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Exercise, nutrition and immune function
MICHAEL GLEESON,
1
* DAVID C. NIEMAN
2
and BENTE K. PEDERSEN
3
1
School of Sport and Exercise Sciences, Loughborough University, Loughborough LE11 3TU, UK,
2
Department of
Health, Leisure and Exercise Science, Appalachian State University, Boone, NC 28608, USA and
3
Department of
Infectious Diseases, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark
Accepted 7 August 2003
Strenuous bouts of prolonged exercise and heavy training are associated with depressed immune cell function.
Furthermore, inadequate or inappropriate nutrition can compound the negative influence of heavy exertion on
immunocompetence. Dietary deficiencies of protein and specific micronutrients have long been associated with
immune dysfunction. An adequate intake of iron, zinc and vitamins A, E, B6 and B12 is particularly important
for the maintenance of immune function, but excess intakes of some micronutrients can also impair immune
function and have other adverse effects on health. Immune system depression has also been associated with an
excess intake of fat. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet
their energy requirements. An athlete exercising in a carbohydrate-depleted state experiences larger increases in
circulating stress hormones and a greater perturbation of several immune function indices. Conversely,
consuming 30–60 g carbohydrate × h
71
during sustained intensive exercise attenuates rises in stress hormones
such as cortisol and appears to limit the degree of exercise-induced immune depression. Convincing evidence
that so-called ‘immune-boosting’ supplements, including high doses of antioxidant vitamins, glutamine, zinc,
probiotics and Echinacea, prevent exercise-induced immune impairment is currently lacking.
Keywords: exercise, immunity, leucocytes, macronutrients, micronutrients, training.
Immune function and the nutrition of elite
athletes
The immune system protects against, recognizes,
attacks and destroys elements that are foreign to the
body. The immun e system can be divided into two
broad functions: innate (natural and non-specific) and
acquired (adapti ve and specific) immunity, which work
together synergistically. The attempt of an infectious
agent to enter the body immediately activates the innate
system. This so-called ‘first-line of defence’ comprises
three general mechanisms with the common goal of
restricting the entry of microorganisms into the body:
(1) physical/structural barriers (skin, epithelial linings,
mucosal secretions); (2) chemical barriers (pH of bodily
fluids and soluble factors such as lysozymes and
complement proteins); and (3) phagocytic cells (e.g.
neutrophils and monocytes/macrophages). Failure of
the innate system and the resulting infection activates
the acquired system, which aids recovery from infec-
tion. Monocytes or macrophages ingest, process and
present foreign material (antigens) to lymphocytes. This
is followed by clonal proliferation of T- and B-
lymphocytes that possess receptors that recognize the
antigen, engendering specificity and ‘memory’ that
enable the immune system to mount an augmented
cell-mediated and humoral response when the host is
reinfected by the same pathogen. Critical to the
activation and regulation of immune function is the
production of cytokines, including interferons, inter-
leukins and colony-stimulating factors. For further
details of the normal immune response, see Gleeson
and Bishop (1999). A fundamental characteristic of the
immune system is that it involves mult iple functionally
different cell types, which permits a large variety of
defence mechanisms. Assessing immune function
status, therefore, requires a thorough methodological
approach targeting a large spectrum of immune system
parameters. However, currently no instruments are
available to predict th e cumulative effects of several
small changes in immune system parameters on host
resistance to infection (Keil et al., 2001).
A heavy schedule of training and competition can
lead to immune impairment in athletes, which is
associated with an increased susceptibility to infections,
particularly upper respiratory tract infections (URTI)
(Peters and Bateman, 1983; Nieman et al., 1990). This
* Author to whom all correspondence should be addressed.
e-mail: m.gleeson@lboro.ac.uk
Journal of Sports Sciences, 2004, 22, 115–125
Journal of Sports Sciences ISSN 0264-0414 print/ISSN 1466-447X online # 2004 Taylor & Francis Ltd
DOI: 10.1080/0264041031000140590
exercise-induced immune dysfunction seems to be
mostly due to the immunosuppressive actions of stress
hormones such as adrenaline and cortisol. Nutritional
deficiencies can also impair immune function and there
is a vast body of evidence that many infections are
increased in prevalence or severity by specific nutri-
tional deficiencies (Scrimshaw and SanGiovanni, 1997;
Calder and Jackson, 2000). However, it is also true that
excessive intakes of individual micronutrients (e.g. n-3
polyunsaturated fatty acids, iron, zinc, vitamins A and
E) can impair immune function and increase the risk of
infection (Chandra, 1997). As most athletes will be
aware, even medically harmless infections can result in
a decrement in athletic performance.
