INFO on TTA

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Tetradecylthioacetic acid (TTA) is a novel thio-fatty acid which cannot undergo beta-oxidation. It induces apoptosis in IPC-81 leukemia cells via depolarization of mitochondrial membrane potential and inhibits glioma cell proliferation. TTA completely prevents high-fat diet induced insulin resistance and adiposity in Wistar rats. Activates rodent PPARs with rank order PPAR α > PPAR Δ > PPAR γ.


Tetradecylthioacetic acid (TTA) which can not be β-oxidized, lowers plasma VLDL-triacylglycerol (TG) and LDL-cholesterol (Chol). Increased mitochondrial β-oxidation with a concomitant decrease in TG synthesis and secretion, seems to be the primary mechanism underlying the hypotriglyceridemic effect not only of TTA but also of w-3 fatty acids as well as fibrates in rats, rabbits, dogs and possibly also in humans. TTA is an inhibitor of HMG-CoA reductase. We have generated results both in vivo and in vitro that present evidence that TTA besides being a lipid-lowering agent, also possesses antioxidant properties. First, TTA inhibits the oxidative modification of LDL, which is considered as the key step in the formation of foam cells and in initiation and progression of atherosclerotic plaque.

 

Also TTA changes the antioxidant defense system in a beneficial way i.e. glutathion (GSH) is increased, the total antioxidant status is elevated and TBARS are decreased. Second, TTA has an alive oil-effect since the plasma was enriched with oleic acid (18:1 n-9) and a 2-desaturated metabolite of TTA. This was due to upregulation of the hepatic enzyme 2-desaturase gene expression. Third, TTA lowers the plasma homocysteine level and inhibits restenosis. Fourth, TTA reduces the proliferation of smooth muscle cells. In conclusion, TTA is a hypolipidemic drug but also a new antioxidant. This novel bioactive compound is promising as a new therapeutic drug against atherosclerosis as it changes the plasma profile from atherogenic to cardioprotective.
 
Enigma76

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Fourth, TTA reduces the proliferation of smooth muscle cells.
Where did you get this from? This is a key point that I've been wanting to look into, as I noticed the more I read about TTA the more it seems to stop cell proliferation throughout. These cramps that people are getting might be dual-caused...electrolyte imbalances and an inability for the body to correctly repair the muscles? This is obviously straight out of my ass, but I'm wondering if toning down the weight training might be a good idea during TTA use...link to a study showing that would be great please.

Also, of note to add is that TTA causes a serious shift in omega-3 concentrations, lowering them in some places and raising them in the heart/diaphram (I believe diaphram...kind of putting a bunch of studies together in my head here). One study said that it resulted probably in a change in membrane makeup due to the influx of omega-3s. Kind of striking seeing that it shifted omega-3 to those muscles that are constantly moving (involuntary ones, like the heart/diaphram, etc).

And, since this is a TTA info thread, I'd like to add some more tidbits.

TTA has been postulated to exert its hypolipidemic effects through "plasma fatty acid drainage", in which the liver turns into a fatty acid oxidizing machine. Plasma fatty acid concentration decreases markedly. The mitochondria in the liver are both enlarged and proliferated compared to controls, which correlates with the increase in fatty acid oxidation. Mitochondria in smooth muscle are also enlarged, both in type1 and type2 muscle fibers.

TTA possibly remains in the body in trace amounts for 6 weeks (this was done in a pig study, so I'm not sure if it can be exactly translated), with more than half of the compound remaining 2 weeks post-dose.

It lowers IL-2 and raises IL-10, resulting in a more non-inflammatory environment. It also has other cytokine effects.

EDIT I'd also like to add (since others might not read the other TTA thread) that because of the proposed hypothesis as to how TTA exerts its hypolipidemic effects (plasma fatty acid drainage by the liver) a compound (or combination thereof) which helps liberate fatty acids from adipocytes (such as ephedrine, forskolin, albuterol/clenbuterol, etc etc) might be of use with TTA, as they would provide a constant fatty acid fuel source to be used by the liver.

