PD can be caused by physical injury like concussion (Muhammad Ali) or a viral infection (encephalitis). But most cases of PD come from some combination of genetic predisposition and environmental insult — in other words, we get PD because of a genetic defect in our ability to deal with some of the things that we eat, drink, breathe or absorb through our skin. If we didn't have the genetic propensity we would be okay; if we were not exposed to the environmental insult we would be okay. It takes the two together to cause PD.
A few rare genes have been identified which cause PD all by themselves. And on the environmental insult side, neurotoxin MPTP (rare contaminant of synthetic heroin) can cause PD in a matter of days. But most PD comes from a combination of genetics and environment and happens very slowly. The most common type of PD, which becomes evident after age 50, probably starts its march some 20 to 40 years before symptoms begin to show. This slow development makes the search for causes more difficult.
Neurons wear out. So we would expect to lose some neurons from normal aging. But the loss of more than half is not normal. In order to lose two thirds of our neurons, it is quite likely that our neuroprotective agents are faulty or inefficient (the genetic component); and that there has been exposure to one or more environmental stressors which accelerate aging. For neuron depletion to take place as slowly as it does, there is some thing (or combination of things) that stresses our defense systems rather than poisoning them. It would have to be something not quite toxic — severe enough to take advantage of genetic weakness over time but not strong enough to overcome the genetically robust. For if the environmental insult were toxic enough to affect everybody, the culprit would get identified. And then, in the best of all possible worlds, steps would be taken to eliminate the toxin.
The list of possible environmental causes of PD usually includes: welding fumes (manganese is the main suspect), insecticides, herbicides, industrial chemicals of various sorts, well water, heavy metals. It is quite likely that in susceptible individuals, more than one of these contribute, depending on exposure.
Conspicuously absent from most such lists is mercury. Mercury is a potent neuropoison which produces symptoms very similar to PD. And most people of my generation carry around a few grams of mercury in their teeth.
The amount of mercury ingested from amalgam is small enough that anyone with all their heavy metal defenses in good working order can handle it without suffering any obvious harm. Among those of us whose defenses against heavy metals in general or mercury in particular are defective, significant harm from amalgam is, I believe, fairly common; but because of the low level at which mercury is released from amalgam, the harm it does is very slow to become apparent, even in sensitive individuals. So it is hard to demonstrate cause and effect. Harm from amalgam has yet to be proven with enough certainty to satisfy a court of law.
Of special interest to me is the possibility that mercury is the main environmental contributor to my PD. I have come to believe that this is the case. This belief comes, in part, from my personal observations of other effects of amalgam on me. And part is from reading the scientific literature.
For the whole 150 years that amalgam has been used by dentists, there have been critics of the practice. But the majority of the scientific community has assumed that the amount of mercury we absorb from amalgam is too small to be a matter of concern. So the first step in making a case for mercury as a cause of PD is to present evidence that the amount of mercury absorbed from amalgam fillings is, in fact, sufficient to cause harm to sensitive individuals. Because if it doesn't cause harm in any other way, it is unlikely to be causing PD. And we should try to get some idea of how many individuals have some sort of mercury sensitivity. If it is rare, say one person in a thousand, that would still affect over 200,000 in North America. If it went as high as 10%, that would mean millions of people are being affected in one way or another by amalgam and by other sources of mercury.
Even though, if amalgam caused my PD, the damage is already done, I have a practical reason for wanting to know. As long as I had amalgam in my mouth, my body burden of mercury was increasing. Now that the fillings have been replaced, the amount of mercury in my body is decreasing but at a very slow rate. It has been estimated that it takes 20 to 40 years for natural processes to remove half of the mercury in the brain.
If mercury was the main cause of my PD then the mercury still in my body is hastening the progress of that PD. And anything I do to slow that progress will get interference from the remaining mercury. So it behooves me to get proactive about removing the mercury.
