, and taking tablets on time.
Well at least Weetman has moved on from denying the use of T3 when suitable, altogether. Somatic syndrome or whatever words he used to explain nonresponders to T4 therapy, seems to have been quietly dropped (without acknowledgement of a change in thinking of course). Nobody in this field is ever wrong.
Dr D-P wrote in his book, "I have written in the manner that I always use in my clinics; that is, that the patient is just as bright as I am, and perfectly able to work things out given the knowledge."
Thank You Diogenes for this Great and Valuable Information . It would be very Welcome to have T-3 that works well and we need not stress over availability's . Hopefully it will be made in several denominations too . Even as low as 2.5mcg .
I am imagining that at some point thyroid hormones will be availale as patches or even hormone implants and slow release for a long time. I think this might make a huge difference to thyroid patients not nessasarily clinically but once the big producers have a new product to sell they will want us all diagnosed for a while to maximise profit.We need new products for this reason.
Read this very paper that diogenes has posted about!
Delivery routes such as through the skin, as commonly used for steroids, seem inviable given the rapid D3-mediated thyroid hormone catabolism in this organ.
Thanks I don’t recall that bit after just reading the summary via the link although I guessed the peaks of T3 might be a limiting factor. With this slow release version is the D3 problem you mention still relevant for patches and impants I wonder
But this poly-zinc-liothyronine is expressly intended to be taken orally.
Being large molecules (the actual number of liothyronine molecules that are combined into a single poly-zinc-liothyronine molecule isn't entirely clear but could be quite a number), I suspect that there is little to no likelihood of them passing through the skin.
Thanks - it is very clever i’d like to see a diagram of it to get an idea of how it’s done and I wonder how it gets undone in the body and becomes active. Why does the zinc slow down the T3 release?
At least 15 years ago my GP was trialling a patch - probably for T4 rather than T3 or NDT. I didn’t ask for details, but it shows that something was available a long time ago. Maybe it wasn’t successful???
I think it might be a matter of checks and balances. poor thyroid treament is very profitable it maybe that currently the production of new products is not as finacially advantagious as driving poor treatment. As treatment improves due to forums like this and politcal pressure they will cave in a bit and come up with some new products.
The paper mentions Synthonics as the supplier of the poly-zinc-liothyronine used in this research. You might find this link of interest from a commercial aspect:
Recipharm and Synthonics join forces to promote novel drug delivery technology
Pharma customers set to benefit from proprietary metal coordination chemistry as Recipharm enters its first dual promotion agreement.
That page says "today" - but I am unsure which day that is/was!
Many will be unaware that Recipharm are the odd-one-out of UK levothyroxine Product Licence holders in that, despite holding three PLs, they market none of them:
PL 32446/0001
Levothyroxine Tablets BP 25 mcg Recipharm Limited
PL 32446/0002
Levothyroxine Tablets BP 50 mcg Recipharm Limited
PL 32446/0003
Levothyroxine Tablets BP 100 mcg Recipharm Limited
Sorry, but which bit are you asking about? Why they have product licences but don't market their products? I have no idea. Maybe they changed their mind at some point? Afraid I don't know what costs would be involved in maintaining the PL over the years - if not very expensive then it might just be a sort of insurance allowing them to supply if the market changes.
Thanks - I did wonder if this slow release T3 might be put in a combination tablet with T4 and they were hedging their bets, but it has probably not been that long in the pipeline. I wonder if it is commonplace practice with pharmaceutical companies to get licences for drugs but never make the stuff
In this case yes! It's the equivalent of T4 as a prodrug being converted steadily into T3 itself in the body. And I'll say further this is a beautiful concept which I wish I'd thought of.
As far as I can work out it may be a CYP gene on pro drugs but my Endo said Levo isn’t affected by that but in not convinced, so if it was Dio2 and CYP that’s not the medication for me
Diogenes had you thought of this idea we would have had on the market already . I'm sure it would have not taken you as long as it's going to take them . It's a shame because the concept is Great . And many can benefit from it already if not yesterday . Is BIG PHARMA going to have a hand in this too ??? I'm hoping that it's going to be with the least fillers and taking into considerations thyroid patients that are very sensitive .
My problem is I really don’t do well on pro drugs never have done I seem to have allergic reactions to them most or they come and go in spurts a bit like a roller coaster ride for me on most .but if it works brilliant I will give it a go but hope they keep the active one just in case it doesn’t work on me
Perhaps Bianco can combine this new form of T3 with a slow release formulation as used for T3 itself. A double-slow uptake and conversion might eliminate the spike altogether.
That would be wonderful! Is he likely to do so though? I would love to be able to use T3 in that form. To be able to feel “human” again enjoying what left of life would be such a bonus and something to look forward to.
Thanks again for your post, much appreciated.
I have just been reading another book by an US Endo he always used compounded T3 in the smallest of quantities plus T4 Levo finding good results. His motto was slow slow slow and small, small, small it was quite successful too. He also suggested taking T3 first thing and Levo at night.
Sorry, very sceptical, both from the point of view of the obvious commercial interests, and from the POV of people like myself, apparently with peripheral resistance to TH, who must take a single, very large dose of T3 once a day for it to work at all. Apart from a brief increase in heart rate 1-2 hours after taking, there is no other obvious effect. I used to multi-dose the same daily amount, with disastrous effect on my health.
I missed the download window, unfortunately, but this is interesting to me at first glance, because I found that I could not tolerate T3 at all. I don't know whether it was due to a badly balanced T3/T4 combination or the volatility that you mention. I look forward to hearing more about this area.
While the focus on the serum levels is important, it seems to me that there is a missed opportunity to correlate the relationship between serum levels of T3 and uptake in the tissues.
I am one of those on combined T3/T4 who does not feel any different (no spike) throughout the day, which makes me wonder if there is an element of tissue-level demand that regulates the flow of T3 from serum to uptake in the tissues.
From my perspective, I feel that there must be a demand element as different parts of our body will have different metabolism demands.
This takes us back to the serum levels vs symptoms debate and whether some of us have a 'broken' demand mechanism that could explain the inconsistencies.
I believe the phenomenon is "damping". That is, the body FT3 sharply rises on taking T3. The tissues respond more slowly to the stimulus, but by the time they have begun to respond, the T3 spike has passed and is going down. So the stimulus is turned off until the next dose spike. If you imagine it as a sharp T3 wave that comes before a shallower tissue stimulus wave that it has produced. Therefore the apparent sharp effect of the T3 is not mirrored by the same following sharp spike in tissue response.
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T3 alone better than Levothyroxine? 
