The Science of the Total Environment, 99 (1990) 23-35 Elsevier Science Publishers B.V., Amsterdam
23
THE R E L A T I O N S H I P B E T W E E N M E R C U R Y FROM D E N T A L AMALGAM AND THE CARDIOVASCULAR
SYSTEM
ROBERT L. SIBLERUD Department of Physiology, College of Veterinary Medicine and Biological Sciences, Colorado State University, Fort Collins, CO 80523 (U.S.A.) (Received October llth, 1989; accepted December 6th, 1989)
ABSTRACT 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.
INTRODUCTION E v i d e n c e l i n k i n g m e r c u r y to the c a r d i o v a s c u l a r s y s t e m h a s b e e n a c c u m u l a t ing o v e r the p a s t s e v e r a l decades. M a n y h e a l t h p r o f e s s i o n a l s s u g g e s t t h a t n u m e r o u s h e a l t h p r o b l e m s e x p e r i e n c e d t o d a y h a v e a n e n v i r o n m e n t a l etiology. A n e c d o t a l e v i d e n c e s u g g e s t s t h a t m e r c u r y from d e n t a l a m a l g a m m a y be an e n v i r o n m e n t a l h e a l t h hazard. A s t u d y was u n d e r t a k e n a t C o l o r a d o S t a t e U n i v e r s i t y to d e t e r m i n e w h e t h e r or not m e r c u r y from d e n t a l a m a l g a m does c a u s e h e a l t h problems. This p a p e r r e p o r t s the r e l a t i o n s h i p of m e r c u r y p o i s o n i n g f r o m d e n t a l a m a l g a m to t h e c a r d i o v a s c u l a r system. M e r c u r y poisoning a n d the heart E l e c t r o c a r d i o g r a p h y studies h a v e s h o w n t h a t the h e a r t is affected by m e r c u r y . T h e QRS ( v e n t r i c u l a r d e p o l a r i z a t i o n ) a n d s e v e n s e g m e n t s of the e l e c t r o c a r d i o g r a m of r a b b i t s w e r e affected by c h r o n i c p o i s o n i n g by m e t a l l i c m e r c u r y v a p o r [1]. A n o t h e r r a b b i t s t u d y [2] found no c h a n g e s in e l e c t r o c a r d i o g r a p h i c r e a d i n g s of r a b b i t s exposed to c h r o n i c m e r c u r y v a p o r s d u r i n g t h e first 3-4 weeks. In t h e second a n d t h i r d m o n t h t h e r e was t a c h y c a r d i a in w h i c h the b e a t was 220-250 b e a t s per m i n u t e . A b r o a d e n i n g of the P ( a t r i a d e p o l a r i z a t i o n ) w a v e a n d a d e c r e a s e in t h e R (highest + v o l t a g e of v e n t r i c u l a r d e p o l a r i z a t i o n )
24 and T (ventricular repolarization) waves were observed, but there were individual variations in each animal. In nine of 14 rabbits there was a shift in the S ( h i g h e s t - - voltage of ventricular depolarization)--T interval with respect to the isoelectric line. In all cases, bradycardia appeared by the end of the experiment. The vagus nerve endings contain acetylcholine, which has a specific effect on the heart muscle's cholinoreceptor protein, the active sites of which involve sulfhydryl groups. Mercury has an affinity for sulfhydryl groups. Studies [2] on excised extracardiac nerves have concluded that cardiac changes produced by mercury are usually toward slowing the rhythm with change in tonus of the vagus nerve.
Studies of human subjects also demonstrate a mercury~cardiac relationship A study [3] of 42 mercury-poisoned patients in Iraq found abnormal electrocardiogram changes in all subjects. A variety of abnormalities occurred, but the most common finding was the S-T depression of all 42 subjects. Cardiovascular pathology is also associated with Kawasaki's disease, a mercury-caused syndrome. Symptoms include AV block, premature contractions and tachycardia. People exposed to low doses of mercury vapor can develop coronary insufficiency and pressure in the cardiac region, which are symptoms in a condition known as micromercurialism [2].
Mercury and blood pressure Mercury is also known to increase blood pressure. Eight mongrel dogs were injected subcutaneously with mercury chloride at a daily dose of 3 mg/kg body weight for 3 days [4]. The blood pressure increased from 10 to 70 mm Hg in all dogs. Before HgC12 administration the blood pressure averaged 131 mm Hg and after administration it was 153 mm Hg. People exposed to chronic doses of mercury may develop an asthenic-vegetative syndrome. A high percentage of these individuals develop functional disorders of the cardiovascular system including chest pain and heart palpitations. Blood pressure can be either high or low. A study [2] of 63 people with asthenic-vegetative syndrome found 40 people with low blood pressure and six people with increased blood pressure. Another study [2] of mercury-exposed workers found that 50% of the men and 68% of the women had hypertension, while hypertension was found among 42% of people working in another mercury-related occupation.
Mercury, the red blood cell, and hemoglobin The rapid absorption of mercury in red blood cells results in an inhibition of glucose as well as a loss of potassium and a decrease in osmotic fragility [5]. The sulfhydryl groups of hemoglobin have a strong affinity for mercury, and
25 heavy metals can impair heme syntheses in erythrocytes by inhibiting several sulfhydryl enzymes. Inorganic mercury has been shown to change the tertiary structure of the hemoglobin molecule, which, in turn, produces a change in the oxygen dissociation curve [6]. Blood studies [2] on individuals who worked daily with mercury found that the percentage of hemoglobin decreased as their length of work time increased. After 1 year of employment, decreased hemoglobin occurred in 29.8% of the cases and people who were employed 10 years or more had a decrease in hemoglobin in 40% of the cases. An analysis of erythrocyte counts found that, with increasing length of employment (1 10 years), the number of people with less than 3 500000 erythrocytes increased almost two-fold, from 14.5 to 25.8%. There was a five-fold decrease in the number of patients with erythrocytic counts of 4 500 000, from 36.7 to 7.9%.
