Review by B. Windham of Seychelles methyl mercury exposure study:


Prenatal methylmercury exposure from ocean fish consumption in the Seychelles child development study, Myers GJ, Clarkson TW, et al, The Lancet, Vol 361, May 17, 2003



The study methodology and design ignored known facts about mercury and study methodology to the extent that the study is flawed and the results are not very reliable or useful for the purpose proposed by the authors.  The following 6 sections summarize the main problems with the study based on other studies in the literature.


I. The Scope and Usefulness of the Study Was Very Limited by Weak Design and Lack of Controls   

The authors and some quoting the study appear to imply broad scope for the study although its scope is extremely limited by its lack of attention to design and lack of attention to cofactors. The fact that several of the assumptions underlying the study design are known not to be valid presents serious problems in assessing its usefulness.  By the design of the study the authors assume that the cognitive measures used in the tests chosen for the study are only or primarily affected by methyl mercury exposure. That this is not true is well documented in the medical literature, and in this case there was no evidence presented that methyl mercury from fish was the primary neurological factor affecting this population. Other toxic metals including mercury vapor from dental amalgam, ethyl mercury from vaccines, and other heavy metals such as lead, arsenic, cadmium, aluminum, etc. are documented to have common significant exposures and to cause significant neurological effects. And other toxic exposures such as organochlorines, PCBs, dioxins, etc. are known to have significant exposures in such populations and to have significant neurological effects. Based on experience with such populations and other studies, many in the study likely had significant neurological effects from other toxic exposures.  Many other studies have considered such factors in their design to a larger extent than this one. As will be demonstrated further in section II, there is no reason to assume that methyl mercury from fish was the primary neurological toxic affecting many in this population.  And even if it were, the effects of the other toxic exposures that were not measured would confound the results significantly. 

In Section III it will be shown that the chosen measure of prenatal exposure to methyl mercury is not a reliable measure of either mercury body burden or mercury toxicity.  While it has been demonstrated that in general there is a significant positive correlation between a mother’s hair mercury level and an infant’s methyl mercury body level, the percentage of variability explained by this measure is relatively low and this does not appear to even be true for the portions of the population most susceptible to neurological effects of mercury.

            . In Section IV it will be shown that the decision to exclude the results of some groups of those tested in the study from consideration may have caused additional confounding of the study results, since there is considerable evidence in the medical literature that mercury exposure commonly causes some of the conditions of those whose test results were excluded.

            Another of the main assumptions underlying the study that is known not to be valid is the assumption that the neurological effects measured are directly or even primarily directly dose related.  It has been well demonstrated in the medical literature that while exposure level is a factor, it is not the primary factor in many cases.  In Section V it will be shown that susceptibility factors such as ability to detoxify or excrete mercury and immune reactivity play a major role in the extent to which a person is affected by mercury toxicity or immune reactive effects, and that the degree to which effects are directly dose related in real life is not very high.   

            In Section VI it will be shown that many studies have found neurological effects and other effects at similar levels of exposure, and many were better designed and controlled.

In Section VII it will be shown that the types of mercury related effects tested for and the tests chosen were extremely limited, even among neurological effects, given the well documented broad scope of neurological, immune, and endocrine effects documented as related to low levels of mercury exposure by the medical literature. Mercury has been documented to block basic cellular enzymatic processes affecting all major functions of all major organs-especially those related to neurological, immune, detoxification, and endocrine functions. And immune effects or effects on other detoxification and endocrine organs that occur at very low levels of exposure have been shown to have long term neurological effects.  Many other studies have considered and demonstrated the significance of such effects at levels of exposure such as those in this study

II. No Controls for Other Comparable Synergistic and Perhaps Larger Mercury Exposure Sources and Other Synergistic Toxic Exposures


A large flaw is that the study ignored and did not control for other mercury or toxic metal exposures such as dental amalgam fillings and vaccinations, which likely in many cases were the largest mercury exposure to the mother and child (1-5). In general it has been documented that dental amalgam is the largest source of total, inorganic, and methyl mercury in most people who have several mercury amalgam dental fillings in most populations (1,2). Mercury vapor and inorganic mercury have been found to commonly be methylated by mouth and intestinal bacteria, as well as yeast and other methyl donors (1,2).  While the Seychelles sample was from a population that eats more fish than average Americans or Europeans, the extent to which exposure from amalgam usually far exceeds that from fish means that it is not clear what the primary source of either total mercury or methyl mercury was in the mothers or children (1,2).  On average, mercury exposure and excretion in adults with several amalgam fillings is approximately 10 times that for those without amalgams in U.S. or European populations, and significantly higher in methyl mercury body burden as well (1,2).   And for those with more than the average number of amalgam fillings, the ratio of mercury exposure for those with several amalgam fillings can often be 100 times that of the average exposure of those without amalgams(2).    Also since the population likely had exposure both to methyl mercury and mercury vapor, the fact that mercury vapor is known to produce developmental effects at lower levels of exposure than methyl mercury, yet was not controlled for,  significantly confounds the results(6).  

Dental amalgam from mother’s amalgam fillings has been documented to be a major source of mercury exposure to the fetus and to infants (5,27).  Mercury in breast milk is positively correlated with the number of the mother’s amalgam fillings.   Mercury in breast milk of mothers with more than 7 amalgam fillings in one population studied was more than 10 times the average for those with no amalgam fillings(27). As previously noted, there is no direct way of knowing exactly which mercury in mother’s milk came from amalgam or from fish.

  Other toxic metals including dental metals also are documented to have significant synergistic neurological effects with mercury on children and to commonly have significant exposures in such populations of children (3,4,8,9,12).  

 Other toxic exposures such as pesticides, PCBs, and other neurotoxic and endocrine disrupting substances are common exposures that could confound these results(18,29). In one study of Inuit children, potential covariates were documented including demographic and familial characteristics, other prenatal neurotoxicants (alcohol, tobacco) and nutrients (selenium (Se), Omega-3 polyunsaturated fatty acids (n-3 PUFA))(29).  Concentrations of polychlorinated biphenyls (PCBs) and mercury were respectively three- and twofold higher, significantly greater, in the subsistence fishing group than in the reference group(33).

