15 Best Supplements to Reduce Cytokine Storm, a Severe Complication from COVID-19 (Updated June 2021)
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Nutritional supplements are meant to tip the scales in favour of you in terms of your immune system and to improve your probability of a smooth recovery, if at all you do get COVID-19. You still need to follow the advice given by CDC, WHO and your local authority in terms of local guidelines such as mask wearing, social distancing and avoiding crowds.
- Vitamin D3
- Vitamin C
- NAC and Glutathione
- Omega 3 (Fish Oil)
- Curcumin and Turmeric
- B Vitamins
- Molecular Hydrogen
- Green Tea (EGCG)
- Vitamin D3
- Vitamin C
- NAC and Glutathione
- Omega 3 (Fish Oil)
- Curcumin and Turmeric
- B Vitamins
- Molecular Hydrogen
- Green Tea (EGCG)
Immune Nutrients to Calm Cytokine Storm
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, we 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 Agents, The Lancet, Microbiol Mol Biol Rev).
1. Vitamin D3 and Cytokine Storm
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.
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.
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.
2. QuercetinQuercetin 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 inflammatory cytokines, infections, and allergies. Research has found that quercetin may be particularly beneficial for viral respiratory infections.
2.1. Quercetin, Vitamin C, D, Zinc and Melatonin - FLCCC Prevention ProtocolThere 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 April 26, 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 and obese. (Amazon)
- Vitamin C: 500 - 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: 30 - 40 mg/day (elemental zinc). Zinc lozenges are preferred. (Amazon)
- Ivermectin for
- prevention in high-risk individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc): 0.2 mg/kg per dose (take with or after meals) — one dose today, repeat after 48 hours, then one dose weekly. (also see ClinTrials.gov NCT04425850).
- Post COVID-19 exposure prevention: 0.2 mg/kg per dose (take with or after meals) — one dose today, repeat after 48 hours.
- 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.
- Quercetin has one moderate drug interaction with warfarin. Do not take quercetin without medical advice if you are using warfarin.
2.2. Quercetin, Vitamin C, D, Zinc, Melatonin, Ivermectin, Fluvoxamine and Aspirin - FLCCC Outpatient Protocol
- Vitamin D3 — 4000 IU/day. (Amazon)
- Vitamin C: 500 - 1,000 mg BID (twice daily) (Amazon)
- Quercetin: 250 mg twice a day. (Amazon)
- Melatonin: 10 mg before bedtime (causes drowsiness). (Amazon)
- Zinc: 100 mg/day. Zinc lozenges are preferred. (Amazon)
- Ivermectin: 0.2–0.4 mg/kg per dose (take with or after meals) — one dose daily, take for 5 days or until recovered. (Find a Doctor)
- Fluvoxamine: 50 mg twice daily for 10–14 days. Add to ivermectin if: 1) minimal response after 2 days of ivermectin; 2) in regions with more aggressive variants; 3) treatment started on or after day 5 of symptoms or in pulmonary phase; or 4) numerous co-morbidities/risk factors. Avoid if patient is already on an SSRI (selective serotonin reuptake inhibitor). (Find a Doctor)
- Nasopharyngeal Sanitation: Steamed essential oil inhalation 3 times a day (i.e. vapo-rub) and/or chlorhexidine/benzydamine mouthwash gargles and Betadine nasal spray 2–3 times a day.
- Aspirin: 325 m/day unless contraindicated.
- Pulse Oximeter: FLCCC also recommend monitoring your oxygen saturation with a pulse oximeter and to go to the hospital if you get below 94%. (Amazon)
2.3. Quercetin, Zinc, Vitamin D and C: AAPS (Association of American Physicians and Surgeons) Guidelines
2.4. EGCG (Green Tea Extract), Quercetin, Zinc, Vitamin C and D - Zelenko Prevention Protocol
2.5. EGCG (Green Tea Extract), Quercetin, Zinc, Vitamin C and D - Zelenko Treatment Protocol
Dr Zelenko's outpatient (over the counter options) 'treatment' protocol recommends the following for COVID-19 treatment for Low Risk Patients:
1. Elemental Zinc 50mg 1 time a day for 7 days (PubMed)
2.2. Epigallocatechin-gallate (EGCG) 400mg 1 time a day for 7 days (J. Agric. Food Chem. 2014)
3. Vitamin C and Cytokine StormVitamin 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.
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.
Temporarily taking megadoses of vitamin C supplements to combat a case of the cold or flu is likely not going to cause a problem.
4. Zinc and Cytokine Storm
Improving zinc intake/zinc status improves/modulates/enhances immune function. The flip side is, while some aspects of immunity slow, others increase. Uncontrolled immune responses drive excess inflammation. Zinc helps to balance all of this.
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.
5. Melatonin and COVID-19
"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."
Melatonin supplementation may reduce the risk of acute viral respiratory infections, help mitigate some chronic health problems that increase infection vulnerability, and protect against neurological and cardiovascular complications of viral respiratory infections (Reiter et al. 2020).
