Long term Effects of TTA

[Popa Murph]

Department of Clinical Biology, University of Bergen, Norway

Administration of tetradecylthioacetic acid (a 3-thia fatty acid) increases mitochondrial and peroxisomal beta-oxidative capacity and carnitine palmitoyltransferase activity, but reduces free fatty acid and triacylglycerol levels in plasma compared to palmitic acid-treated rats and controls. The decrease in plasma triacylglycerol was accompanied by a reduction (56%) in VLDL-triacylglycerol. Prolonged supplementation of tetradecylthioacetic acid caused a significant increase in lipogenic enzyme activities (ATP-citrate lyase and acetyl-CoA carboxylase) and diacylglycerol acyltansferase, but did not affect phosphatidate phosphohydrolase. Plasma cholesterol, LDL- and HDL-cholesterol levels were reduced. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity was, however, stimulated in 3-thia fatty acid-treated rats compared to controls. In addition. the mRNAs of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and LDL-receptor were increased. Tetradecylthioacetic acid administration affected the fatty acid composition in plasma and liver by increasing the amount of monoenes, especially 18:1(n-9), mostly at the expense of omega-3 fatty acids. Compared to liver a large amount of tetradecylthioacetic acid accumulated in the heart, and this accumulation was accompanied by an increase in omega-3 fatty acids, particularly 22:6(n-3) and a decrease in omega-6 fatty acids, mainly 20:4(n-6). The results show that the hypolipidemic effect of tetradecylthioacetic acid is sustained after prolonged administration and may, at least in part, be due to increased fatty acid oxidation and upregulated LDL-receptor gene expression. The increase in lipogenic enzyme activities as well as increased 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity, may be compensatory mechanisms to maintain cellular integrity. Decreased level of 20:4(n-6) combined with increased omega-3/omega-6 ratio in cardiac tissue after tetradecylthioacetic acid treatment may have influence on membrane dynamics and function.


It seems like I remember that TTA is not fat soluble or maybe it's not water soluble or both anyway. If someone could help me out on the solubility of TTA it would be appreciated. I can't figure is TTA concentration in the heart is a good thing or a bad thing. I would think that an increase Omega 3 would be minutly beneficial, cardio protective I really just want to know how long TTA stays concentrated in the heart.

Edit: I had my O fats mixed up earlier and thought decreased 06 was bad. It still might be but I'll search more on that later. Woot Woot

 

[Popa Murph]

Bump Bump Bump

 

[dsade]

Hmm...god did I just have a great idea for a modified TTA supplement

 

[Giantz11]

Hmm...god did I just have a great idea for a modified TTA supplement

TTA plus Omega-6's!:icon_lol:

 

[3clipseGT]

Hmm...god did I just have a great idea for a modified TTA supplement

I was actually thinking today and the idea of you guys making ur own fat burner with a couple simple ingredients would be awesome. Maybe like Omegas Burn3d but with Alcar or something added in.

 

[dsade]

This is going way beyond...luckily I used to work with both DS and Avant...who are involved already.

This is going to rock, and it's already half done. The raws have been ordered and the label is already in design.

By the waym did I mention I work fast?

 

[haiz69]

This is going way beyond...luckily I used to work with both DS and Avant...who are involved already.

This is going to rock, and it's already half done. The raws have been ordered and the label is already in design.

By the waym did I mention I work fast?

Interesting stuff....

 

[Popa Murph]

No love?

Well I've searched and no answer. I did find out that TTA is a non metabolizable fatty acid. This means it will build up in your system and stay even after you stop taking it. How long, who knows. I shouldn't sat non metabolizable I guess they're metabolized by extramitochondrial omega-oxidation and sulfur oxidation in the endoplasmatic reticulum(I'm still looking into this further). Any way Long-chain 3-thia fatty acids are cardio protective and help fight heart disease. I did find some info that said thia fatty acids with sulfer at the 4th position increase your chance of heart disease.

 

[rampage jackson]

bump on this dsade...I need a damage control stack for the holidays!

 

[dsade]

Should be out on the market in around 2 weeks.

