Conjugated Linoleic Acid

Conjugated Linoleic Acids (CLA) – Supplement Profile

With the increased use of thermogenic supplements to aid people in their efforts to lose fat, many have found themselves in a predicament when it comes time to finish their diet. Thermogenics cause a number of beneficial effects that facilitate fat loss, however, when the supplements are discontinued, the metabolic pendulum can swing back the other way, threatening all the hard work it took to lose the fat. When it comes to ephedrine and metabolism it can be said, “what goes up must come down.”

What a person needs at that moment is something that will aid them in keeping off the fat once they finally get it off, but at the same time give them a break for the constant CNS stimulation of thermogenics. Conjugated linoleic acids, or CLA as it is called, may be just what they need.

What it is?

CLA is a naturally occurring fatty acid found primarily in beef and dairy fats. CLA is formed from linoleic acid by bacteria in the gut of ruminants (cows and other herbivores with multiple stomachs). The cows then absorb the CLA and it becomes incorporated into their lipid stores, including milk lipids. We then absorb it when we eat them, or drink their milk.

There is research showing that cows produce CLA endogenously as well. (Griinari JM, Corl BA, Lacy SH, Chouinard PY, Nurmela KV, Bauman DE. Conjugated linoleic acid is synthesized endogenously in lactating dairy cows by Delta(9)-desaturase. J Nutr. 2000 Sep;130(9):2285-91) They found that as much as 64% of CLA in cows milk may be produced by the enzyme Delta(9)-desaturase. It appears that humans also can produce CLA endogenously through similar pathways (Adlof RO, Duval S, Emken EA. Biosynthesis of conjugated linoleic acid in humans. Lipids. 2000 Feb;35(2):131-5).

CLA exists as several isomers (same molecule, different conformation, kind of like your left and right hands being the same but different). Two CLA isomers (cis-9, trans-11 CLA and trans-10, cis-12 CLA) have been shown to exhibit strong biological activity and which appear to exert their effects via different biochemical mechanisms (e.g. one through PPAR alpha, the other through PPAR gamma, etc). Because there are many isomers with seemingly different biological effects, the exact mechanisms of action are still being ironed out. When the exact effects of each isomers are defined look forward to much more powerful CLA supplements with more predictable effects.

How it works?

CLA increases fat oxidation
(West, D. B., J. P. DeLany, P. M. Camet, F. Blohm, A. A. Truett, and J. A. Scimeca. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am. J. Physiol. 275 (Regulatory Integrative Comp. Physiol. 44): R667-R672, 1998) CLA has been shown to increase certain enzymes responsible for fatty acid beta-oxidation and mobilization (e.g. ACO, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase [bi-(tri) functional enzyme], CYP4A, L-FABP, acyl Co-A synthase, lipoprotein lipase, and many others). (Belury, M. A., Moya-Camarena, S. Y., Liu, K-L., Vanden Heuvel, J. P. 1997. Dietary conjugated linoleic acid induces peroxisome-specific enzyme accumulation and ornithine decarboxylase activity in mouse liver. J. Nutr. Biochem. 8:579-584) This means that the body?s ability to mobilize and burn fat goes up with chronic CLA supplementation. Although CLA is only recently coming into its own as far as research goes, data so far points to peroxisome proliferator-activated receptor (PPAR) activity as the most probable mechanism for CLA?s effects on fat metabolism. I?m sure many of you haven?t heard much of these receptor proteins yet, but believe me, you will soon. PPARs are key regulators of lipid homeostasis and are activated by a structurally diverse group of compounds including fatty acids, eicosanoids (prostaglandins), and hypolipidemic drugs. Evidence is mounting that indicates that PPARs serve as physiological sensors of lipid levels and suggests a molecular mechanism whereby dietary fatty acids (like CLA) can modulate lipid homeostasis. (Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ, Sternbach DD, Lehmann JM, Wisely GB, Willson TM, Kliewer SA, Milburn MV. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. 1999 Mar;3(3):397-403) Who knows, I might even tackle them for a future How?z it Work piece considering they are involved in the mechanism of action of not only CLA but also fatty acids such as flax and omega-3s. (Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM, Lehmann JM Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci U S A 1997 Apr 29;94(9):4318-23) For now that?s as far as we?ll go into it.

