Urinary Porphyrin Excretion in Neurotypical and Autistic Children
http://www.medscape.com/viewarticle/730552_2
Full text available.
Comparison of Urinary Porphyrins in NT and AU Children
Our findings suggest that mean concentrations of uro- and precoproporphyrins are comparable between NT and AU children of the same age ranges. In contrast, the concentrations of all remaining porphyrins, particularly hexacarboxyl-, pentacarboxyl-, and coproporphyrins, were significantly higher in AU children than NT children, especially in older age groups. Several possibilities might account for these differences. Of initial concern, Hg exposure appears unlikely to play a role in this effect, because no significant differences were observed between NT and AU 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. As noted recently (Woods et al. 2009a), incipient although statistically nonsignificant changes in urinary porphyrin concentrations were seen among children with urinary Hg concentrations derived from prolonged dental amalgam Hg exposure on the order of 3.2 µg/g creatinine. This is nearly 10 times the mean urinary Hg concentration observed among children in this study. Similar findings describing very low blood Hg levels and insignificant differences between NT and AU children have recently been reported (Hertz-Picciotto et al. 2010). These observations do not preclude a possible role of Hg exposure from sources not measured or validated in the present study, especially during the perinatal period, in the etiology of autism or related neurodevelopmental disorders in some children, particularly in relation to genetic variation that may predispose to increased risk of the neurotoxic effects of Hg as Hg0 as reported in adults (Echeverria et al. 2005, 2006, 2010; Heyer et al. 2009).
Our findings indicate instead 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 apparent in adult subjects. Further studies using a substantially larger population, such as the National Children's Study now in progress (National Children's Study 2010), are required to resolve this question.
Environ Health Perspect. 2010 Oct;118(10):1450-7. Epub 2010 Jun 24.
Urinary porphyrin excretion in neurotypical and autistic children.
Woods JS, Armel SE, Fulton DI, Allen J, Wessels K, Simmonds PL, Granpeesheh D, Mumper E, Bradstreet JJ, Echeverria D, Heyer NJ, Rooney JP.
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98105, USA. [email protected]
Abstract
BACKGROUND: Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU).
OBJECTIVES: This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism.
METHODS: This exploratory study enrolled 278 children 2-12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism.
RESULTS: Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received.
CONCLUSIONS: These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent.
One further comment on Woods et al. I think they need to also do porphyrin testing on a large number of children who have NEVER been vaccinated--as controls--NT children who received thimerosal and aluminum containing vaccines may or may not have truly "normal" porphyrin levels.
Posted by: Sue | November 25, 2010 at 08:36 AM
http://www.medscape.com/viewarticle/730552_4
... another factor that may account for the differences in urinary porphyrin levels between AU and NT children is mitochondrial dysfunction, a disorder commonly associated with autism (Correia et al. 2006; Oliveira et al. 2005; Pons et al. 2004). Of particular interest in this respect is the prospect of deficient mitochondrial porphyrin uptake mediated by the recently identified mammalian mitochondrial porphyrin transporter Abcb6 (Krishnamurthy et al. 2006). Abcb6, one of several identified ATP-binding cassette transporters, is located in the outer mitochondrial membrane and has a particularly high affinity for coproporphyrinogen III. Defects in Abcb6 gene expression or in Abcb6 activity could predispose to impaired mitochondrial porphyrin uptake, leading to cellular accumulation and aberrant porphyrin metabolism and excretion. Similarly, defects in the mitochondrial transmembrane domain that mediates the binding of porphyrins with the Abcb6 transporter could restrict normal porphyrin metabolism, contributing to the disordered porphyrin excretion observed (Krishnamurthy et al. 2006, 2007)....
Posted by: Natasa | November 25, 2010 at 05:33 AM
I think it is a good thing that Woods et al. did this study, but I think it has several weaknesses.
For one thing, as the researchers rightly note, relying on parental recall as to what vaccines a child has had is not fully reliable. I did not know one of my kids actually received a flu vaccine every year, but I discovered that upon requesting a copy of her medical records. My recollection was that she had received 2 or at most 3, rather than 7.
Secondly, not all vaccines of the same type even in the 90's contained the same thimerosal levels. It was clear on looking at doctor records for my kids, that the doctor had switched vaccine manufacturers to obtain thimerosal free vaccines for my second child, so that one got much the same vaccine schedule but far less thimerosal exposure (but far higher amounts of aluminum).
I don't think these authors' assessment of thimerosal exposure in the two groups is accurate enough to warrant any evaluation. The study has a reasonable size sample of boys, but includes only a very small sample of girls with autism (which the authors acknowledge is a limitation).
It would be of interest to see how the porphyrin tests done in the lab used by this study compares to results on the same samples from other labs--porphyrin results I have from 2 different labs yielded higher levels of most of the porphyrins than the extremes reported in this study, and I have seen multiple reports of much higher numbers in the results obtained by other parents from both LabCorp and the French lab. I have also seen many reports with much higher levels of precoproporphyrins than reported in this study.
Although Woods et al. attempted to enumerate some other possible mercury exposures, the researchers also overlooked several potentially important ones, including broken thermometers, broken fluorescent light bulbs, and mercury-laced latex paint, as well as proximity to coal-fired power plants or exposures to wildfire smoke. I also suspect that the number of amalgams one has may be less important than whether or not one has one's teeth worked on while pregnant, whether the mom is a tooth grinder, and whether or not she has gold crowns as well as amalgams--all of which would greatly increase the mercury leakage from the amalgams. The size of the fillings is likely to be important also. So overall, their comparison of mercury exposures between NT and AU children was too poorly done to warrant any conclusion, imo.