        For some of the test outcomes, neuromotor effects of Pb exposure are observed at blood concentrations below 10 microg/dl.   Together the lack of taking into account of these common neurotoxic exposures in this study resulted in a major confounding of the stated conclusions. Nor did the study mention the protective effects of selenium in some of the fish species that were eaten, or attempt to measure selenium levels to assess its differential protective effects on the population. Although methyl mercury is documented to be extremely neurotoxic at low levels of exposure, many species of fish are documented to contain significant levels of selenium which is known to be protective against neurotoxic effects of mercury(23).  Selenium protects from mercury and methyl mercury toxicity by preventing damage from free radicals or by forming inactive selenium mercury complexes (20).  Other nutritional factors are also documented to have significant effects on neurotoxicity of mercury(11,20).



III. Hair Mercury Level Used as a Measure of Mercury Exposure in the Study is Not a Reliable Indicator of Either Mercury Body Burden or Mercury Toxicity


        The authors assumed that hair test mercury levels of mother and infant are reliable indicators of current or future body burden, which isn't supported by experience or research.  A study by  Dr. Haley(PhD) and Dr. Holmes(MD)  found that among some mercury affected populations, those with high mercury body burdens and diagnosed mercury toxicity effects tend to have lower hair levels, not higher(7). Other researchers based on extensive clinical experience treating mercury toxic patients have found similar results(8,9).   Also since the population likely had significant mercury exposure from dental amalgam and vaccinations, the fact that hair mercury level mostly measures methyl mercury, whereas urine mercury levels are a better measure of dental amalgam exposure but weren’t measured, further confounds the results(10).

        Another study concluded that for the so-called normal population, the interpretation potential of heavy metal concentrations in blood, urine, and hair must be qualified: on a group basis, they can provide us with some useful information under the limitation that not every monitor is suitable for every metal.   But despite statistical significant rank correlation,  the confidence intervals of the regressions are so large that it is rather pointless to conclude the heavy metal burden of the target or storage tissue of an individual from the concentration in blood, muscle, urine, or hair(21).

A Japanese study with average maternal hair mercury level of 2.24 ppm found a positive correlation between fetal cord tissue methylmercury level and indicators of cardiac parasympathetic activity and sympathovagal shift indicating cardiovascular effects.   However cord mercury level was not significantly correlated with child hair mercury level, and hair mercury level was not significantly correlated with cardiovascular effects. (28)


        In regression analysis failure to adjust for imprecision in the exposure variable is likely to lead to underestimation of the exposure effect(26). It is shown that, if the exposure error is ignored, then the benchmark approach produces results that are biased toward higher and less protective levels. It is therefore important to take exposure measurement error into account when calculating benchmark doses. . The calculated total imprecision much exceeded the known laboratory variation: the CV was 28-30% for the cord-blood concentration and 52-55% for the maternal hair concentration. The dietary questionnaire response was even more imprecise. These findings illustrate that measurement error may be greatly underestimated if judged solely from reproducibility or laboratory quality data. Adjustment by sensitivity analysis is meaningful only if realistic measurement errors are applied. When exposure measurement errors are overlooked or underestimated, decisions based on the precautionary principle will not appropriately reflect the degree of precaution that was intended.



IV. Deletion from the Study Results of Infants Suffering from Health Conditions Known to be Commonly Caused by Mercury Toxicity


Study Participants.    The authors write:

“We excluded mothers and children with disorders highly associated with adverse neurodevelopment such as traumatic brain injury, meningitis, epilepsy, and severe neonatal illnesses. No data exist to suggest they are associated with MeHg exposure.” 

The authors however clearly were mistaken, as some of these conditions for which children were excluded from the study results have been well documented to be commonly caused by mercury toxicity (12-15,5,7).


The following Table is a summary of data from a large epidemiological study by the National Institute of Health of health statistics related to number of dental amalgam surfaces.


Table 1.

NHanesIII Condition Graphs,  35,000 Americans


(Conditions highly correlated with number of amalgam fillings: fewer of those with this condition have zero fillings than those of the general population while more of those with the condition have 17 or more surfaces than in the general population)


Infectious and parasitic diseases (001-139)

Disorders of thyroid gland (240-246)

Mental disorders (290-319)

Diseases of the nervous system and sense organs (320-389)

Other disorders of the central nervous system(Epilepsy, Seizures, MS) (340-349)


Incidence of the category of neurological conditions made up primarily of Epilepsy and MS was found to be highly correlated with the number of dental amalgam surfaces by the NHANES III study(13).  But medical studies and clinical experience have also found mercury to be a common factor in causing epilepsy and seizures(14).  Thus excluding these infants because they had a condition commonly caused by mercury has another confounding effect on the study results. 

Likewise, the NHANES study and other studies have found that there is a significant correlation between mercury exposure and infectious conditions such as meningitis so exclusion of these children without further consideration may have also been problematic.  (13,16abc)  Mercury is documented to significantly suppress the immune system, and a suppressed immune system is known to result in higher susceptibility to infectious diseases(24).    High levels of mercury exposure has been found to result in meningitis in animal studies and humans(22)  

Mercury and toxic substances effects on suppressing the immune system also are documented to cause increased susceptibility to other pathogens such as viruses, mycoplasma, bacterial infections, and parasites. The majority of those with autoimmune conditions like ALS, CFS, FMS, MS, autism, have been found to also be infected with mycoplasma and other pathogens(16abc, 9,4).


        Likewise mercury has been documented to commonly cause birth defects and neonatal developmental conditions and illnesses, so excluding some of these children without further investigation might also be a further confounding factor(3,4,8,9,14).


V. Neurological effects are not primarily directly dose related as

Susceptibility factors are known to have a major effect


The Study did not take into account that mercury effects on children and adults are well documented in the literature to be highly influenced by susceptibility factors, with effects primarily on  significant groups that have known and testable susceptibility factors(17). Some of the common significant susceptibility factors that determine the extent of mercury toxicity effects on an individual include immune reactivity, ability of the individual’s detoxification systems to detoxify and excrete mercury and other toxics, nutritional factors, etc.  


