Vaccinate or Don’t Vaccinate?
The arguments for and against vaccinating against COVID are in most cases very straightforward. And in most cases, the argument FOR vaccinating are much stronger than the arguments against vaccinating. The arguments against vaccinating are, for most people, based only on safety concerns. There is a great deal of misinformation on the internet regarding the vaccines. Here is a link to the CDC website on “Understanding mRNA COVID-19 Vaccines” or download the information here:
Understanding mRNA COVID-19 Vaccines | CDC.
Given the extensive news coverage directed at educating the public about COVID-19, the purpose of providing an educational section on this website is not to provide general information on COVID-19 because it is assumed that the reader has by now learned the measures that must be taken to reduce the risk of acquiring the infection.
What has been learned now is that a significant percentage of people who are exposed to the virus and develop the infection do not progress to developing the disease. Instead, between 20 to 80% of people who become infected remain without symptoms as the infection runs its course and these people subsequently develop antibodies and recover from the infection without becoming ill. So it is important to understand that infection is not the same as disease. The key question is why is it that some people have an entirely asymptomatic course of infections while others develop the disease, either mild, severe or fatal. The answer to this question remains unknown.
That being said, there is research that suggests that some nutriceutical and botanical substances may offer the potential benefit of reducing the risk of having an infection progress to disease, or, reducing the risk of the disease progressing to a severe or fatal outcome. This page purports to offer the reader approaches to boosting their immunity and overall health through the use of nutriceuticals, botanicals and behavioral approaches in the hope of providing an edge against this virus and possibly reduce these risks.*
For the brief summary of recommendations:
Recommendations for Use of Supplements in the COVID-19 Pandemic 12-12-20
What Are COVID-19 and SARS-CoV-2?
COVID-19 (COrona VIrus Disease 2019) refers to the infection by a novel (new) corona virus named SARS-CoV-2 which stands for “Severe Acute Respiratory Syndrome COrona Virus-2,” with the original SARS coronavirus (SARS-CoV-1) identified in 2003 related to another outbreak first identified in China.
What is a coronavirus?
Coronaviruses are so named because they possess spiked surface proteins, which give the virus surface a crown/corona appearance. Coronaviruses are enveloped viruses (like influenza), which means they are covered by a membrane of cellular matter taken from their host cell while the coronavirus genetic content is a single strand of RNA.
There are seven known coronaviruses that infect humans, including four that are responsible for about 15% of common colds. The four “cold” coronaviruses affect the upper respiratory tract and cause symptoms such as sore throat or runny nose. Three coronaviruses have caused major human disease: SARS-CoV, MERS-CoV, and SARS-CoV-2 virus. These three affect the lower respiratory tract – the lungs.
Reducing Risk & Severity of COVID-19
As of now, there are vaccines that appear to be definitively effective in blocking infection with SARS-CoV-2, and there are now effective treatments for reducing symptom severity or curing COVID-19. This education page presents research evidence for the possible effectiveness of various nutraceutical and botanical substances for reducing the risk of developing COVID-19 as well as potentially reducing the severity of the disease process.
For example, it is known that a signifcant percentage of individuals exposed to the SARS-CoV-2 virus develop antibodies, confirming exposure, but never actually develop any symptoms or their symptoms are minimal. So exposure does not equal development of COVID-19 disease. What is the defining variable(s) that provide some individuals this level of protection? The answer to this question remains an unknown at this time but one may theorize that there may be factors that could be modified to reduce an individual’s risk/severity of disease. This is what this education page is about.
At this stage, research on COVID-19 is very limited and lacks confirmed validity for the effectiveness of the treatment options presented here. Substances presented here, however, do have evidence for their benefits and safety based on previous research directed at their use for non-COVID-19 purposes.
Behavioral Considerations
Stress
Before moving into the arena of adding supplements to one’s daily routine, it should be emphasized that behavioral factors should be appreciated. Anxiety and stress, when severe, may lead to the suppression of one’s immune system and make one more vulnerable to acquiring infections and may contribute to increased severity of infections. Psychological stress is believed to disrupt immune regulation by increasing pro-inflammatory cytokine proteins such as IL-6 and IL-1B via NLRP3 inflammasome activation, a factor that may be important in triggering severe outcomes in COVID-19 (see below).
Sleep
It is important therefore to reduce one’s stress levels as much as possible. One way to help accomplish this by getting enough sleep, a very important component of good immunity and reduction of stress. Inadequate sleep increases the risk of infectious illness. One study found that less than 5 hours of sleep/night for one week increased the risk of developing rhinovirus-associated colds by 350% when compared to individuals who slept at least 7 hours/night. Sleep deprivation increases CXCL9 levels, a monokine protein implicated in activating the NLRP3 inflammasome. Adequate sleep also improves the secretion of melatonin, a molecule which may play a role in reducing severity of COVID-19 infections (see below). It has been shown that supplementing with melatonin 10mg at bedtime improves sleep in ICU patients.
Mindful Exercises
Meditation, prayer, listening to music, animal therapy such as bonding with your dog, and other mindful activities can reduce stress. Aerobic exercise, even just walking 30-60 minutes/day may reduce the effects of stress and otherwise support the immune system. Additionally, there are substances called adaptogens that are available that may reduce the impact of stress on one’s immune system. For more information, please see Anxiety and Stress and Adaptogens.
Diet
Flavonoids
Flavonoids, a diverse group of nutrients found in almost all fruits and vegetables, have been found to reduce NLRP3 inflammasome signaling, and consequently reduce inflammatory proteins including NFkB, TNF-a, IL-6, IL-1B and IL-18 (see below). Some of the specific flavonoids which have been shown to have this effect, and which can be found in the diet and/or dietary supplements include: quercetin, EGCG and curcumin (see below). At least 5-7 servings of vegetables and 2-3 servings of fruit daily provide a healthy amount of flavonoids and is considered the basis of an anti-inflammatory diet.
Ome
ga-3 Fatty Acids
Omega-3 fatty acids are polyunsaturated fatty acids found in foods that have anti-inflammatory properties and play an important role in the resolution of inflammation. Fish are especially rich in omega fatty acids, especially salmon, mackerel, tuna, herring, and sardines. Nuts and seeds such as flaxseed, chia seeds, and walnuts are also good sources as are plant oils such as flaxseed oil, soybean oil, and canola oil. The two crucial omega-3 fatty acids — EPA and DHA — are primarily found in certain fish, while another omega–3 fatty acid, ALA (alpha-linolenic acid), is found in plants.
Prebiotics and Probiotics
Another variable with respect to diet and it’s potential role in enhancement of the immune system is the gut microbiome and the use of prebiotics and probiotics. The term “microbiome” refers to the microbial community, including all the microbes – bacteria, fungi, protozoa and viruses – that live on and inside the human body, particularly the intestinal tract. Over the last decade medical science has learned of the important role that the microbiome, particulary the bacteria in the gut, plays in the immune system and various diseases including inflammatory bowel diseases, respiratory infections and psychiatric illness including depression.
Protecting Against COVID-19
There are 4 approaches for protecting against SARS-CoV 2. First is to enhance one’s underlying immune system which includes reducing those factors that impair it. The second is to block the virus from attaching to the host human cell and impede its entry into the cell. The SARS-CoV 2 virus attaches to and activates receptors on cells called ACE2 receptors which are abundant in the upper and lower respiratory tracts as well as the heart and blood vessels. The third component is to block the subsequent replication of the virus within cells. The fourth component is to block the activation by the virus of damaging, excessive inflammatory processes.
(1) Enhancing the immune system
Much of what one can done to enhance their immune system is behavioral, as noted above, to reduce the variables that have a negative impact on the immune system, especially anxiety and stress. This involves not just reducing stress itself but also the potential use of agents such as adaptogens that may reduce the impact of stress on the immune system (see Anxiety & Stress). Vitamin D, known to be commonly deficient in the population, is believed to potentiate the immune system.
(2) Blocking SARS-CoV binding to ACE Receptors and entering cells
Agents that may impact this process include Astragalus membranaceous, quercetin and Vitamin D3.
(3) Blocking SARS-CoV replication
There is evidence (grade B) that Elderberry (Sambucus nigra) inhibits replication and viral attachment of another human coronavirus, NL63 (HCoV-NL63). Coupled with evidence of elderberry’s effectiveness agains influenze, it is suggested as a recommended agent against COVID-19. Zinc inhibits viral replication also and both EGCG (found in green tea) and quercetin enhance the transport of zinc into cells.
(4) Inflammation, Inflammasomes and Cytokine Storm
One of primary reasons that infection with SARS-CoV 2 can be deadly is that it can trigger overwhelming inflammation and destruction of lung tissue that fatally disrupts air exchange. Understanding the mechanisms behind this process offers the potential for determining ways of reducing the inflammatory process and limiting the severity of disease progression. Inflammation is an important bodily response triggered by invading pathogens or damaged tissues, a response directed at suppressing or destroying the pathogens or isolating the involved site. Moderate inflammatory response contributes to the host defense by removing pathogens or aiding in the repair of damaged tissue. However, uncontrolled or prolonged inflammation may promote further tissue damage and could lead to serious problems due to excessive inflammation.
SARS-CoV-2 is known to stimulate a part of the immune response called the inflammasome. Inflammasomes are intracellular multiprotein complexes that are part of the immune system responsible for the activation of inflammatory responses. Inflammasomes release pro-inflammatory proteins called cytokines, substances that are secreted by cells of the immune system that impact the function of other cells. The overproduction of inflammatory cytokines, a condition referred to as “cytokine storm,” can lead to overwhelmingly severe, sometimes irreversible, inflammation and damage to respiratory tissues. (Cytokine storm is technically called secondary hemophagocytic lymphohistiocytosis, or sHLH).
(5) Management of Mast Cell Dysregulation
Up to 1 in 5 of Covid-19 patients suffer a severe course of Covid-19 infection although a specific cause for this remains unclear. However, it is believed that immune cells called “mast cells” play an important causative role. Mast cells are activated by SARS-CoV-2 virus and are responsible for the release of many of the cytokines including histamine that are involved in severe COVID-19 illness.
