April 5, 2020

Disclaimer: Based on my personal understanding of the scientific underpinnings of the current epidemic sweeping the world, this article in no way represents either a cure or an aid in healing for preventing or recovering from COVID-19 infection.

To recap, our March 20, 2020 recommendations for protecting ourselves and our loved ones in the current health emergency, we recommended: (1)

  1. Social distancing, staying six feet away from others
  2. Relaxation techniques
  3. An anti-inflammatory diet, paying attention to nightshades and gluten
  4. Essential nutritional support with vitamins A, C, and D
  5. Intravenous intervention if the symptoms seem to worsen, with Vitamin C and glutathione
  6. Immune boosting peptide thymosin alpha 1, which was used successfully in a previous, though different corona outbreak in 2006.

At first blush, our plan is like the sandbags we put on the shoreline of the Susquehanna River during the inevitable spring flooding in my native Northeast Pennsylvania.

“Eh, Sparky, what good would any of that do?  You got thirty-eight dead in Nevada and 53,000 dead worldwide.”

And, indeed, the CDC’s original recommendations were to wash our hands and stay away from each other.  Several promising interventions, hydroxychloroquine (HCQ), azithromycin and zinc, drugs, and supplements in existence for decades, carry impressive, anecdotal evidence for outpatient prophylactic use. (Incidentally,my adopted home state and Michigan banned the use of these agents for a diagnosis of COVID-19 due to “non-consensus among the medical community.”(2)

Being a” connect the dots” kind of guy, I asked the question over and over; Why, of all the thousands of drugs in the world, are chloroquine and hydroxychloroquine singled out for study and use? (A secondary bacterial pneumonia develops once the infection takes hold thus the rationale for azithromycin.)Why this specific antimalarial, anti-arthritis drug?

The answer: Hydroxychloroquine inhibits the production of the inflammatory chemicals, known as cytokines, Interleukin-1 (IL-1) and Interleukin-6 (IL-6).(4)Cytokines, inflammatory compounds, immunology, ah!  If it’s all too left brain, let me be Ricky Ricardo for you and ‘splain it. (If you’re too young to remember Ricky Ricardo, look him up.)

Cytokines are small protein particles that regulate host responses to infection, immune responses, inflammation, and trauma.  (5)Cytokines can be anti-inflammatory, Interleukin-4 (IL-4) and IL-10 are examples, or”pro-inflammatory,”including TNFα, IL-1β, IL-2, IL-6, IFNα, IFNβ, IFNγ, and MCP-1.

The new, “novel” coronavirus, COVID-19,creates this”storm”by massively overproducing and (6)A unique characteristic of this virus, and the reason it is so lethal, is that it sets off a”storm”of hyperinflammatory cytokines, chemicals, specifically IL-1β and IL-6. (7)

Elevated Interleukin 1β (IL-1β) expresses as fever, increased sensitivity to pain, sensitivity, vasodilation, and hypotension. (8) IL-1β affects mood, cognitive performance, learning, and memory. (9)

IL-6 activates blood clotting cascades, systemic blood born infections, and inhibits myocardial function. (10)Interleukin-6 also plays a role in cognition. (11)

Not coincidentally, recent reports indicate a sizeable minority of COVID-19 patients present with new-onsetanosmia, an inability to smell, loss of taste, confusion, seizures, and other signs of brain impairment.  (12)

Thus,we come full circle.  The primary rationale for using chloroquine and hydroxychloroquine is to disrupt the Il-1 and IL-6 cytokine storm.

But wait, there’s more! Chloroquine and hydroxychloroquine facilitate zinc penetration through the viral cell wall.  Zinc inhibits corona viral replication by blocking a critical viral enzyme utilized for replication in host cells, RNA polymerase.(13)

 Zinc is involved in metabolic and digestive processes. Zinc aids cells and tissues with oxygen uptake and carbon dioxide release, forms collagen‚, promotes healthy‚ smooth-looking skin‚ shiny hair, and strong nails.  Zinc boosts testosterone and reduces estrogen. Side effects of zinc include diarrhea, abdominal cramps, and vomiting.(14) (Incidentally, testosterone also lowers IL-1 and IL-6.  Estrogen raises them.) (15)

Our go-to, for adults, is Zinc Citrate 30 mg, 1 in am, 1 in pm.

Naturally, I asked myself, “What else do we have experience with and on hand that is proven to reduce IL-1 and IL-6?

Not surprisingly, Quercetin,a bioflavonoid found in red wine, grapefruit, onions, apples, black tea, and green leafy vegetables, our “go-to” for all things histamine and allergy are at the top of the list.

An antioxidant and anti-inflammatory, quercetin inhibits mast cell secretion, limits histamine, and IL-6.

