- Zinc prevents viral replication inside your cells, but is poorly absorbed. Zinc ionophores (zinc transport molecules) such as quercetin, epigallocatechin-gallate (EGCG) and the drug hydroxychloroquine facilitate zinc uptake
- A combination of zinc with a zinc ionophore was in 2010 shown to inhibit SARS coronavirus in vitro. In cell culture, it also blocked viral replication within minutes
- Zinc deficiency impairs immune function
- Preliminary research found COVID-19 patients with plasma zinc levels below 50 mcg/dl at admission had a 2.3 times greater risk of in-hospital death than those with a zinc level of 50 mcg/dl or higher
- Other research found COVID-19 patients were more likely to be deficient in zinc than healthy controls. Zinc deficient patients also had worse outcomes and higher rates of death. While 70.4% of zinc deficient patients developed complications, only 30% of those with sufficient levels developed complications
Your immune system is your first line of defense against all disease, especially infectious disease, and there are many different ways to boost your immune system and improve its function. One nutrient that plays a very important role in your immune system's ability to ward off viral infections is zinc.
The problem is that zinc is largely insoluble and cannot easily enter through the fatty wall of your cells. Getting all the way into the cell is crucial, as this is where the viral replication occurs. This is why zinc ionophores are so important.
Zinc Is Crucial for Healthy Immune FunctionZinc is crucial for healthy immune function7 — like vitamin D, it actually helps regulate your immune function8 — and a combination of zinc with a zinc ionophore was in 2010 shown to inhibit SARS coronavirus in vitro. In cell culture, it also blocked viral replication within minutes.9
"Zinc is a second messenger of immune cells, and intracellular free zinc in these cells participate in signaling events. Zinc ... is very effective in decreasing the incidence of infection in the elderly. Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti-inflammatory agent."Similarly, the September 2020 paper in Medical Hypotheses, "Does Zinc Supplementation Enhance the Clinical Efficacy of Chloroquine / Hydroxychloroquine to Win Todays Battle Against COVID-19?" points out that:12
"Besides direct antiviral effects, CQ/HCQ [chloroquine and hydroxychloroquine] specifically target extracellular zinc to intracellular lysosomes where it interferes with RNA-dependent RNA polymerase activity and coronavirus replication.
As zinc deficiency frequently occurs in elderly patients and in those with cardiovascular disease, chronic pulmonary disease, or diabetes, we hypothesize that CQ/HCQ plus zinc supplementation may be more effective in reducing COVID-19 morbidity and mortality than CQ or HCQ in monotherapy. Therefore, CQ/HCQ in combination with zinc should be considered as additional study arm for COVID-19 clinical trials."
Low Zinc Levels Increase COVID-19 Death RiskPreliminary data also suggest people with low zinc levels are more likely to die from COVID-19 than those with higher levels. The research13,14,15,16,17 was presented at the European Society of Clinical Microbiology and Infectious Disease (ESCMID) Conference on Coronavirus Disease,18 held online September 23 through September 25, 2020, and posted19 on the preprint server medRxiv October 11, 2020.
To evaluate the importance of plasma zinc levels on COVID-19 outcomes, the researchers did a retrospective analysis of 249 COVID-19 patients admitted to a hospital in Barcelona, Spain, between Mach 15 and April 30, 2020, for whom fasting plasma zinc levels were recorded. The average patient age was 63.
"Mean baseline zinc levels among the 249 patients were 61 mcg/dl. Among those who died, the zinc levels at baseline were significantly lower at 43 mcg/dl vs 63.1 mcg/dl in survivors.
Higher zinc levels were associated with lower maximum levels of interleukin-6 (proteins that indicate systemic inflammation) during the period of active infection.
After adjusting by age, sex, severity and receiving hydroxychloroquine, statistical analysis showed each unit increase of plasma zinc at admission to hospital was associated with a 7% reduced risk of in-hospital mortality.
Having a plasma zinc level lower than 50 mcg/dl at admission was associated with a 2.3 times increased risk of in-hospital death compared with those patients with a plasma zinc level of 50 mcg/dl or higher."
Zinc Deficiency Linked to Poor COVID-19 OutcomesAnother paper22 reviewed by Campbell was published in the November 2020 issue of the International Journal of Infectious Diseases. Here, they found that people admitted to the hospital with COVID-19 related symptoms were more likely to be deficient in zinc than healthy controls. The median zinc level among hospitalized COVID-19 patients was 74.5 mcg/dl, compared to 105.8 mcg/dl in the control group. As reported by the authors:23
"Amongst the COVID-19 patients, 27 (57.4%) were found to be zinc deficient. These patients were found to have higher rates of complications, acute respiratory distress syndrome (18.5% vs 0%), corticosteroid therapy, prolonged hospital stay, and increased mortality (18.5% vs 0%). The odds ratio (OR) of developing complications was 5.54 for zinc deficient COVID-19 patients."Importantly, while 70.4% of zinc deficient patients developed complications, only 30% of those with sufficient levels developed complications. As noted by Campbell, here we see that healthy controls had far higher zinc levels than patients with milder illness in the Spanish study.
Zinc Is a Key Component of MATH+ Protocol
In the interview above, Dr. Paul Marik explains how the COVID-19 critical care protocol grew out of his sepsis treatment (a core ingredient of which is vitamin C), as he and other doctors noticed there were many similarities between sepsis and severe COVID-19 infection, in particular the out-of-control inflammatory cascade.
