Neurons and Exercise

Neurons and Exercise

Saturday, March 28, 2020


Selenium and ROS Status Impacts Covid-19 Coronavirus Virulence


Dennis N. Crouse PhD – Updated April 22, 2020 – Draft of Chapter From My New Book

Introduction
In early April this blog post was updated when it was learned that zinc had been identified as a replication inhibitor for SARS-CoV1.  In addition, it was learned that selenomethionine is a replication inhibitor for some viruses.  Two sections were added describing this research and what is known about using  selenomethionine and zinc supplements sequentially to facilitate curing CoV Coronavirus. 
In 2018 I became interested in viruses that cause neurological diseases with reports from the CDC of a number of children in the U.S. suffering from what I call Sudden-Onset Weak Limb Syndrome (SOWLS).  This usually occurs within a few days of being vaccinated in the same limb that soon becomes weak or being injected with saline on the same limb at a former site of vaccination. Both a non-virulent Coxsackievirus and the vaccine adjuvant aluminum were suspects in the neuronal infection and were linked to the syndrome as discussed in my 2018 blog post (see http://prevent-alzheimers-autism-stroke.blogspot.com/search?q=limb+syndrome ).  The mechanism of this infection involves the known creation of mutagenic reactive oxygen species (ROS example hydrogen peroxide) by aluminum that promotes mutagenic evolution of a non-virulent virus to a virulent virus inside neurons. This was found to be reversed in some children by just regularly drinking silica rich water that facilitates the removal of aluminum and cures SOWLS.
This blog post is for a chapter describing how viruses, aluminum, and selenium-deficiency work together to create a perfect-storm for neurological inflammation. An example of this type of inflammation is anosmia (i.e. loss of sense of smell). Since aluminum is known to accumulate in the olfactory lobe of the brain, it is a causal suspect of anosmia. Viruses, such as human CoVs that cause common colds, have been detected in the brain and are also causal suspects. The path from the nose to the olfactory lobe of both the virus and aluminum is likely by retrograde axonal transport. This has been shown to be the case in rats exposed to aluminum and in mice infected with SARS-CoV1 virus. If the Covid-19-CoV2 virus is also axonally transferred from the nasal cavity to the brain in humans, ROS due to aluminum in the brain, including the olfactory lobe, may cause the virus to mutate, become more virulent, and lead to brain inflammation and possible death. I have been praying that sudden-onset anosmia is not found to be a symptom of Covid-19.
I am writing this introduction on March 26th 2020 the day in which the number of deaths due to Covid-19 in the U.S. topped 1,000 and worldwide topped 23,000. Several days ago South Korea, where testing has been more widespread, reported that 30% of Covid-19 cases had anosmia. Then Germany reported that 67% of Covid-19 cases had anosmia. Just a few hours ago Doctor Desruisseaux of Yale Univ. School of Medicine said “We have been seeing more and more anosmia in our institution in younger individuals, in the absence of other symptoms … if someone is having anosmia, even in the absence of other symptoms, they should isolate themselves until they get tested for SARS-CoV2 (Covid-19) so they don’t transmit the disease”           
Viruses

Viruses are microscopic life forms that infect host organisms in which they multiply. Viruses can be benign or virulent. In order for a virulent virus to increasingly spread through a population of host organisms the viral host, before dying, must infect more than just one other host. The odds of this are increased if the host’s acquired virus has two forms (i.e. phenotypes): non-virulent that is contagious and slowly evolves into a virulent form in some hosts. This is an adaptive evolution that can occur weeks after infection potentially causing neutralization of the host’s initial immune response. 

Viruses can have either DNA or RNA as their genetic material.  The RNA retroviruses have a genome encoded on two identical single-stranded RNA molecules.  Once inside a host cell an RNA retrovirus, such as Covid-19 Coronavirus, makes a copy of its genome as DNA and then inserts the copy into the DNA of a host cell. A retrovirus uses its own reverse transcriptase enzyme to produce DNA from its RNA. Because this transcription lacks the usual proofreading of DNA replication, a retrovirus mutates frequently causing viruses to evolve. Adaptive evolution in viruses can be in response to the host’s cellular environment and can have an effect on viral virulence, pathogenesis, and host immune response. Research has found that oxidative stress in hosts with a selenium (Se) deficiency (e.g. blood level less than 1mcMol Se/L) rapidly results in benign variants of RNA viruses evolving into stable virulent phenotypes. Examples of RNA viruses that evolve to virulence in selenium deficient hosts are the Coxsackievirus B3, poliomyelitis, mild influenza H3N2, SARS-CoV1, and possibly Covid-19 Coronavirus.

Keshan disease causes congestive heart failure and claimed thousands of lives in China between 1960 and 1970. Keshan disease infects both humans and sheep. By experimenting with sheep it was discovered that oral administration of a selenium supplement (i.e. sodium selenite, Na2SeO3) prevented and cured Keshan disease in both sheep and humans1.   

In 1985 Melinda A. Beck discovered that Keshan disease is caused by a rapid genomic evolution of a non-virulent Coxsackievirus B3 to a stable virulent phenotype in selenium-deficient host2. The stability was proven by injection of the evolved virus into a selenium adequate mouse inducing significant heart damage2. This rapid genomic evolution also occurs in vitamin E-deficient hosts3. Both selenium and an antioxidant, like vitamin E, work independently to prevent a build-up of reactive oxygen species (ROS) in viral hosts. A deficiency of ether of these nutrients can create a ROS rich environment that allows even a virulent strain of Coxsackievirus B3 to adaptively evolve and become more virulent3.


Keshan disease was confined to areas of China that are selenium-deficient. In these areas food crops are low in selenium. Eating locally grown food left the population living in these areas selenium-deficient and made them vulnerable to a build-up of ROS and the evolution of a more virulent virus.  Figure 1 shows areas of China where Keshan disease was prevalent between 1960 and 19704 and these areas overlap with selenium-deficient soil as shown in figure 2. Selenium-deficient areas account for 72% of China’s total area. This deficiency affects over 70 million people who thereby face potentially adverse health impacts5.


