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Austism and the role of brain glutamate

Full Steam

The renegade master
V.I.P Member
I've been meaning to write a blog post about this "once I've finished my research and tests on myself", but it's been months now and it's still on going, and I also think maybe other people might know stuff about this too.

Background

I've had my genome sequenced at Ancestry DNA. I downloaded my RAW DNA data and uploaded it into a number of tools to find my gene mutations (SNP - Single Nucleo Peptides).

I spent ages researching each and working on them, and then found a local doctor who understand this type of thing and the Methylation cycle which was my main focus. I've had blood tests done that were indicated from my gene results.

I'm only going to talk about one today, and that's GAD1. The reason is that I think it may be a common autism one. A friend of mine also has it and has similar symptoms to me, and I often see these symptoms discussed around here.

GAD1 the core embuggerance.

So, a little about GAD1...

From self hacked;
"
Glutamic Acid Decarboxylase (GAD).
Glutamic Acid Decarboxylase converts glutamate to GABA.

If this protein isn’t working, you’ll have excess glutamate and too little GABA in various brain regions. Glutamate is the main excitatory neurotransmitter and GABA is the main inhibitory neurotransmitter."

Symptoms you may experience;

  • Irritability
  • Anxiety
  • Fatigue
  • OCD
  • Problems sleeping
  • Can't concentrate
  • I get ADHD like symptoms
  • Maybe depression, but I'm not 100% about that
  • I get an electric feeling under my skin when it's really bad.


Because I don't convert glutamate to GABA I think I always have a bit too much glutamate and if I eat glutamate rich foods, especially MSG, Gluten and Casein I have way, way too much.


More problems if we don't address glutamate in the brain.

Glutamate in excess causes excito toxicity (too many excitory neurotransmitters)

(source; Excitotoxicity - Wikipedia)

"
Excitotoxicity may be involved in spinal cord injury, stroke, traumatic brain injury, hearing loss (through noise overexposure or ototoxicity), and in neurodegenerative diseases of the central nervous system (CNS) such as multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, alcoholism or alcohol withdrawal and especially over-rapid benzodiazepine withdrawal, and also Huntington's disease.[3][4] Other common conditions that cause excessive glutamate concentrations around neurons are hypoglycemia.
"
That's a nasty looking list, and it's proven that it leads to neuron death eventually.


Ways to help the problem.

Remove sources of free glutamate.

  • Gluten esp. wheat
  • Dairy, esp cheese
  • MSG and any aadditivewith it in (most ingredients that show "natural flavours" are MSG that is naturally occurring)
  • Soy, esp. soy sauce (OH NO!!!)
  • Long, slow cooked meat.
  • Cured meat.
  • Seeds & nuts (double OH NO!!)

Check out this link for more info; sources of free glutamate.

I've found myself loads better after removing most of the above. The biggest gains were from dropping cheese and gluten, and I find small amounts of dairy and small amounts of non-wheat gluten are often ok.


Supplements to help.

First, why taking GABA is only limited if any help. GABA supplements can't cross the blood brain barrier, but they CAN bind to GABA receptors in the gut. I do find GABA calming, but it's only of limited help and it seems to give me palpitations if I take too much. I think that it's calming me, but not helping the root cause which is too much glutamate in my brain. We need something to reduce the gluamate and the damage it causes.

For glutamate to cause it's damage it needs to bind to NMDA receptors in the brain. Other substances can block this by binding to the same receptors and out competing glutamate.

Here is a list of substances that block the receptor (note, some of these are dangerous and/or illegal, and you should seek medical help before taking anything that you don't know to be safe).
(source; NMDA Antagonists - Supplements) I had a better source but can't find it right now,

"
NMDA antagonists

Magnesium — a potent NMDA inhibitor. High dose transdermal application, or injection, required for maximum effect.

Zinc

Progesterone (a hormonal supplement usually sold as a transdermal cream)

Huperzine A (a supplement)

Taurine (taurine also activates GABA receptors)

Amantadine (antiviral drug, also used for Parkinson's and Alzheimer's)

Agmatine (a supplement)

Lithium

Dextromethorphan (DXM) — an over-the-counter cough mixture (cough suppressant)

Dextrorphan (DXO) is an active metabolite of DXM. DXO a psychedelic drug and cough suppressant, is a much more potent NMDA antagonist than DXM. DXM is converted to DXO in the body by cytochrome P450 2D6 isoenzyme (aka: CYP2D6). Thus cytochrome P450 2D6 inhibitors such as imipramine, propranolol, quinine and citalopram may decrease the effect of DXM.

