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Showing posts with label Porphyrin. Show all posts
Showing posts with label Porphyrin. Show all posts

Monday 30 September 2013

Biomarkers in Autism: Mercury – Science, Bad Science & GSH (again)

You do not need to have any particular view about vaccines and autism; but there are some very strange connections between mercury and autism.

I came back to look at this subject, having noticed that one of the more rational/objective researchers included a chelating agent in his patent for autism treatment.   Chelating agents remove heavy metals like mercury or lead from the body, but they also remove important elements like calcium.  Very high or low levels of electrolytes like Ca or K can kill you.

In 2006 clinical trials on chelation therapy in autism were halted by the US National Institute of Health on “safety reasons”.  But in 2012, a much bigger 5 year long, $30 million study called Trial to Assess ChelationTherapy (TACT) in coronary heart disease reported back that this “fringe” therapy did indeed work, though for reasons unknown.


The autism trial was to use a chemical called DMSA,  while the coronary heart disease trial used a chemical called EDTA.  The 5 year trial appeared to show EDTA was safe.


Measuring Mercury

There are various ways of measuring for mercury; you can measure for it directly in urine, blood, hair and even teeth.  You can also measure for biomarkers of mercury and the popular one is called Porphyrin Testing.

The problem is that if you have been subject of some serious heavy metal contamination the metal may no longer be in your blood or urine in elevated levels.  This is why forensic science laboratories look at hair and teeth.

At this point the bad science and the science start to get mixed up.  There is a chemical called precoproporphyrin, an atypical porphyrin previously identified only in adult humans and animals with prolonged exposure to Mercury or compounds containing mercury.  It is often present in substantial concentrations in urine of younger children with autism.

This has created a nice business with laboratories charging $120 to measure porphyrin in the urine of autistic children.  A handful of researchers keep writing studies about mercury in autism, using porphyrin to “measure” them.

One of the labs used is surprisingly in France.  It seems many US citizens are mailing samples to Laboratoire Philippe Auguste in Paris.

But, at the same time, another group of scientists take the opposite approach and say that urinary porphyrins are biomarkers of autistic spectrum disorder, because a subset of people with ASD have disordered porphyrin excretion as a metabolic characteristic.  They have gone so far as to patent their idea as a test for autism.  By this logic paying $120 to test a kid known to have ASD would be pretty pointless.


The researcher suggests that the elevated Urinary porphyrins have nothing to do with mercury at all.


… Several possibilities might account for these differences. Not to be bound by theory, Hg exposure appears unlikely to play a role in this effect, because no significant differences were observed between NT and AUT subjects for indices of past exposure to Hg from dental or medical sources, as reported by parents/caregivers. Additionally, urinary Hg concentrations, measures of recent Hg exposure, were very low among all subjects in this study (Table 2), and no significant differences between diagnostic groups were observed …


… the present findings indicate that porphyrin metabolism, particularly in preadolescent children, may be too disordered or differently regulated to permit detection of the Hg-mediated changes in urinary porphyrin excretion that are apparent in adult subjects …


… another factor that may account for the differences in urinary porphyrin levels between AUT and NT children is mitochondrial dysfunction, a disorder commonly associated with autism …


Where is the Mercury coming from?

The sources put forward as to where the mercury is coming from include:-

·        Mother’s dental fillings containing mercury

·        Any amalgam fillings the child has

·        Mercury in the environment

·        Mercury in vaccines

If your body is unable remove mercury as fast as it is absorbing it, then the total amount of mercury in your body will increase.  So it is your cumulative past exposure, minus what you have removed, that is the key figure.

The body’s main antioxidant, glutathione (GSH), is its key resource to deal with disposing of heavy metals.  It has been established for years that GSH levels are reduced in almost all cases of autism.  Incidentally, GSH levels are also reduced in old age and so those subjects in the TACT clinical trial for chelation in heart disease that benefited, did do (according to Peter) because the chelator is an antioxidant.  It lowered their oxidative stress and raised their GSH level.


Mercury in Hair Samples

An interesting study measured the level of mercury in babies’ first haircuts.  This is about when the baby is 17 months old.

The study showed much lower levels of mercury in the ASD babies than in the control babies.  This is probably the opposite of what you might have expected.  There is also a nice chart correlating the level of mercury in the control babies with the number of amalgam fillings in the mother.


The authors proposed that the kids with ASD must have higher levels of mercury in their bodies, because they are unable to eliminate mercury like typical children.

“If reduced overall mercury elimination is related to hair elimination, then autistic infants will retain significantly higher levels of mercury in tissue, including the brain, than normal infants.”



