Glutamine Metabolism: Nutritional and Clinical Signicance

Assessment of the Safety of Glutamine and Other Amino Acids

1
Peter J. Garlick
State University of New York at Stony Brook, Stony Brook, NY 11794-8191
ABSTRACT Glutamine is used to supplement intravenous and enteral feeding. Although there have been many
human studies of its efcacy, there have been very few studies with safety as a primary goal. This article analyzes
the literature on the safety of glutamine and also examines the available information on high intakes of total protein
and other amino acids, so that additional indicators of potentially adverse effects can be suggested. Four studies
that specically addressed glutamine safety were identied, from which it was concluded that glutamine is safe in
adults and in preterm infants. However, the published studies of safety have not fully taken account of chronic
consumption by healthy subjects of all age groups. To help identify potential undetected hazards of glutamine
intake, the literature on adverse effects of high dietary intake of protein and other amino acids was examined. High
protein is reputed to cause nausea, vomiting and ultimately death in adults, and has been shown to result in
neurological damage in preterm infants. Individual amino acids cause a variety of adverse effects, some of them
potentially fatal, but neurological effects were the most frequently observed. Because glutamine is metabolized to
glutamate and ammonia, both of which have neurological effects, psychological and behavioral testing may be
especially important. J. Nutr. 131: 2556S2561S, 2001.
KEY WORDS: protein intake glutamine toxicity
During the last decade, there has been increasing research
interest in the amino acid, glutamine, particularly in regard to
its potential clinical use in intravenous and enteral feeding. To
date there have been hundreds of human studies of the efcacy
of glutamine, with few if any reported adverse effects. A review
by Sacks (1999) concluded that glutamine is safe, with the
possible exception of specic patient groups such as those with
liver or kidney disease and preterm neonates. However, there
have been very few studies with safety as a primary goal.
Moreover, in those studies that have investigated safety, the
treatments were of relatively short duration; thus, information
on the possible adverse effects of glutamine over periods longer
than 1 mo is lacking. This may be important because it is
becoming increasingly likely that in various groups of the
population, enhanced glutamine intake [e.g., in total paren-
teral nutrition (TPN)
2
] might occur for extended periods of
time. Of potential importance is the burgeoning use of dietary
supplements in the general population, without any medical
supervision.
This article analyzes the available literature on the safety of
glutamine to determine whether the currently used indicators
of adverse effects are adequate for chronic consumption by the
general population, as well as by medically supervised patients.
The available information on high intakes of total protein and
other amino acids will be examined so that additional indica-
tors of potentially adverse effects can be suggested.
Published studies of glutamine safety
A literature search revealed only four studies that speci-
cally addressed glutamine safety. By far the most comprehen-
sive is that of Ziegler et al. (1990), who performed ve separate
experiments to examine safety under different circumstances,
as follows: 1) six volunteers given oral glutamine at three
different doses (0, 0.1, 0.3 g/kg), and monitored for 4 h; 2)
nine volunteers, given intravenous infusions of glutamine at
three doses [0, 0.0125, 0.025 g/(kg h)] for 4 h; 3) seven
volunteers given TPN plus glutamine at three doses [0, 0.285,
0.570 g/(kg d)] over 5 d; 4) eight bone marrow transplant
patients given glutamine at 3 doses (0, 0.285, 0.570 g/(kg d)]
over 30 2 d; and 5) a pharmacokinetic analysis performed
over 4 h in three volunteers. Measurements that were used to
assess possible toxicity were as follows: blood glutamine, glu-
tamate, other amino acids, glucose, insulin, glucagon and
growth hormone; urinary creatinine, ammonia, urea and total
nitrogen; standard clinical chemistry, complete blood counts,
mental status, vital signs, temperature and clinical and subjec-
tive evidence of toxicity. However, these careful studies, in-
cluding treatments between 4 h and 30 d, doses of glutamine
up to 0.57 g/(kg d) (40 g/d) and both healthy volunteers
and sick patients, were not able to detect any sign of adverse
effects.
A later study by Hornsby-Lewis et al. (1994) examined the
1
Presented at the International Symposium on Glutamine, October 23,
2000, Sonesta Beach, Bermuda. The symposium was sponsored by Ajinomoto
USA, Incorporated. The proceedings are published as a supplement to The
Journal of Nutrition. Editors for the symposium publication were Douglas W.
