What is CLA
CLA (conjugated linoleic acid) is a naturally occurring trans fatty acids with 18-carbon that has reported to promote weight loss by unknown mechanisms. Conjugated linoleic acid (CLA) is a mixture of isomers of linoleic acid (C18:2 n-6), which is mostly found in the ruminant meat and dairy products. CLA is a fat found naturally of ruminant derived products including milk, dairy and beef products 1). The major source of CLA in the human diet is through the consumption of ruminant meats such as beef and lamb 2) and from high fat dairy products such as whole milk (3% fat), full fat cultured milk, mainly sour milk (3% fat), cheese, mainly hard cheese (28% fat), cream (40% fat), full fat sour cream (34% fat), reduced fat sour cream (17% fat) and butter (80% fat) 3). Dairy products are a primary source of cis‐9, trans‐11‐CLA (c9,t11‐CLA), the most prevalent CLA isomer, in the diet of humans 4).
CLA is naturally synthesized from linoleic acid by ruminant animals 5). Grass fed cattle produce the highest levels of CLA. Cattle fed a diet rich in polyunsaturated fatty acids have increased concentrations of CLA in their milk 6); however, human dietary intake from these sources is estimated at 0.1–1.1% of ruminant animal fat leading to possible total intakes of 15–440 mg of CLA/day 7). For larger doses, CLA supplements can be commercially prepared from plant oils containing high amounts of linoleic acid.
There are many CLA isomers. The most common naturally occurring in dairy fat and meat from ruminant animals is the cis-9, trans-11(c9,t11) isomer 8). The cis-9, trans-11 and trans-10, cis-12 (t10,c12)-CLA can also be commercially synthesized from linoleic acid–rich oils such as sunflower and safflower oil 9). These are considered the most physiologically active isomers, and the 50:50 mixture has been shown to be the most effective for weight management or body fat reduction 10). The first studies to identify the antiadiposity characteristics of CLA were performed in laboratory mice 11). The t10,c12 isomer was found to be more effective as an antiadiposity agent, but this isomer caused a slight increase in insulin resistance 12), which generally was not observed when both the c9,t11 and t10,c12 isomers were given together 13).
Different CLA isomers are synthesized through a variety of mechanisms by bacteria and digesta present in the rumen 14). There are 28 known CLA isomers with trans-11, cis- (t11,c9)‐CLA, which accounts for 80% of CLA intake in the diet and trans-10, cis-12 (t10,c12)‐CLA being the two most abundant 15). The biological activities of CLA have received considerable attention over the past number of years due to their documented anti‐cancer, anti‐inflammatory, anti‐atherogenic and anti‐diabetic effects in animal studies. However, in human studies, evidence on the antiatherosclerotic effects of CLA remains contradictory 16). Many studies have shown unfavorable effects of CLA on lipoprotein levels, similar to that of other trans fatty acids 17), 18), whereas others have shown beneficial 19) or no effects 20). Some researchers postulated that it is possible that the 2 isomers – c9,t11‐CLA isomer principal dietary form of CLA, accounting for as much as 85% to 90% of total CLA in dairy products and the trans‐10, cis‐12‐CLA isomer not produced in detectable amounts naturally but is found in larger amounts as a product of commercial CLA synthesis, may have differing effects on cardiovascular risk. Many of the studies on the effects of CLA on cardiovascular risk factors have focused on supplementary CLA, which commonly consists of roughly 50:50 portions of c9,t11‐CLA and trans‐10, cis‐12‐CLA. This may account for the inconsistencies seen between studies on the effects of CLA on cardiovascular risk factors.
It has also been claimed but yet to be proven in clinical studies that eating CLA could reduce your body fat and thus make you lose weight. Animal studies have shown that CLA supplementation reduces body weight and body fat mass and improves glycemic status and lipid profiles 21), but the results in humans are inconsistent 22), 23), 24), 25). CLA has shown no significant effects on lipid profile, fasting blood glucose, insulin resistance, body composition, and body mass index (BMI) among healthy and hyperlipidemic overweight and obese participants 26), 27), as well as diabetic patients 28). In diabetic patients, CLA supplementation (3 g/d) showed negative effects on insulin and glucose metabolism and positive effects on serum HDL metabolism 29), triacylglycerol (TAG), and very low density lipoproteins (VLDL), but did not affect any other biochemical parameters 30). However, in another study it improved body composition, serum glucose, and insulin concentrations without having significant effects on lipid profile 31). In addition, CLA supplementation had no significant effects on lipid peroxidation and antioxidant metabolism among healthy volunteers 32), but had beneficial effects on oxidative stress among atherosclerotic patients 33).
