Neurons and Exercise

Neurons and Exercise

Saturday, March 28, 2020


Selenium and ROS Status Impacts Covid-19 Coronavirus Virulence


Dennis N. Crouse PhD – Updated March 28, 2020 – Draft of Chapter From My New Book

Introduction
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 newly-weak limb 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 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 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 resulting in crops that were low in selenium.  This 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-deficiency in soil as shown in figure 2. Selenium-deficient areas account for 72% of China’s total area and this deficiency affects over 70 million people who as a result 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 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 as 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 Coronavirus? We don’t have this answer today but we do know it likely shaped the evolution of SARS-CoV1 Coronavirus.

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 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 grown.  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 crops16. 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 soil16. 
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)16. This higher selenium status appears to have protected the Finish from Covid-19 (see table 0).

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 declines17.  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 region.  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 rice18.  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; 13,14



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.  

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, the targets of viral attack. Metal ions from these vapors induce ROS in human cells. This induction is ranked by induction severity in table 1.

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 gram20. Some of this aluminum is volatilized during smoking and is absorbed by the lungs during both active and passive smoking20.  This may explain why smokers have a higher body burden of aluminum than nonsmokers20. 
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 countries21.
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 atmosphere4.
Mercury according to the World Health Organization most human exposure to mercury is caused by outgassing of metallic mercury from dental amalgam fillings23. 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 have24. 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% copper25,26.
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 brand25,26. 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 amalgams25.
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 enhanced. 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. 27 for more silica waters) or beer with and without alcohol. 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 perspiration27.

Lead & Mercury are detoxified and eliminated from the body with the following daily supplements28,29:
·         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 - The most bioavailable source of zinc is an amino acid or acid chelate of zinc such as zinc bisglycinate of zinc gluconate. Vendors of zinc supplements include Nature’s Way 30mg capsules of zinc bisglycinate and Carlson Labs 15mg tablets of zinc gluconate. 
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 label28-30. 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 gram31.
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 intake32, however only about 34% may actually be free selenomethionine after gastrointestinal digestion33.  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 yeast31.
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 selenomethionine34.
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.
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 335.

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 attacks36, while at the same time mopping up excess ROS with a selenoenzyme based ROS suppression system37. 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 ROS38. 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. This can be done by preventing the virus from adaptively evolving into a more virulent form by decreasing reactive oxygen species (ROS) in the host’s 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 humans17.  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)15


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 selenium13,14


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 March 28, 2020


Question 1. Why does the ability to smell things have anything to do with the Covid-19 virus?
A1. 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 receptor (Netlan 2008). 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 complications (Xu 2005)
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 infections (Shi 2020) but not with human SARS-CoV1 infections (Yu 2006). 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%).  
[Netland, J., et al.; Severe acute respiratory syndrome Coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2; J. Virol.; Aug.; 82(15):7264-75 (2008); Xu, J., at al.; Detection of severe acute respiratory syndrome Coronavirus in the brain: potential role of the chemokine mig in pathogenesis; Clin. Infect. Dis.; 41:1089-96 (2005); Shi, S., et al.; Association of cardiac injury with mortality in hospitalized patients with Covid-19 in Wuhan, China; JAMA Cardiol.; Mar.; doi:10.1001/jamacardio.2020.0950 (2020); Yu, C.M., et al.; Cardiovascular complications of severe acute respiratory syndrome; Postgrad. Med. J.; 82(964):140-44 (2006)]

Question 2. If selenium is beneficial for “curing” the Covid-19 Coronavirus, why has someone in China not suggested using it?
A2. 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, China.  In this article these doctors cite both Melinda A. Beck’s2 and Michalann Harthill’s15 papers and conclude: “Therefore, selenium supplementation could be an effective choice for the treatment of this novel virus of COVID-19”. [Zhang, L. and Liu, Y; Potential interventions for novel coronavirus in China: A systematic review; J. Med. Virol.; 92:479-90 (2020)]