In early 2002, I got the last of my amalgam fillings replaced. Over the next year, my 50 year headache gradually faded away. The headache had not been continuous. Two 222's would make it go away for a day. From age 30 to 60, the headache returned, on average, 5 days a week. It was not a migraine, so I could live with it if I had to. In my teens and twenties I did just that. It was more intermittent then.
When the headaches got more persistent, I would mention them to my doctor during occasional checkups; he would ask a few questions, discover that 222's were working and then lose interest. This spurred me to do some research on my own. I discovered that headaches were taken seriously by practitioners of alternative medicine. Over the years I tried various vitamin supplements, gave up coffee, and avoided dissolved sugar. I mention these failed attempts because I didn't get much of a placebo effect from them. A few times I thought there might be a slight improvement but it never came close to the relief I have gotten from having my amalgam fillings removed. If the placebo effect were responsible this time, I think it would have been more of a factor in my earlier efforts.
In my early thirties, when I was doing graduate work at the University of Western Ontario, I got dental work done by student dentists — a few new fillings and a lot of old fillings replaced. My headaches got worse while I was at Western, but there was enough of a lag time between the dental work and the increase in frequency and intensity that I didn't make a connection. The following summer, I got hay fever for the first time. Once again, there was enough lag time that I didn't make the amalgam connection. I got hay fever every summer for 30 years; now that the amalgam is gone, I no longer get hay fever.
I had bad teeth as a child with lots of fillings. I don't remember how much time passed between my first filling and my first headache. But it was time enough that I made no connection. In retrospect it is obvious to me that I am more sensitive to mercury than the average person. And the amount of mercury released continuously by amalgam fillings is sufficient to affect me in the ways described (and perhaps in some ways yet to be discovered). I know intellectually that other explanations for the headaches and hay fever are possible but the pieces of this puzzle fit so well (with amalgam as the villain) that I have little doubt.
Every year there are dozens of survey articles in dentistry journals which address the question of amalgam safety. The authors review experiments bearing on this topic and then they pretty well all come to the same conclusion. The following from the abstract for The amalgam controversy. An evidence-based analysis, by JE Dodes (J Am Dent Assoc, 2001, Sep;132(3):p348-56) is typical:
"CONCLUSIONS: There are numerous logical and methodological errors in the anti-amalgam literature. The author concludes that the evidence supporting the safety of amalgam restorations is compelling. CLINICAL IMPLICATIONS: Amalgam restorations remain safe and effective. Dentists should educate patients and other health care professionals who may be mistakenly concerned about amalgam safety."
Congressman Burton, chair of a congressional hearing on amalgam, said on May 8, 2003, "What I want to know is why can't the NIH and the ADA find a connection between mercury and health effects? Sweden found 700 credible papers about the harmful effects of mercury, but the NIH and the ADA can't find one."
Dentistry must have its fair share of dishonest practitioners, but that has not been my experience. Without exception, every dentist that I have met has been a sincere, honest, skilled professional. So how to explain the dismissal of evidence of harm from amalgam?
Proving harm from amalgam is fraught with some of the same difficulties as proving harm from tobacco. When alarmists were trying to show (in the last century) that smoking tobacco was harmful, they kept being undermined by healthy ninety-year olds who had been smoking all their lives. For every study which showed harm, there were ancient nay-sayers demonstrating the opposite by the fact of their continuing survival. Plus, there was an occasional study which showed an absence of harm.
The problem is even worse with amalgam — the majority of people with amalgam in their mouth have no health issues that can be blamed on mercury. So it is easy to conclude that those with problems are being affected by something else. Or, perhaps their complaints are psychosomatic.
The science of toxicology makes a distinction between the amount of a single dose of a toxin required to do immediate obvious harm (acute toxicity) and the amount of repeated or continuous low level doses required to do harm (chronic toxicity) after years of exposure. The threshold amount for acute toxicity is generally much higher than for chronic toxicity. The term chronic doesn't necessarily connote harm. With amalgam we are getting chronic doses of mercury and the question is whether that dose is low enough to be safe or high enough to be toxic.
