Zinc Ionophores: Optimism for the Immune System

Vladimir Zelenko, M.D.

June 3, 2021

Summary

Zinc Ionophores have broad spectrum antiviral properties against RNA viruses such as COVID-19.  The emerging scientific data from peer reviewed journals and clinical trials show that zinc ionophores, including Quercetin, may have significant effects against COVID-19.  Zinc ionophores transport extracellular Zinc (Zn2+) ions across a cell membrane, and have been studied for their antiviral and anti-cancer activities.  Studies show Quercetin is a natural antioxidant and anti-inflammatory compound contained in abundance fruits and vegetables - it can be purchased over the counter in supplement form.^[1]  Optimizations to Quercetin as a supplement can likely provide an even stronger effect against COVID-19 by including Zinc, Vitamin C and Vitamin D.  This paper outlines the scientific research that provides the justification for bringing these four (4) molecules together in one capsule to optimize the immune system to fight COVID-19.

1. Quercetin (Zinc Ionophore)
2. Zinc
3. Vitamin C
4. Vitamin D

Recent data, from peer reviewed studies, scientific data and clinical trials show that synergistic supplement combinations involving zinc and the zinc ionophore quercetin may be effective antiviral prevention and therapeutic agents against COVID-19.  An ionophore transports molecules inside cell membranes.  COVID-19 viral entry and replication in cells is inhibited by zinc - significantly reducing COVID-19 infection and mortality.^[2]  Generally, the more zinc that can be brought into respiratory cells, the better off a COVID-19 patient will be.

Quercetin

Quercetin, a natural anti-oxidant and anti-inflammatory compound contained in abundance in various fruits and vegetables, is a zinc ionophore.  Zinc ionophores help transport zinc inside the cells COVID-19 attacks - respiratory cells, providing significant antiviral action against COVID-19.^[3]  Additionally, Quercetin has been shown to be a potent inhibitor of coronaviruses by inhibiting cellular entry as well as inhibiting proinflammatory cytokines.^[4]  One of the hallmarks of COVID-19 is an imbalanced immune response cascading to cytokine storms and then hyper inflammation which then can lead to acute respiratory distress syndrome (ARDS).  

Quercetin has been shown to inhibit proinflammatory cytokine production as well as inflammation due to its antioxidant properties, amongst others.  By inhibiting destructive inflammation and potentially the entire cascade, quercetin may prevent severe damage to the respiratory system amongst other organs.^[5] 

Specifically with respect to respiratory infections:

• A randomized, double-blinded, placebo-controlled trial suggested Quercetin significantly lowered upper respiratory tract infection (URTI) severity (36% reduction, P = 0.020) and URTI total sick days (31% reduction, P = 0.048) in individuals (>40 years) compared with placebo.^[6]

• With respect to influenza, an RNA respiratory virus like COVID-19, treatment with quercetin produced significant increases in the pulmonary concentrations of various antioxidants and a protective effect on lung morphology and a significant decrease in the number of infiltrating cells.^[7]

 Recent clinical trial data shows that the combination of Vitamin C and Quercetin provided strong preventative protection against COVID-19 infection of healthcare workers when compared to the control group as shown below.^[8] Specifically, 1.4% (1 out of 71 healthcare workers) of healthcare workers using Quercetin and Vitamin C combination were infected with COVID-19 vs. 21.4% (9 out of 42 healthcare workers)  of healthcare workers in the control group were infected with COVID-19 (Total Subjects, n = 113).

Vitamin C

Vitamin C is a potent antioxidant, likely immune system optimizer and has been shown to work synergistically with quercetin, likely increasing quercetin’s bioavailability.^[9]  As per Integrative Medicine’s 4th edition, quercetin is a poorly absorbed nutrient but Vitamin C increases the absorption of quercetin and recommends that Quercetin should be blended with Vitamin C.^[10]  Specifically, there is evidence that vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties and the capacity of ascorbate to recycle quercetin, increasing its efficacy.^[11] It has been shown that Quercetin and Vitamin C markedly inhibited mRNA expression of pro-inflammatory cytokines - as the release of inflammatory cytokines are behind acute respiratory distress syndrome.^[12]  The quercetin and vitamin C combination can prevent the exacerbation of inflammation.

