COVID | Anti-Viral Glossary

"As we know, new research and data about SarsCoV-2 and COVID-19 is coming out daily. It's important to get information from trusted sources.

The Institute for Functional Medicine (IFM) has put together a 'COVID Task Team' of top doctors to track and comment on existing and new research.

The intention is to give accurate recommendations about ways you can strengthen your immune system and, hopefully, lessen symptom intensity and duration if you are exposed to the virus.

The information below is copied directly from the IFM's site

I will keep updating this page as the IFM releases new info so that you can stay abreast of new developments.

The info below if aimed at healthcare practitioners but I have included it on my site because I believe informed, educated patients can make the best decisions about their health.

If it all seems a little complicated, just download the Immune Checklist | Expanded here.

Please email me know if you have any questions." Dr Heidi

Download COVID-19: Nutraceutical and Botanical Recommendations for Patients


Virus-Specific Nutraceutical and Botanical Agents

Background and Introduction

Health professionals and the public must be well informed about the COVID-19 virus, the disease it causes, and how it spreads. This information is readily available and not within the scope of this document.

At this time, there are no specific vaccines or uniformly successful treatments for COVID-19. In this context of insufficient evidence, the scope of this document will be to assess the scientific plausibility of promising prevention approaches and therapeutic (nutraceutical and botanical) interventions and then to offer clinical recommendations.

With respect to interventions, the practice of Functional Medicine emphasizes the primacy of safety, validity, and effectiveness. In the novel context of COVID-19, validity in the form of published evidence is lacking. Therefore, “validity” relies upon inferences from the mechanisms of action of individual agents and/or published outcomes data supporting their mitigating effects on illness from other viral strains.

Likewise, data for the “effectiveness” of interventions targeting the viral mechanisms of COVID-19 are nascent and rapidly emerging. In this context, the following recommendations represent the Functional Medicine approach to the COVID-19 crisis:

  • Adherence to all health recommendations from official sources to decrease viral transmission.
  • Optimizing modifiable lifestyle factors in order to improve overall immune function: 
    • Reduces progression from colonization to illness.
    • *Take a look at this list of things that you can do every day to ‘Strengthen Immunity’*
  • Personalized consideration of therapeutic agents that may:
    • Favorably modulate cellular defense and repair mechanisms.
    • Favorably modulate viral-induced pathological cellular processes.
    • Promote viral eradication or inactivation.
    • Mitigate collateral damage from other therapeutic agents.
    • Promote resolution of collateral damage and restoration of function.
  • Treatment of confirmed COVID-19 illness (as per conventional standards and practice):
    • May reduce the severity and duration of acute symptoms and complications.
    • May support recovery and reduce long-term morbidity and sequelae.
Note: Additional references are being collated continuously and will be made available in the near future.


Clinical Recommendations and Mechanisms of Action


We encourage practitioners to learn about the mechanism of invasion, replication, and pathophysiology of the COVID-19 virus. Much of what we know has been extrapolated from basic science research on SARS-CoV-2. Excellent resources are available online, including the free YouTube lectures through Dr. Roger Seheult: 

This document discusses the mechanisms of action of a number of different botanical and nutraceutical agents. These agents can be considered as immunoadjuvants, defined as substances that act to accelerate, prolong, or enhance antigen-specific immune responses by potentiating or modulating the immune response.[1]

A coronavirus such as SARS-CoV-2 can be deadly because of its ability to stimulate a part of the innate immune response called the inflammasome, which can cause uncontrolled release of pro-inflammatory cytokines, leading to cytokine storm and severe, sometimes irreversible, damage to respiratory epithelium.[2] The SARS-CoV-2 virus has been shown to activate the NLRP3 inflammasome.[3,4] A 2016 review article[5] entitled “Natural compounds as regulators of NLRP3 inflammasome-mediated IL-beta production” notes that “resveratrol, curcumin, EGCG [epigallocatechin gallate], and quercetin are potent inhibitors of NLRP3 inflammasome-mediated IL-1beta production, typically acting at more than one element of the involved pathways. However, it should be noted that these polyphenols have an even much broader biological effect, as they influence a variety of pathways.” For example, these polyphenols modulate NF-kB upregulation, which is useful to counteract the COVID-19 ’hyper-inflammation.[6]

A preprint released on March 23, 2020, identified the ability of plant bioactive compounds to inhibit the COVID-19 main protease (Mpro),[7] which is necessary for viral replication. There is much excitement surrounding the recent identification of Mpro, and it is a current potential pharmaceutical drug target. Kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate were the natural compounds that appeared to have the best potential to act as COVID-19 Mpro inhibitors. Though further research is necessary to prove their efficacy, this study provides the biologic plausibility and mechanistic support (COVID-19 protease inhibition) to justify their use.

For these reasons, we recommend the following compounds, at standard dosages, to prevent activation of the NLRP3 inflammasome, to decrease NF-kB activation, and to potentially inhibit COVID-19 replication.

There is no literature to support a regimen of a single vs. multiple agents. Our recommendation is to use higher dosing and/or multiple agents when patient contextual factors (e.g., patient desire, pre-existing inflammation, multiple co-morbidities, higher risk, etc.) and/or therapeutic decision-making warrant such use.

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

Evaluative Criteria

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

*Slide table from right to left to see all the info*

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 (one of which is LOE = 1 or 2) showing correlation between intervention and outcome; biological mechanism at least partly explained.
StrongTwo 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.
Mild: Risk of self-limited symptoms; no risk of loss of function or corrective intervention anticipated; observation only.
Moderate: Risk of symptoms; no risk of loss of function or quality of life; minor evaluative and/or therapeutic intervention needed.
Significant: Risk of temporary loss of function or quality of life; significant evaluative and/or therapeutic intervention needed.
Severe: Risk of permanent symptoms, loss of function, quality of life, or death; long-term evaluative and/or therapeutic intervention needed.


Recommended Interventions


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]

*Slide table from right to left to see all the info*

Intervention Quercetin
Suggested dose Regular: 1 gm orally twice per day; phytosome 500 mg twice per day.
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



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]

*Slide table from right to left to see all the info*

Intervention Curcumin
Suggested dose 500-1,000 mg orally twice per day (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



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]

*Slide table from right to left to see all the info*

Intervention Epigallocatechin gallate (EGCG)
Suggested dose 4 cups daily or 225 mg orally daily
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



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]

*Slide table from right to left to see all the info*

Intervention N-acetylcysteine (NAC)
Suggested dose 600-900 mg orally twice per day
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



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]

*Slide table from right to left to see all the info*

Intervention Resveratrol
Suggested dose 100-150 mg orally daily
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]
Strength of evidence Conditional
Risk of harm:[46],[47],[48],[49],[50],[51],[52],[53] Mild



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.

*Slide table from right to left to see all the info*

Intervention Vitamin D
Suggested dose 5,000 IU orally daily 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



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]

*Slide table from right to left to see all the info*

Intervention Melatonin
Suggested dose 5-20 mg before bed
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



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] 

*Slide table from right to left to see all the info*

Intervention Vitamin A
Suggested dose Up to 10,000-25,000 IU per day
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



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.

*Slide table from right to left to see all the info*

Intervention Elderberry
Suggested Dose 500 mg orally daily (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



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.

*Slide table from right to left to see all the info*

Intervention Palmitoylethanolamide (PEA)
Suggested dose 300 mg orally twice per day to prevent infection, 600 mg orally twice per day for 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



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. 