Avoiding nutrient deficiencies
The key to maintaining an effective immune system is
to avoid deficiencies of the nutrients that play an
essential role in immune cell triggering, interact ion,
differentiation or functional expression. Malnutrition
decreases immune defences against invading pathogens
and makes the individual more susceptible to infection
(Calder and Jackson, 2000; Calder et al., 2002).
Infections with certain pathogens can also affect
nutritional status by causing appetite suppression,
malabsorption, increased nutrient requirements and
increased losses of endogenous nutrients.
Protein and energy
It is well accepted that an inadequate intake of protein
impairs host immunity with particularly detrimental
effects on the T-cell system, resulting in an increased
incidence of opportunistic infections (Chandra, 1997;
Scrimshaw and SanGiovanni, 1997; Calder et al.,
2002). It is not surprising that protei n deficiency
impairs immunity because immune defences are
dependent on rapid cell replication and the production
of proteins with important biological activities, such as
immunoglobulins, acute phase proteins and cytokines.
In humans, protein-energy malnutrition has been found
to depress the number of mature, fully differentiated T-
lymphocytes and the in vitro proliferative response to
mitogens, although the latter is reversible with nutri-
tional repletion (Daly et al., 1990; Reynolds et al.,
1990). Additionally, in protein-energy malnutrition the
T-lymphocyte CD4+/CD8+ (h elper/suppressor cell)
ratio is markedly decreased and phagocytic cell func-
tion, cytokine production and com plement formation
are all impaired. Essentially, all forms of immunity have
been shown to be affected by pr otein-energy malnutri-
tion in humans, depending on the severity of the protein
deficiency relative to energy intake. Although it is
unlikely that athletes would ever reach a state of such
extreme malnutrition unless dieting very severely, some
impairment of host defence mechanisms is observed
even in moderate protein deficiency (Daly et al., 1990).
Among the athletic population, individuals at most risk
from protein deficiency are those undertaking a
programme of food restriction to lose weight, vegetar-
ians and athletes consuming unbalanced diets (e.g. with
an excessive amount of carbohydrate at the expense of
protein). Often, deficiencies in protein and energy will
be accompanied by deficiencies in micronutrients.
Energy-restricted diets are common in sports where
leanness or low body mass is thought to confer a
performance or aesthetic advantage (e.g. gymnastics,
figure skating, endurance running) or is required to
meet certain body weight criteria (e.g. boxing, martial
arts, weightlifting, rowing). Indeed, this has led to the
identification of a new subclinical eating disorder,
anorexia athletica, which has been associated with an
increased susceptibility to infection (Beals and Manore,
1994). Even short-term dieting can influence immune
function in athletes. For example, it has been shown
that a loss of 2 kg of body mass over 2 weeks adversely
affects macrophage phagocytic function (Kono et al.,
1988).
Vitamins and minerals
Several vitamins are essential for normal immune
function. Deficiencie s of fat-soluble vitamins A and E
and water-soluble vitamins folic acid, B6, B12 and C
impair immune function and decrease the body’s
resistance to infection (Scrimshaw and SanGiovanni,
1997; Calder and Jackson, 2000; Calder et al., 2002).
Correcting existing deficiencies with specific vitamin
supplements can be effective in restoring immune
function to normal (Calder and Jackson, 2000).
Several minerals are known to exert modulatory
effects on immune function, including zinc, iron,
magnesium, manganese, selenium and copper, yet with
the exception of zinc and iron, isolated deficiencies are
rare. Field studies consistently associate iron deficiency
with increased morbidity from infectious disease (Sher-
man, 1992). Furthermore, exercise has a pronounced
effect on both zinc and iron metabolism (Gleeson,
2000). Requirements for these minerals are certainly
higher in athletes than sedentary individuals because of
increased losses in sweat and urine. However, excesses
of some minerals (particularly iron and zinc) can impair
immune function and increase susceptibility to infec-
tion (Chandra, 1984; Sherman, 1992; Gleeson, 2000).
