Mercury Toxicity and Antioxidants: Part I: Role of Glutathione and alpha-Lipoic Acid in the Treatment of Mercury Toxicity

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. (Altern Med Rev 2002;7(6):456-471) Mercury: Sources of Exposure According to the Agency for Toxic Substances and Disease Registry (ATSDR) of the U.S. Department of Health and Human Services, mercury is listed as the third-most frequently found (lead and arsenic are first and second), and the most toxic substance in the United States. This figure originates from the U.S. Government’s Priority List of Hazardous Substances. This list includes, in order of priority, substances that have been found at hazardous waste sites on the National Priorities List (Superfund sites) that “pose the most significant potential threat to human health due to their known or suspected toxicity and the frequency of exposure.” Of 1,467 hazardous waste sites listed on the National Priorities List in 1998, toxic levels of mercury were identified in 714. Mercury toxicity is also considered the second-most common cause of acute heavy metal poisoning, with 3,596 cases reported in 1997 by the American Association of Poison Control Centers. Annual worldwide emissions of mercury into the atmosphere have been estimated at 2,200 metric tons. One-third of these emissions are estimated to originate from natural sources (volcanic eruptions and decay of mercury-containing sediment) and two-thirds from man-made sources. Twenty-five percent of total worldwide emissions come from fossil fuel combustion. In the United States, 26 percent (64.7 tons/year) of atmospheric mercury emissions come from medical waste incineration, such as cremation. There are currently 1,782 advisories (one per body of water) issued by the U.S. Environmental Protection Agency (EPA) in 41 states in the United States restricting the consumption of any locally caught fish or shellfish due to their mercury content. Sixteen states have issued statewide or statewide-coastal advisories recommending restricting the consumption of fish caught in the state or along the coastline due to methylmercury contamination. The Environmental