Conjugated linoleic acid
Encyclopedia
Conjugated linoleic acids (CLA) are a family of at least 28 isomer
Isomer
In chemistry, isomers are compounds with the same molecular formula but different structural formulas. Isomers do not necessarily share similar properties, unless they also have the same functional groups. There are many different classes of isomers, like stereoisomers, enantiomers, geometrical...

s of linoleic acid
Linoleic acid
Linoleic acid is an unsaturated n-6 fatty acid. It is a colorless liquid at room temperature. In physiological literature, it has a lipid number of 18:2...

 found mainly in the meat
Meat
Meat is animal flesh that is used as food. Most often, this means the skeletal muscle and associated fat and other tissues, but it may also describe other edible tissues such as organs and offal...

 and dairy product
Dairy product
Dairy products are generally defined as foods produced from cow's or domestic buffalo's milk. They are usually high-energy-yielding food products. A production plant for such processing is called a dairy or a dairy factory. Raw milk for processing comes mainly from cows, and, to a lesser extent,...

s derived from ruminant
Ruminant
A ruminant is a mammal of the order Artiodactyla that digests plant-based food by initially softening it within the animal's first compartment of the stomach, principally through bacterial actions, then regurgitating the semi-digested mass, now known as cud, and chewing it again...

s. As the name implies, the double bonds of CLAs are conjugated
Conjugated fatty acid
Conjugated fatty acids are polyunsaturated fatty acids in which at least one pair of double bonds are separated by only one single bond, as in conjugated linoleic acid:The conjugation results in delocalization of electrons along the system.-See also:...

, with only one single bond between them.

History

In 1979, researchers from the University of Wisconsin applied a beef extract to mice skin. The mice were then exposed to a strong carcinogen. When the researchers counted the number of tumors developed by the mice 16 weeks later, they found, to their surprise, that the mice exposed to the beef extract had 20% fewer tumors. The identity of this anticarcinogen was not discovered until almost a decade later, in 1987. Michael Pariza, the scientist who discovered CLA, later remarked that "few anticarcinogens, and certainly no other known fatty acids, are as effective as CLA in inhibiting carcinogenesis in these models."
Although CLA is best known for its anticancer properties, researchers have also found that the cis-9, trans-11 form of CLA can reduce the risk for cardiovascular disease and help fight inflammation.
The Nutritional Immunology and Molecular Medicine Laboratory (NIMML) made a seminal discovery demonstrating that oral CLA treatment prevents or ameliorates inflammatory bowel disease by activating the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma).

CLA is also known for its body weight management properties, which include reducing body fat and increasing lean muscle mass. Over 30 clinical studies have been published investigating the effect of CLA on weight management. The trials have quite variable designs, which leads to inconsistency. However a meta-analysis conducted in 2007 concluded CLA has a small impact on fat mass.
In July 2008, CLA received a no objection letter from the FDA on its Generally Recognized as Safe (GRAS
Gras
Gras is a commune in the Ardèche department in southern France.-Population:-References:*...

) status for certain food categories, including fluid milk, yogurt, meal replacement shakes, nutritional bars, fruit juices and soy milk. With GRAS status, food companies are now able to add CLA to products in these food categories.

Biochemistry

Most studies of CLAs have used a mixture of isomers wherein the isomers c9,t11-CLA and t10,c12-CLA were the most abundant. More recent studies using individual isomers indicate that the two isomers have very different health effects.
Conjugated linoleic acid is both a trans fatty acid
Trans fat
Trans fat is the common name for unsaturated fat with trans-isomer fatty acid. Because the term refers to the configuration of a double carbon-carbon bond, trans fats are sometimes monounsaturated or polyunsaturated, but never saturated....

 and a cis fatty acid. The cis bond causes a lower melting point and ostensibly also the observed beneficial health effects. Unlike other trans fatty acids, it may have beneficial effects on human health. CLA is conjugated
Conjugated system
In chemistry, a conjugated system is a system of connected p-orbitals with delocalized electrons in compounds with alternating single and multiple bonds, which in general may lower the overall energy of the molecule and increase stability. Lone pairs, radicals or carbenium ions may be part of the...

