Glutamate, the Brain, and Autism: Revisited

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Article first published as Glutamate, the Brain, and Autism: Revisited on Technorati.

Child with autism self portrait, playing with his iPod Touch.Recently, in a search for another article entirely, I came across an article in the journal Autism Research that found increased glutamate and glutamine levels in children with autism compared to neurotypical children, or even their parents. The article explored possible inheritable glutamate levels, but found none (at least, based on the abstract). I have been unable to access the article directly, so if anyone out there has the full article, I would love to read it!

Anytime I read an article about glutamate, I'm reminded of an exchange I had with several members of the "MSG causes autism" camp. I had been unable to find any research that made that link, but remained open to any research that would make a direct link to autism and the ingestion of increased levels of glutamate.

Thinking this may be the case, I started some reading on neurobiology with relation to glutamate and glutamine, as well as nutritional biology when it comes to ingestion of glutamate.

Now, full disclosure, I am not a biologist, neurobiologist, biochemist, or nutritionist. If anyone out there can better enlighten me on the processes of glutamate through textbook or research article references, that would be great! But please, no articles from "health food" websites or Wikipedia. It's not that I don't trust their intentions, but rather their reference, or lack of, to scientific research.

So, glutamate. Glutamate is a neurotransporter, meaning it activates neurons, nerves, etc. and gets them running. Signals between neurons require glutamate in order to get from one place to another. According to the Centre for Molecular Biology and Neuroscience, glutamate mediates a lot of information. It also regulates brain development and information that determines cellular survival, differentiation, and elimination as well as elimination and formation of nerve contacts (your synapses). You have to have the right amount in your brain in the right place at the right time. Too much or too little glutamate in the brain can be toxic.

Glutamate therefore needs to be in the brain. But how is it stored? It's kept within the brain cells, meaning there is very little free-floating glutamate within the brain, up to 99.99%, in order to have the whole system work. That's because the glutamate receptors are only activated outside the cells, so keeping the glutamate within the cells keeps the system in balance.

So, in order for this to work, the brain needs to have a way to keep glutamate out of the brain fluid and in brain cells. The only way to do that is through the uptake of glutamate, which is a special set of molecular proteins that bind to glutamate and and transfer them to cells. Glutamate is then converted into glutamine, which can then be transferred within the brain fluid without activating the glutamate receptors. It's then turned back into glutamate when needed. There is a lot more to it, and I recommend reading the article from the Centre for Molecular Biology and Neuroscience.

So, we know that glutamate in the brain is necessary, and highly regulated within the neurobiological system. But what happens when you eat a lot of food with Monosodium Glutamate, or other glutamate-producing foods? This same question was the basis of a research survey by various doctors in Germany, the US, and the UK, and the results were published in the European Journal of Clinical Nutrition.

The article found several things of which I was not aware:

  1. Glutamate is found in natural and artificial sources, and the average European ingests an average of 0.3 to 0.5 grams per day. The average Asian, where MSG is used more liberally than other locations, ingests an average of 1.2 to 1.7 grams per day.
  2. Most of the glutamate, up to 95%, is converted into energy directly by the enterocytes of the intestinal mucosa (the predominant cells within the innermost wall of your intestines).
  3. Both natural protein-bound glutamates (those found in fermented foods like cheese or in foods like tomatoes) and salt-bound glutamates (like MSG) are metabolized the same.
  4. The whole reason why MSG is used, the Umami receptors in humans, can also detect and use other amino acids, so MSG isn't necessary for the same flavor enhancement.
  5. Based on animal studies, a "safe" level of glutamate within the average diet can be up to 500 to 1000 milligrams per kilogram of body weight. So an average person weighing 150 pounds can "safely" ingest about 68 grams per day.
  6. There is little research on the effects of increased glutamate inducing asthma attacks, or sensitivity. Some research has supported it, others found little correlation, but the consensus is that it could exist as a potential issue.
  7. The only threat to the nervous system in general, including the brain, is if the blood-brain barrier is damaged. This is a barrier that is developed within the typically developing child by age 6 months. Only illnesses that damage the barrier, such as rubella, can significantly increase the chance of blood-born glutamate getting into the delicate glutamate balance in the brain. Even with development in the womb, the placenta converts maternal blood-born glutamate, and even fetal blood-born glutamate, into energy.

So consumed glutamate is generally converted into energy for the body, which, depending on your activity level, can be helpful or harmful to your muscle structure. It explains, at least to me, why so many people feel their pulse racing after eating a lot of MSG - think of all the energy pumping through your body! And think of all that energy getting deposited somewhere, perhaps your hips, stomach, waist, etc, if not used. So those that say that MSG is bad for your health, it definitely looks that way.

But what does that have to do with increased glutamate and glutamine deposits in the brain of persons with autism? Apparently, absolutely nothing. Consumed glutamate doesn't seem to have a direct affect on brain glutamate concentrations based on existing research (with the exception of those with damaged blood brain barriers). Instead, it's a natural occurrence within the brain.

So the question is, how does that happen? So far, I haven't been able to find any answers. All we know, at least from this research, is that it is not inherited, or at least not as a known condition outside of autism itself. Now, those with autism do generally have larger or thicker brains, which may contribute to the increased levels found in the research study, but without definite concrete evidence, we don't know.

So if anyone out there can help me with the research, that would be great! Please post your links in the comments.