Conjugated Linoleic Acid (CLA)
(CLA)

General Info

Active Forms
The two most active forms of conjugated linoleic acid (CLA) are the cis-9, trans-11 isomer and the trans-10, cis-12 isomer.

Absorption
Since CLA is a fat, CLA supplements will be better absorbed from the gastrointestinal tract if they are taken with meals that contain some fat in the food that is being eaten.

Dietary Sources
Small amounts of CLA occur in most kinds of meat and slightly larger concentrations occur in milk and cheese products. However, foods rich in CLA only contain approximately 7 milligrams of CLA per gram of fat, which means it is virtually impossible to get therapeutic doses of CLA from dietary sources.

Dosage Info

Dosage Range Most of the research with CLA to date has been conducted in animals, often with relatively large doses. Until human trials are conducted, the appropriate dosage range for humans is unknown. Recommendations on available CLA supplement products seems to be in the range of two to four grams daily. Most Common Dosage The most common dosage cannot be determined at this time. Dosage Forms Gelatin capsules		Adult RDI None established Adult ODA None established

Overview

Interactions

Drug/Nutrient Interactions
•	orlistat
•	Olestra containing products
•	Bile acid sequestrants
•	mineral oil
Nutrient/Nutrient Interactions
•	chitosan
•	Lipase inhibitor supplements
•	vitamin A

Conjugated linoleic acid (CLA) refers to a group of 8 isomers that are structurally similar to linoleic acid, which is also known as omega-6. The only structural difference between linoleic acid and the CLA isomers is the location of their two double bonds. Linoleic acid has double bonds at the 9 and 12 positions from the acid end of the molecule. There are two isomers of CLA with significant activity. Cis-9, trans-11 CLA, which is generally thought to be the most active, has its double bonds at the 9 and 11 carbon positions whereas the trans-10, cis-12 CLA and its double bonds at the 10 and 12 carbon positions in the carbon chain. Cis and trans refers to the direction of the carbons in the double bonds. Cis means the carbons on each side of the double bond point in the same direction, whereas trans indicates that the carbons on either side of the double bond point in opposite directions, one up and the other down. The term “trans” here has no relationship to the “bad” trans fats that are produced during the process of partial hydrogenation.

Research is discovering that CLA has a wide range of important biological effects. Studies indicate that it enhances immunity, protects against cancer and heart disease, and helps to build muscle and promote fat loss. Recent research suggests that CLA may also help promote healthy glucose and insulin metabolism.(1) Ruminants (beef, lamb and veal) used to contain substantial amounts of CLA in their muscle tissue, but switching these animals from pasture land (grass diets) to feedlots where they are primarily fed grain has resulted in approximately a 75% decline in these animals. Since the 1960s, the CLA content of dairy products has declined by about two-thirds. It has been speculated that the dramatic decline in available CLA in American diets may be linked to increased rates of cancer, heart disease, and the epidemic of obesity. Small amounts of CLA are probably able to be synthesized in humans from the conversion of vaccenic acid (trans-11 oleic acid) to c9,t11 CLA via the action of delta-9 desaturase enzyme activity.(2)

Toxicities & Precautions

Since CLA is a fat, CLA supplements will be better absorbed from the gastrointestinal tract if they are taken with meals that contain some fat in the food that is being eaten.

General
Most studies have reported that conjugated linoleic acid is quite safe. In one toxicity study, the organs of animals given extremely high doses of CLA for 36 weeks did not exhibit any signs or symptoms of toxicity. Based on these results, the authors of this study suggested that CLA should be considered a substance that is classified as "GRAS", which means generally recognized as safe.(3) However, studies with humans reported that CLA caused increased levels of lipid peroxidation, which prompted authors to state that further studies on CLA are urgently needed.(4, 5) In addition, one study found CLA adversely affects glucose and insulin levels in those with Type 2 Diabetes.(6)

Functions in the Body

Uses

Clinical Applications
	Allergies
	Cancer
	Diabetes
	Elevated Cholesterol
	Weight Loss

Antioxidant Defense
According to the discoverer of conjugated linoleic acid, Dr. Michael Pariza, CLA provides a previously unrecognized form of antioxidant defense against membrane attack by oxygen free radicals.(7) Studies using electron spin resonance (ESR) spectrometry have confirmed that conjugated linoleic acid (CLA) has free radical scavenging attributes whereas its structural cousin linoleic acid (LA) does not.(8)

Enhances Carnitine-palmitoyltransferase Activity
CLA enhances carnitine-palmitoyltransferase activity, which regulates mitochondrial oxidation of long-chain fatty acids and the production of energy.(9) The fact that this enzyme helps regulate glucose and fatty acid metabolism explains why supplementation with CLA may help people with weight loss.

