Re: Occupational exposure to extremely low frequency electric and magnetic fields and Alzheimer disease: a meta-analysis

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Redaktion Buergerwelle e.V. (BI Omega-CI Omega)

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Apr 2, 2008, 4:45:01 PM4/2/08
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Dear Dr Mutter,

All submissions, including letters to the editor, are subject to peer
review and not all letters to the editor are published.

The editorial decision to reject your letter stands. You have the option
of re-writing the letter and re-submitting it, but there is no guarantee
that it will be published.


Sincerely,

Michael A McGuigan, MDCM, MBA
Editor-in-Chief, Clinical Toxicology

On Mon, Mar 31, 2008 at 4:26 PM, Dr. med. Joachim Mutter wrote:

Dear Dr McGuigan,

Your reviewer seem not to overview the scientific literature regarding
mercury toxicity (see comments to his queries below) or is not free of
conflicts of interest regarding the use of dental amalgam.

In my letter, it was not possible to give all references regarding
this topic. But for a "letter to the editor", I wonder, why one
reviewer with less knowledge in mercury science have the right, to
reject a critical opinion in this topic, a letter is normally answered
by the authors of the original article.

Thus, I suggest other reviewers like Prof. Dr. Boyd Haley, Chair,
Department of Chemistry, University of Kentucky, Lexington
beh...@uky.edu
or
Prof. Vera Stejskal
Karolinska , Sweden
Vera Stejskal <ve...@melisa.org>
or
Dr. G. Guzzi, Italy
gianpao...@fastwebnet.it
or
Dr. Stephan Bose o´Reilly
University Hall, Austria
Stephan Boeseoreilly <Stephan.Bo...@umit.at>
or
Prof. Dr. Dr. G. Drasch
Forensic medicine, University Munich
dra...@allacher-apotheke.de

Best regards

Joachim Mutter
(see comments to the reviewer#1 below)

Zitat von clinical....@gmail.com:
31-Mar-2008

Dear Dr. Mutter:

I regret to inform you that our reviewers have now considered your
paper but unfortunately feel it unsuitable for publication in
Clinical Toxicology. For your information I attach the reviewer
comments at the bottom of this email. I hope you will find them to
be constructive and helpful. You are of course now free to submit
the paper elsewhere should you choose to do so.

Thank you for considering Clinical Toxicology. I hope the outcome of
this specific submission will not discourage you from the
submission of future manuscripts.

Sincerely,
Dr. Michael McGuigan
Editor in Chief, Clinical Toxicology
clinical....@gmail.com


Reviewer(s)' Comments to Author:
Reviewer: 1
Comments to the Author
The author states an unproven theory of Hg toxicity that certain
individuals excrete it differently than everybody else. There is no
scientific evidence of impaired excretion.

Here is the alleged "no scientific evidence of impaired excretion":

- Custodio HM et al. Genetic influences of retention of inorganic
mercury. Arch Environ Occup Health 2005; 60:17-22.
- Custodio HM et al. Polymorphisms in glutathione-related genes affect
methylmercury retention. Arch Environ Occup Health 2004; 59: 588-595.
-Stenman S, Grans L. Symptoms and differential diagnosis of patients
fearing mercury toxicity from amalgam fillings. Scand J Work Environ
Health. 1997;23 Suppl 3:59-63.
- Grandjean P, Weihe P, White RF. Milestone development in infants
exposed to methylmercury from human milk. Neurotoxicology 1995;16:27-33.
- Holmes AS, Blaxill MF, Haley BE: Reduced levels of mercury in first
baby haircuts of autistic children. Int J Toxicol 2003; 22: 277-285.
- Kern JK, Grannemann BD, Trivedi MH, Adam JB. Sulfhydryl-reactive
metals in autism. J Toxicol Environ Health A 2007; 70: 715-721.
- Woods, J. Martin, MD, Naleway, CA and Echeverria, D. Urinary
porphyrin profiles as a biomarker of mercury exposure: studies on
dentists with occupational exposure to mercury vapor. J. Toxicol.
Environ. Health 1993 40(2-3) 235-46.
- Geier DA, Geier MR. A prospective assessment of porphyrins in
autistic disorders: a potential marker for heavy metal exposure.
Neurotox Res 2006; 10: 57-64.
- Nataf R, Skorupka C, Amet L, Lam A, Springbett A, Lathe R.
Porphyinuria in childhood autistic disorder: implications for
environmental toxicity. Toxicol Appl Pharmacol 2006; 214: 99-108.
- Heyer NJ, Bittner AC Jr, Echeverria D, Woods JS. A cascade analysis
of the interaction of mercury and coproporphyrinogen oxidase (CPOX)
polymorphism on the heme biosynthetic pathway and porphyrin
production. Toxicol Lett. 2006; 161: 159-166.
- Echeverria D, Woods JS, Heyer NJ et al. The association between a
genetic polymorphism of coproporphyrinogen oxidase, dental mercury
exposure and neurobehavioral response in humans. Neurotoxicol Teratol.
2006; 28: 39-48.
- Heyer NJ, Echeverria D, Bittner AC Jr, Farin FM, Garabedian CC,
Woods JS. Chronic low-level mercury exposure, BDNF polymorphism, and
associations with self-reported symptoms and mood. Toxicol Sci 2004;
81: 354-363.
- Godfrey ME, Wojcik DP, Krone CA: Apolipoprotein E genotyping as a
potential biomarker for mercury neurotoxicity. J Alzheimers Dis 2003;
5: 189-195.
- Wojcik DP, Godfrey ME, Christie D, Haley BE. Mercury toxicity
presenting as chronic fatigue, memory impairment and depression:
diagnosis, treatment, susceptibility, and outcomes in a New Zealand
general practice setting (1994-2006). Neuro Endocrinol Lett. 2006; 27:
415-423.

