Immunity Theory

Covid 19 Theory- possible treatment of Covid-19 using Phytase enzyme

 

*Disclaimer:  I am not an epidemiologist or infectious disease specialist so please forgive any errors in this theory.  This is essentially a review of the literature, combining everything I can, to produce a theory. Some of the notes below are direct quotes from the studies I’ve reviewed, not my words.


Theory overview:  The enzyme Phytase, already GRAS (generally regarded as safe) and widely used in animals and tested in human studies, acts as an ionofore to zinc.  Research shows that zinc can interfere with replication of any virus, but that only some zinc is able to get into cells.  Phytase could be the missing link to the immune system, and possibly to combatting Covid-19. 


Call to Action:  

  1. Implement wide scale testing of plasma zinc levels.
  2. Implement a treatment protocol of phytase (400-800U phytase/day) in combination with zinc supplementation with RDA of 10mg- 75mg per day during acute infection and to patients who are exhibiting severe symptoms.

 

Theory Outline:  


Research has proven that zinc is the gatekeeper to the immune system and is critical for almost all immunological functions.  Phytase is an enzyme which supports zinc homeostasis by affecting the endogenous duodenal pool of zinc, which then creates a stronger and possibly impenetrable  immune system because when zinc levels are adequate, the body can mount an immune response. Zinc supplementation can be ineffective in treating deficiency, because if phytate (the antinutrient that causes micronutrient deficiency) is still present in the gut, it is difficult to achieve zinc homeostasis.  Therefore, the use of a combination of phytase as well as zinc supplements, could work as a prophylactic, specifically with Covid -19 prevention and treatment. This could be incredibly important for the general public, but especially for front line health care workers at risk of exposure. As we watch the spread of Covid-19, it becomes even more critical for third world countries where populations rely heavily on high phytate foods such as grains, beans, nuts and seeds.  Phytase can be easily distributed in capsule form, or sprinkled on food as a powder after preparation.


Men are much more likely to be zinc deficient than women, which would further illustrate why this virus seems to be hitting men harder than women.  Zinc absorption also decreases with age. Almost 70% of the deaths related to Covid-19 are men.  

My hope is that through administration of phytase and small amounts of zinc, or possibly no zinc at all, we could modulate the immune response and prevent the complications of Covid-19, and thus there would be a reduced need for ventilators and hopefully reduced complications and death from the virus.



IMPORTANT TERMINOLOGY


Phytate (IP6):  

Antinutrient which chelates zinc, iron, calcium and magnesium, making them essentially unavailable for absorption in humans.  Seed based foods (grains, seeds, nuts, legumes) contain high levels of phytate, a strong chelator of zinc and other minerals. Because the phytate cannot be digested or absorbed in the human intestinal tract, minerals bound to phytate also pass through the intestine unabsorbed.  “The phytate: zinc molar ratio is the primary dietary factor inhibiting zinc absorption and has been used to estimate the proportion of absorbable zinc. A reduction in the phytate to zinc molar ratio of any diet (through the use of phytase) was shown to significantly improve zinc absorption from food.”

PHYTASE: the enzyme that degrades Phytate, thus giving our bodies access to zinc and other micronutrients.  In this case, phytase acts as an Ionofore (a substance which is able to give cells greater access to zinc).


Phytase:

  • Is involved in strengthening the immune system by enhancing immunocyte activity and inhibiting pathological calcification
  • The degradation products of the action of phytase on phytate regulate immunocyte activity (removing phosphate groups from the phytate)
  • Phytase may improve mucosal immunity by enhancing nutrient uptake for the intestinal immune cells and improve mucin integrity
  • Phytase increases percentages of CD4+ and CD8+ T lymphocyte subsets
  • SigA production was significantly increased by dietary phytase
  • SigA traps invading bacteria so that the bacteria pass through the body before causing an infection
  • SigA is also part of the intestinal immune system- prevents pathogens from attaching to intestinal lining
  • Phytase is active at gut ph of 2.5 to 6, comparable to the stomach and small intestine

The Standard American diet contains about 750mg of phytate/ day.  Vegan and vegetarian diets can be even higher. Anyone relying on subsistence diets (grains) could be as high as 2000 mg of phytate per day.

Zinc is recycled via the pancreas.  Zinc deficiency is controlled by zinc homeostasis.

Only about 25% of dietary zinc is absorbed.

Phytate to zinc molar ratio (below). Endogenously secreted zinc was an important aspect of the observed phenomenon and this formula predicted zinc homeostasis rather than zinc absorption.

