Quercetin, Zinc, Vitamin D, Vitamin C and Melatonin

COVID-19 kills some people and spares others. How do you ensure that you are on the right side of the statistics? There are just too many self-proclaimed medical experts recommending all kinds of treatments and supplements for COVID-19 out there. 

On one side are experts telling you that most supplements don't work as they do not have 'enough' of high quality evidence and you should just rely on wholesome foods, fruits and vegetables. 

On the other, are experts telling you to take all kinds of supplements that are supported by small studies that will help protect you against COVID-19. Confused? How do you navigate through such scientific fog?

FLCCC protocol

When it comes to science and evidence, most consumers are confused with the mixed messages out there. 

The answer unfortunately is not so simple. There are many considerations. If there are many studies and the results are mixed (some positive and some negative results), the scientific community will normally do a process referred to as a 'systematic review'. A systematic review refers to the entire process of selecting, evaluating, and synthesising all available evidence and studies to come out with an aggregated conclusion. Similar to a 5 star overall rating of customer reviews on Amazon or a movie rating score for a particular movie.

Do take note that for optimal effectiveness, each supplement should not be considered as a single intervention as most of the supplements are given as part of a combination protocol. Further, each nutrient will also have influence on another nutrient. 

Below are the handful of supplements under the most intense study for effectiveness against the coronavirus:

Vitamin D and COVID-19

At this point, there is simply no question that vitamin D optimization is a crucial component of COVID-19 prevention and treatment. In addition to the many studies published during 2020 and 2021, since December 2021, four large systematic meta-analyses (RRRR) have been published, looking at either vitamin D levels, supplementation or both.

In all cases, the data consistently show that low vitamin D levels raises your risk of COVID while higher baseline levels and/or supplementation lowers all risks by 1.5 to three times.

Vitamin D, as an immuno-modulator, is a perfect candidate for countering the immune dysregulation common with COVID-19. 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. 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 deficiency is also known to enhance a process known as the “cytokine storm” (Marik 2020).

According to a July 2022 paper:

“Each 10 ng/mL increase in vitamin D levels was associated with a 45 % and 26 % lower risk of 45-day mortality (HR: 0.55, 95 % CI: 0.40–0.74) and ICU mortality due to COVID-19 (HR: 0.74, 95 % CI: 0.60–0.92), respectively.”

Since the outbreak of the pandemic, many vitamin D sufficiency studies have been conducted. Almost all of them show that an adequate vitamin D level reduces the chance of (a) getting ill, (b) ending up in the hospital, and (c) dying.

Almost all studies consider a vitamin D blood serum level of >30 ng/mL ‘adequate/good’. Several studies have shown that people with a blood serum level of >50 ng/mL hardly get sick at all. Results of a systematic review and meta-analysis (Nutrients 2021) suggested that COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3.

In a June 2022 review paper titled “The Role of Diet and Supplements in the Prevention and Progression of COVID-19: Current Knowledge and Open Issues”​ published in the journal Preventive Nutrition and Food Science, researchers said:

"The consumption of vitamin C and D supplements, in addition to a healthy diet, could be promoted as a co-adjuvant therapy for COVID-19..."

For more evidence, check out the evidence tracker on vitamin D and COVID-19 from c19vitamind.com (constantly updated), with more than 80 published treatment studies and more than 120 sufficiency studies by more than 900 scientists.


Trusted Source
Vitamin D has also been shown to have an anticoagulant effect. A decrease in 25-hydroxyvitamin D [25(OH)D] concentration has also been associated with an increased risk of venous thromboembolism (PubMed).

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.

Vitamin D and Omicron

Will Vitamin D Work Against Omicron BA4 and BA 5? Vitamin D is not variant specific because it's primary mode of action is to support the body’s immune system which reacts in a variety of ways against viral attack, not just in a specific antibody reaction to a specific spike protein. 

Vitamin D, Resveratrol and Cytomegalovirus

Dormant cytomegalovirus (CMV) is carried by 70-90% of the adult population and is reactivated by inflammation. One third of patients in hospital intensive care units reactivate CMV which doubles their mortality rate. There is agreement that Covid-19 co-infection with cytomegalovirus is associated with higher rates of mortality in older people who have an aged (senescent) immune system.

Cytomegalovirus also dulls the vitamin D receptors thus preventing the active form of vitamin D to enter living cells.

Resveratrol inhibits replication of cytomegalovirus in infected lung cellsResveratrol also binds to and activates the vitamin D receptors, thus allowing cells in the body to respond to vitamin D.


Quercetin - Anti-inflammatory, anti-coagulant, zinc ionophore and anti-viral

As of August 2022, there have been 9 published studies of quercetin and COVID-19 (c19quercetin.com).


Quercetin is also no. 1 in this prevention studies league table:


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 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. 

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

For an updated list of studies, check out c19quercetin.com

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.

Zinc - Anti-viral 

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 and COVID-19

In this Singapore peer reviewed study, published in the journal Clinical and Translational Medicine (Feb 2022), those who received zinc (80 mg daily) and vitamin C (500 mg daily) were found to subsequently mount a greater antibody response.

