How does fatigue develop over a set?
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Fatigue is a temporary reduction in exercise performance as a result of previous exercise. We can analyze the development of fatigue over the course of a single bout of exercise. In this article, I hope to explain exactly how fatigue develops over the course of a normal strength training set.
What mechanisms of fatigue develop during a normal strength training set?
Introduction
Strength training often involves lifting a weight repeatedly until muscular failure. There are many misconceptions about exactly what muscular failure involves, and I will clarify exactly how the process of reaching muscular failure works in a future article. Indeed, exactly what muscular failure means is very important for understanding how strength training works, because proximity to failure has been revealed as a key training variable that affects muscular adaptations, particularly hypertrophy. Nevertheless, for the purposes of this article, we can proceed on the basis that muscular failure occurs whenever sufficient fatigue is present such that the muscle can no longer produce enough force, even at a very slow velocity, in order to lift the weight. This fatigue can arise due to many different fatigue mechanisms, including mechanisms inside the central nervous system (CNS), which lead to reductions in the level of central motor command that reaches the muscle (thereby reducing motor unit recruitment and motor unit firing rates), and mechanisms inside the muscle itself.
The unique feature of strength training
Since conventional strength training involves lifting at at least a light load (if not a moderate or even a heavy load), each muscular contraction must involve a force that is higher than 25% of maximum whole muscle force. This is a very important point, because this level of whole muscle force is sufficient to cause venous occlusion for as long as the muscle is activated. While venous occlusion is present, the blood cannot leave the muscle while it is contracting, unlike with lower levels of whole muscle force. For this reason, conventional strength training differs from many other types of exercise because it permits metabolite accumulation to occur, and this facilitates the appearance of metabolite-related fatigue mechanisms. Such metabolite-related fatigue mechanisms are not present when lower whole muscle forces are used (such as is often the case during aerobic exercise), because the lack of venous occlusion allows the blood to flow out of the muscle even while it is contracting, and the blood takes the accumulating metabolites with it.
Similarities between strength training and other exercise
In addition to metabolite-related fatigue, other fatigue mechanisms are also possible during a strength training set, since the repeated activation of the muscle fibers causes calcium ion accumulation inside the cytoplasm, which leads to calcium ion-related fatigue mechanisms, and the repeated firing of the motor neurons leads to spinal central nervous system (CNS) fatigue. Additionally, as the environment inside the muscle changes and receptors detect these alterations, they send afferent signals to the brain that generate supraspinal CNS fatigue. Unlike metabolite-related fatigue, these fatigue mechanisms are also shared with all other types of exercise, including endurance exercise.
The difference between CNS fatigue and peripheral fatigue
It is important to note that the peripheral fatigue mechanisms relate only to those single muscle fibers that are working (in contrast, those muscle fibers that are not activated by a muscular contraction do not experience peripheral fatigue), and affect either their maximum muscle fiber shortening velocity or their maximum muscle fiber force. In contrast, the CNS fatigue mechanisms work by reducing central motor command, which reduces motor unit recruitment levels (thereby switching off the muscle fibers belonging to the highest threshold motor units, irrespective of whether they were working at the time) and which also reduces motor unit firing frequency (thereby reducing the muscle fiber force of all muscle fibers, again irrespective of whether they were working at the time). Thus, while we talk about fatigue mechanisms in general terms, the peripheral fatigue mechanisms always only affect the working muscle fibers, while the CNS fatigue mechanisms mainly affect the muscle fibers of high-threshold motor units. While this point is not particularly important for the current analysis, it becomes essential to take into account whenever we want to clarify the effects of different strength training tempos, techniques, and methods on the way in which fatigue develops.
Fatigue mechanisms during a strength training set
Since metabolite-accumulation occurs during strength training, and both calcium ion-related fatigue mechanisms and CNS fatigue mechanisms occur during all types of exercise, we can categorize the various fatigue mechanisms that are working during a strength training set into four groups, as follows: [1] metabolite accumulation, [2] calcium ion accumulation, [3] spinal CNS fatigue, and [4] supraspinal CNS fatigue. Let’s now take a look at each of these fatigue mechanisms in more detail.
