This blog introduces you to my book - Prevent Alzheimer's, Autism, and Stroke with 7 Supplements, 7 Lifestyle Choices, and a Dissolved Mineral.
Neurons and Exercise
Monday, September 14, 2020
Wednesday, August 5, 2020
Saturday, March 28, 2020
Covid-19 - Selenium Supplementation Decreases Viral Load
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.
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
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.
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41. 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)
42. 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)
43. 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)
44. 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)
45. Reashi, M.L., et al.; RNA Viruses: Review Article: ROS-mediated cell death; Int. J. Cell Biol.; Article ID 467452 p1-16 (2014)
46. 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)
47. Netland, J., at 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)
48. 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)
49. 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)
50. Yu, C.M., et al.; Cardiovascular complications of severe acute respiratory syndrome; Postgrad. Med. J.; 82(964):140-44 (2006)
51. Zhang, L. and Liu, Y; Potential interventions for novel coronavirus in China: A systematic review; J. Med. Virol.; 92:479-90 (2020)
52. 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
53. 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)
54. Belshaw, R., et al.; Trends Ecol. Evol.; 23(4):188-93 (2004)
55. Biebricher, C.K., et al.; The error threshold; Virus Res.; 107(2):117-27 (2005)
56. 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)
57. 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)
58. Moraes, E.C., et al.; Mutagenesis by hydrogen peroxide treatment of mammalian cells: a molecular analysis; Carcingenesis; 11(2):283-93 (1990)
59. 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)
60. Gungor, N., et al.; Genotoxic effects of neutrophils and hypochlorous acid; Mutagenesis; Mar.; 25(2):149-54 (2010)
61. Rabenau, H.F., et al.; Stability and inactivation of SARS coronavirus; Med. Microbiol. Immunol.; 194, 1-6 (2005)
62. Kariwa, H., et al.; Inactivation of coronavirus by means of povidoneiodine; Dermatology; 212(Suppl. 1):119-123 (2006)
63. 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)
64. 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)
65. 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)
66. Infante, H., et al.; Current mass spectrometry strategies for selenium speciation in dietary sources of high-selenium; Anal. Bioanal. Chem.; 382:057-67 (2005)
67. Thomson, C.D., et al.; Brazil nuts: an effective way to improve selenium status; Am. J. Clin. Nutr.; 87:379-84 (2008)
68. Seko, T., et al.; Inhibition of angiotensin-converting enzyme by selenoneine; Fishers Science; 85:731-736 (2019)
69. Gurwitz, D.; Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics; Drug Dev. Res.; 1-4 (2020)
70. Ogunlana, O.O., et al.; Comparative in vivo assessment of the antiplasmodial activity of quinine – zinc complex and quinine sulphate; Scientific Res. Essay; Mar.; 4(3):180-84 (2009)
71. Obaleye, J.A., et al.; Synthesis, characterization and crystal structure of a polymeric zinc (II) complex containing the antimalarial quinine as ligand; J. Chem. Crystallogr.; 37:707-12 (2007)
72. Ogunlana, O.O., et al.; Antiplasmodial activity of quinine-zinc complex and chloroquine: A comparative in vitro assessment; African J. Pharm. Pharacol.; Febv.; 6(8):516-19 (2012)
73. Magda, D., et al.; Synthesis and anticancer properties of water-soluble zinc ionophores; Cancer Res.; July; 68(13):5318-25 (2008)
74. Prasad, A.S., et al.; Hypocupremia induced by zinc therapy in adults; JAMA; 240:2166-8 (1978)
75. Hoffman, H.N., et al.; Zinc-induced copper deficiency. Gastroenterology; 94:508-12 (1988)
76. Samman, S., and Roberts, D.C.; The effect of zinc supplements on plasma zinc and copper levels and the reported symptoms in healthy volunteers; Med. J. Aust.; 146:246-9 (1987)
77. Prasad, A.S., et al.; Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate; J. Infect. Dis.; 197:795-802 (2008)
78. Felman, A. and White, C.; What to know about Coronaviruses; Med. News Today; Feb. 27, updated Mar. 23 (2020)
79. Hemila, H.; Zinc acetate lozenges for treating the common cold: an individual patient data meta-analysis; Br. J. Clin. Pharmacol.; 82:1393-98 (2016)
80. New York Times; Massive spike in NYC ‘Cardiac Arrest’ deaths seen as sign of Covid-19 undercounting; Apr. 10 (2020)
