Inorganic Vs Organic Mercury (And What To Do About It)

How Mercury Can Wreak Havoc To The Body

 
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829766/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829766/

 

Although it may have had an important role in scientific history, mercury has been found over the years to cause significant damage to the brain and body. 

In this post, we will discuss the different types of mercury, how they affect the body, and what you can do to effectively remove them.

Contents:

  1. Basics
  2. Types Of Mercury
  3. Uses For Mercury
  4. The Effect Of Mercury On The Body
  5. What Increases Mercury?
  6. How To Protect Against And Remove Mercury From The Body
  7. Testing Mercury Levels
  8. Mercury Levels In Fish
  9. What Makes Mercury Worse?
  10. Mechanism Of Action
  11. Genetics
  12. More Research

Basics

Mercury, or Hg, is a metallic compound found in nature that is considered one of the most toxic heavy metals in the environment. R

Mercury is released into the environment mainly by coal-burning, industrial processes, waste incinerators, and mining of metals. R R R

It's found in low levels in water systems, but in higher concentrations in aquatic life. R R R

Mercury has a long half-life and the human body has no mechanisms to actively excrete mercury.  R

Mercury may cause acute symptoms such as:

  • Chills R
  • Cough R
  • Diarrhea R
  • Fever R
  • Metallic taste in the mouth R
  • Nausea R
  • Shortness of breath R
  • Vomiting R

Long-term symptoms such as cognitive impairment such as impaired memory, attention span, anxiety, and depression. R R R R

Types Of Mercury

Mercury exists in 2 forms: R

  • Elemental/Inorganic - this mercury is used in glass thermometers and found in the body after conversion from other forms R R R R R R
  • Organic - this mercury is found mainly in fish (as methylmercury), in amalgams, and in some vaccines (as ethylmercury, or thimerosal)R R

Elemental Mercury And Inorganic Mercury

Metallic Mercury is usually inhaled mercury vapor (such as amalgams) and primarily targets:  R R R R

  • Adrenals R
  • Brain (easily passing the blood brain barrier) R R
  • Breast (and breast milk) R R R R
  • Gut R R
  • Heart R R
  • Immune cells (binds to T cells) R
  • Liver R R R
  • Lungs R R
  • Kidneys R R R
  • Muscles R
  • Nails R
  • Pancreas R
  • Prostate R
  • Salivary Glands R
  • Skin R
  • Sweat Glands R
  • Testes R
  • Thyroid R R

Mercurous mercury is poorly soluble in water and poorly absorbed by the intestine. R

Mercuric chloride used to be used for photographic film development and could be accidentally ingested, or used for suicide. 

Mercuric chloride is now commonly found in skin-lightening creams. R

Unlike metallic mercury, mercuric chloride doesn't cross the BBB well, but does accumulate in tissue. R

Organic Mercury

Organic mercury (ie methyl/etheyl mercuries) is usually found in fish, and can be absorbed by the gut and skin. R R

Its excretion is 1/3 as long as inorganic mercury. R

Its primarily targets the brain, liver, kidneys, placenta, fetus, breast milk, peripheral nerves and bone marrow. R R R

Uses For Mercury

 
mercury environment pollution
 

There have been a few beneficial uses of mercury over the years. For example, Methylmercury was previously used as a crop fungicide in the early 1900’s. R

In addition, mercury has been used in dental amalgams and mercury thermometers, but over the years innovations such as fiber-reinforced composites and non-invasive continuous temperature devices, respectively, have been found to be safer and more effective for such applications. R R R

The Effect Of Mercury On The Body

Although mercury has had some beneficial use in industry, such use has had a resulting negative impact on health and the environment.

