I’ve beforehand reviewed the similarities between the flavonoid quercetin and the drug hydroxychloroquine, discussing the potential for utilizing quercetin in lieu of the drug towards COVID-19. We’re now additionally beginning to see quercetin talked about extra typically within the scientific literature on COVID-19.
Quercetin Highlighted in COVID-19 Medical Literature
For instance, a assessment article1 printed within the June 19, 2020, concern of Frontiers in Immunology highlights quercetin’s usefulness as a COVID-19 remedy, particularly along side vitamin C. Quercetin can be featured in a assessment2 of rising COVID-19 analysis printed within the Integrative Drugs journal. As reported by MedPage At the moment:3
“Quercetin … promotes SIRT2, which then inhibits the NLRP3 inflammasome meeting concerned with COVID-19 an infection, mentioned Samuel F. Yanuck, DC, of the Program on Integrative Drugs on the College of North Carolina Chapel Hill College of Drugs, who co-authored a assessment4 of rising analysis on the topic. It additionally performs a job in facilitating zinc transportation throughout lipid membranes, Yanuck mentioned.
‘It is not a weird or experimental substance and given it has these potential necessary organic roles, I feel it is price being thought of as a part of an general technique,’ Yanuck advised MedPage At the moment, including that quercetin would should be one a part of a multifactorial remedy routine …
COVID-19 has been related to excessive ranges of interleukin-6, depleted ranges of interferons, and a cytokine storm that damages the physique and is said to respiratory failure, mentioned Ruben Colunga Biancatelli, MD, of Previous Dominion College in Norfolk, Virginia, and first writer of a paper on quercetin and vitamin C as a possible remedy for treating SARS-CoV-2 in Frontiers in Immunology.5
Utilizing this rationale, researchers are postulating that vitamin C ought to be administered with quercetin as a result of it could actually recycle oxidized quercetin, producing a synergistic impact and enhancing quercetin’s antiviral functionality, Biancatelli added.”
Why Quercetin Could Provide Hope In opposition to COVID-19
There are strong causes to suspect quercetin may be efficient towards SARS-CoV-2, the virus that causes COVID-19 illness. For instance, quercetin has been proven to:
Bind to the spike protein of SARS-CoV (the virus accountable for extreme acute respiratory syndrome or SARS), thereby inhibiting its capacity to contaminate host cells.6 Utilizing the supercomputer SUMMIT, researchers at Oak Ridge Nationwide Lab additionally recognized quercetin as one of many molecules which may inhibit the SARS-CoV-2 spike protein from interacting with human cells.7,8
Inhibit lipopolysaccharide (LPS)-induced tumor necrosis issue α (TNF-α) manufacturing in macrophages.9 (TNF-α is a cytokine concerned in systemic irritation, secreted by activated macrophages, a sort of immune cell that digests overseas substances, microbes and different dangerous or broken elements.)
Inhibit the discharge of proinflammatory cytokines and histamine by modulating calcium inflow into the cell.10
Stabilize mast cells and regulate the fundamental purposeful properties of immune cells, thereby permitting it to inhibit “a enormous panoply of molecular targets within the micromolar focus vary, both by down-regulating or suppressing many inflammatory pathways and capabilities.”11
Act as a zinc ionophore, i.e., a compound that shuttles zinc into your cells.12 This is among the mechanisms that may account for the effectiveness seen with hydroxychloroquine, which can be a zinc ionophore.
Enhance interferon response to viruses, together with SARS-CoV-2, by inhibiting the expression of casein kinase II (CK2)13 — CK2 is an enzyme that is key to controlling homeostasis on the mobile stage. There’s proof that it down-regulates the flexibility a cell has to generate Kind 1 interferon when attacked by a virus.
It does this by inhibiting retinoic acid-inducible gene I (RIG-I),14 which has protein sensors that sign genetic expression of sort 1 interferon by figuring out the replication of RNA viruses, akin to SARS-CoV-2. Quercetin inhibits the expression of CK2, which slows the replication of RNA viruses.15
Interferons are a subset of cytokines found in 1957.16 These cells are sometimes the preliminary protection towards viruses. There are two sorts and three types of interferon. Inside Kind 1 interferon, there are alpha and beta. Kind 2 interferon has the gamma kind.17
The completely different sorts are primarily based on the perform of the cytokine. Kind 1 interferons assist cells resist viruses. Kind 2 aids in responding to infections and most cancers development. The title “interferon” got here from the flexibility of Kind 1 to intervene with the virus’s capacity to duplicate. A cell secretes interferons when a overseas substance, like a virus, is detected.
Nonetheless, the interferon doesn’t perform by attacking the virus. As an alternative, it tells the contaminated cell and the cells that encompass the contaminated cell to make proteins that cease viral replication. In a nutshell, quercetin stops CK2 from interfering with the motion of Kind 1 interferon so cells obtain the sign to cease viral replication.
