Central nervous system fatigue

Central Nervous System Fatigue (or just "Central Fatigue") is a type of fatigue caused by changes within the function of the central nervous system that cannot be explained by dysfunction of the muscle.[1] It is brought about by prolonged exercise and the neurochemical changes in the brain associated with it - primarily of serotonin (5HT) and dopamine. Central nervous system fatigue plays an important role in endurance sports, and also highlights the importance of proper nutrition in endurance athletes.

Neurochemical Mechanisms

While many neurochemical changes have been observed during central nervous system fatigue, no current experimental method can provide a direct causal link between the neurochemical changes and fatigue. However, existing methods have provided enough evidence to suggest that serotonin and dopamine are significant drivers of central nervous system fatigue.[1]

Serotonin

In the brain, serotonin is a neurotransmitter and regulates arousal, behavior, sleep, and mood.[2] During prolonged exercise where central nervous system fatigue is present, serotonin levels in the brain are higher than normal physiological conditions; these higher levels can increase perceptions of effort and peripheral muscle fatigue.[2] The increased synthesis of brain serotonin occurs because of a higher level of tryptophan, the serotonin precursor, in the blood and which results in larger amounts of tryptophan crossing the blood-brain barrier. An important factor of serotonin synthesis is the transport mechanism of tryptophan across the blood-brain barrier. The transport mechanism for tryptophan is shared with the branched chain amino acids (BCAAs), leucine, isoleucine, and valine. During extended exercise, BCAAs are consumed for skeletal muscle contraction, allowing for greater transport of tryptophan across the blood-brain barrier. None of the components of the serotonin synthesis reaction are saturated under normal physiological conditions,[3] allowing for the increased production of the neurotransmitter.

Dopamine

Dopamine is an excitatory neurotransmitter that regulates arousal, motivation, muscular coordination, and endurance performance.[4] Dopamine levels have been found to be lower after prolonged exercise.[5] A decrease in dopamine can decrease athletic performance as well as mental motivation. Dopamine itself cannot cross the blood brain barrier and must be synthesized within the brain.
Because the serotonin and dopamine induce opposite states, comparing the two can help determine the physiological situation.[1]

Acetylcholine

Acetylcholine is required for the generation of muscular force. In the central nervous system, acetylcholine modulates arousal and temperature regulation. It also may play a role in fatigue. During exercise, the levels of acetylcholine drop.[6] This is due to the decrease in plasma choline levels. However, there have been conflicting results in studies about the effect of acetylcholine on fatigue. One study found that plasma choline levels had dropped 40% after the subjects ran the Boston Marathon.[6] Later, the subjects ran another long distance race while supplemented with choline citrate - their performance improved. Another study found that choline supplementation did not improve time to exhaustion.[7] This study also found that plasma choline levels had not changed in either the placebo or the choline supplemented groups. More research is needed to investigate acetylcholine's effects on fatigue.

Manipulating Central Nervous System Fatigue

Controlling central nervous system fatigue can help scientists develop a deeper understanding of fatigue as a whole. Numerous approaches have been taken to manipulate neurochemical levels and behavior. In sports, nutrition plays a large role in athletic performance. In addition to fuel, many athletes consume stimulants in order to boost their abilities.

Amphetamine

Amphetamine is a stimulant that has been found to improve both physical and cognitive performance. Amphetamine blocks the reuptake of dopamine, which reduces fatigue by increasing the amount of dopamine in the central nervous system.[8] Amphetamine is a widely used substance among collegiate athletes for its performance enhancing qualities,[9] as it can improve endurance and stamina.[10]

Caffeine

Caffeine is the most widely consumed stimulant in North America, with about 90% of the population ingesting it daily.[11] In small doses, caffeine can improve endurance.[12] Recently, it has also been shown to delay the onset of fatigue in exercise. The most probable mechanism for the delay of fatigue is through the obstruction of adenosine receptors in the central nervous system.[13] Adenosine is a neurotransmitter that decreases arousal and increases sleepiness. By preventing adenosine from acting, caffeine removes a factor that promotes rest and delays fatigue.

Carbohydrates

Carbohydrates are the main source of energy in organisms for metabolism. They are an important source of fuel in exercise. A study conducted by the Institute of Food, Nutrition, and Human Health at Massey University investigated the effect of consuming a carbohydrate and electrolyte solution on muscle glycogen use and running capacity on subjects that were on a high carbohydrate diet.[14] The group that consumed the carbohydrate and electrolyte solution before and during exercise experienced greater endurance capacity. This could not be explained by the varying levels of muscle glycogen; however, higher plasma glucose concentration may have led to this result. Dr. Stephen Bailey posits that the central nervous system can sense the influx of carbohydrates and reduces the perceived effort of the exercise, allowing for greater endurance capacity.

