Branched-chain Amino Acids

The branched-chain amino acids (BCAA) are essential amino acids that include valine, isoleucine and leucine and are important for building muscle and boosting recovery after high impact exercise.  BCAAs are metabolized in skeletal muscle and play an important role in anabolic and anti-catabolic activity.  These 3 amino acids make up approximately 1/3 of the protein found in skeletal muscle.  BCAAs have the ability to maintain glycogen stores, boost protein synthesis while decreasing the breakdown of protein, decrease muscle fatigue and soreness.  If you’re a bodybuilder, it is essential that you supplement with BCAAs to build muscle mass.  Onnit’s T-Plus is not only a testo booster and estrogen blocker, it contains BCAAs necessary for bulking up skeletal muscle and promote faster recovery times.

Some clinical studies report that energy and nutrient (protein) ingestion affects protein anabolism and muscle recovery after a workout.  This means taking in energy and protein sources right after you exercise may allow for faster muscle recovery.  Since protein catabolism increases right after you exercise, it would make sense to consume energy and protein sources immediately after your workout. 

Onnit’s T-plus formulation contains ingredients designed to increase free testosterone levels while blocking estrogen production to maintain virility.  But, T-Plus also contains BCAAs that are important for protein synthesis after hard workouts that allow for bulking up. 

BCAA Catabolism

The breakdown of BCAAs (catabolism) is under the control of a branched-chain alpha-keto acid dehydrogenase in skeletal muscle.  What state this complex is in is controlled by a phosphorylation and dephosphorylation cycle.  Most of this branched-chain complex is in the inactive form (phosphorylated) during times you are not exercising which is when muscle protein synthesis and growth occurs.  When you exercise this complex becomes active and promotes BCAA catabolism (breakdown of branched-chain amino acids).  So, when you exercise you need more BCAAs.  Supplementing before and after exercise with BCAAs slows down protein catabolism and the presence of leucine supports protein anabolism by modulating the mTOR pathway (mammalian target of rapamycin).  This slows down muscle damage brought about by exercise.  Clinical testing has demonstrated that supplementing with 5 grams of mixed BCAAs before exercising decreases delayed-onset muscle soreness and muscle fatigue for up to several days after exercise.        

Leucine and mTOR

The mammalian target of rapamycin (mTOR) pathway is still a work in progress, however a fair amount is known.  Rapamycin is an antibiotic that has been used to elucidate this pathway.  Rapamycin inhibits the activity of this large enzyme complex.  Under normal conditions mTOR is activated by amino acids, insulin and growth factors.  Under times of stress such as lack of proper nutrients or energy, mTOR function is impaired.  mTOR plays a key role in protein synthesis including activation of initiation and elongation factors in protein translation and the making of ribosomes (little protein factories) which are the site of protein synthesis. 

The rate-limiting factor in the regulation of protein synthesis is whether or not amino acids are available.  When a cell is low in amino acids, it employs various homeostatic mechanisms to inhibit protein synthesis.  Muscle cells which contain the highest concentration of protein in the body are often subject to high protein catabolism that requires stringent controls.  That’s were mTOR comes in.  this large protein complex coordinates a network of signaling cascades involved with protein translation, gene transcription and autophagy.

Autophagy (self eating) is a highly conserved pathway throughout evolution that is a catabolic mechanism where unnecessary cell components or dysfunctional cellular components are broken down by lysosomes inside the cell.  Sounds drastic but it is important for the cell to survive in lean times (starvation etc.) by maintaining cellular energy levels.  When autophagy is working properly (regulated), this pathway ensures synthesis, degradation and recycling of various cellular components.  Cellular components that are destined to be broken down and recycled are shuttled to autophagosomes.  These are phospholipid vesicles that are used to accumulate cellular debris.  The autophagosome will eventually fuse with a lysosome which contains enzymes that break apart molecules to be recycled.

