Selenium and Mercury Toxicity

The selenium in our cells is the molecular “target” of toxic mercury. Inhibition of the normal biological activity of seleno-enzymes is the mechanism by which mercury damages our cells, most particularly our brain and nerve cells [Ralston & Raymond 2018].

Conceiving of selenium as the “target” of mercury leads to a better understanding of mercury toxicity than the old theory of selenium as the “tonic” that binds toxic mercury in a form that is no longer harmful [Ralston & Raymond 2018].

Professor Nicholas Ralston and consultant Lisa Raymond have done a review of the research literature about the characteristics of mercury toxicity to identify the selenium-dependent aspects of mercury’s biochemical mechanisms and effects. Their conclusions [Ralston & Raymond 2018]:

• Methylmercury irreversibly inhibits the activity of seleno-enzymes that would normally prevent or reverse oxidative damage in the brain. (Oxidative damage is the damage that harmful free radicals cause to cells and tissues that do not have enough antioxidant protection.)
• Selenium supplementation is needed whenever there is exposure to methylmercury and especially whenever the intake of methylmercury approaches and exceeds the cells’ stores of seleno-enzymes.
• Too much exposure to methylmercury may induced a “conditioned selenium deficiency.”
• Mercury does its toxic damage by interrupting and disrupting normal selenium metabolism.
• The characteristic effects of mercury toxicity are the binding of selenium to mercury, thus rendering the selenium unavailable for its normal biological functions, and the consequent irreversible inhibition of seleno-enzymes.

Exposure to Mercury and the Need for Adequate Selenium Reserves

Ralston and Raymond point to the following sources of exposure to toxic mercury:

• Airborne elemental mercury when inhaled is absorbed at a rate of about 75%.
• Methylmercury, a neurotoxicant, bio-accumulates and bio-magnifies in ocean and freshwater fish (the dominant sources of dietary methylmercury).

Ralston and Raymond do not mention in their 2018 paper the fear that exposure to the mercury in dental amalgam fillings may have toxic effects both for the patients and for the dentists [Rathore 2012].

Nearly everyone is subject to elemental mercury and methylmercury in low exposures, which are generally without severe adverse effects. However, high exposures are neuro-toxic because the mercury crosses the blood-brain barrier.

Mercury binds preferentially with sulfur and selenium; however, mercury’s affinity for selenium is approximately one million times greater than its affinity for sulfur, making selenium the number one target of mercury toxicity [Ralston & Raymond 2018].

High methylmercury exposures resulting from poisoning incidents have given a well-defined picture of the motor and sensory disorders associated with extensive oxidative damage to the brain. The fetal brain is particularly vulnerable to harm from mercury toxicity; the mercury crosses easily across to the placenta [Ralston & Raymond 2018].  Depending on the victim’s age and exposure level, the symptoms of mercury toxicity will include the following motor and sensory disorders:

• metallic taste in the mouth
• nausea and vomiting
• loss of motor skills and coordination
• loss of muscle strength
• loss of feeling in the hands and face
• loss of acuity in vision, hearing, and speech
• difficulty in breathing
• difficulty in standing up straight and in walking

Bio-Medical Mechanisms of Mercury Toxicity

Ralston and Raymond make the following points about how mercury has a toxic effect. They make their points in considerably more detail than I can here; interested readers will want to get a copy of the entire article [Ralston & Raymond 2018].

• The placental and blood brain barriers cannot stop the passage of mercury. The fetal accumulation of mercury has a concentration higher than the mercury concentration in the mother’s blood.
• Once the mercury has crossed the placental and brain barriers, it forms “suicide substrates” that deliver the bound mercury to the seleno-enzymes’ active sites.
• At the seleno-enzymes’ active sites, the mercury forms an extremely stable permanent bond with the selenocysteine component of the seleno-enzymes. As a result, the seleno-enzymes cannot carry out their essential functions. Their selenocysteine component is blocked by the mercury. In this way, the mercury acts as an “irreversible inhibitor of seleno-enzyme activity.” For example, the seleno-enzymes glutathione peroxidase and thioredoxin reductase are inhibited in their antioxidant roles.
• The damage from the loss of seleno-enzyme antioxidant activities is compounded by mercury’s ability to diminish brain selenium concentrations below the minimum threshold of approximately 60% of normal selenium concentration in the brain. The “sequestration of the selenium” together with mercury is manifest not only in the brain but also in the kidney and the liver. In cases of catastrophically high mercury exposures, there will be an ongoing loss of selenium in body and brain tissues. (Note: Ralston and Raymond point out that high mercury accumulations on the order of 10–100 μM in the brain and the endocrine tissues do not seem to have toxic consequences as long as at least approximately 1 μM of “free selenium” remains available for seleno-enzyme synthesis, thus ensuring that the antioxidant activities can continue.)
• It gets worse. The sequestration of the cellular selenium by mercury may not only deprive the cells of the seleno-enzymes they need to prevent and reverse oxidative damage but may also transform the thioredoxin reductases into potent apoptosis initiators. Selenium-deprived cells will commit suicide.
• The seleno-enzyme Selenophosphate synthetase (SEPHS2) is the enzyme that is needed for the synthesis of selenocysteine. If the activity of SEPHS2 is inhibited, then, hypothetically, the cells will have no way to produce selenocysteine. (Note: Selenocysteine is a necessary component of the 25 known seleno-proteins; selenocysteine’s catalytic activity is necessary for the seleno-enzymes to carry out their functions.)