Wilmore, the Department of Surgery, Brigham and Womens Hospital, Harvard
Medical School and John L. Rombeau, the Department of Surgery, the University
of Pennsylvania School of Medicine.
2
Abbreviations used: DRI, Dietary Reference Intakes; EAR, Estimated Aver-
age Requirement; GPT, glutamic pyruvate transaminase; LOAEL, Lowest Ob-
served Adverse Effect Level; NOAEL, No Observed Adverse Effect Level, RDA,
Recommended Dietary Allowance; TPN, total parenteral nutrition; UL, Tolerable
Upper Level.
0022-3166/01 $3.00 2001 American Society for Nutritional Sciences.
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effects of glutamine supplementation in Home TPN patients.
Seven patients were monitored for 4 wk while receiving TPN
plus glutamine at a dose of 0.285 g/(kg d). To monitor safety,
the following were measured: blood ammonia, bilirubin, urea
nitrogen, creatinine, glucose, amino acids, complete cell
count, serum glutamic oxaloacetic transaminase, glutamic
pyruvate transaminase (GPT), alkaline phosphatase and lactic
acid dehydrogenase. Of note was the withdrawal from the
study of two patients who developed high concentrations of
liver enzymes; these resolved, however, after discontinuing
treatment. No other adverse effects were observed, but the
authors noted their concern regarding the possibility of liver
toxicity. The elevated liver enzymes might, however, have
been a complication of intravenous nutrition, rather than of
the glutamine per se, because no control group without sup-
plementation was studied in parallel.
Jiang et al. (1999) studied the effect of the dipeptide,
alanyl-glutamine, on clinical safety in a randomized, double-
blind, controlled study of 120 postoperative patients. Pa-
tients (n 60) were given normal TPN; the other 60 were
given isonitrogenous TPN, including alanyl-glutamine [0.5 g/
(kg d)] for 6 d. They measured hemoglobin, white blood cell
count (plus differential), platelets, blood glutamine, sodium,
potassium, chloride, GPT, alkaline phosphatase, glucose, cho-
lesterol, urea, creatinine, bilirubin, triglycerides, bicarbonate,
urine volume, N balance and infection rate. The comparison
between control and glutamine-treated patients revealed no
indications of adverse effects.
All of the above studies were performed in adult subjects.
Lacey et al. (1996), however, investigated the effects of glu-
tamine-supplemented parenteral nutrition [20% of amino ac-
ids, equivalent to 0.4 g/(kg d) glutamine maximum] for 15 d
in 44 preterm neonates, who might possibly be more sensitive
to adverse effects than adults. Plasma glutamine level rose by
50%, but glutamate and ammonia remained within the normal
range. On the basis of the measurements of plasma ammonia
and glutamate and the absence of clinical signs of neurotox-
icity, it was concluded that glutamine at this dose is safe in
preterm infants.
To summarize, there have been very few indications of
adverse effects in the studies described above that explicitly
investigated safety. Moreover, despite the large number of
published investigations in which glutamine has been admin-
istered to patients or healthy subjects, no adverse effects have
been reported. However, the published studies of toxicity have
not fully taken account of the following:
1) Both acute and chronic treatment must be investigated.
As pointed out above, there is a possibility that glutamine
supplements may be consumed by healthy people for extended
periods of time, but there is no information on chronic con-
sumption.
2) Most of the literature at present involves people who are
ill and under medical supervision, but supplement usage by
healthy subjects should be investigated further. Moreover, the
possibility of specic susceptibilities has to be considered. For
example, children with Crohns disease were given a polymeric
diet containing 4 or 42% [0.1 or 1.0 g/(kg d)] of amino
acids as glutamine (Akobeng et al. 2000). Because of intoler-
ance to the glutamine-supplemented diet, two patients were
withdrawn. Furthermore, in the remainder, there was signi-
cantly less improvement in the Pediatric Crohns Disease
Activity Index than in the control group. A similar observa-
tion was made in rats with experimental colitis induced by
trinitrobenzenesulfonic acid. Glutamine supplementation at
12% of amino acids was without effect, but glutamine at 24%
resulted in signicantly more damage to the colon (Shinozaki
et al. 1997).
