8 Natural Alternatives for Oral Ivermectin 2021

Ivermectin

Ivermectin is a 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.


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

Ivermectin and COVID-19 Updates:

www.onedaymd.com
A Cochrane-standard (=highest) review and meta-analysis of Ivermectin against Covid-19 by Bryant-Lawrie, now peer-reviewed and published, concludes that the evidence justify the global adoption.

Results of Ivermectin's success in treating COVID-19 outbreaks in India, Mexico, Peru, Paraquay, Argentina, Brazil and Slovakia.

June 1, 2021: The Drug that Obliterates 97% of New Delhi Cases by Justus R. Hope, MD

May 16, 2021: Do the NIH and WHO COVID treatment recommendations need to be fixed? By Steve Kirsch. Published on TrialSiteNews.
Great article on where we stand on the COVID-19 treatment front debate - COVID19Crusher

According to a review on peakprosperity.com:
Heads up — go over to TrialSiteNews and read this totally brilliant new (very long) article on Ivermectin, hydroxychloroquine and fluvoxamine. It blows the NIH and WHO’s opposition to these drugs out of the water. A total annihilation job. Surgical and hatchet.

May 4, 2021: Meta-analysis of Mortality, Need for ICU admission, Use of Mechanical Ventilation and Adverse Effects with Ivermectin Use in COVID-19 Patients (N=15,002). Published on medrxiv.org.

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 26, 2021: The new FLCCC outpatient protocol (I-MASK+) with the addition of fluvoxamine and nasal/oral "sanitation". 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).

Apr 26, 2021: The new FLCCC hospital treatment protocol (MATH+) with the notable additions of Fluvoxamine and anti-androgen therapy (Dutasteride/Finasteride).

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. 
  • 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

Check out the evidence tracking on Ivermectin versus COVID-19 from Ivmmeta.com (constantly updated).

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

Natural Alternatives to Ivermectin

In the event that you simply cannot get ivermectin, there are viable natural alternatives. 
Although ivermectin 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 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.

1. Vitamin D3 

Vitamin D deficiency affects the body’s susceptibility to infection and has been associated with influenza, hepatitis C, human immunodeficiency virus (HIV) and other viral diseases [Source]. Surveys indicate that most people in the United States consume less than recommended amounts of vitamin D. Nevertheless, according to a 2011–2014 analysis of serum 25(OH)D concentrations, most people in the United States aged 1 year and older had adequate vitamin D status. Sun exposure, which increases serum 25(OH)D levels, is one of the reasons serum 25(OH)D levels are usually higher than would be predicted on the basis of dietary vitamin D intakes alone.

Vitamin D and COVID-19

Based on several publications and studies, vitamin D seems to be the “most promising” natural supplement for COVID-19 protection. Vitamin D deficiency is known to enhance a process known as the “cytokine storm” (Marik, Jun 2020).

In a study (Frontiers in Immunology, Dec 2020) using bioinformatics and systems biology approach, the pathways associated with cytokine storm in COVID-19 is identified and suggested that the underlying mechanism of vitamin D could be promising in suppressing the cytokine storm.

Trusted Source).
A meta-analysis of 43 vitamin D observational studies (Petrelli, March 2021) points to effectiveness against COVID-19. Two studies in France (C Annweiler, Nov 2020G Annweiler, Nov 2020), one in India (A Rastogi, Nov 2020) and one in Spain (M Castillo, Oct 2020) showed that Vitamin D supplementation seems to decrease the mortality rate, the severity of the disease, and the inflammatory markers' levels among the COVID-19 infected patients, leading to a better prognosis and increased survival.

In a study from Nature (Sci Rep, May 2021) to investigate the effects of daily high-dose supplementation (60,000 IUs) of vitamin D — for eight to 10 days, in addition to standard therapy, for COVID-19 patients deficient in vitamin D; Vitamin D levels increased significantly in the vitamin D group — from 16 ng/ml to 89 ng/ml — while inflammatory markers significantly decreased, without any side effects.

The largest observational study to date, looked at data for 191,779 American patients who were tested for SARS-CoV-2 between March and June 2020 and had had their vitamin D tested sometime in the preceding 12 months.

Of those with a vitamin D level below 20 ng/ml (deficiency), 12.5% tested positive for SARS-CoV-2, compared to 8.1% of those who had a vitamin D level between 30 and 34 ng/ml (adequacy) and 5.9% of those who had an optimal vitamin D level of 55 ng/ml or higher.

