I wrote some time ago here about how CLA causes fat cell apoptosis, based on a Japenese research paper. As it turns out there is more to it than what its abstract revealed.

The relevant experiment has been conducted on mice, so, I don't know how much of its result applies to human beings, but basically what the paper said was that 8 months administration of CLA, at about 2-3% in total calories consumed, caused significant amount of apoptosis of adipocytes. This would be good for bb purposes (if applicable to humans), except that there seemed to be two side effects. (1) development of hyperinsulinemia and (2) enlargement of liver.

As for the development of hyperinsulinemia (insulin insensitivity) caused by CLA administration, in the full article the researchers cite two possible reasons: (1) when blood becomes more full of glucose (from ingested carb, for example), there are not many places for the plasma glucose to go (because fat cells have ... died) and (2) there is market decrease of GLUT4 in adipose tissues. To remove glucose from the blood stream, therefore, it takes lots of insulin.

There is another noteworthy fact from the experiment, and that is CLA caused enlargement of liver. CLA fed mice had liver which were 4 x larger than those mice that were not fed CLA.



I am worried about liver enlargement. (1) I don't know if it is applicable to humans (2) I don't know if it is a reversible process (3) and it might be harmful.

From what has been described in the paper, it seems that liver is trying to compensate for the role of dead subcutaneous fat cells. In other words, fat becomes "redistributed"; subcutaneous fat cells die and fat cells in the liver multiply.

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The abstract of the original paper I am concerned with, is provided below:


"Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice."

Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O.

Division of Clinical Nutrition, National Institute of Health and Nutrition, Tokyo, Japan.

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in beef and dairy products. CLA has been reported to reduce body fat. To examine the mechanism(s) of CLA reduction of fat mass, female C57BL/6J mice were fed standard semipurified diets (10% fat of total energy) with or without CLA (1% wt/wt). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick endlabeling (TUNEL) and DNA fragmentation analysis revealed that fat-mass decrease by CLA was mainly due to apoptosis. Tumor necrosis factor (TNF)-alpha and uncoupling protein (UCP)-2 mRNA levels increased 12- and 6-fold, respectively, in isolated adipocytes from CLA-fed mice compared with control mice. Because it is known that TNF-alpha induces apoptosis of adipocytes and upregulates UCP2 mRNA, a marked increase of TNF-alpha mRNA with an increase of UCP2 in adipocytes caused CLA-induced apoptosis. However, with a decrease of fat mass, CLA supplementation resulted in a state resembling lipoatrophic diabetes: ablation of brown adipose tissue, a marked reduction of white adipose tissue, marked hepatomegaly, and marked insulin resistance. CLA supplementation decreased blood leptin levels, but continuous leptin infusion reversed hyperinsulinemia, indicating that leptin depletion contributes to the development of insulin resistance. These results demonstrate that intake of CLA reduces adipose tissue by apoptosis and results in lipodystrophy, but hyperinsulinemia by CLA can be normalized by leptin administration.

I'm not very well versed in this area (CLA), but this is very good research/info, as I find it very informative and useful... I have been following your discussion of this on the HST forum, keep up the good research. CLA is becoming more and more popular, and the noted side effects are nothing to be overlooked.

I suppose that the blood sugar side effects would be less of a concern for someone who exercises (resistance or cardio) as glycogen always needs to be replaced within the muscle. I don't imagine that mice need glycogen replacement due to exercise too often in a small cage in a Japanese lab.





d.

Udo Erasmus is quite anti-CLA (well anti anything that isn't in his blend), but there is some info on side effects at his site: www.udoerasmus.com.

My two cents are that the benefits of CLA outweigh the potential negative effects.

It is not aplicable to humans. So you needant worry. The lipogenic and peroxisomal pathways of the liver in humans are allmost completely inactive. They exist in us as remnants of evolution but simply do not show up unless an extremely high carb diet is used ( 95% > from what I read). the reason being that our adipose is more advanced than other mamels being that it is quite good at esterfying TAG all on its own where as other animals need the liver to do this. I am really not a fan of CLA but I dont think you would need to worry about this. Plus its very unlikely it will cause cell death of adipose tissue in humans anyway. From what I have read adipose tissue is rather odd in that most of the time when it enters apoptosis it does not die completely but reverts to whats called a pre-adipocyte and then can be differentiated again later in the presence of the proper hormones (i.e. if we over eat it will turn right back in to an adipose cell again).

If this is a concern for you it could easily be eliminated with a fibrate drug. This is exactly what these drugs are prescribed for.

keep them coming. I am formulating a MRP for the Blue-taurus line in which I am planning to include 3.5 grams of CLA per serving. I am aware of the scandanavian studies which showed dosage over 3.5 grams per day did not increase fat loss effects.

To counteract the hyperinsuliemia a MRP with CLA should also include some insulin potentiators or mimickers. I was allready planning on including 1mg vanadyl sulfate and 500mcg of chromium picolinate.

could you elaborate on your reference to fibrate drugs... they are used for/conjunction with high LDL cholesterol treatments correct?

On the CLA-induced insulin resistance, Bryan Haycock summarized some lit on CLA and one of the findings he pointed out was that CLA increased insulin sensitivity.



http://musclemonthly.com/articles/010401/0...owz-it-work.htm

He's talking about Tonalin CLA (I think). I wonder what the isomer profile was of the CLA used in the rats-with-giant-livers research?

Jon Stark:

The isomer profile is as same as that of Tonalin (this was given in the full text of the article).

