t3 and gh

[house1]

will t3 hinder the effects of the gh.

was doing some searching and came across someones post that stated it will.

just wondering if there was any truth to it.

about to run 50 mcgs aday

[jyzza]

Thyroid Hormone for Weight Loss:
Physiologic and Metabolic Effects


Editors Note: We are extremely pleased to have Nandi contributing an
article for us this month (and, hopefully, many to come). One of the
main things Mind and Muscle was missing was a regular "anabolics guy"
- -- and, now, assuming things go as expected for all parties, we have
found ourselves one of the very best out there.

For those who are unaware, Nandi, in addition to being what I consider
a top 5 mind in this arena, is the owner of Cutting Edge Muscle, the
premiere Anabolics board on the internet. It is far and away the closest
thing to our forums as far as quality of info, atmosphere, etc. - I had,
in fact, approached Nandi to run our anabolics board, before he formed
CEM, but got busy and dropped the ball).

If any of you have not seen it, I strongly, strongly recommend that you
head over to their website and do a good deal of reading (but only after
you have finished reading M&M and our forums, of course

Introduction
It has been over 100 years since the discovery by Magnus-Levy that thyroid
hormones play a central role in energy homeostasis, and 75 years since
the hormones were first used for weight loss. Despite this great length
of time, the precise mechanisms by which thyroid hormones exert their
calorigenic effect are not completely characterized, and still actively
debated. Despite numerous clinical studies having shown that the administration
of thyroid hormone induces weight loss, it is not currently indicated
as a weight loss agent. This is probably due to the number of side effects
observed during thyroid hormone use at the relatively high doses used
in the majority of obesity treatment studies. These deleterious effects
include cardiac problems such as tachycardia and atrial arrhythmias,
loss of muscle mass as well as fat, increased bone resorption and muscle
weakness. Nevertheless, thyroid hormones, particularly triiodothyronine
(T3) are a mainstay in the arsenal of drugs used by bodybuilders for
fat loss. The widespread underground use of T3 warrants an understanding
of its mechanism of action, as well as a knowledge of how it is most
effectively and safely used, with an eye to minimizing side effects.


Thyroid Function and Physiology
Before jumping right into a discussion of the use of thyroid hormone
for fat loss, a little review of thyroid function and physiology might
be in order. The thyroid gland secretes two hormones of interest to us,
thyroxine (T4) and triiodothyronine (T3). T3 is considered the physiologically
active hormone, and T4 is converted peripherally into T3 by the action
of the enzyme deiodinase. The bulk of the body's T3 (about 80%) comes
from this conversion. The secretion of T4 is under the control of Thyroid
Stimulating Hormone (TSH) which is produced by the pituitary gland. TSH
secretion is in turn controlled through release of Thyrotropin Releasing
Hormone which is produced in the hypothalamus. This is analogous to testosterone
production, where GnRH from the hypothalamus causes the pituitary to
release LH, which in turn stimulates the testes to produce testosterone.

In addition to T3, it has recently been recognized that there exist two
additional active metabolites of T3: 3,5 and 3,3' diiodothyronines, which
we will collectively call T2. Studies have shown that 3,3'-T2 may be
more effective in raising resting metabolic rate when hypothyroid subjects
are treated with T3, than when normal (euthyroid) subjects are given
T3. Therefore in normal subjects 3,5-T2 may be the principal active metabolite
of T3 (1)

Like the hypothalamic-pituitary-gonadal axis, the thyroid gland is under
negative feedback control. When T3 levels go up, TSH secretion is suppressed.
This is the mechanism whereby exogenous thyroid hormone suppresses natural
thyroid hormone production. There is a difference though between the
way anabolic steroids suppress natural testosterone production and the
way T3 suppresses the thyroid. With steroids, the longer and heavier
the cycle is, the longer your natural testosterone is suppressed. This
is not the case with exogenous thyroid hormone.

An early study that looked at thyroid function and recovery under the
influence of exogenous thyroid hormone was undertaken by Greer (2). He
looked at patients who were misdiagnosed as being hypothyroid and put
on thyroid hormone replacement for as long as 30 years. When the medication
was withdrawn, their thyroids quickly returned to normal.

