It seems that free-form amino acid supplements have gained a large amount of attention in sports nutrition the last few years. However, with branched-chain amino acid (BCAA) supplements being all the hype as of late, it behooves us to ask whether they’re really as effective as we’re made to believe?

Moreover, if BCAAs really aren’t as efficacious as we once thought, what is best (specifically for the pulsatile fashion in which muscle protein synthesis occurs)? Read on as we dive deep into the science of muscle protein synthesis and how it's pulses are driven by amino acids. With that understanding, you’ll be able to maximize your own amino acid pulsing regimen using free-form essential amino acids from PharmGrade.

Key Terminology

Talking about protein synthesis on a molecular level can be a bit confusing without grasping key terms beforehand. Thus, here’s a quick breakdown of some concepts to understand before moving forward:

  • Muscle protein synthesis—denotes the synthesis of protein in skeletal muscle tissue
  • Muscle protein degradation—denotes breakdown of protein in skeletal muscle tissue
  • Protein turnover—a measure which entails the flux between protein synthesis and protein degradation
  • Muscle protein anabolism—denotes accretion of muscle tissue (i.e. protein synthesis exceeds protein breakdown)
  • Muscle protein catabolism—denotes loss/atrophy of muscle tissue (i.e. protein degradation exceeds synthesis)

Hopefully these aren’t too “sciencey” for most readers; don’t worry, we will keep this as simple as possible while being educational.

The Pulsatile Nature of Protein Synthesis

This is one of the more important topics to cover in this book since most gym-goers think you need constant influx of amino acids to repeatedly stimulate muscle protein synthesis. However, as research has been uncovering, it is not necessarily ideal to eat protein frequently throughout the day like traditional bodybuilding dogma would suggest.

What studies seem to find is that the elevation in MPS in response to increased availability of amino acids (such as after feeding) reaches a peak within 1-2 hours and then drops back to baseline, despite continued availability of amino acids. [1, 2] This chart below, taken from the Bohe study depicts the preceding finding:

Continuing on, it appears that the EAA L-leucine appears to be the “re-igniter” of MPS, if you will, in the postprandial state (i.e. after feeding).[3, 4] Also, this effect is independent of concomitant elevation in insulin concentrations; in simpler terms, insulin is not wholly responsible for the anabolic effects of L-leucine.

What this ultimately tells us that it may be more beneficial to space complete meals out roughly 4-5 hours, and in between those meals supplement with free-form L-leucine (or branched-chain amino to re-initiate the MPS process. This method of “amino acid pulsing” was proposed in the Norton Et. al. study cited herein. 

However, there are a variety of ways to use that proposed “pulse-feeding” method. The research we’ve covered supports that a mere 20 to 30 grams of a leucine-rich, complete protein source (e.g. most animal/animal-derived proteins and milk proteins) will provide a sufficient elevation in MPS (and this could be extended even further depending on co-ingestion of other nutrients). Given that whey protein is about 50% EAAs and 50% NEAAs/non-essential amino acids, this suggests that 10 grams of pure EAAs will suffice to fully maximize MPS (which is precisely why PharmGrade contains 10+ grams of EAAs per serving)..

Naturally, you’re thinking, “Don’t we need NEAAs as well?” Frankly, yes. However, anyone consuming even a nominal amount of protein in their diet will rarely lack the NEAAs necessary to carry out protein synthesis. Moreover, NEAAs are constantly being ‘recycled’ when the body breaks down tissue. A key  exception of when NEAAs may be necessary to make sure MPS is not inhibited would be during periods of long-duration exercise since glycine and alanine are often used for gluconeogenesis.

Amino Acid Pulsing When Intermittent Fasting

During this portion of the day, your calorie intake will remain relatively low, which is why pure EAAs are ideal since they can stimulate MPS without much caloric intake. It has been found that at roughly the 3-hour mark after initiating amino acid infusions MPS returns to basal levels. Therefore, anything beyond 3 hours is not helping the positive effects of MPS.

As such, using one serving of PharmGrade every 2-3 hours during a fasting window can help protect muscle tissue and provide energy for training. Remember, as plasma levels of EAAs drop, MPS simultaneously drops accordingly; if the body is short of one or several EAAs, then MPS is blunted.

Amino Acid Pulsing In the Fed State

If you consume several meals throughout the day that are about 4-5 hours apart, then consuming a half serving of PharmGrade between meals will suffice to stimulate MPS. It’s also a good idea to have PharmGradeon hand if you plan to train for several hours at a time, since intense resistance training can deplete essential amino acids.


  1. Bohe, J. (2001). Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids, J Physiol Volume 532, Number 2, 575-579.
  1. Norton LE, Layman DK, Garlick PJ, Brana D, Anthony TG, Zhao L, Devkota S, Walker DA. (2007). Translational controls of skeletal muscle protein synthesis are delayed and prolonged associated with ingestion of a complete meal. Experimental Biology meeting abstracts [on CD-ROM], Abstract #694.6
  1. Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. (2006) A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E381-7.
  1. Anthony, J. C., Anthony, T. G., Kimball, S. R., Vary, T. C., & Jefferson, L. S. (2000). Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased eIF4F formation. The Journal of Nutrition, 130(2), 139-145.