Mercury poisoning and dental amalgam Three factors led us to study the relationships among dental amalgam, mercury poisoning and the cardiovascular system. First, mercury's affinity for the blood stream; second, the relationship between mercury poisoning and cardiovascular disorders; and third, the release of mercury vapor from the amalgam. Mercury is one of the most toxic metals, since it disrupts most biological systems as a result of its affinity for sulfhydryl groups, which are essential constituents of most enzymes and hormones [7]. Even small amounts of mercury exposure over a long period can produce the same devastating effects as a large dose in a short time. Insidious long-term exposure to mercury can produce damage after many years with no trace of the etiology of the problem [8]. Stock [9] found that 3 ttg m 3 of mercury in the air during constant work did not cause noticeable health symptoms, except for people with hypersensitivity to mercury. Daily mercury concentrations of 10-20pgm -3 in the workroom produced physical and mental symptoms in the majority of employees. However, Stock reported that neurological symptoms associated with a mercury concentration of 2.1 pg m 3 in expired air, disappeared after amalgam removal. Occupational exposure limits for inorganic mercury vary around the world. They are based on 8 hours per day, 40 hours per week. In Germany and the U.S. the maximum is 100ggHgm 3, while in Sweden it is 5 0 p g H g m 3, and the World Health Organization (WHO) recommends 2 5 g g H g m -3. In the Soviet Union and Switzerland the value is 10 gg Hg m -3. For the general population, the United States Environmental Protection Agency established the National Standard for mercury as a hazardous air pollutant at a level of 1 ttg Hg m 3 over a 24-h period. In the Soviet Union, the value is 0 . 3 p g H g m -3. Nearly 80% of the world's dental caries are filled with dental amalgam (silver fillings). This unstable alloy is approximately 50% mercury and con-
26 tinuously releases elemental mercury [10, 11]. A direct correlation is found between the amount of mercury released and the number of amalgams. More mercury (up to 87.5pgm 3) is released during chewing. Two-year old fillings release four times as much mercury after chewing than before, and week-old fillings show a 17-fold increase in mercury released after chewing. Vimy and Lorshneider [12] measured intra-oral mercury and calculated that subjects with 12 or more occlused amalgam surfaces received an average daily dose of 29 gg mercury. Subjects with one to four amalgams received an average daily dose of 9 #g. These levels exceed many countries' accepted standards for environmental exposure according to the authors. Radics et al. [13] analyzed the outer corroded area of an amalgam that was depleted of mercury. His calculations suggested that a mouth with many fillings could release up to 560 mg of mercury over several years. Pleva [14] found that the chewing surface of a 5-year-old amalgam had lost almost half its mercury; a 20-year-old amalgam had no mercury left on the chewing surface.
Mercury's path to the blood Mercury is released from dental amalgam as elemental mercury vapor. An average of 75 [15] to 80% [16] of the elemental mercury vapor can be inhaled and absorbed through the alveoli of the lungs where it passes into the blood stream rapidly and completely. Elemental mercury (Hg °) passes through the blood-brain barrier before it is ionized and is retained within the 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 [7]. Another avenue of mercury poisoning from dental amalgam may be absorption through the valveless cranial venous system. Mercury vapor may settle down into the oronasal region and be absorbed directly into the venous system to the brain [17]. After oxidation to the mercurous ion it can react chemically with proteins and other molecules. Approximately 80% of the oxidation takes place in the red blood cells [7]. Immediately after exposure to mercury vapor, there is a much higher content of mercury in the red blood cells than in the plasma. Mercury can then combine with protein or salt molecules only after a prolonged period of enzyme oxidation. After oxidation, most of the mercury is bound to albumin or globulin in the blood. Only a small fraction is found in a free ultrafiltrate form. Once ionized, a mercuric ion can form reversible bonds with certain tissue ligands such as thiol groups in protein. METHODS The strong evidence linking dental amalgam with mercury poisoning and
27 associated cardiovascular disorders led us to design a study which evaluated the cardiovascular health of subjects with and without dental amalgam.
Subjects We selected 70 subjects from respondents to advertisements placed in the local college newspaper. The first asked for volunteers who had no dental fillings, followed by a second soliciting people with dental fillings. Twentythree subjects volunteered from student physiology labs and eight came from a local fraternity house. The amalgam and non-amalgam groups were matched for sex and age. Of the 101 subjects, 50 (30 females and 20 males) had amalgams and 51 (30 females and 21 males) had no dental fillings. The average age of the non-amalgam group was 22.35 compared with 23.28 for the amalgam group. The males averaged 10.1 amalgams and the females 9.8. Nearly 300 subjects who had their amalgams removed by a dentist in the State of Utah were sent a health questionnaire. Eighty-six of the subjects responded, 26 males and 60 females of average age 40.41 years. The mean number of amalgams removed was 10.77 within, on average, a period of 9.95 months before they completed the questionnaire. This epidemiological aspect did not control for any placebo effect.
Mercury tests A hair sample was cut from the nape of the neck and sent to Doctors Data, Chicago, Illinois, and was analyzed for mercury by atomic absorption spectrophotometry. A urine sample, the first upon arising in the morning, was collected in a plastic specimen bottle and was analyzed for mercury by atomic absorption spectrophotometry at the Pathology Lab at Colorado State University.
Blood samples Blood samples were drawn by a phlebotomist at the Colorado State University Health Center and a complete blood count was performed by the lab at the Veterinarian Teaching Hospital at Colorado State University.
Dental assessment A dental assistant and dental hygienist recorded the dental status of each subject.
Cardiovascular questionnaire Volunteers completed a health questionnaire evaluating their cardiovascular history and symptoms relating to it.
28
Blood pressure and pulse Blood pressure was measured with subjects in the sitting position with most readings taken in the evening by the auscultatory method. The pressure was measured in the left arm and several readings were taken on each subject. The pulse was also taken at that sitting.
Data analysis Statistical analysis was performed by computer at the Colorado State University Statistics Lab. Numerical data were analyzed by analysis of variance and the health questionnaire by chi square. Correlations were analyzed by the Pearson correlation coefficient and Spearman correlation coefficient. RESULTS
Mercury in tissues The levels of mercury were 210% higher (P = 0.0002) in the urine samples of the amalgam group and their hair mercury levels were 26.5% higher (P --- 0.008) (Table 1). These findings support those of Abraham et al. [18], who found higher blood mercury levels in amalgam-bearing subjects, and those of Svare and Peterson [19], who measured a decrease in blood mercury levels after amalgam removal. Urine mercury correlated significantly with the number of fillings (n = 42, r = 0.46, P = 0.0001), as did hair mercury (n = 36, r = 0.23, P = 0.008). This data supports that of Nilsson and Nilsson [20], who also found a direct correlation between the number of amalgams and urine mercury.
Blood pressure and heart rate Amalgam subjects had significantly higher blood pressure than the nonamalgam-bearing subjects (Table 2). Both the systolic and diastolic pressures TABLE 1 Mercury in tissues
Hair mercury (ppm) Urine mercury (ppb)
Non-amalgam
SD
Amalgam
SD
Significance
1.13
0.54
1.43
0.50
0.008
1.23
1.79
3.70
3.78
0.0002
Percent difference
26.5 201
29 TABLE 2 Cardiovascular findings (non-amalgam subjects, 51; amalgam subjects, 50) Category
Non-amalgam
SD
Amalgam
SD
Significance
(p) Blood pressure (ram Hg) Systolic (both sexes) Diastolic (both sexes) Male systolic Male diastolic Female systolic Female diastolic Heart rate (rain -I)
100.71 58.67 107.47 61.05 95.97 56.90 72.71
11.48 8.22 12.36 8.28 8.09 7.86 9.06
106.44 63.04 113.50 66.35 101.73 60.83 69.90
9.58 7.91 7.76 8.14 7.78 7.91 9.65
0.0005 0.0015 0.0335 0.0245 0.0035 0.0215 0.074
were higher in each sex when amalgam was present. The heart rate was significantly slower in the amalgam group. Blood tests
The data suggest that mercury may affect hemoglobin and hematocrit levels, as both were significantly lower in the amalgam group. The mean corpuscular hemoglobin concentration was also significantly higher in the amalgam group and the total protein was lower (Table 3).