One specific isoform of CLA, trans-10, cis-12 (t10,c12) CLA, is associated with reduced adiposity, which is beneficial, while simultaneously promoting systemic inflammation, insulin resistance, and dyslipidemia, all of which could be detrimental. These seemingly opposing effects of t10,c12-CLA have not yet been examined in the context of the metabolic syndrome, a common condition in which visceral obesity is associated with adipose tissue inflammation, dyslipidemia, and insulin resistance. Commercially available CLA supplements containing trans-10, cis-12-CLA are widely used to facilitate weight loss, so the opposing effects on body weight and inflammation could put consumers at risk of the potential for long-term adverse health effects. It is therefore important to better understand mechanisms by which t10,c12-CLA affects adipose tissue metabolism. Preliminary studies have begun to investigate mechanisms by which trans-10, cis-12-CLA reduces adiposity. Scientists have determined that mitochondrial metabolism is substantially increased in cultured adipocytes, with concomitant increases in inflammatory and monocyte chemotactic factor gene expression. Specifically, mitochondrial fatty acid oxidation is enhanced by trans-10, cis-12 (t10,c12) CLA in white adipocytes, a process normally reserved for brown adipocytes, skeletal muscle, cardiac muscle, and hepatocytes. Current hypothesis is that trans-10, cis-12 (t10,c12) CLA contributes to impaired lipid storage in adipose tissue by altering the lipid metabolism of white adipocytes towards a unique brown adipocyte-like phenotype at the expense of causing inflammatory changes in adipose tissue. Scientists are currently examining the effects of t10,c12-CLA on adipocyte lipid metabolism and inflammation as it relates to the metabolic state frequently associated with obesity.
CLA isomers have been found to have both synergistic and antagonistic effects on cellular functions resulting in alterations in function and metabolism. The effect of the isomers has been notably different between strains of animals and species, where CLA is primarily associated with advantages to health showing reduced adiposity, improved metabolism of plasma lipoprotein in rabbits 34), insulin sensitivity in Zucker diabetic rat 35) and decreased atherosclerosis in hamsters 36). Unfortunately, not all of these health benefits in animal models have translated well into clinical studies investigating the effects of CLA on human health. However, CLA blends enriched in c9,t11 and t10,c12 isomers have been identified as safe and effective in humans 37).
CLA dietary supplementation, using a 50 : 50 blend of c9,t11 : t10 , c12‐CLA, has shown reductions in fat mass in both overweight and obese adults and children 38), increased HDL cholesterol and decreased the ratio of LDL : HDL cholesterol in type 2 diabetes 39), diminished incidence of atherosclerosis in sedentary young adults 40). Also c9,t11‐CLA supplementation lowered the risk of cardiovascular disease in men 41) and it was found that women who consumed four or more servings of high fat dairy foods rich in CLA reduced their risk of developing distal colon cancer by 34%, when compared with women who consumed less than one serving per day 42). There was also a 35% reduction in the risk of colorectal cancer in women who consumed at least three servings of cheese/day 43). Noone et al. 44) investigated the effects of CLA on cardiovascular disease risk factors in 51 healthy human subjects. In this 8 week, randomized, double‐blind placebo study, c9,t11‐CLA and t10,c12‐CLA isomers were investigated using linoleic acid as the control. The group receiving the 50 : 50 CLA blend showed significantly decreased fasting plasma triacylglycerol concentrations. Elevated plasma triacylglycerol concentrations are a risk factor of ischaemic heart disease 45). Very low density lipoprotein (VLDL) cholesterol concentrations were significantly reduced in the group receiving the 80 : 20 CLA blend 46). The effects of CLA supplementation on the immune system were investigated in 28 young healthy volunteers. In this 12 week study, volunteers received a dietary supplement of 3 g/day of c9,t11 : t10,c11‐CLA blend (50 : 50). In CLA supplemented volunteers there was a significant increase in the anti‐inflammatory cytokine IL‐10, a decrease in pro‐inflammatory cytokines TNF‐α and IL‐1β and a decrease in delayed‐type hypersensitivity response 47). Interestingly in a separate study in humans with birch pollen allergy, c9,t11‐CLA supplementation (2 g/day, 12 weeks) significantly reduced granulocyte M‐CSF (GM‐CSF), a known driver of the pro‐inflammatory MΦ1 phenotype 48). However, other studies have shown there to be no change in body composition 49) or immune function 50) following CLA supplementation. There is a need for further rigorous clinical investigation into the benefits of CLA supplementation and for characterization of the optimum blend of CLA to use in humans.
CLA side effects
Although no severe adverse events have been related to the use of CLA, there are reports of effects of CLA on several risk factors for chronic disease 51), 52). CLA has been shown to slightly increase biomarkers of inflammatory disease (usually within the published normal values), including C-reactive protein 53), white blood cell counts 54), and blood and urinary isoprostanes 55). Elevations of these biomarkers have been suggested to be indicators of inflammatory disease 56) but have also been shown to be antiinflammatory 57). Thus, although CLA has been shown to cause a modest increase in inflammatory markers, it has also been shown to decrease inflammatory disease in several animal models. The relevance of these elevated biomarkers of inflammation taking into account the decrease in inflammatory disease remains to be determined.
CLA has also been reported to increase insulin resistance 58). The trans‐10, cis‐12‐CLA isomer but not a CLA mixture, significantly increased insulin resistance, fasting glucose, and dyslipdemia in abdominally obese men. Such men are prone to develop type 2 diabetes and trans‐10, cis‐12‐CLA might be diabetogenic in the metabolic syndrome 59). This has been most notable in studies of short duration 60), those that used single isomers 61), or both. For example, in one study, insulin resistance was reported in individuals supplemented with only the t10, c12 isomer for 12 weeks, but not with a mixed preparation of predominantly the c9, t11 and t10, c12 isomers 62). In a later study, the same enriched t10, c12 supplement was given for 18 weeks and did not result in insulin resistance 63). With regard to both safety and efficacy, it has been suggested that CLA preparations enriched in c9, t11 and t10, c12 isomers are preferable to preparations containing 4 isomers 64), and this may also be true compared with single isomer preparations. Further investigation into the safety of CLA is warranted.
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