- Melatonin: 6 mg before bedtime (causes drowsiness).
In a paper on NAC for COVID-19, published in the October 2020 issue of Clinical Immunology titled “Therapeutic Blockade of Inflammation in Severe COVID-19 Infection With Intravenous N-acetylcysteine”, which is a case series report of 10 patients (including one with G6PD deficiency) given intravenous NAC. NAC elicited clinical improvement and markedly reduced inflammatory marker, CRP in all patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm.
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.
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.
Different types of exercise can influence your levels as well. In one study, researchers enrolled 80 healthy but sedentary volunteers to measure the type of exercise that may have the greatest effect. They found that aerobic training in combination with circuit weight training showed the greatest benefit.
7. Fish Oil (Omega-3 Fatty Acids) and Omega-6
This protection may have come from the effect EPA and DHA have on the body. An opinion paper published in June 2020 in the journal Frontiers in Physiology expounded on how "EPA and DHA supplementation can alter many biological pathways which may have a direct influence in the outcome of COVID-19."(Front. Physiol., 19 June 2020) The writers listed the many nutrients that play a key role in managing a cytokine storm and continued:
"Among these micronutrients, LC-PUFAs (long-chain polyunsaturated fatty acids) such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are noteworthy because of their direct influence in the immunological response to viral infections.
Among these complex immunomodulatory effects, interleukin-6 (IL-6) and interleukin-1ß (IL-1β)—because of the suspected central regulatory role in the "cytokine storm"—should be highlighted."
Accumulating evidence shows omega-3 fatty acids, administered orally or intravenously, may help control inflammation and improve outcomes in critically ill patients, including those with ARDS.489 A meta-analysis of 12 randomized controlled trials with a total of 1,280 critically ill patients with ARDS found supplementation with omega-3 fatty acids, in combination with gamma-linolenic acid (a less-inflammatory omega-6 fatty acid) and antioxidants, improved markers of lung function; however, only hourly administration, rather than large bolus intravenous dosing, was associated with reduced mortality. Although reductions in mechanical ventilation and length of stay in intensive care were seen, these effects did not reach statistical significance (Ref).
An observational study in 100 patients hospitalized with a severe acute viral respiratory illness found higher levels of EPA plus DHA were associated with lower mortality, though the effect was not statistically significant, possibly due to the small number of participants (Ref). During an outbreak of a severe viral respiratory infection, another study found countries with the highest intake of omega-3 fatty acids from marine sources had lower mortality rates than other regions of the world (Ref). The same research group used computer modeling to show how omega-3 fatty acids might bind to the highly infectious virus and interfere with its ability to enter cells (Ref).
That are more than a dozen studies on-going that examine the effect of EPA and/or DHA on the prevention of or lessening of symptoms of COVID-19.
EPA and DHA have a direct influence in the immunological response to viral infections and can modulate immune response and function.
Animal-based omega-3 fats, especially DHA, also help prevent thrombosis (a blood clot within a blood vessel) by decreasing platelet aggregation. Hypercoagulation is another complication of severe COVID-19 infection that can have lethal consequences.
Omega-3 also lowers your risk of lung dysfunction, protects against lung damage and secondary bacterial infections, and improves mitochondrial function.
Research shows that by lowering triglycerides, the risk of developing a cytokine storm is diminished. Omega-3 supplementation is known to lower triglycerides, but krill oil does so more effectively than fish oil.
8. SeleniumSelenium plays a role in immune cell function and activation through its incorporation into enzymes and other proteins. It also reduces infectivity, replication, and virulence of several respiratory viruses (Ref). Sodium selenite, a form often used in supplements, has been found to block an infectious respiratory virus from entering cells by interacting with its spike protein in the laboratory (Ref).
The soil concentration of selenium varies geographically around the world, affecting selenium status and resulting in endemic insufficiency and deficiency (Ref). A study comparing COVID-19 survival to regional selenium status during a major outbreak in China found survival was more likely in high-selenium regions (Ref). A study done during an outbreak in Germany found higher selenium and selenium-containing protein levels in COVID-19 infection survivors versus non-survivors (Ref).
Blood selenium levels have been noted to diminish in patients with critical illness, and lower levels are correlated with more severe illness and lower chance of survival (Ref). A meta-analysis of 19 randomized controlled trials found intravenous selenium supplementation in critically ill patients reduced total mortality (but not 28-day mortality) and shortened the length of hospital (but not intensive care unit) stay (Ref).
9. Curcumin and TurmericCurcumin, a yellow carotenoid from turmeric, is well known for its anti-inflammatory and free radical-scavenging effects. It has also demonstrated antiviral effects against a range of respiratory viruses, including influenza A virus and others (Ref). Computer models suggest curcumin may interfere with viral entry into cells as well as viral replication inside cells (Ref). Numerous preclinical studies indicate curcumin may activate antiviral immunity; at the same time, curcumin appears to inhibit infection-induced inflammatory signaling and promote anti-inflammatory processes, reducing the potential for a cytokine storm and ARDS and protecting other organ systems (Ref). By suppressing inflammation, curcumin has the potential to help mitigate complications and sequelae of severe acute viral respiratory infections (Ref).
