Important Updates on Supplements and COVID19 - From Mar 2020 to August 2020

The World Health Organization announced COVID-19 outbreak a pandemic in March 2020. As time passes in a pandemic, new evidence has emerged and there are things about supplements that we know now that we didn't know in March 2020. This article will focus on 'supplements and COVID-19' and is a work-in-progress article as new evidence might be added from time to time. We will list the top 10 supplements that can help and may possibly help to prevent or treat COVID-19, based on the available evidence.

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 regarding social distancing as well as mask use. You should also work to stay healthy by 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, as described below. In addition, take steps to control hypertension and blood sugar fluctuations with diabetes, as these conditions are associated with more severe disease if infected. These steps 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 (Anderson, Annals Int Med 2020).



1. Vitamin D and COVID-19

Several publications and studies have suggested that maintaining adequate levels of vitamin D would seem potentially beneficial in fighting the COVID-19 infection.

A German study (published in August 2020, Nfs Journal. 2020), suggests a link between vitamin D deficiency, hypertension, diabetes and higher risk of death in COVID-19 patients. According to the author:

There is ample evidence that various non-communicable diseases (hypertension, diabetes, CVD, metabolic syndrome) are associated with low vitamin D plasma levels. These comorbidities, together with the often concomitant vitamin D deficiency, increase the risk of severe COVID-19 events. Much more attention should be paid to the importance of vitamin D status for the development and course of the disease. Particularly in the methods used to control the pandemic (lockdown), the skin's natural vitamin D synthesis is reduced when people have few opportunities to be exposed to the sun. The short half-lives of the vitamin therefore make an increasing vitamin D deficiency more likely. Specific dietary advice, moderate supplementation or fortified foods can help prevent this deficiency. In the event of hospitalisation, the status should be urgently reviewed and, if possible, improved.

A preprinted study published on June 2020 from Singapore (CW Tan, MedRxiv 2020), among 43 patients age 50 or older who were hospitalised with COVID-19, 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.
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According to an editorial review (Aliment Pharmacol Ther. 2020) published on June 2020 by Irish researchers, people with vitamin D deficiency appear to be far more prone to severe COVID-19 infections.

Another U.S. study (published on May 2020 in ScienceDaily), patient data from 10 countries was analysed. The team found a correlation between low vitamin D levels and hyperactive immune systems. Vitamin D strengthens innate immunity and prevents overactive immune responses. The finding could explain several mysteries, including why children are unlikely to die from COVID-19.

The epidemiology of COVID-19 provides further evidence that vitamin D might be helpful in reducing risk associated with COVID-19 deaths. A May 6, 2020, report published in Aging Clinical and Experimental Research (its prepublication featured in the Daily Mail) found that countries with lower vitamin D levels also have higher mortality rates from COVID-19.

A preprinted study published in May 2020, looked at Vitamin D levels and inflammatory markers in hospitalized COVID-19 patients in Germany, South Korea (S. Korea), China (Hubei), Switzerland, Iran, UK, US, France, Spain, Italy (Daneshkhah, MedRxiv 2020). Patients with the lowest Vitamin D levels were about 15% more likely to get severe COVID-19 and cytokine storm. Vitamin D3 plays a role in inhibiting the cytokine storm that causes viral infections to become lethal.

Another May 6, 2020 report (Nutrients. 2020) in the journal Nutrients pointed out that vitamin D concentrations are lower in patients with positive PCR (polymerase chain reaction) tests for SARS-CoV-2. As noted in this report, which retrospectively investigated the vitamin D levels obtained from a cohort of patients in Switzerland.

The Irish Longitudinal Study on Ageing (TILDA) published in April 2020, suggested that vitamin D deficiency could have serious implications for COVID-19. Results from the Irish Longitudinal Study on Ageing (TILDA), showed that vitamin D plays a critical role in preventing respiratory infections, reducing antibiotic use, and boosting the immune system response to infections.

Another study, published in the journal Nutrients (April 2, 2020), carries the telling title, "Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Death."

Mark Alipio with GrassrootsHealth conducted a retrospective multicenter study involving 212 patients in Southeast Asia who had COVID-19. He too found a strong correlation between vitamin D levels and disease severity. Those with the mildest disease had the highest vitamin D levels, and vice versa.