Dantrolene (muscle relaxant)

Orphenadrine (muscle relaxant)

Methadone (opiate)

Dextropropoxyphene (weak opiate)

Ketamine — an anesthetic and recreational drug.

Riluzole (ALS drug)

Memantine (Namenda)

Ibogaine — the hallucinogenic active principal from the root bark of Tabernanthe iboga. Microdoses of around 50 mg daily of Tabernanthe iboga root bark will not produce a hallucinogenic effect, but still have therapeutic effects. Tabernanthe iboga root bark is legal to buy in the UK, but not in the US.

Nitrous oxide (N2O) — an anesthetic gas (often used in dentistry) and and recreational drug. Also know as laughing gas. Depletes vitamin B12.

Guaifenesin (possibly?) — an over-the-counter decongestant. The guaifenesin protocol is a fibromyalgia and ME/CFS treatment.

Xenon gas. An anesthetic gas.

Cat's claw (Uncaria tomentosa) — the rhynchophylline constituent of this herb may inhibit the NMDA receptor.

Syrian rue (Peganum harmala) — a MAO-inhibitor herb. MAO-inhibitors should never be taken with nexavir/kutapressin.


Dangerous NMDA inhibitors:

Lead is a potent inhibitor of the NMDA receptor

Phencyclidine (PCP, angel dust) Some studies found that, like other NMDA receptor antagonists, phencyclidine can cause a certain kind of brain damage called Olney's lesions in rats.

Kynurenic acid (high levels associated with schizophrenia and pychosis)

NMDA agonists (NOTE stay away from these)

Glutamate
Glycine
Ammonia

"

I take taurine and zinc for now, and I'm trying to find magnesium that I don't react badly to.

I also drink a few beers every night, and ethanol is also an NMDA antagonist which finally explains why it's been so efficient at removing symptoms. 2 -3 beers and my agitation and electric under the skin feeling dissapears.


I'll update as I learn more - hope this helps someone.
 
Update;

Two NMDA antagonists I forgot;

Curcumin
Ginko Biloba.

Also, it's a good idea to get your genome sequenced. It cost me about $150 AUD and about $30 USB for the software.
 
mother tried this diet 20 years ago had pseudo bulbar palsy (one of the motor neurone diseases)did no good what so ever made her weaker.
went back to a high calorie diet, she was 3 and a half stones when she died
 
Full Steam!

First, congrats to you for taking the initiative to have your genetic testing done and researching ways to improve your health! It would be nice if everyone left the hospital after they were born with a copy of their genetic results and instructions on how to optimize their health, based on their genetics, wouldn’t it? Sadly, we all have to navigate this big maze by ourselves and peel back the many layers of this enormous onion!

For your GAD1 mutation, I highly suggest you explore the benefits of adding P5P (active B6). P5P is necessary for GAD to function. One could take B6 with the hopes of one’s body converting it to active B6, but many people have issues with this conversion. Taking P5P bypasses any issues.

Here’s some interesting reading for you to do on the subject:

Glutamate Excitotoxicity: The Brain, The Nervous System & Nutritional Solutions - Metabolic Healing
and
Questioning Answers: GABA Dabba Doo

Another thing you should take the time to read is a presentation by Dr. Stephanie Seneff, a brilliant researcher out of MIT. Take a look at this and especially pay attention to the chart on slide 67 showing the difference in glutamate and glutamine levels in kids with high functioning autism vs. controls. people.csail.mit.edu/seneff/California_glyphosate.pptx

For what it’s worth, I, also, can’t tolerate magnesium well. For me, I believe it’s because of my SOD2 mutations, which increases my need for manganese. Magnesium antagonizes manganese, so doesn’t work well for me.

Having genetic results is so powerful, but, could literally spend months researching everything. I know I wish I had more time to spend on it! :)

Good luck to you in your journey to better health and happy researching!
 
Full Steam!

