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December 17, 2021Science Behind Muscle Fatigue and How We Can Prevent It
Most people experience different types of fatigue on a daily basis. But, what is fatigue, how can we define it, the factors that affect it, and how can we prevent it? In this short article, we will address the phenomenon of muscle fatigue, basic principals of exercise physiology, nutrition and supplementation.
Fatigue can be defined as an overwhelming sense of tiredness, exhaustion, and lack of energy.1 Fatigue accumulation over a more extended time period, if not resolved, leads to prolonged fatigue. Prolonged fatigue can occur due to work exhaustion, insufficient sleep, overtraining, etc. Imagine an „Average Joe“. Joe gets up tired every day, goes to work, and works hard. Day after day, Joe has yet another a hectic day. Such conditions can impair his quality of life, and may even harm his health. „Life happens“, and for the most part, every one of us is sometimes in „Joe’s“ shoes.
Fatigue can be classified as a:
- Acute
- Prolong
- Mental
Further, it can be classified as muscle fatigue, which can be reclassified as a
- Peripheral fatigue
- CNS fatigue
The fundamental question is, what are the factors that limit how much we are able to achieve? The ability to engage in physical activity is conditioned by the amount of energy that muscles can produce, and how quickly that energy can be resynthesized. For example, the maximum speed during a sprint can be maintained for about 10 seconds, after which it gradually slows down.2 In this case, fatigue occurs as a consequence of inadequate energy production in skeletal muscles. We need to understand what limits the ability to exercise in various types of physical activities (e.g aerobic exercise, anaerobic exercise). In that case, we will be able to use that knowledge to improve athletic performance. A few factors can affect muscle or exercise-associated acute fatigue, and it can be explained as:
- Accumulation of lactates
- Inhibition of the Ca2+ release of the sarcoplasmic reticulum
- Glycogen stores decline
- Inhibition on motor neural drive
- Cytokine released during exercise
ATP
The key unit of energy („energy currency“) is adenosine triphosphate (ATP). Every second, ten million molecules of ATP and ADP are converted into each other, thus releasing and enabling energy. ATP is the only direct energy donor in the body. Within a cell, ATP is used for three basic functions:
- transport of matter across cell membranes
- synthesis of chemical substances in various parts of the cell
- mechanical work (muscles contraction)
During muscle contraction, ATP synthesis is directly related to catabolic processes, and because of these reactions, the content of ATP in muscles is relatively stable. ATP is a nucleotide that consists of three main structures: the nitrogenous base, adenine; the sugar, ribose; and a chain of three phosphate groups bound to ribose. Available energy is contained in the bonds between the phosphates and is released through the hydrolysis of ATP, i.e., the hydrolytic separation of one phosphate group by the enzyme adenosine triphosphatase (ATPase, myosin ATPase in muscle), leading to the release of energy (34 kJ per mole of ATP) and forming adenosine diphosphate (ADP). Further hydrolysis of ADP by adenylate kinase (AK) breaks the bond with another phosphate group, and adenosine monophosphate (AMP) is formed.3
The available amount of ATP in the human body is relatively small and amounts to about 80 to 100 g (3 to 5 mmol of ATP / kg of muscle mass). ATP needs to resynthesize during more prolonged exercise episodes. In addition, the physiological reserves of ATP cannot be completely depleted, but are kept at the biological minimum. ATP concentration can be reduced by a maximum of 50 to 60% relative to resting values due to experimentally induced muscle fatigue.4 Metabolic mechanisms-systems for ATP resynthesis are:
- phosphocreatine system
- anaerobic glycolysis
- aerobic energy production
Phosphocreatine system
The phosphocreatine system provides ATP primarily for short-term high-intensity activities and at the beginning of each exercise regardless of intensity.4 Creatine (Cr) in the phosphocreatine system, and his active molecular form phosphocreatine (PCr) as bioenergetics, represents a donor of the phosphate group (Pi) in the metabolic process of ATP synthesis/resynthesis. Creatine kinase (CK) is an enzyme that catalyzes the synthesis and resynthesis of ATP from PCr and ADP.4 This is the fastest form of energy production in our organism, and it is impossible to imagine any physical activity without this reaction.
