Tuesday, May 15, 2007

Autism and Excess Nitrogen – A Possible Connection

I finally got a chance a few nights ago to really pore over the recent findings of the Autism Genome Project (AGP). The most significant finding was that abnormal functioning of glutamate neurons (related to a mutation in a gene called Neurexin 1) may be a key cause of genetic autism. An even more recent study from the University of Iowa found that the same genetic mutation occurred in the sperm cells of a father with two autistic daughters.

What do these finding mean in plain English? As a special education teacher, I have little scientific or medical expertise. What I do have, as a teacher of children with autism, is a huge motivation to understand this stuff. I also have some pretty good instincts when it comes to autism. Some of my instincts come from the fact that, although I am not autistic, I do at least mildly share some of my students’ symptoms, such as sensory sensitivities, patterned thinking, and abnormal metabolism. (I wrote about this in a previous post.)

So a few nights ago, I felt incredibly inspired to understand and interpret the AGP findings. I think I could be onto something, but I could also be a total quack. My theory is just a theory, so please take it as that.

The AGP research leads me to believe that an abnormally low level of glutamate - an amino acid essential for neurotransmission, protein metabolism, and the bodily disposal of excess nitrogen - may be a primary cause of autism.

While AGP’s pinpointing of a specific genetic mutation is groundbreaking, the idea that autism may be caused by insufficient glutamate functioning is not entirely new. In 1998, a Swedish researcher questioned whether autism was a “hypoglutamatergic disorder.” In other words, is autism related to a glutamate deficiency? AGP’s research suggests it is. (Hypoglutamatergic disorders have also, interestingly, been linked to schizophrenia.)

Since the late 1980’s, two parent-run groups, the Purine Research Society and the National Urea Cycles Disorder Foundation, have also been advocating for scientific research related to abnormal glutamate functioning in children. Both groups point to the urea cycle, which involves the bodily disposal of excess ammonia. The National Urea Cycles Disorder Foundation explains on its website, “In urea cycle disorders, the nitrogen accumulates in the form of ammonia, a highly toxic substance, and is not removed from the body, resulting in hyperammonemia.” The Purine Research Society discusses how children with Purine Autism “excrete too much uric acid in their urine,” and the role that metabolism and genetics play in this process.

The Wikipedia glutamate entry explains the metabolic relationship between glutamate and urea (thank god for Wikipedia):

“Glutamate also plays an important role in the body's disposal of excess or waste nitrogen. Glutamate undergoes deamination, an oxidative reaction catalysed by glutamate dehydrogenase, as follows:

glutamate + water + NAD+ → α-ketoglutarate + NADH + ammonia + H+
Ammonia (as ammonium) is then excreted predominantly as urea, synthesised in the liver. Transamination can thus be linked to deamination, effectively allowing nitrogen from the amine groups of amino acids to be removed, via glutamate as an intermediate, and finally excreted from the body in the form of urea.”

Autism, once considered a strictly neurological disorder, is now being viewed by many cutting-edge doctors and researchers as a whole-body disorder, specifically involving the connection between the digestive/metabolic system and the brain.

Dr. Joan Fallon discussed the possible relationship between protein digestion, amino acids, and autism in her article, Is Autism a Brain Disorder or a Gut Disorder?:

“If protein digestion is not taking place, then the proper number and amounts of amino acids will not be present to make other proteins. The body therefore must prioritize the use of the available amino acids, and it is possible or at least theoretical that the body will sacrifice the use of the available amino acids to allow the most function not necessarily the highest function.” (Caveat: I have no idea why this article was published on a chiropractic website.)

Discover Magazine recently published Autism, It’s Not Just in the Head. The article features Harvard pediatric neurologist Martha Herbert, who writes on her website, “After much thought, I have come to the formulation that autism may be most inclusively understood and helped through an inclusive whole-body systems approach, where genes and environment are understood to interplay.”

This makes total sense to me, since our brains don’t function in isolation from the rest of our bodies, and our bodies don’t function in isolation from our environments.

So here’s my theory, based mainly on the AGP findings and other research cited above: In at least some people with autism, protein digestion is impaired. The amino acid glutamate is thus not being properly broken down in the digestive system, and glutamate is not being sufficiently utilized as a neurotransmitter in the brain. Normal glutamate functioning is necessary for the bodily disposal of excess nitrogen. Insufficient glutamate is causing a build-up of excess nitrogen in the body.

To understand how excess nitrogen may affect our bodies, consider how it affects the earth. Nitrogen pollution in soil and water causes algae blooms - similar to bacterial build-up - and reduces oxygen flow. Biodiversity suffers. Bodies of water become cloudy.

In humans, excess nitrogen may result in bacterial growth in the watery areas of the brain. This may explain the brain inflammation common to many people with autism. It may also explain what some people colloquially call, “brain fog,” or mental/communicative confusion. Neurotransmission, already limited by insufficient glutamate, may be further limited by bacterial build-up.

Magnesium supplementation has been shown by some researchers to reduce autistic symptoms. This may be because magnesium aids protein digestion, which perhaps allows for higher glutamate functioning. Could glutamic acid supplementation possibly help reduce autistic symptoms? (There also exist food additives called “magnesium glutamate” and “magnesium aspartate,” which I don’t totally understand yet. I also don’t totally get how Monosodium Glutamate (MSG) is created or why it causes headaches in some people and addictions in others. Also, if any scientists out there are clear on the difference between glutamate and glutamine, please explain.)

