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The Problem with T3
For a long time we have known that thyroid hormones played a role in gene transcription during myoblast proliferation and differentiation. The regulation of gene expression by thyroid hormone (T3) involves binding of the hormone to nuclear receptors [thyroid hormone receptor (TR)] acting as T3-dependent transcription factors encoded by TRalpha (NR1A1) and TRbeta (NR1A2) genes. This in turn leads to the desired increase in the SERCA1 and SERCA2a mRNA proteins we all want because these cod for the Ca++ pumps on the muscle cell that cause use to burn extra calories through increased active Ca++ transport. However new research in spring 2006 revealed an regulatory mechanism that might not make you so happy. In this study, they identified another transcript, TRalpha-DeltaE6, produced by alternative splicing with microexon 6b instead of exon 6. This splicing leads to the synthesis of a protein devoid of a hinge domain. And what this new factor was found to be responsible for was that although TRalpha-DeltaE6 did not bind DNA, its expression induced a TRalpha1 sequestration in the cytoplasm. Functional studies demonstrated that TRalpha-DeltaE6 inhibits the transcriptional activity of TRalpha1 and retinoic X receptor-alpha, but not of retinoic acid receptor-alpha. We also found that TRalpha-DeltaE6 efficiently decreased the ability of TRalpha to inhibit MyoD transcriptional activity during myoblast proliferation. Consequently, when overexpressed (like when people take synthetic T3) in myoblasts, it stimulated terminal differentiation. This suggest that TRalpha-DeltaE6 may act as down regulator of overall T3 receptor activity, including its ability to repress MyoD transcriptional activity during myoblast proliferation.
OK what did I just say????
By taking T3 you basically up regulate a regulatory mechanism that regulates the effect of T3 not by effecting the adult muscle cells, but it actually kills off you muscle stem cells before they have a chance to join with the adult muscle cell. These are the same cells that MGF and IGF and AAS increase, and are the same cells that your body recruits for growth and repair.
In addition say you take MGF, and IGF, and AAS with your T3 to try and combat this effect. (btw I have no research to suggest these would significantly help the situation and people that say they lose less by using them may be an alternative mechanism etc. so you still might be losing the effect of recruitment of muscle stem cells)
T3 up regulates these SERCA1 proteins right. Here is a question that always bothered me, because these proteins have a long half life and t3 itself isn’t increasing your metabolism like a stimulant… you shouldn’t need to slowly come off it. It should be that the slow loss of the CA++ pumps would serve as a slow decline on its own. Here in lies the other problem. Your body responds to up regulated SERCA1 proteins with another group of hormones to catabolize them. Corticosteroids!!! Like the all famous cortisol.
This is done in part by the corticosteroids causing an increase in sarcolipin mRNA which decrease the activity of the SERCA1 pumps. So not only are you losing the energy burning pumps after you come off t3, you are decreasing the effectiveness and levels of the ones you naturally would have and your increasing corticosteroid levels. That makes for a hell of a rebound effects….
So how do I cut then???
Here is an idea.
If you use T4 you are going to have a small conversion to T3, and reduce the negative effects. If you use HGH in with your T4 they will synergistically benefit you and HGH will help reduce the increase in cortisol through negative feedback. Then after you or towards the end of you T4 cycle you should add IGF. This increases the half-life of the SERCA1 proteins making them last longer so there is no fall off effect. If you are going to use T3 I recommend all the above and staying at a low dose as well as adding a cortisol blocker at the end. T3 with a cortisol blocker should have a synergistic effect due to increased SERCA1 activity which means more energy burning.
To be safe you are best not using T3 if you are competitive athlete who depends on performance and can not afford loss of strength or increased risk of injury.
But I will add some more information for those still considering the compound.
How does T3 actually work, here is the non science definition
T3 increases you metabolism by causing your muscle to use more atp to maintain proper calcium levels. It does this by increasing the number of calcium pumps on the surface of your muscle cells. Because of the change in Calcium levels in the muscle it actually puts your muscles in a more relaxed state. This may atribute to the sudden loss of strength some users see while taking T3.
There are no current studies that indicate long term use of T3 results in the permant shut down of the thyroid. However long term use is deterimental for the muscle tissue. T3 can cause protein loss and decreases myotuble formation. Long term use can also result in a rebound effect where a user gains more fat afterwards because it take the body longer to return to its normal basal metabolic rate.
T3 with IGF-I not only increases these effects but prolongs the effect.
The in dept process
Thyroid hormone (L-tri-iodothyronine; T3) has major effects
on Ca2l homeostasis in heart and skeletal muscle [1,2]. One of the
most striking effects is the increased speed of muscle relaxation
in hyperthyroidism and the decreased relaxation rate in
hypothyroidism [3-6]. In the last decade it has become clear
through work by ourselves and others that T3-dependent changes
in the sarcoplasmic reticulum (SR) underlie these phenomena. T3
administration in vivo causes an increase of the amounts of Ca21
pumps (Ca2+-ATPase) and SR, thereby increasing the rate of
Ca2+ removal from the sarcoplasma as well as the capacity for
Ca2+ storage [7-11]. As a consequence of the increased Ca2+
release and re-uptake (Ca2+ cycling) the metabolic rate is
stimulated in skeletal muscle by consuming more ATP, which
contributes to the well known thermogenic effect of thyroid
hormone
This process works continuously because the cell has Ca++ channels that operate solely on the concetratoin gradient. There fore the result is a faster cycleing of Ca++ in and out of the cell.
