Ivermectin vs Hydroxychloroquine vs Quercetin: What are the Differences?

The number of options for the treatment of COVID-19 has increased drastically in recent months, thus making it complicated when it comes to choosing the right combination. In general, there are 3 broad categories of medical interventions:

  1. Prevention or Prophylaxis e.g. vaccine
  2. Early out-patient treatment
  3. Hospital treatment

Image credit: Cleveland Clinic


All these treatments come with various technologies and jargons, thus could be overwhelming and confusing for you as a consumer.

Generally, multiple treatments and strategies are used in combination to achieve the best possible outcome.

In this article, we would like to cover 3 popular treatments i.e. Ivermectin, Hydroxychloroquine and Quercetin.

Ivermectin and COVID-19

As of May 2021, there are more than 80 on-going trials globally on Ivermectin for treatment and prevention of COVID-19 on covid-nma.com.
Source: covid-nma.com

Ivermectin is an anti-parasitic medication widely used in low- and middle-income countries to treat parasitic worm infections in adults and children. It’s been used for decades for this purpose by over 3.7 billion people, and is considered safe and effective. It has an increasing list of indications due to its antiviral and anti-inflammatory properties, and is included on the WHO’s Model List of Essential Medicines.

Ivermectin and COVID-19 Updates:

May 03, 2021 - Joint Statement on Widespread Use of Ivermectin in India for Prevention and Early Treatment by U.K. Evidence-Based Medicine Consultancy Ltd (E-BMC Ltd) and U.S. FLCCC (Front Line Critical Care Alliance).

Apr 14, 2021: Open Letter by U.S. Doctors: JAMA Ivermectin Study (Lopez-Medina et al) Is Fatally Flawed, TrialSiteNews reported.

Apr 9, 2021: FLCCC (Front Line Critical Care Alliance) statement on Washington Post article.

Apr 1, 2021: WHO reaches ivermectin recommendation without a vote, TrialSiteNews reported.

Mar 31, 2021: FLCCC (Front Line Critical Care Alliance) statement on WHO's Ivermectin guide.

Mar 30, 2021: Argentina Ministry of Health Clinical Trial: Ivermectin Shows Benefit Treating Outpatients with Mild COVID-19; TrialSiteNews reported.

Mar 10, 2021: Dr. Satoshi Ōmura, co-author of the newly published paper, “Global trends in clinical studies of ivermectin in COVID-19” was one of the four researchers from Kitasato University in Tokyo,           Japan who received the Nobel Prize in Physiology or Medicine in 2015 for their discovery of ivermectin. 

“When the effectiveness of ivermectin for the COVID-19 pandemic is confirmed with the cooperation of researchers around the world and its clinical use is achieved on a global scale, it could prove to be of great benefit to humanity. It may even turn out to be comparable to the benefits achieved from the discovery of penicillin—said to be one of the greatest discoveries of the twentieth century.”—From Global trends in clinical studies of ivermectin in COVID-19, published in the Japanese Journal of Antibiotics, March, 2021.

Mar 5, 2021: [Europe] Ivermectin is now approved for COVID-19 use in 2 European countries: Czech Republic and Slovakia.

Feb 25, 2021: Drug used to treat lice and scabies drug could cut Covid deaths by up to 75%, research suggests, DailyMail reported (more than 16,000 shares).

Feb 25, 2021: Scabies and head lice drug could be 'global solution to the pandemic' says study; Mirror UK reported.

Jan 19, 2021: A pilot study published in the Lancet on January 19, 2021 showed some promising results but the authors concluded that the study warrants further exploration under larger trials with clinical outcomes in patients with risk factors or more severe disease.

Jan 18, 2021: Updated version of Frequently Asked Questions on Ivermectin in COVID-19 by the FLCCC.

Jan 16, 2021: Apparently, a judge just ordered the Millard Fillmore Suburban Hospital to allow an 80-year old woman to be treated with Ivermectin. According to the family and attorney, the treatment saved the life of Judith Smentkiewicz. Apparently, a doctor ordered the drug off-label in the intensive care unit (ICU), and as she improved, more than likely due to the drug, she was moved to another unit, and the doctor there stepped in and disallowed the use of the drug. Family members immediately involved lawyers and legal action to resume treatment. The New York Supreme Court Judge Henry J. Nowak aligned with the family; TrialSiteNews reported.

Jan 14, 2021: The National Institutes (NIH) has issued a new statement on the use of the anti-parasitic drug ivermectin for the treatment of COVID-19. Previously, it recommended against this treatment, but now states that its Panel “has determined that there are insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19.”

Jan 13, 2021: The BIRD meeting was convened by Dr. Tess Lawrie in order to present the findings from her rapid systematic review and meta-analysis of studies on the use of ivermectin to prevent and treat COVID-19. Dr. Lawrie presented evidence in the form of a DECIDE evidence-to-decision framework, a format used by the World Health Organization for the development of guidelines and recommendations in medical practice. Twenty experts from around the world and the UK attended the meeting, including 13 clinicians, and seven representatives from the public.

