White Paper on Hydroxychloroquine 2021

In 2020, Hydroxychloroquine was touted as the most controversial drug in the world. Is there any new evidence to confirm or to disprove previous evidence?

Hydroxychloroquine, Ivermectin, Vitamin D, Zinc and Azithromycin are among the handful of COVID-19 treatments that have been heavily studied as potential candidates that might influence the outcome in the prevention and management of COVID-19. 

The purpose of this white paper is to present the updated evidence regarding the safety and efficacy of hydroxychloroquine and determine its proper role in the current pandemic.

Database of all HCQ COVID-19 studies. 311 studies, 229 peer reviewed, 259 comparing treatment and control groups. 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.


As you can clearly see above, all the early treatment results are all positive (upper left) 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.



As of June, 2021 there have been 29 studies of HCQ 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%. 

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. 

Hydroxychloroquine, Zinc and Azithromycin - AAPS (Association of American Physicians and Surgeons) Guidelines


Figure Reprinted from The American Journal of Medicine DOI: 10.1016/j.amjmed.2020.07.003, McCullough P, et al Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection 2020

Low Risk COVID-19 patients

The AAPS recommends the following outpatient treatment protocol for low risk (<50 yrs of age) COVID-19 patients:
  • 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.

If you develop symptoms or if your mild symptoms got worse, you will need to start at least 2 anti-infective agents:

1.1. HCQ (hydroxychloroquine) 200 mg orally twice a day (do take note that your intake of zinc will need to continue). Zinc is critical. It helps block the virus from multiplying. Hydroxychloroquine is the carrier taking zinc INTO the cells to do its job. If you are taking hydroxychloroquine, you might not need to take quercetin OR
1.2. Ivermectin 0.2 mg/kg per dose: one dose daily, minimum 2 days; maximum 5 days.

2. Azithromycin 500 mg once daily for 5 days.

High Risk COVID-19 patients

For those who are more than 50 years of age, the AAPS recommends:
  • Hydroxychloroquine (HCQ) with azithromycin (AZM) or doxycycline OR 
  • Ivermectin with azithromycin (AZM) or doxycycline 
Either combination above must also include zinc sulfate or gluconate, plus supplemental vitamin D, and vitamin C.

If your breathing symptoms got worse, you might need to add:
  • Inhaled Budesonide (example of a brand is Pulmicort, from AstraZeneca)
Do not get confused with budesonide 'nasal spray' (Rhinocort). Nasal sprays target the nose and related areas (e.g. nasal sinuses) whereas 'inhaled' budesonide targets the airway tracts.

If you have chronic diseases like hypertension, heart problem, lung problem or diabetes; you might be overwhelmed with the no. of medications that you might need to take on a daily basis. Always discuss with your doctor so that he/she can help you to understand the role and importance of various drugs and supplements, how they might interact and also to ensure that there is no unnecessary duplication or to avoid the confusion that certain drugs can be stopped just because you are having COVID-19.

A New Study Shows, Again, That Hydroxychloroquine and Azithromycin Work

A fascinating new study posted to the medRxiv* (May 31, 2021) preprint server (not peer-reviewed), suggests that such disappointment may have been both premature and unwarranted, based on a re-analysis of over 250 patients on invasive mechanical ventilation (IMV) during the first two months of 
the pandemic.

Using computational modeling, the use of weight-adjusted HCQ and AZM appears to be associated with a more than 100% increase in survival, without a clear correlation with ECG abnormalities.

Most importantly, this is the first clinical study to demonstrate the remarkable benefit of using cumulative doses of HCQ>3g/AZM>1g, compared to those not treated with this combination.

In this startling study, the investigators carefully re-examined the data, showing that among critically ill COVID-19 patients on IMV (invasive mechanical ventilation), less than 4% “walk out of hospital.” In contrast, the survival benefit of combined HCQ/AZM at a cumulative dosage of >80 mg/kg and >1g, respectively, is shown to be both clear and significant.

The safety at such doses is obvious, since survival is increased by almost 130% in this very high-risk population. Moreover, it appears that AZM (azithromycin) is an important component of this therapy in terms of mortality reduction.

Nebulized Hydroxychloroquine for COVID-19 Treatment: 80x Improvement in Breathing

Considering the unique pharmacokinetics of HCQ,  oral HCQ might take 5–10 days to achieve adequate plasma and lung concentrations.

Dr Zelenko, published a white paper on nebulised hydroxychloroquine that resulted in an 80x improvement in time and efficiency when compared to HCQ tablet (400-600 mg per day) combination therapy or Ivermectin combination therapy.