Mast Cell Activation Disease (MCAD) is a condition in which the body produces abnormal mast cells that feature inappropriate mast cell activation in abnormal ways in response to threats and sometimes even activate when there is no threat at all. While once considered a rare disease, MCAD is now recognized as having a continuum spectrum of manifestation and actually affects up to 1 in 6 people in the form of MC activation syndrome (MCAS).
MCAS remains relatively unrecognised and undiagnosed, despite its great prevalence, because of the extreme variability of its clinical presentation. MCAS is a chronic multi-system disorder with inflammatory and allergic manifestations. MCAS may accompany or masquerade as such conditions as asthma, irritable bowel syndrome (IBS), interstitial cystitis, chronic headaches and other common conditions. In many cases the symptoms may be mild and intermittent so that they simply go unreognized and unevaluated.
It is now believed that MCAS might predispose to severe acute COVID-19 infection as well as some chronic post-COVID-19 syndromes. MCAS is diagnosed mainly by clinical presentation and sometimes with laboratory evidence in the absence of any other diseases that better accounts for all of the findings. Unfortunately, the nature of the dysfunctional mast cells of MCAS are not fully understood and not clearly identified with simple laboratory testing. This leaves diagnosing MCAS as difficult at best with no simple screening methods available. As such it has been proposed to consider empirically treating certain patients with the use of antihistamines directed at blocking the effects of dyregulated mast cells as a preventative measure in appropriate circumstances.
Fortunately, the antihistamines (see “Dual-histamine Receptor Blockade” below) proposed for this use are commonly available over the counter, affordable and are very well tolerated with mild side effects only. As such, the benefit/risk ratio may be considered high enough in certain circumtances to warrant their use despite the speculative nature of this treatment.
These circumstances include:
(1) Early onset of symptoms suggestive of acute COVID-19 such as loss of taste and/or smell, fatigue, cough etc.
(2) Recognition of significant recent exposure to someone acutely testing positive for COVID-19.
(3) Strong consideration may be arguable for those patients at risk for MCAS including those diagnosed with asthma, irritable bowel syndrome (IBS), interstitial cystitis, chronic headaches.
(4) Very strong consideration in those patients with established diagnosis of MCAD including mastocytosis.
For those with high risk for MCAS or with other risks for severe outcomes of COVID-19 and those with established MCAD, it may be appropriate to add prescription mast stabilizing medications such as Cromolyn. This should be discussed with a patients physician.
For more information, see Mast Cell Activation Disease (MCAD)
(6) Prevention of Thrombotic complications (blood clots)
In addition to the COVID-19 complications that are related to the hyper-activation of the immune response described above, another source of serious complications is the imappropriate formation of blood clots (thrombosis) that lead to strokes, heart attacks and gangrene of the extremities. These clots form as the result of over-activation of the blood clot forming process (the coagulation cascade and platelet aggregation) which leads to venous and arterial thrombosis.
Aspirin (Acetyl Salicylic Acid or ASA)
While the management of this complication is beyond this website, there is evidence that aspirin (Acetyl Salicylic Acid or ASA) might be a safe and reasonable therapeutic approach to the prevention of inappropriate blood clotting. Aspirin has both anti-inflammatory and anti-thrombotic effects and it has been shown to have antiviral activity against DNA and RNA viruses, including different human coronaviruses. In fact, there is solid evidence from in vitro and experimental models that supports the capacity of ASA to reduce replication, propagation, and infectivity of severalhuman COVID viruses.
Historically, the clinical use of aspirin in patients with different types of infections has been associated with reduced thrombo-inflammation and lower rates of complications and in-hospital mortality. Aspirin is commonly used as a preventative measure for heart attacks and strokes in patients with increased thrombotic risk.
Aspirin Dosing and Safety
In order to obtain a significant inhibition of platelet activity and aggregation, a high level of COX-1 inhibition is necessary and can be obtained rapidly by using higher ASA doses (i.e., ≥ 300 mg daily), or in the long term by using lower doses (i.e., 75–100 mg daily). The effectiveness of low doses of aspirin is believed to be equivalent to higher doses in terms of anti-thrombotic benefit.
While clinical studies evaluating the preventative benefit of aspirin in COVID-19 are still lacking, a recent retrospective, observational study of 412 patients published in October, 2020 demonstrated that aspirin use was independently associated with decreased risk of mechanical ventilation, ICU admission and in-hospital mortality. There were no differences in major bleeding or overt thrombosis between aspirin users and non-aspirin users. The authors concluded aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients.
Safety issues related both to the risk of bleeding and to that of developing rare but serious liver and brain damage (mostly among children i.e. Reye’s syndrome) needs to be considered. As such, the potential benefits and risks of the use of aspirin argue to restrict its use to adults and usual precautions with the use of aspirin still apply.
Hence, while ASA might be a safe and effective therapeutic treatment option needs further testing in clinical trials involving adults with COVID-19, it appears to have favorable risk/benefit ratio and should be considered as a preventative measure in selected patients.
Complementary and Alternative Nutraceuticals
It has been noted that the severe deterioration of some patients with COVID-19 is closely related to the development of cytokine storm, the pathogenesis of which is complex and rapidly progressive. Because definitive prevention of this complication still eludes us, science has turned to establised nutraceuticals with potential for preventing or reducing its severity. Substances that suppress or reverse cytokine storm may play important roles in preventing or treating COVID-19. As such, substances that can regulate inflammasomes and their inflammatory processes may offer benefit in reducing the severity of infection.
NRF2 activators
NRF2 (Nuclear factor erythroid 2-related factor 2) is a protein that regulates the expression of antioxidants that protect against oxidative damage triggered by injury and inflammation. NRF2 activation has been reported to suppress the NLRP3 inflammasome, leading to decreased production of IL-1𝛽, the master regulatory cytokine that activates other cells to produce other inflammatory cytokines. Drugs that stimulate the NRF2 pathway are being studied for treatment of diseases that are caused by oxidative stress. Many of the agents identified here as potential interventions for treatment of COVID-19 are NRF2 activators, including curcumin, resveratrol and quercetin.
For more information, see: NRF2 Activators
The SARS-CoV-2 virus activates the NLRP3 inflammasome. A 2016 study found that micronutrients found in certain plants (“polyphenols”), including many described in more detail below (resveratrol, curcumin, EGCG (epigallocatechin gallate), and quercetin), strongly inhibit the NLRP3 inflammasome release of IL-1𝛽, one of the main pro-inflammatory cytokines that regulate a wide range of immune responses. These polyphenols also modulate inflammatory pathways that trigger SARS-CoV-2-related hyper-inflammation. One of these pathways involves activation of NF-kB, a protein complex that controls transcription of DNA which plays an important role in cytokine production and cell survival. The supplemental use of these polyphenols may counteract these inflammation processes triggered by the SARS-CoV-2 virus. Vitamin C and melatonin are also believed to reduce NLRP3 inflammasome activation.
SARS-CoV-2 Replication
The SARS-CoV-2 virus repicates through the activity of an enzyme, the main protease (Mpro) enzyme. Certain bioactive compounds found in plants have been found to inhibit Mpro and may be effective in reducing viral replication and severity of disease. Kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate are plant-based compounds that appear to have good potential to reduce the activity of Mpro.
Recommendations for Use of Supplements
As noted by the Institute of Functional Medicine (IFM), the substances here may be recommended, at standard dosages, to potentially:
- Inhibit COVID-19 replication and thereby limit simple SARS-CoV-2 colonization from progressing to development of illness and possibly reduce severity of illness.
- Prevent activation of the NLRP3 inflammasomes and decrease activation of NF-kB inflammatory pathways to reduce severity of COVID-19 disease.
There is no research to support a regimen of taking single vs. multiple supplements. The IFM recommends consideration of using higher dosing and/or multiple agents based on individual patient factors (e.g., patient desire, pre-existing inflammation, multiple co-morbidities, higher risk, etc.) and/or when other therapeutic decision-making issues warrant such use.
When making a decision as to what supplements to consider taking, the following variables should be assessed:
- Mechanism of benefit: Enhance immunity and/or Reduce inflammation?
- Mechanism of benefit: Suppress viral replication?
- Strength of evidence of effectiveness for prevention vs treatment Risk of harm
- Secondary benefits from use of the supplement i.e. reduction of chronic pain
- Is it likely you may have a deficiency of this substance already?
For those with no symptoms and the assumption they do not currently have the COVID-19 infection,
Safe, inexpensive interventions which have a sound biological rationale should be prioritized for trial use in the current context of the global health pandemic i n which there are no definitive measures to prevent or reduce the mortality of the disease.
Consider a regimen that includes multiple products with different proposed mechanism of action. The following list represents a brief summary. Please read further down the page to gain more information on each of these substances including dosing, product information, precations and, when available, follow the link to the substances dedicated web page for more in-depth information on the individual substance. Many of the substances here already have individual web pages on my website dedicated to describing their potential pain benefits, even if their immune benefits against COVID-19 have not previously been explored here. This is a work in progress – please return soon for frequent updates on the information presented here.
(1) Zinc – Zinc may have antiviral properties and reduce symptoms of respiratory viral infections as demonstrated with cold virus infections. Zinc is not stored in the body so it must be ingested on a regular basis. It’s rare for people in industrialized countries to be seriously deficient in zinc although is not uncommon to have slightly low levels of zinc. The NIH indicates that 20%–25% of older adults have inadequate zinc intakes.
(2) Vitamin C – Vitamin C has good evidence for its supportive role in immune function and is popularly thought to be protective against respiratory viral infections though evidence remains incomplete. Deficiency of Vitamin C is unlikely, BUT, having optimal blood levels of Vitamin C may not be likely depending on one’s diet and intake of fruits and vegetables regularly. Vitamin C is not stored in the body so it must be ingested on a regular basis.
