Billingset al.1990a; Rowbottom et al.1996; see
also Budgett et al.1998).
In a study on athletes with the overtraining
syndrome (Parry-Billings 1989), the plasma con-
centrations of alanine and branched-chain amino
acids were similar in trained and overtrained
athletes. However, the plasma concentration
of glutamine was lower in overtrained athletes
compared with that in trained athletes and
the concentration in trained subjects was lower
than in recreational runners (Parry-Billings et
al.1990a). Moreover, after a 6-week recovery
period, despite a significant improvement
in the exercise performance of these subjects,
the plasma glutamine concentration remained
below control values. This suggests that
immunodepression due to overtraining may
persist for longer periods than indicated by the
decrease in physical performance.
Exercise-induced immunodepression has
been demonstrated in a large number of different
types of athletes, including runners, swimmers,
skiers (Noakes 1992) and ballet dancers (Sun et al.
1988). It is therefore suggested that intense, pro-
longed exercise, particularly if it is undertaken
regularly, can cause a marked decrease in the
plasma glutamine level, and that this might
result in immunodepression. Can muscle, to-
gether with other tissues, always respond suffi-
ciently to release enough glutamine to maintain
the normal blood concentration? This may be a
particularly relevant question if muscle is
damaged due to excessive exercise. However, the
reason for the decrease in the plasma glutamine
concentration in longer term, strenuous exercise
is not understood.
Enzymes which are normally localized in
muscle fibres appear in the blood and are
assumed to be evidence of disruption or in-
creased permeability of the muscle cell mem-
branes (Altland & Highman 1961; Newham et al.
1983). The occurrence of muscle damage after
prolonged exercise has been reported by Appell
et al.(1992), who observed increased levels of
circulating complement anaphylotoxin, which
is a likely result of tissue damage. Tiidus and
Ianuzzo (1983) observed that the extent of injury
is proportional to the intensity of exercise.
Muscle injuries have been found to be wide-
spread in military personnel during strenuous
training (Greenberg & Arneson 1967; Armstrong
1986).
Although it might be hypothesized that the
marked decrease in plasma glutamine after pro-
longed exhaustive exercise could be due to an
inhibition of the glutamine release mechanism, it
seems unlikely, since increased non-specific per-
meability of muscle cell membranes would be
expected to lead to greater release of glutamine
from muscle. The possibility arises that muscle
damage caused by prolonged exercise presents
an area of tissue which is larger than normal, to
which immune cells might migrate (see Galun
et al.1987; Pabst & Binns 1989, 1992). As the
numbers of these cells increase, activity increases
and/or proliferation of some cells may result
which, in turn, increases the local demand for
glutamine. It is suggested that failure of muscle
to provide enough glutamine could result in an
impairment of the function of the immune
system via lack of precision for the regulation of,
for example, the rates of purine and pyrimidine
nucleotide synthesis for DNA and RNA forma-
tion in lymphocytes (Newsholme 1994). It can be
speculated that excessive damage could produce
resistance to the proposed stimulatory effect of
cytokines and glucocorticoids on glutamine
release, e.g. by a reduction in the number of
cytokine receptors and/or glucocorticoid recep-
tors on muscle.Glutamine feeding in clinical situations
Over many years, there has been considerable
physiological interest in the phenomenon of
hypoglycaemia, since this can cause abnormal
function of the brain, which is normally depen-
dent upon glucose as a fuel. Similar considera-
tions should be applied to the maintenance of
the plasma glutamine level, which can be consid-
ered to be as important a plasma fuel as that of
glucose, but for different cells. Furthermore, the
requirement for glutamine, synthesized within
muscle and other cells, will increase after pro-