Bitter taste receptors in the lungs & Hesperidin’s decongestant properties.

How did citrus peel help my symptoms? In several ways it turns out, potentially. Antiviral actions, decongestant ability within the lungs, and by reducing the risk of blood clot formation within the lungs as the viral load increases and more tissue damage has occurred.

The antiviral capabilities were mentioned in previous posts – hesperidin and neohesperidin may act as antivirals in several ways, the vitamin C also, and quercetin can act as a zinc ionophore. Zinc ionophores are like chemical taxi-cabs – carrying zinc into infected cells preferentially where the zinc then disrupts the viral replication. (this post) No viral replication, no cell bursting to release them to infect other cells, and so on, in an exponentially increasing level of viral load and dead cells for the patient. The dead cell contents can also become a health risk when occurring in too great a quantity for white blood cells to collect it all for safe detoxification and removal at lymph nodes and by the kidneys.

Decongestant action is due to the bitterness of the hesperidin, neohesperidin, and probably other bitter tasting phytonutrients in citrus peel, and also quinine & chloroquines (also bitter tasting). (19) Think of taste or other sensory receptors that can do a variety of different things depending on where they are located and what they are connected to. Receptors are like tiny machines, activate the keyhole/puzzle piece opening with the matching chemical agonist, or inhibit with the matching chemical antagonist, and then the machine will do something if activated, or not do something or stop doing something if inhibited.

The chloroquines and quinines were found to help relax the airway in people with asthma, and increase movement of mucus out of the lungs. Activation of the bitter taste receptors on immune cells led to reduced production of inflammatory chemokines and cytokines. (19)

Taste receptors on the tongue would be connected to nerve cells that tell the brain a bitter taste or other flavor type was sensed and that information would be used to eat more if hungry for the taste or to stop eating if satisfied. Taste receptors for sweet carbohydrates are much less sensitive, more of the sweet taste is needed to activate them, than bitter taste receptors, by a magnitude of thousands – one or a few molecules of a bitter substance might activate the taste bud in the mouth, while thousands of sweet molecules might be needed to activate the sweet taste receptor. Sour is somewhere in between in the amount of sour molecules needed to activate sour taste receptors.

In other areas of the body sensory receptors may be attached to other chemical pathways instead of to nerves that go to the brain. Within the lungs there are many bitter taste receptors which when activated signal the mucus lining of the lung cells to make thinner mucus and to increase the motion of the cilia. Cilia are hair like or tail like projections lining the cell walls that can all work together in a wave like motion to move mucus and any dust or virus or other infectious microbes up and out of the lungs. (2)

Stimulation of these receptors by known bitter compounds activates calcium-dependent nitric oxide (NO) production that increases phosphorylation of ciliary proteins through protein kinase G (PKG). This increases ciliary beat frequency to facilitate the movement mucus out of the airway by increasing mucociliary transport rates. The generated NO also diffuses into the airway surface liquid & acts as an antibacterial defense mechanism. NO damages bacterial cell walls & DNA & may also damage fungal pathogens & inactivate viral proteins .” (Freund & Lee, 2)

Non-productive cough, a dry cough, feeling like something is in the lungs but you just can’t cough it out is part of the typical symptoms of COVID19/SARS-CoV2 infections for people who get sick rather than being asymptomatic carriers*. (*see footnote) To be able to have thin mucus that is protective, able to be traveled through easily by our mobile line of defense – the white blood cells, we need to have adequate water, and electrolytes (ions) within the cells: magnesium and potassium, and outside of the cells: sodium and calcium. Providing magnesium as a supplement (300 mg/day) helped thin mucus for patients with the genetic condition Cystic Firbrosis which causes chronic excess lung congestion. (16)

Mucus is more than 95% water, making water and ions just as important for controlling mucus properties .” (1)

If a person also is having nausea and vomiting and/or diarrhea, at the same time or in progressive stages, then dehydration and electrolyte deficiencies may become a significant problem, even life-threatening if severe. See this post (ACE2…) for digestive tips, and this one for a way to bypass malabsorption of magnesium with a topical source that can be absorbed through hair follicles (which is how ancient people would have gotten plenty – fresh water sources uses to be rich in magnesium).

To activate the bitter taste receptors that help with forming healthy thin mucus and help activate the wave like motion of the cilia we would need to have some bitter chemicals that match the bitter taste receptors found in great quantity within lung tissue. Hesperidin is a tasteless chemical found in citrus peel, with a bitter tasting chemical side chain, (3), and neohesperidin, a similar flavonoid, likely is obviously bitter in taste. (26)

Hesperidin, a flavonoid present in many citrus fruits, provides an example of a multi-domain compound. This molecule was found to contain eight of the substructures that form the nodes of the tree, and a selection of these are given in Figure 6. Of the eight node substructures contained within hesperidin, only one contains a significant proportion of known bitter molecules.” (3)

Anticoagulant action: The vitamin C and flavonoids in citrus peel can also help prevent blood clot formation which in more severely ill patients with COVID19 infections has been found to be part of the mortality risk. (4) Prevention is important – strengthen capillary walls to prevent microvascular damage that can lead to blood collecting and forming clots which then may block larger blood vessels and cause stroke like damage to larger areas of tissue.

More detail about this problem is available in a document with a revised Marik Protocol for treatment of ARDS with Vitamin C Infusion (and contains thiamine, vitamin B1 which may also be needed in greater quantity during a severe infection response, see this document 14, and 15). The revision recommendations are based on COVID19 treatment in China and elsewhere – the lung problems are not typical of ARDS and patients likely need more oxygen than pressure from the ventilator support or worse lung damage may result. (evms.edu/EVMS_Critical_Care_COVID-19_Protocol.pdf) (8)

Important Recommendation for Earlier Treatment for patients suspected of having a COVID19 infection – for homecare/outpatient prescriptions:

The evms.edu pdf includes a recommendation for nutrients to be used as a prevention before infection, and at home for early treatment (see the pdf for that list). Here is their recommendation for prevention dosing:

  • Vitamin C 500 mg BID and Quercetin 250-500 mg BID
  • Zinc 75-100 mg/day (acetate, gluconate or picolinate). Zinc lozenges are preferred. After 1-2 months, reduce the dose to 30-50 mg/day.
  • Melatonin (slow release): Begin with 0.3mg and increase as tolerated to 1-2 mg at night
  • Vitamin D3 1000-4000 u/day (optimal dose unknown). Likely that those with baseline low 25- OH vitamin D levels and those > living at 40o latitude will benefit the most.
  • (evms.edu/EVMS_Critical_Care_COVID-19_Protocol.pdf) (8)
  • Food sources of Quercetin include dock, sorrel, cilantro/coriander leaves, radicchio, kale, watercress, asparagus, onions, and okra: (graphic, via @HiperacusiaCAT), in addition to being found in citrus peel. (23)
  • Quercetin and EGCG are both are zinc ionophores that can carry zinc into infected cells preferentially where the zinc disrupts viral replication, and they may also have direct antiviral effects by inhibiting proteins that are important to the virus. The two phytonutrients may be even more effective at inhibiting the SARS-CoV2/COVID19 proteins than hydroxychloroquine and remsdivar medications based on computer modeling of the molecular shapes of the viral proteins, medications, and phytonutrients. (24)

