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.
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Not much evidence currently exists in human, but the standard dose appears to be 1g of TTA daily taken in divided dosages with meals.
The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Tetradecyl Thioacetic Acid has in your body, and how strong these effects are.
|Grade||Level of Evidence|
|A||Robust research conducted with repeated double blind clinical trials|
|B||Multiple studies where at least two are double-blind and placebo controlled|
|C||Single double blind study or multiple cohort studies|
|D||Uncontrolled or observational studies only|
|Level of Evidence ||Effect||Change||Magnitude of Effect Size ||Scientific Consensus||Comments|
Possible reductions in total cholesterol with supplementation of TTA
The one trial using TTA to reduce triglycerides noted a reduction of around 15%, which is notable and requires replication
A decrease in serum levels of TNF-a has been noted with supplemental TTA
|C||Cell Adhesion Factors|
Expression of VCAM-1 has been noted to be decreased
Possible reductions in LDL cholesterol seen with TTA consumption
No significant influence on liver enzymes in preliminary testing for possible toxicity
No significant alterations in serum uric acid seen with supplemental TTA
No significant influence on C-Reactive Protein levels
No significant alterations in HbA1c concentrations
A slight reduction in blood pressure has been noted in dyslipidemic obese men with TTA supplementation
Although increased mitochondrial fat oxidation was created for underlying the reductions in lipids and blood pressure, no significant influence on body weight was noted... show
An increase in HDL cholesterol has been noted with TTA consumption
Tetradecyl Thioacetic Acid (Henceforth TTA) is known as a modified (thia) fatty acid analogue that cannot be beta-oxidized and can act as a potential adipocyte regulator through PPARa activation.
After ingestion, there appears to be a delay (90 minutes according to this study) followed by rapid absorption of TTA. Full absorption of a 1g dose of TTA may take more than 24 hours, as a pharmacokinetic study done for 7 subsequent days noted a build-up effect where serum TTA increased to 2.5mg/L after one dose (1g) and built up to a circulating level of around 5mg/L at days 6-7.
Given serum parameters in humans are a Tmax of 3.5 hours (2.5-6 hour range) at 200mg, 2.5 hours (2.5-4.5 hour range) at 600mg, and 4.5 (2.5-12 hour range) at 1g, high interindividual differences. The half-life was estimated, via distribution volume and clearance rates, to be between 8.9-14 hours.
The median peak values of TTA were 2.9mg/L at 200mg, and 11.5-11.0mg/L at 600mg and 1000mg; respectively.
A study in persons with psoriasis consumign 1g of TTA (via 5 200mg capsules) daily for 28 days noted that, at the end of the study, circulating TTA levels from from non-existent to 0.44+/-0.03% of total blood lipids, and TTA's metabolite (TTA 1n-8) rose to 0.14+/-0.03%. Another study noted that doses of 200mg TTA did not influence circulating TTA 1n-8 levels at all, and doses of 600mg or 1000mg were required.
Slow absorption and slow metabolism, slight build-up effects
TTA has a volume of distribution ranging from 52.3 to 84.3 L based on oral dose and interindividual differences, which suggest binding to the lipid compartment of the blood.
It cannot be beta-oxidized for energy, despite being a fatty acid, due to the sulfur substitution at the beta-oxidation location which is the cause for its metabolic properties as a PPARalpha, delta, and gamma agonist and its implications in hepatic lipid metabolism.
Although TTA cannot be beta-oxidized, it can be subject to the delta-9 desaturase enzyme and turned into the metabolite TTA 1n-8, and this appears to not be relevant at oral doses of 200mg (only 600mg or 1g).
After 7 days of ingesting 200-1000mg TTA, TTA was still found in the body by day 14 but was not detectable by day 28. Approximately 80% of circulating TTA is eliminated by 1 week of cessation, returning to baseline 3 weeks after cessation (no measurement taken in between).
Rate of clearance was estimated to be 4.1-5.6L per hour based on oral doses of 200,600, and 1000mg.
Clearance rates appear to reflect absorption rates, slow
In rats subject to a controlled diet containing 0.375% TTA over the course of 50 weeks, there appears to be a modification in the fatty acids of cardiac tissue with a decrease in saturated fat and aradchidonic acid content with an increase in Fish Oil fatty acids, and this effect was additive with fish oil supplementation (10.4% of diet).
