The following studies are the most important ones that have apparently found a direct link between amalgam/mercury exposure in the general population and various health problems. There are also other types of evidence I have not mentioned here:
These studies are of varying quality. Some are interesting primarily because they contradict some of the "pro-amalgam" studies. Most of the rest is only suggestive, and none of it is conclusive. For instance, the Salonen et al. study of mercury and heart disease is an excellent study in itself, and there is a reasonable mechanism for mercury to cause heart disease, but this is the only well-controlled, large-scale investigation yet on this particular subject.
For another example, Siblerud, in his study of the cardiovascular system, has made no attempt to control for known risk factors for heart disease. On the other hand, neither has the study by Ahlqwist et al. that found no relationship between amalgam and heart disease. One strong point of Siblerud’s papers is that he has used truly amalgam-free control groups. However, in general I am skeptical of Siblerud's studies, primarily because his results are "too good to be true" from an anti-amalgam point of view.
In some of the studies, there is good reason to ask what is cause and what is effect. Does mercury toxicity cause people to smoke (as Siblerud believes) or does smoking cause tooth decay which makes for more fillings? I don't automatically accept the former explanation; on the other hand, I think we should be open to the possibility. Siblerud presents evidence that many of nicotine's effects on neurotransmitters are the opposite of the effects of mercury, so at least there is a reasonable mechanism for how it might happen.
Amalgam is a hard subject to study epidemiologically, because it is nearly always difficult to be sure what is cause and what is effect. To get conclusive results, it would be necessary to start with children who have not yet received amalgams and follow them for decades. The question is, do we want to wait for these studies, or should we rely on other methods, such as toxicological risk assessment?
Seidler A, Hellenbrand W, Robra BP, Vieregge P, Nischan P, Joerg J, Oertel WH, Ulm G, Schneider E: Possible environmental, occupational, and other etiologic factors for Parkinson's disease: a case-control study in Germany. Neurology 1996; 46 (5): 1275- 84 .
In a case-control study, we investigated the possible etiologic relevance to Parkinson's disease (PD) of rural factors such as farming activity, pesticide exposures, well-water drinking, and animal contacts; toxicologic exposures such as wood preservatives, heavy metals, and solvents; general anesthesia; head trauma; and differences in the intrauterine environment. We recruited 380 patients in nine German clinics, 379 neighborhood control subjects, and 376 regional control subjects in the largest case- control study investigating such factors and collected data in structured personal interviews using conditional logistic regression to control for educational status and cigarette smoking. The latter was strongly inversely associated with PD. There were significantly elevated odds ratios (OR) for pesticide use, in particular, for organochlorines and alkylated phosphates, but no association was present between PD and other rural factors. A significantly elevated OR was present for exposure to wood preservatives. Subjective assessment by the probands indicated that exposure to some heavy metals, solvents, exhaust fumes, and carbon monoxide was significantly more frequent among patients than control subjects, but this was not confirmed by a parallel assessment of job histories according to a job exposure matrix. Patients had undergone general anesthesia and suffered severe head trauma more often than control subjects, but a dose-response gradient was not present. Patients reported a significantly larger number of amalgam-filled teeth before their illness than control subjects. The frequency of premature births and birth order did not differ between patients and control subjects. Patients reported significantly more relatives affected with PD than control subjects. These results support a role for environmental and genetic factors in the etiology of PD.
Ngim CH, Devathasan G: Epidemiologic study on the association between body burden mercury level and idiopathic Parkinson's disease. Neuroepidemiology 1989; 8 (3): 128-4.
A case-control study was conducted among the multiethnic population of Singapore to test the hypothesis that a high level of body burden mercury is associated with an increased risk of Parkinson's disease (PD). Selected factors investigated that could contribute to the body burden of mercury included dietary fish intake, ethnic over-the- counter medications, occupational exposures and possession of dental amalgam fillings. Detailed interviews were completed in 54 cases of idiopathic PD and 95 hospital-based controls, matched for age, sex and ethnicity, between July 1985 and July 1987. After adjusting for potential confounding factors, including dietary fish intake, medications, smoking and alcohol consumption, there was clear monotonic dose-response association between PD and blood mercury levels. The odds ratios (OR) and 95% confidence intervals (CI) for the approximate subject tertiles based upon blood mercury levels were 8.5 (CI = 2.2-33.2) and 9.4 (CI = 2.5-35.9), relative to the tertile with lowest blood mercury levels (less than 5.8 ng Hg/ml). Similar associations were revealed using scalp hair and urinary mercury levels. However, only the comparisons between the highest and lowest tertiles were statistically different from unity (p less than 0.05). When the body burden mercury indicators were mutually adjusted in addition to the four confounding factors, blood and urinary mercury levels showed ORs of 21.00 and 18.65, respectively. These ORs were statistically different from unity (p less than 0.05, 2-sided test). After adjustment, scalp hair mercury was shown to be a poor predictor of PD risk.