Early treatment is critical due to the SARS-CoV-2 virus causing loss of iron from hemoglobin within red blood cells. In later stages of viral replication the lack of functioning hemoglobin alone causes lung damage due to the lack of oxygen. (20) Simply providing extra oxygen can’t help if there is too little functional hemoglobin. Providing blood transfusions with healthy red blood cells might be helpful – preventing the virus from replicating to that point would be better. *This theory was based on computer modeling and has not been verified. (25) The symptom of red blood cell’s having hemoglobin that is unable to transport oxygen is present in symptomatic Covid-19 illness, the theory about why iron is shifted out of hemoglobin was flawed.

Anemia of inflammation (post) could be the reason: the cytokine IL-6 causes an increase in hepcidin, which causes an increased movement of iron out of molecules of hemoglobin in red blood cells, or available for the growing red blood cells still within bone marrow, and into intracellular storage where it can overload the ability to keep it from oxidizing other chemicals and can lead to cell death. Pathogens also need iron so the strategy is a defense mechanism of the body that can become dangerous if the response becomes excessive. See the post Anemia of Chronic Inflammation, IL-6, Hepcidin, Iron, and Vitamin C, for more information.

A different group is recommending to the FDA to fast track approval for preventive, early treatment with zinc and an anti-malarial and an antibiotic that are fairly available and have a long history of use, so risks and dosing have been studied. “It’s important to note that HCQ, zinc, and azithromycin are very well understood drugs with clear safety profiles; they are widely available, generic, inexpensive, and can be scaled rapidly, including to the developing world, which would be expedited by US leadership in recommendations.” More is included in the second half of this post about the zinc and anti-malarial medication and other food/phytonutrient zinc ionophores which include quercetin. See this document for the recommendation to the FDA: (Immediate Treatment for Early Stage SARS-CoV-2 Infections). via (13)

Safety considerations of nutrient/phytonutrient Zinc Ionophore: Quercetin in very large doses may affect kidney health negatively (I can’t find a dose for that) however in an animal based study quercetin was protective of kidney health at a dose that would be about 360-720 milligrams per day for an adult weighing about 160 pounds (5-10 mg/Kg was provided to the experimental animals). (6) The amount of quercetin used as a zinc ionophore by a Canadian team may be 500 mg taken three times per day during or prior to suspected viral infection – but I can’t find the specific dosing. Zinc can be taken in larger amounts (~15-30 mg) for a few weeks but can collect in the body to excessive levels over time. Symptoms of chronic excess might include a decrease in immune function and copper deficiency may occur as the two trace minerals can affect each other (an excess of copper can cause a zinc deficiency). (Symptoms of excess Zinc, 7)

Bonus – Circadian cycles affect immune function – because bonuses are nice – another way phytonutrients, including hesperidin (9), may be helping immune function is by tipping the body towards the anti-inflammatory night-time chemistry and away from the daytime, stress response, inflammatory pathways.

And the bigger picture take-home-point from that is sleep is important for immune function and the sleep needs to have a complete blackout level of lighting for the body to be able to switch over to the anti-inflammatory action of an ancient dark night. We make more melatonin if we get some full spectrum daylight during daytime/wake hours and have complete darkness at nighttime – so a sleep eyemask or folded piece of soft clothing like a Tshirt draped over the eyes may help health. During my untested CoV-19 like illness I did have light sensitivity headaches and found sleeping or resting with a cloth over my eyes to be helpful.

Melatonin is a hormone that helps reduce inflammatory pathways that result in increased cytokines, and inflammasomes such as NLRP3 (10) which has been associated with worse prognosis for patients with COVID19. the role of NLRP3 activity in SARS-CoV (2003 strain) has been a subject of research. (12)

An animal study on oxidative damage from a type of cancer treatment: “Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation.” (10)

Phytonutrients that might inhibit NLRP3 and/or increase p53 activity.

Other phytonutrients including quercetin which is found in citrus peel, also can help inhibit production or activity of the inflammatory NLRP3 inflammasome. Sulfarophane (broccoli, etc), resveratrol (grape skins, etc), EGCG (green tea, pomegranate peel), curcumin (turmeric/curry powder), gensenoside (ginseng), emodin (aloe vera gel), mangiferin (mango) and genipin (from a fruit used as a Traditional Chinese Medicinal) are also phytonutrients that may reduce activity or production of NLRP3 inflammasomes. (17)

Increasing activity of a protein called p53 seems to help inhibit the production or activity of the NLRP3 inflammasome. Phytonutrients and nutrients that may promote p53 activity also include zinc, artemisinin (wormwood herb), goldenseal (berberine, also found in a few other herbs), Black seed oil (Nigella sativa), ginger (6-gingerol), feverfew, chamomile, and cordyceps mushrooms. (18) Replication of human coronaviruses and the SARS-CoV-1,(2003 strain) virus has been found to be inhibited by p53 and have also been found to cause the production of an additional protein that leads to breakdown of the p53 protein which may help explain the dysfunction of immune function in more severe infections. (21, 22)

Inactivating the NLRP3 inflammasome seems to have anti-inflammatory benefits (17) that may help prevent age related changes. It is an area of research being pursued for pharmaceutical development. (11) Sleep masks/pitch blackness during sleep, with the alarm clock and light leaking in the window covered, could help your body inactivate the NLRP3 inflammasome on a nightly basis with no ongoing copay. Options exist and are worth trying in an order of least toxicity risk to greater toxicity risk.

*Asymptomatic carriers: In some people the virus replicates somewhat but not to the point of much cell damage – not growing exponentially to the point of the patient’s life being threatened. Instead the virus seems to just become dormant within some cells and the person isn’t even aware they are sick – a symbiotic host/parasite relationship assures the parasite goes on living – in a living host – which is not abnormal, we typically have virus in us that can even provide some health benefits possibly – symbiotic means benefits both the host and the parasite, but not enough is known about this area of study – called our virome, (5), instead of microbiome.

Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual guidance. Please seek a health care provider for individualized health care guidance.