Selenium Deprivation and Implications for Brain Cells

Again, I rely very much on Ralston and Raymond’s text [Ralston & Raymond 2018]:

• The brain is at an increased risk of oxidative stress because 1) oxygen consumption is approximately 10 times greater in the brain than in other tissues and 2) the brain has few antioxidant enzyme pathways. Consequently, the brain is very dependent upon seleno-enzymes to prevent and reverse oxidative damage in the brain.
• Laboratory studies have shown that, in periods of dietary selenium deficiency, the available selenium is preferentially re-distributed from other body tissues to the brain and endocrine tissues. Moreover, there is a preferential expression of certain selenoproteins in the brain, which suggests a hierarchy of need for brain activities.
• High mercury exposure is the only environmental insult known to impair brain seleno-enzyme activities severely. Mercury poisoning reduces the availability of free selenium in the brain and diminishes brain seleno-enzyme activity, which results in extensive damage to the most active neurons.
• Postmortem examination of the brains of victims of mercury poisoning reveal neuronal cell loss, especially in the sensory regions of the cortex, cerebellar granular cells, primary motor cortex, and peripheral nerves. This pattern is also seen in laboratory animal studies.

Selenium’s Role in Fetal Development

• The fetus does not have significant tissue selenium reserves; consequently, the loss of maternal selenium normally provided to the fetal brain can result in impaired seleno-enzyme activity and oxidative damage. The iodothyronine deiodinase, thioredoxin reductase, and glutathione peroxidase families play critical roles in fetal brain development, fetal growth, fetal thyroid and calcium metabolism, fetal protein folding, and prevention/reversal of oxidative damage in the fetus.
• Research evidence shows that pregnant women who decrease their dietary intakes of fish are likely to increase their children’s risks for lower scores in intelligence, fine motor skills, communication skills, and social skills later in life.
• Research studies suggest that the mercury exposure from eating ocean fish that contain selenium in excess of mercury (which is true of nearly all commercial marine fish species) does not result in developmental harm for children. Instead, it is the reduced maternal consumption of ocean fish during pregnancy that is associated with significant risks. Ocean fish are an important source of selenium and other important nutrients necessary for the health and development of children.

Selenium and the Latency of Mercury Toxicity

Mercury toxicity is characterized by a silent latency; there is a prolonged delay between the ingestion of a harmful and the onset of symptoms. The symptoms may take months to develop. No one has succeeded in finding the cause of this latency period [Ralston & Raymond 2018].

Ralston and Raymond believe that the latency period of mercury toxicity is strong evidence in support of the hypothesis that mercury’s toxic effects result primarily (perhaps exclusively) from mercury’s inhibition of selenium metabolism.

Ralston and Raymond posit that the adverse consequences of mercury toxicity will not develop as long as there is sufficient selenium available to support essential brain seleno-enzyme activity. However, if there is mercury exposure greater in extent than there are selenium reserves, then the mercury exposure is likely eventually to overwhelm the ability of the brain and nervous system to offset the systemic losses of selenium due to selenium sequestration by the mercury. The differences in individual selenium status will affect the duration of the latency.

Continual attrition of selenium reservoirs will gradually impair the ability of the brain to maintain enzymatic function in the neurons. When the activity of the antioxidant seleno-enzymes falls below a critical threshold, the damage to cellular lipids, proteins, and other important bio-molecules will result in the symptoms which characterize mercury toxicity [Ralston & Raymond 2018].

Conclusions: Selenium Sequestration the Mechanism of Mercury Toxicity

Ralston and Raymond [2018] conclude that the distinctive characteristics of mercury toxicity are consistent with mercury’s unique ability to impair brain seleno-enzyme activity.

Ralston and Raymond [2018] warn that children and pregnant women should not eat meat from predatory whales, certain varieties of shark, large specimens of swordfish, halibut, and any other types of fish that contain more mercury than selenium in their tissues.

They note that nearly all other seafood and ocean or freshwater fish provide far more selenium than mercury and will, therefore, improve, rather than diminish, maternal and fetal selenium status and will provide nutritional benefits for health and development [Ralston & Raymond 2018].

Sources

Ralston NVC & Raymond LJ. (2018). Mercury’s neurotoxicity is characterized by its disruption of selenium biochemistry. Biochim Biophys Acta Gen Subj. pii; S0304-4165(18):30141-7.

Rathore M, Singh A & Pant VA. (2012). The dental amalgam toxicity fear: a myth or actuality. Toxicology International. 19 (2): 81–88.

The information contained in this review article is not intended as medical advice and should not be used as such.

4 March 2020