Sustained Release NAC for Autism and Schizophrenia

“Pharmacokinetics” of a typical drug

Today’s post is about what should be the optimal anti-oxidant therapy for autism, schizophrenia, COPD and any other disease in which oxidative stress is present.  You will have to be able to swallow pills, to fully benefit.

NAC seems to be the most potent, safe, anti-oxidant, the only drawbacks are:-

·        Short half-life

·        Can taste/smell bad

In autism, NAC is normally given three times a day, but often it is not practical to give a drug at precise intervals throughout the day.

This is a common problem with many drugs and has been solved long ago – with the sustained release pill.

If you find that four hours after giving NAC there is an increase in irritability, anxiety or stimming, it may be that oxidative stress has already returned.  It may be that other factors have triggered a higher load of oxidative stress.  The way to be sure is just to give a small extra dose of NAC and wait 15 minutes.  If everything returns to normal, you found the problem.

Since you cannot always be present with an extra half dose of NAC, the answer is the sustained release form of NAC.

Since we have seen that oxidative stress triggers all kinds of secondary dysfunctions, the sustained release form of NAC might also help minimize them, since you could have 24 hour protection.  Oxidative stress does not go away while you sleep.

For example, I recall the Polish researcher at Harvard who suggested that oxidative stress might cause central hypothyroidism in autism (low levels of T3 in the brain).

Your body produces the pro-hormone T4 in the thyroid which then circulates throughout the body.  Special enzymes, produced locally, then convert the T4 into the active hormone called T3.  The researcher found that in the autistic brain this enzyme was reduced by oxidative stress.

Many “alternative” doctors, mainly in the US, do prescribe extra T3 hormone to people with autism and indeed other conditions.  Some older ladies across the world are buying T3 hormone, online from Mexico, since their doctor will not prescribe it.  They say it makes them feel better.

As your endocrinologist will tell you, hormones are controlled by so-called feedback loops.  So if you start adding extra T3 hormone, your thyroid will start producing less T4.  Then you need even more supplemental T3.

I did do a little experiment with a small dose of T3, to see if a short term increase in T3 affects “my” kind of autism.  It most definitely does; as does a short term spike in potassium levels.  These are useful diagnostic tests, rather than therapies.

This would suggest that minimizing oxidative stress 24 hours a day, may not just be possible, but also highly beneficial.

 

OTC Sustained Release NAC  (NAC SR)

There actually is an inexpensive Sustained Release NAC , available OTC (without prescription).

  

  

A directly-compressed, controlled release tablet contains N-acetyl cysteine as the active ingredient -   PATENT

The problem with currently-available granulated and effervescent tablet compositions is that they release N-acetyl cysteine very rapidly. Thus, the effervescent compositions as well as the granulate compositions currently available on the market achieve a maximum blood plasma level within 1 hr from administration. One matrix tablet formulation does show a maximum blood plasma level at 2-2.5 hrs after administration, although its recipe indicates that granulation was required. The problem with granulation of acetyl cysteine is that if any dissolves, the dissolved material starts to decompose into impurities.

In accordance with the present invention, this problem of overly-rapid release is obviated by providing the N-acetyl cysteine in the form of a tablet or other article made with the rheology modifying acrylic or methacrylic acid-based polymers, or analogues, described in commonly-assigned application Ser. No. 09/559,687, filed Apr. 27, 2000. Tablets made in this manner exhibit controlled release characteristics, thereby allowing the N-acetyl cysteine active ingredient to be released over a longer period of time.

The rheology modifying polymers used in the present invention provide controlled release of the N-acetyl cysteine and other biologically active compounds contained in the inventive tablet, if any, so that when placed in water or body fluid, the polymer swells to form a viscous gel which retards diffusion of the active material.