*Slide table from right to left to see all the info*

Intervention Vitamin C
Suggested dose 1-3 grams orally daily
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



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.

*Slide table from right to left to see all the info*

Intervention Zinc
Suggested dose 30–60 mg daily, in divided doses throughout the day.
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 harm Mild



Beta glucans are known to modulate immune activity, mostly by priming or training innate immune responses through interactions with pattern recognition receptors (PRRs)1,2 and by increasing anti-inflammatory cytokines such as IL-10.3,4,5,6,7 Beta glucans induce activity against viral attack.8,9 Numerous human trials have shown that beta glucans decrease cold and flu symptoms10,11,12 and upper respiratory tract infections compared to placebo.13,14,15,16,17,18,19

Intervention Beta glucans
Suggested dose 250-500 mg daily
Mechanism(s) of action against non-COVID-19 viruses Priming innate immune function20 Promoting viral eradication or inactivation8,9
Outcomes data supporting their mitigating effects on illness from other viral strains Reduction of symptoms 10,11,12,13,14,15,16,17,18,19
Strength of evidence Strong
Risk of harm Mild



Various mushrooms species have been shown to possess broad immunomodulatory effects. They possess multiple mechanisms of action, including increasing the number of circulating B cells,21 increasing gut immunity,22 stimulating host immunity,23 activating innate immune cells,24 and increasing cytotoxic activity of NK cells.25

Intervention Various medicinal mushrooms, including Shiitake (Lentinula edodes), Lion’s Mane (Hericium erinaceus), Maitake (Grifola frondosa), Reishi (Ganoderma lucidum)
Suggested dose Varied.
Given the variety of active ingredients in mushrooms and the variability of the extraction processes, it is suggested that dosing instructions should be individualized based on research of specific mushroom genus and species.
Mechanism(s) of action against non-COVID-19 viruses Promoting viral eradication or inactivation26,27
Modulation of innate immune response28,29
Outcomes data supporting their mitigating effects on illness from other viral strains Inconclusive, due to variety of species and combinations. Consult knowledgeable healthcare provider.
Strength of evidence Limited
Risk of harm Inconclusive, due to variety of species and combinations.



Chinese skullcap (Scutellaria baicalensis) has been used for centuries in Traditional Chinese Medicine (TCM). In various human trials, participants who took TCM formulations containing Chinese skullcap showed statistically significant decreases in viral infection rates compared to controls.30 Chinese skullcap has anti-inflammatory, antioxidant, antibacterial, and antiviral effects.31,32,33 It has been shown to increase immune surveillance and downregulate NLRP3 inflammasomes,34 IL-6, and TNF-alpha.35

Intervention Chinese skullcap (Scutellaria baicalensis)
Suggested dose 750–1,500 mg daily standardized to flavonoids, baicalin, or baicalein.
Given the variability of standardization, it is suggested that dosing instructions should be based on research of specific standardized extracts.
Mechanism(s) of action against non-COVID-19 viruses Priming innate immune function36,41,42
Promoting viral eradication or inactivation36-41
Favorably modulating pulmonary inflammation38,41,43,44,45,46,47,48
Outcomes data supporting their mitigating effects on illness from other viral strains Reduction of symptoms49
Strength of evidence Limited
Risk of harm Mild, though combination product showed significant hepatotoxicity.50,51,52,53,54



Licorice (Glycyrrhiza species) has multiple mechanisms of action, including inhibition of viral replication55,56,57 blocking the ACE2 receptor,58 promoting the activity of Th1 cells,59 and inhibition of pro-inflammatory cytokines,60prostaglandins, and nitric oxide production.61 The inhibition of hydrocortisone metabolism by 11 beta-HSD has also been suggested as a potential mechanism of licorice’s anti-inflammatory action.62 Licorice has been use in traditional Chinese medicine (TCM) formulations against SARS-CoV-1 and H1N1 and reviewed for its effects on SARS-CoV-2.63,64 Two positive human trials have been performed against SARS-CoV-1 using a TCM formulation containing licorice.65,66

Intervention Licorice (Glycyrrhiza glabra)
Suggested dose Licorice root standardized to glycyrrhizin. 200-400 mg daily in divided doses. Short term use: <4 weeks.
Mechanism(s) of action against non-COVID-19 viruses Promoting viral eradication or inactivation55,56,57,63,64,67,68
Favorably modulating inflammation
Outcomes data supporting their mitigating effects on illness from other viral strains Reduction of symptoms69,70
Strength of evidence Moderate
Risk of harm71, 72, 73, 74 Minimal, if short-term use (< 4 weeks)


*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


Joel Evans, MD (Lead), Robert Rountree, MD, Tom Guilliams, PhD, Michael Stone, MD, Robert Luby, MD, Patrick Hanaway, MD, Kirsten Ramsdell, MS, CN, Sam Yanuck, DC, Helen Messier, MD, and Dan Lukaczer, ND,