81. The Economist; Heart-wrenching – Deaths from cardiac arrests have surged in New York City; Apr. 13 (2020)
82. Allen, J.L., et al.; Alterations in human natural killer cell activity and monocyte cytoxicity induced by zinc deficiency; J. Lab. Clin. Med.; 102:577-89 (1983)
83. Keen, C.L., et al.; Zinc deficiency and immune function; Ann. Rev. Nutr.; 10:415-31 (1990)
84. Fraker, P.J., et al.; The dynamic link between the integrity of the immune system and zinc status; J. Nutr.; 130 (Suppl. 5S):1399S-1406S (2000)
85. Prasad, A.S.; Zinc and immunity; Mol. Chem. Biochem.; 188:63-9 (1998)
86. Depadquale-Jardieu, P. and Fraker, P.J.; Interference in the development of a secondary immune response in mice by zinc deprivation: Persistence of effects; J. Nutr.; 114:1762-9 (1984)
87. Minigari, M.C., et al.; Regulation of KIR expression in human T cells: a safety mechanism that repairs protective T cell responses; Immunol. Today; 19:153-7 (1998)
88. Chandra, R.K.; Effect of vitamin and trace-element supplementation on the immune responses and infection in the elderly; Lancet; 340:1124-37 (1992)
89. Rink, L. and Gabriel, P.; Zinc and the immune system; Proc. Nutr. Soc.; 59:541-52 (2000)
90. Faber, C., et al.; Zinc in pharmacological doses suppress allogenic reaction without affecting the antigenic response; Bone Marrow Transplantation; 33:1241-6 (2004)
91. Duchateau, J., et al.; Beneficial effects of oral zinc supplementation on the immune response of old people; Am. J. Med.; May; 70(5):1001-4 (1981)
92. Plum, L.M., et al.; The essential toxin: Impact of zinc on human health; Int. J. Environ. Res. Public Health; 7:1342-65 (2010)
93. Magagnoli, J., et al.; Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19; medRxiv preprint doi: https://doi.org/10.1101/2020.04.16.20065920
94. Gabriela, M., et al.; Chloroquine diphosphate in two different dosages as adjuvant therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial; medRxiv preprint doi: https://doi.org/10.1101/2020.04.07.20056424
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21. 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)
22. Coronavirus COVID-19 global cases by the Center for Systems Science and Engineering; John Hopkins Univ. (2020)
23. Rayman, M.P.; Dietary selenium: time to act; BMJ; Sat. Feb 8 (1997)
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25. Oldfield, J.E.; World atlas of selenium. Selenium-Tellurium, Grimbergen
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27. 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)
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37. Gosetti, F., et al.; Speciation of selenium in diet supplements by HPLC – MS/MS methods; Food Chem.; 105:1738-47 (2007)
38. Kubachka, K.M., et al.; Evaluation of selenium in dietary supplements using elemental speciation; Food Chem.; March; 218:313-20 (2017)
39. 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)
40. 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)
41. 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)
42. 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)
43. 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)
44. 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)
45. Reashi, M.L., et al.; RNA Viruses: Review Article: ROS-mediated cell death; Int. J. Cell Biol.; Article ID 467452 p1-16 (2014)
46. 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)
47. Netland, J., at 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)
48. 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)
49. 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)
50. Yu, C.M., et al.; Cardiovascular complications of severe acute respiratory syndrome; Postgrad. Med. J.; 82(964):140-44 (2006)
51. Zhang, L. and Liu, Y; Potential interventions for novel coronavirus in China: A systematic review; J. Med. Virol.; 92:479-90 (2020)
52. 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
53. 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)
54. Belshaw, R., et al.; Trends Ecol. Evol.; 23(4):188-93 (2004)
55. Biebricher, C.K., et al.; The error threshold; Virus Res.; 107(2):117-27 (2005)
56. 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)
57. 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)
58. Moraes, E.C., et al.; Mutagenesis by hydrogen peroxide treatment of mammalian cells: a molecular analysis; Carcingenesis; 11(2):283-93 (1990)
59. 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)
60. Gungor, N., et al.; Genotoxic effects of neutrophils and hypochlorous acid; Mutagenesis; Mar.; 25(2):149-54 (2010)
