Wednesday, May 13, 2015

Is Conjugated Linoleic Acid Anabolic? by Jerry Brainum

Conjugated linoleic acid is an isomer of linoleic acid, an essential omega-6 fatty acid. Structurally, CLA contains both cis and trans fat configurations, but it doesn’t function in the body in the negative way that trans fats normally do. In fact, many health benefits are associated with CLA, including cancer prevention as well as prevention of both cardiovascular disease and obesity.
    Those potent effects were initially noted in a mouse experiment conducted in 1979. A meat extract was applied to a rodent’s skin, followed by a strong carcinogen, or cancer-causing substance. The meat extract blocked tumor formation in the mice by 20 percent. There was something clearly present in meat that seemed to help prevent cancer.
     It wasn’t until 1987 that the mysterious ingredient was isolated by Michael Pariza at the University of Wisconsin. He discovered it in, of all things, Cheez-Whiz, and named it conjugated linoleic acid, which reflects its complex structure. It turns out that both meat and dairy products are rich in CLA, and much of their health effects can be directly attributed to it.
     One of the richest natural sources of CLA is egg yolks, which are routinely discarded by many misguided bodybuilders. In terms of meat, grass-fed beef is far richer in CLA than beef produced from grain-fed animals—one of the primary reasons that grass-fed beef is considered nutritionally superior.
    Not long after its isolation in 1987, a few supplement companies began to market CLA supplements. They usually contained a 1-1 ratio of two CLA isomers, namely cis-9, trans-11, known as C9, and trans-10, cis-12—C10. That’s important because further research with CLA showed that those two isomers have often-opposing actions. Unlike its parent compound, linoleic acid, CLA is not considered essential in human nutrition.
     Some studies show that CLA may exert antioxidant activity because it promotes in-the-body antioxidants, such as catalase and glutathione peroxidase. As noted, much of the animal research has focused on its anticancer effects. Although having antioxidant properties would aid in cancer prevention, CLA also stimulates the activity of a specific gene that has a tumor-suppressive effect, and it appears to modify several inflammatory mediators in the body called cytokines. Since cancer is known to have an inflammatory component, the significance is obvious.
    Perhaps the most controversial aspect of CLA is its effect on body composition, including building muscle and losing fat, the two primary goals of most bodybuilders. On paper CLA would seem to provide a potent fat-loss effect through several mechanisms. For one thing, it is known to upgrade the activity of several substances in the body that speed fat burning and the conversion of fat calories into energy. Here’s where differences in the two basic CLA isomers come in. While C10 is known to boost fat burning and help retain lean mass, it is also associated with insulin resistance. C9 , on the other hand, lowers insulin resistance. Thus, it makes sense that most commercial CLA supplements contain both isomers in balanced levels, since one would likely cancel the possible side effects of the other.
     The published studies that have examined body composition changes with CLA are paradoxical. Generally, however, it seems to work better at reducing higher bodyfat in animals than it does in humans. One reason is that the dose of CLA supplied in animal studies is comparatively far larger than what human subjects get. While human-based studies have averaged three to six grams of CLA daily, to get the equivalent dose of what is used in animal studies, human trials would have to involve 50 grams a day or more. That could lead to problems, since similarly to other natural substances, CLA has a U-shaped curve of effectiveness—in massive doses its antioxidant effect converts into a pro-oxidant effect, which can damage cells and cause cell mutations. The same is true for resveratrol, another highly touted natural substance.
     Again, human studies done with CLA have shown either small losses of bodyfat or no changes at all. That may be due to not only the smaller doses but also the differences in subjects. The animal studies usually feature young, growing animals that may respond better to CLA than the obese older females who form the majority of subjects in human published studies. And as noted, one form of CLA may be more effective at altering body composition than the other.
    In relation to exercise, the ergogenic effect of CLA is considered unimpressive. In one study sedentary men and women took five grams a day of CLA and also engaged in a weight-training program. They were tested for the effects of CLA on body composition, strength and muscle -breakdown markers.The study lasted for seven weeks. Those using the CLA supplement showed a slight but significant increase in lean mass plus a greater loss of bodyfat than those getting a placebo. The supplemented male subjects also increased their bench press strength more than those getting the placebo. CLA appeared to exert anticatabolic effects in muscle as well, judging by a decreased excretion of muscle-breakdown products.
    It sounds good, but in another placebo-controlled study, the subjects were not sedentary but, rather, experienced weight trainers. Once again, the focus was on changes in body comp, strength and muscle catabolism induced by CLA supplementation. The subjects got six grams daily while engaged in a weight-training program during the monthlong study. In this case the results showed no changes in body comp, lean mass or markers of muscle breakdown in those taking  CLA compared to the placebo group. The subjects did, however, report some ergogenic effects in their training due to the CLA.
     Based on the small amount of data suggesting that CLA may provide anticatabolic effects in exercising people, a more recent study tested its effects on testosterone.1 It had both an in vitro and in vivo design: The in vitro, or test tube, portion involved exposing isolated testicular Leydig cells from rats to CLA. (The Leydig cells are where testosterone is synthesized in men.) The cells were treated with varying concentrations of CLA for 24 and 48 hours. The results showed increased testosterone concentration in the cells at the 48-hour mark.
    The in vivo, or “in the body,” portion of the study featured 10 resistance-trained men who got either six grams a day of CLA or a placebo for three weeks. They provided blood samples both before and after their weight workout, and they were tested for total testosterone as well as sex-hormone-binding globulin, which is the protein carrier of testosterone in the blood. Those in the CLA group showed a large boost in testosterone after the workout, while those in the placebo group got a moderate rise, which is not a surprise, as exercise alone can boost testosterone.
    How might CLA increase testosterone? It has to do with a protein called perilipin, which modifies the body’s use of fat. Perilipin promotes the activity of the enzyme cholesterol esterase, which in turn promotes free cholesterol, the basic substrate for the formation of steroid hormones, including testosterone.
     Simply put, CLA may kick-start the “factory line” in the Leydig cells that produces testosterone. In the men who exercised and used CLA, testosterone increased more after exercise than what the placebo group experienced, while levels of cortisol also rose. That was related to the exercise itself, since exercise is a form of stress. Even so, levels of cortisol, estrogen and sex-hormone-binding globulin didn’t differ between the placebo and CLA groups.
    What is confusing is that in one section of the study the researchers say that CLA promoted a significant increase in testosterone in the exercising men, while elsewhere they say, “CLA supplementation does not significantly increase testosterone synthesis after an unmarkedly stressful bout of acute resistance exercise.” So which is it? Does CLA promote a rise in testosterone, or doesn’t it? It may be a late-occurring effect, since the test tube part of the study showed that CLA didn’t boost testosterone release until after two days. At this point the effects of CLA remain as confusing and obscure as ever. For example, what would be the correct dose to boost testosterone? No one yet knows.
   There are, however, good reasons not to go overboard with CLA. For example, the C10 form has been linked to increased oxidative stress, increased incidence of gallstones and a lowering of DHA by 25 percent in animal hearts. DHA is an omega-3 fatty acid that, when increased in heart tissue, may exert protective effects. Lowering it could prove detrimental to heart function. Women with suspected breast cancer or the genes for breast cancer should also avoid using CLA, despite its reputation as a cancer preventive. In truth, however, here is little evidence that the small amount of CLA found in supplements is dangerous to health. That would be about three to six grams taken daily.
1 Macaluso, F., et al. (2012). Effect of conjugated linoleic acid on testosterone levels in vitro and in vivo after an acute bout of resistance exercise. J Str Cond Res. 26:1667-74.
 

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