Reference List

  1. Hansson GC. Mucus and mucins in diseases of the intestinal and respiratory tracts. J Intern Med. 2019;285(5):479–490. doi:10.1111/joim.12910 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497544/
  2. Jenna R. Freund, Robert J.Lee, Taste receptors in the upper airway. World Journal of Otorhinolaryngology – Head and Neck Surgery, 4;1, March 2018, pp 67-76 https://www.sciencedirect.com/science/article/pii/S2095881118300167
  3. Sarah Rodgers, Johanneke Busch, Hans Peters, Elly Christ-Hazelhof, Building a Tree of Knowledge: Analysis of Bitter Molecules. https://academic.oup.com/chemse/article/30/7/547/360693
  4. Here’s the Damage Coronavirus (COVID-19) Can Do to Your Lungs. March 20, 2020, health.clevelandclinic.org, https://health.clevelandclinic.org/heres-the-damage-coronavirus-covid-19-can-do-to-your-lungs/
  5. Virgin HW. The virome in mammalian physiology and disease. Cell. 2014;157(1):142–150. doi:10.1016/j.cell.2014.02.032 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977141/
  6. Yang H, Song Y, Liang YN, Li R. Quercetin Treatment Improves Renal Function and Protects the Kidney in a Rat Model of Adenine-Induced Chronic Kidney Disease. Med Sci Monit. 2018;24:4760–4766. Published 2018 Jul 10. doi:10.12659/MSM.909259 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069490/
  7. Too much Zinc: Symptoms, Causes, and Treatments, MedicalNewsToday.com, https://www.medicalnewstoday.com/articles/326760#symptoms
  8. EVMS Critical Care COVID-19 Management Protocol, *Marik protocol revised, evms.edu https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf
  9. A. Manjula, R. Subashini, R. Punitha & P. Subramanian (2017) Modulating effects of hesperidin on circadian pattern indices of rotenone induced redox homeostasis in clock mutant (cryb) of Drosophila melanogaster, Biological Rhythm Research, 48:6, 897-906, DOI: 10.1080/09291016.2017.1319641 https://www.tandfonline.com/doi/abs/10.1080/09291016.2017.1319641?journalCode=nbrr20
  10. Beatriz Fernández-Gil, Ahmed EA Moneim, Francisco Ortiz, et al, Melatonin protects rats from radiotherapy-induced small intestine toxicity. PLOS One, April 12, 2017 https://doi.org/10.1371/journal.pone.0174474 https://dx.plos.org/10.1371/journal.pone.0174474
  11. Hannah Balfour, NLRP3 inflammasome ‘off switch’ reverses effects of chronic inflammation. Feb 6, 2020, drugtargetreview.com, https://www.drugtargetreview.com/news/55776/nlrp3-inflammasome-off-switch-reverses-effects-of-chronic-inflammation/
  12. I-Yin Chen, Miyu Moriyama, Ming-Fu Chang and Takeshi Ichinohe, Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome. https://www.frontiersin.org/articles/10.3389/fmicb.2019.00050/full
  13. Immediate Treatment for Early Stage SARS-CoV-2 Infections. via Avery J. Knapp, Jr. MD (https://twitter.com/aknappjr/status/1247497984431943680?s=20) https://docs.google.com/document/d/1ka76CL50hR_a0b5oIhEAVY4gfyqkJcBxXBcP0r2nrz0/edit?fbclid=IwAR0ss1p0lsPhLkSFhO6_8vJK19BUispAREVcn0oi09iajG-Pq4HDCMFTQdg
  14. James Ludell, Operation CAI-Reducing Peak Load on Hospitals from COVD-19, April 5, 2020, last updat April 10, 2020, (father of a child with a rare condition for which high dose thiamine helps – making him a very well-informed patient advocate sharing information that typically would not be used/studied for standard patient care – but can be helpful for critically ill and/or malnourished patients, see 15), https://docs.google.com/document/d/1vnYosVsgChnGVecOXp96T5i2UibTsnHVaDUVF6Us2uM/edit?usp=sharing
  15. Manzanares W, Hardy G. Thiamine supplementation in the critically ill. Curr Opin Clin Nutr Metab Care. 2011;14(6):610–617. doi:10.1097/MCO.0b013e32834b8911 https://pubmed.ncbi.nlm.nih.gov/21912244/
  16. Magnesium Clears up Mucus and Improves Breathing in Cystic Fibrosis Patients. Feb 10, 2014, Natural Health Research Institute, naturalhealthresearch.org, https://www.naturalhealthresearch.org/magnesium-mucus-cystic-fibrosis/
  17. József Tőzsér and Szilvia Benkő, Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1β Production. Mediators of Inflammation, 2016, Article ID 5460302, 16 pages, https://doi.org/10.1155/2016/5460302 https://www.hindawi.com/journals/mi/2016/5460302/
  18. Pack GL, Natural Promotion of p53 Protein Activity. Dr. Pack’s Summary #763, Rainbow Grocery, San Francisco, CA, USA. https://www.rainbow.coop/library/natural-promotion-of-p53-protein-activity/
  19. (Nayak, Shah, Deshpande, 2019) Nayak AP, Shah SD, Michael JV, Deshpande DA. Bitter Taste Receptors for Asthma Therapeutics. Front Physiol. 2019;10:884. Published 2019 Jul 16. doi:10.3389/fphys.2019.00884 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647873/
  20. *This paper has been found to have flaws in the interpretation. (25) Wenzhong Liu, Hualan Li, COVID-19: Attacks the 1Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. covid19-2020004-9-EN.pdf ChemRxiv, https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173
  21. LMU Press Release, contact person Dr. Albrecht von Brunn, How a Tumor Suppressor Indirectly Inhibits Coronaviruses. Aug 12, 2016, DZIF German Center for Infection Research, https://www.dzif.de/en/how-tumor-suppressor-indirectly-inhibits-coronaviruses
  22. Yue Ma-Lauer, Javier Carbajo-Lozoya, Marco Y. Hein, et al., p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1. Proceedings of the National Academy of Sciences Aug 2016, 201603435; DOI: 10.1073/pnas.1603435113 https://www.pnas.org/content/early/2016/08/11/1603435113.abstract
  23. Shafiya Rafiqa, Rajkumari Kaula, S.A.Sofi, et al., Citrus Peel as a Source of Functional Ingredient: A Review, J Saudi Society of Ag Sci, 17;4, Oct 2018, pp 351-358, https://www.sciencedirect.com/science/article/pii/S1658077X16300960
  24. Michael Lustgarten, Coronavirus – Can Diet Help?, April 11, 2020, michaellustgarten.com, https://michaellustgarten.com/2020/04/11/sars-cov-2-can-diet-help-in-the-fight/
  25. Randy J Read, Flawed methods in“COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism” ChemRxiv.org, https://chemrxiv.org/articles/Flawed_methods_in_COVID-19_Attacks_the_1-Beta_Chain_of_Hemoglobin_and_Captures_the_Porphyrin_to_Inhibit_Human_Heme_Metabolism_/12120912
  26. Adam Drewnowski, Carmen Gomez-Carneros, Bitter taste, phytonutrients, and the consumer: a review, Amer J of Clinical Nutrition, 72;6, December 2000, Pages 1424–1435, https://doi.org/10.1093/ajcn/72.6.1424 https://academic.oup.com/ajcn/article/72/6/1424/4729430 Addition – “neohesperidoside, and neohesperidin are very bitter, whereas hesperidin is tasteless