#1. Metabolite accumulation
INTRODUCTION
During a normal strength training set, metabolites accumulate. The two primary metabolites are hydrogen ions (acidosis) and inorganic phosphates. When the muscular contractions of a normal strength training set involve venous occlusion (which happens either when whole muscle force exceeds 25% of maximum or when blood flow restriction is implemented), these metabolites cannot leave the muscle during the set, and often even remain in the muscle fiber in which they originated. Therefore, they accumulate, and this is what causes their fatigue mechanisms to occur.
ACIDOSIS
The accumulation of hydrogen ions produces a fatigue mechanism with two very important characteristics. Firstly, it exerts fatiguing effects very quickly on the muscle fibers that it affects, and therefore it is probably the first mechanism to influence exercise performance during a strength training set. Hence, when we are trying to understand the effects of fatigue mechanisms in the early part of a strength training set, we can focus primarily on acidosis. Secondly, acidosis primarily acts on the attachment and detachment rates of the actin-myosin crossbridges inside the muscle fibers, with the result that it reduces their maximum muscle fiber shortening velocities. Therefore, when we are considering the effects of acidosis, we need to take into account that it primarily reduces exercise performance in the strength training set by reducing muscle fiber shortening speed and not by reducing muscle fiber force (and therefore mechanical tension).
PHOSPHATES
Conversely, the accumulation of inorganic phosphate takes longer to produce an effect, and it exerts its effects on the supply of energy into the crossbridge cycle. For myosin heads to bind repeatedly with actin and form crossbridges to generate force, they require a steady supply of ATP. The reaction that provides energy to the crossbridge cycle involves breaking ATP down into ADP and an inorganic phosphate. As this reaction occurs multiple times, the amount of ADP and phosphate ions accumulating inside the cytoplasm increases. And since the reaction is reversible, the accumulation of phosphate ions eventually suppresses the ability of ATP to break down and produce additional phosphate ions. This causes crossbridge formation to grind to a halt, which in turn eventually reduces muscle fiber force (and hence also mechanical tension). Importantly, since it is the presence of too many phosphate ions that stops additional phosphate ions being produced, the breakdown of ATP can be stopped even in the presence of an existing supply of ATP (and intramuscular glycogen). Thus, we need to be aware that this fatigue mechanism does not involve running out of fuel, but rather the refusal of the actin-myosin motors to accept any more fuel due to the presence of unwanted byproducts.
#2. Calcium ion accumulation
INTRODUCTION
During a normal strength training set, calcium ions accumulate and cause peripheral fatigue mechanisms. In some ways, the accumulation of calcium ions might be perceived as similar to the accumulation of metabolites, but there are important differences in terms of the way that the fatigue mechanisms are produced. Firstly (unlike metabolites), calcium ions do not accumulate inside the cytoplasm due to the metabolic processes that provide energy to the crossbridge cycle. Instead, they are placed into (and then removed from) the cytoplasm by the sarcoplasmic reticulum in response to the repeated activation of the muscle fiber. Secondly (unlike metabolites), calcium ions cannot easily leave the cytoplasm, so it does not matter whether venous occlusion is achieved during each of the muscular contractions in the set (which means that calcium ion-related fatigue occurs even when whole muscle force is less than 25% of maximum force).
Calcium ions accumulate inside muscle fibers because the process that places them into the cytoplasm and then removes them again is not entirely perfect. Electrical signals propagate along muscle cell membranes and go down inside the transverse tubules, where they interact with the sarcoplasmic reticulum at the triadic junction. This interaction causes the sarcoplasmic reticulum to deposit calcium ions into the cytoplasm, which then trigger crossbridges to form. Whenever the electrical signal stops, the calcium ions are pulled back into the sarcoplasmic reticulum. Since the muscle fiber is switched on and off many times per second during any muscular contraction, the process of putting calcium ions into the cytoplasm of a muscle fiber and removing them again also occurs many times per second. Nevertheless, not all of the calcium ions that are placed into a muscle fiber are successfully pulled back into the sarcoplasmic reticulum, and this leads to calcium ion accumulation. Some of these accumulating calcium ions are removed by mitochondria (and this delays the onset of calcium ion-related fatigue, especially in the more oxidative, slow twitch muscle fibers that have more mitochondria), but eventually the ions accumulate, and this is what leads to calcium ion-related fatigue mechanisms.
