Mercury-Caused Endocrine Conditions Causing Widespread Adverse Health Effects, Cognitive Effects,  and Fertility Effects              B.Windham(Ed.)

 

Introduction.

As will be documented in this paper, the majority of the population receives significant mercury exposures and significant adverse health effects are common.  Mercury has been found to be an endocrine system disrupting chemical in animals and people, disrupting function of the pituitary gland, thyroid gland, parathyroid gland,  thymus gland, adrenal gland, pineal gland, enzyme production processes, and affecting many hormonal and enzymatic functions at very low levels of exposure .  The main factors determining whether chronic conditions are induced by metals appear to be exposure and genetic susceptibility, which determines individuals immune sensitivity and ability to detoxify metals(405).  Very low levels of exposure have been found to seriously affect  large groups of individuals who are immune sensitive to toxic metals, or have an inability to detoxify metals   due to  such as deficient sulfoxidation or metallothionein function or other inhibited enzymatic processes related to detoxification or excretion of metals.

 

Common Exposures to Significant Levels of Mercury and Distribution in the Body

 Most people with several amalgam fillings get daily exposure of mercury at levels well above

 U.S. government health guidelines(16,19,20,49,199,211,501), which amount to about 4 to 8 micrograms per day(217).  Mixed metals in the mouth such as amalgam dental fillings, metal crowns, and metal braces have been found to result in galvanic currents in the metals which drive the metals into the saliva and tissues of the oral cavity at high levels as well as systemically, with accumulations in the brain and hormonal glands (14,19,84,85,183,192,348,369, 381,500). Additionally, electric and electromagnetic fields from appliances, computer monitors, power lines, etc. cause electric currents in metals in the mouth which further increase exposures to mercury and other metals(28).   Mercury and nickel, which are highly neurotoxic (19,84,217,372, 500) and immunotoxic (181,91,114ab,380b,369,383ab,405), are often found at high levels in tests of those with mixed metals in the mouth and are known to commonly cause DNA damage(296,458,114), immune reactivity (234,330,331,342,369,375,383,405,91), and hormonal effects in animals and humans(50,84,104,105,369,382,459), including related reproductive effects.   Government health agencies in other countries such as Health Canada and  amalgam manufacturers have warned against using amalgam near other metals(209,500), but this is still common in the U.S.  and several other countries.   Children typically also get high levels of exposure to highly toxic organic mercury compounds such as ethyl mercury through thimerosal, used as a preservative in vaccines (160,409,476,555), and  to methyl mercury from fish(2). Warnings to ban or limit consumption of fish have been issued for over 30 percent of all U.S. lakes, including all Great Lakes, as well as U.S. river miles and bays(2).

 

Studies have documented that mercury causes hypothyroidism (50,84,390,392,407), damage of thyroid RNA(458), autoimmune thyroiditis (369,382,91), and impairment of conversion of thyroid T4 hormone to the active T3 form(369,382,390,392,407,50d). The thyroid gland has iodine binding sites where the iodine needed for its function is obtained.  For those with chronic mercury exposure the mercury occupies some of the iodine binding sites, blocking full utilization of iodine by the thyroid, in addition to the direct damage to the thyroid since mercury is highly cytotoxic (392,394,etc.).  These studies and clinical experience indicate that mercury and toxic metal exposures appear to be the most common cause of hypothyroidism and the majority treated by metals detoxification recover or significantly improve (503).  

The estimated prevalence of hypothyroidism from a large federal health survey, NHANES III, was 4.6%, but the incidence was twice as high for women as for men and many with sub clinical hypothyroidism are not aware of their condition(3a).  Another large study(3b) found that 11.7% tested had abnormal thyroid TSH levels with 9.5% being hypothyroid and 2.1% hyperthyroid.  According to survey tests, 8 to 10 % of untreated women were found to have thyroid imbalances so the actual level of hypothyroidism is higher than commonly recognized(508).  Even larger percentages of women had elevated levels of antithyroglobulin(anti-TG) or antithyroid peroxidase antibody(anti-TP). Tests have found approx. 30% of pregnant women to have low free T4 in the first trimester(509b).    

