Natural Ways To Boost Your Immune System During The PandemicBecause of the rapidly changing and novel nature of the COVID-19 infection we do not have any direct patient data or studies showing us how to treat this particular infection. We can extrapolate data from other coronavirus infections such as SARS (Severe Acute Respiratory Syndrome) from 2002 and MERS (Middle Eastern Respiratory Syndrome) from 2012 as well as the several mild strains of  Coronavirus that are one of the causes of the common cold. We can also use evidence-based medicine—from treating influenza viruses—to reason which herbs and supplements can help mitigate the expression and severity of this current coronavirus outbreak. In the absence of perfect information, the Institute of Functional Medicine (IFM), considered by most the authority in alternative medicine, has made recommendations on supplements that may help during this pandemic. Please note that these vitamin, supplement, and herbal strategies are not a panacea. Rather, they can help stimulate the immune system or have anti-viral effects, offering some protection that may very likely decrease overall symptoms, length of illness, or severity of illness. But, there is no guarantee. These strategies do not take the place of defending your sleep, eating a nutritious diet, exercising regularly, decreasing stress, stopping smoking, and limiting alcohol consumption significantly, etc. (and of course, washing your hands!)

We don’t recommend you take all these supplements.  But taking 2-3 might be a good idea considering the benign nature of these supplements. If you need any help obtaining supplements, just email us at info@bostonosteopathichealth.com or call 617-431-4451.  You can also try https://wellevate.me/ if you don’t have a username and password, contact us and we can help you.

Here are the IFM Recommended Interventions:

  1. QUERCETIN

Quercetin has been shown to have antiviral effects against both RNA (e.g., influenza and coronavirus) and DNA viruses (e.g., herpesvirus). Quercetin has a pleiotropic role as an antioxidant and anti-inflammatory, modulating signaling pathways that are associated with post-transcriptional modulators affecting post-viral healing.[8]

Intervention Quercetin
Suggested dose Regular: 1 gm po bid; phytosome 500 mg bid
Mechanism(s) of action against non-COVID-19 viruses Promote viral eradication or inactivation:[9],[10],[11],[12],[13]
•Inhibition of viral replication
Favorably modulate viral-induced pathological cellular processes:
•Modulation of NLRP3 inflammasome activation[5],[14],[15]
Mechanistically promote resolution of collateral damage and restoration of function:
•Modulation of mast cell stabilization (anti-fibrotic)
Outcomes data supporting their mitigating Reduction of symptoms
Strength of evidence Moderate
Risk of harm:[16],[17] Mild
  1. CURCUMIN

Curcumin has been shown to modulate the NLRP3 inflammasome,[5] and a preprint suggests that curcumin can target the COVID-19 main protease to reduce viral replication.[18]

Intervention Curcumin
Suggested dose 500-1,000 mg po bid (of absorption-enhanced curcumin)
Mechanism(s) of action against non-COVID-19 viruses Favorably modulate viral-induced pathological cellular processes:
•Modulation of NLRP3 inflammasome activation[5],[19],[20],[21]
Outcomes data supporting their mitigating effects on illness from other viral strains No data available No data available
Strength of evidence Conditional
Risk of harm:[22],[23],[24],[25],[26],[27] Mild
  1. EPIGALLOCATECHIN GALLATE (EGCG)

Green tea, in addition to modulating the NLRP3 inflammasome and, based on a preprint, potentially targeting the COVID-19 main protease (Mpro)[31] to reduce viral replication, has also been shown to prevent influenza in healthcare workers.[28]

Intervention Epigallocatechin gallate (EGCG)
Suggested dose 4 cups daily or 225 mg po qd
Mechanism(s) of action against non-COVID-19 viruses Favorably modulate viral-induced pathological cellular processes:
•Modulation of NLRP3 inflammasome activation[5],[28],[29]
Outcomes data supporting their mitigating effects on illness from other viral strains No data available
Strength of evidence Conditional
Risk of harm:[30],[31],[32],[33],[34],[35] Significant (rare) – Hepatotoxicity
  1. N-ACETYLCYSTEINE (NAC)

N-acetylcysteine promotes glutathione production, which has been shown to be protective in rodents infected with influenza. In a little-noticed six-month controlled clinical study enrolling 262 primarily elderly subjects, those receiving 600 mg NAC twice daily, as opposed to those receiving placebo, experienced significantly fewer influenza-like episodes and days of bed confinement.[36]

Intervention N-acetylcysteine (NAC)
Suggested dose 600-900 mg po bid
Mechanism(s) of action against non-COVID-19 viruses:[36] Favorably modulate cellular defense and repair mechanisms:
•Hypothetical: repletion of glutathione and cysteine
Outcomes data supporting their mitigating effects on illness from other viral strains Reduce progression from colonization to illness
Reduce the severity and duration of acute symptoms
Strength of evidence Limited
Risk of harm:[37],[38],[39],[40],[41] Mild
  1. RESVERATROL

