Quercetin vs Hydroxychloroquine: What's the Difference?

Hydroxychloroquine is among the handful of COVID-19 treatments that are being studied as potential candidates that might influence the outcome in the management of COVID-19. According to a real time meta-analysis of more than 200 studies, early treatment is most successful.

Hydroxychloroquine, Quercetin and EGCG (EpiGalloCatechin Gallate) are all zinc ionophores. Meaning they all transport zinc into the cells. We will dive deeper into the science for each of them.

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. Now, some doctors are advocating its use against SARS-CoV-2, in combination with vitamin C, noting that the two have synergistic effects.
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 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. 

The initial MATH+ protocol was released in April 2020. In early July and August, it was updated to include quercetin and a number of optional nutrients and drugs, not only for critical care but also for prophylaxis and mild disease being treated at home.

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. (Find a Doctor)
    • 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). (Find a Doctor)
    • 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%. (Amazon)
    The medical evidence to support each drug and nutrient can be found under “Medical Evidence” on the FLCCC’s website.





    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've recovered.

    A word about quercetin: Some physicians are recommending this supplement 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.


    Hydroxychloroquine and COVID-19

    Hydroxychloroquine, a less toxic derivative of Chloroquine is a widely used medication by people with lupus or arthritis. It was first approved in the 1950s. 

    Hydroxychloroquine (HCQ) is not effective when used very late with high dosages over a long period (RECOVERY/SOLIDARITY), effectiveness improves with earlier usage and improved dosing. Early treatment consistently shows positive effects. Negative evaluations typically ignore treatment time, often focusing on a subset of late stage studies.

    As of June, 2021 there have been 29 studies of Hydroxychloroquine for early treatment – all with zero negative results for the most serious outcome reported. The average risk reduction for the most serious outcome reported in these trials was 65%. Here’s a chart from c19hcq.com that shows this: 



    According to Steve Kirsch (published on TrialSiteNews):

    Skeptics might argue the reason all the studies are positive is that journals are more likely to publish positive results than negative results. But in fact, there is a good argument that the bias is the reverse for HCQ, where negative studies are more likely to be published than positive studies. But in this case, those arguments don’t matter as the skeptics can’t point to a negative early treatment trial that has not been published so the debate is moot.

    Now, let’s talk safety. HCQ is on the WHO list of essential medicines, i.e., one of the safest and most effective drugs in a health system

    Lupus patients are put on HCQ and remain on the drug for life. The drug was FDA-approved more than 65 years ago. In 2016, it was the 135th most-prescribed medication in the United States, with more than 4 million prescriptions. Dose escalation studies in lupus patients and in rheumatoid arthritis patients established that 800 mg per day for life and 1,200 mg per day for 6 weeks are extremely well-tolerated.

    The WHO says HCQ is safe to take for autoimmune diseases or malaria. However, they admit that there is weak evidence supporting their contention that HCQ is unsafe to take for COVID. But the problem with this is 1) they admit that the certainty of the evidence is “low” to “very low” and 2) they don’t break it out by the disease phase. We are interested in early treatment, not late treatment. You can’t just lump all the studies into one analysis.

    In order to see what is actually happening in early treatment patients when they take HCQ, I reached out to Brian Tyson and George Fareed, whose practice has used HCQ in treating more than 6,000 people of all ages with COVID. The risk of diarrhea and nausea/vomiting claimed by the WHO is both “very rare and very minimal.” In general, diarrhea is more likely to be caused by COVID than the drug. 

    Fareed said he has had “zero cardiac issues” with any patients. They have never had any reason to drop HCQ from their treatment protocol and I don’t know of any physician in the US who has a lower rate of hospitalization for COVID than Tyson and Fareed. If the WHO is right, then how do they explain this anomaly? Tyson and Fareed certainly didn’t get lucky on 6,000 patients and the average age of their patients is 60 years old. 

    So the bottom line so far is 29 studies all positive, and real-world evidence on thousands of cases is also         consistent with the studies. Our hypothesis that the drug is effective is consistent with the data. But the WHO and NIH say we should not use this drug, yet have no plausible explanation for the consistently positive data. 

    Some scientists will cite the HCQ analysis published in Nature which definitively shows that HCQ is harmful. But that was a meta analysis, which heavily weighted studies of high dose HCQ given to very late stage hospitalized patients. No early treatment outpatient trials were included. The paper says “Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.” I agree! 

