Some science behind the scenes

Mercury poisoning treatment

There cannot be one treatment for all the forms of mercury poisoning because each of the different types of mercury – elemental, organic and inorganic work their destructive influences in different ways.  In effect you need to know the compound that poisoned you before you can effectively treat the poisoning.

But of course, most of the time, we don’t, which means a rather unsatisfactory form of crude blanket treatment has emerged which occasionally helps and occasionally does not.  Given the prevalence of the problem and the increasing risks we all face, there is a sort of urgency about finding a better way of dealing with this [aside from banning mercury in all things, which might be the best solution].

Chelation

The treatment devised for all heavy metal poisoning is called chelation therapy.  Chelation therapy is the administration of ‘chelating agents’ to remove heavy metals from the body.

It has a long history of use in clinical toxicology, however, self-administration of chelating agents for suspected poisoning is a hazardous thing to do and has caused problems.  As the medics say “Chelation therapy can be hazardous if administered incorrectly”. For the most common forms of heavy metal intoxication—those involving lead, arsenic or mercury — a number of chelating agents have been suggested.

  • DMSA dimercaptosuccinic acid has been recommended for the treatment of lead and mercury poisoning.  DMSA is the most frequently used for severe methylmercury poisoning, as it is given orally, has fewer side-effects, and has been found to be superior to BAL, DPCN, and DMPS.
  • DMPS - 2,3-dimercapto-1-propanesulfonic acid 

The clinical analysis of mercury poisoning in 92 cases]. - [Article in Chinese] - Liu XL et al ;  Department of Nephrology, Affiliated Hospital of the Academy of Military Medical Sciences, Poison Control Center of PLA, Beijing 100071, China.

OBJECTIVE:
To summarize the clinical features of mercury poisoning diagnosed by blood and urine tests for improving the diagnosis and treatment of the disease.

METHODS:
Poisoning causes, clinical manifestations, diagnosis, treatment and prognosis were retrospectively reviewed in 92 in-patients with mercury poisoning in our hospital from January 2000 to April 2010.

RESULTS:
Of the 92 patients, 37 were male and 55 were female with an average age of 33.1 (2 - 65) years old. The mercury poisoning was caused by occupational exposure and non-occupational exposure, such as iatrogenic exposure, life exposure and wrong intake or suicidal intake of mercury-containing substances, mainly through respiratory tract, digestive tract and skin absorption. The most common clinical symptoms were as the followings:

  • nervous system symptom, such as memory loss in 50 cases (54.3%),
  • fatigue in 34 (37.0%),
  • numb limb in 25 (27.2%),
  • dizziness and headache in 22 (23.9%),
  • cacesthesia in 20 (21.7%),
  • fine tremor (finger tip, tongue tip, eyelids) in 15 (16.3%),
  • insomnia and more dreams in 12 (13.0%);
  • gastrointestinal symptoms: nausea in 16 (17.4%), abdominal pain in 14 (15.2%), stomatitis in 5 (5.4%);
  • joint and muscle symptoms: muscle pain in 16 (17.4%), joint pain in 5 (5.4%);
  • cardiovascular system: chest tightness, heart palpitations in 6 (6.5%);
  • urinary system: edema in 9 (9.8%);
  • other system: hidrosis in 20 (21.7%).

After the treatment with sodium dimercaptopropane sulfonate (DMPS), the symptoms were gradually alleviated. Their gastrointestinal, cardiovascular symptoms were alleviated within 2 weeks; neurological symptoms were alleviated within 3 months; kidney damage showed a slower recovery and could be completely alleviated within 6 months.

CONCLUSIONS:
Because of its diverse clinical symptoms, the mercury poisoning was easy to misdiagnosis and missed diagnosis; therefore the awareness of the disease should be further enhanced. Leaving from the poisoning environment timely and giving appropriate treatment with DMPS will lead to a satisfactory prognosis.

  • DHLA - dihydrolipoic acid
  • DPCN - D-penicillamine
  • NAP - The drug NAP (n-acetyl penicillamine) has been used to treat mercury poisoning with limited success.
  • BAL - dimercaprol
  • ALA - alpha lipoic acid  - Alpha-lipoic acid (ALA) has been shown to be protective against acute mercury poisoning in several mammalian species when it is given soon after exposure; correct dosage is required, as inappropriate dosages increase toxicity. Although it has been hypothesized that frequent low dosages of ALA may have potential as a mercury chelator, studies in rats have been contradictory.  This is one product that has to be used with considerable care….

Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity - Patrick L

Many unanswered questions remain regarding ALA and heavy metal detoxification, especially pertaining to mercury. The amount of ALA supplemented versus the amount of toxic metal stored in the tissues is important, and has been clearly detailed in animal trials. A molar ratio of 6-8:1 (ALA:mercury) is necessary for protection and viability in mercury studies; a ratio of 2:3 has been seen in arsenic studies.

The ability of ALA to assist or prevent movement of heavy metals from the liver appears to be element-specific.  In a previously mentioned study, the biliary release of methylmercury, cadmium, zinc, and copper was inhibited by ALA. The evidence that ALA may mobilize heavy metals to other tissues from tissues where the metals are most concentrated, specifically the brain, is troublesome. An explanation for this finding may lie in the complexing of heavy metals with glutathione and lipoic acid.

Inorganic mercury forms stable complexes with ALA or DHLA and could be excreted with DHLA independent of available glutathione. As Gregus et al hypothesize, injected lipoic acid could complex with glutathione as it passes through the liver, preventing glutathione from carrying other heavy metals such as cadmium, or transition metals such as zinc and copper, into bile. Speculation aside, there is clear evidence ALA and its reduced form DHLA have the ability to act as both intra- and extracellular heavy metal-complexing agents, with little known toxicity and patterns of heavy metal mobilization and transport not yet understood in humans.

In the absence of data from human trials, however, it can only be suggested that ALA be used as an adjunct to chelation with the standard dithiols, DMPS and DMSA.

PMID: 12495372

Antioxidants, vitamins and minerals

In addition to the chelating agents, whose aim is to rid the body of the mercury, there are added suggestions for protective chemicals such as Vitamin C, glutathione, selenium and zinc.

Generally speaking the more competent alternative medicine community recommends the use of either chelation or antioxidants etc , but not both at the same time, although for some reason those in research and the medical community appear to believe that they should be tested together……..

Mercury elimination with oral DMPS, DMSA, vitamin C, and glutathione: an observational clinical review - Muran PJ.;  Longevity Healthcare Center, San Luis Obispo, CA, USA.

Tissue mercury levels in humans have increased during the past 50 years to an alarming concentration, with possible deleterious effects that may involve neurological, cardiovascular, and immunological pathology.

This article reviews the protocol for the use of oral 2,3-dimercaptopropane-1-sulfonate (DMPS) and oral meso-2, 3-dimercaptosuccinic acid (DMSA) in combination with intravenous glutathione and high-dose vitamin C for treatment of high-level mercury.

This protocol yielded an average 69% reduction of urine mercury by provocation analysis.

So even used together they have some effect.  BUT this is not the recommended route, the recommended route is either chelation or antioxidant and mineral but not both.

The use of selenium and zinc as protective agents appears to get support from the research community as well as the alternative medicine community.  It is clear why when you see what effects mercury has on selenium – it depletes it.  But it is clear that selenium must not be used with the chelation agents. 

The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury - Rooney JP;   Centre for Synthesis and Chemical Biology, Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, Dublin 2, Ireland.

Mercury has been a known as a toxic substance for centuries. Whilst the clinical features of acute mercury poisoning have been well described, chronic low dose exposure to mercury remains poorly characterised and its potential role in various chronic disease states remains controversial. …...

Chelation agents such as the dithiols sodium 2,3-dimercaptopropanesulfate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) are the treatments of choice for mercury toxicity. Alpha-lipoic acid (ALA), a disulfide, and its metabolite dihydrolipoic acid (DHLA), a dithiol, have also been shown to have chelation properties when used in an appropriate manner. ……

Zinc and selenium have also been shown to exert protective effects against mercury toxicity, most likely mediated by induction of the metal binding proteins metallothionein and selenoprotein-P.

Evidence suggests however that the co-administration of selenium and dithiol chelation agents during treatment may be counter-productive.

