Fact Check: Melatonin, aspirin, vitamins, zinc and quercetin can prevent or treat COVID-19?

The claim: Melatonin, aspirin, vitamins, zinc and quercetin can prevent or treat COVID-19?

Since the early stages of the pandemic, people have claimed supplements like quercetin, zinc, vitamin D and melatonin can help treat and prevent COVID-19. But public health organizations and experts say there is little evidence these products are effective at treating or preventing COVID-19? Most of the studies on supplements are small and are of low quality? We shall wait for bigger and better quality evidence before we can make formal recommendations?

Science requires questioning and testing. Trusting science without questioning is not science. The world does not exist in a 'black or white' manner and most of the time, things do fall into the 'gray' area.

Medical science is dynamic and evidence development is constantly in a continuous work-in-progress mode. If a supplement has been shown to work in a small study, would you wait for a bigger study or should you just take it after considering the benefit and risk ratio; especially if the supplement is actually a nutrient that your body needs? Do your own research and the final decision should be yours, after a consultation with your trusted medical professional of course.

This guide is based on various references to scientific literature and hopefully, can help you make sense of the options and to separate the facts from fiction.

As of December 2021, there are more than 70 types of supplements that are being tested for COVID-19. You can review the details of these trials on clinicaltrials.gov. Vitamin D remains the most tested vitamin with the most evidence followed by zinc and vitamin C, for COVID-19.

The medical community themselves are battling over supplements on whether they should be used to treat and prevent COVID-19. On one side are experts telling you that supplements don't work and you should avoid them and just rely on wholesome foods. On the other, are experts telling you to take all kinds of supplements that will help protect you against COVID-19. Do they actually work? 

How do you deal with different expert groups dishing out conflicting guides? A common issue is that certain groups have pre-defined narrative that they would like to support. Therefore, only studies that support that pre-defined narrative are picked and cited as references. This is what we call as 'cherry-picking'. Cherry picking will naturally lead to a 'biased' decision. In order to avoid that, scientific information needs to be analyzed in a comprehensive, updated and non-biased manner in order to come up with the best 'evidence-based' decision.

The largest observational study on self-reported dietary supplement use and SARS-CoV-2 infection found that, among 372,720 people in the U.K. who were tested for SARS-CoV-2, those who used probiotics, fish oil, multivitamins, or vitamin D had a 14%, 12%, 13%, or 9% lower risk of infection, respectively, compared to those who did not. Similar findings were observed among 45,757 people in the U.S. and 27,373 people in Sweden, although only in the U.K. were the reductions driven by benefits only among women. There was no association between zinc, vitamin C or garlic supplementation and COVID-19 risk (Louca, medRxiv preprint, 2020 - Now accepted for publication in BMJ Nutrition). 

Do take note that for optimal effectiveness, each supplement should not be considered on their own merit as most of the supplements are given as part of a combination protocol. Further, each nutrient will also have influence on another nutrient.  To illustrate this multi-approach thinking, vitamin K2 and magnesium are synergistic with vitamin D and act as co-nutrients that can improve your vitamin D level. On the other hand, vitamin C and zinc might cause copper deficiency, if given at the same time.

Note: This is a highly dynamic topic; therefore, we will be updating this article as new information emerges. 

Here are the handful of over the counter supplements under the most intense study for effectiveness against the coronavirus:

1. Vitamin D

Based on several publications and studies, vitamin D seems to be the “most promising” supplement for COVID-19 protection. Many studies have showed the link between vitamin D deficiency and 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.

Update: Newest of many Vitamin D3 papers estimates level above 50 associated with "close to zero mortality": 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: Results of a Systematic Review and Meta-Analysis (Nutrients. 2021 Oct)

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).

Check out the evidence tracker on vitamin D and COVID-19 from c19vitamind.com (constantly updated), with more than 100 published studies by more than 900 scientists.


According to the statement released on 2 October 2020 by the previous 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.”

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.

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).

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

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.


Co-Nutrients Reduce Your Vitamin D Requirement

You can minimize your vitamin D requirement by making sure you’re also getting enough magnesium. Magnesium is required for the conversion of vitamin D into its active form and research has confirmed higher magnesium intake helps reduce your risk of vitamin D deficiency by activating more of it. 

Vitamin K2 is another important cofactor, and taking both magnesium and vitamin K2 can lower your vitamin D requirement.

Cod liver oil (1,360 IU per tablespoon), eggs (44 IU per egg), along with fortified foods including milk and some cereals are excellent sources. 

Do take note that you can also get good amounts of vitamins C and D, zinc and other essential vitamins and minerals from a basic multivitamin. If you are taking a multivitamin, your D-vitamin needs may be covered, but be careful not to let the total exceed 4,000 IU or 100 mcg.

To maintain healthy levels, only 400 to 800 IU (15 to 20 mcg) of vitamin D is required daily, but, to boost low levels, higher doses, such as 2,000 IU daily, are used and are generally safe on a short term basis.

A group of researchers from the US, UK, Netherlands and New Zealand, said that the RDA of vitamin D should be increased to 2,000 IU and vitamin C to 200 mg in their review published in Nutrients 2020.

Vitamin D3 supplements appear to be more effective at raising vitamin D levels than D2 supplements. One should also take vitamin K2 together with D3 as vitamin K2 works synergistically with vitamin D3. 


2. Quercetin

In 2003, Quercetin was found to provide broad-spectrum protection against SARS coronavirus (SARS-CoV-1 and not the current SARS-CoV-2) in the aftermath of the SARS epidemic that broke out across 26 countries in 2003 (Source). 
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.

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.
 
Check out the evidence tracker on quercetin and COVID-19 from c19quercetin.com (constantly updated).

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

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.