Here is a remark about Greer's classic paper from a later author:

"In 1951, Greer reported the pattern of recovery of thyroid function
after stopping suppressive treatment with thyroid hormone in euthyroid
[normal] subjects based on sequential measurements of their thyroidal
uptake of radioiodine. He observed that after withdrawal of exogenous
thyroid therapy, thyroid function, in terms of radioiodine uptake, returned
to normal in most subjects within two weeks. He further observed that
thyroid function returned as rapidly in those subjects whose glands had
been depressed by several years of thyroid medication as it did in those
whose gland had been depressed for only a few days" (3)

These results have been subsequently verified in several studies.(3)(4)
So contrary to what has been stated in the bodybuilding literature, there
is no evidence that long term thyroid supplementation will somehow damage
your thyroid gland. Nevertheless, most bodybuilders will choose to cycle
their T3 (or T4 which in most cases works just as well) as part of a
cutting strategy, since T3 is catabolic with respect to muscle just as
it is with fat. As previously mentioned, long term T3 induced hyperthyroidism
is also catabolic to bone as well as muscle.

The proviso about T4 vs T3 for weight loss alluded to above needs some
elaboration. There have been a number of studies that have shown that
during starvation, or when carbohydrate intake is reduced to approximately
25 to 50 grams per day, levels of deiodinase decline, hindering the conversion
of T4 to the physiologically active T3.(5) From an evolutionary standpoint
this makes sense: during periods of starvation the body, teleologically
speaking, would like to reduce its basal metabolic rate to preserve fat
and especially muscle stores. However, a recent study demonstrating the
effectiveness and safety of the ketogenic diet for weight loss recorded
no change in circulating T3 levels.(6) So this issue not completely settled.
Nevertheless, persons contemplating thyroid supplementation during ketogenic
dieting might prefer T3 over T4 since the bulk of the research does suggest
a decline in the peripheral conversion of T4 to T3 during low carb dieting.

Now that we have reviewed a little about thyroid function, let's consider
just how it is that thyroid hormone exerts its fat burning effects.

Increased Oxidative Energy Metabolism
Thyroid hormone has long been recognized as a major regulator of the
oxidative metabolism of energy producing substrates (food or stored substrates
like fat, muscle, and glycogen) by the mitochondria. The mitochondria
are often called the "cell's powerhouses" because this is where foodstuffs
are turned into useful energy in the form of ATP. T3 and T2 increase
the flux of nutrients into the mitochondria as well as the rate at which
they are oxidized, by increasing the activities of the enzymes involved
in the oxidative metabolic pathway. The increased rate of oxidation is
reflected by an increase in oxygen consumption by the body.

T3 and T2 appear to act by different mechanisms to produce different
results. T2 is believed to act on the mitochondria directly, increasing
the rate of mitochondrial respiration, with a consequent increase in
ATP production. T3 on the other hand acts at the nuclear level, inducing
the transcription of genes controlling energy metabolism, primarily the
genes for so-called uncoupling proteins, or UCP (see below). The time
course of these two actions is quite different. T2 begins to increase
mitochondrial respiration and metabolic rate immediately. T3 on the other
hand requires a day or longer to increase RMR since the synthesis of
new proteins, the UCP, is required (1).

There are a number of putative mechanisms whereby T2 is believed to increase
mitochondrial energy production rates, resulting in increased ATP levels.
These include an increased influx of Ca++ into the mitochondria, with
a resulting increase in mitochondrial dehydrogenases. This in turn would
lead to an increase in reduced substrates available for oxidation. An
increase in cytochrome oxidase activity has also been observed. This
would hasten the reduction of O2, speeding up respiration. These and
a number of other proposed mechanisms for the action of T2 are reviewed
by Lannie et al.(7)

What is the fate of the extra ATP produced during hyperthyroidism? There
are a number of ways by which the increased ATP promotes an increase
in metabolic activity, including the following:

Increased Na+/K+ATPase. This is the enzyme responsible for controlling
the Na/K pump, which regulates the relative intracellular and extracellular
concentrations of these ions, maintaining the normal transmembrane ion
gradient. Sestoft(7) has estimated this effect may account for up to
to 10% of the increased ATP usage.


Increased Ca++-dependent ATPase. The intracellular concentration of calcium
must be kept lower than the extracellular concentration to maintain normal
cellular function. ATP is required to pump out excess calcium. It has
been estimated that 10% of a cell's energy expenditure is used just to
maintain Ca++ homeostasis. (1)


Substrate cycling. Hyperthyroidism induces a futile cycle of lipogenesis/lipolysis
in fat cells. The stored triglycerides are broken down into free fatty
acids and glycerol, then reformed back into triglycerides again. This
is an energy dependent process that utilizes some of the excess ATP produced
in the hyperthyroid state (8). Futile cycling has been estimated to use
approximately 15% of the excess ATP created during hyperthyroidism (8)