Data from 14 observational studies — suggest that vitamin D blood levels are negatively correlated with the incidence and/or severity of COVID-19; meaning if your vitamin D level is high, your risk for COVID-19 is low and vice versa.

A study published in November 2020 from Singapore (CW Tan, Nutrition 2020), found that those who were started on a daily oral dose of vitamin D3 (1,000 IU), magnesium (150 mg) and vitamin B12 (500 mcg) within the first day of hospitalisation and continued up to 14 days were significantly less likely to require oxygen therapy and further intensive care.

According to the statement released on 2 October 2020 by the U.S. president’s physician said that in addition to the antibodies, Trump “has been taking zinc, vitamin D, famotidine, melatonin and a daily aspirin.”

Another study, published in JAMA (JAMA Netw Open - Sep 2020) found that persons who are likely to have deficient vitamin D levels at the time of COVID-19 testing were at substantially higher risk of testing positive for COVID-19 than were persons who were likely to have sufficient levels.

study of 20 European countries found a link between low levels of vitamin D and higher percentages of COVID-19 cases and mortality. Separately, more than 80% of 200 people hospitalized for COVID-19 in Spain were found to be deficient in vitamin D, according to a study published in October 2020 in the Journal of Clinical Endocrinology & Metabolism.

A review by Dinicolantonio et al (Mo Med Feb 2021) also suggested vitamin D and magnesium deficiency as a potential cause of cytokine storm in COVID-19 patients and recommended that vitamin D and magnesium supplementation to be considered.

There are many vitamin D studies underway. You can review the status of these trials on clinicaltrials.gov. As of July 2021, more than 40 studies have been launched to investigate the benefits of vitamin D against COVID-19.

Check out the evidence tracker on vitamin D and COVID-19 from c19vitamind.com (constantly updated).

Safety: Daily intakes of up to 25–100 mcg (1,000 IU–4,000 IU) vitamin D in foods and dietary supplements are safe for children (depending on their age) and up to 100 mcg (4,000 IU) are safe for adults. These values, however, do not apply to individuals receiving vitamin D treatment under the care of a physician. Higher intakes (usually from supplements) can lead to nausea, vomiting, muscle weakness, confusion, pain, loss of appetite, dehydration, excessive urination and thirst, and kidney stones. In extreme cases, vitamin D toxicity causes renal failure, calcification of soft tissues throughout the body (including in coronary vessels and heart valves), cardiac arrhythmias, and even death.

2. Quercetin

Quercetin is a pigment that is found in plants, vegetables, and fruits, and serves as an immune nutrient offering many health benefits. Elderberry, red onions, white onions and cranberries are the richest sources of quercetin. It is a flavonoid and antioxidant that may help to reduce inflammatory cytokines, infections, allergies and anti-blood clot property. Research has found that quercetin may be particularly beneficial for viral respiratory infections.

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.
Quercetin and ivermectin interactions? According to Drugs.com: "No interactions were found between ivermectin and Quercetin. This does not necessarily mean no interactions exist. Always consult your healthcare provider."
Quercetin and COVID-19

An Italo-Pakistani, randomized trial of Quercetin (Di Pierro et al 2021) in high bioavailability form in Covid outpatients (n=152) yields spectacular results that beg for immediate reproduction: > 68% less hospitalizations, which are 78% shorter and 100% less ICU admissions or deaths.

As of September 2021, more than 10 studies have been launched to investigate the benefits of quercetin against COVID-19. Ultimately, the results of the above trials will offer more definitive evidence.

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.

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. 

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.


3. Vitamin C

Vitamin C may be one of the most well-known immune nutrients that protect against immune deficiencies and which supports the prevention and recovery from the common cold and upper-respiratory issues, and also protects your cardiovascular system, eyes, skin, and other parts of your body. Research has found that vitamin C may help to optimize the immune system.

Vitamin C and COVID-19

There are many vitamin C studies underway and you can review the status of these trials on clinicaltrials.gov. As of July 2021, there are more than 20 studies that have been launched to investigate the benefits of vitamin C against COVID-19.