Modulate the NLRP3 inflammasome, an immune system part concerned within the uncontrolled launch of proinflammatory cytokines that happens throughout a cytokine storm.18
Forestall a huge number of harmful viruses from getting into cells, together with Ebola.19
Exert a direct antiviral exercise towards SARS-CoV20,21,22 — Quercetin’s common antiviral capability has been attributed to a few major mechanisms of motion:
Inhibit the SARS-CoV-2 foremost protease.23
Quercetin Studied as COVID-19 Remedy and Prophylaxis
As reported by MedPage At the moment,24 Dr. Hasan Önal is at present conducting an open-label nonrandomized trial25 on quercetin in Turkey. COVID-19 sufferers are given 1,000 milligram (mg) of quercetin per day as an energetic remedy, whereas front-line well being care employees are receiving 500-mg doses as a prophylaxis. As famous by the researchers:26
“Quercetin is reported to be efficient on remedy and prophylaxis of different SARS like coronavirus infections, as a robust antioxidant and scavenger flavonoid with none opposed occasions. Upon this information, the investigators hypothesize that quercetin may be efficient on each prophylaxis and remedy of COVID-19 circumstances. Due to this fact, the goal of this research to guage the potential position of quercetin on prophylaxis and remedy of COVID-19.”
Vitamin C Enhances Quercetin’s Efficacy
Vitamin C has been proven to reinforce plasma quercetin ranges,27,28 and the duo is the topic of the Frontiers in Immunology assessment article,29 “Quercetin and Vitamin C: An Experimental, Synergistic Remedy for the Prevention and Remedy of SARS-CoV-2 Associated Illness (COVID-19),” talked about earlier.
That assessment, by the way in which, was co-written by Dr. Paul Marik, who in 2017 found a extremely efficient vitamin C-based sepsis remedy. In “Quercetin and Vitamin C,” Marik and co-authors level out that:30
“Ascorbic acid is an important vitamin crucial for the right functioning of the immune system. It performs a position in stress response and has proven promising outcomes when administered to the critically unwell.
Quercetin is a well known flavonoid whose antiviral properties have been investigated in quite a few research. There’s proof that vitamin C and quercetin co-administration exerts a synergistic antiviral motion attributable to overlapping antiviral and immunomodulatory properties and the capability of ascorbate to recycle quercetin, growing its efficacy.
Protected, low-cost interventions which have a sound organic rationale ought to be prioritized for experimental use within the present context of a world well being pandemic.
We current the present proof for the usage of vitamin C and quercetin each for prophylaxis in high-risk populations and for the remedy of COVID-19 sufferers as an adjunct to promising pharmacological brokers akin to Remdesivir or convalescent plasma.”
Vitamin C and Quercetin Each Present Antiviral Safety
In abstract, other than having direct viricidal results, vitamin C:31
Helps lymphocyte exercise
Will increase interferon-alpha manufacturing
Improves endothelial dysfunction
Restores mitochondrial perform
All of those results contribute to vitamin C’s antiviral results. Like vitamin C, quercetin additionally has antioxidant, anti-inflammatory, antiviral, immunoprotective and immunomodulatory properties. In line with Marik’s assessment paper, lots of quercetin’s antiviral results are attributable to its inhibition of:32
- Reverse transcriptase
- DNA gyrase
- Viral capsid proteins
Quercetin additionally inhibits platelet aggregation,33 which is pertinent with regard to COVID-19, seeing what number of sufferers undergo irregular blood clotting. It additionally has highly effective anti-inflammatory results, inhibiting lipid peroxidation and proinflammatory mediators.34
Quercetin and Vitamin C Work Synergistically
Marik’s paper goes on to clarify the synergistic antiviral motion of the 2 compounds collectively:35
“Quercetin spontaneously oxidizes to kind O-semiquinone and O-quinone/quinone methide (QQ), which might bind protein thiols forming poisonous compounds. This technique of each anti- and pro-oxidant results has been named the “quercetin paradox.”
Nonetheless, QQ may be recycled into quercetin by electron donors like NADPH or ascorbate, or kind collectively, with glutathione both 6-glutathionyl-quercetin or 8-glutathionyl-quercetin (GSQs).
Importantly, if ascorbate or glutathione ranges are inadequate, quercetin could also be shunted to QQ and exert prooxidant results. Due to this fact, we stress the significance for its co-administration with vitamin C …
Though QQ displays a greater affinity for glutathione than for vitamin C, the methylated metabolites of quercetin present the next choice for ascorbate than for thiols, suggesting a biking of exercise which can exert anti-oxidant results …
The supraphysiological concentrations of ascorbate achieved with intravenous administration (i.v. Three gr q6) are able to free radical scavenging and electron donation, stopping both quercetin or glutathione oxidation.
