Bromelain, Quercetin, Zinc, Vitamin C and D: Can They Help Against Coronavirus?

COVID-19 kills some people and spares others. How do you ensure that you are on the right side of the statistics? There are 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. Is the information you've been fed bias or controlled? This guide can help you make sense of the options and to separate the facts from fiction on your own, independently.



As of February 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 quercetin. 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.

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). While interesting, this is a non peer-reviewed article and these results can not be taken as proving cause-and-effect.

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:

Bromelain and Quercetin

The major benefit of Quercetin and bromelain is they both fight inflammation. Quercetin is not soluble in water, however, so it is a poorly absorbed nutrient. Bromelain, a protein-digesting enzyme extracted from pineapples, increases the absorption of quercetin, as does vitamin C. Therefore quercetin is typically sold blended with one or both additives (PubChem).

Bromelain, Quercetin, Zinc 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 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. 

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. 

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 January 12, 2021):
  • 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. Vitamin D deficiency 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. (Amazon)
  • Vitamin C - 1,000 mg BID (twice daily) 
  • 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. (Amazon)
  • Melatonin: 6 mg before bedtime (causes drowsiness). (Amazon)
  • Zinc: 50 mg/day (elemental zinc). Zinc lozenges are preferred. (Amazon)
  • Ivermectin for prophylaxis in high-risk individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc). 0.2 mg/kg Day 1, Day 3 and then followed by biweekly dosing (one dose every two weeks). (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. 
For early outpatient protocol (COVID-19 positive), the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated January 12, 2021):
  • Vitamin D3 — 4000 IU/day. (Amazon)
  • Vitamin C - 2,000 mg BID (twice daily) 
  • Quercetin 250 mg twice a day.
  • Melatonin: 10 mg before bedtime (causes drowsiness).
  • Zinc: 100 mg/day. Zinc lozenges are preferred. (Amazon)
  • Ivermectin 0.2 mg/kg per dose. One dose daily - minimum 2 days, maximum 5 days.
  • FLCCC also recommend monitoring your oxygen saturation with a pulse oximeter and to go to 
    the hospital if you get below 94%.
  • Aspirin 325 m/day unless contraindicated.
The medical evidence to support each drug and nutrient can be found under “Medical Evidence” on the FLCCC’s website.



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.

Best Quercetin Zinc Supplement:
Related: Best Quercetin Supplement 2021

Vitamin D and COVID-19

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. However, the causal relation between the two is still unclear. 

Two studies in France (C Annweiler, Nov 2020G Annweiler, Nov 2020), one in India (A Rastogi, Nov 2020) and one in Spain (M Castillo, Oct 2020) showed that Vitamin D supplementation seems to decrease the mortality rate, the severity of the disease, and the inflammatory markers' levels among the COVID-19 infected patients, leading to a better prognosis and increased survival.

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.

Association of American Physicians and Surgeons' Home-based Guide

According to the Association of American Physicians and Surgeons’ home-based guide to treating COVID-19, vitamin D, C and zinc are necessary.

Some doctors also recommend adding a B complex vitamin. Zinc is critical. It helps block the virus from multiplying. Hydroxychloroquine is the carrier taking zinc INTO the cells to do its job.

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.

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.

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. 


Vitamin C and COVID-19 

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."

Interestingly, many of the risk factors for COVID-19 overlap with those for vitamin C deficiency. Certain sub-groups (male, African American, older, those suffering with co-morbidities of diabetes, hypertension, COPD), all at higher risk of severe COVID-19, have also been shown to have lower serum vitamin C levels . Average plasma vitamin C levels are generally lower in men than women, even with comparative intakes of vitamin C, which has been attributed to their higher body weight . 

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 largest registered trial is the Lessening Organ Dysfunction with Vitamin C-COVID (LOVIT-COVID) trial in Canada, which is recruiting 800 patients who are randomly assigned to vitamin C (intravenous, 50 mg/kg every 6 h) or a placebo for 96 h, i.e., equivalent to 15 g/day for a 75 kg person (NCT04401150). 

This protocol has also been added as a vitamin C arm in the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP; NCT02735707). The study design provides further rationale for the use of vitamin C in COVID-19 patients . 

There is also a high-dose (10 g/day) vitamin C intervention study in 500 adults is in progress in Palermo, Italy (NCT04323514).

In the UK, the Chelsea and Westminster hospital ICU, where adult ICU patients were administered 1 g of intravenous vitamin C every 12 h together with anticoagulants , has reported 29% mortality , compared to the average 41% reported by the Intensive Care National Audit and Research Centre (ICNARC) for all UK ICUs . While the authors have stated that the addition of an antioxidant in the form of vitamin C could have contributed to the lower mortality rate, it should be noted that other clinical factors and procedures could also account for the improved mortality and that the Chelsea and Westminster ICU serves a more affluent sector of the population with less deprivation on the basis of the Index of Multiple Deprivation (IMD). Deprivation, while a risk factor for COVID-19 mortality, is also a predictor of low vitamin C status. In the UK, an estimated 25% of men and 16% of women in the low-income/materially deprived population are deficient in vitamin C > 11 µmol/L .

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.

As of February 2021, more than 50 studies have been launched to investigate the benefits of vitamin C against COVID-19. There are many such studies underway and you can review the status of these trials on clinicaltrials.gov

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.

Related: Best Vitamin C Supplements


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 February 2021, there are more than 45 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.

A retrospective observational study (Carlucci P, Sep 2020) compared zinc supplementation to no zinc supplementation in hospitalized patients with COVID-19 who received hydroxychloroquine and azithromycin from March 2 to April 5, 2020. A total of 932 patients were included in this analysis; 411 patients received zinc, and 521 did not. After adjusting for the time at which zinc sulphate was added to the protocol, an increased frequency of being discharged home and reduction in mortality or transfer to hospice among patients who did not require ICU level of care remained significant. This study provides the first in vivo evidence that zinc sulphate may play a role in therapeutic management for COVID-19.

study in Spain (Gonzalez, The Lancet preprint, Oct 2020) among people hospitalised with COVID-19 found that having very low blood levels of zinc was associated with more severe disease and higher mortality rates.

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 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).


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. 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, 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, 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').
  • Consult your nearest local healthcare provider if you have any doubt.
More COVID-19 related topics > COVID-19


Supplements you can purchase from Amazon for COVID-19 prevention based on the FLCCC prevention protocol >

Update: Many of the products do go out of stock on Amazon. This list will be updated from time to time. 

Here is the list of nutrients and their respective directions based on the FLCCC and Dr Zelenko's prevention protocol.
  • Nature's Bounty Vitamin D3 - 2,000 IU > One dose daily (Amazon)
  • Nature's Bounty Vitamin C - 1,000 mg > One caplet twice daily (Amazon)
  • Now Foods Quercetin - 400 mg > One capsule daily (Amazon)
  • Nature's Bounty Melatonin 5 mg > One tablet before bedtime (Amazon)
  • Nature's Bounty Zinc 50 mg/day > One caplet daily (Amazon)
Be aware that most of the dosages are above the recommended dietary allowance (RDA) and therefore such dosages should not be maintained on a long term basis. 

You might need this: Pulse Oximeter > (Check Price and Availability on Amazon)


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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