Most people turn to vitamin C after they've caught a cold. That’s because it helps build up your immune system. Vitamin C is thought to increase the production of white blood cells. These are key to fighting infections. Some of the most vitamin C-rich foods include citrus fruits, from tangerines to limes, along with leafy greens, bell peppers, papaya and broccoli. Berries are another great source, and they all provide this and other potent antioxidants, which support your immune response and help to rebuild collagen. Because your body doesn't produce or store it, you need daily vitamin C for continued health. Almost all citrus fruits are high in vitamin C.

Vitamin C might help prevent COVID-19 and also lessen the inflammatory reactions behind some severe COVID-19 cases, according to a review of research on the topic published in the latest issue of the journal Nutrition. 

Check out the evidence tracker on vitamin C and COVID-19 from c19vitaminc.com (constantly updated).

The U.S. Recommended Dietary Allowance (RDA) for vitamin C is 75 to 120 milligrams per day.

Safety: Taking large doses of vitamin C (ascorbic acid) on a regular basis lowers your level of copper, so if you are already deficient in copper and take high doses of vitamin C, you can compromise your immune system.

While generally considered safe even in high doses, way too much vitamin C — anything above 2,000 milligrams daily—can cause headaches, insomnia, diarrhea, heartburn, and other issues.

Temporarily taking megadoses of vitamin C supplements to combat a case of the cold or flu is likely not going to cause a problem. 

Many vitamin C supplements that are above the US RDA are sold in the market. It’s important to seek a physician’s advice if you intend to take high dose vitamin C on a long term basis. To be on the safe side, you may also request for your kidney functions to be monitored.

For long-term, daily use, your best bet is to eat a diet that is full of high quality organic vegetables and fruits that are minimally processed. Not only will you get vitamin C, but you will get all the other accessory nutrients and micronutrients that are needed to optimize it. 


4. Zinc

Zinc is another powerful immune nutrient known for its benefits for providing immune health support and inflammation reduction as well as for improving cold and respiratory symptoms, wound healing, acne reduction, and lowering the risk of age-related diseases. This trace element is essential to to cell function and involved in over 100 enzymes. Research on atherosclerosis and diabetes mellitus suggests that zinc deficiency may contribute to low-grade systemic inflammation.

Aging is associated with compromised immunity, that just means that your immune response to pathogens and infections starts to slow and is less robust, including a reduced vaccine immune response/efficacy. ⁣

Improving zinc intake/zinc status improves/modulates/enhances immune function. The flip side is, while some aspects of immunity slow, others increase. Uncontrolled immune responses drive excess inflammation. Zinc helps to balance all of this. ⁣

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.
Zinc and COVID-19

A retrospective study (Carlucci et al, Oct 2020) analyzed outcomes in 411 patients hospitalized with an acute viral respiratory infection who were treated with 440 mg of zinc sulfate (providing 100 mg of elemental zinc) daily for five days in addition to hydroxychloroquine and azithromycin. When these patients’ outcomes were compared with those of 521 similar patients who received the same treatment but without zinc, those who received zinc were more likely to have been discharged home and, among those who did not require intensive care, the individuals given zinc were less likely to die or be transferred to hospice care than those who received no zinc.

Interestingly, some researchers have proposed low zinc status may contribute to the loss of smell that sometimes accompanies respiratory viral infections (J Clin Biochem Nutr. 2021 Jan); while one study found no significant relationship between zinc status and loss of smell in 134 patients with a viral respiratory infection, it did note those who received 50 mg elemental zinc twice daily recovered their sense of smell more quickly than those who received no zinc (Abdelmaksoud et al. 2021 Jan).

There are many Zinc studies underway and you can review the status of these trials on clinicaltrials.gov. As of September 2021, there are more than 20 studies that have been launched to investigate the benefits of Zinc against COVID-19.

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.

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

Check out the evidence tracker on zinc and COVID-19 from c19zinc.com (constantly updated).

Safety: 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 and potentially permanent nerve damage. Zinc can also impair the absorption of antibiotics, and use of zinc nasal gels or swabs has been linked to temporary or permanent 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.

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

5. Curcumin and Turmeric

Curcumin, a yellow carotenoid from turmeric, is well known for its anti-inflammatory and free radical-scavenging effects. 

Curcumin and COVID-19

There are 4 studies of curcumin in COVID-19 published, including 3 double-blind randomized controlled trials and 1 review. And the results are promising.