Vitamin C, IL-6, and respiratory failure in COVID19

Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients“, a higher level of interleukin-6 is predictive of greater risk of respiratory failure, (1) and Vitamin C reduces IL-6: “Vitamin C blocks vascular dysfunction and release of interleukin-6.” (2)

The Vitamin C Infusion therapy has had minimal adverse reactions in studies with the use of it in addition to standard chemotherapy treatments for patients with cancer, (3), or for patients with sepsis which is similar problem to an excess production of cytokines due to an infection. (Fowler 2014) It is given with thiamine, a B vitamin, which is also water soluble. (Protocol used in China for Vitamin C Infusion IV treatment)

Both nutrients may be needed in greater quantity due to the infection process so it isn’t normal health – the RDAs – Recommended Daily Allowances or DRIs – Daily Recommended Intake amounts for nutrients are for normal health, not guidance for illness or chronic conditions that may affect nutrient balance.

Vitamin C also helps prevent capillary breakdown and risk of easy bruising or blood clots (Tyml, 2017) which have been found to be part of the risk for more severe lung symptoms and respiratory failure with CoV-19 infection. (farid_jalali/pdf) Some of the questions brought up in that pdf are answered in this video update: Roger Seheult, MD, Coronavirus Pandemic Update 37: The ACE-2 Receptor – The Doorway to COVID-19 (ACE Inhibitors & ARBs). March 16, 2020, MedCram.com, (youtu.be/1vZDVbqRhyM), which I included in this post along with foods that might help digestive symptoms associated with COVID19.

Life or death, essential nutrients are called essential for a reason – essential for life.

Home, self-care could include a variety of vitamin C rich foods. Vitamin C helps the immune system fight infection. Good sources include: cabbage, tomatoes, green peppers, broccoli, asparagus, peas, kale, & citrus, strawberries, kiwi, papayas, cantaloupe, and many other foods. (Vit C Fact Sheet)

Use of the citrus peel can more than double the amount of vitamin C compared to using only the fruit wedges, (nourishingjoy.com/Vit C Powder), and it provides many other beneficial flavonoids, see recent post). The pithy white part of the peel is mild compared to the outer zest and can be eaten along with the orange slices and the zest could be dried and powdered to add to other foods (after cooking, add it at the table) or made into an orange marmalade type sauce to add to salad dressing or for use in baking, (recipe post). Heating with lower temperatures can help preserve more vitamin C content than higher heat.

Cytokine Storm Syndrome & Vitamin C Infusion, — webinar for medical professionals.

The webinar is now available as a video that can be viewed at any time, see the website: isom.ca. The Vitamin C Infusion technique is being used for COVID19 patients in a large hospital chain in New York, based on the improved survival rate seen in Shanghai China, (NYPost)

An over-reaction of the immune system called Cytokine Storm Syndrome or sepsis shock can be the cause of death from COVID-19 infection rather than the breathing problems and pneumonia symptoms. Some people may be more genetically at risk of having the inflammatory over-production of cytokines. (Cytokine Storm Syndrome/genetics) They are involved in killing infected cells but an excess can cause organ failure and lead to death. Intravenous Vitamin C Infusion can be safe and nontoxic for treating sepsis shock (Fowler 2014) and may improve survival rates (ScienceDaily) and is a strategy that was used in Wuhan, China for COVID-19 patients. (Video update by Dr. Cheng) (Clinical Trial/Peng) (Protocol used in China for Vitamin C Infusion IV treatment)

Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual guidance. Please seek a health care provider for individualized health care guidance.

Reference List

  1. Tobias Herold III, Vindi Jurinovic, Chiara Arnreich, et al., Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients. April 04, 2020. MedRxIV.org https://doi.org/10.1101/2020.04.01.20047381 https://medrxiv.org/content/10.1101/2020.04.01.20047381v1
  2. Böhm F, Settergren M, Pernow J. Vitamin C blocks vascular dysfunction and release of interleukin-6 induced by endothelin-1 in humans in vivo. Atherosclerosis. 2007 Feb;190(2):408-15. Epub 2006 Mar 9. https://ncbi.nlm.nih.gov/pubmed/16527283
  3. van Gorkom GNY, Lookermans EL, Van Elssen CHMJ, Bos GMJ. The Effect of Vitamin C (Ascorbic Acid) in the Treatment of Patients with Cancer: A Systematic Review. Nutrients. 2019;11(5):977. Published 2019 Apr 28. doi:10.3390/nu11050977 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566697/

Dark Chocolate Orange Peel Cookies – recipe

This recipe uses dark chocolate baker’s cocoa and fresh orange peel rather than candied dark chocolate orange peel, however the taste and texture is similar. The ingredients are gluten free and vegan (egg free, dairy free) because I have to be able to taste a recipe to create it. Recipes can be modified with substitutions once you are familiar with the basic ratios of baking or cooking.

I have provided a second list of the basic ingredients I would use instead if I was making it with butter, eggs, sugar and wheat flour. The citrus peel along with zinc in the nut butter might provide some antiviral benefits and the tapioca starch is beneficial for the intestinal microbiome. The recipe is somewhat low sugar for a cookie but they do taste sweet. If Gumbo file is used as the emulsifier it is likely adding some hydrolyzable tannins which may also have an antiviral effect and is beneficial for intestinal health.

Dark Chocolate Orange Peel Cookies

  • Made approximately 40-48 small cookies. One to three cookies would be a serving, roughly. Bake at 300-325’F oven, rotate racks for even baking of the cookies. Once cooled store in an airtight container at refrigerator temperature to create resistant starch from the tapioca, which is a good thing because it supports beneficial intestinal bacteria that turn resistant starch into a positive type of fatty acid – “short chain fatty acids (SCFA). “. (1)

Ingredients/Preparation

  • 1 large orange, wash the orange, and remove the outer peel, leaving the white part on the orange to eat fresh (I eat half the orange as a serving), mince the orange zest peel, yield was 6 tablespoons.
  • 1 cup water, simmer the orange peel in a sauce pan with:
  • 1 tablespoon Stevia (my stevia sweetener is 1/2 cup to = 1 cup sugar)
  • 2 tablespoons coconut oil
    • bring to a simmer briefly then remove from heat and stir into:
  • 1/4 cup Gumbo file, premeasured in a small mixing bowl, stir until the consistency thickens and turns a dark greenish/brown (Gumbo file is powdered sassafras leaves and acts as an egg substitute and provide some hydrolyzable tannins which can have an antiviral effect.)
  • 1/2 cup almond butter or cashew butter, add to hot emulsifier & stir
  • 3/8 cup coconut oil, melted, add to emulsifier mixture & stir

In a separate large mixing bowl stir the dry ingredients together:

  • 1/4 cup Stevia sugar substitute
  • 1/2 cup Brown rice flour
  • 1/2 cup Tapioca starch
  • 1/2 cup Coconut flour
  • 1/2 teaspoon salt
  • 1/2 teaspoon Baking Soda
  • 1/4 cup Cocoa Powder, Dutch style is darker & smoother in flavor

Add the emulsifier mixture to the dry ingredients along with:

  • 1 cup Coconut milk, (part of a 13.5 oz can), or a little more until the batter is moist and could be used in a pastry bag if desired or a cookie press with a large opening (the minced orange makes it slightly lumpy).