Here is what Lyle had to say about the potential negative effects of CLA, from misc.fitness.weights (usenet). Someone asked Lyle if " does that (the study) contra-indicate CLA use in humans??"

He replied:



Lyle is basically saying he does not see real reason why one should stop using CLA.

One more vote of confidence from Lyle ...

correct but they are also prescribed for "fatty liver", insulin resistance due to intra cellular TAG content, Type II diabetes induced by hypertryacylglycerimia (to much fat in the blood). Fibrates and jsut very potent PPARalpha agonists like "fish oil" but stronger. They activate the peroxisomal (the first P in PPAR) system that is normally dormant in our metabolism. This is why I recomended fibrates as an adjuct to SU in another post as the mitochondria will not be working to well so we need a way to oxidize fat and that is peroxisomes. Its just in people the peroxisomal pathway is inactive unless things are out of the ordinary.

So in summary. activating PPAR will vurn off that fat thats just hanging around in the liver cells. This is what was increasing the liver size of the rats. when adipose wont store them fats go right to the liver in most mamels (humans being one of the exceptions) where they are stored as esterfied TAG. fish oil EPA would do the same thing it would jsut take longer and require larger dosages.

New/old research....

J. Nutr., Mar 2008; 138: 509 - 514

Marianne Raff, Tine Tholstrup, Samar Basu, Pernille Nonboe, Martin Tang Sørensen, and Ellen Marie Straarup

Intake of conjugated linoleic acid (CLA) has been demonstrated to beneficially affect risk markers of atherosclerosis and diabetes in rats. CLA is naturally found in milk fat, especially from cows fed a diet high in oleic acid, and increased CLA intake can occur concomitantly with increased milk fat intake. Our objective was to investigate the effect of CLA as part of a diet rich in butter as a source of milk fat on risk markers of atherosclerosis, inflammation, diabetes type II, and lipid peroxidation. A total of 38 healthy young men were given a diet with 115 g/d of CLA-rich fat (5.5 g/d CLA oil, a mixture of 39.4% cis9, trans11 and 38.5% trans10, cis12) or of control fat with a low content of CLA in a 5-wk double-blind, randomized, parallel intervention study. We collected blood and urine before and after the intervention. The fatty acid composition of plasma triacylglycerol, cholesterol esters, and phospholipids reflected that of the intervention diets. The CLA diet resulted in increased lipid peroxidation measured as an 83% higher 8-iso-prostaglandin F2 concentration compared with the control, P < 0.0001. We observed no other significant differences in the effect of the interventions diets. In conclusion, when given as part of a diet rich in butter, a mixture of CLA isomers increased lipid peroxidation but did not affect risk markers of cardiovascular disease, inflammation, or fasting insulin and glucose concentrations.
PMID: 18287358

HL,

If one has a topic where there is uniform agreement and then one runs across one or two abstracts which say the opposite, then it is reasonable to disregard that one or two abstract. But if there are numerous studies with a very mixed bag (see all the stuff posted in previous threads) what is one or two more abstracts either way? Particularly when some of the outcomes were not just failure to be helpful, but potentially harmful.

Colin wanted new research. I didn't even read the abstract, having no interest in CLA.

The reason I bumped this thread was Spook's post on CLA induced liver enlargement being a non-issue with humans....and his post that CLA would not cause cell apotosis and that fibrates were pererable.From what I've seen i think it's a mixed bag and beza with CLA would likely do the trick as far as adipose/mammory cell apotosis is concerned.

FTR,I think commercially available CLA is overpriced.

From everything I've read one would need 15-30 grams of it per day to see fat loss.At that dosage there would also be side effects,insulin sensitivity and the like-which could be ameliorated with fish oil,sesamin,vinegar and ALA....to some extent.

FWIW,David Tolson is in agreement with me WTR the above.

I was interested and still am in using it orally at a high dose,given it (the 50/50 mix) can be bought pretty cheaply in bullk from chem/food suppliers.I think high dosing it along with insulin friendly supps is worth it over the long term for body comp benefitts,particularly for endos or for those prone to easily hold fat despite ample exercise.I plan on picking up a bunch of it in a month or so,when I have some extra dough.

The other application CLA has is towards mammory cell apotosis so I will begin experimenting with injecting CLA into my moobs,as soon as I aqquire filtering syringes.

Unless one is willing to get into all this esoteric shit,using Sesathin along with epa/dha would be boatloads better for fat loss than moderate dosing of CLA-high end dosing is way too expensive if you go the supplement route with fancy bottled product.

Taking substances which have some good and some bad effects and having to take other substances to counter the bad effects of the first substance is the way western medicine operates and I've always thought that was silly to be tactful. Yes if you must take CLA, that sounds at least like a semi-intelligent way to go about it.

Now about that ribose, etc you were going to send me....

I sent the ribose and some misc goods yesterday along with a bottle of SyntheSIZE beta.

Thanks.

...and that HEAT coming my way.

Boo-yah,mailed as well.

I threw in some 200mg theophylloine caps for ya,they compliment the HEAT nicely-no excessive CNS stimulation.Supremedan started a thread up on theo and listed the many attributes which sold me on it right off.Also chucked in some promo All The Whey packets.

Only reservation I have is that long term/chornic use may tax the tyhyroid.....dejususran (sp?) posted some shit on that but I don't think it was all that conclusive.

I hit up Pubmed to find something supporting D's commentary but I don't think I was successful in doing so...but I can't remember much about it right now as I haven't eaten yet today and feel hypoglycemic from this IF shit...the 10mg percocet,6 HEAT and 4 Scorch I took a little while ago is doing a number on my head as well.

Awesome, thanks Colin.