And there is another problem with mercury. It is very slow to be removed from our body. The result of this is that even at a chronic dose which our internal defenses can handcuff with ease, mercury accumulates in our kidney, liver, heart, prostate, pituitary gland, pineal gland, brain. It may take a while — five or ten or twenty years — but eventually, enough mercury will accumulate to interfere with normal function, especially in times of stress.
There was a time when dentists claimed that amalgam (50% mercury) was completely inert. This despite the fact that old fillings kept getting smaller. What were they thinking? That the disappearing amalgam was going straight to mercury heaven? It is now generally agreed that mercury is continuously absorbed from amalgam fillings. But the amount is still a matter of debate. And whether that amount is sufficient to do harm. A further complication is that some forms of mercury are much more reactive than others so it may matter whether the mercury is released as a gas, metal, mercury compound or microscopic pieces of amalgam. This makes theoretical determinations very difficult. One way around this difficulty is to examine people and animals that have amalgam in their teeth. The advantage of such experiments is that it doesn't matter how much mercury is being released or what form it is in. What matters is whether a certain number of fillings is capable of doing harm. A matched pair of such experiments illustrates some of the problems in reaching a conclusion that everybody can agree on.
Researchers Boyd et al at the University of Calgary put 12 fillings in the molars of six sheep. They measured how this affected the sheep's kidneys and called their report Mercury from dental "silver" tooth fillings impairs sheep kidney function (Am J. Physiol. 261: R1010-R1014, 1991). The title says it all. Though it should be noted that, while kidney efficiency was reduced, the animals were not obviously sick. The impaired kidney function would presumably be responsible for health problems somewhere down the road — far enough that (in a non-experimental setting) the root cause would escape detection.
Five years later, Sandburgh-Englund et al, at Karolinska Institute, Sweden, did an experiment with 10 humans and called their report No evidence of renal toxicity from amalgam fillings (Am J. Physiol. 271: R941-945, 1996). This study was intended as an answer to the Boyd study but there was an important difference in procedure. The authors conceded that the "optimal study design would be to insert a large number of amalgam fillings in subjects previously unexposed to amalgam fillings and matched with a control group receiving other dental filling materials. However, such a design is not realistic to conduct from an ethical, clinical, and practical point of view."
It is not clear to me why this design would be unrealistic. Agreed that inserting amalgam fillings in mouths that had no need for dental work would be immoral. But, every year, there must be thousands of young people who receive their first amalgam fillings (and are going to be getting amalgam whether they participate in an experiment or not). It shouldn't be too hard to find a few dozen willing to have their kidney function tested before and after. Instead of doing this, Sandburgh-Englund et al opted for a severely flawed design.
They found 10 healthy subjects with 13 to 34 amalgam fillings who were willing to have all fillings removed in one sitting (and replaced with something appropriate). A series of urine and blood samples were taken to measure kidney function and blood mercury.
Plasma mercury levels increased, as expected, by about 50% in the days immediately after amalgam removal; and then tapered off until, 2 months later, plasma mercury was half what it had been when the amalgam was still in place. Kidney function was unaffected. Their conclusion: "From the current investigation, it is concluded that there are no signs of renal toxicity in conjunction to and after mercury exposure from the removal of amalgam fillings."
If we take this conclusion at face value, it means that humans are less sensitive than sheep to mercury and that mercury levels from amalgam fillings are low enough to be safe for humans. The authors do concede, however, that "the present study obviously does not rule out the possibility that certain individuals susceptible to mercury do exist." This is an admission that it is possible that some humans could have the same reaction as the sheep.