The author claims mercury vapor in the mouth is dangerous and causes
cellular injury. There is no scientific evidence of that.
The reviewer#1 claims that one of the most toxic element in the
universe, especially in the form of vapor, in human mouth, is not
dangerous because of alleged "no scientific evidence". But there is
scientific consense that mercury vapor in the human mouth is inhaled
by loungs and is easely absorbed. Autospy studies revealed up to 12
times more mercury in body tissues of amalgam bearers. The levels are
well above toxic levels in cells and animals. Attached some scientific
studies , overlooked by the reviewer, which question the safety of
dental amalgam:

In vivo effects of dental casting alloys.
Neuro Endocrinol Lett. 2006 Dec;27 Suppl 1:61-8.
Cell death effects of resin-based dental material compounds and
mercurials in human gingival fibroblasts.
Arch Toxicol. 2006 Jun;80(6):370-7.
Wojcik DP, Godfrey ME, Christie D, Haley BE. Mercury toxicity
presenting as chronic fatigue, memory impairment and depression:
diagnosis, treatment, susceptibility, and outcomes in a New Zealand
general practice setting (1994-2006). Neuro Endocrinol Lett. 2006; 27:
415-423.
Renal effects of dental amalgam in children: the New England
children's amalgam trial.
Environ Health Perspect. 2008 Mar;116(3):394-9.
Cracked mercury dental amalgam as a possible cause of fever of unknown
origin: a case report.
J Med Case Reports. 2008 Mar 6;2(1):72
Migration of mercury from dental amalgam through human teeth.
J Synchrotron Radiat. 2008 Mar;15(Pt 2):123-8.
Perioral dermatitis after dental filling in a 12-year-old girl:
involvement of cholinergic system in skin neuroinflammation?
ScientificWorldJournal. 2008 Feb 6;8:157-63.
Need for informed consent for dentists who use mercury amalgam
restorative material as well as technical considerations in removal of
dental amalgam restorations.
Assessment of some elements in human permanent healthy teeth, their
dependence on number of metallic amalgam fillings, and interelements
relationships.
Biol Trace Elem Res. 2007 May;116(2):155-69
J Environ Pathol Toxicol Oncol. 2007;26(4):305-22.
Biomonitoring of DNA damage in peripheral blood lymphocytes of
subjects with dental restorative fillings.
Mutat Res. 2008 Feb 29;650(2):115-22.
Mercury in human brain, blood, muscle and toenails in relation to
exposure: an autopsy study.
Environ Health. 2007 Oct 11;6:30.
Maternal amalgam dental fillings as the source of mercury exposure in
developing fetus and newborn.
J Expo Sci Environ Epidemiol. 2007
A 30-year follow-up of residual effects on New Zealand School Dental
Nurses, from occupational mercury exposure.
Hum Exp Toxicol. 2007 Apr;26(4):367-74.
Mercuric dichloride induces DNA damage in human salivary gland tissue
cells and lymphocytes.
Arch Toxicol. 2007 Nov;81(11):759-67.
The effect of amalgam exposure on mercury- and antibiotic-resistant
bacteria.
Int J Antimicrob Agents. 2007 Jul;30(1):34-9.
Dental amalgam and multiple sclerosis: a systematic review and
meta-analysis.
J Public Health Dent. 2007 Winter;67(1):64-6.
Dependence of kinetic variables in the short-term release of Hg2+,
Cu2+ and Zn2+ ions into synthetic saliva from an high-copper dental
amalgam.
J Mater Sci Mater Med. 2007 Aug;18(8):1521-7.
Are mercury amalgam fillings safe for children? An evaluation of
recent research results.
Altern Ther Health Med. 2006 Jul-Aug;12(4):16-7
Metal alloys in the oral cavity as a cause of oral discomfort in
sensitive patients.