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

A3. 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 hosts [Duffy 2018]. But more errors come with high rates of replications and mutations, taking single stranded viruses to the edge of lethality [Vignuzzi 2012, Belshaw 2008].  Researchers have suggested that RNA viruses have evolved so their mutation rate is just under the threshold for lethal mutagenesis called the “error threshold [Biebricher 2004]. 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 errors [Duffy 2018, Smith 2013]. 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. The 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 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 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.
[Duffy, S.; Why are RNA virus mutation rates so damn high?; PLoS Biol.; Aug.; 16(8):e3000003 (2018) https://doi.org/10.1371/journal.pbio.3000003 ; Vignuzzi,  M., and Andino, R.; Closing the gap: the challenges in converging theoretical, computational, experimental and real-life studies in virus evolution; Curr. Opin. Virol.; 2(5):515-8 (2012); Belshaw, R., et al.; Trends Ecol. Evol.; 23(4):188-93 (2004); Biebricher, C.K., et al.; The error threshold; Virus Res.; 107(2):117-27 (2005); Smith, E.C., et al.; Coronaviruses lacking exoribonuclease are susceptible to lethal mutagenesis: Evidence for proofreading and potential therapeutics; PLoSONE; Aug.; 9(8)e1003565 (2013)]

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.
A4. Paradoxically 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.  This is a threshold level of selenium status in the blood required to avoid viral adaptive mutations and the evolution of more virulent phenotypes12.
However, once the virus mutates in the host to the virulent phenotype, the host and anyone infected by the host’s mutated virus can’t be cured by selenium only by a quick working immune system2. This means that although asymptomatic individuals infected with the non-virulant virus can be cured by selenium, a symptomatic individual and those infected by a symptomatic individual can’t be cured by selenium. Currently in the world there are many more asymptomatic people than symptomatic people. So there is hope that selenium supplementation could stop the pandemic. This means selenium 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?

A5. 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. In this blog on the Coronavirus three ROS inducing metals are listed that impact the lungs: 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 book “Silica Water for Healthy Blue Zone Longevity in the Aluminum Age.”   

Examples of ROS from liquor and disinfectants are ethanol (Obe 1986), acetaldehyde (Obe 1986), hydrogen peroxide (Moraes 1990, Krone 2007), and hypochlorous acid (Gungor 2010).  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 
[Obe, G., et al.; Metabolism of ethanol in vitro produces a compound which induces sister-chromatid exchanges in human peripheral lymphocytes in vitro: acetaldehyde not ethanol is mutagenic; Mutat. Res.; May; 174(1):47-51 (1986); Moraes, E.C., et al.; Mutagenesis by hydrogen peroxide treatment of mammalian cells: a molecular analysis; Carcingenesis; 11(2):283-93 (1990); Krohn, K., et al.; Mechanisms of disease: hydrogen peroxide, DNA damage and mutagenesis in the development of thyroid tumors; Nature Clin. Pract. Endocrin. Metab.; 3:713-20 (2007); Gungor, N., et al.; Genotoxic effects of neutrophils and hypochlorous acid; Mutagenesis; Mar.; 25(2):149-54 (2010)]

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

A6. 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, respectively (Rabenau 2005, Kariwa 2006). Povidone-iodine (PVP-I) applied for 2 min. as a hand-rub reduces Coronavirus SARS CoV-1 to undetectable levels (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 infection (Theisen 2014).[Rabenau, H.F., et al.; Stability and inactivation of SARS coronavirus; Med. Microbiol. Immunol.; 194, 1-6 (2005); Kariwa, H., et al.; Inactivation of coronavirus by means of povidoneiodine; Dermatology; 212(Suppl. 1):119-123 (2006); Theisen, L.L., et al.; Tannins from Hamamelis virginiana Bark Extract: Characterization and improvement of the antiviral efficacy against Influenza A Virus and Human Papillomavirus; PLoS ONE; Jan.; 9(1) (2014)].

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)?