Quercetin -> Zinc

  1. Hotchkiss RS, Opal SM. Activating immunity to fight a foe – a new path.
  2. Hotchkiss RS, Opal SM. Activating immunity to fight a foe – a new path. N Engl J Med. 2020;382(13):1270-1272. doi:10.1056/NEJMcibr1917242
  3. Conti P, Ronconi G, Caraffa A, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34(2):1. doi:10.23812/CONTI-E
  4. Ding S, Xu S, Ma Y, Liu G, Jang H, Fang J. Modulatory mechanisms of the NLRP3 inflammasomes in diabetes. Biomolecules. 2019;9(12):E850. doi:10.3390/biom9120850
  5. Chen IY, Moriyama M, Chang MF, Ichinohe T. Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome. Front Microbiol. 2019;10:50. doi:10.3389/fmicb.2019.00050
  6. T?zsér J, Benk? S. Natural compounds as regulators of NLRP3 inflammasome-mediated IL-1? production. Mediators Inflamm. 2016;2016:5460302.  doi:10.1155/2016/5460302
  7. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-1034. doi:10.1016/S0140-6736(20)30628-0
  8. Adem S, Eyupoglu V, Sarfraz I, Rasul A, Ali M. Identification of potent COVID-19 main protease (Mpro) inhibitors from natural polyphenols: an in silico strategy unveils a hope against CORONA. Preprints. Published online March 23, 2020. doi:10.20944/preprints202003.0333.v1
  9. Dostal Z, Modriansky M. The effect of quercetin on microRNA expression: a critical review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019;163(2):95-106. doi:10.5507/bp.2019.030
  10. Wu W, Li R, Li X, et al. Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry. Viruses. 2015;8(1):E6. doi:10.3390/v8010006
  11. Kinker B, Comstock AT, Sajjan US. Quercetin: a promising treatment for the common cold. J Anc Dis Prev Rem.2014;2:2:1000111. doi:10.4172/2329-8731.1000111
  12. Somerville VS, Braakhuis AJ, Hopkins WG. Effect of flavonoids on upper respiratory tract infections and immune function: a systematic review and meta-analysis. Adv Nutr. 2016;7(3):488-497. doi:10.3945/an.115.010538
  13. Qiu X, Kroeker A, He S, et al. Prophylactic efficacy of quercetin 3-?-O-D-glucoside against Ebola virus infection. Antimicrob Agents Chemother. 2016;60(9):5182-5188. doi:10.1128/AAC.00307-16
  14. Wong G, He S, Siragam V, et al. Antiviral activity of quercetin-3-?-O-D-glucoside against Zika virus infection. Virol Sin. 2017;32(6):545-547. doi:10.1007/s12250-017-4057-9
  15. Yi YS. Regulatory roles of flavonoids on inflammasome activation during inflammatory responses. Mol Nutr Food Res. 2018;62(13):e1800147. doi:10.1002/mnfr.201800147
  16. Sun Y, Liu W, Zhang H, et al. Curcumin prevents osteoarthritis by inhibiting the activation of inflammasome NLRP3. J Interferon Cytokine Res. 2017;37(10):449-455. doi:10.1089/jir.2017.0069
  17. Andres S, Pevny S, Ziegenhagen R, et al. Safety aspects of the use of quercetin as a dietary supplement. Mol Nutr Food Res. 2018;62(1). doi:10.1002/mnfr.201700447
  18. O?arowski M, Miko?ajczak P?, Kujawski R, et al. Pharmacological effect of quercetin in hypertension and its potential application in pregnancy-induced hypertension: review of in vitroin vivo, and clinical studies. Evid Based Complement Alternat Med. 2018;2018:7421489. doi:10.1155/2018/7421489
  19. Khaerunnisa S, Kurniawan H, Awaluddin R, Suhartati S, Soetjipto S. Potential inhibitor of COVID-19 main protease (Mpro) from several medicinal plant compounds by molecular docking study. Preprints. Published online March 13, 2020. doi:10.20944/preprints202003.0226.v1
  20. Yin H, Guo Q, Li X, et al. Curcumin suppresses IL-1? secretion and prevents inflammation through inhibition of the NLRP3 inflammasome. J Immunol. 2018;200(8):2835-2846. doi:10.4049/jimmunol.1701495
  21. Gong Z, Zhao S, Zhou J, et al. Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1? production. Mol Immunol. 2018;104:11-19. doi:10.1016/j.molimm.2018.09.004
  22. Zhao J, Wang J, Zhou M, Li M, Li M, Tan H. Curcumin attenuates murine lupus via inhibiting NLRP3 inflammasome. Int Immunopharmacol. 2019;69:213-216. doi:10.1016/j.intimp.2019.01.046
  23. Kunnumakkara AB, Bordoloi D, Padmavathi G, et al. Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br J Pharmacol. 2017;174(11):1325-1348. doi:10.1111/bph.13621
  24. Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J Altern Complement Med. 2003;9(1):161-168. doi:10.1089/107555303321223035
  25. Ng QX, Koh SSH, Chan HW, Ho CYX. Clinical use of curcumin in depression: a meta-analysis. J Am Med Dir Assoc. 2017;18(6):503-508. doi:10.1016/j.jamda.2016.12.071
  26. Ng QX, Soh AYS, Loke W, Venkatanarayanan N, Lim DY, Yeo WS. A meta-analysis of the clinical use of curcumin for irritable bowel syndrome (IBS). J Clin Med. 2018;7(10):E298. doi:10.3390/jcm7100298
  27. Bahramsoltani R, Rahimi R, Farzaei MH. Pharmacokinetic interactions of curcuminoids with conventional drugs: a review. J Ethnopharmacol. 2017;209:1-12. doi:10.1016/j.jep.2017.07.022
  28. Xu J, Qiu JC, Ji X, et al. Potential pharmacokinetic herb-drug interactions: have we overlooked the importance of human carboxylesterases 1 and 2? Curr Drug Metab. 2019;20(2):130-137. doi:10.2174/1389200219666180330124050
  29. Matsumoto K, Yamada H, Takuma N, Niino H, Sagesaka YM. Effects of green tea catechins and theanine on preventing influenza infection among healthcare workers: a randomized controlled trial. BMC Complement Altern Med. 2011;11:15. doi:10.1186/1472-6882-11-15
  30. Lee HE, Yang G, Park YB, et al. Epigallocatechin-3-gallate prevents acute gout by suppressing NLRP3 inflammasome activation and mitochondrial DNA synthesis. Molecules. 2019;24(11):E2138. doi:10.3390/molecules24112138
  31. Mereles D, Hunstein W. Epigallocatechin-3-gallate (EGCG) for clinical trials: more pitfalls than promises? Int J Mol Sci. 2011;12(9):5592-5603. doi:10.3390/ijms12095592
  32. Chow HH, Cai Y, Hakim IA, et al. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin Cancer Res.2003;9(9):3312-3319.
  33. Isomura T, Suzuki S, Origasa H, et al. Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials [published correction appears in Eur J Clin Nutr.2016;70(11):1221-1229]. Eur J Clin Nutr. 2016;70(11):1340. doi:10.1038/ejcn.2016.78
