Mercury Clearence and d-Penicillamine

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Exogenous mercury

My initial interest is largely attributed to a recent Swedish book [1]. Although I remain skeptical to many suggestions given there (and in many other "saved patient's books"), I am not so certain that this aspect can be regarded unimportant. The mercury load may not be so impressive in most cases - and may indeed be so in singular ones.
Amalgam is widely dissepated among people and can only be considered one among several factors which worsens MS in predisposed persons but not strictly a causative factor. It has been used in dentristy since its invention in 1833 (mercury already since 1819 in other combinations), was forbidden the first time in New York in 1839 but returned in 1855. In 1898, a case of mercury neurosis caused by amalgam fillings was published. In Germany, 1928, Alfred Stock tried to get amalgam fillings prohibited - as we know in vain [1]. In 1966, Baasch suggested a connection between amalgam and MS and thereby opened an emotional discussion pro-&-contra [2,3]; for discussion is referred to some review articles [4,5]. In a Swedish publication, Ahlot-Westerlund found an 8-fold increase in the mercury levels in MS. Firnhaber et al. [6] found that 51 MS patients suffered more recently from carious teeth than a "control group" of 51 epileptics. Ingalls [7] suggests the amalgam causality and makes aware that a second heavy metal, lead, may operate almost interchangeable with mercury. Siblerud et al. [8] found a depressed red blood cell picture, decreased thyroxine and se-IgG levels, increased blood urea nitrogen level and fewer T-lymphocytes and T-8 (CD8) suppressor cells in MS patients with amalgam fillings preserved compared to MS patients who had their amalgam removed. Hair mercury was higher in the amalgam group. In the amalgam group there were 33.7% more exacerbations during the last 12 months.
Huggins and Levy [9] found dramatic changes of photolabelling of cerebrospinal fluid proteins following these dental interventions. They gave an exellant explanation of mercurys neural toxicology which is reproduced in the following:
" ... mercury is released from dental amalgam in the form of Hg0 ... [this] is more likely than Hg2+ to concentrate in the CNS after it has passed the blood-brain barrier ... Once in the brain, it is oxidized by the intracellular hydrogen peroxide-catalase system to its divalent cation, Hg2+. Since the Hg2+ form cannot diffuse out of the different nerve cells after this transformation, mercury gradually accumulates in the brain.
"Mercury has a number of mechanisms leading to toxicity in biological systems. These include the following:


"Mercury is unevenly distributed in the brain and spinal chord, with the heaviest deposits found within the motor nuclei of the rhomboencephalon ...".
In contrast, in a recent publication, Brieger et al. [10] warned against the error performed by MS patients in seing their disease as a result of mercury poisoning. Fung et al. [11] found that the concentrations of mercury and the mercury/selenium molar ratios in autopsy brain preparations were significantly lower in the hippocampi of multiple sclerosis patients as compared to age-matched controls. No statistically significant differences were detected for the concentrations of mercury and the mercury/selenium molar ratios for the remaining six brain regions among these groups. In a similar study, Clausen [12] found no significant differences between the deceased patients with and without MS concerning total mercury. However, the lipid-soluble mercury (preferably methyl-mercury) expressed per cell unit (DNA) was found significantly decreased in MS. These data may be explained either by a wash-out of lipid soluble mercury due to break-down of the blood-brain barrier in MS or to abnormalities in methylation processes probably related to the vitamin B12-metabolism in MS. In some contrast to these observations, McGrother et al. [19] found excess dental caries among MS cases as compared to controls in a case-control study. (Unknown position: [13]).

In conclusion, this question (as most other clinical ones) cannot be solved in the contradictory literature, unless these are selected according to the bias of the seacher. Small studies on a limited amount of patients are as little impressive as enthusiastic claims of success with amalgam removal. Although the toxicity of mercury is out of question, its pathological role in MS remains speculative. Even if it plays a role in some patients (accepting MS as a group of diseases rather than a single entity), it is still not proved that removal of ancient amalgam fillings causes any improvement. As almost usual in medical reasoning, also the opposite remains unproved.
Various measures have been suggested in order to avoid too large serum-mercury levels exactly in connection to the removal of dental amalgam. They may include the ingestion of various antioxidants and penicillamine both before and after this measure. More important are especially "physical measures" to be taken by the dentist, in order to avoid swallowing off amalgam particles - aparently not an easy topic.

d-Penicillamine

As a scavenging agent of various heavy-metal poisonings, including mercury and lead, the drug d-penicillamine has gained a prominent position. Indeed, some studies suggest a positive effect of d-penicillamine in MS [14,15,16], including a recent experimental study [17], whereas one turned out negatively [18]. This is, however, no proof that heavy metals are ethiologically important in MS: penicillamine has been found effective in rheumatoid arthritis and other autoimmune diseases, and quite possibly for different reasons. Both the tissue-type plasminogen activator (t-PA) and the metalloproteinase gelatinase B (MMP-9) are interconnected in an enzyme cascade which contributes to destruction of the blood brain barrier and demyelination, and both enzymes are inhibited by d-penicillamine [16]. Moreover, additional antiviral properties have been attributed to this drug, thus providing similarity to interferon-beta (IFB) which was first used in MS due to the infectious theory and later preferred for its modulation of the immune system, including inhibition of MMP-9. However, the adverse effects of penicillamine are much more pronounced than those of IFB and will probably not allow a prolonged therapy. For "pulsation therapy" of a few weeks duration in response to relapses of the disease, it remains an interesting, though currently insufficiently studied alternative.

