Cy/Lowery: Sulphur Containing Fatty-Acids

Diet and Nutrition
1

Someone peaked my interest to these compounds on another website. They are a saturated fatty-acid’s w/ a added sulphur molecule. The one I am specifically interested in is called “3-thia”. I did a pubmed search and was astounded to find more then a few studies on their possible health benefits. Here is an abstract from a review article that summarizes some of the possible health benefits:

“Thia substituted fatty acids are saturated fatty acids which are modified by insertion of a sulfur atom at specific positions in the carbon backbone. During the last few years pleiotropic effects of the 3-thia fatty acid tetradecylthioacetic acid have been revealed. The biological responses to tetradecylthioacetic acid 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 tetradecylthioacetic acid changes the plasma profile from atherogenic to cardioprotective. As a pan-peroxisome proliferator-activated receptor ligand, tetradecylthioacetic acid regulates the adipose tissue mass and the expression of lipid metabolizing enzymes, particularly those involved in catabolic pathways. In contrast, circumstantial evidences suggest that peroxisome proliferator-activated receptor-independent metabolic pathways may be of importance for the antioxidant, antiproliferative and antiinflammatory action of tetradecylthioacetic acid.”

Cliffs:

  • cardio protective
  • increased mitochondria proliferation
  • Positive impact on metabolism and body composition
  • Anti-O activity
  • cancer fighting

All this at a dosage similiar to 1 gram a day.

Many of the studies were in vivo or in rats but I still had difficulties finding ANY negative effects in the literature. Some of the researchers seemed to suggest they worked via PPAR antagonists which I have read isnt always a good thing.

Anyways, I was hoping you two could shed some light on these compounds for me. I know Lowery loves his fats :slight_smile:

For anyone interested search pubmed or google for “3-Thia”.

2

Bump. Sounds interesting

3

I’ve never heard of it. Interesting. I’ll let Lonnie comment as I don’t really know much about it.

I will say however, the purported effects upon body composition in mice and rats, as it relates to being a PPAR alpha agonist at least, do not transfer well to humans. Again, this is a classic case in point where a difference in species causes a discrepancy in certain aspects. Rodents have more PPAR alpha receptors than humans and also differ from humans in terms of which genes are activated by agonists binding to the receptor.

This is very important because if one takes a look at what happens in mice and rats which end up reducing fat mass and so forth due to peroxisome proliferation and such, they end up developing liver tumors/cancer. This is a case where it’s actually a good thing that we don’t experience this same effect. In rodents, you see a huge increase in peroxisome proliferation and as a result, a large increase in beta-oxidation of certain fatty acids. However, as a result of this, they then begin to develop hepatic tumors.

In short, PPAR alpha agonists simply don’t have a place in fat loss when it comes to humans. Now in respect to other benefits such as improving blood lipids, that’s much more likely, as evidenced by fibrates.

4

Some folks think that Melting Point is going to contain something along these lines.

A lot of people thing the the 3-thia fatty acids or Medica-16 will be the “next thing” in fat-loss.

Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E795-803. Epub 2002 Dec 17. Related Articles, Links
Click here to read
Adipose tissue sensitization to insulin induced by troglitazone and MEDICA 16 in obese Zucker rats in vivo.

Kalderon B, Mayorek N, Ben-Yaacov L, Bar-Tana J.

Department of Human Nutrition and Metabolism, Hebrew University Medical School, Jerusalem, Israel 91120. bella@pob.huji.ac.il

The putative role played by insulin sensitizers in modulating adipose tissue lipolysis in the fasting state was evaluated in obese conscious Zucker rats treated with troglitazone or beta,beta'-tetramethylhexadecanedioic acid (MEDICA 16) and compared with nontreated lean and obese animals. The rates of appearance (R(a)) of glycerol and free fatty acid (FFA), primary intra-adipose reesterification, and secondary reuptake of plasma FFA in adipose fat were measured using constant infusion of stable isotope-labeled [(2)H(5)]glycerol, [2,2-(2)H(2)]palmitate, and radioactive [(3)H]palmitate. The overall lipolytic flux (R(a) glycerol) was increased 1.7- and 1.4-fold in obese animals treated with troglitazone or MEDICA 16, respectively, resulting in increased FFA export (R(a) FFA) in the troglitazone-treated rats. Primary intra-adipose reesterification of lipolysis-derived fatty acids was enhanced twofold by insulin sensitizers, whereas reesterification of plasma fatty acids was unaffected by either treatment. Despite the unchanged R(a) FFA in MEDICA 16 or the increased R(a) FFA induced by troglitazone, very low density lipoprotein production rates were robustly curtailed. Total adipose tissue reesterification, used as an estimate of glucose conversion to glyceride-glycerol, was increased 1.9-fold by treatment with the insulin sensitizers. Our results indicate that, in the fasting state, insulin sensitizers induce, in vivo, a significant activation rather than suppression of adipose tissue lipolysis together with stimulation of glucose conversion to glyceride-glycerol.

