Evidence that mercury from silver dental fillings may be an etiological factor in multiple sclerosis.
Sci Total Environ. 1994 Mar 15;142(3):191-205.
Siblerud RL, Kienholz E.
Source: Rocky Mountain Research Institute, Inc., Fort Collins, CO 80524.
This paper investigates the hypothesis that mercury from silver dental fillings (amalgam) may be related to multiple sclerosis (MS). It compares blood findings between MS subjects who had their amalgams removed to MS subjects with amalgams.
MS subjects with amalgams were found to have significantly lower levels of red blood cells, hemoglobin and hematocrit compared to MS subjects with amalgam removal.
Thyroxine levels were also significantly lower in the MS amalgam group and they had significantly lower levels of total T Lymphocytes and T-8 (CD8) suppressor cells. The MS amalgam group had significantly higher blood urea nitrogen and lower serum IgG.
Hair mercury was significantly higher in the MS subjects compared to the non-MS control group. A health questionnaire found that MS subjects with amalgams had significantly more (33.7%) exacerbations during the past 12 months compared to the MS volunteers with amalgam removal.
The paper also examines epidemiological correlations between dental caries and MS; as well as how mercury could be causing the pathological and physiological changes found in multiple sclerosis.
The past decade has seen an increased awareness by the public of the potential hazards of dental amalgam which is composed of approximately 50% mercury. As a result of this awareness, many people have had their dental amalgams removed, including many multiple sclerosis patients. Several papers have been published on the improved health status experience by subjects who have had their amalgams removed.
It is nearly impossible to do an adequate double blind study on the health effects of amalgam removal and thus adequately control for a placebo effect. Because of this dilemma, much of the amalgam/mercury research has had to compare health and physiology of subjects with amalgams to those without amalgams as well as research subjects who had their amalgams removed.
The purpose of this paper is to investigate a hypothesis that multiple sclerosis may be linked to mercury derived from silver dental fillings.
The intention of this paper is not to prove or disprove whether amalgam mercury causes multiple sclerosis but to investigate whether mercury could be associated with the syndrome of multiple sclerosis. The paper looks at the epidemiological, pathological and physiological changes found in the multiple sclerosis population and tries to determine if mercury could be related to these findings. A comparison is also made between multiple sclerosis subjects with dental amalgam and multiple sclerosis subjects who had their dental amalgams removed.
MERCURY FROM AMALGAMS:
Nearly 80% of all dental caries are filled with amalgam . Studies [8,9] have shown that mercury vapors leach from the amalgam restoration in the form of elemental mercury. An average of 75%  to 80% [1 1] of the inhaled elemental mercury vapor is absorbed through the alveoli of the lungs where it rapidly and completely passes into the blood. This mercury is distributed to most parts of the body [12,13].
2.1. Mercury in the blood and brain
Dissolved elemental mercury is detectable in the blood up to 15 min after exposure to mercury vapor . Mercury vapor can remain in the blood for more than one circulation and is oxidized by the catalase system to the toxic mercuric ion [l4]. Elemental mercury passes through the blood-brain barrier before it is oxidized and is retained within the brain after oxidation.
After oxidation to the ionic form, mercuric ions can react chemically with proteins and other molecules . Immediately after exposure to mercury vapor, there is a much higher content 0fmercury in the red blood cells than in the plasma. Mercury can then combine with proteins or salt molecules only after a prolonged period of enzyme oxidation . Once ionized, a mercuric ion can form reversible bonds with certain tissue ligands such as sulfhydryl groups in protein .
2.2. Mercury, dental caries and multiple sclerosis Evidence has suggested that there may be a relationship between multiple sclerosis and amalgam mercury .
Epidemiology studies have linked dental caries with MS In Australia, the rates of death due to MS are linearly related to the number of decayed, missing and filled teeth (R 0.9, P 0.002) . In the United States, a direct correlation between dental caries and MS is also found (R 0.55, P 0.005) [l6]. The incidence of MS in 45 other countries correlates highly with the frequency of decayed, missing and filled teeth among children of school age (R 0.78, P 0.001) .
The highest frequency of MS is found in Northern Ireland and the Scottish Islands of Orkney and Shetland. These areas of the world also are ranked highest in dental caries .
The first reports of MS among non-whites in South Africa was reported by Ames and Louis in 1977. Their dental health has been declining recently as well .
The incidence of dental caries and multiple sclerosis is lower for the following groups [l6]: the incidence is less in the lower income class in the United States; Asian immigrants to England compared with British natives; blacks compared to whites; and males compared to females. Women during pregnancy and lactation are at higher risk for dental caries and multiple sclerosis. Orientals living in California and Washington had a much lower risk for MS than Caucasians. Likewise, Chinese residents of the US were found to have the lowest rate of dental caries of any ethnic group studied by the military.