Thyroid hormones are of primary importance for the perinatal development of the central nervous system, and for normal function of the adult brain (10a). Hypothyroidism of the adults causes most frequently dementia and depression.  Nearly all the hyperthyroid patients show minor psychiatric signs, and sometimes psychosis, dementia, confusion state, depression, apathetic thyrotoxicosis, thyrotoxic crisis, seizures, pyramidal signs, or chorea occur(10a). These hormones primarily regulate the transcription of specific target genes. They increase the cortical serotonergic neurotransmission, and play an important role in regulating central noradrenergic and GABA function.

 Studies indicate that slight thyroid deficiency/imbalance(sub clinical) during the perinatal period can result in delayed neuropsychological development in neonate and child or permanent neuropsychiatric damage in the developing fetus or autism or mental retardation  (10,509,511).    Low first trimester levels of free T4 and positive levels of anti-TP antibodies in the mother during pregnancy have been found to result in significantly reduced IQs (509a-e) and causes psychomotor deficits(509f). Women with the highest levels of thyroid-stimulating-hormone(TSH) and lowest free levels of thyroxin 17 weeks into their pregnancies were significantly more likely to have children who tested at least one standard deviation below normal on an IQ test taken at age 8(509a).  Based on study findings, maternal hypothyroidism appears to play a role in at least 15% of children whose IQs are more than 1 standard deviation below the mean, millions of children. Overt autoimmune thyroiditis is preceded by a rise in levels of thyroid peroxidase antibodies. "Collectively, reports show that 30-60% of women positive for TPO antibodies in pregnancy develop postpartum thyroiditis," the researchers point out (561,8), calling it "a strong association." Without treatment, many of the women with thyroiditis  go on to develop overt clinical hypothyroidism as they age and, eventually, associated complications such as cardiovascular disease. About 7.5% of pregnant women develop thyroiditis after birth(8).  Studies have also established  a connection between maternal thyroid disease and babies born with heart defects(509h). 

Infants of women with hypothyroxinemia at 12 weeks' gestation had significantly lower scores on the Neonatal Behavioral Assessment Scale orientation index compared with subjects(10b). Regression analysis showed that first-trimester maternal free thyroid hormone T4 was a significant predictor of orientation scores. This study confirmed that maternal hypothyroxinemia constitutes a serious risk factor for neurodevelopmental difficulties that can be identified in neonates as young as 3 weeks of age.

 

     Mercury (especially mercury vapor from dental amalgam or organic mercury) rapidly crosses the blood brain barrier and is stored preferentially in the pituitary gland, thyroid gland,  hypothalamus, and occipital cortex in direct proportion to the number and extent of dental amalgam surfaces (14,19,85,99,273,274,407), and likewise rapidly crosses the placenta and accumulates in the fetus including the fetal brain and hormone glands at levels commonly higher than the level in the mother(20,22-27).    Milk from mothers with 7 or more mercury amalgam dental fillings was found to have levels of mercury approximately 10 times that of amalgam free mothers(22b). The milk sampled ranged from 0.2 to 57 ug/L.    In a population of German women, the concentration of mercury in early breast milk ranged from 0.2 to 20.3 ug/L (26).    A Japanese study found that the average mercury level in samples tested increased 60% between 1980 and 1990[25].    The study found that prenatal Hg exposure is correlated with lower scores in neurodevelopmental screening, but more so in the linguistic pathway(25).   The level of mercury in umbilical cord blood, meconium, and placenta is usually higher than that in mother's blood[23-25]. 

 

        Alterations of cortical neuronal migration and cerebellar Purkinje cells have been observed in autism. Neuronal migration, via reelin regulation, requires triiodothyronine (T3) produced by deiodination of thyroxine (T4) by fetal brain deiodinases(407). Experimental animal models have shown that transient intrauterine deficits of thyroid hormones (as brief as 3 days) result in permanent alterations of cerebral cortical architecture reminiscent of those observed in brains of patients with autism. Early maternal hypothyroxinemia resulting in low T3 in the fetal brain during the period of neuronal cell migration (weeks 8-12 of pregnancy) may produce morphological brain changes leading to autism. Insufficient dietary iodine intake and a number of environmental antithyroid and goitrogenic agents such as mercury, soy, and peanuts can affect maternal thyroid function during pregnancy.