  34. Sarma DN, Barrett ML, Chavez ML, et al. Safety of green tea extracts: a systematic review by the US Pharmacopeia. Drug Saf. 2008;31(6):469-484. doi:10.2165/00002018-200831060-00003
  35. Oketch-Rabah HA, Roe AL, Rider CV, et al. United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts. Toxicol Rep. 2020;7:386-402. doi:10.1016/j.toxrep.2020.02.008
  36. Younes M, Aggett P, Aguilar F, et al. Scientific opinion on the safety of green tea catechins. EFSA J.2018;16(4):e05239. doi:10.2903/j.efsa.2018.5239
  37. McCarty MF, DiNicolantonio JJ. Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus. Prog Cardiovasc Dis. Published online February 12, 2020. doi:10.1016/j.pcad.2020.02.007
  38. Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A. A review on various uses of N-acetyl cysteine. Cell J. 2017;19(1):11-17. doi:10.22074/cellj.2016.4872
  39. Bauer IE, Green C, Colpo GD, et al. A double-blind, randomized, placebo-controlled study of aspirin and N-acetylcysteine as adjunctive treatments for bipolar depression. J Clin Psychiatry. 2018;80(1):18m12200. doi:10.4088/JCP.18m12200
  40. Berk M, Turner A, Malhi GS, et al. A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo [published correction appears in BMC Med. 2019;17(1):35]. BMC Med. 2019;17(1):18. doi:10.1186/s12916-019-1257-1
  41. Clark RSB, Empey PE, Bay?r H, et al. Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children. PLoS One. 2017;12(7):e0180280. doi:10.1371/journal.pone.0180280
  42. Bhatti J, Nascimento B, Akhtar U, et al. Systematic review of human and animal studies examining the efficacy and safety of N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) in traumatic brain injury: impact on neurofunctional outcome and biomarkers of oxidative stress and inflammation. Front Neurol. 2018;8:744. doi:10.3389/fneur.2017.00744
  43. Brisdelli F, D’Andrea G, Bozzi A. Resveratrol: a natural polyphenol with multiple chemopreventive properties. Curr Drug Metab. 2009;10(6):530-546. doi:10.2174/138920009789375423
  44. Lin SC, Ho CT, Chuo WH, Li S, Wang TT, Lin CC. Effective inhibition of MERS-CoV infection by resveratrol. BMC Infect Dis. 2017;17(1):144. doi:10.1186/s12879-017-2253-8
  45. Palamara AT, Nencioni L, Aquilano K, et al. Inhibition of influenza A virus replication by resveratrol. J Infect Dis. 2005;191(10):1719-1729. doi:10.1086/429694
  46. Euba B, López-López N, Rodríguez-Arce I, et al. Resveratrol therapeutics combines both antimicrobial and immunomodulatory properties against respiratory infection by nontypeable Haemophilus influenzaeSci Rep. 2017;7(1):12860. doi:10.1038/s41598-017-13034-7
  47. Mendes da Silva D, Gross LA, Neto EPG, Lessey BA, Savaris RF. The use of resveratrol as an adjuvant treatment of pain in endometriosis: a randomized clinical trial. J Endocr Soc. 2017;1(4):359-369. doi:10.1210/js.2017-00053
  48. Zhu CW, Grossman H, Neugroschl J, et al. A randomized, double-blind, placebo-controlled trial of resveratrol with glucose and malate (RGM) to slow the progression of Alzheimer’s disease: a pilot study. Alzheimers Dement (N Y). 2018;4:609-616. doi:10.1016/j.trci.2018.09.009
  49. Roberts VH, Pound LD, Thorn SR, et al. Beneficial and cautionary outcomes of resveratrol supplementation in pregnant nonhuman primates. FASEB J. 2014;28(6):2466-2477. doi:10.1096/fj.13-245472
  50. Klink JC, Tewari AK, Masko EM, et al. Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell-line specific manner, through paradoxical effects on oncogenic pathways. Prostate. 2013;73(7):754-762. doi:10.1002/pros.22619
  51. Shaito A, Posadino AM, Younes N, et al. Potential adverse effects of resveratrol: a literature review. Int J Mol Sci. 2020;21(6):E2084. doi:10.3390/ijms21062084
  52. Salehi B, Mishra AP, Nigam M, et al. Resveratrol: a double-edged sword in health benefits. Biomedicines. 2018;6(3):E91. doi:10.3390/biomedicines6030091
  53. Patel KR, Scott E, Brown VA, Gescher AJ, Steward WP, Brown K. Clinical trials of resveratrol. Ann N Y Acad Sci.2011;1215:161-169. doi:10.1111/j.1749-6632.2010.05853.x
  54. Brantley SJ, Argikar AA, Lin YS, Nagar S, Paine MF. Herb-drug interactions: challenges and opportunities for improved predictions. Drug Metab Dispos. 2014;42(3):301-317. doi:10.1124/dmd.113.055236
  55. Mawson AR. Role of fat-soluble vitamins A and D in the pathogenesis of influenza: a new perspective. 2013;2013:246737. Int Sch Res Notices. doi:10.5402/2013/246737
  56. Martineau AR, Jolliffe DA, Greenberg L, et al. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess. 2019;23(2):1-44. doi:10.3310/hta23020
  57. Zhou J, Du J, Huang L, Wang Y, Shi Y, Lin H. Preventive effects of vitamin D on seasonal influenza A in infants: multicenter, randomized, open, controlled clinical trial. Pediatr Infect Dis J. 2018;37(8):749-754. doi:10.1097/INF.0000000000001890
  58. Tzilas V, Bouros E, Barbayianni I, et al. Vitamin D prevents experimental lung fibrosis and predicts survival in patients with idiopathic pulmonary fibrosis. Pulm Pharmacol Ther. 2019;55:17-24. doi:10.1016/j.pupt.2019.01.003
  59. Ricca C, Aillon A, Viano M, Bergandi L, Aldieri E, Silvagno F. Vitamin D inhibits the epithelial-mesenchymal transition by a negative feedback regulation of TGF-? activity. J Steroid Biochem Mol Biol. 2019;187:97-105. doi:10.1016/j.jsbmb.2018.11.006
  60. Fischer KD, Agrawal DK. Vitamin D regulating TGF-? induced epithelial-mesenchymal transition [published correction appears in Respir Res. 2015;16:139]. Respir Res. 2014;15:146. doi:10.1186/s12931-014-0146-6
  61. Schrumpf JA, Ninaber DK, van der Does AM, Hiemstra PS. TGF-?1 impairs vitamin D-induced and constitutive airway epithelial host defense mechanisms. J Innate Immun. 2020;12(1):74-89. doi:10.1159/000497415
  62. Liu RM, Gaston Pravia KA. Oxidative stress and glutathione in TGF-beta-mediated fibrogenesis. Free Radic Biol Med. 2010;48(1):1-15. doi:10.1016/j.freeradbiomed.2009.09.026
  63. Lu L, Lu Q, Chen W, Li J, Li C, Zheng Z. Vitamin D3 protects against diabetic retinopathy by inhibiting high-glucose-induced activation of the ROS/TXNIP/NLRP3 inflammasome pathway. J Diabetes Res. 2018;2018:8193523. doi:10.1155/2018/8193523