Increased Heart Work. This puts perhaps the greatest single demand on
ATP usage, with increased heart rate and force of contraction accounting
for up to 30% to 40% of ATP usage in hyperthyroidism (9)



Mitochondrial Uncoupling


As mentioned, the mitochondria are often characterized as the cell's
powerhouse. They convert foodstuffs into ATP, which is used to fuel all
the body's metabolic processes. Much research suggests that T3, like
another much more potent agent DNP, has the ability to uncouple oxidation
of substrates from ATP production. T3 is believed to increase the production
of so called uncoupling proteins. Uncoupling protein (UCP) is a transporter
family that is present in the mitochondrial inner membrane, and as its
name suggests, it uncouples respiration from ATP synthesis by dissipating
the transmembrane proton gradient as heat. Instead of useful ATP being
produced from energy substrates, heat is generated instead. There are
conflicting studies about the importance of T3 induced uncoupling. Animal
studies have demonstrated an actual increase in ATP production commensurate
with increased oxygen consumption as we discussed above. Other studies
in humans have shown that in fact uncoupling in skeletal muscle does
occur. This would contribute to T3 induced thermogenesis, with a resulting
increase in basal metabolic rate.(10)

To make up for the deficit in ATP production (as well as provide fuel
for the extra ATP production discussed above) more substrates must be
burned for fuel, resulting in fat loss. Unfortunately, along with the
fat that is burned, some protein from muscle is also catabolized for
energy. This is the downside of T3 use, and the reason many people choose
to use an anabolic steroid or prohormone during a T3 cycle to help preserve
muscle mass. Studies have shown this to be an effective strategy (11).
(Muscle glycogen is also more rapidly depleted, and less efficiently
stored during hyperthyroidism. This may account for some of the muscle
weakness generally associated with T3 use.)

Countering T3 induced muscle loss with AAS or prohormones makes sense
from a physiological viewpoint as well. Thyroid hormone muscle protein
breakdown is mainly mediated via the so-called ubiquitin-proteasome pathway.
(12). (There are several independent metabolic pathways of protein breakdown
in the body. For instance, another pathway, the lysosomal pathway, is
responsible for the accelerated rate of muscle protein breakdown during
and after exercise.) Testosterone administration has been shown to decrease
ubiquitin-proteasome activity. (13) So AAS specifically target the muscle
protein breakdown process stimulated by T3.

What may not be an effective strategy to maintain muscle mass during
a T3 cycle is the use of exogenous growth hormone (GH). Studies have
shown that when GH and T3 are administered concurrently, the increased
nitrogen retention normally associated with GH use is abolished. This
has been attributed to the observation that T3 increases levels of insulin
like growth factor binding protein, reducing the bioavailability of igf-
1 (14). Nevertheless, GH has fat burning properties independent of igf-
1, so using GH with T3 would act additively to speed fat burning, but
with little if any preservation of lean body mass. So again, if GH is
used in conjunction with T3, anabolic steroid/prohormone use would be
indicated.



Andregenic Receptor Modulation


Administration of T3 has been shown to upregulate the so-called beta
2 adrenergic receptor in fat tissue. What is the significance of this
effect for fat loss? Before fat can be used as fuel, it must be mobilized
from the fat cells where it is stored. An enzyme called Hormone Sensitive
Lipase (HSL) is the rate-controlling enzyme in lipolysis, or fat mobilization.
The body produces two catecholamines, epinephrine and norepinephrine,
which bind to the beta 2 receptor and activate HSL. The upregulation
of the beta 2 receptor due to T3 results in an increased ability of catecholamines
to activate HSL, leading to increased lipolysis.

Bodybuilders often use drugs like clenbuterol, which bind to the beta
2 receptors and activate them in the same way as the body's endogenous
catecholamines. The use of clenbuterol along with T3 can produce an additive
lipolytic effect: T3 increases the number of receptors, while clenbuterol
binds to the receptors activating HSL and increasing lipolysis. Since
clenbuterol itself downregulates the beta 2 receptor, most bodybuilders
use clenbuterol in a two week on/ two week off cycle, the rationale being
that this minimizes downregulation and allows receptor recovery. Another
option is to use the antihistamine ketotifen concurrently with the clenbuterol.
Studies have shown that ketotifen attenuates the beta 2 receptor downregulation
caused by clenbuterol (15). Moreover, research in AIDS patients has shown
that ketotifen blocks the production of the proinflammatory and catabolic
cytokine TNF-alpha (16). This may be of relevance to bodybuilders since
there is evidence showing TNF lowers both testosterone and IGF-1 levels
quite significantly (17) (18), while strenuous exercise elevates TNF
levels. (19)

