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Functional Medicine/TCM/Covid19


Functional Medicine: offerings and suggestions in prevention of Covid19 disease.

(For Traditional Chinese Medicine approach please see my previous blog).


Originally this blog was to look at all the similarities between the Functional and Eastern Medicine. However, since the recent pandemic of covid-19, I decided to start, to focus on what is in front of us. Please watch video by IFM MDs who put together fantastic presentation explaining immunology, virology, preventative medicine and modifyable life style factors in Covid19:


Functional Medicine approach to Covid19


IFM material explains that: "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 "cytokine storm, happens only in some infected individuals, the suspected theory is the patients that develop this potentially dangerous situation, do have pre-existing inflammatory conditions.

"Cytokine Storm Syndromes (CSS) are a group of disorders representing a variety of inflammatory etiologies with the final common result of overwhelming systemic inflammation, hemodynamic instability, multiple organ dysfunction, and potentially death. The hemophagocytic syndromes hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) represent two clinically similar CSS with an unknown degree of pathoetiologic overlap."(13)



Here are the most important risk factors on developing Cov19 from SARS2nCOV19.

"AGE: Young people have more ACE2 receptors (lower risk) and the number of receptors goes down with age (increased risk). This may explain why children are at such low risk of severe disease – they are protected by having lots of these ACE2 receptors.
SEX: Women have more ACE2 receptors than men, and in fact we see women tend to have less severe disease than men. 
HORMONES: The researchers surmised that estrogen may be protecting women. They looked at women on estrogen treatment and found that women on estrogen had more ACE2 receptors (associated with less risk). They also looked at men on testosterone therapy and found a slight increase in receptors (although not nearly as much as with estrogen). When they looked at male to female transgender people (on estrogen replacement and testosterone blocking medicine) they found significantly higher ACE2 receptors.  
DIABETES: People with type 2 diabetes have significantly fewer ACE2 receptors, and more risk for disease. The study did not include information about other diseases but perhaps other disease conditions also reduce receptors – more research will be needed here.
MEDICATION: ACE inhibitor medications are often used for high blood pressure. These medicines block the effect of the protein produced when the ACE2 receptor is activated We don’t yet know what effect the medications could have (if any) on disease risk. It is possible that ACE inhibitors could reduce risk, but we just don’t know. It is not recommended to change medications at this time since we just don’t have enough information yet." (16)




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]"



In more simple terms the innate immune respond, gets activated within hours of the viral exposure, and adaptive (specific) antigen specific immune system, which we did not develop yet as a cohort, in relationship to covid 19 disease. The innate, is the less specific ( and the non-induced and induced), it has certain natural barriers against infections. Than, if the virus cannot bind to the barriers, they cannot bind to receptor of those barriers, and cause us harm. Once it found the receptor of a cell in the cell barrier, and it binds to it, it becomes most dangerous. The barriers are epithelial specific, as well as pH can play the role in the vulnerability of cell and tissue. Adaptive, the antigen specific immune system, requires prior exposure to the pathogen. At the present moment RNA COV19 is new, so we have not trained and strategic response yet, to this virus. Barriers are most important starting point, mucus, PH Cellia, all can help to keep the virus out.
If the virus gets through the barrier, we are dealing with the intra-cellular respond, that will determine the life or death.
"TLR9 is critical nucleotide - makes it enter and replicate its RNA in the cell, its being Tall like receptor activated: NFkappa B (inflammation) plus type 1 interferon, NALP3 activated, central to fight of viruses, TLR9, virus than binds to NOD receptor, NLRP3 if activated will produce Interleucin 1 beta, "little is helpful than lots is a trouble!" Interferon Gamma, recruits other cells, Natural Killer Cells can recognize when cell was attacked by the virus and together with with cytotoxic lymphocytes, helps with its cell self-destruction. When there are a lot of cytokines production out-of-control, we deal with the so called Cytokine Storm, there are many cells dying causing systemic organ shut down."


If innate system works well, there are no symptoms or light symptoms of Covid19 disease.
The goal than, is to create healthy innate immune respond.

Possible modern/western pharmacological treatment:

The research that explains why than, chloroquine would be effective in nCov19 is this:Severe acute respiratory syndrome (SARS) is caused by a newly discovered coronavirus (SARS-CoV). No effective prophylactic or post-exposure therapy is currently available. (..)
Many different TCM herbal treatment protocols were used in China during the pandemic. More than 80% of patients and health care workers were administered TCM Herbs. "Traditional Chinese Medicine in Fight of Covid 19"- my previos blog.

