Can Glutamine Supplementation Lead to Toxicity?

Glutamine is an amino acid that makes up the majority of our skeletal muscle. There is some controversy over whether oral glutamine supplementation is toxic or helpful to healthy people. In a past article, Dr. Robert Crayhon expressed the view of many natural medicine experts, "After reviewing the literature, I am unconvinced that high-dose oral glutamine supplementation is toxic to neurons in healthy persons."

However, Dr. Russell Blaylock, a board-certified neurosurgeon and author of the highly recommended Excitotoxins: The Taste that Kills wrote in to me with another viewpoint and his response is below.

By Russell L. Blaylock, M.D.
Advanced Nutritional Concepts, LLC.

Dr. Robert Crayhon posted comments on this site indicating that I was terribly mistaken in my caution concerning the use of glutamine and that he had consulted several "cell biologists" who were also concerned with my statements on glutamine safety. In fact it was stated that I apparently did not understand that glutamine was not an excitotoxin and was not converted into an excitotoxin.

Of course, I never stated glutamine was an excitotoxin, but I do state that it is converted into the excitotoxin glutamate within neurons. Numerous recent studies as well as Siegel’s Basic Neurochemistry textbook emphatically state that the major source of glutamate is from glutamine in the brain. Normally, when the brain finishes using glutamate for chemical communication between brain cells at the synapse the glutamate is taken up by surrounding glial cells and changed by the enzyme glutamine synthease into glutamine, where it is stored.

The Problem With Excitotoxins


The glutamine is then transported to the neuron and by the enzyme glutaminase, it is converted to glutamate--the potential excitotoxin. I say potential because unless it accumulates outside the brain cell it is harmless.

This is the major source of glutamate within the brain. Excitotoxins are usually amino acids, such as glutamate and aspartate. These special amino acids cause particular brain cells to become excessively excited, to the point they will quickly die. Excitotoxins can also cause a loss of brain synapses and connecting fibers. Food-borne excitotoxins include such additives as MSG, aspartame, hydrolyzed protein and soy protein extract.

In two recent studies it was found that the amount of glutamine in the brain could predict the brain damage seen both in pediatric brain injuries and brain damage secondary to seizures. Adding large amounts of glutamine to the diet increases significantly brain levels of glutamine and, hence, glutamate. Another study found that by adding glutamine to the diet of animals exposed to another powerful excitotoxin called quinolinic acid, brain cell damage was increased significantly. Quinolinic acid is known to accumulate in the brain in most cases of viral brain infection as seen with HIV dementia and viral encephalitis.

Glutamine and Liver Toxicity


Individuals with liver toxicity tend to accumulate ammonia in their blood and brain. Until recently, it was assumed that it was the ammonia that caused liver disease-associated brain injury and that glutamine was protective.

Newer studies indicate that actually it is the glutamine that is causing the brain’s injury. Increasing glutamine in the diet would significantly aggravate this damage.

Free Radicals in the Brain


Glutamine accumulation has also been found in Alzheimer’s disease, Huntington’s disease and high levels of brain glutamine have been associated with a worse prognosis in Lou Gehrig’s disease. Likewise, recent studies have shown that high brain glutamine levels increase brain levels of free radicals and impair the ability of brain mitochondria to produce energy. When the brain produces low energy, excitotoxins, such as glutamate, become even more toxic. It has been shown that the reason for glutamine toxicity under these conditions is because it is converted to the excitotoxin--glutamate.

Glutamine and Multiple Sclerosis


Of particular concern is the finding that people with multiple sclerosis have increased levels of the enzyme glutaminase (the enzyme that converts glutamine into glutamate) in areas of nerve fiber damage. High levels of glutamine in the diet would increase glutamate levels near these injured areas magnifying the damage. It has been shown that excitotoxicity plays a major role in multiple sclerosis by destroying the cells (oligodendrocytes) that produce myelin.

Glutamine and Pregnant Women


Another area of concern would be pregnant women. Glutamine passes through the placenta and may actually be concentrated in the baby’s blood, producing very high levels. Glutamate plays a major role in the development of the baby’s brain. Excess glutamate has been shown to cause significant impairment of brain development in babies and can lead to mental retardation.

When to Use Glutamine


The major use for high-dose glutamine would be to repair gastrointestinal injury. In such cases, I would recommend short-term use only. Those with a history of the following conditions should avoid glutamine, even for short-term use:
•Stroke
•Neurodegenerative disease
•Pregnancy
•Malignancy
•Recent vaccinations
•ADHD
•Hypoglycemia
•Autism
•Multiple sclerosis
•Other neurological disorders

Glutamine has recently been shown to produce extreme hypoglycemia, even more so than leucine, which is known to produce fatal hypoglycemia in infants.

The reason Chinese Restaurant Syndrome is not seen with glutamine challenge is that the glutamate receptors in the lungs and esophagus are stimulated by glutamate, not glutamine. The glutamine must be converted first and this occurs primarily in the brain.

The only safe situation for glutamine use is in the vigorous athlete. Glutamine is used as a muscle fuel, so that vigorous exercise will consume most of the glutamine before it can accumulate in the brain. I would still avoid long-term use in high doses. I would caution readers to avoid excess glutamine, especially in the above named conditions and situations.