Neuro Endocrinol Lett. 2006 Dec;27 Suppl 1:53-8.
Removal of dental amalgam decreases anti-TPO and anti-Tg
autoantibodies in patients with autoimmune thyroiditis.
Neuro Endocrinol Lett. 2006 Dec;27 Suppl 1:25-30.
Cytotoxicity of dental composite (co)monomers and the amalgam
component Hg(2+) in human gingival fibroblasts.
Arch Toxicol. 2006 Aug;80(8):465-72.
Chronic inflammation and pain inside the mandibular jaw and a 10-year
forgotten amalgam filling in an alveolar cavity of an extracted molar
tooth.
Ultrastruct Pathol. 2005 Sep-Oct;29(5):405-13.
Oral lichen planus and allergy to dental amalgam restorations.
Arch Dermatol. 2004 Dec;140(12):1434-8.
Healing of oral lichenoid lesions after replacing amalgam
restorations: a systematic review.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004 Nov;98(5):553-65.
Recovery from mercury-induced burning mouth syndrome due to mercury
allergy.
Dermatitis. 2004 Jun;15(2):75-7.
The beneficial effect of amalgam replacement on health in patients
with autoimmunity.
Neuro Endocrinol Lett. 2004 Jun;25(3):211-8.
Dental amalgam as one of the risk factors in autoimmune diseases.
Neuro Endocrinol Lett. 2003 Feb-Apr;24(1-2):65-7.
Oral lichenoid reactions associated with amalgam: improvement after
amalgam removal.
Br J Dermatol. 2003 Jan;148(1):70-6.
Removal of dental amalgam and other metal alloys supported by
antioxidant therapy alleviates symptoms and improves quality of life
in patients with amalgam-associated ill health.
Neuro Endocrinol Lett. 2002 Oct-Dec;23(5-6):459-82.
Influence of amalgam fillings on Hg levels and total antioxidant
activity in plasma of healthy donors.
Sci Total Environ. 2003 Jan 1;301(1-3):43-50.
Health and neuropsychological functioning of dentists exposed to
mercury.
Occup Environ Med. 2002 May;59(5):287-93.
Siblerud, R.L. (1989). The relationship between mercury from dental
amalgam and mental health. Am. J. Psychother. 43:575-587.
Siblerud, R.L. (1992). A comparison of mental health of multiple
sclerosis patients with silver/mercury dental fillings and those with
fillings removed. Psychol. Rep. 70:1139-1151.
Siblerud, R.L., Kienholz, E., and Motl, J. (1993). Evidence that
mercury from silver dental fillings may be an etiological factor in
smoking. Toxicol. Lett. 68:307-310.
Siblerud, R.L., Motl, J., and Kienholz, E. (1994). Psychometric
evidence that mercury from silver dental fillings may be an
etiological factor in depression, excessive anger, and anxiety.
Psychol. Rep. 74:67-80.
Can the author produce previously published evidence of high mercury
vapor concentrations in the mouths of amalgam wearers?
Yes:
? Chew et al. Clinical Preventive Dentistry 13(3) 5-7, 1991. In a
study of long term dissolution of mercury from an non-mercury
releasing amalgam it was determined that 43.5 microgram/cm2/day Hg was
released and this remained constant for 2 years.
Release of mercury from dental amalgam and its influence on salivary
antioxidant activity.Sci Total Environ. 2002 Feb 4;284(1-3):19-25.
Mercury exposure from "silver" tooth fillings: emerging evidence
questions a traditional dental paradigm.
FASEB J. 1995 Apr;9(7):504-8.
[Release of mercury vapor from dental amalgam under oral conditions]
ZWR. 1985 Feb;94(2):131-4, 137-9.
Dental amalgam related mercury vapor exposure.
CDA J. 1984 Oct;12(10):54-60.
Intra-oral air mercury released from dental amalgam.
J Dent Res. 1985 Aug;64(8):1069-71.
Dental "silver" tooth fillings: a source of mercury exposure revealed
by whole-body image scan and tissue analysis.
FASEB J. 1989 Dec;3(14):2641-6.