Hence, supplements should be taken only as required
and regular monitoring of iron status (serum ferritin
and blood haemoglobin) and zinc status (erythrocyte
zinc) is probably a good ide a. The efficacy of zinc
116 Gleeson et al.
supplementation as a treatment for the common cold
has been investigated in at least 11 studies that have
been published since 1984. The findings have been
equivocal and recent reviews of this topic have
concluded that further research is necessary before the
use of zinc supplements to treat the common cold can
be recommended (Macknin, 1999; Marshall, 2000).
Although there is only limited evidence that taking zinc
supplements reduces the incidence of URTI (McElroy
and Miller, 2002), in the studies that have reported a
beneficial effect of zinc in treating the common cold
(i.e. reduction of symptom duration and/or severity) it
has been emphasized that zinc must be taken within
24 h of the onset of symptoms to be of any benefit.
Potential problems with zinc supplements include
nausea, bad taste reactions, lowering of high-density
lipoprotein cholesterol, depression of some immune cell
functions (e.g. neutrophil oxidative burst) and inter-
ference with the absorption of copper (Gleeson, 2000).
Eating the right amount and type of fat
Relatively little is known about the potential contribu-
tion of dietary fatty acids to the regulation of exercise-
induced modification of immune function. Two groups
of polyunsaturated fatty acids (PUFA) are essential to
the body: the omega-6 (n-6) series, derived from
linoleic acid, and the omega-3 (n-3) series, derived
from linolenic acid. These fatt y acids cannot be
synthesized in the body and therefore must be derived
from the diet. There are reports that diets rich in either
of these polyunsaturated fatty acids improve the
conditions of patients suffering from diseases charac-
terized by an over-active immune system, such as
rheumatoid arthritis; that is, they have anti-in flamma-
tory effects (Calder, 1996; Calder et al., 2002). It has
been suggested that high intakes of arachidonic acid
relative to intakes of fatty acids of the n-3 group may
exert an undesirable influence on inflammation and
immune function during and after exercise (Konig et
al., 1997). However, a recent study showed that n-3
PUFA supplementation did not influence the exercise-
induced elevation of pro- or anti-inflammatory cyto-
kines (Toft et al., 2000). More research is needed on the
effects of altering essential fatty acid intake on immune
function after exercise and during periods of heavy
training.
A recent study that investigated the effects of
endurance training for 7 weeks on a carbohydrate-rich
diet (65% of dietary energy from carbohydrate) or a fat-
rich diet (62% of dietary energy from fat) concluded
that diet composition during training may influence
natural immunity since natural killer (NK) cell activity
increased on the carbohydrate-rich diet compared with
the fat-rich diet in response to training (Pedersen et al.,
2000). The results of this study suggest that a fat-rich
diet is detrimental to immune function compared with a
carbohydrate-rich diet, but do not clarify whether this
effect is due to a lack of dietary carbohydrate or an
excess of a specific dietary fat component.
Are megadoses of vitamins needed?
Moderately increasing the intake of some vitamins
(notably vitamins A and E) above the amounts normally
recommended may enhance immune function in the
very young (Coutsoudis et al., 1992) and the elderly
(Meydani et al., 1990), but is probably not effective in
young adults. Consuming megadoses of individual
vitamins, which appears to be a common practice in
athletes, can impair immune function and have other
toxic effects (Calder et al., 2002; Food Standards
Agency, 2003). For example, 300 mg of vi tamin E
given daily to men (the UK reference nutrient intake for
men is 4 mg × day
71
; COMA, 1991) for 3 weeks
significantly depressed phagocyte function and lym-
phocyte proliferation (Prasad, 1980). In a recent
exercise study, supplementation of athletes with
600 mg × day
71
vitamin E for 2 months before an
Ironman triathlon event resulted in elevated oxidative
stress and inflammatory cytokine responses during the
triathlon compared with placebo (D.C. Nieman et al.,
unpublished). In elderly people (n = 652), a daily 200-
mg vitamin E supplement increased the severity of
infections, including total ill ness duration, duration of
fever and restriction of physical activity (Graat et al.,
2002). Recently, vitamin E supplementation
(600 mg × day
71
) in patients with ischaemic heart
disease has been demonstrated to have either no effect
on all-cause mortality (MRC/BHF Heart Protection
Study, 2002) or to increase the number of cases who
died compared with placebo (Waters et al., 2002).
