Quercetin, Green Tea and Black Seed Oil as Natural Alternatives to Hydroxychloroquine: Evidence based Review 2022

Hydroxychloroquine was discovered during efforts to synthesize alternatives to quinine as anti-malarials. Is quinine similar to hydroxychloroquine? Hydroxychloroquine and quinine are both anti-malarial drugs. However, hydroxychloroquine is not the same as quinine as hydroxychloroquine is a synthetic drug while quinine is a naturally occurring compound found in cinchona bark. 

Quinine, was first recognized as a potent antimalarial agent hundreds of years ago. Since then, the beneficial effects of quinine and its more advanced synthetic forms, chloroquine and hydroxychloroquine, have been increasingly recognized in a myriad of other diseases in addition to malaria.

Hydroxychloroquine, developed in the 1950s from chloroquine, an old anti-malarial drug, is registered in around 60 countries under trade names such as Plaquenil, Quensyl and Plaquinol.
 
Hydroxychloroquine, a less toxic derivative of Chloroquine is a widely used medication by people with lupus or arthritis. 

Hydroxychloroquine and COVID-19

Is hydroxychloroquine old news? 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 January 2022, there have been more than 30 studies of Hydroxychloroquine for early treatment – all with zero negative results and an overall average improvement of 64%. 

Here’s a chart from c19early.com that shows that hydroxychloroquine is better than ivermectin: 


The overall improvement for hydroxychloroquine is better than ivermectin (for early treatment); 75% vs 52% in terms of death rate. Crucial point to note is that hydroxychloroquine needs to be given 'early'.

The difference in terms of effectiveness for hydroxychloroquine is distinctly different when given early vs late treatment (75% vs 19%), as shown in the summary chart below:


The evidence tracking on Hydroxychloroquine versus COVID-19 is available at c19hcq.com (constantly updated).

This article, we will dive deeper to provide the scientific background, related references and rationale of natural alternatives for hydroxychloroquine that you can easily purchase over the counter.

Natural Alternatives to Hydroxychloroquine

In the event that you simply cannot get hydroxychloroquine, there are viable natural alternatives. 
Although hydroxychloroquine is a relatively safe drug, it's still a synthetic chemical that can have side effects. Nutrients are natural alternatives that will benefit your body for optimal health. 

Nutrients and supplements 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.

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 below 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 as an informed patient.

That said, here are some of the substitutes for hydroxychloroquine that, in some parts of the country, will be easier to buy whenever we want them:
  1. Quercetin
  2. EGCG (Green Tea Extract)
  3. Black Seed Oil (Nigella Sativa)

Zinc Ionophores

Quercetin, Hydroxychloroquine, green tea extract, Zinc and black seed oil are among the handful of COVID-19 treatments that are being studied as potential candidates that might influence the outcome in the prevention and management of COVID-19. 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 the above treatment and supplement.

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. 

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.

The Front Line COVID-19 Critical Care (FLCCC) Alliance was initially formed as a working group during the early COVID-19 pandemic days in response to multiple early reports of COVID patients with an inexplicably high need for prolonged mechanical ventilation and an excessive death rate. 

Based on rapidly emerging clinical trials evidence, the FLCCC team has developed the I-MASK+ protocol for prophylaxis and at home treatment of early stage COVID-19.

For updated prevention and early outpatient treatment protocol, please check out FLCCC I-MASK+ protocol.


Green Tea Extract - EGCG (EpiGalloCatechin Gallate)

EGCG is a powerful plant compound and immune nutrient primarily found in green tea. The beauty of green tea is that it also contains quercetin, another zinc ionophore. Both are known for its many health benefits. EGCG is rich in polyphenols and antioxidants. It may help to lower oxidative stress, decrease inflammation, improve heart health, support brain health, aid weight loss and help you live longer.

EGCG also acts as a zinc ionophore (PubMed 2014), the same mechanism of action that hydroxychloroquine has via helping zinc pass the cell wall and get into cells where it might halt viral replication. Conversely, zinc helps to make EGCG more bioavailable, meaning the two nutrients work hand in hand to enhance each other’s therapeutic potential.

An Indian study found that EGCG has the ability to target numerous key structures inside the virus, disabling its functional capacity.

“EGCG showed a very high binding affinity and a low inhibition constant among all the phytoconstituents screened, especially in the case of 6vw1, which is a potential target of SARS-CoV-2,” the paper found.

“EGCG exhibited better binding with the viral proteins and hence, is expected to show better antiviral activity than the reference drugs, remdesivir and chloroquine,” it added.

It is important to remember, though, that by itself, EGCG is both unstable and bio-unavailable unless coupled with nutrients like zinc that studies show help to maximize its transport into cells.