 

[Popa Murph]

You don't want to tease us with a little sneek peak do you...:bb2:

 

[protomike]

if the "clue" dsade gave me yesterday was what i think it is... it should be really good. this could be the cadillac of tta products.

 

[Jason Pegg]

Should be out on the market in around 2 weeks.

:woohoo:

Jason

 

[rampage jackson]

Should be out on the market in around 2 weeks.

Good show ol chap! Now....sneak peek sounds good.

 

[TheMyth]

Bump dsade you coniving bastard!

 

[dsade]

This should be ready for sale this coming week. It's going to be called DCP: Damage Control Protocol.

details to come, but this will be a MUST HAVE for the holidays, for sure.

We are going to release it through the Recomp Performance Nutrition brand, but Sam will have it right away as well.

 

[rampage jackson]

Yay!

 

[dontknowaboutme]

It seems like I remember that TTA is not fat soluble or maybe it's not water soluble or both anyway. If someone could help me out on the solubility of TTA it would be appreciated. I can't figure is TTA concentration in the heart is a good thing or a bad thing. I would think that an increase Omega 3 would be minutly beneficial, cardio protective I really just want to know how long TTA stays concentrated in the heart.

Edit: I had my O fats mixed up earlier and thought decreased 06 was bad. It still might be but I'll search more on that later. Woot Woot

Well it depends, anything overabundant is bad. But I am pretty sure the importance in fats is their balance. The problem is that most diets are high[er] in Omega-6. This throws off the ratio of Omega-6:Omega-3. Supplementing with Omega-3 attempts to balance the ratio, creating positive health effects.

This would mean that even a higher Omega-3 than Omega-6 ratio might cause issues. Both Omega-6 and Omega-3 are important. So it really depends on how much it decreases Omega-6.

 

[RexGrandis]

Well it depends, anything overabundant is bad. But I am pretty sure the importance in fats is their balance. The problem is that most diets are high[er] in Omega-6. This throws off the ratio of Omega-6:Omega-3. Supplementing with Omega-3 attempts to balance the ratio, creating positive health effects.

This would mean that even a higher Omega-3 than Omega-6 ratio might cause issues. Both Omega-6 and Omega-3 are important. So it really depends on how much it decreases Omega-6.

Bump, can anyone provide more info on what effect on the heart disrupting the balance of omega 3 and 6s?

 

[T-Bone]

Department of Clinical Biology, University of Bergen, Norway

Administration of tetradecylthioacetic acid (a 3-thia fatty acid) increases mitochondrial and peroxisomal beta-oxidative capacity and carnitine palmitoyltransferase activity, but reduces free fatty acid and triacylglycerol levels in plasma compared to palmitic acid-treated rats and controls. The decrease in plasma triacylglycerol was accompanied by a reduction (56%) in VLDL-triacylglycerol. Prolonged supplementation of tetradecylthioacetic acid caused a significant increase in lipogenic enzyme activities (ATP-citrate lyase and acetyl-CoA carboxylase) and diacylglycerol acyltansferase, but did not affect phosphatidate phosphohydrolase. Plasma cholesterol, LDL- and HDL-cholesterol levels were reduced. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity was, however, stimulated in 3-thia fatty acid-treated rats compared to controls. In addition. the mRNAs of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and LDL-receptor were increased. Tetradecylthioacetic acid administration affected the fatty acid composition in plasma and liver by increasing the amount of monoenes, especially 18:1(n-9), mostly at the expense of omega-3 fatty acids. Compared to liver a large amount of tetradecylthioacetic acid accumulated in the heart, and this accumulation was accompanied by an increase in omega-3 fatty acids, particularly 22:6(n-3) and a decrease in omega-6 fatty acids, mainly 20:4(n-6). The results show that the hypolipidemic effect of tetradecylthioacetic acid is sustained after prolonged administration and may, at least in part, be due to increased fatty acid oxidation and upregulated LDL-receptor gene expression. The increase in lipogenic enzyme activities as well as increased 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity, may be compensatory mechanisms to maintain cellular integrity. Decreased level of 20:4(n-6) combined with increased omega-3/omega-6 ratio in cardiac tissue after tetradecylthioacetic acid treatment may have influence on membrane dynamics and function.