Med Hypotheses. 1999 Oct;53(4):272-6. Related Articles, Links
Click here to read
Peroxisome proliferators as adjuvants for the reverse-electron-transport therapy of obesity: an explanation for the large increase in metabolic rate of MEDICA 16-treated rats.

McCarty MF.

Nutrition 21/AMBI, San Diego, CA 92109, USA.

The efficacy of reverse-electron-transport therapy of obesity should be promoted by agents which up-regulate hepatocyte enzymes that are potentially rate-limiting for mitochondrial fatty acid oxidation and electron shuttles. Peroxisome proliferator drugs, including the fibrates used to treat hyperlipidemia, may be useful in this regard, as they induce malic enzyme, the mitochondrial glycerol-3-phosphate dehydrogenase, and carnitine palmitoyl transferase I in rodent hepatocytes. An agent of this class, MEDICA 16, has the additional property of potently inhibiting both citrate lyase and acetyl-CoA carboxylase. As a result, methyl-substituted diacarboxylic acids (MEDICA) 16 can be expected to disinhibit hepatic fatty acid oxidation while up-regulating electron shuttle mechanisms, and thus should stimulate reverse electron transport. This may explain the remarkable 40% increase in basal metabolic rate observed in normal rats ingesting MEDICA 16--an effect not associated with any compensatory increase in food intake. Relative to controls, the MEDICA 16-treated rats achieved a 50% reduction in body fat and a modest increase in lean mass, such that weight and growth were not changed. In other rodent strains, MEDICA 16 has prevented obesity diabetes and atherogenesis. However, whether MEDICA 16 and other peroxisome proliferator drugs will have clinical utility in reverse-electron-transport therapy may hinge on their ability to induce key enzymes in human hepatocytes; cell culture studies to evaluate this are required.

PMID: 10608261 [PubMed - indexed for MEDLINE]
5

Whats “Melting Point”?

6

Its the new fatloss supp by Designer Supplements. Super secret ingrediant is supposed to a fatty acid of some sort.

Although the rat studies may not translate into human benefits, the 50% fat loss and increase in lean mass from the second article sounds impressive.

7

[quote]Cy Willson wrote:
I’ve never heard of it. Interesting. I’ll let Lonnie comment as I don’t really know much about it.

I will say however, the purported effects upon body composition in mice and rats, as it relates to being a PPAR alpha agonist at least, do not transfer well to humans. Again, this is a classic case in point where a difference in species causes a discrepancy in certain aspects. Rodents have more PPAR alpha receptors than humans and also differ from humans in terms of which genes are activated by agonists binding to the receptor.

This is very important because if one takes a look at what happens in mice and rats which end up reducing fat mass and so forth due to peroxisome proliferation and such, they end up developing liver tumors/cancer. This is a case where it’s actually a good thing that we don’t experience this same effect. In rodents, you see a huge increase in peroxisome proliferation and as a result, a large increase in beta-oxidation of certain fatty acids. However, as a result of this, they then begin to develop hepatic tumors.

In short, PPAR alpha agonists simply don’t have a place in fat loss when it comes to humans. Now in respect to other benefits such as improving blood lipids, that’s much more likely, as evidenced by fibrates.[/quote]

Cy, I thought that although PPAR Alpha antagonists dont have a good human carry over PPAR Beta antagonists would have a huge impact in humans due to relative receptor quantities.

8

Type in PPAR in Pubmed. It seems the researchers are off and running. Look how many abstracts are in 2005.

9

[quote]Tallen234 wrote:
Type in PPAR in Pubmed. It seems the researchers are off and running. Look how many abstracts are in 2005. [/quote]

Yes, much of this is dealing with the applications to inflammation and insulin sensitivity.

10

[quote]Helix wrote:
Cy Willson wrote:
I’ve never heard of it. Interesting. I’ll let Lonnie comment as I don’t really know much about it.

I will say however, the purported effects upon body composition in mice and rats, as it relates to being a PPAR alpha agonist at least, do not transfer well to humans. Again, this is a classic case in point where a difference in species causes a discrepancy in certain aspects. Rodents have more PPAR alpha receptors than humans and also differ from humans in terms of which genes are activated by agonists binding to the receptor.