1. Oxidation Status And Mitochondrial Function

At sublethal doses, mercury can increase reactive oxygen species (ROS) in the cell. R

This then turns on the transcription pathway NRF2, thus causing increased activity of glutathione peroxidase (GPX) and thioredoxin reductase (Trx), two important antioxidant response genes (ARE). R R R

Increased glutathione is good, but the problem with mercury is that if it is not bound to a chelating agent, it can get reabsorbed back into the cells and reactivate NRF2/ARE. R R

Higher doses of mercury absorbed into the body inhibit NRF2 form working. R

Mercury suppresses mitochondrial function as it can cause mitochondrial swelling, increased ROS, collapse of mitochondrial membrane potential (MMP), and cytochrome c release. R R

2. Immune System

By chronic modulation of the immune system, mercury (even sub-toxic levels) may induce autoimmunity. R R R

It shifts the immune system towards a TH2 response. R

Mercury can cause mast cells to degranulate and release histamine (a major pathology of histamine intolerance). R

3. Central Nervous System

Mercury increases oxidative stress which can increase risk of neurodegenerative diseases. R 

Methyl mercury exposure can cause neuromotor effects in rats such as reducing the levels of Brain Derived Neurotrophic Factor (BDNF) in the hippocampus in animals. R R R

Furthermore, mercury disrupts brain development in turn producing cognitive, altered motor function, and memory, and learning disabilities (more discussed in development section). R R R R

For example, mercury can inactivate the enzyme catechol-O-methyltransferase (COMT), thus increasing epinephrine, norepinephrine, and dopamine (mercury increases COMT during gestation). R

Studies have also shown that mercuric chloride induces oxidative stress, amyloid-beta peptide (Aβ) production, and elevated phosphorylated tau levels in neuroblastoma SH-SY5Y cells, which these effects may be reduced or reversed by melatonin. R R

Methylmercury can also increase levels of glutamate by inhibiting glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (EAAT/GLT-1) in the brain, causing excitoxicity. R R

Mercury may contribute to the formation of Autism spectrum disorders (ASD). R

Mercury can over activate NMDA and increase interferon-gamma (IFN-gamma), causing problems with ASD. R

For example, mercury causes mast cells to create a leaky blood-brain-barrier (BBB). R

Mercury can cause demylenation, the main pathogenesis of multiple sclerosis (MS). R

For example, repeated exposure of mercury causes brain damage in models of MS through mitochondrial dysfunction. R

4. Eyes

For example, color vision impairment has been seen from occupational exposure to mercury. R

These visual impairments may be a result of the structural and physiological damage that mercury has been shown to have on the mammalian eye. R

5. Heart

 
mercury blood
 

Recent studies have also linked mercury exposure has been shown to increase risk and progression of atherosclerosis and cardiovascular disease. R

For example, mercury chloride exposure can cause rapid heart rate and increased blood pressure, as mercury reduces nitric oxideR R

Mercury can affect cardiovascular health by reducing antioxidant function, thus promoting free radical stress and lipid peroxidation in cell membranes and lipoproteins. R R R

For example, it may increase oxidized low-density lipoprotein (Ox-LDL) levels, which are found in atherosclerosis lesions. R R R R R

Mercury found in fish could offset the cardiovascular protective effect of omega-3 fatty acids from fish oil and may cause an increased risk of heart attack and death from cardiovascular events. R R

6. Gut And Kidneys

Mercury has also been shown to have health effects on the gastrointestinal system such as methylmercury’s potential to damage the lining of the intestines and kidneys. R

Mercury can shift the gut microbiome to more mercury-resistant bacteria. R

In the kidneys, it increases the risk of acute tubular necrosis in epithelial cells R

Technical:

  • Increases risk of acute tubular necrosis in epithelial cells, which triggers the onset of HgCl2-induced acute renal failure. R

7. Endocrine System

Low exposure levels of mercury may also affect the endocrine system in animals and people through disruption of the pituitary, thyroid, adrenal glands and pancreas. R R

In the adrenals, mercury can lower plasma levels of corticosterone, leading to high adrenocorticotropic hormone (ACTH) levels. R

This stress on the adrenal glands may eventually create enough destruction to cause Addison’s Disease. R

Mercury buildup in the pituitary system may also inhibit release of Arginine Vasopressin (AVP). R R

Mercury in the thyroid blocks thyroid hormone production by which may cause dysregulation of body temperature control, hypothyroidism, thyroid inflammation and depression. R R

Mercury can also inhibit pancreatic cells of insulin, thus causing problems with hyperglycemia. R

8. Weight And Diabetes

Mecury can store itself in fat and act on it.