Thyroid hormone (T3) is a major determinant of the fast-type
sarcoplasmic-reticulum Ca2+-ATPase (SERCAl) level in skeletal
muscle [1-4]. This Ca2+-transporting protein is responsible for
the removal of Ca2+ from the cytosol during a contractionrelaxation
cycle. The T3-induced increase in SERCAl expression
is mainly responsible for the enhanced muscle relaxation rate
which is characteristic of the hyperthyroid status [5-7]. Evidence
that T3 regulates SERCAI expression in vivo at least partly at a
pre-translational level was provided in one of our previous
studies, in which it was shown that T3increases SERCAI mRNA
levels in rat soleus and extensor digitorum longus muscle
More in depth on the IGF synergy
T3 administration in vivo causes an increase of the amounts of Ca21
pumps (Ca2+-ATPase) and SR (sarcoplasimic reticulum), thereby increasing the rate of Ca2+ removal from the sarcoplasma as well as the capacity for Ca2+ storage. The muscle cell has natural calcium channels that Ca2+ can flow through according to the gradient requiring no energy expenditure. As a consequence of the increased Ca2+ release and re-uptake (Ca2+ cycling) the metabolic rate is stimulated in skeletal muscle by consuming more ATP to run the pumps, which contributes to the well known thermogenic effect of thyroid hormone. T3’s mechanism of action occurs at the nuclear level upregulating the transcription of the mRNA’s for these Ca@= ATPase’s. IGF-I assist in the maturation of the SR where these pumps are located on the cell. It has alsop been reported that through an insulin like mechanism the IGF actually increases the stability of the mRNA. A quote from research:
“The SERCAI mRNA (the discussed above) half-life was twice as long in IGF-I + T3-treated cultures
compared with T3-treated cultures, which is in reasonable agreement
with the 1.6-fold greater increase in the SERCAI mRNA
levels by IGF-I + T3 compared with T3. T3 or IGF-I alone did not
affect the SERCAI mRNA half-life, which indicates that both T3
and IGF-I are involved in the process leading to the T3 + IGF-I
induced increase in SERCA1 mRNA stability.”
For a long time we have known that thyroid hormones played a role in gene transcription during myoblast proliferation and differentiation. The regulation of gene expression by thyroid hormone (T3) involves binding of the hormone to nuclear receptors [thyroid hormone receptor (TR)] acting as T3-dependent transcription factors encoded by TRalpha (NR1A1) and TRbeta (NR1A2) genes. This in turn leads to the desired increase in the SERCA1 and SERCA2a mRNA proteins we all want because these cod for the Ca++ pumps on the muscle cell that cause use to burn extra calories through increased active Ca++ transport. However new research in spring 2006 revealed an regulatory mechanism that might not make you so happy. In this study, they identified another transcript, TRalpha-DeltaE6, produced by alternative splicing with microexon 6b instead of exon 6. This splicing leads to the synthesis of a protein devoid of a hinge domain. And what this new factor was found to be responsible for was that although TRalpha-DeltaE6 did not bind DNA, its expression induced a TRalpha1 sequestration in the cytoplasm. Functional studies demonstrated that TRalpha-DeltaE6 inhibits the transcriptional activity of TRalpha1 and retinoic X receptor-alpha, but not of retinoic acid receptor-alpha. We also found that TRalpha-DeltaE6 efficiently decreased the ability of TRalpha to inhibit MyoD transcriptional activity during myoblast proliferation. Consequently, when overexpressed (like when people take synthetic T3) in myoblasts, it stimulated terminal differentiation. This suggest that TRalpha-DeltaE6 may act as down regulator of overall T3 receptor activity, including its ability to repress MyoD transcriptional activity during myoblast proliferation.
OK what did I just say????
By taking T3 you basically up regulate a regulatory mechanism that regulates the effect of T3 not by effecting the adult muscle cells, but it actually kills off you muscle stem cells before they have a chance to join with the adult muscle cell. These are the same cells that MGF and IGF and AAS increase, and are the same cells that your body recruits for growth and repair.
In addition say you take MGF, and IGF, and AAS with your T3 to try and combat this effect. (btw I have no research to suggest these would significantly help the situation and people that say they lose less by using them may be an alternative mechanism etc. so you still might be losing the effect of recruitment of muscle stem cells)
T3 up regulates these SERCA1 proteins right. Here is a question that always bothered me, because these proteins have a long half life and t3 itself isn’t increasing your metabolism like a stimulant… you shouldn’t need to slowly come off it. It should be that the slow loss of the CA++ pumps would serve as a slow decline on its own. Here in lies the other problem. Your body responds to up regulated SERCA1 proteins with another group of hormones to catabolize them. Corticosteroids!!! Like the all famous cortisol.