A7. 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 controls. 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 rates. [Seronella, S., et al.; Ethanol and reactive oxygen species increase basal sequence heterogeneity of Hepatitus C Virus and produce variants with reduced susceptibility to antivirals; PLoS ONE; Nov.; 6(11):e27436 (2011)]

Question 8. Are there any nanosized particles in the inactive ingredients (i.e. excipients) of PharmNord’s Bio-SelenoPrecise, such as silicon dioxide and titanium dioxide?   
A8. “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?
A9. The answer is yes with a caveat. Brazil nuts have been found to have high levels of selenomethionine, selenothionine, and selenocystine (Vanderheide 2002). 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/gr (Infante 2005). 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 adults (Thomson).  This variability in selenium concentration makes Brazil nuts an unreliable daily selenium supplement unless a number of nuts are ground and a teaspoon of nut powder is eaten every day. [Vanderheide, A.P., et al.; Characterization of selenium species in Brazil nuts by HPLC-ICP-MS and ES-MS; J. Agric. Food Chem.; 50205722-5728 (2002); Infante, H., et al.; Current mass spectrometry strategies for selenium speciation in dietary sources of high-selenium; Anal. Bioanal. Chem.; 382:057-67 (2005) – data from ref. 29; Thomson, C.D., et al.; Brazil nuts: an effective way to improve selenium status; Am. J. Clin. Nutr.; 87:379-84 (2008)]

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?

A10. 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 ACE2 (Seko 2019). 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 Coronavirus (Gurwitz 2020). Therefore selenium does not facilitate entry of the virus into lung tissue.  [Seko, T., et al.; Inhibition of angiotensin-converting enzyme by selenoneine; Fishers Science; 85:731-736 (2019) and Gurwitz, D.; Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics; Drug Dev. Res.; 1-4 (2020)]

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

References

1.   Tungsheng, L.; Selenium; Chem. Eng. News (2003)

2.   Beck, M.A., et al.; Rapid genomic evolution of a non-virulent Coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates; Nature Med.; 1:433-36 (1995)

3.   Beck, M.A.; Increased virulence of Coxsachievirus B3 in mice due to vitamin E or selenium deficiency; Am. Soc. Nutri. Sci.; 966S-970S (1997)

4.   Li, S., et al.; The changing selenium nutritional status of Chinese residents; Nutrients; 6:1103-14 (2014)

5.   Gao, J., et al.; Daily selenium intake in a moderate selenium deficiency are of Suzhou, China; Food Chem.; 126:1088-93 (2011) 

6.   Coronavirus COVID-19 global cases by the Center for Systems Science and Engineering; John Hopkins Univ. (2020) https://www.extremetech.com/wp-content/uploads/2020/01/JH-coronavirus.jpg  

7.   How SARS terrified the world in 2003, infecting more than 8,000 people and killing774; businessinsider.com; Feb. 20th (2020)

8.   Song, H.D., et al.; Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and humans; Proc. Natl. Acad. Sci. USA; 102:2430-35 (2005)

9.   Liu, L., et al.; Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus; J. Virol.; 81(9):4694-4700 (2007)

10. Wong, S.K., et al.; A 193-Amino acid fragment of the SARS Coronavirus S protein efficiently binds angiotensin-converting enzyme 2; J. Biol. Chem.; 279(5):3197-201 (2004)

11. Nelson, H.K., et al.; Host nutritional selenium status as a driving force for influenza virus mutations; FASEB J.; 15:1846-48 (2001)

12. Broome, C.S., et al,; An increase in selenium intake improves immune functions and poliovirus handling in adults with marginal selenium status; Am. J. Clin. Nutr.; 80:154-64 (2004)

13. Oldfield, J.E.; World atlas of selenium. Selenium-Tellurium, Grimbergen

14. Harthill, M.; Review; Micronutrient selenium deficiency influences evolution of some viral infectious diseases; Biol. Trace Elem. Res.; 143:1325-36 (2011)

15. Coronavirus COVID-19 global cases by the Center for Systems Science and Engineering; John Hopkins Univ. (2020)

16. Alfthan, G., et al.; Effects of nationwide addition of selenium to fertilizers on foods, and animal and human health in Finland: From deficiency to optimal selenium status of the population; J. Trace Elem. Med. Biol.; 31:142-7 (2015)