  64. Rao Z, Chen X, Wu J, et al. Vitamin D receptor inhibits NLRP3 activation by impeding its BRCC3-mediated deubiquitination. Front Immunol. 2019;10:2783. doi:10.3389/fimmu.2019.02783
  65. Hewison M. Vitamin D and immune function: an overview. Proc Nutr Soc. 2012;71(1):50-61. doi:10.1017/S0029665111001650
  66. Fitch N, Becker AB, HayGlass KT. Vitamin D [1,25(OH)2D3] differentially regulates human innate cytokine responses to bacterial versus viral pattern recognition receptor stimuli. J Immunol. 2016;196(7):2965-2972. doi:10.4049/jimmunol.1500460
  67. Zdrenghea MT, Makrinioti H, Bagacean C, Bush A, Johnston SL, Stanciu LA. Vitamin D modulation of innate immune responses to respiratory viral infections. Rev Med Virol. 2017;27(1). doi:10.1002/rmv.1909
  68. Verway M, Bouttier M, Wang TT, et al. Vitamin D induces interleukin-1? expression: paracrine macrophage epithelial signaling controls M. tuberculosis infection. PLoS Pathog. 2013;9(6):e1003407. doi:10.1371/journal.ppat.1003407
  69. Tulk SE, Liao KC, Muruve DA, Li Y, Beck PL, MacDonald JA. Vitamin D3 metabolites enhance the NLRP3-dependent secretion of IL-1? from human THP-1 monocytic cells. J Cell Biochem. 2015;116(5):711-720. doi:10.1002/jcb.24985
  70. Lee MT, Kattan M, Fennoy I, et al. Randomized phase 2 trial of monthly vitamin D to prevent respiratory complications in children with sickle cell disease. Blood Adv. 2018;2(9):969-978. doi:10.1182/bloodadvances.2017013979
  71. Autier P, Mullie P, Macacu A, et al. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017;5(12):986-1004. doi:10.1016/S2213-8587(17)30357-1
  72. Sluyter JD, Camargo CA, Waayer D, et al. Effect of monthly, high-dose, long-term vitamin D on lung function: a randomized controlled trial. Nutrients. 2017;9(12):E1353. doi:10.3390/nu9121353
  73. Scragg R. The vitamin D assessment (ViDA) study – design and main findings. J Steroid Biochem Mol Biol. 2020;198:105562. doi:10.1016/j.jsbmb.2019.105562
  74. Turin A, Bax JJ, Doukas D, et al. Interactions among vitamin D, atrial fibrillation, and the renin-angiotensin-aldosterone system. Am J Cardiol. 2018;122(5):780-784. doi:10.1016/j.amjcard.2018.05.013
  75. Zaheer S, Taquechel K, Brown JM, Adler GK, Williams JS, Vaidya A. A randomized intervention study to evaluate the effect of calcitriol therapy on the renin-angiotensin system in diabetes. J Renin Angiotensin Aldosterone Syst. 2018;19(1):1470320317754178. doi:10.1177/1470320317754178
  76. Cremer A, Tambosco C, Corcuff JB, et al. Investigating the association of vitamin D with blood pressure and the renin-angiotensin-aldosterone system in hypertensive subjects: a cross-sectional prospective study. J Hum Hypertens. 2018;32(2):114-121. doi:10.1038/s41371-017-0005-2
  77. Zittermann A, Ernst JB, Prokop S, et al. Effects of vitamin D supplementation on renin and aldosterone concentrations in patients with advanced heart failure: the EVITA trial. Int J Endocrinol. 2018;2018:5015417. doi:10.1155/2018/5015417
  78. Yang P, Gu H, Zhao Z, et al. Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury. Sci Rep. 2014;4:7027. doi:10.1038/srep07027
  79. Xu J, Yang J, Chen J, Luo Q, Zhang Q, Zhang H. Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system. Mol Med Rep. 2017;16(5):7432-7438. doi:10.3892/mmr.2017.7546
  80. Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815-1822. doi:10.1001/jama.2010.594
  81. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, et al. Monthly high-dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial. JAMA Intern Med. 2016;176(2):175-183. doi:10.1001/jamainternmed.2015.7148
  82. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: a new drug interaction with an unexpected consequence. Clin Pharmacol Ther. 2009;85(2):198-203. doi:10.1038/clpt.2008.165
  83. Žofková I. Hypercalcemia. Pathophysiological aspects. Physiol Res. 2016;65(1):1-10. doi:10.33549/physiolres.933059
  84. Favero G, Franceschetti L, Bonomini F, Rodella LF, Rezzani R. Melatonin as an anti-inflammatory agent modulating inflammasome activation. Int J Endocrinol. 2017;2017:1835195. doi:10.1155/2017/1835195
  85. Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020;6:14. doi:10.1038/s41421-020-0153-3
  86. Zhang R, Wang X, Ni L, et al. COVID-19: melatonin as a potential adjuvant treatment. Life Sci. Published online March 23, 2020. doi:10.1016/j.lfs.2020.117583
  87. Foley HM, Steel AE. Adverse events associated with oral administration of melatonin: a critical systematic review of clinical evidence. Complement Ther Med. 2019;42:65-81. doi:10.1016/j.ctim.2018.11.003
  88. Andersen LP, Gögenur I, Rosenberg J, Reiter RJ. The safety of melatonin in humans. Clin Drug Investig.2016;36(3):169-175. doi:10.1007/s40261-015-0368-5
  89. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev.2002;2:CD001520. doi:10.1002/14651858.CD001520
  90. Leite Pacheco R, de Oliveira Cruz Latorraca C, Adriano Leal Freitas da Costa A, Luiza Cabrera Martimbianco A, Vianna Pachito D, Riera R. Melatonin for preventing primary headache: a systematic review. Int J Clin Pract.2018;72(7):e13203. doi:10.1111/ijcp.13203
  91. Abdelgadir IS, Gordon MA, Akobeng AK. Melatonin for the management of sleep problems in children with neurodevelopmental disorders: a systematic review and meta-analysis. Arch Dis Child. 2018;103(12):1155-1162. doi:10.1136/archdischild-2017-314181
  92. Besag FMC, Vasey MJ, Lao KSJ, Wong ICK. Adverse events associated with melatonin for the treatment of primary or secondary sleep disorders: a systematic review. CNS Drugs. 2019;33(12):1167-1186. doi:10.1007/s40263-019-00680-w
  93. Harpsøe NG, Andersen LP, Gögenur I, Rosenberg J. Clinical pharmacokinetics of melatonin: a systematic review. Eur J Clin Pharmacol. 2015;71(8):901-909. doi:10.1007/s00228-015-1873-4
  94. Wirtz PH, Spillmann M, Bärtschi C, Ehlert U, von Känel R. Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men. J Pineal Res. 2008;44(2):127-133. doi:10.1111/j.1600-079X.2007.00499.x
  95. McGlashan EM, Nandam LS, Vidafar P, Mansfield DR, Rajaratnam SMW, Cain SW. The SSRI citalopram increases the sensitivity of the human circadian system to light in an acute dose. Psychopharmacology (Berl).2018;235(11):3201-3209. doi:10.1007/s00213-018-5019-0