It seems like I remember that TTA is not fat soluble or maybe it's not water soluble or both anyway. If someone could help me out on the solubility of TTA it would be appreciated. I can't figure is TTA concentration in the heart is a good thing or a bad thing. I would think that an increase Omega 3 would be minutly beneficial, cardio protective I really just want to know how long TTA stays concentrated in the heart.

Edit: I had my O fats mixed up earlier and thought decreased 06 was bad. It still might be but I'll search more on that later. Woot Woot

Whats the English translation of this scientific nerd talk?

 

[william3162]

If TTA is not metabolized and builds up, I think it will have a negative impact even acompanied with omega-6's or whatever. Any opinions?

 

[Enigma76]

Regarding the TTA duration in cardiac tissue, refer to this study:

Entrez PubMed

Long-term retention of a novel antioxidant sulphur-substituted fatty acid analogue after local delivery in porcine coronary arteries.

* Pettersen RJ,
* Kuiper KK,
* Froyland L,
* Berge RK,
* Nordrehaug JE.

Department of Heart Disease, Haukeland University Hospital, Bergen, Norway. [email protected]

OBJECTIVE: Antioxidants have been suggested to reduce restenosis after balloon angioplasty. A novel sulphur-containing fatty acid, tetradecylthioacetic acid (TTA), with antioxidant properties, is efficiently incorporated into cellular phospholipids. We have determined the uptake and retention of TTA after local coronary artery delivery in 20 pigs. DESIGN: Radiolabelled TTA was delivered to 40 main coronary arteries via a multiporous coronary angioplasty balloon catheter inflated before, after, or without overstretch vessel injury. The animals were killed at intervals of up to 6 weeks post-procedure. The radioactivity of the tissue sections was determined as nmol TTA/g tissue. RESULTS: Concentrations of TTA in the coronary arteries were 1.84 +/- 0.45 nmol/g up to 24 h, 1.50 +/- 0.96 nmol/g at 2 weeks, 0.22 +/- 0.11 nmol/g at 4 weeks and a trace was present at 6 weeks (p-value for trend <0.01). The arterial wall uptake at the delivery site was higher than distal to delivery (1.84 +/- 0.37 vs 0.55 +/- 0.13 nmol/g, p = 0.006) and perivascular fat (p < 0.01) but not higher than in the myocardium. Infusion before, after or without vessel injury was not important for tissue concentration. CONCLUSIONS: After local coronary artery delivery, the antioxidant TTA is taken up by the arterial wall in which it is retained for at least 4 weeks.

PMID: 11405484 [PubMed - indexed for MEDLINE]



I think the first bolded statement is interesting for two reasons; first, that TTA has antioxidant properties (as well as anti-inflammatory properties). Second, that TTA is incorporated iinto cellular phospholipids (the phospholipid bilayer probably?), and is most likely why the concentration remains in trace amounts for up to 6 weeks post-dose.

 

[bludevil]

Well, I'm interested, but still can't seem to decipher if it's good or bad for the heart?

 

[saludable24]

I too wuld like to have this answered. From what I understand as I read this, it seems like it would be beneficial if they are using it to help after sugery. Also if it is eliminated after about 6 weeks it sounds like it wouldn't cause long term damage or any permanent changes.

 

[Popa Murph]

Regarding the TTA duration in cardiac tissue, refer to this study:

Entrez PubMed

Long-term retention of a novel antioxidant sulphur-substituted fatty acid analogue after local delivery in porcine coronary arteries.

* Pettersen RJ,
* Kuiper KK,
* Froyland L,
* Berge RK,
* Nordrehaug JE.