Spoon the batter onto two oiled cookie sheets in small teaspoon mounds, 20-24 per cookie sheet. Bake for about 25 minutes at 300-325’F. Remove from oven when they have formed a slight crust but are still moist. Let cool on a cookie rack and then store in an airtight container in a refrigerator overnight. The tapioca changes to resistant starch once the cooked product it is made with is chilled (Bubble Tea fans – the bubbles are tapioca pearls (like round noodles but made from tapioca starch).

Modified recipe, roughly, for people with standard ingredients in their cupboard:

  • Prepare the orange peel in the same way, except 2 tablespoons of butter could be used – fat to help draw some of the fat soluble phytonutrients from the citrus peel,and 2 tablespoons sugar.
  • 2 eggs
  • 1/2 cup peanut butter, almond butter, or cashew butter – for protein & zinc
  • 3/8 cup butter – soften, or melt depending on if you use a mixer or are hand stirring.
  • 1/2 cup sugar – this is low sugar for a cookie but if health is the goal, less sugar is healthier and the coconut adds a little sweetness too.
  • 1/2 cup tapioca starch or flour
  • 1 cup flour
  • 1/2 teaspoon salt
  • 1/2 teaspoon Baking Soda or 2 teaspoons Baking Powder (it contains starch so is less concentrated)
  • 1/4 cup baking cocoa powder
  • 1 cup milk or less if the eggs add enough moisture.

For other cookie recipes and information about modifying recipes see: G8. Cookies & Bean Soup.

For more about hydrolyzable tannins, see ACE2, Diarrhea, COVID19…It gets complicated.

For more about pomegranate peel benefits and preparation (may have antiviral benefits and is a much richer source of hydrolyzable tannins which can be soothing for an inflammatory bowel condition/diarrhea) see: G13: Pomegranate, and G10: Nrf2 Promoting Foods.

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference List

  1. Bruna L. B. Pereira, Magali Leonel, Resistant starch in cassava products., Food Sci. Technol (Campinas) vol.34 no.2 Campinas April/June 2014, https://doi.org/10.1590/fst.2014.0039 http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0101-20612014000200012
  2. Dr Andrew Weil, Sassafras Tea Safety, DrWeil.com *Which is made with the root which would contain significantly more than the leaves. https://www.drweil.com/diet-nutrition/food-safety/sassafras-tea-safety/
  3. Forum topic: Safrole is not nearly as dangerous as you would think. Jan 16, 2011, HomeBrewTalk.com, https://www.homebrewtalk.com/forum/threads/safrole-is-not-nearly-as-dangerous-as-you-would-think.218174/
  4. Yamaguchi, M.U., Garcia, F.P., Cortez, D.A.G. et al. Antifungal effects of Ellagitannin isolated from leaves of Ocotea odorifera (Lauraceae). Antonie van Leeuwenhoek 99, 507–514 (2011). https://doi.org/10.1007/s10482-010-9516-3 https://link.springer.com/article/10.1007/s10482-010-9516-3 *Ocotea odorifera is related to the North American Sassafras tree and has hydrolyzable tannins – egallic acid.
  5. pg 37, hydrolyzable and condensed tannins in the diet. https://nepis.epa.gov/Exe/ZyNET.exe/91014TYI.txt?ZyActionD=ZyDocument&Client=EPA&Index=1986%20Thru%201990&Docs=&Query=%28hydrolyzable%20tannins%29%20OR%20FNAME%3D%2291014TYI.txt%22%20AND%20FNAME%3D%2291014TYI.txt%22&Time=&EndTime=&SearchMethod=1&TocRestrict=n&Toc=&TocEntry=&QField=&QFieldYear=&QFieldMonth=&QFieldDay=&UseQField=&IntQFieldOp=0&ExtQFieldOp=0&XmlQuery=&File=D%3A%5CZYFILES%5CINDEX%20DATA%5C86THRU90%5CTXT%5C00000027%5C91014TYI.txt&User=ANONYMOUS&Password=anonymous&SortMethod=h%7C-&MaximumDocuments=1&FuzzyDegree=0&ImageQuality=r75g8/r75g8/x150y150g16/i425&Display=hpfr&DefSeekPage=x&SearchBack=ZyActionL&Back=ZyActionS&BackDesc=Results%20page&MaximumPages=1&ZyEntry=37

Treatments vs ‘a cure’

The question of what is a treatment versus what is a cure has been an issue online, while writing and communicating about dietary foods, supplements, or medications that might help treat patients with SARS-CoV(2) – Coranovirus Disease 2019, or COVID-19. The definition of the words suggest that a treatment is anything that helps with management of symptoms of a chronic or acute/short term illness, while a cure – to be cured – is something that resolves an illness.

Addition: It is being recommended to the FDA to fast track approval for preventive, early treatment with zinc and an anti-malarial and an antibiotic that are fairly available and have a long history of use, so risks and dosing have been studied. “It’s important to note that HCQ, zinc, and azithromycin are very well understood drugs with clear safety profiles; they are widely available, generic, inexpensive, and can be scaled rapidly, including to the developing world, which would be expedited by US leadership in recommendations.” More is included in the second half of this post about the zinc and anti-malarial medication. See this document for the recommendation to the FDA: (Immediate Treatment for Early Stage SARS-CoV-2 Infections).

Many treatments might be used to help a person become cured of a curable illness – so every single person that has recovered from being ill with the viral COVID-19 infection can be said to have been cured – with whatever treatments they used at home or were provided in a health care setting. I was sick with an untested illness that included symptoms matching the description and time-frame of the current pandemic infection. Once blood serology tests for antibodies becomes more widely available I may be able to have confirmation that the illness I had was due to the SARS-CoV(2) virus, (2/20 suspected exposure, 2/28 symptoms began, recovery took weeks).

Symptoms for me, and many people, started with a couple days of headache, exhaustion, nausea, vomiting, hot and cold feverish chills, and diarrhea. I coped by not eating, even water was nauseating. I stayed hydrated by sipping small amounts of water with a tablespoon or two of lime juice in it. Lemon juice or apple cider vinegar would also have provided similar acidity to stomach acid – if even water is nauseated then there is a problem with stomach acidity.