Significant correlations A number of very significant correlations occurred with urine mercury within the amalgam group (Table 4). Hemoglobin, hematocrit, and the red blood cell count were significantly lower when correlated to increased levels of urine mercury. The mean corpuscular volume and the mean corpuscular TABLE 3 Blood tests (non-amalgam subjects, 44; amalgam subjects, 47) Test
Non-amalgam
SD
Amalgam
SD
Significance
Hemoglobin (g dl- 1) Red blood cell count (106 cellsmm -3) Hematocrit (% packed cell volume) Mean corpuscular volume (micro micrograms) Mean corpuscular hemoglobin concentration (%) Total protein (gdl -~)
14.88
1.14
14.66
1.09
0.016
4.86
0.41
4.82
0.46
0.143
43.91
3.61
43.15
3.66
0.013
90.34
3.17
89.65
3.10
0.148
33.98 7.63
0.46 0.40
34.17 7.54
0.60 0.31
0.027 0.098
30 TABLE 4 Significant correlations with urine mercury of a m a l g a m group Finding
_+
Correlation
Significance
Number
(P) Systolic blood pressure Diastolic blood pressure Heart rate Hemoglobin Hematocrit Red blood cells M e a n corpuscular volume M e a n corpuscular Hb volume
+ -
0.3013 0.3041 0.2993 0.4208 0.3934 0.4681
0.023 0.024 0.024 0.003 0.005 0.001
44 44 44 44 44 44
+
0.3370
0.013
44
+
0.2251
0.017
44
hemoglobin volumes were related directly to urine mercury. An unexpected finding found blood pressure negatively related to high levels of urine mercury, which will be discussed later. The heart rate was positively correlated.
Cardiovascular questionnaire Two findings that are typical of mercury toxicity were reported more frequently by the amalgam subjects (Table 5). They had a greater incidence of heart or chest pains and tachycardia.
Health questionnaire The amalgam volunteers also complained significantly more of tiring easily and being tired in the morning. They also suffered more from chronic fatigue and anemia (Table 6). TABLE 5 Cardiovascular questionnaire Symptom Heart or chest pains Tachycardia (heartbeat racing) Heart m u r m u r High blood pressure Low blood pressure Other h e a r t problems Total
Non-amalgam
Amalgam
Significance (P)
1
5
0.098
0 5 2 4 1 13
3 5 1 2 0 16
0.127 0.50 0.346 0.346 0.485 0.204
Non-amalgam: 48 subjects; 13 symptoms; 0.27 symptoms/subject. Amalgam: 47 subjects; 16 symptoms; 0.34 symptoms/subject. Twenty-six percent more symptoms/subject in group with amalgams.
31 TABLE 6 Health questionnaire Symptom
Non-amalgam
Amalgam
Significance (P)
Tired in morning Tire easily Chronic fatigue Anemia
10 2 1 3
25 11 3 6
0.001 0.007 0.297 0.231
Effects after amalgam removal S u b j e c t s w h o h a d t h e i r a m a l g a m s r e m o v e d r e p o r t e d b e i n g less t i r e d a n d less f a t i g u e d ( T a b l e 7). T h e five s u b j e c t s w h o r e p o r t e d h a v i n g a n a e m i a s a i d t h a t t h e c o n d i t i o n got b e t t e r after a m a l g a m removal. All categories of c a r d i o v a s c u l a r symptoms improved after amalgam removal, including chest pains, tachycardia, h e a r t m u r m u r , a n d h i g h a n d l o w b l o o d p r e s s u r e . A c o n t r o l l e d s t u d y n e e d s to be c a r r i e d o u t to d e t e r m i n e a n y p l a c e b o effect. DISCUSSION
Dental amalgam and mercury toxicity T h e r e l a t i o n s h i p s b e t w e e n d e n t a l a m a l g a m , m e r c u r y p o i s o n i n g , a n d cardiovascular disorders are provocative and may have significant implications TABLE 7 Health and cardiovascular questionnaire after amalgam removal (T = total number of subjects with symptom; NC = no change in symptom after amalgam removal; E = symptom eliminated after amalgam removal; I = symptom improved after amalgam removal; W = symptom worse after amalgam removal)
Tire easily Fatigue Tired in morning Anaemia Chest pain Tachycardia Heart murmur High blood pressure Low blood pressure Other Total Percent
T
NC
E
39 34 36 5 13 15 3 7 8 5 51
17 13 17 0 2 1 0 2 2 1 8 16%
3 6 4 3 1 2 2 2 2 2 ll 22%
I
W
E+I
18 12 14 2 10 12 1 3 3 2 31 61%
1 3 1 0 0 0 0 0 1 0 1 2%
53% 53% 50% 100% 85% 93% 100% 71% 63% 80% 83%
The questionnaire was answered an average of 9.95 months after amalgam removal.
32 for effective health treatment. Although the number of subjects in this study is small (50 subjects with amalgam and 51 subjects without), the results are statistically significant and warrant additional research. Perhaps this is one reason why health problems manifest more frequently with increasing age. The body may be unable to handle the additional environmental stress of mercury toxicity over time.
Mercury and blood pressure As the literature demonstrates, mercury can affect the blood pressure. In some cases it can raise the blood pressure and in other instances it can lower it. The probable reason is that mercury can affect different biological functions that control blood pressure. The amalgam group exhibited significantly higher blood pressure than the non-amalgram group in both sexes with both diastolic and systolic pressures being higher. The pressures exhibited by the amalgam group were closer to the accepted normal values, while the non-amalgam group was somewhat below the normal values. With most of the world's population having dental amalgam, the norm for blood pressure would have been established by people with amalgams. Mercury-induced hypertension appears to be caused by an increase in peripheral resistance rather than cardiac output [21]. Small amounts of mercury ions produce rapid and marked increases in both systolic and diastolic pressure in rats. The cardiac output is not increased in mercury-induced hypertension. Mercury causes a pressor effect, and a small concentration of mercury will increase peripheral resistance. Mercury chloride can also impair the kidney and lower the activity of the plasma fibrinolytic system, which removes clots from the millions of tiny peripheral vessels. Worowski and Prokopowicz [4] intoxicated dogs with mercury and induced a rise in blood pressure due to inhibition of the fibrinolytic system. Mercury chloride injected into rats caused a significant increase in renin substrate, which results in increased peripheral resistance [22]. Approximately 90% of all people who have hypertension are said to have '~essential hypertension", meaning hypertension of unknown origin [23]. Perhaps mercury from dental amalgam should be considered a possible etiology. If mercury accumulates with age in the kidney, as Schmidt and Wilbur [24] discovered in post-mortem studies, this may contribute to increased blood pressure, as the kidney plays a key role in controlling blood pressure. Of the seven subjects reporting high blood pressure before amalgam removal, five reported their high blood pressure improved or eliminated after amalgam removal. Five of eight subjects also reported improved or eliminated low blood pressure (Table 7).
