Sports-Pictorial.com
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GLUTAMINE:
A
CONDITIONALLY
ESSENTIAL
AMINO
ACID
WITH
REMARKABLE
IMPLICATIONS
FOR
HEALTH
AND
PERFORMANCE
Bill
Misner
Ph.D.*
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The
human
body
replenishes
its
glutamine
needs
from
pre-glutamine
amino
acid
substrates
in
the
muscles
and
lungs.
It
also
may
be
replenished
by
glutamine-rich
foods
or
supplements
when
the
body
fails
to
keep
up
with
the
supply
and
demand
process.
Deficiencies
in
glutamine
may
occur
as
a
result
of
trauma,
cancer,
and
extreme
endurance
exercise
training.
Since
it
is
the
main
fuel
source
for
miles
and
miles
of
intestinal
enterocytes,
millions
of
specific
immune
cells
such
as
lymphocytes,
macrophages,
and
fibroblasts,
it
is
scavenged
from
the
blood
stream
circulating
glutamine
to
"feed"
these
cells.
Glutamine
is
recruited
for
the
Krebs
Cycle
to
produce
energy
[see
figure
1].
How
then
is
glutamine
catabolized
in
the
energy
cycle?
Mitochondria
enzymatically
manufactures
glutamine
from
other
amino
acids
[especially
BCAA's],
for
transfer
of
energy
through
ATP
end
product
within
the
Krebs
cycle.
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GLUTAMINE
DEPLETION
CYCLE*
[Figure
1]
GLUTAMINE
¯
GLUTAMINASE
Þ
NH4
[Nitrogen
+]
¯
GLUTAMATE
¯
TRANSAMINASE
Þ
PYRUVATE
+
ALANINE
¯
ALPHA-KETOGLUTARATE
¯
ATP
Þ
KREBS
CYCLE
¯
ENERGY!
*
KEY:
Enzymes
colored
in
green.
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Glutamine
is
the
most
abundant
free
amino
acid
in
human
muscle
and
plasma
and
is
utilized
at
high
rates
by
rapidly
dividing
cells,
including
leucocytes,
to
provide
energy
and
optimal
conditions
for
nucleotide
biosynthesis.
As
such,
it
is
considered
to
be
essential
for
proper
immune
function.
During
various
catabolic
states
including
surgical
trauma,
infection,
starvation
and
prolonged
exercise,
glutamine
homeostasis
is
placed
under
stress.
Heavy
exercise
from
overtraining
or
over-reaching
depletes
both
circulating
and
muscle
stores
of
glutamine.
Glutamine
is
also
the
most
abundant
free
amino
acid
in
muscles,
generating
over
50%
of
the
muscle-bound
free
amino
acids,
with
alanine
a
distant
2nd
in
providing
10%
of
the
free
muscle
aminos.
During
and
following
exercise
60%
of
the
aminos
cannibalized
during
exercise
are
from
glutamine
and
alanine
muscle
stores.
Generally,
the
Branched
Chain
Amino
Acids[BCAA]
are
then
selectively
induced
to
replete
losses
of
glutamine
and
alanine.
This
is
why
a
number
of
energy
products[such
as
Hammer
Gel],
formulate
the
ingredient
BCAA's[Leucine,
Valine,
Isoleucine]
for
replacing
glutamine
and
alanine
expenditures
due
to
their
loss
in
exercise
and
their
dietary
exogenous
absence.
High
protein
sources
of
Glutamine
are
Hammer
Whey
Pro[1000
milligrams
glutamine/serving],
fish,
legumes,
raw
cabbage,
raw
beets,
and
other
meats.
One
of
the
problems
with
getting
enough
glutamine
is
that
heating
tends
to
destroy
it.
Repletion
then
may
depend
on
our
body's
capacity
to
replenish
it
from
other
amino
acids
or
exogenous
donation
in
supplemental
form.
Glutamine
is
the
most
abundant
amino
acid
in
the
bloodstream;
at
levels
as
high
as
35%
amino
acid
nitrogen.
The
bloodstream's
circulating
glutamine
is
tapped
when
intestinal
enterocytes
do
not
have
enough
glutamine
as
their
primary
source
of
energy.
When
the
intestinal
epithelial
cell
requirements
for
glutamine
are
lacking,
muscle
glutamine
depletion
is
an
indirect
result
as
observed
in
hospital
settings
when
critically
ill
patients
suffer
from
muscle-waisting
syndrome
[Cachexia].
The
same
syndrome
may
occur
in
ENDURANCE
ATHLETES
WHO
OVERTRAIN.
When
plasma
and/or
intestinal
glutamine
levels
fail
or
"get
behind",
bacteria,
fungus
and
other
toxins
may
translocate
across
intestinal
membranes
causing
the
body
to
be
predisposed
to
react
allergically
or
to
contract
gastric
stress,
irritable
bowel,
and
cold
or
flu-like
illness.
