Glutamine: The Essential "Non-Essential" Amino
Acid
by Ivy Greenwell
Rapidly dividing cells, including certain immune cells, utilize glutamine as
a source of energy. Glutamine is classified as a "non-essential amino
acid." This label may mislead some people into believing that we don't
need it. But, in essence, "non-essential" means only that the
body can synthesize this amino acid. It does not mean "unimportant."
In fact, glutamine is of crucial importance; we are lucky that we do not have to
depend totally on dietary sources. It seems that every cell in the body uses
glutamine. Some tissue types, however, depend on glutamine much more than
others.
Specifically, glutamine is utilized as a source of energy and for nucleotide
synthesis by all rapidly dividing cells, such as the cells of the intestinal
lining and certain immune cells (thymocytes, lymphocytes and macrophages).
Without sufficient glutamine, the intestines atrophy and the immune function
breaks down.
Hair follicles, the fetus, and unfortunately also many types of tumors also
greatly depend on glutamine for energy production and DNA and RNA synthesis. In
addition, glutamine serves as a nitrogen donor and a carbon donor, and is thus
an important muscle-building amino acid; it also helps replenish muscle glycogen
after exercise. Without sufficient glutamine, muscles begin to atrophy. Thus
glutamine is in fact essential for intestinal, immune and muscle functions, to
mention just the most obvious.
And this is not the end of the story. The synthesis of glutamine protects the
body, and the brain in particular, from ammonia toxicity. In fact, the synthesis
of glutamine from glutamate is the key pathway for detoxifying ammonia. Excess
ammonia is a crucial factor in the development of neurodegenerative diseases,
since ammonia interferes with the oxidative metabolism of neurons and thus
reduces the production of ATP, our "energy molecule." In addition,
ammonia gives rise to very harmful nitrogen-based free radicals.
In the brain, glutamine is a substrate for the production of both excitatory
and inhibitory neurotransmitters (glutamate and gamma-aminobutyric acid,
popularly known as GABA). Glutamine is also an important source of energy for
the nervous system. If the brain is not receiving enough glucose, it compensates
by increasing glutamine metabolism for energy-hence the popular perception of
glutamine as "brain food" and its use as a pick-me-up. Glutamine users often
report more energy, less fatigue and better mood.
Glutamine also plays a part in maintaining proper blood glucose levels and
the right pH range. The body has an exquisite mechanism for maintaining pH
homeostasis. If the pH of the blood is too acidic, more glutamine is directed to
the kidneys, where a certain type of glutamine results in the release of
bicarbonate ions to correct acidosis. If the pH is too alkaline, more glutamine
is sent to the liver, where a different kind of metabolism releases hydrogen
ions to correct alkalosis.
And there is still more. Due to its dependence on sodium transport, glutamine
is one of the amino acids that control the volume of water in the cells, and the
osmotic pressure (osmoregulation) in various tissues. Glutamine also plays a
vital part in the control of blood sugar. It helps prevent hypoglycemia, since it
is easily converted to glucose when blood sugar is low. In addition,
glutamine regulates the expression of certain genes, including those that govern
certain protective enzymes, and helps regulate the biosynthesis of DNA and RNA.
Recently it has been discovered that glutamine is important for the
cardiovascular system as well.
Thus, to say that glutamine is important for our health is an understatement.
In view of its multiple functions, it is no surprise that glutamine is the most
abundant free amino acid in the serum, muscle and cerebrospinal fluid. It
constitutes 50% of all amino acids in the serum, and more than 60% of free amino
acids within the body.
Glutamine is plentiful in both animal and plant protein. The typical American
diet provides between 3.5 g and 7 g of glutamine; more is synthesized according
to need. Even so, heavy stress, such as strenuous exercise, infectious disease,
surgery, burn injury or other acute trauma leads to glutamine depletion with
consequent immune dysfunction, intestinal problems and muscle wasting.
Consequently, it has been proposed that glutamine should be classified as a
"conditionally essential amino acid." During exceptionally severe stress,
supplementing with glutamine (in the hospital setting, doses as high as 20-40 g
may be used) can be a matter of life or death.
