Leucine Builds Muscle But Can It Make You Fat? | Muscular Development
Leucine Builds Muscle But Can It Make You Fat?
As much as I hate texting lingo, when I first read the abstract of the relevant study, the first thing to come to mind was, WTF? Of course, the F stands for frack, being a sci-fi fan and a gentleman. L-leucine is one of the dietary essential amino acids; more importantly to athletes and bodybuilders, it is one of three branched-chain amino acids (BCAA) that comprises a significant percentage (roughly one-third) of the contractile proteins of skeletal muscle.
One of the most popular sports nutrition ingredients is whey protein— widely used due to its ease of use and high concentration of BCAA, particularly leucine (nearly 10 percent by weight). Study after study has proven that whey protein and leucine supplementation promote the anabolic effect of exercise.1-4 Academic evidence often fails in the “real world,” but the popularity of whey protein evinces its effectiveness among the skeptical and demanding market of recreational and competitive bodybuilders.
In competitive bodybuilding, modeling, the pursuit of buffness, etc., size and strength do not provide the complete package. As muscle is being built, body fat needs to be reduced until it is in the mid-to-low single digits.
Through experience and experimentation, drug-using bodybuilders have evolved pharmaceutical regimens that allow them to develop physiques that are literally incredible. [Merriam-Webster defines incredible as “too extraordinary and improbable to be believed”]. Knowledgeable application of the various anabolic and fat-reducing drugs allows individuals who apply themselves to exceed natural boundaries and limits. This is particularly true when it comes to fat loss.
Gaining size is rarely a problem in the United States, where many have a higher body mass index than the largest bodybuilders; of course, that is due to obesity’s prevalence. Achieving the sculpted, lean appearance of a bodybuilder is out of the reach of pretty much everyone. Even the anorexics who literally kill themselves through starvation, or cancer patients whose bodies are wasted by the metabolic pillage of growing tumors, do not deplete body fat to the degree of bodybuilders— without sacrificing equal or greater muscle mass.5,6
Drug-free bodybuilders tread the thin line between losing fat and wasting muscle. Drop calories too low— you get muscle loss; cut out carbohydrates too severely and too long— muscle loss; big meals— fat and water gain; too much cardio— muscle loss; too much rest or not enough— fat gain and muscle loss; etc.
Fat responds to a number of drugs and hormones. The dominant player is insulin; type 1 (insulin-dependent) diabetics often present with severe weight loss, among other symptoms, when they are first diagnosed.7 Type 2 diabetics— people who maintain a high concentration of insulin— are obese and gain weight easily.8 The Zone Diet promoted healthy weight loss through controlling insulin; a more extreme approach is typified by The Atkins Diet, which has a ketogenic induction phase; some even promote chronic (long-term) ketogenic dieting.9
Insulin acts on adipocytes (fat cells) by turning on lipogenic (fat-storing), and turning off lipolytic (fat-releasing) pathways.10 It is not able to do this directly, as it is too large a protein to enter the cell intact. Instead, insulin locks into receptors on the outside of a fat cell. In turn, a number of related mechanisms are turned on or off, resulting in the breakdown of stored fat.11
mTOR Pathway to Fat Breakdown
One such pathway is the mTOR pathway. This pathway is not unique to the fat cell— it is present in other cells, including skeletal muscle. mTOR is responsible for much of the anabolic/anti-catabolic effect of insulin on muscle growth.12 Likewise, mTOR has anabolic effects on the fat cell.13,14 The term “anabolic” may seem misplaced when applied to fat cells, but it is a general term that describes a process that leads to an increase in the mass of a tissue or organism. Thus, it should be of no surprise that a potently (net) anabolic hormone like insulin should increase fat mass.
Astute amateur endocrinologists might note how other anabolic hormones, such as growth hormone and testosterone, actually decrease fat mass. Rather than becoming frustrated and confused, revel in the intricate complexity of life. As one learns more of the body’s wonders, one becomes more awed and amazed.
Low-carbohydrate diets work by minimizing insulin release and total daily exposure to insulin. As the fat cell loses its major signal to store fat— and simultaneously, the greatest obstacle against fat release— fat loss is rapid and consistent. To avoid excess loss of lean mass, those on low-carbohydrate diets need to consume maintenance calories, with a significant protein component. Of course, it is possible to sabotage the insulin-suppressive intent of low-carbohydrate dieting. Insulin does not respond only to carbohydrate intake, but also to protein and amino acids.15-18 The duration and intensity of insulin released to protein is related to how rapidly the protein is absorbed, the accompanying fat, and other factors.
One protein source that is widely used by bodybuilders following a low-carbohydrate diet is whey. Whey is a wonderful protein to consume during periods when one is trying to promote an anabolic environment, such as immediately post-workout. However, recall that insulin has net anabolic effects, though many effects might be described as anti-catabolic, due in part to whey’s leucine content. Thus, it should not be surprising that whey protein intake (even leucine, as an amino acid supplement) is associated with an insulin surge. For building muscle, or protecting it from breakdown, this insulin surge is beneficial. However, if the primary goal or overriding need is to promote fat loss, the insulinemic effect of whey protein may make using the product counter-productive.