The advanced bilayer Sustain™ tablets combine 1/3 Quick Release and 2/3 Sustained Release formats to both immediately raise and to maintain blood levels over a longer period of time.* NAC Sustain^®  releases in the small intestine over a 8 hour period, compared to the 1.5 hour biological half-life of NAC in the bloodstream.*

NAC in published research

Much currently available data is from very early studies on NAC that indicated that the half-life was about 5 hours, but subsequent studies suggested it is very much shorter, perhaps just 90 minutes.

The following study is quite old, but compares the behaviour of different NAC formulations in 10 volunteers.

Pharmacokinetics of N-Acetylcysteine in Man 

Some definitions:-

Half Life

A biological half-life or elimination half-life is the time it takes for a substance (drug, radioactive nuclide, or other) to lose one-half of its pharmacologic, physiologic, or radiological activity. In a medical context, the half-life may also describe the time that it takes for the concentration in blood plasma of a substance to reach one-half of its steady-state value (the "plasma half-life").

The relationship between the biological and plasma half-lives of a substance can be complex, due to factors including accumulation in tissues, active metabolites, and receptor interactions

Mean Residence Time

For the medical field, residence time often refers to the amount of time that a drug spends in the body. This is dependent on an individual’s body size, the rate at which the Drug will move through and react within the person’s body, and the amount of the Drug administered. The Mean Residence Time (MRT) in Drug deviates from the previous equations as it is based on a statistical derivation. This still runs off a steady-state volume assumption but then uses the area under a distribution curve to find the average drug dose clearance time. The distribution is determined by numerical data derived from either urinary or plasma data collected. Each drug will have a different residence time based on its chemical composition and technique of administration. Some of these drug molecules will remain in the system for a very short time while others may remain for a lifetime. Since individual molecules are hard to trace, groups of molecules are tracked and the distribution of these is plotted to find a mean residence time.

Conclusion

This post may have been more useful for adult readers, with Asperger’s, who are self-treating.  Many people with Schizophrenia also self-treat with NAC, but they probably do not read autism blogs.

For those unable (yet) to swallow, pills you can have the option of breaking the effervescent tablets in half (or even quarters) to try and maintain a more stable level of NAC.  We sometimes do this, half a 600 mg tablet at school at 11 am,  when needed.  It only seems to be really needed in the pollen allergy season, which seems to trigger more oxidative stress as well as histamine and IL-6.  It works.

One reader of this blog is doing something similar with Bumetanide, he/she is giving it in three daily doses.  Bumetanide also has a short half-life, as does Verapamil.  There is no sustained release form of Bumetanide, but there is for Verapamil.

A final point raised is whether the benefit from NAC comes from it being a precursor to Glutathione (GSH), the body' own master antioxidant, or whether it is actually NAC's own free radical scavenging properties that really matter. It would appear to be the latter, based on the short half life of NAC and the short term beneficial effect.  This would imply that just normalizing GSH is not enough. Studies have shown that normalizing the reduced levels of GSH levels found in autism is readily achievable.

Sulforaphane (Broccoli) for Cancer, Autism and COPD

A reference to the other Broccoli

One advantage this blog has is that it looks at the comorbidities of autism, so we are aware of useful findings in related areas.  So it then does not come as a big surprise when a therapy effective in related areas also helps with autism.

One of the most useful is asthma.  Chronic obstructive pulmonary disease (COPD) is a related condition, brought on by smoking or pollution.  It kills 3 million people a year; COPD is made much worse by chronic oxidative stress.  We saw in an earlier post that oxidative stress stops the asthma drugs from working.  The current treatment for oxidative stress in COPD is N-acetyl cysteine (NAC).  I recall they are still looking for a better treatment; perhaps the search is over.  (see later).

We also saw that there is already some overlap between “emerging” research findings in cancer and those in autism. These include:-

·        PAK1, mTOR (Rapamycin), Wnt signaling

·        Ivermectin treatment for Leukemia and Autism

·        Quercetin and NAC aiding recovery for specific cancers and helping some in autism

For twenty years researchers have known about the potential cancer fighting benefits of Sulforaphane, which is produced by a chemical reaction when you eat fresh broccoli that was only lightly cooked.