, and in the United States, trans linkages in a conjugated system are not counted as trans fats for the purposes of nutritional regulations and labeling. CLA and some trans isomers of oleic acid
Oleic acid
Oleic acid is a monounsaturated omega-9 fatty acid found in various animal and vegetable fats. It has the formula CH37CH=CH7COOH. It is an odorless, colourless oil, although commercial samples may be yellowish. The trans isomer of oleic acid is called elaidic acid...

 are produced by microorganisms in the rumen
Rumen
The rumen, also known as a paunch, forms the larger part of the reticulorumen, which is the first chamber in the alimentary canal of ruminant animals. It serves as the primary site for microbial fermentation of ingested feed...

s of ruminants. Non-ruminants, including humans, produce certain isomers of CLA from trans isomers of oleic acid, such as vaccenic acid
Vaccenic acid
Vaccenic acid is an omega-7 fatty acid. It is a naturally occurring trans-fatty acid found in the fat of ruminants and in dairy products such as milk, butter, and yogurt. It is also the predominant fatty acid comprising trans fat in human milk....

, which is converted to CLA by delta-9-desaturase
Desaturase
A fatty acid desaturase is an enzyme that removes two hydrogen atoms from a fatty acid, creating a carbon/carbon double bond. These desaturases are classified as...

.

Diet and health

Anticancer properties have been attributed to CLA, and studies on mice and rats show encouraging results in hindering the growth of tumors in mammary, skin, and colon tissues. It has been reported that CLA can up-regulate the tumor suppressor gene PTPRG
PTPRG
Receptor-type tyrosine-protein phosphatase gamma is an enzyme that in humans is encoded by the PTPRG gene.-Further reading:...

, and may have anti-cancer properties.

A European team led by the Swiss scientist Lukas Rist has found that mothers consuming mostly organic milk and meat products have about 50 percent higher levels of rumenic acid
Rumenic acid
Rumenic acid, also known as bovinic acid, is a conjugated linoleic acid found in the fat of ruminants and in dairy products. It is an omega-7 trans fat. Its lipid shorthand name is cis-9, trans-11 18:2 acid....

 in their breast milk.

According to studies that targeted the effects of conjugated linoleic acid on the belly firmness and fatty acid composition of genetically lean pigs, the supplemental CLA usage had a positive effect on the improvement of belly firmness and may provide a nutritional solution to carcass fat and belly firmness problems.

The most promising science around CLA concerns its effect on weight management. Thirty-five intervention studies have been conducted using CLA in humans to investigate the effects of CLA on weight management. These studies, which vary widely in CLA dose and duration, show the most significant effect of CLA on weight management is on body composition, a reduction in total body fat and an increase in lean body mass. The effect of CLA on fat mass is modest and at the recommended dosage of 3.2g/day produces a statistically significant 90 g fat loss per week (ca. 1 lb in 5 weeks) as shown by a 2007 meta-analysis. Doses higher than the recommended 3.2g do not seem to have any additional effects on body fat reduction. Another meta-analysis found that CLA supplementation produces about 1% increase in lean body mass per week. With the simultaneous decrease in fat mass coupled with increases in lean body mass, often the net change in weight is small. However, the effects of CLA on body composition is a healthy effect, since the degree of fat mass is related to all cause mortality and lean body mass burns more calories than fat mass which may help to increase resting metabolic rates. CLA use itself is not an answer to the prevalence of obesity, but it can be a useful tool in addition to a healthy lifestyle and exercise program to achieve and maintain a healthy body weight.

Some studies have found no significant effects of CLA supplementation on fat mass loss . These results are likely due to a number of reasons. The study duration may have been too short to observe significant effects. The instrumentation used may not have been sensitive enough to detect significant fat losses . CLA has also been used in combination with other ingredients which may skew results .