But, because of the difference in design of the experiment, we can't take their conclusions at face value — producing a plasma mercury increase of 50% for a few days, by removing fillings, is not the same as placing amalgam fillings where none existed before and having them release mercury continuously every day for the two month duration of the trial as happened with the sheep. There are several points to be made here:
More recently, a study was done in Egypt which also measured kidney function but their experiment was much better designed than the Sandborgh-England experiment. Mortada et al called their report: Mercury in dental restoration: Is there a risk of nephrotoxicity? (J Nephrol 2002; 15: p.171-176). They recruited 49 subjects aged 26 to 36 with an average of 4.4 amalgam fillings. Then, for controls they found 52 subjects of a similar age and economic background who had no amalgam fillings. Then they did tests to determine how well their kidneys were working.
The kidney is a selective filter which cleans up the blood, keeping what is useful and discarding what isn't. There are standard tests which analyze urine for the efficiency with which the kidney is recycling the good stuff. In particular, if there is too much protein in the urine, something is wrong. They found that most of the markers of kidney efficiency were the same in both groups. But the amalgam group was losing twice as much albumin as the control group. This is a clear sign of kidney damage. The damage is not yet causing poor health but a few fillings are causing measurable kidney damage.
This experiment, like the others above, makes no attempt to address the question of mercury sensitivity. If we assume that the subjects were not especially sensitive, then this study shows that a small number of amalgam fillings is sufficient to cause harm in normal subjects. If, on the other hand, we assume that it was mercury sensitive individuals who affected the group average then there must have been a significant number of sensitive individuals in this group. Either way, we should be concerned.
Mercury sensitivity is central to the approach taken by Maths Berlin, Professor emeritus (University of Lund), who was commissioned by Swedish authorities, in 2003, to look at the published research. His report is summarized in: Mercury in dental amalgam: a risk analysis (SMJD, Vol 7, No 1, Nov 2004). He started by looking at the generally accepted range of mercury being absorbed, per day, from amalgam. The World Health Organization (WHO) gives a range of 3 to 17 mg for an average of 10 mg. Berlin observes that the size of variation and worst case scenarios are especially important in risk assessment. This is because he is interested in the level at which a small but significant percent of the population would be affected. The 3 to 17 mg given by the WHO is a normal range which means that those people with lots of filling will seldom absorb more than 17 mg. But this is not even close to being the highest possible amount. In fact, tooth grinders and compulsive gum chewers have had mercury absorption measured at 100 mg. And there are enough tooth grinders and gum chewers that the range to be considered in a risk assessment should take them into account
Berlin then turns to studies which document risk of harm, for exposures well within the expanded range: central nervous system (CNS), kidney, thyroid, immune system, foetal development. Most of the harmful effects would be sub-clinical. In other words, those harmed would be unaware for the time being. "However, as with other potent substances or pharmaceuticals, mercury is likely to induce more serious side effects with illness, or in those who are especially susceptible genetically."
When they got his report, the Swedish commission observed, "Professor Berlin reports that researchers have been able to show effects of mercury at lower concentrations than before. The conclusion he draws is that ‘the safety margin that it was thought existed with respect to mercury exposure from amalgam has been erased.’
Berlin ended his report with, "It is also recommended that use of amalgam for dental restorations in the population in general is abandoned and substituted with less toxic material, whenever this is available and affordable."
Not a complete condemnation, but a warning that we can no longer assume that amalgam is safe.
There are many ways in which the body protects itself against the poisonous effects of mercury. A defect in any of the systems for protection or elimination will lower the level at which a chronic dose goes from safe to toxic. Also, stress from sickness or some other environmental insult can reduce our ability to handle mercury. ApoE is of special interest to me, as one of the systems that govern mercury sensitivity, because it has been shown to be protective against harm from mercury and because it also has been demonstrated to have some influence on whether we get PD.
Our blood is mainly water, and oil and water don't mix, so oils cannot use the bloodstream (on their own) to get around. Enter lipoproteins, the truckers of the bloodstream. Their job is to take fat and cholesterol wherever it is needed and to cart away the garbage. Apolipoproteins are the protein part of the lipoprotein and behave a little like the tractor part of a transport where a bundle of lipids is the trailer.