  
A later study has some equally surprising findings.  The study in Poland, looked at kids aged 3-4 and also 7-9.  They found, as in the baby study, that the youngest kids had lower levels of mercury in their hair than the typical kids.  But the older kids had higher mercury levels in their hair than the kids in the control group. 


The conclusion was that:-
The results suggest that autistic children differ from healthy children in metabolism of mercury, which seems to change with age.

Mercury in baby teeth

 So now we come to teeth.  If the ASD kids have low mercury, it will be claimed that this means they must have high internal levels since they have not eliminated it in their teeth.  If they have high mercury then they will say that this proves there is a high level of mercury in kids with ASD.  Read on and find out.

Well the study tells us that baby teeth are a good measure of cumulative exposure to toxic metals during fetal development and early infancy.  They found that 6 year old children with autism had twice as much mercury in their teeth as neurotypical children.



This study determined the level of mercury, lead, and zinc in baby teeth of children with autism spectrum disorder (n = 15, age 6.1 +/- 2.2 yr) and typically developing children (n = 11, age = 7 +/- 1.7 yr). Children with autism had significantly (2.1-fold) higher levels of mercury but similar levels of lead and similar levels of zinc. Children with autism also had significantly higher usage of oral antibiotics during their first 12 mo of life, and possibly higher usage of oral antibiotics during their first 36 mo of life. Baby teeth are a good measure of cumulative exposure to toxic metals during fetal development and early infancy, so this study suggests that children with autism had a higher body burden of mercury during fetal/infant development. Antibiotic use is known to almost completely inhibit excretion of mercury in rats due to alteration of gut flora. Thus, higher use of oral antibiotics in the children with autism may have reduced their ability to excrete mercury, and hence may partially explain the higher level in baby teeth. Higher usage of oral antibiotics in infancy may also partially explain the high incidence of chronic gastrointestinal problems in individuals with autism.


How much Mercury is bad for you?

Mercury is definitely not good for you, but just how much is actually bad for you?

Eating a lot of fish will raise maternal levels of mercury, so in the US women are advised to eat less fish during pregnancy.

In the Seychelles (islands in the Indian Ocean) the diet included 10 times as much fish and since they eat big fish, mercury consumption is 20 times higher.  The level of vaccination was near 100% and the vaccines contained thimerosal.



Using linear and nonlinear regression analyses, the researchers found no consistent correlation between prenatal exposure to methyl mercury and scores on ASD screening instruments.

Parent feedback

If you look on the web, it is pretty clear that many parents think their chelation therapy had a positive impact.  There is even a very unscientific survey showing this somewhere; I cannot find it today.


Since the chelation is like a big anti-oxidant infusion, I would expect to see a big positive improvement, regardless of whether mercury has anything at all to do with it.

Big Sceptics

There are some big sceptics about chelation.  Here is one site called chelation watch
and here is an interesting article by a Doctor who followed ”his dark side” into the world of alternative therapy and emerged a big sceptic.

James R. Laidler, MD    -  My Involvement with Autism Quackery

My personal journey through the looking glass has ended. I stepped into “alternative” medicine up to my neck and waded out again, poorer but wiser. I now realize that the thing the “alternative” practitioners are really selling is hope—usually false hope—and hope is a very seductive thing to those who have lost it.

Other research

There is plenty of other research on the subject of my post.  Normally you can tell by who funded the study or who worked on it, what the likely conclusion is to be.



This paper again shows that urinary porphyrins are a biomarker for autism, rather than mercury.


This paper repeats the story about urinary porphyrins indicating high mercury in autism  



Conclusion

If the US National Institute of Health removed its ban on the clinical trial of chelation in autism, then there would be some high quality facts to judge.  Sadly, this all seems to be linked to “big brother” trying to halt the debate about autism and vaccinations, all for the very sound reason of public health.

I think it is quite possible that the culprit is oxidative stress and low GSH and that the bizarre results of mercury levels in hair, teeth and urine are in fact no more than a consequence of low levels of GSH.  The oxidative stress is clearly damaging, perhaps the slightly elevated levels of heavy metals are themselves harmless.

Perhaps the best thing would be to measure the level of GSH (GSH redox) in babies, children and then again after middle age.  High levels of oxidative stress, whether linked to autism or other conditions could then be treated.

There is a cheap and effective antioxidant called NAC (N-acetyl cysteine), it is known to raise GSH.  If you want to call it a chelating agent, you would also be correct.

Since mercury is known to be a very harmful substance, we should of course try to minimize it in humans.