Their measurements of mercury body burden were also not meaningful in the context of the questions at hand. It is known that blood mercury levels decline rapidly post exposure and urine tests are pretty unreliable in detecting mercury bound to tissues, organs, or in the brain--even provoked urine tests are not consistently reliable, which apparently these urine samples were not.
Thus I think most of the conclusions of this paper are largely unsupported by the data provided. To the authors' credit, they state this is a preliminary study and a larger sample size and further study is needed. I think it would be interesting to have (blinded) hair elements testing on all the subjects to see whether or not Cutler's counting rules for evaluation of mercury toxicity yield detectable differences between the NT and AU groups.
Overall, I think that Woods et al. finding of significantly higher porphyrin markers in male children with diagnosed autism is interesting, relevant, important--and confirms some of what parents and DAN doctors have been saying for quite some time.
I also see the fact that they were actually looking at kids diagnosed with autism and testing them for porphyrins as a very positive step in the right direction. I hope that in future iterations of this study, that split porphyrin samples are sent to two or more labs for analysis, that hair elements testing is included, and that much more detailed information on known and potential exposures to mercury is acquired.
I would also be interested to see how the porphyrin tests of the children who had been treated with chelation compared to those who had not (with subgrouping of chelated porphyrin results per chelation agent(s) used, chelation protocol/method, and length/intensity of chelation treatment. Most reports I have seen indicate test results showing clear decreases in levels of most porphyrins, especially the precoproporphyins and coproporphyrins, following chelation rounds. I give Woods et al. credit for listening to what parents are saying and actually doing some research, instead of just ignoring or pooh-poohing parents’ and Dan doctor observations.
Sue
Posted by: Sue | November 25, 2010 at 01:05 AM
Speaking of Liver;
L-carnitine something else that is low in acquired mitochondria cyopathies, epilepsy, and found significantly low in my family can be obtain from diet of beef and lamb, made and stored in the "LIVER".
L-carnitine is very important in the transport of long chain carbs across the cell membranes.
Co-enzyme Q 10 comes from cholesterol that is controlled and made in the liver as well as vitamin D.
Posted by: Medicine can be hard on the Liver | November 24, 2010 at 05:14 PM
NO Jen in TX I had not heard. This article is dated Nov 11/2010 very recent.
All tobbaco science, so science is like everything else now a days - cannot be trusted.
I know this is frustrating to you especially, and it is an unanswered question like every thing else that surrounds our sick kids.
How much of a role did Tylenol play - while kicking out the asprin.
Posted by: Benedeetta | November 24, 2010 at 01:16 PM
Oh, haven't you heard, Benedetta? Tylenol doesn't cause liver damage in kids. Teh McNeil funded scientists said so. No worries! /snark
"Acetaminophen Not Linked to Liver Damage in Kids"
http://children.webmd.com/news/20101121/acetaminophen-not-linked-to-liver-toxicity-in-kids
Posted by: Jen in TX | November 24, 2010 at 11:09 AM
Oh, a lot of antibiotics are known mitochondrial disruptors or can cause liver damage too.
Posted by: Benedeetta | November 24, 2010 at 10:07 AM
Thanks Teresa Conrick; that was helpful esp the editor's note on the bottom.
My son's urine was extensivly tested by an allergist when he was nine. He did not have real high porphyrins only slightly elevated, and I was told at the time it was not enough difference to be hardly out of the normal range. I looked them up (I have the records still).
Hemes also do not just carry oxygen but other things too like thyroid horomones.
But once again it all starts from the energy cycle, the Kreb's cycle - as B12 from the liver.
What was that book by a Merck researcher about mitochondrial disorders - I cannot remember. I could not afford the book but I did listen to him through a link provided by a blogger here.
He said that there were tons of medicines that are mitochondrial disruptors. They had made it through the drug safty test because they grew it up on glucose rich media. If they reduce the glucose to more normal (like found in the real body) it really showed to be a poison.
He said that you could guess which ones were mitochondrial disruptors though by looking at the side effects in the human population as those that cause liver damage, or liver failure.
Tylenol once again.
But once again I have to say I was being told to triple the recommended dose in my kids to keep down seizure producing fevers. It was only with the DPT shot and not with Tylenol I had problems.
I do have to ask though - could I have kept the fevers down form the pertusis if I had been using asprin instead of Tylenol.
Oh Advil is now been advertised on Televsion to replace Tylenol.
What is Advil? Is that acteminophen too?
Posted by: Benedeetta | November 24, 2010 at 10:05 AM
Hi.
This should take you to the whole study w/o signing in.
http://tinyurl.com/2cn6dfs
Posted by: Teresa Conrick | November 24, 2010 at 09:18 AM
When you start talking about porhyrins - you are talking about the "Heme"
That is the molecules that pick up and carry oxygen around in the body. Right?
They are suppose to really - really know the whole pathway of producing the hemes.
They are not so good at figuring out what could interfer with the development of the heme.
Most of the enzymes nessacary for the heme is made in the liver, as is cholesterol.
My husband after his first reaction to the supposed tetanus shot (I am beginning to think it was really a DPT shot) developed high cholesterol and he was only 27 years old.
He also over the years for short periods of times had very low oxygen(the last time however lasted two years).
My son has a brain injury on his MIR that is thought to be ischemia, lack of oxygen - a stroke, could it be--- his heme was compromised and he could not carry enough oxygen to his brain the night of his vaccine reaction?
My daughter had Kawaski's and it seemed like every capillary could be seen under her skin. Is this similiar to those that have a supposely "hertiage type of illness- beginning to doubt most of this stuff is really genetic) purple porphyrin - skin turns purple in the presents of cold- and other diseases and problems.
Posted by: Benedeetta | November 24, 2010 at 09:08 AM