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What is the most anabolic nutrient?

7301-eat7The expression “anabolic nutrient” is much bandied about these days in articles and ads. It suggests that a particular nutrient may promote growth processes, particularly in muscle tissue. Despite the hype and hyperbole attached to the term, however, the only real anabolic nutrients are protein and amino acids.

Protein is made up of 22 amino acids, some of which are considered essential, while others are nonessential. The difference is that the essential amino acids, of which there are nine, must be supplied in the diet, while the unessential aminos can be synthesized from the essential amino acids and other nutrients.

Research in recent years has shown that when it comes to muscle protein synthesis, which is the main process that results in muscle growth, essential amino acids are the key. And you don’t need a lot. As little as six to eight grams of essential aminos is all that’s required for promoting maximum muscle protein synthesis after training. You can get that in about 25 grams of whey protein.

Of the essential amino acids, the most anabolic are the branched-chain aminos. They are often referred to as “the muscle aminos” because, unlike other aminos, which are metabolized in the liver, the BCAAs are metabolized primarily in muscle. In fact, muscle itself consists of 60 percent BCAAs.

There are three BCAAs—leucine, isoleucine and valine—with leucine being the most potent in aiding the growth process. That relates to its ability to stimulate directly a protein complex called mammalian target of rapamycin—mTOR for short. When mTOR is stimulated, it initiates a cascade of other signaling factors that results in upgraded protein synthesis. No other amino acid comes close to the potency of leucine in triggering mTOR activity.

One recent study examined four varied protein sources—wheat, soy, eggs and whey—in terms of their ability to stimulate protein synthesis in rats.1 Their leucine contents vary as follows: wheat, 6.8 percent; soy, 8 percent; egg, 8.8 percent; and whey, 10.09 percent. The rats were deprived of food for 12 hours to slow down their muscle protein synthesis activity and then got meals that contained one of the above sources of protein.

The whey and egg meals produced the highest rates of muscle protein synthesis, which correlates to their higher leucine contents; however, an important point was what the study showed about dosage. Once a critical amount of leucine was ingested, consuming any more didn’t further extend the protein-synthesis effect.

Looking at it another way, there is a minimal threshold of leucine in a meal that promotes muscle protein synthesis. So the take-home point of this study is that when you’re eating smaller protein meals, the leucine content is the critical factor for stimulating growth. A corollary is that you can get all the benefits of protein, even with small meals, by choosing higher-quality proteins that are richer in leucine, such as eggs, milk and whey.

Leucine’s potent effect was illustrated in the study when the researchers supplemented the wheat protein with additional leucine. That produced a protein-stimulating effect similar to that of whey. My interpretation is that if you’re eating lower-quality protein foods, such as wheat or vegetables, you can considerably boost the protein-synthesis effect simply by also taking in a higher-quality protein, such as whey, at the same time.

Another study examined just how potent leucine is in promoting muscle protein synthesis.2 Twenty-four men took part in the experiment, in which the researchers tested a dose of whey that was considerably less than the 25 grams that has been found to maximize protein synthesis. Instead, the subjects got 6.25 grams, which contains 0.75 grams of leucine, as compared to the three grams contained in 25 grams of whey. The men first did a set of one-legged extensions before having one of the following meals:

1) 25 grams of whey protein

2) 6.25 grams of whey with added leucine, enough to equal the content of 25 grams of whey

3) 6.25 grams of whey with essential amino acid content equal to that of whey for all aminos except leucine

The results showed that adding the leucine to a smaller dose of whey did provide a postmeal boost in muscle protein synthesis, but it was short-lived, lasting only one to three hours. Even the whey with the added aminos minus leucine led to only a temporary boost. Only the greater dose of whey produced a sustained boost in protein synthesis that lasted three to five hours. That was true even though the blood amino acid elevations provided by all the sources usually return to baseline about 2 1/2 hours after the peak plasma amino spike.