There are three primary calcium ion-related fatigue mechanisms, which are: [1] excitation-contraction coupling failure (ECCF), [2] reduced calcium ion sensitivity, and [3] reduced sarcolemmal excitability. ECCF and reduced sarcolemmal excitability appear to share a common mechanistic pathway that involves the stimulation of proteases or lipases by the accumulation of calcium ions inside the cytoplasm, while reduced calcium ion sensitivity probably works slightly differently.
EXCITATION–CONTRACTION COUPLING FAILURE (ECCF)
At a high level, ECCF occurs when the electrical signal that propagates along the cell membrane and reaches the transverse tubules fails to cause the release of calcium ions into the cytoplasm from the sarcoplasmic reticulum. Normally, excitation-contraction coupling occurs when the electrical signal being propagated along the cell membrane goes down into the transverse tubules and reaches the voltage sensor at the triadic junction, where it interacts with the sarcoplasmic reticulum calcium ion store to trigger the release of those calcium ions into the cytoplasm. These calcium ions in turn signal to actin and myosin myofibrils to form crossbridges that generate force.
At a more granular level, ECCF occurs when the two sides of the triadic junction drift apart from one another, such that the arrival of the electrical signal at the voltage sensor fails to interact with the sarcoplasmic reticulum calcium ion store. This appears to occur when excess calcium ions inside the cytoplasm stimulate the release of calpains, which degrade the minor proteins that hold the triadic junction in place. The calcium ions accumulate inside the cytoplasm after repeated entry and removal due to the excitation-contraction coupling process itself. Indeed, when a batch of calcium ions is dropped into the cytoplasm from the sarcoplasmic reticulum, all of them are not always taken back up into the sarcoplasmic reticulum. The ones remaining are left to accumulate, and if they are not removed by mitochondria, they stimulate the release of calpains.
Therefore, the process of ECCF involves several steps and so it takes time to appear, in contrast to metabolite-related fatigue mechanisms, which are much faster. In practice, ECCF appears to occur just in time for the last two reps of a strength training set with moderate loads (albeit it probably appears slightly earlier when training with lighter loads and slightly later when training with heavier loads, which is a key point that we will return to when considering the effects of load on fatigue both during and after a workout).
REDUCED SARCOLEMMAL EXCITABILITY
Reduced sarcolemmal excitability involves a very similar mechanism to ECCF, except it is the release of reactive oxygen species (ROS) that stimulates the release of phospholipases that damage the inside of the cell membrane, which in turn prevents the propagation of the electrical signal along the muscle fiber surface. These ROS are stimulated to appear by several mechanisms, including the actions of mitochondria in collecting any calcium ions that accumulate inside the cytoplasm subsequent to excitation-contraction coupling. When this mechanism stops the propagation of the electrical signal along the muscle fiber surface, the level of muscle activation is reduced despite the presence of a strong central motor command reaching the neuromuscular junction. Like ECCF, the process of reducing sarcolemmal excitability involves several steps and takes time to appear, in contrast to metabolite-related fatigue. In practice, reduced sarcolemmal excitability may in fact only become apparent several minutes after finishing a strength training set, making it largely irrelevant for understanding how fatigue works during strength training itself.
REDUCED CALCIUM ION SENSITIVITY
Exactly how reduced calcium ion sensitivity works, how quickly it appears, and how long it lasts are all relatively unclear at the present time. Essentially, a reduction in calcium ion sensitivity involves a reduction in the ability of actin myofibrils to detect the presence of calcium ions, most likely due to the presence of another signaling molecule inside the cytoplasm. Whether this occurs in tandem with the same mechanisms and signaling molecules that cause ECCF and/or the reduction in sarcolemmal excitability is unknown. Thus, the role of reduced calcium ion sensitivity during a strength training set is difficult to identify.
