various stress hormones. Similar results were
also found in human subjects in which brain 5-
HT activity was increased by the administration
of paroxetine (Paxil; Wilson & Maughan 1992) or
fluoxetine (Prozac; Davis et al.1993) prior to
running or cycling. These results clearly support
the hypothesized relationship between increased
brain 5-HT activity and central fatigue. However,
as with all pharmacological experiments, it is not
possible to rule out possible crossover effects of
the drug on other neurotransmitter systems or
other side-effects.
Nutritional effects on brain 5-HT
and CNS fatigue
An interesting aspect of the neurotransmitter
hypotheses of CNS fatigue is the fact that nutri-
tion can alter brain neurochemistry in ways that
might offset CNS fatigue. With respect to brain 5-
HT and fatigue, the focus has been on two main
nutritional strategies. These strategies involve
feedings of BCAA and/or CHO during exercise.
Intake of BCAA would lower plasma f-TRP/
BCAA (by increasing plasma BCAA concentra-
tion) and presumably 5-HT due to decreased f-
TRP transport across the blood–brain barrier
(mechanisms explained earlier in this chapter).
The postulated benefits of CHO feedings is based
primarily on the premise that the normally large
exercise-induced increase in circulating FFAs
would be attenuated by the maintenance of
blood glucose and slightly elevated insulin
(Daviset al.1992). Since FFAs have a higher affin-
ity for albumin than the loosely bound TRP, this
would attenuate the normally large increase in f-
TRP and therefore f-TRP/BCAA would remain
lower (Fig. 12.2). This is unlike the situation at
rest, in which a high CHO meal would elicit a
large increase in plasma insulin and a corre-
spondingly large decrease in BCAA levels that
have been linked to meal-induced sleepiness and
fatigue (Fernstrom 1994). The insulin response is
substantially blunted during exercise to the
extent that little or no decrease in plasma BCAA
occurs (Davis et al.1992).
Blomstrandet al.(1991) focused primarily on
174 nutrition and exercise
administration of BCAAs to delay central fatigue
during activities such as marathon racing and
30-km running. Upon administration of 7.5–
16 g BCAAs prior to and during exercise, small
improvements were reported in both physical
and mental performance in some subjects.
However, it should be noted that while field
studies such as these are designed to mimic the
real world situation in which athletes find them-
selves, they are often limited in scientific value.
This is because the subject groups are often
not appropriately matched for performance or
‘blinded’ to the treatment they are receiving, and
there is little or no control over important
variables such as exercise intensity, food and
water intake, and environmental conditions.
This increases the likelihood that a potential
nutritional benefit may have actually resulted
from inherent differences in the groups of sub-
jects, subject bias and/or uncontrolled variables.
This is perhaps illustrated by the fact that well-
controlled laboratory experiments have gener-
ally not confirmed the benefit of BCAA on
exercise performance. Varnier et al.(1994) found
no differences in performance of a graded incre-
mental exercise test to fatigue following infusion
of approximately 20 g BCAA or saline over
70 min prior to exercise using a double-blinded,
cross-over design. Verger et al. (1994) also
reported in rats that feeding relatively large
amounts of BCAAs actually caused early fatigue
during prolonged treadmill running as com-
pared to rats fed glucose.
Recent well-controlled laboratory studies
involving endurance cycling in humans also fail
to confirm a performance benefit of BCAA
administration. Blomstrand et al.(1995) studied
five endurance trained male cyclists during a
ride to fatigue at 75% V.
o2max., which was pre-
ceded by a muscle glycogen-depleting regimen,
presumably to increase the likelihood that an
effect would occur. All subjects were given in
random order one of the following drinks during
the ride: a 6% CHO solution, a 6% CHO solution
containing 7 g · l–1BCAA, or a flavoured water
placebo. Increases in performance were seen in
both CHO and CHO+BCAA treatments when