Vitamin C has been shown to have beneficial effects in different types of viral infections including:
- Inhibiting virus entry into cells
- Inhibition of early stage viral replication
- Interfering With DNA and RNA Polymerases
Vitamin C exerts its antiviral properties by supporting lymphocyte activity, increasing interferon-α production, modulating cytokines, reducing inflammation, improving endothelial dysfunction, and restoring mitochondrial function. Vitamin C may also be directly viricidal. There have been a growing number of case reports of virus-related acute respiratory distress syndromes (ARDS) indicate successful treatment with intravenous high doses of Vitamin C
Quercetin with Vitamin C
Quercetin has a broad range of antiviral properties which can interfere at multiple steps of the COVID-19 infection: virus entry into cells, virus replication and viral protein assembly These therapeutic benefits can be enhanced by the co-administration of vitamin C. Furthermore, based on their lack of severe side effects and low-costs, the combined administration of these two compounds for both the prophylaxis and the early treatment of respiratory tract infections, especially including COVID-19 (see below for more information on vitamin C and quercetin).
(3) Vitamin D – Vitamin D is purported to support immune function and may reduce viral replication. Vitamin D deficiency is of epidemic proportion in this country and more likely in the obese population. Overall, the correlation between low vitamin D levels and mortality from COVID-19 is statistically significant. In other words, people with low vitamin D levels have a greater risk of dying when infected with COVID-19. Additionally, it likely offers benefit in chronic pain.Dosing of vitamin D ideally should be guided by blood levels, with optimal levels 50-80 ng/ml. In the absence of blood levels to guide dosing, a daily dose of 5,000 IU (125mcg)/day is recommended.
(4) Curcumin – Curcumin is the king of anti-inflammatories and has the greatest body of evidence for its effectiveness against inflammation, It is a NRF2 activator (see below). Absorption of basic curcumin is poor so one should consider a liposomal formulation. Additionally, it likely offers benefit in chronic arthritis pain.
(5) Palmitoylethanolamide (PEA) – PEA has excellent evidence as an neuroanti-inflammatory and some evidence it may improve recovery from viral respiratory infections. Additionally, it offers benefit in chronic nerve pain.
Dosing: 600 mg 2-3 times a day
(6) Plant-based polyphenols (Resveratrol, Green Tea etc.) – These compounds all seem to offer similar mechanisms of action and similar benefits. They are NRF2 activators and reduce inflammation. While there are no optimal levels of dietary intake established for any of them, they are all found in fruits and vegetables. Supplementation with these might be encouraged especially in those who do not eat a lot of fruits and vegetables in their diet. Resveratrol may have the highest level of evidence.
For those with symptoms and expectation they have the COVID-19 infection
OR
For those with recent significant exposure to someone testing positive for COVID-19
Consider continuing the same regimen as above, but for advanced protection add:
(1) Dual Antihistamine Therapy:
Antihistamines are most commonly of two types: H1 antihistamines and H2 antihistamines:
H1 antihistamines are used to treat allergic symptoms including hives and itching. Common H1 antihistamines include Benadryl (diphenhydramine), Zyrtec (cetirizine) and Xyzal(levocetirizine).
H2 antihistamines are used to treat heartburn, gastric reflux (GERD), gastritis and ulcers. Common H2 antihistamines include Pepcid® (famitodine), Axid (Nizatidine) and Tagamet (cimetidine).
Histamine receptors are widely distributed in the body in nerves and smooth muscle (vascular, gastric and bronchial) and are found in the blood, lungs, heart and immune system. In the case of COVID-19, “dual-histamine receptor blockade,” using both H1 and H2 antagonists in combination is advised as a means of increasing effective histamine blockade and reduce the likelihood of serious illness, particularly related to overwhelming lung dysfunction due to cytokine storm caused by massive release of histamines and other active peptides.
Unfortunately. there are currently no FDA-approved H1-H2 receptor combination drugs available so it is necessary to take both H1 and H2 antihistamines individually in combination with each other, called “Dual-histamine Receptor Blockade.”
Dual-histamine Receptor Blockade
The combined use of both H1 and H2 antihistamines, or “dual-histamine receptor blockade,” is recommended to consider as advanced protection.
Preferred antistamine combination:
Zyrtec® (cetirizine) OTC – 10 mg twice a day; plus
Pepcid® (famitodine) OTC – 20 mg twice a day
Other H1 antihistamines include:
(a) Xyzal (levocetirizine) OTC – 2.5-5mg once a day;
(b) Benadryl (diphenhydramine) OTC – 25-50mg 2-4 times/day;
(c) Atarax/Vistaril (hydroxyzine) Rx – 25-50mg 2-4 times/day;
Side effects potentially associated with H1 antihistamines include:
Dry mouth, fatigue, drowsiness, sedation and dizziness. Difficulty urinating may occur in those with enlarged prostate.
Other H2 antihistamines include:
(a) Axid (Nizatidine)
(b) Tagamet (cimetidine)
Side effects potentially associated with H2 antihistamines include: Headache, constipation, or diarrhea
Dual-histamine Receptor Blockade and COVID-19 Studies
When the combination of cetirizine (10 mg twice a day) and famitodine (20 mg twice a day) was studied and reported in a June 2020 publication, it was found this combination exhibited beneficial reductions in inpatient mortality and symptom progression. While this was a small “proof-of-concept” study that needs further research to confirm their findings, the authors concluded this dual combination is safe and effective in management of COVID-19.
Additionally, another COVID-19 study evaluating famitodine alone in doses ranging from 10 to 40 mg found a reduced risk of death and intubation. In comparison, use of proton pump inhibitors (that reduce gastric acid independent of a histamine mechanism) were not associated with reduced risk of death or intubation, reinforcing the conclusion that the famitodine benefit is histamine-mediated.
(2) Quercetin with Vitamin C
Combining quercetin with vitamin C may be especially protective and is highly recommended.
Proposed dosing:
Prophylaxis and mildly symptomatic cases of COVID-19: Quercetin (quercetin aglycone): 250-500 mg Twice a day
Vitamin C (either D- or L-ascorbate but not dehydroascorbate): 500 mg Twice a day
Severely symptomatic cases of COVID-19:
Quercetin (quercetin aglycone): 500 mg Twice a day
Vitamin C (either D- or L-ascorbate but not dehydroascorbate): 3000 mg 4x/day a day
(2) Palmitoylethanolamide (PEA) – PEA has evidence that it may reduce symptoms of viral respiratory infections such as colds and flu and that may hasten recovery from viral respiratory infections. It has been shown to reduce inflammation, including suppressing the NLRP3 inflammasome associated with the cytokine storm or COVID-19. Additionally, it offers benefit in chronic nerve pain.
Dosing: 600 mg 2-3 times a day
(3) Elderberry – Elderberry has been used extensively to prevent viral respiratory infections like colds and flu but the evidence that it prevents these infections is very weak. However, the evidence that Elderberry extracts reduce the symptoms and time course of these infections is also weak, it is promising nevertheless and its use should be considered by those with symptoms of upper respiratory infection, COVID or non-COVID.
Sambucol Dosing:
2 tsp (10ml) once a day for preventative management
1 tbsp (15ml) four times daily for treatment of influenza-like symptoms
Evidence-based Medicine (EBM)
In the medical community, evidence-based medicine (EBM) is put forth as the standard of care, but unfortunately it is not always as feasible as desired and it is recognised that not all practices can be based on strong evidence. The fundamental question is, ‘How good is the evidence?’ EBM uses the best available evidence to inform decisions and considers patients’ values and preferences. Experts responsible for converting evidence into guidelines must still rely substantially on judgement, leaving open the question of how much evidence is needed to claim an evidence base for medical practice.
Clearly, there will never be empirical support for all decisions in the complex world of medicine, but the situation today is quite short of that goal. Relatively little evidence exists for improving many health outcomes, pain management and the CDC’s “Pain Management Guidelines” being a perfect example. Every effort will be made to assess the evidence available for the following substances to allow the reader the best opportunity to make informed decisions regarding their health care, particularly in this time of pandemic.
Strength of Evidence as Defined by IFM:
Conditional
Clinical experience and/or expert opinion and/or conflicting studies; biological mechanism at least partly explained.
Limited
One study showing correlation between intervention and outcome; compelling ATMs and/or PCFs; biological mechanism at least partly explained.
Moderate
Two independent studies showing a correlation between intervention and outcome; biological mechanism at least partly explained.
Strong
Two independent studies showing acorrelation between intervention and outcome; biological mechanism fully explained or partly explained and having one additional correlative study.
Antiviral Agents
Currently, there is no approved medication that is effective for most viral infections and vaccination is limited to just a few viral diseases such as hepatitis A & B, mumps, zoster and varicella. Classic antiviral drugs such as interferon and ribavirin which are effective against most viruses in a laboratory setting are often ineffective in patients. Additionally, these medications are often costly, ineffective due to viral resistance and associated with many side effects. With that in mind, the medical community is evaluating natural plant-based pharmacotherapy as an alternative for treating viral diseases.
Various plants have been used in traditional medicine since ancient times and are known for their antiviral activity and therapeutic benefits. Compounds with antiviral activity are present in many plants and a variety of these plant-based chemicals (phytochemicals) have now been identified, isolated and purified. These bioactive phytochemicals include alkaloids, terpenes, flavonoids, glycosides, and proteins. Examples of these that are explored below include curcumin, quercetin and resveratrol.
One of the major challenges in applying antiviral phytochemicals for therapeutic use is overcoming the multiple biological barriers that limit the ability of these agents to successfully reach their intended site(s) of action. First, if taken orally, these agents must be absorbed from the gastrointestinal tract to be delivered to the blood stream and made available to tissues. Many phytochemicals such as curcumin are poorly absorbed in their natural state. Also, due to the nature of viral infection disease processes that involve attacking cellular DNA and RNA, these phytochemicals must be delivered to the intracellular space to be effective.
