What are the key fatigue mechanisms?
Please subscribe to my newsletter to read the future articles in this series!
In the fitness industry (as well as in real life), fatigue is often referred to as a single phenomenon. Yet, this characterization of fatigue is a detrimental oversimplification that stops us from understanding how it works in practice. In contrast, if we break fatigue down into its component parts or mechanisms, we can learn a great deal about how it works, how each mechanism negatively affects the type of adaptation we are interested in, and how we can mitigate all of these negative effects.
In my previous article, I explained how fatigue can be analyzed by looking at its four main pathways or outputs (reduced coordination, reduced motor unit recruitment, reduced muscle fiber shortening velocity, and reduced muscle fiber force). This article is essentially a direct follow-up to that earlier article, providing more detail about how those four pathways come about inside the central nervous system and the muscles of the body.
How can we break fatigue down into parts?
Fatigue can be defined as a temporary and reversible reduction in exercise performance, as a result of a previous bout of exercise. Consequently, we can understand fatigue as a series of mechanisms that interfere with the normal operations of motor units and muscle fibers.
In practice, this means that if we study the normal operations that generate the performance of a muscular contraction, starting from the inception of the movement in the brain, and proceeding through to the shortening of muscle fibers inside a muscle that create the movement, then we can then assess how various fatigue mechanisms might affect all of the events in that chain.
What are the normal operations?
During the production of a movement, we can identify the following normal operations in various parts of the body that lead to force production due to muscle fiber shortening:
Generation of central motor command (brain)
Transmission of central motor command from brain to neuromuscular junction (spinal cord)
Propagation of electrical signal within muscle (the outer surface of activated muscle fiber cell membranes)
Conversion of electrical signal into chemical signal (at the base of the transverse tubules, at the triadic junction of muscle fibers)
Detection of chemical signal by actin myofibrils (cytoplasm of muscle fiber)
Binding (and subsequent unbinding) of myosin heads to actin myofibrils to form crossbridges, thereby generating force (cytoplasm of muscle fiber)
Transmission of crossbridge force to the surrounding cytoskeleton (cytoplasm of muscle fiber)
The first two of these steps take place within the central nervous system (CNS), while the last five steps taken place inside the muscle. Therefore, any fatigue mechanisms that occur within the first two steps are described as CNS fatigue, while any fatigue mechanisms that occur within the final four steps are described as peripheral fatigue.
Let’s now look at how fatigue mechanisms can occur by disrupting the normal operations of each of those steps.
How do fatigue mechanisms affect these normal operations?
#1. Generation of central motor command
Fatigue mechanisms can cause a reduction of the magnitude of central motor command generated by the motor cortex.
Under certain circumstances, the amount of central motor command that the brain is able to produce is reduced, despite us deliberately attempting to exert the greatest possible effort (and exactly how this happens is a very important topic that we will return to in more detail in a subsequent article). When this happens, the level of motor unit recruitment that occurs within the muscle is reduced, which in turn reduces muscle force, which we then measure as fatigue.
#2. Transmission of central motor command
Fatigue mechanisms can cause a reduction of the amount of central motor command that is transmitted from the brain to the neuromuscular junction.
Under certain circumstances, the amount of central motor command that the spinal cord transmits from the brain is reduced. Therefore, the level of central motor command that reaches the muscle is reduced even when the brain generates a maximal level of central motor command. Obviously, when this happens, the level of motor unit recruitment that occurs within the muscle is reduced, which in turn reduces muscle force, which we then measure as fatigue.
#.3 Propagation of electrical signal within muscle
Fatigue mechanisms can cause a reduction in the size of the electrical signal that is transmitted along the outside of activated muscle fiber membranes.
For muscle fibers to produce force, they must be activated, and this activation occurs by means of the propagation of electrical signals along the outer membranes of the muscle fibers themselves. However, when the polarity of the cell membrane is disrupted (which can occur either by ion movements across the membrane during exercise or by oxidative damage experienced by the membrane itself), the propagation of the electrical signal is disrupted, which prevents the activation of the muscle fiber (either partly or in its entirety). When this happens, some of the muscle fibers in the muscle, which were signaled to switch on and produce force, fail to activate. This in turn reduces muscle force, which we measure as fatigue.
#4. Conversion of electrical signal into chemical signal
Fatigue mechanisms can prevent the electrical signal from being converted into a chemical signal at the triadic junction of muscle fibers.
For muscle fibers to produce force, their myofibrils must detect a chemical signal that takes the form of calcium ions released from stores within the sarcoplasmic reticulum. For the chemical signal to be generated, the electrical signal that was propagated along the outside of the muscle fiber cell membrane and down into the transverse tubule must be converted into the chemical signal at the junction with the sarcoplasmic reticulum (this junction is called the “triadic junction” because it has three sides: one being the side with the voltage sensor at the bottom of the transverse tubule, one being the side with the calcium ion store of the sarcoplasmic reticulum, and the third being a structure that holds the two other sides close to one another). When a fatigue mechanism happens that stops the electrical signal triggering the release of calcium ions at the triadic junction, the myofibrils inside the muscle fiber do not receive a chemical signal that tells them to form crossbridges, so they do not make any. When this happens, some of the muscle fibers, which were fully activated, do not produce force in spite of being activated. This in turn reduces muscle force, which we measure as fatigue.