Research  comparing dental caries of5l MS patients showed an abnormally high rate of dental caries in that group compared to an age-matched group of epileptics.
Dental caries increase along with geographic latitude. This finding has led many researchers to theorize that the incidence of dental caries increases with decreasing levels of sunlight, and that sunlight-provides protection against dental caries . The sunshine hypothesis has been applied to MS as well .
In 1983 Ingall  theorized that Craelius's  correlation between dental caries and MS might be related to mercury from dental amalgams. Ingalls also hypothesized that another source of mercury may be from pesticides used in agriculture, suggesting that amalgam mercury is not the only source.
In the late 1940s when mercury was determined to be the etiology factor in acrodynia , it was thought that MS could be an adult form of acrodynia. Acrodynia is a disease of children that was associated with mercury poisoning in the 1940s. Symptoms include muscular weakness and painful joints. The source of mercury was HgCl2 found in laxatives, in verrnifuges (for destroying worms) and in teething powder. However, there was no recognition of a widespread source of mercury. In 1966 Baasch , a Swiss neurologist, recognized the possibility of amalgam fillings being such a source. He believed MS was a neuroallergic reaction to mercury from dental amalgam.
Multiple sclerosis was first reported in the literature during the last century shortly after the dental amalgam was introduced to the public as a restoration for dental caries. M. Taveau, in 1826, advocated the use of 'silver paste' for permanent ings and Paris dentists began to use it. In 1833, the amalgam was introduced in the United States by the Crowcour brothers who came to New York from Great Britain . The lesions of multiple sclerosis were probably first described as early as 1838 , but it was Charcot in 1868 who recognized the characteristic clinical and pathological features of the disease. Mercury had been commonly used for medicinal purposes during the past century as well. When amalgam mercury started being widely used, multiple sclerosis also became more prevalent.
2.3. Physiological similarities between mercury toxicity and MS T-lymphocytes
It is known that T-lymphocytes are suppressed in MS patients with the subclass CD8 (T-8 suppressor lymphocytes) being reduced during periods of exacerbations of MS symptoms [23,24].
According to Eggleston , the T-lymphocyte count in several patients increased after amalgam removal. When amalgams were placed in the mouth, the T-lymphocyte count fell. However, a recent study found no significant difference of lymphocytes and their subsets between subjects with dental amalgam and subjects without amalgam .
A study  at Colorado State University found that 20 females without amalgams had a significantly higher percentage of T-lymphocytes when compared to a group of 20 age-matched females with amalgams (non-amalgams 55.55%, amalgarns 53.00%, P 0.045). These conflicting data support the need for further study.
One of the leading hypotheses on the etiology of MS is that it is an autoimmune response against the nervous system. Mercury could contribute to this etiology as it is known to produce autoimmune reactions [28,29]
Rabbit studies  have shown that within two weeks after injections with HgCl2, the rabbits developed antimembrane antibodies binding to renal and extrarenal basement membranes as well as endomysium of skeletal muscles. HgCl2 induced a biphasic disease. It was first characterized by production of antibodies to basement membranes and subsequently to antigen-Ab complex formed in situ. Connective tissue antigens were found to be involved in the pathogenesis of the toxicity.
Mercuric chloride has also been shown to cause autoimmune disease in the Brown-Norway rat as well .
2.5. Blood-brain barrier
Studies  have shown that the blood-brain barrier is impaired in MS patients and it is thought this may be a contributing factor in MS. Chang  found that when mercury ions are absorbed into the blood stream in minute 1.0 ppm) amounts, they are capable of impairing the bloodbrain barrier in rats within hours and mercury then enters the parachyma of the central nervous system. When mercury bound to the blood-brain barrier and neuro plasma membrane, it caused a leaky membrane. As a result, there was a decrease in the uptake of active metabolites such as sugar, amino acids and nucleotides. A leaky membrane could allow viruses and foreign protein to pass through as well.
MacDonald  believes that alteration of the blood-brain barrier is of crucial importance in MS because this could be the step which permits entry of the immunocompetent cells, antibody, or other effectors which lead to myelin destruction. Mercury could cause just such an alteration in the blood-brain barrier.
Chang  demonstrated that after HgCl2 poisoning, a large axonal space was created in many axons as a result of detachment of the axolemma from the myelin sheath and axonal shrinkage. Axonal degeneration, vacuolation and collapse were found in numerous nerve fibers. There was occasional myelin destruction. However, regular lamination and periodicity of the myelin sheath were usually preserved.
After CH3HgCl exposure , the myelin sheaths seemed to have lost their lamination. Extensive axoplasmic degeneration was observed along with axonal collapse and myelin destruction. Demyelination of the nerve fiber is the pathogenesis of multiple sclerosis and mercury's ability to affect the myelin sheath should be investigated further in MS.