Benefits for the liver and the intestines
People who use glutamine virtually ensure superior health of their intestinal
lining. They need not worry about the "leaky gut syndrome" and all its
troublesome consequences, including the "leaking out" of pathogens and possible
arthritis. In fact, when it was first discovered, glutamine used to be called
"intestinal permeability factor." It is by far the most important
nutrient for intestinal health.
The importance of glutamine for the intestines is enormous-glutamine is the
chief source of energy for the cells of the intestinal lining. Most glutamine in
the diet (and also most dietary glutamate and aspartate) is metabolized by the
intestines, both to serve as intestinal fuel and also to produce glutathione,
nitric oxide, polyamines, nucleotides and the amino acids alanine, citrulline
and proline, making these available to the rest of the body. Glutamine also
maintains the structural integrity of the intestinal lining, supporting its
quick turnover.
Those who use NSAIDs (non-steroidal anti-inflammatories) such as ibuprofen
and indomethacin may have a special need for supplemental glutamine.
Fortunately, sufficient glutamine can undo the damage caused by NSAIDs,
maintaining permeability at a healthy level. For heavy NSAID users,
supplementing with glutamine can spell the difference between healthy
gastrointestinal tract versus ulcers and the "leaky gut syndrome."
Besides treating the "leaky gut syndrome" and ulcers, glutamine can also be
used to treat colitis, Crohn's disease and diarrhea, in doses of up to 20 g/day.
The soothing intestinal effect of glutamine taken as powder dissolved in water
makes itself known quite soon after ingestion (by the way, the taste is quite
pleasant, slightly sweet, so there is no need to mask it with juice). Even a
small dose, such as 2-3 g, can quickly calm that "queasy" feeling.
In high doses, glutamine also alleviates the devastating damage to the
gastrointestinal tract that results from chemotherapy.
Likewise, glutamine protects the liver from the ravages of chemotherapy
toxicity. But even under normal conditions, glutamine is beneficial for the
liver, since it cleanses the liver of the waste products of fat metabolism, and
helps prevent fatty buildup. It can aid in the treatment of early-stage
cirrhosis. Once liver damage is advanced, however, glutamine cannot help since
the liver can no longer metabolize it properly. People who take glutamine tend
to have a healthier liver and healthier intestines, and thus better digestion
and absorption of nutrients. That alone should be reason enough to add this
super amino to your supplement regimen. But this is just the beginning of its
benefits.
Strengthens the immune system
Glutamine is the primary source of energy for the various cells of the immune
system, including T cells and macrophages. Strenuous exercise, viral and
bacterial infections, and stress and trauma in general cause glutamine depletion
that starves the immune cells. They decline in number and/or show diminished
activity. Up to 40 g of glutamine a day can be used to sustain the immune system
of AIDS patients or cancer patients undergoing bone marrow transplantation. More
typical doses, such as 2-5 mg/day, should be sufficient for healthy people. Athletes
may want to increase their dosage on an as-needed basis if they tend to succumb to
infections after heavy exercise such as marathon running.
In addition, glutamine is a substrate for glutathione, a tripeptide amino
acid that acts as one of our master antioxidants, and also helps enhance the
immune function. Though large doses of glutamine stimulate the immune response
even under heavy stress, it is important to reduce stress as much as possible. Stress
hormones may interfere with glutamine metabolism in the immune cells. This is where
relaxation and DHEA supplementation might prove to be very helpful in addition
to glutamine.
Maintains muscle mass
Glutamine is one of the favorite supplements of body builders and others who
exercise a lot. In its role as a carbon donor, glutamine is "muscle food,"
helping to replenish glycogen. But actually the function of glutamine as a
nitrogen-donor might be even more important. Strenuous exercise such as weight
lifting causes micro-injuries to the muscle tissue. By donating nitrogen,
glutamine helps build proteins and repair the muscle, as well as help build up
more muscle. Part of its muscle-building action may be due to its ability to
induce the release of growth hormone. Serious fitness fans take glutamine both
before and after workout. Taking 2-3 g after workout is particularly
recommended. Long-term users of anti-inflammatory steroids tend to suffer from
muscle atrophy. The concomitant use of glutamine has been shown to prevent most
of this muscle loss.
