Mercury Toxicity Complexities

OVERVIEW

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If you think you may have or do have mercury toxicity or poisoning, reading this rather lengthy article is an absolute must for you! Similarly, if you think you should be tested for mercury toxicity, this is required reading to ensure that your health care provider understands the complexity of diagnosis and treatment of your condition, while minimizing any further damage that may occur as a result of mercury detoxification. Of all the toxic metals, mercury is the most complex in its biochemistry, toxicity and elimination. Because mercury is ubiquitous in nature, most living entities have systems for detoxifying, sequestering or elimination it from their bodies. Since the Industrial Revolution, the amount of mercury in our environment has increased significantly. Despite many years of protesting from the Dental profession, there is no longer any doubt that mercury from “Silver” fillings (Dental Amalgams) is also a contributing source. Deliberate removal of mercury from the body by the use of biochemical agents (termed “Chelation), when properly employed, can assist in reducing elevated mercury levels. Maximizing the body’s natural ability to detoxify mercury and practical avoidance are also important measures to apply.

ENVIRONMENTAL SOURCES

Taking a closer look at sources of mercury, the most obvious is from Dental Amalgams. It has been shown conclusively that these amalgams either leech mercury or that minute but significant quantities vapor off from the fillings. It is possible that these fillings may either cause or contribute to elevated mercury levels. Further complicating the issue is that mercury may not only be directly toxic to numerous body systems, but can also cause an antibody-antigen reaction by binding to amino acids on proteins, thereby changing their structure enough to be recognized as foreign, eliciting an antibody response. Mercury has a high affinity for certain amino acids that contain sulfur (cysteine, cystine, methionine and taurine are amino acids that contain sulfhydryl groups).  This chemical group is one that is often the site on proteins and enzymes where important chemical reactions occur. By attaching to the sulfhydryl group mercury can block, inactivate or change the three-dimensional structure of the protein, making it inoperable.

Another, much less recognized source of mercury comes from natural out-gassing of elemental mercury (Chemical symbol is Hg), from volcanoes, earth’s crust and oceans. It is estimated up to 6,000 tons/year enter our environment in this manner. Because mercury has unique physical properties, such as being an excellent conductor of electricity, its ability to expand and contract and to form alloys with other metals (Dental Amalgams), industrial wastes are another significant source. Mercury is a common ingredient in many chemicals, fungicides, pesticides and even medications (Thimerosal contains a significant amount of mercury). Mining, smelting, manufacturing, electronic equipment, catalysts, pigments, equipment, instruments and especially the fossil fuel plants that burn “Dirty” coal, contribute a huge amount of elemental or inorganic mercury to the environment. Whereas in this country new environmental regulations are designed to substantially reduce the release of mercury and other toxic chemicals, this is not true in China, where it is estimated that one new, “Dirty” coal fired power plant is coming on line every week. Up to 30,000 tons of elemental and inorganic mercury may be released in this fashion each year. It obviously does not remain in China, but circumnavigates the globe.

FACTORS AFFECTING TOXICITY

Toxic effects of mercury are dependent upon many factors, including: route of exposure, chemical form of the mercury, dose, frequency of dose, nutritional status and ability to detoxify, the bacterial composition of your GI tract and genetic factors. Inhaled mercury is generally more easily absorbed than is that either eaten or absorbed through intact skin. Amalgam fillings may contribute up to 3 micrograms/day, environmental uptake up to 6 micrograms and fish as much as 25 micrograms. Factors that increase mercury vapor from fillings include: Chewing, tooth brushing and consuming hot beverages. Certain occupations are at risk because of frequent or continuous exposure to inorganic mercury vapors, including: dental office staff, manufacturing, chemical and metal processing, mining construction workers and electrical component assembly. Family members of the above may be affected due to mercury dust on worker’s clothing.