Research into drug delivery systems is still in its infancy but a variety of approaches are being investigated to facilitate getting the medicine to its intended target. New delivery methods are constantly being explored and introduced including phytosomes, nano-particles, hydrogels, microspheres, transferosomes and ethosomes, self-microemulsifying drug delivery systems (SMEDDS), self-nanoemulsifying drug delivery systems (SNEDDS) and others, mostly beyond the scope of this page. But these delivery technologies may offer benefits over older phytochemical drug formulations due to enhanced solubility and oral absorption, systemic bioavailability, safety, delayed metabolism, and better overall antiviral activity.
Currently the use of phytosomes and liposomes, in which a phytochemical is coated with a compound that enhances absorption, has improved many products’ effectiveness. Some of the recommended phytochemicals below are now available as liposomal formulations including curcumin, quercetin and resveratrol. Nanotechnology, allowing for extreme microformulations of phytochemicals, is promising as well and some new nano-based products are now becoming available. Other new strategies for the delivery of poorly soluble phytochemicals and plant extracts are being introduced that offer improved pharmacokinetic and clinical outcomes.
While a thorough review of which products are best is beyond the scope of this page, the reader is encouraged to explore products that incorporate some of these newer technologies to identify the most effective means of benefiting from a chosen substance.
For a quick summary of recommended supplements, per IFM:
Botanical and Nutraceuticial Recommendations for Patients (A Checklist)
The following snapshots of therapeutic substances is based primarily on IFM publications. Additional research is listed at the bottom of this page and will be reviewed in further depth in the near future – working on it every day. As a substance has been explored in more depth, a link with be provided for that substance to a separate web page that will explore that substance in more detail.
ELDERBERRY (Sambucus nigra)
Elderberry is found in many medicinal products and is currently one of the most-used medicinal plants worldwide as an antiviral herb. The flowers and berries (blue and black only) are used most often medicinally. They contain flavonoids, which have been found preclinically to possess a variety of biochemical and pharmacological actions, including antioxidant and immunologic properties.
For more information on Elderberry, see: Elderberry
Elderberry benefits with common cold and influenza.
A meta-analysis published in 2019 evaluating a total of 180 participants concluded that supplementation with elderberry was found to substantially reduce upper respiratory symptoms in routine cases of the common cold and influenza. While the extent of black Elderberry’s antiviral effects are not fully known, antiviral and antimicrobial properties have been found in Elderberry extracts.
Elderberry benefits with other corona viruses
Elderberry has been studied in other corona viruses including Human coronavirus NL63 (HCoV-NL63), one of the main circulating HCoVs in the fall and winter worldwide, causes respiratory tract illnesses like runny nose, cough, bronchiolitis and pneumonia and was responsible for a recent severe respiratory illness outbreak in a long-term care facility in Louisiana in winter 2017. Among the 20 cases aged from 66 to 96 in this outbreak, 6 patients developed pneumonia and had to be hospitalized and 3 patients died.
There is preclinical evidence that elderberry inhibits replication and viral attachment of Human coronavirus NL63 (HCoV-NL63),26 which although different than COVID-19, is also a member of the same coronavirus family. Sambucus appears most effective in the prevention or early stage of corona virus infections. One small study published in 2001 found that Sambucus may significantly increase inflammatory cytokines, including IL-1 beta, TNF-alpha (44.9 fold), IL-6 and IL-8. The authors suggested therefore that Sambucol Elderberry Extract and its formulations might be beneficial to the immune system activation and in the inflammatory process in healthy individuals or in patients with various diseases. However, other authors argue that because of this immune system activation, Sambucol should be discontinued when symptoms of infection begin (or a positive RNA test).
Benefits
Prevention of infection with respiratory viruses
Dose
Per IFM: 500 mg per day (of USP standard of 17% anthocyanosides)
Sambucol Dosing:
2 tsp (10ml) once a day for preventative management
1 tbsp (15ml) four times daily for treatment of influenza-like symptoms
Product variability
Different elderberry products may vary widely in their quality based on their bioactive constituent content. Factors that come into play included the species variety, the source of extract, be it flower, stem or fruit, the conditions where it was grown and variables related to the product’s storage.
With natural products it is often not clear what the optimal doses are to balance effectiveness and safety. Preparation of products may vary from manufacturer to manufacturer, and from batch to batch within one manufacturer. Because it is often not clear what the active component(s) of a product is, standardization may not be possible, and the clinical effects of different brands may not be comparable. Therefore, along with the notes above outlining the variability amongst elderberry plants and plant parts, caution is advised in the choice of product and it is recommended to use only standardized products such as Sambucol.
Available Products
“Sambucol” (Razei Bar Industries, Jerusalem, Israel) This standardized elderberry product is a syrup containing elderberry juice, raspberry extract, glucose, citric acid, and honey), is a 38% standardized black elderberry extract containing three flavonoids.
“Sambucol Active Defense” contains a 38% standardized black elderberry extract, plus vitamin C, zinc, propolis, and a proprietary blend of Echinacea angustifolia and Echinacea purpurea.
Rubini BioFlavonoides Elderberry Extract (Zertifikationsnr: IT-CDX 5987) is a monotherapy derived from elderberries, with no additives from animals or col- orings, and no preservatives
Sinupret (Quanterra Sinus Defense) is an herbal mixture of 18 mg of flos Sambucus nigra (elderflower), 18 mg of herba Verbenae off. (vervain wort), 6 mg of radix Gentianae luteae (gentian root), 18 mg of flos Primulae veris cum
Mechanism of Action
A placebo controlled, double-blind study of Sambucol documented a rapid recovery from influenza and associated with the inhibition of replications of multiple strains of the flu virus. In this study the mechanism of action is believed to be rendering viruses nonfunctional by staining and coating them.
Elderberry modulate cellular defense and repair mechanisms and viral-induced pathological cellular processes. Caffeic acid significantly inhibited the replication of HCoV-NL63 and specifically blocked virus attachment. Caffeic acid has also been reported to possess antiviral activity against hepatitis B and C viruses, influenza A virus, and herpes simplex virus. Other phenolic acid constituents found in elderberry, chlorogenic acid and gallic acid, have also been demonstrated to suppress replication of influenza A virus, enterovirus 71 and hepatitis B and C viruses.
Quercetin, also present in elderberry, promotes viral eradication or inactivation by inhibiting viral replication and reduces viral-induced pathological cellular processes (see below).
Pharmacology
The flowers and leaves contain flavonoids, including quercetin (up to 3%), rutin, hyperoside and anthocyanins, as well as essential oils that are responsible for the muscat aroma characteristic of elder flowers. In the elderberry stems a pre-clinical study evaluating six phenolic acid constituents in a Sambucus FormosanaNakai stem ethanol extract, caffeic acid, chlorogenic acid and gallic acid sustained anti-HCoV-NL63 activity that was ranked in the following order of virus yield reduction: caffeic acid > chlorogenic acid > coumaric acid. The results revealed that Sambucus FormosanaNakai stem ethanol extract displayed strong anti- HCoV-NL63 potential and the caffeic acid had the highest anti-HCoV-NL63 potency and could be the vital component with anti-HCoV-NL63 activity.
Strength of evidence: Strong
Risk of Harm: Mild; caution w/autoimmune disease; uncooked/unripe plant parts toxic; USDA rated as Generally Recognized As Safe (GRAS).
PALMITOYLETHANOLAMIDE (PEA)
PEA is a naturally occurring anti-inflammatory substance manufactured by the body and found in foods such as dairy products. At dosing with 600 mg three times daily for up to three weeks, PEA provided significantly favorable outcome in five of six double blind placebo-controlled trials evaluating acute respiratory disease due to influenza. PEA has been strongly encouraged for its potential benefit in treating chronic pain on multiple levels. It has been shown to reduce symptoms of neuropathic pain (nerve pain) such as the burning and electric or tingling associated with diabetic neuropathy. Furthermore, it may reduce the progression of central sensitization, the process in which the perception of pain and other noxious stimuli becomes magnified over time. It may reduce the build-up of tolerance to some opioids and it may work in synergy with cannabis products to enhance their therapeutic benefits. PEA is also noted to be virtually without side effects.
For more information: Palmitoylethanoamide (PEA)
Benefits
Prevention and treatment of infection with respiratory viruses
Additionally, PEA has multiple benefits related to pain, reducing neuropathic pain, central sensitization
Dose
300 mg po twice a day to prevent infection;
600 mg po three times a day for two weeks to treat infection
Available Products
“Discomfort Relief”
Accurate Clinic’s Supplement Store or, call Toll-Free: 877-846-7122 (Option 1) – Available only for patients of Accurate Clinic
Mechanism of Action
Supports cellular defense and repair mechanisms and suppresses viral-induced pathological cellular processes. There are multiple mechanisms of action associated with PEA, from inhibition of TNF-alpha and NF-kB to mast cell stabilization. In influenza, it is thought that PEA works by suppressing the potentially fatal cytokine storm. Other proposed mechanisms of action include interacting with the body’s endocannabinoid system, allowing it to possibly enhance the therapeutic benefits of THC and other cannabinoids.
Strength of evidence: Conditional (treatment); Strong (prevention)
Risk of Harm: Minimal. The FDA rates PEA as a food.
CURCUMIN
Curcumin is considered the grandfather of antioxidants and anti-inflammatories. It has been used for arthritis and chronic pain for centuries. Its benefits for supporting the immune system are being explored.
For more information: Curcumin
Benefits: Prevention and treatment of infection with respiratory viruses
Dose: 500-1,000 mg twice a day (of absorption-enhanced curcumin such as phytosomal)
Available Products: Meriva (phytosomal curcumin)
Accurate Clinic’s Supplement Store or, call Toll-Free: 877-846-7122 (Option 1) – Available only for patients of Accurate Clinic
Mechanism of Action
Curcumin has been shown to modulate the NLRP3 inflammasome and evidence suggests that curcumin can target the COVID-19 main protease to reduce viral replication.
