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Wow! EGCG and Myostatin

Was doing some research on natural myostatin inhibitors today and this is what i got:

06-04-2007, 11:57 AM
I just read an abstract on Pubmed that indicates EGCG (from green tea) inhibits Smad3 and promotes Smad7 signalling. From what I understand myostatin exerts it’s negative effect on muscle growth via Smad3 signalling, and Smad7 actually inhibits myostatin activity. Could EGCG act as a natural myostatin inhibitor? Any input from the science minded among you would be welcome.


Dr.Dave106-05-2007, 05:26 AM
I just read an abstract on Pubmed that indicates EGCG (from green tea) inhibits Smad3 and promotes Smad7 signalling. From what I understand myostatin exerts it’s negative effect on muscle growth via Smad3 signalling, and Smad7 actually inhibits myostatin activity. Could EGCG act as a natural myostatin inhibitor? Any input from the science minded among you would be welcome.

myostatin and Smads
1: Cytokine. 2004 Jun 21;26(6):262-72. Links
Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism.
Zhu X, Topouzis S, Liang LF, Stotish RL.

As a member of the TGF-beta superfamily, myostatin is a specific negative regulator of skeletal muscle mass. To identify the downstream components in the myostatin signal transduction pathway, we used a luciferase reporter assay to elucidate myostatin-induced activity. The myostatin-induced transcription requires the participation of regulatory Smads (Smad2/3) and Co-Smads (Smad4). Conversely, inhibitory Smad7, but not Smad6, dramatically reduces the myostatin-induced transcription. This Smad7 inhibition is enhanced by co-expression of Smurf1. We have also shown that Smad7 expression is stimulated by myostatin via the interaction between Smad2, Smad3, Smad4 and the SBE (Smad binding element) in the Smad7 promoter. These results suggest that the myostatin signal transduction pathway is regulated by Smad7 through a negative feedback mechanism.

It seems that if what the researchers found was true that might happen. However, based on the huge numbers of individuals that use EGCG w/o seeing any large effect on muscle mass this seems unlikely. Can you share the pubmed reference as I would be interested to see the article.

And this is the amazing bit!

EGCG Research: Muscular Dystrophy and EGCG research
Duchenne/Becker Muscular Dystrophy (DBMD or DMD), is an inherited genetic condition causing muscles to deteriorate. It occurs in approximately 500 newborn boys in the United States every year. It is extremely rare for a girl to have muscular dystrophy, although women can carry the gene.

The boys are usually diagnosed between the age of 3 and 6 years old, and by age 12 are usually unable to walk. It is almost always fatal in the teenage years or by the early 20’s.

There is currently no cure for muscular dystrophy, but steroids have been used to slow the muscular degeneration (CDC).

Now a new study may open doors for more research on muscular dystrophy.

Using an animal model of muscular dystrophy, researchers injected EGCG, the primary antioxidant catechin in green tea, under the skin of the backs of mice. This was done 4 times a week for 8 weeks.

Compared to controls, the EGCG injections lowered the serum creatine kinase levels to normal. Lipofuscin granules in the muscles were reduced by 50%. Lipofuscin, also called liver spots when found on the skin, is a fatty pigment considered a sign of early aging.

The EGCG research mice also had almost double the amount of normal muscle tissue, with a substantial reduction in damaged muscle and connective tissue. The strength of the muscles also increased to almost normal (Nakae Y, Histochemistry and Cell Biology, 2008).

This research is considered very preliminary and further studies are needed to know if EGCG benefits would be long term, or would be useful for people with muscular dystrophy.

They could be on to something.

EGCG-the new Surge??

That dog looks like it could take on a fucking lion, I want one.

I’d be kind of bummed out if a true myostatin inhibitor was produced.

Muscle building would be so easy and unsatisfying…

There are always the questions of dosages and bio-availability. Also, what about the side effects of high EGCG dosages? Would a SERM be necessary along side such presumably high dosages?

