were infused into the stomach of rats at regular
intervals during treadmill running. Subgroups of
rats in each group were killed at 60, 90 and
120 min of exercise for determination of 5-HT
and 5-HIAA in the brainstem and striatum
regions of the brain. The results showed that
neither BCAA nor CHO feedings affected brain
5-HT or 5-HIAA at 60 and 90 min of exercise.
However, at 120 min, both BCAA and CHO feed-
ings lowered 5-HT and 5-HIAA in the brainstem
and CHO lowered 5-HT in the striatum. There-
fore, at least in this preliminary study, BCAA and
CHO feedings were able to influence brain 5-HT
metabolism in a presumably positive direction
during exercise. However, since exercise time to
fatigue was not measured in this study, the ques-
tion of whether a direct link exists between these
nutritional strategies, lower brain 5-HT metabo-
lism and fatigue during exercise remains to be
firmly established.
Even if BCAA supplementation is found to
alter brain 5-HT during exercise, there is still a
question of potential negative side-effects. For
BCAA to be physiologically effective in reducing
brain 5-HT metabolism, relatively large doses are
likely to be required and this increases the likeli-
hood that plasma ammonia will result (van Hall
et al.1995). Ammonia is known to be toxic to the
brain and may also impair muscle metabolism.
The buffering of ammonia could cause fatigue
in working muscles by depleting glycolytically
derived carbon skeletons (pyruvate) and by
draining intermediates of the Krebs cycle that
are coupled to glutamine production by transa-
mination reactions (Wagenmakers et al.1990).
Elevated plasma ammonia can also increase
brain TRP uptake and 5-HT metabolism in
various brain regions (Mans et al.1987). Other
potential side-effects include slower water
absorption across the gut, gastrointestinal dis-
turbances and decreased drink palatability. It
should be noted, however, that when these
potential side-effects were minimized by provid-
ing a small, more palatable, dose of BCAA in a
sports drink (0.5 g · h–1 consumed in a CHO–
electrolyte drink), no benefits were found
176 nutrition and exercise
during cycling to fatigue at 70% V.
o2max.in
trained cyclists. No measurable side-effects were
reported, but ride time to fatigue, perceived exer-
tion and various cardiovascular, metabolic and
endocrine responses were similar in the BCAA
and placebo groups (Galiano et al.1991). In fact,
to the author’s knowledge there is only one
recent controlled laboratory study that shows a
performance benefit of BCAA supplementation
(Mittlemanet al.1998). In this study, BCAA were
given during a 2-h pre-exercise exposure to high
heat that was followed by a ride to fatigue at 40%
V.
o2peak. As expected, the f-TRP/BCAA ratio was
significantly lower during the 2-h period prior
to exercise and during exercise when subjects
received the BCAA supplement. However, in this
case fatigue was apparently delayed by the
supplement. It is possible that administration of
BCAA during the rest period in the heat prior to
exercise may have provided a beneficial effect
that would otherwise not occur, or be offset by
other negative side-effects, if the supplements
are given only during exercise. However,
support for this hypothesis from other physio-
logical and psychological data in this paper were
equivocal.
This led us to consider another, perhaps more
reasonable nutritional approach involving CHO
feedings alone to offset the increase in 5-HT and
CNS fatigue. The literature is consistent in
showing that CHO feedings can delay fatigue
in a variety of exercise protocols, which is not
surprising given the well-known benefit of
CHO feedings in maintaining blood glucose and
muscle glycogen as important sources of energy
for the working muscle (Coyle 1998). However, it
now appears possible that CHO feedings may
also delay CNS fatigue as well as peripheral
fatigue (Davis et al.1992).
This effect is based on the premise that CHO
feedings suppress normally large rises in FFA
and therefore f-TRP and f-TRP/BCAA during
exercise without the potential negative conse-
quences of administering large doses of BCAA.
This hypothesis was tested in a double-blinded,
placebo-controlled laboratory study in which