Resveratrol, a naturally occurring polyphenol, shows many beneficial health effects. It has been shown to modulate the NLRP3 inflammasome.[5] In addition, resveratrol was shown to have in vitro activity against MERS-CoV.[43]

Intervention Resveratrol
Suggested dose 100-150 mg po qd
Mechanism(s) of action against non-COVID-19 viruses Favorably modulate viral-induced pathological cellular processes
•Modulation of NLRP3 inflammasome activation[5]
Outcomes data supporting their mitigating effects on illness from other viral strains MERS-CoV[43]
Influenza[44],[45]
Strength of evidence Conditional
Risk of harm:[46],[47],[48],[49],[50],[51],[52],[53] Mild
  1. VITAMIN D

Activated vitamin D,1,25(OH) D, a steroid hormone, is an immune system modulator that reduces the expression of inflammatory cytokines and increases macrophage function. Vitamin D also stimulates the expression of potent antimicrobial peptides (AMPs), which exist in neutrophils, monocytes, natural killer cells, and epithelial cells of the respiratory tract.[54] Vitamin D increases anti-pathogen peptides through defensins and has a dual effect due to suppressing superinfection. Evidence suggests vitamin D supplementation may prevent upper respiratory infections.[55] However, there is some controversy as to whether it should be used and the laboratory value that should be achieved. Research suggests that concerns about vitamin D (increased IL-1beta in cell culture) are not seen clinically. The guidance we suggest is that a laboratory range of >50 and < 80ng/mL serum 25-hydroxy vitamin D may help to mitigate morbidity from COVID-19 infection.

Intervention Vitamin D
Suggested dose 5,000 IU po qd in the absence of serum levels
Mechanism(s) of action against non-COVID-19 viruses[55],[56],[57],[58],[59],[60],[61],[62],[63],[64],[65],[66],[67],[68],[69],[70],[71],[72],[73],[74],[75],[76],[77],[78] Favorably modulate cellular defense and repair mechanisms:
•Activation of macrophages
•Stimulation of anti-microbial peptides
•Modulation of defensins
•Modulation of TH17 cells
Favorably modulate viral-induced pathological cellular processes:
•Reduction in cytokine expression
•Modulation of TGF beta
Outcomes data supporting their mitigating effects on illness from other viral strains Reduce progression from colonization to illness Reduce the severity and duration of acute symptoms and complications
Strength of evidence Limited
Risk of harm:[79],[80],[81],[82] Mild
  1. MELATONIN

Melatonin has been shown to have an inhibitory effect on the NLRP3 inflammasome.[94] This has not gone unnoticed by the COVID-19 research community, with two recent published papers proposing the use of melatonin as a therapeutic agent in the treatment of patients with COVID-19.[84],[85]

Intervention Melatonin
Suggested dose 5-20 mg qd
Mechanism(s) of action against non-COVID-19 viruses .[83],[84] Favorably modulate viral-induced pathological cellular processes
• Modulation of NLRP3 inflammasome activation .[83],[84]
Outcomes data supporting their mitigating effects on illness from other viral strains Research in progress
Strength of evidence Conditional
Risk of harm:[86],[87],[88],[89],[90],[91],[92],[93],[94] Mild
  1. 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. Vitamin A is known as an anti-inflammation vitamin because of its critical role in enhancing immune function. Vitamin A is involved in the development of the immune system and plays regulatory roles in cellular immune responses and humoral immune processes through the modulation of T helper cells, sIgA, and cytokine production. Vitamin A has demonstrated a therapeutic effect in the treatment of various infectious diseases.[95]

Intervention Vitamin A
Suggested dose Up to 10,000-25,000 IU/d
Mechanism(s) of action against non-COVID-19 viruses [95],[96] Favorably modulate cellular defense and repair mechanisms:
• Modulation of T helper cells
• Modulation of sIgA
Favorably modulate viral-induced pathological cellular processes:
• Modulation of cytokine production
Outcomes data supporting their mitigating effects on illness from other viral strains No data available
Strength of evidence Conditional
Risk of harm:[97],[98],[99],[100],[101],[102] Mild if does not exceed this dose; caution: pregnancy
  1. ELDERBERRY

Elderberry (Sambucus nigra) is seen in many medicinal preparations and has widespread historical use as an anti-viral herb.[103] Based on animal research, elderberry is likely most effective in the prevention of and early infection with respiratory viruses.[104] One in-vitro study reported an increase in TNF-alpha levels related to a specific commercial preparation of elderberry[105] leading some to caution that its use could initiate a “cytokine storm.” However, these data were not confirmed when the same group performed similar studies, which were published in 2002.[106] Therefore, these data suggest it is highly implausible that consumption of properly prepared elderberry products (from berries or flowers) would contribute to an adverse outcome related to overproduction of cytokines or lead to an adverse response in someone infected with COVID-19.