It is my hypothesis alone with this, but I think it makes sense. Forskolin will liberate fatty acids from the adipocytes, which will go right back in unless utilized for energy. With TTA, the liver burns plasma fatty acids readily, lowering the plasma concentration. Why not combine the two?
 

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There is a thread on Avant that discusses how fat loss as a whole is limited by the rate of oxidation rather than rate of lipolysis.

Use of these extra "liberators" might not be needed as lipolysis appears to remain pretty excessive to oxidation. Given TTA these substances might be warranted but I would doubt it given the side effect profiles of some of the above (clenbuterol, probably albuterol, ephedrine to an extent). I'll try to dredge up the link when I've got some more time.

Kevin.

Edit:

Was actually able to find something when I wanted to this time.

http://forum.avantlabs.com/index.php?showtopic=11624&hl=debating+my+lipolysis
 
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Also, of note to add is that TTA causes a serious shift in omega-3 concentrations, lowering them in some places and raising them in the heart/diaphram
Is that a good or bad thing?
 
Enigma76

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but I would doubt it given the side effect profiles of some of the above (clenbuterol, probably albuterol, ephedrine to an extent).

http://forum.avantlabs.com/index.php?showtopic=11624&hl=debating+my+lipolysis
Could you clarify what you mean here?


Oxidation clearly seems to be the rate limiting step in fat-loss. However, TTA clearly increases fatty acid oxidation, to a very large extent. I guess I dont understand why one wouldnt benefit from a lipolysis agent when coadministered with TTA? It just seems like a natural 1+1 here...

I'm not talking about in a non-TTA individual, as then of course any increase in lipolysis will be futile without a corresponding increase in energy use...

Bottom line is I'm just trying to think of ways to find some synergy with TTA, as I think it is one of the best compounds out there right now. Cardioprotective, antioxidant, anti-inflammatory...
 
Robboe

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Where did you get this from? This is a key point that I've been wanting to look into, as I noticed the more I read about TTA the more it seems to stop cell proliferation throughout. These cramps that people are getting might be dual-caused...electrolyte imbalances and an inability for the body to correctly repair the muscles? This is obviously straight out of my ass, but I'm wondering if toning down the weight training might be a good idea during TTA use...link to a study showing that would be great please.
Nice theory, but you do know what smooth muscle cells are right? It not voluntary muscle - ie you don't control it.

There may yet be validity into TTA affecting skeletal muscle repair, but i'm not sure that there is any research into it.
 
Enigma76

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Nice theory, but you do know what smooth muscle cells are right? It not voluntary muscle - ie you don't control it.

There may yet be validity into TTA affecting skeletal muscle repair, but i'm not sure that there is any research into it.
I'm just trying to find out why this cramping occurs. I hadnt previously seen anything about muscle cell proliferation being affected however. While smooth muscle wouldnt explain striated muscle, there might be a link somehow/somewhere. In general it just seems that TTA is very anti-proliferative of cells in general, with most studies done on cancer cells. Striated muscle needs to proliferate to repair, right?

There doesnt look like theres any research into it; there also isnt any research explaining any electrolyte imbalance or showing cramping in general (for the AIDS patient studies) as a side effect.

I do see shifts in interleukin concentrations, but I dont know enough about them to figure any of it out.
 
Robboe

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:)

I think it's a combination of electrolyte imbalance and a build-up of waste product from accelerated fat burning. I'm just not sure which waste product. If i find something solid on this, i'll try and find some sort of buffering agent.

The electrolyte imbalance is definately part of the issue though. The water retention while "on" and the fact that many offset the cramping by supplementing with magnesium and potassium suggests this.
 
Enigma76

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You think the interleukins might have anything to do with the electrolyte imbalance? I know certain ILs can influence ion channels (I guess changing the amount of inter/intra cellular ions), but as I said I dont know at all anything about them. Prior to two days ago I didnt know what an interleukin was.

Also, what are your thoughts to using a lipolytic agent to increase substrate for these new, plentiful megamitochondrion we are making with TTA?
 
