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  1. #1
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    Exclamation Open Letter to Mark Vanderpump


    Levothyroxine: from sheep thyroid injections to synthetic formulations

    The Pharmaceutical Journal, 18 JUL 2013

    Jenny Bryan takes a look at the colourful and interesting history of levothryoxine sodium, and the ongoing debate over combination treatment versus monotherapy.

    By Jenny Bryan

    Although synthetic forms of levothyroxine have been available since the 1950s,1 there is continued public demand for porcine thyroxine as a more “natural” product than the synthetic version.

    “Synthetic levothyroxine is exactly the same as human thyroxine and has the obvious advantage that you don’t need to go to an abattoir to get it. But no randomised controlled trials were done to compare the effectiveness of the two products before patients were switched to synthetic treatment, and some patients feel that their symptoms are better controlled with pig thyroid hormone preparations,” says Dr Vanderpump.


    Read more: http://www.pharmaceutical-journal.co...123454.article

    Author of this Article, Jenny Bryan has interviewed the doctor Mark Vanderpump and his claims I have commented in the following e-mail to which by the way (of course?) I has not received a reply.

    Subject: "Article: "Levothyroxine: from sheep thyroid injections to synthetic formulations"
    Date: Fri, 22 May 2015 15:51:43 +0200
    From: Me
    To: drvanderpump@kentmedical.co.uk

    Dear dr. Mark Vanderpump

    I read with great interest the article "Levothyroxine: from sheep thyroid injections to synthetic formulations" by Jenny Bryan. http://www.pharmaceutical-journal.co...123454.article

    Based on this article, I would like to make you aware that there is no longer such a thing as "exactly the same as human thyroxine" in relation to synthetic T4 products. Since nature-identical hormone molecules are not patentable, the industry has developed a long range of so-called "thyroxine analogues" consisting many kinds of structure changed molecules which are no longer built exactly as human thyroxine.

    I have studied this issue for several years. After having examined several synthetic levothyroxine patents I found the first 29 patented molecular "versions" of "artificial levothyroxine", it was no longer necessary to continue because my point was already confirmed for 29th time: there is in fact no such a thing as "synthetic levothyroxine is exactly the same as human thyroxine".

    Regardless that in almost all inventions of those artificial T4-molecules, the number of atoms of the basic elements remains the same as in human T4-molecule, those atoms are arranged differently, or rotated different from the "real" human thyroxine. Only the first commercial forms of synthetic thyroxine was "nature identical", which has been the reason for the reasonable good effect, far better than from the following patented T4 analogues.

    When a specific molecular structure of a hormone is required before the body can successfully utilize it, it can not be surprising that treatment with the "changed" thyroxine is insufficient and causes side effects.

    But even if al those marketed synthetic thyroxine-products consisted exact molecular copies of the human thyroid hormone, exists the critical biochemical difference between those synthetics T4-analogues and preparations of animal thyroid gland.

    There is no such a thing as a "free thyroxine" in human or animal thyroid gland, while the synthetic thyroxine analogues are only in the free form. Therefore, one can not compare these two biochemical forms of medications because their pharmacokinetics and pharmacodynamics are quite different from each other.

    In a normal healthy human body the blood contains less than 1% free thyroxine of the body's total (at the time) content of thyroxine. More than 99% of thyroxine in the blood is bound to carrier proteins which are thyroxine-binding globulin, transhyretin and albumin. In this state the thyroxine (as well as triiodothyronine/T3) is biochemically inert (not active). This means that in the normal human body the thyroxine frees from protein binding only just so much/little that the body's levels of free thyroxine are constantly maintained less than 1%.

    Therefor, in relation to pharmacokinetic and pharmacodynamic, the drugs made from animal thyroid gland - in the body's metabolism of thyroid hormones works exactly the same way as if these hormones were released from the thyroid gland it self.