Figure 1. Map of prevalence Keshan disease with circle indicating epicenter

of Covid-19 Coronavirus outbreak in Hubei Province, China4     

Figure 2. Map of China with levels of water soluble selenium (mcg/kg)

in soil and the circle indicates epicenter of Covid-19 Coronavirus outbreak

Covid-19 Coronavirus was first identified in late 2019 in Wuhan, China as causing an acute respiratory syndrome. By January 28, 2020 when there were just 106 reported deaths due to the coronavirus, the virus had a prevalence shown in figure 36 with an epicenter that coincides with the circles in figure 1 and 2. 

Figure 3.  Prevalence of Covid-19 Coronavirus as of Jan. 28, 2020 1PM EST
With epicenter in Hubei Province, China
Total confirmed cases 4,690 (red); total deaths 106 with 100 in Hubei6
Figure 3 is a snapshot of Covid-19 Coronavirus in February 2020 when only 106 deaths were reported in China, with 100 of these deaths in Hubei Province, China located with the largest red circle6. The size of each red circle represents the number of confirmed cases, not deaths. Note that Covid-19 Coronavirus, unlike Keshan disease, has spread beyond the areas of China with selenium-deficiency (see figure 2). Selenium status measured by hair analysis of China’s population has declined 24-46% when compared with inhabitants living in the same geographic region between 1994 and 2014 and this may account for the spread of Covid-19 Coronavirus in 20204


          Figure 4. Map of Hubei Province, China the epicenter of
          Coronavirus outbreak

Does selenium-deficiency shape the adaptive evolution of the Covid-19 CoV2? We don’t have an answer for this question today but we do know it likely shaped the evolution of SARS-CoV1.

SARS Coronavirus (SARS-CoV1) originated in Foshan, China in Guangdong Province in November of 2002. Ultimately over 8,000 people were infected and 774 died worldwide between 2002 and 20047. The palm civet (Paguma larvata) is the intermediary host for the SARS-CoV8. The civet is a raccoon like animal. The palm civet is found in both selenium-available Guangdong Province and in selenium-deficient Hubei Province, China. But the civet-CoV virus is different from the human-SARS-CoV19.

Virulence of SARS-CoV1 Coronavirus in humans starts with entry into pulmonary cells in the lungs. A glycoprotein called “Spike” on the surface of the virus has a receptor binding domain (RBD) involved in entry of host cells10. There are six critical amino acids in the RBD that are required for efficient entry of the virus into host cells. It was found that civet-CoV from selenium-deficient Hubei is identical to human SARS-CoV1 at position 360 as opposed to civet-CoV from selenium-available Guandong9. This could be due to low-selenium status civets as viral hosts promoting the adaptive evolution of less virulent civet-CoV into more virulent human SARS-CoV1 by changing one of the 6 amino acids in the RBD.

Mild Influenza A Virus (H3N2) has both a benign and virulent status. Both selenium-deficient and selenium-available mice were infected with H3N2. Only in the mice with selenium-deficiency did the H3N2 virus rapidly evolve into the more virulent status11.

Poliomyelitis virus used as a live attenuated vaccine was found to rapidly mutate when injected into humans with less than 1mcMol Se/L, while above this level, selenium in host blood deterred rapid mutation of this virus12.  This is a threshold level of selenium status in the blood required to avoid viral adaptive mutations resulting in more virulent phenotypes.

Selenium Supplementation Decreases Viral Load

In addition to decreasing ROS and viral mutation rates, selenium supplementation has been shown to suppress the population of some viruses in the human body.  Selenomethionine (200mcg per capsule) in high selenium yeast was taken daily by 91 HIV-1-seropositive men and women (18-55 years of age) and compared with a similar group of 83 HIV-1-seropositive patients who were given a placebo.  After 9 months the group taking selenomethionine increased their mean serum selenium level by 32mcg/L and significantly suppressed their viral load of HIV-1 with no significant changes observed in the placebo group13.  Taking a selenium supplement every day for at least 3 months is required to significantly increase serum selenium level and have a potential impact on viral load in the body.

Some viruses replicate on macrophages that are vacuoles formed inside host cells. Macrophages vacuum up foreign intruders, such as viruses. This process, called autophagy, has been found to be induced by some viruses. These viruses use the macrophage as a nursery for replicating more viruses14. Selenomethionine has been found to attenuate virus replication by inhibiting autophagy induced by some viruses15. Therefore taking a selenomethionine supplement for at least 3 months could suppress the replication of even the more virulent phenotype of Covid-19 Coronavirus and thereby facilitate curing the disease.

Zinc Supplementation Decreases Viral Load

Zinc supplementation for decreasing the duration of a respiratory virus infection has so far only been proven to be efficacious for the common cold19. There is scientific evidence that it may work similarly for patients with symptoms of virus infections due to SARS CoV1 or Covid-19 CoV2 Coronavirus.    

Researchers have had almost 20 years to find the “Achilles Heel” of the SARS-CoV1 Coronavirus.  During this time they have successfully found two enzymes (PLP2 and 3CL both proteases) made from RNA code of the SARS-CoV1 Coronavirus that are required for virus replication. The active site on both enzymes involves the same amino-acid dyad of one cysteine and one histidine16,17.  If either PLP2 or 3CL enzyme is inhibited virus replication is also inhibited17,18.

Amazingly, something as simple and inexpensive as zinc inhibits both PLP2 and 3CL thereby inhibiting SARS-CoV2 replication16,17. In the case of PLP2, zinc ion reduced enzymatic catalysis at a concentration for 50% of maximum inhibition of IC50 = 1.3mcM (85ppb)17. In the case of 3CL, zinc ion reduced catalysis with an inhibitory dissociation constant of Ki = 1.1mcM (72ppb) 18. Other ions such as magnesium, manganese, calcium, nickel, and cobalt had no effect on catalysis and with PLP2 copper had approximately an 8 fold lower effect than did zinc17.

The large zinc chelates were found to be less effective at inhibiting PLP2 than zinc ions derived from zinc salts, such as zinc acetate or zinc gluconate17. This was likely due to the active site on PLP2 being recessed and thereby sterically blocking molecules larger than zinc ions and zinc acetate17. Zinc acetate is ionized and releases free zinc ions more than zinc chelates. Zinc acetate is also smaller than zinc gluconate. Daily doses of zinc acetate (75mg or more) taken as throat lozenges spread throughout the day has been found to be more effective than zinc gluconate at shorting the duration of viral infections that cause the common cold19. Adult dosage of zinc acetate is 75 to 150mg per day as lozenges spread throughout the day. No more than 40mg per day should be given to children.                     

