Complementing T3 WithTriiodothyroacetic Acid (triac) -

Discussion in 'Ray Peat Topics' started by LeeLemonoil, Nov 3, 2019.

  1. LeeLemonoil

    LeeLemonoil Member

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    Triiodothyroacetic acid (triac) is T3 esterified with acetic acid. It acts similar to T3 but intriguingly there are
    publications out there where TRIAC helped in disease-therapies that were "resistant" to standard-T3/Lio.

    It's a more stable compound than T3 and could be easily worked into lotions, oils and so forth for topical use. It's a bit hard to obtain though.

    Will compile some of the interesting studies here. Discuss why it works sometimes "even better" than t3 and the like...
     
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    LeeLemonoil

    LeeLemonoil Member

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    A thyroid hormone analogue, triiodothyroacetic acid, corrects corticosteroid-downregulated collagen synthesis. - PubMed - NCBI

    Action of topical thyroid hormone analogues on glucocorticoid-induced skin atrophy in mice. - PubMed - NCBI

    Differentiated thyroid carcinoma in a girl with resistance to thyroid hormone management with triiodothyroacetic acid. - PubMed - NCBI

    Diabetes mellitus in a girl with thyroid hormone resistance syndrome: a little recognized interaction between the two diseases. - PubMed - NCBI

    Therapeutic applications of thyroid hormone analogues in resistance to thyroid hormone (RTH) syndromes. - PubMed - NCBI

    Non-mammalian models reveal the role of alternative ligands for thyroid hormone receptors. - PubMed - NCBI

    Triiodothyroacetic acid in health and disease. - PubMed - NCBI

    Thyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer. - PubMed - NCBI

    3, 5, 3'-Triiodothyroacetic acid (TRIAC) is an anti-inflammatory drug that targets toll-like receptor 2. - PubMed - NCBI

    Anticonvulsant and Neuroprotective Effects of the Thyroid Hormone Metabolite 3-Iodothyroacetic Acid. - PubMed - NCBI

    Mutated Thyroid Hormone Transporter OATP1C1 Associates with Severe Brain Hypometabolism and Juvenile Neurodegeneration. - PubMed - NCBI

    Bioactivity of Thyroid Hormone Analogs at Cancer Cells. - PubMed - NCBI

    Alternative ligands for thyroid hormone receptors. - PubMed - NCBI

    The Colorful Diversity of Thyroid Hormone Metabolites. - PubMed - NCBI

    Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis. - PubMed - NCBI
     
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    LeeLemonoil

    LeeLemonoil Member

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    this article would be nice to have for general TH-knowledge and the state of the art of the science. It’s a single author who researches Thyroid hormones since a long time

    The Colorful Diversity of Thyroid Hormone Metabolites. - PubMed - NCBI

    Abstract

    Since the discovery of L-thyroxine, the main secretory product of the thyroid gland, and its major metabolite T3, which exerts the majority of thyroid hormone action via ligand-dependent modulation of the function of T3 receptors in nuclei, mitochondria, and other subcellular compartments, various other T4-derived endogenous metabolites have been identified in blood and tissues of humans, animals, and early protochordates. This review addresses major historical milestones and experimental findings resulting in the discovery of the key enzymes of thyroid hormone metabolism, the three selenoprotein deiodinases, as well as the decarboxylases and amine oxidases involved in formation and degradation of recently identified endogenous thyroid hormone metabolites, i.e. 3-iodothyronamine and 3-thyroacetic acid. The concerted action of deiodinases 2 and 3 in regulation of local T3 availability is discussed. Special attention is given to the role of the thyromimetic “hot” metabolite 3,5-T2 and the “cool” 3-iodothyronamine, especially after administration of pharmacological doses of these endogenous thyroid hormone metabolites in various animal experimental models. In addition, available information on the biological roles of the two major acetic acid derivatives of thyroid hormones, i.e. Tetrac and Triac, as well as sulfated metabolites of thyroid hormones is reviewed. This review addresses the consequences of the existence of this broad spectrum of endogenous thyroid hormone metabolites, the “thyronome,” beyond the classical thyroid hormone profile comprising T4, T3, and rT3 for appropriate analytical coverage and clinical diagnostics using mass spectrometry versus immunoassays for determination of total and free concentrations of thyroid hormone metabolites in blood and tissues.
     
  4. Amazoniac

    Amazoniac Member

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    Thank you for collecting these!

    :nomnompopcorn
     
  5. Inaut

    Inaut Member

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    Ditto
     
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    LeeLemonoil

    LeeLemonoil Member

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    Those are all gems with valuable info that further our understanding about Peat‘s favourite T3.
    3-iodothyronamine is another Metabolite that sees a lot of newer research. Rabbit holes, but I‘m about to climb them
     
  7. ecstatichamster

    ecstatichamster Member

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    Exceptional post and I thank you.
     