In the intervening years vast amounts of research has been going on to tinker with broccoli to maximize/harness the potential health benefit, and also to develop related synthetic drugs (analogs of Sulforaphane) like Sulforadex.

Twenty years later, and a vast amount of broccoli supplement pills later, not many people have benefitted.  When you look into the matter, it really is rather bizarre.

Fresh raw broccoli was found to contain large amounts of both Glucoraphanin and an enzyme called Myrosinase.  When you eat the raw broccoli the Glucoraphanin and Myrosinase react to produce a potent substance called Sulforaphane, which seems to have numerous positive effects.  A powerful anti-oxidative process is triggered that was shown to have a strong anti-cancer effect.

The problem is that myrosinase from broccoli is not stable; when you cook it, freeze it, or process it, you lose it.  So, soggy cooked broccoli, crisp frozen broccoli and almost all the broccoli pills on the market have no myrosinase and therefore no Sulforaphane will be produced.

There have been numerous studies showing this and also a few clever ideas to get around it have been investigated.

Sulforaphane is itself also unstable and has to be used immediately or kept frozen.

Johns Hopkins and Sulforaphane

Sulforaphane was discovered in 1992 at Johns Hopkins and much related research still comes from there.  They hold the key patents and indeed went as far as to try to stop other people growing/selling broccoli sprouts.  They have developed a way to produce Sulforaphane in the laboratory and then it is freeze dried and kept frozen at -20 Celsius.

Cancer research

The cancers where Sulforaphane has shown promise include:-

§  Carcinogen detoxification

• Tumor progression and activity
• Stomach cancer
• Skin tumors
• Breast cancer
• Prostate cancer
• Colon cancer
• Bladder cancer
• Impact on developing or developed cancers

COPD

What caught my attention was a paper from 2008 by Peter Barnes, one of only two Englishmen on my Dean’s list and the only one that lives there.

Defective Antioxidant Gene Regulation in COPD: A Case for Broccoli

This has been followed up and there is now a Phase 2 clinical trial of Sulforaphane for treatment of COPD.

Broccoli Sprout Extracts Trial (BEST)

Barnes is my kind of scientist.  He has noted that the most potent, safe antioxidant to treat COPD is NAC (N-acetyl cysteine) but he wanted more, and has been on the look-out for years for a stronger, but safe, alternative.  He concluded that

“It has been difficult to find new more effective antioxidants that are not toxic. A more attractive approach may be to restore Nrf2 levels to normal through inhibiting the action of Keap1. This has been achieved in vitro and in vivo by isothiocyanate compounds, such as Sulforaphane, which occur naturally in broccoli”

And finally to Autism

So the recent big news that Sulforaphane was remarkable successful in a small trial at Massachusetts General Hospital (MGH) and Johns Hopkins maybe should not be such a surprise.

Sulforaphane treatment of autism spectrum disorder (ASD)

Autism spectrum disorder (ASD), characterized by both impaired communication and social interaction, and by stereotypic behavior, affects about 1 in 68, predominantly males. The medicoeconomic burdens of ASD are enormous, and no recognized treatment targets the core features of ASD. In a placebo-controlled,double-blind, randomized trial, young men (aged 13–27) with moderate to severe ASD received the phytochemical sulforaphane (n = 29)—derived from broccoli sprout extracts—or indistinguishable placebo (n = 15). The effects on behavior of daily oral doses of sulforaphane (50–150 μmol) for 18 wk, followed by 4 wk without treatment, were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians: the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Clinical Global Impression Improvement Scale (CGI-I). Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane. After 18 wk, participants receiving placebo experienced minimal change (<3.3%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior): 34% for ABC (P < 0.001, comparing treatments) and 17% for SRS scores (P = 0.017). On CGI-I, a significantly greater number of participants receiving sulforaphane had improvement in social interaction, abnormal behavior, and verbal communication (P = 0.015–0.007). Upon discontinuation of sulforaphane, total scores on all scales rose toward pretreatment levels. Dietary sulforaphane, of recognized low toxicity, was selected for its capacity to reverse abnormalities that have been associated with ASD, including oxidative stress and lower antioxidant capacity, depressed glutathione synthesis, reduced mitochondrial function and oxidative phosphorylation, increased lipid peroxidation, and neuroinflammmation.