Getting back to mTOR and protein synthesis, muscle growth and hence protein synthesis is governed by the cells amino acid supply and signal transduction through mTOR.  That’s where the BCAA L-leucine comes in as it is involved with activation of mTOR and critical for muscle growth.  Recent research indicates that mTOR signaling is coordinated at the membranes of lysosomes.  There are several molecules (enzymes) involved in transducing the amino acid signal to mTOR.  Leucine is involved with the regulation of amino acid transport via the L and A transporters (LAT1 and SNAT2) as well as degradation of proteins in phagosomes.  The L-type amino acid transporter contains a permease and glycoprotein that spans the cell membrane (L-type amino acid transporter LAT1).  The A-type amino acid transporter (sodium-coupled neutral amino acid transport SNAT2) is also a transmembrane transporter.  LAT1 and SNAT2 work together in activating mTOR by increasing the cells internal concentration of leucine.  SNAT2 brings the amino acid glutamine into the cell in order for LAT1 to  export glutamine back out of the cell while increasing the influx of leucine.  The influx of the branched-chain amino acid leucine activates mTOR priming the cell for protein synthesis. 

It has been demonstrated that supplementation of BCAAs in humans increases the expression of mRNAs for several transporters of the L and A types (LAT1 and SNAT2 amongst others).  These transporters are found in the cell membrane and are responsible for amino acid transport into and out of the cell.  This is a regulatory pathway associated with protein anabolism following an increase in BCAA administration.  Onnit’s T-Plus may assist as a testo booster and estrogen blocker but it also contains the branched-chain amino acids which includes leucine, isoleucine and valine.  These essential BCAAs have been demonstrated to be involved with protein synthesis by way of the mTOR pathway allowing for the building of skeletal muscle. 

Glycogen-depletion and BCAAs

Research has demonstrated that BCAA transaminase activation occurs at the same time that glycogen reduction occurs during exercise.  Meaning, BCAA supplementation plays an energetic role at this time.  During exercise, increases in lipid oxidation and increases in exercise capacity during endurance workouts is increased with BCAA supplementation when glycogen levels drop.   

A double-blind study was done on 7 individuals using 300mg of mixed BCAAs or placebo (maltodextrine) for three days.  On the second day, these individuals were subjected to an exercise-induced glycogen depletion routine.  This was repeated on the third day.  Measurements were taken on the 3rd day for time to exhaustion, respiratory exchange ratio (RER), plasma glucose, free fatty acids, blood ketones and lactic acid.  Data indicates that administration of BCAAs provided greater resistance to fatigue by 17.2 percent.  Furthermore, BCAA supplemented individuals demonstrated a reduction in respiratory exchange ratio along with increases in blood glucose levels.  These researchers concluded that administration of BCAAs imparted resistance to fatigue and enhanced lipid oxidation (burning fat) when glycogen (branched-chain glucoses) stores were depleted.  Onnit’s T-Plus has included BCAAs to promote energy levels by burning fats and support muscle building.


The ingredients in Onnit’s T-Plus go beyond being a testo booster and estrogen blocker by adding branched-chain amino acids (BCAAs).  BCAAs promote the building of muscle mass while speeding up recovery time when glycogen stores are depleted.  The BCAA leucine promotes protein synthesis (anabolism) byway of the mTOR pathway.  Oral administration of BCAAs in humans increases the transcription of several amino acid transporters such as LAT1 and SNAT2.  These are transmembrane carriers that shuttle amino acids.  The presence of high levels of the amino acid leucine (BCAA) activates the mTOR pathway and initiates the production of initation and tranlational factors along with biogenesis of ribosomes for protein translation.  This brings about the building of skeletal muscle.   

Suggested Reading:

Administration of branched-chain amino acids during sustained exercise — effects on performance and on plasma concentration of some amino acids

Nutraceutical Effects of Branched-Chain Amino Acids on Skeletal Muscle (search by above title)

Branched-chain amino acids supplementation enhances exercise capacity and lipid oxidation during endurance exercise after muscle glycogen depletion.

Branched Chain Amino Acid Supplementation

Mordier S, Deval C, Bechet D, Tassa A, Ferrara M. Leucine limitation induces autophagy and activation of lysosome-dependent proteolysis in C2C12 myotubes through a mammalian target of rapamycin-independent signaling pathway.

J Biol Chem. 2000;275:29900–6.

Bolster DR, Jefferson LS, Kimball SR. Regulation of protein synthesis associated with skeletal muscle hypertrophy by insulin-, amino acid- and exercise-induced signalling. Proc Nutr Soc. 2004;63:351–6.

Role of Leucine in the Regulation of mTOR by Amino Acids: Revelations from Structure–Activity Studies

Leucine and mTORC1: a complex relationship