#5. Detection of chemical signal by actin myofibrils
Fatigue can cause a the actin myofibrils to be unable to detect the presence of the chemical signal released from the sarcoplasmic reticulum.
For muscle fibers to produce force, their myofibrils must detect a chemical signal that takes the form of calcium ions released from stores within the sarcoplasmic reticulum. Yet, various events can occur within the muscle fiber cytoplasm that stop actin myofibrils from detecting the presence of calcium ions. Therefore, even when calcium ions are being adequately supplied by the sarcoplasmic reticulum, the actin myofibrils can still fail to form crossbridges, simply because they cannot detect the calcium ions. When this happens, some of the muscle fibers, which were fully activated, do not produce force in spite of being activated. This in turn reduces muscle force, which we measure as fatigue.
#6. Binding (and subsequent unbinding) of myosin heads to actin myofibrils
Fatigue can disrupt the rate at which crossbridges bind and unbind, which impacts both muscle fiber force and muscle fiber shortening velocity.
For muscle fibers to produce force, their myofibrils must form crossbridges, and the rate of crossbridge binding and unbinding is what determines muscle fiber force and muscle fiber shortening velocity. Therefore, any fatigue mechanism that causes slowing of either binding or unbinding can affect muscle fiber force or muscle fiber shortening velocity. In fact, there are a number of mechanisms involving the actions of acidosis (protons) and inorganic phosphates that cause disruptions to this process, mainly as a result of metabolic processes providing energy to the muscle fiber for the purposes of both excitation-contraction coupling and crossbridge formation. Thus, this type of fatigue is often referred to as “metabolite-related fatigue” and it has been extensively studied by researchers. Indeed, when reading some early textbooks, you might even be forgiven for thinking that this is the only type of fatigue mechanism that exists during exercise, it has been given so much prominence.
#7. Transmission of crossbridge force to the surrounding cytoskeleton
Fatigue can disrupt transmission of forces within the muscle fiber, if any of the myofibrils or cytoskeletal structures are damaged.
For muscles to produce force, the shortening of myofibrils inside muscle fibers by the creation of actin-myosin crossbridges must lead to the shortening of the muscle fiber itself. This occurs by the transmission of forces from the myofibrils to the cytoskeleton and through the cell membrane to the surrounding endomysium of the muscle fiber. Yet, if any of the myofibrillar or cytoskeletal structures are damaged, then this transmission of crossbridge forces is impaired, even though the muscle fiber might be fully activated, even though calcium ions might be flowing freely into the cytoplasm, and even though many of the actin myofibrils inside the muscle fiber might be responding to the presence of those calcium ions to form crossbridges. Evidently, this reduction in muscle fiber force can reduce muscle force and thereby be detected as fatigue. Like metabolite-related fatigue, this fatigue mechanism has been extensively studied by researchers and for many years it was believed to be the sole mechanism that produced fatigue in the days after a strength training workout (which is why fatigue in the days after a strength training workout was often simply called “muscle damage” without actually any direct confirmation that the reduction in strength was in fact the result of structural damage to muscle fibers).
What about fuel availability?
It is commonly believed that the availability of muscle glycogen is a key factor that determines strength recovery (and therefore by definition recovery from fatigue) in the days after a strength training workout. Yet, while the availability of muscle glycogen probably does impact on exercise performance more generally (and therefore it does deserve to be described in the context of the various fatigue mechanisms), it does not impact on any of the four key fatigue pathways (reduced coordination, reduced motor unit recruitment, reduced muscle fiber force, and reduced muscle fiber shortening velocity). In reality, it only impacts on repetition strength or work capacity, and thereby can greatly affect endurance exercise performance, but rarely impacts fatigue in the context of strength training.
Nevertheless, for athletes who compete in sports that require high levels of strength and speed as well as high levels of aerobic fitness, the availability of muscle glycogen is important. I will address this specifically in a future article.
Does this analysis affect how we describe fatigue mechanisms?
Having analyzed the various places within the process that leads to movement that can experience fatigue, we can now attempt a slightly more accurate grouping of fatigue mechanisms (rather than just central mechanisms and peripheral mechanisms).
Indeed, the two CNS fatigue mechanisms can now be subdivided into supraspinal (brain) CNS fatigue and spinal CNS fatigue mechanisms, when we want to be more specific about their nature. This is important because researchers have identified that CNS fatigue can and does occur in both locations, and for different reasons. Moreover, it is possible that fatigue in each of these locations within the CNS might affect adaptations in slightly different ways.
Similarly, the peripheral fatigue mechanisms can now be grouped into those that are caused by the presence of calcium ions (being reductions in the electrical signal that is transmitted along the muscle cell membrane, prevention of the conversion of the electrical signal into a chemical signal, failure to detect the chemical signal by actin myofibrils, and the damage that is experienced inside muscle fibers) and those that are caused by the presence of metabolites (which comprises those mechanisms that directly influence crossbridge formation as a result of metabolic activity). This classification is very important, because these two types of peripheral mechanism have totally different effects in terms of outcomes and therefore also alter adaptations in quite different ways.
