Conjugated linoleic acid and exercise

I have written several blogs about the health benefits of conjugated linoleic acid (CLA), a fatty acid or fat in plain English, found primarily in foods of ruminant origin, such as the milk and meat products from cows, buffaloes, sheep, goat, etc. While I have also written several peer reviewed scientific articles on the topic in many international journals, this is based on an invited book chapter I did not submit eventually. Here I discuss a few things about the potential relationship of CLA with exercise.

There have been some studies over the past several years about the effect of CLA on exercise. In a study with growing mice over a period of 10 weeks, the maximum running time in CLA-fed (1% of the diet) animals was significantly longer, by 26%, compared to that of the control mice, while also decreasing the serum concentrations of triglycerides, nonesterified fatty acids, and urea nitrogen and significantly reducing the consumption of liver glycogen (Kim et al., 2010). It demonstrated that dietary CLA enhanced the endurance capacity of mice by increasing fat utilization and reducing the consumption of stored liver glycogen as substrates for energy metabolism. When five-week-old male BALB/c mice were fed a control diet containing 1.0% linoleic acid or a diet containing 0.5% CLA that replaced an equivalent amount of linoleic acid for 1 wk, the maximum swimming time until fatigue was significantly higher in the CLA-fed group than in the control group (Mizunoya et al., 2005). In the same experiment, the respiratory exchange ratio was significantly lower in the CLA-fed group during treadmill running, but oxygen consumption did not differ between groups, suggesting that fatty acids contributed more as an energy substrate in the CLA-fed mice. The muscle lipoprotein lipase activity was significantly higher in the CLA-fed group than in the control group (Mizunoya et al., 2005). These results suggested that CLA ingestion increases endurance exercise capacity by promoting fat oxidation during exercise. However, when given at 0.5% of the diet there was no effect of CLA on swimming endurance of mice (Zhang et al., 2009).

In an experiment with forty-four healthy female young subjects subject to exercise, exercise with CLA (3.6 g/d) or supplemented with CLA without exercise for six weeks and compared to control subjects, fat ratio, fat mass, waist and hip girths were reduced in all experimental groups and fat-free mass increased in and CLA groups and body weight reduced in the CLA group when compared to baseline levels (Colakoglu et al., 2006). While endurance performance significantly increased in animals subject to exercise + CLA, CLA alone was not effective in doing the same even though it seemed effective on serum glucose and insulin concentrations (Colakoglu et al., 2006). Similarly, waist and hip circumferences were reduced significantly by addition 1.6 g/d of CLA to healthy overweight humans before and after exercise that were supplemented with lysine, proline, alanine and arginine or their mixtures at 0.76 or 1.52 g/d (Michisita et al., 2010). Taken together, effects of CLA on endurance capacity in humans appears to be cumulative with other factors that increase it, but its independent ability to do the same, if any, needs further investigation.

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

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.

Conjugated Linoleic Acid and Immune System

Conjugated linoleic acids (CLA) are a family of more than two dozen isomers of linoleic acid. They are synthesized by the microbes during fatty acid biohydrogenation in the rumen. Therefore, foods of ruminant origin, such as dairy, beef, mutton, and chevon products are the primary sources of CLAs. Although one of the essential nutrients, fats in general are perceived to have negative health effects. However, research has shown that CLAs are highly beneficial for our health, at least as shown in many experimental cell culture and animal research models. Of all the isomers, c-9, t-11 and t-10, c-12 CLAs are the primary ones deemed important from health perspective. Moreover, these are the only ones that are present in ruminant foods in any appreciable amounts.  In general, food products from grass-fed ruminants are good sources of CLA, and contain much more of it than those from grain-fed animals. 