Intervention Elderberry
Suggested Dose 500 mg po qd (of USP standard of 17% anthocyanosides)
Mechanism(s) of action against non-COVID-19 viruses[103],[107],[108],[109],[110],[111],[112] Favorably modulate cellular defense and repair mechanisms
Favorably modulate viral-induced pathological cellular processes
Outcomes data supporting their mitigating effects on illness from other viral strains No data available
Strength of evidence Strong
Risk of harm:[103],[107],[113],[114] Mild; caution w/autoimmune disease; uncooked/unripe plant parts toxic; USDA GRAS
  1. PALMITOYLETHANOLAMIDE (PEA)

PEA is a naturally occurring anti-inflammatory palmitic acid derivative that interfaces with the endocannabinoid system. There was a significantly favorable outcome in five of six double blind placebo-controlled trials looking at acute respiratory disease due to influenza.[115] Dosing was generally 600 mg three times daily for up to three weeks. 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 attenuating the potentially fatal cytokine storm.

Intervention Palmitoylethanolamide (PEA)
Suggested dose 300 mg po bid to prevent infection, 600 mg po tid x two weeks to treat infection
 Mechanism(s) of action against non-COVID-19 viruses[115] Favorably modulate cellular defense and repair mechanisms
Favorably modulate viral-induced pathological cellular processes
Outcomes data supporting their mitigating effects on illness from other viral strains No data available
Strength of evidence Conditional (treatment) Strong (prevention)
Risk of harm:[116],[117],[118],[119] Mild
  1. VITAMIN C

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. Supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections.[120] Vitamin C has been used in hospital ICUs to treat COVID-19 infection.

Intervention Vitamin C
Suggested dose 1-3 grams po qd
Mechanism(s) of action against non-COVID-19 viruses [120] Favorably modulate cellular defense and repair mechanisms
Favorably modulate viral-induced pathological cellular processes
Outcomes data supporting their mitigating effects on illness from other viral strains No data available
Strength of evidence Strong
Risk of harm[121] Mild
  1. ZINC

Zinc contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. There is also evidence that it suppresses viral attachment and replication. Zinc deficiency is common, especially in those populations most at risk for severe COVID-19 infections, and it is challenging to accurately diagnosis with laboratory measures. Supplementation with zinc is supported by evidence that it both prevents viral infections and reduces their severity and duration. Moreover, it has been shown to reduce the risk of lower respiratory infection, which may be of particular significance in the context of COVID-19.

Intervention Zinc
Suggested dose 30–60 mg daily, in divided doses
Zinc acetate, citrate, picolinate, or glycinate orally
Zinc gluconate as lozenge
Mechanism(s) of action against non-COVID-19 viruses120,121,122,123,124,125,126,127 Favorably modulate innate and adaptive immune system
Favorably modulate viral-induced pathological cellular processes, attachment, and replication
Outcomes data supporting their mitigating effects on illness from other viral strains Prevention, reduced severity of symptoms, reduced duration of illness, prevention of lower respiratory tract infection
Strength of evidence Strong
Risk of harm128 Mild

Evaluative Criteria

In the recommendations above, the following criteria are used to identify strength of evidence and risk of harm.

Strength of Evidence Risk of Harm
Strength of EvidenceConditional

Clinical experience and/or expert opinion and/or conflicting studies; biological mechanism at least partly explained.

Risk of HarmMildRisk of self-limited symptoms; no risk of loss of function or corrective intervention anticipated; observation only.
Strength of EvidenceLimitedOne study showing correlation between intervention and outcome; compelling ATMs and/or PCFs; biological mechanism at least partly explained. Risk of HarmModerateRisk of symptoms; no risk of loss of function or quality of life; minor evaluative and/or therapeutic intervention needed.
Strength of EvidenceModerateTwo independent studies (one of which is LOE = 1 or 2) showing correlation between intervention and outcome; biological mechanism at least partly explained. Risk of HarmSignificantRisk of temporary loss of function or quality of life; significant evaluative and/or therapeutic intervention needed.
Strength of EvidenceStrongTwo independent studies (both LOE = 1 or 2) showing correlation between intervention and outcome; biological mechanism fully explained or partly explained and having one additional correlative study. Risk of HarmSevereRisk of permanent symptoms, loss of function, quality of life, or death; long-term evaluative and/or therapeutic intervention needed.

*This resource is only intended to identify nutraceutical and botanical agents that may boost your immune system. It is not meant to recommend any treatments, nor have any of these been proven effective against COVID-19. None of these practices are intended to be used in lieu of other recommended treatments. Always consult your physician or healthcare provider prior to initiation. For up-to-date information on COVID-19, please consult the Centers for Disease Control and Prevention at www.cdc.gov.

Below is a list of references if you are interested. Remember, no treatment or prevention is definitive with this disease, but we wanted to share this information.

REFERENCES

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