Re: msg

Hi 87,

Also,
http://www.smartbodyz.com/L-Glutamine-Benefits-Side-Effects-Supplements-Powde...
thought you might be interested.

L-Glutamine - Benefits, Side-Effects, Supplements, Powder - Pg 5

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. Mono-Sodium-Glutamat (Natrium Glutamat) does, however, raise glutamate levels. In fact, when the use of glutamate is called for in clinical settings, Mono-Sodium-Glutamat (Natrium Glutamat) infusions are used.

"Glutamate" is the term used interchangeably with "glutamic acid." 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 nitrogen whenever it may 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, Mono-Sodium-Glutamat (Natrium Glutamat) 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. It's true that the body can use MSG as a source of glutamate but there is also abundant 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 young children with immature nervous systems are most susceptible to MSG damage -- not the elderly.

Stress
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 (hyper-ammonemia) by stimulating the conversion of glutamate to glutamine. Thus, both glutamate (as MSG) and glutamine are used by conventional medicine for treating several serious conditions.

Stroke and Neurotransmitters
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. 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 -- opposite of irritability, distractibility, and cognitive dysfunction which are 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, 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 is very hard to find. Glutamine, on the other hand, is very popular with bodybuilders. One of the ironies is that glutamine is used mainly by the very fit and the very sick.

Side Effects
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 glutamate). Some glutamate is used for energy, some for synthesis of glutathione and niacin and, some as a neurotransmitter. After either glutamate or GABA are released into the synaptic junction, the supportive cells called glia take up the glutamate or GABA and re-synthesize glutamine -- detoxifying ammonia in the process. The glutamate that is not converted to l-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.

Cognitive Dysfunction
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), lethargy and cognitive dysfunction can be the result. 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 GABA can lead to lethargy. 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 which is 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."

Schizophrenia, Alzheimer's, AIDS and Cancer
One current hypothesis is that glutamate is also deficient in those diagnosed with schizophrenia. However, most likely, there are many neurotransmitters 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, 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 consistently better moods.

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, AIDS patients, and cancer patients. HIV inhibits glutamate uptake by the glia. According to one hypothesis, cancer 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. They are 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.

Pro-inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha inhibit the induction of glutamine synthase. These pro-inflammatory 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 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.) Bioflavonoids, such as the catechins in green tea or proanthocyanidins in grape seed extract, can help protect against the excitotoxic injury due to glutamate build-up. Uric acid (one of our endogenous antioxidants) and the amino acid taurine is also beneficial in controlling glutamate build-up. 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 methylcobalamin (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.