17. Rayman, M.P.; Dietary selenium: time to act; BMJ; Sat. Feb 8 (1997)

18. Li, S., et al.; The changing selenium nutritional status of Chinese residents; Nutrients; 61103-14 (2014)

19. Pogue, A.I., et al.; Metal-sulfate induced generation of ROS in human brain cells: detection using an isomeric mixture of 5- and 6-carboxy-2’,7’-dichlorofluoresein diacetate (carboxy-DCFDA) as a cell permeant tracer, Int. J. Mol.; 13:9615-26 (2012)

20. Exley, C., et al.; Aluminum in tobacco and cannabis and smoking-related disease; Am. J. Med.; 118:276 (2006)

21. Wikipedia – Tetraethyllead https://en.wikipedia.org/wiki/Tetraethyllead

22. Technical Note – Estimating lead (Pb) emissions from coal combustion sources; U.S. EPA Office of Air Quality Planning and Standards; Revised (2011)

23. World Health Organization, Inorganic mercury: environmental health criteria 118; International Programme on Chemical Safety; World Health Organization, Geneva, Switzerland (1991)

24. ATSDR Agency for Toxic Substances & Disease Registry; Public health statement for mercury; March (1999)

25. Bengtsson, U.G., and Hylander, L.D.; Increased mercury emissions from modern dental amalgams; Biometals; 30:277-83 (2017)

26. Ferracane, J.L.; Mercury vaporization from amalgams with varied alloy compositions; J. Dent. Res.; 74(7):1414-7 (1995)

27. Crouse, D.N., Silica water the secret of healthy blue zone longevity in the aluminum age; Etiological Publishing (2018) Second Edition (2020)

28. Bakidere, S., et al.; Speciation of selenium in supplements by high performance liquid chromatography  - inductively coupled plasma  - mass spectrometry; Anal. Lett.; 48(9):1511-23 (2015)

29. Gosetti, F., et al.; Speciation of selenium in diet supplements by HPLC – MS/MS methods; Food Chem.; 105:1738-47 (2007)

30. Kubachka, K.M., et al.; Evaluation of selenium in dietary supplements using elemental speciation; Food Chem.; March; 218:313-20 (2017)

31. Aguilar, F., et al.; Selenium-enriched yeast as source for selenium added for nutritional purposes in foods for particular nutritional uses and foods (including food supplements) for the general population; Scientific Opinion of the Panel on Food Additives; The EFSA J.; 766:1-42 (2008)

32. Bugel, S., et al.; Absorption, excretion, and retention of selenium from a high selenium yeast in men with a high intake of selenium; Food Nutr. Res.; (2008)  

33. Reyes, L.H., et al.; Selenium bioaccessibility assessment in selenized yeast after “in vitro” gastrointestinal digestion using two-dimensional chromatography and mass spectrometry; J. Chromatogr. A.; 1110(1-2):108-116 (2006) 

34. Larsen, E.H., et al.; Speciation and bioavailability of selenium in yeast-based intervention agents used in cancer chemoprevention studies; J AOAC Int.; Jan.-Feb.; 87(1):225-32 (2004) 

35. Food and Nutrition Board, Institute of Medicine, Selenium. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, D.C.: National Academy Press; 284-324 (2000)

36. Sharma, V., et al.; Oxidative stress and coxsackievirus infections mediators of beta cell damage; A review;  Sci. Res. Essay Vol.; 4(2):042-058 (2009)

37. Reashi, M.L., et al.; RNA Viruses: Review Article: ROS-mediated cell death; Int. J. Cell Biol.; Article ID 467452 p1-16 (2014)

38. Grossi, V., et al.; The longevity SNP rs2802292 uncovered: HSF1 activates stress-dependent expression of FOXO3 through an intronic enhancer; Nucl. Acids Res.; 46(11):5587-5600 (2018)