Besides increasing beta 2 receptor density in adipose tissue, T3 upregulates
this receptor in human skeletal muscle (12). This has some very intriguing
if somewhat speculative implications for the combined use of clenbuterol
and T3. Animal studies have shown that catecholamines, particularly clenbuterol,
inhibit Ca++ dependent skeletal muscle proteolysis (20). Like the lysosomal
and ubiquitin-proteasome pathways discussed above, Ca++ regulated proteolysis
is yet another way for the body to degrade muscle protein. Again the
implications are enticing: Increased beta 2 receptor density from T3
use, coupled with the beta 2 agonist clenbuterol, could slow this pathway
of muscle catabolism.

Another adrenergic receptor important to lipolysis is the alpha 2 receptor,
which impedes fat mobilization by counteracting the effects of the beta
2 receptor. There are some conflicting studies about the effects of T3
on the alpha 2 receptor, with studies showing either a downregulation
(21) or no effect (22). If T3 does in fact downregulate alpha 2 receptors,
this would further aid lipolysis.

Studies in rats have shown that inducing hyperthyroidism increases the
lipolytic beta 3 receptor density in white adipose tissue by 70% (23).
Beta 3 receptors are abundant in human white adipose tissue as well,
and if T3 administration has the same effect in humans, this could could
contribute significantly to T3 induced fat loss. This might also argue
for taking a currently available beta 3 agonist such as octopamine along
with T3 and perhaps clenbuterol.



Decreased Phosphodiesterase Expression


In hyperthyroid patients as well as in normal subjects given T3, levels
of the enzyme phosphodiesterase are lowered in fat cells (20). When lipolytic
hormones like epinephrine (adrenaline) bind to the beta 2 receptor described
above, they initiate a signaling cascade mediated by the so called “second
messenger” cyclic AMP (cAMP). cAMP in turn acts on other cellular enzymes
to initiate and maintain lipolysis. The original signal is terminated
when cAMP is degraded by the enzyme phosphodiesterase. Clearly, maintaining
elevated cAMP levels, by lowering phosphodiesterase concentrations with
T3, will prolong lipolysis.

As an aside, caffeine is thought to exert at least a portion of its lipolytic
action by lowering phosphodiesterase in fat cells. Interestingly, Viagra
and Cialis are also phosphodiesterase inhibitors but their action seems
to be limited to relaxing vascular smooth muscles.



Increased Growth Hormone Secretion


In vitro, animal, and human studies have all demonstrated that T3 administration
increases growth hormone production. (24)(25) Since GH is calorigenic
aside from any increase in igf-1, elevated GH may contribute to some
of the fat burning associated with T3 administration. This effect may
obviate the need for the use of expensive recombinant HGH, as mentioned
above.



Decreased Insulin Secretion


Insulin is well known as a lipogenic hormone. It promotes fat storage
by facilitating the uptake of fatty acids by adipocytes, and reducing
lipid oxidation in muscle tissue. Several studies have shown that thyroid
hormone is associated with glucose intolerance resulting from decreased
glucose stimulated insulin secretion (26).

This defect in insulin secretion is believed to result from an increase
in the rate of apoptosis (programmed cell death) of pancreatic beta cells
as a direct effect of thyroid hormone excess.(27) This process is reversible,
since when thyroid hormone is withdrawn the rate of beta cell replication
increases until homeostasis returns. However, there are conflicting studies
regarding the effects of T3 on insulin. For example, Dimitriadis et al
(28) showed a decrease in glucose stimulated insulin secretion, consistent
with (25), but an increase in basal insulin. They also observed increased
insulin clearance, with a compensatory increase in basal insulin secretion.

So if in fact the hyperthyroid state is associated with lower insulin
levels, this could explain a portion of hyperthyroid stimulated lipolysis.
The obvious downside here is that insulin is also an anabolic hormone.
Basal insulin concentration is thought to limit the action of the ubiquitin-
proteasome degradative pathway of muscle protein breakdown (29). Of course
supplementing with insulin during T3 use would be counterproductive.
However, as mentioned above, anabolic steroids inhibit ubiquitin-proteasome
activity, so their use could counter any loss in muscle anabolism resulting
from a drop insulin levels.