Improves Blood Lipids
CLA improves blood lipids by lowering triglycerides and cholesterol levels. Studies in hamsters and rabbits indicate that this slows the onset of atherosclerosis compared to control animals.(10, 11)

Lipid and Insulin Metabolism
CLA seems to help normalize impaired glucose tolerance and improve hyperinsulinemia due to its influence on hormone receptors that regulate genes involved in lipid and insulin metabolism.(12)

Modulates Fatty Acid Composition
Studies indicate that CLA modulates fatty acid composition and metabolism in the liver, which is the primary organ for lipid metabolism. CLA is incorporated into phospholipids, which results in a displacement omega-6 fatty acids in cellular membranes. This in turn results in a decrease in the production of series 2 prostaglandins that are derived from arachidonic acid.(13)

Reductions In Body Fat
Conjugated linoleic acid inhibits the activity of the enzyme lipoprotein lipase. This is an enzyme that breaks down fat particles in the blood so that they can be taken up by fat cells called adipocytes for storage. Thus, CLA helps to prevent the deposition and buildup of fat in the body. In animal studies, CLA resulted in a 66% reduction in lipoprotein lipase activity, which resulted in substantial reductions in body fat coupled with 5% to 14% increases in lean body mass.(14) Results of a study indicated that CLA reduced body fat mass and increased lean body mass in healthy overweight adults.(15)

Clinical Applications

Allergies
Compared to controls, feeding animals CLA results in a decrease in the production of inflammatory leukotrienes and series 2 prostaglandins, which suggests that CLA will help to reduce food-induced allergic reactions.(16)

Cancer
In a prominent cancer journal, CLA has been referred to as “a new class of anticarcinogens.”(17) Results from animal studies indicate that CLA has important anti-cancer activity against a variety of cancers including melanoma, colorectal, breast, lung, and prostate.(18, 19, 20, 21)

Diabetes
Animal studies indicate that CLA may be helpful in the prevention and treatment of type 2, or adult onset diabetes. This benefit is apparently the result of CLA's ability to normalize impaired glucose tolerance and improve hyperinsulinemia.(22)

Elevated Cholesterol
CLA has a beneficial effect on blood lipids. Hamsters receiving diets supplemented with CLA had significantly reduced levels of plasma total cholesterol, LDL and VLDL cholesterol, and triglycerides with no effect on HDL-cholesterol, compared to controls. Analysis of aortas revealed that the animals receiving the CLA-supplemented diets also had a reduction in the development of early atherosclerosis.(23)

Weight Loss
The authors of one study report that CLA reduces fat body fat by several mechanisms, including a reduced energy intake, increased metabolic rate, and a shift in the nocturnal fuel mix.(24) In laboratory mice, CLA supplementation produces a rapid, marked decrease in fat accumulation, and an increase in body protein (muscle tissue) at relatively low doses without any major effects on food intake.(25, 26) In another study CLA reportedly reduced the levels of triglycerides and non-esterified fatty acid in the liver and white adipose tissue of animals without producing significant change in the brown adipose tissue. These results offer further support for CLA's obesity-preventing effects.(27) In a small human trial, obese men who took 4.2 g CLA/day for 4 weeks exhibited a significant decrease in abdominal fat compared to no loss in the placebo group.(28)

Symptoms & Causes of Deficiency

CLA is a relatively new and no deficiency condition has been established. It has been determined that there has been a substantial decline in the amount of CLA that is consumed in the diet by most people over the past fifty years. Factors contributing to this decline include:

a) Taking animals off pasture land and grass diets and transferring them to feedlots where they get fed grain.

b) Many people attempt to avoid fat in their efforts to consume low-fat diets

c) Many people avoid milk, or have switched to skin of low fat milk. Since CLA is a fat, these low fat milk products have had the CLA removed.

Footnotes

Conjugated Linoleic Acid (CLA)(CLA)

Conjugated Linoleic Acid (CLA)
(CLA)