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Monday, 18 March 2013

Glutathione (GSH) Part II - N-Acetylcysteine (NAC)

Please take a look at Part I before reading this post.  Remember this is a blog, not medical research or medical advice.  Always read the full clinical study and then go talk to your paediatrician.
 

Here is the final part of my current research into GSH which, you will be pleased to learn, leads to where it should; a successful clinical trial.  This time it is not in France, the trial will be in Palo Alto, California, home of Stanford University.

You will recall, that while researching one evening in February, I had rather stumbled upon the subject of GSH.  In Part I you learned all about GSH, Redox and came across a funny type of stinky chemical called a thiol.  I asked you to make a note of one particular thiol called Cysteine.

 

1.     Brain region-specific glutathione redox imbalance in autism

 We now go inside the autistic brain.  Last year some very smart Americans did some research measuring GSH and GSH Redox  (the ratio of GSH/GSSG) in different regions of the brain of autistic subjects.  You will probably prefer not to know how they managed to do this.

 They were able to prove that in certain parts of the brain, GSH Redox was decreased by more than half in the autistic subjects, compared to typical subjects of the same age.  That means GSH was low and GSSG was high.  By consequence, the autistic brains had a much higher level of oxidative stress (always a bad thing) than the other subjects.

They suggested that this might leads directly to the neurodevelopmental abnormalities in autism.


 

2.    Regulation of cellular glutathione

So now I was on a roll, I had found a serious biological abnormality in autism, but would it lead me to another Epiphany? Highly unlikely I thought, but onwards I went.

The next step was to find out a bit more about GSH

This part is both interesting and rather complicated, so I am going to give you just the highlights.


  • Glutathione synthesis and metabolism
The way GSH is synthesized in the body seems well understood in the literature.  While hoping to simplify this text I do need to point out I just noticed another odd coincidence that I have to follow up on later (NADP/NADPH the actual chemical required for the GSH Redox chemical reaction to take place also has other known functions in human biology NADPH is used for processes such as lipid synthesis, cholesterol synthesis and fatty acid elongation.  I have another parallel investigation into omega 3 and autism, where I have learnt that in autistic children  there is a proven lipid metabolism disorder that causes high cholesterol and low omega3/omega6 ratio.  So have to add NADP/NADPH to my list of things to investigate).

GSH is all over your body - brain, lungs, liver, kidneys and in all these places some of it gets converted to GSSH.  But on balance, if your body is in good shape GSH should be greater than 99% and GSSH less than 1%.  If not, bad stuff will happen.

There are five known ways to increase the level of GSH (a good thing to do):-

1.    Enhancement of uptake of cystine

2.    Reduction of cystine to cysteine  (add a reducing agent such as NAC)

3.    Provision of alternative sources of cyst(e)ine

4.    Provide a GSH precursor (γ-Glutamylcysteine) directly

5.    Add GSH directly (intravenously, not by eating it)

 
3.    Clinical trial of glutathione supplementation in autism spectrum disorders

I came across a study from 2011 when some well-meaning folk wanted to test GSH supplementation in autism.  Now the problem is that they neglected to spend 4 hours on Google Scholar before they started.  Now, if you think I am beginning to sound smug, well you are entirely correct.  It seems Peter, doing research in the spare room, knows more about something than some white coated researchers.

They just had to look on Wikipedia to learn that “Raising GSH levels through direct supplementation of glutathione is difficult.  Research suggests that glutathione taken orally is not well absorbed across the gastrointestinal tract”  They quote research from 1992, so it must be widely known by 2011.

The study used oral GSH and a commercial transdermal GSH preparation called KIRKMAN Reduced L-Glutathione Lotion (50 g will set you back  EUR 45)

 But at least the idea behind the trial was good.

 

4.     Glutathione precursors to raise GSH levels in plasma (N-acetylcysteine, whey protein)

Going back to hard science, you quickly find that there are already well established methods to successfully raise GSH levels, via the administration of certain supplements.

 ·         Whey protein, as used by body builders, but not so cheap

 ·         N-acetylcysteine, otherwise known as NAC and pretty cheap.

 
So I follow up both and later opted for NAC.


5.     N-acetylcysteine (NAC)  in the Emergency Room and  Psychiatry

NAC has been used as a precursor to GSH for more than 30 years.  It is the standard Emergency Room treatment in the case of paracetamol overdose.

It turns out that NAC is another little wonder.  It is already used in obsessive compulsive disorder, schizophrenia, trichotillomania (a new one to me) and bipolar disorder.  It is even used in HIV therapy.

But no mention of Autism.

NAC is available as a drug or as a supplement without prescription.


6.    A Randomized Controlled Pilot Trial of Oral N-Acetylcysteine in Children with Autism

Finally, the bit you have been waiting for.  When I found this clinical trial at the end of  my 4 hour Googling session, I would have fallen off my chair, had I not been lying down at the time.

A eureka moment perhaps;  I found a clinical trial testing just what I wanted to test -  a serious study of NAC on the behaviour of kids with autism.  This study was carried out by Antonio Hardan at Stanford University, California.

Enough said.


  

 
If you want the full version they expect you to pay $31.50.

Well that was a productive 4 hours, but it set me back another $31.50.

Sadly, finding all the references again and writing my two posts on GSH has taken another 4 hours.

That was of course a few weeks ago.  The rest is history.  I suggest that you turn on your speakers., and click the link below.

 

 
1965 was an important year.  One of them was that this song was produced and is apparently  #89 in  Rolling Stones list of the 500 greatest songs of all time.

2 comments:

  1. This is fascinating. Like you, my husband and I spend hours and hours reading research about autism because our son has it (high-functioning...quite bright and creative..) This is so interesting. Do you have any updated information about NAC? Is anyone else trying it in studies?

    ReplyDelete
    Replies
    1. Many people use NAC and other antioxidants (ALA, carnosine etc) and find it helps autism. These are all cheap and available widely so there is no money to be made and no incentive for large expensive trials.

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