There are also distinct differences between the two conditions, and to address those, Marik and nine other physicians founded the FLCCC and began developing a modified protocol specifically for COVID-19.
Natural Zinc Transporters — Quercetin and EGCGAs mentioned, quercetin28 and EGCG are natural zinc ionophores that can do the same job as HCQ. According to a study29 published in 2014, many of the biological actions of quercetin and EGCG actually appear to be related to their ability to increase cellular zinc uptake. As explained by the authors:30
"Labile zinc, a tiny fraction of total intracellular zinc that is loosely bound to proteins and easily interchangeable, modulates the activity of numerous signaling and metabolic pathways. Dietary plant polyphenols such as the flavonoids quercetin (QCT) and epigallocatechin-gallate act as antioxidants and as signaling molecules.
Remarkably, the activities of numerous enzymes that are targeted by polyphenols are dependent on zinc. We have previously shown that these polyphenols chelate zinc cations and hypothesized that these flavonoids might be also acting as zinc ionophores, transporting zinc cations through the plasma membrane.
To prove this hypothesis, herein, we have demonstrated the capacity of QCT and epigallocatechin-gallate to rapidly increase labile zinc in mouse hepatocarcinoma Hepa 1-6 cells as well as, for the first time, in liposomes ... The ionophore activity of dietary polyphenols may underlay the raising of labile zinc levels triggered in cells by polyphenols and thus many of their biological actions."Aside from increasing zinc uptake, both quercetin and EGCG also inhibit 3CL protease31 — an enzyme used by SARS coronaviruses to infect healthy cells.32 As explained in a 2020 paper33 in Nature, 3CL protease "is essential for processing the polyproteins that are translated from the viral RNA."
More Support for QuercetinSupport for the use of quercetin against COVID-19 has also been reported by the Green Stars Project.37 Using the supercomputer SUMMIT, Oak Ridge National Lab researchers looked for molecules capable of inhibiting the COVID-19 spike protein from interacting with human cells. Quercetin is fifth on that list.38
- Inhibiting virus' ability to infect cells
- Inhibiting replication of already infected cells
- Reducing infected cells' resistance to treatment with antiviral medication
- Inhibiting lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF-α) production in macrophages. TNF-α is a cytokine involved in systemic inflammation, secreted by activated macrophages, a type of immune cell that digests foreign substances, microbes and other harmful or damaged components 
- Inhibiting release of proinflammatory cytokines and histamine by modulating calcium influx into the cell
- Stabilizing mast cells
- Regulating the basic functional properties of immune cells
- Down-regulating or suppressing inflammatory pathways and functions
Zinc-to-Copper Ratio Can Impact Immune FunctionWhen it comes to zinc supplementation, more is not necessarily better. In fact, it can frequently backfire is you do not also maintain a healthy zinc-to-copper ratio. As explained by Chris Masterjohn, who has a Ph.D. in nutritional sciences,45 in an article46 and series of Twitter posts:47
"In one study, 300mg/day of zinc as two divided doses of 150 mg zinc sulfate decreased important markers of immune function, such as the ability of immune cells known as polymorphonuclear leukocytes to migrate toward and consume bacteria.
The most concerning effect in the context of COVID-19 is that it lowered the lymphocyte stimulation index 3 fold. This is a measure of the ability of T cells to increase their numbers in response to a perceived threat. The reason this is so concerning in the context of COVID-19 is that poor outcomes are associated with low lymphocytes ...
The negative effect on lymphocyte proliferation found with 300 mg/day and the apparent safety in this regard of 150 mg/d suggests that the potential for hurting the immune system may begin somewhere between 150-300 mg/d ...
It is quite possible that the harmful effect of 300 mg/d zinc on the lymphocyte stimulation index is mediated mostly or completely by induction of copper deficiency ...
The negative effect of zinc on copper status has been shown with as little as 60 mg/d zinc. This intake lowers the activity of superoxide dismutase, an enzyme important to antioxidant defense and immune function that depends both on zinc and copper ...
A study done with relatively low intakes of zinc suggested that acceptable ratios of zinc to copper range from 2:1 to 15:1 in favor of zinc. Copper appears safe to consume up to a maximum of 10 mg/d.
Notably, the maximum amount of zinc one could consume while staying in the acceptable range of zinc-to-copper ratios and also staying within the upper limit for copper is 150 mg/d."Another factor to keep in mind is that certain additives can inhibit zinc absorption, which is the complete opposite of what you're looking for. For instance, research has shown citric acid, glycine, mannitol and sorbitol can reduce zinc absorption,48 so zinc lozenges containing these ingredients may be less useful.
How Much Zinc Do You Need?That said, the recommended dietary allowance for zinc in the U.S is 11 mg for adult men and 8 mg for adult women, with slightly higher doses recommended for pregnant and breastfeeding women.49
As a prophylactic against COVID-19 and other viral infections, Masterjohn recommends taking 7 mg to 15 mg of zinc four times a day, ideally on an empty stomach, or with a phytate-free food. He also recommends getting at least 1 mg of copper from food and supplements for every 15 mg of zinc you take.
Last but not least, remember there are many food sources of zinc, so a supplement may not be necessary. I eat about three-quarters of a pound of ground bison or lamb a day, which provides 20 mg of zinc. I personally don't take any zinc supplement other than what I get from my food.
Sources and References
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- 38 ChemRxiv.org March 11, 2020 (PDF full study), Table 3
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