The active site cysteine and histidine dyad is likely conserved in both the non-virulent and virulent phenotypes of SARS and Covid-19 Coronavirus and this may well be their “Achilles Heel”.

Selenium Status of the World’s Population

A major factor in the selenium status of humans is soil selenium levels in areas where food crops are grown20. Figure 5 shows that many viral infectious diseases originate in selenium deficient areas of the world. The U.S. is lucky to have extremely high selenium (dark green areas in figures 5 and 8) for Midwestern wheat production and for California fruit and vegetable production. These crops are shipped nationwide and result in a population with an average U.S. selenium status higher than 1mcMol Se/L as shown in figure 6. Midwestern wheat is a major dietary source of selenium in the U.S. Because of an increased intolerance to wheat gluten in the U.S., there is less wheat consumption. In addition, because of our relatively recent demand for locally grown food, there may be segments of the U.S. population with selenium status lower than 1mcMol Se/L. These regions are shown in yellow in figures 5 and 8 and include some of our largest coastal cities.  

In some counties selenium status has historically been low and has recently been rising:

Finland - Although crops take selenium from the soil and thereby slowly deplete the soil of selenium, in general no effort is made to replace or enhance the soil by fertilization with selenium.  Due to extremely low selenium intake (25mcg/day) by the people of Finland in the 1970’s, the government made a decision to require selenium crop fertilization. Starting in 1984 Finland became the first county in the world to use sodium selenate as a fertilizer ingredient for food crops21. Currently all crop fertilizers used in Finland contain 15mg of selenium per kilogram. Unfortunately Finland is still the only country to implement this country-wide measure even though many countries in Europe have selenium-deficient soil20


After implementation of this program in Finland selenium concentration in spring cereals has increased 15-fold and the mean increase of selenium in beef, pork, and milk has increased 6-, 2-, and 3-fold, respectively. This has resulted in the mean human plasma selenium concentration of the Finish people increasing from almost deficiency (0.9mcMol Se/L) to normal selenium status (1.4mcMol Se/L)21. This higher selenium status appears to have protected the Finish from Covid-19 (see table 022).

In other countries selenium status has been recently declining these include: 

United Kingdom - From 1984 to 1995 serum, plasma, and whole blood selenium declined by as much as 42% in Scotland and the rest of the U.K. saw similarly steep declines23.  The dietary selenium intake of the European population in general has fallen 50% over the period 1975-200520. These declines were due to levies imposed on wheat imports from the U.S. and Canada after Britain joined the European Union in the early 1970’s resulting in increased use of selenium-deficient wheat from other European countries. Unfortunately most countries in Europe have selenium-deficient soil unlike the U.S. and Canada (see figure 5).

China – From 1996 to 2014 the selenium status of the Chinese declined by 24 – 46% when compared with inhabitants living in the same geographic region24.  The selenium content of human hair was found to be a useful indicator of human selenium intake and status. The decline in selenium status in China was found to be due to an overall decrease in grain consumption and the lower selenium content of rice24.  Without selenium fertilization rice can’t continue to provide sufficient amounts of this essential nutrient to the population.    


In general the world’s population is selenium deficient (see figure 6) and this deficiency is getting worse because we do not require adding selenium to our food, fertilizer for food crops, or feed for animals. This selenium supplementation could be done by requiring the addition of selenium to fertilizers, animal feed, and bread. Without these requirements we as individuals must act by supplementing our families and ourselves with selenium.   



Figure 5. Origins of viral infectious diseases correlate with geologic regions of poor Se

bioavailability:
yellow = <0.01, light green = 0.01 to 1.0, dark green = >1.0 mg/kg of selenium
Gray ovals depict nutrient iodine deficiency and brown patches indicate high arsenic
concentrations, which seem not to influence the etiology of viral infectious diseases; 25,26



Figure 6. Human blood selenium values with the 1mcMol Se/L marked
with a green line. Values below this line provide insufficient protection
for hosts against adaptively mutating viruses.26  

ROS Due to Airborne Environmental Toxins

Selenium deficiency is not the only cause of reactive oxygen species (ROS). Three airborne metal vapors are also causal factors of excessive ROS in lung and brain tissue. Metal ions from these vapors induce ROS in human cells. The amount of ROS generated is ranked by induction severity in table 127.



Preventing these vapors from entering the lungs and brain is the best method of preventing ROS in these organs. Table 2 is a list of common sources of these metal vapors.

