10 Best Nutrients and Supplements to Reduce Cytokine Storm, a Severe Complication from COVID-19

As of December, 2020, there are more than 2,000 clinical trials of COVID-19 treatments or vaccines that are either ongoing or recruiting patients have been registered. New ones are being added every day. The drugs or treatments being tested range from repurposed flu treatments to failed ebola drugs, to stem cell therapy, to malaria treatments that were first developed decades ago.

So, this is a situation where there is not much difference between experts and self-proclaimed experts. This is when the mixing of credible scientific information and marketing hypes will confuse the public at large. It's important to stress that what is more important is 'what' is right rather than 'who' is right.

We know that while a large percentage of the population only experiences mild to moderate symptoms of COVID-19 and won’t require hospitalization, others experience severe symptoms and complications, require hospitalization, or may even die. The cytokine storm may be one possible way to explain the severe reaction of those in our hospitals. This may also explain why younger people and those with a healthy immune system and without preexisting health conditions tend to have an easier time. Their bodies may release lower levels of cytokines creating just enough inflammation for healing.


Immune Nutrients to Calm Cytokine Storm

If you want to optimize your immune health and reduce your risk of a cytokine storm, there are various immune nutrients that may help you. It is important to note that since COVID-19 is a new virus, there is no research suggesting that these immune nutrients would specifically benefit COVID-19 prevention or recovery.

However, there are scientific studies that show their immune benefits for other viral infections, including the flu, other coronavirus infections, and other respiratory infections. As with other infections, I recommend protecting your body and optimizing your immune health with the best immune nutrients.

While at this point, research is on-going and scientists are working hard to understand COVID-19 and find treatment options, these are some promising developments. The good news is that you don’t have to wait to take steps to protect your health. There are a number of things that you can do to improve your immune system, including using immune nutrients that may help to calm a cytokine storm (J Biol Regul Homeost AgentsThe Lancet).


1. Vitamin D

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.

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.
2. Quercetin 

Quercetin is a pigment that is found in plants, vegetables, and fruits, and serves as an immune nutrient offering many health benefits. Elderberry, red onions, white onions and cranberries are the richest sources of quercetin. It is a flavonoid and antioxidant that may help to reduce inflammation, infections, and allergies. Research has found that quercetin may be particularly beneficial for viral respiratory infections.

quercetin

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.


3. 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).


4. 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. It may even be helpful when it comes to 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.

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. 


5. Vitamin C 

Vitamin C may be one of the most well-known immune nutrients that protect against immune deficiencies and which supports the prevention and recovery from the common cold and upper-respiratory issues, and also protects your cardiovascular system, eyes, skin, and other parts of your body. Research has found that vitamin C may help to optimize the innate and adaptive immune system.

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.

immune nutrients, Immune Nutrients to Calm COVID-19 and Cytokine Storm
6. Zinc 

Zinc is another powerful immune nutrient known for its benefits for providing immune health support and inflammation reduction as well as for improving cold and respiratory symptoms, wound healing, acne reduction, and lowering the risk of age-related diseases. Research on atherosclerosis and diabetes mellitus suggests that zinc deficiency may contribute to low-grade systemic inflammation.

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.”

Related: Can Quercetin and Zinc Help Against COVID-19?


7. Astaxanthin

Most recently, the paper (SSRN) “COVID-19: Potential of Microalgae Derived Natural Astaxanthin as Adjunctive Supplement in Alleviating Cytokine Storm,” published April 21, 2020, on the research library website SSRN, addresses the use of astaxanthin, a potent antioxidant supplement derived from microalgae. The full paper is downloadable from the link.

As explained in this paper, astaxanthin has a very unique molecular structure that allows it to penetrate the bilayer membrane of cells. The ability to quench reactive oxygen species (ROS) and free radicals in both the inner and outer layers of the cellular membrane allows it to provide superior protection against oxidative stress, compared to other antioxidants.

Vitamin E and beta-carotene, for example, only work in the inner side of the membrane, and vitamin C only works on the outer side.



In short, astaxanthin ticks many important boxes when it comes to ameliorating COVID-19, including immune response regulation and the enhancement of both cell-mediated and humoral immune responses, as well as the simultaneous protection against oxidative damage and inflammation.


8. 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.

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. 


9. 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.”


10. Molecular Hydrogen

Molecular hydrogen has been tested in several registered clinical trials right now as a potential treatment option for COVID-19.

There have been a plethora of studies on hydrogen’s effects on inflammation, in particular in regulating/controlling inflammatory cytokines. For example:
  • In a 2017 lab study published in the World Journal of Gastroenterology, “HRW treatment significantly reduced EtOH-induced increases in serum alanine aminotransferase, aspartate aminotransferase, triglycerol and total cholesterol levels, hepatic lipid accumulation and inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6.”
  • Another study in 2013 stated “The serum levels of cytokines such as IL-10, TNF-α, IL-12p70, and GM-CSF of mice administered with HW (hydrogen water) was significantly reduced as compared to PW (placebo water) group.”
There are at least 30 other high-impact scientific studies that mention hydrogen’s observed balancing and lowering effect on inflammatory cytokines.

Beyond the existing scientific studies that show a reason for excitement, hydrogen gas is also now being recommended in China as a therapy for individuals suffering from COVID-19, and there are very positive recorded anecdotal reports from patients.
The Director of the Molecular Hydrogen Institute has also created a YouTube video below clearly laying out the rationale behind the recommendation.

 

The science behind the virus and potential treatment is, of course, far more complex than this, and we do not intend to simplify the situation whatsoever. Nonetheless, the potential here is extraordinarily exciting — especially when you factor in the 100% safety factor of hydrogen as well. We will have to see what happens as the science develops and the clinical trials are conducted, and we will update this article with more information as it becomes available.


Conclusion

Macronutrients and micronutrients are essential to a human body, there are no ifs and buts about it.

Optimizing your immune system is critical to improve your health whether there is a pandemic or not.

Cytokines are an important part of your immune response. However, when your body releases excessive or uncontrolled levels of cytokines it results in hyperinflammation called a cytokine storm. A cytokine storm may lead to serious complications and even death in serious COVID-19 cases and in other infections.

Optimizing your immune system is critical to improve your health and to decrease your risk of a cytokine storm.


Read more: coronavirus

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