In a May 18, 2020, letter to the Federal Chancellor of Germany, Angela Merkel; Bernd Glauner and Lorenz Borsche highlight these and other studies and ask whether a nationwide supply of vitamin D has been considered in Germany.

While large controlled studies demonstrating vitamin D's effectiveness in COVID-19 are still lacking, there are many such studies underway. You can review the status of these trials on clinicaltrials.gov. As of July 2020, 20 studies have been launched to investigate the benefits of vitamin D against COVID-19.

Buy Online: You can purchase Vitamin D as a dietary supplement online and from local health stores i.e. Guardian and Watson.

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.


2. Vitamin C and COVID-19

Most people turn to vitamin C after they've caught a cold. Because your body doesn't produce or store it, you need daily vitamin C for continued health. The recommended daily intake of vitamin C for adults from the diet and/or supplements is 75 to 120 mg. It is easy to get this amount and most people do. You can get about 80 to 90 mg from just a cup of orange juice or sliced orange, or even more from a cup of sweet peppers, tomato juice, or cut kiwi fruit.

Higher intakes of vitamin C may potentially help people who are critically ill with COVID-19 and on ventilators. A review of several studies performed prior to the emergence of COVID-19 found a dose of 1,000 to 6,000 mg of vitamin C daily (intravenously or by mouth) shortened the time on ventilation by about 25% for people who required ventilation for over 10 hours, but it appeared to be less helpful for those on ventilators for shorter periods (Hemila J Intens Care 2020). High doses of vitamin C, given intravenously, are currently being tested in COVID-19 patients in China who have developed pneumonia, but the benefit of this approach has yet to be proven.

Be aware that there are side effects and risks associated with taking high doses of vitamin C. People sometimes assume there is no harm in taking large doses because vitamin C is water-soluble (i.e. excess vitamin C is excreted from the body), but this is not the case. In addition to causing gastric distress and diarrhea, 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.

While large controlled studies demonstrating vitamin C's effectiveness in COVID-19 are still lacking, there are many such studies underway. You can review the status of these trials on clinicaltrials.gov. As of August 2020, 14 studies have been launched to investigate the benefits of vitamin C against COVID-19.

Time will tell what the outcome will be.

For a more comprehensive review on Vitamin C, check out Vitamin C: An Updated Review.

Related: 10 Best Vitamin C Supplements in Malaysia


3. Zinc and COVID-19

Zinc has become one of the most popular suggestions for reducing symptoms of coronavirus. Notably, an email written by a pathologist, Dr. James Robb, that recommends using zinc lozenges such as Cold-Eeze to ward off the virus, along with other tips, has gone viral.

Although there is no direct evidence at this time to suggest that using zinc lozenges can prevent or treat COVID-19 in people, zinc does have anti-viral properties and was shown in a laboratory study to inhibit the replication of coronaviruses in cells (te Velthuis, PLoS Pathog 2010). One physician has reported that four people with apparent COVID-19 reported significant improvements in symptoms within 24 hours of taking various zinc lozenges, but this was not a controlled clinical study (Finzi, Int J INf Dis — preproof).

Zinc lozenges or other orally dissolving zinc formulas containing certain forms of zinc have been shown to reduce the severity and duration of colds, which are caused by viruses. They appear to do this by acting directly in the throat, which is why the timing and duration of use matters when treating colds with zinc. The connection with coronavirus and zinc lozenges is that the major cause of illness and death among people who are symptomatic with COVID-19 is respiratory disease and it is in the upper airway that zinc lozenges can have some activity. However, zinc from lozenges has not been shown to directly help with lower respiratory illness (i.e., in the lungs), which is of greatest concern in COVID-19, because the dissolved zinc will leave the throat and move to the stomach instead of the lungs.

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 intake of zinc can cause copper deficiency, which could compromise your immune system. Zinc can impair the absorption of antibiotics, and use of zinc nasal gels or swabs has been linked to temporary or permanent loss of smell.

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).

You can purchase Zinc as a dietary supplement online and from local health stores i.e. Guardian and Watsons.


4. Quercetin and COVID-19

Considering the risks of chloroquine and hydroxychloroquine, and the evidence suggesting the reason these drugs work for COVID-19 is because they act as zinc ionophores, it’s worth questioning whether other more natural zinc ionophores can be used. Quercetin is a naturally occurring zinc ionophore (Journal of Agricultural and Food Chemistry 2014). Other than its viral blocking property, it also has a indirect anti-viral property by facilitating the transport of zinc into the cell; as a 'zinc ionophore'.

