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This article is a modification of the original article that appeared in a supplemental issue to the International Journal of SportsNutrition, Vol. 5, 1995. The supplement represented the proceedings of the Gatorade Sports Science Institute Ergogenic AidsConference, held in Chicago, November, 1994.
J. Mark Davis
Department of Exercise Science
The University of South Carolina
Columbia, SC 29208

1. The mechanisms of central fatigue are largely unexplored, but the central fatigue hypothesis suggests that increased brain sero-
tonin (5-HT) can cause a deterioration in sport and exercise performance. There is now convincing evidence thatexercise-induced increases in the plasma free tryptophan (f-TRP)/branched-chain amino acids (BCCA) ratio are associated withincreased brain 5-HT and the onset of fatigue during prolonged exercise.
2. When drugs are administered to alter brain 5-HT, they have the predicted effects on exercise performance. The influence of nutritional manipulations of f-TRP/BCCA on performance is less well established.
3. The effects of BCCA supplementation on exercise performance are mixed, and the published studies often suffer from method- ological flaws. Alternatively, dramatic reductions in f-TRP/BCCA and enhanced performance accompany carbohydrate feedingsduring prolonged exercise. However, it is difficult to distinguish between the effects of carbohydrate feedings on mechanismsthat reside in the brain versus the muscles themselves.
Muscular fatigue is commonly defined as a failure to maintain the required or expected force or power output (22). The causes of muscular fatigue involve specific impairments within the muscle itself, including transmission of the neural stimulus to themuscle at the motor end plate and propagation of that stimulus throughout the muscle (35, 38), disruption of calcium release anduptake within the sarcoplasmic reticulum (23), substrate depletion (19), and various other metabolic events that impair energyprovision and muscle contraction (27). Fatigue can also result from alterations within the central nervous system (CNS) althoughessentially nothing is known about the specific mechanisms underlying this type of fatigue (central fatigue).
The potential role of central fatigue during prolonged exercise has received very little scientific attention, even though it is well known that “psychological factors” can affect exercise performance (3). In fact, the lack of adequate CNS drive to the workingmuscles is the most likely explanation of fatigue in most people during normal activities. Furthermore, the often debilitating fatiguethat accompanies viral or bacterial infections, recovery from injury or surgery, chronic fatigue syndrome, and depression almostcertainly cannot be explained by a dysfunction within the muscles themselves. Fatigue under these circumstances probablyinvolves the CNS, but the specific causes have not been elucidated.
An important role for central fatigue during exercise in healthy people has been suggested in a number of studies (3, 9, 34), but most of these investigations have failed to provide plausible physiological mechanisms. Recently, however, interestingnew theories have been proposed that implicate various neurotransmitters such as serotonin (5-hydroxytryptamine, or 5-HT)(32), norepinephrine, and dopamine (8, 28, 30, 33) in central fatigue during exercise. This review will focus primarily on thescientific evidence regarding brain 5-HT as a potential mediator of central fatigue during prolonged exercise. The exciting, butmore limited, evidence that proper nutrition may be able to alter brain 5-HT synthesis and delay central fatigue will also bediscussed. For this review, a working definition of central fatigue will be used which suggests that central fatigue is a subsetof fatigue that is associated with specific alterations in CNS function and that cannot reasonably be explained by peripheralmarkers of muscle fatigue.
(32). There is a large body of literature increase when there is an increase in the primary factor leading to this response.
fatty acids (FFAs) increase in the blood, cise and thereby cause a deterioration in (˜180 min. run time) and untrained (˜72 sport and exercise performance (32).
increases in brain concentrations of 5-HT after 1 hr. of treadmill exercise, and at VO2max in rats (20 m • min-1, 5% grade).
After 1 hr. of exercise, the concentrations even further in the midbrain andstriatum. DA and DOPAC also increasedin the midbrain, striatum, and hypothal- ASSOCIATION BETWEEN
to baseline levels at fatigue. These results Figure 1: Primary components of the central fatigue
hypothesis at rest and during prolonged exercise. (a)
The situation at rest with regard to plasma concentra- tions of branched-chain amino acids (BCAAs), free appears to peak at the time of fatigue.
fatty acids (FFAs), and tryptophan (TRP) (bound and Chaouloff (14-18) and Newsholme (13).
unbound to albumin) and their proposed effects on transport of TRP across the blood-brain barrier for the that is usually associated with increased synthesis of serotonin (5-HT) in serotonergic neurons.
(b) What happens during prolonged exercise to
increase the synthesis of 5-HT in the brain and lead to central fatigue. Adapted from J.D. Fernstrom. Dietary prolonged exercise as fatigue develops.
amino acids and brain function. J. Am. Diet. Assoc. The significance of this apparent inverse EXPERIMENTAL ALTERATIONS
that this may cause central fatigue.
central fatigue may occur as a result.
(5-HT antagonists) would delay fatigue.
f-TRP to the brain for 5-HT synthesis.
hypothesis is that a low ratio of 5-HT:DA athletes’ actual situations, such studies are often limited in scientific value. For NUTRITIONAL EFFECTS ON 5-HT
or other factors. In addition, studies of treatments to prevent bias on the part of these studies often fail to control impor- tant variables such as exercise intensity time to fatigue occurred earlier (41) and effects, and there were no differences in slightly lower (˜19%) after the race.
between the drug and placebo trials.
exercise test to fatigue. Verger et al.
mechanisms have not been established.
their peaks at fatigue, (b) the increase in severe symptoms of central fatigue (7).
peripheral markers of muscle fatigue.
subjects drank 5 ml • kg-1 • hr-1 of either a role in delaying central fatigue during prolonged exercise, the scientific data in tion to plasma free fatty acids), whereas are reasons to believe that this approach strategy. In this case, however, it is not tions and to decrease the likelihood that large attenuation (fivefold to sevenfold) edge in this area is rudimentary at best.
moregulatory, and metabolic functions.
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