Mercury (Hg) is a heavy metal which is considered a global pollutant and well-known neurotoxin. Exposure to mercury has a variety of significant and documented adverse effects on human health.

Chronic human exposure may occur through a variety of pathways, including industrial processes, occupational and household uses, dental amalgams, Hg-containing vaccines, and consumption of contaminated fish and seafood.

 

New scientific evidence on genetic backgrounds shows that susceptibility genes can make certain individuals more or less vulnerable to mercury toxicity.

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Routes of exposure

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Methyl Hg (organic Hg) is one of the best-known toxic biohazards. It forms in marine ecosystems and enters the aquatic food chain, where it undergoes a remarkable bioaccumulation process in muscle tissues of fish, particularly of long-lived predatory species. These include shark, swordfish, fresh tuna, marlin, king mackerel, tilefish from the Gulf of Mexico, northern pike and more. When eating fish, about 95% of the methyl mercury content is absorbed in our body.

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Prolonged exposure to mercury through additional sources is also associated with adverse health effects. These include skin whitening creams, laxatives, Hg salts, Hg-containing vaccines and fluorescent tubes. Many other articles contain mercury, but for the most part are not a major route of exposure. These include batteries, jewels with mercury encased in glass, switches, LCD screens and monitors, preservative or antibacterial agent in pharmaceuticals

Occupational exposure to mercury is of great concern. It is mostly relevant to workers exposed to vapors of elemental mercury, which readily vaporizes at room temperature and quickly absorbed via the lungs. Doctors and lab technicians preparing dental amalgams fillings (“silver filling”) are at high risk. As for the patients themselves, amalgam tooth fillings are considered safe by the FDA and EPA, but some studies found that amalgam is a source of life-long exposure to mercury.

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Metabolism

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Metabolism of mercury depends on the route of exposure, as methyl mercury enters through ingestion, and elemental mercury enters through inhalation of elemental mercury.

 

In general, it can be said that mercury distributes throughout the body, as it easily passes through most cell membranes including the blood-brain barrier (BBB) and the placenta. In cells, mercury ions react with molecules or structures (such as enzymes, ion channels, or transporters), inhibiting their activities and interfering with normal cellular functions and detoxification processes.

Mercury has a relatively long half-life of approximately 70–80 days in the human body.

Approximately 10% of the stored mercury is in the head region, as the brain has stronger affinity for methyl mercury, showing concentrations 3–6 times higher than in the blood. 

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Free methyl mercury is finally transported out of liver cells into the bile and excreted as mercuric Hg in the feces.

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Health effects

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Exposure to mercury can be differently associated to over 250 symptoms, involving the neurological, renal, respiratory, gastrointestinal, cardiovascular, hepatic, reproductive, and immune systems.

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Hg exposure represents a significant concern during the course of pregnancy, because of the risk to the fetus. Methyl mercury readily passes across the placental barrier to the fetus. 

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As for occupational exposure, inhalation of Hg vapor was found associated with neurological and behavioral signs and symptoms, such as depression, paranoia, extreme irritability, hallucinations, inability to concentrate, memory loss, hand tremors, weight loss, perpetually low body temperature, drowsiness, headaches, insomnia, and fatigue, may also occur.
 

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Genetic sensitivity to mercury 

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Hg toxicity and associated health effects can vary remarkably at an individual level, depending not only on its chemical speciation, concentrations, and time of exposure, but also on the individual susceptibility to Hg hazards. In fact, not all individuals respond similarly under the same Hg exposure conditions, and they often display significant individual differences in Hg accumulation, distribution and elimination. 

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A certain variation in CPOX4,  a gene encoding for a red blood cell heme pathway enzyme,is known to modify performance on multiple neurobehavioral tests. Among boys carrying this CPOX4 variant, chronic mercury exposure reduced scores in attention, learning & memory, executive function, visual spatial acuity and motor function.

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Taken from Woods et al. Neurotoxicology. 2014 Sep; 44: 288–302.

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The figure above illustrates the effect of mercury on cognitive abilities. It measures the association between performance on the Stroop Word test (an attention test) and chronic Hg exposure among boys. It was found that Hg exposure accounted for 1.1% of performance variance among boys without the variant, but for 25.1% of performance variance among boys who carry the variant form of the CPOX4 gene.

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The Metallothioneins (MT) are a multigene family of proteins that are involved in Hg distribution and excretion. Two MT isoforms, MT1 and MT2, in particular, are implicated in the dispersal and storage of Hg in the Central Nervous System. Numerous significant adverse effects found, particularly in relation to chronic Hg exposure, among boys carrying either MT1M or MT2A variants. These effects were principally within the domains of visual spatial acuity and learning & memory, but also on tests of attention and motor function. As with other genetic risk factors, girls were found much less susceptible. 

 

Catechol-O-methyltransferase (COMT) is an enzyme that maintains neurologic functions by regulating the availability of key neurotransmitters such as dopamine. Polymorphisms in the COMT gene that modify the activity of the COMT enzyme are known to underlie a number of neuropsychiatric disorders as well as process-specific functions that accompany neurobehavioral tasks. Exposure to mercury was associated with risk of neurobehavioral deficits among elementary school students who carry COMT variants. Carriers working as dentists and technicians show altered cognitive flexibility, working and visual memory, as well as bad mood.

