New Study on Heavy Metal Toxicity and Detoxification By…….
September 30, 2008 by Kristina Chew, PhD
Filed under Health
Translating Autism, a blog about autism research by Nestor L. Lopez-Duran, Ph.D., has posted a summary of a recently published study about heavy metal toxicity and detoxification capacity in autism. The study is published in the Journal of the Neurological Sciences, and is based on the notion that autistic children have a diminished ability to remove toxins—such as mercury—-from their bodies. In an effort to prove this theory, the researchers looked at urinary porphyrins as a measure of mercury exposure; specifically, they examined “urinary porphyrin metabolites (a proposed measure of heavy metal toxicity) and plasma sulfates (a proposed measure of detoxification capacity)” in autistic children. Here’s the abstract, with some words put in italics by me:
Autism spectrum disorders (ASDs) may result from a combination of genetic/biochemical susceptibilities in the form of a reduced ability to excrete mercury and/or increased environmental exposure at key developmental times. Urinary porphyrins and transsulfuration metabolites in participants diagnosed with an ASD were examined. A prospective, blinded study was undertaken to evaluate a cohort of 28 participants with an ASD diagnosis for Childhood Autism Rating Scale (CARS) scores, urinary porphyrins, and transsulfuration metabolites. Testing was conducted using Vitamin Diagnostics, Inc. (CLIA-approved) and Laboratoire Philippe Auguste (ISO-approved). Participants with severe ASDs had significantly increased mercury intoxication-associated urinary porphyrins (pentacarboxyporphyrin, precoproporphyrin, and coproporphyrin) in comparison to participants with mild ASDs, whereas other urinary porphyrins were similar in both groups. Significantly decreased plasma levels of reduced glutathione (GSH), cysteine, and sulfate were observed among study participants relative to controls. In contrast, study participants had significantly increased plasma oxidized glutathione (GSSG) relative to controls. Mercury intoxication-associated urinary porphyrins were significantly correlated with increasing CARS scores and GSSG levels, whereas other urinary porphyrins did not show these relationships. The urinary porphyrin and CARS score correlations observed among study participants suggest that mercury intoxication is significantly associated with autistic symptoms. The transsulfuration abnormalities observed among study participants indicate that mercury intoxication was associated with increased oxidative stress and decreased detoxification capacity.
This study has noted some correlations or associations between “increased mercury intoxication-associated urinary porphyrins” and subjects with “severe,” or more severe, autism. While the authors note that ASDs “may result” in children having “reduced ability to excrete mercury and/or increased environmental exposure at key developmental times,” the abstract at least does not note specifically when those “key developmental times” are, and what the age of the subjects are. (When exactly did the subjects beging to display “reduced ability to excrete mercury and/or increased environmental exposure”?).
Translating Autism has a concise review of the study; it’s underscored that the researchers have found an association or correlation between autism and urinary porphyrins, but that no causal relationship is clearly proven:
In conclusion, the study presents some compelling evidence regarding differences in urinary porphyrin metabolites between kids with mild and severe autism symptoms, as well as differences in plasma sulfates between kids with autism when compared to neurotypical kids. This is consistent with the author’s theory that mercury exposure plays a role in autism. However, given the controversy regarding the mercury-autism association, I would like to clarify that these results do not indicate that mercury causes autism. Yes, it is possible that mercury toxicity and reduced detoxification capacity plays a role in autism, both, in the onset and severity. However, it is also possible that Autism itself results in reduced detoxification capacity and mercury toxicity via other mechanisms, but that such toxicity is not associated at all with the development of the disorder. For example, erythrocyte sedimentation rate and C-reactive protein are tests used in arthritis. Atypical results on these tests are found in people with arthritis. Yet, neither one is related to any of the proposed causes of arthritis, and instead reflect a consequence of the disorder itself (inflammation).
The authors of the paper include: David Geier and his father, Dr. Mark Geier, who are somewhat (in)famous in autism circles for research which has sought to prove a link between autism and vaccines or something in vaccines (such as this study on thimerosal), for creating alternative treatments for autism such as the Lupron protocol, and for serving as consults in vaccine-litigation court cases. James B. Adams is a professor of Materials Science and Engineering at Arizona State University; he was interviewed in a 2006 Dateline special on chelation. Vitamin Diagnostics, which another author, Tapan Audhyaf, is affiliated with, is located in Cliffwood Beach, New Jersey and offers “specialized nutritiontal testing” of a kind familiar to those who’ve read the DAN! Protocol; tests include a “toxic metal panel” and also one which examine “salivary mercury levels.” As the abstract notes, some of the testing for the study was conducted at Vitamin Diagnostics’ laboratory (which, based on their address at Industrial Drive & Route 35, I think we’ve driven past).