It has also demonstrated antiviral effects against a range of respiratory viruses, including influenza A virus and others (Ref). Computer models suggest curcumin may interfere with viral entry into cells as well as viral replication inside cells (Ref). Numerous preclinical studies indicate curcumin may activate antiviral immunity; at the same time, curcumin appears to inhibit infection-induced inflammatory signaling and promote anti-inflammatory processes, reducing the potential for a cytokine storm and ARDS and protecting other organ systems (Ref). By suppressing inflammation, curcumin has the potential to help mitigate complications and sequelae of severe acute viral respiratory infections (Ref).

Curcumin also acts as natural zinc ionophores and can promote the cellular uptake of zinc and can be used with zinc to increase the effectiveness of these compounds in the inhibition of the virus (Ref).

Curcumin has been demonstrated (Ref) to suppress several inflammatory cytokines and mediators of their release such as tumor necrosis factor-alpha (TNF-alpha), IL-1, IL-8 and nitric oxide synthase.

In an open-label trial, 21 patients hospitalized with mild-to-moderate illness due to a highly infectious respiratory virus were treated with a nano-curcumin preparation providing 80 mg curcuminoids (curcumin and its related compounds) twice daily for two weeks in conjunction with standard therapies; their progress was compared with 20 similar patients treated with standard therapies alone. Those who received curcumin had better oxygenation status beginning on day two of treatment, as well as faster resolution of most symptoms, faster normalization of immune cell numbers, less likelihood of worsening of their clinical status, shorter time requiring supplemental oxygen, and shorter hospital stays (Ref).

In a double-blind placebo-controlled trial of 40 participants with a viral respiratory illness, those who received 160 mg nano-curcumin per day for 14 days along with standard therapy had greater reductions in some inflammatory cytokines, including IL-6. They also experienced significant improvement in more symptoms and had a lower fatality rate than those receiving placebo (Ref).

The same research group conducted another double-blind placebo-controlled trial in hospitalized patients with the same virulent respiratory virus, 40 with severe illness receiving intensive care and 40 with mild illness; half of the participants in each group received 160 mg nano-curcumin per day for 14 days and the other half received placebo. Curcumin-treated patients had lower numbers and activity of immune cells known to be involved in cytokine storm and hyper-inflammation. They also had greater improvement in fever, cough, and shortness of breath, and had lower mortality rates (0% vs. 5% in those with mild illness and 5% vs. 25% in those with severe illness [p<.0001 for both mild and severe cases]) than those who received placebo (Ref).

6. Melatonin

Melatonin is a hormone produced by the pineal gland in the brain, mainly during the night, that helps regulate circadian rhythms [Source]. Its levels decrease with aging. Most melatonin supplementation studies have evaluated its ability to control sleep and wake cycles, promote sleep, and reduce jet lag.

Laboratory and animal studies suggest that melatonin enhances immune response by increasing the proliferation and maturation of natural killer cells, T and B lymphocytes, granulocytes and monocytes . Melatonin also appears to have anti-inflammatory and antioxidant effects [Source]. However, whether these properties have a clinically significant effect on immunity in humans is not clear.

Melatonin and COVID-19

The potential utility of melatonin in treating COVID patients has not gone unnoticed, with a PubMed search combining melatonin and COVID producing more than 50 citations.

Assisting sleep and rest is already an immune system-supporting benefit, but melatonin has more to offer. It is a powerful antioxidant that supports your immune health, brain, eyes, digestion, and more. It may even be helpful when it comes to COVID-19.

Melatonin is a hormone synthesized in your pineal gland and many other organs. While it is most well-known as a natural sleep regulator, it also has many other important functions. For example, melatonin is a potent antioxidant (Antioxidants, 2020) with the rare ability to enter your mitochondria, where it helps “prevent mitochondrial impairment, energy failure and apoptosis of mitochondria damaged by oxidation.” It also helps recharge glutathione and glutathione deficiency has been linked to COVID-19 severity.

As discussed in a review (Cardinali et al. 2020), melatonin might counteract the consequences of COVID-19 via salutary effects on the sleep/wake cycle and more generally on chronobiology, as well as through its antioxidant and anti-inflammatory effects. 

Based on melatonin’s therapeutic potential and well-established safety profile, it has been suggested those at higher risk for severe illness and complications from viral respiratory infection, including the elderly and those with chronic medical conditions, may benefit most from regular use of 3–10 mg melatonin at bedtime (Ref). 