    That's why in patients treated with Dessicated Thyroid Extract, the blood values of free T4 has to be low because of the long half-life of T4, and because of the short half-life of T3, the values of free T3 has to be in the top of the reference range in patients who are optimal dosed in the treatment with preparations of animal thyroid gland.

    As in healthy human bodies, blessed with a healthy metabolism, thyroid hormones are working exact in this way, exactly same effect is achiewed in hypothyroid patients treated with DTE. This explains why so many patients prosper so much better with this treatment.

    Please note: It is an expression of pharmaceutical ignorance when individual doctors choose to "supplement" the DTE-treatment with an amount of synthetic T4 analog to raise blood levels of free T4, and after treatment for that reason fails, they say that it is DTE which does not work.

    In relation to pharmacokinetics and pharmacodynamics of synthetic thyroxine analogues in the human body, works these drugs so the body becomes flooded with free thyroxine to a degree, that in a normal human body this would be called "hyperthyroxinemia", whereas for some inexplicable reasons - in a hypothyroid bodies this condition is considered - by the doctors - as "normal".

    It's NOT normal!

    Too much free thyroxine in the blood at a time, is not normal and the body's genetic control will always try continuously to break down the excess of free thyroxine. This explains why so many patients treated with synthetic thyroxine analogues, nevertheless remains sick.

    I wrote once in the past as an comment to another relevant article:

    Now we just hope that at some point we can succeed in explaining to our doctors that the missing link in understanding that the protein binding is the difference between DTE (Dessicated Thyroid Extract) and synthetic T4 analogues.

    Because more than 99% of thyroid hormones in the DTE are carrier-protein-bound, it means that the pharmacodynamics of DTE occurss with Slow Release Effect, eliminating all the talk about the Ratio of T4/T3 and TSH, and making it pointless.

    All reflections on the ratio of T4 / T3 in thyroid glands of pigs could only makes sense in the context of issues associated with transplant surgery between two different species, but in orally ingested drugs it does not matter.

    Our doctors need to learn about the difference between the pharmacokinetics and pharmacodynamics of these two types of drugs, because right now they consider those two medications as synonymous (which they are not) and consequently doctors are committing so many serious mistakes, that their patients basically remains sick.

    It is almost impossible, touch briefly every detail, including corresponding metabolic aspects of artificial free triiodothyronine (synthetic T3) versus protein-bound triiodothyronine (T3) in preparations of animal thyroid gland, which in principle is exactly the same as the difference between metabolic aspects of "real" and "artificial" thyroxine, as well as briefly respond to claims that most patients are comfortable with synthetic T4 alone therapy, but I try anyway...

    The problem is that most hypothyroid patients are mature women, and a large number of symptoms associated with inadequate treatment of hormone deficiency, are overlapping the most characteristic early and following later signs and symptoms of menopause. This means that as long as doctors choose to interpret the results of inadequate treatment of hypothyroidism, as simple state of menopause (or simple signs of age in men) - will no positive development happen. Doctors will remain dogmatic instead of knowing, while patients will remain sick.

    Please, be aware that while the preparations of animal thyroid gland over the last 120 years has proved their effectiveness and efficiency in the treatment of hypothyroidism, no matter how many new patents are filed in still new artificial synthetic thyroxine "designs" over the last 65 years, they have still not proven their value for the hypothyroid patients. Only for the doctors.

    Basically continues this controversy only because those old, animal derived drugs works very satisfactory, while those new artificial synthetic hormone analogs works only temporarily and incompletely, because of their deviant molecular structures.

    I remember someone once said: "Hypothyroid patients will continue to suffer as a result of the synthetic treatment, as long as doctors prefer the synthetic treatment more than they love their patients."

    Please, always be aware of the difference between knowledge and dogma, because they are so dangerous easy not to notice the difference between.