As always when the topic is mercury and autism, read with care.
Hi Kristina –
A few notes:
(a proposed measure of heavy metal toxicity) and plasma sulfates (a proposed measure of detoxification capacity)”
1) Urinary porphryin metabolites have been found to be correlated with mercury exposure in a variety of studies for a long time. Take a look at: “Urinary porphyrin profiles as a biomarker of mercury exposure: studies on dentists with occupational exposure to mercury vapor” from 1993. Dentists with more mercury in their blood had increased porphyrin levels as compared to dentists with lower mercury levels. Another study you might be interested in is “Quantitative evaluation of urinary porphyrins as a measure of kidney mercury content and mercury body burden during prolonged methylmercury exposure in rats.” Animals were dosed with mercury, and an increase in porphyrins was observed. The animals were chelated, and a decrease in porphyins was observed. This would seem to have a nice correlation to the original Nataf paper, wherein a subset of children with autism were chelated, and subsequently, their porphyin levels were observed to decrease. There are many other human and animal studies with similar findings. There could, of course, be other things in autism that cause similar porphryin profiles; though I’ve yet to see one posited, but we’d still need an explanation as to why children with autism have more mercury in their blood than their non diagnosed peers but for the observed profiles not to be related.
2) Glutatione levels and the oxidized/reduced ratios of glutathione are a measure of detoxification capacity. What would be a proposal, would be a mechanism by which you could have less glutathione, but without a consequent impact on detoxification capabilities. Do you have one?
3) This discussion is almost always about mercury; which I find unfortunate. Pesticides, other heavy metals, or other things can almost certainly have an impact on the same pathway and consequent porphyrin profiles.
I’m liking the guy you linked to, who previously had a peice on a study from Australia in regards to porphyrins (I believe you posted to it). He more or less had the same analysis, impossible to pinpoint a cause, but again, strong evidence for an association.
It isn’t that mercury causes autism; it’s that having autism causes you to be succeptible to mercury (and a bunch of other things). Both sides of the debate need to try this point of view out for a while.
- pD
From the Boston Globe:
http://www.boston.com/news/education/higher/articles/2008/09/30/colleges_calling_sleep_a_success_prerequisite/
Would you post this to your blog? Thanks!
Discovery Health channel will be showing a documentary on Oct. 1st at 8PM ET/PT. The title is: “Autism X 6″ and it is the story about our family. It will rebroadcast on Oct 4, check listings for time.
We hope that by allowing our story to be told that it will do three things:
1) Increase the awareness of Autism
2) Increase the understanding and tolerance of Autism
3) We hope that we can be of some help to other ‘Parents of Autism’
Please tell everyone you know to watch it. Your family, friends, neighbors, religious and political leaders, etc. Also post it, email it to any and all groups, forums and email lists you have.
If you would like to contact us personally go to autism_bites@yahoo.com or our website: AutismBites.com
Thank you!
@Passionles Drone; You said that it is not the mercury that causes autism. It is after you get autism you seem to have more porphiryin metabolites assocated with mercury so why does that happen. Did the researcher look to see if happened with other metals or just the mercury and again where does that mercury seem to come from. I wounder if you could get the same resuts with lead, tin, arsenic or some metal.
One note:
The study had 23 participants.
This isn’t conclusive evidence for this correlation; the sample size simply isn’t big enough–there’s too much uncertainty.
At the most, this is a preliminary study that can conclude no more than “This topic is a worthwhile target for further research.”
Oops. Typo–28, not 23. Still too small.
Hi Donald Savitz -
It is after you get autism you seem to have more porphiryin metabolites assocated with mercury so why does that happen.
That’s the big question, isn’t it. A general state of inflammation might be the cause; or the noted differences in glutathione and/or a state of high oxidative stress. There are likely many causes; or many small causes that build up.
Did the researcher look to see if happened with other metals or just the mercury and again where does that mercury seem to come from. I wounder if you could get the same resuts with lead, tin, arsenic or some metal.
Indeed, you can get different porphyrin profiles based on other insults. Of particular interest here is that this isn’t just a case of having more of a particular component, but a specific profile of porphyrins. My (admittedly primitive) understanding is that different insults affect the heme processing chain at different locations; thus the ratio of different porphyrins is different when exposure to mercury versus arsenic, for example.
See:
“Urinary arsenic and porphyrin profile in C57BL/6J mice chronically exposed to monomethylarsonous acid (MMAIII) for two years” –
As a part of 2-year arsenic carcinogenicity study, young female C57BL/6J mice were given drinking water containing 0, 100, 250 and 500 microg/L arsenic as MMA(III)ad libitum. 24 h urine samples were collected at 0, 1, 2, 4, 8 weeks and every 8 weeks for up to 104 weeks. Urinary arsenic speciation and porphyrins were measured using HPLC-ICP-MS and HPLC with fluorescence detection respectively. DMA(V) was a major urinary metabolite detected. Significant dose-response relationship was observed between control and treatment groups after 1, 4, 24, 32, 48, 56, 88, 96 and 104 weeks. The level of uroporphyrin in 250 and 500 microg As/L group is significantly different from the control group after 4, 8, 16, 32, 56, 72, 80, 96 and 104 weeks.