  96. Huang Z, Liu Y, Qi G, Brand D, Zheng SG. Role of vitamin A in the immune system. J Clin Med. 2018;7(9):E258. doi:10.3390/jcm7090258
  97. Cui D, Moldoveanu Z, Stephensen CB. High-level dietary vitamin A enhances T-helper type 2 cytokine production and secretory immunoglobulin A response to influenza A virus infection in BALB/c mice. J Nutr. 2000;130(5):1132-1139. doi:10.1093/jn/130.5.1132
  98. Rothman KJ, Moore LL, Singer MR, Nguyen US, Mannino S, Milunsky A. Teratogenicity of high vitamin A intake. N Engl J Med. 1995;333(21):1369-1373. doi:10.1056/NEJM199511233332101
  99. Bartlett H, Eperjesi F. Possible contraindications and adverse reactions associated with the use of ocular nutritional supplements. Ophthalmic Physiol Opt. 2005;25(3):179-194. doi:10.1111/j.1475-1313.2005.00294.x
  100. Bendich A, Langseth L. Safety of vitamin A. Am J Clin Nutr. 1989;49(2):358-371. doi:10.1093/ajcn/49.2.358
  101. Cruz S, da Cruz SP, Ramalho A. Impact of vitamin A supplementation on pregnant women and on women who have just given birth: a systematic review. J Am Coll Nutr. 2018;37(3):243-250. doi:10.1080/07315724.2017.1364182
  102. Oliveira JM, Allert R, East CE. Vitamin A supplementation for postpartum women. Cochrane Database Syst Rev.2016;3:CD005944. doi:10.1002/14651858.CD005944.pub3
  103. García-Cortés M, Robles-Díaz M, Ortega-Alonso A, Medina-Caliz I, Andrade RJ. Hepatotoxicity by dietary supplements: a tabular listing and clinical characteristics. Int J Mol Sci. 2016;17(4):537. doi:10.3390/ijms17040537
  104. Porter RS, Bode RF. A review of the antiviral properties of black elder (Sambucus nigra L.) products. Phytother Res. 2017;31(4):533-554. doi:10.1002/ptr.5782
  105. Chen C, Zuckerman DM, Brantley S, et al. Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication. BMC Vet Res. 2014;10:24. doi:10.1186/1746-6148-10-24
  106. Barak V, Halperin T, Kalickman I. The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. Eur Cytokine Netw. 2001;12(2):290-296.
  107. Barak V, Birkenfeld S, Halperin T, Kalickman I. The effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines. Isr Med Assoc J. 2002;4(11 Suppl):919-922.
  108. Ulbricht C, Basch E, Cheung L, et al. An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration. J Diet Suppl. 2014;11(1):80-120. doi:10.3109/19390211.2013.859852
  109. Frank T, Janssen M, Netzet G, Christian B, Bitsch I, Netzel M. Absorption and excretion of elderberry (Sambucus nigra L.) anthocyanins in healthy humans. Methods Find Exp Clin Pharmacol. 2007;29(8):525-533. doi:10.1358/mf.2007.29.8.1116309
  110. Badescu M, Badulescu O, Badescu L, Ciocoiu M. Effects of Sambucus nigra and Aronia melanocarpa extracts on immune system disorders within diabetes mellitus. Pharm Biol. 2015;53(4):533-539. doi:10.3109/13880209.2014.931441
  111. Curtis PJ, Kroon PA, Hollands WJ, et al. Cardiovascular disease risk biomarkers and liver and kidney function are not altered in postmenopausal women after ingesting an elderberry extract rich in anthocyanins for 12 weeks. J Nutr. 2009;139(12):2266-2271. doi:10.3945/jn.109.113126
  112. Fallah AA, Sarmast E, Fatehi P, Jafari T. Impact of dietary anthocyanins on systemic and vascular inflammation: systematic review and meta-analysis on randomised clinical trials. Food Chem Toxicol. 2020;135:110922. doi:10.1016/j.fct.2019.110922
  113. Li S, Wu B, Fu W, Reddivari L. The anti-inflammatory effects of dietary anthocyanins against ulcerative colitis. Int J Mol Sci. 2019;20(10):E2588. doi:10.3390/ijms20102588
  114. Elderberry for influenza. Med Lett Drugs Ther. 2019;61(1566):32. []
  115. Hawkins J, Baker C, Cherry L, Dunne E. Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: a meta-analysis of randomized, controlled clinical trials. Complement Ther Med. 2019;42:361-365. doi:10.1016/j.ctim.2018.12.004
  116. Keppel Hesselink JM, de Boer T, Witkamp RF. Palmitoylethanolamide: a natural body-own anti-inflammatory agent, effective and safe against influenza and common cold. Int J Inflam. 2013;2013:151028. doi:10.1155/2013/151028
  117. Cordaro M, Cuzzocrea S, Crupi R. An update of palmitoylethanolamide and luteolin effects in preclinical and clinical studies of neuroinflammatory events. Antioxidants (Basel). 2020;9(3):E216. doi:10.3390/antiox9030216
  118. Davis MP, Behm B, Mehta Z, Fernandez C. The potential benefits of palmitoylethanolamide in palliation: a qualitative systematic review. Am J Hosp Palliat Care. 2019;36(12):1134-1154. doi:10.1177/1049909119850807
  119. Gabrielsson L, Mattsson S, Fowler CJ. Palmitoulethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. Br J Clin Pharmacol. 2016;82(4):932-942. doi:10.1111/bcp.13020
  120. Natural Medicines Database. Palmitoylethanolamide (PEA). Accessed March 30, 2020.,-herbs-supplements/professional.aspx?productid=1596
  121. Fischer Walker C, Black RE. Zinc and the risk for infectious disease. Annu Rev Nutr. 2004;24:255-275. doi:10.1146/annurev.nutr.23.011702.073054
  122. Fraker PJ, King LE, Laakko T, Vollmer TL. The dynamic link between the integrity of the immune system and zinc status. J Nutr. 2000;130(5S Suppl):1399S-1406S. doi:10.1093/jn/130.5.1399S
  123. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68(2 Suppl):447S-463S. doi:10.1093/ajcn/68.2.447S
  124. Gao H, Dai W, Zhao L, Min J, Wang F. The role of zinc and zinc homeostasis in macrophage function. J Immunol Res. 2018;2018:6872621. doi:10.1155/2018/6872621
  125. Meydani SN, Barnett JB, Dallal GE, et al. Serum zinc and pneumonia in nursing home elderly. Am J Clin Nutr. 2007;86(4):1167-1173. doi:10.1093/ajcn/86.4.1167
  126. Barnett JB, Dao MC, Hamer DH, et al. Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2016;103(3):942-951. doi:10.3945/ajcn.115.115188
  127. Maares M, Haase H. Zinc and immunity: an essential interrelation. Arch Biochem Biophys. 2016;611:58-65. doi:10.1016/
  128. te Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010;6(11):e1001176. doi:10.1371/journal.ppat.1001176
  129. King JC, Brown KH, Gibson RS, et al. Biomarkers of nutrition for development (BOND)—zinc review. J Nutr. 2015;146(4):858S-885S. doi:10.3945/jn.115.220079


