Tetradecylthioacetic acid

[SuperBane]

Where it comes from: Tetradecylthioacetic Acid (also known—and more easily pronounced—as TTA) is a fatty acid that does not get used for fuel by the body, but instead helps to regulate how much fat the body stores by influencing genes that control the metabolism. It's delivered to the body in supplement form.

What it'll do for you: "Early studies are suggesting that [TTA] helps to burn fat from the body without the need for exercise," explains Amy Shapiro, RD and CDN of AWS Nutrition. Often used in conjunction with other supplements (such as sesamin), TTA can help individuals feel full more quickly while the fatty acid decreases overall hunger and burns fat. In addition to regulating fat metabolism, this fatty acid has antioxidant, anti-inflammatory and immunity-enhancing properties. Here, a closer look at the key benefits:

May aid in fat-loss efforts
TTA has been found to enhance mitochondrial function and therefore increase the energy level in cells (also known as the metabolism), which further equals an increased fat loss. In 2009, a Norwegian study observed rats on a high-fat diet for seven weeks. Despite eating even more food than usual during the final two weeks, the rats fed TTA gained less body weight than the other rats not getting TTA. This effect has been found independent exercise. "If you exercise, too, it will speed up your fat loss because your body will continue to burn fat at rest and when exercising," explains Shapiro.

May lower cholesterol
Research suggests that TTA activates receptors that are responsible for decreasing the creation of LDL particles (the bad cholesterol). Eighteen healthy men between the ages of 18 and 55 were given doses of TTA for one week—and were studied for an additional week after supplementation stopped. The researchers concluded that TTA reduced the total plasma cholesterol and triacylglycerol levels by 17 percent by increasing the number of mitochondria and by stimulating the oxidation of normal fatty acids. What do Triglycerides matter? Shapiro explains it: "These are fats in the blood so, if TTA helps to increase fat burn, it makes sense that there would also be less fat floating in the blood."

Boosts insulin sensitivity
Due to the mitochondria's increased activity, the body's cells use glucose more efficiently with less insulin, which is known to increase fat storage. Accordingly, with less insulin, less fat buildup results.

Suggested intake: TTA is often found in fat-lass products such as LipidFX by SciVation and is also marketed as the headliner ingredient with bonus minerals (TTA with electrolytes!).

Studies have demonstrated that TTA is safe and well tolerated when given once daily for seven consecutive days at doses up to 1000 mg. However, more research is still needed.

"In terms of fat burning, since there is so little research done on this product, I would opt to take something that has more proven results and background research that it is safe in the short and long term such as CLA, another popular fat burner," suggests Shaprio.

Associated risks/scrutiny: At this time, not much is known about TTA however some users report cramping and headaches. It is important to note that toxicological and pharmacological properties of this product have not yet been fully investigated.

- "Men's Health"

 

[SuperBane]

Tetradecyl Thioacetic Acid, otherwise known as TTA, is what is known as a PPAR-alpha activator. It is actually an omega-3 fatty acid, but has a sulfur group at the omega-3 position; because of this addition it cannot be burnt for energy and thus has no relevant caloric value to humans.

PPARa activation can be seen as protecting the body from excess fats (similar to PPARy activation). PPARa tends to clear fats from the blood into muscle or liver cells, and encourage them to be burnt for energy in these locations (by comparison, PPARy makes new fat cells for fats to reside in which minimizes their potential toxicity).

The clearing of fat from the blood causes a drop in lipoproteins and a lowering of LDL cholesterol, and the burning of fats causes either fat burning or reduced fat gain. TTA can also decrease blood pressure and exert an anti-oxidant effect, the four mechanisms making it a cardioprotective compound.

It is commonly used with the appetite suppressant Oleoylethanolamide as a fat-burning combination.


Oleoylethanolamide (OEA) is a fatty acid that is produced by the gut to signal to the brain the sensation of being full. Oral ingestion might confer these benefits, but OEA is understudied in humans. It is commonly paired with TTA as a fat burning stack, but no evidence for synergism exists.

