How to Improve Zinc Uptake with Quercetin

Analysis by Dr. Joseph Mercola Fact Checked

Story at-a-glance

  • Your immune system is your first line of defense against infectious diseases, and there are many different ways to boost and improve its function
  • Zinc is one nutrient that plays a very important role in your immune system’s ability to ward off viral infections, and may play a vastly underrated role in the COVID-19 pandemic
  • Zinc is vital for healthy immune function and a combination of zinc with a zinc ionophore (zinc transport molecule) was in 2010 shown to block viral replication of SARS coronavirus in cell culture within minutes
  • Zinc alone is incapable of fully stopping viral replication as it cannot easily enter through the fatty wall of a cell. Getting all the way into the cell is crucial, as this is where the viral replication occurs
  • The antimalarial drug hydroxychloroquine appears to work against COVID-19 by improving zinc uptake into cells. Natural zinc ionophores that improve zinc absorption include quercetin and epigallocatechin-gallate (EGCG)

WARNING!

This is an older article that may not reflect Dr. Mercola’s current view on this topic. Use our search engine to find Dr. Mercola’s latest position on any health topic.

EDITOR’S NOTE: A section of this article that originally referenced Bill Sardi and his commentary on zinc ionophores has been removed at Sardi’s request. Other sections have been modified to include additional information on ionophores, zinc and the cellular processes by which zinc works.

Remarkably, prominent physicians have been paraded in the media saying it's impossible to strengthen your immune system to beat the SARS-CoV-2 virus. It’s hard to understand this kind of ignorance still pervades the conventional medical system — and that they can get away with criticizing people who offer proof to the contrary.

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.

In the MedCram video above, Dr. Roger Seheult reviews compelling evidence suggesting the reason the antimalarial drug chloroquine appears so useful in the treatment of COVID-19 is in fact because it improves zinc uptake into the cell. (Hydroxychloroquine (Plaquenil) uses the same pathway as chloroquine, but has a safer side effect profile.1)

While the antimalarial drugs chloroquine and hydroxychloroquine act as a zinc ionophore (zinc transport molecule) in that they facilitate zinc absorption in your body, other natural compounds can have the same effect.

Zinc Binding Compounds Boost Immune System

Zinc may be a vastly underrated player in the COVID-19 pandemic. It is vital for healthy immune function2 and a combination of zinc with a zinc ionophore (zinc transport molecule) was in 2010 shown to inhibit SARS coronavirus in vitro. In cell culture, it also blocked viral replication within minutes.3

More recently, Dr. Vladimir Zelenko, who has a medical practice in New York, claims4 to have successfully treated 699 consecutive COVID-19 cases with a combination of oral zinc, chloroquine (a zinc ionophore) and the antibiotic azithromycin. Importantly, zinc deficiency has been shown to impair immune function.5 As noted in a 2013 paper on zinc deficiency:6

“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.”

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 where zinc ionophores come in, and the fact that the antimalarial drugs chloroquine and hydroxychloroquine act as zinc ionophores may explain why they appear so useful against COVID-19.

Other Natural Zinc Transporters — Quercetin and EGCG

The good news is drugs like chloroquine and hydroxychloroquine probably would not be necessary either (except for perhaps the most serious cases), as other natural compounds can do the same job.

A comparative study7 published in 2014 looked at two zinc ionophores: quercetin and epigallocatechin-gallate (EGCG found in green tea), noting many of the biological actions of these compounds may in fact be related to their ability to increase cellular zinc uptake. As explained by the authors:

“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.”

Quercetin is also a potent antiviral in its own right, and both quercetin and epigallocatechin gallate also have the added advantage of inhibiting the 3CL protease8 — an enzyme used by SARS coronaviruses to infect healthy cells.9 As explained in a 2020 paper in Nature, 3CL protease “is essential for processing the polyproteins that are translated from the viral RNA.”

And, according to another 2020 study,10 the ability of quercetin, epigallocatechin gallate and certain other flavonoids to inhibit SARS coronaviruses “is presumed to be directly linked to suppress the activity of SARS-CoV 3CLpro in some cases.”

Quercetin + Zinc + Niacin + Selenium May Be a Winning Combo

If you wanted to try a holistic version of Zelenko’s COVID-19 protocol, you could use a natural antibiotic such as oil of oregano, quercetin (as a zinc ionophore in lieu of chloroquine) along with oral zinc (Chris Masterjohn recommends11 taking 7 mg to 15 mg of zinc four times a day, ideally on an empty stomach).

Should zinc turn out to be in short supply, consider eating more zinc-rich foods.12 Examples include hemp, sesame and pumpkin seeds, cacao powder, cheddar cheese, and seafood such as oysters, Alaskan crab, shrimp and mussels.

To this you could also add niacin (vitamin B3) and selenium, as both play a role in the absorption and bioavailability of zinc in the body. For example, a study13 published in 1991 demonstrated that when young women were on a vitamin B3-deficient diet, their serum zinc declined, suggesting B3 deficiency affected zinc metabolism such that “absorbed zinc was not available for utilization.”

A more in-depth exploration and explanation of both niacin and selenium’s relationship to zinc is provided in the 2008 paper, “Zinc, Metallothioneins and Longevity: Interrelationships With Niacin and Selenium”:14

“Ageing is an inevitable biological process with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases.

Some nutritional factors (zinc, niacin, selenium) may remodel these changes leading to a possible escaping of diseases, with the consequence of healthy ageing, because they are involved in improving immune functions, metabolic homeostasis and antioxidant defense.

Experiments … show that zinc is important for immune efficiency (both innate and adaptive), metabolic homeostasis (energy utilization and hormone turnover) and antioxidant activity (SOD enzyme).

Niacin is a precursor of NAD+, the substrate for the activity of DNA repair enzyme PARP-1 and, consequently, may contribute to maintaining genomic stability. Selenium provokes zinc release by metallothioneins (MT), via reduction of glutathione peroxidase.

This fact is crucial in ageing because high MT may be unable to release zinc with subsequent low intracellular free zinc ion availability for immune efficiency, metabolic harmony and antioxidant activity.

Taking into account the existence of zinc transporters … for cellular zinc efflux and influx, respectively, the association between zinc transporters and MT is crucial in maintaining satisfactory intracellular zinc homeostasis in ageing.

Improved immune performance, metabolic homeostasis, antioxidant defense occur in elderly after physiological zinc supplementation … The association ‘zinc plus selenium’ improves humoral immunity in old subjects after influenza vaccination.”

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