This is done in part by the corticosteroids causing an increase in sarcolipin mRNA which decrease the activity of the SERCA1 pumps. So not only are you losing the energy burning pumps after you come off t3, you are decreasing the effectiveness and levels of the ones you naturally would have and your increasing corticosteroid levels. That makes for a hell of a rebound effects….
So how do I cut then???
Here is an idea.
If you use T4 you are going to have a small conversion to T3, and reduce the negative effects. If you use HGH in with your T4 they will synergistically benefit you and HGH will help reduce the increase in cortisol through negative feedback. Then after you or towards the end of you T4 cycle you should add IGF. This increases the half-life of the SERCA1 proteins making them last longer so there is no fall off effect. If you are going to use T3 I recommend all the above and staying at a low dose as well as adding a cortisol blocker at the end. T3 with a cortisol blocker should have a synergistic effect due to increased SERCA1 activity which means more energy burning.
To be safe you are best not using T3 if you are competitive athlete who depends on performance and can not afford loss of strength or increased risk of injury.
But I will add some more information for those still considering the compound.
How does T3 actually work, here is the non science definition
T3 increases you metabolism by causing your muscle to use more atp to maintain proper calcium levels. It does this by increasing the number of calcium pumps on the surface of your muscle cells. Because of the change in Calcium levels in the muscle it actually puts your muscles in a more relaxed state. This may atribute to the sudden loss of strength some users see while taking T3.
There are no current studies that indicate long term use of T3 results in the permant shut down of the thyroid. However long term use is deterimental for the muscle tissue. T3 can cause protein loss and decreases myotuble formation. Long term use can also result in a rebound effect where a user gains more fat afterwards because it take the body longer to return to its normal basal metabolic rate.
T3 with IGF-I not only increases these effects but prolongs the effect.
The in dept process
Thyroid hormone (L-tri-iodothyronine; T3) has major effects
on Ca2l homeostasis in heart and skeletal muscle [1,2]. One of the
most striking effects is the increased speed of muscle relaxation
in hyperthyroidism and the decreased relaxation rate in
hypothyroidism [3-6]. In the last decade it has become clear
through work by ourselves and others that T3-dependent changes
in the sarcoplasmic reticulum (SR) underlie these phenomena. T3
administration in vivo causes an increase of the amounts of Ca21
pumps (Ca2+-ATPase) and SR, thereby increasing the rate of
Ca2+ removal from the sarcoplasma as well as the capacity for
Ca2+ storage [7-11]. As a consequence of the increased Ca2+
release and re-uptake (Ca2+ cycling) the metabolic rate is
stimulated in skeletal muscle by consuming more ATP, which
contributes to the well known thermogenic effect of thyroid
hormone
This process works continuously because the cell has Ca++ channels that operate solely on the concetratoin gradient. There fore the result is a faster cycleing of Ca++ in and out of the cell.
Thyroid hormone (T3) is a major determinant of the fast-type
sarcoplasmic-reticulum Ca2+-ATPase (SERCAl) level in skeletal
muscle [1-4]. This Ca2+-transporting protein is responsible for
the removal of Ca2+ from the cytosol during a contractionrelaxation
cycle. The T3-induced increase in SERCAl expression
is mainly responsible for the enhanced muscle relaxation rate
which is characteristic of the hyperthyroid status [5-7]. Evidence
that T3 regulates SERCAI expression in vivo at least partly at a
pre-translational level was provided in one of our previous
studies, in which it was shown that T3increases SERCAI mRNA
levels in rat soleus and extensor digitorum longus muscle
More in depth on the IGF synergy
T3 administration in vivo causes an increase of the amounts of Ca21
pumps (Ca2+-ATPase) and SR (sarcoplasimic reticulum), thereby increasing the rate of Ca2+ removal from the sarcoplasma as well as the capacity for Ca2+ storage. The muscle cell has natural calcium channels that Ca2+ can flow through according to the gradient requiring no energy expenditure. As a consequence of the increased Ca2+ release and re-uptake (Ca2+ cycling) the metabolic rate is stimulated in skeletal muscle by consuming more ATP to run the pumps, which contributes to the well known thermogenic effect of thyroid hormone. T3’s mechanism of action occurs at the nuclear level upregulating the transcription of the mRNA’s for these Ca@= ATPase’s. IGF-I assist in the maturation of the SR where these pumps are located on the cell. It has alsop been reported that through an insulin like mechanism the IGF actually increases the stability of the mRNA. A quote from research:
“The SERCAI mRNA (the discussed above) half-life was twice as long in IGF-I + T3-treated cultures
compared with T3-treated cultures, which is in reasonable agreement
with the 1.6-fold greater increase in the SERCAI mRNA
levels by IGF-I + T3 compared with T3. T3 or IGF-I alone did not
affect the SERCAI mRNA half-life, which indicates that both T3
and IGF-I are involved in the process leading to the T3 + IGF-I
induced increase in SERCA1 mRNA stability.”