On this situation, ascorbate could exert antioxidant and immunoprotective results, quercetin and its metabolites exert a concurrent antiviral response and, if quercetin-oxidized compounds are shaped, they are often partially recycled by ascorbate and transported by glutathione, thus stopping their potential toxicity.
A multi-drug strategy with quercetin and vitamin C could disrupt virus entry, replication, enzyme exercise and meeting, and concurrently fortify the immune response selling early IFNs manufacturing, modulating interleukins, selling T cell maturation, and phagocytic exercise.
Quercetin and ascorbic acid co-administration represents an experimental technique for prophylaxis and remedy of a number of respiratory viruses, akin to SARS-CoV-2.”
In line with “Quercetin and Vitamin C,”36 each vitamin C and quercetin have wonderful security profiles, and oral supplementation with quercetin at doses as much as 1 gram (1,000 mg) per day for 3 months has not resulted in any vital unintended effects.
“Solely greater intravenously administered doses as much as 51.Three mg/Kg (round 3,591 mg per particular person) have been related to renal toxicity,” the paper notes. The following desk exhibits the proposed dosages for concurrent use of vitamin C and quercetin, both as a prophylactic for high-risk teams, and/or remedy for gentle to extreme COVID-19 illness.
The Significance of Zinc
Whereas Marik’s paper doesn’t deal with the usage of zinc, it appears cheap to suggest oral zinc supplementation as nicely, particularly if you happen to’re older. Actually, two oft-noted early signs of COVID-19 — the lack of style and scent — are each signs of zinc deficiency.
As famous within the Integrative Drugs journal’s assessment37 of rising COVID-19 analysis, “Zinc performs an important position within the perform of basically all immune cells,” and “Deficiency of this crucial aspect has a profound influence on immune response, growing susceptibility to quite a lot of infections.” Like quercetin and vitamin C, zinc additionally has well-known antiviral properties in its personal proper. As famous within the Integrative Drugs journal’s assessment:38
“Growing intracellular zinc concentrations in cell tradition impairs the replication of a number of RNA viruses together with SARS-CoV-1 … In vivo proof for zinc’s antiviral position comes from a Cochrane assessment that discovered zinc consumption was related to a big discount within the period of the widespread chilly.
Lots of the research displaying profit when taken in the course of the course of an an infection have been within the type of a zinc lozenge. It is smart to make the most of this mode of supply in the course of the acute an infection section …
Anosmia (lack of scent) and dysgeusia (distorted sense of style) are generally being reported in sufferers at each section of COVID-19. These are additionally basic signs of zinc deficiency.
It’s too early within the discovery course of to find out if that is trigger or impact, nonetheless zinc deficiency drastically impairs immune perform, particularly resistance to viral infections. Notably, insufficient dietary consumption of zinc is present in virtually half the older inhabitants.”
My Private Tackle This and Sturdy Suggestions
I’m an enormous fan of zinc, quercetin and vitamin C, however you will need to perceive some very fundamental ideas earlier than utilizing them. It’s clear in my thoughts that quercetin is far cheaper, is safer and is probably going equally efficient to hydroxychloroquine at driving zinc into the cell, the place it does its job of inhibiting viral replication, and in contrast to hydroxychloroquine, it reduces inflammatory cytokines and in addition will increase interferon.
Nonetheless, it’s necessary to grasp that if this wonderful technique goes to be optimally efficient it must be administered early within the illness section — the earlier the higher. Utilizing quercetin and zinc can be greatest completed if you happen to have been not too long ago uncovered to the virus. This fashion you possibly can inhibit viral replication and hold the viral load low whereas your innate immune system does its work in clearing the virus.
With respect to vitamin C, it’s my notion that there’s main confusion on this space. It can be utilized in low doses of a number of hundred milligrams to satisfy dietary necessities and help your immune system within the early section of the sickness.
Nonetheless, if you’re actually sick and have shortness of breath, and are contemplating being hospitalized or are already within the hospital, then you definately want very excessive doses of vitamin C within the 10 gram to 100 gram-dose per day, both via liposomal or IV administration.
I don’t suggest taking excessive doses of vitamin C until you might be acutely sick. The majority of the literature reviewed right here is selling the usage of vitamin C to regenerate quercetin, however I consider there are way more highly effective approaches. What would possibly that be?
It appears apparent to me that quercetin is greatest taken at evening (with zinc) earlier than you go to mattress and also you haven’t eaten for at the least three to 4 hours. You’ll sleep for eight hours, and in case you are metabolically versatile, that is the time that you’ll dive into dietary ketosis. Ketosis will enhance your NADPH ranges, which is FAR superior to vitamin C at recycling antioxidants like quercetin.
The opposite good thing about taking quercetin at evening is to reap the benefits of its senolytic motion to take away senescent cells, that are much like nonreplicating most cancers cells that secrete highly effective proinflammatory cytokines that destroy your well being. You’ll be able to optimize quercetin’s senolytic properties if you happen to take it while you’re fasting.