        Effect of CLA on immunomodulation is also emerging slowly. It has been demonstrated that the two active CLA isomers (c-9, t-11 and t-10, c-12 CLAs) can elicit both the innate and adaptive immune responses (Albers et al., 2003; O’Shea et al., 2004; He et al., 2007). Sugano et al. (1999) initially proposed that the immune enhancing effect of CLA was by modulating eicosanoid and immunoglobulin production, which were later affirmed by other investigators (Cheng et al., 2003; Ramakers et al., 2005; Ringseis et al., 2006), as well as the ability of CLAs to modify cytokines (Hur et al., 2007). Indeed, Song et al. (2005) investigated the effect of dietary CLA supplementation (3 g/day; 50:50 mixture of c,9, t-11 and t-10, c-12 CLA isomers) on the immune system of healthy human (male and female) volunteers. It was found that the levels of plasma immunoglobulins (Ig) A and M were increased with decreased plasma levels of E. CLA supplementation also decreased the levels of the proinflammatory cytokines, TNF-α and IL-1β, but increased the levels of anti-inflammatory cytokine, IL-10.

Enhanced immune function is usually associated with anorexia and wasting. In a detailed review, Cook et al. (2003) showed that CLA not only enhances immune response, but also protects tissues from collateral damage. CLA also diminished lipopolysaccharide-induced inflammatory events in macrophages through reduced mRNA and protein expression of nitric oxide synthase and cyclooxigenase-2 as well as subsequent production of nitric oxide and prostaglandin E₂ (Cheng et al., 2004), both of which are also implicated in carcinogenesis. Cook et al. (1999) suggested that CLA prevents immune associated wasting by protecting nonlymphoid tissues from the adverse effects of cytokines, which are growth suppressants, because CLA influences the immune system by altering the effects of cytokine, interleukin, leukotriene and many immunoglobulins (Sébédio et al., 2000). Although dietary CLA enhanced antibody production in broiler chickens (Takahashi et al., 2003), ameliorated viral infectivity in a pig model of virally induced immunosuppression (Bassaganaya-Riera et al., 2003), and enhanced lymphocyte proliferation in nursery pigs (Bassaganaya-Riera et al., 2001), no change in immune status was observed in young healthy women (Kelley et al., 2000). Whigham et al. (2002) indicated that CLA might induce a change in immune response in favor of cell-mediated response rather than an allergic one, while Nichenametla et al. (2004) showed higher natural killer cell cytotoxicity in rats fed CLA in diet than the control group without CLA. It appears that c-9, t-11 and t-10, c-12 isomers of CLA stimulate different immunological events in mice with c-9, t-11 increasing tumor necrosis factor α while t-10, c-12 increasing immunoglobulin A and M production (Yamasaki et al., 2003).

Foregoing in vitro studies demonstrate that CLA modulate immune function. In a double blind parallel reference-controlled intervention study in adult humans, almost twice as many subjects reached protective antibody levels to hepatitis B when consuming a 50:50 mixture of c-9, t-11 and t-10, c-12 CLA isomers for 12 weeks compared with sunflower oil fed reference subjects, but the response to 80:20 mixture of c-9, t-11 and t-10, c-12 CLA was similar to that of reference (Albers et al., 2003). This is probably the first of its kind about the effects of CLA on immune function using actual human subjects. In contrast, CLA feeding to young healthy women did not alter any of the indices of immune status tested (Kelly et al., 2000). Recently, Kwak et al. (2009) observed in obese pre-menopausal Korean females that CLA (c-9, t-11 and t-10, c-12 CLA mixture) supplementation modulated the increased release of markers (C-reactive protein, IL10, IgM) related with inflammation and immune function, and this effect was much more subtle than those found in animals and few other clinical studies.

To date there have been limited attempts at identifying the effects of specific isomers of CLA on the immune system. In one such study, CLA (80:20 c-9, t-11:t10, c12) supplementation at 1% diet administered from gestation to adulthood enhanced specific systemic cell-mediated immunity as well as the mucosal IgA immune response, whereas it downregulated the polyclonal activation of the immune system suggesting the long-term effects of probably c-9, t-11 CLA isomer on the immune system (Ramirez-Santana et al., 2009). In another study, Whigham et al. (2000) concluded that t-10, c-12 isomer competitively inhibited the conversion of arachidonic acid to prostaglandin E₂, a principal mediator of inflammation in diseases such as rheumatoid arthritis and osteoarthritis.

While the positive effects of CLA in cell culture and animal models appear encouraging, not very many studies in humans have been conducted. As a result, more such studies are needed to ascertain the effects of individual isomers of CLA or their mixtures.

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