Branch Chained Amino Acids

Several studies have attempted to decrease the synthesis of serotonin by increasing BCAAs and inhibiting the transport of tryptophan across the blood brain barrier.[15] The studies performed resulted in little or no change in performance between increased BCAA intake and placebo groups. One study in particular administered a carbohydrate solution and a carbohydrate + BCAA solution.[16] Both of the groups were able to run for longer before fatigue compared to the water placebo group. However, both the carbohydrate and the carbohydrate + BCAA groups had no differences in their performance. Branch chained amino acid supplementation has proven to have little to no effect on performance. There has been little success utilizing neurotransmitter precursors to control central nervous system fatigue.

Role in the Body

Central nervous system fatigue is a key component in preventing peripheral muscle injury.[17] Through a deeper understanding of this fatigue, we can elicit greater knowledge on how the brain manages the body and to what extent it does so. The brain has numerous receptors, such as osmoreceptors, to track dehydration, nutrition, and body temperature. With that information as well as peripheral muscle fatigue information, the brain can reduce the quantity of motor commands sent from the central nervous system. This is crucial in order to protect the homeostasis of the body and to keep it in a proper physiological state capable of full recovery. The reduction of motor commands sent from the brain increases the amount of perceived effort an individual experiences. By forcing the body through a higher perceived intensity, the individual becomes more likely to cease exercise by means of exhaustion. Perceived effort is greatly influenced by the intensity of corollary discharge from the motor cortex that affects the primary somatosensory cortex.[18] Endurance athletes learn to listen to their body. Protecting organs from potentially dangerous core temperatures and nutritional lows is an important brain function. Central nervous system fatigue alerts the athlete when physiological conditions are not optimal so either rest or refueling can occur. It is important to avoid hyperthermia and dehydration, as they are detrimental to athletic performance and can be fatal.[19]

Chronic Fatigue Syndrome

Chronic Fatigue Syndrome is name for a group of diseases that are dominated by persistent fatigue. The fatigue is not due to exercise and is not relieved by rest.[20]
Through numerous studies, it has been shown that people with chronic fatigue syndrome have an integral central fatigue component.[1] In one study, the subjects' skeletal muscles were checked to ensure they had no defects that prevented their total use. It was found that the muscles functioned normally on a local level, but they failed to function to their full extent as a whole. The subjects were unable to consistently activate their muscles during sustained use, despite having normal muscle tissue.[21] In another study, the subjects experienced higher perceived effort in relation to heart rate as compared to the control during a graded exercise test.[22] The chronic fatigue subjects would stop before any sort of limit on the body was reached. Both studies proved that peripheral muscle fatigue was not causing the subjects with chronic fatigue syndrome to cease exercising. It is possible that the higher perception of effort required to utilize the muscles results in great difficulty in accomplishing consistent exercise.[1]
The main cause of fatigue in chronic fatigue syndrome most likely lies in the central nervous system. A defect in one of its components could cause a greater requirement of input to result in sustained force. It has been shown that with very high motivation, subjects with chronic fatigue can exert force effectively.[23] Further investigation into central nervous system fatigue may result in medical applications.

