r-ALA plus CLA....could be fun to try!

[MS]

Here's an interesting bit of research that shows that r-ALA by itself, is less than impressive when given to obese, diabetic rats. BUT, when combined with conjugated-linoleic acid (CLA) it acted synergistically to dramtically enhance whole body glucose uptake.

Wonder what it would do in non-obese, exercising humans?

Interactions of Conjugated-Linoleic Acid and Alpha-Lipoic Acid
on Insulin Action in the Insulin-resistant Obese Zucker Rat.

Taylor ZC, Teachey MK, Saengsirisuwan V, O'Keefe MP, and Henriksen EJ,
Muscle Metabolism Laboratory, Department of Physiology, University of Arizona
College of Medicine, Tucson, AZ

The essential fatty acid conjugated-linoleic acid (CLA) and the antioxidant
R-alpha-lipoic acid (R-ALA) individually have been shown to enhance glucose
tolerance and insulin action on skeletal muscle glucose transport in insulin-resistant
states. However, to date, no study has assessed the potential interactions between
these two interventions in treating insulin resistance. Therefore, the purpose of this
study was to assess the interactions of low doses of CLA and R-ALA on
whole-body insulin sensitivity and insulin-stimulated glucose transport in skeletal
muscle of the insulin-resistant obese Zucker (fa/fa) rat. Female obese Zucker rats
(~7-8 wk old) were treated with either vehicle or submaximal doses of CLA (0.3
g/kg body wt) or R-ALA (10 mg/kg), individually and in combination, for 21 days.
The glucose-insulin index, an indirect indicator of whole-body insulin sensitivity
derived from an oral glucose tolerance test, was not altered by this dose of R-ALA
compared to the vehicle-treated control group. However, CLA alone caused a 17%
decrease (p<0.05) in this variable, indicating an enhancement of insulin sensitivity.
The greatest improvement in whole-body insulin sensitivity was associated with the
combination treatment, as the largest decrease (21%) in the glucose-insulin index
was observed. Insulin-mediated (5 mU/ml) glucose transport activity (as assessed
by in vitro 2-deoxyglucose uptake) in both the type I soleus and the type IIb
epitrochlearis was not altered by treatment with R-ALA. CLA induced a 37%
increase in insulin-mediated glucose transport in the epitrochlearis only. Most
importantly, the combination of R-ALA and CLA induced the greatest improvements
in insulin-mediated glucose transport in both the epitrochlearis (77%) and the soleus
(54%) muscles. These results suggest that R-ALA and CLA treatment in
combination improves whole-body insulin sensitivity and insulin-stimulated glucose
transport activity in skeletal muscle of the insulin-resistant obese Zucker rat to a
greater degree than either intervention individually. (Supported by BASF AG,
Ludwigshafen, Germany (EJH) and the University of Arizona Undergraduate Biology
Research Program (ZCT).)

 

[SteelWeaver]

Wonder what it would do in non-obese, exercising humans?

Guess you're just gonna have to TRY

Didn't W6 mention something about CLA + r-ALA on the ALA thread? Or was that GLA?

What's the deal with CLA anyway? Some magazines are touting it as being able to aid fat loss in some or other way ....

 

[MR. BMJ]

MS, I was wondering if you have looked into CLA in regards to its different isomers? From what I understand, some of the isomers that are commercially sold do not do squat. However, there are the isomers that are effective. In other words, the isomerization of this compound determines its success or failure. Have you read anything in regards to this?

I know when Bill Phillips came out with EAS's CLA formula a few years back, it was very hyped up, then it died down. Later, TC Luoma, who is now one of the guys at Test.net mentioned that BP drew the gun early and released the CLA that was a different isomer than the one used in studies, and was basically trash. He said that BP knew it was the wrong isomer, but didn't want to wait for the real thing. NOW, I KNOW TESTOSTERONE MAG IS A LOT OF HYPE, AND HAS THEIR OWN LINE OF SUPPLEMENTS (had to get that clear before I got flamed), but it does raise an eyebrow or two if it is true...ya think? Or am I wrong? A lot of the research I have read seems to be very conflicting on results.

Well, i'll try and get the pride to go over and find that article by TC at Testosterone.net, and copy and paste it here if I can.

Well, at any rate, the studies do look promising with CLA combined with that of the r-enantiomer ALA. I predict that an R-ALA + GLA + CLA combo will be the next great combo for the future.

