Wednesday, May 23, 2007

New Study

Soden et al. (2007) just came out. The authors compared both children diagnosed with autism and without autism. The study included a baseline 24-hour urine collection, and a DMSA-provoked urine collection.

The results showed “In the absence a proven novel mode of heavy metal toxicity, the proportion of autistic participants in this study whose DMSA provoked excretion results demonstrate an excess chelatable body burden of As, Cd, Pb, or Hg is zero”.

I will offer a guess that the advocates of complementary and alternative practices in autism, will not respond to this article well. I will predict that the authors will be called shills within the next 2 weeks. I will post a link or citation if this occurs.

Reference

Soden, S, E., Lowry, J, A., Garrison, C, B., Wasserman GS. (2007). 24-hour provoked urine excretion test for heavy metals in children with autism and typically developing controls, a pilot study. Clinical Toxicology, 45(5), 476-481.

9 Comments:

Blogger Do'C said...

"Bubba" Neubrander appears to have taken a "predictable" approach - a variation of what you've suggested.

"You can set up any study for failure. You don't want to do a 24 hour urine because that will dilute out the metals and give you a normal result. Pretty sneaky the way they did it."

Source

Another poster on the forum this appeared on, called him on it.

Rick, you are implying intent on part of the researchers to arrange the procedures to produce a particular result.

Source

1:05 AM  
Blogger María Luján said...

Hi Jonathan
Please find my comments on this manuscript on AW
Source

Only some of my concerns about.

4:35 AM  
Blogger Interverbal said...

Thanks D'oC, good work not leeting the half life issue, slip away.

I think Mr. Blaxill will not disapoint however. I expect to see his take very soon.

Your comments are noted Maria, thank you for sharing them.

7:05 AM  
Anonymous Anonymous said...

Jon, Fombonne seems to have made a similar study, but I don't see it on Google Scholar. It might be unpublished yet.

"In other research, Eric Fombonne, of Montreal Children's Hospital, said in a news conference that samples of blood, hair and toenails taken from 71 newly diagnosed children and their mothers showed levels of mercury no different from children who didn't have autism."
http://seattletimes.nwsource.com/html/localnews/2003692973_autism04m.html

also,
MUHC study reveals no difference between mercury levels in autistic children and general population
"The research team, led by Dr. Eric Fombonne, tested mercury levels in the hair and blood samples from autistic children and their mothers and found that the levels did not differ statistically from those samples taken from non-autistic children. They also demonstrated that there was no correlation between the mercury level and the severity of symptoms and level of functioning of autistic children. The results were announced today at the 6th International Meeting For Autism Research (IMFAR) held at the University of Washington State."

Consecutive referrals of young children to the Autism Spectrum Disorders clinic at the MCH were invited to participate in the study. In total, 71 children were included in the study alongside 76 pediatric controls recruited from clinics at the same hospital.
http://www.innovations-report.de/html/berichte/medizin_gesundheit/bericht-83804.html

One critique is at: http://www.americanchronicle.com/articles/viewArticle.asp?articleID=26477
"If he had talked to any reputable toxicologist, they would have told him that the ethylmercury from vaccines clears the blood in about seven days. Ethylmercury, a short-chain alkyl mercury compound, is rapidly distributed to the brain, kidneys and other tissue. The hair tested would need to be from a first haircut to show this mercury exposure. Even if this was the case, research has shown that autistic kids do not excrete mercury efficiently. The hair would not contain any measurable amounts of mercury."

Ahem...

7:01 PM  
Anonymous mike stanton said...

I second that "ahem." Wagnitz cites Nataf et al and the Geiers in defence of urinary porphyrin profile analysis.

2:53 AM  
Anonymous Anonymous said...

According to this "reputable" toxicologist, ethylmercury "clears" the bloodstream within a week.
It would show up in the hair of the controls, but NOT in the hair of autistic children.
After 7 days, or from hair taken from a later haircut not covering that period, he expects to see no difference in mercury levels in the hair or blood of either autistic or NT children.

But the mercury is there, there, deep in the brain of autistic children, doing damage, as unreferenced "research" has "demonstrated" ...

11:33 AM  
Anonymous passionlessDrone said...

Hi Interverbal -

Does anyone know what dosage was used in this study? That would seem to be pretty important.

Also, can someone please explain to me why creatine ratios are used only during spot urine evaluations, but not 24 hour collections? Any insight would be appreciated.

My entry level statistics class taken 10 years ago has failed me. Can anyone explain to a guy like me what this sentence means:

"The confidence interval for this proportion is 0-22%"

[Sorry to be asking for so many explanations!]


As for Fombonne's results, there are animal studies that have shown that blood analysis for mercury exposure doesn't tell the tale of how much mercury is stored in tissues like the brain or liver.

