Nemnogo dannyh iz drugogo lagerja:
(izvinite, net vremeni perevodit').
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http://www.optexinc....taminerisks.htm
Can too much glutamine cause disease?
"Cause" may be too strong a word. The words precipitate or aggravate might however be appropriate. It is very possible that excess glutamate from glutamine can precipitate and/or aggravate many neurodegenerative diseases, including the disease of ordinary senility.
Senile Dementia
Some neuroscientists believe the symptoms of ordinary senility are "caused" by accumulations of excess glutamate, GABA and ammonia in the brain, which result from the gradual age-related degeneration of the brain's ability to regulate these chemicals properly.
"If the glia are dysfunctional due to reduced aerobic metabolism, or the release and/or activity of the glial cell 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."
-Glutamine: The 'Essential' Non Essential Amino Acid, Life Extension Magazine, Sept 99
Glutamine acts in the brain as a precursor to glutamate, GABA and ammonia. As above, these are three chemicals which in excess are thought to cause symptoms of senility (lethargy and cognitive dysfunction). It is therefore at least possible if not likely that pushing unnaturally high amounts of glutamine into the aging brain on a daily basis can promote excess production of one or more of these chemicals and precipitate or aggravate the symptoms of senility. The addition of precursors tends to promote production of metabolites and experimental evidence suggests that this is true for the production of glutamate from glutamine in brain tissue.
From the point of view of the nervous system, it appears glutamine GH supplementation may actually add fuel to the fire of aging. In older people it might cause a temporary increase in alertness but at a dear price.
Glaucoma
Glutamate excitotoxicity can cause blindness and is thought to be the cause of retinal nerve damage in glaucoma. People with glaucoma or at risk of glaucoma should probably avoid glutamine.
Title
Chronic low-dose glutamate is toxic to retinal ganglion cells. Toxicity
blocked by memantine.
Author
Vorwerk CK ; Lipton SA ; Zurakowski D ; Hyman BT ; Sabel BA ; Dreyer EB
Address
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA
02114, USA.
Source
Invest Ophthalmol Vis Sci, 37(8):1618-24 1996 Jul
Abstract
PURPOSE: It is well known that acute exposure to high concentrations of
glutamate is toxic to central mammalian neurons. However, the effect of a
chronic, minor elevation over endogenous glutamate levels has not been
explored. The authors have suggested that such chronic exposure may play a
role in glaucomatous neuronal loss. In the current study, they sought to
explore whether a chronic, low-dose elevation in vitreal glutamate was toxic
to retinal ganglion cells and whether this toxicity could be prevented with
memantine, a glutamate antagonist. METHODS: Rats were injected serially and
intravitreally with glutamate to induce chronic elevations in glutamate
concentration. A second group of rats was treated with intraperitoneal
memantine and glutamate. Control groups received vehicle injection with or
without concurrent memantine therapy. After 3 months, the animals were
killed, and ganglion cell survival was evaluated. RESULTS: Intravitreal
injections raised the intravitreal glutamate levels from an endogenous range
of 5 to 12 microM glutamate to 26 to 34 microM. This chronic glutamate
elevation killed 42% of the retinal ganglion cells after 3 months. Memantine
treatment alone had no effect on ganglion cell survival. However, when
memantine was given concurrently with low-dose glutamate, memantine was
partially protective against glutamate toxicity. CONCLUSIONS: These data
suggest that minor elevations in glutamate concentration can be toxic to
ganglion cells if this elevation is maintained for 3 months. Furthermore,
memantine is efficacious at protecting ganglion cells from chronic low-dose
glutamate toxicity.
Language
Eng
Unique Identifier
96295379
Mental Illness
This is a summary of two case studies that appeared in a report in the American Journal of Psychiatry in 1984, in which glutamine supplementation appears to have caused mania.
GLUTAMINE/MENTAL SYMPTOMS
Two men taking L-glutamine, an amino acid sold in health food stores, developed manic behavior (excitement unstable attention, increased activity). Symptoms disappeared after the glutamine use was stopped. Glutamine is sold as a cognitive aid and brain stimulant.
(American Journal of Psychiatry 141:1302-1303, 1984)
Glutamine is seldom marketed today as a "cognitive aid" or "brain stimulant". I suspect this is because neuroscientists have learned much in the last two decades about the function of glutamate in the brain as well as its dangers, such that responsible supplement vendors no longer recklessly promote glutamine/glutamate as a cognitive aid or brain stimulant.
In addition to mania, glutamine GH supplementation might also cause depression in some people. Here is the testimony of a person I met on the internet. I have removed the name of the Australian who recommended the glutamine.
I tried [someone's] suggested 2 grams of L-Glutamine before bed. I did this for 2 weeks, but was having so much trouble sleeping, I switched to taking it in the morning, which I did for another 2 weeks. The main result was an incredible crop of cold sores - I used to get them a lot in the 70's, haven't had more than 1 per year since then.
I had a bad situation during the time I was on the L-Glutamine - an incident which seriously depressed me. (Again, I used to have serious problems with depression back in the 60's and 70's - none at all in the last 15 years at least.) I got even more depressed because no one else understood why that incident would concern me, let alone depress me. Toward the end of that time, I felt that if I could just lay undisturbed for an hour or so, I would have a stroke and be out of my misery. I was really upset with all the people who kept disturbing me.