Anaerobic glycolysis
When the need for energy exceeds our capacity of our phosphocreatine system, the energy is produced by the process called anaerobic glycolysis. For example, we have some low-intensity activities such as walking and steady-state jogging, where energy is provided mainly through the aerobic system. However, when we increase the intensity, we start to produce energy through anaerobic glycolysis. Glycolysis itself is the breakdown of carbohydrates under anaerobic conditions. More precisely, the breakdown of glucose from blood and glycogen stored in muscles in order to maintain the balance of ATP concentration. Thus, under anaerobic conditions and at high-intensity activities, ATP resynthesizes is provided by the conversion of pyruvate to lactate (Lac), by a rapid reaction involving nicotinamide adenine dinucleotide (NAD +), with the reaction being limited in time due to increased hydrogen ion (H +) production and decreased pH in the cytosol.4 This decreased pH is mainly responsible for fatigue, and everyone has felt that burning feeling in their muscles during high-intensity activities ( such as CrossFit, prolonged sprinting, and many other high intensity exercises).
Aerobic energy production
Oxidative, or the aerobic energy system, is the primary source of ATP at rest and during low-intensity activities. As a substrate, fats, proteins, carbohydrates, and pyruvates are used and transformed by a series of chemical reactions into molecules that can be utilized through aerobic metabolism.5 At rest, approximately 70% of ATP produced comes from fat and about 30% from carbohydrates.4 With the beginning of the physical activity, as the intensity of exercise increases, the share of carbohydrates in the total energy production increases. During high-intensity aerobic exercise, almost 100% of the total energy produced is obtained by decomposition carbohydrates. The process by which energy is created during the Krebs cycle (also known as the citric acid cycle).
Choosing the right supplement
Understanding the basic principles of physiology is the first step to a better understanding of exercise and sports training. The focus in this specific article will not be on exercise tips. Instead, we will focus on the strategies how to improve your nutrition and supplementation. First of all, many of the supplements have false advertising. The Anti-Doping Agency (WADA) does not have an obligation to evaluate the contexture of the supplements. It is a close line between doping and supplementation. Within the topic of supplementation in sports, it is by no means rare for sports coaches, scientists and other expert to defer to the lesser or very poor evidence-based methods while striving to enhance their athlete’s performance and achieve better results. Even today with advanced technology and worldwide access to information, people are still prone to using the less evidence-based supplements.
As a reader, you always need to strive to “drink water from a spring” and continuously follow scientifically-based information. In addition, is the table of supplements based on the latest research.
Build and fatigue
BUILD, a strength and muscle gain formula from the TRUE|PERFORMANCE line of Drink HRW, is a mixture containing 5 g of creatine monohydrate, 3 g of hydroxymethylbutyrate (HMB), and 3 g of β-alanine. Although BUILD is not on the list, due to being a branded mixture of multiple ingredients, we can analyze BUILD through its ingredients, and consider whether these ingredients reduce fatigue and improve performance.
Creatine is one of the most researched supplements with over 63 000 papers published. It is a major component of energy metabolism that is abundant in human skeletal muscle, brain, and heart. Since we produce creatine endogenously in our bodies, creatine is considered as a nonessential amino acid. Nowadays, we are starting to understand the importance of creatine and its deficiency through diet, and the story is changing. Two months ago, professor Ostojic published the paper6 “Perspective: Creatine, a Conditionally Essential Nutrient: Building the Case” to point out the essential role of creatine. Creatine is evaluated as a performance-enhancing supplement,7 but also validated among clinical populations for various states.8 Despite all the evidence, there is some anecdotal delusions regarding creatine’s safety. Nevertheless, creatine is the most examined supplement, and almost all of the studies confirmed that it is safe to use for an extended time period. For those who are curious, read this fantastic study by Antonino and collegues.9 Newer studies highlight malnutrition of creatine among the general population.10,11 This malnutrition has certain consequences on mental health and depression.10 Also, as a fuel, creatine contributes to the basic cellular energy transport. If we go back to the factors contributing to muscle fatigue, creatine supplementation can act as an antioxidant and thus reduce cytokines released during exercise.12 Furthermore, creatine can suppress inhibition on the neural motor drive and increase energy reservoirs by increasing creatine phosphate. As we can see, creatine, among other already proven capabilities,7 can significantly reduce fatigue during and after training. In figure 1., detailed creatine metabolism are presented.