BMJ

 

[MS]

"From what I understand, some of the isomers that are commercially sold do not do squat"


It's actually a lot worse than that. There are many isomers of CLA, and one of the more commonly found ones (trans-10 cis-12), reproducibly INCREASES insulin resistance in humans, while reducing BAT thermogenesis (by inhibiting norepinephrine induced uncoupling protein induction), AND reduces leptin expression. Bad shit, just like many other trans fats. On the other hand, this isomer may also inhibit adipogenesis, so it's STILL not a clear-cut good or bad supp by itself. As a side note, the 'negative' side effects of this isomer are most likely due to it's reduction of leptin, and there may be a therapeutic potential for combined treatment with the trans-10 cis 12 isomer AND leptin....... As another SIDE side note, this isomer (trans-10 cis-12) appears more likely to posses antioxidant activity, whereas the other isomer may have pro-oxidant activity. I have a strong feeling in my gut that this may be where the r-ALA comes into play, both as a balancing anti-oxidant to the other common isomer (cis-9,trans-11) and as a leptinergic supp (via increased glucose flux), not to mention decreasing insulin resistance. This is pure speculation, but at this stage I would aim for something close to a 50:50 blend of the two common isomers (plus r-ALA). Note that most naturally occuring CLA is closer to 80:20, and this is prolly what was marketed because it would be a lot cheaper to produce.

Geesh, I've just put everyone to sleep for the night

 

[SteelWeaver]

Zzzzzzzz



lol

 

[MR. BMJ]

Hey thanks for the great info MS! Here is that article written by TC. It is fairly long, but it is a good read. I believe it is about a year old or so...give or take a few months. Therefore, it may or not be a little outdated from newer research that may have arisen.

Here it is:

CLA Revisited
by TC Luoma

Back in 1994, when I was working as Editor-in-Chief of Muscle Media 2000 (not to be confused with the watered-down version that's on the stands today), I stumbled on a pretty interesting compound. It was called Conjugated Linoleic Acid, or CLA. Chemically speaking, linoleic acid is an essential fatty acid, the kind you find in flax and other oils. It has two double bonds, but when you subject it to any number of chemical reactions, the double bonds shift so that they're only separated by one bond. The molecule that results is known as a conjugated fatty acid.

There are probably a couple of dozen of these conjugated isomers, and the names indicate whether there's a "hiccup" or kink in the molecule (a cis double bond) or the absence of a hiccup (a trans double bond). For example, according to the research I stumbled on, cis-9, trans-11 was considered to be a "magic" CLA isomer, one with very unusual biological effects.

Anyhow, according to the research conducted by scientists at the University of Wisconsin, CLA, when given in sufficient amounts, could completely lean out fat mice. It also seemed to literally erase certain types of mouse tumors. Mice everywhere were excited over the prospect of longer lives and svelter physiques. What's more, there seemed to be strong evidence that it muscled up rats, mice, chickens, and pigs.

I literally freaked. I thought that CLA, might, could, possibly, turn out to be an incredible supplement for athletes of the non-mus musculus species (and the general public, too).

But try as I might, I couldn't find anybody who could/would make it for me. Unless I talked my employer, EAS, into buying a large volume of the stuff, the per-unit costs would be prohibitive. Besides, human studies hadn't been done yet, so we didn't know if the cash expenditure would pan out or not.

So, I sat on it.

About a year later, though, a company in Norway contacted me. They were a leading manufacturer of fish oils and they claimed that they could easily make CLA. I figured that we could order some and begin doing some human trials. In the meantime, I'd work with the scientists at the University of Wisconsin who had discovered the stuff.

It didn't quite work the way I wanted it to. When I told the CEO of EAS about the product, he wanted to forgo human trials and go straight into production. So he did. Back in late 1995, EAS introduced CLA to the market.

It fizzled. Athletes weren't making any muscle gains on the stuff, nor were they losing any noticeable amounts of fat. A study using humans was conducted and it, too, showed indeterminate results.

So CLA was reviled as a useless supplement. Other companies started making it for the general public, but sales never took off, perhaps because of the bad rap earned by the EAS product.

I just couldn't figure it out. There was no reason for it not to work. Still, it became a pariah of the supplement industry. Unsold bottles sat on the shelves of health food stores, marks on their dusty containers from where people had been touching them with ten-foot poles.