For example, blood mercury concentrations are significantly associated with visceral adipose tissue (VAT, aka fat). R

As said above, mercury can affect the pancreas and mercury levels in the blood are associated with insulin resistance. R R R

9. Reproductive System

Exposure to toxic levels of mercury may cause subfertility, infertility, intrauterine growth retardation, spontaneous abortions, malformations, birth defects, postnatal death, learning and behavior deficits, and premature aging. R

It has been linked to menstrual disorders including abnormal bleeding, short, long, irregular cycles, and painful periods. R

For example, mercury has been shown to inhibit the release of FSH and LH from the anterior pituitary which in turn can effect estrogen and progesterone levels leading to ovarial dysfunction. R

It also reduces sperm production and testicular weight, and mercury exposure has been linked to causing erectile dysfunction (ED). R R

10. Development

 
mercury pregnancy
 

Concentrations of methylmercury have been shown to cause significant genotoxic alterations such as delayed psychomotor development with minimal signs of methylmercury poisoning. R R R

Mercury can easily pass from mother to child during development and may cause: R

  • Brain damage R R R R
  • Cerebral palsy and psychomotor retardation R R
  • Miscarriage, spontaneous abortions, stillbirth, and low birth weights R
  • Neural tube defects, craniofacial malformations, and delayed growth R

For example, a study of 64 children that were exposed to mercury during development showed signs and symptoms of: R

  • mental retardation (100%)
  • primitive reflexes (100%)
  • strabismus (77%)
  • cerebellar ataxia (100%)
  • dysarthria (100%)
  • chorea and athetosis (95%)
  • deformed limbs (100%)
  • hyper salivation (95%)
  • epileptic attacks (82%)
  • growth disorders (100%)

11. Cancer

Mercury has also been classified as a human carcinogen by the International Agency for Research on Cancer and by the German MAK Commission, although there is limited data to support this statement. R R

Mercury lows natural killer (NK) cells. R

Technical info about Hg and Cancer:

  • Increases the secretion of beta-amyloid 1-40 and 1-42 and induces oxidative stress of SHSY5Y neuroblastoma cells R
  • Increases induced apoptosis of CD4+ T cells at concentrations as low as 0.5 μM R
  • Increases cell death in rat hepatoma AS-30D cells by way of necrosis and apoptosis. R
  • Increases intracellular Ca2+ concentration ([Ca2+]i) in brain cells in the nerve terminal R

What Increases Mercury?

Due to its toxic nature, you would likely not want to increase mercury levels, but the following are ways in which mercury exposure may be increased:

In addition, natural health products made in China such as shark cartilage may contain unsafe levels of mercury. R R R

Furthermore, mercury exposure from the traditional Chinese medicine Cinnabar is considered low, but it is suggested that interaction with the other herbal ingredients in the supplement as well as the bioactivity in the gastrointestinal tract may affect Hg exposure after high dose or long-term use. R

Other natural health product applications that may contain unsafe levels of mercury include the plant-based paint henna, which is used to create temporary paint tattoos. R R

How To Protect Against And Remove Mercury From The Body

Bile (via defecation), sweating, and urination are the major excretion pathways for mercury, so it is important to combine chelating promoters and binders. R R

It's also important to know if you have organic (stores in cells/brain) or inorganic (from amalgams, inhalation) mercury in your body.

