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Teresa
Binstock
Researcher in Developmental & Behavioral
Neuroanatomy
October 21, 2009
Irva Hertz-Picciotto &
colleagues have published results of a study comparing mercury
(Hg) levels in children with and without autism (1). The study
does not report findings about total body burden of Hg in
children, nor does the study evaluate levels of Hg in the brain or
other specific organs in autistic and non-autistic children.
Indeed, the researchers who did the blood-Hg study state:
"As only 5% of body burdens of Hg are estimated to be in
circulation, (Burbacher et al. 2005; Stinson et al. 1989) reliable
conclusions about distribution are not possible from one-time
observational measurements in blood." (1) Since various forms
of mercury can enter the brain and remain there (17), and since
different tissues of humans and other species retain mercury at
various rates (16), the larger context of Hertz-Picciotto et al's
findings need be considered.
Relevant questions include:
What do Hg levels in blood signify? Alternatively, what don't they
signify? And what does intra-body and intra-brain mercury mean for
children with weak alleles in glutathione-related pathways or born
to mothers with weak alleles in glutathione-related
pathways?
Although the new study purports to offer a review
of autism genetics, Hertz-Picciotto et al (1) omit an important
category of citations related to mercury, glutathione,
methylation, and autism (eg, 2-14).
Furthermore, the
researchers cite two studies of in vivo thimerosal levels
(Pichichero et al 2002, 2008) while omitting consideration of Waly
et al 2004, who investigated thimerosal levels lower than those
described by Pichichero et al 2002 in human infants, found that
methionine synthase was inhibited, and concluded that "The
potent inhibition of this pathway by ethanol, lead, mercury,
aluminum and thimerosal suggests that it may be an important
target of neurodevelopmental toxins." (15)
Why
were these important findings omitted? Weren't the reviewers aware
of cites 1-15 hereinbelow?
In seeking to understand
intra-body and intra-brain Hg, Lorscheider et al provide important
insights.
In a study available free online, data reviewed
by Lorscheider et al (16) indicate that Hg exposure does not lead
to equivalent concentration in all tissues. For instance, from
chronic exposure via amalgam vapors, some tissues accumulate more
Hg than do other tissues (16).
Caveat: ingesting one's own
amalgam vapors probably includes olfactory exposure as well as
oral/gastrointestinal exposure and therefore is not perfectly akin
to ingesting Hg by eating fish. Nonetheless, Hg distribution
findings due to amalgams may be instructive.
"The
degree to which body tissues can sequester amalgam Hg after
exposure has been demonstrated in a variety of human and animal
experiments... The brain/CSF Hg ratio had increased threefold by 4
wk after amalgam fillings had been installed..."
(16)
"Repeated observations in adult sheep...
demonstrate that after placement of amalgam fillings the blood Hg
levels remain relatively low even though the surrounding body
tissue concentrations of Hg become many fold higher than blood.
This suggests that tissues rapidly sequester amalgam Hg at a rate
equivalent to its initial appearance in the circulation. Such a
phenomenon may explain why monitoring blood levels of Hg in humans
is a poor indicator of the actual tissue body burden directly
attributable to continuous low-dose Hg exposure from amalgam."
(16)
Lorscheider et al (16) summarize another important
point:
"Both intracellular Hg2 and Hg are ultimately
bound covalently to glutathione (GSH) and protein cysteine groups.
Hg2 is the toxic product responsible for the adverse effects of
inhaled Hg0. Body tissues have various retention half-lives for Hg
and Hg2 ranging from days to years... "
Implications
ensue from the Hg/GSH genetics findings in autism and from the
Hg-distribution studies reviewed in Lorscheider et al:
a)
Tissue levels of Hg are are likely differ from and to be greater
than Hg levels found in blood.
b)
Subgroups of children who have developed autism are known to have
one or more problems in pathways related to glutathione and
methylation (eg, 2-14) may detoxify Hg and related compounds
poorly and thus may sequester Hg and related compounds
disadvantegeously.
c) Blood
levels of Hg in autistic children (1) tell us little about Hg in
their brain and other tissues.
As Hertz-Picciotto et al
mention, several studies have found associations between autism
rates and environmental mercury (18-20), and these findings
conjoin with the often ignored fact that thimerosal in early life
vaccines increases risk for autism and for developmental
disabilities requiring special education (21-22).
Be
aware: some brands of H1N1 ("swine") flu vaccine and
non-H1N1 influenza vaccines contain substantial amounts of
thimerosal (eg, 23).
1. Blood
Mercury Concentrations in CHARGE Study Children with and without
Autism
Irva Hertz-Picciotto et
al.
http://www.ehponline.org/members/2009/0900736/0900736.pdf
2:
James SJ et al. Cellular and mitochondrial glutathione redox
imbalance in lymphoblastoid cells derived from children with
autism. FASEB J. 2009 Aug;23(8):2374-83.