Strength of evidence: Conditional
Risk of Harm: Mild
QUERCETIN
Quercetin, found in onions and apples, has a tremendous amount of literature that suggests that quercetin supplementation may promote antioxidant, anti-inflammatory, antiviral, and immunoprotective benefits.
Anti-inflammatory
Quercetin is a NRF2 activator and may offer signficant benefits in reducing inflammation. The anti-inflammatory benefits of quercetin has beem well established and it has been suggested quercetin is the key mediator in the cardiovascular protective element of the “Mediterranean” diet. Quercetin, along with othr flavonoids, has also been shown to stabilize mast cells.
Antiviral
It has has been shown to have antiviral effects against both RNA (e.g., influenza and coronavirus) and DNA viruses (e.g., herpesvirus) and may diminish the replication of many viruses: highly pathogenic influenza virus, rhinovirus, dengue virus type 2, HSV-1, poliovirus, adenovirus, Epstein-Barr virus, Mayaro virus, Japanese encephalitis virus, respiratory syncytial virus, and Hepatitis C virus. Quercetin has been shown to have inhibitory activity against SARS-CoV.
Quercetin Synergy with Vitamin C
Quercetin and ascorbic acid co-administration represents an experimental strategy with current evidence supporting their use for prophylaxis and treatment of several respiratory viruses, including SARS-CoV-2 (COVID-19). Vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties. The blockage of virus entry represents a key strategy and quercetin impedes viral membrane fusion for both influenza and SARS-Cov. Quercetin also targets viral polymerases and may disrupt replication via the inhibition of reverse transcriptase enzymes.
Vitamin C prevents the spontaneous degradation of quercetin and it also has the capacity to recycle quercetin, increasing its efficacy. They have both also consistently shown excellent safety profiles, arguing strongly for a favorable risk to benefit ratio.
Quercetin Synergy with Zinc
Quercetin also chelates, or binds, to zinc and transports it into cells which could, theoretically, enhance the anti-viral actions of zinc.
For more information: Quercetin, NRF2 Activators
Benefits: Reduction of viral respiratory infection symptoms
Dose: Regular Quercetin: 1 gm twice a day; Quercetin phytosome: 250-500 mg twice a day
Available Products:
Accurate Clinic’s Supplement Store or, call Toll-Free: 877-846-7122 (Option 1) – Available only for patients of Accurate Clinic
Mechanism of Action
Promotes viral eradication or inactivation by inhibiting viral replication and reduces viral-induced pathological cellular processes including:
- Suppression of NLRP3 inflammasome activation
- Promote resolution of collateral damage and restoration of function by promoting mast cell stabilization (anti-fibrotic)
- Modulation of signaling pathways that are associated with post-transcriptional modulators affecting post-viral healing.
Strength of evidence: Moderate
Risk of Harm: Mild. Oral supplementation with quercetin up to 1 g/day for 3 months has not resulted in significant adverse effects.
GREEN TEA (EPIGALLOCATECHIN GALLATE – EGCG)
Green tea contains multiple catechins, including (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG). Catechins are natural phenols, part of the chemical family of flavonoids and are very abundant in tea, cocoa and berries. Catechins are potent antioxidants. Green tea catechins are oxidized and dimerized during the manufacture of black tea and oolong tea to form orange-red pigments, theaflavins. Studies indicate tha the antioxidant capacity of theaflavins meet or exceed those of green tea catechins. EGCG has many purported health benefits including protection against degenerative diseases and has been shown to have antitumorigenic, antioxidative, hypoglycemic, antimutagenic, antimicrobial antiviral anti-inflammatory and immunomodulatory properties.
Benefits
Prevention and treatment of infection with respiratory viruses. EGCG has also been shown to prevent influenza in healthcare workers. Recent research, including a 2021 publication, “EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection,” provides compelling evidence suggesting that EGCG may reduce acute lung injury in COVID-19 disease by regulating inflammatory cytokines and may offer profound benefits in pre- or post-COVID-19 disease stages.
Dose: Drink 4 cups of green tea daily or take green tea extract 225 mg per day
Available Products
Green Tea extract (phytosomal)
Accurate Clinic’s Supplement Store or, call Toll-Free: 877-846-7122 (Option 1) – Available only for patients of Accurate Clinic
Mechanism of Action
In addition to modulating the NLRP3 inflammasome, EGCG potentially targets the COVID-19 main protease (Mpro) and SARS-CoV-2 S protein to reduce viral replication. EGCG has been found to have antiviral activity against a wide range of DNA and RNA viruses, especially in the early stages of infection by preventing viral attachment, entry and membrane fusion with human cells thus inhibiting the virus’s ability to cause disease. EGCG has been demonstrated to impact Zika virus, Dengue virus, influenza A virus H1N1, human immunodeficiency virus [HIV] and Ebola virus. Also, like quercetin, EGCG also chelates, or binds, to zinc and transports it into cells which could, theoretically, enhance the anti-viral actions of zinc.
Strength of evidence: Conditional
Risk of Harm: Significant, but rare toxic to the liver. Likely to be avoided in those with liver disease.
RESVERATROL
Resveratrol is a polyphenol found in grapes, peanuts, red wine, strawberries, blueberries and blackberries. It has been shown to have many beneficial health effects.
Benefits
Prevention and treatment of infection with respiratory viruses including influenza and it may have activity against MERS Corona virus.
Dose
100-150 mg per day
Available Products
Accurate Clinic’s Supplement Store or, call Toll-Free: 877-846-7122 (Option 1) – Available only for patients of Accurate Clinic
Mechanism of Action
Favorably modulates viral-induced pathological cellular processes and suppresses activation of NLRP3 inflammasome.
Strength of evidence Conditional
Risk of Harm Mild
N-ACETYLCYSTEINE (NAC)
N-acetylcysteine, a compound found naturally in the body, is converted to a chemical called glutathione, a powerful antioxidant which prevents damage to important cellular components caused by reactive oxygen species such as free radicals. NAC has been shown to be protective against influenza in animal studies and a six-month clinical study of 262 elderly people showed that those receiving 600 mg NAC twice daily experienced significantly fewer influenza-like episodes and days of bed confinement as opposed to those receiving placebo.
Benefits Reduce progression from colonization to illness and reduce the severity and duration of acute symptoms
Dose 600-900 mg twice a day
Available Products
Accurate Clinic’s Supplement Store or, call Toll-Free: 877-846-7122 (Option 1) – Available only for patients of Accurate Clinic
Mechanism of Action
Favorably modulate cellular defense and repair mechanisms and may restore levels of glutathione when depleted.
Strength of evidence Limited
Risk of Harm Mild
VITAMIN D
Vitamin D, a steroid hormone, plays an important role in the immune system and evidence suggests vitamin D supplementation may help prevent upper respiratory infections. Recent research strongly suggests that Vitamin D may play an important role in the immune response to COVID-19. It is evident that the role of Vitamin D supplementation in antiviral immunity against respiratory infections is likely to depend on the vitamin D status of the individual. It has been shown that people who are deficient in Vitamin D appear to be at greater risk for dying if they become infected with the COVID-19 virus, SARS CoV-2. Vitamin D is required to maintain the stability of mast cells and deficiency of vitamin D results in mast cell activation, a contributing factor in the development of cytokine storm and pulmonary failure. For this reason it is strongly advised during this time of pandemic that people maintain good levels of Vitamin D. (See Vitamin D).
Benefits
Vitamin D may reduce progression from colonization to illness and reduce the severity and duration of acute symptoms and complications. A recent study determined that the risk of severe COVID-19 cases among patients with severe Vitamin D deficiency was 17.3%, whereas the equivalent figure for patients with normal Vitamin D levels was 14.6% (a reduction of 15.6%). n fact, there was about an eightfold higher risk of having severe illness among those who developed COVID-19 with vitamin D deficiency compared with those who had sufficient vitamin D levels. In another study, the risk of having a severe illness was almost twenty times higher if serum vitamin D levels were deficient (<20). Studies suggest this potential benefit may be attributed to Vitamin D’s ability to suppress the adaptive immune system and maintain the stability of mast cells, regulating cytokine levels and thereby reducing the risk of developing severe COVID-19 associated with cytokine storm. Dose The dose of Vitamin D (the D3 form) will depend on the individual’s blood levels. In the absence of a known blood level, 5,000 IU per day is generally recommended. When one’s blood levels are less than 20-30 ng/ml, doses as high as 50,000 IU per week at least for a short course may be advised to raise blood levels to the optimum range. However, there is some controversy as to what the optimum level of vitamin D should be. The guidance IFM suggests is that a blood level in the range of >50 and < 80 ng/mL may help to reduce morbidity from COVID-19 infection.
Mechanism of Action
Vitamin D reduces the expression of inflammatory cytokines and increases immune cells (macrophage) function. It also stimulates the expression of potent antimicrobial peptides in neutrophils, monocytes, natural killer cells, and epithelial cells of the respiratory tract. Vitamin D increases anti-pathogen peptides through defensins and has a dual effect of suppressing superinfection. Vitamin D modulates viral-induced pathological cellular processes including reduction of cytokine expression and modulation of TGF beta.
It has been shown that Vitamin D decreases NLRP3 inflamasome activation and Vitamin D receptor activation reduces IL-1b secretion. However, 1,25(OH) vitamin D has also been found in some pre-clinical laboratory studies to increase IL-1b levels, and therefore some advise that it be used with caution and perhaps discontinued with symptoms of infection. Perhaps the reasonable approach would be to supplement with Vitamin D to maintain optimal blood levels and avoid excessive supplementation beyond that.
Strength of evidence Limited
Risk of Harm Mild
VITAMIN C
Vitamin C has long maintained a reputation for its supportive role in the prevention and treatment of colds and viral inections. Vitamin C has been used in hospital ICUs as a supplement to treat COVID-19 infection. While supporting evidence of vitamin C supplementation in the prevention and treatment of acute respiratory diseases is inconclusive, supplementation could benefit the individual with vitamin C deficiency. It has been reported that megadoses administration of Vitamin C before or after the appearance of flu symptoms may prevent and relieve some flu symptoms.