Aluminum is in both tobacco and cannabis at concentrations that vary from 0.1 to 3.7 mg per gram28. Some of this aluminum is volatilized during smoking and is absorbed by the lungs during both active and passive smoking28.  This may explain why smokers have a higher body burden of aluminum than nonsmokers28. 
Lead as tetraethyl lead (TEL) is a gasoline additive. TEL was phased out as a road vehicle fuel additive in the U.S. by early 2000’s. However, TEL is still used in aviation gasoline (a.k.a. avgas) for planes with internal combustion engines and in gasoline for road vehicles in some developing countries29.
Lead is emitted as vapor into the atmosphere by burning coal. In 2008 103 coal-fired power plants in the U.S. were identified as emitting more than 1,000 pounds of lead per year into the atmosphere30.
Mercury according to the World Health Organization most human exposure to mercury is caused by outgassing of metallic mercury from dental amalgam fillings31. The metallic form of mercury is slowly outgassed or emitted as vapor by dental amalgams. It is estimated that the amounts of metallic mercury released from dental amalgam fillings range from 3 to 17 micrograms per day depending upon the type and number of amalgam fillings you have32. Mercury vapor is absorbed through the mucus membranes of the lung and nose.
In the 1970’s new high copper amalgams (a.k.a. non-Y2-amalgams) were developed and introduced for better mechanical strength and corrosion resistance in the U.S. and Europe.  Unfortunately these new high copper amalgams with a maximum of 30% copper have significantly increased emission of metallic mercury vapor as compared to low copper amalgams used before 1970 with a maximum of 6% copper33,34.
When high copper amalgam fillings are subjected to wear, droplets rich in metallic mercury are formed on their surface and emit as much as 3 to 43 times more metallic mercury than low copper amalgam fillings depending upon brand33,34. Increased emission of mercury vapor may be provoked by a slight touch of the filling surface by chewing or polishing or by a slight increase in temperature, such as consuming hot beverages or hot food. This behavior demonstrates that mercury is not bonded strongly to the base or alloy metals in high copper amalgams. This is the reason for increased outgassing of metallic mercury from these new high copper amalgams33.
Targeted Detox of Aluminum, Lead, and Mercury
Targeted detox methods for these three toxins involving nutrients required by the human body can safely be orally taken daily:
Aluminum accumulates in the body’s organs, including the lungs and brain. If 3 to 4 cups a day of an essential nutrient called orthosilicic acid (OSA) in water is routinely consumed at concentrations of 50 to 200ppm the elimination of aluminum from organs, such as the lungs and brain, into urine and perspiration is significantly enhanced35. Silica water enriched with OSA can be either made synthetically by diluting and acidifying sodium silicate or purchased as either silica rich bottled drinking water (i.e. Fiji, Volvic, see table 34 in ref. 34 for more silica waters) or beer with and without alcohol35. These sources of OSA have been tested for their ability to enhance aluminum excretion by measuring aluminum-26 or aluminum-28 in blood plasma, urine, and perspiration35.
Lead & Mercury are detoxified and eliminated from the body with the following daily supplements36,37:
·         Thiamine (a.k.a. vitamin B1, thiamin) - 50mg for children and 50-100mg for adults twice a day (morning and evening) or a time-released B50 or B100 complex once a day.
·         Zinc - 15mg for children and 30mg for adults per day (do not exceed 40mg per day)
·         Selenomethionine - The following amounts are recommended for targeted detox of not only lead but also mercury and arsenic:
·         Children 0 to 3 years of age: 25mcg/day
·         Children 4 to 8 years of age: 50mcg/day
·         Children 9 to 13 years of age: 100mcg/day
·         Adolescents 14 to 18 years of age and adults: 100-200mcg/day
Note that too much selenium will give you garlic-breath. So cut back on the amount of selenium per day if you are accused of having garlic-breath without eating garlic. 
Supplement Vendors
Thiamine (Vitamin B1) Supplements - Thiamine (a.k.a. vitamin B1, B-1) can be taken as a supplement in pure form or in a B vitamin complex.  For instance a B50 complex tablet contains 50mg of thiamine and a B100 complex tablet contains 100mg of thiamine. Time-release B50 or B100 complexes are available from CVS and Puritan Pride. Non-time released tablets of just B-1 are available from Now Foods Company as 100mg tablets of B-1 (thiamine hydrochloride HCl) and Seeking Health as 50mg vegetarian capsules of B-1 (thiamine hydrochloride HCl). 
Zinc Supplements for Targeted Lead Detox - The most bioavailable sources of zinc are either an acid salt of zinc, such as zinc acetate and zinc gluconate or an amino acid chelate of zinc, such as zinc bisglycinate or zinc picolinate.  Recommended daily dose is 30mg for adults and 15mg for children. Maximal prophylactic dose of zinc for adults is 40mg/day unless used during treatment for the symptoms of a respiratory virus (such as the common cold or Covid-19 Coronavirus - see next section).
·       
         Vendors of zinc salt supplements include: Advanced bionutritionals as 15mg tablets of zinc acetate, Life Extensions as 18.75mg lozenges as zinc acetate, and Carlson Labs 15mg tablets of zinc gluconate. 
·         Vendors of zinc chelate supplements include: Nature’s Way as 30mg capsules of zinc bisglycinate, NutraBio as 30mg as vegetable capsules of zinc bisglycinate, and Allergy Research Group as 25mg capsules of zinc picolinate.         

Zinc Acetate Supplements for Reduction in Duration of Respiratory Virus Infections – Zinc acetate (at least 75mg/day) has been shown to decrease duration of the common cold by on average 42%19,79. Zinc acetate has not been proven to decrease the duration of Covid-19 Coronavirus CoV2, but two Coronaviruses (e.g. OC43 and 229E) are responsible for a large proportion of the common cold78. Zinc acetate is preferred as a zinc supplement because it releases more zinc ions than zinc chelates such as citrate, tartarate, picolinate, and glycinate19. Zinc acetate is also smaller than zinc chelates and zinc gluconate making it more effective as a PLP2 and 3CL enzyme inhibitor16,17,18.

Vendors of zinc acetate include: Advanced Bionutritionals as small 15mg lozenges/tablets and Life Extensions as thick 18.75mg lozenges/tablets. Recommended adult daily dose of zinc acetate for respiratory viruses is 75 to 150mg per day and for children less than 40mg/day. Zinc acetate at these high levels should be taken in smaller doses throughout the day. Taking these high levels of zinc should be begun after symptoms of a respiratory virus become apparent and should be terminated when symptoms abate. Chronic use of these high levels of zinc can result in a copper deficiency74,75.  However, a 6 week experiment found no effect on plasma copper levels from taking 150mg per day of zinc, This indicates taking high levels of zinc for several weeks is safe76. A trial of zinc acetate taken daily at a dose of 92mg/day showed no significant differences in the occurrence of adverse effects when compared with a similar group taking a placebo77.


The lozenges from Advanced Bionutritionals can be taken 6 times a day (90mg/day) and are small tablets that dissolve in the mouth with a citrus flavor in approximately 4 to 6 minutes when not chewed. The lozenges from Life Extensions can be taken 5 to 8 times a day (94 to 150mg/day) and are thick tablets that dissolved in the mouth in approximately 15 to 20 minutes when not chewed and have a peppermint flavor. These thick tablets may be a choking hazard for children. 

Selenomethionine Supplements - Supplements for human use are not regulated by the U.S. FDA. Because of this lack of regulation some selenomethionine supplements contain no selenomethionine or less than the amount stated on the label36-38. Therefore products with third party certification are recommended.  Certifying agencies include: Consumerlab.com, NSF International, U.S. Pharmacopeia (USP), and UL.  There are commercial test laboratories that also perform third party testing for purity and percent of selenium as selenomethionine.   

The European Food Safety Authority (EFSA) has published a scientific opinion on acceptable selenium-enriched yeasts produced as selenomethionine supplements for human use. The source of selenium must be sodium selenite and the resulting product should contain 60 to 85% selenomethionine with less the 10% additional organic selenium and less than 1% inorganic selenium, such as residual sodium selenite. The dried product should contain no more than 2.5mg of selenium per gram39.