Fluvoxamine (Selective Serotonin Reuptake Inhibitor) might also exert beneficial effects in COVID patients through its well-characterized ability to substantially increase (~ 2–3-fold) night-time plasma levels of melatonin. This increase appears to result from fluvoxamine’s inhibition of the melatonin-metabolizing liver enzymes (von Bahr et al. 2000).

An Iranian randomised controlled trial (Arch Med Res 2021), studied 74 mild to moderate hospitalized patients. The study showed that adjuvant use of melatonin has a potential to improve clinical symptoms of COVID-19 patients and contribute to a faster return of patients to baseline health.

Data from Cleveland Clinic supports the use of melatonin. Here, the researchers analyzed patient data from the Cleveland Clinic’s COVID-19 registry using an artificial intelligence platform designed to identify drugs that may be repurposed.

"Patients who used melatonin as a supplement had, on average, a 28% lower risk of testing positive for SARS-CoV-2. Blacks who used melatonin were 52% less likely to test positive for the virus."

Some researchers have suggested high doses of melatonin, ranging from 50 to 200 mg twice daily, might help treat patients hospitalized for severe acute respiratory illness (Ref).

In a small Philippine case series study of 10 hospitalised COVID-19 patients, high dose melatonin (hdM) was given in addition (adjuvant) to standard therapy. According to the authors:

"High dose melatonin may have a beneficial role in patients treated for COVID19 pneumonia, in terms of shorter time to clinical improvement, less need for MV, shorter hospital stay, and possibly lower mortality."

Production of melatonin diminishes with age, contributing to immune dysfunction and increasing oxidative stress, inflammation, and infection susceptibility (Ref). In addition, infectious viruses can suppress melatonin production, disrupting circadian controls and impairing immune function (Ref).

Melatonin supplementation may reduce the risk of acute viral respiratory infections, help mitigate some chronic health problems that increase infection vulnerability, and protect against neurological and cardiovascular complications of viral respiratory infections (Reiter et al. 2020). 

One study found that among 26,779 people tested for COVID-19, those who reported using melatonin supplements were less likely to have the disease (PLoS Biol. 2020).

In another observational study that followed 11,672 individuals, melatonin use was associated with a reduced risk of testing positive for a common, highly infectious respiratory virus (Ref).

Another study looked at data from 791 patients intubated for respiratory support during an outbreak of a severe acute viral respiratory illness and 2,981 patients needing the same level of respiratory support for other reasons. The use of melatonin, most often for sleep issues, during the intubation period was associated with significantly improved outcomes in both groups and increased the likelihood of survival in virus-infected patients who required mechanical ventilation (Ref).

As of July 2021, more than 8 studies are currently underway to investigate the benefits of melatonin against COVID-19. Ultimately, the results of the above trials will offer more definitive evidence.

Safety: If you take a melatonin supplement, be careful: Too much can cause daytime sleepiness. There is no federal RDA nor any formal advice on supplement dose ranges. Based on an on-going Spanish study, a 2 mg daily dose protocol is being investigated for prevention of COVID-19. Do take note that the dosage for 'prevention' and 'treatment' is different, For prevention or maintenance, a lower dosage is normally recommended whereas a 'treatment' or 'therapeutic' dosage is normally higher.

Typical doses of 1–10 mg/day melatonin appear to be safe for short-term use (Source). Reported side effects, which are usually minor, include dizziness, headache, nausea, upset stomach, rash, and sleepiness. However, some reports have linked high blood levels of melatonin with delayed puberty and hypogonadism.

Studies have not evaluated melatonin supplementation during pregnancy and breastfeeding, but some research suggests that these supplements might inhibit ovarian function (Source). Therefore, some experts recommend that women who are pregnant or breastfeeding avoid taking melatonin.

Related: Nature's Bounty Melatonin 5 mg > One tablet before bedtime (Amazon)

7. Glutathione, NAC and COVID-19

N-acetylcysteine (NAC) is a precursor to glutathione. It is an antioxidant and increases glutathione levels in the body (Source). NAC has mucolytic activity, so it helps reduce respiratory mucus levels. Laboratory research suggests that NAC might boost immune system function and suppress viral replication. NAC also decreases levels of interleukin-6 and has other anti-inflammatory effects.

Much of the research on NAC has used an inhaled, liquid form of this compound. This form—which is classified as a drug, not a dietary supplement—is approved by the U.S. Food and Drug Administration (FDA) as a mucolytic agent and for decreasing respiratory secretion viscosity  (Source). Products containing NAC are also sold as dietary supplements.