Update 2009:

Finally, the American FDA admitted what was long a fact in other nations (e.g. Sweden, Canada and France) where the use of amalgam is forbidden or restricted: "The mercury contained in silver dental fillings may pose neurological risks to children and pregnant women" [20]. The first step on a strangely neglected way of who are else exposed to the risk of amalgam.

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Literature:
 
  1. Birgitta Brunes, Adina Bergli: "Från MS-diagnos till bättre hälsa". Larson's Forlag, 1996. (ISBN 91-514-0305-6)
  2. Baasch E. [Theoretical considerations on the etiology of multiple sclerosis. is multiple sclerosis a mercury allergy?] Schweiz Arch Neurol Neurochir Psychiatr 1966;98:1-19.
  3. Baasch E. [Supplements to the heavy metals allergy theory of multiple sclerosis and follow-up investigations in patients following amalgam restauration.] Schweiz Arch Neurol Neurochir Psychiatr 1968;101:104.
  4. Eneström S, Hultman P. Does amalgam affect the immune system? a controversial issue. Int Arch Allergy Immunology 1995;106:180-203.
  5. Eley BM, Cox SW. The release, absorption and possible health effects of mercury from dental amalgam: a review of recent findings. British Dental J 1993;175:355-62.
  6. Firnhaber W, Orth H. The pathogenic importance of tooth disease in multiple sclerosis. comparative study of 51 multiple sclerosis patients and epileptics. J Neurol 1977;215:141-50.
  7. Ingalls TH. Epidemiology, etiology, and prevention of multiple sclerosis. hypothesis and fact. Am J Forensic Med Pathol 1983;4:55-61.
  8. Siblerud RL, Kienholz E. Evidence that mercury from silver dental fillings may be an etiological factor in multiple sclerosis. Sci Total Environ 1994;142:191-205.
  9. Huggins HA, Levy TE. Cerebrospinal fluid protein changes in multiple sclerosis after dental amalgam removal. Altern Med Rev 1998;3:295-300.
  10. Brieger P, Schulte-Mattler W, Zierz S. [Delusion of mercury poisoning in multiple sclerosis] Nervenarzt 1996;67:785-8.
  11. Fung YK. Meade AG. Rack EP. Blotcky AJ. Brain mercury in neurodegenerative disorders. J Toxicol - Clin Toxicol 1997;35:49-54.
  12. Clausen J. Mercury and multiple sclerosis. Acta Neurol Scand 1993;87:461-4.
  13. Warren HV, Horksy SJ, Gould CE. Quantitative analysis of zinc, copper, lead, molybdenum, bismuth, mercury and arsenic in brain and other tissues from multiple sclerosis and non-multiple sclerosis cases. Sci Total Environ 1983;29:163-9.
  14. Seelig MS, Alba A, Berger AR, Rudez A, Tarlau M. Pilot study of d-penicillamine, vitamins and minerals in multiple sclerosis. J Clin Psychiatry 1978;39:170-4.
  15. Lodemann E. [D-Penacillamine. From constituent of penicillins to significant drug]. [In German] Naturwissenschaften 1979;66:462-6.
  16. Dubois B, D'Hooghe MB, De Lepeleire K, Ketelaer P, Opdenakker G, Carton H. Toxicity in a double-blind, placebo-controlled pilot trial with D-penicillamine and metacycline in secondary progressive multiple sclerosis. Multiple Sclerosis 1998;4:74-8.
  17. Norga K, Paemen L, Masure S, et al. Prevention of acute autoimmune encephalomyelitis and abrogation of relapses in murine models of multiple sclerosis by the protease inhibitor D-penicillamine. Inflammation Research 1995;44:529-34.
  18. Cendrowski W Czlonkowska A. Penicillamine in multiple sclerosis. Therapeutic trial and design of uncontrolled pilot drug study. Acta Neurol Scand 1976;54:281-6.
  19. McGrother CW, Dugmore C, Phillips MJ, Raymond NT, Garrick P, Baird WO. Multiple sclerosis, dental caries and fillings: a case-control study. Br Dental J 1999:187:261-4.
  20. http://www.prisonplanet.com/fda-reluctantly-admits-mercury-fillings-have-neurotoxic-effects-on-children.html
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Revised Jan. 6, 2009