Conjugated Linoleic Acid (CLA)
CLA is a collective term used to describe a mixture of geometric and positional isomers of octa-decadienoic acid containing a conjugated double bond. Each of these positional conjugated diene isomers can occur in cis-trans, trans-cis, cis-cis or trans-trans geometrical configuration. Conjugated linoleic acid is produced in the rumen as a result of incomplete bio-hydrogenation of linoleic acid as well as during the commercial manufacture of dairy products. In the rumen, dietary lipids are rapidly hydrolyzed and the resulting unsaturated free fatty acids can undergo bio-hydrogenation by the rumen microorganisms. As a result, ruminant animals absorb mainly saturated fatty acids, and foods made from ruminants contain mainly saturated fatty acids, regardless of the fatty acid composition of the ruminant’s diet. However, when bio-hydrogenation is not complete, CLA can escape the rumen and be absorbed from the gastrointestinal tract, thereby providing the peripheral tissues with various isomers of CLA.
The predominant CLA in ruminant fats is the cis-9, trans-11 isomer which accounts for more than 80% of total CLA isomers in dairy products. In the human diet, dairy products are the main source of CLA, with the cis-9, trans-11 isomer accounting for between 70 and 80% of total CLA intake. It originates from CLA produced by the rumen bacteria as an intermediate in the biohydrogenation of LA (C18:2). Milk fat concentration of CLA varies widely among dairy herds and is affected by a number of dietary factors including the type and amount of fatty acid substrate, the forage to grain ratio and the nitrogen content of the diet. Grazing cows had a 5.7 times higher concentration of CLA in milk than did cow with feeds containing preserved forage.
The average intake of CLA in human diet ranges between 95 and 440 mg per day and the value is influenced by the country, individual behaviour etc. A number of studies have proved that there is a strong evidence of various isomers of CLA inhibit the growth of a number of human cancer cell lines, reduce the rate of chemically induced tumour development, alter lipoprotein metabolism, modify immune function, and enhance lean body mass in animal models.
Isomers of conjugated linoleic acids have also been proved to have other beneficial health effects in scientific studies with animal models which include a decrease in plasma lipids, a reduction in the onset and severity of diabetes and obesity, immune modulation and a change in the rate of bone formation. Recent scientific studies indicate that an inverse relationship exists between milk fat intake and risk of colorectal cancer. Overall, the evidence from animal biomedical studies points toward a number of potential benefits of cis-9, trans-11 CLA in humans, including reductions in atherosclerosis and improved blood lipid profiles, in addition to potential protection against cancer.
Effect of CLA on Weight Loss and promotion of lean muscle mass
Dietary CLA has been shown to affect body composition in several animal species including mice, rats and pigs. It has been proved that the reduction in body fat accumulation by dietary CLA was due to increased oxidation of fatty acids, as reflected by enhanced activity of the enzyme carnitine palmitoyl transferase-1 in fat pads and skeletal muscle. In another study, livers from CLA-fed rats produced more ketone bodies, but synthesized significantly less triacylglycerol and cholesterol than control rats suggesting that, in the rodent model, dietary CLA may lower blood and tissue lipid levels through enhanced oxidation of fatty acids at the expense of reesterification of fatty acids in the liver. Pigs fed with CLA had reduced feed intake (5.2%), improved feed efficiency (5.9%) and had similar rates of gain relative to sunflower oil-fed pigs. In addition, pigs fed CLA deposited less subcutaneous fat (6.8%) and gained more lean tissue (2.3%) than pigs fed sunflower oil. In finisher pigs, feed efficiency was improved and fat deposition decreased linearly with increasing concentration of CLA in the diet. The carcass lean tissue deposition was quadratic in nature and was maximized at 5 g of dietary CLA per kg of body weight. Taken together, these observations suggest that dietary CLA can be used as a nutrient partitioning agent that favors lean tissue deposition over fat accretion, further enhancing the quality and health benefit of animal products.
It may safely be concluded that the CLA promotes lean muscle mass and decreases deposition of excess fat in the body, thus promoting weight loss in the consumers at the recommended level.
CLA and Anti cancer properties
Interest in CLA as an anticarcinogen stemmed from the original observation by Pariza and colleagues that both raw and grilled ground beef contained a component that could inhibit mutagenesis. The inhibitor, which was later shown to possess anticarcinogenic properties, was purified and identified as four isomers of linoleic acid with conjugated diene unsaturations. Dietary studies with rat mammary tumor models have established CLA as a potent anticarcinogen. Supplementation of a basal diet with 0.5, 1.0 or 1.5% CLA resulted in a reduction of tumor incidence of 17, 42 and 50%, respectively. Dietary CLA inhibited local tumor growth by 73% and prevented metastatic spread to the lungs, peripheral blood and bone marrow. In cell culture studies, physiological concentrations of CLA inhibited the proliferation of human malignant melanoma colorectal and breast cancer cells. In contrast, linoleic acid had no inhibitory effects on the cell lines.
Mechanisms by which CLA affects carcinogenesis are largely unresolved and may vary for different sites, age, duration of exposure and stage of carcinogenesis. Various studies suggest that CLA may act by antioxidant mechanisms, pro-oxidant cytotoxicity, inhibition of nucleotide synthesis, reduction of proliferative activity and inhibition of both DNA-adduct formation and carcinogen activation.
CLA and Modulation of Immune Response
Considerable evidence indicates that aging is associated with a decline in the immune response in mammals and that intervention with antioxidant nutrients (e.g. Vitamin E, beta carotene and glutathione) can enhance the immune response in rodents and humans. Based on the well documented antioxidant properties of CLA, it is hypothesized that this LA isomer may have an impact on the immune response in aging mammalian species. Chicks fed CLA and injected with the endotoxin lipopolysaccharide (LPS) continued to grow, whereas those not fed CLA either failed to grow or lost weight following LPS injection. In addition, dietary CLA enhanced the phytohemagglutinin response and alleviated the catabolic effect of immune stimulation in rats. Conjugated LA-supplemented young mice had significantly higher splenocyte interleukin-2 production than those fed the control diet. These findings suggest that CLA is effective in preventing the catabolic effect of immune stimulation, and possesses a potent immunostimulatory effect in mammalian species. The potential of preventing the catabolic losses without affecting the generation of adaptive immunity could provide benefit to growth and development.
To conclude, the potential health benefits arising from CLA consumption, there is a considerable research effort directed to increasing the CLA content of milk and meat products. Conjugated linoleic acid is an intermediate in the biohydrogenation of linoleic acid by rumen bacteria with potent anticarcinogenic, antiatherogenic and antidiebetogenic actions in rodents and humans. Experiments using several animal models indicate that dietary CLA is a potent nutrient partitioning agent that favors lean tissue deposition over body fat accumulation. Additionally, dietary CLA alleviates the catabolic response to immune stimulation, which could provide benefit to growth and development. While exact mechanisms by which CLA exerts its beneficial health and growth promoting effects are not fully elucidated, current experimental evidence indicates that dietary CLA is more than an anticancer factor and may provide a novel nutritional strategy for improving food, cow milk and carcass characteristics through dietary management that is readily applicable to producers.