I am aware of only one selenium-enriched yeast supplement that has been tested by third parties. This is Bio-SelenoPrecise® tablets manufactured in Denmark by Pharma Nord under patent no. 1 478 732 B1. This type of L-selenomethionine supplement is 88.7% absorbed in Danish men with high habitual selenium intake40, however only about 34% may actually be free selenomethionine after gastrointestinal digestion41.  Pharma Nord packages tablets of Bio-SelenoPrecise® as 50, 100, and 200mcg of selenomethionine that can be cut in half with a pill-cutter.

Pharma Nord selenomethionine has been checked by two laboratories and it has 69-83% L-selenomethionine, 5% or less additional organic selenium, including selenocysteine, less than 1% inorganic selenium, and less than 2.2mg per gram of selenium. These results are summarized as product 3a, 3b, and 4 in EFSA’s Table 1 and they meet EFSA specifications for selenium-enriched yeast39.

Some selenomethionine supplements are made with higher purity than supplements made from selenium-enhanced yeast. However, it has been reported that plasma selenium is significantly higher when taking Pharma Nord Bio-SelenoPrecise® than seen in a comparable population of human subjects taking the same dose of higher purity selenomethionine42.

Manufactures of high purity yeast-free selenomethionine who have their product third party certified and/or tested include Sabinsa Corporation. Their Selenium SeLECT® product contains a minimum of 1.25% of L-selenomethionine, measured by HPLC, and 98.75% of dicalcium phosphate, measured by titration. Therefore it is 100% selenium as selenomethionine. Sabinsa Corp. has both UPC and NSF International product certification. Selenium SeLECT® is packaged and sold by Swanson (100mcg capsules) and Vitacost (200mcg capsules). Make sure the Supplement Facts on the bottles state: “Selenium from (as) Selenium SeLECT® L-selenomethionine”.  In addition, Bluebonnet’s L-seleniomethionine (100 and 200mcg vcaps vegan) have NSF International product certification and Now’s L-selenomethionine (200mcg veg. capsules) has UL product certification.


The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine has set the tolerable upper intake levels (UL) for selenium based upon age, including both selenium obtained from food and selenium obtained from supplements, as indicated in Table 343.

Note: The author has no financial interest in silica rich water sales or supplement sales. Most of the information on these methods of detox is posted at blogs, on You Tube, or in Facebook groups (see conclusion for links).

Final Food For Thought

Resilience in a pandemic depends on genetics and making wise decisions. Humans evolved in regions of the world with selenium-deficient soil (see Africa in figure 5) and with viruses being our constant companions. Our biochemistry is preprogrammed to create ROS as a disinfectant for viral attacks44, while at the same time mopping up excess ROS with a selenoenzyme based ROS suppression system45. Some of us are lucky to have a gene that provides a super-sensitive ROS detection system. Those with this gene have on average increased longevity because the gene provides a quicker response to ROS46. However, with or without this gene the ROS suppression system only works optimally in those people with sufficient selenium status. Therefore it is a wise decision to take a daily selenomethionine supplement.
      
Conclusion

The resilience to a disease caused by a viral infection depends heavily upon the steps taken both by the population as a whole and by individuals to prevent and/or minimize the severity of the disease. Individuals can prevent and/or minimize the severity of RNA retroviruses that cause acute respiratory syndrome and/or brain damage, such as Covid-19 Coronavirus, in two ways:

If you have symptoms of Covid-19 Coronavirus infection consider taking zinc acetate as described in this blog to shorten the duration and possibly the severity of the disease.

If you do not have symptoms prevent Covid-19 Coronavirus from adaptively evolving into a more virulent form by decreasing reactive oxygen species (ROS) in your lung tissue and brain. The human body has a ROS suppression system based upon selenium containing enzymes (selenoenzymes). Therefore orally taking selenium as a nutrient required by the human body or eating natural selenium enriched food, such as U.S., Canadian, or Finnish wheat, will vitalize the body’s ROS suppression system. There are toxic metals that are inhaled and accumulate in lung tissue and brain causing ROS either by lowering selenium levels and/or by creating ROS chemically. These airborne environmental toxins include: mercury from dental amalgams, aluminum from smoking tobacco or cannabis, lead from tetraethyl lead containing gasoline and coal-fired power plant emissions.

Targeted detox methods for these three toxins involving nutrients required by the human body can safely be orally taken daily. See blog (http://prevent-alzheimers-autism-stroke.com), facebook page (“Silica Water the Secret of Healthy Blue Zone Longevity in the Aluminum Age”, You Tube Videos, or read books for complete details:
·         Blog Post and Facebook Group: “Mercury Detox using the Selenium Method”
·         Facebook Group: “Fiji Water Detox Epilepsy Autism Support Group”
·         Blog Post: “Targeted Lead Detox with Thiamine, Zinc, and Selenomethionine” 
·         Book: “Prevent Alzheimer’s, Autism, and Stroke with 7 supplements, 7 lifestyle choices, and a dissolved mineral”
·         Book: “Silica Water the Secret of Healthy Blue Zone Longevity in the Aluminum Age”
·         You Tube Video: “Silica Water – How to Make it at Home”
Steps can be taken by the population as a whole through government action to prevent ROS from accumulating in lung tissue and these include:
·         Require selenium enrichment in all fertilizers, bread flour, and animal feed
·         Require silica enrichment in all community drinking water
·         Prohibit mercury amalgam dental fillings
·         Prohibit tetraethyl lead in all gasoline including aviation fuel
·         Require an aluminum warning on cigarettes and cannabis

Others have pleaded with governments to take action and add more selenium to the diet. Margret P. Rayman (Research Fellow, Dept. of Chem., Univ. Surrey) in 1997 published an editorial in the British Medical Journal strongly recommending for medical reasons the U.K. start requiring selenium in fertilizers, like Finland, and in both feed for animals and bread for humans23.  I can only hope that all countries will finally take action in 2020 as Covid-19 Coronavirus will not be the last pandemic.


I am writing this conclusion early in the morning on March 18th 2020 and deaths due to Covid-19 Coronavirus have surpassed 100 in the U.S. (see figure 7). Comparing the prevalence of confirmed cases with bioavailable soil selenium two of the three hot spots (e.g. in Washington and New York State) correlate (see figure 8 – a blowup of figure 5). All three hot spots correlate with the location of nearby international airports. In the U.S. we don’t have the palm civet as an intermediate host for coronavirus but we do have returning international travelers as viral vectors. 