May increase fish oil fatty acid content of the heart independent of fish oil supplementation
In addition to the above mechanisms (reduction of fatty acids in the blood, reduced fat mass) TTA can alleviate the decrease in insulin sensitivity from a fat promoting diet. and has antioxidant abilities. Thus TTA may be a potent cardioprotective agent, and appears to be more protective in the metabolically impaired.
In non-metabolically impaired hearts, TTA may suppress overall cardiac output via the increase in fatty acid oxidation causing a decrease in glucose oxidation.
In isolated human liver cells, 10-30umol/L TTA was able to induce activation of PPARa and PPARd with preference for PPARa activation. In these liver cells, PPARy was not significantly activated until 75umol/L concentration, and was still less potent than rosiglitazone (about 60% potency, as assessed by luciferase activity relative to control).
In isolated myotubes (muscle cells), TTA was able to increase fatty acid oxidation via PPARd in a dose-dependent response with similar efficacy as the research standard GW501516. After 96 hours of incubation, protein content of CPT-1 (almost 2-fold) and CD36/FAT (almost 3-fold), downstream of PPAR, were increased.
When tested in mouse liver cells, increase fat oxidation is seen even after PPARa is deleted (normally a route of fat oxidation in the liver); this was hypothesized to be through PPARd activation, possibly vicariously through other factors (PGC-1a, SRC-1 and 2) due to having more potency when their levels were elevated.
When supplemented to an obesity-inducing and insulin resistance promoting diet, TTA shows promise in negating a fair bit of the gain in mass and completely ameliorating the onset of peripheral insulin resistance. It seems to do this effect via increasing uptake of fats from the blood into tissues that express PPARa (muscle and liver mostly, some kidney) and then to oxidize the fats. With superloading of TTA (at 200mg/kg bodyweight) rats experienced weight loss despite eating a greater amount of calories.
The one study in humans currently to measure body weight found no significant effects of TTA at 1g daily over 28 days in dyslipidemic diabetic men, weight remained stable at 96.3+/-15.9kg.
TTA appears to induce mitochondrial β-oxidation in liver cells (mice) via activation of PPARα and in cultured cells treated with TTA a decrease in triglycerides is noted; this is thought to underlie both antiobese and lipid lowering properties of TTA. Beyond activation of PPARα, PPARδ may also be a target as are the stress factors mTOR and ERK1/2.
Increasing fatty acid oxidation in the liver may underlie some antiobese and lipid lowering properties of supplemental TTA
In several cases, the addition of TTA to a diet has increased the body's relative serum content of oleic acid; a omega-9 monounsaturated fatty acid found in Olive Oil, although it reduced the overall content of fatty acids. This appears to be via upregulation of the enzyme delta-9-desaturase (D9D) mRNA, which produces oleic acid from dietary saturated fatty acids such as palmitic acid and the decrease in total fatty acids was due to general oxidation (burning) of them. The upregulation of D9D does not appear to be related to PPARα activation.
May induce activity of the delta-9-desaturase enzyme and increase bodily stores of oleic acid
28 days supplementation of TTA was able to significantly reduce circulating Vitamin E levels by about 2nmol/L, which was said to be due to its correlation with serum lipids and the general decrease in serum lipids seen with TTA.
The two main fatty acids in Fish Oil, EPA and DHA, had their circulating levels decreased by 10% and 13% respectively, after 28 days of 1g TTA supplementation in diabetic and hyperlipidemic men, which the authors attributed to increase peroxisomal fatty acid oxidation favoring omega-3 polyunsaturated fatty acids, which is seen in rats.
Due to the potential of TTA (like any fatty acid) to be stored in the body for longer periods of time, caution with superloading should be exerted.
Preliminary investigation into human consumption have found no adverse effects at doses of 300-1000mg a day for 7 consecutive days. with another study noted no side effects at 1000mg for 28 days in diabetic males.
Unpublished preclinical toxicity studies in dogs and rats (unpublished, but mentioned in citation) have apparently concluded little to no risk of toxicity.
No apparent toxicity at this moment in time, but not enough evidence to really draw solid conclusions from either; would be prudent to stick to 1,000mg for now
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