Conjugated linoleic acid

c9, t11 conjugated linoleic acid
IUPAC name (9Z,11E)-octadeca-9,11-dienoic acid
Other names Bovinic acid, Rumenic acid
Identifiers
CAS number	2540-56-9
PubChem	5280644
ChemSpider	4444245
Jmol-3D images	Image 1
SMILES O=C(O)CCCCCCC/C=C\C=C\CCCCCC
InChI InChI=1/C18H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h7-10H,2-6,11-17H2,1H3,(H,19,20)/b8-7+,10-9- Key: JBYXPOFIGCOSSB-GOJKSUSPBK
Properties
Molecular formula	C18H32O2
Molar mass	280.44548
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Conjugated linoleic acids (CLA) are a family of at least 28^[1] isomers of linoleic acid found mainly in the meat and dairy products derived from ruminants. As the name implies, the double bonds of CLAs are conjugated, with only one single bond between them.

Contents 1 History 2 Biochemistry 3 Diet and health 3.1 Possible adverse effects of CLA supplements in humans 3.2 Dietary sources 4 See also 5 References 5.1 General references

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." ^[2][3] 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. ^[4][5]

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. ^[6]

In July 2008, CLA received a no objection letter from the FDA on its Generally Recognized as Safe (GRAS) 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.^[7] More recent studies using individual isomers indicate that the two isomers have very different health effects. ^{[4] [8]}

Conjugated linoleic acid is both a trans fatty acid 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.^[9] CLA is conjugated, 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 are produced by microorganisms in the rumens of ruminants. Non-ruminants, including humans, produce certain isomers of CLA from trans isomers of oleic acid, such as vaccenic acid, which is converted to CLA by delta-9-desaturase.^[10][11]

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.^{[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]} It has been reported that CLA can up-regulate the tumor suppressor gene PTPRG, and may have anti-cancer properties.^[13][27]

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 in their breast milk.^[28]

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.^[29]

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.^[30] 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 ^[31] 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.^{[32][33][34][35][36][37]} 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.^[34][35][36] CLA has also been used in combination with other ingredients which may skew results.^[38]

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.^[8] 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.^[8] However, the evidence is controversial, and some studies using a mixture of c9t11 and t10c12 CLA showed no changes in insulin sensitivity.^[39][40] 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.^[41]In one study, t10c12 CLA produced a 32% increase in biliary cholesterol concentration, which increases the chance of gallstone formation.^[42] In 2006, a study by the US Department of Agriculture suggested CLA can induce essential fatty acid redistribution in mice. Changes in docosahexaenoic acid (DHA) and arachidonic acid (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.^[7] 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 [1]. 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.

The general consensus is that the use of this supplement should be carefully examined if the person using the supplement is greatly overweight.^[43]

Dietary sources

Kangaroo meat may have the highest concentration of CLA.^[44] Food products from grass-fed ruminants (e.g. mutton and beef) are good sources of CLA, and contain much more of it than those from grain-fed animals.^[45] 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, and 50% grain.^[46]

Eggs are also rich in CLA, and CLA in eggs has been shown to survive the temperatures encountered during frying.^[47]

Some mushrooms, such as Agaricus bisporus and Agaricus subrufescens, are rare nonanimal sources of CLA.^[48][49]

See also

• Conjugated fatty acids

References