 

[SuperBane]

Abstract
This study describes the clinical, hematological, and biochemical safety of tetradecylthioacetic acid (TTA). A total of 18 healthy volunteers were included. Subjects were randomly assigned into 3 groups according to the daily given dose of TTA: group 1 (200 mg), group 2 (600 mg), and group 3 (1000 mg). TTA was given as a single oral dose for 7 consecutive days. Safety was evaluated by following the adverse events, vital signs, and hematological and biochemical parameters in blood and urine samples. Efficacy was estimated through its effects on plasma lipids profile. Few adverse events of mild severity were reported. No clinically significant changes were observed in the hematological or clinical chemical parameters in blood/urine. TTA did not induce significant changes in the blood lipids or free fatty acids, but it did result in an increase in plasma concentration of Δ9 desaturated TTA (TTA: 1n-8). Serum concentration pattern of TTA at day 1 showed a 1.5-hour lag time followed by a rapid absorption and a slower elimination phase. The median peak values were 2.9 mg/L (range, 1.1 to 5.4 mg/L), 11.5 mg/L (range, 4 to 35 mg/L), and 11 mg/L (range, 5 to 25 mg/L), in groups 1, 2, and 3, respectively (P = 0.006). The time to peak levels were 3.5 hours (range, 2.5 to 6.5 hours), 2.5 hours (range, 2.5 to 4.5 hours), and 4.5 hours (range, 2.5 to 12 hours), respectively (P = 0.2). TTA is safe and well tolerated.

INTRODUCTION

It has been found that structurally modified fatty acids show an enhanced potency in modulating critical steps in lipid metabolism. The substituted fatty acids are saturated fatty acids that are modified by insertion of a sulfur atom at specific positions in the carbon backbone. One such modified fatty acid is the sulfur-containing tetradecylthioacetic acid (TTA), which has been found to beneficially affect disorders in lipid metabolism.1-4 It has structural similarity to the ordinary fatty acids, but it differs by the substitution of a sulfur atom for a methylene group in the 3-position of the fatty acid chain.5 The biological responses to TTA include mitochondrial proliferation, increased catabolism of fatty acids, antiadiposity, improvement in insulin sensitivity, antioxidant properties, reduced proliferation and induction of apoptosis in rapidly proliferating cells, cell differentiation, and antiinflammatory action. These biological responses indicate that TTA changes the plasma profile from atherogenic to cardioprotective.1 Different mechanisms are involved in the hypolipidemic effects of TTA. As a panperoxisome proliferator-activated receptor ligand, TTA regulates the adipose tissue mass and the expression of lipid metabolizing enzymes, particularly those involved in catabolic pathways. TTA reduced the total plasma cholesterol and triacylglycerol levels by 17% by increasing the number of mitochondria and by stimulating the mitochondrial β-oxidation of normal fatty acids.1,6TTA affects antioxidant status at different levels by having the potential of changing the antioxidant defense system in addition to being an antioxidant itself through its free radical scavenging capacity. It may prevent the oxidative modification of LDL particles in plasma and reduce the generation of lipid peroxides.7 The potent antioxidant and antiproliferative properties of TTA were reported in both in vitro and in vivo studies.7-9 TTA, given as peroral supplements or delivered locally reduced negative remodeling after balloon angioplasty injury in a rabbit iliac model9 and porcine coronary arteries.10 It seems to be well tolerated in mice, rats, and dogs. Studies with administration of a single dose of TTA in mice and rats showed no significant acute toxicity.11 Long-term (3 months) administration to rats had an effect on the lipid levels in liver and blood, but only minor signs of toxicity were observed.12Dyslipidemia and restenosis after percutaneous coronary interventions could be the targets for TTA therapy in the future. Toxicity, plasma concentration of TTA, and effects on blood biochemistry has not been evaluated in humans. In this study, we aimed to assess clinical safety and efficacy of TTA in terms of hematological and biochemical tolerance to increasing multiple doses of TTA and the short-term effects on blood lipids as well as its pharmacokinetics after single and multiple oral doses.