Recently, though, new answers have arisen. It turns out that back then, the company that made the stuff used toxic solvents and harsh catalysts to produce the stuff. Now that doesn't necessarily mean that the product itself was toxic — it only meant that the manufacturing process wasn't refined, wasn't elegant, and that mishaps were a possibility. No one turned into a toxic swamp monster from using the stuff, least of all me, but the thought of having used that product for many months is a little unsettling when I think back on it.

Additionally, as a result of this crude manufacturing process, the final product contained about 25 different CLA isomers, when all we wanted was the cis-9, trans-11 variety. Looking back, probably only 20-25% of the EAS product consisted of the magic isomer. To even have a chance of affecting some sort of physical change on the body, a person would have to consumer 15 to 20 of the huge pills a day.

That wasn't the only problem. Even though we were trying to harvest large amounts of the cis-9, trans-11 isomer, recent research seems to indicate that it might have been the cis-10, trans-12 isomer that was the "magic" isomer all along.

No wonder the EAS product didn't work!

Regardless of all that, is there still any evidence we should give CLA a second look?

I definitely think so. Michael Pariza, one of the CLA pioneers, presented the preliminary results of a new CLA study to members of the American Chemical Society last fall. Pariza recruited 80 obese men and women. He gave 3 grams of CLA per day to half of them, and the other half received the same dosage of sunflower oil. Even though Pariza's more recent studies had shown that it really is the cis-10, trans-12 isomer that's responsible for altering fat accumulation, he used a 50:50 mix (of the cis-9, trans-11 and the cis-10, trans-12 isomers) to keep costs down.

At the end of 6 months, all of the subjects had lost weight (about 5 pounds each), but a third of the subjects taking CLA increased muscle mass. Pariza theorized that a "nutrient partitioning" effect was happening. In other words, calories that might originally be stored as fat were, because of the CLA, being partitioned into muscle.

Pariza, as quoted in the March 3, 2001 edition of "Science News," tried to explain the fat-loss phenomenon: "Every fat cell in the body wants to get big. What the cis-10, trans-12 CLA does is force that fat cell to stay little by affecting a number of enzymes that are ordinarily responsible for filling it with lipids."

Another similar study was conducted in Norway, the results of which appear in the December, 2000, edition of "The Journal of Nutrition." Ola Gudmundsen of the Scandinavian Clinical Research Center in Norway engaged 60 overweight volunteers in a 3-month trial. Half of them got 9 grams of olive oil per day while the other half got from between 1.7 and 6.8 grams of CLA per day (again, they used the same 50:50 blend mentioned previously).

Those who swallowed 3.4 grams or more of CLA per day ended up weighing 2 to 3 pounds less than the others. While that doesn't sound like much, consider that 2 to 3 pounds is the statistical mean, and that some might have lost considerably more. The group at the higher end of the CLA intake didn't end up losing any more weight, but they did gain more muscle mass.

Consider what the supplement might do if put in the hands of someone who knew a thing or two about training or diet.

Although Pariza mentioned that CLA might have a "nutrient partitioning" effect, it doesn't really give much insight to the alleged mechanisms of the food supplement. Theories abound, though. Perhaps it somehow helps maintain a positive nitrogen balance; maybe it's such a powerful antioxidant that it simply prevents cell damage from a variety of factors and thus leads to a net increase in growth; or maybe it's an undiscovered growth factor.

Whatever the reason, it seems that the substance is still something to be reckoned with, especially when you look at some of its other alleged benefits.

A researcher named Martha Bleury, who's affiliated with Northwest Hospital in Seattle, reported another mind-blowing study at that same ACS society meeting. She started giving Type II diabetes patients, 6 grams of CLA or 6 grams of plain old safflower oil. The CLA group showed a marked decrease in triglyceride levels, along with a significant drop in fasting blood sugar levels.

Although she's not sure how it works, she assumes that CLA is binding to receptors the same way as some antidiabetes drugs.

The substance has even been shown to reduce arterial plaques by 30 percent (Science News, March 3, 2001)! Granted, the experiments were done with rabbits, but it's still compelling.

Of course, in our field, it's the getting-bigger thing that probably arouses the most interest. Although human studies are still sorely lacking, you can't easily dismiss some of the animal studies. Earlier studies on rats showed that those whose diets were supplemented with CLA gained weight much more quickly than control groups. The authors theorized that all living creatures — at least mammals — are continually confronted by immune stimulation, so much so that it partitions energy away from other biological factors, including growth (Chin, et al, 1994). By reducing this response—through CLA supplementation — food efficiency and growth is enhanced.