Along with the diarrhea there was intestinal pain with eating. The only foods that were very soothing were oranges with the white pith part of the peel left on and bean soup or sweet potato made with hydrolyzable tannins from pomegranate peel or walnuts. See the post ACE2, Diarrhea, COVID19, – It gets complicated.

The nausea and vomiting for me only lasted a couple days, the diarrhea lasted longer, a week or so, and as that was improving my cough, sore throat and difficulty breathing worsened. The cough became non-productive which translated from medical jargon equals – sticky thick mucus that just couldn’t be coughed out. There was an urge to cough and it would get bad enough to become oxygen deprived and see ‘stars’ – those little sparkly specks of whatever your brain/eyes are doing when you get too low in oxygen or with a severe headache.

The oranges with white part of the peel left on were soothing to the digestive system and helped thin the sticky mucus, can’t cough anything out problem. Hot steamy soup also helped thin the too-thick mucus problem so I was able to cough and feel better instead of worse. I was also using chewable vitamin C tablets, 100 milligram, which I had on hand and typically take one a day. I was using an extra one or two a day during the worst of the coughing.

Self-care strategies using nutrients/phytonutrients in moderate doses are considered First Aid rather than a medical treatment. Vitamin C Infusion given intravenously in high doses provided by a medical professional would be considered a medical treatment while my use of a chewable Vitamin C tablet in a 100 milligram dose for a sore throat would be considered First Aid, based on a definition within an employment policy about Workman’s Compensation. (wisconsin.edu/Medical Treatment Beyond First Aid).

Vitamin C has a recommended daily minimum intake of 60 milligrams for non-pregnant adults and 100 milligrams is only slightly more. High dose intravenous treatments may provide 15 grams over the course of the day. Adverse reactions are rare and the treatment has been successful for improving survival rate in the case of sepsis shock which can involve an excess of cytokines.

Many herbal nutrients can help the body have an immune reaction that is enough to cope with an infection without becoming an overactive response that results in an excessive amount of cytokines to be produced. I may have been lucky in my recovery or it may have been aided by the variety of nutrients and phytonutrients that I take as supplements or within my diet in the form of nutrient dense foods – or citrus peel and pomegranate peel – not typically considered food but very edible when the outer layer is removed and the white inner part is eaten, or the outer layer is prepared so only small amounts are used.

Traditional Chinese Medicinals (TCM) are used in combinations and are thought to be more effective than the herbs would be used singly. Individualized care by a trained practitioner is recommended as with any other medical care. The herbs have also been studied for potential use as anti-inflammatory medications if an active phytonutrient can be identified. Corylin from Psoralea corylifolia L. (Fabaceae) an herb used in both TCM and Ayurveda traditional healing has been found to have immunomodulatory effects which means it can help the body have enough of an immune response but not an overactive sepsis response. (2)

A computer modeling of the genetic structure of the SARS-CoV(2) virus was compared to a database of western medicines and a database of Traditional Chinese Medicinal herbs for potential treatments. Different areas of viral replication or cell entry were identified as possible targets for therapeutic agents and the potential treatments identified from the databases were grouped by the mechanism of action. (3)

Going through the list suggested that my routine use of multiple herbs, nutrient supplements, and nutrient dense foods may have helped my recovery as I use several of the potential therapeutic agents including some with different mechanisms of action.

  • In the first section PLpro inhibitors, I used citrus peel daily which includes hesperidin and neohesperidin and L(+)-Ascorbic acid – vitamin C, (13): “hesperidin and neohesperidin…might be the potential 3CLpro inhibitors and could probably be used for treating SARS-CoV-2.” (3)
  • The section also includes Riboflavin-vitamin B2 which I take a high dose of as it is water soluble and not available singly in RDA doses;
  • Silybin- which I would have in my Milk Thistle supplement;
  • and “…epigallocatechin gallate, [EGCG]…exhibited high binding affinity to PLpro protein, suggesting the potential utility of these compounds in the treatment of SARS-CoV-2.” (3) I use EGCG daily within pomegranate peel and/or green tea. It can also act as a zinc ionophore when zinc is available. (11)
  • (–)- Rosmarinic acid – is found in rosemary, an anti-inflammatory herb that I use generously in cooking because of the pain relieving/anti-inflammatory properties.
  • In the second section, 3C-like main protease (3CLpro) inhibitors: I would have a metabolite of riboflavin, Flavin mononucleotide, from my high dose vitamin B2 supplement, and Lutein which is found in cooked kale and other produce. The citrus peel phytonutrients hesperidin and neohesperidin also have this mechanism of action and rosmarinic acid from rosemary.
  • In the third section, RNA-dependent RNA polymerase (RdRp) inhibitors: silybin, in Milk Thistle is included again.
  • In the fourth section, Helicase (Nsp13) inhibitors, the citrus peel phytonutrients hesperidin and neohespiridin are mentioned along with other plant flavanoids: “The natural products, such as many flavanoids from different sources (α-glucosyl hesperidin, hesperidin, rutin, quercetagetin 6-O-β-D-glucopyranoside and homovitexin), …showed high binding affinity to this target.” (3) Rutin is found in green and black tea and a few other foods. Quercetagetin… seems to be a form of quercetin, which also can act as a zinc ionophore, (11) and is in citrus peel. Homovitexin is also called isovitexin and is found in cannabis and flaxseed and in a few other foods. (4)
  • In the fifth section, Targets inhibiting virus structural proteins, flavonoids are included again, with hesperidin and neohesperidin from citrus peel in my diet and “licoflavonol from Glycyrrhiza uralensis” in my supplement of licorice root. “By superimposing the ACE2–RBD complex to the hesperidin–RBD complex, a distinct overlap of hesperidin with the interface of ACE2 could be observed (Fig. 6C), suggesting hesperidin may disrupt the interaction of ACE2 with RBD [the RBD section of the SPIKE protein]. ” (3)
  • The sixth section Targets inhibiting virulence factor did not include any herbals that I take or eat regularly.
  • The seventh section Targets blocking host specific receptor or enzymes included neohesperidin and hesperidin from Citrus aurantium again, the two phytonutrients are also in the peel of other citrus species. (5) “The natural products, such as phyllaemblicin G7 from Phyllanthus emblica, xanthones from the plants of Swertiagenus, neohesperidin and hesperidin from Citrus aurantium, exhibited potentially high binding affinity to ACE2 protein. ” (3)

Six out of seven sections – and multiple possible phytonutrients or nutrients within the different potential areas targeting the virus mode of entry into the human cell at the ACE2 receptor or the viral replication process – I am recovered, and my use of the white part of the orange peel may have helped in five of the seven targets of action. Is it a cure? I am cured, recovered, not on a ventilator. I did have to stop smoking medical marijuana because I could tell I was heading for needing an asthma inhaler but I continued to use edible sources of cannabis as it helps a variety of health issues for me. I also use a high dose of zinc and the quercetin in citrus peel and onions, and EGCG in pomegranate peel and green tea, are both zinc ionophores – meaning they act as transport carriers to get zinc into an infected cell where the zinc can disrupt viral replication.