33
Blood pressure and urine mercury An interesting dichotomy was found in the correlation of urine mercury and blood pressure in the amalgam group. If an increase in blood pressure was caused by mercury, a positive correlation would be expected. In fact, a significant negative correlation was found within the amalgam group. One of the therapies for hypertension is a mercury diuretic which reduces the blood pressure. Urine mercury reflects more acute exposure and perhaps the mercury would be acting as a mercury diuretic, thus explaining the negative correlation. However, long-term exposure would be reflected in the overall comparison of blood pressures between the amalgam and non-amalgam subjects, as this study demonstrated with the amalgam group having significantly higher blood pressure.
Mercury and heart rate The heart rate was significantly slower in subjects with amalgams, averaging almost three beats per minute less. One may have expected a faster heart rate in the amalgam group because tachycardia is usually associated with mercury toxicity. In Iraq, many of the mercury-poisoned patients experienced tachycardia with only a few experiencing bradycardia [3]. However, in the initial stage of micromercurialism, there is a tendency to tachycardia with an increased tonus of the sympathetic nervous system [2]. Bradycardia develops after longer exposure with a predominance of inhibition and increased tonus of the vagus nerve. Perhaps this could explain the slower rate. Within the amalgam group a positive correlation was seen between heart rate and urine mercury. This reflects the short-term exposure to mercury, which results in a faster heart rate. The comparison between the groups with and without amalgams reflects long-term exposure and thus the slower heart rate of the amalgam group.
Mercury and blood Mercury may be affecting the blood in several ways, which may explain the significantly lower hemoglobin and hematocrit values found in the amalgam group. With the rapid absorption of mercury into the red blood cells there is an affinity of mercury for the sulfhydryl groups of hemoglobin. This does affect the biochemistry of the molecule and may contribute to its demise. We have shown that mercury chloride produces free oxy-radicals in oxyhemoglobin. The free oxy-radicals destroy tissue and accelerate the oxidation rate of the hemoglobin molecule [25]. To support the hypothesis that mercury affects hemoglobin, hematocrit, and the red blood cell, there is a significant negative correlation between these
34 factors and u r i n e m e r c u r y w i t h i n the amalgam group, i.e. h i g h e r m e r c u r y levels c o r r e l a t e d with lower levels of hemoglobin, h e m a t o c r i t , and red blood cells.
Questionnaire A v e r y c o m m o n symptom of m e r c u r y t o x i c i t y is h e a r t or chest pains. Signific a n t l y more subjects in the a m a l g a m group e x p e r i e n c e d this condition. T h e y also had more symptoms of t a c h y c a r d i a , which is typical of m e r c u r y toxicity. If h e m o g l o b i n levels were lower in the a m a l g a m group, one would expect more symptoms of fatigue. This was observed. T h e a m a l g a m group was m o r e tired in the morning, tired m o r e easily, and had more c h r o n i c fatigue. T h e y also e x p e r i e n c e d more cases of anemia. All these conditions m a y reflect lower h e m o g l o b i n levels [26]. In a n o n - c o n t r o l l e d study of 86 subjects who h a d t h e i r amalgams removed, 53% of 34 p a t i e n t s said t h e y did not tire as easily; 53% of 34 p a t i e n t s said t h e i r fatigue had e i t h e r been e l i m i n a t e d or improved, while a n o t h e r 50% of 36 individuals said t h e y were not as tired in the morning. All five people who r e p o r t e d a n e m i a said t h a t the c o n d i t i o n was e i t h e r e l i m i n a t e d or improved after amalgam r e m o v a l [26] (Table 6). P l e v a [14] r e p o r t e d t h a t his i r r e g u l a r h e a r t beat disappeared after a m a l g a m removal. Roue, a G e r m a n ophthalmologist, r e p o r t s of c a r d i o v a s c u l a r problems disappearing in his s t u d y of 100 patients who had t h e i r amalgams r e m o v e d [27]. SUMMARY M a n y c o m m o n symptoms of m e r c u r y poisoning are r e l a t e d to the cardiovasc u l a r system. The d a t a p r e s e n t e d h e r e suggest t h a t the release of m e r c u r y v a p o r from d e n t a l a m a l g a m m a y cause m e r c u r y t o x i c i t y and p r o d u c e physiological changes in the h e a r t and blood, D e n t a l m e r c u r y , which is u n i v e r s a l l y used, m a y be a significant h e a l t h hazard. H e a l t h care p r a c t i t i o n e r s should consider m e r c u r y t o x i c i t y a possible cause in the t r e a t m e n t of c a r d i o v a s c u l a r disorders. REFERENCES 1 J. Brake, G. Thaxton and P.Y. Hester, Mercury induced cardiovascular abnormalities in the chicken, Arch. Environ. Contam. Toxicol., (1977) 26~277. 2 I.M. Trachtenberg, Chronic effects of mercury on organisms, U.S. Dept. Health, Education, Welfare, NIH, DHEW Publ. 74-473, Washington, DC, 1974. 3 S.S. Dahhan and H. Orfaly, Electrocardiographic changes in mercury poisoning, Am. J. Cardiol., 14 (1972) 178-187. 4 K. Worowski and J. Prokopowicz, Effect of mercuric chloride on the arterial blood pressure of dogs, Pol. Akad. Nauk, Bull. Ser. Sci. Biol., 17 (1969) 349-351. 5 R. Weed, J. Eber and A. Rothstein, Interaction of mercury with human erythrocytes, J. Gen. Physiol., 45 (1962) 395-410. 6 A.F.Riggs, Sulfhydryl groups and the interaction between the hemes in hemoglobin, J. Gen. Physiol., (1952) 1-14.