There is another short term study out that shows mice when injected with egcg lost up to 21 percent bodyfat, particuarly from the abdominal region and just under the skin.

[quote]LiftSmart wrote:
I’d be kind of bummed out if a true myostatin inhibitor was produced.

Muscle building would be so easy and unsatisfying…[/quote]

Read up on the history of Biotest supplements and you might be bummed. I’m not sure anymore why they discontinued it.

[quote]yorik wrote:

Read up on the history of Biotest supplements and you might be bummed. I’m not sure anymore why they discontinued it.[/quote]

Well… because it didn’t work. That seems to be the general consensus.

It has poor bioavailability when taken orally. These studies were done using injections of the pure extract egcg.

[quote]etaco wrote:
There are always the questions of dosages and bio-availability. Also, what about the side effects of high EGCG dosages? Would a SERM be necessary along side such presumably high dosages?[/quote]

Here is the actual study abstract:

Dystrophic muscles suffer from enhanced oxidative stress. We have investigated whether administration of an antioxidant, epigallocatechin-3-gallate (EGCG), a component of green tea, reduces their oxidative stress and pathophysiology in mdx mice, a mild phenotype model of human Duchenne-type muscular dystrophy. EGCG (5 mg/kg body weight in saline) was injected subcutaneously 4�? a week into the backs of C57 normal and dystrophin-deficient mdx mice for 8 weeks after birth. Saline was injected into normal and mdx controls. EGCG had almost no observable effects on normal mice or on the body weights of mdx mice. In contrast, it produced the following improvements in the blood chemistry, muscle histology, and electrophysiology of the treated mdx mice. First, the activities of serum creatine kinase were reduced to normal levels. Second, the numbers of fluorescent lipofuscin granules per unit volume of soleus and diaphragm muscles were significantly decreased by about 50% compared to the numbers in the corresponding saline-treated controls. Third, in sections of diaphragm and soleus muscles, the relative area occupied by histologically normal muscle fibres increased significantly 1.5- to 2-fold whereas the relative areas of connective tissue and necrotic muscle fibres were substantially reduced. Fourth, the times for the maximum tetanic force of soleus muscles to fall by a half increased to almost normal values. Fifth, the amount of utrophin in diaphragm muscles increased significantly by 17%, partially compensating for the lack of dystrophin expression.

Here is what i have concluded from the abstract of the study:

There was no effect on normal mice.
The dosing was 5mg per kg of bodyweight. So for an 80kg man 400mg would need to be injected 4 times a week.

If you didn’t want to inject you would have to drink 40 cups of green tea a day! This is because of there being around 100mgs of egcg in an average cup with only 20 percent be digested.

But as i said it seems it had no effect on normal mice, but i could be wrong.

I have found out from another study that drinking it with citric juice, ascorbic acid or vitamin c dramatically increases bioavailability.

[quote]Schmazz wrote:
yorik wrote:

Read up on the history of Biotest supplements and you might be bummed. I’m not sure anymore why they discontinued it.

Well… because it didn’t work. That seems to be the general consensus.[/quote]

And yet they published this back in 2002…

http://www.T-

Nation.com/article/product/new_myostat_study_pro

ves_hypertrophy_in_humans&cr=

This thread explains what happened to Myostat. (scroll down the page)

http://www.T-Nation.com/tmagnum/readTopic.do?id=824825

Myostat was based on CSP-3, not ECGC, so it was a different beast. (Unless the two are related compounds.) It would be interesting to combine CSP-3 and ECGC and see what happens. (Anaconda v2 anybody?)

After 6 years I would think it might be time to re-release a CSP-3 product and avoid the earlier marketing mistakes.

ERROR:

The tea calculations were wrong. Theres only around 25mgs of egcg in a cup. Apparently only up to 5 percent of egcg gets into the blood after digestion and liver clearance. Near on 400 cups worth.