The chemical form of the mercury is probably the critical factor in whether it exerts toxic effects. Mercury may be in elemental (pure mercury), inorganic (combined with a non-carbon element) or organic (combined with a biochemical that includes carbon). To further complicate matters, mercury that is not organic may become so. Mercury vapor from environmental sources is either elemental or inorganic. However when it precipitates and is taken up by a living organism, it can be bio-transformed into an organic form! This process may occur in your body, where inorganic mercury is converted into organic by the action of intestinal bacteria. It is the accumulation of organic mercury that is generally more significant in causing toxicity. Elemental mercury is almost totally non-toxic when ingested. (If you ate it, less than 1 part in 10,000 is absorbed). However- up to 80% of inhaled elemental or inorganic mercury is absorbed through the lungs and finds its way into the bloodstream. Here it may once again be converted to organic mercury through an oxidation reaction (removal of electrons) and then being reduced by the aforementioned sulfhydryl groups where it then becomes attached to proteins. So in summary- you can eat elemental (metallic) mercury without any negative effect, but you can’t inhale it.

MERCURY PHYSIOLOGY

Mercury comes in three “flavors”, elemental, inorganic and organic. Each type has different implications for absorption, toxicity and elimination.

Elemental mercury from fillings may be absorbed from inhalation or ingestion. Fillings do constantly vapor off small quantities which are increased by the reasons stated above. This may then be inhaled and absorbed from the lungs through the bloodstream. Direct absorption may occur through the oral mucosal membrane, migration through the dental pulp into adjacent bone or it may become dissolved by saliva into a positive ion where it will be swallowed and a small percentage absorbed (15%). In a Swedish study of people with no amalgam fillings the mercury content of the brain was half that of people with amalgam fillings. Various studies show that amalgam fillings may contribute 3-17 micrograms/day of mercury and may contribute 0-75% of your total daily mercury exposure (depending upon the number of fillings you have).

Inhaled elemental mercury has a high affinity for the nervous system. A single equivalent exposure to mercury vapor causes retention of up to ten times more mercury in the brain than does an IV injection! Mercury accumulates in the gray matter (thinking part) and cerebellum. The half-life (time it takes to be reduced by 50%) of inhaled vapor in the whole body is about 60 days. Unfortunately in the brain it is much longer. Elemental mercury is primarily excreted by the kidney where it may accumulate and cause damage.

Inorganic Mercury is found as various salts where mercury (a positive ion) is bound in an ionic bond with a negative element (such as chloride, sulfide iodide, nitrate, oxide etc). Common sources are: pesticides, fungicides, antiseptics, vaccines, cosmetics and occupational exposure. Inorganic mercury, unlike elemental can be absorbed by the GI tract (About 10%). The half-life is about 40 days. The primary target of inorganic mercury is the kidney. It does not have the neurotoxicity of elemental mercury as inorganic mercury can not easily pass through the blood-brain barrier. Inorganic mercury tends to be less easily absorbed and more easily excreted than organic and therefore, in general does not accumulate as easily.

Organic Mercury is highly toxic. As noted above, it is created from elemental and inorganic mercury from biotransformation by microorganisms. Unfortunately, atmospheric elemental and inorganic mercury do not remain so. They precipitate onto land and water. In the oceans, the additional mercury enters the food chain at the bottom. As it works its way up the food chain, it concentrates in the tissues of the animals that feed on the ones beneath them. Because mercury is more soluble inside cells than in the surrounding ocean water, it accumulates. The higher one goes in the food chain the more it accumulates, leading to bioamplification of mercury in tissues of the higher organisms. Unlike elemental or inorganic mercury, organic mercury is almost totally (>95%) absorbed through the GI tract. The most prevalent form is methylmercury (MM) which is very stable and difficult to decompose. (Mercury poisoning in children is most commonly the result of eating fish contaminated with MM). Methylmercury is lipophilic, which means that it has a strong affinity for biological membranes and can easily pass through them to the insides of cells thereby causing damage to both the cell membrane and the organelles inside the cell. MM readily binds to hemoglobin and is twenty times higher in red blood cells than in plasma. MM also has a high affinity for growing hair, because hair contains a high quantity of the amino acid cysteine, which as noted above, contains a sulfhydryl group that tightly binds MM. Hair mercury accumulates up to 250 times the levels seen in whole blood, making it a good index for assessing the body burden of MM.