The Future
As mentioned at the beginning of this article, a major roadblock in the
adoption of T3 by the medical community as an antiobesity agent is its
deleterious effect on the heart. Recent research has identified two isoforms
of the thyroid hormone receptor, TRalpha and TRbeta. The TRalpha-form
may preferentially regulate the heart rate, and an experimental agent,
GC-1, has been developed that selectively binds the TRbeta receptor,
with minimal effects on the heart (30). The distribution and actions
of TRalpha and TRbeta throughout the body are not yet well characterized.
However should it turn out that TRalpha is specific to the heart, then
drugs like GC-1 may turn out to be effective fat burning agents with
a much safer profile that T3 or T4.

One alleged “futuristic” agent that is here now is T2, or 3,5-Di-iodo-
L-thyronine, the T3 metabolite discussed above. Unfortunately, this product
does not live up to its hype. It has been claimed to be as or more effective
that T3 for fat burning with minimal suppression of endogenous thyroid
production. Regarding the relative effectiveness of T2 as a lipolytic
agent, and its effect on TSH, this topic was thoroughly covered in a
recent article by Bryan Haycock in Muscle Monthly:

All of my research into this subject has led me to the same conclusion
reached by Mr. Haycock. That is, T2 is only slightly less suppressive
of TSH than is T3, and only packs a portion of the lipolytic punch of
T3, with no ability to increase the expression of the UCPs, which is
a major determinant of the action of thyroid hormone.

Summary

We have discussed a number of ways by which T3, and its active metabolite
T2 act to increase resting energy expenditure. Also discussed were some
drawbacks of T3 use, such as cardiac stress, as well as the potential
loss of muscle mass. It is ironic that the latter may be of more concern
to many bodybuilders that the other more serious potential impacts on
health. Nevertheless, used moderately and for short periods (a couple
of months or less) in people with no preexisting cardiovascular disease
T3 has a relatively safe medical profile, compared to other lipolytic
agents like DNP. Perhaps most importantly we have presented substantial
evidence that even the long-term use of supraphysiological levels of
T3 does not damage the thyroid gland.

[house1]

thanks bro

will bag the t3 for now

[jyzza]

House...post some pics bro......I want to see how you are coming along.....

[Bouncer]

Originally posted by house1
thanks bro

will bag the t3 for now

I dont know house, maybe you should think about it. I have heard that combing GH and T-3 melts fat off like butter. I would like to hear doom's thoughts on this.

[house1]

bump for doom, definitley would like to hear more on this


jyzza, i was going to today but was not happy with them, need to get the wife to take them holding the camera and trying to shoot yourself in the mirror is a pain in the ass lol . will try and get some done this weekend

not happy though, i put on 10 lbs since i took a break from my diet ummm 2 weeks ago lol

going back on diet monday

[Bouncer]

Originally posted by house1
bump for doom, definitley would like to hear more on this


jyzza, i was going to today but was not happy with them, need to get the wife to take them holding the camera and trying to shoot yourself in the mirror is a pain in the ass lol . will try and get some done this weekend

not happy though, i put on 10 lbs since i took a break from my diet ummm 2 weeks ago lol

going back on diet monday

its the slin bro. drop the slin for now and im telling you the fat will go.

[ShawnRay]

My .02

It is a must to run very low doses of T3 with your HGH because it will eventually slow your thyroid down. T3 at 12.5 to 25mcgs will aid in protein synthesis.....Just add as little as 12.5mcgs to your Gh and Slin and your body comp will change up nicely....SR

[house1]

bouncer,

good point on the slin bro

going to leave it alone for a bit

[house1]

bump

[big N]

i second the 12.5 mcg .not enough to shut u dwon and not enough to hinder gh levels ,

[scotty2]

GH will eventually slow the thyroid. It has been suggested to introduce some T3 a little ways into your GH regiment.

[Doom]

my bad folks, went away last minute over the weekend

House it all depends on what you feel like using the T3 for, its leaning effects, or to help ease thyroid supression. As mentioned, eventually GH will sslow thyroid production down, but its generally only after long peroids of time. Now if you feel as though you want an extra boost for protein synthesis, as well as lean out, you can go as high as 62.5mcg-100mcg. Pyramiding the dose, 5 days, then 7, then a max of 10 days at the highest dose, and then back on down the same way you came up. You can do this in rotations of 6 weeks on, and 8 weeks off.

If you hold fat easily like I do, then yes you must watch the slin, but use highre than 12.5 mcg

And side note for Big N, one tab of T3 is enough to upset the balance of the tyroid, Ive never heard of it happening, buit anything is possible

[big N]

yeah one tab bro ,12.5 is half a tab .tyhat works good for me raing my slin sensetivity enough to where im not as tired and incresed preotein synthesis ,aslo it helsp me keep some stubborn fat away at times.

[house1]

thanks doom