But muscle isn't the only tissue where protein is being synthesized.
Glutamine serves the anabolic (tissue-building) needs of the whole body. Since
it can very easily donate nitrogen, it functions as a "nitrogen shuttle,"
delivering nitrogen wherever it is needed.
Very ill patients suffer both a decrease in glutamine levels and muscle loss.
One way to counteract this is to add glutamine to their diet, or, if they can no
longer consume food, to the iv drip that delivers parenteral nutrition. The use
of glutamine has been documented to aid the survival of severely ill surgical
and burn patients. It also speeds up wound and burn healing, and improves
recovery in general.
Helps the heart
It has recently been discovered that glutamine is an important source of fuel
for the heart muscle. It is converted to glutamate, which then enters the Krebs
cycle to produce ATP, our energy molecule. This is yet another reason why
glutamine is so important during exercise, increasing endurance. In heart
patients, glutamate infusions can be used during heart surgery to ensure a
better outcome.
The action of the heart is under considerable control of the nervous system,
and the pathways involved in the neural control of cardiovascular function
happen to rely on glutamate and GABA.
If the brain has a faulty glutamine / glutamate / GABA metabolism, we can expect
the development of cardiovascular dysfunction as well. In addition, glutamine
serves as a substrate for the synthesis of a special type of beta-endorphin,
glycyl-l-glutamine. This dipeptide appears to be important for the regulation of
blood pressure and prevention of cardiorespiratory depression. Glycyl-l-glutamine
is also important for the immune response, since it enhances the activity of the
natural killer (NK) cells.
Combats hypoglycemia by raising serum glucose
Glutamine can enter the Krebs cycle and serve as a non-carbohydrate source of
energy. In fact, this is the main way it usually contributes to the production
of energy. However, if the blood sugar is low (hypoglycemia), glutamine is
readily catabolized (broken down) in the liver to provide more
glucose. Together with alanine, glycine, serine and threonine, glutamine is an
important "gluconeogenic" amino acid, in fact the primary one. This production
of glucose from glutamine takes place mainly in the liver. Recently, however, it
has been discovered that the kidneys can contribute as much as 25% to whole-body
glucose production, a phenomenon that occurs only during hypoglycemia. Actually
this is not surprising, since the kidneys are especially equipped to process
glutamine due to its importance in the detoxification of ammonia.
Providing abundant glutamine through diet and supplementation means that less
muscle tissue (if any) will be broken down to provide glucose. This is of great
importance to people on calorie-restricted diets, whose great problem is losing
muscle mass more so than fatty tissue. Since it is the metabolically active
muscle mass that helps keep us slender (not to mention strong and fit), extra
glutamine can help dieters lose girth around the waist while preserving muscle
mass.
Considering the effectiveness of glutamine in combating hypoglycemia, it is
no wonder that alternative medicine recommends it for the purpose of eliminating
sugar cravings, and alcohol cravings in the fight against alcoholism (many
alcoholics appear to suffer from hypoglycemia).
Diabetics, however, need to exercise caution, since they have an abnormal glutamine
metabolism. A much higher percentage of their glutamine is broken down for the
production of glucose by the liver and the kidneys, a process called glutamine
gluconeogenesis. This increased production of glucose from glutamine (and also
from alanine, an amino acid in the same family) is probably related to the
diabetes-related excess levels of the serum glucose-raising pancreatic hormone
called glucagon. True, this excessive breakdown of glutamine into glucose in
diabetes occurs without any supplementation, since the muscle and the fatty
tissue release so much glutamine in response to the endocrine pathology.
Diabetics also show other enzymatic abnormalities in relation to glutamine,
including poor function of the retinal glia (glia are cells that have various
supportive functions in the nervous system, including detoxifying ammonia
through the production of glutamine). Thus the diabetic retina is prone to
damage through glutamate excitotoxicity, since the glia are not converting
enough glutamate to glutamine. While a plausible argument could be made for the
benefits of glutamine even for diabetics-sparing of muscle mass, improved
intestinal function, enhanced immune response-caution must be urged. A diabetic
considering taking any amino acids should discuss the matter with his/her
physician. The use of high doses of antioxidants, including vitamin E and various
polyphenols, should be beneficial, as well as supplementation with taurine.