Department of Heart Disease, Haukeland University Hospital, Bergen, Norway. [email protected]

OBJECTIVE: Antioxidants have been suggested to reduce restenosis after balloon angioplasty. A novel sulphur-containing fatty acid, tetradecylthioacetic acid (TTA), with antioxidant properties, is efficiently incorporated into cellular phospholipids. We have determined the uptake and retention of TTA after local coronary artery delivery in 20 pigs. DESIGN: Radiolabelled TTA was delivered to 40 main coronary arteries via a multiporous coronary angioplasty balloon catheter inflated before, after, or without overstretch vessel injury. The animals were killed at intervals of up to 6 weeks post-procedure. The radioactivity of the tissue sections was determined as nmol TTA/g tissue. RESULTS: Concentrations of TTA in the coronary arteries were 1.84 +/- 0.45 nmol/g up to 24 h, 1.50 +/- 0.96 nmol/g at 2 weeks, 0.22 +/- 0.11 nmol/g at 4 weeks and a trace was present at 6 weeks (p-value for trend <0.01). The arterial wall uptake at the delivery site was higher than distal to delivery (1.84 +/- 0.37 vs 0.55 +/- 0.13 nmol/g, p = 0.006) and perivascular fat (p < 0.01) but not higher than in the myocardium. Infusion before, after or without vessel injury was not important for tissue concentration. CONCLUSIONS: After local coronary artery delivery, the antioxidant TTA is taken up by the arterial wall in which it is retained for at least 4 weeks.

PMID: 11405484 [PubMed - indexed for MEDLINE]



I think the first bolded statement is interesting for two reasons; first, that TTA has antioxidant properties (as well as anti-inflammatory properties). Second, that TTA is incorporated iinto cellular phospholipids (the phospholipid bilayer probably?), and is most likely why the concentration remains in trace amounts for up to 6 weeks post-dose.

Thanks for the info,
Now I wonder about other tissues. I know TTA is a biznatch for the body to breakdown. I.E. liver, Kidneys, skeletal muscle.

 

[Grant]

So is it good or bad for the heart?

 

[jvangard]

I think we would all like the answer to your question to be yes it is good for your heart, but the truth is no one really knows. I have done a several pubmed searches (another just a minute ago) on TTA toxicity, and come up empty so far. Lab studies don't report any overt toxicity, and I haven't heard of anyone dropping dead from TTA yet, so that pretty much shows acute toxicity is pretty low. Hey, in the tox biz, you can't beat human data. As for long term toxicity, like cumulative organ damage or carcinogenesis, your guess is as good as anyone else's.

 

[kabuki]

I think we would all like the answer to your question to be yes it is good for your heart, but the truth is no one really knows. I have done a several pubmed searches (another just a minute ago) on TTA toxicity, and come up empty so far. Lab studies don't report any overt toxicity, and I haven't heard of anyone dropping dead from TTA yet, so that pretty much shows acute toxicity is pretty low. Hey, in the tox biz, you can't beat human data. As for long term toxicity, like cumulative organ damage or carcinogenesis, your guess is as good as anyone else's.

Do a search on uncouplers...which TTA is. You WILL find people that have died and products taken off the market due to liver toxicity. It's not everyone that is affected this way by uncouplers...but be carefull.

I found this out the hard way. While taking TTA my AST/ALT levels shot up to 653/384 last summer!!! My doc thought I was heading for liver failure. After discontinuation they dropped to 140 and 83 respectivly in the first week. And over the next 6 months slowly returned to normal levels.

What makes it worse is I normally take a number of antioxidents that also help liver Toxicity and it had no impact. At the time I was taking:
Sesamin, Glucophase XR, Liv52, Milk thistle, Fish Oil, CLA, Vitamin C

I have since had bloodwork taken on a monthly basis and have a good idea how each supplement affects me.

I am by no means saying TTA will have this affect on everyone, but it does affect some. But please research uncouplers and toxicty. Here is a link in regards to another uncoupler
Safety Issues Affecting Herbs: Usnea - an herb used in Western and Chinese medicine

Some pharmaceutical products that inhibit oxidative phosphorylation are also associated with liver failure in a small number of users. For example, tolcapone, a drug for Parkinson's disease, was withdrawn from the European market due to three cases of hepatic damage attributed to its use. It was thought that mitochondrial uncoupling of oxidative phosphorylation by tolcapone, and consequent impairment of energy production by hepatocytes, could be responsible for the observed effects (8). These adverse events may occur in those with heightened sensitivity to the mitochondrial reaction or by unusual patterns of drug metabolism, explaining their infrequent effects (9).

