Quercetin and COVID-19: Research Review 2021

Good, valuable and unbiased articles are hard to come by. Before you continue to read this article, let's start with the end in mind and begin with the conclusion that you may have been told. Most of the studies on supplements are small and are of low quality? We shall wait for bigger and better quality evidence before we can make formal recommendations?

Science requires questioning and testing. The world does not exist in a 'black or white' manner and most of the time, things do fall into the 'gray' area. Medical science is dynamic and evidence development is constantly in a continuous work-in-progress mode. If a supplement has been shown to work in a small study, would you wait for a bigger study or should you just take it after considering the benefit and risk ratio; especially if the supplement is actually a nutrient that your body needs? Do your own research and the final decision should be yours, after a consultation with your trusted medical professional of course.

COVID-19 kills some people and spares others. How do you ensure that you are on the right side of the statistics? There are just too many self-proclaimed medical experts recommending all kinds of supplements for COVID-19 out there.  On one side are experts telling you that supplements don't work and you should avoid them and just rely on wholesome foods. On the other, are experts telling you to take all kinds of supplements that will help protect you against COVID-19. Do they actually work? Some supplements do have evidence and some don't. 

This guide is based on various references to scientific literature and hopefully, can help you make sense of the options and to separate the facts from fiction.

Update: The FLCCC protocol has been updated (April 26, 2021 version) below.

cytokine storm and COVID-19
Image credit: ClevelandClinic

As of June 2021, there are more than 80 types of supplements that are being tested for COVID-19. You can review the details of these trials on clinicaltrials.gov. There are more than 120 trials testing the various nutrients and dietary supplements including vitamin D, vitamin C, zinc and melatonin. Vitamin D remains the most tested vitamin with the most evidence followed by zinc and vitamin C, for COVID-19.

The medical community themselves are battling over supplements on whether they should be used to treat and prevent COVID-19. On one side are experts telling you that supplements don't work and you should avoid them and just rely on wholesome foods. On the other, are experts telling you to take all kinds of supplements that will help protect you against COVID-19. Do they actually work? 

How do you deal with different expert groups dishing out conflicting guides? A common issue is that certain groups have pre-defined narrative that they would like to support. Therefore, only studies that support that pre-defined narrative are picked and cited as references. This is what we call as 'cherry-picking'. Cherry picking will naturally lead to a 'biased' decision. In order to avoid that, scientific information needs to be analysed in a comprehensive, updated and non-biased manner in order to come up with the best 'evidence-based' decision.

Note: This is a highly dynamic topic; therefore, we will be updating this article as new information emerges. 

While at this point, research is on-going and scientists are working hard to understand COVID-19 and find treatment options, these are some promising developments. The good news is that you don’t have to wait to take steps to protect your health. There are a number of things that you can do to improve your immune system and one of them is to focus on immune supporting nutrients.

Quercetin and COVID-19

Quercetin was initially found to provide broad-spectrum protection against SARS coronavirus in the aftermath of the SARS epidemic that broke out across 26 countries in 2003. 
Quercetin

Quercetin acts as a zinc ionophore (PubMed 2014), the same mechanism of action that hydroxychloroquine has via helping zinc pass the cell wall where it might halt viral replication.

This zinc ionophore activity of quercetin facilitates the transport of zinc across the cell membrane. It is known that zinc will slow down the replication of coronavirus through inhibition of enzyme RNA polymerase (PubMed 2010). The COVID-19 is an RNA (RiboNucleicAcid) virus and requires the RNA polymerase to replicate. Do take note that the study publication was a 2010 publication and is referring to a different coronavirus as compared to the latest coronavirus (COVID-19); though both are from the same family of coronaviruses.

Quercetin, Zinc and Vitamin C

Incidentally, ascorbic acid (vitamin C) and the bioflavonoid quercetin (originally labeled vitamin P) were both discovered by the same scientist — Nobel prize winner Albert Szent-Györgyi. Quercetin and vitamin C also act as an antiviral drug, effectively inactivating viruses. 