First, congrats to you for taking the initiative to have your genetic testing done and researching ways to improve your health! It would be nice if everyone left the hospital after they were born with a copy of their genetic results and instructions on how to optimize their health, based on their genetics, wouldn’t it? Sadly, we all have to navigate this big maze by ourselves and peel back the many layers of this enormous onion!

For your GAD1 mutation, I highly suggest you explore the benefits of adding P5P (active B6). P5P is necessary for GAD to function. One could take B6 with the hopes of one’s body converting it to active B6, but many people have issues with this conversion. Taking P5P bypasses any issues.

Here’s some interesting reading for you to do on the subject:

Glutamate Excitotoxicity: The Brain, The Nervous System & Nutritional Solutions - Metabolic Healing
and
Questioning Answers: GABA Dabba Doo

Another thing you should take the time to read is a presentation by Dr. Stephanie Seneff, a brilliant researcher out of MIT. Take a look at this and especially pay attention to the chart on slide 67 showing the difference in glutamate and glutamine levels in kids with high functioning autism vs. controls. people.csail.mit.edu/seneff/California_glyphosate.pptx

For what it’s worth, I, also, can’t tolerate magnesium well. For me, I believe it’s because of my SOD2 mutations, which increases my need for manganese. Magnesium antagonizes manganese, so doesn’t work well for me.

Having genetic results is so powerful, but, could literally spend months researching everything. I know I wish I had more time to spend on it! :)

Good luck to you in your journey to better health and happy researching!

Thanks, I'll definitely read through those.

Interestingly I already take p5p as I have pyroluria. Maybe GAD1 is the smoking gun for that too? I've been wondering about why I need it.

Just checked and i have one heterozygous mutation in SOD2, and one in SOD1. The rest are the common allele or not found in my data.

I'm checking into the magnesium / manganese reactions. It seems I have heterozygous mutations that impair manganese transport, meaning I may not handle manganese well. I have medication with it in that's been causing problems, and I've quit using it.
 
Interestingly I already take p5p as I have pyroluria. Maybe GAD1 is the smoking gun for that too? I've been wondering about why I need it.

That's so interesting and a great question!

Which mutations do you have in manganese transport? Just thinking out loud, it would seem that it could mean one can't tolerate any manganese or it could mean that one needs increased manganese to overcome the transport issues. For me, I distinctly remember the first time I took manganese three years ago. I literally could feel my ears opening up. It was both scary and amazing, all at the same time! LOL Turns out there are some tiny bones in your ear that require manganese. All my life, I had issues with my ears and had horrible time flying with the pressure changes. All those issues are now gone. Wish I had known this many years ago!

Another interesting thing genetic results taught me is that I shouldn't take Methyl B12 and explains why I always felt bad - total brain fog- when taking it. Based on COMT and VDR Taq results, it points one to what type of B12 to take. Fascinating research by Dr. Amy Yasko. If you haven't come across this, here's some info - Best Form of B12 - Methyl-Life (ignore the sales ad, I just have this in my research for the chart of combinations).
 
I've read a lot of Amy Yasuo. It was partly her that led me to start investigating autism and doing an online test.

She stared treating autism and still does I think.

I'll drop some interesting mutations in when I get a sec. I have some COMT and Vdr, but also have homozygous MTRR so I do need B12. My doctor seems to think I'm ok on methyl B12, and it doesnt cause any obvious issues.

I'm going to try hydroxy B12 at some point though. There's a place in Australia that makes B12 oils which are supposed to be good. My supplement budget is a bit high already though!

I also have some heterozygous cbs and mat1a, and maoa.
 
Supplement budgets are always high! :) Beats paying the pharma companies, doctors, and hospitals! :)

Good luck with the Hydroxy B12. I've tried it several times over the years and tried different manufacturers and I always immediately get acne from it. I've researched it and found others with the same issue, but haven't pinpointed the reason why. I'm definitely in the minority, though, as most people don't have issues. For now, I just take Adeno B12.

Your P5P should help your CBS mutation. Are you taking R5P for your MAOA? Haven't researched anything with MAT1A, so totally unfamiliar with that, though I do have one hetero mutation.
 
Trytophan makes you calm its in french green beans,peanuts,chocolate ,beer,you can get trytophan on prescription in some countries
 

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