Figure 7.  Prevalence of Covid-19 Coronavirus as of March 18, 2020
8AM EST; epicenters of Seattle, Washington and New Rochelle, NY:
confirmed cases tot. 6,496 (red); tot.deaths 114 (WA 55, NY 16, CA 13)22


Figure 8. Covid-19 Coronavirus infection hotspots correlate with both geologic

regions of poor Se bioavailability and international airports in the U.S.
yellow = <0.01, light green = 0.01 to 1.0, dark green = >1.0 mg/kg of selenium26,25




The yellow areas in figure 8 are predicted to have the highest prevalence of Covid-19 Coronavirus cases due to their lack of soil selenium availability.



Frequently Asked Questions (FAQs) regarding the blog post entitled: “Selenium and ROS Status Impacts Covid-19 Coronavirus Virulence” Last Update April 6, 2020

Question 1. Why does the ability to smell things have anything to do with the Covid-19 virus?

Answer 1. Good question. When a person suddenly loses their sense of smell they have sudden-onset anosmia. This is an indicator of a either a viral attack on nerves leading from the nasal cavity to the olfactory lobe of the brain or an attack on the olfactory lobe. This attack also causes neuronal inflammation. Sudden-onset anosmia can be sometimes experienced when infected with the virus causing the common cold. In the case of the common cold virus there is no permanent brain damage. This may not be the case with Covid-19 Coronavirus. 

The SARS-CoV1 virus has been tested with mice transgenic for the human ACE2 receptor47. ACE2 is the receptor used as a ”landing pad” for both SARS-CoV1 and Covid-19 Corona Viruses. SARS-CoV1 was found to replicate to high levels in the lungs of infected mice and extensive replication was also observed in the brain leading to pathology seen in mice and humans infected with SARS-CoV1:
      
  • SARS-CoV1 infected transgenic mice died of CNS infection in 4 days after infection
  • Parts of the brain responsible for cardiorespiratory function are attacked by the virus
  • The virus is first detected 60 to 66 hours after infection in the olfactory lobe
  • SARS-CoV1 spreads in the brain from the olfactory lobe and induces neuronal loss
  • A patient developed neurological symptoms 28 days after SARS-CoV1 infection and died of cardiovascular complications48

It is recommended that if a person develops sudden onset anosmia with no other symptoms they should self-isolate for 14 days and get tested for SARS-CoV2. Also, cardiac injury resulting in higher mortality is associated with human Covid-19 Coronavirus infections49 but not with human SARS-CoV1 infections50. Of 416 patients testing positive for Covid-19 Coronavirus and hospitalized at Renmin Hospital of Wuhan University, 82 of them (20%) had cardiac injury due to the infection. The mortality rate was higher in those with cardiac injury 48 (58.5%) versus those without cardiac injury 15 (4.5%). 


Question 2. If selenium is beneficial for “curing” the Covid-19 Coronavirus, why has someone in China not suggested using it?

Answer 2. On January 30th 2020 a paper was published by Lei Zhang and Yunhui Liu of the Dept. of Neurosurgery, Shengling Hospital of China Medical University, Shenyang Uaoning, China51.  In this article these doctors cite both Melinda A. Beck’s2 and Michalann Harthill’s26 papers and conclude: “Therefore, selenium supplementation could be an effective choice for the treatment of this novel virus of COVID-19” 51.


Question 3. Is there something unique about Covid-19 Coronavirus as compared with other single stranded RNA viruses?

Answer 3. Yes. The Covid-19 (CoV-2), SARS CoV-1, and MERS (CoVs) all have much larger genomes (more nucleotides) than do other single stranded RNA viruses. Prior to the evolution of these three viruses it was believed that the genomes of single stranded RNA viruses were constrained to a small size due to their high mutation rates. These mutation rates can be a million times higher than their hosts52. But more errors come with high rates of replications and mutations, taking single stranded viruses to the edge of lethality53,54.  Researchers have suggested that RNA viruses have evolved so their mutation rate is just under the threshold for lethal mutagenesis called the “error threshold55. Infected cells respond to RNA viruses by using their mitochondria to generate excess ROS in an attempt to kill the viruses by lethal mutagenesis. This worked with RNA viruses in the past but backfires with the 3 CoVs.
The 3 Coronaviruses (CoVs) responding to adaptive selection evolved slower mutation rates and larger genomes than other RNA retroviruses. These 3 large CoV genomes encode an additional processing function that is expressed as an exoribonuclease (nsp14-ExoN conserved in the 3 CoV phenotypes) that makes DNA from viral RNA less prone to errors52,56. This made the CoVs’ genomes more stable to environments such as those with low selenium and high ROS that are more mutagenic. This is not surprising because CoVs evolved in a region of the world that has selenium-deficient soil and selenoenzyme-deficient human and animal populations with high ROS.
This genome stability does make it easier for humans to develop immunity to CoVs. However, CoVs still mutate and adaptively evolve in a mutagenic high ROS and low selenium intracellular environment. But both CoV’s mutation rates and replication speeds are slower than other RNA viruses in such an environment. These characteristics of CoVs allow them a longer duration post infection time during which they can slowly mutate and replicate and be transferred to other hosts while allowing time for the human immune system to wipe them out.
Unlike “flash-in-the-pan viruses” that infect and kill their hosts so quickly that each host can’t infect more than one person, the CoVs are “slow-cooked viruses” that give their asymptomatic hosts plenty of time to infect many others. This gives “legs” to the CoVs, allowing them to quickly spread around the world with the help of air travel by human hosts.
In their travels to selenium rich area of the world, CoVs still infect populations with high ROS due to the following factors:
  • ROS inducing metal ions, such as aluminum, lead, and mercury, as environmental toxins are in human lungs and brains due to smoking, coal-fired power plant exhaust, and dental amalgams.
  • ROS inducing chemicals, such as ethanol, hydrogen peroxide, and hydrochlorous acid, as environmental toxins are in human lungs and brains due to drinking liquor, using some mouth wash, and throat and nasal sprays.
  • Low plasma selenium levels in populations living in areas with selenium rich soil are due to gluten intolerance lowering the population’s average wheat consumption.
  • Low plasma selenium levels in populations living in areas of selenium-deficient soil are due to the “eat only locally grown food” craze.