The effect of phytate is on the duodenal pool of zinc (dietary plus pancreatic secretion) rather than dietary absorption alone.

 

ZINC


The importance of zinc for human health has been well documented; zinc has critical structural and functional roles in multiple enzyme systems that are involved in gene expression, cell division and growth, and immunologic and reproductive functions.  Zinc deficiency reduces the generation of Tcells, depresses humoral and cell mediated immunity, leads to lymphopenia and thymic atrophy and increases the frequency and number of infections. Men are particularly susceptible to zinc deficiency, and zinc deficiency increases with age.

  • zinc is intimately involved in cell division
  • serves as a cofactor in RNA polymerase and reverse transcriptase and in zinc finger proteins that are adducts to DNA and regulates the expression of DNA by serving as receptor sites for hormone and other in vivo factors
  • zinc influences not only NK cell mediated killing but also affects activity of cytotoxic Tcells
  • studies show that supplementation and optimal intake of zinc restores impaired immune response and decreases infection incidence in vivo.
  • Plasma levels of zinc should never exceed 30u/mol of zinc/L
  • Therefore, rather than supplement with zinc, the more effective approach is to use phytase to impact the endogenous pool of zinc and zinc homeostasis 

ABSENCE OF ZINC

  • protein moieties may be synthesized but the regulation fails
  • Thymedine kinase and Lactic dehydrogenase:  synthesis is compromised by zinc deficiency, and therefore zinc finger proteins are not synthesized
  • Zinc finger proteins render cells 30 fold more resistant to viral infection
  • The production of viral RNA in the cytoplasm is inhibited
  • ZAP:  zinc finger antiretroviral protein
  • Tcells are reduced during zinc deficiency
  • Thymus is affected by zinc deficiency
  • Antigens are Tcell dependent, therefore with zinc deficiency, the body is unable to respond with antibody production in response to neo-antigens
  • B-lymphocyte antibody production is also disturbed during zinc deficiency

  

ZINC DEFICIENCY AND IMMUNE DYSFUNCTION

  • Zinc deficiency produces reversible immune dysfunction

Enzymes sensitive to zinc deficiency: 

  • Thymidine kinase
  • RNA polymerase
  • Ribonuclease (RNA)

 

Thymedine kinase is essential for DNA synthesis and cell division

  • Particularly Tcell lymphocyte mediated immunity

Zinc supplementation has been shown to reduce morbidity from respiratory and diarrheal disease.  (https://www.who.int/elena/titles/bbc/zinc_pneumonia_children/en/)


Adequate zinc eases pneumonia in elderly, study finds


Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months

Zinc deficiency most prominently impairs t-lymphocyte cell mediated immunity

  • Zinc deficiency causes an imbalance between TH1 and TH2 functions with proportionally greater impairment of CMI (cell mediated immunity) and prevents regeneration of new CD4 + Tlymphocytes
  • B and T cells of the specific immune system have a great variety of specific receptors (antibodies and Tcell receptors) and can produce memory cells that respond quickly and powerfully to antigens to which they have been primed (paper: zinc altered immune function)
  • “When zinc deficiency is not severe enough to cause clinical signs and symptoms, it may still have a subclinical effect on immune function, the synthesis and action of hormones, and neurological function.”
  • “In zinc deficiency, there is a reduction in the activity of serum thymulin, the thymus-specific hormone that is involved in T-cell function and an imbalance develops between Th1 and Th2 helper cells.  The lytic activity of natural killer cells also decreases. Morever, zinc is also necessary for intracellular bindings of tyrosine kinase to the T-cell receptors CD4 and CD8, which are required for T-lymphocyte activation.  These complex changes result in an impairment of cell mediated immunity and may be the basis for increased infection rates seen in marginal zinc depletion.”
  • The thymus gland is the organ most severely affected by zinc deficiency.  Thus the thymus glad, a very important part of the immune system and effective against both bacteria and viruses, was severely compromised by zinc deficiency.
  • Zinc is secreted by the pancreas back into the duodenum.  It is therefore important to understand the effect of phytate on the endogenous pool of zinc.  Endogenous secretion is 2-4 times the dietary intake in species without fortification. Thus, the endogenous pool of zinc is larger and thus more vulnerable to complexation by phytate than the dietary pool and the problem becomes zinc homeostasis rather than absorption or availability.
  • Supplying adequate zinc from phytate containing proteins by hydrolysis of the phytate within the human gastrointestinal tract, by phytase, thus allowing greater zinc REABSORPTION and subsequently HOMEOSTASIS is the goal.
  • Supplementing with zinc does not achieve the same results.  Phytase is needed. Phytase releases sufficient amounts of zinc and phosphorus from food, without supplements.
  • Zinc deficient humans have thymic atrophy and an increased susceptibility to infections.
  • Zinc deficiency is controlled by zinc homeostasis because the endogenous secretion of zinc is considered as an important factor influencing zinc deficiency, and the critical molar ratio is 10.
  • The problem is zinc homeostasis, because the effect of phytate is on the duodenal pool of zinc (dietary plus pancreatic secretion) rather than dietary absorption alone.  Zinc is the only essential cation secreted via the pancreas and is the essential divalent cation that binds tighter to phytate than other essential cations (Oberleas: Treatment of zinc deficiency without zinc fortification).

