What is Muscle Failure?!

May 28, 2019

The Physiology of Muscle Failure


The minute AMRAP is written next to your not-so-favourite exercise, you know you’ll be hitting a point where your muscles simply stop responding. A point where you’ve completely and utterly hit “muscle failure”.

Why is that?

What is the limiting factor determining an inability for your muscles to contract just one more time?

Muscle fatigue has two contributing components; central and peripheral1,2. Its exact physiology is a phenomenon involving a complex interaction between the two.


Peripheral Fatigue

Peripheral fatigue is the one that is better understood of the two yet not the primary cause of reaching complete so-called “muscle failure”. Peripheral fatigue is a multi-factorial event in that it is a combination of the following3:

  • An accumulation of metabolic byproducts
  • A decrease in high-energy phosphate groups
  • A decrease in glycogen levels

Metabolic byproducts, including lactic acid, are associated with the burning sensation you get in your muscles after producing short bursts of energy. It occurs with a depletion of high-energy phosphate groups used for this anaerobic form of energy production. Glycogen, on the other hand, is the fuel used for aerobic energy expenditure required for activities such as long-distance running3.

Peripheral fatigue, i.e. the events above, occur during training where there is an increase in muscle energy output demand. This can either be in the form of high energy output for a short period of time (anaerobic) or low energy output for an extended period of time (aerobic). These events are normal physiological processes that occur but are not necessarily the limiting factor in performance. By this I mean complete depletion of the energy supply being used is rarely met. Therefore, the feelings of fatigue people associate with exercise is rather due to the effect that central fatigue has on the body in response to peripheral fatigue events occurring2.


Central Fatigue

Whilst central fatigue is the main determinant of ‘max effort’, it is poorly understood. The best explanation uses the ‘Serotonin-Fatigue Hypothesis’ which explores serotonin levels during exercise4. As expected, these levels increase and actually cause central fatigue and decrease Central Motor Drive (CMD), with prolonged exposure. This is explained by the inverse relationship between dopamine and serotonin. When serotonin is high, dopamine is low, and visa versa. High levels of serotonin (centrally) result in decreased motor unit recruitment (peripherally) which in turn affects the mental and physical capacity of the exercising athlete. This in itself demonstrates how, as mentioned previously, peripheral factors impact the central nervous system, which in turn affects the peripheries i.e. muscle contraction.

So, simply put, the rise in serotonin as well as peripheral factors both contribute to central fatigue which is the primary influencer on muscle contraction in the periphery.

It’s this series of events that is required to drive the symptoms associated with “muscle failure”.


So rather than thinking max effort is limited by lactic acid build up or the lack of “fuel” available in your system, those are only contributing factors. It has very much to do with your central nervous system and the impact it has on muscle contraction.
This is why recovery (sleep, rest, nutrition, mental space) is such an important part of programming to improve exercise performance – but let’s save that discussion for another time..!



  1. Amann, M. Central and Peripheral Fatigue: Interaction during Cycling Exercise in Humans. American College of Sports Medicine. 2011;43:11:2039-2045.
  2. Lloyd, A, Hodder, S, Havenith, G. The interaction between peripheral and central fatigue at different muscle temperatures during sustained isometric contractions. American Journal of Physiology. 15 August 2015;10.1152
  3. Coffey VG, Hawley JA. The molecular bases of training adaptation. Sports Med 2007; 37:737
  4. Weicker, H, Struder, HK. Influence of exercise on serotonergic neuromodulation in the brain. Department of Sports Medicine. February 2001; 20:35-47.