 

Mercury can have significant effects on thyroid function even though the main hormone levels remain in the normal range, so the usual thyroid tests are not adequate in such cases.   Prenatal methylmercury exposure severely affects  the activity of selenoenzymes, including glutathione peroxidase (GPx) and 5-iodothyronine deiodinases(5-Di and 5'-DI) in the fetal brain, even though thyroxine(T4) levels are normal(390de). Another mechanism by which mercury exerts such effects is mercury’s effects on selenium levels which are required for conversion of T4 to T3(392,390d).    Gpx activity is severely inhibited, while 5-DI levels are decreased and 5'-DI increased in the fetal brain, similar to hypothyroidism.   Thus normal thyroid tests will not pick up this condition. 

 

Mercury reduces the bloods ability to transport oxygen to fetus and transport of essential nutrients including amino acids, glucose, magnesium, zinc, selenium, and Vit B12 (43,96,198,263,264,338, 339,347,392,427); depresses enzyme isocitric dehydrogenase (ICD) in fetus, causes reduced iodine uptake, autoimmune thyroiditis,  & hypothyroidism. (50,91,212,222,369,382,407,459,35).  Because of the evidence of widespread effects on infants,  the American Assoc. of Clinical Endocrinologists advises that all women considering becoming pregnant should get a serum thyrotropin test so that hypothyroidism can be diagnosed and treated early(558,7b).   Since mercury and toxic metals are common causes of hypothyroidism, another test that should be considered is a hair element test for mercury or toxic metal exposures and essential mineral imbalances.

 

 

       Studies have also established a “clear association” between the presence of thyroid antibodies and spontaneous abortions(511).  Levels of recurrent abortions in a population with positive levels of thyroid antibodies in one study were 40%, 5 times the normal rate(511).  Hypothyroidism is a well documented risk factor in spontaneous abortions and infertility(9,511).    Another study of pregnant women who suffer from hypothyroidism (underactive thyroid) found a four-times greater  risk for miscarriage during the second trimester than those who don’t(511), and women with untreated thyroid deficiency were four-times more likely to have a child with a developmental disabilities(509f-h).  Mercury through its affects on the endocrine system is also documented to cause other reproductive effects including infertility, low sperm counts, abnormal sperm, endometriosis, PMS, adverse effects on reproductive organs, etc.  (9,50,104,105,390,500,559). 

Mercury blocks thyroid hormone production by occupying iodine binding sites and inhibiting hormone action even when the measured thyroid level appears to be in proper range(390,35).   The thyroid and hypothalamus regulate body temperature and many metabolic processes including enzymatic processes that when inhibited result in higher dental decay(35) . Mercury damage thus commonly results in poor bodily temperature control, in addition to many problems caused by hormonal imbalances such as depression.  Such hormonal secretions are affected at levels of mercury exposure much lower than the acute toxicity effects normally tested (50,390,84), as previously confirmed by hormonal/reproductive problems in animal populations (104,381c,50d).  Mercury also damages the blood brain barrier and facilitates penetration of the brain by other toxic metals and substances(311).   Hypothyroidism is also known to be a major factor in cardiovascular disease(510,509h).                                