 

Even mild zinc deficiency, which is widely spread in contrast to severe zinc deficiency, depresses immunity in humans.  The three groups of people at high risk of zinc deficiency are: elderly people, vegetarians and patients with renal insufficiency

 

Viral Inhibition with zinc

Zinc directly inhibits RNA transcription of the virus without being toxic to the host cell

Zinc directly inhibits virus protease by binding at the active site

Therefore:  could adequate zinc concentrations inhibit viral replication?  To achieve adequate zinc homeostasis, use the phytase enzyme.

Over production of cytokines in sick patients may increase renal wasting

Poor GI absorption also leads to zinc deficiency, so even with supplementation, unless we improve absorption, zinc may not get to adequate levels to support a healthy immune system.

Selective blockade of active zinc finger sites may inhibit the virus, while sparing host immune cells 

Bioavailability of zinc is key.  Phytate binds to zinc, inhibits its absorption, and thus affects the risk of zinc deficiency.

Calcium also inhibits zinc absorption and augments the inhibition of zinc absorption by  phytate

 

Bioavailability of zinc from supplements:

Very low bio-availability:  zinc oxide

Relatively high bio-availability:  zinc salts: zinc acetate

FAO states that zinc deficiency may be as high as 40% worldwide

Zinc deficiency can lead to pneumonia at it’s most severe and late stage

 

How to measure zinc:  biomarkers of zinc status

 -plasma or serum zinc

 Zinc requirements:  a 70kg adult contains 2-3g of zinc in their body

Healthy adults need:  Anywhere from 2-16mg of zinc per day

This amount needs to be adjusted for bioavailability

For example: if only 20% of zinc is bioavailable: 

Men need:  11.0 mg per day and women need 8.3mg per day

 

And this is just in healthy people.  When zinc deficiency exists, the issue becomes absorbing the zinc.  Phytase helps with absorption.  Some studies have suggested therapeutic zinc supplementation as high as 75mg per day.

 

*Important to monitor zinc as it could cause toxicity and impair copper status

Other studies suggest 20mg of zinc per day

 

Wilson’s disease treatment (copper excess)

50mg of zinc acetate 3X daily or more

 

"Worldwide, zinc supplementation is an enormously important intervention against mortality from pneumonia, diarrhea and malaria."

"Zinc supplementation could reduce child death globally by 63%"

 "Zinc deficiency is a cause of disease and determines the progression of disease."

  

Formulas to understand:

 

Phytate to zinc molar ratio (Dr. Oberleas):

=(mp/660)/(mzn/65.4)

Mp is the weight of dietary phytate (g)

Mzn is the weight of dietary zinc (g)

660 and 65.4 are molecular weight of undissociated phytic acid and atomic weight of zinc respectively



A phytate: zinc molar ratio under 10 should provide sufficient zinc, but not always.  Sometimes a ratio of 6 could still indicate zinc deficiency

 

1 unit of phytase is the activity that liberates 1umol of phosphate in one minute from phytate

 


References 

(please note these are a list of references for my book, but not for this concept sheet)




  1.  Treatment of Zinc deficiency without zinc fortification:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266882/
  2. Zinc alterened immune function:  https://academic.oup.com/jn/article/133/5/1452S/4558525
  3. Meals and Dephytinization affect calcium and zinc absorption in Nigerian children:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714392/
  4. Supplemental microbial phytase improves bioavailability of dietary zinc to weaning pigs:  https://www.researchgate.net/publication/14810707_Supplemental_microbial_phytase_improves_bioavailability_of_dietary_zinc_to_weaning_pigs
  5. Effect of phytate and phytase on the performance and immune function of broilers fed nutritionally marginal diets:  https://www.sciencedirect.com/science/article/pii/S0032579119393071
  6. A Micronutrient Powder with Low doses of highly absorbable iron and zinc reduces iron and zinc deficiency and improces weight for age Z scores in South African Children: https://www.ncbi.nlm.nih.gov/pubmed/21178093
  7. Zinc supplementation increases zinc status and thymopoiesis in aged mice:  https://www.ncbi.nlm.nih.gov/pubmed/19474155
  8. Zinc requirements and the risks and benefits of zinc supplementation:  https://www.ncbi.nlm.nih.gov/pubmed/16632171
  9. Black RE. Zinc deficiency, infectious disease and mortality in the developing world. Journal of Nutrition. 2003; 133:1485S–1489S.






