Hertz-Picciotto's blood mercury autism study: what the researchers omitted
by Teresa
Binstock
Researcher in Developmental & Behavioral Neuroanatomy
October 21, 2009
http://www.generationrescue.org/binstock/091021-blood-mercury-autism-study-misleads.htm
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