Inhibition of triglyceride uptake into fat cells
The best way to get fat is to send the fat you eat straight to the fat cell to be stored. This is generally what happens when we eat fat, however CLA supplementation has been shown to decrease the enzyme necessary for fat cells to take up fat and triglycerides from the blood. (Park, Y., K. J. Albright, W. Liu, J. M. Storkson, M. E. Cook, and M. W. Pariza. Effect of conjugated linoleic acid on body composition in mice. Lipids 32: 853-858, 1997) Lipoprotein lipase activity is decreased by dietary CLA supplementation thereby decreasing the ability of fat cells to take up lipids from the blood. At the same time, Carnitine palmitoyltransferase activity is increased in both fat and skeletal muscle thereby increasing the capacity of these tissues to oxidize fatty acids. This alone could be largely responsible for the effects of CLA on body composition.

Increases insulin sensitivity
The reason CLA has been labeled a “partitioning agent” is because of its ability to increase the uptake of energy into muscle tissue and the ability to blunt energy intake into fat cells. As mentioned above, this ability to increase insulin sensitivity in muscle tissue is also attributed to CLA activity as a PPAR agonist. (Houseknecht, K. L., J. P. Vanden Heuvel, S. Y. Moya-Camarena, C. P. Portocarrero, L. W. Peck, K. P. Nickel, and M. A. Belury. Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat. Biochem. Biophys. Res. Commun. 244: 678-682, 1998) So you are starving the fat and feeding your muscle, the end result being an increase or maintenance of muscle mass and a reduction in fat.

CLA acts to reduce body fat stores by chronically increasing metabolic rate.
Treatment with CLA chronically increases basal metabolic rate in test animals. (West DB, Blohm FY, Truett AA, DeLany JP. Conjugated linoleic acid persistently increases total energy expenditure in AKR/J mice without increasing uncoupling protein gene expression. J Nutr. 2000 Oct;130(10):2471-7.) Over time this elevation leads to significant reductions in fat mass. The exact mechanism by which CLA raises energy expenditure has yet to be elucidated.

Human studies?

Before we begin I think a little disclosure is in order. Natural Ltd. ASA, the Norwegian parent company of Natural Inc., and the Wisconsin Alumni Research Foundation (WARF) hold CLA patents. WARF administers patents on the intellectual properties of the faculty at the University of Wisconsin-Madison. So, whenever you see a study done in Norway or Wisconsin there is a good chance that Natural Ltd. put up some funding.

One of the first studies done on humans was done in Norway. They looked at the dose-response relationships of conjugated linoleic acid and body fat (BF) reductions. A randomized, double-blind study including 60 overweight or obese volunteers was performed. The subjects were divided into five groups receiving placebo (9 g olive oil), 1.7, 3.4, 5.1 or 6.8 g conjugated linoleic acid per day for 12 wk, respectively. Repeated-measures analysis showed that a significantly higher reduction in BFM was found in the conjugated linoleic acid groups compared with the placebo group. The reduction of body fat within the groups was significant for the 3.4 and 6.8 g CLA groups.

Adapted from Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O. Conjugated linoleic acid reduces body fat mass in overweight and obese humans J Nutr. 2000 Dec;130(12):2943-8.

One thing that still has me confused is the lack of dose response between 3.4 grams per day and 6.8 grams per day. In animal models before this they have all shown a dose response far above 3.4 grams/day, relatively speaking. Still, there was a significant effect on body fat in all groups.

Anybody familiar with CLA research is also familiar with the name Michael W. Pariza. Pariza presented a study, performed at the University of Wisconsin-Madison, August 22nd, 2000 at the American Chemical Society Meeting in Washington, D.C.

The study involved eighty people who were placed on a diet, coupled with a moderate physical exercise program. Half received about 3 grams of CLA daily, while the others took a placebo of sunflower oil. After six months, all had lost roughly 5 pounds. There is nothing particularly astounding about that, but here is where that surprise came.

About one-third of those taking CLA actually gained muscle and lost fat, Pariza said. While those taking the sunflower oil regained their weight at a ratio of about 75 percent fat to 25 percent muscle once the study finished, which is typical, those taking CLA who regained weight put on equal proportions of fat to muscle.

When a person comes to the end of their diet, what they most need is for their metabolic rate to increase to accommodate the slight increase in calories that comes with maintaining ones weight, rather than losing weight. As CLA causes a greater increase in muscle mass when the diet returns to normal, and individual will be better adapted to maintain weight loss while on a normal diet. Combine this with the nutrient partitioning effects and you have a very good solution for an inevitable rebound problem.