 The pituitary gland controls many of the body’s endocrine system functions and secretes hormones that control most bodily processes, including the immune system and reproductive  systems .  One study found mercury levels in the pituitary gland ranged from 6.3 to 77 ppb(85), while another(348) found the mean level to be 30ppb- levels found to be neurotoxic and cytotoxic in animal studies.  Some of the effect on depression is related to mercury’s effect of reducing the level of posterior pituitary hormone(oxytocin).   Low levels of pituitary function are associated with depression and suicidal thoughts, and appear to be a major factor in suicide of teenagers and other vulnerable groups.   The pituitary glands of a group of dentists had 800 times more mercury than controls(99).  This may explain why dentists have much higher levels of emotional problems, depression, suicide, etc(500,Section VIII.).  Amalgam fillings, nickel and gold crowns are major factors in reducing pituitary function(35,50,369,etc.).  Supplementary oxytocin extract has been found to alleviate many of these mood problems(35), along with replacement of metals in the mouth(107,500-Section VI.).  The normalization of pituitary function also often normalizes menstrual cycle problems, endometriosis, and increases fertility(35,9,500).

          Mercury accumulates in the adrenal gland and disrupts adrenal gland function(84,369,381).

In general immune activation from toxics such as heavy metals resulting in cytokine release and abnormalities of the hypothalamus-pituitary-adrenal axis can cause changes in the brain, fatigue, and severe psychological symptoms(369,375,379-383,107) such as depression,  profound fatigue, muscoskeletal pain, sleep disturbances, gastrointestinal and neurological problems as are seen in CFS, Fibromyalgia, and autoimmune thyroiditis. Such symptoms usually improve significantly after amalgam removal(500,Section VI).   Such hypersensitivity has been found most common in those with  genetic predisposition to heavy metal sensitivity (342,369,375,382) such as  found more frequently in patients with HLA-DRA antigens(375,381,383). A significant portion of the population appears to fall in this category and adrenal problems have been increasing significantly in recent years(570).               

Mercury(and other toxic metals) has been found to accumulate in the pineal gland and reduce  melatonin levels, which is thought to be a significant factor in mercury’s toxic effects(569). Melatonin has found to have a significant protective action against methyl mercury toxicity, likely from antioxidative effect of melatonin on the MMC induced neurotoxicity(567).

There is also evidence that mercury affects neurotransmitter levels which has effects on conditions like depression, mood disorders, ADHD, etc.  There is evidence that mercury can block the dopamine-beta-hydroxylase (DBH) enzyme(571).   DBH is used to make the noradrenaline  neurotransmitter and low noradrenaline can cause fatigue and depression. Mercury molecules can block all copper catalyzed dithiolane oxidases, such as coproporphyrin oxidase(260)  and DBH.

Thyroid imbalances,  which are documented to be commonly caused by mercury (369,382,459,35,50,91,212), have been found to play a major  role in chronic heart conditions such as clogged arteries, mycardial infarction, and chronic heart failure(510).  In a recent study, published in the Annals of Internal Medicine, researchers reported that subclinical hypothyroidism is highly prevalent in elderly women and is strongly and independently associated with cardiac atherosclerosis and myocardial infarction(510c).  People who tested hypothyroid usually have significantly higher levels of homocysteine and cholesterol, which are documented factors in heart disease.  50% of those testing hypothyroid, also had high levels of homocysteine (hyperhomocysteinenic) and 90% were either hyperhomocystemic or hypercholesterolemic(510a). These are also known factors in developing arteriosclerotic vascular disease. Homocysteine levels  are significantly increased in hypothtyroid patients and normalize with treatment(510efg).


 

The thymus gland plays a significant part in the establishment of the immune system and lymphatic system from the 12th week of gestation until puberty.   Inhibition of thymus function can thus affect proper development of the immune and lymphatic systems.  Lymphocyte differentiation, maturation and peripheral functions are affected by the thymic protein hormone thymulin. Mercury at very low concentrations has been seen to impair some lymphocytic functions causing subclinical manifestations in exposed workers. Animal studies have shown mercury significantly inhibits thymulin production at very low micromolar levels of exposure(513a).    The metal allergens mercuric chloride and nickel sulfate were found to stimulate DNA synthesis of both immature and mature thymocytes at low levels of exposure, so chronic exposure can have long term effects(513b). Also, micromolar levels of mercuric ions specifically blocked synthesis of ribosomal RNA, causing fibrillarin relocation from the nucleolus to the nucleoplasm in epithelial cells as a  consequence of the blockade of ribosomal RNA synthesis.  This appears to be a factor in deregulation of basic cellular events and in autoimmunity caused by mercury.     There were specific immunotoxic and biochemical alterations in lymphoid organs of mice treated at the lower doses of mercury. The immunological defects were consistent with altered T-cell function as evidenced by decreases in both T-cell mitogen and mixed leukocyte responses. Mercury caused increased immunoreactivity for glial fibrillary protein at 1 nanamole (0.2 ppb) concentration, and microglial response at even lower levels(175).  There was a particular association between the T-cell defects and inhibition of thymic pyruvate kinase, the rate-limiting enzyme for glycolysis(513c).    Pyruvate and glycolysis problems are often seen in mercury toxic children being treated for autism(409).         