Nebulized hydroxychloroquine as 150 mg HCQ in 6 ml (25 mg/ml) of isotonic sterile solution within the first five (5) days of COVID-19 symptoms (“Nebu HCQ”) has resulted in immediate improvement (<1 hour after use) in breathing in COVID-19 infected patients. Nebulized HCQ served as a rescue medication with an 80x improvement in time and efficiency when compared to HCQ tablet (400-600 mg per day) combination therapy or Ivermectin combination therapy. No adverse events were reported outside of a bitter taste that quickly subsided.

Natural Alternatives to Hydroxychloroquine

If hydroxychloroquine could stop the virus, was this because the medications act as zinc ionophores? If so, its begs the question, “Do other zinc ionophores do the same thing?”

In the event that you simply cannot get hydroxychloroquine; quercetin, EGCG and zinc supplements are viable natural alternatives. 
Quercetin as a Zinc Ionophore

Quercetin is a zinc ionophore (J Agric Food Chem. 2014). A 2015 study found that that Quercetin shows inhibitory activity in the early stages of a wide range of influenza viruses, including H1N1 and H5N1 (Viruses 2016). Although influenza is not in the same family of viruses as the coronavirus, it’s plausible that a similar mechanism could apply here. There is actually some evidence that Quercetin has already proven effective at treating Ebola and Zika viruses.

Quercetin Dosage

The FLCCC I-MASK+ protocol recommends 250 mg daily for prevention and 250 mg twice daily for early treatment.

Quercetin works best when taken with vitamin C and Bromelain, as vitamin C helps activate it and bromelain helps with the absorption.

Precaution: Quercetin should be used with caution in patients with hypothyroidism (low thyroid hormone) and relevant thyroid hormone levels should be monitored.

 

Effect of QCT, EGCG, and CQ on the uptake of zinc cations by liposomes. Zinc-dependent fluorescence emission of FluoZin-3 encapsulated within liposomes treated with zinc cations, polyphenols, and CQ (J Agric Food Chem. 2014).

Epigallocatechin 3-Gallate (EGCG)

EGCG is a catechin found primarily in green tea and touted as the most effective chemopreventive polyphenol (19). A study (J Agric Food Chem. 2014) found EGCG amplified the effectiveness of Quercetin as a zinc ionophore. This suggests that ECGC and Quercetin provide a synergistic effect with enhanced bioavailability.

A new in-vitro study posted to BioRxiv (June 21, 2021), provided evidence of the potential of green tea catechin against COVID-19 virus.

EGCG Dosage

The Zelenko protocol recommends 400 mg once a day for prevention and 400 mg twice daily for early treatment taken together with zinc.
A common question, “Will drinking green tea provide enough ECGC?” No, you cannot get enough only from drinking green tea. Get your hands on the standardized supplement form.

Zinc
This trace element is essential to to cell function and involved in over 100 enzymes. Zinc has long been tauted for it’s potential to support the immune system, but also plays an important role in wound healing, fertility, preventing and treating pneumonia and preserving community between neurons (memory).
The National Institutes of Health (NIH) states:

“Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of approximately 100 enzymes and it plays a role in immune function, protein synthesis, wound healing, DNA synthesis, and cell division. Zinc also supports normal growth and development during pregnancy, childhood, and adolescence and is required for proper sense of taste and smell.”

Zinc Form and Dosage

There are several types of zinc supplements. Supplements contain several forms of zinc, including zinc gluconate, zinc citrate and zinc picolinate. The percentage of elemental zinc varies by form. To find out the percentage of elemental zinc in each form, check out elemental zinc percentage.
Chelated zinc is a general form of supplementary zinc in which the zinc is chelated — or bound — to a compound to make it easier for the body to absorb. Zinc picolinate or zinc gluconate are formed when zinc is chelated to picolinic acid or gluconic acid, so the main difference between zinc gluconate and picolinate is what compound it is bound to.

To find out which zinc supplement to consider, check out best zinc supplement 2021.

Most people do not lack an intake of zinc, but in disease state, there might be an increase in demand by the body. The FLCCC I-MASK+ protocol recommends 30 mg a day for prevention and 100 mg a day for early treatment of COVID-19. This should not be taken long term without evaluation of your zinc/copper ratios.

Hydroxychloroquine vs Ivermectin 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).

However, if you simply cannot get ivermectin, consider hydroxychloroquine AND zinc as alternatives.

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. 

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



Summary

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.

Nutrients are safer alternatives especially if your risk is low e.g. age below 50 and no other chronic illness (hypertension, diabetes, obesity). 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 early treatment is important and your doctor should be able to provide you with the best possible options. That said, 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.

If you are looking to find a doctor for early treatment, you can check out Find a Doctor for Early Treatment.

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