Salonen JT, Seppanen K, Nyyssonen K, Korpela H, Kauhanen J, Kantola M, Tuomilehto J, Esterbauer H, Tatzber F, Salonen R: Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men. Circulation 1995; 91 (3): 645-55.
BACKGROUND: Even though previous studies have suggested an association between high fish intake and reduced coronary heart disease (CHD) mortality, men in Eastern Finland, who have a high fish intake, have an exceptionally high CHD mortality. We hypothesized that this paradox could be in part explained by high mercury content in fish. METHODS AND RESULTS: We studied the relation of the dietary intake of fish and mercury, as well as hair content and urinary excretion of mercury, to the risk of acute myocardial infarction (AMI) and death from CHD, cardiovascular disease (CVD), and any cause in 1833 men aged 42 to 60 years who were free of clinical CHD, stroke, claudication, and cancer. Of these, 73 experienced an AMI in 2 to 7 years. Of the 78 decreased men, 18 died of CHD and 24 died of CVD. Men who had consumed local nonfatty fish species had elevated hair mercury contents. In Cox models with the major cardiovascular risk factors as covariates, dietary intakes of fish and mercury were associated with significantly increased risk of AMI and death from CHD, CVD, and any death. Men in the highest tertile (> or = 2.0 micrograms/g) of hair mercury content had a 2.0-fold (95% confidence interval, 1.2 to 3.1; P = .005) age- and CHD-adjusted risk of AMI and a 2.9-fold (95% CI, 1.2 to 6.6; P = .014) adjusted risk of cardiovascular death compared with those with a lower hair mercury content. In a nested case-control subsample, the 24-hour urinary mercury excretion had a significant (P = .042) independent association with the risk of AMI. Both the hair and urinary mercury associated significantly with titers of immune complexes containing oxidized LDL. CONCLUSIONS: These data suggest that a high intake of mercury from nonfatty freshwater fish and the consequent accumulation of mercury in the body are associated with an excess risk of AMI as well as death from CHD, CVD, and any cause in Eastern Finnish men and this increased risk may be due to the promotion of lipid peroxidation by mercury.
Comment: This is an extremely well-controlled study that found a doubled risk of coronary heart disease in men with high fish consumption and high mercury levels in hair. The mechanism indicated by this study is lipid peroxidation caused by mercury (measures of lipid peroxidation were also correlated with mercury). Since lipid peroxidation is a phenomenon which is primarily known to occur with inorganic mercury, there is reason to assume that amalgam mercury has the same effect.
(Eti S, Weisman R, Hoffman R, Reidenberg MM: Slight renal effect of mercury from amalgam fillings. Pharmacology & Toxicology 1995; 76 (1): 47-9.)
The current study was to answer the
question: Is enough mercury absorbed from dental amalgam fillings
to produce renal damage? One hundred healthy adults (18-44 years
old) filled out health questionnaires and voided urine samples.
Urine mercury concentration and N-acetyl-beta-glucosaminidase
(NAG) were measured. Subjects were grouped into those having
amalgam fillings (N = 66) and those without (N = 34). Median (95%
Confidence Interval) urine mercury was 1 (1-2) and 0 (0-0.6)
ng/ml (P <0.01) and median urine NAG was 23 (18-27) and 16 (11-18) units (P < 0.05) in the two groups respectively. People with mercury amalgam fillings excreted slightly more mercury than people without them, and have a very small increase in urinary NAG excretion that is probably of no clinical significance. This dose of mercury absorbed from amalgam appears to be too little to be a public health hazard for renal injury. Comment: It is true that the differences found
indicate only a “slight effect”, but it is worth noting
that this is a relatively small study with an average age of 30.
Discrepancies much larger than the average difference were found
in single individuals, and older people would probably be more
susceptible to nephrotoxic effects of mercury, as is known to be
the case with cadmium. The statement that it is not a public
health hazard is not warranted. Even something that affects fewer
than 1 in 100 (the number of subjects in this investigation) can
be considered a public health problem. For instance, the lifetime
risk of schizophrenia is only 1%.
Lindqvist B, Mornstad H: Effects of removing amalgam fillings from patients with diseases affecting the immune system. Med Sci Res 1996; 24 (5): 355-356.