With
overtraining,
immune
system
failure
is
accurately
measured
proportionately
to
the
athlete's
circulating
glutamine
levels.
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Falls
in
the
plasma
glutamine
level
(normal
range
is
500
to
750
mumol/L
after
an
overnight
fast)
are
observed
following
endurance
events
and
prolonged
exercise.
These
levels
remain
unchanged
or
temporarily
elevated
after
short
term,
high
intensity
exercise.
Plasma
glutamine
has
also
been
reported
to
fall
in
patients
with
untreated
diabetes
mellitus,
in
diet-induced
metabolic
acidosis
and
in
the
recovery
period
following
high
intensity
intermittent
exercise.
Common
factors
among
all
these
stress
states
are
rises
in
the
plasma
concentrations
of
cortisol
and
glucagon
and
an
increased
tissue
requirement
for
glutamine
for
gluconeogenesis.
It
is
suggested
that
increased
gluconeogenesis
and
associated
increases
in
hepatic,
gut
and
renal
glutamine
uptake
account
for
the
depletion
of
plasma
glutamine
in
catabolic
stress
states,
including
prolonged
exercise.
The
short
term
effects
of
exercise
on
the
plasma
glutamine
level
may
be
CUMULATIVE,
since
heavy
training
has
been
shown
to
result
in
low
plasma
glutamine
levels
(<
500
mumol/L)
requiring
long
periods
of
recovery.
Furthermore,
athletes
experiencing
discomfort
from
the
overtraining
syndrome
exhibit
lower
resting
levels
of
plasma
glutamine
than
active
healthy
athletes.
Therefore,
physical
activity
directly
affects
the
availability
of
glutamine
to
the
leucocytes
and
thus
may
influence
immune
function.
The
utility
of
plasma
glutamine
level
as
a
marker
of
overtraining
has
recently
been
highlighted,
but
a
consensus
has
not
yet
been
reached
concerning
the
best
method
of
determining
the
level.
Since
injury,
infection,
nutritional
status
and
acute
exercise
can
all
influence
plasma
glutamine
level,
these
factors
must
be
controlled
and/or
taken
into
consideration
if
plasma
glutamine
is
to
prove
a
useful
marker
of
impending
overtraining.
[1]
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| Indications
of
glutamine
depletion
incidence
appear
as
a
higher
rate
of
infections
and
allergies
in
subjects
whose
endurance
training
is
extreme.
Researchers
compared
the
effects
of
exercise
at
80%
VO2max
resulting
in
fatigue
within
1
hour
with
more
prolonged
exercise
at
a
lower
work
rate
of
55%
VO2max
for
up
to
3
hours
on
blood
neutrophil
function
and
plasma
concentrations
of
cortisol,
glutamine
and
glucose.
Eighteen
healthy
male
subjects
(19-26
years,
VO2max
54-66
ml
x
kg(-1)
x
min(-1))
cycled
on
an
electrically
braked
ergometer
at
80%
VO2max
to
fatigue
from
18-56
minutes.
On
another
occasion,
separated
by
at
least
one
week,
subjects
performed
exercise
on
the
same
ergometer
at
55%
VO2max
for
3
hours
or
to
fatigue,
whichever
came
first.
Mean
exercise
time
range
to
fatigue
was
141-187
minutes.
Both
exercise
bouts
caused
significant
elevations
of
the
blood
leukocyte
count
and
plasma
cortisol
concentration
and
reductions
in
the
in
vitro
neutrophil
degranulation
response
to
bacterial
lipopolysaccharide
and
oxidative
burst
activity.
After
exercise
at
the
lower
work
rate
for
a
longer
duration,
plasma
cortisol
concentration
was
higher,
blood
leucocyte
and
neutrophil
counts
were
higher,
blood
lymphocytes,
plasma
glucose
and
indices
of
neutrophil
function
were
lower
than
those
observed
at
80%
VO2max.
PLASMA
GLUTAMINE
ONLY
FELL
SIGNIFICANTLY
DURING
RECOVERY
AFTER
THE
MORE
PROLONGED
EXERCISE.
These
researchers
concluded
that
when
exercise
is
very
prolonged,
the
diminution
of
innate
immune
function
is
greater,
or
at
least
as
great
as
that
observed
after
fatiguing
exercise
at
higher
work
rates.
Furthermore,
reductions
in
neutrophil
function
after
exercise
at
80%
VO2max
WERE
NOT
RELATED
to
changes
in
the
plasma
glutamine
concentration,
although
both
plasma
glutamine
and
neutrophil
function
were
decreased
at
1
hours
and
2.5
hours
post-exercise
in
the
long
duration
exercise
trial.