To use a sports metaphor – I like to cover all my bases, and shortstop, and center field, left and right field too. The wonder of nutrients and phytonutrients is they tend to be very low risk, some may have risk of overdose but not typically.

Treatments, multiple treatments might help provide a ‘cure‘, which refers to a recovery from illness. The idea that one medication is all you need to be ‘cured‘ became more of an expectation after antibiotics were discovered – however microbes mutate and become resistant when one drug is used consistently – and then the drug is no longer a cure. Using multiple treatments, that target different aspects of a pathogen’s mode of infection and replication needs, may help prevent mutations that make a single ‘cure‘ obsolete due to the pathogen developing resistance to the drug.

Many treatments might be needed for the various stages and range of symptoms that can occur with the COVID19, SARS-CoV(2) virus. It is new, waiting for clinical trials isn’t very helpful for people who are already sick. Citrus peel is readily available in fresh fruit or in Middle Eastern groceries as whole dried limes or powdered dried lemon or lime, and in the Traditional Chinese Medicinal Chen Pi. The whole peel includes the more bitter and potent outer part of the peel. One to two teaspoons is a more typical dose of the TCM Chen Pi and it would be used with a few others. The TCM guidance for COVID19 included licorice and astragalus which I also use daily as a supplement.

The inner white part of the peel is milder in flavor, I have been using an entire orange daily, half in the morning and half in the evening. This is my story, which I’m sharing as an example. Food is a personal choice, and fairly safe compared to many medications.

An orange peeled so the white pith remains.
The orange zest layer of the orange peel can be trimmed to leave the white pith with the sweet orange wedges. It is a rich source of quercetin, hesperidin, neohespidin and vitamin C..

Best of health, and best of appetite to all. – Severe lack of appetite, and also loss of sense of smell and taste, can all be symptoms of zinc deficiency. The infection process can use up nutrients faster than during normal health. Providing extra nutrients may be needed to promote healing – is that just expensive urine or an inexpensive ‘cure‘. If the person recovers from an illness – then they are cured. Waiting for clinical trials when nontoxic inexpensive solutions might be sitting on the grocery shelf seems like a mistake that can cost unnecessary lives.

Zinc with the aid of Zinc Ionophores also disrupt Viral Replication.

Zinc also has antiviral properties. Once it is carried into a cell by a zinc ionophore, whether nontoxic quercetin, EGCG, (11, 12) or potentially toxic Chloroquine or Hydroxychloroquine, (10), then it disrupts viral replication (6) by the mechanism of action in the third section – RNA-dependent RNA polymerase (RdRp) (3) of the computer modeling article.

Chloroquine and Hydroxychloroquine preferentially collect in the lungs which helps increase potency with smaller doses, part of risk is due to the medications also collecting more in cells with melanin which include skin and eye cells – damage to the eyes can be a risk with large doses or extended us for years as a malaria or autoimmune disease treatment. People with cardiac problems may also be more at risk of adverse cardiac reactions. (7)

Low magnesium (hypmagnesemia) or low potassium (hypokalemia) blood levels can be an indicator of cardiac risk with the use of Chloroquine or Hydroxychloroquine. (7) Dietary consult (me) would include in a hospital chart note the reminder that low magnesium levels can cause a suppression of potassium levels and therefore correcting the low magnesium might improve the potassium level too, and help protect against the risk of adverse cardiac events. (8)

With poor intestinal absorption low magnesium can become an acute risk – sudden, short term, or it can be a problem with chronic intestinal malabsorption of magnesium. Topical sources of magnesium can be absorbed through hair follicle pores. Magnesium chloride in lotions or liquid can be applied to the skin, or a foot soak or a bath with Epsom Salt, magnesium sulfate, can also be a beneficial source of bioactive sulfate. Foot soak, approximately 40 minutes for me, 1 cup Epsom Salt in a large wastepaper basket size container where the lower legs will also be covered by the magnesium rich water. Bath, approximately 20 minutes for me, research based also, with 1-2 cups of Epsom salt in a half-full bathtub. (9)

Just because a treatment is low cost, readily available, low toxicity risk, and effective, does not mean it is bad, it may just be bad for someone’s profit margin. Quercetin is readily available in many foods, raw red onion it the best source, although citrus peel may not have been included as a typical ‘food’ source. (14, 17) EGCG supplements are available derived from green tea, pomegranate peel is also a very good source and pomegranate season may be just near the end of availability for southern hemisphere consumers. Powdered pomegranate peel may be available in limited amounts. Citrus peel is readily available as fresh or dried products. Epsom salt is available in drugstores and the pharmacy section of department stores.

There has been some controversy in the US regarding use of chloroquine or hydroxychloroquine for treatment of patients with COVID19 infections. Supply issues can be resolved with increased production. The medication is also used for autoimmune patients (18) (who might be able to use artemisinin instead (15) or pomegranate peel (16), but ideally provide the pomegranate peel with zinc also, (11, 12) ) and there has been some trouble with filling their prescriptions due to an increase in demand due to the COVID19 epidemic. Production can be increased, the cardiac risk might be able to be reduced if topical sources of magnesium are provided to patients.

Whether the dose used is enough for effective control of viral replication is the theme of pdf presentation. Too low a dose may have been used in clinical trials that didn’t show efficacy for COVID19 treatment. Tere is a narrow range before toxicity is reached. Having a larger loading dose followed by smaller daily doses broken up into several small doses may be safer, while providing enough to be effective against the viral infection. (7) My big question would be – how much zinc was provided to patients in those trials? The pdf (7) never mentions zinc at all — while the chloroquines may also have some other antiviral capability, they have been shown to be effective against malaria when zinc is present in almost an equal weight to the chloroquine dose. (19)

Returning to my own health story – I do take a high dose zinc supplement for suspected pyroluria symptoms (might be genetic condition affecting an enzyme that would preserve the body supply of zinc and vitamin B6) and I did have more severe muscle cramps as part of my symptoms which is fairly normal for me and Epsom salt baths or footsoaks every 5-7 days helps to prevent or resolve the muscle cramps. Some individuals or conditions may cause long term problems with absorption of magnesium from the diet, or due to increased urinary loss of magnesium. Illness can increase need for magnesium as well as possibly decreasing absorption and increasing loss in sweating more, due to a high fever, or in urinary losses.

The heart is a muscle and all types of muscle use calcium to contract and magnesium to relax. Magnesium is given intravenously as a treatment for the long QT interval/Torsades de Pointes tachycardia that can be a cardiac adverse reaction with chloroquine treatment. (20) Why not give magnesium in a footsoak, before having a dangerous cardiac reaction?