Question 4. There appears to be jumps of logic in here. Selenium and therefore ROS are invoked as affecting the mutation of the various viruses discussed to a form that is more virulent.  Once the mutations have occurred, those viruses would remain more virulent.  But the author later states that selenium “cured” Keshan disease.  That would appear to be inconsistent with the mutational model.

Answer 4. There is no inconsistency in logic. Before a single strand RNA virus adaptively evolves in the host from the non-virulent phenotype to the virulent phenotype2, a high selenium status in the host allows selenoenzymes to “mop-up” any excess mutagenic ROS. Thereby the mutation rate of the virus will be slowed and the host’s immune system will have time to “wipe-out” the virus. This results in the host being cured by selenium with the help of the host’s immune system and antibodies for the virus.
An example is the Poliomyelitis virus used as a live attenuated (i.e. non-virulent phenotype) vaccine that was found to rapidly mutate when injected into humans with less than 1mcMol Se/L in host blood. While above this level rapid mutation of this virus was deterred allowing the host’s immune system time to “wipe- out” the virus making the vaccine efficacious12.  One mcMol Se/L is a threshold level of selenium status in the blood required to avoid the evolution of more virulent phenotypes12.
Once the virus mutates in the host to the virulent phenotype, the host and anyone infected by the host’s mutated virus may only be cured by selenium if the host has a sufficient selenium blood level to inhibit autophagy and thereby inhibit viral replication15. This means long term selenium supplementation could cure the pandemic as it did in the case of Keshan disease.  


Question 5. Are there any foods that should be avoided because they contain ROS or promote ROS and what exactly is ROS?


Answer 5. ROS are reactive oxygen species (i.e. chemicals) that can be found in the body and are normally reduced to innocuous chemicals by selenoenzymes, making selenium an essential nutrient in our bodies.  There are two sources of ROS: ROS induced by metals and ROS contained in liquor and disinfectant solutions. ROS inducing metals are listed that impact the lungs include: aluminum, lead, and mercury. These metals induce increased ROS in lung cells. This ROS is primarily hydrogen peroxide from superoxide and hydroxyl radicles. These three metals can also be ingested and induce ROS in all organs of the body.  A complete list of daily sources of aluminum is in Appendix II of my book35 “Silica Water for Healthy Blue Zone Longevity in the Aluminum Age.”

Examples of ROS from liquor and disinfectants are ethanol57, acetaldehyde57, hydrogen peroxide58,59, and hypochlorous acid60.  These chemicals are mutagenic, meaning they cause mutations in both DNA and RNA. Ethanol by itself is not mutagenic but the enzyme alcohol dehydrogenase quickly metabolizes ethanol after ingestion to acetaldehyde a known mutagen. Therefore in the body both ethanol and acetaldehyde are considered mutagenic.  Note that all of these chemicals can easily become airborne, inhaled, and absorbed into lung cells that may be attacked by the Coronavirus. It is strongly recommended that ROS in the diet and as a throat, mouth, or nasal disinfectant be avoided at all times particularly during a viral pandemic involving lung disease.
 
ROS products to avoid entirely during a viral pandemic are:

  • Ethanol in liquor and in hand sanitizers
  • Hydrogen peroxide in mouth wash and vaporizers
  • Hypochlorous acid in mouth wash and nasal spray 


Question 6. What do you recommend as an antiviral hand sanitizer for Coronavirus CoV-2?

Answer 6. Isopropanol (at least 70% in water for 30sec.) is best.  Ethanol (70% in water for 60sec. or 78% in water for 30sec.) is effective but not recommended as it may be absorbed and converted by the liver into acetaldehyde, a known mutagen (see question 5). Ethanol (78%) and isopropanol (70%) were both tested for 30 seconds as hand-rub formulations and they reduced Coronavirus SARS CoV-1 by 100,000 times and 2,040 times, respectively61,62 (Rabenau 2005, Kariwa 2006). Povidone-iodine (PVP-I) applied for 2 min. as a hand-rub reduces Coronavirus SARS CoV-1 to undetectable levels62 (Kariwa 2006). Witch hazel extract (100%) as a hand-rub is available as an inexpensive clear liquid at most drug stores. Witch hazel has not been tested as a hand sanitizer for SARS CoV-2. But has been tested as an antiviral for several single stranded RNA viruses (i.e. pandemic influenza A virus H1N1 and seasonal H3N2 virus). It was found to completely abolish the viruses and the antiviral effect and lasts for at least 24 hours post infection63.


Question 7. Increasing plasma selenium slows the mutation rate of viruses but is there any evidence that the mutation rate of viruses is increased by reactive oxygen species (ROS)?

Answer 7. Yes. In 2011 Human Hepatitis C (HCV) RNA viruses in liver cells were exposed to ethanol, acetaldehyde, and hydrogen peroxide and then tested for RNA mutation rates compared with non-exposed controls64. Ethanol exposure was 0.1% corresponding to a blood alcohol concentration of 17.2mM, which is approximately the legal driving limit in many countries including the U.S. Acetaldehyde was 10mcM and hydrogen peroxide was 100mcM. All three ROS species caused significantly higher RNA mutation rates than controls. In some cases (e.g. ethanol and hydrogen peroxide) there were 10 to 12 fold higher mutation rates64.


Question 8. Are there any nanosized particles in the inactive ingredients (i.e. excipients) of Pharma Nord’s Bio-SelenoPrecise, such as silicon dioxide and titanium dioxide?   

Answer 8. This was the response we got from Pharma Nord: “We are so glad you asked us about the excipients. They are NOT nanosize particles, so the research with nanosize particles does not apply. Please feel free to call me directly with any questions. You can reach me at (609) 575-6508.”
Quote by Marianne Hovgaard,  Business and Operations Manager, Pharma Nord, Inc., Marlton, NJ, USA
mhovgaard@pharmanord.com

Question 9. Can I use Brazil nuts as a selenium supplement rather than taking a pill?

Answer 9. The answer is yes with a caveat. Brazil nuts have been found to have high levels of selenomethionine, selenothionine, and selenocystine65. However, there is a problem with Brazil nuts.  In a random sample of 20 Brazil nuts it has been found that the selenium concentration varied from 0.816mcg/gr to 1390mcg/gr66. Since the mean weight of a single Brazil nut is 4 grams, it is possible by eating just one Brazil nut to either exceed the upper tolerable selenium intake level for adults (400mcg/day - see Table 1) by 1400% or consume only 0.8% of the upper tolerable selenium intake level for adults67.  This variability in selenium concentration makes Brazil nuts are an unreliable daily selenium supplement unless a number of nuts are ground together and a teaspoon of nut powder is eaten every day.