Why does it matter how fatigue mechanisms affect normal operations?
As I explained in my my previous article, the specific outcome of a fatigue mechanisms matters a great deal (whether it is reduced coordination, reduced motor unit recruitment, reduced muscle fiber shortening velocity, or reduced muscle fiber force) because these outputs during exercise are what determine the adaptations after exercise.
If we experience a fatigue mechanism that reduces coordination during exercise, we will not improve coordination after that workout. Similarly, if we experience a fatigue mechanism that reduces the central motor command that reaches the muscle to produce motor unit recruitment during exercise, we will not improve the ability to recruit high-threshold motor units after that workout. In other words, fatigue acts primarily as a mechanism that stops many important strength training adaptations from happening (although it does cause some other, less useful adaptations instead). I acknowledge that this sentence is the exact opposite from what is commonly believed!
By considering the flow of events in the list above, we can now appreciate that reduced motor unit recruitment will occur whenever there is supraspinal CNS fatigue or spinal CNS fatigue. Similarly, reduced muscle fiber force will occur whenever there is calcium ion-related peripheral fatigue mechanisms, while reduced muscle fiber shortening velocity will occur when metabolite-related fatigue is present (as only acidosis can cause this to occur).
Exactly which fatigue mechanism is the most problematic for coordination is not clear, but it actually seems likely that peripheral fatigue would be more problematic than CNS fatigue, because this creates a scenario in which muscle force is not generated at the expected level for a given amount of effort, thereby reducing the predictability of a movement and hence the coordination of that action.
What does this mean from a practical perspective? (part one)
From a practical perspective, if we want to maximize increases in the ability to recruit high-threshold motor units, we know that we need to maximize motor unit recruitment levels during strength training. To achieve this, we can look for methods of strength training that minimize the presence of supraspinal CNS fatigue and spinal CNS fatigue.
Similarly, if we want to maximize increases in muscle fiber force (through hypertrophy and increases in lateral force transmission), then we want to maximize muscle fiber force during strength training by avoiding calcium ion-related peripheral fatigue mechanisms. Indeed, this should be obvious, given that the critical mechanism for producing hypertrophy is mechanical tension, which is just another way of saying muscle fiber force.
And if we want to maximize increases in muscle fiber shortening velocity, then we want to avoid the presence of metabolite-related fatigue in general (and acidosis in particular) because this causes reduced muscle fiber shortening velocity during exercise. Again, this should be very obvious, given that fast movements are key for the improvement in muscle fiber shortening velocity.
For improving coordination, it seems likely that just avoiding fatigue in general is probably a good idea!
What does this mean from a practical perspective? (part two)
It is useful to know how each type of fatigue mechanism affects the various outcomes during exercise and therefore the various adaptations that occur after exercise, because research has revealed that different types of exercise cause different types of fatigue mechanism during and after exercise.
Some types of exercise involve more CNS fatigue during exercise (such as aerobic exercise), some types of exercise cause more calcium ion-related peripheral fatigue mechanisms during exercise (such as eccentric training), and some types of exercise cause more metabolite-related peripheral fatigue during exercise (such conventional strength training with moderate loads). Additionally, some types of exercise cause more CNS fatigue as well as more calcium ion-related peripheral fatigue mechanisms after exercise (such as eccentric training) than others.
This starts to help us plan exercise programs to avoid the negative effects of the various types of fatigue both during a workout and also on subsequent workouts within a training program.
Taking this analysis to an even more detailed level, we can see that some strength training approaches or techniques likely also affect the types of fatigue mechanisms that are experienced during exercise.
For example, training several reps away from muscular failure likely involves only metabolite-related peripheral fatigue, while training to muscular failure likely involves calcium ion-related peripheral fatigue mechanisms. Similarly, strength training with cluster set configurations likely involves much less CNS fatigue than training with conventional set configurations, while training with light loads to failure likely involves much more CNS fatigue than conventional, moderate load strength training.
Again, by looking more closely at the fatigue mechanisms, and their underlying physiology, we can understand why such important differences might exist. Furthermore, by understanding the general principles, we can begin to design strength training programs that maximize long-term adaptations to training by working around the problems that each fatigue mechanism causes, rather than simply ignoring its effects and battling with it directly.
What is the takeaway?
Characterizing fatigue as a single phenomenon is a huge oversimplification that makes it difficult to learn anything about it (which is probably why fatigue is dealt with in entirely the wrong way by much of the fitness industry). In contrast, if we break fatigue down into its component parts or mechanisms, we can understand a great deal about how each mechanism negatively influences exercise performance during a workout and therefore negatively impacts on the adaptations that occur afterwards. This knowledge then allows us to choose strength training methods, structure single strength training workouts, and link multiple strength training workouts to create a program, in such a way as to avoid (or at least mitigate) the negative effects of each fatigue mechanism, and thereby maximize the specific strength training adaptations that we are seeking to achieve.