Megadoses of vitamin A may impair the inflammatory
response and complement formation as well as having
other pathological effects, including causing an in-
creased risk of foetal abnormalities when consumed by
pregnant women (Food Standards Agency, 2003).
Vitamins with antioxidant properties including vita-
mins A, C, E and b-caro tene (provitamin A) may be
required in increased quantities in athletes to inactivate
the products of exercise-induced lipid peroxidation
(Packer, 1997). However, there are no convincing data
to demonstrate an effect of nutritional antioxidants on
muscle damage or delayed-onset muscle soreness.
Increased oxygen free-radical formation that accom-
panies the dramatic rise in oxidative metabolism during
exercise could potentially inhibit immune responses
(Peters, 1997; Petersen and Pedersen, 2002). Reactive
117Exercise, nutrition and immune function
oxygen species inhibit locomotory and bactericidal
activity of neutrophils, reduce the proliferation of T-
and B-lymphocytes and inhibit natural killer cell
cytotoxic activit y. Sustained endurance training appears
to be associated with an adaptive up-regulation of the
antioxidant defence system (Duthie et al., 1996).
However, such adaptations may be insufficient to
protect athletes who train extensively (Clarkson, 1992;
Packer, 1997).
Vitamin C (ascorbic acid) is found in high concen-
trations in leucocytes and has been implicated in a
variety of anti-infective functions, including promotion
of T-lymphocyte proliferation, prevention of cortico-
steroid-induced suppression of neutrophil activity and
inhibition of virus replication (Peters, 2000). It is also a
major wa ter-soluble antioxidant that is effective as a
scavenger of reactive oxygen species in both intracel-
lular and ext racellular fluids. Vitamin C is also required
for the regeneration of the reduced form of the lipid-
soluble antioxidant, vitamin E. The UK reference
nutrient intake (RNI) for vitamin C is 40 mg × day
71
(COMA, 1991).
In a study by Peters et al. (1993), using a double-
blind placebo research design, it was determined that
daily supplementation of 600 mg (15 times the RNI) of
vitamin C for 3 weeks before a 90-km ultramarathon
reduced the incidence of symptoms of URTI (68%
compared with 33% in age- and sex-matched control
runners) in the 2 weeks after the race. In a follow-up
study, Peters et al. (1996) randomly divided participants
in a 90-km ultramara thon (n = 178) and their matched
controls (n = 162) into four treatment groups receiving
one of 500 mg vitamin C alone, 500 mg vitamin C plus
400 IU vitamin E (1 IU is equivalent to 0.67 mg),
300 mg vitamin C plus 300 IU vitamin E plus 18 mg b-
carotene, or placebo. As runners were requested to
continue with their usual habits in terms of dietary
intake and the use of nutritional supplements, total
vitamin C intake of the four groups was 1004, 893, 665
and 585 mg × day
71
, respectively. The study confirmed
previous findings of a lower incidence of symptoms of
URTI in those runners with the highest mean daily
intake of vitamin C and also indicated that the
combination of water-soluble and fat-soluble antiox-
idants was not more successful in atten uating the post-
exercise infection risk than vitamin C alone. This study
certainly provides some support for the notion that
megadoses of vitamin C reduce URTI risk in endurance
athletes. However, some similar studies have not been
able to replicate these findings: Him melstein et al.
(1998), for example, reported no difference in URTI
incidence among 44 marathon runners and 48 seden-
tary individuals randomly assigned to a 2-month
regimen of 1000 mg × day
71
vitamin C or placebo.
Furthermore, a subsequent double-blind, placebo-
controlled study found no effect of vitamin C supple-
mentation (1000 mg × day
71
for 8 days) on the immune
response to 2.5 h running (Nieman et al ., 1997a),
although a larger dose of vitamin C supplementation
(1500 mg × day
71
for 7 days before the race and on race
day) did reduce the cortisol and cytokine response to a
90-km ultramarathon race (Nieman et al., 2000).