For more evidence, check out the evidence tracker on zinc and COVID-19 from c19zinc.com (constantly updated). 


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.

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.

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.

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.
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.

Melatonin- Anti-inflammatory and anti-viral

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.

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.

Check out the evidence tracker on melatonin and COVID-19 from c19melatonin.com (constantly updated).

As of August 2022, there are more than 15 published clinical studies of melatonin for treatment and prevention in COVID-19 and the results are promising even when it's given as a late treatment.



Melatonin and 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.

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).

According to 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.

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."

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.

Vitamin C - Anti-inflammatory

Vitamin C, which most of us reach for with any cold or flu, was used in high doses to great effect by COVID-19 early treatment doctors.

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.

Do take note that the vitamin C dosages given in the hospitals intravenously are different from those over the counter vitamin C supplements. Therefore, when you come across studies on vitamin C, you need to differentiate those that are given intravenously vs oral vitamin C.

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


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

Vitamin C, Omicron and Deltacron

Will Vitamin C Work Against Omicron or Deltracron? Vitamin C is not variant specific because it's primary mode of action is to support the body’s immune system which reacts in a variety of ways against viral attack, not just in a specific antibody reaction to a specific spike protein. 


FLCCC (Front Line COVID-19 Critical Care) I-MASK+ Protocol

The Front Line COVID-19 Critical Care (FLCCC) Alliance was initially formed as a working group under “emergency” conditions of the early COVID-19 pandemic in response to multiple early reports of COVID patients with an inexplicably high need for prolonged mechanical ventilation and an excessive mortality associated with the prevailing “supportive care only” recommendations disseminated by the majority of national and international health care organizations.

There are many COVID-19 treatment protocols out there on the internet. We have reviewed many protocols and believe the FLCCC I-CARE protocol is one of the easiest and effective protocols to follow. 

Based on recent clinical experience treating Omicron patients, the Front Line COVID-19 Critical Care Alliance (FLCCC) modified its early treatment protocol to include hydroxychloroquine as "preferred for Omicron".

The Omicron variant of the SARS-CoV-2 virus apparently enters human cells differently than do other variants. Analysis of biological mechanisms for hydroxychloroquine indicate that it has enhanced efficacy for the early treatment of Omicron, especially when coupled with zinc.

The Front Line COVID-19 Critical Care Working Group (FLCCC) recommends hydroxychloroquine and ivermectin as part of their I-CARE protocol for early outpatient treatment of COVID-19 (June 29, 2022 version). 

Specifically, they recommend hydroxychloroquine (preferred for Omicron) and ivermectin as first line anti-viral agents:
  • Ivermectin: 0.4–0.6 mg/kg per dose (take with or after meals) — one dose daily, take for 5 days or until recovered. (Find a Doctor). Use upper dose range if:  1) in regions with more aggressive variants (e.g. Delta); 2) treatment started on or after day 5 of symptoms or in pulmonary phase; or 3) multiple comorbidities/risk factors. (Ref)
  • Hydroxychloroquine (preferred for Omicron): 200mg PO twice daily; take for 5 days or until recovered. (Find a Doctor)
Most of the other component treatments in the I-CARE protocol have various mode of actions and may not be affected by the changes in the Omicron variant spike protein.

Always consult your trusted medical professional before you take any medication or supplement.

Note: Although ivermectin and hydroxychloroquine are relatively safe drugs, they are still synthetic chemicals that can have side effects. Vitamin D, C, Zinc and Quercetin 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.

Conclusion

Do take note that zinc, vitamin D, vitamin C and quercetin are nutrients that you need regardless whether there is a pandemic or not. What you need to be careful is that the dosages for micronutrients or vitamins are higher for treatment as opposed to maintenance or preventive. This is probably due to higher demand of the body, or the deficiency of the micronutrients are worse during a complicated viral infection. However, for prevention or maintenance, the dosages for most of the micronutrients should be much lower. Please discuss with your doctor before you take any supplement or medication related to COVID-19.


Aside from supplements, 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, using hand sanitizer and cooking meats thoroughly.
  • Try to minimize stress.
  • Drink enough water to keep your body hydrated.
  • Avoid excess alcohol.
  • Avoid enclosed crowded areas.
  • Regular physical activity (outdoor activities may not be allowed in countries with 'lock-down').
  • Consult your nearest local healthcare provider if you have any doubt.

Disclaimer: Always see your doctor before taking these supplements. Be aware that most of the dosages are above the recommended dietary allowance (RDA) and therefore such dosages should not be maintained on a long term basis. 

Our aim here isn't to replace your doctors' advice. It is intended as a sharing of knowledge and information. Do take note that supplements are not 100% protective or curative against COVID-19. 

You still need to follow the advice given by CDC, WHO and your local authority in terms of local guidelines such as mask wearing, social distancing and avoiding crowds. If you combine multiple strategies, it's going to be difficult for the virus to spread and survive.

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