Taurine is the one amino acid that seems to be very helpful to diabetics.
Effects on cancer, including breast cancer
We have already said that glutamine is heavily used by all rapidly dividing
cells. This includes many types of tumors. Thus is would seem plausible to argue
that this is certainly the amino acid that cancer patients should avoid.
In reality, however, glutamine is frequently used as an adjuvant
treatment of advanced cancer. It has been shown to prolong survival by
slowing down catabolic wasting. In addition, since low immune function is a
hallmark of cancer, glutamine is considered beneficial for the depleted immune
system. It helps preserve intestinal function as well. Both clinical practice
and animal studies suggest that glutamine can be given to cancer patients
without stimulating tumor growth or metastasis. Nevertheless, the use of any
amino acids in cancer remains controversial, and patients are urged to consult
with their physicians first.
The most fascinating findings regarding glutamine and cancer, however,
suggest that glutamine may be another weapon against breast cancer>. In one
animal study, rats implanted with breast cancer were given glutamine at the dose
of 1g/kg/day. Their tumor growth was 40% less than in the
control group. The natural killer cells in glutamine-supplemented rats showed
2.5 times greater activity. In addition, there was a 25% rise in glutathione
levels and a decrease in inflammatory prostaglandins. Inflammatory
prostaglandins (PGE2) have been found to fuel tumor growth. Glutamine can also
be used as adjuvant therapy with chemotherapy such as methotrexate. Glutamine
lowers the toxicity of methotrexate, augmenting its effectiveness against
inflammatory breast cancer. In the words of the authors, "No toxicity of oral
glutamine was detected. No patient showed any sign of chemotherapy-related
toxicity." This is an extraordinary statement since the biggest problem with
chemotherapy is its toxicity. The glutamine dose used in conjunction with
methotrexate was .5g/kg/day.
One interesting clinical application of high doses of glutamine (30 g/day) is
as adjuvant therapy for sickle cell anemia. In alternative medicine, glutamine
is also used as part of the treatment for AIDS.
Is there a danger to the brain?
First, let us try to clear up possible confusion by defining some terms.
"Glutamate" as it functions within the body does not mean monosodium glutamate,
a flavor enhancer discovered by East Asians, and originally manufactured from
seaweed, its most abundant natural source. Monosodium glutamate is the sodium
salt of glutamic acid-just as sodium ascorbate and calcium ascorbate are salts
of ascorbic acid. MSG does, however, raise glutamate levels. In fact, when the
use of glutamate is called for in clinical settings, MSG infusions are used.
"Glutamate" is the term used interchangeably with "glutamic
acid," though strictly speaking glutamate is an anionic amino acid, or the
anionic form (meaning it's a negative ion) of glutamic acid. ("Folate" and
"pyruvate" are likewise increasingly used instead of folic acid and pyruvic acid.)
Glutamine differs from glutamate in that it has been formed from glutamate
and ammonia, and thus has an extra nitrogen it can easily donate whenever
nitrogen might be needed. The enzyme that catalyzes the addition of ammonia to
glutamate is called glutamine synthase. An abundant supply of glutamine synthase
is essential for our health, since the biosynthesis of glutamine is the process
through which the body eliminates excess ammonia. As we will see later,
glutamine synthase is of incredible importance in brain function. One could say
that our very survival depends on this enzyme, and on the glial cells that
secrete it.
Thus, MSG is the sodium salt of glutamic acid, while "glutamate," as the term
is used most often these days, is the ionic form of glutamic acid. True, the
body can use MSG as a source of glutamate, but there is also all that sodium
coming in, perhaps causing sodium/potassium imbalance, dehydration, and
disturbances in the constriction and dilation of blood vessels. Dehydration
alone is enough to cause the kind of dull headache that some Western patrons of
Chinese restaurants have complained about. I suspect that some (most?)