Black Seed Oil (Nigella Sativa)

A computer-model molecular docking study published in Biological and Medicinal Chemistry revealed that the bioactive compounds nigellidine and α-hederin found in black seed oil were able to inhibit SARS-CoV-2 with a greater potential than favipiravir, chloroquine and hydroxychloroquine.

Evidence from a second paper that reviewed the biological effects of the active compounds in black seed oil suggested that thymoquinone may block ACE2 receptors, which is where the SARS-CoV-2 binds to the cell and releases the viral RNA into the cytoplasm.

The body uses zinc in several pathways to support the immune system, including (ScienceDirect):
  • Proliferation and activation of natural killer cells, macrophages, neutrophils, and T and B cells
  • Mediating protection against reactive oxygen species produced during an inflammatory response
  • Stopping recombinant RNA dependent RNA polymerase activity needed to replicate SARS-CoV-2
  • Inhibiting replicase processing
Therefore, moving zinc into the cytoplasm is crucial to help prevent the replication of the SARS-CoV-2 virus and thus effectively stop infected cells from infecting other cells.

Oral supplementation of zinc alone is not sufficiently effective since zinc cannot move easily across the cell wall. It needs another compound to provide transportation. The second compound is called a zinc ionophore. The application of zinc with an ionophore has demonstrated improved outcomes in patients hospitalized with COVID.

Research has identified several zinc ionophores, including chloroquinehydroxychloroquinequercetin and EGCGScientists have suggested that several of the terpenes in black seed oil, such as nigellimine, are similar in structure to chloroquine. They hypothesize that this may mean they can function in a similar manner as a zinc ionophore.

Thus, recent data have shown that the active ingredients found in black seed oil may have greater potential in the treatment of COVID-19 than antiviral drugs, may act as a zinc ionophore and may help block the ACE2 receptors the virus uses to infect cells.

Zinc and COVID-19

Technically, zinc is not a natural alternative for hydroxychloroquine. For the sake of completeness, we have included a section on zinc in this post.

For a zinc ionophore to be effective as a treatment or as an anti-viral, it needs to be given with zinc. There are many clinical studies that studied hydroxychloroquine as a monotherapy. Hydroxychloroquine is not as effective when given alone as compared to when given in combination with zinc.

Zinc has been shown in a lab study to inhibit regular coronavirus (not the current SARS-CoV-2) in a 2010 publication.

As of December 2021, there are more than 40 studies that have been launched to investigate the benefits of Zinc against COVID-19. You can review the status of these trials on clinicaltrials.gov.

At the Cleveland Clinic, researchers are enrolling people into a study to see if zinc or vitamin C — or a combination of the two — can reduce the duration of COVID-19 symptoms. Patients will be given the supplements after they have tested positive for COVID-19.

study in Spain (Gonzalez, The Lancet preprint, Oct 2020) among people hospitalised with COVID-19 found that having very low blood levels of zinc was associated with more severe disease and higher mortality rates. This research has not been peer-reviewed, so it should be viewed with some caution.

Taking zinc long term is typically safe for healthy adults, as long as the daily dose is under the set upper limit of 40 mg of elemental zinc (PubMed).

Be aware that typical daily doses of zinc provided by zinc lozenges generally exceed tolerable upper limits for zinc, and for this reason, they should not be used for longer than about a week. 

Excessive doses may interfere with copper absorption, which could negatively affect your immune system as it can cause copper deficiencies, blood disorders, impair the absorption of antibiotics and potentially permanent nerve damage or loss of smell.

The ideal dose for prevention while the COVID-19 risk is high is 40-100 mg/d, a portion of which comes from zinc lozenges to spread the zinc through the tissues of the nose, mouth and throat. It should be accompanied by at least 1 mg copper from food and supplements for every 15 mg zinc.

Foods that are high in zinc include oysters, crab, lobster, mussels, red meat, and poultry. Cereals are often fortified with zinc. Most multivitamin and nutritional supplements contain zinc.

Do take note that you should keep the dosage back to within 40 mg/d once the exposure risk is back to normal.

Editor's note: Hydroxychloroquine is a zinc ionophore. If increased intracellular Zn ion concentration is required to disrupt viral replication, perhaps using multiple zinc ionophores would increase that concentration thus decreasing viral replication further. Other OTC (over the counter) zinc ionophores include quercetin (QCT) and epigallocatechin-gallate (EGCG – green tea extract).

Does Zinc Ionophore require a prescription?

Zinc ionophore supplements such as quercetin and green tea extract do not require a prescription and can be easily available at your nearest pharmacy and available online on Amazon as well.

However, a zinc ionophore like hydroxychloroquine would require a prescription in the US.

Conclusion

Viral infections like the COVID-19 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, vaccination 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 healthcare provider if you have any doubt.

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