VI. Other Studies Finding Neurological Effects from Similar Levels of Exposure


          One study was of a Faroese birth cohort prenatally exposed to methylmercury from maternal intake of contaminated pilot whale meat. At seven years of age, clear dose-response relationships were observed for deficits in attention, language, and memory. An increase in blood pressure was also associated with the prenatal exposure level. The exposure limit for mercury has therefore been decreased(30).  A follow-up for the same population at age 14 found that the child's hair mercury level at age 14 years was associated with prolonged III-V interpeak latencies. All benchmark dose results were similar to those obtained for dose-response relationships at age 7 years. It was concluded that the persistence of prolonged I-III interpeak intervals indicates that some neurotoxic effects from intrauterine MeHg exposure are irreversible(30). There was also an assessment of possible confounding effects of PCBs in the population. The association between cord PCB and cord-blood mercury (r=.42) suggested possible confounding. While no PCB effects were apparent in children with low mercury exposure, PCB-associated deficits within the highest tertile of mercury exposure indicated a possible interaction between the two neurotoxicants. PCB-associated increased thresholds were seen at two of eight frequencies on audiometry, but only on the left side, and no deficits occurred on evoked potentials or contrast sensitivity. The limited PCB-related neurotoxicity in this cohort appears to be affected by concomitant methylmercury exposure(30b).


          Another study of Greenland infants at exposure levels slightly less than the Seychelles study found that “data from the present study therefore appears in accordance with other evidence that prenatal or early postnatal exposures to methylmercury may cause subtle neurobehavioral deficits” (31).  In a study of Inuit children, cord blood, maternal blood, and maternal hair mercury concentrations averaged 18.5 microg/L, 10.4 microg/L, and 3.7 microg/g, respectively, and were similar to those found in the Faeroe Islands but lower than those documented in the Seychelles Islands and New Zealand cohorts(29). Concentrations of PCB congener 153 averaged 86.9, 105.3, and 131.6 microg/kg (lipids) in cord plasma, maternal plasma, and maternal milk, respectively; prenatal exposure to PCBs in the Nunavik cohort is similar to that reported in the Dutch but much lower than those in other Arctic cohorts. Levels of n3-PUFA in plasma phospholipids and selenium in blood are relatively high.  Tremor amplitude was related to blood Hg concentrations at testing time, which corroborate an effect already reported among adults.  
Cord blood Hg in a study of a population living along the           St Lawrence River was significantly higher than maternal blood at birth. Maternal hair was correlated with Hg blood concentration and was highly predictive of the organic fraction in cord blood. A strong dose relation was observed between the frequency of fish consumption before and during pregnancy and Hg exposure in mothers and newborns. Fish consumption prior to and during pregnancy explained 26% and 20% of cord blood Hg variance, respectively(32).  

          Another study assessed infant cognition by the percent novelty preference on visual recognition memory (VRM) testing at 6 months of age.  An increase of 1 ppm in mercury was associated with a decrement in VRM score of 7.5 (95% CI, -13.7 to -1.2) points.  (11)  VRM scores were highest among infants of women who consumed greater than 2 weekly fish servings but had mercury levels less than 1.2 ppm.  Levels of mercury in mothers greater than 1.2 ppm were found to have negative health effects on infants.  And without the positive omega 3 effects, this level of exposure likely would produce even more adverse effects.

             Concentrations of polychlorinated biphenyls (PCBs) and mercury were respectively three- and twofold higher, significantly greater, in the subsistence fishing group than in the reference group(33). Compared to the reference group, the subsistence fishing group showed significant decreases in the proportion of the naive helper T-cell subset CD4+CD45RA, T-cell proliferation following an in vitro mitogenic stimulation, and plasma immunoglobulin M (IgM) level, while plasma IgC level was increased. NK cytolytic activities were similar in both groups. The proportion of CD4+CD45RA cells was inversely correlated to mercury and PCBs, while T-cell clonal expansion was negatively associated with PCBs and p,p'-DDE. Mercury was inversely correlated to plasma IgM.  Data show that subtle functional alterations of the developing human immune system may result from in utero exposure to OrganoChlorines and mercury.

A Polish study found that the mean blood mercury level of the mothers of a group of normal infants was significantly lower than that of a group of neurocognitively delayed infants and the cord blood mercury level of the normal infants was significantly less than for the group with delayed cognitive performance (34).  The relative risk of delayed performance for those with cord blood level greater than 0.8 micrograms per liter was 3.5 times that of those with level less than 0.5 ug/L. 

         Autopsy studies have also found that chronic mercury exposures result in cumulative increases in mercury in the brain and other body organs over time, and that mercury damage is cumulative and often only noticed later in life(24).  Studies have also found that neurotoxic effects of developmental mercury exposures are often delayed(35). Mercury exposures in a population of adults studied were associated with fish consumption(36). The hair mercury concentration in the 129 subjects ranged from 0.56 to 13.6 microg/g; the mean concentration was 4.2 +/- 2.4 micrograms/g and the median was 3.7 microg/g. Hair mercury levels were associated with detectable alterations in performance on tests of fine motor speed and dexterity, and concentration. Some aspects of verbal learning and memory were also disrupted by mercury exposure. This study found that adults exposed to MeHg may be at risk for deficits in neurocognitive function. The functions disrupted in adults, namely attention, fine-motor function and verbal memory, are similar to some of those previously reported in children with prenatal exposures(36).


VII.  Limited Types of Mercury Related Effects Tested for

The paper used a limited number of neurological tests and did not include other tests for neurological conditions or other types of conditions and effects that mercury has been documented to cause. Yet the authors tend to imply that the study represents a broad generally applicable assessment of mercury effects on children due to prenatal exposures.  This is clearly not the case and is counter to extensive documentation in the medical literature of chronic effects due to mercury at comparable or lower levels of exposure. (3-9, 11-15,24) 

Chronic exposure to mercury has been documented in the medical literature to result in distribution of mercury in the blood to all parts of the body where it accumulates in major organs receiving large amounts of blood and damages or blocks all bodily enzymatic or hormonal processes(24,etc.).  These effects have been documented in the medical literature to commonly result in neurological, immune, and endocrine system effects.  The mechanisms by which mercury commonly causes over 30 chronic health conditions has been documented by thousands of peer-reviewed studies(24,etc.), with susceptibility factors having a major role in the resulting conditions affecting an individual(17). 