  8. ecstatichamster

    ecstatichamster Member

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    Has anyone emailed Dr. Peat about this?
     
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    LeeLemonoil

    LeeLemonoil Member

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    I haven’t.

    It would be nice if some peaters on here could read the odd study or publication related to TRIA and highlight and post anything worth mentioning from it.
    That goes for the links provided above but there are also other articles on the pubmed about worth reading. Not too many though, it’s a manageable field and some synopsis-meta-reviews.

    My initial hunch after reading into it is that these minor metabolites of T3 -TRIAC, but also the mentioned amine, are no less important for thyroid function and general health as are metabolites of major steroids. There are different actions on different receptors and so on.
    I like the fact it’s an arctic acid-ester. Those are often „very good“ in effect and act very broadly in cellular systems. That’s just another semi-informed hunch from other acetic acid compounds unrelated to thyroid hormones.

    Then there are sulfated T3-metabolites as yet another realm.
    It‘s a bit strange that Peat don’t discusses much of that, but one can easily lose track.

    Finally @haidut
    Any opinion on TRIAC for chance? Obtainability? Maybe a worthwhile substance for a research-product?
     
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    LeeLemonoil

    LeeLemonoil Member

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    LeeLemonoil

    LeeLemonoil Member

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    LeeLemonoil

    LeeLemonoil Member

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    LeeLemonoil

    LeeLemonoil Member

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    LeeLemonoil

    LeeLemonoil Member

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    LeeLemonoil

    LeeLemonoil Member

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  16. Broken man

    Broken man Member

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    Awesome, thank you !!!
     
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    LeeLemonoil

    LeeLemonoil Member

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    Some first take-aways:

    TRIA works in T3-resistant states becuase it need'nt be actively transported into cells by transporter-proteins. What goes for this pathology and nerve cells is valid to other cells and tissue too.

    "Public summary of opinion on orphan designationEMA/695502/2017Page 2/4How is this medicine expected to work?This medicine has a similar structure to and works in the same way as the thyroid hormone T3. The difference is that, unlike T3, it can enter developing nerve cells without the MCT8 transporter protein. This is expected to allow the medicine to enter nerve cells in patients with Allan-Herndon-Dudley syndrome, replacing the hormone that they cannot transport, and thereby allowing the nerves to develop properly and relieving symptoms of the disease. "

    It's also theorized that TRIA is evolutionarily more ancient than T3. It's an active endosubstance in many species still. Given that old orgnisms used fermentation and produced lots of acetic acid, it's probably logical that the first iodotyrosine-compounds reacted with acetic acid.





    Very interesting are TRIACs effects on reversing glucocorticoid/stress-induced tissue defects. Highly effective in that it seems. I wonder why this compound never made it into medicinal skincare, it's very effectful even in small amounts like 0.1% topical.

    Dose-response effects of tri-iodothyroacetic acid (Triac) and other thyroid hormone analogues on glucocorticoid-induced skin atrophy in the haired mouse.

    Abstract
    Thyroid hormones have an influence on the connective tissue biology of the skin and, theoretically, topically applied thyroid hormones or hormone analogues could have a stimulatory effect on collagen synthesis. In this investigation the effect of topical tri-iodothyroacetic acid (Triac) and other thyroid hormone analogues were tested for their effect in preventing betamethasone-induced skin atrophy in the normal haired mouse. Triac, tri-iodoproprionic acid (Triprop) and the synthetically developed thyroid hormone analogue KB-026 and 2 different Triac cream formulations were applied along with betamethasone on shaved mouse skin. Triac in daily doses of 1 nmol/cm2 and higher was able to block the betamethasone-induced skin atrophy in mice skin. In high doses, Triprop and KB-026 also had a blocking effect. Triac alone had a stimulatory effect on dermal thickness. This study indicates that thyroid hormone analogues may be used to prevent corticosteroid-induced skin atrophy.



    A thyroid hormone analogue, triiodothyroacetic acid, corrects corticosteroid-downregulated collagen synthesis.