#3. Spinal central nervous system (CNS) fatigue
During a strength training set, the brain generates a central motor command that is transmitted down the spinal cord to the neuromuscular junction of the muscle, where it recruits motor units (and those motor units activate groups of muscle fibers). This central motor command is sent repeatedly by the brain down the spinal cord to the muscle, many times per second. The repetitive transmission of the signal down the spinal cord appears to be what triggers spinal CNS fatigue (although the exact way in which this occurs is unclear), and it can be measured as a reduced signal emerging at the neuromuscular junction despite a similar (or larger) signal being created by the brain.
Importantly, the duration of time that the spinal cord carries the signal seems to be the key determinant of the amount of spinal CNS fatigue that is experienced. This means that spinal CNS fatigue is fairly minimal at the start of a set, and only reaches its maximal level at the very end of a set. It also means that when muscular failure takes less time to occur (either because heavy loads are used or because blood flow restriction is applied), the level of spinal CNS fatigue is probably low. Conversely, when muscular failure takes more time to occur (because light loads are used), the amount of spinal CNS fatigue is probably much greater.
#4. Supraspinal central nervous system (CNS) fatigue
During a strength training set, supraspinal CNS fatigue involves a reduction in the level of central motor command that the brain can produce, despite us exerting a maximal effort. Such a reduction in the level of central motor command seems to occur by means of afferent feedback from the working muscles.
In order to understand how afferent feedback creates supraspinal CNS fatigue, we first have to establish how the maximum level of central motor command that can be produced by the brain is limited. The maximum central motor command that the brain can produce at any moment in time is determined by our maximum tolerable level of perceived effort, because the central motor command signal itself contributes to the perception of effort signal (by means of the corollary discharge), and reaching an intolerable level of perceived effort is not possible. Since increases in central motor command increase the perception of effort, and since perceived effort has a threshold that we cannot exceed (the maximum tolerable level of perceived effort), central motor command is by definition limited by perceived effort.
Our maximum tolerable level of perceived effort varies slightly from one day to the next as a result of our motivation levels, which is why strength training techniques that are motivating can be valuable for increasing gains in muscle size and maximum strength, because they facilitate a greater level of central motor command (and hence a higher level of motor unit recruitment) during exercise. Additionally, the level of central motor command that can be attained at a given level of perceived effort can vary if other factors arise that increase the perceived level of effort, without also increasing the level of central motor command. Such factors reduce the maximum level of central motor command that corresponds to the maximum tolerable level of perceived effort. Common factors that increase perceived effort in this way are those that can generate afferent feedback.
For example, during a strength training set, metabolite accumulation occurs that produces afferent feedback to the brain that we experience as fatiguing and burning sensations inside the muscle. This increases the perception of effort for the existing level of central motor command, thereby producing supraspinal CNS fatigue. In this way, the amount of supraspinal CNS fatigue is dependent upon the extent to which metabolites build up inside the muscle, which is greater during light load strength training or when using certain intensification techniques (such as rest pause, drop sets, and pre-exhaustion). Similarly, over the course of a long strength training workout, inflammatory mediators are slowly released into the bloodstream that also produce afferent feedback to the brain that we probably experience as more systemic fatigue sensations. In the same way, this increases the perception of effort for the existing level of central motor command, thereby also producing supraspinal CNS fatigue. For this reason, the amount of supraspinal CNS fatigue is greater during exercises performed at the end of a workout compared to during exercises performed at the beginning.
Practical implications
HYPERTROPHY AND THE STIMULATING REPS MODEL
Currently, the stimulating reps model of hypertrophy proposes that the final reps of a strength training set are those that cause muscle growth because they are those reps that simultaneously involve [1] a high level of motor unit recruitment such that the responsive muscle fibers are being exercised, and [2] a slow bar speed, such that the responsive muscle fibers experience a high level of mechanical tension due to the force-velocity relationship. Our best estimates suggest that there are only five or six such reps in a set. However, this model only works if fatigue does not substantially impair the muscle fiber force produced over the course of a strength training set.