The extract option:

You can get 40-50 percent egcg green tea extract. Even then you would need to eat 8 grams a day. Apparently it absorbs well in the mouth lining though so that could be an option though its meant to taste bad.

OTOH, there’s this study that says CSP-3 does NOT work.

Who knows?

Since I doubt we will see much published research on the effects on normal subjects beyond this it would be interesting to see if the dosing threshold is higher for normals or more generally why they didnt show changes in this study. So if some people want to help…

Too bad we can’t get together amateur clinical trials. I’d even break out my stats package for it.

If 5mg/kg was the dosage in mice it should be considerably lower in humans due to the metabolic differences I believe. Even at that dosage and assuming ~20% oral bioavailability it should be reasonably doable if anyone wants to try.

It would be useful before embarking to find the side effects (obviously) of that range and the half life of the relevant constituents and metabolites.

[edit]
Well there goes that with the adjusted figures.

Why doesn’t someone try it on their dog? Any takers?

[quote]big balls wrote:
ERROR:

The tea calculations were wrong. Theres only around 25mgs of egcg in a cup. Apparently only up to 5 percent of egcg gets into the blood after digestion and liver clearance. Near on 400 cups worth.

The extract option:

You can get 40-50 percent egcg green tea extract. Even then you would need to eat 8 grams a day. Apparently it absorbs well in the mouth lining though so that could be an option though its meant to taste bad.[/quote]

Sublingual absorption passes the first digestion so less would be broken down by the stomach.

[quote]etaco wrote:
Since I doubt we will see much published research on the effects on normal subjects beyond this it would be interesting to see if the dosing threshold is higher for normals or more generally why they didnt show changes in this study. So if some people want to help…

Too bad we can’t get together amateur clinical trials. I’d even break out my stats package for it.

If 5mg/kg was the dosage in mice it should be considerably lower in humans due to the metabolic differences I believe. Even at that dosage and assuming ~20% oral bioavailability it should be reasonably doable if anyone wants to try.

It would be useful before embarking to find the side effects (obviously) of that range and the half life of the relevant constituents and metabolites.

[edit]
Well there goes that with the adjusted figures.[/quote]

Yes altough only 20 percent passes through the intestines even less makes it through because of the liver.

[quote]big balls wrote:
etaco wrote:
There are always the questions of dosages and bio-availability. Also, what about the side effects of high EGCG dosages? Would a SERM be necessary along side such presumably high dosages?

Here is the actual study abstract:

Dystrophic muscles suffer from enhanced oxidative stress. We have investigated whether administration of an antioxidant, epigallocatechin-3-gallate (EGCG), a component of green tea, reduces their oxidative stress and pathophysiology in mdx mice, a mild phenotype model of human Duchenne-type muscular dystrophy. EGCG (5 mg/kg body weight in saline) was injected subcutaneously 4�? a week into the backs of C57 normal and dystrophin-deficient mdx mice for 8 weeks after birth. Saline was injected into normal and mdx controls. EGCG had almost no observable effects on normal mice or on the body weights of mdx mice. In contrast, it produced the following improvements in the blood chemistry, muscle histology, and electrophysiology of the treated mdx mice. First, the activities of serum creatine kinase were reduced to normal levels. Second, the numbers of fluorescent lipofuscin granules per unit volume of soleus and diaphragm muscles were significantly decreased by about 50% compared to the numbers in the corresponding saline-treated controls. Third, in sections of diaphragm and soleus muscles, the relative area occupied by histologically normal muscle fibres increased significantly 1.5- to 2-fold whereas the relative areas of connective tissue and necrotic muscle fibres were substantially reduced. Fourth, the times for the maximum tetanic force of soleus muscles to fall by a half increased to almost normal values. Fifth, the amount of utrophin in diaphragm muscles increased significantly by 17%, partially compensating for the lack of dystrophin expression.
[/quote]

Can you post the citation into for this one please so I can look up the full text? I’m interested in the implications of the 4 times per week dosing protocol.