Figure 1. Creatine metabolism. The first step in endogenous creatine synthesis is forming GAA from arginine and glycine throw the catalyzed reaction by the enzyme arginine: glycine aminotransferase (AGAT). GAA is then methylated via the activity of guanidinoacetate methyltransferase (GAMT) to produce creatine. Once synthesized, creatine is released into the bloodstream and taken up by most tissues via the creatine transporter (SLC6A8/CT1). Here it is phosphorylated (PCr) via creatine kinase (CK) activity and stored.
Beta-alanine (β-Alanine) is a nonessential amino acid produced in the liver, and when combined with L-histidine forms a dipeptide called carnosine.13 Intracellular acid-base regulation is considered to be the main physiological role of carnosine, but other physiological functions of carnosine, such as protection from oxidative damage, glycation, and regulation of calcium sensitivity have also been revealed.14 As the training load increases, there is an increase in lactate production and H+, leading further to a decrease in PH values.15 Furthermore, this leads to a string of metabolic processes, a decrease of force production, and to an increase in fatigue.16 Increased concentration of H+ instigates a diminution of actin and myosin cross-bridge formation which further causes a decrement in muscle contraction.17 Improvement of intracellular buffering capacity causes a delay of fatigue and prolongation of exercise.16 A study by Haris indicates that the limiting factor for carnosine synthesis is his availability in nutrition,18 while a number of studies covering β-Alanine supplementation achieved results that showcased an increase in muscle carnosine,18,19 indicating that β-Alanine supplementation is justified and more efficient than absorbing it through nutrition. β-Alanine is an important nutrient, highly efficient and effective in reducing fatigue during and after the training.
Beta-hydroxy beta-methyl butyrate (HMB) is a metabolite derived from the essential amino acid leucine. Under normal conditions, approximately 5% of leucine is converted to HMB.20 For example, to get 3gr of HMB from our diet, we would have to ingest 60gr of Leucine from the food sources, which is practically impossible. One of the multiple effects of HMB could be increase in strength gains, improved aerobic and anaerobic performance,21 and body compositions improvements.22 Besides this, HMB could also reduce muscle fatigue. As a derivate of leucine, it is highly important in muscle regeneration after training. There are only few studies that investigated the effect of HMB on fatigue. HMB decreased fatigue and improved exercise performance,23 but the actions of HMB aren’t clear, and they may include physiological adaptations, such as:
- improved recovery
- increased mitochondrial biogenesis
- increased capacity to transport lactate and H+out of the muscle or into mitochondria for oxidative metabolism
In conclusion, with all of the above mentioned, BUILD is a super-strong mixture of highly effective and safe supplements, ideal for improving exercise performance. It can affect and reduce fatigue in multiple pathways and significantly improve training, recovery, and, most importantly, quality of life.
References
- Enoka, R. M., & Duchateau, J. (2008). Muscle fatigue: what, why and how it influences muscle function. The Journal of physiology, 586(1), 11-23.
- Farrell, P. A., Joyner, M. J., & Caiozzo, V. (2011). ACSM’s advanced exercise physiology. Wolters Kluwer Health Adis (ESP).
- Neumann, D., Schlattner, U., i Wallimann, T. (2003). A molecular approach to the concerted action of kinases involved in energy homoeostasis. Biochemical Society Transactions, 31, 169–174.
- Herda, J. T., i Cramer, T. J. (2016). Bioenergetics of Exercise and Training. ED. Haff i N. T. Triplett, Essentials of strength training and conditioning 4th edition (43–63). Champaign, IL: Human Kinetics: National Strength and Conditioning Association.
- Ostojic, S. M. (2007). Osnovi fiziologije sporta: odabrana poglavlja. Novi Sad: TIMS Fakultet za sport i turizam.