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.

For prevention, the Front Line COVID-19 Critical Care Working Group (FLCCC) recommends (updated April 26, 2021):
  • Vitamin D3: 1000–3000 IU/day. Note RDA (Recommended Daily Allowance) is 800–1000 IU/day. The safe upper-dose daily limit is likely < 4000 IU/day. Vitamin D deficiency has been associated with an increased risk of acquiring COVID-19 and from dying from the disease. Vitamin D supplementation may therefore prove to be an effective and cheap intervention to lessen the impact of this disease, particularly in vulnerable populations, i.e. the elderly and obese. (Amazon)
  • Vitamin C: 500 - 1,000 mg BID (twice daily) 
  • Quercetin: 250 mg daily. It is likely that vitamin C and quercetin have synergistic prophylactic benefit. Quercetin should be used with caution in patients with hypothyroidism and TSH levels should be monitored. (Amazon)
  • Melatonin: 6 mg before bedtime (causes drowsiness). (Amazon)
  • Zinc: 30 - 40 mg/day (elemental zinc). Zinc lozenges are preferred. (Amazon)
  • Ivermectin for 
    • prevention in high-risk individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc): 0.2 mg/kg per dose (take with or after meals) — one dose today, repeat after 48 hours, then one dose weekly. (also see ClinTrials.gov NCT04425850). 
    • Post COVID-19 exposure prevention: 0.2 mg/kg per dose (take with or after meals)  — one dose today, repeat after 48 hours.
Drug interactions: 
  • Ivermectin has a number of potentially serious drug-drug interactions. Please check for potential drug interaction at Ivermectin Drug Interactions - Drugs.com. The most important drug interactions occur with cyclosporin, tacrolimus, anti-retroviral drugs, and certain anti-fungal drugs. 
  • Quercetin has one moderate drug interaction with warfarin. Do not take quercetin without medical advice if you are using warfarin.
For early outpatient protocol (COVID-19 positive), the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated Apr 26, 2021):
  • Vitamin D3 — 4000 IU/day. (Amazon)
  • Vitamin C: 500 - 1,000 mg BID (twice daily) (Amazon)
  • Quercetin: 250 mg twice a day. (Amazon)
  • Melatonin: 10 mg before bedtime (causes drowsiness). (Amazon)
  • Zinc: 100 mg/day. Zinc lozenges are preferred. (Amazon)
  • Ivermectin: 0.2–0.4 mg/kg per dose (take with or after meals) — one dose daily, take for 5 days or until recovered.
  • Fluvoxamine: 50 mg twice daily for 10–14 days. Add to ivermectin if: 1) minimal response after 2 days of ivermectin; 2) in regions with more aggressive variants; 3) treatment started on or after day 5 of symptoms or in pulmonary phase; or 4) numerous co-morbidities/risk factors. Avoid if patient is already on an SSRI (selective serotonin reuptake inhibitor).
  • Nasopharyngeal Sanitation: Steamed essential oil inhalation 3 times a day (i.e. vapo-rub) and/or chlorhexidine/benzydamine mouthwash gargles and Betadine nasal spray 2–3 times a day.
  • Aspirin: 325 m/day unless contraindicated.
  • Pulse Oximeter: FLCCC also recommend monitoring your oxygen saturation with a pulse oximeter and to go to the hospital if you get below 94%.
The medical evidence to support each drug and nutrient can be found under “Medical Evidence” on the FLCCC’s website.


Quercetin, Zinc, Bromelain and Vitamin C

A case series of 22 patients, published in Medrxiv revealed that quercetin 800 mg once daily with bromelain 165 mg, in addition to zinc acetate 50 mg and vitamin C 1 g supplements are safe with COVID-19 patients who were on multiple therapies including antivirals and antibacterial medications. The effectiveness of quercetin, bromelain, zinc and ascorbic acid combination was not clear in this study, because of lacking placebo or comparable group.