Quercetin plus zinc has FDA approval for use in treatment of COVID19, Canadian research team.

  • CBC News Interview with “Dr. Michel Chrétien’s team at the Clinical Research Institute of Montreal” : Canadian team invited to do clinical trials in China for antiviral drug. *Quercetin deriviative plus zinc given 3-4 times per day, I hven’t found any results online yet. Feb 28, 2020, (youtube).

Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference List

  1. Medical Treatment Beyond First Aid, wisconsin.edu,
  2. Hung, Y., Fang, S., Wang, S. et al. Corylin protects LPS-induced sepsis and attenuates LPS-induced inflammatory response. Sci Rep7, 46299 (2017). https://doi.org/10.1038/srep46299 https://www.nature.com/articles/srep46299
  3. Canrong Wu, Yang Liu, Yueying Yang, et al., Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B, 27 February 2020, https://doi.org/10.1016/j.apsb.2020.02.008 https://www.sciencedirect.com/science/article/pii/S2211383520302999 * the genetic structure of the SARS-CoV(2) virus more closely matches the first, 2003, SARS-CoV virus in the way it can enter at ACE2 Receptors than it resembles the genetic structure of the coronavirus from bats native to China. There has also not been research support of the theory that the bat virus can infect humans as the shape does not fit the human ACE2 receptor: “…4 among the 5 most important amino acids (L465, L495, Y502, D510, and H514) that bind to ACE2 12 in Bat-CoV RaTG13 differ from SARS-CoV-2 (Fig. 3C). And there is no related research literature about whether Bat-CoV RaTG13 can infect human yet.”
  4. Showing Compound Isovitexin (FDB000614), Foodb.ca, https://foodb.ca/compounds/FDB000614
  5. Rhyu, Meera & Kim, Eun-Young & Bae, In Young & Park, Yong-Kon. (2002). Contents of Naringin, Hesperidin and Neohesperidin in Premature Korean Citrus Fruits. Korean Journal of Food Science and Technology. 34. https://www.researchgate.net/publication/263398834_Contents_of_Naringin_Hesperidin_and_Neohesperidin_in_Premature_Korean_Citrus_Fruits
  6. Aartjan J. W. te Velthuis, Sjoerd H. E. van den Worm, Amy C. Sims, et al., Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture. PLOS Pathogens, Nov. 4, 2010, https://doi.org/10.1371/journal.ppat.1001176 https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1001176
  7. Umer, PDF about dosing and safety risks of the medications chloroquine and hydroxychloroquine.  Hypokalemia and hypomagnesemia can increase risks of cardiac side effects – Epsom salt foot soaks might be helpful, hypokalemia can be due to low magnesium availability in addition to low potassium intake or other metabolic imbalance due to hormones.  https://drive.google.com/file/d/19T-QIaE6FT-PzfWcnbTr5g6ZnV34WcL2/view?usp=drivesdk 
  8. Hypomagnesemia, MedicalNewsToday.com, https://www.medicalnewstoday.com/articles/321735
  9. J. Depew, Epsom salt footsoaks, Feb. 19, 2019, transcendingsquare.com, https://transcendingsquare.com/2019/02/19/epsom-salt-footsoaks/
  10. Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding W-Q (2014) Chloroquine Is a Zinc Ionophore. PLoS ONE 9(10): e109180. https://doi.org/10.1371/journal.pone.0109180 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109180
  11. Dabbagh-Bazarbachi H, Clergeaud G, Quesada IM, et al., Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1-6 cells to a liposome model. J Agric Food Chem. 2014 Aug 13;62(32):8085-93. doi: 10.1021/jf5014633. Epub 2014 Jul 31. https://www.ncbi.nlm.nih.gov/pubmed/25050823
  12. Houston DMJ, Bugert JJ, Denyer SP, Heard CM. Potentiated virucidal activity of pomegranate rind extract (PRE) and punicalagin against Herpes simplex virus (HSV) when co-administered with zinc (II) ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV [published correction appears in PLoS One. 2017 Nov 20;12 (11):e0188609]. PLoS One. 2017;12(6):e0179291. Published 2017 Jun 30. doi:10.1371/journal.pone.0179291 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493292/
  13. Shafiya Rafiqa, Rajkumari Kaula, S.A. Sofia, et al., Citrus peel as a source of functional ingredient: A review. J of the Saudi Society of Ag Sci, 17;4, Oct. 2018, pp 351-358 https://www.sciencedirect.com/science/article/pii/S1658077X16300960
  14. Quercetin, Pharmacology, Toxicology and Pharmaceutical Science/Quercetin, ScienceDirect.com, https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/quercetin
  15. Hou L, Huang H. Immune suppressive properties of artemisinin family drugs. Pharmacol Ther. 2016;166:123–127. doi:10.1016/j.pharmthera.2016.07.002 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035609/
  16. Wang T1, Men R1, Hu M, et al., Protective effects of Punica granatum (pomegranate) peel extract on concanavalin A-induced autoimmune hepatitis in mice. Biomed Pharmacother. 2018 Apr;100:213-220. doi: 10.1016/j.biopha.2017.12.110. Epub 2018 Feb 9. https://www.ncbi.nlm.nih.gov/pubmed/29428670
  17. Gorinstein S, Leontowicz H, Leontowicz M, et al., Comparison of the main bioactive compounds and antioxidant activities in garlic and white and red onions after treatment protocols. J Agric Food Chem. 2008 Jun 25;56(12):4418-26. doi: 10.1021/jf800038h. Epub 2008 May 22. https://www.ncbi.nlm.nih.gov/pubmed/18494496
  18. Eva Schrezenmeier, Thomas Dörner, Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol 16, 155–166 (2020). https://doi.org/10.1038/s41584-020-0372-x https://www.nature.com/articles/s41584-020-0372-x
  19. Derek Lowe, Chloroquine, Past and Present, In the Pipeline, March 20, 2020, Science Translational Medicine, blogs.sciencemag.org, https://blogs.sciencemag.org/pipeline/archives/2020/03/20/chloroquine-past-and-present
  20. L. Brent Mitchell, Long QT Syndrome and Torsades de Pointes Ventricular Tachycardia. Last full review/revision Jul 2019, Merck Manual, Professional Edition, https://www.merckmanuals.com/professional/cardiovascular-disorders/arrhythmias-and-conduction-disorders/long-qt-syndrome-and-torsades-de-pointes-ventricular-tachycardia
  1. Vitamin C Is an Essential Factor on the Anti-viral Immune Responses through the Production of Interferon-α/β at the Initial Stage of Influenza A Virus (H3N2) Infection https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659258/
  2. Sy Mukherjee, China’s high smoking rate may be exacerbating the coronavirus outbreak,  Feb. 19, 2020, Forbes.com, https://www.google.com/amp/s/fortune.com/2020/02/19/coronavirus-china-smoking-rate-men/amp/