Mercury has several forms and exists in solid, liquid, and gaseous states that are converted to other forms and states in the body, moving rapidly through the blood, crossing cell membranes, and forming compounds in the cells that result in accumulation in major organs, depending on the individuals systematic ability to detoxify and excrete mercury. For these reasons as has been documented in the literature, there is no simple test that is a reliable indicator of mercury body burden or mercury toxicity effects(37). Because the effects of mercury are systematic and diverse it is not possible to do a simple epidemiological study to develop a benchmark exposure level that is reliable for all of the diverse systematic effects of mercury which affect different individuals in very different ways depending on their individual susceptibilities.  And the many other toxic exposures that most populations are exposed to and the fact that susceptibility and nutritional factors have major impacts on mercury toxicity effects further complicates any effort in using an epidemiological study to develop a benchmark or baseline exposure level below which exposures are unlikely to have significant effects. The many bodily processes and organs affected by mercury are affected at different exposure levels depending on the organ/function and the individual.   It has been documented for example that some who are immune reactive to mercury have very significant effects at extremely low levels of exposure.  The following provides documentation on the mechanisms by which mercury causes significant systematic effects on all enzymatic processes in all organs of the body.  


Studies have  found heavy metals such as mercury to deplete glutathione and bind to protein-bound sulfhydryl SH groups, resulting in inhibiting SH-containing enzymes and production of reactive oxygen species such as superoxide ion, hydrogen peroxide, and hydroxyl radical(40-44).  In addition to forming strong bonds with SH and other groups like OH,NH2, and Cl in amino acids and thus interfering with basic enzymatic processes, toxic metals exert part of their toxic effects by replacing essential metals such as zinc and magnesium at their sites in enzymes (45-47,14).  .    Mercury has also been found to play a part in neuronal problems through blockage of the P‑450 enzymatic process(48,43).  Such affects have been found to commonly result in mental retardation, lowered IQ, and learning disabilities (40).


Mercury induced lipid peroxidation has been found to be a major factor in mercury’s neurotoxicity, along with leading to decreased levels of glutathione peroxidation and superoxide dismustase(SOD)(41,42,47-53). Mercury also blocks the enzyme functions of magnesium and zinc (45-47,14), whose deficiencies are known to cause significant neurological effects(54,55,14). The low Zn levels result in deficient  CuZnSuperoxide dismustase (CuZnSOD), which in turn leads to increased levels of superoxide due to toxic metal exposure. This condition can result in zinc deficient SOD and oxidative damage involving  nitric oxide, peroxynitrite, and lipid peroxidation(50-52,56), which have been found to affect glutamate mediated excitability and apoptosis of nerve cells and effects on mitochondria

(45,51,52,56,59,61). Additional cellular level enzymatic effects of mercury’s binding with proteins include blockage of sulfur oxidation processes such as cysteine dioxygenase, gamma‑  glutamyltranspeptidase(GGT), and sulfite oxydase, along with neurotransmitter amino acids which have been found to be significant factors in many autistics(57-60), plus enzymatic processes involving vitamins B6 and B12, with effects on the cytochrome-C energy processes as well. 

          Mercury by forming strong bonds with and modification of the-SH

groups of proteins and enzymes causes mitochondrial release of calcium

(45,61),as well as changing the permeability of cell membranes(62),

damaging mitochondria (45,59,61,51,52) altering molecular function of

amino acids and damaging enzymatic process(59,62-64). This results in

improper cysteine regulation(63,65), inhibited glucose transfer and

uptake(62,49), damaged sulfur oxidation processes (59,62,65), reduced

glutathione availability (necessary for  detoxification) (41,67),  and damaging



TNFa(tumor necrosis factor-alpha) is a cytokine that controls a wide range of immune cell response in mammals, including cell death(apoptosis).  This process is involved in inflamatory and degenerative neurological conditions like ALS, MS, Parkinson’s, rheumatoid arthritis, lupus, etc.  Cell signaling mechanisms like sphingolipids are part of the control mechansim for the TNFa apoptosis mechanism(67a). Mercury has been shown to induce TNFa and deplete glutathione, causing inflamatory effects and cellular apoptosis in neuronal and immune cells(67bc,181).  Gluthathione is an amino acid that is a  normal cellular mechanism for controlling apoptosis.  When glutathione is depleted in the brain, reactive oxidative species increased, and CNS and cell signaling mechinsisms are disrupted by toxic exposures such as mercury, neuronal cell apoptosis results and neurological damage.      

          Metalloprotein(MT) are involved in metals transport and detoxification(69,14). Mercury inhibits sulfur ligands in MT and in cell membranes inactivates MT that normally bind cuprous ions(70), thus allowing buildup of copper to toxic levels in many people and malfunction of the Zn/Cu SOD function.    Exposure to mercury results in changes in  metalloprotein compounds that have genetic effects, having both structural and catalytic effects on gene expression(66,69-71,14,51,).  Some of the processes affected by such MT control of genes include cellular respiration, metabolism, enzymatic processes, metal-specific homeostasis, and adrenal stress response systems. Significant physiological changes occur when metal ion concentrations exceed threshold levels. Copper is an essential trace metal which plays a fundamental role in the biochemistry of the nervous system through the SOD and MT functions(50,51,14).   Mutations in the copper/zinc enzyme superoxide dismustase(SOD) have been shown to be a major factor in the motor neuron degeneration in conditions like familial ALS and similar effects on Cu/Zn SOD to be a factor in other conditions such as autism, Alzheimer’s, Parkinson’s, and non-familial ALS(50,51,14,63).  Out of a population of several hundred autistic children tested, over 95% were found to have Cu/Zn MT disfunction(14), which appears to be a major mechanism involved in autism and by which mercury and other toxic metals can cause such conditions. The majority treated for this condition through mercury/metals detoxification and/or nutritional measures to restore MT function have been found to have significant improvement(14,9).

          Such MT formation and disfunction also appears to have a relation to

autoimmune reactions in significant numbers of people (64,69,71-73,14).  

The enzymatic processes blocked by such toxic substances as mercury also

result in chronic formation of metal‑protein compounds (HLA antigens or

antigen-presenting macrophages)  that the body’s immune system(T-

lymphocytes)  does not recognize, resulting in autoimmune reactions and

autoimmune conditions (64,68,71-73).  Of the over 3,000 patients with

chronic conditions tested using the MELISA test for lymphocyte reactivity to

metals(72), 20% tested positive for inorganic mercury and 8% for methyl

mercury.  For people with autoimmune conditions such as CFS, Fibromyalgia,

or Multiple Chemical Sensitivity,  the percentage testing immune reactive to

mercury was  higher-  23% to inorganic mercury, and 12% to methyl

mercury, as compared to less than 5% for controls.