NAC and COVID-19

According to this paper (2021), SARS-CoV2 infection impairs the metabolism and redox function of cellular glutathione. According to the authors, NAC can prevent this damage and the role of NAC in COVID-19 therapy is worth investigating.

Studies published in ACS Infectious Disease (ACS Infect Dis. 2020) and Antioxidants proposed that glutathione plays a crucial role in the body's fight against the severe inflammatory response triggered by the SARS-CoV-2 virus. The research group in the ACS Infectious Disease study called it the “most likely cause of serious manifestations and deaths in COVID-19 patients.”
NAC inhibits cellular entry and replication of some respiratory viruses, assists in clearing thickened mucous from the airways, suppresses inflammatory signaling, and may help mitigate viral infection-induced cytokine storm (Ref).

In a paper on NAC for COVID-19, published in the October 2020 issue of Clinical Immunology titled “Therapeutic Blockade of Inflammation in Severe COVID-19 Infection With Intravenous N-acetylcysteine”, which is a case series report of 10 patients (including one with G6PD deficiency) given intravenous NAC. NAC elicited clinical improvement and markedly reduced inflammatory marker, CRP in all patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm.
Another paper from US researchers, titled "N-Acetylcysteine to Combat COVID-19: An Evidence Review", offers a thorough analysis of NAC and discusses its potential use for treatment of COVID-19.
Another study, "Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients" was led by Dr Alexey Polonikov from Russia (ACS Infect Dis. 2020).

What he found was that the reactive-oxygen-species-to-glutathione ratio was able to predict the severity of COVID-19 and the patient’s outcome. When the patient had a low ROS-to-glutathione ratio, the patient had a very mild case. The fever disappeared on the fourth day without any treatment whatsoever.

When the ROS-to-glutathione ratio was high, the patient developed air hunger on the fourth day, experienced significant fever, hoarseness, myalgia and fatigue persisting for 13 days. A patient with even higher ROS and lower reduced glutathione had critical disease requiring hospitalisation for COVID-19-related pneumonia. 
In another publication on Respiratory Medicine Case Reports:

Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms.

Foods that have a positive impact on glutathione production include cruciferous vegetables such as broccoli, green tea, curcumin, rosemary and milk thistle. Getting quality sleep may also help.

Different types of exercise can influence your levels as well. In one study, researchers enrolled 80 healthy but sedentary volunteers to measure the type of exercise that may have the greatest effect. They found that aerobic training in combination with circuit weight training showed the greatest benefit.
As of July 2021, more than 10 clinical trials are underway to assess the efficacy of NAC in the context of highly infectious respiratory viral infections.
What Is the Primary Cause of Severe COVID-19 Illness: Glutathione or Vitamin D Deficiency?
The hypothesis that vitamin D (VD) deficiency is responsible for severe manifestations and death in COVID-19 patients has been proposed and is actively being discussed by the scientific community. 
Several studies reported that glutathione levels positively correlate with active vitamin D. (PubMedPubMed
Interestingly, a recent experimental study (PubMed) showed that Glutathione deficiency and the associated increased oxidative stress epigenetically alters vitamin D regulatory genes and, as a result, the suppressed gene expression decreases Vitamin D production, ultimately leading to a secondary deficiency of vitamin D. This study provides important information that glutathione is essential for the control of endogenous vitamin D production and demonstrates potential benefits of Glutathione treatment in reducing the deficiency of vitamin D. Taken together, these findings suggest that glutathione deficiency rather than vitamin D deficiency is a primary cause underlying biochemical abnormalities, including the decreased biosynthesis of vitamin D, and is responsible for serious manifestations and death in COVID-19 patients.
NAC (N-Acetyl Cysteine) vs Glutathione
N-acetyl L-cysteine (NAC), as a precursor of glutathione, helps to replenish intracellular glutathione, a vital cellular antioxidant. NAC has a low molecular weight and is well absorbed via oral administration as compared to glutathione.

NAC may also protect against coagulation problems associated with COVID-19, as it counteracts hypercoagulation and breaks down blood clots.

Glutathione and Zinc

To improve your glutathione, you need zinc, and zinc in combination with hydroxychloroquine (a zinc ionophore or zinc transporter) has been shown effective in the treatment of COVID-19.