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  8. Troesch B, Van Stuijvenberg ME, Smuts CM, Kruger HS, Biebinger R, Hurrell RF, Baumgartner J, Zimmermann MB. A micronutrient powder with low doses of highly absorbable iron and zinc reduces iron and zinc deficiency and improves weight-for-age Z-scores in South African children. J Nutr. 2011;141(2):237-42.
  9. Troesch B, Egli I, Zeder C, Hurrell RF, de Pee S, Zimmerman MB. Optimization of a phytase-containing micronutrient powder with low amounts of highly bioavailable iron for in-home fortification of complementary foods. Am J Clin Nutr. 2009;89(2):539-44.
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  20. Troesch B, Egli I, Zeder C, Hurrell RF, de Pee S, Zimmerman MB. Optimization of a phytase-containing micronutrient powder with low amounts of highly bioavailable iron for in-home fortification of complementary foods. Am J Clin Nutr. 2009;89(2):539-44.
  21. Troesch B, van Stuijvenberg ME, Smuts CM, Kruger HS, Biebinger R, Hurrell RF, Baumgartner J, Zimmermann MB. A micronutrient powder with low doses of highly absorbable iron and zinc reduces iron and zinc deficiency and improves weight-for-age Z-scores in South African children. J Nutr. 2011;141(2):237-42.



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In 2009, Amy Puzey was working as a nutritionist when she began researching micronutrient deficiency in impoverished populations. Her passion for and desire to cure HIV/AIDS led her to find and develop the EMPATH immunity theory.

EMPATH stands for Enzyme Modification of Phyate to Assist in the Treatment of HIV/AIDS.

Her hypothesis is that phytate, through micronutrient depletion, could be largely responsible for the backslide in the immune system and may play a key role in the HIV/AIDS epidemic, as well as other diseases where populations are solely dependant on foods high in phytate (whole grains, pulses, seeds, beans, lentils etc). Further, she proposed that a study be done to see if a phytase supplement could boost CD4 count, which is how we measure AIDS progression, and protect the CD4 count from dropping.  Could humans live with the HIV virus in them, but keep CD4 high enough to stay healthy? 

New research is focused on zinc being key to the immune system and the problem of zinc deficiency worldwide. Phytate is one of the primary reasons for zinc deficiency. Because phytate affects the endogenous pool of zinc, you literally cannot absorb zinc from food if phytate is present in your gut. However, by simply treating food with the phytase enzyme, or taking it in capsule or any other form, we are able to degrade phytate to a point where it cannot harm us. The theory postulates that the phytase enzyme, or any method that removes phytate, could lead to an almost impenetrable immune system.

Not only will acute malnutrition be affected, but many other diseases would have difficulty taking hold in our bodies.

This theory means that the fields of nutrition and medicine have to talk and collaborate, something not commonly done. Amy challenges anyone out there, to test her theory and to try to disprove it. She is particularly interested in how phytase could help with HIV/AIDS, iron deficiency and anemia, TB, malaria and other diseases endemic in the developing world.

Without the ability to run clinical trials, Access Nutrients was developed to educate immunologists, researchers, doctors, clinicians and NGOs. Amy’s dream is that nutrition and medicine will finally talk to each other, and that by using phytase to deplete phytate, our immune system might actually stand a chance at fighting off some of the diseases of modern civilization.

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Almost all Food Aid given to impoverished communities and refugee camps is made up of foods that are extremely high in phytate (such as corn soy blends). Despite efforts to fortify these foods with micronutrients, when phytate is present, many of the nutrients are not able to be absorbed. Acute malnutrition and hidden hunger are serious issues, affecting over 2 billion people on the planet. These foods (mainly corn/soy blends), could also be pre-treated with the phytase enzyme before being fed to humans. It is an inexpensive and simple way to ensure that anyone eating the food is able to access the nutrients in those foods. It could be revolutionary for preventing disease outbreaks in these populations.