In an open-label trial, 21 patients hospitalized with mild-to-moderate illness due to a highly infectious respiratory virus were treated with a nano-curcumin preparation providing 80 mg curcuminoids (curcumin and its related compounds) twice daily for two weeks in conjunction with standard therapies; their progress was compared with 20 similar patients treated with standard therapies alone. Those who received curcumin had better oxygenation status beginning on day two of treatment, as well as faster resolution of most symptoms, faster normalization of immune cell numbers, less likelihood of worsening of their clinical status, shorter time requiring supplemental oxygen, and shorter hospital stays (Ref).
In a double-blind placebo-controlled trial of 40 participants with a viral respiratory illness, those who received 160 mg nano-curcumin per day for 14 days along with standard therapy had greater reductions in some inflammatory cytokines, including IL-6. They also experienced significant improvement in more symptoms and had a lower fatality rate than those receiving placebo (Ref).
10. B Vitamins and COVID-19
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.
11. Molecular Hydrogen
- A group of scientists 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 (SOJ Microbiol Infect Dis. 2017).
- In a 2017 lab study published in the World Journal of Gastroenterology, “HRW (hydrogen rich water) treatment significantly reduced EtOH-induced increases in serum alanine amino transferase, 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.”
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 epidemiologist who discovered the SARS Coronavirus back in 2003, Dr. Zhong Nanshan, is now recommending H2 therapy for COVID-19 — you can watch the video where he does so here.
- Other individuals in the scientific community are talking about hydrogen as a possible treatment for COVID-19.
12. LactoferrinLactoferrin is an iron-binding protein made by cells such as those in secretory glands and activated neutrophils (a type of immune cell). It is found in most bodily fluids, including tears and breast milk, and lactoferrin derived from bovine whey is frequently used in supplements (Ref). Lactoferrin is an immune modulator, capable of enhancing antimicrobial immune activity while reducing inflammation, and has exhibited a broad spectrum of activity against bacteria, fungi, protozoa, and viruses (Ref). Laboratory research also suggested lactoferrin may inhibit entry of a highly infectious respiratory virus into cells by blocking its interactions with cell membrane components (Ref).
Lactoferrin may slow pathogen multiplication through its iron binding capacity. While iron is required for DNA replication and energy production, the presence of excess iron increases free radical generation, stimulates inflammatory processes, and exacerbates viral infection by promoting increased viral replication (Ref). Furthermore, patients with a severe acute viral respiratory infection have been found to have elevated levels of ferritin, and these levels correlated with increased risk of death (Ref). In its iron-free state (apolactoferrin), lactoferrin can sequester pro-oxidant free iron, lowering oxidative stress and suppressing the growth of pathogens, and possibly mitigating the serious complications of infection (Ref).
In a pilot trial, 75 patients who tested positive for an acute viral respiratory tract infection were treated at home with a liposomal preparation of a combination of 32 mg bovine lactoferrin with 12 mg vitamin C, with or without 10 mg liposomal zinc, four to six times daily for 10 days. In addition, lactoferrin nasal drops, mouth spray, and aerosol were used as needed by participants with headaches, loss of sense of smell and taste, nasal congestion, dry cough, or difficulty breathing. After 48 hours, all symptoms had diminished except loss of smell and taste, and by day five, all infected participants recovered from their illness with only loss of smell and taste remaining as residual symptoms (Ref).
Physiological changes in the human microbiota with age leads to a “physiological dysbiosis”, with less diversification in microbial composition, aggravated in case of comorbidity (hypertension, diabetes, chronic inflammatory bowel diseases, etc.) (Ref). Therefore, to establish the condition of eubiosis (healthy condition), “good” bacteria are required. The concept of probiotics as a food with positive effects was firstly used by Parker RB in 1974 and then recognized by the Food and Agriculture Organization (FAO), and more recently by the Word Health Organization (WHO) (Ref).
14. Green Tea (EGCG)The strong oxidative stress-reducing and anti-inflammatory effects of green tea catechins, including epigallocatechin gallate (EGCG), have been well established. A solution of green tea catechins was found to inactivate COVID-19 virus in the laboratory (Ref).
15. AstaxanthinThe 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.
Frequently Asked Questions
WHO trial (Solidarity) interim trial results (NEJM, Dec 2020) reported that remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon regimens appeared to have little or no beneficial effect among hospitalized COVID-19 patients.
ConclusionMacronutrients 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 with diet and lifestyle changes are critical to improving your health and to decrease your risk of a cytokine storm. However, therapeutics, vaccines and other physical strategies such as social distancing and mask wearing are also needed in order to protect yourself and your loved ones. It doesn't have to be an 'either or' situation. Combination strategies are normally more effective.