Conjugated linoleic acid is a fatty acid found in nature, predominately in meat and dairy products. Researchers from Wisconsin-Madison first identified this compound as an anti-carcinogen, then as more research was obtained, CLA was introduced to the supplement market in late 1995 and promoted for its body composition effects. However, more recent evidence from animal and tissue culture studies suggests CLA has the potential to do a lot more. For example, it may help reduce risk factors associated with heart disease, increase bone density, reduce chronic inflammation (immune response) and even help normalize elevated glucose levels in the blood and increase sensitivity to insulin. Over 300 scientific studies on CLA have been done to date.

Immune Response. The role of CLA to enhance the immune response is perhaps one of the most exciting areas currently being pursued by the research community. Because it is a fatty acid, CLA has the ability to become part of the cell membrane (as a phospholipid) and change the synthesis of “cellular messengers.” These messengers are produced when the immune system is stimulated (receives a signal) by such things as foreign proteins, injury or even exercise. CLA has been shown to decrease the negative effects of these cellular messengers. For example, studies have found CLA reduced the inflammation or adverse effects of immune stimulation in animals1,2 by significantly reducing a cell messenger (prostaglandin) called PGE-2. This prostaglandin promotes inflammation, artery constriction and blood clotting, which is associated with negative physiological effects, such as heart disease. Thus, by decreasing this compound, CLA not only helps decrease inflammation, but also reduces parameters typically associated with heart disease.

Heart Health. As stated, risk factors affecting heart disease such as plasma lipids appear to be reduced by supplementing with CLA. Studies have shown CLA reduces serum triglycerides and cholesterol and decreases atherosclerotic plaque formation in rabbits and hamsters fed high-fat and cholesterol diets3. In a study using hamsters fed a high fat and cholesterol-containing diet, CLA reduced fatty streak formation and reduced total serum cholesterol levels4. In another study, CLA even reduced the severity of pre-existing atherosclerotic lesions induced by pre-feeding an atherogenic5. While these studies provide an intriguing insight into possible means by which CLA may effect atherosclerosis, there is still much to be explained. Confirming CLA’s role in atherosclerosis, and learning the specific mechanisms by which CLA exerts such effects, requires further research in animals and most importantly in humans.

Glucose and Insulin. Not only does CLA help regulate cellular messengers for immune responses and reduce risk factors associated with heart disease; researchers have discovered that CLA may also have favorable effects on glucose homeostasis. In one series of studies, CLA normalized glucose metabolism, while in another study, CLA restored insulin sensitivity6,7. Although the mechanism for this action is not confirmed, it appears that CLA may influence genetic receptors (peroxisome proliferator activator receptors) involved with lipid metabolism8. Human data to support CLA’s effect on glucose and insulin is currently underway and may provide evidence for an exciting alternative to insulin injections and pharmaceutical agents.

Body Composition and Bone Density. Substantial evidence in animals shows CLA enhances lipolysis, the breakdown of fat. In addition, CLA also increases lean body mass (LBM)9-16. Human data is limited and variable. In novice body builders, for example, men ingesting seven grams of CLA per day had greater arm girth and body mass and could do more leg presses than the control group17. However, there were no detectable changes in body fat. The primary message from data generated to date is that CLA is more likely to increase LBM while decreasing fat when there is a concurrent anabolic stimulus such as growth or exercise.

Cancer. CLA exhibits strong anticarcinogenic properties in several species, as well as in human ex vivo systems18-20. While the exact mechanism of action may still be a matter of inquiry and confirmation, the potency of CLA as a therapeutic intervention shows promise. For example, while fish oil may inhibit tumors, the amount needed usually exceeds 10% in the diet21-24. However, as little as 0.1% CLA in the diet produces a significant reduction in mammary tumor yield25. While an abundance of animal data exists supporting anticarcinogenic effects of CLA, only one case-control study in humans has been reported to suggest anti-cancer effects of CLA26. However, with ongoing efforts of researchers within the academic environment, and continuing support from the business sector, knowledge of CLA’s benefit in human health will continue to evolve.

References

1Park Y, Storkson JM, Liu W, et al. Effects of conjugated linoleic acid (CLA) on prostaglandin E2 and tumor necrosis factor-a in cultured RAW 264.7 cells. Abstract #169.5 FASEB 2000}

2Sugano M. et. al Conjugated linoleic acid modulates tissue levels of chemical mediators and immunoglobulins in rats. Lipids 33(5):521-7, 1998.

3Belury MA Vanden Heuvel JP. Invited Review: Protection against cancer and heart disease by the dietary fat, conjugated linoleic acid; potential mechanisms of action. Nutr Disease Update J 1:58-63, 1997.

4Nicolosi RJ, Rogers EJ, Kritchevsky D, et al. Dietary conjugated linoleic acid reduced plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters. Artery 22:266-77, 1997.