What surprised me was just how big an impact the Sulforaphane had and the fact that these are very serious researchers, unlike many others.

Since we are talking about a therapy that has a strong anti-oxidant connection I compared the trial results from the Stanford NAC trial, with those from the Sulforaphane trial at MGH.

Monty, aged 11 with ASD, responded almost immediately to NAC and so of course I am interested in any additional, even overlapping, therapy.

For anyone interested, the following table shows the results from the NAC study:-

The data shows a large drop in irritability and hyperactivity and a moderate improvement in stereotypy, compulsions and SIB.  On the Social Responsiveness Scale, the people on NAC dropped by 18 , versus a drop of 6 for the placebo group.

Now we have the results from the Sulforaphane (broccoli) study.

On the Social Responsiveness Scale (SRS) , the people on Sulforaphane dropped by 20, versus a drop of 2 for the placebo group.

Moving on to the Aberrant Behavior Checklist (ABC) we can compare the improvement in four sub-categories:-

NAC               Sulforaphane

Irritability                 -9.7                     -4

Lethargy                  -4.2                     -4.5

Stereotypy              -3.5                      -2.7

Hyperactivity           -11                      -4.8

Now these figures are averages.  In reality you are likely either a responder or non-responder, nobody is likely to be Mr. Average.

I found these results very encouraging, albeit less so than the NAC trial.  The Sulforaphane trial was conducted among young adults whereas NAC was trialed on children.  You might expect children to be more responsive, since their autism tends to be less controlled than it tends to be in adulthood.

Since both trials are drawn from a population with behavioral autism and not any biological specific dysfunction both groups will likely include people with :-

·        Classic early onset autism caused by multiple genetic and epigenetic (environmental) hits

·        Mitochondrial disease triggered regressive autism, with no inherent prior dysfunction

·        Single gene disorders, probably never identified

Any trial with responders > 30% is therefore very interesting.  This trial was much better than that.

Now, both classic autism and Mitochondrial disease triggered regressive autism are associated with oxidative stress.  People with classic autism do seem to respond to NAC, whereas some people with Mitochondrial disease do not.

In the NAC trial the dose was stepped up every 4 weeks  (0.9g 1.8g 2.7g).  In the Sulforaphane trial the dose remained the same but the effect grew.

So the method of action of both drugs may be similar, but it is not identical.  NAC is a ”primary anti-oxidant”, in that NAC and its end product Glutathione (GSH) are themselves anti-oxidants.   

Sulforaphane appears to be a “secondary anti-oxidant”, it activates Nrf2 which then triggers a set of reactions that promotes an anti-oxidant response.  So it is logical that there is a time delay.

But after week 18, Sulforaphane treatment was stopped and at week 22 all benefit had been lost.

So we can conclude, even though these are two different trials with different groups of people, that if anything NAC looks more potent than Sulforaphane.

The question is whether Sulforaphane plus NAC would be even better than NAC (or Sulforaphane) alone.

  

Mode of Action

I know that NAC is a “direct” anti-oxidant and it is a precursor for glutathione (GSH); its effect is almost immediate, whereas the MGH researchers inform us that Sulforaphane became effective over a matter of weeks.  We know that Sulforaphane activates a transcription factor, Nrf2 in the cell. Once activated, Nrf2 then translocates to the nucleus of the cell, where it aligns itself with the antioxidant response element (ARE) in the promoter region of target genes. The target genes are associated with process which assists in regulating cellular defences. Such cytoprotective genes include that for glutathione (GSH).

