Quercetin, Zinc, Vitamin C, Vitamin D and Melatonin: Synergistic Therapy for Coronavirus (updated January 2021)

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 supplements for COVID-19 out there.  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? Some supplements do have evidence and some don't. This guide can help you make sense of the options and to separate the facts from fiction.



As of January 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. There are more than 120 trials testing the various nutrients and dietary supplements including vitamin D, vitamin C, zinc and melatonin. Vitamin D remains the most tested vitamin followed by vitamin C, for COVID-19.

The lung injury in COVID-19 patients is associated with ROS (reactive oxygen species) released by white cells in the blood, and thus the use of antioxidants is necessary for the management of COVID-19.

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. For example, vitamin C and zinc need to be given together with copper. Also, vitamin D3 needs to be given with vitamin K2 and magnesium.

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

Quercetin and COVID-19

Quercetin was initially found to provide broad-spectrum protection against SARS coronavirus in the aftermath of the SARS epidemic that broke out across 26 countries in 2003. Now, some doctors are advocating its use against SARS-CoV-2, in combination with vitamin C, noting that the two have synergistic effects.
Quercetin

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 and Vitamin C

The initial MATH+ protocol was released in April 2020. In early July and August, it was updated to include quercetin and a number of optional nutrients and drugs, not only for critical care but also for prophylaxis and mild disease being treated at home.

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 prevention, the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated December 17th, 2020):
  • Quercetin 250 mg daily and Vitamin C 500 mg twice daily (SSRN, 16 Nov 2020Natural Product Communications, 3 Dec 2020Front Immunol. 2020). It is likely that vitamin C and quercetin have synergistic prophylactic benefit. Quercetin should be used with caution in patients with hypothyroidism and TSH levels should be monitored.  
  • Vitamin D3 — 1000–3000 IU/day. Note RDA (Recommended Daily Allowance) is 800–1000 IU/day. The safe upper-dose daily limit is likely < 4000 IU/day. [1-22] Vitamin D insufficiency has been associated with an increased risk of acquiring COVID-19 and from dying from the disease. Vitamin D supplementation may therefore prove to be an effective and cheap intervention to lessen the impact of this disease, particularly in vulnerable populations, i.e. the elderly, those of color and obese.
  • Melatonin (slow release): Begin with 0.3 mg and increase as tolerated to 2 mg at night. 
  • Zinc: 30–50 mg/day (elemental zinc). Zinc lozenges are preferred.
  • B complex vitamins
  • Ivermectin for prophylaxis in high-risk individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc). 0.15–0.2 mg/kg Day 1, Day 3 and then weekly for 10 weeks, followed by biweekly dosing. (also see ClinTrials.gov NCT04425850). NB. 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. 
They also recommend monitoring your oxygen saturation with a pulse oximeter and to go to the hospital if you get below 94%. The medical evidence to support each drug and nutrient can be found under “Medical Evidence” on the FLCCC’s website.


You can purchase Quercetin as a dietary supplement online at Lazada Malaysia.

Vitamin D and COVID-19

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

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 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.

The same team above, has also published a preprint article: A study at the University of Chicago of over 4,000 patients that found that untreated vitamin D deficiency was associated with an increased risk for COVID-19 infection.

study early this year 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 in the Journal of Clinical Endocrinology & Metabolism.

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.

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.

Buy Vitamin D supplement in Malaysia: 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. D3 capsules are available in most supermarkets and health food stores such as Guardian and Watsons, as well as online.


Vitamin C and 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. 

However, large controlled studies demonstrating vitamin C's effectiveness in COVID-19 are still lacking. There are many such studies underway and you can review the status of these trials on clinicaltrials.gov. As of December 2020, more than 45 studies have been launched to investigate the benefits of vitamin C against COVID-19.

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

Word of Caution - 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.

Related: 10 Best Vitamin C Supplements in Malaysia

Zinc and 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) in a 2010 publication.

As of December 2020, there are 40 studies that have been launched to investigate the benefits of Zinc against COVID-19. You can review the status of these trials on clinicaltrials.gov.

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).

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.

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 by the U.S. president’s 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).

You can purchase Zinc (+copper) as a dietary supplement online and from local health stores in Malaysia i.e. Guardian and Watsons.

Melatonin and COVID-19

You may know about melatonin as a supplement that can support your healthy sleep cycle. 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.

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 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.

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."

As of November 2020, 8 studies have been launched to investigate the benefits of melatonin against COVID-19. Ultimately, the results of the above trials will offer more definitive evidence.

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.

Molecular Hydrogen and COVID-19

Molecular hydrogen has been shown to have anti-oxidant and anti-inflammatory properties. It is 'the one and only' antioxidant that can both penetrate the mitochondria and neutralize the reactive oxygen species (ROS) (Med Gas Res. 2020).

Published in June 2020 (Reactive Oxygen Species), the aim is to review the current research into COVID-19 and to better understand how treatment with molecular hydrogen is likely to affect cellular responses during COVID-19 infection.