35 7 8 9 10 11
12 13 14 15
16 17 18 19 20 21 22 23 24 25 26 27
T.W. Clarkson, The pharmacology of mercury compounds, Ann. Rev. Pharmacol., 12 (1972) 375406. M. Hanson, Amalgam - - hazards in your teeth, J. Orthomol. Psychiatry, 12 (1983) 194~201. A. Stock, Die chronische quecksilber und amalgam vergistung, Arch. Gewerbepathol., 7 (1936) 388. D.D. Gay, R.O. Cox and J.W. Reinhardt, Chewing releases mercury from fillings, Lancet, i (1979) 984 985. C.W. Svare, L.C. Peterson, J.W. Reinhardt, D.B. Boyer, C.W. Frank, D.D. Gay and R.O. Cox, The effect of dental amalgams on mercury levels in expired air, J. Dent. Res., 60 (1981) 1668~1671. M.I. Vimy and F.L. Lorsehneider, Serial measurements of intra-oral air mercury: Estimation of daily dose from dental amalgam, J. Dent. Res., 64 (1985) 1072 1075. J. Radics, H. Schwander and B. Gasser, Die kristallinem dompuneten der silberamalgam utersuehungen mit der electronisehen rontgen mikrosonde, Zahn~irztl. Welt, 79 (1970) 1031. J. Pleva, Mercury poisoning from dental amalgam, J. Orthomol. Psychiatry, 12 (1983) 184-193. J.B. Hursh, T.W. Clarkson, M.G. Cherian, J.J. Vostal and A. van der Millie, Clearance of mercury (Hg-197, Hg-203) vapor inhaled by human subjects, Arch. Environ. Health, 31 (1976) 302-309. L. Friberg and J. Vostal, Mercury in the Environment, CRC Press, Cleveland, Ohio, 1972. P. Stortebecker, Mercury poisoning from dental amalgam, Stortebecker Foundation for Research, Bioprobe, Orlando, FL, 1985, pp. 138, 149, 151-154. J.E. Abraham, C.W. Svare and C.W. Frank, The effect of dental amalgam restorations on blood mercury levels, J. Dent. Res., 63 (1984) 71-73. C.W. Svare and L.L. Peterson, The effect of removing dental amalgam on mercury blood levels, J. Dent. Res., IADR Abstr. 896, 1984. B. Nilsson and B. Nilsson, Mercury in dental practice. III. Urinary mercury excretion in dental personnel, Swed. Dent. J., 10 (1986) 221 232. H.M. Perry and M.W. Erlanger, Metal-induced hypertension following chronic feeding of low doses of cadmium and mercury, J. Lab. Clin. Med., 83 (1974) 541-547. S. Sen, Q.R. Smeby and F.M. Bumpus, Effect of mercuric chloride on plasma renin substrate levels in rats, Am. J. Physiol., 222 (1972) 3044. A.C. Guyton, Textbook of Medical Physiology, W.B, Saunders Co., Philadelphia, PA, 1981, 270 pp. R. Schmidt and C.G. Wilber, Mercury and lead content of human body tissues from a selected population, Med., Sci. Law, 18(3) (1978) 155-158. R.L. Siblerud, Ph.D. dissertation in process. The relationship between mercury from dental amalgam and health, Colorado State University, Department of Physiology, 1989. R.L. Siberlund, The relationship between mercury from dental amalgam and mental health, Am. J. Psychother., XLIII(4) (1989) 57~587. H. Roue, Resistance to therapy. Think of tooth fillings, Med. Pr., 32 (1980) 230~2309.
23
THE R E L A T I O N S H I P B E T W E E N M E R C U R Y FROM D E N T A L AMALGAM AND THE CARDIOVASCULAR
SYSTEM
ROBERT L. SIBLERUD Department of Physiology, College of Veterinary Medicine and Biological Sciences, Colorado State University, Fort Collins, CO 80523 (U.S.A.) (Received October llth, 1989; accepted December 6th, 1989)
ABSTRACT 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.
INTRODUCTION E v i d e n c e l i n k i n g m e r c u r y to the c a r d i o v a s c u l a r s y s t e m h a s b e e n a c c u m u l a t ing o v e r the p a s t s e v e r a l decades. M a n y h e a l t h p r o f e s s i o n a l s s u g g e s t t h a t n u m e r o u s h e a l t h p r o b l e m s e x p e r i e n c e d t o d a y h a v e a n e n v i r o n m e n t a l etiology. A n e c d o t a l e v i d e n c e s u g g e s t s t h a t m e r c u r y from d e n t a l a m a l g a m m a y be an e n v i r o n m e n t a l h e a l t h hazard. A s t u d y was u n d e r t a k e n a t C o l o r a d o S t a t e U n i v e r s i t y to d e t e r m i n e w h e t h e r or not m e r c u r y from d e n t a l a m a l g a m does c a u s e h e a l t h problems. This p a p e r r e p o r t s the r e l a t i o n s h i p of m e r c u r y p o i s o n i n g f r o m d e n t a l a m a l g a m to t h e c a r d i o v a s c u l a r system. M e r c u r y poisoning a n d the heart E l e c t r o c a r d i o g r a p h y studies h a v e s h o w n t h a t the h e a r t is affected by m e r c u r y . T h e QRS ( v e n t r i c u l a r d e p o l a r i z a t i o n ) a n d s e v e n s e g m e n t s of the e l e c t r o c a r d i o g r a m of r a b b i t s w e r e affected by c h r o n i c p o i s o n i n g by m e t a l l i c m e r c u r y v a p o r [1]. A n o t h e r r a b b i t s t u d y [2] found no c h a n g e s in e l e c t r o c a r d i o g r a p h i c r e a d i n g s of r a b b i t s exposed to c h r o n i c m e r c u r y v a p o r s d u r i n g t h e first 3-4 weeks. In t h e second a n d t h i r d m o n t h t h e r e was t a c h y c a r d i a in w h i c h the b e a t was 220-250 b e a t s per m i n u t e . A b r o a d e n i n g of the P ( a t r i a d e p o l a r i z a t i o n ) w a v e a n d a d e c r e a s e in t h e R (highest + v o l t a g e of v e n t r i c u l a r d e p o l a r i z a t i o n )
24 and T (ventricular repolarization) waves were observed, but there were individual variations in each animal. In nine of 14 rabbits there was a shift in the S ( h i g h e s t - - voltage of ventricular depolarization)--T interval with respect to the isoelectric line. In all cases, bradycardia appeared by the end of the experiment. The vagus nerve endings contain acetylcholine, which has a specific effect on the heart muscle's cholinoreceptor protein, the active sites of which involve sulfhydryl groups. Mercury has an affinity for sulfhydryl groups. Studies [2] on excised extracardiac nerves have concluded that cardiac changes produced by mercury are usually toward slowing the rhythm with change in tonus of the vagus nerve.
Studies of human subjects also demonstrate a mercury~cardiac relationship A study [3] of 42 mercury-poisoned patients in Iraq found abnormal electrocardiogram changes in all subjects. A variety of abnormalities occurred, but the most common finding was the S-T depression of all 42 subjects. Cardiovascular pathology is also associated with Kawasaki's disease, a mercury-caused syndrome. Symptoms include AV block, premature contractions and tachycardia. People exposed to low doses of mercury vapor can develop coronary insufficiency and pressure in the cardiac region, which are symptoms in a condition known as micromercurialism [2].
Mercury and blood pressure Mercury is also known to increase blood pressure. Eight mongrel dogs were injected subcutaneously with mercury chloride at a daily dose of 3 mg/kg body weight for 3 days [4]. The blood pressure increased from 10 to 70 mm Hg in all dogs. Before HgC12 administration the blood pressure averaged 131 mm Hg and after administration it was 153 mm Hg. People exposed to chronic doses of mercury may develop an asthenic-vegetative syndrome. A high percentage of these individuals develop functional disorders of the cardiovascular system including chest pain and heart palpitations. Blood pressure can be either high or low. A study [2] of 63 people with asthenic-vegetative syndrome found 40 people with low blood pressure and six people with increased blood pressure. Another study [2] of mercury-exposed workers found that 50% of the men and 68% of the women had hypertension, while hypertension was found among 42% of people working in another mercury-related occupation.
Mercury, the red blood cell, and hemoglobin The rapid absorption of mercury in red blood cells results in an inhibition of glucose as well as a loss of potassium and a decrease in osmotic fragility [5]. The sulfhydryl groups of hemoglobin have a strong affinity for mercury, and
25 heavy metals can impair heme syntheses in erythrocytes by inhibiting several sulfhydryl enzymes. Inorganic mercury has been shown to change the tertiary structure of the hemoglobin molecule, which, in turn, produces a change in the oxygen dissociation curve [6]. Blood studies [2] on individuals who worked daily with mercury found that the percentage of hemoglobin decreased as their length of work time increased. After 1 year of employment, decreased hemoglobin occurred in 29.8% of the cases and people who were employed 10 years or more had a decrease in hemoglobin in 40% of the cases. An analysis of erythrocyte counts found that, with increasing length of employment (1 10 years), the number of people with less than 3 500000 erythrocytes increased almost two-fold, from 14.5 to 25.8%. There was a five-fold decrease in the number of patients with erythrocytic counts of 4 500 000, from 36.7 to 7.9%.