And the percentage of those with MS testing positive to mercury was over

70%, with significant reductions in reactivity and symptoms when mercury

levels were reduced(73). The mechanisms by which mercury exposure

causes over 30 chronic conditions has been documented in the medical

literature(24), as well as documentation of common recovery from these

conditions after treatment for mercury toxicity(25,9.14).




(1) Leistevuo J et al,  Dental amalgam fillings and the amount of organic mercury in human saliva.  Caries Res 2001 May-Jun;35(3):163-6;

(2) Dental Amalgam is the Largest Source of Inorganic and Methyl Mercury in Most People with Several Amalgam Dental Fillings,  B. Windham, Review, FS1,

(3) Neurological and Behavioral Effects of Toxic Metals on Children,  B. Windham, Review,

(4) Neurological and Developmental Effects of Mercury from Vaccines, B. Windham, Review,

(5) Natal and Neonatal Effects of Mercury Exposure,  B. Windham, Review,

(6) Mercury Vapor Causes Neurological Developmental and Behavioral Effects at Lower Levels than Other Forms of Mercury. B. Windham, Review, DAMS FS13

(7) A.S. Holmes, M.F. Blaxill and B.E. Haley, Reduced Levels of Mercury in First Baby Haircuts of Autistic Children; International Journal of Toxicology, 2003, & Baby hair, mercury toxicity and autism.  Int J Toxicol. 2004 Jul-Aug;23(4):275-6. Grether J, Croen L, Theis C, Blaxill M, Haley B, Holmes A.

 (8) Andrew Hall Cutler, PhD, PE; Amalgam Illness:Diagnosis and Treatment; 1996 ,

(9) Autism Treatment Center, Baton Rouge, La, Experience from Treating 300 Mercury Toxic Autism Patients,

(10) Mercury concentrations in urine, scalp hair, and saliva in children from Germany. Pesch A, Wilhelm M et al,  J Expo Anal Environ Epidemiol. 2002 Jul;12(4):252-8.


(11) Maternal Fish Consumption, Hair Mercury, and Infant Cognition in a U.S. Cohort, Emily Oken, Robert O. Wright, et al; Environmental Health Perspectives Volume 113, Number 10, October 2005


(12) Metal Metabolism and Autism: Disablement of Metallothionein Proteins


(13) NHanesIII Condition Graphs ;  NHANES III Screening – 35,000 Americans

(14) Walsh, WJ, Health Research Institute, Autism and Metal Metabolism, , Oct 20, 2000; & Walsh WJ, Pfeiffer Treatment Center, Metal‑Metabolism and Human Functioning, 2000, ;

  &  Metal-Metabolism and Autism:  Defective Functioning of Metallothionein Protein, Amy Holmes, MD;

(15) Mechanisms by which mercury has been documented to cause epilepsy and seizures,  B. Windham, Review,

(16) (a)Dr. Garth Nicholson, Institute for Molecular Medicine, Huntington Beach,  Calif.,        &  Michael Guthrie, R.Ph.     07‑18‑2001  Mycoplasmas – The Missing Link in Fatiguing  Illnesses,; &

 (b) M.M. van Benschoten, ““Acupoint Energetics of Mercury Toxicity and Amalgam Removal with Case Studies,”” American Journal of Acupuncture, Vol. 22, No. 3, 1994, pp. 251-262;


     & © Hulda Clark, The Cure for all Diseases, New Century Publishing, 2000,


(17) Susceptibility factors in mercury toxicity effects, B. Windham, Review,  

(18) Health Effects of Pesticides, Review, B.Windham(Ed),  Adverse Effects of Endocrine Disrupting Chemicals, Review, B. Windham,

(19)  Agency for Toxic Substances and Disease Registry, U.S. Public Health   Service, Toxicological Profile for Mercury , 1999; & Jan 2003 Media Advisory, New MRLs for toxic substances, MRL:elemental mercury vapor/inhalation/chronic & MRL:   methyl mercury/ oral/acute; &

(20) Goyer RA. Nutrition and metal toxicity. Am J Clin Nutr. 1995 Mar;61(3 Suppl):646S-650S; & Furst A , Can nutrition affect chemical toxicity? Int J Toxicol. 2002 Sep-Oct;21(5):419-24; & Fredriksson A, Gardlund AT, et al, Effects of maternal dietary supplementation with selenite on the postnatal development of rat offspring exposed to methyl mercury

(21) Drasch, G;Wanghofer, E;Roider, G, Are blood, urine, hair, and muscle valid biomonitors for the internal burden of men with the heavy metals mercury, lead and cadmium? - An investigation on 150 deceased, Trace Elements & Electrolytes, 1997, 14(3): 116-123.

(22) Davies TS, Nielsen SW, Kircher CH. The pathology of subacute methylmerculialism in swine. Cornell Vet. 1976 Jan;66(1):32-55; &

Stark AM, Barth H, Grabner JP, Mehdorn HM.  Accidental intrathecal mercury application. Eur Spine J. 2004 May;13(3):241-3. Epub 2003 Oct 28


(23) Cardellicchio N, Decataldo A, Di LA, Misino A. Accumulation and tissue distribution of mercury and selenium in striped dolphins (Stenella coeruleoalba) from the Mediterranean Sea (southern Italy). Environ Pollut. 2002;116(2):265-71; & Dietz R, Riget F, Born EW. An assessment of selenium to mercury in Greenland marine animals. Sci Total Environ. 2000 Jan 17;245(1-3):15-24; & Kim EY, Saeki K, et al,  Specific accumulation of mercury and selenium in seabirds.    Environ Pollut. 1996;94(3):261-5.