 
 

Diet and Lifestyle Changes

  • Avoidance of certain fish (see list of fish below) - the FDA advises that young children, pregnant women, and nursing women avoid shark, swordfish, king mackerel, and tilefish and no more than 12 ounces of fish and shellfish lower in mercury per week R R R
  • Sauna - mercury can be removed from the body through sweat (intense exercise or being exposed to hot environments) R
  • Decrease your risk of mercury exposure by limiting or abstaining from smoking cigarettes and cigars along with reducing overall exposure to such smoke. R
  • Removal of dental amalgams - one dental amalgam filling is estimated to release about 3 to 17 µg of mercury vapor daily R R
  • Avoid creams and lotions with mercury in it as it can be absorbed through skin R
  • Isothocyanites (DIM and sulforaphane) - found in cruciferous veggies such as broccoli sprouts, wasabi, horseradish, mustard, radish, Brussels sprouts, watercress, papaya seeds, nasturtiums, and capers R
  • NRF2 activation - if mercury chelation is making your worse, be sure to read about NRF2 or take DIM R
  • HDAC inhibition (HDAC2/4) - may prevent psychomotor changes from mercury R R

Supplements:

  • Alpha Lipoic Acid (ALA) - increases GSH to inhibit ROS, passes blood-brain barrier, and binds to mercury (needs to be taken with other chelators and chronically due to its short half life of 3-4hrs to avoid redistribution) R
  • Ascorbate (such as vitamin C) - has protective action against mercury genotoxicity in vitro by preventing sister chromatid exchanges and abnormal mitosis R R R
  • Bacopa - protects the brain and mitochondria against mercury oxidative stress R R
  • Caffeine - protects brain against glutamate neurotoxicity from mercury R
  • Calcium (and calmodulin) - have a protective action of L-type calcium channel blockers against mercury cytotoxicity in the vascular system R
  • Carnosine - chelates heavy metals, but may not be strong for mercury R
  • CDP-choline - protects against mercury-induced mitochondrial damage and renal dysfunction R
  • Charcoal - strong binder of mercury toxicity R R
  • Chlorella - increases elimination of mercury from the GI tract, muscles, ligaments, connective tissue, and bone, while chlorella and cilantro as food materials can detoxify some neurotoxins such as heavy metals (e.g. mercury) and toxic chemicals (e.g. phthalates, plasticizers and insecticides) R R R
  • Cilantro - similar to the chelating effects of chlorella R
  • DHA/EPA (not necessary but if you  use fish oil, it needs to be a good source) R R
  • Estrogen (as β-estradiol) - has a neuroprotective effect on SHSY5Y neuroblastoma cells by reducing oxidative stress and β-amyloid secretion R
  • Fisetin - may decrease effects of mercury on developmental R 
  • Garlic - decreases accumulation of cadmium, methylmercury and phenylmercury in the liver, kidneys, bone and testes. R
  • Glutamine - combines well with caffeine to inhibit glutamate excitotoxicity R
  • Glutathione - prevents mercury toxicity by exerting antioxidant activity and chelating mercury R R R R R
  • Melatonin - protects brain against neurodegeneration from mercury R R
  • Molybdenum - must be taken if you have a problem with sulfur R
  • N-Acetyl-L-Cysteine (NAC) - has found to be effective in enhancing methyl mercury excretion R R
  • Purslane - helps remove mercury and prevents neurotoxic effects R
  • Selenium - paramount as mercury depletes selenium stores and helps prevent neurotoxicity (bypasses mercury's ability to inhibit NRF2, but methyl-mercury may need to be demethylated first) R R
  • Silica (such as IMD or Ultra Binder) - binds to heavy metals R
  • Taurine - prevents liver damage from mercury R
  • Thiamine - may prevent methylmercury toxicity R
  • Valerian - prevents mercury induced mitochondrial damage R
  • Vitamin E - protects against mecury-induced hepatotoxicity (not completely) R

Other compounds:

  • Captopril - prevents mercury induced toxicity on kidney mitochondria R
  • Dizocilpine - by antagonizing NMDA receptors, it can prevent neurotoxicity in the cerebral cortex R
  • Ebelson - prevents glutamate-induced damage from mercury in the brain R
  • Memantine - protects brain against glutamate excitotoxcity from mercury R
  • Microbial biosorbents overexpressing metalloregulatory proteins may be used for the excretion of mercury from the body. R
  • Metallothionein protein - rich in sulfhydryl groups, helps in scavenging and reducing the toxic effects of mercury. R R
  • Dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA. succimer) and Dimercaptopropanesulfoxid acid (DMPS) - can be used as chelating agents. R
  • Tamoxifen - prevents mercury induced toxicity on kidney mitochondria R
  • Myogenin (as a negative regulator of HDAC4) R
  • IL-12 - helps induce Th1 response R
  • D-penicillamine and N-acetyl-d, l, penicillamine (NAP) R
  • Plasma exchange R
  • Chromolaena odorata - gathers and isolates Hg ions through the production of Hg peptides R

Testing Mercury Levels

The US Environmental Protection Agency has reduced the recommended safe daily intakes of methylmercury from 0.5 to 0.1 μg/kg of body weight. R R

Asian populations have higher MeHg intake than the Non-Asian populations in the U.S. and seafood intake is a key predictor of blood Hg concentration. R

Hair and toenails can be used to test for levels of mercury and can be used as an indicator for long-term exposure. R

Urinary concentration is a good indicator of elemental/inorganic mercury, but organic mercury (e.g. methyl mercury) can be detected easily in feces or hair. R R

Mercury also increases inflammatory markers so these could be checked as well (but does not show it is definitely mercury):

  • IFN-gamma R
  • IL-6 R R
  • TNF-alpha R

Mercury Levels In Fish

 
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988285/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988285/

 

What Makes Mercury Worse?

Mechanism Of Action

Simple:

  • Increases R
  • Increases ACTH R
  • Increases APP R R
  • Increases ALT R
  • Increases AST R
  • Increases Cholesterol (ox-LDL) R R R R R
  • Increases Glutamate R R
  • Increases GLUT-1R
  • Increases GST-α1 R
  • Increases HDAC4 R
  • Increases Histamine R
  • Increases IFN-gamma R
  • Increases IL-4 R
  • Increases IL-6 R R
  • Increases MMP2 R
  • Increases MMP9 R
  • Increases NMDA R
  • Increases Phos-tauR R
  • Increases P38 R
  • Increases TNF-alpha R
  • Increases Tri R
  • Increases VEGF R
  • Reduces ALAD R
  • Reduces BDNF R R R
  • Reduces Ca2+ (the influx in brain cells following nerve stimulation) R
  • Reduces CD4+ T cells R
  • Reduces COMT R
  • Reduces EAAT/GLT-1 R
  • Reduces FSH R
  • Reduces GLAST R
  • Reduces GlutathioneR
  • Reduces GSTα2 R
  • Reduces LH R
  • Reduces NO R
  • Reduces NRF2 R

Advanced:

  • The excretory half life of methyl mercury in man is about 70 days, with approximately 90% being excreted in stool. R
  • Methylmercury-cysteine complex mimics methionine readily cross the blood brain and placental barrier and cell membrane. R
  • Mercury is absorbed through optic membranes or from the circulation to accumulate in the vitreous leading to local or systemic action. R
  • The potential teratogenic effect of mercury is through the pentose phosphate pathway. R
  • Methylmercury has been shown to impair tail development in zebrafish embryo at least partially by activation of the tissue remodeling proteases Mmp9 and Mmp13. R
  • Mercury has been shown to significantly activate phospholipase D in bovine pulmonary artery endothelial cells. R
  • Mercury induces the production of ROS (e.g., hydroxyl peroxide and superoxide radicals) and RNS (e.g., nitric oxide, peroxynitrite and S-nitrosothiols) in both in vivo and in vitro systems, and these radicals have been found to cause oxidative damage to DNA, proteins, and lipids. R
  • Chronic exposure to relatively low levels of mercury may inhibit antioxidant enzymatic activity due to persistent oxidative stress. R
  • Metallothionein (a thiol moiety) plays an important role in the initial binding of mercury in astrocytes in the brain, hepatocytes and renal tubular cells in the kidney and may be the first protective mechanism, but increases in dose and over time, mercury shifts from these low weight thiol proteins to the higher affinity selenium containing selenoproteins. R
  • MeHg is able to enter in neural cells mainly through the L-type neutral amino acid carrier transport (LAT) system by a mimicry mechanism. In addition, experimental studies were important in showing that MeHg is transported across the placenta from pregnant animals to their fetuses. R
  • Thimerosal specifically increased HDAC4 protein expression but not that of HDACs 5, 6, 7, and 9. R