Like elemental mercury, MM penetrates the blood-brain barrier and accumulates. In the brain it becomes demethylated and becomes inorganic mercury, so with chronic exposure the levels of inorganic/organic mercury in the brain become higher. When levels reach 10 parts per million overt signs and symptoms of neurotoxicity appear. This means that more subtle signs and symptoms occur at levels below 10ppm! Once in the brain, MM is more resistant to elimination. The half-life in the rest of the body is 40-70 days, but is longer in the brain. MM is eliminated mainly through detoxification in the liver, which then excretes it into the bile, where the majority is eliminated in the feces.

How much MM is in fish? Generally in America, most common fish contain low levels, especially pollock, most tuna and salmon. The top 10 most commonly consumed fish contain less than 0.20ppm of mercury, a safe level. Other species that may contain higher amounts are predator fish higher in the food chain including: swordfish, shark, various bass, orange roughy, mackerel, pike and porgy. Interestingly farm fish are lower in mercury than wild caught (but are also lower in omega-3 essential fatty acids). Fish from areas with contaminated water may contain significantly higher levels, so rivers and lakes that have runoff from mining or manufacturing may have fish with unacceptable MM levels.

ELIMINATING MERCURY

There are multiple factors that affect the ability of mercury to cause toxicity. At least as critical as the amounts ingested, inhaled and absorbed are many factors that determine how much the body is able to eliminate. Elemental mercury is eliminated mainly through the kidneys; inorganic through kidneys and the hepato-biliary (liver and gall bladder) system and most MM is eliminated through the hepato-biliary system.

Absorption of MM from the gut is almost 100%. Elimination through the gut can be difficult if there are significant gastro-intestinal issues. It appears that the rate-limiting step in eliminating MM is the ability of the body to convert it into inorganic mercuric salts. Equally important is to ensure that bacterial overgrowth (dysbiosis) does not lead to conversion back into organic MM, which can then be reabsorbed, creating a “Catch-22” no-win situation. Treating mice with antibiotics (which kills off the intestinal flora), caused not only an increased retention of mercury, but a significantly higher rate of brain damage as well as lower levels of inorganic mercuric salts, demonstrating the importance of intestinal bacteria in its elimination. In other studies it was shown that certain bacteria (Specifically Streptococci, E.Coli, Staphylococci and yeasts) increased the conversion of the more easily excreted inorganic mercuric salts back to MM. The species generally considered “Friendly” including most of the obligate anaerobes and lactobacillus, did not convert inorganic to organic mercury, leading to higher rates of excretion. The take home message is that the condition of your GI system may play a large roll in determining whether mercury will be toxic to you as a unique individual.

 
THE GREAT VACCINE DEBATE

In the past decade there has been great controversy regarding whether vaccines cause or contribute to autism.    Without weighing in, here is what one can say. Until recently, many vaccines contain Thimerosal, a preservative containing ethylmercury (EM), which is 50% by weight mercury. In the past there have been many incidences of fatal poisoning caused by EM. Unlike MM, EM breaks down rapidly into inorganic mercuric salts, in the brain, where they are difficult to remove and cause toxicity. It is foolish to assume that, as genetically diverse as humans are, that we will all react the same when faced with a potentially toxic challenge. What is more reasonable is to assume that there is a continuum extending from individuals with high resistance to those who are highly susceptible to an injection with a toxic substance. How many times has the FDA proclaimed something safe, only to reverse themselves many years later. (Google how many people now dead had wished the FDA had protected them from Vioxx).