Westerners eat much larger portions than Asians, and thus perhaps consume more
MSG in one meal than is typical of Asians.
Nevertheless, those prone to migraines should avoid MSG and aspartame, and
all of us should avoid these compounds in large doses. There is no question that
very high doses of MSG can overwhelm brain defenses and cause neural damage. It
is interesting that it is young children with immature nervous systems who are
most susceptible to MSG damage, and not the elderly.
Stress has been shown to increase the permeability of the blood-brain barrier
to exogenous glutamate. If you expect a business lunch to be stressful, it might
be best to stay away from Chinese cuisine. The good news is that more and more
Chinese restaurants advertise that they do not use MSG, or else MSG can be
omitted by request.
Actually only a small percentage of people are truly sensitive to the small
doses of MSG used as a seasoning. Billions of Asians consume it daily; the
Japanese also consume seaweed, the richest natural source of monosodium
glutamate. This chronic long-term consumption does not seem to cause any
problems. In regard to Alzheimer's disease in particular, the Asian rates
(including Japan) are a fraction of what they are in the West. It is also of
interest that infusions of MSG are used in mainstream clinical practice to reduce
high ammonia levels in the blood (hyperammonemia) by stimulating the conversion of
glutamate to glutamine. Thus both glutamate (as MSG) and glutamine are used
by conventional medicine for treating several very serious conditions.
The consumption of either glutamine, even in large doses, or glutamate in
small doses by healthy people is unlikely to cause any problems, neural or
otherwise. The reason for this is that, except in cases of severe pathology such
as stroke, the metabolism of glutamine/glutamate is strictly regulated. Even though
glutamine supplementation is indeed likely to raise glutamate levels in the
brain, this does not mean that excess glutamate will therefore accumulate at the
synapses and damage the neurons. On the contrary: clinical experience shows that
better neural energy production and better neurotransmitter balance are a
typical result, with improved mental performance and a sense of well-being, so
opposite of the irritability and distractibility, along with cognitive
dysfunction, characteristic of states where neurotransmitters are low.
In addition, we need to remember that most of the glutamate is used for
energy production rather than as a neurotransmitter. As for the possibility of
insomnia, it seems that some people take glutamine at bedtime as a growth hormone
releaser, yet complaints of insomnia are not prevalent in the literature. And
remember that in clinical settings, as much as 40 g of glutamine may be
administered, and yet the literature makes no mention of any side effects. On
the contrary, the non-toxicity of glutamine is emphasized as an important
advantage. With some important exceptions that will be summarized at the end of
this article, it seems that even the severely ill have no trouble metabolizing
glutamine.
Glutamic acid has become very hard to find. Glutamine, on the other hand, is
in all health food stores, being popular with body builders. One of the ironies
is that glutamine is used mainly by the very fit and the very sick.
The apparent lack of side effects of glutamine supplementation is not
surprising, considering the abundance of glutamine in the human body. Serum
levels of glutamine are in the range of 390-650 mg/dl for adults, compared to
18-98 range for glutamate. Children have higher upper values for both glutamate
and glutamine (140 and 730 mg/dl).
The glutamine cycle in the brain is simple and elegant. Glutamine readily
crosses the blood-brain barrier. Neurons take up glutamine and convert it to
glutamate or GABA (through the additional step of decarboxylating the
glutamate). Some glutamate is used for energy, some for synthesis of glutathione
and niacin, some as neurotransmitter. After either glutamate or GABA are
released into the synaptic junction, the supportive cells called glia, with
their high supply of glutamine synthase, take up the glutamate or GABA and
resynthesize glutamine, detoxifying ammonia in the process. The glutamate that
is not converted to glutamine is used by the glia as a source of energy, and
also to produce energy nutrients alanine and alpha-ketoglutarate, which are then
released to the neurons.
If excess glutamine accumulates through the action of the glia, the brain
donates it to the body. Normally, however, very little glutamine is released by
the brain, in contrast to muscle and adipose tissue, which donate a lot. In the
brain, it's pretty much an internal affair. What we see is the glutamine
glutamate GABA glutamine cycle.
