COVID-19 and Supplements: 10 Best Supplements for Your Immune System (Updated December 2020)

There are just too many self-proclaimed medical experts recommending all kinds of supplements for COVID-19 out there. 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.

Of course, the most important thing you can do to avoid infection with coronavirus is to prevent exposure by following the latest recommendations of the CDC and World Health Organization and take steps to stay healthy, including getting adequate sleep and exercise and eating a healthful diet that includes adequate (but not excessive) intakes of essential nutrients, such as vitamins C and D. Also take steps to control hypertension and blood sugar fluctuations with diabetes, as these conditions are associated with more severe disease if infected.

Can Supplements help against COVID-19? 

Research has shown that supplementing with certain vitamins, minerals and other substances can improve immune response and potentially protect against illness.

However, note that some supplements can interact with prescription or over-the-counter medications you’re taking. Some may not be appropriate for people with certain health conditions. If you are on medications, be sure to talk with your doctor before starting any supplements.

We have searched through electronic databases which included PubMed.gov and ClinicalTrials.gov in order to compile and organize the relevant information related to supplements and COVID-19. We have selected the 'best 10' based on the quality and quantity of available evidence.

Here's the top 10 supplements that might help against COVID-19.

1. Vitamin D and COVID-19

Based on several publications and studies, vitamin D seems to be the “most promising” supplement for COVID-19 protection. There are many vitamin D studies underway. You can review the status of these trials on clinicaltrials.gov. As of December 2020, 36 studies have been launched to investigate the benefits of vitamin D against COVID-19.

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.

A 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.

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. 

Read more: COVID-19 and Vitamin D

2. Vitamin C and COVID-19 

There are many vitamin C studies underway and you can review the status of these trials on clinicaltrials.gov. As of December 2020, there are 19 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.

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.

3. Zinc and COVID-19

There are many Zinc studies underway and you can review the status of these trials on clinicaltrials.gov. As of December 2020, there are 18 studies that have been launched to investigate the benefits of Zinc against COVID-19.

Foods that are high in zinc include oysters, crab, lobster, mussels, red meat, and poultry. Cereals are often fortified with zinc. Most multivitamin and nutritional supplements contain zinc.

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

Taking zinc long term is typically safe for healthy adults, as long as the daily dose is under the set upper limit of 40 mg of elemental zinc (PubMed). Be aware that typical daily doses of zinc provided by zinc lozenges generally exceed tolerable upper limits for zinc, and for this reason, they should not be used for longer than about a week. 

Excessive doses may interfere with copper absorption, which could negatively affect your immune system as it can cause copper deficiencies, blood disorders and potentially permanent nerve damage. Zinc can also impair the absorption of antibiotics, and use of zinc nasal gels or swabs has been linked to temporary or permanent loss of smell.

The ideal dose for prevention while the COVID-19 risk is high is 40-100 mg/d, a portion of which comes from zinc lozenges to spread the zinc through the tissues of the nose, mouth and throat. It should be accompanied by at least 1 mg copper from food and supplements for every 15 mg zinc.

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

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.”

4. Quercetin and COVID-19

As of December 2020, 4 studies have been launched to investigate the benefits of quercetin against COVID-19. Ultimately, the results of the above trials will offer more definitive evidence.

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

Incidentally, ascorbic acid (vitamin C) and the bioflavonoid quercetin (originally labeled vitamin P) were both discovered by the same scientist — Nobel prize winner Albert Szent-Györgyi. Quercetin and vitamin C also act as an antiviral drug, effectively inactivating viruses. 

Quercetin and Vitamin C

The initial MATH+ protocol (for in-hospital treatment) 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):

• 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.
• Vitamin C - 500 mg BID (twice daily) and Quercetin 250 mg daily. 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.  
• 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.

5. Melatonin and COVID-19

As of December 2020, 7 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.

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."

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.

FLCCC recommends (updated December 17th, 2020):

• Melatonin (slow release): Begin with 0.3 mg and increase as tolerated to 2 mg at night. 

6. Molecular Hydrogen and COVID-19

As of December 2020, 6 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.

Molecular hydrogen has been shown to have anti-oxidant and anti-inflammatory properties. 

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.

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.

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.

H2 selectively reduces peroxynitrites and hydroxyl radicals. This gives H2 a significant advantage over other antioxidants such as vitamin C, which act indiscriminately with superoxide and nitric oxide — both of which also have important and beneficial functions. H2 does not interact with either superoxide or nitric oxide. The only thing H2 can react with are the most dangerous ROS such as peroxynitrites and hydroxyl radicals (Nature in 2007).

7. B Vitamins and COVID-19

The topic 'B vitamins' is a complicated subject and that's probably why they are called 'B Complex'. 

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 a 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. NMN (Nicotinamide MonoNucleotide), is also another precursor to NAD. 

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.

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. 

8. Glutathione and COVID-19

A study, "Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients" was led by Dr Alexey Polonikov from Russia (ACS Infect Dis. 2020).

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

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

In another publication on Respiratory Medicine Case Reports:

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

What Is the Primary Cause of Severe COVID-19 Illness: Glutathione or Vitamin D Deficiency?
The hypothesis that vitamin D (VD) deficiency is responsible for severe manifestations and death in COVID-19 patients has been proposed and is actively being discussed by the scientific community. 

Several studies reported that glutathione levels positively correlate with active vitamin D. (PubMed, PubMed) 

Interestingly, a recent experimental study (PubMed) showed that Glutathione deficiency and the associated increased oxidative stress epigenetically alters vitamin D regulatory genes and, as a result, the suppressed gene expression decreases Vitamin D production, ultimately leading to a secondary deficiency of vitamin D. This study provides important information that glutathione is essential for the control of endogenous vitamin D production and demonstrates potential benefits of Glutathione treatment in reducing the deficiency of vitamin D. Taken together, these findings suggest that glutathione deficiency rather than vitamin D deficiency is a primary cause underlying biochemical abnormalities, including the decreased biosynthesis of vitamin D, and is responsible for serious manifestations and death in COVID-19 patients.

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.

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

9. Alpha Lipoic Acid and COVID-19

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).

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

There were 2 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.

10. Green Tea - EGCG (EpiGalloCatechin Gallate)

EGCG is a powerful plant compound and immune nutrient primarily found in green tea. It is known for its many health benefits. This immune nutrient is rich in polyphenols and antioxidants. It may help to lower oxidative stress, decrease inflammation, improve heart health, support brain health, aid weight loss and help you live longer (Healthline).

A lab study in 2020 that has yet to be peer-reviewed, demonstrated that EGCG and other compounds showed promise in blocking the SARS-CoV-2 novel coronavirus from entering cells.

The study above found that EGCG among other natural compounds may show benefits as a potential treatment for COVID-19. The study also indicated that EGCG may also act as a COVID-19 inhibitor, and recommends it for further treatment and drug treatment research.

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 hospitalizations, 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.

Related: 

• Top 10 Most Studied Treatments for COVID-19

• Ways to boost your immune system during this COVID-19 pandemic

More COVID-19 related topics > COVID-19

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