DISCUSSION

The concentration pattern of TTA during and after the study period allowed for analysis of its pharmacokinetics. With the estimated half-lives of about 9 to 14 hours, daily dosing resulted in accumulation of the drug. The large distribution volumes observed (52 to 84 L) and the fatty acid nature of the drug indicate binding of the drug to lipid compartments of the organism. After a 1-week washout period, there was only a small fraction of the drug left; 3 weeks later, TTA could not be detected in any of the dose groups.We have previously reported that TTA induces antioxidant and antiproliferative effects in in vitro and in in vivo studies.7-9 In experimental models, the inhibitory effects of TTA on the restenosis process after balloon angioplasty, particularly on negative remodeling, were proven.9,10 In this study, clinical, hematological, and biochemical tolerance to increasing multiple oral doses of TTA were tested. The drug was well tolerated when administered at a dose level of 200, 600, and 1000 mg/d for 7 consecutive days. Relatively few adverse events were reported, all of mild severity. Biochemical and hematological parameters did not change significantly throughout the 7-day treatment and 1-week washout periods. In addition, TTA had no clinically significant effect on vital signs. Safety of TTA was reported in prior experimental studies.11,12 Single dose11 as well as 3-month administration12 of TTA in mice and rats showed none or only minor signs of toxicity.Administration of TTA did not cause a marked change in the total fatty acid composition of plasma lipids. The increase in Δ9 desaturated by TTA therapy may reflect attenuated Δ9 desaturase activity, and that TTA is a good substitute for this enzyme. However, no correlation was found between the level of TTA:1n-8 and the amount of oleic acid (18:1n-9). Fredriksen et al report that TTA in combination with dietary intervention reduces total cholesterol, LDL-cholesterol, and triglyceride in HIV-infected patients on PI-based HAART.13 TTA has previously been found to have hypolipidaemic effects in rats and dogs.5 The hypolipidemic effect of TTA seems to involve activation of peroxisome proliferator-activated receptor (PPAR) α in the liver, and it has recently been shown that TTA is a ligand for all PPAR subtypes.1 In addition, TTA may upregulate the scavenger and LDL-receptor expression.13

CONCLUSION

This study has demonstrated that TTA was safe and well tolerated when given once daily for 7 consecutive days at doses up to 1000 mg. No major changes were observed in hematological or biochemical parameters. Further studies in humans are needed to determine optimal dose, dose intervals, and long-term safety and efficacy.

http://journals.lww.com/cardiovascu...thioacetic.10.aspx?WT.mc_id=HPxADx20100319xMP

 

[SuperBane]

Additional study: http://www.jlr.org/content/43/5/742.full

Different POV:

TTA + Fish Oil - Fat Burning Superfats or Hepatoxic Pro-Oxidants? Why You Better Avoid Large Amounts of Omega-3 and Tetradecylthioacetic Acid in the Long Run


Image 1: Even if you align them like that, it is at least debatable whether capped fish oil is much more natural than the structurally modified 16 -carbon saturated fatty acid tetradecylthioacetic acid (TTA). As far as their effects on weight loss are concerned, the latter is certainly more potent,... the debate on the side-effects of both is yet still far from being settled. Despite the mainstream hoopla around the former...
At least for those of you who have been around the supplement world for some time, the acronym TTA, which stands for tetradecylthioacetic acid, a structurally modified 16 -carbon saturated fatty acid (SFA), which has been shown to increase fatty acid oxidation and reduce triglyceride levels via interactions with purportedly all PPAR-receptors, should ring a bell. For the rest, it will yet probably be news that, back in the early 2000s, TTA was all the rave as the new star among OTC-fat burners. And in fact, the weight loss people experienced on respective products was non-negligible... yet so were the side-effects which crept up over time (and with ever-increasing dosages): Headaches, cramps, dehydration and water retention specifically in the abdominal area were only the minor complaints. Unbearable fatigue and even palpitations were at the other extreme of the spectrum and probably the actual reason why company after company altered the formulation of their "effective" and above all commercially successful tetradecylthioacetic acid containing fat burners.

