June 21, 2007

Assessment of Chronic Mercury Exposure and Neurodegenerative Disease

Just got an email from someone at UC Berkely. He sent me his Thesis:

I just finished my M.S. thesis at UC Berkeley, Environmental Health Sciences division and have spent the last 3 years asssessing the links between mercury exposure and neurodegenerative disease. Attached is a pdf of the results. I think that it may be illuminating on such a complicated topic.

Dan R. Laks, M.S.

Assessment of Chronic Mercury Exposure and Neurodegenerative Disease - additional pdf
Dan R Laks, Environmental Health Science
M.S. Thesis, U.C. Berkeley

It is a long read (130 pages) but looks to be interesting and comprehensive. Thought I would post if for you.

His conclusions recommendations:


At this time, a scientific consensus suggests that the global rate of atmospheric mercury deposition may be increasing over time1. In addition, the latest studies suggest that as global mercury deposition increases, the incidence of the most closely associated neurodegenerative diseases such as Autism and Alzheimer’s Disease are rising as well 2, 3. Recent studies suggest that the incidence of Autism and Alzheimer’s Disease may be rising in heavily industrialized countries around the world, in the same regions where unprecedented mercury levels have recently been found in women and children, fish and animals, rice and soil 4. These trends support the theory that both chronic mercury exposure and associated risks of neurodegenerative disease may rise over time within the general U.S. population.

Due to the bioaccumulation of organic mercury in food sources, atmospheric deposition of mercury vapor ultimately deposits mercury in the human pituitary, liver, immune system, adrenals, and kidney. The accumulation of targeted mercury deposition may disrupt the endocrine and immune systems, damage the delicate balance between inflammation and suppression, and elevate risks of neurodegenerative disease. As emissions of mercury into the atmosphere increase on a global scale, it is
logical to assume that the rate of chronic mercury exposure and deposition in target areas of the human body will increase as well.

Our analysis of chronic mercury exposure trials tested a hypothesis that a suitable method for assessment of chronic mercury exposure would observe the change of I-Hg that results from CH3Hg exposure, demethylation, and deposition. The regression of I-Hg to CH3Hg was effective at distinguishing different exposure groups in a trial of chronic mercury exposure. This is significant as it provides a method for assessment of chronic, organic mercury exposure by the rate of inorganic mercury deposition.

From the NHANES study, data are sufficient to conclude there is an association between chronic, organic mercury exposure and inorganic mercury deposition in target systems of the human body. This study concludes that blood I-Hg and methyl mercury levels should both be accurately measured in order to serve as bioindicators for the assessment of chronic mercury exposure. Our analysis of the NHANES population reports an association between organic and inorganic mercury levels in the blood. This is consistent with other studies that demonstrate demethylation of organic mercury as a contributing source of I-Hg deposition within the body. Our study reports evidence that chronic mercury exposure and resultant deposition are associated with changes in biochemical markers for the liver, immune system, and pituitary. Luteinizing hormone, white blood cell count, and bilirubin levels are all biomarkers associated with chronic, organic mercury exposure. This is significant as it demonstrates for the first time within the U.S. population, that chronic, organic mercury exposure is
associated with targets of inorganic mercury deposition. Blood I-Hg was the most accurate bioindicator to characterize susceoptible subpopulations, women ages 35-39 years, and African American women ages 16-49 years. The method presented here for the assessment of chronic mercury exposure should be further tested as a method to define subpoplations most susceptible to further mercury exposure.

Biological Mechanism for Mercury Exposure and the Risks of Neurodegenerative Disease

The 2004, IOM report on vaccines gave an assessment of a biological mechanism regarding vaccines and Autism and concluded that there was no human evidence of an immune response that associates thimerosal exposure with autism 110. Results from this thesis report provide human evidence, within the U.S. population, of a biological mechanism and a causative relationship between mercury exposure, immune dysregulation, and the risk of Autism.

Reported, direct associations between I-Hg and organic mercury suggest that demethylation of organic mercury within the body is a contributing source of I-Hg deposition. The process of I-Hg deposition occurs in targets of the endocrine and immune system and may lead to an elevated risk of neurodegeneration. As Webster et al. discuss in their review, “disturbances at any level of the hypothalamic-pituitary-adrenal axis or glucocorticoid action lead to an imbalance of this system and enhanced susceptibility to infection and inflammatory or autoimmune disease60”. I-Hg deposition in white blood cells would produce a similar effect on the immune system, with resulting immune imbalance leading to increased risks of autoimmune disease.