But it is more reliable, to measure mercury concentrations not in the
mouth but in the internal organs of amalgam bearers. This autopsy
studies find consistently high mercury levels in amalgam bearers.
? Guzzi G, Grandi M, Cattaneo C et al. Dental amalgam and mercury
levels in autopsy tissues. Food for thought. Am J Forensic Med Pathol
2006; 27: 42-45.
Drasch, G., Wanghofer, E., and Roider, G. (1997). Are blood, urine,
hair, and muscle valid bio-monitoring parameters for the internal
burden of men with the heavy metals mercury, lead and cadmium? Trace
Elem. Electrolyt. 14:116-123.
Drasch, G., Schupp, I., Riedl, G., and Günther, G. (1992). Einfluß von
Amalgamfüllungen auf die Quecksilberkonzentration in menschlichen
Organen. Dtsch. Zahnärztl. Z. 47:490-496.
Drasch, G., Schupp, I., Hofl, H., Reinke, R., and Roider, G. (1994).
Mercury burden of human fetal and infant tissues. Eur. J. Ped.
153:607-610.
Eggleston, D.W. and Nylander, M. (1987). Correlation of dental amalgam
with mercury in brain tissue. J. Prosth. Dent. 58:704-707.
Nylander, M. (1986). Mercury in pituitary glands of dentists. Lancet
22:442.
Nylander, M., Friberg, L., and Lind, B. (1987). Mercury
concentrations in the human brain and kidneys in relation to exposure
from dental amalgam fillings. Swed. Dent. J. 11: 179-187.
There is no presented evidence that the amalgam-free group in the
study ate more fish than the other groups. Why would they?
Because their socio-economic status was higher (higher socio-e. status
may correlate with fish consumption:
Fish consumption among pregnant women in London, Ontario: associations
with socio-demographic and health and lifestyle factors.
Can J Public Health. 2007 Sep-Oct;98(5):389-94. )


and their blood mercury levels was as high than the levels of the
amalgam bearers. Normally, amalgam bearers have 2-5 fold more mercury
in blood than people without amalgam:

Mercury concentrations in urine and whole blood associated with
amalgam exposure in a US military population.
J Dent Res. 1998 Mar;77(3):461-71.
Influence of amalgam fillings on Hg levels and total antioxidant
activity in plasma of healthy donors.
Sci Total Environ. 2003 Jan 1;301(1-3):43-50.
People with high mercury uptake from their own dental amalgam fillings.
Occup Environ Med. 1995 Feb;52(2):124-8.

Therefore, amalgam free control group may have another source of
mercury exposure, most likely fish consumption.
The Letter ask the authors, why frequency of fish consumption was not
assesed in a study, which measure mercury levels in dependence of
dental amalgam. This is an important question!

There is no scientific evidence that selenium either binds to or
'protects' mercury in fish from being toxic.
Again, the reviewer#1 seem not to overlook the published literature,
which suggest that selenium bind to mercury and the mercury-selenium
complex may be less toxic than unbound mercury:
Mercury-selenium species ratio in representative fish samples and
their bioaccessibility by an in vitro digestion method.
Biol Trace Elem Res. 2007 Dec;119(3):195-211.
Importance of molar ratios in selenium-dependent protection against
methylmercury toxicity.
Biol Trace Elem Res. 2007 Dec;119(3):255-68.
The roles of selenium and mercury in the pathogenesis of viral
cardiomyopathy.
Congest Heart Fail. 2007 Jul-Aug;13(4):193-9
The roles of serum selenium and selenoproteins on mercury toxicity in
environmental and occupational exposure.
Environ Health Perspect. 2006 Feb;114(2):297-301.
The interaction of selenium and mercury in the accumulations and
oxidative stress of rat tissues.
Ecotoxicol Environ Saf. 2007 Jul 16;
Effect of selenium pretreatment in chronic mercury intoxication in rats.
Bull Environ Contam Toxicol. 2007 Sep;79(3):306-10.
Kosta, L., Byrne, A.R., and Zelenko, V. (1975). Correlation between
selenium and mercury in man following exposure to inorganic mercury.
Nature 254:238-239.
Nylander, M. and Weiner, J. (1991). Mercury and selenium
concentrations and their interrelations in organs from dental staff
and the general population. Br. J. Ind. Med. 48:729-734.