A direct mechanism involving mercury’s inhibition of hormones and cellular enzymatic processes by binding with the hydroxyl radical(SH) in amino acids appears to be a major part of the connection to allergic/immune reactive/autoimmune conditions such as autism/ADHD(409-411,439,464,468,476,33,160), schizophrenia(409,410), lupus(113,126,234,330,331,33,468), Scleroderma(468),   eczema and psoriasis (323,375,385,419,33), and allergies (271,313,330,331, 369,375,468).  Mercury and other toxic metals also form inorganic compounds with OH, NH2, CL, in addition to the SH radical and thus inhibits many cellular enzyme processes, coenzymes, hormones, and blood cells(405,409,500,555).     For example mercury has been found to strongly inhibit the activity of dipeptyl peptidase (DPP IV) which is required in the digestion of the milk protein casein(411,412) as well as of xanthine oxidase(439). Studies involving a large sample of autistic and schizophrenic patients found that over 90 % of those tested had high levels of the neurotoxic milk protein beta-casomorphine-7 in their blood and urine and defective enzymatic processes for digesting milk protein(410).  Elimination of milk products from the diet has been found to improve the condition. Similar results have been seen in similarly but lesser affected patients with other pervasive developmental conditions such as ADHD.    Such populations have also been found to have many with high levels of mercury who recover after mercury detox (409,413,369,160).  As mercury levels are reduced the protein binding is reduced and improvement in the enzymatic process occurs. Additional cellular level enzymatic effects of mercury’s binding with proteins include blockage of sulfur oxidation processes (33,114,194,330,331,412), enzymatic processes involving vitamins B6 and B12(418), effects on the cytochrome-C energy processes (43,84,338c,35), along with mercury’s adverse effects on cellular mineral levels of calcium, magnesium, zinc, and lithium (43,96,333,338,160,500).    Thus some of the main mechanisms of toxic effects of metals include cytotoxicity; changes in cellular membrane permeability; inhibition of enzymes, coenzymes, and hormones; and  generation of lipid peroxides or  free radicals- which result in neurotoxicity, immunotoxicity, impaired cellular respiration, gastrointestinal/metabolic effects, hormonal effects,  and immune reactivity or autoimmunity.  

 

       Mercury has been found to cause hormonal changes which cause hair loss and greying of hair.  In a large German study where 20,000 were tested, allergies and hair-loss were found to be 2-3 times as high in a group with large numbers of amalgam fillings compared to controls(199,9).    Levels of mercury in follicular fluid was significantly higher for those with amalgam fillings (9,146). Based on this finding, a Gynecological Clinic that sees a large number of women suffering from alopecia/hair loss that was not responding to treatment had amalgams replaced in 132 women who had not responded to treatment.     68 % of the women then responded to treatment and alopecia was alleviated(187).  In other studies involving amalgam removal, the majority had significant improvement (40,317,500).  Higher levels of hormone disturbances, immune disturbances, infertility, and recurrent fungal infections were also found in the amalgam group. The results of hormone tests, cell culture studies, and intervention studies agree(9,146).  Other clinics have also found alleviation of hair loss/alopecia after amalgam removal and detox(40,317). Another study in Japan found significantly higher levels of mercury in gray hair than in dark hair(402). 

 

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