Antioxidants and Coronavirus - Updates and Reviews in 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.

It's widely accepted that natural antioxidants from fruits and vegetables may help prevent a variety of serious diseases. That said, antioxidant deficiency gets worse with aging.

Here are the handful of antioxidant supplements under the most intense study for effectiveness against the coronavirus. This list is a work-in-progress list as new evidence might be added from time to time.

Vitamin C (Updated)

A review, published December 7, 2020, in the journal Nutrients, recommended the use of vitamin C as an additional therapy for respiratory infections, sepsis and COVID-19.

In December 16, 2020, Rob Verkerk, Ph.D., founder and scientific director of the Alliance for Natural Health, announced the launch of an international vitamin C campaign in response to the Nutrients review, which "puts all the arguments and science in one, neat place."



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 January 2021, more than 50 studies have been launched to investigate the benefits of vitamin C against COVID-19.

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.

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, 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.
Buy online: You can purchase liposomal Vitamin C as a dietary supplement online.


Quercetin

One of the functions of flavonoids such as Quercetin is to act as an antioxidant.

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. 

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.

Quercetin, Zinc 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. 

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 prophylaxis or 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.


Quercetin, Zinc, Bromelain and Vitamin C

A case series of 22 patients, published in Medrxiv revealed that quercetin 800 mg once daily with bromelain 165 mg, in addition to zinc acetate 50 mg and vitamin C 1 g supplements are safe with COVID-19 patients who were on multiple therapies including antivirals and antibacterial medications. The effectiveness of quercetin, bromelain, zinc and ascorbic acid combination was not clear in this study, because of lacking placebo or comparable group.


Quercetin: Anti-viral Significance

A review published in The Sage Journal (Dec 2020), summarizes the antiviral significance of quercetin and proposes a possible strategy for the effective utilization of natural polyphenols in our daily diet for the prevention of viral infection.



The AAPS recommends the following outpatient treatment protocol for COVID-19:
  • Quercetin oral 500 mg twice a day.
  • Vitamin C 3000 mg
  • Vitamin D3 5000 IU
  • Zinc sulphate 220 mg
Please take note the above dosages are relatively high and is meant for 'treatment'. If you wish to continue taking these nutrients for health maintenance, you'll need to go back to the usual 'RDA or RDI' dosages after you recover.

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.



Molecular Hydrogen

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 January 2021, 21 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.


Alpha Lipoic Acid

Lipoic Acid (often called Alpha-lipoic acid) is an organic compound found in all human cells.

It’s made inside the mitochondrion — also known as the powerhouse of cells — where it helps enzymes turn nutrients into energy (PubMed).

Most other antioxidants are either water- or fat-soluble (PubMed). Alpha-lipoic acid is both water- and fat-soluble, which allows it to work in every cell or tissue in the body. Meanwhile,

As of Mar 28, 2020, there were 2 new studies related to Alpha Lipoic Acid for COVID-19 on the Chinese Clinical Trial Registry. One on Mar 8, 2020 and another on Feb 15, 2020.

Other than your local health stores, you can purchase Alpha Lipoic Acid as a dietary supplement online from Amazon.


Melatonin

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.

Through a “big data” approach, 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."

A 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).

As of January 2021, 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.


Conclusion

The dosage could be complicated. Please discuss with your doctor or pharmacist. This list is a work-in-progress list as new evidence might be added from time to time.

Let's not lose to this virus. The virus cannot survive without a human host. If we do get the virus into our bodies, most of us will recover. However, when the infection is active, the virus will try to jump to another host knowing that they will not survive within the human body for long. As long as we do not allow that to happen, that should be the end of Mr COVID-19. Let's battle this virus together!

When it comes to boosting your immune system, there are other means other than antioxidants. Check out Immune Boosting Tips during this Coronavirus Pandemic (Scientifically Referenced).


More COVID-19 related topics > COVID-19

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