Beta Glucans -> Licorice 

  1. Castro E, Calder PC, Roche HM. ?-1,3/1,6-glucans and immunity: state of the art and future directions. Mol Nutr Food Res. Published online March 29, 2020. doi:1002/mnfr.201901071
  2. Vetvicka V, Vannucci L, Sima P, Richter J. Beta glucan: supplement or drug? From laboratory to clinical trials. Molecules. 2019;24(7):E1251. doi:3390/molecules24071251
  3. Mosikanon K, Arthan D, Kettawan A, Tungtrongchitr R, Prangthip P. Yeast ß-glucan modulates inflammation and waist circumference in overweight and obese subjects. J Diet Suppl. 2017;14(2):173-185. doi:1080/19390211.2016.1207005
  4. Bobov?ák M, Kuniaková R, Gabriž J, Majtán J. Effect of Pleuran (?-glucan from Pleurotus ostreatus) supplementation on cellular immune response after intensive exercise in elite athletes. Appl Physiol Nutr Metab. 2010;35(6):755-762. doi:1139/H10-070
  5. Gaullier JM, Sleboda J, Øfjord ES. Supplementation with a soluble ?-glucan exported from Shiitake medicinal mushroom, Lentinus edodes (Berk.) singer mycelium: a crossover, placebo-controlled study in healthy elderly. Int J Med Mushrooms. 2011;13(4):319-326. doi:1615/intjmedmushr.v13.i4.10
  6. Leentjens J, Quintin J, Gerretsen J, Kox M, Pickkers P, Netea MG. The effects of orally administered beta-glucan on innate immune responses in humans, a randomized open-label intervention pilot-study. PLoS One. 2014;9(9):e108794. doi:1371/journal.pone.0108794
  7. Nieman DC, Henson DA, McMahon M, et al. Beta-glucan, immune function, and upper respiratory tract infections in athletes. Med Sci Sports Exerc. 2008;40(8):1463-1471. doi:1249/MSS.0b013e31817057c2
  8. Yun CH, Estrada A, Van Kessel A, Park BC, Laarveld B. Beta-glucan, extracted from oat, enhances disease resistance against bacterial and parasitic infections. FEMS Immunol Med Microbiol. 2003;35(1):67-75. doi:1016/S0928-8244(02)00460-1
  9. Volman JJ, Ramakers JD, Plat J. Dietary modulation of immune function by beta-glucans. Physiol Behav. 2008;94(2):276-284. doi:1016/j.physbeh.2007.11.045
  10. McFarlin BK, Carpenter KC, Davidson T, McFarlin MA. Baker’s yeast beta glucan supplementation increases salivary IgA and decreases cold/flu symptomatic days after intense exercise. J Diet Suppl. 2013;10(3):171-183. doi:3109/19390211.2013.820248
  11. Auinger A, Riede L, Bothe G, Busch R, Gruenwald J. Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body’s defence against pathogens: a double blind, randomized, placebo-controlled, multicentric study in healthy subjects. Eur J Nutr. 2013;52(8):1913-1918. doi:1007/s00394-013-0492-z
  12. Graubaum HJ, Busch R, Stier H, Gruenwald J. A double-blind, randomized, placebo-controlled nutritional study using an insoluble yeast beta-glucan to improve the immune defense system. Food Nutr Sci. 2012;3(6):738-746. doi:4236/fns.2012.36100
  13. Fuller R, Moore MV, Lewith G, et al. Yeast-derived ?-1,3/1,6 glucan, upper respiratory tract infection and innate immunity in older adults. Nutrition. 2017;39-40:30-35. doi:1016/j.nut.2017.03.003
  14. Dharsono T, Rudnicka K, Wilhelm M, Schoen C. Effects of yeast (1,3)-(1,6)-beta-glucan on severity of upper respiratory tract infections: a double-blind, randomized, placebo-controlled study in healthy subjects. J Am Coll Nutr. 2019;38(1):40-50. doi:1080/07315724.2018.1478339
  15. Mah E, Kaden VN, Kelley KM, Liska DJ. Beverage containing dispersible yeast ?-glucan decreases cold/flu symptomatic days after intense exercise: a randomized controlled trial. J Diet Suppl. 2020;17(2):200-210. doi:1080/19390211.2018.1495676
  16. Fuller R, Butt H, Noakes PS, Kenyon J, Yam TS, Calder PC. Influence of yeast-derived 1,3/1,6 glucopolysaccharide on circulating cytokines and chemokines with respect to upper respiratory tract infections. Nutrition. 2012;28(6):665-669. doi:1016/j.nut.2011.11.012
  17. Talbott SM, Talbott JA. Baker’s yeast beta-glucan supplement reduces upper respiratory symptoms and improves mood state in stressed women. J Am Coll Nutr. 2012;31(4):295-300. doi:1080/07315724.2012.10720441
  18. Talbott S, Talbott J. Beta 1,3/1,6 glucan decreases upper respiratory tract infection symptoms and improves psychological well-being in moderate to highly-stressed subjects. Agro Food Ind Hi Tech. 2010;21:21-24.
  19. Jesenak M, Urbancikova I, Banovcin P. Respiratory tract infections and the role of biologically active polysaccharides in their management and prevention. Nutrients. 2017;9(7):E779. doi:3390/nu9070779
  20. Geller A, Shrestha R, Yan J. Yeast-derived ?-glucan in cancer: novel uses of a traditional therapeutic. Int J Mol Sci. 2019;20(15):E3618. doi:3390/ijms20153618
  21. Gaullier JM, Sleboda J, Øfjord ES, et al. Supplementation with a soluble ?-glucan exported from Shiitake medicinal mushroom, Lentinus edodes (Berk.) singer mycelium: a crossover, placebo-controlled study in healthy elderly. Int J Med Mushrooms. 2011;13(4):319-326. doi:1615/intjmedmushr.v13.i4.10
  22. Dai X, Stanilka JM, Rowe CA, et al. Consuming Lentinula edodes (Shiitake) mushrooms daily improves human immunity: a randomized dietary intervention in healthy young adults. J Am Coll Nutr. 2015;34(6):478-487. doi:1080/07315724.2014.950391
  23. Jin X, Ruiz Beguerie J, Sze DM, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev. 2012;(6):CD007731. doi:1002/14651858.CD007731.pub2
  24. Kim SP, Moon E, Nam SH, Friedman M. Hericium erinaceus mushroom extracts protect infected mice against Salmonella typhimurium-induced liver damage and mortality by stimulation of innate immune cells. J Agric Food Chem. 2012;60(22):5590-5596. doi:1021/jf300897w
  25. Kodama N, Komuta K, Nanba H. Effect of Maitake (Grifola frondosa) D-fraction on the activation of NK cells in cancer patients. J Med Food. 2003;6(4):371-377. doi:1089/109662003772519949
  26. Nogusa S, Gerbino J, Ritz BW. Low-dose supplementation with active hexose correlated compound improves the immune response to acute influenza infection in C57BL/6 mice. Nutr Res. 2009;29(2):139-143. doi:1016/j.nutres.2009.01.005
  27. Fujii H, Nishioka H, Wakame K, Sun B. Nutritional food active hexose correlated compound (AHCC) enhances resistance against bird flu. JCAM. 2007;4(1):37-40. doi:1625/jcam.4.37
  28. Ritz BW, Nogusa S, Ackerman EA, Gardner EM. Supplementation with active hexose correlated compound increases the innate immune response of young mice to primary influenza infection. J Nutr. 2006;136(11):2868-2873. doi:1093/jn/136.11.2868
  29. Wang S, Welte T, Fang H, et al. Oral administration of active hexose correlated compound enhances host resistance to West Nile encephalitis in mice. J Nutr. 2009;139(3):598-602. doi:3945/jn.108.100297
  30. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective. Int J Biol Sci. 2020;16(10):1708-1717. doi:7150/ijbs.45538
  31. Li C, Lin G, Zuo Z. Pharmacological effects and pharmacokinetics properties of Radix Scutellariae and its bioactive flavones. Biopharm Drug Dispos. 2011;32(8):427-445. doi:1002/bdd.771
  32. Zhao T, Tang H, Xie L, et al. Scutellaria baicalensis (Lamiaceae): a review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. J Pharm Pharmacol. 2019;71(9):1353-1369. doi:10.1111/jphp.13129
  33. Wang ZL, Wang S, Kuang Y, Hu ZM, Qiao X, Ye M. A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis. Pharm Biol. 2018;56(1):465-484. doi:1080/13880209.2018.1492620
  34. Liu Y, Jing YY, Zeng CY, et al. Scutellarin suppresses NLRP3 inflammasome activation in macrophages and protects mice against bacterial sepsis. Front Pharmacol. 2018;8:975. doi:3389/fphar.2017.00975
  35. Hu S, Chen Y, Wang ZF, et al. The analgesic and antineuroinflammatory effect of baicalein in cancer-induced bone pain. Evid Based Complement Alternat Med. 2015;2015:973524. doi:1155/2015/973524
  36. Orzechowska B, Chaber R, Wi?niewska A, et al. Baicalin from the extract of Scutellaria baicalensis affects the innate immunity and apoptosis in leukocytes of children with acute lymphocytic leukemia. Int Immunopharmacol. 2014;23(2):558-567. doi:1016/j.intimp.2014.10.005