Glutathione and Molecular Hydrogen 

One of the best ways to increase glutathione, though, is molecular hydrogen. Molecular hydrogen does so selectively and will not increase glutathione unnecessarily if you don’t need it. You can view Tyler LeBaron’s lecture on the details of how it does this in “How Molecular Hydrogen Can Help Your Immune System.”

Glutathione and Selenium

Selenium is also important, as some of the enzymes involved in glutathione production are selenium-dependent.

Safety: As an FDA-approved drug, the safety profile of NAC has been evaluated (Source) [88]. Reported side effects of oral NAC include nausea, vomiting, abdominal pain, diarrhea, indigestion, and epigastric discomfort (Source). No safety concerns have been reported for products labeled as dietary supplements that contain NAC.

NB: NAC supplements are not available on Amazon US. You can buy NAC Supplements from Lazada Singapore.

8. Green Tea (EGCG)

Quercetin and EGCG act as zinc ionophores (J. Agric. Food Chem. 2014), the same mechanism of action that hydroxychloroquine has via helping zinc pass the cell wall where it might halt viral replication.

Epigallocatechin-gallate (EGCG) 200mg (prevention) or 400 mg (early treatment) 1 time a day (J. Agric. Food Chem. 2014) is part of the Zelenko protocol for prevention and early treatment of COVID-19. EGCG acts as a zinc ionophore and therefore needs to be combined with zinc.

The strong oxidative stress-reducing and anti-inflammatory effects of green tea catechins, including epigallocatechin gallate (EGCG), have been well established. A solution of green tea catechins was found to inactivate COVID-19 virus in the laboratory (Ref). 

Other laboratory and computer models suggest tea catechins may inhibit viral infectivity and growth (Ref). It has been proposed that EGCG, due to its immune-modulating effect, could have a role in suppressing hyper-inflammation and preventing lung fibrosis in patients with severe acute viral respiratory illness (Ref).

EGCG (Green Tea Extract), Quercetin, Zinc, Vitamin C and D - Zelenko Prevention Protocol

Dr Zelenko's prevention protocol recommends the following for COVID-19 prevention for Low and Moderate Risk Patients:

1. Elemental Zinc 25mg 1 time a day (PubMed(Amazon)
2.1. Quercetin (Amazon) 500mg 1 time a day until a safe and efficacious vaccine becomes available. If Quercetin is unavailable, then use 
2.2. Epigallocatechin-gallate (EGCG) 400mg 1 time a day (J. Agric. Food Chem. 2014(Amazon)
3. Vitamin D3 5000 iu 1 time a day (Amazon)
4. Vitamin C 1000mg 1 time a day (PubMed(Amazon)

EGCG (Green Tea Extract), Quercetin, Zinc, Vitamin C and D - Zelenko Treatment Protocol

Dr Zelenko's outpatient (over the counter options) 'treatment' protocol recommends the following for COVID-19 treatment for Low Risk Patients:


1. Elemental Zinc 50mg 1 time a day for 7 days (PubMed)

2.1. Quercetin (Amazon) 500mg 2 times a day for 7 days (PubMed) OR

2.2. Epigallocatechin-gallate (EGCG) 400mg 1 time a day for 7 days (J. Agric. Food Chem. 2014)

3. Vitamin D3 5000iu 1 time a day for 7 days (Amazon)
4. Vitamin C 1000mg 1 time a day for 7 days

Quercetin, Vitamin C, D, Zinc and Melatonin - FLCCC I-MASK+ Protocol

Quercetin, Vitamin C, D, Zinc and Melatonin are part of the FLCCC I-MASK+ prevention and early treatment protocols.

For updated prevention and early outpatient protocol  for COVID-19 positive, please check out FLCCC I-MASK+ protocol.


Other Potential Treatments

For a list of COVID-19 early treatment studies, check out c19early.com (constantly updated).

Summary

The combination of quercetin, zinc, vitamin D, vitamin C and melatonin offer a high virus inhibiting and anti-inflammatory potential with a valuable degree of safety at a time of great uncertainty. Quercetin, zinc, vitamin D and C are also part of the FLCCC protocol and Zelenko protocol.

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.

However, if your risk is high e.g. age above 60, hypertensive, diabetic and obese; you might wish to consult a doctor and discuss more potent alternatives such as the FLCCC I-MASK+ protocol.

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. 
Also, please follow other precautions (as advised by your local health authorities and doctors) in order to minimise your risk.

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