Conjugated linoleic acid (CLA), and heart health and atherosclerosis

Studies on the effect of CLA on the severity or incidence of atherosclerotic lesions and heart health have remained inconclusive. Antiatherosclerotic effect of CLA was shown initially in rabbit aortas (Lee et al., 1994). There was a 34% reduction in atherosclerosis in rabbits when CLA was included at 0.1% of the diet for 12 weeks, which increased to 64% when included at 0.5% of the diet with a slight reduction to 58% at 1% of the diet (Lee et al., 1994). A significant reduction in total cholesterol, non-high density lipoprotein cholesterol, and aortic fatty streak areas in hamsters occurred even at 0.06% of CLA in the diet (Nicolisi et al., 1997). Inhibition of atherosclerosis and regression of established atherosclerosis (Kritchevsky et al, 2000) as well as a reduction in the severity of established lesions (Kritchevsky, 2003) in rabbits has been observed. Sher et al. (2003) showed a reduction in plasma cholesterol during cholesterol supplementation, but accentuation of the atherogenic lipid profile during acute phase response in hamsters when CLA was supplemented in the diet at 1%. Since a mixture of CLA isomers was used in most of these studies, the effects of specific isomers is not known.

In a study with a population consisting of 1813 incident cases of a first nonfatal acute myocardial infarction and 1813 population-based controls matched for age, sex, and area of residence, adipose tissue c9, t11 CLA was associated with a lower risk of MI in basic and multivariate models (Smit et al., 2010). In a simulation study, CLA treatment mitigated pro-atherogenic eNOS, ET-1, PPARα and γ mRNA expression profiles and nitric oxide and ET-1 secretion patterns during asynchronous hemodynamics demonstrating the potential for a pharmacological treatment to normalize pro-atherogenic gene expression profiles induced by hemodynamics inherent to the circulation (Dancu et al., 2007). It has been suggested that the anti-atherogenic effects observed with CLAs are presumably mediated not only by CLAs themselves but also by their metabolites (Eder and Ringseis, 2010). However, in a double blind, randomized, controlled cross-over intervention study, compared to t10, c12 CLA or the mixtures of CLA, c9, t11 was found to be weaker in exerting its effects on gene expression in human adipose tissues depending on PPARγ P12A polymorphism suggesting that the isomer specific influence of CLA on glucose and lipid metabolism is genotype dependent and at least in part mediated by PPARγ (Hermann et al., 2009). In another study on apoE-/- mice fed a high-cholesterol diet, conjugated linoleic acid isomers had no effect on atherosclerosis and adverse effects on lipoprotein and liver lipid metabolism (Cooper et al., 2008).

Since it is difficult to study the effect of CLA on atherosclerosis in humans, an indirect approach by measuring various potential heart disease markers is required (Belury, 2002a). Lipid atherogenic risk markers were more favorably influenced by c-9, t-11 isomer than a mixture of CLA or fish oil (Valeille et al., 2004, 2005), which is known to influence several aspects of atherogenesis. Based on another study, same group suggested that the atherogenic potential of milk fat can be greatly reduced in products with a naturally high abundance of CLA, and argued for increased CLA in milk (Valeille et al., 2006). In vitro, CLA prevented indicators of cardiomyocyte hypertrophy elicited by endothelin-1, including cell size augmentation, protein synthesis, and fetal gene activation with similar anti-hypertrophic effects of CLA on hypertrophy induced by angiotensin II, fibroblast growth factor, and mechanical strain (Alibin et al., 2008). They also demonstrated that dietary CLA supplementation significantly reduced blood pressure and cardiac hypertrophy in spontaneously hypertensive heart failure rats in vivo. Their data suggested that dietary supplementation with CLA may be a viable strategy to prevent pathological cardiac hypertrophy, a major risk factor for heart failure.

When healthy human subjects were used in a double-blind placebo controlled intervention trial, Noone et al. (2002) demonstrated that a blend of c-9, t-11 and t-10, c-12 isomers (80:20 and 50:50) improved very low-density lipoprotein cholesterol and plasma triacylglycerol metabolism suggesting that some of the cardio-protective effects of CLA shown in animal studies were relevant to humans as well. However, there was no effect of supplementing CLA on total cholesterol or high-density lipoprotein cholesterol in healthy human subjects (Mougios et al., 2001). In another study in humans, supplementation of CLA did not affect any of the atherogenic parameters (Benito et al., 2001). Similarly, in a double-blind, randomized, placebo-controlled, parallel-group trial, supplementation of c9,t11 CLA for six months had no effect on anti-atherosclerotic or cardiovascular risk factors, such as aortic pulse wave velocity, blood pressure, anthropometric characteristics, and concentrations of fasting lipid, glucose, insulin, and C-reactive protein before was observed (Slujis et al., 2010). When given as part of a diet rich in butter, a mixture of CLA isomers increased lipid peroxidation but did not affect risk markers of cardiovascular disease, inflammation, or fasting insulin and glucose concentrations in healthy young men (Raff et al., 2008).

While the effects of CLA on atherosclerosis appear mostly positive and highly encouraging in many cell culture and animal studies, its effect in humans have been relatively inconsistent. Regardless, its effects on atherogenesis appear to be dose-, isomer-, tissue-, and species-specific. Further studies, particularly in humans, are needed to fully understand the effect before it can be used as a remedy for atherosclerotic lesions.

Contact the author for complete details about the references or if you have any questions.