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The APOE gene provides instructions for making a protein called apolipoprotein E. This protein combines with fats (lipids) to form molecules called lipoproteins, responsible for packaging and carrying cholesterol and other fats. This gene may also detoxify methyl mercury when it crosses the Blood Brain Barrier. However, individuals carrying one variant form of the gene perform a less efficient elimination process.

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Selenium (Se) plays an important role in the storage of mercury and its tissue distribution. Seleno-enzymes metabolize this essential mineral, and play two important roles in protecting against mercury toxicity. First, they may bind more mercury through their highly reactive selenol group, and secondly, their anti-oxidative properties help eliminate the reactive oxygen species induced by mercury.

 

Inhibition of seleno-enzyme appears to be the cause of the pathological effects known to accompany methyl mercury toxicity. Methyl mercury inexorably sequesters selenium, directly impairing seleno-enzyme activities and their synthesis. This may explain why studies of maternal populations exposed to foods that contain high mercury levels but low selenium levels were found to have more adverse child outcomes, while studies of populations eating ocean fish high in mercury but rich in selenium found no harm.

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The SEPP1 gene products interact with dietary selenium, allowing certain antioxidant defense properties in tissues such as brain and testis. The SEPP1 variant form reduces protective binding of seleno-proteins to mercury.

 

A variation in the INMT gene is a major predictor for the rate of selenium excretion out of the body. The variant form of the gene lowers selenium levels and allow higher levels of mercury to accumulate.

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How to reduce the risk from exposure to mercury 

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• Eating fish has many nutritional benefits and is a great source of protein, micronutrients and healthy fats. These benefits are thought to outweigh the risk of exposure to mercury, as long as you don't each too much fish. The FDA and EPA agencies advising and promoting a minimum level of fish consumption, but recommend sensitive populations to limit fish consumption to 2-3 servings per week, each serving is of 4 ounces of fish for adults and 2 ounces for children 4-7 years old.  Sensitive populations that should limit fish consumption are women who may become pregnant, pregnant women, breastfeeding mothers and children. For individuals with a genetic sensitivity to mercury, we advise a maximum of 2–3 servings (227–340 grams) of a variety of fish every week. Eat more lower-mercury fish and seafood, and avoid higher-mercury fish. Use the following table to make your choices:

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• As for dental filling treatments, next time you are in for a tooth filling choose amalgam-alternatives like composite resin, glass and porcelain, if possible. For an existing amalgam filling, removal will reduce exposure to mercury in the long run but may expose you to high mercury levels in the process. Some studies show significant decrease in urine and hair mercury levels and improvement in overall symptoms following amalgam removal. Others claim that the risk and effort outweigh the benefits. The FDA view is that amalgam fillings are safe for adults and children over the age of six, and that removal of amalgam fillings is not beneficial, and may release considerable amount of mercury in the process.

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• There are concerns over the use of thimerosal in vaccines, as a mercury-containing preservative. Robust studies support the safety of thimerosal-containing vaccines, and this is the current view of the FDA. With that, informed individuals can avoid thimerosal in their vaccines. The use of this preservative in vaccines is less common these days, and mainly used in multi-dose vials of vaccines, so look for vaccines in single-use presentations. All vaccines routinely recommended for children 6 years of age and younger in the U.S. are also available in formulations that do not contain thimerosal. Vaccines that do not contain thimerosal as a preservative are also available for adolescents and adults.

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• Some cosmetics contain mercury. These are usually imported to the US as skin lightening or freckle creams. About 6% of of lightening products purchased in the United States were found to contain mercury in significant excess. 

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• Mercury thermometers, some batteries and different fluorescent light bulbs contain mercury. In case one of these breaks, stay away and allow 5-10 minutes of air flow​ by opening a window or door to the outdoor environment. Shut off the central forced air heating/air-conditioning system and don't use a vacuum cleaner before collecting all remains. Avoid skin contact when cleaning up and dispose into a a sealable container.

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• Recent studies have shown that selenium-enriched diets not only prevent mercury toxicity, but can also reverse some of its most severe symptoms. Selenium is also important for thyroid function, antioxidant activity and cancer prevention. Supplement your selenium intake if your test results show you tend towards selenium deficiency.                                                                                                            Selenium is a mineral naturally found in food and water. The recommended dietary allowance (RDA) for selenium is 55 micrograms a day for adults, and up to 70 micrograms for pregnant and breastfeeding mothers. One serving of fish provides an adult daily intake, as well as two to three servings of any meat, eggs or cheese. Vegetarian sources for selenium include brown rice, barley, baked beans, sunflower seeds, mushrooms and oatmeal, among others. The safe upper limit for selenium is 400 micrograms a day in adults. Anything above that is considered an overdose. Brazil nuts are the number one source of selenium in the human diet. One Brazil nut contains about 85 micrograms of selenium, so avoid eating more than 4-5 a day.

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