Mercury poisoning and dental amalgam Three factors led us to study the relationships among dental amalgam, mercury poisoning and the cardiovascular system. First, mercury's affinity for the blood stream; second, the relationship between mercury poisoning and cardiovascular disorders; and third, the release of mercury vapor from the amalgam. Mercury is one of the most toxic metals, since it disrupts most biological systems as a result of its affinity for sulfhydryl groups, which are essential constituents of most enzymes and hormones [7]. Even small amounts of mercury exposure over a long period can produce the same devastating effects as a large dose in a short time. Insidious long-term exposure to mercury can produce damage after many years with no trace of the etiology of the problem [8]. Stock [9] found that 3 ttg m 3 of mercury in the air during constant work did not cause noticeable health symptoms, except for people with hypersensitivity to mercury. Daily mercury concentrations of 10-20pgm -3 in the workroom produced physical and mental symptoms in the majority of employees. However, Stock reported that neurological symptoms associated with a mercury concentration of 2.1 pg m 3 in expired air, disappeared after amalgam removal. Occupational exposure limits for inorganic mercury vary around the world. They are based on 8 hours per day, 40 hours per week. In Germany and the U.S. the maximum is 100ggHgm 3, while in Sweden it is 5 0 p g H g m 3, and the World Health Organization (WHO) recommends 2 5 g g H g m -3. In the Soviet Union and Switzerland the value is 10 gg Hg m -3. For the general population, the United States Environmental Protection Agency established the National Standard for mercury as a hazardous air pollutant at a level of 1 ttg Hg m 3 over a 24-h period. In the Soviet Union, the value is 0 . 3 p g H g m -3. Nearly 80% of the world's dental caries are filled with dental amalgam (silver fillings). This unstable alloy is approximately 50% mercury and con-
26 tinuously releases elemental mercury [10, 11]. A direct correlation is found between the amount of mercury released and the number of amalgams. More mercury (up to 87.5pgm 3) is released during chewing. Two-year old fillings release four times as much mercury after chewing than before, and week-old fillings show a 17-fold increase in mercury released after chewing. Vimy and Lorshneider [12] measured intra-oral mercury and calculated that subjects with 12 or more occlused amalgam surfaces received an average daily dose of 29 gg mercury. Subjects with one to four amalgams received an average daily dose of 9 #g. These levels exceed many countries' accepted standards for environmental exposure according to the authors. Radics et al. [13] analyzed the outer corroded area of an amalgam that was depleted of mercury. His calculations suggested that a mouth with many fillings could release up to 560 mg of mercury over several years. Pleva [14] found that the chewing surface of a 5-year-old amalgam had lost almost half its mercury; a 20-year-old amalgam had no mercury left on the chewing surface.
Mercury's path to the blood Mercury is released from dental amalgam as elemental mercury vapor. An average of 75 [15] to 80% [16] of the elemental mercury vapor can be inhaled and absorbed through the alveoli of the lungs where it passes into the blood stream rapidly and completely. Elemental mercury (Hg °) passes through the blood-brain barrier before it is ionized and is retained within the 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 [7]. Another avenue of mercury poisoning from dental amalgam may be absorption through the valveless cranial venous system. Mercury vapor may settle down into the oronasal region and be absorbed directly into the venous system to the brain [17]. After oxidation to the mercurous ion it can react chemically with proteins and other molecules. Approximately 80% of the oxidation takes place in the red blood cells [7]. Immediately after exposure to mercury vapor, there is a much higher content of mercury in the red blood cells than in the plasma. Mercury can then combine with protein or salt molecules only after a prolonged period of enzyme oxidation. After oxidation, most of the mercury is bound to albumin or globulin in the blood. Only a small fraction is found in a free ultrafiltrate form. Once ionized, a mercuric ion can form reversible bonds with certain tissue ligands such as thiol groups in protein. METHODS The strong evidence linking dental amalgam with mercury poisoning and
27 associated cardiovascular disorders led us to design a study which evaluated the cardiovascular health of subjects with and without dental amalgam.
Subjects We selected 70 subjects from respondents to advertisements placed in the local college newspaper. The first asked for volunteers who had no dental fillings, followed by a second soliciting people with dental fillings. Twentythree subjects volunteered from student physiology labs and eight came from a local fraternity house. The amalgam and non-amalgam groups were matched for sex and age. Of the 101 subjects, 50 (30 females and 20 males) had amalgams and 51 (30 females and 21 males) had no dental fillings. The average age of the non-amalgam group was 22.35 compared with 23.28 for the amalgam group. The males averaged 10.1 amalgams and the females 9.8. Nearly 300 subjects who had their amalgams removed by a dentist in the State of Utah were sent a health questionnaire. Eighty-six of the subjects responded, 26 males and 60 females of average age 40.41 years. The mean number of amalgams removed was 10.77 within, on average, a period of 9.95 months before they completed the questionnaire. This epidemiological aspect did not control for any placebo effect.
Mercury tests A hair sample was cut from the nape of the neck and sent to Doctors Data, Chicago, Illinois, and was analyzed for mercury by atomic absorption spectrophotometry. A urine sample, the first upon arising in the morning, was collected in a plastic specimen bottle and was analyzed for mercury by atomic absorption spectrophotometry at the Pathology Lab at Colorado State University.
Blood samples Blood samples were drawn by a phlebotomist at the Colorado State University Health Center and a complete blood count was performed by the lab at the Veterinarian Teaching Hospital at Colorado State University.
Dental assessment A dental assistant and dental hygienist recorded the dental status of each subject.
Cardiovascular questionnaire Volunteers completed a health questionnaire evaluating their cardiovascular history and symptoms relating to it.
28
Blood pressure and pulse Blood pressure was measured with subjects in the sitting position with most readings taken in the evening by the auscultatory method. The pressure was measured in the left arm and several readings were taken on each subject. The pulse was also taken at that sitting.
Data analysis Statistical analysis was performed by computer at the Colorado State University Statistics Lab. Numerical data were analyzed by analysis of variance and the health questionnaire by chi square. Correlations were analyzed by the Pearson correlation coefficient and Spearman correlation coefficient. RESULTS
Mercury in tissues The levels of mercury were 210% higher (P = 0.0002) in the urine samples of the amalgam group and their hair mercury levels were 26.5% higher (P --- 0.008) (Table 1). These findings support those of Abraham et al. [18], who found higher blood mercury levels in amalgam-bearing subjects, and those of Svare and Peterson [19], who measured a decrease in blood mercury levels after amalgam removal. Urine mercury correlated significantly with the number of fillings (n = 42, r = 0.46, P = 0.0001), as did hair mercury (n = 36, r = 0.23, P = 0.008). This data supports that of Nilsson and Nilsson [20], who also found a direct correlation between the number of amalgams and urine mercury.