There are a number of apolipoproteins (identified by letters from A through to E), all of them transport tractors, but with slight differences depending on their home and destination and also on some secondary functions they are able to perform. ApoE comes in three forms, apoE2, apoE3, and apoE4, but nobody has all three forms. Our genes are coded to manufacture apoE in pairs and the pair can be a matched pair of the same type, or an unmatched pair in any combination. The pair we are born producing is the pair we are stuck with for life. A matched pair of two apoE3's is the most common — 60%. 21% of us have an apoE3/apoE4 combo. 11% have apoE3/apoE2. The remaining 8% of the population has one of 2/4, 4/4 or 2/2.
All three forms do the trucking job, though apoE3 and apoE4 are best at that. The apoE2 combinations are just barely adequate under the best of circumstances; and the few people (less than 1%) who have the apoE2/apoE2 combination are most likely to have health problems connected with fat or cholesterol transport.
ApoE has been known and studied for many years, but it wasn't until 1979 that scientists realized that there were different forms of apoE. Over the next decade, the three types were identified and one of the first discoveries was that people with ApoE4 have the greatest tendency to develop Alzheimer's Disease. ApoE4 does not guarantee AD, it just creates a predisposition to getting AD — a 4/4 person is 15 times as likely as a 3/3 person to get AD.
Godfrey et al looked at mercury body burden in 400 patients with a lot of fillings: Apolipoprotein E genotyping as a potential biomarker for mercury neurotoxicity (Journal of Alzheimer's Disease, Vol 5, No 3, 2003, p.189 –195). They found higher mercury levels in patients with apoE4.
ApoE2 and apoE3 give some protection against mercury, whereas apoE4 does not. And since apoE4 creates a predisposition to AD, the question arises as to whether the lack of protection against mercury poisoning by apoE4 is the reason for this predisposition. Alzheimer Disease: Mercury as a pathogenic factor and apolipoprotein E as a moderator (Neuroendocrinology Letters, 2004, 25(5), 331-339), by Mutter et al, is a review article which argues that mercury from amalgam is a cause of AD. The argument is very persuasive to someone like myself who is inclined to think poorly of amalgam. It would not be quite so persuasive to those with a vested interest in maintaining that amalgam is safe.
Several studies have looked at the possibility that apoE4 is a risk factor for PD and got mixed results. More recently, twenty researchers collaborated on a large study which was designed to overcome some of the difficulties in the previous studies. Their report: YJ Li et al, Apolipoprotein E controls the risk and age at onset of Parkinson disease (Neurology 2004; 62: p.2005 – 2009). They concluded that their trial provided strong evidence that apoE4 is a risk factor for PD.
Since apoE3 and apoE2 provide greater protection than apoE4 against mercury, there is a connection to be made here (as well as in the case of AD) that amalgam is a contributing cause of PD. Not that the correlation is proof that mercury is a cause of PD. Just that the correlation should make mercury a suspect.
The fact that mercury is not even mentioned in the Li paper is interesting in itself. I have written to authors of scientific papers, from time to time, and found them very helpful. Unless, that is, I mentioned the word amalgam. Then I would get no reply. The exception was Dr. Michael Godfrey of New Zealand who wrote: "There are people on the planet who have financial fears regarding mercury and they have huge resources to lobby at the highest levels. These people include the tertiary insurance industry and thus world banking. They are far more of a problem than the ADA (American Dental Association) with their ego fears of being shown to have been wrong for 160 years."
A few North American researchers have stated publicly that they never had any problem getting funding for their research until they tried to do something on mercury from amalgam or thimerosal (mercury containing preservative used in vaccines and implicated in autism). Then the funding dried up.
The threat of billion dollar lawsuits may be part of the reason that no large epidemiological study has been done in North America to look for a connection between amalgam and PD. The only major study of this sort was done in Germany. Seidler et al reported their study of 380 PD patients from 9 German clinics in: Possible environmental, occupational, and other etiological factors for Parkinson's disease (Neurology 1996, 46: p.1275 – 1284).