While TTA works well, but has well-known side-effects,...

A recent long-duration rodent study that was conducted by a group of European researchers and which my friend Sean Casey from CasePerformance has brought back up onto my radar (Vigerust. 2012), did now investigate the long term (50 weeks) effects of supplemental tetradecylthioacetic acid and another purportedly saver PPAR-agonist, with similarly beneficial effects on triglycerides yet hardly noticeable effects on weight management - my all-time favorite fish oil! To this extend, the scientist kept their rats on their infamous interpretation of a "high fat" diet, which, as you will probably already have expected, had a moderate fat content of 25% tons of carbs and little protein and had thusly more of the standard American diet than of what people in the bloggosphere usually refer to as a "high fat" diet, i.e. a diet that is really high in fat (>50%) and low in carbohydrates.

Figure 1: Relative body weight (compared to identical baseline) in rats at different time points during 50 weeks on high fat diet (control) with either TTA, fish oil or both (data calculated based on Vigerust. 2012).
It is thusly not surprising that replacing 10% of the fat by fish oil (~11g EPA + 6g DHA for avg. human) had absolutely no effect on the weight gain of the hyperphagic (overeating) rodents. The miniscule amount of 0.365% TTA, which would be equivalent to a daily intake of ~912.4mg of TTA for someone consuming 2000kcal/day, on the other hand, lead to statistically highly significant reduction in weight gain over the whole 50 week feeding period (cf. figure 1).

Figure 2: Relative expression of uncoupling protein 3 (UCP3, primary axis) and enzymes involved in fatty acid metabolism (secondary axis) at the end of the 50-week dietary intervention; expressed relative to high fat control (data calculated based on Vigerust. 2012).
As evidenced by the elevations in carnitine palmitoyltransferase II (CPT II), which is necessary to shuttle the fat into the cell, HMG-CoA, which is one of the key players in ketogenesis, and peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), which initiates the first enzymatic reaction during beta oxidation, the hepatic fatty acids oxidation in the TTA (and TTA + FO) group was profoundly increased, in conjunction with the exorbitant increase in UCP-3 expression (>1500x in the TTA only, and >1300x in the TTA + FO group) and the subsequent "leakage" of energy in the form of protons, this easily explains the -11% / -19% reduction in total body weight in the TTA and the TTA + FO groups at the end of the 50 week study period.

....fish oil hardly works and has less-known side-effects

In that, it is important to note, that only TTA (respectively its addition to FO), not fish oil, was able to reduce the diet-induced elevations in hepatic triacylglycerol (TAG) levels. This leads to scientists to speculate, that despite similar effects on TAG and cholesterol transport in the liver, ...
[...] animals given the FO diet are less able to metabolize the excess hepatic lipid levels [... so that] FO redistributed lipids without affecting the total lipid level and body weight.
This would also explain the detrimental effects the fish oil supplement had on hepatic cholesterol levels and lipid oxidation, which would suggest that, at least under these dietary conditions (relatively high fat + high carb + high energy = typical western diet), one would be better off taking no fish oil at all, or a combination of fish oil and TTA.