Blood pressure and heart rate Amalgam subjects had significantly higher blood pressure than the nonamalgam-bearing subjects (Table 2). Both the systolic and diastolic pressures TABLE 1 Mercury in tissues
Hair mercury (ppm) Urine mercury (ppb)
Non-amalgam
SD
Amalgam
SD
Significance
1.13
0.54
1.43
0.50
0.008
1.23
1.79
3.70
3.78
0.0002
Percent difference
26.5 201
29 TABLE 2 Cardiovascular findings (non-amalgam subjects, 51; amalgam subjects, 50) Category
Non-amalgam
SD
Amalgam
SD
Significance
(p) Blood pressure (ram Hg) Systolic (both sexes) Diastolic (both sexes) Male systolic Male diastolic Female systolic Female diastolic Heart rate (rain -I)
100.71 58.67 107.47 61.05 95.97 56.90 72.71
11.48 8.22 12.36 8.28 8.09 7.86 9.06
106.44 63.04 113.50 66.35 101.73 60.83 69.90
9.58 7.91 7.76 8.14 7.78 7.91 9.65
0.0005 0.0015 0.0335 0.0245 0.0035 0.0215 0.074
were higher in each sex when amalgam was present. The heart rate was significantly slower in the amalgam group. Blood tests
The data suggest that mercury may affect hemoglobin and hematocrit levels, as both were significantly lower in the amalgam group. The mean corpuscular hemoglobin concentration was also significantly higher in the amalgam group and the total protein was lower (Table 3).
Significant correlations A number of very significant correlations occurred with urine mercury within the amalgam group (Table 4). Hemoglobin, hematocrit, and the red blood cell count were significantly lower when correlated to increased levels of urine mercury. The mean corpuscular volume and the mean corpuscular TABLE 3 Blood tests (non-amalgam subjects, 44; amalgam subjects, 47) Test
Non-amalgam
SD
Amalgam
SD
Significance
Hemoglobin (g dl- 1) Red blood cell count (106 cellsmm -3) Hematocrit (% packed cell volume) Mean corpuscular volume (micro micrograms) Mean corpuscular hemoglobin concentration (%) Total protein (gdl -~)
14.88
1.14
14.66
1.09
0.016
4.86
0.41
4.82
0.46
0.143
43.91
3.61
43.15
3.66
0.013
90.34
3.17
89.65
3.10
0.148
33.98 7.63
0.46 0.40
34.17 7.54
0.60 0.31
0.027 0.098
30 TABLE 4 Significant correlations with urine mercury of a m a l g a m group Finding
_+
Correlation
Significance
Number
(P) Systolic blood pressure Diastolic blood pressure Heart rate Hemoglobin Hematocrit Red blood cells M e a n corpuscular volume M e a n corpuscular Hb volume
+ -
0.3013 0.3041 0.2993 0.4208 0.3934 0.4681
0.023 0.024 0.024 0.003 0.005 0.001
44 44 44 44 44 44
+
0.3370
0.013
44
+
0.2251
0.017
44
hemoglobin volumes were related directly to urine mercury. An unexpected finding found blood pressure negatively related to high levels of urine mercury, which will be discussed later. The heart rate was positively correlated.
Cardiovascular questionnaire Two findings that are typical of mercury toxicity were reported more frequently by the amalgam subjects (Table 5). They had a greater incidence of heart or chest pains and tachycardia.
Health questionnaire The amalgam volunteers also complained significantly more of tiring easily and being tired in the morning. They also suffered more from chronic fatigue and anemia (Table 6). TABLE 5 Cardiovascular questionnaire Symptom Heart or chest pains Tachycardia (heartbeat racing) Heart m u r m u r High blood pressure Low blood pressure Other h e a r t problems Total
Non-amalgam
Amalgam
Significance (P)
1
5
0.098
0 5 2 4 1 13
3 5 1 2 0 16
0.127 0.50 0.346 0.346 0.485 0.204
Non-amalgam: 48 subjects; 13 symptoms; 0.27 symptoms/subject. Amalgam: 47 subjects; 16 symptoms; 0.34 symptoms/subject. Twenty-six percent more symptoms/subject in group with amalgams.
31 TABLE 6 Health questionnaire Symptom
Non-amalgam
Amalgam
Significance (P)
Tired in morning Tire easily Chronic fatigue Anemia
10 2 1 3
25 11 3 6
0.001 0.007 0.297 0.231
Effects after amalgam removal S u b j e c t s w h o h a d t h e i r a m a l g a m s r e m o v e d r e p o r t e d b e i n g less t i r e d a n d less f a t i g u e d ( T a b l e 7). T h e five s u b j e c t s w h o r e p o r t e d h a v i n g a n a e m i a s a i d t h a t t h e c o n d i t i o n got b e t t e r after a m a l g a m removal. All categories of c a r d i o v a s c u l a r symptoms improved after amalgam removal, including chest pains, tachycardia, h e a r t m u r m u r , a n d h i g h a n d l o w b l o o d p r e s s u r e . A c o n t r o l l e d s t u d y n e e d s to be c a r r i e d o u t to d e t e r m i n e a n y p l a c e b o effect. DISCUSSION
Dental amalgam and mercury toxicity T h e r e l a t i o n s h i p s b e t w e e n d e n t a l a m a l g a m , m e r c u r y p o i s o n i n g , a n d cardiovascular disorders are provocative and may have significant implications TABLE 7 Health and cardiovascular questionnaire after amalgam removal (T = total number of subjects with symptom; NC = no change in symptom after amalgam removal; E = symptom eliminated after amalgam removal; I = symptom improved after amalgam removal; W = symptom worse after amalgam removal)
Tire easily Fatigue Tired in morning Anaemia Chest pain Tachycardia Heart murmur High blood pressure Low blood pressure Other Total Percent
T
NC
E
39 34 36 5 13 15 3 7 8 5 51
17 13 17 0 2 1 0 2 2 1 8 16%
3 6 4 3 1 2 2 2 2 2 ll 22%
I
W
E+I
18 12 14 2 10 12 1 3 3 2 31 61%
1 3 1 0 0 0 0 0 1 0 1 2%
53% 53% 50% 100% 85% 93% 100% 71% 63% 80% 83%
The questionnaire was answered an average of 9.95 months after amalgam removal.
32 for effective health treatment. Although the number of subjects in this study is small (50 subjects with amalgam and 51 subjects without), the results are statistically significant and warrant additional research. Perhaps this is one reason why health problems manifest more frequently with increasing age. The body may be unable to handle the additional environmental stress of mercury toxicity over time.
