An overview of Fatigue

Topics Covered:

• What is fatigue
• What Causes Fatigue
• Central Fatigue Factors
• Peripheral Fatigue Factors
• How to Delay Fatigue for Increased Performance

What is Fatigue?

Fatigue can be defined as the decrease of performance and an increase in difficulty as energy demands exceed what can be sustained.

“Fatigue is defined as an internal homeostasis breakdown caused by an increase in energy production demanded by an external stimulus. “[1]

“Fatigue can be generally defined as a decrease in physical performance related to a rise within the real/perceived difficulty of a task or exercise, as well as the inability of the muscles to keep up with the specified level of strength during exercises”[1]

What Causes Fatigue?

The onset of fatigue is attributed to multiple factors effecting the central and peripheral nervous system. This means that fatigue onset originates from the brain as well as the muscles at work.

“The point of fatigue onset itself is difficult to pinpoint as there are multiple factors, both central and peripheral, that attribute to the body’s inability to produce a maximum force.”[2]

The central nervous system (CNS)

Includes the brain and the spinal cord.

“Central fatigue results from the brain reducing neural activation to the working muscles during exercise, subsequently causing a decrease in power output, motivation, and the up-regulation of the neurotransmitter serotonin”[2]

 “ultra-endurance events have a significant component of central nervous system fatigue compared to shorter athletic activities or events”[1]

“CNS fatigue also causes cognitive fatigue phenomena, which is associated with behavioral and mood disorders. Prolonging an acute state of CNS fatigue can lead to sleep disturbances, depression, pain, the feeling of fatigue, difficulty in maintaining cognitive vigilance, and problems maintaining mental attention”[1]

Serotonin

• Serotonin is synthesized from tryptophan.
• Lipolysis is induced during exercise for energy, releasing free fatty acids, which augments tryptophan.
• The increased tryptophan induces more serotonin synthesis.
• “serotonergic activity increases, producing a feeling of lethargy, a loss of the neural drive, and, consequently, loss of motor unit recruitment”[1]

Dopamine

• Dopamine influences drive, motivation, pursuit, movement, and your perception of time.
• As serotonin levels rise, dopamine levels fall.

“a reduction in dopamine secretion from the SNpc (substantia nigra pars compacta) can damage the activation of the basal ganglia and reduce the stimulation of the cortex motor, contributing to the onset of central fatigue.”[1]

“The secretion of dopamine is related to producing a delay to fatigue and exhaustion”[1]

Adrenaline/Epinephrine

• Adrenaline ready’s you for action and promotes the continuation of action.
• Think of when your mind is racing before bed or when you are feeling antsy/fidgety when pent up inside, those are effects of adrenaline.
• Adrenaline is made from dopamine.
• Lower dopamine levels would correlate with lower levels of adrenaline.

The Peripheral Nervous System (PNS)

Includes the nerves outside of the brain and spinal cord.

“Peripheral fatigue is defined by mechanisms that affect the muscle directly and that are distal to the neuromuscular junction (1, 2). While mechanisms of peripheral fatigue include depletion of substrate availability, excitation-contraction coupling failure and oxidative stress, during high intensity exercise one of the largest contributors to fatigue is metabolite accumulation, specifically hydrogen ions (H+)”[2]

 “explosive or team sports show a wide range of both peripheral and central pathway factors.”[1]

Oxygen Demand

• Oxygen is necessary for the metabolism of glucose and the removal of carbon and hydrogen byproducts as CO₂ and H₂O.
• Oxygen demand increases as energy demands increase.
• As energy demand surpasses oxygen availability, anaerobic metabolism prevails, which produces less atp (energy) than aerobic (with oxygen) metabolism.

Acidosis (lower pH)

• An accumulation of metabolites (byproducts of metabolism), mainly hydrogen ions (H+), lower pH.
• Enzymatic function occurs within a specific pH range. A rise in acidity in blood and the local tissue will prevent proper function of muscle.
• While there are mechanisms (lactate, bicarb, carnosine) that buffer the accumulation of H+, continued exertion will lead to an inevitable lowering of pH.
• Read my blog on lactate to learn more about acidosis.

“During exercise, an increase in metabolism leads to excess accumulation of H+ by-products from the hydrolysis of ATP (3). “[2]

“An increase [H+] combined with a corresponding decreasing in intramuscular pH, has been identified as one of the primary causes of peripheral fatigue (3). “[2]

“Correspondingly, research has demonstrated that delaying the accumulation of H+ through buffering mechanisms can delay fatigue onset (4-7).” [2]

Muscle Temperature

• Just as enzymatic function is effected by pH, it is also sensitive to temperature.
• As temperature rises performance falls, to the point of shutdown if exertion continues.

 “In 2009, it was discovered that muscle pyruvate kinase, or MPK, an enzyme that muscles need in order to generate chemical energy, was highly temperature sensitive. At normal body temperature, the enzyme is active – but as temperatures rise, some of the enzyme begins to deform into the inactive state. By the time muscle temperatures near 104 degrees Fahrenheit, MPK activity completely shuts down.”[3]

“There’s a very good biological reason for this shutdown. As a muscle cell increases its activity, it heats up. But if this process continues for too long, the cell will self-destruct. By shutting itself down below a critical temperature threshold, MPK serves as an elegant self-regulation system for the muscle.”[3]

How to Delay Fatigue for Increased Performance (In development)

1. Buffer Acidity
   • Sodium Bicarbonate
   • Beta Alanine
   • Read my blog on lactate to learn more about acidity.
2. Increase Energy Availability
   • Induce increases of glycogen stores in the local muscle tissue through repeated exercise
   • Creatine supplementation to increase creatine phosphate (fuel) in muscle
   • Pre and intra workout carbohydrate consumption to replenish glycogen stores and raise blood sugar
   • Exogeneous ketone supplementation
3. Increase Oxygen Availability
   • Practice deep breathing emphasizing the expansion of the chest (intercostals) as well as the stomach (diaphragm). This will strengthen those muscles allowing for stronger and larger inhales and exhales.
   • Practice in nose only breathing while doing low intensity cardio. This will teach you how to breath efficiently.
   • Incorporate more low intensity cardio into your routine encourage slow twitch muscle growth. Slow twitch muscles are saturated with more oxygen that can be used when performing higher intensity exercises.
4. Lower Core Body Temperature
   • Google “Palmar Cooling”
5. Lower Serotonin
6. Increase Dopamine
7. Increase Adrenaline

Sources

1. Tornero-Aguilera JF, Jimenez-Morcillo J, Rubio-Zarapuz A, Clemente-Suárez VJ. Central and Peripheral Fatigue in Physical Exercise Explained: A Narrative Review. Int J Environ Res Public Health. 2022 Mar 25;19(7):3909. doi: 10.3390/ijerph19073909. PMID: 35409591; PMCID: PMC8997532.

2. Smith-Ryan AE, Woessner MN, Melvin MN, Wingfield HL, Hackney AC. The effects of beta-alanine supplementation on physical working capacity at heart rate threshold. Clin Physiol Funct Imaging. 2014 Sep;34(5):397-404. doi: 10.1111/cpf.12111. Epub 2013 Dec 5. PMID: 24308676.

3. McClure, Max. "Stanford researchers' cooling glove 'better than steroids' – and helps solve physiological mystery, too " Stanford News, AUGUST 29, 2012, Stanford University Communications

4. Foley TE, Fleshner M. Neuroplasticity of dopamine circuits after exercise: implications for central fatigue. Neuromolecular Med. 2008;10(2):67-80. doi: 10.1007/s12017-008-8032-3. Epub 2008 Feb 15. PMID: 18274707.