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


3. Vitamin C and COVID-19 

Check out the evidence tracker on vitamin C and COVID-19 from c19vitaminc.com (constantly updated).
 
There are also many vitamin C studies underway and you can review the status of these trials on clinicaltrials.gov. As of December 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.

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



In the first RCT (Randomised Controlled Trial) to test the value of vitamin C in critically ill COVID-19 patients, 56 ventilated patients in Wuhan, China, were treated with a placebo (sterile water) or intravenous vitamin C at a dose of 24 g/day for 7 days. The trial was originally designed for 140 subjects and was thus underpowered, with only 54 patients due to a lack of new admissions. The authors concluded that HDIVC (high dose intravenous Vitamin C) might show a potential signal of benefit for critically ill patients with COVID-19.

The Frontline COVID-19 Critical Care Expert Group (FLCCC), a group of emergency medicine experts, have reported that, with the combined use of 6 g/day intravenous vitamin C (1.5 g every 6 h), plus steroids and anticoagulants, mortality was 5% in two ICUs in the US (United Memorial Hospital in Houston, Texas, and Norfolk General Hospital in Norfolk, Virginia), the lowest mortality rates in their respective counties .

At the Cleveland Clinic, researchers are enrolling people into a study to see if vitamin C or zinc — 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.

Word of Caution - 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, gastric discomfort, 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. High doses of vitamin C (over 500 mg per day) over the long-term may increase the risk of cataracts. High-dose vitamin C can also reduce the effectiveness of certain medications and interfere with certain blood tests.

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.

That said, there are also several reasons to consider taking supplemental vitamin C. First, your body cannot make it. Second, most people do not get sufficient amounts from their diet and, third, your body’s requirement for vitamin C can increase 10-fold whenever your immune system is challenged by an infection, disease or physical trauma.


4. 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.

Check out the evidence tracker on zinc and COVID-19 from c19zinc.com (constantly updated). There are many Zinc studies underway and you can review the status of these trials on clinicaltrials.gov. As of December 2021, there are more than 20 studies that have been launched to investigate the benefits of Zinc against COVID-19.

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.

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

Zinc Sulphate is also part of Dr. Vladimir Zelenko anti-coronavirus experimental protocol. Please take note that the protocol is experimental and has not been 100% proven. Do discuss with your doctor before taking the medication as per the protocol. You can check out his publication in the International Journal of Antimicrobial Agents

Based on the statement released on 2 October (2020) by the previous U.S. president’s (Donald Trump) physician, zinc is also part of the treatment given to the US President. According to the president's physician, "Trump has been taking zinc, vitamin D, famotidine, melatonin and a daily aspirin.”

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).

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

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

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


5. Melatonin 

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.

You may know about melatonin as a supplement that can support your healthy sleep cycle. Melatonin is released by the brain’s pineal gland in response to nighttime darkness and is a key regulator of circadian synchrony.

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.

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).

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) nighttime plasma levels of melatonin. This increase appears to result from fluvoxamine’s inhibition of the melatonin-metabolizing liver enzymes (von Bahr et al. 2000).

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."

Another study of patients tested for COVID-19 found that those who reported taking melatonin were less likely to test positive, but this does not prove that taking melatonin supplements can prevent COVID-19 (Jehi, Chest 2020).

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). 

In an 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 December 2021, 11 studies (c19melatonin.com) have been published to offer clinical evidence on the benefits of melatonin against COVID-19.

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.

For prevention, the Front Line COVID-19 Critical Care Working Group, FLCCC recommends:
  • Melatonin: 6 mg before bedtime (causes drowsiness).
Related: Nature's Bounty Melatonin 5 mg > One tablet before bedtime (Amazon)

6. Aspirin

Some research has associated aspirin with improved outcomes for hospitalized COVID-19 patients. 

As of December 2021, 23 clinical studies have been published on c19aspirin.com (constantly updated). 


Of the 23 aspirin and COVID-19 studies, 12 were for treatment and 11 for prevention. For treatment, there is an overall improvement of 27% as compared to control. However, for prevention, the improvement is less obvious; with some studies showing negative improvement as compared to control.

Conclusion

Do take note that the doses 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 are much lower.

The risk for hospitalizations, ventilation, and death from COVID-19 are all elevated in people with preexisting conditions, especially high blood pressure and diabetes. Take steps to control hypertension and blood sugar fluctuations with diabetes, as these conditions are associated with more severe disease if infected. This may also help you maintain a healthy weight, which is important because obesity has been associated with an increased risk of requiring intubation or dying among people hospitalized with COVID-19, particularly those under 65 years of age. Risk was 60% greater among those with severe obesity (BMI > 34.9 kg/m2) compared to patients of normal weight (BMI of 18.5 to 24.9 kg/m2) (Anderson, Annals Int Med 2020).

Viral infections like the COVID-19 also 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, for those with high blood pressure, do make sure your blood pressure is well controlled during this pandemic.

Aside from supplements, there are other ways that may help improve immune response and to prevent you from catching the coronavirus.
  • Vaccination
  • 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 crowded areas.
  • Regular physical activity (outdoor activities may not be allowed in countries with 'lock-down'). Those with active lifestyle has lower risk if hospitalized as compared to those with sedentary lifestyle (Infectious Diseases and Therapy, 2021)
  • Consult your nearest local healthcare provider if you have any doubt.
Be aware that most of the supplement dosages are above the recommended dietary allowance (RDA) and therefore such dosages should not be maintained on a long term basis. 

Disclaimer: The information on this website is not intended to replace a one-on-one relationship with a qualified health care professional and is not intended as medical advice. It is intended as a sharing of knowledge and information from the research and experience of third party sites. If you are pregnant, nursing, taking medication, or have a medical condition, consult your health care professional before using products based on this content.

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