The thing that really disturbs me now, is that the day after I quit taking the Glutamine, I suddenly saw this incident just as everyone else saw it - no reason to even be upset - let alone depressed about it, certainly not that depressed. While I was on the Glutamine, I didn't even consider that the two could be related. The way the problem just evaporated so soon after I quit the Glutamine, I personally am convinced the depression was a direct result of the Glutamine.
While these reports of mania and depression are a bit alarming, I do not believe they are common side effects of glutamine supplementation. If mental illness were a major problem with glutamine then there would likely be more reports such as these and researchers would be studying the problem with stricter controls. However these reports do underscore the important fact that glutamine can have psychoactive properties; it acts on the delicate mechanisms of the brain via the excitatory and potentially excitotoxic neurotransmitter glutamate, of which it is the direct precursor.
Insomnia
Insomnia and nervous stimulation are very common side-effects of glutamine GH supplementation. These common side-effects are almost certainly due to the unnaturally high levels of glutamate in the brain and nervous system created by glutamine supplementation. The insomnia and stimulation side-effects are important evidence in support of my hypothesis that megadoses of glutamine create potentially dangerous surges in brain glutamate; glutamine itself has no excitatory properties. Only its metabolite glutamate is excitatory. This means insomnia is strong evidence that glutamate production increases to unhealthy levels following ingestion of glutamine.
Apparently some people believe the nervous stimulation from glutamine is a "good" side-effect because it "feels good" and makes them feel "awake". I note that the drug amphetamine is also reported to feel good and that amphetamine causes people to feel very healthy and strong and awake. And like excess glutamate, amphetamine stimulates the release of growth hormone. Amphetamine and its derivatives like methamphetamine ("speed") are drugs of abuse and known neurotoxins. Glutamate is not a chemical analog to these dangerous drugs, however. My point is simply that one should not assume that nervous stimulation from glutamine is beneficial merely because it might cause a pleasant stimulating sensation. I believe the opposite is more likely to be true. No one knows for certain but it seems at least intuitively reasonable to think those who feel the excitatory effects of glutamate on their nervous systems are at greater than average risk of damage from glutamate excitotoxicity.
Amyotropic Lateral Sclerosis (ALS, or "Lou Gehrig's Disease") and other neurodegenerative diseases including ordinary senility
The following research abstracts are interesting and worthy of study. However I would caution the casual reader from drawing any premature conclusions.
1H-MRS evidence of neurodegeneration and excess glutamate + glutamine in ALS medulla.
This research shows that glutamine and glutamate are found in high concentrations in the brains of ALS patients. While the fundamental cause of ALS is unknown, it is well known that glutamate exitotoxicity is is the mechanism underlying the devastating nervous degeneration that characterizes this disease. The FDA approved a drug for treating ALS called Riluzole. The drug slows the progression of the disease by inhibiting glutamate.
Trinucleotide-repeat expansions and neurodegenerative disease: a mechanism of pathogenesis.
These neuroscience researchers propose that changes in brain glutamine levels may precipitate hereditary neurodegenerative diseases in people who are genetically at risk for them. We see that the researchers have postulated that "subtle alterations in glutamine" are responsible for the onset of some neurodegenerative diseases. We see also from the same sentence that subtle alterations in glutamine levels are known to change glutamate levels.
Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses?
In this study researchers explore the relationship between age-related impairment of energy metabolism and excitotoxicity. "The delayed onset of neurodegenerative illnesses could be related to the progressive impairment of mitochondrial oxidative phosphorylation, which accompanies normal aging." The general implication is that neurons become more vulnerable to glutamate in age, and that exposure to glutamate in age might precipitate or aggravate neurodegenerative diseases like Huntington's disease, Parkinson's disease, ALS, and Alzheimer's disease.
Neurotoxicity at the N-methyl-D-aspartate receptor in energy-compromised neurons. An hypothesis for cell death in aging and disease.
In this study researchers examine the close relationship between normal aging and increased risk of neuron loss from glutamate excitotoxicity.
Glutamate excitotoxicity in a model of multiple sclerosis
These researchers report about the role of glutamate excitotoxicity in MS.
Chronic Fatigue Syndrome
Glutathione is an important antioxidant. People of any age with depleted levels of reduced glutathione are especially vulnerable to the free-radical damage associated with glutamate excitotoxicity. CFS is a condition associated with low glutathione.
"There is evidence that depletion of reduced glutathione makes neurons more susceptible to excitotoxicity, and that intact mitochondrial function is essential for neuronal resistance to to excitotoxic attack. It is believed, for example, that reduced levels of the energy currency of the cell (ATP) that accompanies loss of mitochondrial function causes depolarization of neuronal membrane, which exposes NMDA receptors to excessive levels of glutamate. The resulting neurohormonal cascade leads, in many cases, to the death of neurons in the brain, and central and peripheral nervous systems. "
- LEF Magazine March 1996
In discussions with people on the internet I found at least one person who suffers from CFS who was also taking glutamine on an empty stomach. She started taking two grams at night as recommended by someone she met on the internet. She suffered from insomnia as a result of nervous stimulation from the two grams and found that she was able to sleep at night only if she reduced her dose to one gram. I question whether she should be supplementing glutamine in any amount on an empty stomach. On the one hand glutamine is a substrate of glutathione but on the other hand its metabolite glutamate poses a special risk to her nervous system. Probably she should take modest amounts of glutamine with meals containing complete proteins and find another method for increasing GH.