 

[dsade]

Do a search on uncouplers...which TTA is. You WILL find people that have died and products taken off the market due to liver toxicity. It's not everyone that is affected this way by uncouplers...but be carefull.

I found this out the hard way. While taking TTA my AST/ALT levels shot up to 653/384 last summer!!! My doc thought I was heading for liver failure. After discontinuation they dropped to 140 and 83 respectivly in the first week. And over the next 6 months slowly returned to normal levels.

What makes it worse is I normally take a number of antioxidents that also help liver Toxicity and it had no impact. At the time I was taking:
Sesamin, Glucophase XR, Liv52, Milk thistle, Fish Oil, CLA, Vitamin C

I have since had bloodwork taken on a monthly basis and have a good idea how each supplement affects me.

I am by no means saying TTA will have this affect on everyone, but it does affect some. But please research uncouplers and toxicty. Here is a link in regards to another uncoupler
Safety Issues Affecting Herbs: Usnea - an herb used in Western and Chinese medicine

Look again...TTA is not like mitochondrial uncouplers like Usnic Acid or DNP.

 

[warnerve]

has anyone seen any bloodwork in regard to the liver with TTA? although i am skeptical, this still has me a tad worried

 

[kabuki]

Look again...TTA is not like mitochondrial uncouplers like Usnic Acid or DNP.

i will look. What kind of Uncoupler is TTA?

However it won't change the fact that for me it significantly elevates my liver enzymes. I have 7 months of monthly bloodwork showing that none of the other supps i take caused this.

But again, even that is not definitive as i could have unknownly taken in some chemical or had some viral infection i didn't know about. Many possiblities...but certainly not worth testing it again to see what it does.

 

[bludevil]

I wish somebody would find something out as I have 2 bottles ready to be used for my next cut. Kabuki's liver enzyme levels already have me a little freaked.

 

[bludevil]

I did a quick google search and did find the following research article that stated blood results from a 7 day trial with 18 people showed no adverse effects. Direct quote was "Biochemical analysis showed that TTA administration was not associated with endocrinological disturbances, abnormal blood coagulation, or major changes in serum levels of electrolytes, creatinine, bilirubin, liver enzymes and albumin (data not shown)."

This report can be found at Antiproliferative effects of a non--oxidizable fatty acid, tetradecylthioacetic acid, in native human acute myelogenous leukemia blast cultures

 

[rockhard_4eva]

I did a quick google search and did find the following research article that stated blood results from a 7 day trial with 18 people showed no adverse effects. Direct quote was "Biochemical analysis showed that TTA administration was not associated with endocrinological disturbances, abnormal blood coagulation, or major changes in serum levels of electrolytes, creatinine, bilirubin, liver enzymes and albumin (data not shown)."

This report can be found at Antiproliferative effects of a non--oxidizable fatty acid, tetradecylthioacetic acid, in native human acute myelogenous leukemia blast cultures

Look at table 4. TTA increases something in blood...

 

[rogermoore]

I just found this:

Tetradecylthioacetic acid a 3-thia fatty acid, is a novel bioactive compound. Besides being an antioxidant, it changes the plasma profile from atherogenic to cardioprotective

Ziad A. Muna, Lise Madsen, and Rolf K. Berge
Department of Clinical Biology, Division of Biochemistry, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway

Tetradecylthioacetic acid (TTA) which can not be ß-oxidized, lowers plasma VLDL-triacylglycerol (TG) and LDL-cholesterol (Chol). Increased mitochondrial ß-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 ³olive oil² effect since the plasma was enriched with oleic acid (18:1 n-9) and a ￾9-desaturated metabolite of TTA. This was due to upregulation of the hepatic enzyme ￾9-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.

 

[dsade]

Yep...we were reviewing that study last night...good stuff.