If the glia are dysfunctional due to reduced aerobic metabolism, or the
release and/or activity of the glial glutamine synthase is inhibited in any way
(free-radical damage, toxins, certain drugs), not only glutamate, but GABA as
well might accumulate in excess, possibly causing lethargy and cognitive
dysfunction. It has been suggested that this too is one of the phenomena we see
in the aging brain. On the one hand, glutamate excitotoxicity damages or
destroys some neurons, leading to deficiencies in memory and learning; on the
other hand, excess of GABA can lead to lethargy. At the same time, excess
ammonia, not detoxified through sufficient glutamine synthesis by the glia,
leads to further neural damage.
An interesting development related to glutamate is the increasing use of
ampakines, a new class of drugs for Alzheimer's disease. Apparently an important
factor in the pathogenesis of Alzheimer's disease is stroke or a series of
undiagnosed mini-strokes. During stroke, the dying neurons release glutamate,
which then unfortunately can cause more neuron death. Furthermore, ischemic
episodes damage the glutamate receptors, so that later the glutamate can't work
as a neurotransmitter. Without glutamate, there is no memory and no learning.
Ampakines amplify the glutamate signal through a yet unknown mechanism, possibly
by rebuilding glutamate receptors. In healthy people and in animals, ampakines
have been shown to enhance cognitive performance, and can thus be classified as
"smart drugs."
One
current hypothesis is that glutamate is also deficient in schizophrenia,
though probably many neurotransmitters are out of balance in neurological
disorders.
At normal physiological levels, glutamate is beneficial and safe. It is an
indispensable neurotransmitter that the brain produces according to need. When
the central nervous system is aroused, surprisingly enough we do not see higher
glucose consumption. Instead, some of the glucose is converted to glutamate. The
other source of glutamate is, of course, glutamine. An abundant supply of
glutamine makes it easier for the brain to maintain neurotransmitter balance, by
increasing the production of glutamate when required for alertness, learning and
memory, and the production of GABA when its inhibitory properties are needed. In
fact, some people report feeling more centered and calm after they start taking
glutamine. Others report a lifting of depression.
Glutamate is our chief excitatory neurotransmitter. It is essential for
learning and both short-term and long-term memory. Problems arise only if the
normal process of glutamate removal and conversion to glutamine malfunctions and
an excess of this excitatory neurotransmitter builds up in the synaptic
junctions. Excess glutamate causes excessive influx of calcium ions into the
neurons, causing excitotoxicity and ultimately even death of the neurons. It
also destroys glutathione, a crucial brain-protective antioxidant. Low levels of brain
glutathione are associated with neurodegenerative disorders. Glutathione
depletion further leads to neuronal death.
Under what conditions do we see excess levels of glutamate at the synapses?
Not surprisingly, we see evidence of damage associated with excess glutamate in
Alzheimer's disease patients, AIDS patients (the AIDS virus inhibits glutamate
uptake by the glia), cancer patients (according to one hypothesis, cancer
basically starts with brain dysfunction), and in those who have suffered a
severe brain injury. Very high fever or artificially induced hyperthermia can
also result in excess glutamate release, leading to seizures.
However, the use of glutamine as a free amino acid has never been associated
with any form of brain damage. Glutamine is in fact abundantly produced in the
brain as a vital defense against ammonia and also against excess glutamate. The
main defense against glutamate excitotoxicity is the synthesis of glutamine by
cells called the glia, or, more specifically, astroglia or astrocytes, the most
abundant type of cell in the central nervous system, exhibiting high amounts of
glutamine synthase. The healthy brain is very well equipped to deal with
glutamate. But when the brain is damaged, due to stroke or injury or the
accumulation of various neurotoxins including certain drugs, the stage is set
for glial dysfunction and hence for glutamate excitotoxicity.
Proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha
inhibit the induction of glutamine synthase. These proinflammatory cytokines are
released after a brain injury and in neurodegenerative disorders. Thus, neuronal
death may occur because the inflammatory process interferes with the conversion
of glutamate into glutamine.