Researcher Mark Cook has conducted similar immune stimulation experiments in rats, mice, chicks, and pigs. CLA supplementation blocked wasting without reducing the animal's ability to fight disease. Part of this, Cook theorizes, comes from CLA's ability to dramatically increase several families of infection-fighting white blood cells.

Whatever the mechanism, I maintain that CLA deserves a second look, a new trial. However, some of the same rotten manufacturing processes that were around when I first helped bring CLA to the market are still around. So, as far as buying CLA off the shelves, it's caveat emptor.

Mark Pariza, the father of CLA, recommends that you only buy products that use CLA from Loders Croklaan and Natural Inc, both of Sandvika, Norway. They test each batch to make sure that it contains at least a 50:50 mix of the two biologically active isomers. And, with time — should the cis-10, trans-12 isomer prove without a doubt that it's the one we should be looking at — manufacturers will be able to produce versions that are 100% cis-10, trans-12.

While CLA exists naturally in almost all foods, particularly dairy food, the average person probably ingests about 1 gram a day. To get any noticeable benefits, though, you'd probably have to ingest anywhere from 3 to 6 grams a day.

Personally, I think CLA might be one of those supplements that we end up taking every day, forever, regardless of whether we're in a bulking phase, a dieting phase, or a sit-on-the-couch phase. With all its possible fat-burning, muscle-building, blood-sugar lowering, immune-enhancing effects, it just makes sense.

MR. BMJ

 

[MR. BMJ]

I posted this study a few days ago on AF.

Circulation 2002 Oct 8;106(15):1925-9 Links


Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein: a potential link to fatty acid-induced insulin resistance.

Riserus U, Basu S, Jovinge S, Fredrikson GN, Arnlov J, Vessby B.

Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden. [email protected]

BACKGROUND: Conjugated linoleic acids (CLAs), a group of fatty acids shown to have beneficial effects in animals, are also used as weight loss supplements. Recently, we reported that the t10c12 CLA-isomer caused insulin resistance in abdominally obese men via unknown mechanisms. The aim of the present study was to examine whether CLA has isomer-specific effects on oxidative stress or inflammatory biomarkers and to investigate the relationship between these factors and induced insulin resistance.

METHODS AND RESULTS: In a double-blind placebo-controlled trial, 60 men with metabolic syndrome were randomized to one of 3 groups receiving t10c12 CLA, a CLA mixture, or placebo for 12 weeks. Insulin sensitivity (euglycemic clamp), serum lipids, in vivo lipid peroxidation (determined as urinary 8-iso-PGF(2alpha) [F2-isoprostanes]), 15-ketodihydro PGF(2alpha), plasma vitamin E, plasma C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 were assessed before and after treatment. Supplementation with t10c12 CLA markedly increased 8-iso-PGF(2alpha) (578%) and C-reactive protein (110%) compared with placebo (P<0.0001 and P<0.01, respectively) and independent of changes in hyperglycemia or dyslipidemia. The increases in 8-iso-PGF[2alpha), but not in C-reactive protein, were significantly and independently related to aggravated insulin resistance. Oxidative stress was related to increased vitamin E levels, suggesting a compensatory mechanism.

CONCLUSIONS: t10c12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men. The oxidative stress seems closely related to induced insulin resistance, suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance. These unfavorable effects of t10c12 CLA might be of clinical importance with regard to cardiovascular disease, in consideration of the widespread use of dietary supplements containing this fatty acid.

PMID: 12370214 [PubMed - in process]

All this CLA stuff is still too damn conflicting

I don't really know what to think yet.

BMJ

 

[MS]

Sure, it's all confusing on one level, but on another level it appears that a good quality mixture of the two common isomers IS beneficial. I think of CLA as a yin/yang supplement. For whatever reasons, taking either of the purified isomers on their own is useless or even harmful, but when taken together they seem to work synergistically. Funny really, nature sometimes knows best. r-ALA just MAY turn out to salvage the t10c12 CLA-isomer via reduced insulin resistance and increased leptin. I guess THAT's why I got excited by the study I posted.....as a dieting aid it could be a dynamite combo!

Of course, there is also the arguement that just eating more range fed (as opposed to feedlot fattened) meat and dairy products, as well as oily fish could have the same effect. Our ancestors seemed to do OK on it! Honestly I often feel that we're just trying to re-invent the wheel when it comes to reducing obesity. But I guess 6 billion people can't ALL go free range hunting and foraging That just means there's too many damn people on this planet.