    Best regards
    (me)
    Denmark


    I really begin to suspect that doctors are not as clever as they think they are. There are almost as many interpretations of medical sciences, as there are fractions of doctors on each of the continents. And each of these fractions, mutually monitor each other, terrorizing each other to obedience and punishes those who think more about patients' best than they wish obey their colleagues (just remember Dr. Skinner and his fate) ...

    I am so close to hate every white coat I see around me, and you know what? They deserve every crumb of this hatred. Millions of people suffers because doctors refuse a drug that works, and favors another drug that does not. This attitude and this decision is pure commercial, and so far from medical sciences as possible.

    Shame on them.
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  2. #2
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    Standard Sv: "Levothyroxine: from sheep thyroid injections to synthetic formulations"

    Jeg hadde ikke en anelse om at så lite av de hormonene vi har i blodet faktisk er frie... i forhold til proteinbundede. Med syntetiske tilskudd må da kroppen gå og kjempe imot en tilstand av "kronisk overdosering" ... Ikke rart at det går feil og at omdanningen til fT3 for mange strupes i stedet for å normaliseres.

    Det fremsetter jo også implisitt hvorfor at fT3-produkter "ikke fungerer" og må deles i mikroskopiske doser og pulsdoseres for å gi en brukbar virkning...

    Jeg har forøvrig en kollega, en mann i begynnelsen av 60årene som har fått konstatert stoffskiftesykdom (en tidligere meget aktiv mann) ... som nå er "velregulert", men har gått fra å komme tilbake i jobb, ned i 50% og nå ut i full sykemelding. Legen mener det må være utbrenthet, fordi stoffskiftet er som kjent; "velregulert".

    Har sendt et par artikler og snakket litt, men "man kan leie hesten til krybba, men ikke tvinge ham til å spise". Jeg håper at frøet jeg har sådd vil spire, men har ikke høye håp. Er redd for at hans yrkeskarriere er over.

    Som jeg har sagt før... det er lett å kjøre over pasienter som ikke har overskudd og kognitive evner til å protestere lenger... og med standardbehandlingen så gjelder dessverre det mange.
    Diagnostisert etter "depresjonsymptomer" - mai 2010 & smgjs private side ...
    -- og det som er deilig er at NÅ er avataren min ironisk

  3. #3
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    Standard Sv: "Levothyroxine: from sheep thyroid injections to synthetic formulations"

    Sitat Opprinnelig skrevet av smgj Vis post
    Jeg hadde ikke en anelse om at så lite av de hormonene vi har i blodet faktisk er frie... i forhold til proteinbundede. Med syntetiske tilskudd må da kroppen gå og kjempe imot en tilstand av "kronisk overdosering" ... Ikke rart at det går feil og at omdanningen til fT3 for mange strupes i stedet for å normaliseres.

    Det fremsetter jo også implisitt hvorfor at fT3-produkter "ikke fungerer" og må deles i mikroskopiske doser og pulsdoseres for å gi en brukbar virkning...

    Jeg har forøvrig en kollega, en mann i begynnelsen av 60årene som har fått konstatert stoffskiftesykdom (en tidligere meget aktiv mann) ... som nå er "velregulert", men har gått fra å komme tilbake i jobb, ned i 50% og nå ut i full sykemelding. Legen mener det må være utbrenthet, fordi stoffskiftet er som kjent; "velregulert".

    Har sendt et par artikler og snakket litt, men "man kan leie hesten til krybba, men ikke tvinge ham til å spise". Jeg håper at frøet jeg har sådd vil spire, men har ikke høye håp. Er redd for at hans yrkeskarriere er over.

    Som jeg har sagt før... det er lett å kjøre over pasienter som ikke har overskudd og kognitive evner til å protestere lenger... og med standardbehandlingen så gjelder dessverre det mange.
    Ops – I realized that this is supposed to be an English only-thread, so I will supply a translation of my small rant above:

    I had no idea that so little of the thyroid hormones in serum was "free" compared to being protein bound. On synthetic fT4 substitution, the body probably will have to fight all the signs of being chronically overdosed.