Associations with the liver (bilirubin) reiterate concern that mercury deposition may increase enterohepatic circulation, raise the absorption rate of mercury, and thereby elevate susceptibility to future exposure such as from vaccines containing ethyl mercury. As the rate of mercury deposition accelerates with exposure, so do the risks of disease. I-Hg deposits accumulate over years in targets of the immune and endocrine system. Infants are particularly susceptible to exposure as they have no
microflora in their GI tract to help eliminate mercury. During gestation, a hereditary burden of exposure would include inheritance of mercury exposure from the mother’s mercury burden. After birth, exposure would include diet, mother’s milk, and a regimen of vaccines. Geographic clustering of direct exposure from point source plumes is another possible influence on the rate of deposition.

According to the biological mechanism presented here, the subpopulation most susceptible to mercury exposure and the risks of disease would be characterized by quantifying the rate of I-Hg deposition. Proper assessment of chronic mercury exposure and neurodegenerative disease would consist of the most accurate measurement of blood I-Hg to serve as bioindicator for chronic mercury exposure and targeted deposition. The sum of all thimerosal-containing vaccines would then predict the
relative risks of a disease response for each subpopulation characterized by I-Hg deposition.

In 2004, the IOM concluded that toxicological data may support a biological mechanism of causation, that there may be a genetically susceptible subpopulation to mercury exposure, and that there is evidence of immune dysregulation in the serum of autistic patients. Results from our NHANES analysis present evidence that African Americans face the highest risk of I-Hg deposition and associated effect on the pituitary (LH). Due to increased risk of chornic mercury exposure and targeted I-Hg deposition in the endocrine system, the African American subpopulation may face elevated risks of
associated neurodegenerative disease. Indeed, several epidemiological studies have found a higher prevalence of Autism in African American children than in white children.

Associations of chronic mercury exposure with the immune system (white blood cell) and pituitary (luteinizing hormone) within the general U.S. population establish links with mercury deposition, Autism and Alzheimer’s Disease. Deposition in target areas may decrease the amount of future exposure or acute dose (e.g. vaccines) needed to surpass a threshold concentration and trigger mercury’s targeted, neurotoxic effect. Once the critical threshold concentration is reached, simultaneous neurotoxic events may cause focal damage in the pituitary, adrenals, immune system, and liver and induce a cascade of inflammation, autoimmune responses, neurodegeneration, and disease.

Policy recommendations
• Limit all sources of mercury exposure.
• Reduce dietary intake of contaminated fish.
• Monitor and measure mercury content in food and diet.
• Remove mercury from vaccines and dental amalgams.
• Regulate coal burning power plant emissions to limit mercury emissions into the atmosphere.
• Restrict mining of mercury.
• Chronic mercury exposure should be measured with the method for assessment of chronic mercury exposure presented in this paper.
• Chronic mercury exposure should be monitored in the general population and within
susceptible populations such as the elderly, expectant mothers, and newborn infants.
• Continued research in the fields of mercury speciation, detection and elimination therapy should be developed.

Future Research
• Future research should adopt the method for assessment of mercury exposure presented in this study that relies on both blood I-Hg and methylmercury as bioindicators of chronic mercury exposure.
• Bioindicators for chronic mercury exposure within the U.S. population should be monitored to assess risks of disease.
• Accurate methods of inorganic and dimethyl mercury detection should be developed.
• A causative role for chronic mercury exposure and neurodegenerative disease may be linked through impairment of the pituitary, and secretion of Luteinizing Hormone. Investigate a causative role for mercury deposition and the process from LH disruption to Alzheimer’s Disease and Autism.
• Investigate the cellular mechanism for the demethylation of organic mercury in mammalian tissue. This mechanism is unknown and may be an important area for future research in molecular biology.
• Study the effects of liver function, the role of bilirubin, gastric motility, and the role of variable flora populations on the rate of mercury elimination.
•Perform clinical research on mercury elimination and chelation therapy to apply towards susceptible populations such as pregnant mothers, children, and elderly populations.
• Present and Test the following hypothesis:
Hypothesis 1: In this biological mechanism, chronic, organic mercury exposure is linked to elevated risks of neurodegenerative disease, specifically types of Autism, and Alzheimer’s Disease. Elevated risks of neurodegenerative disease may be due to immune and endocrine disruption caused by targeted I-Hg deposition in the liver, pituitary, and white blood cells. A process of focal I-Hg accumulation may lead to elevated risks for mercury’s neurotoxic effect.
Once this neurotoxic concentration is surpassed, resultant endocrine and immune system impairment may instigate a cascade of neuroinflammatory reactions, autoimmune disorders, impaired cell migration and neural development, neurodegeneration, and associated disease.
Hypothesis 2: Accurate assessment of blood I-Hg concentration will define the subpopulation most susceptible to cumulative mercury exposure (vaccines, diet, amalgams) and at highest risk of associated neurodegenerative disease (Autism and Alzheimer’s Disease).

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