    The aim of this study was to compare the change in collagen synthesis between topical treatments with two doses of triiodothyroacetic acid (TRIAC), a thyroid hormone analogue, and placebo, after pretreatment with topical betamethasone 17-valerate (BM). Eighteen healthy volunteers were pretreated with BM on abdominal skin for 3 days, and were then treated for 14 days with a cream containing TRIAC (0.03% or 0.1%) or a placebo cream. Collagen production was assessed by quantifying the amino terminal propeptides of human type I and type III procollagen (PINP and PIIINP) in fluids from suction-induced blisters on the treated skin. Three days of treatment with BM led to an average reduction of PINP of 70% and of PIIINP of 50%. Seven days after treatment, the median increase in PINP was 230% (p = 0.03) in the Triac 0.03% group, 148% (p = 0.2) in the TRIAC 0.1% and 5% in the placebo group. The median increase in PINP in the skin area from the start of treatment to the end of treatment was 521% (p = 0.06) in the TRIAC 0.03% group, 339% (p = 0.2) in the TRIAC 0.1% group, and 55% in the placebo group (the p values are related to baseline). Seven days after treatment, the median increase in PIIINP was 24% (p = 0.6) in the Triac 0.03% group, 23% (p = 0.6) in the TRIAC 0.1% group, and -12% in the placebo group. The median increase in PIIINP in the skin area from the start of treatment to the end of treatment was 137% (p = 0.7) in the TRIAC 0.03% group, 230% (p = 0.9) in the TRIAC 0.1% group and 58% in the placebo group (the p values are related to baseline). Histologic examinations of sections from punch biopsies taken at the end of the treatment showed more thickened collagen fibers and increased density of PINP-producing dermal fibroblasts in the TRIAC groups compared to the placebo group. The result suggests a potential role for TRIAC-containing cream concomitant with anti-inflammatory topical treatment with potent glucocorticoids to prevent their suppressive activity on dermal collagen production



    Action of topical thyroid hormone analogues on glucocorticoid-induced skin atrophy in mice.

    Previously we demonstrated the stimulation of collagen synthesis in triiodothyroacetic acid (TRIAC)-topically treated human and mice. In the present study, we have evaluated the dose response effect of thyroid hormone (TH) analogues and tretinoin on glucocorticoid-induced skin atrophy in a haired mouse model. For this investigation, we treated haired mice twice daily for 7 days with various topically administered doses of TRIAC, triiodothyronine-sodium salt (T(3)-Na), diiodothyroacetic acid (DIAC), 3,5-diiodothyropropionic acid (DITPA), and tretinoin with 0.2 mM betamethasone17-valerate (BM), or with the vehicle as a control group. We also investigated a combination of commercial betamethasone dipropionate (BD) 0.05% cream and various doses of TRIAC on mouse skin. TRIAC was able to reverse the skin atrophy by 25% in a daily dose of 1 nmol/cm(2) in the presence of 0.2 mM BM (p < 0.05). Neither other TH analogues nor TRIAC in lower and higher concentrations had a significant inhibitory effect on dermal atrophy (p > 0.05). A combination of 0.2 mM BM and 10 nmol/cm(2) TRIAC was able to prevent dermal atrophy by 18%. The addition of TRIAC to 0.05% BD cream in a final concentration of 0.1% was able partially to reverse the dermal atrophy by 15% (p < 0.05). TRIAC alone in a concentration of 1,000 nmol/cm(2) stimulated dermal proliferation by 34% (p < 0.05). Other TH analogues alone had no stimulatory effect on dermal proliferation. Tretinoin 0.8 mM was able to inhibit dermal atrophy by 20% (p < 0.05) and had an effect on dermal thickness of 85% (p < 0.05). However, severe side effects with edema, erythema, and scaling were commonly observed in all tretinoin-treated mouse skin, which could partly explain the increase in dermal thickness. In contrast, no skin side effects were observed after treatment with TRIAC. This study indicates that TRIAC may have a therapeutic effect on BM-induced dermal atrophy in mouse skin and a direct stimulatory effect on dermal proliferation when given alone.




    I found that TRIAC is a prescription-medicine in FRance today (Triatricol) but was OTC before. A shame it's not freely available anymore. I've seen a chemical synthesize-business that seels research/lab-chmeiclas offer it for ~150€ for 50mg which seems a bit steep. There are peptide-vendors out there that offer Lio-T3 and I think esterifying that with acetic acid wouldnt be a big problem or very costly, but no one offers it.
     
  18. Amazoniac

    Amazoniac Member

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    - Triac (3,5,3’Triiodo-Thyroacetic Acid) Induced « Pseudohypothyroidism »

    "Triac, a metabolite of T3 and T4, is normally present in blood at low concentrations (5.5-15.2 ng/dl, mean 8.7 ng/dl), independently of the thyroid status (3). A high affinity of Triac for the thyroid hormone nuclear receptor has been reported (8, 9), equivalent to the affinity of T3 itself."

    "However, the in vivo activity of Triac is low. Doses 15 times higher of Triac are necessary to obtain metabolic effects comparable to those of T3 (10). A selective and preferential lowering effect of low doses of Triac (2 mg daily or less) on plasma cholesterol, appearing before modification of other metabolic parameters, has been demonstrated in hypothyroid patients, but not in euthyroid subjects (5, 11). Triac has a short half-life (5.5 h) in the exchangeable compartment, compared to 11 h for T3; this could explain its low metabolic potency despite its high affinity for nuclear receptors (12)."​

    I still think it's worth looking into it because it might have unique properties.
     
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    LeeLemonoil

    LeeLemonoil Member

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    I think so. And it might be useful to have some tyhroid-hormone effects without the metabolic-supercharging of T3.
     
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    LeeLemonoil

    LeeLemonoil Member

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