However, in the latter study, no difference in URTI
incidence was found between participants on vitamin C
and placebo treatments; also, the participants con-
sumed carbohydrate during the race ad libitum and this
was retrospectively es timated.
In a more recent randomized, double-blind, placebo-
controlled study, ingestion of 1500 mg vitamin
C × day
71
for 7 days before an ultramarathon race with
consumption of vitamin C in a carb ohydrate beverage
during the race (participants in the placebo group
consumed the same carbohydrate beverage without
added vitamin C) did not affect oxidative stress,
cytokines or immune function during or after the race
(Nieman et al., 2002a). In contrast, it has recently been
reported that 7 days supplementation with vitamin C
(800 mg × day
71
) before a downhill treadmill run
reduced the exercise-induced rise in plasma interleukin
(IL)-6, monocyte respiratory burst and natural killer
cell numbers compared with a placebo treatment
(Hurst et al., 2001). Nieman et al. (2002a) summarized
the available literature on vitamin C supplementation
and immune responses to exercise and concluded that
vitamin C supplementation before prolonged intensive
exercise ‘does not have a consistent effect on blo od
measures of oxidative stress and muscle damage and
that any linkage to immune perturbations remains
speculative and more than likely improbable’. It should
be noted that consumption of doses in excess of
1000 mg can cause abdominal pain and diarrhoea
(Food Standards Agency, 2003), although there are
insufficient data on adverse effects to set a safe upper
level for vitamin C intake.
Nutritional manipulations to decrease
exercise-induced immune impairment in
athletes
Since exercise-induced immune function impairment
appears mainly to be caused by elevated concentra-
tions of stress hormon es, nutritional strategies that
effectively reduce the stress hormone response to
exercise should limit the degree of exercise-induced
immune dysfunction (Nieman and Pedersen, 2000).
There is certainly considerable experimental evidence
to support this notion, although it is not clear if the
magnitude of such effects is suffici ent to affect
infection risk.
118 Gleeson et al.
Carbohydrate intake before and during exercise
In recent years, several studies have examined the
impact of dietary carbohydrate on hormonal and
immune responses to exercise. These studies (Gleeson
et al., 1998; Mitchell et al., 1998; Bishop et al., 2001b)
have found that when individuals perform prolonged
exercise after several days on very low carbohydrate
diets (typically 510% of dietary energy intake from
carbohydrate), the magnitude of the stress hormone
(e.g. adrenaline and cortisol) and cytokine (e.g. IL-6,
IL-1ra and IL-10) response is markedly higher than on
normal or high carbohydrate diets. It has been
speculated that athletes deficient in carbohydrate are
placing themselves at risk from the known immuno-
suppressive effects of cortisol, including the suppression
of antibody production, lymphocyte proliferation and
natural killer cell cytotoxic activity. Mitchell et al.
(1998) observed that exercising (1 h at 75% V
˙
O
2max
)in
a glycogen-depleted state (induced by prior exercise
and 2 days on a low carbohydrate diet) resulted in a
greater fall in circulating lymphocyte numbers 2 h after
exercise compared with the same exercise performed
after 2 days on a high carbohydrate diet. However, the
manipulation of carbohydrate status did not affect the
decrease in mitogen-stimulated lymphocyte prolifera-
tion that occurred after exercise.
Consumption of carbohydrate during exercise also
attenuates rises in plasma catecholamines, adrenocorti-
cotrophic hormone, growth hormone, cortisol and
cytokines (Nehlsen-Cannarella et al., 1997; Nieman,
1998). Carbohydrate intake during exercise also
attenuates the trafficking of most leucocyte and
lymphocyte subsets, including the rise in the neutro-
phil : lymphocyte ratio (Nieman et al., 1997b; Bishop et
al., 1999a), prevents the exercise-induced fall in
neutrophil fu nction (Bishop et al., 2000b) and reduces
the extent of the diminution of mitogen-stimulated T-
lymphocyte proliferation (Henson et al., 1998) follow-
ing prolonged exercise. Very recen tly, it was shown that
consuming 30–60 g carbohydrate × h
71
during 2.5 h of
strenuous cycling prevented both the decrease in the
number and percentage of interferon (IFN)-g-positive
T-lymphocytes and the suppression of IFN-g produc-
tion from stimulated T-lymphocytes observed on the
placebo control trial (Lancaster et al., 2003). Interferon-
g production is critical to anti-viral defence and it has
been sugges ted that the suppression of IFN-g produc-
tion may be an important mechanism leading to an
increased risk of infection after prolonged exercise
bouts (Northoff et al., 1998).