Robboe

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You think the interleukins might have anything to do with the electrolyte imbalance? I know certain ILs can influence ion channels (I guess changing the amount of inter/intra cellular ions), but as I said I dont know at all anything about them. Prior to two days ago I didnt know what an interleukin was.
Honestly, i dunno. I know little about interleukins, other than they are involved in the immune response and used by white blood cells as a means of communication.

I wouldn't expect this to cause the electrolyte imbalance though. I expect the fact that TTA appears to completely alter the way the cell is regulated to cause this. It clearly upsets the sodium/potassium pump.

Also, what are your thoughts to using a lipolytic agent to increase substrate for these new, plentiful megamitochondrion we are making with TTA?
It's not just the mega-mitochondria to consider. TTA also proliferates peroxisomes, and these metabolise moretypes of fat ty chains than mitochondria and don't require as many enzymes to do it.

Ironically, the mega-mito's increased endurance in rats. In humans, TTA seems to hinder endurance quite significantly.

Anyhoo, it's been a while since i read any research on TTA, but i'm pretty sure there is evidence that it helps liberate fat itself, also. That said, using ephedrine wouldn't be a bad thing as such because it targets another fat burning pathway that TTA doesn't (adrenergic system).

Clenbuterol might not be the best idea though, because it depletes taurine from the liver, and taurine is pretty helpful for aiding cellular uptake. As i recall, taurine is also important for ensuring the calcium channels in muscle cells are hunky-dory. If not, you're looking at cramp city a whole lot quicker.
 

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:goodpost: liking the info, I'm getting some ideas
 

kdent7

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Could you clarify what you mean here?

Oxidation clearly seems to be the rate limiting step in fat-loss. However, TTA clearly increases fatty acid oxidation, to a very large extent. I guess I dont understand why one wouldnt benefit from a lipolysis agent when coadministered with TTA? It just seems like a natural 1+1 here...

I'm not talking about in a non-TTA individual, as then of course any increase in lipolysis will be futile without a corresponding increase in energy use...

Bottom line is I'm just trying to think of ways to find some synergy with TTA, as I think it is one of the best compounds out there right now. Cardioprotective, antioxidant, anti-inflammatory...
:goodpost: And I do like your ideas.

Enigma,

The rate of oxidation w/ TTA has not been quantified when compared to w/o TTA.

TTA clearly increases fatty acid oxidation, to a very large extent.
This really does not tell us anything relative to rate of lipolysis. I did not know that as Robboe pointed out that TTA could possibly increase lipolysis in and of itself. My question is, why add more to try to get to 2 when all that is needed is 1.

The increase in FFA could have deleterious effects on other factors, CV, Insulin Sensitivity etc...

The side effect stuff I mentioned is akin to what Robboe said about clen, although what he said was beyond what I could have come up with. It Can be some dangerous stuff and possibly not worth the risk when combined with a relatively new substance.

Bottom line, more doesnt always = better. Especially in a situation where we have no baseline.

Kevin.
 
Robboe

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Someone has used clenbuterol with MP before and did get bad cramping so i don't think his trial lasted all too long.

I see no huge problem with ephedrine with MP, but i'd go easy on the caffiene (just have it with your ephedrine and don't drink coffee or just have it from your coffee and with with your ephedrine) otherwise you're going to dehydrate cells and get cramping quicker.
 

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do any of you guys theorize that maybe blood becomes more acidic due to the huge release of fatty acids (along the lines of ketones causing ketoacidosis)
 
Robboe

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do any of you guys theorize that maybe blood becomes more acidic due to the huge release of fatty acids (along the lines of ketones causing ketoacidosis)
There's a hypothesis that TTA actually removes FFA from the bloodstream and dumps it directly into liver mitochondria, so i'd wager no.
 

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there goes my theory, however I have a great IV mix that I use for hangovers that would be great for electrolyte replenishment
 
Enigma76

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there goes my theory, however I have a great IV mix that I use for hangovers that would be great for electrolyte replenishment
Whatever the ratios, make sure its Ca heavy, as it seems that some find better results taking loads of Ca.

