Conjugated Linoleic Acid (CLA)

Overview

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)

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

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.

Toxicities & Precautions

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

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)

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. (9)

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. (10) Results of a study indicated that CLA reduced body fat mass and increased lean body mass in healthy overweight adults. (11)

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. (12) , (13)

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. (14)

Enhances Carnitine-palmitoyltransferase Activity

CLA enhances carnitine-palmitoyltransferase activity, which regulates mitochondrial oxidation of long-chain fatty acids and the production of energy. (15) The fact that this enzyme helps regulate glucose and fatty acid metabolism explains why supplementation with CLA may help people with weight loss.

Clinical Applications

Cancer

In a prominent cancer journal, CLA has been referred to as “a new class of anticarcinogens." (16) Results from animal studies indicate that CLA has important anti-cancer activity against a variety of cancers including melanoma, colorectal, breast, lung, and prostate. (17) , (18) , (19) , (20)

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. (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)

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. (23) 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. (24) , (25) 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. (26) 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. (27)

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. (28)

Symptoms and 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.

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.

References

  1. View Abstract: Houseknecht KL, Vanden Heuvel JP, Moya-Camarena SY, Portocarrero CP. Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat. Biochem Biophys Res Commun. Jun1998;247(3):911.
  2. View Abstract: Santora JE, et al. Trans-vaccenic acid is desaturated to conjugated linoleic acid in mice. J Nutr. 2000 Feb;130(2):208-15.
  3. View Abstract: Scimeca JA. Toxicological evaluation of dietary conjugated linoleic acid in male Fischer 344 rats. Food Chem Toxicol. May1998;36(5):391-5.
  4. View Abstract: Basu S, et al. Conjugated linoleic acid induces lipid peroxidation in humans. FEBS Lett. Feb 2000;468(1):33-6.
  5. View Abstract: Riserus U, Vessby B, Arnlov J, Basu S. Effects of cis-9,trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men. Am J Clin Nutr. Aug2004;80(2):279-83.
  6. View Abstract: Moloney F, et al. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Am J Clin Nutr. 2004 Oct;80(4):887-95.
  7. View Abstract: Pariza MW, Ha YL. Conjugated dienoic derivatives of linoleic acid: a new class of anticarcinogens. Med Oncol Tumor Pharmacother. 1990;7(2-3):169-171.
  8. View Abstract: Yu L. Free radical scavenging properties of conjugated linoleic acids. J Agric Food Chem. Jul2001;49(7):3452-6.
  9. View Abstract: Belury MA, et al. Conjugated linoleic acid modulates hepatic lipid composition in mice. Lipids. Feb1997;32(2):199-204.
  10. View Abstract: Park Y, et al. Effect of conjugated linoleic acid on body composition in mice. Lipids. Aug1997;32(8):853-8.
  11. View Abstract: Gaullier JM, Halse J, Hoye K, et al. Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Am J Clin Nutr. Jun2004;79(6):1118-25.
  12. View Abstract: Nicolosi RJ, et al. Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters. Artery. 1997;22(5):266-77.
  13. View Abstract: Lee KN, et al. Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis. Jul1994;108(1):19-25.
  14. View Abstract: Houseknecht KL, et al. Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat. Biochem Biophys Res Commun. Mar1998;244(3):678-82.
  15. View Abstract: Rahman SM, Wang Y, Yotsumoto H, et al. Effects of conjugated linoleic acid on serum leptin concentration, body-fat accumulation, and beta-oxidation of fatty acid in OLETF rats. Nutrition. May2001;17(5):385-90.
  16. View Abstract: Pariza MW, Ha YL. Conjugated dienoic derivatives of linoleic acid: a new class of anticarcinogen. Med Oncol Tumor Pharmacother. 1990;7(2-3):169-171.
  17. View Abstract: MacDonald HB. Conjugated linoleic acid and disease prevention: a review of current knowledge. J Am Coll Nutr. Apr2000;19(2 Suppl):111S-118S.
  18. View Abstract: Hubbard NE, et al. Reduction of murine mammary tumor metastasis by conjugated linoleic acid. Cancer Lett. Mar 2000;150(1):93-100.
  19. View Abstract: Cesano A, et al. Opposite effects of linoleic acid and conjugated linoleic acid on human prostatic cancer in SCID mice. Anticancer Res. May1998;18(3A):1429-34.
  20. View Abstract: Parodi PW. Cows' milk fat components as potential anticarcinogenic agents. J Nutr. Jun1997;127(6):1055-60.
  21. View Abstract: Sugano M, et al. Conjugated linoleic acid modulates tissue levels of chemical mediators and immunoglobulins in rats. Lipids. May1998;33(5):521-7.
  22. View Abstract: Houseknecht KL, et al. Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat. Biochem Biophys Res Commun. Mar1998;244(3):678-82.
  23. View Abstract: West DB, et al. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am J Physiol. Sep1998;275(3 Pt 2):R667-72.
  24. View Abstract: DeLany JP, et al. Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake. Am J Physiol. Apr1999;276(4 Pt 2):R1172-9.
  25. View Abstract: Park Y, et al. Changes in body composition in mice during feeding and withdrawal of conjugated linoleic acid. Lipids. Mar1999;34(3):243-8.
  26. View Abstract: Yamasaki M, et al. Dietary effect of conjugated linoleic acid on lipid levels in white adipose tissue of Sprague-Dawley rats. Biosci Biotechnol Biochem. Jun1999;63(6):1104-6.
  27. View Abstract: Riserus U, Berglund L, Vessby B. Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial. Int J Obes Relat Metab Disord. Aug2001;25(8):1129-35.
  28. View Abstract: Nicolosi RJ, et al. Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters. Artery. 1997;22(5):266-77.