Quercetin works best when taken with vitamin C and Bromelain, as vitamin C helps activate it and bromelain helps with the absorption. In this study (PubMed), Bromelain also has anti-viral property against COVID-19 virus and anti-clotting property, and therefore may be useful against COVID-19.


Quercetin: Anti-viral Significance

A review published in The Sage Journal (Dec 2020), summarizes the antiviral significance of quercetin and proposes a possible strategy for the effective utilization of natural polyphenols in our daily diet for the prevention of viral infection.



The AAPS recommends the following outpatient treatment protocol for COVID-19:
  • Quercetin oral 500 mg twice a day.
  • Vitamin C 3000 mg
  • Vitamin D3 5000 IU
  • Zinc sulphate 220 mg
Please take note the above dosages are relatively high and is meant for 'treatment'. If you wish to continue taking these nutrients for health maintenance, you'll need to go back to the usual 'RDA or RDI' dosages after you recover.

Is quercetin similar to hydroxychloroquine? Some physicians are recommending quercetin to reduce viral illnesses because quercetin acts as a zinc ionophore to improve zinc uptake into cells. It is much less potent than HCQ (hydroxychloroquine) as a zinc transporter, and it does not reach high concentrations in lung cells that HCQ does. Quercetin may help reduce risk of viral illness if you are basically healthy. But it is not potent enough to replace HCQ for treatment of COVID once you have symptoms, and it does not adequately get into lung tissue unless you take massive doses (3-5 grams a day), which cause significant GI (gastrointestinal) side effects such as diarrhea.

That said, if you simply cannot get hydroxychloroquine or ivermectin, quercetin is a viable stand-in. Quercetin works best when taken with vitamin C and Bromelain, as vitamin C helps activate it and bromelain helps with the absorption. 

Best Quercetin Zinc Supplement:

Conclusion

Do take note that the dosages for micronutrients or vitamins are higher for treatment as opposed to maintenance or preventive. This is probably due to higher demand of the body or the deficiency of the micronutrients are worse during a complicated viral infection. However, for prevention or maintenance, the dosages for most of the micronutrients are much lower.

Viral infections like the COVID-19 also put added stress on your body, which can affect your blood pressure, heart rate, and overall heart function. That can raise your probability of having a heart attack or stroke. Therefore, make sure your blood pressure is well controlled during this pandemic.

Aside from supplements, there are other ways that may help improve immune response and to prevent you from catching the coronavirus.
  • Wear protective face mask. This is to protect not only yourself but others.
  • Abundant evidence suggests that eating whole in fruits, vegetables and whole grains—all rich in networks of naturally occurring antioxidants and their helper molecules—provides protection against free radicals.
  • Getting Enough Sleep
  • Avoid Sugar, red meat and processed foods.
  • Don't smoke.
  • Take steps to avoid infection, such as washing your hands frequently, using hand sanitizer and cooking meats thoroughly.
  • Try to minimize stress.
  • Drink enough water to keep your body hydrated.
  • Avoid excess alcohol.
  • Avoid crowded areas.
  • Regular physical activity (outdoor activities may not be allowed in countries with 'lock-down'). Those with active lifestyle has lower risk if hospitalised as compared to those with sedentary lifestyle (Infectious Diseases and Therapy, 2021)
  • Consult your nearest local healthcare provider if you have any doubt.

More COVID-19 related topics > COVID-19


Be aware that most of the supplement dosages are above the recommended dietary allowance (RDA) and therefore such dosages should not be maintained on a long term basis. 

Disclaimer: The information on this website is not intended to replace a one-on-one relationship with a qualified health care professional and is not intended as medical advice. It is intended as a sharing of knowledge and information from the research and experience of third party sites. If you are pregnant, nursing, taking medication, or have a medical condition, consult your health care professional before using products based on this content.

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