Genetics

ABC

  • MDR1, MRP1 and MRP2, respectively codified by ABCB1 gene, Sub-Family B; and ABCC1ABCC2 genes, Sub-Family C: are found in BBB, placenta, liver, gut, and kidney. Functional suppression of ABCs activity increases Hg content in cells and sensitivity to Hg toxicity in vitro R

APOE

  • APO-E4 (apolipoprotein E-4): entails a greater risk of developing Hg-induced neurological outcomes R R R

COMT

  • rs4680, rs4633, and rs6269: has been found to modify the effects of mercury exposure on a wide range of neurobehavioral functions in Attention, learning, and memory in young boys. R

COPX4

  • rs1131857 or COPX5: rs1729995- a nonsynonymous CPOX4 mutation in exon 4 of the gene has been found to convert asparagine-to-histidine at amino acid 272 in the protein structure, with the expression of an enzymatic form at lower activity leading to insufficient heme synthesis. Some studies in humans suggested that this variant may increase genetic susceptibility to the adverse neurobehavioral effects of Hg exposure in adults and children R R R

GCLC

  • rs1555903: showed a highly significant (p = 0.007) main effect on mercury retention in the umbilical cord in a UK birth cohort R R

Glutathione S-transferase (GST): is known to be a risk factor for acrodynia and may also increase susceptibility to mercury  R

  • GSTP1 Val105 polymorphism modified effects of prenatal p,p′-Dichlorodiphenyltrichloroethane (p,p′-DDT) exposure on cognitive functioning in preschoolers, thus suggesting oxidative stress as a potential neurotoxicity mechanism R R
  • GSTP1 polymorphisms (rs1138272 and rs1695) in Hg toxicokinetics have been associated to MeHg biomarker levels in epidemiological studies, with multiethnic, multicultural and bio-diverse features R R R R R R
  • GSTT1−/− and GSTM1−/− (GSTP1  rs1138272 and GSTP1 rs1695/GCLC rs1788390): may present higher levels of intermediates of oxidative metabolism, which unbalance the antioxidant status, which lead to exacerbation of the pathological effects of reactive oxygen species. R

MMP

  • MMP-9 promoter (CA)n repeats (rs 3222264) and a MMP-2 promoter polymorphism (rs243865), which likely increased the cardiovascular risk by affecting circulating MMPs levels in fish-consuming Brazilians R R R

MT1

  • MT1A (rs8052394) and MT1M (rs9936471): it is likely that they may alter the molecular structures of different isoforms, affecting Hg retention in terms of metal–binding capabilities, and subsequently biomarker levels R R
     
  • MT1M(rs2270836) and MT4 (rs11643815): it is likely that they may alter the molecular structures of different isoforms, affecting Hg retention in terms of metal–binding capabilities, and subsequently biomarker levels R R
     

NOS3

  • NOS3 (27 bp VNTR-4a/4b): increases susceptibility to cardiovascular diseases after MeHg exposure by modulating nitric oxide levels  R R

OAT

  • OAT1 (SLC22A6 gene) and OAT3 (SLC22A8 gene), expressed on the basolateral membrane of the proximal tubule, are well-studied organic anion transporters. In vivo studies demonstrated their involvement in the cellular uptake of Hg conjugates in multiple districts. R R

More Research

  • A simple, sensitive and selective fluorescent assay based on peptide PHg-Au cluster has been developed for the detection of Hg2+ ions. R
  • The development of reliable and ultrasensitive detection marker for mercury ions (Hg2+) in drinking water has potentially been found in a fluorescence and SERS-based detection sensor platform. R
  • As the frozen Arctic ice freezes, it may release up to 2x the amount of mercury as already found in the soil and water. R