Pubmed Link


Chronic, low-level exposures to environmental toxicants, because they often begin prenatally and then persist throughout the individual's lifetime, pose challenging issues to risk assessment. Exposure to low levels of methylmercury through the diet, based largely on consumption of fish and sea mammals, follows this pattern. Early development is considered to be a period of heightened vulnerability during which even low-level exposures may produce undetected, "silent", damage that is revealed only under conditions that challenge the functional capacities of the individual. Aging, with its diminished functional capacities and compensatory reserves provides such a challenge, but, to explore this possibility, requires basic information about blood and brain levels under conditions of chronic lifetime exposure. The current research was undertaken to provide such information. One hundred female B6C3F1/HSD mice were assigned to one of three dose groups, 0, 1, or 3 ppm methylmercury chloride administered in a 5 nM sodium carbonate drinking solution. They were bred with male CBA/J HSD mice to produce the trihybrid offspring B6C3F1/ HSD x CBA/J HSD. Dosing of the females began 4 weeks prior to breeding and continued for the two methylmercury-exposed groups throughout breeding and gestation. The methylmercury-treated litters were split into two subgroups, one exposed throughout its lifetime (set at 26 months) to the original dose, the other exposed through postnatal day 13 (PND 13). Brain and blood concentrations were assayed by cold-vapor atomic absorption. Samples were obtained on PND 4 and 21, and then at the end of months 14 and 26. On PND 4, brain and blood levels closely reflected maternal dosing. In all groups, concentrations fell sharply from PND 4 to 21, but to a greater extent in the perinatal groups. Blood levels in the 1 ppm lifetime group remained unchanged between months 14 and 26, but brain levels rose modestly. In the 3 ppm lifetime group, both brain and blood levels rose significantly between months 14 and 26, suggesting an interaction between dose and age.

Pub Med Link

Squirrel monkeys were dosed intranasally with saline or thiomersal (sodium ethylmercurithiosalicylate, 0.002 percent w/v) daily for six months. The total amounts of thiomersal given during the six months period were 418 mug (low dose group) and 2280 mug (high dose group). This was equivalent to 207 and 1125 mug mercury. The dose differential was achieved by more frequent administration to the high dose group. Mercury concentrations were significantly raised over control values in brain (high dose group only), liver, muscle and kidney, but not in blood. Concentrations were highest in the kidney, moderate in liver and lowest in brain and muscle. Much of the mercury was present in the inorganic form (37-91 percent). No evidence of toxicity due to thiomersal was seen in any animal. Nevertheless accumulation of mercury from chronic use of thiomersal-preserved medicines is viewed as a potential health hazard for man.

Of course, these are rats and monkeys, but it does seem to tell us that blood measurements do not always provide valid information as to total body load of heavy metals. There are likely other studies, but lunch time has ended.


I guess I'd also be curious as to the sensitivity of Fombonne's analysis. (?) I found this paper, which seems to show statistically strong associations between mercury and adhd in Chinese children. It would appear, they were detecting very low levels in the bloodstream with this study. [and it also is, admittedly, adhd not autism] Does anyone know what levels of detection Mr. Fombonne used?


Pubmed Link

"hyperactivity disorder (ADHD) in Chinese children in Hong Kong. METHODS: Fifty-two children with ADHD aged below 18 years diagnosed by DSM IV criteria without perinatal brain insults, mental retardation or neurological deficits were recruited from a developmental assessment center. Fifty-nine normal controls were recruited from a nearby hospital. Blood mercury levels were measured by cold vapor atomic absorption spectrophotometry. RESULTS: The mean ages of cases and controls were 7.06 and 7.81 years respectively. Boys predominated (case = 44 [84.6 %], control = 44 [74.6 %]). There was significant difference in blood mercury levels between cases and controls (geometric mean 18.2 nmol/L [95 % CI 15.4 - 21.5 nmol/L] vs. 11.6 nmol/L [95 % CI 9.9 - 13.7 nmol/L], p < 0.001), which persists after adjustment for age, gender and parental occupational status (p < 0.001). The geometric mean blood mercury level was also significantly higher in children with inattentive (19.4 nmol/L, 95 % CI 13.3 - 28.5 nmol/L) and combined (18.0 nmol/L, 95 % CI 14.9 - 21.8 nmol/L) subtypes of ADHD. Blood mercury levels were above 29 nmol/L in 17 (26.9 %) cases and 6 (10.2 %) controls. Children with blood mercury level above 29 nmol/L had 9.69 times (95 % CI 2.57 - 36.5) higher risk of having ADHD after adjustment for confounding variables. CONCLUSION: High blood mercury level was associated with ADHD. Whether the relationship is causal requires further studies"

Take care, all!

pD

10:40 AM  
Blogger daedalus2u said...

The reason to normalize urinary mercury for creatinine in a spot test is because the quantity and concentration of urine is quite variable during a 24 hour period. By normalizing mercury to the creatinine level, the total mercury excretion for a 24 hour period can be estimated because the normal creatinine excretion is 15–25 mg/kg/day.

If you actually measure the total mercury in 24 hours, that is a much more accurate and precise measure of how much mercury has actually been excreted.

Of course if all you want is a "high number", to justify chelation, then you don't care about the total excretion and do a spot test at the peak of the excretion profile.

2:16 PM  
Blogger Interverbal said...

Hi PD,

Judt got back from a trip.

You ask "Does anyone know what dosage was used in this study?"

3 doses of 100 mg DMSA.

This statement in the abstract: "The confidence interval for this proportion is 0-22%"

Is the range of confidence intervals of the things they were measuring for e.g. (Hg, Pb, etc).

A confidence interval is how certain we can be statistically speaking. In behavioral research we demand very high confidence intervals usually either 95% or 99% levels. I have no idea if biochemistry has similar demands. So, just because it is low in this case, may not mean much. Maria, might know more, I will check with here tonight.

This study statistically speaking, is kind of difficult. There are 5 dependent variables in 2 conditions and 2 groups. This stacks the deck in favor finding an association, so it is suprising that they did not.

I am suprised the authors did not use a more complex statistical design like a MANOVA.However, just to be clear, even if they had used such a design it would not have changed the finding, it just would have given more specific data.

3:29 PM  

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