3) The limited literature on safety does not include studies
employing doses higher than 0.3 g/kg orally as a single dose, or
0.57 g/(kg d) given intravenously over 30 d. There have been
some brief reports in which larger doses than those in the
studies described above (2040 g/d) have been given. For
example, 24 intensive care patients were randomized into four
groups receiving 0, 0.28, 0.56 and 0.86 g/(kg d) of glutamine
intravenously for 3 d (Tjader et al. 2000). In other studies, six
children with cystic brosis were given oral glutamine [0.7
g/(kg d)] for 4 wk (Hayes et al. 2000), and eight very-low-
birth-weight infants were given enteral supplements of glu-
tamine [0.6 g/(kg d); Poulet-Young et al. 2000]. Although no
information about safety was presented in these studies, no
adverse effects were reported, suggesting that higher doses
than those given in the more detailed descriptions of safety
studies may be tolerated, but this requires further investiga-
tion.
4) Specic age groups. The very young or the elderly might
have specic susceptibilities. Although the study in preterm
infants described above (Lacey et al. 1996) showed no ill
effects at a dose of 0.4 g/(kg d)g/kg/d, this is lower than the
doses used in a number of studies in adults. In another study,
very-low-birth-weight infants were given enteral supplements
of glutamine for 17 d [0.6 g/(kg d); Poulet-Young et al. 2000]
and no adverse affects were noted. This suggests that doses
higher than 0.4 g/(kg d) may be safe, but this brief report
contained no safety evaluation. No information is available in
the elderly; it is possible that with high doses they might not
be able to process the increased nitrogen load through the liver
and kidney.
Because there are still areas of uncertainty about the safety
of glutamine, it is therefore appropriate that the investigation
of potentially adverse effects should continue. The remainder
of this article will therefore examine the approach that has
been used to assess the toxicity of nutrients, and specically
the evidence of adverse effects of high intakes of protein and
other amino acids, as a guide for future studies to fully assess
the safety of glutamine.
Evaluating the intake of a nutrient
The Food and Nutrition Board of the Institute of Medicine
(USA) provides assessments of the intake of specic nutrients
required to maintain health, which include a recommendation
for the maximum amount to be consumed. Intake for healthy
individuals in a particular life stage or group is evaluated in
terms of four Dietary Reference Intakes (DRI) (Institute of
Medicine 2000), which are used to dene a range of intakes
that is consistent with optimum health. At the lower end of
the scale, the RDA (Recommended Dietary Allowance) and
EAR (Estimated Average Requirement) dene the intake be-
low which deciency is likely to occur, and at the high end of
the scale, the UL (Tolerable Upper Level) denes the intake
above which adverse or toxic effects are likely to occur. The
last-mentioned DRI, the UL, is the one that is appropriate for
assessing the safety of glutamine. The process for determining
the UL involves risk assessment, which is undertaken in four
steps as follows: 1) hazard identication, to reveal specic
adverse effects, 2) dose response, to identify the UL, 3) the
exposure, to characterize the population distribution of dietary
intakes, and 4) risk characterization, to identify the proportion
of the population at risk.
The risk assessment process must take account of the spe-
cic populations under consideration. For example, risk is
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likely to vary with age and with route of administration (i.e.,
oral vs. intravenous intake). It is also generally assumed that
the risk occurs only at or above a certain threshold level, so that
lower levels are associated with no risk. For the purposes of
quantifying the risk, two further parameters are used, i.e., the
Lowest Observed Adverse Effect Level (LOAEL) and the No
Observed Adverse Effect Level (NOAEL). Ideally, both of these
values are needed to set a UL with condence, but often only one
of these can be determined from the literature; thus, the deriva-
tion of the UL value must be approached with more caution.
Application of the DRI process to glutamine does not imme-
diately give very useful insights. Because glutamine is not an
indispensable amino acid, there is no clear EAR and RDA.
Moreover, the evidence suggesting benets of glutamine supple-
ments was obtained at doses well above the normal dietary intake.
In particular, there is an absence of data from which to identify a
specic hazard or hazards. The studies to date have shown no
effects of glutamine (NOAEL) for a range of clinical measure-
ments, including the following: blood hemoglobin, white blood
cell counts (including differential), platelets, plasma/serumNa, K,
Cl, bicarbonate, NH
4

, GPT, glutamate oxaloacetate transami-

nase, alkaline phosphatase, lactate dehydrogenase, glucose, cho-
lesterol, triglycerides, urea, creatinine, bilirubin, total protein,
albumin, insulin, glucagon, growth hormone, glutamine, gluta-
mate, amino acid prole, mental status, attention span, infection
rate (blood cultures), temperature, blood pressure, pulse and res-
piration. Although none of these indices have suggested that
glutamine has toxic effects, there remains the possibility that a
real hazard has not been identied, and that the wrong measure-
ments have been made. The question posed in this article, there-
fore, is whether we can use evidence derived from high dietary
intakes of protein or of other amino acids, some of which are
known to be toxic at high levels, to help select indicators of
toxicity of glutamine.