(24) Mechanisms by which mercury is documented to cause over 30 chronic health conditions,  B.Windham, Review, over 4,000 peer-reviewed studies cited,                              (a)     & by each condition                                                                                    (b)

 (25)  Documentation of over 50,000 cases of recovery from over 30 chronic conditions after proper dental amalgam replacement and detoxification,  including many peer-reviewed studies,

 (26) Effects of exposure imprecision on estimation of the benchmark dose.  Budtz-Jorgensen E, Keiding N, Grandjean P.  Risk Anal. 2004 Dec;24(6):1689-96; & Underestimation of risk due to exposure misclassification. Grandjean P, Budtz-Jorgensen E, Keiding N, Weihe P. Int J Occup Med Environ Health. 2004;17(1):131-6.
(27) Mercury in human colostrum and early breast milk. Its dependence on dental amalgam and other factors. Drasch G, Aigner S, Roider G, Staiger F, Lipowsky G. J Trace Elem Med Biol. 1998 Mar; 12(1):23-7.                                                                                                          (28)  Murata K, Satoh H et al; Subclinical effects of prenatal methylmercury exposure on cardiac autonomic function in Japanese children.  Int Arch Occup Environ Health. 2005 Dec 20;:1-8;
Prenatal exposure of the northern Quebec Inuit infants to environmental contaminants.  Environ Health Perspect. 2001 Dec;109(12):1291-9. Muckle G, Ayotte P, Dewailly E E, Jacobson SW, Jacobson JL: & Despres C, Muckle G et al, Neuromotor functions in Inuit preschool children exposed to Pb, PCBs, and Hg.    Neurotoxicol Teratol. 2005 Mar-Apr;27(2):245-57. Epub 2005 Jan 11
(30)Weihe P, Grandjean P et al; Environmental epidemiology research leads to a decrease of the exposure limit for mercury] Ugeskr Laeger. 2003 Jan 6;165(2):107-11: &

Murata K, Weihe P, Budtz-Jorgensen E, Jorgensen PJ, Grandjean P; Delayed brainstem auditory evoked potential latencies in 14-year-old children exposed to methylmercury.  J Pediatr. 2004 Feb;144(2):177-83; & (b) Grandjean P,  White RF, et al; Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants Neurotoxicol Teratol. 2001 Jul-Aug;23(4):305-17.

 (31) Neurobehavioral performance of Inuit children with increased prenatal exposure to methylmercury.  Weihe P,, Grandjean P et al . Int J Circumpolar Health. 2002 Feb;61(1):41-9.

(32)  Temporal variation of blood and hair mercury levels in pregnancy in relation to fish consumption history in a population living along the St. Lawrence River. Environ Res. 2004 Jul;95(3):363-74.  Morrissette J, Takser L,  Lafond J, Mergler D, et al.

(33) Cord blood lymphocyte functions in newborns from a remote maritime population exposed                      to organochlorines and methylmercury. Belles-Isles M, Ayotte P, Dewailly E, Weber JP, Roy R. J Toxicol Environ Health A. 2002 Jan 25;65(2):165-82.

(34) Jedrychowski W,  Perera F et al; Effects of Prenatal Exposure to Mercury on Cognitive and Psychomotor Function in One-Year-Old Infants: Epidemiologic Cohort Study in Poland. Ann Epidemiol. 2005 Nov 4;

(35) D.C. Rice, “Evidence of delayed neurotoxicity produced by methyl mercury developmental exposure”, Neurotoxicology, Fall 1996, 17(3-4), p583-96; & Weiss B, Clarkson TW, Simon W.  Silent  latency periods in methylmercury poisoning and in neurodegenerative disease. Environ Health Perspect. 2002 Oct;110 Suppl 5:851-4.

(36) Low level methylmercury exposure affects neuropsychological function in adults. Environ Health. 2003 Jun 4;2(1):8.  Yokoo EM,  Silbergeld EK et al.

(37) Test options for mercury body burden and toxicity, and complications in assessment of mercury body burden or toxicity, B. Windham, Review:


(40) Rodier P.M.  Developing brain as a target of toxicity.  Environ Health Perspect 1995; 103(Supp 6): 73-76; &(b) Rice DC, Barone S, Critical Periods of Vulnerability for the Developing Nervous System: Evidence from human and animal models.  Environ Health Persect 2000, 108(supp 3):511-533; & (c)  Trasande L, Schechter CB, Haynes KA, Landrigan PJ.  Mental retardation and prenatal methylmercury toxicity.  Am J Ind Med. 2006 Mar;49(3):153-8

(41)(a) S.Hussain et al, “Mercuric chloride‑induced reactive oxygen species and its effect on

antioxidant enzymes in different regions of rat brain”,J Environ Sci Health B 1997 May;32(3):395‑409;  & P.Bulat, “Activity of Gpx and SOD in workers occupationally exposed to mercury”, Arch Occup Environ Health, 1998, Sept, 71 Suppl:S37-9; &(b) S.Tan et al, “Oxidative stress induces programmed cell death in neuronal cells”, J Neurochem, 1998, 71(1):95-105

(42)(a) A.Nicole et al, “Direct evidence for glutathione as mediator of apoptosis in neuronal cells”, Biomed Pharmacother, 1998; 52(9):349-55, & J.S. Bains et al, “Neurodegenerative disorders in humans and role of glutathione in oxidative stress mediated neuronal death”, Brain Res Rev, 1997, 25(3):335-58

(43)Makani A, Gollapudi S, Yel L, Chiplunkar S, Gupta S; Biochemical and molecular basis for thimerosal-induced apoptosis in T-cells; a major role of mitochondrial pathway; Genes and Immunity, 2002, 3:270-278; & (b)

James S.J., Slikker W, Melnyk S, New E, Pogribna M, Jernigan S; Thimerosal neurotoxicity is associated with glutathione depletion: Protection with nutritional supplementation; Dept. of Pediatrics, College of Medicine, Univ. of Arkansas, and Arkansas Children’s Hospital Reserch Institute, Little Rock, Ark; Neurotoxicology Conference, Hawaii, February 2004

(44)      C.K.Mittal et al, “Interaction of heavy metals with the nitric  oxide  synthase”, Mol Cell Biochem,149-150:263-5, Aug 1995; & J.P.Bolanos et al, “Nitric Oxide mediated mitochondrial damage in the brain”, 

(45)      (a)Knapp LT; Klann E.   Superoxide‑induced stimulation of protein kinase C via  thiol

modification and modulation of zinc content. J Biol Chem 2000 May 22;  & A.Badou et al, “HgCl2-induced IL-4 gene expression in T cells involves a protein kinase C-dependent calcium influx through L-type calcium channels”J Biol Chem. 1997 Dec 19;272(51):32411-8.,

(46) Chetty CS, McBride V, Sands S, Rajanna B.   Effects in vitro on rat brain Mg(++)-ATPase.  