  37. Ma Q, Yu Q, Xing X, Liu S, Shi C, Luo J. San Wu Huangqin decoction, a Chinese herbal formula, inhibits influenza a/PR/8/34 (H1N1) virus infection in vitro and in vivo. Viruses. 2018;10(3):E117. doi:3390/v10030117
  38. Ma QH, Ren MY, Luo JB. San Wu Huangqin decoction regulates inflammation and immune dysfunction induced by influenza virus by regulating the NF-?B signaling pathway in H1N1-infected mice. J Ethnopharmacol. Published online March 26, 2020. doi:1016/j.jep.2020.112800
  39. Shi H, Ren K, Lv B, et al. Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice. Sci Rep. 2016;6:35851. doi:1038/srep35851
  40. Chu M, Chu ZY, Wang DD. The extract of compound Radix Scutellariae on mRNA replication and IFN expression of influenza virus in mice. Zhong Yao Cai. 2007;30(1):63-65.
  41. Zhi HJ, Zhu HY, Zhang YY, Lu Y, Li H, Chen DF. In vivo effect of quantified flavonoids-enriched extract of Scutellaria baicalensis root on acute lung injury induced by influenza A virus. Phytomedicine. 2019;57:105-116. doi:1016/j.phymed.2018.12.009
  42. Chu M, Xu L, Zhang MB, Chu ZY, Wang YD. Role of baicalin in anti-influenza virus A as a potent inducer of IFN-gamma. Biomed Res Int. 2015;2015:263630. doi:1155/2015/263630
  43. Liu T, Dai W, Li C, et al. Baicalin alleviates silica-induced lung inflammation and fibrosis by inhibiting the Th17 response in C57BL/6 mice. J Nat Prod. 2015;78(12):3049-3057. doi:1021/acs.jnatprod.5b00868
  44. Ryu EK, Kim TH, Jang EJ, et al. Wogonin, a plant flavone from Scutellariae radix, attenuated ovalbumin-induced airway inflammation in mouse model of asthma via the suppression of IL-4/STAT6 signaling. J Clin Biochem Nutr. 2015;57(2):105-112. doi:3164/jcbn.15-45
  45. Wu YH, Chuang SY, Hong WC, Lai YJ, Chang YL, Pang JH. In vivo and in vitro inhibitory effects of a traditional Chinese formulation on LPS-stimulated leukocyte-endothelial cell adhesion and VCAM-1 gene expression. J Ethnopharmacol. 2012;140(1):55-63. doi:1016/j.jep.2011.12.002
  46. Chen JJ, Huang CC, Chang HY, et al. Scutellaria baicalensis ameliorates acute lung injury by suppressing inflammation in vitro and in vivo. Am J Chin Med. 2017;45(1):137-157. doi:1142/S0192415X17500100
  47. Yang WK, Kim SH, Jung IC, Park YC. Effects of Scutellaria baicalensis extract on cigarette smoke-induced airway inflammation in a murine model of chronic obstructive pulmonary disease. J Med Food. 2019;22(1):87-96. doi:1089/jmf.2018.4200
  48. Liu J, Wei Y, Luo Q, et al. Baicalin attenuates inflammation in mice with OVA-induced asthma by inhibiting NF-?B and suppressing CCR7/CCL19/CCL21. Int J Mol Med. 2016;38(5):1541-1548. doi:3892/ijmm.2016.2743
  49. Lin H, Zhou J, Lin K, et al. Efficacy of Scutellaria baicalensis for the treatment of hand, foot, and mouth disease associated with encephalitis in patients infected with EV71: a multicenter, retrospective analysis. Biomed Res Int. 2016;2016:5697571. doi:1155/2016/5697571
  50. Li M, Shi A, Pang H, et al. Safety, tolerability, and pharmacokinetics of a single ascending dose of baicalein chewable tablets in healthy subjects. J Ethnopharmacol. 2014;156:210-215. doi:1016/j.jep.2014.08.031
  51. Chalasani N, Vuppalanchi R, Navarro V, et al. Acute liver injury due to flavocoxid (Limbrel), a medical food for osteoarthritis: a case series. Ann Intern Med. 2012;156(12):857-860, W297-W300. doi:7326/0003-4819-156-12-201206190-00006
  52. Linnebur SA, Rapacchietta OC, Vejar M. Hepatotoxicity associated with Chinese skullcap contained in Move Free Advanced dietary supplement: two case reports and review of the literature. Pharmacotherapy. 2010;30(7):750, 258e-262e. doi:1592/phco.30.7.750
  53. Braude MR, Bassily R. Drug-induced liver injury secondary to Scutellaria baicalensis (Chinese skullcap). Intern Med J. 2019;49(4):544-546. doi:1111/imj.14252
  54. Papafragkakis C, Ona MA, Reddy M, Anand S. Acute hepatitis after ingestion of a preparation of Chinese skullcap and black catechu for joint pain. Case Reports Hepatol. 2016;2016:4356749. doi:1155/2016/4356749
  55. Fiore C, Eisenhut M, Krausse R, et al. Antiviral effects of Glycyrrhiza Phytother Res. 2008;22(2):141-148. doi:10.1002/ptr.2295
  56. Sun ZG, Zhao TT, Lu N, Yang YA, Zhu HL. Research progress of glycyrrhizic acid on antiviral activity. Mini Rev Med Chem. 2019;19(10):826-832. doi:2174/1389557519666190119111125
  57. Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003;361(9374):2045-2046. doi:1016/s0140-6736(03)13615-x
  58. Chen H, Du Q. Potential natural compounds for preventing 2019-nCoV infection. Preprints. Published online March 10, 2020.
  59. Wang L, Yang R, Yuan B, Liu Y, Liu C. The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. Acta Pharm Sin B. 2015;5(4):310-315. doi:1016/j.apsb.2015.05.005
  60. Jin CY, Wang DL, Fang ZD. [Effect of integrative Chinese and Western medicine in treating chronic urticaria and its impact on interleukin-10 and interleukin-8 in peripheral blood]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2008;28(4):358-360.
  61. Dimmito MP, Stefanucci A, Pieretti S, et al. Discovery of orexant and anorexant agents with indazole scaffold endowed with peripheral antiedema activity. Biomolecules. 2019;9(9):E492. doi:3390/biom9090492
  62. Schleimer RP. Potential regulation of inflammation in the lung by local metabolism of hydrocortisone. Am J Respir Cell Mol Biol. 1991;4(2):166-173. doi:1165/ajrcmb/4.2.166
  63. Luo H, Tang QL, Shang YX, et al. 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. Chin J Integr Med. 2020;26(4):243-250. doi:1007/s11655-020-3192-6
  64. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective. Int J Biol Sci. 2020;16(10):1708-1717. doi:7150/ijbs.45538
  65. Lau JT, Leung PC, Wong EL, et al. The use of an herbal formula by hospital care workers during the severe acute respiratory syndrome epidemic in Hong Kong to prevent severe acute respiratory syndrome transmission, relieve influenza-related symptoms, and improve quality of life: a prospective cohort study. J Alternat Complement Med. 2005;11(1):49-55. doi:1089/acm.2005.11.49
  66. Zhang L, Chen B, Zeng H. Analysis of fangdu decoction on SARS and zero infection in hospital. Chin J Hosp Pharm (Chin). 2005;25:59-60.
  67. Michaelis M, Geiler J, Naczk P, et al. Glycyrrhizin exerts antioxidative effects in H5N1 influenza A virus-infected cells and inhibits virus replication and pro-inflammatory gene expression. PLoS One. 2011;6(5):e19705. doi:1371/journal.pone.0019705
  68. Tong T, Hu H, Zhou J, et al. Glycyrrhizic-acid-based carbon dots with high antiviral activity by multisite inhibition mechanisms. Small. 2020;16(13):e1906206. doi:1002/smll.201906206
  69. Manns MP, Wedemeyer H, Singer A, et al. Glycyrrhizin in patients who failed previous interferon alpha-based therapies: biochemical and histological effects after 52 weeks. J Viral Hepat. 2012;19(8):537?546. doi:1111/j.1365-2893.2011.01579.x
  70. Orlent H, Hansen BE, Willems M, et al. Biochemical and histological effects of 26 weeks of glycyrrhizin treatment in chronic hepatitis C: a randomized phase II trial. J Hepatol. 2006;45(4):539-546. doi:1016/j.jhep.2006.05.015
  71. Omar HR, Komarova I, El-Ghonemi M, et al. Licorice abuse: time to send a warning message. Ther Adv Endocrinol Metab. 2012;3(4):125-138. doi:1177/2042018812454322
  72. Russo S, Mastropasqua M, Mosetti MA, Persegani C, Paggi A. Low doses of liquorice can induce hypertension encephalopathy. Am J Nephrol. 2000;20(2):145-148. doi:1159/000013572
  73. Dellow EL, Unwin RJ, Honour JW. Pontefract cakes can be bad for you: refractory hypertension and liquorice excess. Nephrol Dial Transplant. 1999;14(1):218-220. doi:1093/ndt/14.1.218
  74. de Klerk GJ, Nieuwenhuis MG, Beutler JJ. Hypokalaemia and hypertension associated with use of liquorice flavoured chewing gum. BMJ. 1997;314(7082):731-732. doi:1136/bmj.314.7082.731