Neuroendocrinology Letters Volume 27 No. 4 September 2006
Mercury toxicity presenting as chronic fatigue, memory impairment and depression: Diagnosis, treatment, susceptibility, and outcomes in a New Zealand general practice setting (1994–2006).
In a group of 465 patients diagnosed as having chronic mercury toxicity (CMT), 32.3% had severe fatigue, 88.8% had memory loss, and 27.5% had depression. A significant correlation was found between CMT and the Apo-lipoprotein E4. Removal of amalgam mercury fillings when combined with appropriate treatment resulted in a significant symptom reduction to levels reported by healthy subjects.
In the 1991 WHO Environmental Health Criteria No.118 (Inorganic Mercury) a list of 9 recommendations for further research was given and amongst them was the development of tests to identify individuals with special sensitivity to mercury . In 1997, homozygous apolipoprotein (APO-E)-E4/4 was identified as a significant risk factor for early onset Alzheimer’s senile dementia (AD) with APO-E2 being identified as protective against AD . Several subsequent papers failed to clarify the reason. APO-E has 299 amino acids with different ratios of cysteine and arginine at position 112 and 158. APO-E2 has 2 cysteines, apo-E3 one cysteine and one arginine, and APO-E4 two arginines . As arginine, unlike cysteine, lacks the sulphydryl (SH) groups to potentially bind bivalent metals such as mercury, lead, copper or zinc, it would be logical to suspect the possibility of increased metal accumulation in those chronically exposed individuals who had not inherited APO-E2.
In 2003, Godfrey and associates presented evidence that the APO-E4 allele was unable to bind to mercury and assist in its elimination . Additional evidence has shown that mercury creates the unique brain lesions found in the AD brain [10, 13, 23]. The literature on the relative APO-E distribution since 1995 indicates that 1–2% of the population has homozygous APO-E4, approximately 20% heterozygous APO-E3/4, 50–60% APO-E3/3, and the remainder having small percentages of E2/2 or E2/3 and E2/4 . In patients with evidence of chronic mercury toxicity (CMT) there was a statistically significant shift to the right with 3.6% having APO-E4/4 and 30% having APO- 3/4 . The study presented here was designed to test the clinical validity of our earlier findings.
Excerpts from the Discussion section:
In our opinion based on APO-E genotyping, for controls with unrecognised homozygous APO-E4, any exposures to mercury could place them potentially at greater risk of adverse neuro-psychiatric effects than someone with amalgam but an inherited APO-E2. Further strength to this was given by Jin et al. reporting on the adverse effects of thimerosal an ethyl-mercury preservative. They showed that thimerosal increased inflammatory pain receptor activity by oxidizing SH on cysteine residues but that this could be prevented by the co-application of a reducing agent, di-thiothreitol. It is therefore biologically plausible that those with less SH groups would be more prone to CMT than others. A 50% reduction in methionine synthetase has also recently been confirmed several days after exposures to ethylmercury as thimerosal . Notably, methionine synthetase is a vital prerequisite for glutathione production.
Biochemistry is thus beginning to explain the predominantly limbic dysregulation and autonomic nervous system malfunction that typifies these chronically ill patients with their numerous complaints of chronic fatigue, headaches, irritability, myalgias, impaired thermo-regulation and short-term memory loss.
Although these symptoms are all-too-often dismissed as neuroses they appear to be due to a heavy metal organic brain toxicity syndrome in many cases.
Others experienced in environmental and heavy metal toxicology, have observed the real clinical benefits of protected removal of amalgam when combined with appropriate detoxification . Lindh et al. from Uppsala University, Sweden, included 796 patients in their retrospective study using a similar symptom questionnaire. In the Lindh study they categorized the subjects into 3 groups for comparison. The smallest group became worse within the three year period after amalgam removal, the next smallest group showed no change in relative health and the third group, the largest (70%), showed marked improvement. Reviewing the mercury levels in their blood showed the group with marked improvement had the highest pre-amalgam removal blood mercury levels and the lowest three years after removal.
The group that continued to get worse had the lowest pre-amalgam removal blood mercury levels and the highest three years after removal. The intermediate group fell in between these levels.
This data can be explained by implying the group with marked improvement was better at excreting mercury than the group that continued to deteriorate. Also, blood levels in low level mercury exposures seem to be a measure of ability to excrete more than a measure of level of exposure.
Lindh et al. thus recognised that there was a previously unidentified factor, where some people were apparently better able to eliminate mercury from amalgam, whereas others were not and recommended further research into the development of laboratory tests to help identify these patients. Our study was therefore designed to see if patients in the primary health or general practice environment could be assisted by early identification of an underlying genetic factor.
Correct diagnosis and appropriate treatment would then obviate the often costly and inappropriate investigations experienced by patients in their previous search for medical help that can span decades as also mentioned in the Lindh paper. The significant reduction in the properly treated CMT patients’ symptom score to that of the non-CMT patients bears this out.
According to the WHO, dental amalgam is the greatest source of mercury body burden in the nonoccupationally exposed populations . Furthermore, the 1996 Health Canada report on dental amalgam revealed that the maximum tolerable daily intake (TDI) of mercury vapour would be reached from 4 average sized amalgam fillings (or 8 tooth surfaces) for a 70 kg adult when based on industrial safety levels . Even though we used post-DMPS urine Hg levels to indicate exposures and accumulation, stool mercury levels could apparently be even more relevant. In this regard,
Osterblad et al. found that 92 subjects with amalgam had 13 times more fecal mercury than 43 never exposed to amalgam and 56 in whom amalgam had been removed.. Further recent mercury research involving PET scans and MRI showed severe reductions in metabolism in hippocampus, medial thalamus, mammillary bodies and posterior cyngulate .
The conclusions of these authors that “The amnesia of very early AD reflects severe but localised limbic dysfunction” thus supports our memory loss findings in the field of primary health medicine.
This research supports a correlation between a genetic inability to eliminate mercury when the APOE4 allele has been inherited and an increased incidence of common symptoms and signs of chronic mercury toxicity. APO-E genotyping is thus a clinically useful additional investigation to help identify these susceptible patients and dental amalgam needs to be considered as a potential underlying and treatable cause of chronic non-specific ill-health in the predominantly middle-aged population.