Compared with placebo, carbohydrate ingestion
during a 3-h treadmill run attenuated plasma concen-
trations of IL-1ra, IL-6 and IL-10, as well as muscle
gene expression for IL-6 and IL-8 (Nieman et al.,
2003). The 3-h treadmill run in both the carbohydrate
and placebo trials induced gene expression within the
muscle for two primary pro-inflammatory cytokines,
IL-1b and TNF-a. Interleukin-6 and IL-8, which are
often considered to be components of the secondary
inflammatory cascade, were also expressed, but to a
lesser extent in the carbohydrate trial. Anti-inflamma-
tory indicators, including plasma IL-1ra , IL-10 and
cortisol, were also decreased with carbohydrate feeding.
These results suggest that carbohydrate ingestion
attenuates the secondary but not the primary pro-
inflammatory cascade, decreasing the need for immune
responses related to anti-inflammatio n. However, when
carbohydrate is ingested duri ng prolonged exercise, the
release of IL-6 from working muscles can be totally
inhibited (Febbraio et al., 2003) and the exercise-
induced expression of several metabolic genes are
blunted comp ared with exercise in th e fasted sta te
(Pilegaard et al., 2002). Infusion of IL-6 in humans
stimulates cortisol secretion (with plasma cortisol
reaching similar values to those observed during
exercise and with a similar time-course) and induces
lipolysis as well as eliciti ng a strong anti-inflammatory
response (Pedersen et al., 2003; Starkie et al., 2003).
Thus, although carbohydrate ingestion during exercise
attenuates the IL-6 response and so reduces the
magnitude of the cortisol-induced lymphocytopaenia,
it will, at the same time, inhibit lipolysis, reduce the
anti-inflammatory effects of exercise and attenuate the
expression of several metabolic genes in the exercised
muscle. In other words, it is possible that carbohydrate
ingestion during exercise sessions could limit adapta-
tion to training. However, it can also be argued that
carbohydrate intake during training allows the athlete to
work harder and for longer and as yet there is no
evidence that physiological and performance adapta-
tions are impaired by carbohydrate intake during
training sessions. Further research is needed to
determine how nutrient intake might affect the tran-
scriptional regulation of metabolic genes in skeletal
muscle and what, if any, consequences this has for
training adaptation.
While carbohydrate feeding during exercise appears
to be effective in minimizing some of the immune
perturbations associated with prolonged continuous
strenuous exercise, it appears less effective for less
demanding exercise of an intermittent nature, for
example football (Bishop et al., 1999b) or rowing
(Nieman et al., 1999) training. It is also apparent that
carbohydrate feeding is not as effective in reducing
immune cell trafficking and functional depression when
continuous prolonged exercise is performed to the point
of fatigue (Bishop et al., 2001a). Pre-exercise feeding of
carbohydrate does not seem to be very effective in
limiting exercise-induced leucocytosis or depression of
119Exercise, nutrition and immune function
neutrophil function (Lancaster et al., 2001). Also, there
is no evidence that the beneficial effect of feeding
carbohydrate on immune responses to exercise trans-
lates into a reduced incidence of URTI after prolonged
exercise such as marathon races. Although a trend for a
beneficial effect of carbohydrate ingestion on post-race
URTI was reported in a study of 98 marathon runners
(Nieman et al., 2002b), this did not achieve statistical
significance and larger-scale studies are needed to
investigate this possibility.
Fluid intake during exercise
The consumption of beverages during exercise not
only helps prevent dehydration (which is associated
with an increased stress hormone response) but also
helps to maintain saliva flow rate during exercise.
Saliva contains several proteins with antimicrobial
properties, including immunoglobulin-A (IgA), lyso-
zyme and a-amylase. Saliva secretion usually falls
during exercise. Regul ar fluid intake during exercise is
reported to prevent this effect and a recent study
(Bishop et al., 2000a) has confirmed that regular
consumption of lemon- flavoured carbohydrate-con-
taining drinks helps to maintain saliva flow rate and
hence saliva IgA secretion rate during prolonged
exercise compared with a restricted fluid intake regi-
men.
