I regularly get questions about branched-chain amino acids (BCAAs), and there seems to be a fair amount of confusion about them. For instance, I’ve recently been asked whether they can be interchanged with creatine or n-acetylcysteine. (The answer is no in both cases; all three have different functions.) So here’s a brief review on BCAAs, what they are, how they can benefit you in terms of athletic performance, increased lean mass, greater fat loss, and probably even extending maximum lifespan.
Amino acids are small molecules that, when chemically bonded together in specific ways, form proteins; branched-chain amino acids refers to those that have branched side chains, and there are three of them: leucine, isoleucine, and valine. Researchers used to talk a lot about all of the BCAAs, but it’s now understood that only one of them is truly critical: leucine.
Leucine is the most important nutritional signal for muscle protein synthesis. It does this by activating the mammalian target of rapamycin (mTOR).
Ingestion of a leucine-enriched essential amino acid nutrient solution rapidly and potently activates the mammalian target of rapamycin signalling pathway and protein synthesis in human skeletal muscle. Further, mTOR signalling and muscle protein synthesis are enhanced when leucine-enriched nutrients are ingested following resistance exercise. The addition of leucine to regular meals may improve the ability of feeding to stimulate protein synthesis in old human muscle. (Link.)
From just this one review paper we already see that leucine not only potently stimulates muscle protein synthesis, but that it has additive effects when ingested after weightlifting.
Way back when I started looking into this topic, one of the first papers I came across was one in which a mixture of BCAAs was given to rugby players. (Paper is here.) The players took 3.6 grams twice daily during their regular playing season, and “reported improvement in vigor and earlier recovery from fatigue.” They also had significant increases in hemoglobin, hematocrit, and RBC count; since a declining hemoglobin level is one characteristic of overtraining, this may account for, or be correlated with, the athletes increased energy and fatigue recovery.
So, not only does leucine promote muscle, but the BCAAs in general promote fatigue recovery and help prevent overtraining.
The amino acids in whey protein are approximately 25% BCAAs. Tons of research has been done on whey as a potent stimulant of muscle protein synthesis both with and without resistance training. An excellent review can be found in the article Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: A case for whey protein. Suffice it to say that whey protein stimulates muscle protein synthesis better than any other protein source. The reason for the superiority of whey is that it results in higher bloodstream levels of both leucine and essential amino acids than other forms of protein, as can be seen in the graph below.
As leucine rises, mTOR is stimulated, and muscle protein synthesis increases. The area under the curve for blood leucine after whey ingestion was ∼73% greater than soy and ∼200% greater than casein. (From Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men.) After resistance training, muscle protein synthesis with whey was about twice as high as with casein, and 50% higher than soy. (You don’t want to use soy anyway because, you know, soy.)
Leucine can actually cause greater burning of fat and hence fat loss. A nutraceutical containing 2.25 grams leucine, along with 30 mg vitamin B6, taken twice daily, caused the loss of nearly two kilograms of fat on a caloric maintenance diet, and on a hypocaloric diet (500 calorie a day deficit), subjects on leucine and B6 lost twice as much fat, 5 vs 2.3 kilograms, as the placebo group. The same researchers also found that leucine “decreased fatty acid synthase (FAS) expression and triglyceride content in adipocytes, and PLP [vitamin B6] addition significantly augmented this effect.” This appears to be its mechanism of action in fat loss, at least in part.
Pretty remarkable, I’d say. I’m unaware of any other non-drug fat loss aid that has such a potent effect.
An amino acid mixture supplemented with BCAAs increased median lifespan in mice: Branched-Chain Amino Acid Supplementation Promotes Survival and Supports Cardiac and Skeletal Muscle Mitochondrial Biogenesis in Middle-Aged Mice.
Recent evidence points to a strong relationship between increased mitochondrial biogenesis and increased survival in eukaryotes. Branched-chain amino acids (BCAAs) have been shown to extend chronological life span in yeast… Here, we show that a BCAA-enriched mixture (BCAAem) increased the average life span of mice. BCAAem supplementation increased mitochondrial biogenesis and sirtuin 1 expression in primary cardiac and skeletal myocytes and in cardiac and skeletal muscle, but not in adipose tissue and liver of middle-aged mice, and this was accompanied by enhanced physical endurance. Moreover, the reactive oxygen species (ROS) defense system genes were upregulated, and ROS production was reduced by BCAAem supplementation… These data reveal an important antiaging role of BCAAs mediated by mitochondrial biogenesis in mammals.
Mitochondrial dysfunction and oxidative stress are two important components of aging, and the BCAA-enhanced mixture decreased both: there was increased mitochondrial biogenesis and decreased oxidative damage. The “was accompanied by enhanced physical endurance”, and increased expression of antioxidant enzymes.
The mice received 1.5 grams of the mixture per kilogram of body weight. The mixture (the composition of which you can find in a supplemental paper) was basically essential amino acids supplemented with BCAAs, such that we could double it for whey protein, since the latter is about 25% BCAA and 50% EAA. A human equivalent dose, setting mouse metabolism at 12 times higher than human, might be about 25 grams daily, or one large whey drink.
As noted above, leucine potently stimulates muscle protein synthesis, and it does this by activating mTOR. However, muscle protein synthesis also requires the presence of other amino acids, especially the essential amino acids, since muscle is composed of them. Therefore, if you use leucine or BCAAs to build muscle, you need other EAAs present at the same time.
If you take your leucine in the form of whey, this is not a problem, as whey is about 50% essential amino acids.
But, you can’t really drink whey all day long. So the way to use leucine otherwise is to take it with a protein-rich meal, which ensures the presence of other EAAs. The amount of leucine in 25 grams of whey is about 2 grams, so that amount of leucine taken with a meal ought to stimulate muscle protein synthesis much better than the protein in your meal alone.
It appears that the same regimen ought to be used for fat loss: around 2 grams leucine, with a meal, twice daily. The addition of 30 mg vitamin B6 will increase fat oxidation.
Importantly, since it activates mTOR, leucine abolishes autophagy, so it should be taken only in the fed state. If taken while fasting, it will eliminate many of fasting’s health benefits. If you are fasting only for the effect on fat loss, then the use of leucine may be appropriate. I expanded on this theme in my post Intermittent fasting for fat loss or anti-aging?
Leucine can increase muscle mass not only in those who resistance train, but can be useful for the elderly, who may suffer from sarcopenia as a result of anabolic resistance.