Dec 30, 2020: An essential updated review of COVID-19 early-treatment best practices was published. (abstract | PDF | HTML)

This international collaboration — comprised of physicians, like lead author Peter McCullough, MD, courageously treating patients despite the prevalence of “therapeutic nihilism” among government agencies like the NIH and FDA — outlines the urgency of, “prompt early initiation of sequenced multidrug therapy (SMDT) … to stem the tide of hospitalizations and death.”

The authors wrote: 

The early stage of viral replication provides a therapeutic window of tremendous opportunity to potentially reduce the risk of more severe sequelae in high risk patients. Precious time is squandered with a ‘wait and see’ approach … resulting in unnecessary hospitalization, morbidity, and death. … In newly diagnosed, high-risk, symptomatic patients with COVID-19, SMDT has a reasonable chance of therapeutic gain with an acceptable benefit-to-risk profile. 

Included in the paper is a “sequential multidrug treatment algorithm” and summaries of the rationale and evidence for each component.

outpatient treatment COVID-19

Related Ivermectin and COVID-19 Publications:

  • Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 by Kory et al., published on American Journal of Therapeutics.
  • Dr. Satoshi Ōmura, co-author of the newly published paper, “Global trends in clinical studies of ivermectin in COVID-19” was one of the four researchers from Kitasato University in Tokyo, Japan who received the Nobel Prize in Physiology or Medicine in 2015 for their discovery of ivermectin. Global trends in clinical studies of ivermectin in COVID-19, published in the Japanese Journal of Antibiotics, March, 2021.
  • A multi-centre randomised controlled study in Egypt (Elgazzar, Research Square) reported that the death rate was significantly lower in Ivermectin treated patients group (severe patients) vs non-Ivermectin group (2% vs 20%). 1,300 patients were included in this randomized controlled trial. 
  • This randomized controlled trial out of Iran (Hashim, pre-print) used Ivermectin and Doxycycline in mild, moderate, and severe hospitalized COVID-19 patients. No patients in the mild and moderate COVID-19 category died and 18% of the severe patients perished taking this medication combo. In the control group, no mild-moderate patients died, but 27% of the severe COVID patients died. The patients who also got Ivermectin had a shorter recovery.
  • A randomized, double-blind, placebo-controlled, multicenter, phase 2 clinical trial at five hospitals (Iran) and 180 patients with mild to severe disease (Niaee, ResearchSquare, Nov 2020). Ivermectin as an adjunct reduced the rate of mortality, the duration of low oxygen saturation, and the duration of hospitalization.
  • The ICON study in US, published in Chest, Oct 2020 reported that Ivermectin treatment was associated with lower death rate vs Control (13.3% vs 24.5%) during treatment of COVID-19, especially in patients with severe pulmonary involvement.
  • A double-blinded randomised controlled study in Bangladesh (Mahmud et al) reported that the death rate was 0% (0/183) in the Ivermectin arm vs 1.67% (3/180) in the control arm in mild to moderate COVID-19 patients.
  • The IDEA (Ivermectin, Dexamethasone, Enoxaparin and Aspirin) study from Argentina reported 1 death out of 167 patients studied. The patient that died was a severe COVID-19 patient that required ventilator support.
  • The pre-AndroCoV trial from Brazil reported that early detection of COVID-19 followed by a pharmaceutical approach with different drug combinations (Azithromycin, Hydroxychloroquine, Nitazonide, Ivermectin) yielded irrefutable differences compared to non-treated controls in terms of clinical outcomes, ethically disallowing placebo-control randomized clinical trials in the early stage of COVID-19 due to the marked improvements.
  • A retrospective study out of Bangladesh (Khan, Archivos de Bronconeumologia 2020). This retrospective study enrolled a total of 325 from April to June 2020. 248 adult COVID-19 patients were looked at in two groups, 115 received ivermectin plus standard care (SC), while 133 received only standard care (SC). This study showed that Ivermectin was efficient at rapidly clearing SARS-CoV-2 from nasal swabs (median 4 days). This was much shorter than in the COVID-19 patients receiving only SC (15 days) or receiving a combination of three antiviral drugs (7–12 days). In addition, fewer Ivermectin patients developed respiratory distress leading to ICU admission. In fact, with Ivermectin, there was a quick hospital discharge (median 9 days) in 114 out of 115 patients; the one remaining patient had been admitted with advanced disease.

Ivermectin for COVID-19: Real-time meta analysis of 52 studies

  • 98% of the 52 studies to date report positive effects (25 statistically significant in isolation). Random effects meta-analysis for early treatment and pooled effects shows an 81% reduction, RR 0.19 [0.09-0.39], and prophylactic use shows 85% improvement, RR 0.15 [0.09-0.25]. Mortality results show 76% lower mortality, RR 0.24 [0.14-0.42] for all treatment delays, and 84% lower, RR 0.16 [0.04-0.63] for early treatment.
  • 96% of the 27 Randomized Controlled Trials (RCTs) report positive effects, with an estimated 64% improvement, RR 0.36 [0.24-0.52].
  • The probability that an ineffective treatment generated results as positive as the 52 studies to date is estimated to be 1 in 85 trillion (p = 0.000000000000012).
  • Heterogeneity arises from many factors including treatment delay, patient population, the effect measured, distribution of SARS-CoV-2 variants, ivermectin dosage, and other treatment details. There is high heterogeneity across all studies, however for ivermectin the consistency of positive results is remarkable. Heterogeneity is low when looking at specific cases, for example early treatment mortality.