So it is clear that both NAC and Sulforaphane will affect the level of the boy’s most important antioxidant glutathione (GSH).

That may possibly be the end of the story.

Science does tell us that Sulforaphane has many other effects that may also be beneficial in autism.  They do seem to have an effect in cancer and some do relate to reversing epigenetic “errors”.  Classic autism is also likely triggered, in part, by epigenetic “markers” on undamaged parts of the DNA.  Any method of selectively removing these markers and turning genes “off” that were “on” in error and vice versa is very interesting.

Sulforaphane’s effect in cancer appears to be more than just an antioxidant.  Research has shown that it is indeed active epigenetically (switching on and off genes).

The logical next step would be to test NAC vs Sulforaphane vs (NAC + Sulforaphane).

Since we live in an imperfect world, rather than wait half a century for a clinical trial, you might have to do a home trial.

In the next post we will see how to make Sulforaphane at home.

As is often the case, it is not as simple as buying some on Amazon.

Sulforaphane survives for 30  minutes outside the freezer and almost all broccoli supplements have been shown to have no active Myrosinase.  Without this enzyme almost no Sulforaphane will be produced, no matter how many broccoli tablets you take.

This reminds me of people buying oxytocin over the internet.  If it is not kept chilled, by the time it arrives at your place, a few days later, it will be totally inactive and so ineffective.  You will have wasted your money and perhaps falsely concluded that oxytocin is ineffective.

This is how the Sulforaphane is made by Johns Hopkins:-

Preparation of Sulforaphane-Rich Broccoli Sprout Extracts.

Sulforaphane rich broccoli sprout extract (SF-BSE) was prepared by the Cullman Chemoprotection Center at The Johns Hopkins University essentially as described in Egner et al. In brief, specially selected broccoli seeds were surface-disinfected and grown (sprouted) for 3 d in a commercial sprouting facility under controlled light and moisture conditions. A boiling water extract was prepared, filtered, cooled, and treated with the enzyme myrosinase (from daikon sprouts) to convert precursor glucosinolates to isothiocyanates, and

then lyophilized at a food processing facility (Oregon Freeze Dry, Albany, OR). The lyophilized powder (216 μmol SF/g powder) was encapsulated into #1 gelcaps by ALFA Specialty Pharmacy (Columbia, MD); each capsule contained 50 μmol SF (232 mg of SFBSE); placebo capsules were filled with microcrystalline cellulose.

The powders (bulk and capsules) were maintained at approximately

−20 °C and repeatedly checked for microbial contaminants and SF

titer before conveyance to the study site pharmacy (Massachusetts

General Hospital) to be dispensed to patients.

  

Thanks to all the research done on Sulforaphane/broccoli as chemoprotective agent, all the pieces of the puzzle exist.  My first choice would always be the stable analog of Sulforaphane, but it is not yet available and will no doubt be ultra expensive.  So I will work with second best.

The nice people at Johns Hopkins did reply to my questions, so I think I have figured out what I needed to know.

                                           How to make Sulforaphane at home

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.

Chelation Therapy: What To Do With Inconvenient Evidence

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.

Urinary porphyrins as biomarkers of autistic spectrum disorder risk  -  PATENT

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.”

Reduced Levels of Mercury in First Baby Haircuts of Autistic Children

  

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. 

Age-dependent lower or higher levels of hair mercury in autisticchildren than in healthy controls.

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.

 Mercury, lead, and zinc in baby teeth of children withautism versus controls.

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.

Autism Spectrum Disorder Phenotypes and Prenatal Exposure to Methyl mercury

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.

Here is a typical chelation approach.

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.

Toxicological Status of Children with Autism vs. Neurotypical Children and the Association with Autism Severity

Mercury and autism: Accelerating Evidence?

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

Disordered Porphyrin Metabolism: A Potential Biological Marker for Autism Risk Assessment

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

Toxicity biomarkers in autism spectrum disorder: A blinded study of urinary porphyrins

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.