Glutamine supplements
Glutamine is the most abundant free amino acid in
human muscle and plasma and is utilized at very high
rates by leucocytes to provide energy and optimal
conditions for nucleotide biosynthesis (Ardawi and
Newsholme, 1983, 1994). Indeed, glutamine is con-
sidered important, if not essential, to lymphocytes and
other rapidly dividing cells, including th e gut mucosa
and bone marrow stem cells. Prolonged exercise is
associated with a fall in the plasma concentration of
glutamine and it has been hypothesized that such a
decrease could impair immune function (Parry-Billings
et al., 1992; Castell, 2003).
It has been suggested that exogenous provision of
glutamine supplements may be beneficial by maintain-
ing the plasma glutamine concentration and hence
preventing the impairment of immune function after
prolonged exercise. Castell et al. (1996) have provided
the only prophylactic evidence that an oral glutamine
supplement (5 g in 330 ml water) consumed immedi-
ately after and 2 h after a marathon reduces the
incidence of URTI (in the 7 days after the race).
However, it is unlikely that this amount of glutamine
supplementation could actually have prevented the
post-exercise fall in the plasma glutamine concentra-
tion. Provision of glutamine has been shown to have a
beneficial effect on gut function, morbidity and
mortality and on some aspects of immune cell function
in clinical studies of diseased or traumatized patients.
However, several recent studies that have investigated
the effect of large amounts of glutamine supplementa-
tion during and after exerc ise on the exercise-induced
fall in lymphokine-activated killer cell activity, neutro-
phil function and mitogen-stimulated lymphocyte pro-
liferation have failed to find any beneficial effect (Rohde
et al., 1998; Walsh et al., 2000). Very recently, Bassit et
al. (2002) reported that supplementation of branched-
chain amino acids (BCAA) (6 g × day
71
for 15 days)
before a triathlon or 30-km run prevented the approxi-
mately 40% decline in mitogen-stimulated lymphocyte
proliferation observed in the placebo control group after
exercise. Supplementation with BCAA prevented the
post-exercise fall in plasma glutamine concentration
and was also associated with increased lymphocyte IL-2
and IFN-g production. More research is needed to
resolve these conflicting findings of BCAA and gluta-
mine supplementation on the immune responses to
exercise.
Dietary immunostimulants
b-Carotene (pro-vitamin A) acts both as an antiox-
idant and an immunostimulant, increasing the number
of T-helper cells in healthy humans (Alexander et al.,
1985) and stimulating natural killer cell activity when
added in vitro to human lymphatic cultures (Watson et
al., 1991). Furthermore, elderly men who had been
taking b-carotene supplements (50 m g on alternate
days) for 10–12 years were reported to have signifi-
cantly higher natura l killer cell activity than elderly
men on placebo (Santos et al., 1996). However,
supplementing runners with b-carotene was found to
have an insignificant effect on the incidence of URTI
after a 90-km ultramarathon (Peters et al., 1992).
Furthermore, intakes of supplements in excess of
7mg× day
71
are not advised because of a possible
increased risk of lung cancer in smokers (Food
Standards Agency, 2003).
Several herbal preparations are reputed to have
immunostimulatory effects and consumption of pro-
ducts containing Echinacea purpurea is widespread
among athletes. However, few controlled studies have
examined the effects of dietary immunostimulants on
exercise-induced changes in immune function. In one
recent double-bli nd, placebo-controlled study, the
effect of a daily oral pre-treatment for 28 days with
pressed juice of E. pur purea was investigated in 42
triathletes before and after a sprint triathlon (Berg et al.,
1998). A sub-group of athletes was also treated with
120 Gleeson et al.
magnesium as a reference for supplementation with a
micronutrient important for opt imal muscular function.
The most important finding was that during the 28-day
pre-treatment period, none of the athletes in the
Echinacea group fell ill, compared with three individuals
in the magnesium group and four in the placebo group
who became ill. Pre-treatment with Echinacea appeared
to reduce the release of soluble IL-2 receptor before and
after the race and increased the exercise-induced rise in
IL-6.
