Branched-chain amino acids (BCAAs), and especially L-leucine, have garnered a ton of attention in the scientific community over the past two decades. Data continues to uncover the usefulness of BCAAs for building muscle and preventing muscle tissue breakdown, among many other beneficial properties.



However, there doesn’t seem to be much information out there that describes the science behind BCAAs when the body is in the fasted and fed states. Moreover, the information that is available on the aforementioned topics seems to lack understanding of what actually happens. Read on as this article takes an in-depth look at the applications of BCAAs for physique enhancement.



The Role of Amino Acids in the Fasted State


Almost all of the body tissues use glucose as the primary source of energy and red blood cells subsist solely on glucose as they lack mitochondria. When the body is in a truly fasted state (12+ hours of no energy intake) your liver is doing everything it can to produce enough glucose to keep your body euglycemic (i.e. having blood sugar in a nominal range).

As liver glycogen is depleted, other substrates start to be incorporated into the hepatic gluconeogenesis cycle to keep blood glucose levels in a nominal range. Proteins from muscle tissue are one of the main reservoirs of amino acids which provide carbon for this gluconeogenic pathway.

So to summarize, during a fasted state, proteolysis (protein breakdown) increases in order to supply amino acids as substrate for gluconeogenesis. Obviously, this is not so great for building muscle and enhancing body composition



The (likely) Fate of BCAAs in the Fasted State


Since the plasma amino acid pool during a fast is being replenished via proteolysis/protein breakdown (as opposed to intake of protein-rich foods), then the fate of BCAAs is changed accordingly.

This is to say that since the plasma amino acid pool is likely depleted of one or several essential amino acids (EAAs) necessary for synthesis of new proteins in muscle and other body tissue, then L-leucine - the trigger for muscle protein synthesis - ingested from BCAAs is now rendered as a fuel source for hepatic gluconeogenesis.

In other words, when all nine of the EAAs required for protein synthesis are not present in the bloods amino acid pool, muscle protein synthesis can't proceed.[1] Therefore, if one (or more) of the EAAs is "missing" and you ingest BCAAs (which contain only 3 of the EAAs) then you're ultimately just providing the body with a fuel/carbon source for hepatic gluconeogenesis.



This is precisely why MPA formulated PharmGrade with all nine essential amino acids and a plentiful amount of BCAAs.





Further Considerations--Cell Sensory of Nutrient Status
Another important aspect to touch on is how cell's sense nutrient status. The muscle protein synthesis pathway is initiated by a complex of proteins called mTOR protein complexes. This pathway is an energy consuming process and without the necessary substrates it will not proceed. When the body is in a state of nutrient deficiency, AMPk is the dominant pathway that proceeds which tells the body to break down fatty acids for energy (lipolysis). That's a great thing for "cutting" purposes, but the issue is that AMPK inhibits mTOR (and vice versa).

So we now see that you can't have your cake and eat it too when it comes to these pathways and they are antagonists of one another. If your body is in a fasted state (and thus deprived of energy/nutrients in the blood), then BCAAs alone will not suffice to stimulate the mTOR pathway.

Potential Mechanism for BCAAs Sparing Protein during a Fast
I've often wondered why BCAAs would be anti-catabolic during a fast but not anabolic. It finally occurred to me that BCAAs are insulinogenic amino acids and then it hit me--insulin is an antiproteolytic/anticatabolic hormone.

Essentially by ingesting BCAAs, even modest increases in blood insulin can suppress gluconeogenesis in the liver by decreasing protein breakdown in muscle and other tissues. [2]

Also, as many of you hopefully know, insulin is inherently anabolic, particularly when the necessary substrates are available. Insulin increases muscle protein synthesis (MPS) by utilizing amino acids in the blood and amino acid pool within cells, as is demonstrated by administration of insulin during periods when amino acid concentrations are maintained at nominal levels.[3] Therefore, insulin on its own does not create an anabolic environment as it could theoretically “use up” all the readily available amino acids.





Given this, BCAAs during a fasting period may have an anti-catabolic/antiproteolytic property likely as a result of their insulinogenic nature. However, they are not anabolic in a fasted state as we covered earlier (though, it wouldn’t make much sense to be seeking anabolism during a fasted state).

Usefulness of BCAAs in the Fed State
The efficacy of BCAAs in the fed state makes them much more appealing than their uses during a fasted state. Reason being is that in the fed state (assuming you've eaten a generous meal with a complete protein source within a few hours) you'll likely have plenty of amino acids in the blood for the BCAAs (and specifically L-leucine) to initiate a MPS response.

Based on research, it appears that the MPS response to feeding of a complete, leucine-rich protein peaks at about the 3-hour mark post meal[4]; thereafter, MPS (and L-leucine levels) falls back to baseline. Therefore, anything after the 3-hour mark that re-triggers muscle protein synthesis is worthwhile.

Let's take a practical look at what you could do to optimize your BCAA use in a fed state:

12:00pm--Meal with 30+g of complete protein source, carbs and fats if desired
3:00pm (or so)—2 Scoops PharmGrade (providing 12g BCAAs)
3:30-5:00pm--Workout
5:30pm—Post-Training Meal

The above layout is just one of many possible implementations of BCAAs during the fed state and around the training window. You could also use BCAAs post-workout, wait an hour or so to let muscle protein synthesis (since pure BCAAs cause MPS to elevate and drop quicker than whole proteins) return to baseline and then hit the body with another meal.

I hope this makes sense, it's a complicated topic and research continues to grow on protein metabolism. It's safe to say that when utilized in a smart fashion, and at the proper times, BCAAs can certainly benefit those looking to improve their performance and body composition.

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