Reading through a medical study conducted by Bishop et al (2) on Central Nervous System and Peripheral Nervous System Fatigue, I stumbled across an interesting fact. The findings of another study conducted by Davis et al. (1) were cited and it was proposed that central nervous system fatigue is driven by serotonin (5-hydroxytryptamine) levels in the brain in response to intense exercise and that carbohydrate or BCAA ingestion may mitigate 5-HT increases thereby reducing signs of fatigue. Increased levels of 5-HT are associated with its effects on depression, sensory perception, sleepiness, and mood. They could not substantiate their claim with solid scientific evidence but there does seem to be a relationship between brain 5-HT and central fatigue and there is data to suggest a beneficial role of Carbohydrate and/or BCAA on 5-HT levels!


Defining the Terms

Intra-Workout Shake – All references made are referring specifically to a shake with a 3:1 Carbohydrate to Protein Ratio.

Fatigue – Drop in physical performance either intra-workout or from session to session.

A cursory look at current literature suggest intra-workout drinks serve two distinct purposes:

  • Maintain workout intensity due to increased amount of BCAA (Branch Chain Amino Acids) and Glucose in the bloodstream.
  • Insulin levels are kept high setting muscles up for post-workout recovery. (After a training session, there is a 30–60-minute phase, in which muscles induction of glycogen is increased. After this comes a slower phase where muscle glycogen induction is dependent upon (among other factors) the presence of insulin.)


Glucose – The Brain’s Primary Fuel Source


Most people know that the brain runs on sugar — glucose to be exact — and if it doesn’t have enough, it will go looking for reserves. Skeletal muscles are the brain’s biggest competitors for glucose. During physical exertion, their glucose needs also rise sharply. The liver and skeletal muscle have the unique ability to store glucose that is not used right away in another form called glycogen. The brain, however, cannot even store even the smallest amount of reserves.

Because of its simple form, Glucose travels very fast to wherever it is needed.

If glucose is present in its purest form (as a monosacharide), it can travel freely straight to the blood. It is able to pass easier through the intestinal walls and into the bloodstream.

There are really only two sources from which the brain can pull glucose from:

  1.  The bloodstream
  2. Stores in the liver.

If there is a risk that supply will drop too low, the “Selfish Brain” mode kicks in: The brain draws as much glucose from the blood as it wants not accounting for the needs of other body parts. Only once the brain has been supplied sufficiently, are other parts allowed to take their share.

If glucose levels in the body dramatically decrease during training, maybe the central nervous system kicks in at a certain point to protect the brain from low glucose levels.

That would mean that fatigue of the central nervous system during and post-workout could be part of a defense mechanism designed to keep your brain working optimally. This would then be one of several factors along with muscle cell damage that contribute to Fatigue.


Extra benefit of the Intra-Workout shake


Following the aforementioned hypothesis that Carbohydrates and/or BCAA lower 5-HT levels in the brain. We could use good theoretical rationale to say that Intra-Workout drinks containing CHO and BCAA can improve central nervous system function under fatigue and thereby increase athletic performance. Due to the increased blood glucose levels, the brain is supplied with the fuel it needs to function without having to fight with skeletal muscle. Likewise, in-line with conventional wisdom, skeletal muscle is provided with a steady flow of BCAA’s and much needed glucose for glycogen synthesis. Both aspects are important for improving the quality of short-term (intra-workout) and training recovery.



  1. Davis, JM, Alderson, NL, and Welsh, RS. Serotonin and central nervous system fatigue: nutritional considerations. Am J Clin Nutr 72: 573S–578S, 2000.
  2. RECOVERY FROM TRAINING: A BRIEF REVIEW PHILLIP A. BISHOP, ERIC JONES, AND A. KRISTA WOODS Kinesiology Department, Human Performance Laboratory, University of Alabama, Tuscaloosa, Alabama