53 patients with complaints which they attributed to their amalgam fillings, and with pathological tests indicating abnormality of the immune system, were followed for 1-3 years after the removal of all, part of, or none of their amalgam fillings. Within the group of 34 individuals who had all their amalgam fillings replaced, there was a significant number of decreased antibody titres, but only two had normalised their laboratory tests after 1-3 years. A significant improvement in subjective symptoms occurred in 20 (59%) of cases. In the group of patients who still had amalgam fillings, there were no statistically significant changes in the antibody titres. It thus seems that mercury released from amalgam fillings may initiate or support an ongoing immune disease. However. this study group was rather heterogeneous, and had received various pharmacological treatments. Further studies, are, therefore, needed to confirm, or refute, the results.
Kuntz WD, Pitkin RM, Bostrom AW, Hughes MS: Maternal and cord blood background mercury levels: a longitudinal surveillance. American Journal of Obstetrics & Gynecology 1982; 143 (4): 440-3.
Fifty-seven prenatal patients with no known exposure to the element mercury, or any of its compounds, were observed for change in whole blood total mercury concentration from the initial prenatal clinic examination through delivery and postpartum hospitalization. On hospital admission for labor and delivery, whole blood total mercury averaged 1.15 parts per billion (ppb), compared to 0.79 ppb from the first prenatal clinic visit; these levels represent a 46% increase and significant difference in maternal concentration of a substance previously recognized for its peculiar ease at crossing the placental barrier. Previous stillbirths, as well as history of birth defects, exhibited significant positive correlation with background mercury levels. Search of the literature of the last 5 years revealed no other report of cohort heavy metal surveillance throughout pregnancy.
Comment: There are apparently other studies that have not found such correlations, so the evidence is ambiguous. The WHO recommended in 1980 and 1991 that mercury exposure of the developing fetus be kept as low as possible.
Kampe T, Edman G & Molin C: Personality traits of adolescents with intact and repaired dentitions. Acta Odont Scand 1986; 44 (44): 95-102.
The personality pattern of 29 subjects aged 15 years with intact dentitions was studied by means of a personality inventory (KSP) and compared with that of 41 subjects of the same age with repaired dentitions. The subjects with repaired dentitions showed significantly higher scores in the somatic anxiety and the muscular tension scales; that is, dental restorations were commoner in subjects with autonomic and motor disturbances related to anxiety-proneness. Furthermore, subjects in the control group with high clinical dysfunction index (CDI) had higher scores in the muscular tension, the inhibition of aggression, and the irritability scales. The finding of higher scores in the muscular tension scale was validated in the clinical examination. Possible explanations of the differences in the personality patterns between individuals with intact and repaired dentitions are discussed. Clenching and gnashing of the teeth was also studied in relation to the personality variables. Teeth clenchers in both groups were more anxiety-prone, less self-assertive, and less socialized.
Comment: Since the study is from 1986, we can safely assume that the fillings were mostly amalgam. These dental researchers apparently haven’t even considered the possibility that mercury might be to blame for the “personality problems”, although the problems they describe are similar to the problems mercury causes in dentists. Instead, they hypothesize that personality problems cause caries, which causes people to have more fillings. Clearly, the study does not prove a cause-effect relationship. The most interesting aspect of it is that it clearly contradicts some of the most-used “pro-amalgam” evidence: the studies that have not found any correlation between amalgam surfaces and symptoms.
Siblerud RL, Kienholz E, Motl J: Evidence that mercury from silver dental fillings may be an etiological factor in smoking. Toxicology Letters 1993; 68 (3): 307-10.
The smoking habits of 119 subjects without silver/mercury dental fillings were compared to 115 subjects with amalgams. The amalgam group had 2.5-times more smokers per group than the non-amalgam group, which was highly significant. Because mercury decreases dopamine, serotonin, norepinephrine, and acetylcholine in the brain, and nicotine has just the opposite effect on these neurotransmitters, this may help explain why persons with dental amalgams smoke more than persons without amalgams.
Comment: Again, it’s impossible to be sure what is cause and what is effect. Siblerud et al. hypothesize that mercury from amalgam causes people to smoke, citing the fact that mercury and nicotine have opposite effects on neurotransmitters. But the cause-effect relationship may be the opposite: smoking may cause caries. One other study al
Ma R, Epstein JB, Emerton S, Hay JH: A preliminary investigation of an association between dental restorations and carcinoma of the tongue. European Journal of Cancer. Part B, Oral Oncology 1995; 31B (4): 232-4.