The PD patients had a higher number of amalgam fillings than controls. This study confirms that amalgam is a risk factor for PD — the controls had less amalgam in their mouths than did the PD patients But there is a problem — the controls also had more missing teeth than the PD patients. And the history of those missing teeth is relevant. If most of the missing teeth were simply pulled rather than filled with amalgam, then the controls would have had less exposure to amalgam than the patients (as was assumed). But if those missing teeth had spent some number of years filled with amalgam before being pulled, then the controls' exposure to mercury could have been even greater than that of the PD patients. In that case, the conclusion would have to be reversed, ie. that amalgam protects against PD.
When I was a teenager and went to the dentist with a badly decayed tooth, the dentist would simply pull it rather than fill it. It wasn't until my late 20's that a dentist suggested a root canal. Since most of the controls were older than me, I'm inclined to accept that the controls in the German study had less amalgam exposure than the PD patients. But that conclusion is weakened by the lack of a dental history for both patients and controls.
Epidemiologist Michael Bates et al designed a study which avoids this problem. The armed forces of New Zealand have their own dental service and keep pretty good records. The researchers obtained records for 20,000 members of the NZDF from 1977 to 1997 and used National Health records to discover if there was any correlation between number of fillings and health problems. The original intention was to follow this group into old age. If this is done it will be definitive. For now we have an interim report of limited usefulness: Health effects of dental amalgam exposure: a retrospective cohort study (Int J Epidemiol, 2004; 33: p.894-902).
The problem with this interim report is the youth of the participants. In 1997, the average participant was in their 30's; there were a few seniors but 84% of the cohort was 45 or less. At this age, those among them who were mercury sensitive would have nuisance problems like headache, hay fever, memory loss, excessive salivation or perspiration (precursors to more serious problems) but they wouldn't necessarily report their symptoms to the Health Service. Nobody likes to be thought a hypochondriac.
In another 20 years, cases of PD and AD will just be starting to show up in sufficient numbers to allow a statistical evaluation of whether they are correlated with number of fillings. And it will be twice that long (ie. 2037) before most such cases appear. In this interim report there are a few cases of MS and they appear to be related to a high number of fillings, but there are too few cases for the correlation to be statistically significant.
Bates et al have funding problems, so this study may never bear fruit. But even if this study were continued and showed, beyond doubt, a connection between amalgam and PD, that would not be the end of the matter. A weakness of epidemiological studies is that they find correlations — they don't prove cause and effect. Two oddball correlations have cropped up in epidemiological studies: (1) smokers are less likely to get PD; (2) the more education you have, the more likely you are to get PD. Further study has revealed that nicotine stimulates defense systems and probably does protect against PD so there is a direct cause and effect relationship.
In the second case, there is nobody contending that education causes PD. Rather, there must be something, that educated people have in common, that predisposes them to PD. One possibility is that educated people are less likely to smoke. This is true at the present time, but was it true 40 years ago when those with PD today started to lose neurons? Think of the number of doctors in the 1960's and 70's who were smokers. Maybe not. My preferred explanation is that people with higher education and income take better care of their teeth. Unfortunately, this means catching cavities early and getting teeth filled rather than pulled. So more exposure to amalgam.
In sum, there are a lot of arrows pointing at amalgam as a possible cause of PD. But no irrefutable proof. And there is no experiment on the horizon which is capable of proving, beyond doubt, that amalgam is, or is not, a cause of PD. On the other hand, on the general question of harm from amalgam, we are getting into duck territory here, as in it looks, walks, and quacks like one. Could it be a harmless pigeon? Of course. Even though the Egyptian trial clearly showed kidney damage, nothing becomes established fact, in the land of science, until an experiment has been repeated several times by different scientists who test different subjects and arrive at the same conclusion.
But with so many studies showing some degree of harm, even at very low mercury levels, it has become unrealistic to maintain that amalgam is safe. At the very least this is an annoying duck. And there are strong indications that it is more than just annoying. Worst case, this is a duck from hell.