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Davis, J. M., & Bailey, S. P. (1997). Possible mechanisms of central nervous system fatigue during exercise. Medicine & Science in Sports & Exercise, 29(1), 45-57.
  2. ↑ 2.0 2.1 Young, S. N. The clinical psychopharmacology of tryptophan. In: Nutrition and the Brain. Vol. 7, R. J. Wurtman and J. J. Wurtman, (Eds.). New York: Raven, 1986, pp. 49-88
  3. ↑ Newsholme, E. A., I. N. Acworth, and E. Bloomstrand. Amino acids, brain neurotransmitters and a functional link between muscle and brain that is important in sustained exercise. In: Advances in Myochemistry, G. Benzi (Ed.). London: John Libbey Eurotext Ltd., 1987
  4. ↑ Chaouloff, F., D. Laude, and J. L. Elghozi. Physical exercise: evidence for differential consequences of tryptophan on 5-HT synthesis and metabolism in central serotonergic cell bodies and terminals.J. Neural Transm. 78:121-130, 1989.
  5. ↑ Bailey, S. P., J. M. Davis and E. N. Ahlborn. Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue. J. Appl. Physiol. 74:3006-3012, 1993
  6. ↑ 6.0 6.1 Conlay, L. A., Sabournjian, L. A., and Wurtman, R. J. Exercise and neuromodulators: choline and acetylcholine in marathon runners.Int. J. Sports Med. 13(Suppl. 1):S141-142, 1992
  7. ↑ Spector, S. A., M. R. Jackman, L. A. Sabounjian, C. Sakkas, D. M. Landers, and W. T. Willis. Effects of choline supplementation on fatigue in trained cyclists. Med. Sci. Sports Exerc. 27:668-673, 1995
  8. ↑ Roelands B, de Koning J, Foster C, Hettinga F, Meeusen R (May 2013). "Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing". Sports Med. 43 (5): 301–311. doi:10.1007/s40279-013-0030-4. PMID 23456493.
  9. ↑ Bracken NM (January 2012). "National Study of Substance Use Trends Among NCAA College Student-Athletes". NCAA Publications. National Collegiate Athletic Association. Retrieved 8 October 2013.
  10. ↑ Roelands B, de Koning J, Foster C, Hettinga F, Meeusen R (May 2013). "Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing". Sports Med. 43 (5): 301–311. doi:10.1007/s40279-013-0030-4. PMID 23456493
  11. ↑ Lovett R (2005-09-24). "Coffee: The demon drink?". New Scientist (2518). Retrieved 2009-08-03.(subscription needed)
  12. ↑ Conger SA, Warren GL, Hardy MA, Millard-Stafford ML (2011). "Does caffeine added to carbohydrate provide additional ergogenic benefit for endurance?". Int J Sport Nutr Exerc Metab 21 (1): 71–84. PMID 21411838.
  13. ↑ Central nervous system effects of caffeine and adenosine on fatigue. J. Mark Davis , Zuowei Zhao , Howard S. Stock , Kristen A. Mehl , James Buggy , Gregory A. Hand. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology Published 1 February 2003 Vol. 284 no. R399-R404DOI: 10.1152/ajpregu.00386.2002
  14. ↑ Foskett, A., Williams, C., Boobis, L., & Tsintzas, K. (2008). Carbohydrate availability and muscle energy metabolism during intermittent running. Med Sci Sports Exerc, 40(1), 96-103. doi: 10.1249/mss.0b013e3181586b2c
  15. ↑ Meeusen, R., & Watson, P. (2007). Amino acids and the brain: do they play a role in "central fatigue"? Int J Sport Nutr Exerc Metab, 17 Suppl, S37-46
  16. ↑ Blomstrand, E., S. Andersson, P. Hassmen, B. Ekblom, and E. A. Newsholme. Effect of branched-chain amino acid and carbohydrate supplementation on the exercise-induced change in plasma and muscle concentration of amino acids in human subjects. Acta Phys. Scand. 153:87-96, 1995
  17. ↑ Fatigue is a Brain-Derived Emotion that Regulates the Exercise Behavior to Ensure the Protection of Whole Body Homeostasis. Timothy David Noakes. Front Physiol. 2012; 3: 82. Prepublished online 2012 January 9. Published online 2012 April 11. doi: 10.3389/fphys.2012.00082.
  18. ↑ Enoka, R. M. and D.G. Stuart. Neurobiology of muscle fatigue. J. Appl. Physiol. 72:1631-1648, 1992.
  19. ↑ Murray R. Dehydration, hyperthermia, and athletes: science and practice. J Athl Train. 1996;31(3):248–252.
  20. ↑ Evangard B, Schacterie R.S., Komaroff A. L. (Nov 1999). "Chronic fatigue syndrome: new insights and old ignorance". Journal of Internal Medicine 246 (5): 455–469. doi:10.1046/j.1365-2796.1999.00513.x. PMID 10583715
  21. ↑ Kent-Braun, J. A., K. R. Sharma, M. W. Weiner, B. Massie, and R. G. Miller. Central basis of muscle fatigue in chronic fatigue syndrome. Neurology 43:125-131, 1993
  22. ↑ Riley, M. S., C. J. O'Brien, D. R. McCluskey, N. P. Bell, and D. P. Nicholls. Aerobic work capacity in patients with chronic fatigue syndrome. Br. Med. J. 301:953-956, 1990
  23. ↑ Stokes, M. J., R. G. Cooper, and R. H. Edwards. Normal muscle strength and fatigability in patients with effort syndromes. Br. Med. J. 297:1014-1017, 1988.