3: James SJ et
al. Efficacy of methylcobalamin and folinic acid treatment on
glutathione redox status in children with autism. Am J Clin Nutr.
2009 Jan;89(1):425-30.
4: James SJ et al. Abnormal
transmethylation/transsulfuration metabolism and DNA
hypomethylation among parents of children with autism. J Autism
Dev Disord. 2008 Nov;38(10):1966-75.
5: James SJ et al.
Metabolic endophenotype and related genotypes are associated with
oxidative stress in children with autism. Am J Med Genet B
Neuropsychiatr Genet. 2006 Dec 5;141B(8):947-56.
6: James
SJ et al. Metabolic biomarkers of increased oxidative stress and
impaired methylation capacity in children with autism. Am J Clin
Nutr. 2004 Dec;80(6):1611-7.
7: Deth R et al. How
environmental and genetic factors combine to cause autism: A
redox/methylation hypothesis. Neurotoxicology. 2008
Jan;29(1):190-201.
8: Westphal GA et al. Homozygous gene
deletions of the glutathione S-transferases M1 and T1 are
associated with thimerosal sensitization. Int Arch Occup Environ
Health. 2000 Aug;73(6):384-8.
9: Müller M et al.
Inhibition of the human erythrocytic glutathione-S-transferase T1
(GST T1) by thimerosal. Int J Hyg Environ Health. 2001
Jul;203(5-6):479-81.
10. Williams TA et al. Risk of
autistic disorder in affected offspring of mothers with a
glutathione S-transferase P1 haplotype. Arch Pediatr Adolesc Med.
2007 Apr;161(4):356-61
11. Geier DA et al. Biomarkers of
environmental toxicity and susceptibility in autism. J Neurol Sci.
2009 May 15;280(1-2):101-8.
12. Ming X et al. Genetic
variant of glutathione peroxidase 1 in autism. Brain Dev. 2009 Feb
3. [Epub ahead of print]
13. Al-Gadani Y et al. Metabolic
biomarkers related to oxidative stress and antioxidant status in
Saudi autistic children. Clin Biochem. 2009
Jul;42(10-11):1032-40.
14. Pasca SP et al. One Carbon
Metabolism Disturbances and the C667T MTHFR Gene Polymorphism in
Children with Autism Spectrum Disorders. J Cell Mol Med. 2008 Aug
9.
15. Waly M et al. Activation of methionine synthase by
insulin-like growth factor-1 and dopamine: a target for
neurodevelopmental toxins and thimerosal. Mol Psychiatry. 2004
Apr;9(4):358-70.
16. Lorscheider FL et al. Mercury exposure
from "silver" tooth fillings: emerging evidence
questions a traditional dental paradigm. FASEB J. 1995
Apr;9(7):504-8.
http://www.fasebj.org/cgi/reprint/9/7/504
17.
Burbacher TM et al. Comparison of blood and brain mercury levels
in infant monkeys exposed to methylmercury or vaccines containing
thimerosal. Environ Health Perspect. 2005
Aug;113(8):1015-21.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280342/pdf/ehp0113-001015.pdf
18.
Palmer RF et al. Environmental mercury release, special education
rates, and autism disorder: an ecological study of Texas. Health
Place. 2006 Jun;12(2):203-9.
19.Windham GC et al. Autism
spectrum disorders in relation to distribution of hazardous air
pollutants in the san francisco bay area. Environ Health
Perspect. 2006 Sep;114(9):1438-44.
20. Palmer RF et al.
Proximity to point sources of environmental mercury release as a
predictor of autism prevalence. Health Place. 2009
Mar;15(1):18-24.
21. Hepatitis
B vaccination of male neonates and autism
[conference
abstract as published]
CM Gallagher, MS Goodman, Graduate
Program in Public
Health, Stony Brook University Medical
Center, Stony Brook, NY
Annals of Epidemiology, p659
Vol.
19, No. 9 Abstracts (ACE) September 2009: 651–680
[triple
the rate of autism among boys vaccinated with thimerosal versus
boys not so vaccinated]
22. Hepatitis
B triple series vaccine and developmental disability in US
children aged 1-9 years
Gallagher C,
Goodman M. Toxicol Environ Chem 2008 90(5):997-1008.
{free
online}
http://fourteenstudies.org/pdf/hep_b.pdf
"The
odds of receiving EIS were approximately nine times as great for
vaccinated boys... as for unvaccinated boys..., after adjustment
for confounders.
23. H1N1 Vaccines Approved: What's In It
For You?
By Jackie
Lombardo
http://nontoxicchildhood.blogspot.com/2009/10/h1n1-vaccines-approved-whats-in-it-for.html
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