But also, other chemical forms of mercury in fish seem to be less
toxic as previously assumed:

Harris HH, Pickering IJ, George GN. The chemical form of mercury in
fish. Science 2003; 301: 1203.

So, why neglect the reviewer#1 this facts for rejecting my letter?
What does the first sentence on page 2 mean?
Here is the sentence:
"Mercury levels in body fluids of 27 patients who complained of health
problems from dental amalgam (?cases?), of 27 healthy patients with
amalgam, and 27 amalgam free volunteers were presented (1)."

What is the problem with this sentence for the reviewer#1, which give
a brief overview of the study? (word acount schould be less than 400
words!)

Minor Edits
page 1 2nd para: 'dietary' is misspelled
page 1 "show" should be "shown"
page 1 "proofed" should be "proven"
page 2 ln 5 "there' is misspelled and should be 'their'
page 2 ln 6 'may' is misspelled

There is no word "intracellulary"
This was mispelled. But there is the word "intracellularly", which was
meant.


Mit freundlichen Gruessen

Dr. med. Joachim Mutter
---------------------------------------------------------------------
Institut fuer Umweltmedizin und Krankenhaushygiene
Universitätsklinikum Freiburg
Department of Environmental Health Sciences
University Medical Center Freiburg
Breisacher Straße 115 B, 79106 Freiburg
Tel. +49/(0)761/270-8201 (-8320)
Fax +49/(0)761/270-8323

>
> Department of Preventive Medicine and Public Health, University of Valencia,
> Spain.
>
> BACKGROUND: Among potential environmental risk factors for Alzheimer disease
> (AD), occupational exposures have received some attention, including
> extremely low frequency electromagnetic fields (ELF-EMF). A systematic
> review and meta-analysis of published epidemiological studies on this
> subject was carried out. METHODS: The search was concluded in April 2006.
> Bibliographic databases consulted included PubMed, EMBASE, Cochrane Library
> and NIOSHTIC2. Pooled estimates were obtained using random-effects
> meta-analysis. Sources of heterogeneity between studies were explored, as
> was publication bias. RESULTS: Fourteen different studies (nine case-control
> and five cohort studies) accomplished inclusion criteria. All these studies
> followed standardized criteria for AD diagnosis and most of them obtained
> quantitative estimates of exposure. Pooled estimates suggest an increased
> risk of AD from case-control studies (OR(pooled) 2.03; 95% CI 1.38-3.00) and
> from cohort studies (RR(pooled) 1.62; 95% CI 1.16-2.27), with moderate to
> high statistical heterogeneity in both cases (respectively, I(2) = 58% and
> I(2) = 54%). Cohort studies showed consistently increased risks for exposed
> men (RR(pooled) 2.05; 95% CI 1.51-2.80, I(2) = 0%). Evidence of
> dose-response relationship was not present. Test for publication bias
> suggests small study effects, mostly for case-control studies. CONCLUSIONS:
> Available epidemiological evidence suggests an association between
> occupational exposure to ELF-EMF and AD. However, some limitations affecting
> the results from this meta-analysis should be considered. More information
> on relevant duration and time windows of exposure, on biological mechanisms
> for this potential association and on interactions between electromagnetic
> fields exposure and established risk factors for AD is needed.
>
> PMID: 18245151 [PubMed - as supplied by publisher]
>

Mit freundlichen Gruessen

Dr. med. Joachim Mutter
---------------------------------------------------------------------
Institut fuer Umweltmedizin und Krankenhaushygiene
Universitätsklinikum Freiburg
Department of Environmental Health Sciences
University Medical Center Freiburg
Breisacher Straße 115 B, 79106 Freiburg
Tel. +49/(0)761/270-8201 (-8320)
Fax +49/(0)761/270-8323

Unterschriftsaktion bis 31.12.2008: Luxemburger Appell wegen Amalgam
http://www.europaem.org/frameset2.html

Undersignment until 31.12.2008: Luxembourg Appeal regarding Amalgam
http://www.europaem.org/frameset2.html


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