During a normal strength training set, the first fatigue mechanism to become apparent is acidosis, which primarily reduces muscle fiber shortening velocity (while having a much smaller effect on muscle fiber force and therefore single muscle fiber mechanical tension). Thus, when fatigue is apparent in the initial reps of a strength training set (either as indicated by reduced bar speed during maximal effort reps or by increased effort during self-selected tempo reps), it does not necessarily imply reduced mechanical tension for the working muscle fibers. Rather, the reduced exercise performance occurs primarily by means of a reduced muscle fiber shortening velocity. In practice, this means that mechanical tension can stimulate hypertrophy very effectively for much of a strength training set despite the presence of metabolite-related fatigue, because single muscle fiber force is not impaired. This provides physiological support for the stimulating reps model of hypertrophy, except for the final two reps of a set performed with moderate loads.
Indeed, the appearance of calcium ion-related mechanisms during the final two reps at the end of a strength training set is a problem for the stimulating reps model, because such peripheral fatigue mechanisms do reduce muscle fiber force. Nevertheless, it is noteworthy that bar speed exponentially slows for the final two reps of a set with moderate loads. Consequently, we can say that the force-time integral (which is a better metric than either magnitude of tension or time under tension alone for measuring the hypertrophic stimulus experienced by the working muscle fibers of high-threshold motor units) is quite likely similar across the final five or six reps of a strength training set. Although the duration of the final two reps dramatically increases, the magnitude of single fiber mechanical tension simultaneously decreases. Thus, each of the stimulating reps probably do provide a similar hypertrophic stimulus, despite their differences in rep duration and single muscle fiber force magnitude.
INCREASES IN HIGH–THRESHOLD MOTOR UNIT RECRUITMENT
One very important mechanism by which strength gains occur is an increase in the ability to recruit high-threshold motor units. The stimulus for producing gains in the ability to recruit high-threshold motor units is probably sending a very high level of central motor command to the muscle. This is important, because the presence of spinal and supraspinal CNS fatigue suppress the size of this stimulus.
Spinal and supraspinal CNS fatigue both increase over the course of a single strength training set, and are maximal on the final rep, precisely at the point when muscular failure is reached. This is incredibly important, because it tells us that training with either a slow tempo or a self-selected tempo, and therefore only using a completely maximal effort at muscular failure, is a wasted opportunity to achieve gains in the ability to recruit high-threshold motor units. Indeed, it likely makes more sense to perform maximal efforts earlier in the set (as is common during velocity-based training), as these will likely provide a much better stimulus in the ability to recruit high-threshold motor units than the very last rep of a set, when high levels of spinal and supraspinal CNS fatigue are present.
What is the takeaway?
During a normal strength training set, various fatigue mechanisms develop over time, which together ultimately lead to a reduction in the ability of the lifter to perform the exercise, leading to muscular failure. Since strength training involves metabolite accumulation due to the venous occlusion that occurs, the first fatigue mechanism to appear is acidosis, which predominantly reduces muscle fiber shortening speed. This allows single muscle fiber force to remain high despite an increase in effort (and therefore motor unit recruitment) being needed in order to maintain self-selected tempo. This provides a physiological rationale for the stimulating reps model, in which mechanical tension needs to be high during the final five or six reps prior to muscular failure.
Nevertheless, in the two reps prior to muscular failure, calcium ion-related mechanisms appear that do reduce single muscle fiber force. However, at the same time, bar speed dramatically slows, which leads to these reps providing a much longer time under tension, which compensates for the reduced level of force, at least in terms of the stimulus for hypertrophy. Thus, the loss of muscle fiber force at this point is still consistent with the stimulating reps model, in which mechanical tension is assumed to be similar during each of the final five or six reps prior to muscular failure.
Additionally, over the course of a normal strength training set, spinal and supraspinal CNS fatigue both increase progressively over time. Thus, even though the greatest possible effort might be exerted at muscular failure, this may not coincide with the greatest level of central motor command or even motor unit recruitment. Since it is achieving a high level of central motor command that is what stimulates strength gains by means of an increase in the ability to recruit high-threshold motor units, using maximal efforts on the earlier reps of a set is probably very important for maximizing gains in maximum strength by means of this mechanism.