This is very important because if one takes a look at what happens in mice and rats which end up reducing fat mass and so forth due to peroxisome proliferation and such, they end up developing liver tumors/cancer. This is a case where it’s actually a good thing that we don’t experience this same effect. In rodents, you see a huge increase in peroxisome proliferation and as a result, a large increase in beta-oxidation of certain fatty acids. However, as a result of this, they then begin to develop hepatic tumors.

In short, PPAR alpha agonists simply don’t have a place in fat loss when it comes to humans. Now in respect to other benefits such as improving blood lipids, that’s much more likely, as evidenced by fibrates.

Cy, I thought that although PPAR Alpha antagonists dont have a good human carry over PPAR Beta antagonists would have a huge impact in humans due to relative receptor quantities.[/quote]

That’s an interesting point, Helix. I have seen data which indicates that perhaps some type of putative PPAR beta agonist could increase UCP-2 expression in human skeletal muscle, so you bring up a good point. Questions I don’t have answered (perhaps you’ve seen some papers and could share) are to what degree is fat mass altered, in an entire organism and which compounds are potent agonists thereof.

I wasn’t aware that the content of the receptor had been known. Do you know of a paper regarding that?

From what you’ve said, there definitely seems to be some potential here, but I don’t know that I’d go as far as to say (both safety and efficacy wise) that this would have a definite huge impact in humans.

11

Hi Helix,
I can only supply the comment used in our last conversation:

“Actually, I’m not familiar with them to be honest. They sound more pharmaceutical than dietary to me.”

Waiting for human trials is important. Comments on species-specificity are already here.

PS Just as an FYI, the last I looked into such things, the potential PPAR-mediated carcinogenic effects seen in rats are due to oxidative by-products of peroxisomal beta-oxidation (hydrogen peroxide).

12

One last point. Since humans have about 1/10th the PPARalpha of rats, the carcinogenicity issue seems far less, I agree (there are some 2004, 2005 papers on the continuing debate) and PPAR (various types) are getting a serious look by the pharm industry.
But judging by your posts, it looks like this is already known, eh?

13

Anyone have any new opinions on tetradecylthioacetic acid (TTA) which is the active ingrediant in some new supps (Melting Point, Red Acid, CNW bulk TTA, etc.). It appears it would be a killer supp on a low carb diet.

Biochimie. 2005 Jan;87(1):15-20. Related Articles, Links

The metabolic syndrome and the hepatic fatty acid drainage hypothesis.

Berge RK, Tronstad KJ, Berge K, Rost TH, Wergedahl H, Gudbrandsen OA, Skorve J.

Institute of Medicine, The Lipid Research Group, Haukeland University Hospital, University of Bergen, 5021 Bergen, Norway. rolf.berge@med.uib.no

Much data indicates that lowering of plasma triglyceride levels by hypolipidemic agents is caused by a shift in the liver metabolism towards activation of peroxisome proliferator activated receptor (PPAR)alpha-regulated fatty acid catabolism in mitochondria. Feeding rats with lipid lowering agents leads to hypolipidemia, possibly by increased channeling of fatty acids to mitochondrial fatty acid oxidation at the expense of triglyceride synthesis. Our hypothesis is that increased hepatic fatty acid oxidation and ketogenesis drain fatty acids from blood and extrahepatic tissues and that this contributes significantly to the beneficial effects on fat mass accumulation and improved peripheral insulin sensitivity. To investigate this theory we employ modified fatty acids that change the plasma profile from atherogenic to cardioprotective. One of these novel agents, tetradecylthioacetic acid (TTA), is of particular interest due to its beneficial effects on lipid transport and utilization. These hypolipidemic effects are associated with increased fatty acid oxidation and altered energy state parameters of the liver. Experiments in PPAR alpha-null mice have demonstrated that the effects hypolipidemic of TTA cannot be explained by altered PPAR alpha regulation alone. TTA also activates the other PPARs (e.g., PPAR delta) and this might compensate for deficiency of PPAR alpha. Altogether, TTA-mediated clearance of blood triglycerides may result from a lowered level of apo C-III, with a subsequently induction of hepatic lipoprotein lipase activity and (re)uptake of fatty acids from very low density lipoprotein (VLDL). This is associated with an increased hepatic capacity for fatty acid oxidation, causing drainage of fatty acids from the blood stream. This can ultimately be linked to hypolipidemia, anti-adiposity, and improved insulin sensitivity.

14

Bump?

Any opinions on TTA, Red Acid, Melting Point?