        Zinc^[13] is a well known supplement that is generally contained in standard multivitamins.  It provides immune support amongst other functions.  Zinc inhibits coronavirus replication and is a general stimulant of antiviral immunity.^[14]  Higher levels of intracellular zinc showed to increase intracellular pH; which affect on RNA-dependent RNA polymerase and decreases the replication mechanism of RNA viruses (e.g. COVID-19).^[15] Therefore, zinc ionophores (e.g. Quercetin) can likely be used with zinc supplement to act as antiviral against many RNA viruses including influenza and COVID-19.  Suggested benefits of zinc supplementation along with zinc ionophores to prevent and treat COVID-19 and other respiratory tract infections are supported by countless studies.^[16] In most cases, prophylactic and early use of zinc supplementation was more effective than late therapeutic proceedings. Up to 30% of the everyday respiratory infections, briefly named “common cold,” are due to infections with coronaviruses.  Studies showed reduced symptom severity, reduced frequency, and duration of the common cold after zinc administration depending on dosage, zinc compound and the start time after initial symptoms.^[17]

 Zinc deficiency is very common especially in the elderly, diabetics, cancer patients, asthma, immunosuppressed and obese - all of which have higher levels of mortality for COVID-19.   Furthermore, zinc deficiency is associated with increased risk of infectious disease, pneumonia and severity of COVID-19.  Conversely, zinc supplementation is associated with a significant decrease in COVID-19 mortality as long as it is delivered with a zinc ionophore.^[18] 

        In short, a balanced zinc homeostasis is essential.  Zinc supplementation improves the mucociliary clearance, strengthens the integrity of the epithelium, decreases viral replication, preserves antiviral immunity, attenuates the risk of hyper-inflammation, supports anti-oxidative effects and thus reduces lung damage and minimizes secondary infections.  Especially older subjects, patients with chronic diseases and most of the remaining COVID-19 risk groups would most likely benefit.

Vitamin D-3^[19]

Vitamin D is essential to a healthy immune system as it initiates the adaptive immune response.  Clinical trial data shows that Vitamin D supplementation is safe and protects against acute respiratory tract infection mortality whereas low levels of vitamin D are associated with higher risk for infection and mortality.^[20]  In addition, a meta-analysis of COVID-19 studies shows that over 90% of studies report positive effects of Vitamin D against COVID-19.^[21] 

Vitamin D promotes the expression of a protein called cathelicidin which is crucial to antiviral immunity via the induction of cathelicidin and defensins, which can block viral entry into cells as well as suppress viral replication.  Additionally, Vitamin D via cathelicidin promotes antimicrobial function as well as other functions including the stimulation of T cells into the site of infection which inhibit the proinflammatory processes, and promotion of the clearance of respiratory pathogens by inducing apoptosis and autophagy of infected epithelial cells. In addition vitamin D promotes the killing of pneumococcus by stimulating neutrophils via a range of mechanisms.  Over the last 10 years, vitamin D deficiency has also been linked to a wide range of common infectious diseases, such as pneumonia, influenza, amongst others.

The link between vitamin D and viral infections arose from the observation of the seasonality of vitamin D with lower levels in the winter and concomitant increases in influenza. Conversely, in summer, serum levels of Vitamin D increase and influenza virtually disappears, except during pandemics. Even in pandemics, most deaths occur during cold months.

The Zelenko Protocol^[22]

Since March 2020, my team has successfully treated over 3,000 patients with Covid-19 with the Zelenko Protocol.  Our high-risk patient survival rate was >99.3% (0.7% mortality) which represents a radical improvement when compared to national data of high-risk patients with a survival rate of 92.5% (7.5% mortality).  My team has successfully prophylaxed (prevention) a similar number of patients against COVID-19 with the Zelenko Protocol, with a patient survival rate of 100%.  I have provided counsel to governments, physicians and hospital networks regarding prophylaxis and prehospital care of Covid-19 and I am fully familiar with their results.  

Based on this real world experience, peer reviewed literature and clinical trial data, this supplement combination has significantly improved patient outcomes and should be considered as part of the armamentaria against Covid-19.  

As part of the Zelenko Protocol for COVID-19, I recommend the following for the prophylaxis of low and moderate risk patients:

• Elemental Zinc 25mg 1 time a day^[23]
• Vitamin D 5000iu 1 time a day
• Vitamin C 800mg 1 time a day^[24] 
• Quercetin 500mg 1 time a day

Treatment of low risk patients:

• Elemental Zinc 50mg 1 time a day for 7 days^[25]
• Quercetin 500mg 2-3 times a day for 7 days^[26] 
• Vitamin C 800mg 1 time a day for 7 days     
• Vitamin D3 5000iu 1 time a day for 7 days

Disclaimer

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License

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In all other circumstances, the GNU General Public License v3.0 applies.