The authors suggest that the nonessential amino acids may be the key to the sustained rate of protein synthesis produced by whey. This study also underscores the fact that while leucine may be a key arbiter of muscle protein synthesis, you still need the presence of other amino acids for it to proceed at an optimal rate. Specifically, if you provide a large amount of other amino acids, you don’t need a large dose of leucine to trigger protein production.

Although leucine is most known for its positive effect on protein synthesis, it has a few other attributes that can be very helpful for bodybuilding purposes. Relating to body composition, in the hypothalamus section of the brain, leucine helps to reduce appetite by modifying the activity of leptin, a protein produced by fat cells. Leptin signals the brain, which turns off sensations of hunger.

Once leucine has done its work in relation to muscle protein synthesis, excess leucine can be converted into other amino acids, such as alanine and glutamine. That helps to maintain blood glucose under carbohydrate-restricted conditions. In other words, it helps you maintain energy when on a low-carb diet.

In addition, leucine appears to aid in the creation of mitochondria, the cellular structures where energy is produced as ATP and fat is burned. Leucine also blunts the release of certain peptides in the brain that are associated with intense food cravings, and as such it helps in the fat-loss process.

Mice that are fed a high-fat diet but supplemented with leucine show a 32 percent reduction in weight gain along with 25 percent less bodyfat. The fat loss is related to an uptick in the activity of thermogenic proteins that turn fat calories into heat. The effect may be more potent in mice, as they have more of the highly thermogenic brown adipose tissue than humans. In one study of mice on a high-fat diet, the subjects showed all the symptoms of the metabolic syndrome, including obesity, fatty liver, insulin resistance and negative inflammatory changes in fat cells. Yet, giving them leucine blocked most of those negative metabolic syndrome effects.

Another recent study found that a combination of leucine and vitamin B6 may significantly boost bodyfat loss.3The supplement consisted of 2.25 grams of leucine and 30 milligrams of B6. Cell culture studies had previously shown that leucine exerts a partitioning effect, diverting energy from being stored in fat to being burned in muscle. Leucine increases the activity of genes that control fat release and encourages muscle-fat oxidation. The B6 is added because its actions appear to blunt an enzyme called fatty acid synthase that is an important player in the fat-storage process. The combination of leucine and B6 boosted fat burning in human subjects by 33.6 grams a day while also reducing oxidative and inflammatory markers. In addition, the supplement boosted by 67 percent levels of adiponectin, a fat-cell protein associated with reduced inflammation and increased insulin sensitivity.

The same authors also published a study that examined the effects of combining either leucine or its metabolite, HMB, with resveratrol. Resveratrol is currently a superstar nutrient because numerous animal studies have shown that it blunts many of the processes in the body associated with aging.

Animal-based studies also show that resveratrol can dramatically boost exercise tolerance and may aid in helping to control insulin resistance while encouraging bodyfat loss. That said, the doses that accomplished those effects in animals were massive compared to the levels of resveratrol found naturally. You would need to drink thousands of bottles of red wine (a good natural source of resveratrol) to obtain similar doses. Still, the new study showed that when low doses of resveratrol are combined with either leucine or HMB, the effect is synergistic, leading to body-composition changes similar to those seen with huge doses of resveratrol. Of course, this study involved rodents, so we don’t know yet whether the effect also occurs in humans. We do, however, know that the mechanisms behind the effect exist in humans.

So how much leucine should you get to promote muscle protein synthesis and fat loss? The usual suggested dose is 2.5 grams per meal and another 2.5 grams taken 1 1/2 hours after the meal to help extend muscle protein synthesis.

—Jerry Brainum


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1Norton, L., et al. (2012). Leucine content of dietary proteins is a determinant of postprandial skeletal muscle protein synthesis in adult rats. Nut and Metabol. 9:67.

2Churchward-Venne, T.A., et al. (2012). Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol. 590:2751-2765.

3Zemel, M.B., et al. (2012). Effect of a leucine and pyridoxine-containing nutraceutical on fat oxidation and oxidative and inflammatory stress in overweight and obese subjects. Nutrients. 4:529-41.

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