Figure 3: Relative mRNA expression of markers of protein and lipid oxidation in liver and liver mitochondrial fraction of the rodents at the end of the 50-week study period (data calculated based on Vigerust. 2012)
The latter is all the more indicated in view of the fact that the use of the highly oxidizable fish oil alone lead to non-negligible increases in protein oxidative damage (cf. GSA, alpha-AASA, figure 3) and an increase in total hepatic glyco- and lipooxidation, as evidenced by the increase in Ne-Carboxymethyl-lysine (NCL, figure 3) in the whole-liver samples and a corresponding increase in Nɛ-Malondialdehyde-lysine (MDAL), a lipid-specific marker of oxidative damage in whole-liver and the mitichondrial homogenate (liver M-fraction) of the animals in the fish oil (only) group (cf. figure 3).

These detrimental oxidative longterm effects of fish oil supplementation, which "showed a significant positive correlation with DHA content" of the liver (meaning more DHA in tissue = more oxidation), were only ameliorated, yet not totally prevented by co-treatment with tetradecylthioacetic acid (TTA), which reduced the amount of oxidizable PUFA in plasma and tissue and reduced the mitochondrial ROS production via the UCP-3 induced energy leakage and the subsequent relative reduction in oxidative energy production (remember the overall energy expenditure was still increased by TTA, yet not by FO treatment).

Bottom line: Avoid the dietary PUFA burden, eat healthy and exercise...

As far as the amelioration of negative side-effects of the typical Western high carbohydrate, relatively high fat diet are concerned, the results of this study would argue against the longterm use of omega-3 polyunsaturated fatty acids from fish oil (DHA in particular) and for the use of structurally modified 16-carbon saturated fatty acid TTA in order to reduce weight gain, triglyceride and liver cholesterol levels in individuals who are either unwilling or unable to make the necessary life-style-changes that would, instead of just prolonging their suffering, help them finally escape from the maelstrom of the metabolic syndrome (cf. yesterday's blogpost on "High Carb vs. High Fat, When Science Meets Real Life").

Whether the same holds true for athletes, fitness enthusiasts or at least moderately active human beings, who stick to an overall anti-inflammatory low(-er) carb (not "no carb" and not necessarily, but possibly "paleo") diet, would certainly warrant further investigation. It would nevertheless, my previously voiced concerns over the injudicious (over-)use of omega-3 supplements in the futile effort to "balance" the dietary over-indulgence of omega-6s... after all, the most straight-forward explanation for the increase in oxidative damage in the fish oil only group is the increased amount of PUFAs in the liver tissue, which are - across the board, i.e. omega-6 and omega-3 - much more susceptible to oxidative damage due to radical oxygen specimen (ROS). I thusly stick to my previous recommendation to just watch your overall PUFA intake and resort to alternative fat sources, such as coconut oil (which is, by the way, the topic of the first "non-SuppVersity" article of mine in the all-new article-section of the VPX-website; don't worry I won't neglect the SuppVersity and stick to topics without potential "conflicts of interest and objectivity" ;-), butter, dairy and meat products from grass-fed animals, eggs and obviously real fish!

... and you won't need TTA to lose weight or ward off unwanted body fat

Moreover, I strongly caution against a similar injudicious (ab-)use of large amounts of TTA especially over longer periods of time. The latter was probably the underlying reason for the initially mentioned side-effects, due to which most supplement manufacturers either totally removed tetradecylthioacetic acid from their products or reduced the amounts per servings to levels, where the other ingredients would give you palpitations before you would achieve dosages way beyond the 1g range, which, as previous human trials would suggest, appears to be save at least in the short term (<30days, cf. Lovas. 2009). With respect to longer durations and/or higher dosages, you should yet be aware that the very same depletion of plasma and tissue PUFAs which is partly responsible for the overall reduction in oxidative damage in the study at hand, may well backfire and produce exactly those cramps, the water retention, and the profound lethargy reports of which you will find in the archives of various health and fitness boards, all over the web.

http://suppversity.blogspot.com/2012/02/tta-fish-oil-fat-burning-superfats-or.html

 

[SuperBane]

Still have some TTA unopened unused from my pro-supplement days when I was a member at A.M. bought it from N.P. I may give it a whirl at some point small dosed short cycle perhaps.