MECHANISMS OF TOXICITY AND ELIMINATION

Once mercury enters the circulatory system, it targets primarily the kidneys, liver and blood cells. The effects and elimination of organic and inorganic mercury largely relate to its ability to bind to the antioxidant glutathione, which contains a sulfhydryl group. Glutathione is one of the body’s most potent and prevalent antioxidants. It is composed of three amino acids; cysteine, glycine and glutamic acid. The body can manufacture it through a series of biochemical reactions that require many co-factors (vitamins and essential elements). Mercury depletes glutathione, to which it tightly binds. For every molecule of mercury, the body loses two molecules of glutathione. The complex is excreted in the bile into the feces as discussed above. Mercury also has the ability to down-regulate or reduce the ability to produce two key enzymes necessary for the manufacture and recycling of glutathione, further decreasing its availability. If the ability of the liver and blood cells to handle mercury is exceeded, it ends up in the kidney. Red blood cells (RBC’s) have a significant ability to make and recycle glutathione, so they act as the first line of defense against mercury and other chemicals that cause oxidative damage. If glutathione concentration is adequate, mercury is bound and transported to the liver for excretion. Bile is required for mercury to be eliminated. In the absence of adequate liver and gall bladder function, mercury then accumulates in the kidneys where it causes damage. Mercury can destroy tissues by causing oxidative stress, peroxidation of lipids, mitochondrial dysfunction and changes in hemoglobin metabolism. In the kidneys there appears to be a threshold concentration, below which mercury causes no damage.

There does not appear to be a direct linear relationship between the total amount of mercury in the body and the development of signs and symptoms. Research on this provides conflicting studies. Similarly there is inconclusive evidence that the use of chelating agents, when used alone, is beneficial. In fact, under the wrong conditions, chelating mercury may cause increased problems. What are the reasons behind these apparent discrepancies? The answer lays with endogenous detoxification- the body’s inherent ability to detoxify mercury.

So what are the factors that cause variations in the ability to endogenously detoxify mercury, and hence the development of toxicity, or conversely its prevention? Since it is a complex issue there are multiple factors:

  1. Quantity and quality of dietary protein, specifically those amino acids mentioned above that contain sulfur (especially cysteine). The more sulfur, the greater the protection. This is logical since you already know that the sulfur containing tri-peptide (three amino acids) glutathione is a primary detoxifier of mercury.
  2. Selenium concentration- Selenium is a highly protective micro-trace element. Deficiencies of selenium will aggravate mercury toxicity. Research has repeatedly shown that eating fish contaminated with mercury causes little or no toxic effect as long as the fish contains more selenium than mercury. Additionally, fish in a mercury contaminated lake in Sweden where selenium was added to the water experienced a 75% reduction in mercury after three years.  Only when the ratio is low, does toxicity appear. Selenium is found in selenoproteins in high concentration in neurons where they exert protective effects as antioxidants. Selenium also binds directly with mercury, creating mercury selenide, which is highly insoluble and therefore of very low toxicity. Research shows that people with more dental amalgams excrete less selenium, indicating that it is binding with emitted mercury and being sequestered in the body. Toothpastes that contain selenium cause a decrease in emission of mercury vapor from amalgams, whereas brushing regular toothpaste increases vapors.
  3. General Antioxidant status- Antioxidants do not exist in isolation but function as a group. A deficiency of one can affect others, so adequate levels of antioxidants without gross excess of a single one optimizes their overall efficacy.

DIAGNOSIS

Diagnosis of mercury poisoning is of course, not straightforward. In the absence of another established cause of peripheral neuropathy (e.g. diabetes) the primary symptom of MM toxicity is primary sensory neuropathy, which is one of the most sensitive indicators of mercury poisoning.

There is a negative correlation between hair levels of selenium and mercury in brain tissue (the higher the selenium the lower the mercury). Mercury (mainly MM) is highly concentrated in hair. Elevated levels of hair mercury are representative of organic but not inorganic or elemental levels in the body, so normal mercury levels in hair are not a guarantee of safe levels in the brain or kidney, whereas elevated levels do imply the need for additional assessment.