Thinking along bio/environmental lines, I find it interesting that Dr. Herbert earned a doctoral degree in History of Consciousness from U.C. Santa Cruz (my undergrad alma-matter), where she focused on the “evolution and development of learning processes in biology and culture.” She then earned her medical degree at Columbia University, and she trained in neurology and child neurology at the Massachusetts General Hospital. I find her approach to autism research refreshing, and I believe it will take doctors like her, who think outside the neurological box, to uncover the mysteries of autism.

Again, the above theories are a special education teacher’s interpretation of the Autism Genome Project’s recent findings, and they may be on or off the mark. If nothing else, I hope the links I've provided above will help a few people understand the scientific aspects of autism a bit better. Hopefully, in the next year, we’ll be hearing more from the likes of Dr. Herbert and the AGP researchers.

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Anonymous Linda Galeana said...

I wish a study would be done of this. i have 2 autistic grandchildren. i wish someday for something to help them have a better life as they grow.

12:44 AM  
Anonymous Jules said...

wow. i have been thinking along similar lines, but haven't had a chance to research it as thoroughly as you. thanks for posting this!

11:48 AM  
Anonymous Anonymous said...

I am an Aspergers adult and I am doing really well with nutritional therapy. I take magnesium supplements every day and it helps my stress level. My lab work confirmed blood chemistry was off a bit and my doc went on to explore that and found my magnesium levels were low. I am also soy intolerant and avoiding soy and red or blue dyes helps me with focus and overstimulation. I think AS kids should be tested for celiac and lactose intolerance. Many AS adults I know are sensitive to the oddest sorts of things!

My IQ has always been measured as quite high so I don't know how I stack up against your students.....I attended a school for the gifted at one point. I have edetic memory and unusual spatial ability for certain maths. I read three languages well and some others roughly.

I am concerned about the HBOT fad....putting kids in an HBOT lite bag (few military/hospitals with real dive tanks let children in them. period.) is NOT going to help. I bring this up because the manufacturer's of this product claim the nitrogen issue as the root of autism and are telling parents that their pressurized bag is the cure parents are looking for. I am not sure that the HBOT lite bags make much pressure over what an oxygen mask can provide! Expensive though.....

I had a gifted teacher named Mrs. Massengill when I was in 6th grade. I never got to thank her because she died of Parkinson's.

Keep the faith. We are a difficult population to serve but lotus flowers grow from the mud. You might be surprised when your students come back in 20 years to see you.


9:42 PM  
Anonymous Anonymous said...

I admire your passion to understand
this complex disorder, just cause you are special ed teacher.
It is teachers like that have made it possible for these "special" yet talented kids to acheive their potenial.
Sept 5th is celebrated as teachers day in India and we revere teacher only next to GOD. God Bless you !

4:02 PM  
Anonymous Anonymous said...

"In humans, excess nitrogen may result in bacterial growth in the watery areas of the brain."

Where is the evidence for this?

"Neurotransmission, already limited by insufficient glutamate, may be further limited by bacterial build-up."

It works both ways (and probably has little, if anything, to do with bacteria). Too much glutamate can impede neurotransmission through the process of depolarization. This is the "excititoxin" theory of glutamate, which has problems of its own, but for which there is plenty of evidence. However glutamate is the most common amino acid in foods and is one of the most dominant neurotransmitters. Some people would have you believe that avoiding all glutamate is a valid approach, but that's practically impossible. It's better to focus on what happens with glutamate downstream.

"This may be because magnesium aids protein digestion, which perhaps allows for higher glutamate functioning."

That's kind of a long shot. The more likely explanation is that Mg serves as a cellular gatekeeper, preventing the entry of calcium, which would otherwise facilitate depolarization and eventual cell death due to overstimulation. Search for information about the relationship between Mg and NMDA receptors. This is the opposite of your theory: magnesium helps certain people because it reduces the activity of the glutamate-releasing NMDA receptor.

"Also, if any scientists out there are clear on the difference between glutamate and glutamine, please explain."

I'm no scientist but I can tell you that glutamine is essentially a molecule of glutamate bound to a molecule of ammonia. They are two related but functionally different amino acids.

Despite the wild speculation explored in your blog post, there is a grain of truth here. People who have high ammonia will probably have lower glutamate because the body binds glutamate and ammonia to create glutamine. This is a defense mechanism against the high toxicity of ammonia. Supplements such as arginine and biotin can help stimulate the urea cycle and get rid of ammonia through different pathways. Arginine is also pro-viral and is required for production of nitric oxide, which can have toxic effects of its own, and which is also involved in feedback loops related to the aforementioned NMDA receptors and calcium flux.

All of this - red blood cell levels of Mg, glutamate levels, glutamine levels, urea, ammonia – can be easily tested. Why guess when you can test?

1:24 PM  
Blogger Chrissy G said...

Thanks for the challenge and the call for more scientific rigor, anonymous. It is sorely needed. This theory was a shot in the dark from a self-identified non-scientist from several years ago. Looking back, I was probably off on many points, but the glutamate amino acid to neurotransmitter connection is finally being explored in more depth by real scientists!

8:12 PM  

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