    I’m not arguing for high dose HCQ in late-stage hospitalized patients. That’s a losing proposition. As you can clearly see, all the early treatment results are all positive (top graph) whereas if you look at all stages, that’s when the negative results occur, so it is very important to pay attention to segregating the data when doing meta-analyses.


    Here’s a simple analogy as to why drug timing makes a huge difference: a small bucket of water works great if the fire is small (early stage). After the house burns down, the same bucket of water will do nothing to repair the damage, even if we increase the amount of water, and will probably further damage any remains.
      
    Other scientists might reference the fact that the FDA revoked the EUA on HCQ, but the revocation was based on studies on hospitalized patientsnot outpatients. So that argument doesn’t hold water.
     
      
    Finally, some people may reference the Skipper study, an outpatient HCQ early treatment trial that concluded that “hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.” I know a few things about that particular study because I was one of the “private donors” who funded it. The summary means that the study was underpowered, not that the drug didn’t work. Indeed, if you look at each metric they looked at, the cohort who got the HCQ always did better. See this analysis for detailsThere is much more to this study that will come out later that will show that HCQ works even better than the 51.7% drop in hospitalization rate reported in the paper. 

    In short, HCQ is both effective and safe for early treatment at dosages of 600mg per day and more. If anyone tells you otherwise, please ask them for both clinical studies and real-world evidence to back up their claim. At that point, they will say that they don’t have time to talk to you and walk away. This happens to me all the time. It’s frustrating.

    Do you need a prescription for hydroxychloroquine? 

    Yes, hydroxychloroquine is a prescription drug and you do need it to be prescribed to you by a doctor. 
    Editor's Note on Hydroxychloroquine (HCQ): The use of HCQ is highly controversial. The best scientific evidence from randomized controlled trials suggests that HCQ has limited/no proven benefit for post exposure prophylaxis, for the early symptomatic phase and in hospitalized patients. Considering, the unique pharmacokinetics of HCQ it is unlikely that HCQ would be of benefit in patients with COVID-19 infection (it takes 5–10 days to achieve adequate plasma and lung concentrations). Finally, it should be recognized that those studies which are widely promoted to support the use of HCQ are methodologically flawed.
    Source: Page 16 of FLCCC Alliance – COVID-19 Management Protocol (version May 25, 2021)

    Hydroxychloroquine and COVID-19 Updates

    June 9, 2021: Study shows hydroxychloroquine treatments increased coronavirus survival rate by almost three times.

    Apr, 2021: Prevention study from Singapore (N=3,037) showed "Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial."

    Jan 24, 2021: Dr Vladimir Zelenko published a white paper on "Nebulized Hydroxychloroquine for COVID-19 Treatment: 80x Improvement in Breathing".

    Conclusion

    While treatments and supplements are important factors that might influence the COVID-19 outcomes, do take note that factors like pre-existing health conditions, especially high blood pressure, diabetes and obesity might elevate the risk. Take steps to control hypertension and blood sugar fluctuations with diabetes, as these conditions are associated with more severe disease if infected. This may also help you maintain a healthy weight, which is important because obesity has been associated with an increased risk of requiring intubation or dying among people hospitalized with COVID-19, particularly those under 65 years of age. Risk was 60% greater among those with severe obesity (BMI > 34.9 kg/m2) compared to patients of normal weight (BMI of 18.5 to 24.9 kg/m2) (Anderson, Annals Int Med 2020).

    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 and preventive treatments, 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 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').
    • Consult your nearest local healthcare provider if you have any doubt.


    More COVID-19 related topics > COVID-19

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    Supplements you can purchase from Amazon for COVID-19 prevention based on the FLCCC prevention protocol >
    • Vitamin D3: 1,000 - 3,000 IU daily (Amazon)
    • Vitamin C: 500 - 1,000 mg twice daily (Amazon)
    • Quercetin: 250 mg daily (Amazon)
    • Melatonin: 6 mg before bedtime (causes drowsiness) (Amazon)
    • Zinc: 30 - 40 mg/day (elemental zinc). Zinc lozenges are preferred. (Amazon)
    Be aware that most of the dosages are above the recommended daily value and therefore should not be taken on a long term basis. 

    Related item: Fingertip Pulse Oximeter (Amazon)

    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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