PMID: 1740884

 

Glutathione has not been proven and would have to be very carefully used depending on the particular mercury compound with which one has been poisoned. Glutathione occurs naturally in the body, as such logic might infer that adding glutathione tablets might help by boosting the body’s glutathione store.  But the very fact it is unable to deal with some mercury compounds naturally,  - that despite the fact it exists in the body with a role of combating toxins, under some circumstances it appears to be unable to do so – does leave a shadow of doubt in the mind of most researchers

Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity - Patrick L

Mercury exposure is the second-most common cause of toxic metal poisoning. Public health concern over mercury exposure, due to contamination of fish with methylmercury and the elemental mercury content of dental amalgams, has long been a topic of political and medical debate.

Although the toxicology of mercury is complex, there is evidence for antioxidant protection in the prevention of neurological and renal damage caused by mercury toxicity. Alpha-lipoic acid, a coenzyme of pyruvate and alpha-ketoglutarate dehydrogenase, has been used in Germany as an antioxidant and approved treatment for diabetic polyneuropathy for 40 years.

Research has attempted to identify the role of antioxidants, glutathione and alpha-lipoic acid specifically, in both mitigation of heavy metal toxicity and direct chelation of heavy metals. This review of the literature will assess the role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity.

PMID: 12495372

The endogenous thiol-containing molecules – glutathione, cysteine, homocysteine, metallothionein, and albumin – all contain reduced sulfur atoms that bind to mercuric ions and determine the biological fate of mercury compounds in the body.  On the whole, endogenous thiols transport mercury compounds and act to protect them from binding to other proteins, preventing functional damage in that tissue.  Furthermore, the higher the cysteine or thiol concentration in a cell medium, the lower the concentration of intracellular divalent mercury. In other words, higher concentrations of thiols appear to protect against accumulation of mercury, both in vivo and in vitro.

On the other hand, after being released from cells in a complex with reduced glutathione, methylmercury is degraded in the bile duct to an L-cysteine complex and is able to cross the blood-brain barrier complexed with Lcysteine in a molecule resembling methionine.

I make no comment for very obvious reasons, but I will leave the last word to a researcher……………

Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity - Patrick L

Glutathione has been shown to be a significant factor in heavy metal mobilization and excretion, specifically with application to mercury, cadmium, and arsenic. Glutathione depletion and glutathione supplementation have specific effects on mercury toxicity, both by altering antioxidant status in the body and by directly affecting excretion of mercury and other heavy metals in the bile.

Lipoic acid has been shown, by its increasing of cellular glutathione levels, to support the mobilization and excretion of mercury, and to decrease cellular damage and neurotoxicity.

PMID: 12495372

Neurotoxicology 2012 Jun;33(3):476-81. Epub 2012 Mar 20;  Glutathione-mediated neuroprotection against methylmercury neurotoxicity in cortical culture is dependent on MRP1 - Rush T, Liu X, Nowakowski AB, Petering DH, Lobner D;   Department of Biomedical Sciences, Marquette University, Milwaukee, WI 53233, USA.

Methylmercury (MeHg) exposure at high concentrations poses significant neurotoxic threat to humans worldwide. The present study investigated the mechanisms of glutathione-mediated attenuation of MeHg neurotoxicity in primary cortical culture.

MeHg (5 mu-M) caused depletion of mono- and disulfide glutathione in neuronal, glial and mixed cultures

Supplementation with exogenous glutathione, specifically glutathione monoethyl ester (GSHME) protected against the MeHg induced neuronal death. MeHg caused increased reactive oxygen species (ROS) formation measured by dichlorodihydrofluorescein (DCF) fluorescence with an early increase at 30 min and a late increase at 6h. This oxidative stress was prevented by the presence of either GSHME or the free radical scavenger, trolox. While trolox was capable of quenching the ROS, it showed no neuroprotection.

Exposure to MeHg at subtoxic concentrations (3 ?M) caused an increase in system x(c)(-) mediated (14)C-cystine uptake that was blocked by the protein synthesis inhibitor, cycloheximide (CHX). Interestingly, blockade of the early ROS burst prevented the functional upregulation of system x(c)(-). Inhibition of multidrug resistance protein-1 (MRP1) potentiated MeHg neurotoxicity and increased cellular MeHg.

 Taken together, these data suggest glutathione offers neuroprotection against MeHg toxicity in a manner dependent on MRP1-mediated efflux