High protein intake
There is evidence from historical records that very high in-
takes of protein (200 g/d), might be toxic, and that consump-
tion of more than 40% of the dietary energy as protein results
in nausea and diarrhea within 3 d and to death in a few weeks;
this condition is known as rabbit starvation and refers to the
very low fat content of rabbit meat (Speth and Spielmann 1983).
However, it is possible to remain healthy while living on an
exclusively meat diet, providing it contains enough fat to main-
tain a protein intake that is 40% of energy, and preferably in
the range 1525% (Lieb 1929, McClellan and DuBois 1931). It
has been suggested that the reason for this toxicity is the limited
capacity of the liver to synthesize urea. It was shown by Rudman
et al. (1973) that as the protein content of meals was increased,
the rate of urea synthesis reached a maximum, so that with meals
containing more than this maximum, the plasma amino acid and
ammonia levels increased, and the duration of maximum urea
synthesis was prolonged. The maximum rate corresponded to a
protein intake of 230 g/d for a 70-kg person, or 40%of dietary
energy. It seems unlikely that glutamine would be taken in
sufciently large amounts to exceed this limit for urea synthesis.
There is more direct evidence of protein toxicity in preterm
neonates. Goldman et al. (1969) studied 304 preterm infants
given diets containing either 3.03.6 or 6.07.2 g/(kg d) of
cows milk protein. The higher protein intake was associated
with more fever, lethargy and poor feeding, as well as higher
plasma protein levels and less edema than the lower protein
group. A follow-up study of these children for physical and
psychological testing was made after 3 and 6 y (Goldman et al.
1971 and 1974). The results showed that at both 3 and 6 y,
there was an excess incidence of strabismus and low IQ scores
in the children with lowest birth weight who had been fed the
high protein diet.
High protein diets have also been suggested to be associated
with a variety of other pathological conditions. It is well
recognized that urinary calcium excretion increases in propor-
tion to the protein content of the diet (Linkswiler et al. 1981).
However, it has been suggested that there is little risk of bone
loss because calcium intake is usually increased with higher
protein diets, and bone loss does not occur if calcium intake is
adequate (Heaney 1998). There is also the possibility that
calcium oxalate stone formation in the kidney might be in-
creased. Although there have been several studies that support
this hypothesis, the only long-term prospective trial of chronic
protein restriction (4.5 y) on stone formation in patients who
were newly diagnosed with calcium stones did not conrm the
hypothesis (Hiatt et al. 1996). In addition, high protein in-
takes have also been implicated in the progression of renal
disease. However, although it is standard practice to lower the
protein intake in patients diagnosed with renal disease to delay
its progression, it is not now believed that the intake of protein
has any inuence on the incidence of renal disease in healthy
people (Walser 1993).
Effects of high intakes of individual amino acids: lessons to
be learned regarding glutamine safety
Table 1 summarizes reported adverse effects and some met-
abolic products of individual amino acids given to animals or
humans. From this list, a number of factors that are of rele-
vance for determining the toxicity of glutamine become ap-
parent.
Direct effects. For several amino acids, it is probable that
adverse effects are direct consequences of the elevated con-
centration in blood or target tissue, e.g., glutamate (Takasaki
et al. 1979) or phenylalanine (Batshaw et al. 1981). The
measurements of plasma glutamine concentrations in the stud-
ies described above, showing little change from normal, there-
fore suggest a low chance of adverse effects.
Metabolic end products. Products of metabolism are im-
portant because these might in themselves be toxic at in-
creased levels (e.g., branched-chain keto acids from branched-
chain amino acids). Alternatively, a large increase in the
concentration of a product might provide an indication that
the normal metabolism of that amino acid was overloaded.
However, studies of high intakes of glutamine have shown that
concentrations of ammonia and glutamate are not much in-
creased (see above).