5Kritchevsky D. Conjugated linoleic acid and experimental atherosclerosis in rabbits. In: Advances in Conjugated Linoleic Acid Research, Volume 1. Eds: Yurawecz MP, Mossoba MM, et al. AOCS Press, Champaign, IL USA. pp 397-403, 1999.

6Salminen I, Mutanen M, Jauhiainen M, Aro A. Dietary trans fatty acids increase conjugated linoleic acid levels in human serum. J Nutr Biochem 9:93-8, 1998.

7Houseknecht K, Heuvel JV, Moya-Camarena S, et al. Diabetes 47:A425, 1998.

8Belury MA. Steroid hormone receptor and nutrient interactions: Implications for cancer prevention. J Nutr 129(2S Suppl):569S-570S, 1999.

9Albright KW, Liu J, Storkson E, et al. Body composition repartitioning following the removal of dietary conjugated linoleic acid. J Anim Sci 74:152, 1996.

10Pariza M, Park Y, Cook M, et al. Conjugated linoleic acid (CLA) reduces body fat. FASEB J 10:A560, 1996.

11Pariza M, Park Y, Kim S, et al. Mechanism of body fat reduction by conjugated linoleic acid. FASEB Journal 11: A139, 1997.

12Park Y, Storkson JM, Albright KJ, et al. .Evidence that the trans-10,cis-12 isomer of conjugated linoleic acid induces body composition changes in mice. Lipids 34: 235-241, 1999.

13Park Y, Storkson JM, Albright KJ, et al. The trans-10,cis-12 isomer of conjugated linoleic acid (CLA) induces body composition changes in mice. FASEB Journal 13: A875., 1999.

14Chin SF, Storkson JM, Albright KJ, et al. Conjugated linoleic acid is a growth factor for rats as shown by enhanced weight gain and improved feed efficiency. J Nutr 124:694-701, 1994.

15Cook ME, Jerome DL, Crenshaw TD, et al. Feeding conjugated linoleic acid improves feed efficiency and reduces carcass fat in pigs. FASEB J 12:A836, 1998.

16Park Y, Albright KJ, Storkson JM, et al. Effect of conjugated linoleic acid on body composition in mice. Lipids 32:853-8, 1997.

17Lowery LM, Appicelli PA, Lemon PWR. Conjugated linoleic acid enhances muscle size and strength gains in novice bodybuilders. Med Sci in Sports Exercise. 30;5:S182, 1998.

18Cesano A, Visonneau S, Scimeca JA, et al. Opposite effects of linoleic acid and conjugated linoleic acid on human prostatic cancer in SCID mice. Anticancer Res 18: 1429-34, 1998.

19Cornell K, Waters DJ, Watkins B, Robinson JP. The role of apoptosis in conjugated linoleic acid (CLA) inhibition of prostate cancer cell lines in vitro. Cytometry: 71, 1998.

20Gallagher PA, Harrell A, Howell PE, Godley P. Conjugated linoleic acid (CLA) decreases the mono-unsaturated fatty acid content of human prostate cancer cells in a dose dependent manner. FASEB J 13: A540., 1999.

21Cannizzo F, Broitman SA. Postpromotional effects of dietary marine or safflower oils on large bowel or pulmonary implants of CT-26 in mice. Cancer Res 49: 4289-94, 1989.

22Karmali RA. Effect of dietary fatty acids on experimental manifestation of Salmonella-associated arthritis in rats. II. Effect of dietary fatty acids on experimental manifestation of Salmonella-associated arthritis in rats. Prostaglan Leuk Med 29: 199-204, 1987.

23O’Connor TP, Roebuck BD, Peterson FJ, et al. Effect of dietary omega-3 and omega-6 fatty acids on development of azaserine-induced pre-neoplastic lesions in rat pancreas. J Natl Cancer Inst 81: 858-63, 1989.

24Reddy BS, Burill C, Rigotty J. Effect of diets high in omega-3 and omega-6 fatty acids on initiation and post-initiation stages of colon carcinogenesis. Cancer Res 51: 487-91, 1991.

25Ip C. Conjugated linoleic acid in cancer prevention research: A report of current status and issues. Chicago: National live stock and meat board, p. 10, 1994,.

26Bougnoux P, Lavillonniere F, Riboli E, et al. Inverse relation between CLA in adipose breast tissue and risk of breast cancer: A case-control study in France. INFORM 10;5:S43, 1999.

About the authors:
Dr. Rockway and Dr. Menard are with ingredient supplier Pharmanutrients, Lake Bluff, IL, a provider of branded, patented bio-active compounds. They can be reached at Pharmanutrients, Inc., 918 Sherwood Drive, Lake Bluff, IL 60044; 847-234-2334; Fax: 847-234-5545; E-mail: susier@pharmanutrients.com.