Possible adverse effects of CLA supplements in humans

There are concerns that the use of CLA supplements by extremely overweight people may tend to cause or to aggravate insulin resistance, which may increase their risk of developing diabetes. Commercially available supplements contain equal mixtures of two CLA isomers: the cis-9, trans-11 isomer (also known as rumenic acid, the predominant CLA isomer in milk and beef), as well as the trans-10, cis-12 (t10c12) isomer. All other isomers ratios found in the scientific literature are not commercially available. The trans-10, cis-12 isomer is linked to many adverse side effects. Research indicates that supplementation with t10c12 CLA dramatically increases rates of oxidative stress, to levels considerably higher than that observed in heavy smokers.
However, the evidence is controversial, and some studies using a mixture of c9t11 and t10c12 CLA showed no changes in insulin sensitivity. A study in 2007 used the euglycemic hyperinsulinemic clamp method, which is the gold standard, to evaluate insulin resistance. The study performed on 49 obese or overweight individuals taking 3.2g CLA per day for six months found no adverse effects on blood glucose management. In addition, the long term studies of one and two years have found CLA supplementation to be safe with no outstanding adverse events .In one study, t10c12 CLA produced a 32% increase in biliary cholesterol concentration, which increases the chance of gallstone formation .
In 2006, a study by the US Department of Agriculture suggested CLA can induce essential fatty acid redistribution in mice. Changes in docosahexaenoic acid
Docosahexaenoic acid
Docosahexaenoic acid is an omega-3 fatty acid that is a primary structural component of the human brain and retina. In chemical structure, DHA is a carboxylic acid with a 22-carbon chain and six cis double bonds; the first double bond is located at the third carbon from the omega end...

 (DHA) and arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...

 (AA) levels were observed in some organs. For instance, the t10,c12 CLA reduced the DHA content of heart tissue by 25%, while in the spleen, DHA content rose, and AA fell. DHA is an omega-3 fatty acid important to cardiovascular health, and the dramatic reduction of DHA in heart tissue can have serious health consequences. In contrast, c9,t11 CLA did not alter DHA content in the heart, but did reduce spleen DHA slightly. A study of CLA supplementation (equal amounts of c9,t11 and t10,c12) in hatchling chicks (2005) showed high mortality and low hatchability rates among CLA-supplemented groups, and also a decrease in brain DHA levels of CLA-treated chicks http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15884760&dopt=Abstract. These studies raise the question of whether CLA may increase the risk of cardiovascular and inflammatory diseases, but it has yet to be established whether such changes occur in humans, and whether they are clinically relevant. Some experience migraine a few hours after taking CLA supplements.

The general consensus is that the use of this supplement should be carefully examined if the person using the supplement is greatly overweight.

Dietary sources

Kangaroo meat may have the highest concentration of CLA.
Food products from grass-fed ruminant
Ruminant
A ruminant is a mammal of the order Artiodactyla that digests plant-based food by initially softening it within the animal's first compartment of the stomach, principally through bacterial actions, then regurgitating the semi-digested mass, now known as cud, and chewing it again...

s (e.g. mutton and beef) are good sources of CLA, and contain much more of it than those from grain-fed animals.
In fact, meat and dairy products from grass-fed animals can produce 300-500% more CLA than those of cattle fed the usual diet of 50% hay and silage
Silage
Silage is fermented, high-moisture fodder that can be fed to ruminants or used as a biofuel feedstock for anaerobic digesters. It is fermented and stored in a process called ensiling or silaging, and is usually made from grass crops, including corn , sorghum or other cereals, using the entire...

, and 50% grain.

Egg
Egg (food)
Eggs are laid by females of many different species, including birds, reptiles, amphibians, and fish, and have probably been eaten by mankind for millennia. Bird and reptile eggs consist of a protective eggshell, albumen , and vitellus , contained within various thin membranes...

s are also rich in CLA, and CLA in eggs has been shown to survive the temperatures encountered during frying.