Several experiments have demonstrated that E.
purpurea extracts do indeed demonstrate significant
immunomodulatory activities. Among the many phar-
macological properties reported, macrophage activa-
tion has been demonstrated most convincingly
(Stimpel et al., 1984; Steinmuller et al., 1993).
Phagocytotic indices and macrophage-derived cytokine
concentrations have been shown to be Echinacea-
responsive in a variety of assays and activation of
polymorphonuclear leucocytes and natural killer cells
has also been reasonably demonstrated (Barrett,
2003). Changes in the numbers and activities of T-
and B-lymphocytes have been reported, but are less
certain. Despite this cellular evidence of immuno-
stimulation, the pathways leading to enhanced resis-
tance to infectious disease have not been desc ribed
adequately. Several dozen human experiments, includ-
ing a number of blind randomized trials, have reported
health benefits. The most robust data come from trials
testing E. purpurea extracts in the treatment for acute
URTI. Although suggestive of modest benefit, these
trials are limited both in size and in methodological
quality. In a recent randomized, double-blind, place-
bo-controlled trial, administering unrefined Echinacea
at the onset of symptoms of URTI in 148 college
students did not provide any detectable benefit or
harm compared with placebo (Barrett et al., 2002).
Hence, while there is a great deal of moderately good-
quality scientific data on Echinacea , its effectiveness in
treating illness or in enhancing human health has not
yet been proven beyond a reasonable doubt.
Probiotics are food supplements that contain
‘friendly’ gut bacteria. There is now a reasonable body
of evidence that regular consumption of probiotics can
modify the population of the gut microflora and
influence immune function (Calder et al., 2002). Some
studies have shown that probiotic intake can improve
rates of recovery from rotavirus diarrhoea, increase
resistance to enteric pathogens and promote anti-
tumour activity; there is even some evidence that
probiotics may be effective in alleviating some allergic
and respiratory disorders in young children (see Kopp-
Hoolihan, 2001, for a review). However, to date, there
are no published studies of the effectiveness of probiotic
use in athletes.
Summary and recommendations
1. Both heavy exercise and nutrition exert separate
influences on immune function; these influences
appear to be stronger when exercise stress and poor
nutrition act synergistically.
2. Dietary deficiencies of energy, protein and specific
micronutrients are associated with depressed im-
mune function and increased susceptibility to
infection. An adequate intake of iron, zinc and
vitamins A, E, B6 and B12 is particularly important
for the maintenance of immune function. Athletes
need to avoid micronutrient deficiencies.
3. To maintain immune function, athletes should eat
a well-balanced diet sufficient to meet their energy
requirements. This should ensure an adequate
intake of protein and micronutrients.
4. For athletes on energy-restricted diets, vitamin
supplements are desirable.
5. An athlete exercising in a carbohydrate-depleted
state experiences larger incre ases in circulating
stress hormones and a greater perturbation of
several immune function indices.
6. Consumption of carbohydrate (30–60 g × h
71
)in
drinks during prolonged exercise is recommended,
as this practice appears to attenuate some of the
immunosuppressive effects of prolonged exercise.
However, the clinical significance of this has to be
determined.
7. Consumption of megadoses of vitamins and miner-
als is not advised. Excess intakes of some micro-
nutrients (e.g. iron, zinc, vitamin E) can impair
immune function.
8. High fat diets suppress some aspects of immune
cell function.
9. Convincing evidenc e that so-called ‘immune-boost-
ing’ supplements, such as high doses of antioxidant
vitamins, glutamine, zinc, probiotics and Echinacea,
prevent exercise-induced immune impairment is
currently lacking. Current evidence regarding the
efficacy of Echinacea extracts, zinc lozenges and
probiotics in preventing or treating common infec-
tions is limited and there is insufficient evidence to
recommend these supplements at this time.
10. It is still debatable as to whether antioxidant
supplements are required or are desirable for
athletes. There is conflicting evidence of the effects
of high-dose vitamin C in reducing the post-
exercise incidence of URTI and this practice has
not been shown to prevent exercise-induced
immune impairment.
11. Glutamine supplementation is beneficial to im-
mune function in the clinical setting but has not
proved effective in abolishi ng the post-exercise
impairment of immune cell function.
121Exercise, nutrition and immune function
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