Arch  Int Physiol Biochem  1990

(47) Troy CM, Shelanski ML.  Down-regulation of copper/zinc superoxide dismustase causes apoptotic death in PC12 neuronal cells. Proc. National Acad Sci, USA, 1994, 91(14):6384-7; & Rothstein JD, Dristol LA,           Hosier B, Brown RH, Kunci RW.  Chronic inhibition of superoxide dismustase produces apoptotic death     of spinal neurons.  Proc Nat Acad Sci, USA, 1994, 91(10):4155-9.

(48)   J.C.Veltman et al, "Alterations of heme, cytochrome P‑450, and steroid metabolism by mercury in rat adrenal gland", Arch Biochem Biophys,1986, 248(2):467‑78; & A.G.Riedl et al, Neurodegenerative Disease Research Center, King's College,UK, "P450 and hemeoxygenase enzymes in the basal ganglia and their role's in Parkinson's disease", Adv Neurol, 1999; 80:271‑86

(49)  Zabinski Z; Dabrowski Z; Moszczynski P; Rutowski J.   The activity of erythrocyte

enzymes and basic indices of peripheral blood  erythrocytes from workers chronically exposed to mercury              vapors.             Toxicol Ind Health 2000 Feb;16(2):58‑64.

(50)  Waggoner DJ, Bartnikas TB, Gitlin JD.  The role of copper in neurodegenerative disease. 

         Neurobiol Dis 1999 Aug;6(4):221‑30; & (b) Estevez AG,Beckman JS et al,   Induction of     nitric oxide‑dependent apoptosis in motor neurons by  zinc‑deficient superoxide dismustase.  Science 1999 Dec 24;286(5449): 2498‑500;

(51)Kruman II, Pedersen WA, Springer JE, Mattson MP.   ALS‑linked Cu/Zn‑SOD mutation increases vulnerability of motor  neurons to excitotoxicity by a mechanism involving increased oxidative stress and perturbed calcium homeostasis.  Exp Neurol 1999 Nov;160(1):28‑39

(52)  Doble A. The role of excitotoxicity in neurodegenerative disease: implications   for therapy.  Pharmacol Ther   1999 Mar;81(3):163‑221; &   Cookson MR, Shaw PJ.   Oxidative stress and motor neurons disease.  Brain Pathol 1999 Jan;9(1):165‑86

(53) Joachim Mutter et al, Alzheimer Disease: Mercury as pathogenetic factor and

apolipoprotein E as a moderator,  Neuroendocrinol Lett 2004; 25(5):331–339

(54)Rasmussen HH, Mortensen PB, Jensen IW. Depression  and magnesium deficiency. Int J Psychiatry Med        1989;19(1):57‑63: &   Bekaroglu M, Aslan Y, Gedik Y, Karahan C.  Relationships between serum free          fatty  acids and zinc with ADHD.  J Child Psychol Psychiatry 1996; 37(2):225-7; &  Maes M,         Vandoolaeghe E, Neels H, Demedts P, Wauters,  A, Meltzer HY, Altamura C, Desnyder R. Lower  serum zinc in major depression is a sensitive marker of treatment resistance and of the

        immune/inflammatory response in that illness. Biol Psychiatry 1997;42(5):349‑358.

 (55)  Johnson S.  The possible role of gradual accumulation of copper, cadmium, lead and iron

depletion of zinc, magnesium, selenium, vitamins B2, B6, D, and E and essential fatty acids in multiple  sclerosis.  Med Hypotheses 2000 Sep;55(3):239‑41

(56)(a) Urushitani M, Shimohama S.  The role of nitric oxide in amyotrophic lateral sclerosis. Amyotroph Lateral    Scler Other Motor Neuron Disord 2001 Jun;2(2):71-81; &(b) Torreilles F, Salman-Tabcheh S, Guerin M,         Torreilles J. Neurodegenerative disorders: the role of peroxynitrite.Brain Res Brain Res Rev 1999 Aug;30(2):153-63; & (c)Aoyama K, Matsubara K, Kobayashi S.  Nitration of manganese superoxide dismutase      in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases.     

         Ann Neurol 2000 Apr;47(4):524-7; &(d) Guermonprez L, Ducrocq C, Gaudry-Talarmain YM.  Inhibition of acetylcholine synthesis and tyrosine nitration induced by peroxynitrite are differentially prevented by antioxidants.  Mol Pharmacol 2001 Oct;60(4):838-46

(57) Sastry KV, Gupta PK.  In vitro inhibition of digestive enzymes by heavy metals and their reversal by chelating agents: Part 1, mercuric chloride intoxication.  Bull Environ Contam Toxicol 1978; 20(6): 729-35; & W.Y.Boadi et al, Dept. Of Food Engineering and Biotechnology, T-I Inst of Tech., Haifa, Israel, In vitro effect of mercury on enzyme activities, Environ Res, 1992, 57(1):96-106; & Horvath K, Papadimitriou JC, Rabsztyn A, Drachenberg C, Tildon JT; Gastrointestinal abnormalities in children with autistic disorder.  J Pediatr 1999,  135:559-63.

(58)  Matts RL, Schatz JR, Hurst R, Kagen R.   Toxic heavy metal ions inhibit reduction of disulfide bonds.  J Biol Chem 1991; 266(19): 12695-702; &  Ceaurriz et al, Role of gamma‑  glutamyltraspeptidase(GGC) and extracellular glutathione in disposition of inorganic mercury",J Appl Toxicol,1994, 14(3): 201‑

(59) (a)  Markovich et al,  "Heavy          metals (Hg,Cd) inhibit the activity of the liver and kidney sulfate transporter Sat‑1", Toxicol  Appl Pharmacol,           1999,154(2):181‑7; & (b)S.A.McFadden, “Xenobiotic metabolism and adverse environmental response: sulfur-dependent detox pathways”,Toxicology, 1996, 111(1-3):43-65; &(c) Alberti A, Pirrone P, Elia M, Waring RH, Romano C.  Sulphation deficit in “low-functioning” autistic children. Biol Psychiatry 1999, 46(3):420-4.