Whey protein’s insulinemic effect may be particularly relevant for ketogenic diets— diets so severely carbohydrate-restricted that the body relies almost exclusively on fatty acids and amino acids (released by breaking down proteins, including skeletal muscle). Insulin not only protects against skeletal muscle breakdown (anti-catabolic), and promotes fat cell anabolism, but it also reduces ketogenesis directly and indirectly, by decreasing free fatty acid availability.19,20
Most people with an interest in sports nutrition have learned that much of whey protein’s anabolic effect is due to its leucine content. Leucine is not just a dietary amino acid that forms muscle protein, like a brick in a wall. Leucine is also a signaling-hormone to many cells, informing the fat cells and skeletal muscle cells of the relative availability of quality nutrition.21
Functionally, the body does not want to add mass if there are not enough calories and quality protein to support it. Thus, it closely monitors, and responds to, specific nutrients to correctly adjust the metabolism to the needs of the surrounding environment. Leucine activates mTOR; in the muscle, this is wonderful, but the same process is also seen in the fat cell— possibly resulting in fat tissue anabolism.22,23
Leucine, and likely KIC, interferes with fat loss through two possible mechanisms. By stimulating the anabolic pathways through mTOR activation, leucine may be capable of promoting lipogenic pathways— through a 20 percent decrease in insulin-stimulated lipogenesis, in one study. What’s more, lipolytic pathways are impaired when leucine’s effects are present in the fat cell.24-26
Leucine and Weight Loss
Researchers have looked at the response of adipocytes to leucine deprivation (taking leucine from the diet).26,27 Much of the following is based on animal research, as it is difficult to justify refusing human subjects an essential micronutrient.
When mice were provided with a leucine-depleted diet, fat loss was greater. Lipolysis, the release of stored fat, was increased; lipogenic enzymes, including fatty acid synthase, were reduced; and uncoupling protein was increased in brown fat, which results in burning more fat for heat production.26
How much weight loss was experienced by the leucine-deprived mice, and how did it occur? The leucine-deprived mice lost about 15 percent of body mass, related in part to a near-equivalent reduction in daily calorie intake (15 percent). However, an increase in energy expenditure was also present; typically, when energy intake goes down, so does energy expenditure, as the body tries to conserve in an environment of limited resources (food).28
A separate group of mice that was fed an equal number of calories, containing a normal leucine content, lost only 5 percent of bodyweight. Of the weight lost, the leucine-deprived mice lost a significant amount from the abdominal fat depot, roughly 40 percent; the leucine-fed mice fed the same number of calories did not lose a significant amount of abdominal fat. Total body fat was similarly affected.
Markers of metabolism supported the hypothesis that energy expenditure was increased in leucine-deprived mice. Serum (blood) norepinephrine and T3 were elevated in the leucine-deprived group; body temperature was elevated; and brown fat was activated, turning fat calories into heat as opposed to energy; the leucine-deprived mice managed to burn more calories, specifically fat for calories, without any increase in physical activity.26
The net result was a marked 42 percent decrease in white adipose (the storage form of fat) volume. This was accomplished by increasing the activity of hormones involved in breaking down the stored fat, and burning much of that fat in the adipocyte. A 200 percent increase in PPAR-alpha was recorded, along with increases in the fat-burning enzymes stimulated by PPAR-alpha protein. As more fat was being lost, less was being made. One enzyme important to storing fat, called fatty acid synthase, was suppressed over 30 percent in white adipose tissue. A prior study by the same authors showed a similar effect on suppressing fatty acid synthase in the liver of leucine-deprived mice.27
Of course, bodybuilders are scoffing at the notion, regardless of fat loss, because everyone knows depriving the body of the essential branched-chain amino acid leucine would lead to catastrophic losses in lean mass… right?
Actually, the leucine-deprived mice showed no difference in lean mass, from either the control mice or those that were restricted to the same number of (reduced) calories consumed by the leucine-deprived mice. The control mice are normal mice, eating as much as they will; the pair-fed mice are normal mice eating a normal diet, but only as much as the leucine-deprived mice chose to eat; the leucine-deprived mice ate as much as they wanted, but they chose to eat 15 percent less than the control mice, (thus, the pair-fed also ate 15 percent less than control, but it was a diet that contained a normal amount of leucine).
Pair-fed mice lost only 5 percent of bodyweight, and their lean mass did not change appreciably; leucine-deprived mice lost 15 percent of bodyweight, and their lean mass was the same as the control mice, and unchanged. There were no strength or endurance challenges, but when one considers that the mice lost ~50 percent of abdominal fat, 15 percent of bodyweight, and had no loss of lean mass, that is incredible.
So, we have figured out how to provide mice with bodies they can proudly display on the beach— if we can convince them to shave. How does this apply to humans, and more importantly to this audience, bodybuilders and athletes? It’s impossible to say, at this point. The mice were not subjected to stress or exercise, so it is difficult to say whether the anti-catabolic protection of leucine would play a role in preventing muscle or strength loss in conditions similar to athletic training or competition.
Bodybuilders have to balance the need for promoting muscle gain and the demand for fat loss. It is difficult to believe that a leucine-deprived diet would support lean mass gains. For those prioritizing fat loss, whether it is a pre-competition diet or pursuing “The Biggest Loser” challenge, these findings certainly are intriguing.
Leucine is an essential amino acid, but the body maintains a substantial store of this nutrient that can be liberated from skeletal muscle. Perhaps there may be a place for a short-term leucine-deprived challenge, until weight-loss goals are met. This is certainly an area of research to be followed.
References:
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