Benefits Prevention and treatment of infection with respiratory viruses and systemic infections.
Dose 1-3 grams per day
Mechanism of Action
Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. Also, Vitamin C reduces NLRP3 inflammasome activation.
Strength of evidence Strong
Risk of Harm Mild
VITAMIN A
Vitamin A is a micronutrient that is crucial for maintaining vision, promoting growth and development, and protecting epithelium and mucus integrity in the body. It also has anti-inflammatory properties and has a critical role in enhancing immune function and has demonstrated a therapeutic effect in the treatment of various infectious diseases. Despite vitamin A having an established roles in supporting the immune functions, there is inadequate evidence to support the supplementation benefit in healthy individuals for the prevention of acute viral respiratory infection. However, people with vitamin A deficiency are prone to the increased risk, greater severity, and impaired immune responses to viral infections, including the respiratory syncytial virus, measle virus, and influenza viruses. Vitamin A deficiency has been shown to affect all age groups, especially the malnourished, elderly, and chronically sick. However, children and women of reproductive age, particularly pregnant and breast-feeding women, represent the groups that are most at risk,
Benefits Prevention and treatment of infection with respiratory viruses.
Dose Up to 10,000-25,000 IU/day
Note: Excessive supplementation with Vitamin A can cause toxicity, especially at doses greater than 25,000 IU daily for more than 6 years or 100,000 IU daily for more than 6 months. Symptoms of chronic vitamin A toxicity include: blurry vision or other vision changes, bone pain, poor appetite, dizziness, nausea and vomiting, sensitivity to sunlight and dry, rough skin. Monitoring liver function tests for liver toxicity during Vitamin A supplementation, even at lower doses, may be advised.
Mechanism of Action
Vitamin A is involved in the development of the immune system and plays regulatory roles in cellular immune responses and humoral immune processes. The immune-supporting roles of vitamin A include the promotion of mucins and keratins, lymphopoiesis, apoptosis, cytokine expression, antibody production, and the enhanced functions of neutrophils, natural killer cells, monocytes or macrophages, T cells, and B cells. One study found that 25,000 IU daily for 4 months in 84 women resulted in lower serum IL-1b and IL-1b/ IL-4 ratios in obese women.
Strength of evidence Conditional
Risk of Harm Mild, in the absence of excessive doses; caution should be used in pregnancy
MELATONIN
Melatonin offers potential benefits for the treatment of COVID-19 and two recent published papers proposed the use of melatonin as a therapeutic agent in the treatment of patients with COVID-19. The age-related decline in melatonin production is one proposed mechanism to explain why children do not appear to have severe symptoms as frequently as do older adults.
Benefits Prevention and treatment of infection with respiratory viruses
Dose 5-20 mg per day at bedtime
Available Products
Accurate Clinic’s Supplement Store or, call Toll-Free: 877-846-7122 (Option 1) – Available only for patients of Accurate Clinic
Mechanism of Action
Melatonin has been shown to inhibit NFkB activation and NLRP3 inflammasome activation and may reduce the severity if COVID-19 disease. Melatonin also reduces oxidative lung injury and inflammatory cell recruitment during viral infections.
Strength of evidence Conditional
Risk of Harm Mild, including sedation
Luteolin
The flavone luteolin has broad antiviral properties and specifically binds to the surface spike protein of SARS-Cov-2 and inhibits entry of the virus into host cells. Furthermore, luteolin inhibits serine proteases, including, the SARS-CoV 3CL protease required for viral infectivity. Additionally, luteolin inhibits mast cells and has anti-inflammatory properties.
ZINC
There is a great deal of research indicating that zinc supports the body’s natural immune response and has strong anti-viral properties. Zinc may prevent coronavirus entry into cells and it appears to reduce the severity of coronavirus infection. But zinc deficiency is common, especially in older people, which can contribute to aging-related decline in immune function and impaired antiviral immunity, particularly to herpes simplex, common cold, herpes simplex virus, hepatitis C, and the human immunodeficiency virus (HIV). Zinc deficiency is associated with higher corticosterone levels which is indicative of hyperactivity of the stress system involving the brain (hypothalmus and pituitary gland) and the adrenal glands, the “HPA axis.” Hyperactivity of the HPA axis can lead to suppression of the immune system, leading to greater susceptibility to infection. Zinc supplementation supports aging immune systems, as well as healthy inflammatory and antioxidant responses.
For more information: Zinc
Benefits Zinc enhances the immune system, decrease viral growth and may reduce symptoms
Dose The recommended daily allowance (RDA) of zinc for adults is 8 – 11 mg/day, but doses from 15-30 mg/day up to 60 mg/day have been advised.
Note: Zinc nasal sprays may cause some people to lose their sense of smell.
Available Products
Accurate Clinic’s Supplement Store or, call Toll-Free: 877-846-7122 (Option 1) – Available only for patients of Accurate Clinic
Mechanism of Action
Strength of evidence Limited
Risk of Harm Mild
Ivermectin
Ivermectin has been described as a ‘Wonder drug,’ based on its history improving the nutrition, general health and wellbeing of people worldwide ever since it was first used to treat parasitic infections in humans in 1988. It is safe, well tolerated and can be easily administered. In addition to having antiparasitic effects, it also has potent anti-inflammatory properties and inhibits viral replication and has immunomodulation effects.
Ivermectin has already been approved for treatment for SARS-CoV-2 in a number of countries, including Peru and Northeastern Beni region of Bolivia. Close to 70 trials worldwide are currently testing the clinical benefit of ivermectin to treat or prevent SARS-CoV-2. Preliminary results from a recently completed study NCT04422561 evaluating asymptomatic family close contacts of confirmed COVID patients, revealed that two doses of ivermectin 72 h apart resulted in only 7.4% of 203 subjects reporting symptoms of SARS-CoV-2 infection, in stark contrast to control untreated subjects, of whom 58.4% reported symptoms, underlining ivermectin’s potential as a prophylactic.
A recent study demonstrated that Ivermectin-treated patients became SARS-CoV-2 negative significantly faster (median 4 compared to 15 days), had significantly shorter hospital stays (median 9 versus 15 days), and significantly lower mortality (0.9 vs 6.8 %). Ivermectin has also been recently reported to have a role in the treatment of post-covid-19 syndrome (long haulers), likely due to its anti-inflammatory properties.
Ivermectin has emerged as the “wonder drug” for prevention and treatment of COVID-19, with clinical benefit across the spectrum of all phases of the disease, i.e pre-exposure prophylaxis, post-exposure prophylaxis, during the symptomatic phase and during the pulmonary phase. In the recommended dosages, Ivermectin is remarkably safe but there is the potential for serious drug-drug interactions so careful prescribing is necessary. Although early studies are consistent with effectiveness, only the results from large randomised clinical trials will definitively establish Ivermectin’s appropriateness to treat or prevent SARS-CoV-2 infection. Additional, studies are urgently required to confirm these very impressive preliminary findings.
Ivermectin dosing
Ivermectin has been highly recommended for pre-exposure prophylactic treatment for individuals at high risk for serious outcomes with COVID-19. Recommended prophylactic dosing is 0.2mg/kg on day 1 and day 3, then one dose every 4 weeks.
Ivermectin has also been recommended for post-exposure prophylactic treatment for high risk individuals at a dose of 0.2mg/kg on day 1 and day 3.
Traditional Chinese Medicine (TCM)
Treatment of viral illnesses with Chinese herbal medicines has been recorded for a long time in Chinese history, and previous studies have shown that Chinese herbal medicines have great potential for preventing SARS transmission. Constitutents found in Chinese herbal medicines, readily available and generally of low toxicity, are being evaluated as potential strategies for treating COVID-19. For example, Qingfei Paidu Decoction (QFPD) and Ma Xing Shi Gan Decoction (MXSG) are traditional Chinese herbal medicines used for treating COVID-19 patients in China that have Glycyrrhizin as a major constituent. Compounds currently being evaluated include: curcumin (see above), quercetin (see above), Licorice Root (Glycyrrhizin), andrographolide, baicalin, patchouli alcohol, and luteolin.
Qingfei Paidu Decoction is derived from the combination of five classical prescriptions of TCM, namely Ma Xing Shi Gan Decoction (MXSG), Shegan Mahuang Decoction, Xiaochaihu Decoction and Wuling Powder. These classic prescriptions were recorded in ” Treatise on Febrile and Miscellaneous Diseases ” written by Zhang Zhong- jing in the Han Dynasty. Most of these are classic prescriptions for treating febrile diseases caused by cold pathogens. According to statistics, 214 confirmed COVID-19 cases were treated with Qingfei Paidu Decoction in four provinces. A three day course of treatment showed a total effective rate of more than 90%, of which more than 60% patients’ symptoms and imaging improved significantly, and 30% patients’ symptoms were stable without worsening.
A recently published systematic review of four randomized controlled trials (RCTs) and seven case-control studies (CCSs) of Integrated Traditional Chinese and Western Medicine on treatment of COVID-19 supported the early use of TCM in therapy of COVID-19 for mild cases to rapidly improve symptoms of fever, cough, shortness of breath, shorten hospitalization days and reduce progression of mild symptoms to critically illness.
LICORICE ROOT
Licorice root, commonly used in Traditional Chinese Medicine, is a plant product isolated from the traditional Chinese medicine licorice (Chinese name: Gan Cao). It has significant antiviral and bactericidal effects and a large number of studies have shown that it has a protective effect on lung inflammation. It showed promise for treating SARS-CoV by inhibiting viral adsorption and penetration. and recent studies suggest it may have therapeutic effects against SARS-CoV-2.
Benefits
Glycyrrhizin, a major constituent found in licorice root supports immune system function and reduces viral growth. In addition to inhibition of virus replication, glycyrrhizin inhibits adsorption and penetration of the virus—early steps of the replicative cycle.