So has Quercetin been shown to do anything that prevents the COVID-19 virus from entering cells? 

study published in 2020 by the University of Tennessee and Oak Ridge National Labs used the most powerful IBM supercomputer to model which FDA approved compounds or supplements might interfere with the coronavirus binding to cells. To review, the coronavirus uses the ACE 2 (Angiotensin Converting Enzyme) receptor to enter cells. Once in a cell, the coronavirus virus empties its RNA contents and hijacks the cell to start producing more viruses. So preventing the coronavirus from binding to the ACE 2 receptor is a good thing as it means the virus can’t get into your cells. The study modeled various compounds and at number 5 on the list as those that has the potential to block the virus was Quercetin.

A clinical trial that will investigate the use of oral quercetin in patients with COVID-19 has been planned, or may already be underway, in China. Details about the exact form (quercetin or 3-beta-O-d-glucoside) and dose of the formula (produced by Swiss drug manufacturer, Quercegen Pharmaceuticals) do not appear to have been made public, but in a February 2020 interview posted online by the Canadian Broadcasting Company (CBC News), researcher Michel Chr├ętien stated he hopes to have preliminary results in the upcoming months. However, he cautioned that he does not want to give "false hope" about the potential benefits of quercetin until more research is conducted.

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


5. 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.

A paper that was published in July 2020 (Fundam Clin Pharmacol. 2020) discussed the potential benefits of melatonin as an antioxidant, anti inflammatory and immuno-modulator (to calm the cytokine storm) in the prevention and treatment of COVID-19.

Published on Jun 2020, 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). 

clinical study is underway in Spain to test this.

Rationale for use of melatonin in COVID-19 appears to stem from the fact that it can affect immune responses. Experiments in mice, for example, have shown melatonin to increase levels of certain cytokines (immune-regulating molecules) in those infected with various viruses and to reduce virus-related mortality, but this benefit has yet to be demonstrated in human clinical trials — and, theoretically, there could be a risk to increasing cytokines during COVID-19. Melatonin may also indirectly cause fewer ACE2 receptors to be available for the SARS-CoV-2 coronavirus to attach to cells in the body.

As of August 2020, 4 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.


6. 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. (PubMedPubMed
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.”


7. Molecular Hydrogen and COVID-19

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

The first preliminary report on COVID-19 patients (n=90) from China has been published on June 2020, demonstrating that H2-O2 inhalation has superior effects compared to O2 alone (Journal of Thoracic Disease. 2020).

Yes, we are referring to the hydrogen gas (H2) and not some fancy new chemical entity. 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.

Published in 2017, a group of researchers in China suggested that hydrogen-rich solution therapy may be a safe, reliable, and effective treatment for Multiple Organ Dysfunction Syndrome (MODS) induced by influenza and other viral infectious diseases (Ref).

A review in 2019 that included 113 references, has also focused on the potential mechanisms of molecular hydrogen against sepsis to provide a theoretical basis for clinical treatment (PubMed).

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).

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


8. 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).

As of March 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.


9. Selenium

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

In a compelling article in Progress in Cardiovascular Diseases (2020), Mark McCarty of the Catalytic Longevity Foundation, San Diego, CA, USA, and James DiNicolantonio, PharmD, a cardiovascular research scientist at Saint Luke's Mid America Heart Institute, Kansas City, MO, propose that certain nutraceuticals may help provide relief to people infected with encapsulated RNA viruses such as influenza and coronavirus.

The authors wrote, "Since selenium is an essential cofactor for certain peroxidases, and selenium deficiency has been endemic in certain regions of China and other parts of the world, insuring adequacy of selenium nutrition might also be appropriate in this context. Selenium deficiency also increases the rate at which viruses can mutate, promoting the evolution of strains that are more pathogenic and capable of evading immune surveillance."


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, and aid weight loss. Research on COVID-19 treatment and prevention found it to be potentially beneficial (Healthline).

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.


Wrap-up

Do we have large randomised controlled trials to prove that the right supplement/s can combat COVID-19. The answer is No. However, the only real defence against COVID-19 is your own immune system, which works best when fed right. What have you got to lose? As long as you are taking the supplements under medical supervision and within a safe range, you have a low down-side but high up-side.

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