Just to note; upon reading Tolson's article over on 1fast about calcium, if there is an abundance of calcium in relation to vitamen D (or along these lines) lipolysis is increased somehow.
 
jmh80

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Bobo mentioned to me just to take Calcium supps by themselves.
The whole "vit. D is needed for absorption" was apparently a misguided interpretation of some really old research.

Unless you do not go outside, that is.
 

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TTA / Adiponectin

These metabolic effects sound quite similar to Adipnectin:

Adiponectin:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14624132&query_hl=3

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15149866&query_hl=3

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15892649&query_hl=3

EDIT: Should also decrease hepatic gluconeogenesis and increase fat oxidation.

One more interesting one:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15826474&query_hl=85


TTA:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15920037&query_hl=75

On a somewhat tangential note:

[SIZE=+1]Adiponectin and adiponectin receptors.

[/SIZE]Endocr Rev. 2005 May;26(3):439-51.

Kadowaki T, Yamauchi T.

Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Metabolic syndrome is thought to result from obesity and obesity-linked insulin resistance. Obesity in adulthood is characterized by adipocyte hypertrophy. Adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active "adipokines."Heterozygous peroxisome proliferator-activated receptor-gamma knockout mice were protected from high-fat diet induced obesity, adipocyte hypertrophy, and insulin resistance. Systematic gene profiling analysis of these mice revealed that adiponectin/Acrp30 was overexpressed. Functional analyses including generation of adiponectin transgenic or knockout mice have revealed that adiponectin serves as an insulin-sensitizing adipokine. In fact, obesity-linked down-regulation of adiponectin was a mechanism whereby obesity could cause insulin resistance and diabetes. Recently, we have cloned adiponectin receptors in the skeletal muscle (AdipoR1) and liver (AdipoR2), which appear to comprise a novel cell-surface receptor family. We showed that AdipoR1 and AdipoR2 serve as receptors for globular and full-length adiponectin and mediate increased AMP-activated protein kinase,peroxisome proliferator-activated receptor-alpha ligand activities , and glucose uptake and fatty-acid oxidation by adiponectin. Obesity decreased expression levels of AdipoR1/R2, thereby reducing adiponectin sensitivity, which finally leads to insulin resistance, the so-called "vicious cycle." Most recently, we showed that osmotin, which is a ligand for the yeast homolog of AdipoR (PHO36), activated AMPK via AdipoR in C2C12 myocytes. This may facilitate efficient development of adiponectin receptor agonists. Adiponectin receptor agonists and adiponectin sensitizers should serve as versatile treatment strategies for obesity-linked diseases such as diabetes and metabolic syndrome.


It may not apply that well to our "population" but get a pre-diabetic or T2DM person with gradually increasing Adiponectin and AdipR1 (skeletal muscle)/AdipoR2 (Hepatic) levels it appears that TTA or other PPAR-Alpha ligands will work that much better.

Now we gotta find AdipoR1/AdipoR2 agonists, j/k.

Need to get my fat ass parents and friends who sit on their can and watch TV all day to get up, move around and take their TTA... or Sesathin.

Kevin.
 

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ummm... adiponectin has a slew of unwanted effects as well.
 
milwood

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Someone has used clenbuterol with MP before and did get bad cramping so i don't think his trial lasted all too long.

I see no huge problem with ephedrine with MP, but i'd go easy on the caffiene (just have it with your ephedrine and don't drink coffee or just have it from your coffee and with with your ephedrine) otherwise you're going to dehydrate cells and get cramping quicker.
I ran MP with clen for over a week with no intense cramping. I was well hydrated, however, and used a taurine/potassium drink twice a day, which I believe is helpful.
 
Robboe

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I ran MP with clen for over a week with no intense cramping. I was well hydrated, however, and used a taurine/potassium drink twice a day, which I believe is helpful.
Clenbuterol depeltes liver taurine, so yes, i think it's pretty certain that the taurine/potassium drink twice daily helped stave off the cramping!
 

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