Some mushrooms, such as Agaricus bisporus and Agaricus subrufescens, are rare nonanimal sources of CLA.

General references

  • Tokuşoğlu Ö. (2008). Conjugated linoleic acid (CLA) cis 9, trans 11 and trans 10, cis 12 isomer detection in crude and refined corn oils by capillary GC. Grasas y Aceites (Spain). Vol.59(2) Abril-Junio 2008, 146-151.
  • Tokuşoğlu Ö., Durucasu İ., Akalın A.S., Serin E., Akşit S. (2007). Fatty Acid (FA) and Conjugated Linoleic Acid (CLA) Profiles of Infant Formulas Through Direct Transesterification of Acyl Lipids. Italian J Food Sci. No:4 Vol.19, 477-484.
  • Akalın A.S., Tokuşoğlu Ö., Gonc S., Aycan Ş. (2007). Occurrence of conjugated linoleic acid in probiotic yoghurts supplemented with fructooligosaccharide. International Dairy Journal. Vol 17/9, 1089-1095.
  • Schmid A., Collomb M., Sieber R., Bee G. Conjugated linoleic acid in meat and meat products: A review // Meat Science. – 2006. – 73. – P. 29–41.
  • Jenkins T. C., McGuire M. A. Major advances in nutrition: impact on milk composition // J. Dairy Sci. – 2006. – 89 (4) – Р. 1302–1310.
  • Akalın A.S., Tokuşoğlu Ö., Gönç S., Ökten S.(2005). “Detection of Biologically Active Isomers of Conjugated Linoleic Acid in "Kaymak". Grasas Aceties 56(4), 298-302.
  • Al Sarakbi W, Salhab M, Mokbel K. Dairy products and breast cancer risk: a review of the literature. Int J Fertil Women's Med. 2005 Nov-Dec;50(6):244-9. Review.
  • Bhattacharya A, Banu J, Rahman M, Causey J, Fernandes G. Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem. 2006 Dec;17(12):789-810. Epub 2006 May 2. Review.
  • Ip MM, Masso-Welch PA, Ip C. Prevention of mammary cancer with conjugated linoleic acid: role of the stroma and the epithelium. J Mammary Gland Biol Neoplasia. 2003 Jan;8(1):103-18. Review.
  • Kritchevsky D. Antimutagenic and some other effects of conjugated linoleic acid // British Journal of Nutrition. – 2000. – 83, N 5. – P. 459-465.
  • Larsson S. C., Bergkvist L., Wolk A. High-fat dairy food and conjugated linoleic acid intakes in relation to colorectal cancer incidence in the Swedish Mammography Cohort // American Journal of Clinical Nutrition. – 2005. – 82, N 4. – P. 894-900.
  • Lee KW, Lee HJ, Cho HY, Kim YJ. Role of the conjugated linoleic acid in the prevention of cancer. Crit Rev Food Sci Nutr. 2005;45(2):135-44. Review.
  • Maynard L. J., Franklin S. T. Functional foods as a value-added strategy: the commercial potential of "cancer-fighting" dairy products // Review of Agricultural Economics. – 2003. – 25, N 2. – P. 316-331.
  • Miller Á., Stanton C., Murphy J., Devery R. Conjugated linoleic acid (CLA)-enriched milk fat inhibits growth and modulates CLA-responsive biomarkers in MCF-7 and SW480 human cancer cell lines // British Journal of Nutrition. – 2003. – 90, N 5. – P. 877-885.
  • Pariza MW, Park Y, Cook ME. Conjugated linoleic acid and the control of cancer and obesity. Toxicol Sci. 1999 Dec;52 (2 Suppl):107-10. Review.
  • Tanaka K. Occurrence of conjugated linoleic acid in ruminant products and its physiological functions // Animal Science Journal. – 2005. – 76, N 4. – P. 291-303.