Application of H2, may provide an effective adjunctive medicament to O2 inhalation in the treatment of COVID-19 for the critically ill. Although this method is recommended and practiced in the People’s Republic of China with oxygen/hydrogen mixed gas noted to significantly reduce dyspnea, it is not widely used elsewhere. To date, only one clinical trial using oxyhydrogen for the treatment of COVID-19 infection has been registered with the US National Library of Medicine, with a further four clinical trials registered with The Centre for Evidence-Based Medicine (CEBM). 

It is the authors’ opinion that inhalation of H2 would be a more effective delivery mechanism for patients with moderate/severe symptoms of COVID19. Also worthy of notation is that currently, most, but not all clinical trials have been based on inhalation of H2, with this also being the preferred delivery method as recommended by The National Health Commission of the People's Republic of China.

Published in June 2020 (Journal of Thoracic Disease. 2020), this China study is the first multicenter randomized clinical trial that verifies the efficacy and safety of H2-O2 (mixed hydrogen gas and oxygen gas) inhalation in patients (n=90) with COVID-19.

Patients with COVID-19 frequently presented with dyspnea, coughing, chest pain and distress, and oxygen desaturation which cannot be rapidly relieved with other existing therapies (including oxygen therapy). The therapeutic effects of H2-O2 became significant as early as days 2 and 3 and the reduction of most respiratory symptoms persisted till the end-of-treatment.

The authors also concluded that the safety profiles of H2-O2 have rendered H2-O2 inhalation particularly suitable for relieving difficulty in breathing and other breathing symptoms in patients with COVID-19, regardless of the disease severity.

It was discovered and reported in Nature in 2007 by a team in Japan, that inhaled hydrogen gas could act as an antioxidant and protect the brain from free radicals. This sparked the interest in its potential health benefits worldwide and led to many published and on-going clinical research.

As of November 2020, 18 studies have been launched to investigate the benefits of molecular hydrogen against COVID-19. Ultimately, the results of the trials will offer more definitive evidence.

You can purchase Izumio (hydrogen infused water) from an authorised distributor in Malaysia. For more information, please feel free to WhatsApp: +60 12-749 2112.

B Vitamins

B vitamins may constitute a long list, but each one is important for different reasons. B vitamins are especially effective in boosting your immunity when you combine the foods containing them so they can all work together for maximum effect. These include vitamin B1 (thiamin), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid) and B7 (biotin).

B12, also known as cobalamin, is a powerful cold- and flu-fighting nutrient in your system, as is vitamin B6, another important, germ-combating vitamin that naturally benefits and strengthens your immune system and even protects against the damaging effects of air pollution.

Vitamin B9 and folic acid help repair tissues and aid in cell metabolism and immune support. They’re found in dark leafy greens, wild-caught, cold water fish like herring, mackerel, sardines, anchovies and wild-caught Alaskan salmon, and pastured, organic chicken.

Niacin or vitamin B3 is another precursor to nicotinamide adenine dinucleotide (NAD+). There are three main forms of niacin, which are dietary precursors to nicotinamide adenine dinucleotide (NAD). These are nicotinamide riboside, nicotinic acid and nicotinamide.

Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor in all living cells that is involved in fundamental biological processes. Emerging evidence implicates that elevation of NAD+ levels may slow or even reverse the aspects of aging and also delay the progression of age-related diseases.

NMN (Nicotinamide MonoNucleotide), is also another precursor to NAD. A case series (published in September 2020) of 9 elderly COVID-19 patients treated with a combination of NMN, zinc, betaine and sodium chloride resulted in rapid improvement.

Adequate amounts of folate, vitamin B6 and vitamin B12 are also needed for your body to make the amino acid cysteine. N-acetyl cysteine (NAC) is a supplement form of cysteine. Consuming adequate cysteine and NAC is important for a variety of health reasons — including replenishing the most powerful antioxidant in your body, glutathione. 

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.

N-acetyl cysteine (NAC), meanwhile, is a precursor of glutathione, and may protect against coagulation problems associated with COVID-19, as it counteracts hypercoagulation and breaks down blood clots.

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

You can find B-vitamin supplements on Lazada Malaysia.

Conclusion

Do take note 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 are much lower.

The risk for hospitalisations, ventilation, and death from COVID-19 are all elevated in people with preexisting conditions, especially high blood pressure and diabetes. 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, 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.
  • Wear protective face mask. This is to protect not only yourself but others.
  • Abundant evidence suggests that eating whole in fruits, vegetables and whole grains—all rich in networks of naturally occurring antioxidants and their helper molecules—provides protection against free radicals.
  • Getting Enough Sleep
  • Avoid Sugar, red meat and processed foods.
  • Don't smoke.
  • Take steps to avoid infection, such as washing your hands frequently and cooking meats thoroughly.
  • Try to minimize stress.
  • Drink enough water to keep your body hydrated.
  • Avoid excess alcohol.
  • Avoid crowded areas.
  • Regular physical activity (outdoor activities may not be allowed in countries with 'lock-down').
  • Consult your nearest local healthcare provider if you have any doubt.


More COVID-19 related topics > COVID-19

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