Performing what is termed a “Provocative Challenge” where the patient is given an exogenous chelating agent (DMSA, EDTA or both) and then subsequently collects their urine or feces is a method of determining elevated levels of stored mercury. However there are several issues with this as well. First, urine is where one finds most inorganic mercury, so if the poisoning is chronic one may miss the organic mercury component which is excreted mainly in the feces. Elevated mercury in a hair test would imply the need to collect a stool sample post provocation challenge and would help confirm MM toxicity. On the other hand, normal hair mercury combined with elevated urinary mercury post challenge implies inorganic mercury being the main culprit. In this case and in conjunction with signs and symptoms of mercury toxicity, removal of dental amalgams by a dentist familiar with such removal might be entertained (First ruling out other exposure).

To optimize the provocative challenge it would be wise to first prime the body by using endogenous detoxification procedures noted below under “TREATMENT”. DMSA does not effectively cross either cell membranes or the blood-brain barrier so you will not be removing mercury from its major storage locations. By using endogenous detoxification coupled with antioxidant support first, one may mobilize stored mercury.

Erythrocyte (RBC) mercury is another valuable too, mainly assessing for MM since it binds tightly to RBC membranes.

The above tests are all simply ways to quantify the amount of mercury in the body. None of them are functional tests- they don’t tell you if mercury is causing metabolic, biochemical and physiological changes. Fortunately such a test exists. It is called urinary porphyrins. Porphyrins are intermediates in the formation and degradation of heme (as in hemoglobin) synthesis, which occurs mainly in the liver, kidney bone marrow and spleen. Whereas heme is the central component of hemoglobin, the essential oxygen-carrying molecule found in RBC, it is also a key component of the mitochondrial system of energy production. Disturbances of heme formation affect every cell in your body. Mercury interferes with specific enzymes in the heme metabolic pathway by blocking their normal function. This leads to accumulation of specific metabolic intermediates whose presence in excess acts as metabolic markers of dysfunction. (Genetic variations or polymorphisms also cause blocks which can be more serious and incompatible with life). By measuring the various porphyrins excreted in the urine, one may determine whether mercury is causing functional problems, and confirming toxicity and indicating the need for treatment.

TREATMENT

An integrated approach to detoxification that ensures optimal antioxidant status, optimizes hepato-biliary detoxification processes, balances GI flora to reduce methylation of inorganic mercury, ensures adequate bile production, provides adequate dietary fiber, and uses endogenous detoxification and possibly exogenous chelation will optimize elimination of mercury from the body. Beginning with maximizing GI function and proceeding to supplementing the body’s metabolic systems responsible for mercury removal prior to initiating exogenous chelation makes sense. Using selenium, cysteine, glutathione, and glutathione recycler nutrients and broad based antioxidant support prior to a provocative challenge or chelation reduces the possibility that the mercury mobilized from storage sites will cause additional damage. Other antioxidants to consider include Vitamins C and E, Alpha Lipoic  Acid, Melatonin and Vitamin B12.

DMSA is an exogenous chelating agent that is commonly used for chelating mercury. There are three types of DMSA: oral, IV, and rectal suppositories. Oral chelation should never be considered by someone with serious metal toxicity. It is highly ineffective and may cause additional problems. IV chelation is most effective but also extremely costly. Rectal suppositories are about 50% as effective at about 10% of the cost. In addition, one does not have to spend three hours at least once per week in a doctor’s office attached to an IV. If you are just getting exogenous chelation therapy- you are probably doing it wrong and could be causing additional damage.

In summary, mercury toxicity is a complex issue. The total body burden on mercury only tells part of the story. The type of mercury and your inherent ability to endogenously detoxify mercury along with the status of your GI system and levels of antioxidants, especially glutathione, are all factors in determining susceptibility and resistance to the toxic effects of mercury as well as your ability to eliminate it. Diagnosis and treatment should be performed by a health care provider familiar with this most complex toxin.

 

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