Mercury and blood pressure As the literature demonstrates, mercury can affect the blood pressure. In some cases it can raise the blood pressure and in other instances it can lower it. The probable reason is that mercury can affect different biological functions that control blood pressure. The amalgam group exhibited significantly higher blood pressure than the non-amalgram group in both sexes with both diastolic and systolic pressures being higher. The pressures exhibited by the amalgam group were closer to the accepted normal values, while the non-amalgam group was somewhat below the normal values. With most of the world's population having dental amalgam, the norm for blood pressure would have been established by people with amalgams. Mercury-induced hypertension appears to be caused by an increase in peripheral resistance rather than cardiac output [21]. Small amounts of mercury ions produce rapid and marked increases in both systolic and diastolic pressure in rats. The cardiac output is not increased in mercury-induced hypertension. Mercury causes a pressor effect, and a small concentration of mercury will increase peripheral resistance. Mercury chloride can also impair the kidney and lower the activity of the plasma fibrinolytic system, which removes clots from the millions of tiny peripheral vessels. Worowski and Prokopowicz [4] intoxicated dogs with mercury and induced a rise in blood pressure due to inhibition of the fibrinolytic system. Mercury chloride injected into rats caused a significant increase in renin substrate, which results in increased peripheral resistance [22]. Approximately 90% of all people who have hypertension are said to have '~essential hypertension", meaning hypertension of unknown origin [23]. Perhaps mercury from dental amalgam should be considered a possible etiology. If mercury accumulates with age in the kidney, as Schmidt and Wilbur [24] discovered in post-mortem studies, this may contribute to increased blood pressure, as the kidney plays a key role in controlling blood pressure. Of the seven subjects reporting high blood pressure before amalgam removal, five reported their high blood pressure improved or eliminated after amalgam removal. Five of eight subjects also reported improved or eliminated low blood pressure (Table 7).
33
Blood pressure and urine mercury An interesting dichotomy was found in the correlation of urine mercury and blood pressure in the amalgam group. If an increase in blood pressure was caused by mercury, a positive correlation would be expected. In fact, a significant negative correlation was found within the amalgam group. One of the therapies for hypertension is a mercury diuretic which reduces the blood pressure. Urine mercury reflects more acute exposure and perhaps the mercury would be acting as a mercury diuretic, thus explaining the negative correlation. However, long-term exposure would be reflected in the overall comparison of blood pressures between the amalgam and non-amalgam subjects, as this study demonstrated with the amalgam group having significantly higher blood pressure.
Mercury and heart rate The heart rate was significantly slower in subjects with amalgams, averaging almost three beats per minute less. One may have expected a faster heart rate in the amalgam group because tachycardia is usually associated with mercury toxicity. In Iraq, many of the mercury-poisoned patients experienced tachycardia with only a few experiencing bradycardia [3]. However, in the initial stage of micromercurialism, there is a tendency to tachycardia with an increased tonus of the sympathetic nervous system [2]. Bradycardia develops after longer exposure with a predominance of inhibition and increased tonus of the vagus nerve. Perhaps this could explain the slower rate. Within the amalgam group a positive correlation was seen between heart rate and urine mercury. This reflects the short-term exposure to mercury, which results in a faster heart rate. The comparison between the groups with and without amalgams reflects long-term exposure and thus the slower heart rate of the amalgam group.
Mercury and blood Mercury may be affecting the blood in several ways, which may explain the significantly lower hemoglobin and hematocrit values found in the amalgam group. With the rapid absorption of mercury into the red blood cells there is an affinity of mercury for the sulfhydryl groups of hemoglobin. This does affect the biochemistry of the molecule and may contribute to its demise. We have shown that mercury chloride produces free oxy-radicals in oxyhemoglobin. The free oxy-radicals destroy tissue and accelerate the oxidation rate of the hemoglobin molecule [25]. To support the hypothesis that mercury affects hemoglobin, hematocrit, and the red blood cell, there is a significant negative correlation between these
34 factors and u r i n e m e r c u r y w i t h i n the amalgam group, i.e. h i g h e r m e r c u r y levels c o r r e l a t e d with lower levels of hemoglobin, h e m a t o c r i t , and red blood cells.
Questionnaire A v e r y c o m m o n symptom of m e r c u r y t o x i c i t y is h e a r t or chest pains. Signific a n t l y more subjects in the a m a l g a m group e x p e r i e n c e d this condition. T h e y also had more symptoms of t a c h y c a r d i a , which is typical of m e r c u r y toxicity. If h e m o g l o b i n levels were lower in the a m a l g a m group, one would expect more symptoms of fatigue. This was observed. T h e a m a l g a m group was m o r e tired in the morning, tired m o r e easily, and had more c h r o n i c fatigue. T h e y also e x p e r i e n c e d more cases of anemia. All these conditions m a y reflect lower h e m o g l o b i n levels [26]. In a n o n - c o n t r o l l e d study of 86 subjects who h a d t h e i r amalgams removed, 53% of 34 p a t i e n t s said t h e y did not tire as easily; 53% of 34 p a t i e n t s said t h e i r fatigue had e i t h e r been e l i m i n a t e d or improved, while a n o t h e r 50% of 36 individuals said t h e y were not as tired in the morning. All five people who r e p o r t e d a n e m i a said t h a t the c o n d i t i o n was e i t h e r e l i m i n a t e d or improved after amalgam r e m o v a l [26] (Table 6). P l e v a [14] r e p o r t e d t h a t his i r r e g u l a r h e a r t beat disappeared after a m a l g a m removal. Roue, a G e r m a n ophthalmologist, r e p o r t s of c a r d i o v a s c u l a r problems disappearing in his s t u d y of 100 patients who had t h e i r amalgams r e m o v e d [27]. SUMMARY M a n y c o m m o n symptoms of m e r c u r y poisoning are r e l a t e d to the cardiovasc u l a r system. The d a t a p r e s e n t e d h e r e suggest t h a t the release of m e r c u r y v a p o r from d e n t a l a m a l g a m m a y cause m e r c u r y t o x i c i t y and p r o d u c e physiological changes in the h e a r t and blood, D e n t a l m e r c u r y , which is u n i v e r s a l l y used, m a y be a significant h e a l t h hazard. H e a l t h care p r a c t i t i o n e r s should consider m e r c u r y t o x i c i t y a possible cause in the t r e a t m e n t of c a r d i o v a s c u l a r disorders. REFERENCES 1 J. Brake, G. Thaxton and P.Y. Hester, Mercury induced cardiovascular abnormalities in the chicken, Arch. Environ. Contam. Toxicol., (1977) 26~277. 2 I.M. Trachtenberg, Chronic effects of mercury on organisms, U.S. Dept. Health, Education, Welfare, NIH, DHEW Publ. 74-473, Washington, DC, 1974. 3 S.S. Dahhan and H. Orfaly, Electrocardiographic changes in mercury poisoning, Am. J. Cardiol., 14 (1972) 178-187. 4 K. Worowski and J. Prokopowicz, Effect of mercuric chloride on the arterial blood pressure of dogs, Pol. Akad. Nauk, Bull. Ser. Sci. Biol., 17 (1969) 349-351. 5 R. Weed, J. Eber and A. Rothstein, Interaction of mercury with human erythrocytes, J. Gen. Physiol., 45 (1962) 395-410. 6 A.F.Riggs, Sulfhydryl groups and the interaction between the hemes in hemoglobin, J. Gen. Physiol., (1952) 1-14.
35 7 8 9 10 11
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