[2]
Another
researcher
concludes,
"Chronic
overexercising
depletes
glutamine
from
skeletal
muscle
causing
the
body
to
not
recover
completely
by
the
next
workout."
[3]
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Immunosuppression
by
athletes
involved
in
heavy
training
has
numerous
origins.
Training
and
competitive
surroundings
may
increase
the
athlete's
exposure
to
pathogens
and
provide
optimal
conditions
for
pathogen
transmission.
Heavy
prolonged
exertion
is
associated
with
numerous
hormonal
and
biochemical
changes,
many
of
which
potentially
have
detrimental
effects
on
immune
function.
Furthermore,
IMPROPER
NUTRITION
can
compound
the
negative
influence
of
heavy
exertion
on
immunocompetence.
An
athlete
exercising
in
carbohydrate-depleted
state
experiences
larger
increases
in
circulating
stress
hormones
and
a
greater
perturbation
of
several
immune
function
indices.
The
poor
nutritional
status
of
some
athletes
may
predispose
them
to
immunosuppression.
For
example,
dietary
deficiencies
of
protein
and
specific
micronutrients
have
long
been
associated
with
IMMUNE
DYSFUNCTION.
Although
it
is
impossible
to
counter
the
effects
of
all
of
the
factors
that
contribute
to
exercise-induced
immunosuppression,
it
has
been
shown
to
be
possible
to
minimize
the
effects
of
many
factors.
Athletes
can
help
themselves
by
EATING
A
WELL-BALANCED
DIET
that
includes
ADEQUATE
PROTEIN
AND
CARBOHYDRATE,
sufficient
to
meet
their
energy
requirements.
This
will
ensure
a
more
than
adequate
intake
of
trace
elements
without
the
need
for
special
supplements.
CONSUMING
CARBOHYDRATES
(but
not
glutamine
or
other
amino
acids)
DURING
EXERCISE
attenuates
rises
in
stress
hormones,
such
as
cortisol,
and
appears
to
limit
the
degree
of
exercise-induced
immunosuppression,
at
least
for
non-fatiguing
bouts
of
exercise.
[4]
What
applications
will
resolve
exercise-induced
glutamine
deficiency?
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CONCLUSION
Endurance
athletes
are
predisposed
to
immune
compromise
by
depressed
gastric
functions
from
prolonged
aerobic
exercise
more
than
short-term
sessions.
A
preventive
resolution
of
this
disorder
suggests
increasing
specific
glutamine-rich
supplements
or
following
dietary-exercise
protocols:
A-Glutamine-enhanced
whey
protein
concentrates
may
be
taken
post-exercise.
[1.5
scoops
Hammer
Whey
Pro
per
100
lbs.
body
weight]
B-Fish,
raw
legumes,
raw
cabbage,
raw
cabbage
juice
may
be
ingested
post-exercise.
C-Free-form
Glutamine
should
be
consumed
post-exercise
or
3
hours
prior.
[2000
mg]
D-Carbohydrates
should
be
taken
during
exercises.
[240-280
calories/hour]
E-Short-term
"easy"
aerobic
exercise
need
to
be
alternated
prior
to
and
following
prolonged
exercise.
F-Periodic
rest
days
should
be
imposed
post-workout
of
over
1
hour
or
if
morning
resting
heart
rate
exceeds
5
beats
per
minute
above
base
rate.
G-Do
not
take
Glutamine
during
exercise
due
to
the
initial
increase
in
NH4-
[Nitrogen
release
during
glutamine
metabolism].
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REFERENCES
[1]-Walsh
NP,
Blannin
AK,
Robson
PJ,
Gleeson
M.,
Glutamine,
exercise
and
immune
function.
Links
and
possible
mechanisms.
Sports
Med.
1998
Sep;26(3):177-91.
Review.
[2]-Robson
PJ,
Blannin
AK,
Walsh
NP,
Castell
LM,
Gleeson
M.,
Effects
of
exercise
intensity,
duration
and
recovery
on
in
vitro
neutrophil
function
in
male
athletes.
Int
J
Sports
Med.
1999
Feb;
20(2):
128-35.
[3]-Nick
GL.,
Medicinal
Properties
in
Whole
Foods.
Townsend
Letter,
April
2002:149.
[4]-Gleeson
M,
Bishop
NC.
Special
feature
for
the
Olympics:
effects
of
exercise
on
the
immune
system:
modification
of
immune
responses
to
exercise
by
carbohydrate,
glutamine
and
anti-oxidant
supplements.,
Immunol
Cell
Biol.
2000
Oct;78(5):554-61.
Review.
*Bill
Misner
Ph.D
is
the
Director
of
Research
&
Product
Development
for
E-CAPS
Inc.
1-800-336-1977
http://www.e-caps.com/
E-MAIL:
askdrbill@e-caps.com
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