Competition/antagonism. It is recognized that some
amino acids given as supplements inhibit growth in animals,
possibly by interfering with the metabolism of other amino
acids by competing for transport or for common pathways of
metabolism (Sauberlich 1961) e.g., lysine/arginine antago-
nism, because these amino acids share a transporter for cellular
uptake. Measurement of the amino acid prole in plasma
and/or tissues would enable competition for transport to be
detected. Glutamine does not appear to alter the plasma
amino acid prole to any extent, which is consistent with the
biochemical data showing that glutamine has a specic trans-
porter that is not shared with any other amino acid.
Effects on metabolism. An amino acid supplement could
cause alterations of metabolism of both related and unrelated
systems. For example, arginine has been shown to cause hy-
potension, through its conversion to NO (Petros et al. 1991),
which acts directly on blood vessels (closely related), whereas
high tyrosine intake has been reported to cause eye and skin
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lesions (Goldsmith and Reed 1976), which are more distantly
related. For glutamine, closely related systems that might be
monitored are gluconeogenesis and blood glucose; increases in
those systems could possibly lead to diabetes in the long term.
In addition, the possibility of effects on more distantly related
systems, e.g., cardiovascular disease (plasma cholesterol and
triglycerides) and immune function, should not be ignored
because they have been shown to be altered by high intakes of
other amino acids.
Hormone secretion. A variety of amino acids have well-
described effects on the secretion of specic hormones, when
given in large quantities (e.g., leucine and arginine stimulate
secretion of insulin and growth hormone, respectively). The
consequences of this might have short-term [e.g., leucine-
induced hypoglycemia (Table 1)], or long-term effects (e.g.,
the potential for activating cell division and thus promoting
malignancy). However, glutamine administration has not been
demonstrated to result in elevated secretion of any hormone.
Neurological effects. Of the 15 amino acids represented in
Table 1, 9 are associated with neurological or neurotoxic
effects, as is high protein intake. Glutamine degradation yields
glutamate and ammonia, both of which are known to be
neurotoxic, although glutamate has only been shown to be
neurotoxic in animal studies (Airoldi et al. 1979). However, in
those studies of glutamine safety in which neurological symp-
toms were assessed, no signs of adverse effects were detected
(see above).
Electrolyte disturbances. A large dose of a single amino
acid can give rise to electrolyte disturbances, such as the
hyponatremia resulting from glycine administration (Table 1)
and the acidosis and hyperkalemia resulting from consumption
of arginine hydrochloride (Table 1). Moreover, an amino acid
given in free form without food might be absorbed very quickly
and have osmotic consequences. However, glutamine admin-
istration does not seem to result in any pronounced effects on
electrolyte concentrations.
Effects due to impurities. Although it is generally be-
lieved that the outbreak of eosinophilia-myalgia syndrome in
subjects given tryptophan was caused by an impurity in the
product of a single supplier, the evidence is not denitive
(Young 1991). Although glutamine is stable as a dry solid, it is
known to be unstable in solution, resulting in a toxic product
(Furst et al. 1997). However, such problems can be avoided by
preparing solutions freshly from solid or by administering in
the form of a dipeptide, in which form it is completely stable
(Furst et al. 1990).
Immunity. Some amino acids, including glutamine, have
been shown to stimulate aspects of the immune system, e.g.,
arginine and ornithine (Barbul 1986). However, the studies of
glutamine safety described above, including only white blood
cell counts (including differential), infection rate (blood cul-
tures) and body temperature, have been of short duration.
Much longer-term studies, including more specialized methods
of assessment (e.g., delayed hypersensitivity, activation mark-
ers, response to vaccination) are required to show whether
these effects persist with chronic consumption.
Clinical and physiologic signs. Arginine has been shown
to cause diarrhea in some subjects (Barbul 1986) and gluta-
mate is believed by some to cause Chinese Restaurant Syn-
drome (Geha et al. 2000). There appear to be no similar
effects associated with glutamine, and vital signs have been
shown to be unaltered (see above).
