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Saturday, 13 July 2013

Endothelial Dysfunction - Oxidative Stress, Inflammation and BH4

This post is rather out of sequence, but it draws together several different topics that I have been investigating and introduces another chemical often mentioned in autism research, BH4.  The factor that links them all together is something called Endothelial Dysfunction.

This blog has already established that oxidative stress and neuroinflammation are the key drivers behind autism.  It has not been clear whether the oxidative stress causes the inflammation, vice versa, or perhaps they are self perpetuating.

In my ongoing investigation into the autism comorbidities of asthma and high cholesterol (proxy for cardiovascular disease), I have come across some tantalising fact, such as:-
  • Asthma research shows that cigarette smoking gives you oxidative stress and this continues even after stopping smoking.  The oxidative stress reduces the effectiveness of asthma drugs.
  • Oxidative stress is a key factor in cardiovascular disease.
  • BH4 also known as Tetrahydrobiopterin, THB, trade name Kuvan or sapropterin is an enzymatic cofactor that is the subject of lots of research in cardiovascular disease and even in autism research.  As a drug, BH4 is so expensive that many national health services and insurers will not pay for it.  A pack of 30 pills of 100 mg cost $900.  The typical dose is 10-20mg per kg per day.  The cost per patient was reported to be over $100,000 per year.

The BH4 drug, Kuvan, is used to treat an extremely rare, but debilitating condition called Phenylketonuria, when the body cannot produce its own BH4.  In the UK, the National Health Service will not pay for Kuvan for the very small number of people who suffer Phenylketonuria.


A very interesting chart from the American Heart Association

The following chart was meant for cardiologists, but is extremely relevant if you want to understand autism.  I highlighted the parts in yellow.

























In autism, people suffer from oxidative stress and typically exhibit hypercholesterolemia (high cholesterol).  They also suffer from neuroinflammation in the brain.  In my therapy, I use NAC to reduce oxidative stress and the behavioral impact is very marked.  In some autism trials they have given BH4 and the result have been visible, but not dramatic.  From the graphic above it would seem that BH4 is an extremely expensive way to reduce oxidative stress.

The latest BH4 autism trial was funded by the drug producer with 20 mg/kg/day.
 

More interesting for me is to now look into Endothelial Dysfunction and see if that is occurring in autism.











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