For scientific data on TCM in fight of Covid 19 please watch Dr. John Chen presentation:

Coronavirus (Covid-19) and TCM: Scientific Research and Clinical Evidence of Chinese Herbs

Western/Modern Medicine wise, there has been some positive headway presented by researchgate.come:
"We report, however, that chloroquine has strong antiviral effects on SARS-CoV infection of primate cells. These inhibitory effects are observed when the cells are treated with the drug either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantage. In addition to the well-known functions of chloroquine such as elevations of endosomal pH, the drug appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2. This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in the inhibition of infection and spread of SARS CoV at clinically admissible concentrations. Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds."(12)

Institute of Functional Medicine in the Covid19 resources list already well researched biocompunds research that helps with the Innate Immune response regulatory mechanism, and in theory should play essential role in prevention of Sars2nCov infection, and development of Covid19 disease:

"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."

Supplements Recommendations (prevention).

These supplements are natural NLRP3 Inhibitors:

Curcumin 

Quercitn 
MelationinECGG
Reservartol



the-functional-medicine-approach-to-covid-19-virus-specific-nutraceutical-and-botanical-agents


Quercitine (also modulating immune responce in seasonal allergies):
500-1000 bid - research shows that consuming quercitine with curcumin inhences its efficasy, modulate viral-induced pathological cellular processes:
modulation of NLRP3 inflammasome activation.

Green tea: (ECGG) 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]8

N-acetylcysteine (NAC) 600-900 mg po bid (18)
modulate cellular defense and repair mechanisms:

Hypothetical: repletion of glutathione and cysteine.

Resveratrol 100-150mg po qd
Favorably modulate viral-induced pathological cellular processes.
Modulation of NLRP3 inflammasome activation[5] MERS-CoV[43]Influenza[44],[45]
It is important to not that Reservatrol also has been research in studies regarding longevity, it has shown effect on telomerase resilience. (17)


Vitamin D (check your blood saturation with your practitioner before deciding on the dosage)

Although originally it was advised against supplementing with Vitamin D other than regular dietary intake, the research shows clear benefit of its supplementation:
favorably modulate cellular defense and repair mechanisms: Activation of macrophages
stimulation of anti-microbial peptides
modulation of defensins
modulation of TH17 cells modulate viral-induced pathological cellular processes:
reduction in cytokine expression
modulation of TGF beta

Melatonin: 5-20 mg qd
modulate viral-induced pathological cellular processes:
modulation of NLRP3 inflammasome activation .[83],[84]


Vitamin A 10000-25000 IU/d
modulate cellular defense and repair mechanisms: modulation of T helper cells
modulation of sIgA, modulate viral-induced pathological cellular processes: modulation of cytokine production;

Elderberry 500 mg po qd (of USP standard of 17% anthocyanosides),
modulate cellular defense and repair mechanismsFavorably modulate viral-induced pathological cellular processes
(caution: patients with autoimmune disorders)


Those botanical above, work on inflammatory processes, as well as protease inhibitors.For mechanisms, risks, exact research data, please visit the ifm.org or contact me at info@oriri.ca.

the-functional-medicine-approach-to-covid-19-virus-specific-nutraceutical-and-botanical-agents 


Summary: Mentioned in this article virus effects mostly individuals with other comorbidity, If you are in that group, the modifiable life factors such as: reduction of stress, better diet, exercise, nutritional supplements and herbs to regulate your metabolism and improving your hormonal balance, can play a major role in keeping you alive in the incident of being invected.

Please ask your Practitioner for more information how to adjust the Modifyable Life Style Factors as well as how to follow best Programs and Nutritional Protocols for your body type requirements.




Wishing you all health, 
Dr. Katrine B. Hegillman


References:
(1)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 
(2) 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 
(3) 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 
(4)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 
(5) 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 
(6) 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
(7)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.v
(28) 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
(43) 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
(83)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
(84) 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
(12)https://www.researchgate.net/publication/7646092_Chloroquine_is_a_potent_inhibitor_of_SARS_coronavirus_infection_and_spread
(13) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368378
(14) https://signaturewellness.org/2020/03/15/does-estrogen-protect-women-from-coronavirus/?fbclid=IwAR2UpO-3HNKqmlklklj9YxlzyYZHibBB_zc6CrcbMu0Gh0mFnSh5-n0HZ0Y
(15) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144611/
(16)https://signaturewellness.org/2020/03/15/does-estrogen-protect-women-from-coronavirus/?fbclid=IwAR2UpO-3HNKqmlklklj9YxlzyYZHibBB_zc6CrcbMu0Gh0mFnSh5-n0HZ0Y
(17) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501037/ 
(18) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562654/ 
(19) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241507/https://www.ncbi.nlm.nih.gov/pubmed/18694818/

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