Nutritional Effects on Central Fatigue

Fatigue during voluntary muscular effort is a complex phenomenon involving the
central nervous system (CNS) as well as the muscle itself. The mechanisms of
fatigue within muscle (peripheral fatigue) are well studied and include
impairments in neuromuscular transmission and propagation down the sarcolemma,
dysfunction within the sarcoplasmic reticulum involving calcium release and
uptake, availability of metabolic substrates and accumulation of metabolites,
and actin-myosin cross bridge interactions.1 Optimal nutritional strategies to
delay peripheral fatigue are well documented.2,3 Conversely, CNS influences on
fatigue (central fatigue) have been largely ignored even though the
inability/unwillingness to generate and maintain central activation of
muscle is the most likely explanation of fatigue for most people during
normal daily activities.1,4

Recently, central fatigue has begun to receive more attention with the development
of several theories that may provide a clue to the biological mechanisms. Some
theories have focused on the possibility that alterations in various
neurotransmitters, including serotonin (5-hydroxytryptamine [5-HT]), dopamine,
and acetylcholine may be responsible for heightened perception of effort and/or
depressed central activation of muscle. An intriguing aspect of these theories
involves the likelihood that nutritional strategies may affect the synthesis
of these neurotransmitters by altering the availability of their amino

The most well studied of these theories involves an increase in brain 5-HT concentration and the associated deterioration in sport and exercise performance.6,7 Good evidence suggests that increases and decreases in brain 5-HT activity during prolonged exercise hasten and delay fatigue, respectively. Several studies also show that nutritional manipulations involving carbohydrates and branched-chain amino acids that are designed to attenuate brain 5-HT synthesis can improve endurance performance.6,7 However, some studies show no performance benefits and studies often suffer from methodological flaws.3 Even less is clear
about the proposed benefits of supplementation with tyrosine or choline, both
of which are thought to increase dopamine and acetylcholine, respectively.9,10

Unfortunately, progress in this area as a whole is seriously hampered by the lack of good methodologies to measure specific alterations in neurotransmitters during fatiguing exercise in humans or to distinguish central from peripheral mechanisms of fatigue during dynamic whole body exercise. Therefore, although good theoretical reasons exist for believing that proper nutrition might delay central fatigue and thereby enhance physical performance, the scientific data to support the theory are tenuous at this time. The exciting possibility that important relationships exist among nutrition, brain neurochemistry, and physical performance is likely to develop into a new frontier in nutrition research. However, although the evidence is intriguing and makes good intuitive sense, our knowledge in this area is rudimentary at best.

Finding the cause(s) and possible treatments for central fatigue is important not only for sports competitors but also for the general population in which “generalized fatigue” is the primary cause of lost productivity at home and in the workplace, and for those who are sick from infection or other diseases in which debilitating fatigue is often a primary symptom.


1. Enoka RM, Stuart DG. Neurobiology of muscle fatigue. J Appl Physiol 1992;72(5):1631~8.

2. Murray R. Fluid needs in hot and cold environments. Int J Sport Nutr 1995;5:S62-S73.

3. Walberg-Rankin J. Dietary carbohydrate as an ergogenic aid for prolonged and brief competitions in sport. Int J Sport Nutr 1995;5:S13-S28.

4. Gandevia SC, Allen GM, McKenzie DK. Central Fatigue: critical issues, quantification and practical implications. In: Gandevia S. Enoka RM, McComas AJ, Stuart DG, Thomas CK, eds. Fatigue: neural and muscular mechanisms. Adv Exp Med Biol 1995;384:281-94.

5. Chaouloff F. Physical exercise and brain monoamines: a review. Acta Physiol Scand 1989;137:1-13, 1989.

6. Davis, J.M. Carbohydrates, branched-chain amino acids, and endurance: The central fatigue hypothesis. Int J Sport Nutr 1995;5:S29-S38.

7. Newsholme EA, Blomstrand E. Tryptophan, 5-hydroxytryptamine and a possible explanation for central fatigue. In: Gandevia S. Enoka RM, McComas AJ, Stuart DG, Thomas CK, eds. Fatigue: neural and muscular mechanisms. Adv Exp Med Biol 1995;384:315-20.

8. Wurtman RJ. Effects of dietary animo acids, carbohydrates, and choline on neurotransmitter synthesis. Mt Sinai J Med 1988;55:75-86.

9. Laties VG. Weiss B. The amphetamine margin in sports. Fed Proc 1981;40:2689-92.

10. Spector SA, Jackman MR, Sabounjian LA, Sakkas C, Landers DM, Willis WT. Effects of choline supplementation on fatigue in trained cyclists. Med Sci Sports Exerc 1995:27(5):668-73.

11. Conlay LA, Sabournjian LA, and Wurtman, R.J. Exercise and neuromodulators: choline and acetylcholine in marathon runners. Int J Sports Med 1992;13(suppll):S141-2.

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Written by J. Mark Davis PhD

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