Conjugated Linoleic Acid Introduction

Conjugated linoleic acid (CLA) is not a single substance. However, it is classified as an omega-6 essential fatty acid, existing as an isomer of linoleic acid. The structure of CLA is very similar to that of linoleic acid, except that it has two double bonds separated by a single bond. Because Conjugated linoleic acid has two double bonds, it is able to have several different isomers. The most important isomers include; cis-9, cis-12, trans-10, and the trans-11 isomers. The formation of each isomer is dependant upon the location of the double bonds and the relationship in the space of the arranged molecules.

Conjugated linoleic acid is produced naturally in the rumen of animals by the bacterial metabolism of both linoleic and linolenic acids. Animal sources and dairy products represent the greatest source of conjugated linoleic acid. Gamma-linolenic acid (GLA) is an Omega-3 essential fatty acid that is found in the fatty acid fraction of some plant seed oils, including those of flax, borage, and hemp. GLA may provide certain antithrombotic and anti-inflammatory actions.

Conjugated linoleic acid is readily absorbed by the small intestine. Its exact mechanism of action is not clearly understood. Being a fatty acid, it may have a role in the prostaglandin pathways similar to other fatty acids.

Most of what is known about Conjugated linoleic acid comes from in vivo animal and in vitro studies. Because of the promising results yielded by such studies, human research is currently being carried out. These trials will be able to provide more concrete information about the mechanisms of action regarding CLA, within the human body.

To date, Conjugated linoleic acid is believed to possess anti-carcinogenic activity. It has shown benefit for breast, colon, prostate, lung, and melanoma cancers. [1] It has been equally effective as a modulator of carcinogenesis at the stages of initiation, promotion, and progression. Conjugated linoleic acid also has the ability to cause or promote cell death (apoptosis).

Conjugated linoleic acid is also thought to possess certain anti-diabetic and anti-atherogenic properties. This nutrient may also be able to decrease the total percentage of body fat, while promoting increases in lean muscle mass.

Conjugated linoleic acid may provide an effective, adjunctive treatment for certain cancers, diabetes, cardiovascular disease, and obesity.

Conjugated linoleic acid can be found in the meats of ruminant animals, such as sheep and cows. It is also found in poultry, eggs, and dairy products that have undergone specialized heat treatment. Safflower and sunflower oil are often processed to also contain varying amounts of CLA. [2] Conjugated linoleic acid is also found in the milk fats of certain mammals.

Most of the abovementioned food sources cannot provide sufficient amounts of Conjugated linoleic acid, necessary for achieving therapeutic benefit. This is largely the result of the shift in livestock care. Elevated Conjugated linoleic acid are typical in those animals fed on grasses, not on grains. It is believed that up to 75% of the Conjugated linoleic acid is lost by feeding grain instead of grass.

The most reliable and abundant sources of Conjugated linoleic acids are found in nutritional/dietary supplements.

Conjugated linoleic acid has been extensively researched for its potential anti-cancer effects. It has been shown to be anti-neoplastic and pro-apoptotic towards most cancer cell lines, excluding mammary cancer. CLA is also effective against the increasing stages or severities of malignancy. [3] It was far superior to linoleic acid in its ability to prevent the progression of certain cancers, as well as with promoting cancer cell death.

CLA may provide a useful adjunctive treatment for breast cancer. [4] In study, Conjugated linoleic acid has exhibited certain anti-estrogenic properties and has also been effective against the spread of estrogen positive breast cancer cells. [5] CLA was shown to block estrogen signals, which are responsible for the proliferation of the cancer.

Conjugated linoleic acid has also shown some benefit in bladder cancer. In vitro studies suggest that Conjugated linoleic acid may inhibit the growth of cancer cells in the bladder, while also inducing cell death. [6]

Prostate cancer is another cancer positively affected by CLA, in vitro. Several different isomers of Conjugated linoleic acid have been effective at halting the cell cycle in cancerous prostate cells and also furthering apoptosis. [7]

In addition to cancer treatment, Conjugated linoleic acid may also be useful in treatment protocols for cardiovascular diseases at large. It has been shown to decrease the low-density lipoproteins (LDLs). LDL is also known as the bad cholesterol. Conjugated linoleic acid can also provide substantial increases in high-density lipoproteins, or HDLs. HDL is referenced as the good form of cholesterol. [8]