Or,
“Porphyrins as the early biomarkers for arsenic exposure of human”
Analytical data showed that urinary uroporphyrin-III and coproporphyrin-III were significantly elevated in arsenic-exposed group compared with those in control group, while urinary coproporphyrin-I was not significantly higher in arsenic-exposed group than that in control group.
There are many, many others. Note that they are paying attention not just to an increase, but which particular porphyrins are being increased. This speaks towards where the heme pathway is being disrupted, and thus, somewhat of a marker of what is causing the problem.
It turns out, that the specific profile many children with autism have corresponds closely to those that have previously been identified with mercury exposure. That doesn’t mean that ONLY mercury could cause such a profile, just that there is a match. Perhaps there is another insult, or combination of insults, which could cause a backup in the same location.
- pD
Given the authors of the article, it would be of interest to note how the subjects were recruited.
Yes, pD, Translating Autism has some really good reviews of research and he’s rigorous and reasonable—-
Hi ChaoticIdealism –
You may be interested in knowing that, to date, I believe there have been four analysis of porphyrin profiles in children with autism with similar results.
Porphyrinuria in childhood autistic disorder: implications for environmental toxicity – 106 autitic participants; not unsurprizingly, children with Aspergers did not show abnormal porphryin profiles.
A prospective assessment of porphyrins in autistic disorders: a potential marker for heavy metal exposure – 37 autistic participants. Similar findings as far as profiles and differences between autism, Aspergers, and PDD-NOS.
An investigation of porphyrinuria in Australian children with autism – Unknown number of participants, but similar findings to above.
The study referenced above.
HTH
- pD
Of much more importance it seems to me than the “jump-to” conclusion here of “mercury causes/contributes-to autism” was this, which has been reported many times before:
“Significantly decreased plasma levels of reduced glutathione (GSH), cysteine, and sulfate were observed among study participants relative to controls”
This shows once again that autism is not solely a neurological “disorder”. It is metabolic, and the metabolic dysfunctions caused are very widespread (they go beyond just the methylation and transulfation pathways).
Yes, yes, I know – this has been reported by the same “quack DAN!” researchers you love to hate. You say GPL and the other labs who do testing for DAN! doctors are faking it.
Fine. You want to prove whether the testing is quack or not? Pony up your own money to do your own independent tests, and then faithfully respond to any criticisms that may be leveled against your study). Tell me why the NImH appears to refuse to even DO a study on chelation, which might settle once and for all the question of whether all the thousands if not tens of thousands of parents who say it works are *all* lying. They say it’s unethical to use DMSA? Then why the hell is it already approved for lead poisoning?
Incidentally, I put the word “disorder” above in quotes for a very good reason. The “neurodiverse movement” DOES have a point – and a very good one. Autistics must be respected and treated like other people, within the limits of what they can and can’t do (as for the ‘can’t do’ part – automatic social processing of sensory stimuli comes to mind). It also appears from the results of the preliminary rTMS experiments being done at the Center For Noninvasive Brain Stimulation (look it up on that hereitical ‘newspaper’ AgeOfAutism..), *as reported by a person with Asperger’s himself* that the ‘gifts’ that are imparted-by/developed-because-of autism are not necessarily lost when ‘missing’ functionality of the brain is restored (hereabovesaid automatic social processing).
Jim Witte
@Jim Witte, thanks for highlighting again that post by a “person with Asperger’s himself.”
If you’d like to see scientists study your theory of autism as metabolic disorder perhaps you might lobby for such studies through an organization like the IACC?
Please note that the values for transsulfuration metabolites obtained in this study (and also those in a related study by Geier et al in Neurochem Res) are highly questionable. Reference metabolite values in the literature (which includes refs cited by Geier et al in JNS) for cysteine, oxidized glutathione, and total sulfate are at least one order of magnitude off those measured by Geier et al.
A detailed discussion of Geiers’ metabolite values can be found at http://bmartinmd.com/2008/10/geiers-metabolite-values.html.
I am connected with autism families in Iowa, and a few in MO. Next week there may be a federal hearing on the topic.
I would like to have each family impacted by autism and the asd to contact all federal senators……..to ask them to work a bit harder on getting the vaccines cleaned up, getting the FDA to being honest and forthright……on getting this plague stopped.
Keep me posted.
thanks…………ejhs