It thus appears plausible that reducing inflammation can prevent glutamate
excitotoxicity by protecting the glia. This may be a partial explanation for the
role of anti-inflammatories in the prevention of Alzheimer's disease. In
addition, it has been shown that normal levels of anti-inflammatory hormones
called glucocorticoids induce glutamine synthase. (Excess cortisol, however, can
inhibit the uptake of glutamate by the glia.) Flavonoids, such as the catechins
in green tea or proanthocyanidins in grape seed extract, can help protect
against the excitotoxic injury due to glutamate buildup. So can uric acid, one
of our endogenous antioxidants, and the amino acid taurine. It seems that the
brain can produce its own taurine. Nevertheless, if high doses of glutamine are
taken, or if foods seasoned with MSG are regularly consumed, it might be an
extra precaution to take supplemental taurine.
Certain B vitamins, including methylcobalamine (one of the active forms of
vitamin B12), are likewise protective. The real star here, however, seems to be
Ginkgo biloba. A Chinese study found that a ginkgo extract, as well as one
of its constituents, ginkolide B, protects against glutamate excitotoxicity by
reducing the rise in calcium ions. Thus it is an excellent idea to include
ginkgo in your supplement regimen. You may also consider drinking
green tea or taking green tea extract, as well as eating berries or taking
bilberry extract, in order to obtain a good dose of flavonoids for general
neural protection and prevention of neurodegenerative diseases.
Retinal damage in diabetes is also partly due to excitotoxic glutamate
buildup. In this case we again see insufficient conversion of glutamate to
glutamine, probably due to the malfunction of glial cells (both insufficient or
excessive glucose levels can lead to cell dysfunction; diabetics also show
higher levels of free radicals).
Finally, alcohol also inhibits glutamine synthase, which explains at least in
part the neurotoxicity of alcohol. Certain drugs, including many anti-epileptic
drugs, likewise inhibit glutamine synthase, and this may be partly responsible
for their toxic side effects. One anti-epileptic drug, however, a fairly new
medication called vigabatrin, has been shown to raise both GABA and glutamine
while decreasing glutamate. This drug is considered both safe and effective.
There is also a suspicion that toxic residues from the compounds formerly
used for bleaching white flour may have contributed to the increase in
neurodegenerative diseases, again by inhibiting glutamine synthase. A big
challenge in neuro protection is avoiding neurotoxins that might impair the
quick conversion of glutamate to glutamine, and seeking to enhance the
production of glutamine synthase, one of our most critical enzymes.
Malnutrition can likewise lead to glial malfunction, and thus to the
inability of glia to remove excitatory neurotransmitters (glutamate and
aspartate) from the synaptic junctions. In summary, glutamate excitotoxicity
arises only under certain pathological conditions such as stroke, extremely high
fever, certain viral infections, the presence of neurotoxins or severe
inflammation. It can be due to excess release of glutamate by the neurons
(stroke) and/or to glial malfunction, where the glia are incapable of secreting
enough glutamine synthase in order to convert glutamate to glutamine. Glutamine
as such cannot harm the brain. On the contrary, it is very beneficial to the
brain. Any excess glutamine simply leaves the brain, being donated to the body.
Summary of benefits
There are many reasons for taking glutamine: healthier intestines, a stronger
immune system, bigger muscles, better blood sugar control and a more agile
brain. For therapeutic uses, glutamine is especially recommended for people who
suffer from intestinal problems, frequent NSAID users who need to protect their
gastrointestinal tract, those with immune dysfunction, and anyone under heavy
stress (including strenuous exercise) or recovering from injury or other trauma.
It may also be helpful as adjunct therapy in the treatment of addictions such as
alcoholism.
Glutamine is especially popular with body builders, and with those who wish
to perk up their physical and mental energy. And-it tastes good!
| Precautions: Even though glutamine is nontoxic, it is
recommended that you consult a health practitioner before using high doses.
Diabetics, cancer patients, patients with advanced liver disease, and those
with neurological diseases including stroke and epilepsy should use
glutamine only with the permission of their doctor. |
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