By altering the lipid metabolism and having positive effects on total cholesterol levels, Conjugated linoleic acid may prove to be an effective treatment, and possibly preventative supplement, against the development of atherosclerosis. Conjugated linoleic acid is purported to reduce early plaque formations, common in the development of atherosclerosis. [9]

Conjugated linoleic acid may also be a practical adjunctive treatment for Type II diabetes mellitus. It has been proven effective at altering the lipid metabolism of non-insulin- dependent diabetes mellitus (NIDDM) patients by lowering LDL levels and providing increases in HDL serum levels. [10] In study, CLA has also been shown to increase sensitivity to insulin in the tissues, which may provide long-term reductions in the elevated blood sugar levels often exhibited in persons suffering from this condition. [11]

CLA also impacts the overall metabolism of glucose and fatty acids in the body. This may be especially relevant to diabetics, as decreased levels of triglyceride accumulation in the liver are paralleled with lessening one’s risk of developing heart disease. [12] In the referenced study, body fat deposition was also reduced as a direct result of Conjugated linoleic acid supplementation.

The standard dosage, recommended and used in various clinical trials, remains at 1 - 2 grams of conjugated linoleic acid per day. Dosages up to 6 grams per day have been used with no side effects. [13]

There are no known toxicities or interactions regarding the past administration of CLA in or out of study. Ongoing research continues to further understand the many physiological benefits associated with Conjugated linoleic acid supplementation. By market standards, CLA-containing supplements are still considered newly marketed supplements. In fact, human studies are just beginning after promising results in initial animal and in vitro studies. It is certain that more information concerning the mechanisms and interactions in human subjects will be made available within the next several years. Until that time, it is advised to contact your physician and inform him/her of any supplements you may be using to insure personal safety.

Because of the lipid lowering effect of Conjugated linoleic acid, there is a potential for additive effects in individuals who are taking a lipid lowering medication for elevated cholesterol levels.

[1] Shultz TD, Chew BP, Seaman WR, Luedecke LO. Inhibiting effects of conjugated dienoic derivatives of linoleic acid and beta-carotene on the in vitro growth of human cancer cells. Cancer Lett. 1992 Apr 15; 63(2): 125-133.

[2] www.pdrhealth.com Conjugated Linoleic Acid. January 2005.

[3] Maggiora M et al. An overview of the effect of linoleic and conjugated linoleic acid on the growth of several human tumor cell lines. Int J Cancer. 2004 Dec 20; 112(6): 909-919.

[4] Kemp MQ, Jeffy BD, Romangelo DF. Conjugated linoleic acid inhibits cell proliferation through a p53 dependent mechanism: effects on the expression of G1 restriction patients in breast and colon cancer cells. J Nutr. 2003 Nov; 133(11): 3670-3677.

[5] Tanmanasamut P, Liu J, Hendry LB, Sidell N. Conjugates linoleic acid blocks estrogen signaling in human breast cancer cells. J Nutr. 2004 Mar; 134(3): 674-680.

[6] Oh YS, Lee HS, Cho HJ, Lee SG, Jung KC, Park JH. Conjugated linoleic acid inhibits DNA synthesis and induces apoptosis in TSU-Pr1 human bladder cancer cells. Anticancer Res. 2003 Nov-Dec; 23(6c): 4765-4772.

[7] Ochoa JJ, Farquharson AJ, Grant I, Moffatt LE, Heys SD, Wahle KW. Conjugated linoleic acids (CLAs) decrease prostate cancer cell proliferation: different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers. Carcinogenesis. 2004 Jul; 25(7): 1185-1191.

[8] Moloney F, Yeow TP, Mullen A, Nolan JJ, Roche HM. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Am J Clin Nutr. 2004 Oct; 80(4): 887-895.

[9] McLeod RS, LeBlanc AM, Langille MA, Mitchell PL, Currie DL. Conjugated linoleic acid, atherosclerosis, and hepatic very low-density lipoprotein metabolism. Am J Clin Nutr. 2004 Jun; 79(6Suppl): 1169S-1174S.

[10] Moloney F, Yeow TP, Mullen A, Nolan JJ, Roche HM. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Am J Clin Nutr. 2004 Oct; 80(4): 887-895.

[11] Brown JM, McIntosh MK. Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity. J Nutr. 2003 Oct; 133(10): 3041-3046.

[12] Brown JM, McIntosh MK. Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity. J Nutr. 2003 Oct; 133(10): 3041-3046.

[13] www.pdrhealth.com Conjugated Linoleic Acid. January 2005.