61. Rabenau, H.F., et al.; Stability and inactivation of SARS coronavirus; Med. Microbiol. Immunol.; 194, 1-6 (2005)
62. Kariwa, H., et al.; Inactivation of coronavirus by means of povidoneiodine; Dermatology; 212(Suppl. 1):119-123 (2006)
63. 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)
64. 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)
65. 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)
66. Infante, H., et al.; Current mass spectrometry strategies for selenium speciation in dietary sources of high-selenium; Anal. Bioanal. Chem.; 382:057-67 (2005)
67. Thomson, C.D., et al.; Brazil nuts: an effective way to improve selenium status; Am. J. Clin. Nutr.; 87:379-84 (2008)
68. Seko, T., et al.; Inhibition of angiotensin-converting enzyme by selenoneine; Fishers Science; 85:731-736 (2019)
69. Gurwitz, D.; Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics; Drug Dev. Res.; 1-4 (2020)
70. Ogunlana, O.O., et al.; Comparative in vivo assessment of the antiplasmodial activity of quinine – zinc complex and quinine sulphate; Scientific Res. Essay; Mar.; 4(3):180-84 (2009)
71. Obaleye, J.A., et al.; Synthesis, characterization and crystal structure of a polymeric zinc (II) complex containing the antimalarial quinine as ligand; J. Chem. Crystallogr.; 37:707-12 (2007)
72. Ogunlana, O.O., et al.; Antiplasmodial activity of quinine-zinc complex and chloroquine: A comparative in vitro assessment; African J. Pharm. Pharacol.; Febv.; 6(8):516-19 (2012)
73. Magda, D., et al.; Synthesis and anticancer properties of water-soluble zinc ionophores; Cancer Res.; July; 68(13):5318-25 (2008)
74. Prasad, A.S., et al.; Hypocupremia induced by zinc therapy in adults; JAMA; 240:2166-8 (1978)
75. Hoffman, H.N., et al.; Zinc-induced copper deficiency. Gastroenterology; 94:508-12 (1988)
76. Samman, S., and Roberts, D.C.; The effect of zinc supplements on plasma zinc and copper levels and the reported symptoms in healthy volunteers; Med. J. Aust.; 146:246-9 (1987)
77. Prasad, A.S., et al.; Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate; J. Infect. Dis.; 197:795-802 (2008)
78. Felman, A. and White, C.; What to know about Coronaviruses; Med. News Today; Feb. 27, updated Mar. 23 (2020)
79. Hemila, H.; Zinc acetate lozenges for treating the common cold: an individual patient data meta-analysis; Br. J. Clin. Pharmacol.; 82:1393-98 (2016)
80. New York Times; Massive spike in NYC ‘Cardiac Arrest’ deaths seen as sign of Covid-19 undercounting; Apr. 10 (2020)
81. The Economist; Heart-wrenching – Deaths from cardiac arrests have surged in New York City; Apr. 13 (2020)
82. Allen, J.L., et al.; Alterations in human natural killer cell activity and monocyte cytoxicity induced by zinc deficiency; J. Lab. Clin. Med.; 102:577-89 (1983)
83. Keen, C.L., et al.; Zinc deficiency and immune function; Ann. Rev. Nutr.; 10:415-31 (1990)
84. Fraker, P.J., et al.; The dynamic link between the integrity of the immune system and zinc status; J. Nutr.; 130 (Suppl. 5S):1399S-1406S (2000)
85. Prasad, A.S.; Zinc and immunity; Mol. Chem. Biochem.; 188:63-9 (1998)
86. Depadquale-Jardieu, P. and Fraker, P.J.; Interference in the development of a secondary immune response in mice by zinc deprivation: Persistence of effects; J. Nutr.; 114:1762-9 (1984)
87. Minigari, M.C., et al.; Regulation of KIR expression in human T cells: a safety mechanism that repairs protective T cell responses; Immunol. Today; 19:153-7 (1998)
88. Chandra, R.K.; Effect of vitamin and trace-element supplementation on the immune responses and infection in the elderly; Lancet; 340:1124-37 (1992)
89. Rink, L. and Gabriel, P.; Zinc and the immune system; Proc. Nutr. Soc.; 59:541-52 (2000)
90. Faber, C., et al.; Zinc in pharmacological doses suppress allogenic reaction without affecting the antigenic response; Bone Marrow Transplantation; 33:1241-6 (2004)
91. Duchateau, J., et al.; Beneficial effects of oral zinc supplementation on the immune response of old people; Am. J. Med.; May; 70(5):1001-4 (1981)
92. Plum, L.M., et al.; The essential toxin: Impact of zinc on human health; Int. J. Environ. Res. Public Health; 7:1342-65 (2010)
93. Magagnoli, J., et al.; Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19; medRxiv preprint doi: https://doi.org/10.1101/2020.04.16.20065920
94. Gabriela, M., et al.; Chloroquine diphosphate in two different dosages as adjuvant therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial; medRxiv preprint doi: https://doi.org/10.1101/2020.04.07.20056424
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