Source: ivmmeta.com (constantly updated)

Precautionary Note: 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. 

Due to the possible drug interaction between quercetin and ivermectin (may increase ivermectin levels), these drugs should not be taken simultaneously (i.e. should be staggered morning and night). 

Ivermectin is also lipophilic and therefore, bioavailability is maximised on a full stomach; or best to be taken with meal.

Related: List of Doctors that will prescribe Ivermectin


Hydroxychloroquine and COVID-19

We have combined hydroxychloroquine and chloroquine under 1 category. 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. Chloroquine is used to treat and prevent malaria and amebiasis.

According to a real time meta-analysis of 233 hydroxychloroquine studies:
  • HCQ is effective for COVID-19. The probability that an ineffective treatment generated results as positive as the 231 studies to date is estimated to be 1 in 3 quadrillion (p = 0.0000000000000003).           
  • Early treatment is most successful, with 100% of 28 studies reporting a positive effect (12 statistically significant in isolation) and an estimated reduction of 64% in the effect measured (death, hospitalization, etc.) using a random effects meta-analysis, RR 0.36 [0.25-0.51].
  • 92% of Randomized Controlled Trials (RCTs) for early, PrEP, or PEP treatment report positive effects, the probability of this happening for an ineffective treatment is 0.0032.
  • There is evidence of bias towards publishing negative results. 88% of prospective studies report positive effects, and only 73% of retrospective studies do.
  • Studies from North America are 3.9 times more likely to report negative results than studies from the rest of the world combined, p = 0.0000000013.
Source: hcqmeta.com (constantly updated)

Do you need a prescription for hydroxychloroquine? Yes, you do. 

Hydroxychloroquine and COVID-19 Updates:

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".

Quercetin and COVID-19

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 immuno-modulatory properties and the capacity of ascorbate to recycle         quercetin, increasing its efficacy.

June 19, 2020, Dr Marik published the paper “Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19)” in the journal Frontiers in Immunology. The paper presents evidence for the use of vitamin C and quercetin — based on their biological actions and pharmacokinetics profiles — both as prophylaxis in high-risk populations, and as an adjunct to drugs such as Remdesivir or convalescent plasma in the treatment of hospitalized COVID-19 patients.

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.
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).
  • 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.


Note on Zinc supplements: How much zinc you should take per day depends on the type and forms of zinc, as each supplement contains a different amount of 'elemental zinc'. The percentage of elemental zinc varies by form. 

For example, approximately 23% of zinc sulfate consists of elemental zinc; thus, 220 mg of zinc sulfate contains 50 mg of elemental zinc (NIH). Zinc picolinate (20% of elemental zinc), zinc ascorbate (15%), zinc chloride (48%), zinc carbonate (52%), zinc citrate (31%), zinc bisglycinate (25%) (Ref) and zinc gluconate (14%) and zinc oxide (80%) (Ref).

The AAPS (Association of American Physicians and Surgeons) recommends zinc sulfate, gluconate or citrate. These forms are available in pharmacies, health food stores, and sold online. Zinc sulfate 220 mg provides 50 mg elemental zinc, the recommended anti-viral dose. Zinc in the form of zinc picolinate form is not recommended following reports of liver damage and tumors from studies about 20 years ago. Following these reports, the German Commission E that regulates supplements used in medical practice in Germany banned this form of zinc.

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: 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.

Precaution: Quercetin has one moderate drug interaction with warfarin. Do not take quercetin without medical advice if you are using warfarin.

Ivermectin vs Hydroxychloroquine vs Quercetin

Clinical evidence to date has reported promising results (see above) for Ivermectin in prevention, early treatment as well as late treatment for COVID-19. While both Ivermectin and Hydroxychloroquine might be useful for early treatment, Ivermectin has a broader potential benefit i.e. prevention, early treatment as well as late treatment / hospital treatment (please refer to table below).

Hydroxychloroquine and Quercetin are both zinc ionophores i.e. they transport zinc into the cells. 

However, quercetin is 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.

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. 

Although ivermectin and hydroxychloroquine are relatively safe drugs, they are still synthetic chemicals that can have side effects. Quercetin and Vitamin D, C, Zinc are nutrients that your body require for optimal health. Nutrients are safer alternatives especially if your risk is low e.g. age below 50 and no other chronic illness. Discuss with your doctor on the benefit vs risk for each treatment. If you are on multiple medications, be aware of supplement-drug interactions that might enhance the possibilities of adverse effects.

A summary table analysing more than 600 studies for COVID-19 treatments is provided below (credit: c19early.com):



Key Takeaways

The important key takeaway is that you should never attempt to self medicate without the guidance of a licensed medical provider. If you are not a medical doctor, you are likely to find the above information overwhelming. The aim of this article is to empower you with a better understanding of the options available and to discuss the options with your medical doctor.

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