  • Voorrips L. E., Brants H. A. M., Kardinaal A. F. M., Hiddink G. J., Brandt P. A., van den Goldbohm R. A. Intake of conjugated linoleic acid, fat, and other fatty acids in relation to postmenopausal breast cancer: the Netherlands cohort study on diet and cancer // American Journal of Clinical Nutrition. – 2002. – 76, N 4. – P. 873-882.
  • Belury M. A. Dietary conjugated linoleic acid in health: physiological effects and mechanisms of action // Annu. Rev. Nutr. – 2002. – 22. – P. 505–531.
  • Bauman D. E., Corl B. A., Baumgard L. H., Griinari J. M. Conjugated linoleic acid (CLA) and the dairy cow // In Recent Advances in Animal Nutrition / Ed. P. C. Garnsworthy, J. Wiseman; Nottingham Univ. Press. – Nottingham, UK, 2001 – P. 221–250.
  • Harefoot C. G., Hazlewood G. P. Lipid metabolism in the rumen / In: Hobson P. N., Stewart C. S. (Eds.), The Rumen Microbial Ecosystem, second ed. Blackie Academic, London, 1999. – P. 382–426.
  • Whingham LD, Watras CA, Scholler DA. Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. Am J Clin Nutr 2007;85(5):1203-1200.
  • Bassaganya-Riera, J., R. Hontecillas, D. R. Zimmerman, and, M. J. Wannemuehler. (2001) Dietary conjugated linoleic acid modulates phenotype and effector functions of porcine CD8+ lymphocytes. J. Nutr. 131: 2370-2377.
  • Bassaganya-Riera, J., R. Hontecillas-Magarzo, K. Bregendahl, M. J. Wannemuehler, and D. R. Zimmerman. (2001) Effects of dietary conjugated linoleic acid in nursery pigs of dirty and clean environments on growth, empty body composition and immune competence. J. Anim. Sci. 79: 714-721.
  • Bassaganya-Riera, J., R. Hontecillas, D. R. Zimmerman, and, M. J. Wannemuehler. (2001) Long-term influence of lipid nutrition on CD8+ responses to viral and bacterial antigens. Vaccine 20: 1435-1444.
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  • R. Hontecillas, D.L. Hutto, D. U. Ahn, J. H. Wilson, M. J. Wannemuehler,and J.Bassaganya-Riera. (2002) Nutritional regulation of bacterial-induced colitis by dietary conjugated linoleic acid. J. Nutr. 132: 2019-2027.
  • Bassaganya-Riera, J., R. Hontecillas, D.C. Beitz. (2002) Colonic Anti-inflammatory Mechanisms of Conjugated Linoleic Acid. Clinical Nutrition 21 (6): 451-459.
  • Bassaganya-Riera, J., Pogranichnyi, R., Jobgen, S.C., Halbur, P.G., Yoon, K-Y, O’Shea, M., Mohede, I., Hontecillas, R. (2003) CLA Ameliorates Viral Infectivity in a Pig Model of Virally Induced Immunosuppression. J. Nutr. 133: 3204-3214.
  • Bassaganya-Riera, J., K. Reynolds, S. Martino-Catt, Y. Cui, L. Hennighausen, F. Gonzalez, J. Rohrer, A. Uribe Benninghoff, and R. Hontecillas (2004) Activation of peroxisome proliferator-activated receptor γ and δ by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Gastroenterology. 127: 777-791.
  • O’Shea, M., J. Bassaganya-Riera, and I. Mohede. (2004) Immunomodulatory Properties of Conjugated Linoleic Acid. Am. J. Clin. Nutr. 79 (6): 1199S-1206S.
  • Bassaganya-Riera, J., J. King, and R. Hontecillas. (2004) Health Benefits of CLA: Lessons from Pig Models in Biomedical Research. Eur. Journal of Lipid Science and Technology 106: 856-861.
  • Bassaganya-Riera, J., and R. Hontecillas (2006) CLA and n-3 PUFA differentially modulate clinical activity and colonic PPAR-responsive gene expression in a pig model of experimental IBD. Clinical Nutrition. 25: 454-465.
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