 (60)  Moreno-Fuenmayor H, Borjas L, Arrieta A, Valera V,   Plasma excitatory amino acids in autism.  Invest Clin 1996, 37(2):113-28;   

(61) A.J.Freitas et al, “Effects of Hg2+ and CH3Hg+ on Ca2+ fluxes in the rat brain”,      Brain

Research, 1996, 738(2): 257-64; & P.R.Yallapragoda et al,“Inhibition of calcium transport by Hg salts” in rat cerebellum and cerebral cortex”, J Appl toxicol, 1996, 164(4): 325-30;      & A. Szucs et al, Effects of inorganic mercury and methylmercury on the ionic currents of cultured rat hippocampal neurons. Cell Mol Neurobiol, 1997,17(3): 273-8;

(62) (a)W.Y.Boadi et al, Dept. Of Food Engineering and Biotechnology, T-I Inst of Tech., Haifa,

Israel, “In vitro effect of mercury on enzyme activities and its accumulation in the first-trimester human placenta”, Environ Res, 1992, 57(1):96-106;& “In vitro exposure to mercury and cadmium alters term human placental membrane fluidity”, Pharmacol, 1992, 116(1): 17-23;  & (b)J.Urbach et al, Dept. of Obstetrics & Gynecology, Rambam Medical Center, Haifa, Israel, “Effect of inorganic mercury on in vitro placental nutrient transfer and oxygen consumption”, Reprod Toxicol, 1992,6(1):69-75;& (d)  Boot JH.  Effects of SH‑blocking compounds on the energy metabolism and glucose uptake in isolated rat  hepatocytes.  Cell Struct Funct 1995 Jun;20(3):233‑8; &  Semczuk M, Semczuk‑Sikora A.  New data on toxic metal intoxication (Cd, Pb, and Hg in particular)  and Mg status during pregnancy.  Med Sci Monit 2001 Mar;7(2):332‑340;

 (63) (a) Quig D, Doctors Data Lab,"Cysteine  metabolism and metal  toxicity", Altern Med Rev,  

      1998;3:4, p262‑270, & (b)  Ceaurriz et al, Role of gamma‑  glutamyltraspeptidase(GGC) and extracellular       glutathione in dissipation of inorganic mercury",J Appl Toxicol,1994, 14(3): 201 & T.W.Clarkson et al, "Billiary secretion of glutathione‑metal complexes",   Fundam Appl   Toxicol, 1985, 5(5):816‑31;  

(64)  Stejskal J, Stejskal V. The role of metals in autoimmune diseases and

  the link to neuroendocrinology          Neuroendocrinology Letters, 20:345‑358, 1999;

(65)      Lu SC, FASEB J, 1999, 13(10):1169‑83, “Regulation of hepatic glutathione synthesis:

current concepts and controversies”;

(66)   L.Bucio et al, Uptake, cellular distribution and DNA damage produced by mercuric chloride in a human fetal hepatic cell line.  Mutat Res 1999 Jan 25;423(1‑2):65‑72; &  (b)   L.Verschaeve et al, “Comparative in vitro cytogenetic studies in mercury-exposed human lymphocytes”, Muta Res, 1985, 157(2-3):221-6; 

(67)      (a) Xu J, Yeh CH, et al, Involvement of de novo ceramide biosynthesis in tumor necrosis


factor-alpha/cycloheximide-induced cerebral endothelial cell death.  J Biol Chem. 1998 Jun 26;273(26):16521-6; & Dbaibo GS, El-Assaad W, et al,   Ceramide generation by two distinct pathways in tumor necrosis factor alpha-induced cell death.   FEBS Lett. 2001 Aug 10;503(1):7-12; & Liu B, Hannun al, Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death.J Biol Chem. 1998 May 1;273(18):11313-20;     & (b) Kim SH, Johnson VJ, Sharma RP.    Mercury inhibits nitric oxide production but activates proinflammatory cytokine expression in murine macrophage: differential modulation of NF-kappaB and p38 MAPK signaling pathways.    Nitric Oxide. 2002 Aug;7(1):67-74; & Dastych J, Metcalfe DD et al, Murine mast cells exposed to mercuric chloride release granule-associated N-acetyl-beta-D-hexosaminidase and secrete IL-4 and TNF-alpha. J Allergy Clin Immunol. 1999 Jun;103(6):1108-14. & Noda M, Wataha JC, et al, Sublethal, 2-week exposures of dental material components alter TNF-alpha secretion of THP-1 monocytes. Dent Mater. 2003 Mar;19(2):101-5 &(c) Tortarolo M, Veglianese P, et al,  Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression..  Mol Cell Neurosci. 2003 Jun;23(2):180-92

(68)P.W. Mathieson, “Mercury: god of TH2 cells”,1995, Clinical Exp Immunol.,102(2):229-30;

(69) Olanow CW, Arendash GW. Metals and free radicals in neurodegeneration. Curr Opin Neurol 1994, 7(6):548-58; & Kasarskis EJ(MD), Metallothionein in ALS Motor Neurons(IRB #91-22026), FEDRIP                      DATABASE, National Technical Information Service(NTIS), ID: FEDRIP/1999/07802766

(70) Lars Landner and Lennart Lindestrom.   Swedish Environmental Research Group(MFG),

        Copper in society and the Environment, 2nd revised edition. 1999.

(71)      M.Aschner et al, “Metallothionein induction in fetal rat brain by in utero exposure to elemental mercury vapor”, Brain Research, 1997, dec 5, 778(1):222-32; &  Aschner M, Rising L, Mullaney KJ.   Differential sensitivity of neonatal rat astrocyte cultures to mercuric chloride (MC) and methylmercury (MeHg): studies on K+ and amino acid transport and metallothionein (MT) induction.   Neurotoxicology. 1996 Spring;17(1):107-16

 (72) Stejskal VDM, Danersund A, Lindvall A, Hudecek R, Nordman V, Yaqob A et al. Metal-

specific memory lymphocytes: biomarkers of sensitivity in man.  Neuroendocrinology Letters, 1999; 20: 289-98.

(73)Prochazkova J, Sterzl I, Kucerova H, Bartova J, Stejskal VD; The

beneficial effect of amalgam replacement on health in patients with autoimmunity. Neuro Endocrinol Lett. 2004 Jun;25(3):211-8.