    No wonder that the treatment is less than successful for many sufferers, and that the result is poor conversion from fT4 to fT3.
    The article also hints at why synthetic fT3 substitution is so poorly tolerated by most and why it most often need a rigorously pulse dose regime to be successful.

    I have a colleague, a man in his early sixties, diagnosed with low thyroid (he has always enjoyed actively biking the nearly ten years I have known the man). The doctor says the thyroid is "well regulated", but the man has gone from "getting back at work", "down to 50%" and now into "full sick leave". The doctor says it has to be "long time stress/ he has to be burnt out" … because it can't possibly be the thyroid since it is "well regulated" on fT4 substitution.

    I've mailed him a couple of articles and talked a bit, but there is a Norwegian saying that "you can lead the horse to its trough but you can't force it to drink". I hope that the seed I have sown will germinate, but I do not have high hope. I am afraid that (he will continue to trust that his doctor knows best and that) his working career is over.

    As I have said earlier as well. It is all too easy to run over patients with no physical or cognitive reserve left. With today's standard treatment regime, many will unfortunately meet that faith.
    Diagnostisert etter "depresjonsymptomer" - mai 2010 & smgjs private side ...
    -- og det som er deilig er at NÅ er avataren min ironisk

  4. #4
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    Standard Sv: Open Letter to Mark Vanderpump


    Hello smgj

    I appreciate your response. I have known for some time that the blood of a healthy human body contains no more than 1% of free thyroid hormones. That is why I have criticized the idea of mixing synthetic T4 with NDT.

    Otherwise I'm thinking about another major problem, because I suspect that the modern methods of blood analysis seems to be designed primarily to handle blood levels of synthetic thyroid hormones ... but that's another story I will deal with later on.

    Right now I have other things to be angry about, as well as I'm reading about huge compensations granted as a result of a big number of lawsuits filed by patients injured by a drug manufactured from molecule-modified progesterone, which has caused cancer to a lot of patients, who were treated with this drug.

    In principle, it is the same healthproblem with modified progesterone molecules, as with these many versions of patented, artificial thyroxine, hopefully with less lethal consequences. And yet... who the hell can look into the future...

    I have also long wondered whether the artificial thyroxine can be converted into "real" triiodothyronine (T3), or deiodinase enzymes can "see" the difference. I think they can "see" the difference. Why else the synthetic-treated patients consistently shows almost 1/3 lower values of T3 than healthy controls?

    Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment.
    Referred at Thyroid UK
    Abstract
    Full text PDF
    And here in Danish

    And...

    Psychological well-being in patients on 'adequate' doses of l-thyroxine: results of a large, controlled community-based questionnaire study.
    http://www.ncbi.nlm.nih.gov/pubmed/12390330
    http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract
    http://onlinelibrary.wiley.com/doi/1...654.x/abstract
    http://www.sonjas-stoffskifteforum.i...ad.php?t=17011
    (Danish)

    I'll be back with more information on this artificial progesterone case and all these lawsuits.
    • Tak for at du læste mit indlæg.
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  5. #5
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    Standard Sv: Open Letter to Mark Vanderpump

    Of course the REAL bio-identical = identical hormones are better. There is a reason that they evolved to have exactly the structure they have. It should be obvious.

    What I'm most concerned about is not to alienate fellow sufferers still on synthetics. When we're at the bottom, even the meager help one gets from synthetics are better than no help, and may even be just enough to reclaim enough energy and wit to go looking for that doctor that will prescribe the really effective stuff.

    Just how one should go about telling people (barley keeping their heads above water on synthetics) that they really should use their energy in a fight to get desiccated thyroid "now" instead of focusing that energy on getting back to work and family, because getting thyroid is a better long-run strategy … I don't know.
    Diagnostisert etter "depresjonsymptomer" - mai 2010 & smgjs private side ...
    -- og det som er deilig er at NÅ er avataren min ironisk

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