2.7. Nerve conduction velocity
One of the diagnostic findings of multiple sclerosis is a reduction of nerve conduction velocity as measured by the visual evoked response (VER) test. One characteristic of mercury toxicity is a slowing of the nerve conduction velocity . The authors presently have a paper under review showing that the nerve conduction velocity of MS patients significantly increases after amalgam removal.
One of the diagnostic tests for MS is elevated IgG levels in the cerebral spinal fluid [30,33]. It has been shown that when T-8 suppressor lymphocytes are reduced, the levels of IgG are increased . One function of the T-8 suppressor cells is to control production of IgG. Some researchers believe that demyelination results from an elevated IgG and an overactive immune system .
A study  at Colorado State University found no significant differences of IgG, IgM, IgA and IgE serum levels when comparing 14 females with amalgams to 14 females without amalgams (agematched). However, there were significant correlations with IgG, IgA and lgE to the number of amalgams and urine mercury (Table 1).
2.9. Multiple sclerosis, dental amalgam and mercury
A study by Knolle and Gunther  reported that not all MS patients had amalgam fillings when the disease started. Their study also found that out of 100 MS patients, 1 l had been previously treated with mercury ointments, so other sources of mercury must be considered.
Other sources of mercury may be from mercury preservatives used in vaccines as well as mercury pesticides and fungicides used in agriculture. Currier  noted the 'unusual amount of dental work' among MS patients but he also noted a lack of fillings in some patients.
Schalin  and Irvine  gave evidence of an association between geographic areas low in selenium and a high incidence of MS. Selenium is one of natures protectors against the harmful effects of mercury  as it is the main functioning element found in glutathionc peroxidase. Glutathione peroxidase is of primary importance because it destroys the free oxy-radical peroxides before they can attack the cellular membrane . Ifdeficient, it would result in lipid peroxidation of nerve fibers. Lipid peroxidation is thought to be one of the factors in the pathophysiology of MS. Mercury has been found to produce free oxyradicals [4,39]. Glutathione peroxidase activity in MS patients is suppressed in their red blood cells 
Aholrot-Westerlund ] found that mercury levels in the cerebral spinal fluid were eight times higher in MS patients (N = 12) compared to a control group (N = 14) of non-MS subjects. This evidence shows that mercury may be associated with MS.
Many MS subjects have had their amalgams removed after hearing the hypothesis that mercury poisoning from dental amalgam may be the cause of MS. This study was undertaken to investigate this hypothesis by comparing the physiological and health status of 50 MS subjects who had their amalgams removed, to a control group of 47 subjects with their amalgams intact. This paper reports on the relationships among the blood factors sampled in these subjects.
The considerable number of significant findings are suggestive that there may be a relationship between mercury from dental amalgam and multiple sclerosis.
Evidence has been presented exploring the hypothesis that mercury from dental amalgam may be associated with multiple sclerosis. Supporting this hypothesis is epidemiological evidence as well as physiological and pathological similarities between mercury toxicity and multiple sclerosis. Mercury is known to destroy the myelin sheath, reduce nerve conduction velocity, cause autoimmune responses, reduce immunity to viruses and damage the blood brain barrier all of which have been associated with multiple sclerosis.
This study was undertaken to compare physiological differences between multiple sclerosis subjects with amalgams and multiple sclerosis subjects with amalgams removed. Many of the significant physiological differences between the two groups can be explained by mercury. The multiple sclerosis amalgam group had a significantly lower red blood cell count, hematocrit and hemoglobin.
Mercury has the ability to destroy the red blood cell. Mercury is known to affect the kidney and the multiple sclerosis amalgam group had a significantly higher blood urea nitrogen (BUN), higher BUN/creatinine ratio and lower potassium level which suggests a kidney involvement. Thyroxin levels were significantly lower in the amalgam removal group and mercury is known to reduce thyroxine levels.
A significant difference between the immune systems between the two groups was also observed. The total T- lymphocytes count and T-8 suppression cells (CDS) were significantly lower in the amalgam multiple sclerosis group as were the IgG levels compared to the non-amalgam group. Mercury has been associated with these immune factors as well.
The multiple sclerosis amalgam removal group reports 33% more neuromuscular exacerbations during the past 12 months. If this was entirely a placebo effect, it would not explain why there was only a 17% difference in the two groups of reported present symptoms.
If mercury is involved in multiple sclerosis there are other sources of mercury besides dental amalgam which include fish, preservatives, pesticides, fungicides and other food sources. Even after amalgam removal there is much residual amalgam mercury in the body as well as these other sources of mercury.
At this time the mercury/multiple sclerosis association is only a hypothesis. There are too many similarities between mercury toxicity and multiple sclerosis that should not be ignored. Hopefully, further research wll be done to explore this hypothesis.