Dose
200-400 mg (standardized to glycyrrhizin) daily in divided doses (short-term use <4 weeks)
ANDROGRAPHOLIDE
Andrographolide is the main active component isolated from the extract of the herb andrographis paniculata and has low cytotoxicity and anti-virus and immunity regulation activity. Previous studies have shown that andrographolide inhibits various virus infections including influenza A virus. Andrographolide binds well to key SARS-CoV-2 targets, indicating that andrographolide has potential effectiveness against SARS-CoV-2.
BAICALIN
Baicalin is a component of Scutellaria baicalensis Georgi (Chinese name: Huang Qin) and has low toxicity with a wide range of therapeutic effects, including antiviral activity against SARS-CoV. Due to the similarities between SARS-CoV and SARS-CoV-2, it is speculated that baicalin may also have an antiviral effect on SARS-CoV-2 and studies suggest that baicalin has potential for COVID-19 treatment.
Other Supplements
Garlic
In addition to the substances reviewed above, other agents have been suggested as having potential benefit include garlic (Allium sativum). Organosulfur compounds in garlic such as allicin activate innate immune cells but also have immunoregulatory and antiinflammatory actions, specifically suppressing inflammatory cytokines such as IL-6 and TNF-a.
Mushrooms
Extracts of Mycelium/fruiting body mushrooms* activate innate immunity and increase interferon production, while also exerting anti-inflammatory actions, specifically IL-1Ra – which inhibits the inflammatory effects of IL-1.
*Mushrooms include: Agaricus, Cordyceps, Enokitake, Amadou, Agaikon, Reishi, Maitake, Lion’s Mane, Chaga, Shiitake, Mesima, Birch Polypore, Pearl Oyster, Split Gill Polypore, Turkey Tail.
Other potential agents that may be helpful include Astragalus membranaceus, Beta Glucans and Chinese Skullcap. More information on these substances coming soon.
Diet, the Microbiome, Probiotics and Prebiotics
As introduced above, a person’s diet is the primary determinant of the types of bacteria that colonize their gut and it has been shown that some families of bacteria promote health and reduce inflammation whereas other families may impair health and contribute to inflammation. The anti-inflammatory diet that includes an abundance of fruits, vegetables and fiber, as noted above, promotes a healthy microbiome and enhances the immune system.
For example, a healthy anti-inflammatory diet should include at least five portions of fruit and vegetables each day to provide vitamins and flavonoids and other micronutrients. All main meals should contain some starchy carbohydrate preferably a wholegrain variety and two to three portions of meat or equivalent (for vegetarians) for protein.
The Mediterranean diet is highly regarded as a healthy and balanced anti-inflammatory diet. It has a beneficial fatty acid profile that is rich in both monounsaturated and polyunsaturated fatty acids, high levels of polyphenols, flavenoids and other antioxidants, high intake of fiber and other low glycemic carbohydrates, and relatively greater vegetable than animal protein intake. Specifically, olive oil, assorted fruits, vegetables, cereals, legumes, and nuts; moderate consumption of fish, poultry, and red wine; and a lower intake of dairy products, red meat, processed meat and sweets characterize the traditional Mediterranean diet.
Evidence is growing that the use of dietary supplements including prebiotics and probiotics can modify a person’s microbiome and potentially enhance the immune system amd offer protection against respiratory infections, possibly including COVID-19. Probiotics are defined as live micro-organisms that confer a health benefit to the host, including on the gastrointestinal tract, when administered in adequate amounts. Probiotics can stimulate the immune response by increasing antibody production. Research suggests that probiotics have a modest effect in reducing common colds and other respiratory viral infections. In particular, two families of bacterial probiotics appear to increase immune function, the Lactobacillus and Bifidobacterium strains, which are generally consumed as part of fermented foods, such as yogurts or dietary supplements. Studies suggest supplementing with these probiotics may reduce the severity or shorten the duration of respiratory infections.
Prebiotics are compounds in food that induce the growth or activity of beneficial microorganisms such as the Lactobacillus and Bifidobacterium bacteria strains. Supplementation with prebiotis along with probiotics may further enhance the potential support of the immune system as a means of protecting against a severe outcome with COVID-19.
The mechanisms by which the microbiome imparts health benefits remains incompletely understood. Lactic acid bacteria and Bifidobacteria secrete factors that reduce inflammation by downregulating NF-κB dependent gene expression, IL-8 secretion, and levels of macrophage-attracting chemokines. Lactic acid bacteria and Bifidobacteria have also been shown to directly downregulate T effector-mediated inflammatory responses while upregulating anti-inflammatory T regula- tory cell expression. Gut flora can also impact host immunity through epigenetic modifications, in which genes may be activated or inactivated with subsequent effects.
It should be emphasized, however, that the studies of the microbiome and the role of supplementing with probiotics and prebiotics is still in its infancy. Further research will be necessary to provide more specific recommendations regarding their use, particularly in regard to COVID-19. Recent journal publications are listed below to provide more information than provided here. In the future, additional summations will be available here to offer further knowledge and guidance.
Burdock root
Burdock root, used in Traditional Chinese Medicine to improve digestion, contains inulin, a natural prebiotic – a complex carbohydrate dietary fiber type of Fructo-Oligo-Saccharides (FOS). FOS are known to significantly increase bifidobacteria within the gastrointestinaI tract. Burdock root eaten as a food is considered safe.
Inflammasomes
Inflammasomes are intracellular multiprotein complexes that are part of the immune system responsible for the activation of inflammatory responses. Inflammasomes, found in immune cells including macrophages, release pro-inflammatory proteins called cytokines, substances that are secreted by cells of the immune system that impact the function of other cells.
In the severe acute respiratory syndrome coronavirus (SARS-CoV) [SARS] epidemic of 2002-2003, at least 8,098 human cases were laboratory-confirmed, with a fatality rate of 9.6%. It was determined that the SARS-CoV virus activates the NLRP3 inflammasome (the Nod-like receptor family, pyrin domain-containing 3) which regulates the secretion of proinflammatory cytokines interleukin 1 beta (IL-1β) and IL-18. It is believed that the recent COVID-19 pandemic, caused by the SARS-CoV-2 virus, also activates the NLRP3 inflammasome and this mechanism leads to the overwhelming collapse of lung function in severe cases.
Thet NLRP3 detects RNA viruses by sensing the cellular damage induced by viroporins, transmembrane pore-forming proteins, encoded by certain RNA viruses that alter membrane permeability to ions by forming membrane channels. In the case of SARS-CoV, viroporins open ion channels and activate the NLRP3 inflammasome. Both opening of ion channels and mitochondrial ROS (Reactive Oxidation Species) production are required for SARS-CoV 3a-mediated IL-1β secretion. These observations indicate that the SARS- CoV 3a protein disrupts intracellular ionic concentrations and causes mitochondrial damages, thereby activating the NLRP3 inflammasome.
The balance between reactive oxygen species (ROS) production and antioxidant defenses is essential for maintaining cellular balance and homeostasis. Under physiologic conditions, cells maintain redox balance through the generation and elimination of ROS. Mitochondria are a major source of cellular ROS, where O2− is generated by electron leakage in the electron-transport chain. When there is an over-abundance of ROS, the condition of oxidative stress is established which leads to cellular and tissue damage. In a recent study, treatment of macrophages with an antioxidant specific for mitochondrial ROS completely blocked IL-1β secretion. Similarly, IL-1β release induced by the SARS- CoV E and 3a proteins was significantly inhibited by the antioxidant.
See: Antioxidants and Oxidative Stress
Excessive ROS attack lipids, proteins, and DNA in cells, leading to severe and irreversible oxidative damage. Various antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx)) and Vitamins C and E eliminate ROS and maintaining redox homeostasis. This may be the role that the antioxidants such as resveratrol and others noted above may provide their benefit. Studies have shown that increased oxidative damage and mitochondrial dysfunction play a crucial role in a variety of conditions.
See: Mitochondrial Dysfunction
A Note of Caution:
Based on the integral role of inflammatory cytokines (especially IL-1B and IL-18) in the development of COVID-19 and “cytokine storm,” it has been advised by some to avoid high and regular use of the immunostimulatory agents which increase these cytokines. Therefore, in the absence of human clinical information, caution is warranted during symptoms of infection or positive test for COVID-19, with the following immune-activating agents due to preclinical evidence of increased IL-1B and/or IL-18 production in infected immune cells:
- Sambucus nigra (Elderberry) – (i.e. Elderberry may be used for prevention but should be stopped if any symptoms of infection appear.)
- Isolated polysaccharide extracts from medicinal mushrooms or mycelium
- Echinacea angustifolia and E. purpurea
- Vitamin D
Resources
Institute of Functional Medicine
- What is Functional Medicine?