The potential association of dental restorations and tongue carcinoma was studied. We reviewed the available pretreatment dental records of 133 patients with carcinoma of the tongue seen at the British Columbia Cancer Agency between 1958 and 1992. 75 patients had teeth adjacent to the ipsilateral side of the cancer (involved side) and the contralateral (control) side of the tongue, resulting in 150 tongue/teeth pairings. Overall there was no significant association between the presence of dental fillings and tongue carcinoma, as the prevalence of bilateral dental restorations was high. Dental restorations were found in 6 patients on the involved side only. Only 1 patient developed a cancer adjacent to normal teeth with contralateral restorations. We feel that this observation merits more study. Meanwhile, careful assessment of dentition and aggressive treatment of dysplastic lesions are warranted.
Comment: The researchers offer two possible explanations for their findings. One is chemical carcinogenesis. They quote evidence for carcinogenic effects of mercury, and since very high mercury concentrations have been found in mouth tissues in human and animal experiments, this is a likely possibility. The alternative explanation is “chronic physical irritation of the tongue’s squamous epithelium by a rough restoration”.
Sandborgh Englund G, Dahlqvist R, Lindelof B, Soderman E, Jonzon B, Vesterberg O, Larsson KS: DMSA administration to patients with alleged mercury poisoning from dental amalgams: a placebo-controlled study. Journal of Dental Research 1994; 73 (3): 620-8.
The present investigation was performed to determine the effect of 14-day oral administration of meso-2.3-dimercaptosuccinic acid (DMSA) on the urinary mercury excretion and the potential reduction of blood and plasma mercury concentrations, and also to relate these effects to possible decrease of symptoms, allegedly associated with amalgam fillings. Twenty subjects, relating their symptoms to mercury from amalgam fillings, received 20 mg/kg DMSA or placebo for 14 days. Their symptoms and mood states were recorded during the study and at a check-up 3 months later. Interpretation was based on intra-individual differences. DMSA-treatment resulted in an average increase in urinary mercury excretion by 65% and a decrease in blood mercury levels of 0.04 microgram/L/day. At the check-up after 3 months, urinary mercury excretion had returned to the pre-treatment level. No treatment effect of DMSA was apparent on subjective symptoms and mood state. One statistically significant treatment effect was noted-a decrease in fatigue-inertia in the DMSA-group-but there was no demonstrable correlation with increased urinary excretion or decreased blood concentration of mercury. Three subjects showed hypersensitive reactions, probably DMSA-specific, at the end of the treatment period. This placebo-controlled study provides no scientific support for diagnostic or therapeutic administration of DMSA for symptoms allegedly associated with chronic mercury exposition from dental amalgam fillings.
Comment: The researchers themselves focus on what I consider a red herring, a lack of sufficient therapeutic success with DMSA. However, they did find one statistically significant improvement. Whether or not this is good enough reason to give these patients DMSA is really not the main issue. What is important is that the finding provides support for the hypothesis that these patients’ complaints are related to mercury.
Siblerud RL, Motl J, Kienholz E: Psychometric evidence that mercury from silver dental fillings may be an etiological factor in depression, excessive anger, and anxiety. Psychological Reports 1994; 74 (1): 67-80.
Scores on the Beck Depression Inventory were compared for 25 women who had silver dental fillings (amalgams) and for 23 women without amalgams. Women with amalgams had significantly higher scores and reported more symptoms of fatigue and insomnia. Anger scores from the State-Trait Anger Expression Inventory showed that the women with amalgams had statistically significantly higher mean scores on expressing anger without provocation and experiencing more intense angry feelings. The women without amalgams scored significantly higher on controlling anger, which suggested they invested more energy in monitoring and preventing the experience and expression of anger. Anxiety scores from the State-Trait Anxiety Inventory showed the women with amalgams scored significantly less pleasant, satisfied, happy, secure, and steady, and had a more difficult time making decisions. They had significantly higher Trait Anxiety scores. The women with amalgams also had significantly higher levels of mercury in the oral cavity before and after chewing gum. The study suggests that amalgam mercury may be an etiological factor in depression, excessive anger, and anxiety because mercury can produce such symptoms perhaps by affecting the neurotransmitters in the brain.
Siblerud RL: The relationship between mercury from dental amalgam and the cardiovascular system. Science of the Total Environment 1990; 99 (1-2): 23-35.
The findings presented here suggest that mercury poisoning from dental amalgam may play a role in the etiology of cardiovascular disorders. Comparisons between subjects with and without amalgam showed amalgam-bearing subjects had significantly higher blood pressure, lower heart rate, lower hemoglobin, and lower hematocrit. Hemoglobin, hematocrit, and red blood cells were significantly lower when correlated to increased levels of urine mercury. The amalgam subjects had a greater incidence of chest pains, tachycardia, anemia, fatigue, tiring easily, and being tired in the morning. The data suggest that inorganic mercury poisoning from dental amalgam does affect the cardiovascular system.