- Ostojic, S. M., & Forbes, S. C. (2021). Perspective: Creatine, a Conditionally Essential Nutrient: Building the Case. Advances in Nutrition.
- Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.
- Kreider, R. B., & Stout, J. R. (2021). Creatine in health and disease. Nutrients, 13(2), 447.
- Antonio, J., Candow, D. G., Forbes, S. C., Gualano, B., Jagim, A. R., Kreider, R. B., … & Ziegenfuss, T. N. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?. Journal of the International Society of Sports Nutrition, 18(1), 1-17.
- Korovljev, D., Todorovic, N., Stajer, V., & Ostojic, S. M. (2021). Temporal trends in dietary creatine intake from 1999 to 2018: an ecological study with 89,161 participants. Journal of the International Society of Sports Nutrition, 18(1), 1-4.
- Ostojic, S. M., Korovljev, D., & Stajer, V. (2021). Dietary intake of creatine and risk of medical conditions in US older men and women: Data from the 2017–2018 National Health and Nutrition Examination Survey. Food Science & Nutrition, 9(10), 5746-5754.
- Lawler, J. M., Barnes, W. S., Wu, G., Song, W., & Demaree, S. (2002). Direct antioxidant properties of creatine. Biochemical and biophysical research communications, 290(1), 47-52.
- Varanoske, A., Stout, J.R. and Hoffman, J.R. (2019). Effects of β-Alanine Supplementation and Intramuscular Carnosine Content on Exercise Performance and Health. In: Bagchi, D., Nair, S., and Sen, C., eds. Nutrition and Enhanced Sports Performance. Muscle Building, Endurance, and Strength., 2nd ed. Cambridge, MA: Academic Press, 327–344.
- Boldyrev, A.A., Aldini, G. and Derave, W. (2013). Physiology and Pathophysiology of Carnosine. Physiological Reviews, 93 (4), 1803–1845.
- Derave, W. et al. (2010). Muscle Carnosine Metabolism and β-Alanine Supplementation in Relation to Exercise and Training. Sports Medicine, 40 (3), 247–263.
- Hobson, R.M. et al. (2012). Effects of β-alanine supplementation on exercise performance: A meta-analysis. Amino Acids, 43 (1), 25–37.
- Cady, E.B. et al. (1989). Changes in force and intracellular metabolites during fatigue of human skeletal muscle. Journal of Physiology, 418, 311–25.
- Harris, R.C. et al. (2006). The absorption of orally supplied β-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids, 30 (3 SPEC. ISS.), 279–289.
- Hill, C.A. et al. (2007). Influence of β-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids, 32 (2), 225–233.
- van Koverin M, Nissen SL (1992) Oxidation of leucine and alpha-ketoisocaproate to β-hydroxy-β-methylbutyrate Rowlands, D.S. and Thomson, J.S. (2009). Effects of β-hydroxy-β-methylbutyrate supplementation during resistance training on strength, body composition, and muscle damage in trained and untrained young men: A meta-analysis. The Journal of Strength & Conditioning Research, 23(3), 836–846.
- Robinson, E. H., Stout, J. R., Miramonti, A. A., Fukuda, D. H., Wang, R., Townsend, J. R., … & Hoffman, J. R. (2014). High-intensity interval training and β-hydroxy-β-methylbutyric free acid improves aerobic power and metabolic thresholds. Journal of the International Society of Sports Nutrition, 11(1), 1-11.
- Faramarzi, M., Nuri, R. and Banitalebi, E. (2009). The effect of short-term combination of HMB (beta-hydroxy-beta-methylbutyrate) and creatine supplementation on anaerobic performance and muscle injury markers in soccer. Brazilian Journal of Biomotricity, 3(4), 366–375.
- Miramonti, A. A., Stout, J. R., Fukuda, D. H., Robinson IV, E. H., Wang, R., La Monica, M. B., & Hoffman, J. R. (2016). Effects of 4 weeks of high-intensity interval training and β-Hydroxy-β-Methylbutyric free acid supplementation on the onset of neuromuscular fatigue. The Journal of Strength & Conditioning Research, 30(3), 626-634.