- Top 6 Strategies for Managing Stress Around Infectious Disease – 2020
- The Institute for Functional Medicine COVID-19- Botanical and Nutraceuticial Recommendations for Patients (A Checklist)
- Boosting Immunity- Functional Medicine Tips on Prevention & Optimizing Immune Function During the COVID-19 (Coronavirus) Outbreak – 2020
- The Functional Medicine Approach to COVID-19- Virus-Specific Nutraceutical and Botanical Agents – 2020
- The Functional Medicine Approach to COVID-19- Additional Research on Nutraceuticals and Botanicals 5-2020
- COVID-19_Nutraceutical-and-Botanical-Recommendations-for-Patients_v4
Andrew Weil Center for Integrative Medicine
References
COVID-19 – Overviews
COVID-19 – Mast Cells & Dual Histamine Blockade
- Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome – 2020
- COVID‐19, pulmonary mast cells, cytokine storms, and beneficial actions of luteolin – 2020
- Dual-histamine receptor blockade with cetirizine – famotidine reduces pulmonary symptoms in COVID-19 patients – 2020
- Diagnosis of mast cell activation syndrome – a global “consensus-2” – 2020
COVID-19 – Immunothrombosis
- Preventing the development of severe COVID-19 by modifying immunothrombosis – 2020
- Clinical trials for the prevention and treatment of COVID‐19 – current state of play – 2020
- Cardiovascular Complications of COVID-19 – Pharmacotherapy Perspective – 020
- New Data and the Covid-19 Pandemic Mandate a Rethink of Antiplatelet Strategies in Patients With TIA or Minor Stroke Associated With Atherosclerotic Carotid Stenosis – 2020
- Is Acetylsalicylic Acid a Safe and Potentially Useful Choice for Adult Patients with COVID-19 ? – 2020
- Aspirin use reduces risk of death in hospitalized COVID-19 patients – 2020
- Aspirin Use is Associated with Decreased Mechanical Ventilation, ICU Admission, and In-Hospital Mortality in Hospitalized Patients with COVID-19 – PubMed 2020
Inflammation and Inflammasomes
- Inflammasomes – Mechanism of Action, Role in Disease, and Therapeutics – 2015
- NF-κB signaling in inflammation – 2017
- Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1β Production – 2016
- Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome – 2019
Nutraceuticals – Overviews
- New Concepts in Nutraceuticals as Alternative for Pharmaceuticals
- Examining the quality of evidence to support the effectiveness of interventions – an analysis of systematic reviews – 2016
- Diagnosis and treatment of novel coronavirus pneumonia based on the theory of traditional Chinese medicine – 2020
- Potential interventions for novel coronavirus in China – A systematic review – 2020
- Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic – 2020
- Enhancing immunity in viral infections, with special emphasis on COVID-19 – A review – 2020
- Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections – 2020
- EVMS_Critical_Care_COVID-19_Protocol
COVID-19 – CAM Treatment, Botanicals
- In the News: Coronavirus and “Alternative” Treatments | NCCIH – 2020
- Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1β Production – 2016
- Potential Inhibitor of COVID-19 Main Protease (Mpro) From Several Medicinal Plant Compounds by Molecular Docking Study – 2020
- Implication of Fructans in Health – Immunomodulatory and Antioxidant Mechanisms – 2015
- Fructose and Fructans: Opposite Effects on Health? – PubMed – 2015
- Antiviral effect of phytochemicals from medicinal plants – Applications and drug delivery strategies – 2020
- Andrew Weil Integrative considerations during the COVID-19 pandemic
- Essential Oils and Coronaviruses – 2020
- Phytochemical Analysis and in vitro Antiviral Activities of the Essential Oils of Seven Lebanon Species – 2008
- EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection – 2021
COVID-19 – Ivermectin
- Ivermectin, ‘Wonder drug’ from Japan – the human use perspective – 2011
- Ivermectin – a systematic review from antiviral effects to COVID-19 complementary regimen
- The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2? – 2020
- Ivermectin Moves Towards Mainstream
COVID-19 – SSRIs
- JAMA reports fluvoxamine as potential early treatment for COVID-19 | EurekAlert! Science News – 2020
- Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19 – 2020
CAM Treatment – Colds & Flu, Overviews
- Colds and Influenza – A Review of Diagnosis and Conventional, Botanical, and Nutritional Considerations – 2007
- Vaccines for the common cold – 2017
- Roles of Zinc Signaling in the Immune System – 2016
COVID-19 – Traditional Chinese Medicine
- Can Chinese Medicine Be Used for Prevention of Corona Virus Disease 2019 (COVID-19)? A Review of Historical Classics, Research Evidence and Current Prevention Programs – 2020
- A review of therapeutic agents and Chinese herbal medicines against SARS-COV-2 (COVID-19) – 2020
- Glycyrrhizin, an active component of liquorice roots, and replication of SARS‐associated coronavirus – 2003
- Pay attention to situation of SARS-CoV-2 and TCM advantages in treatment of novel coronavirus infection – 2020
- Chemical composition and pharmacological mechanism of Qingfei Paidu Decoction and Ma Xing Shi Gan Decoction against Coronavirus Disease 2019 (COVID-19)
- Efficacy and Safety of Integrated Traditional Chinese and Western Medicine for Corona Virus Disease 2019 (COVID-19) – a systematic review and meta-analysis
- Herbal medicine and pattern identification for treating COVID-19 – a rapid review of guidelines
Nutriceuticals – Curcumin
- Anti-infective Properties of the Golden Spice Curcumin – 2019
- Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF-κB signaling pathway – 2017
- Curcumin Suppression of Cytokine Release and Cytokine Storm – A Potential Therapy for Patients with Ebola and Other Severe Viral Infections – 2015
- Twenty-first century mast cell stabilizers – 2013
- Curcumin and Health – 2016
- Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy – 2015
- Curcumin, a constituent of curry, suppresses IgE-mediated allergic response and mast cell activation at the level of Syk – PubMed 2007
Nutraceuticals – Echinacea
- The Safety of Herbal Medicinal Products Derived From Echinacea Species: A Systematic Review – PubMed – 2005
- A Critical Evaluation of Drug Interactions With Echinacea Spp – PubMed – 2008
- Herbal Extracts Used for Upper Respiratory Tract Infections: Are There Clinically Relevant Interactions With the Cytochrome P450 Enzyme System? – PubMed – 2008
- Applications of the Phytomedicine Echinacea purpurea (Purple Coneflower) in Infectious Diseases – 2011
- Randomised, Double Blind, Placebo-Controlled Trial of Echinacea Supplementation in Air Travellers – 2011
- Echinacea for preventing and treating the common cold – 2015
- Echinacea Purpurea: A Proprietary Extract of Echinacea Purpurea Is Shown to Be Safe and Effective in the Prevention of the Common Cold – PubMed – 2016
- Immunomodulators Inspired by Nature – A Review on Curcumin and Echinacea – 2018
- Antiviral Potential of Medicinal Plants Against HIV, HSV, Influenza, Hepatitis, and Coxsackievirus: A Systematic Review – PubMed – 2018
- Fructans as Immunomodulatory and Antiviral Agents – The Case of Echinacea – 2019
- Structure of Mpro from COVID-19 virus and discovery of its inhibitors – 2020
Nutraceuticals – Elderberry
- Elderberry Flavonoids Bind to and Prevent H1N1 Infection in Vitro – PubMed – 2009
- Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses – 2011
- An Evidence-Based Systematic Review of Elderberry and Elderflower (Sambucus Nigra) by the Natural Standard Research Collaboration – PubMed – 2014
- The Pathogenesis and Treatment of the `Cytokine Storm’ in COVID-19 – 2020
- Black Elderberry (Sambucus Nigra) Supplementation Effectively Treats Upper Respiratory Symptoms- A Meta-Analysis of Randomized, Controlled Clinical Trials – 2019
- A Review of the Antiviral Properties of Black Elder (Sambucus Nigra L.) Products – 2017
- Antiviral activity of Sambucus FormosanaNakai ethanol extract and related phenolic acid constituents against human coronavirus NL63 – 2019
- Astragalus Root and Elderberry Fruit Extracts Enhance the IFN-β Stimulatory Effects of Lactobacillus acidophilus in Murine-Derived Dendritic Cells – 2012
- A Systematic Review on the Sambuci Fructus Effect and Efficacy Profiles – 2010
- Inhibition of microglial activation by elderberry extracts and its phenolic components – 2015
- Randomized Study of the Efficacy and Safety of Oral Elderberry Extract in the Treatment of Influenza A and B Virus Infections – 2004
- The Efficacy of Administering Fruit-Derived Polyphenols to Improve Health Biomarkers, Exercise Performance and Related Physiological Responses – 2019
- Impact of Frozen Storage on the Anthocyanin and Polyphenol Content of American Elderberry Fruit Juice – 2015
- Elderberry (Sambucus Nigra L.) Wine- A Product Rich in Health Promoting Compounds – 2010
- Effect of Harvesting Year and Elderberry Cultivar on the Chemical Composition and Potential Bioactivity- A Three-Year Study – 2019
- The Content of Selected Minerals, Bioactive Compounds, and the Antioxidant Properties of the Flowers and Fruit of Selected Cultivars and Wildly Growing Plants of Sambucus nigra L. – 2020
- The Phenolic Contents and Antioxidant Activities of Infusions of Sambucus nigra L – 2017
- The Effect of Sambucol, a Black Elderberry-Based, Natural Product, on the Production of Human Cytokines: I. Inflammatory Cytokines – PubMed – 2001
Nutriceutical – Green Tea (EGCG)
Nutriceutical – Pamitoylethanolamide (PEA)
Nutriceutical – Probiotics
- Probiotics in respiratory virus infections – 2014
- Prevention of respiratory syncytial virus infection with probiotic lactic acid bacterium Lactobacillus gasseri SBT2055 – 2019
- Probiotics and Paraprobiotics in Viral Infection – Clinical Application and Effects on the Innate and Acquired Immune Systems – 2018
- Dietary Fiber Confers Protection against Flu by Shaping Ly6c– Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism – 2018
- Influence of diet on the gut microbiome and implications for human health – 2017
- Enhancing immunity in viral infections, with special emphasis on COVID-19 – A review – 2020
Nutriceutical – Quercetin
- Quercetin and Vitamin C – An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19) – 2020
- Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans – 2012
- Quercetin Inhibits the Production of IL-1β-Induced Inflammatory Cytokines and Chemokines in ARPE-19 Cells via the MAPK and NF-κB Signaling Pathways – 2020
- Nrf2-interacting nutrients and COVID-19 – time for research to develop adaptation strategies – 2020
- Impact of polyphenols on mast cells with special emphasis on the effect of quercetin and luteolin – 2018
Nutriceutical – Vitamin D
- Vitamin D – NHS.UK
- Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19) – 2020
- The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients – 2020
- LARGE, SINGLE-DOSE, ORAL VITAMIN D SUPPLEMENTATION IN ADULT POPULATIONS – A SYSTEMATIC REVIEW – 2014
- Vitamin D supplementation to prevent acute respiratory tract infections – systematic review and meta-analysis of individual participant data – 2016
- The Hidden Function of Vitamin D – 2016
- Vitamin D contributes to mast cell stabilization – 2017
Nutriceutical – Licorice Root
Nutriceutical – Zinc