Conclusions and suggestions for future studies to conrm
the safety of glutamine
From the above discussion, the following conclusions can
be made:
1) A number of individual amino acids show characteristic
TABLE 1
Some metabolic products and documented adverse effects of individual or groups of amino acids
a
Amino acid Metabolism Reported adverse effect
Alanine Urea, lactate, glucose Hyperammonemia
1
Arginine Urea, ornithine, citrulline, NO,
polyamines
Hypotension,
2
tumor stimulation,
3
acidosis,
4
hyperkalemia,
5,6
cardiac arrest
7
Aspartate Urea, asparagine, glucose Neurotoxicity
8
Cysteine SO
4
2
, glutamate Hypercholesterolemia,
9,10,11
fatty liver,
11
neurotoxicity
8
Glutamate Urea, glutamine, glucose Neurotoxicity,
8
Chinese Restaurant Syndrome
12
Glycine Serine, NH
4

Neurotoxicity,
13
hypernatremia
14
Histidine Histamine, formiminoglutamate,
urocanate, glutamate
Hypercholesterolemia
15,16
Isoleucine Glutamine, alanine ketomethylvalerate Mental retardation
17
Leucine Glutamine, alanine, ketoisocapriate Hypoglycemia,
18,19
mental retardation,
17
hypovalinemia,
20
hypoisoleucinemia
20
Lysine Saccharopine, aminoadipate Arginine antagonism,
21
tubulointerstitial nephritis
22
Methionine Cysteine, homocysteine, cystathionine Hyperhomocysteinemia,
23
serum folate deciency
24
Phenylalanine Tyrosine, phenylpyruvate Mental retardation,
25
exacerbates tardive diskinesia in schizophrenics
26
Tryptophan Serotonin, melatonin Eosinophilia-myalgia syndrome,
27
serotonin syndrome
27
Tyrosine Tyramine, catecholamines, thyroid
hormones, parahydroxyphenylpyruvate
Eye and skin lesions,
28,29
mental retardation
28
Valine Glutamine, alanine, ketoisovalerate Mental retardation
17
a
Data are taken from studies in humans, except those marked

. Studies of arginine used arginine hydrochloride except the reference
3
which
used the free base. Mental retardation is a result of specic inborn errors of metabolism causing high plasma concentrations of branched-chain amino
acids, phenylalanine or tyrosine.
References:
1
Chowet al. (1976);
2
Petros et al. (1991);
3
Park et al. (1992);
4
Barbul (1986);
5
Bushinsky and Gennari (1978);
6
Massara et al. (1981);
7
Gerard and Luisiri (1997);
8
Olney and Ho (1970);
9
Rukaj and Se rougne (1983);
10
Aoyama et al. (1999);
11
Aoyama et al. (1992);
12
Geha et
al. (2000);
13
DeGroot and Everts (1982);
14
Santosham et al. (1986);
15
Harvey et al. (1981);
16
Solomon and Gieson (1978);
17
Elsas (2000);
18
Bicknell and Crome (1969);
19
Snyder and Robinson (1967);
20
May et al. (1991);
21
Flodin (1997);
22
Lo et al. (1996);
23
Boers et al. (1983);
24
Connor et al. (1978);
25
Batshaw et al. (1981);
26
Mosnik et al. (1997);
27
Young (1991);
28
Goldsmith and Reed (1976);
29
Datta and Ghosh (1977).
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patterns of toxicity when given in excess, whereas no adverse
effects of glutamine have been demonstrated when given in
doses of 5060 g/d. However, this assessment, made in short-
term studies in hospital patients, may not be appropriate for
chronic supplementation in healthy subjects of all age groups.
2) The possibility of cancer has been dismissed previously
because studies in animals have shown that glutamine supports
the host metabolism in preference to the tumor (Klimburg and
McClellan 1996). However, by analogy with arginine, for
which supplements have been shown to either inhibit or
stimulate the tumor growth, depending on the tumor type and
immunogenicity (Levy et al. 1954, Reynolds et al. 1988),
continued research in this area is suggested.
3) A number of short-term studies have demonstrated ben-
ecial effects of glutamine on the immune system, but it is not
known whether there may be detrimental effects with chronic
usage. There is a need for more specialized methods for assess-
ing immune status to answer this question.
4) Modication of intermediary metabolism by glutamine
could potentially lead to the development of metabolic dis-
eases such as diabetes or coronary artery disease. These could
be monitored by such measurements as plasma glucose or
homocysteine, or by isotopic tracer studies of glucose or li-
poprotein kinetics.
5) Neurological effects have been demonstrated for gluta-
mate and ammonia, the two products of glutamine degrada-
tion, as well as for a number of other amino acids and total
protein. Therefore, psychological and behavioral testing is
especially important.
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SUPPLEMENT 2560S

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GLUTAMINE SAFETY 2561S

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