Question 10. COVID-19 needs the ACE2 enzymes in the cell walls of alveoli to dock onto the alveoli and infect the lung. Selenium compounds inhibit ACE2 and increase the expression of ACE2. Does this mean that selenium compounds facilitate the entry of the virus into the lung tissue?

Answer 10. Only selenoneine, which is a novel selenium compound found in fish (not all selenium compounds), inhibits ACE (not ACE2) and increases the expression of the enzyme ACE not the enzyme ACE268. It is not known and unlikely that the Covid-19 Coronovirus binds to ACE but it is known that it binds to ACE2. It is also known that binding Coronavirus spike protein to the binding site on ACE2 leads to ACE2 down regulation (i.e. decreased expression of ACE2 not increased expression). Therefore large inhibitors that bind to the Coronavirus spike protein binding site on ACE2 may provide protection from Coronavirus, rather than putting them at risk to develop Covid-19 Coronavirus69. Therefore selenium does not facilitate entry of the virus into lung tissue. 



Question 11. Does the classic anti-malarial Quinine work as a zinc ionophore like the chloroquine?

Answer 11. Ionophores are chemicals that facilitate the transfer of particular ions across cell and organelle membranes. In order to be effective, ionophores must only weakly bond with the ion being transferred and release the ion once it is transferred. The release of the ion is usually triggered by a pH differential that exists across cell and organelle membranes.

Ions, such as zinc, reduce replication of cancer cells and viruses. Ions, such as zinc, also kill parasites, such as the one that causes malaria. Ionophores, such as chloroquine and HPT (a.k.a. 1-hydroxypyridine-2-thione), enhance zinc transport across cell membranes. Therefore, zinc weakly bonded to chloroquine or HPT can have antiplasmodial and anticancer properties that kill parasites and stop cancer cells from replicating. 

Quinine-zinc complexes, made by adding either zinc sulfate or zinc chloride to quinine, are stable and have been isolated and characterized70-71. Therefore, zinc weakly bonds to quinine. A quinine-zinc complex may therefore be transported across cell and macrophage membranes making quinine an ionophore.  This statement is supported by the fact that the quinine-zinc complex made from zinc sulfate had three fold more antiplasmodial activity when compared with quinine sulfate70 and significantly more antiplasmodial activity than chloroquin72. Therefore the quinine-zinc complex has better therapeutic activity against malaria than does either quinine sulfate or chloroquine, possibly because the quinine-zinc complex is an ionophore70,72. However, two studies have been published that indicate chloroquine treatment of Covid-19 Coronavirus CoV2 leads to significantly higher mortality than no chloroquine treatment93,94. There is currently no evidence that quinine treatment will be safer than chloroquine treatment.

Zinc ionophores have been shown to be useful in treating some cancers. When zinc acetate was used with the ionophore HPT (a.k.a. 1-hydroxypyridine-2-thione) there was enhanced zinc transport across cell membranes, leading to decreased lung cancer cell proliferation73.

Zinc ionophores have not proven to be as useful for the inhibition of the protease PLP2 that is the Achilles Heel of the SARS-CoV virus (as described previously in this blog). Ionic zinc (e.g. zinc acetate IC50 = 1.3mcM) was 3-fold better than the zinc ionophore ZnHPT (IC50 = 3.7mcM) at inhibiting SARS-CoV PLP2 protease required for viral replication17.  However, zinc acetate (Ki = 1.1mcM) was proven to be not as effective as the zinc ionophore ZnHPT (Ki = 0.17mcM) at inhibiting SARA-CoV 3CL protease required for viral replication18.    These mixed results make it clear that there may be no real benefit of using an ionophore when combating Covid-19 Coronavirus CoV2. Zinc acetate works better than some ionophores at inhibiting PLP2, the Achilles Heel of SARS-CoV1, and is an inexpensive biochemical normally found in our bodies. 

Warning: Zinc is a ROS generator27 and therefore high dose zinc acetate should only be used after the virus has mutated to the more virulent form and symptoms are present. Low dose zinc supplements (15 - 25mg) should be taken routinely for enhancement of the immune system (see question 12).


Question 12. Does chronic ingestion of more than 100mg of zinc per day interfere with developing immunity to viruses?

Answer 12. A working immune system involves clearance of viral infected cells by natural killer (NK) cell activity and high T and B lymphocyte cell counts82,83. A zinc deficiency has been shown to negatively impact NK cell activity, T and B cell counts, and the killing activity of T cells84-87.  Zinc supplementation in response to zinc deficiency has been shown to restore impaired immune function and decrease the incidence of infections in vivo 88. The USA Food and Nutrition Board’s recommended daily intake of zinc by adults is 11mg per day. Zinc is actively maintained by homeostasis at 12-16mcM in the plasma89. Zinc deficiencies are common among people over 60 and among people who ingest alcohol on a regular basis88.

Taking high doses of zinc orally as 10mg lozenges every 2 wakeful hours resulting in 80mg/day for a week does not impair the antigenic response to tetanus toxoid in humans90. In addition, zinc at these levels increases zinc levels in plasma but not exceeding normal physiological values (i.e. less than 16mcM) 90. Zinc at these levels does suppress allogenic immune response to organ transplants and potentially lowers the frequency of organ rejection90. Fifteen human volunteers over 70 years of age were given 89mg of zinc twice a day for a month (178mg/day). As a result they had higher T cell counts and greater antibody response to tetanus vaccine as compared with 15 age-matched controls91. Higher levels of zinc supplementation in 83 human volunteers given 110mg of zinc three times a day (330mg/day) for one month had an immune-regulatory influence in their response to foreign antigens, such as viruses, by decreasing lymphocyte response in high responders and increasing lymphocyte response in low responders91,92. Therefore taking 80 to 150mg/day of zinc enhances the immune response particularly of those over 70 years of age who are most at risk of mortality due to Covid-19 Coronavirus CoV2.


Chronic use of high dose zinc supplements can inhibit the absorption of copper. If taking more than 50mg/day of zinc on a regular basis, a daily copper supplement (2mg/day) should also be taken to prevent copper deficiency.    

Additional questions, if not already answered, will be answered as received with the new question and answer posted at the bottom of the list.

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