Branched-chain amino acids

Leucine, isoleucine, and valine are three of the nine essential amino acids, and they are unusual in being oxidised largely in skeletal muscle rather than the liver, via branched-chain aminotransferase and the BCKDH complex. That single fact is the seed of the entire marketing category: muscle burns them, therefore muscle must want them.

Leucine really is a signal. It is sensed upstream of mTORC1 (through Sestrin2 and leucyl-tRNA synthetase), and mTORC1 phosphorylates p70S6K and 4E-BP1 to raise translation initiation. There is nothing fake about that biochemistry. The problem is what it is being asked to imply. Signalling is a permission slip. Construction needs bricks.

Muscle protein is built from all twenty residues in fixed proportion. Supply leucine and its two companions alone and muscle protein synthesis rises briefly, then falls, and plasma concentrations of the other essential amino acids drop as they are pulled into new protein. You have not started a build. You have accelerated a queue that is missing a part.

There is also a timing problem the marketing never mentions. If you ate protein in the last few hours, plasma essential amino acids are already elevated and BCAAs add nothing measurable. The intra-workout sipping ritual is aimed at a fasted state most athletes are not in.

As for anti-catabolism: net protein balance across a short fasted training session is only slightly negative, and whole protein or, radically, breakfast, fixes it more completely and for less money.

Wolfe's 2017 review is the cleanest summary available: no study demonstrates that BCAAs alone increase net muscle protein accretion in humans. Not a shortage of studies. A shortage of results.

Jackman et al. 2017 measured it directly. BCAA ingestion after resistance exercise raised myofibrillar protein synthesis about 22 percent, which is real, and far less than the roughly 50 percent or more produced by an equivalent dose of whole whey protein. Same grams, half the outcome, because the whey brought the other six essential amino acids with it.

The soreness literature is where you learn to read a control group. Fouré and Bendahan's 2017 review found the damage and DOMS trials to be small, mostly in untrained subjects performing unfamiliar eccentric protocols, and inconsistent. Where an effect appears it is on the order of one point on a ten-point soreness scale with no accompanying difference in force recovery. Critically, many positive trials compare BCAAs against nothing in subjects on a low-protein diet, which tests whether some amino acids beat no amino acids. They do. That is not the question on the label.

This audit scores high on evidence quality and near zero on effect, and that combination is the point of scoring the two separately. BCAAs are not a mystery. They have been examined thoroughly and they lost.

Where BCAAs are not silly: supervised management of hepatic encephalopathy in liver disease, and possibly a small effect on perceived exertion in prolonged endurance work through competition with tryptophan at the blood-brain barrier. Neither is what is being sold in a gym.