A second, unique characteristic of the COVID-19 virus is its’ ability to attach itself and enter cells through “ACE 2 receptors.” Once connected, the virus enters a cell, reproduces hijacking the cell’s function.  Quercetin blocks the virus’s ability to attach to these receptors. (16)

 Quercetin Dose:  400-1000 mg/day

 Curcumin is the active ingredient in turmeric or “Indian saffron.”Curcumin is especially intriguing in both oral and an intravenous liposomal form as it suppresses both IL-1 beta and IL-6 along with several other inflammatory cytokines.

Curcumin Dose 500-1000 mg. 2x/day.

The SARS-CoV-2 virus has a Spike Protein on its surface that potentially interacts with three molecules on the surface of lung cells: heparin sulfate, furin, an enzyme for protein processing, and angiotensin-converting enzyme 2 (ACE), a cell surface receptor. These interactions are needed for the virus to infect cells.(17)

Glutathione, the most potent antioxidant in the body, is composed of three proteins, cysteine, glycine, and glutamine, glutathione. Touted as the secret to preventing aging, heart disease, radiation poisoning, dementia, autism, and Alzheimer’s disease, glutathione acts as a free radical scavenger.

Glutathione blocks the cell surface receptor angiotensin-converting enzyme 2 as well as IL-6 and IL-8. (18)

Due to its’ nature, three proteins linked together glutathione in its’ natural form would dissolve in the milieu of stomach acid.  It must be administered either in a coated, liposomal vehicle or as N-acetyl cysteine, its’oral precursor.

Dose:  N-Acetyl Cysteine; 600-900 mg 2x/d.

In future articles, we will cover other IL-1, IL-6 inhibitors, and any newer mechanisms of disruption as information breaks.  As of this writing, this is the protocol I am following myself, recommending for my family, friends, and patients:

  1. Social distancing, staying six feet away from others
  2. Relaxation techniques
  3. An anti-inflammatory diet, paying attention to nightshades and gluten
  4. Nutritional Support
    1. Zinc Citrate 30 mg 1 in am, 1 in pm
    2. Quercetin (combined with nettle and bromelain) 400 mg, 1 in am, 1 in pm
    3. Curcumin 500 mg. 1 in am, 1 in pm.
    4. N-acetyl-cysteine 900 mg. 1 in am., 1 in pm.

There is no “cure” as of this writing for the SARS-CoV-2 virus.  We have no sophisticated double-blind studies, the gold-standard for proclaiming a definitive link between disease entity and relief.  The above recommendations are, in my opinion, common sense remedies and suggestions of immune-boosting supplements based on the science as I understand it as of this date, April 5, 2020.

Dr. William Clearfield, the Executive Director of the American Osteopathic Society of Rheumatic Diseases, is prominent in the Reno, NV area for all things anti-aging and wellness. He is a frequent lecturer at the Age Management Medical Group, the American Academy of Anti-Aging Medicine, the Nevada Osteopathic Medical Society, American Osteopathic Society of Rheumatic Diseases. Call the Clearfield Medical Group at 775-359-1222 or DrClearfield.net. We are available for virtual consults. Email us at doctrbil9@gmail.com

References

  1. Fujita, Y., Matsuoka, N., Temmoku, J. et al. hydroxychloroquine inhibits IL-1β production from amyloid-stimulated human neutrophils. Arthritis Res Ther21, 250 (2019). https://doi.org/10.1186/s13075-019-2040-6https://www.webmd.com/drugs/2/drug-5482/hydroxychloroquine-oral/details
  2. Clearfield, W.”Until There is A Cure: What to do to Protect Yourself and Your Loved Ones in this Time of Peril.”Healthy Beginnings MagazineMarch 22, 2020; https://hbmag.com/until-there-is-a-cure-what-to-do-to-protect-yourself-and-your-loved-ones-in-this-time-of-peril/
  3. https://nvhealthresponse.nv.gov/wp-content/uploads/2020/03/3.24-RX-regulation.pdf
  4. Sperber K1Quraishi HKalb THPanja AStecher VMayer L. Selective regulation of cytokine secretion by hydroxychloroquine: inhibition of interleukin 1 alpha (IL-1-alpha) and IL-6 in human monocytes and T cells. J Rheumatol.1993 May;20(5):803-8.
  5. https://www.consumerreports.org/cro/2012/05/off-label-drug-prescribing-what-does-it-mean-for-you/index.htm
  6. Dinarello, C., “Proinflammatory Cytokines,”Chest 2000 Aug;118 (2):503-508
  7. Contassot E1Beer HDFrench LE., Interleukin-1, inflammasomes, autoinflammation, and the skin.Swiss Med Wkly. 2012 May 31;142:w13590. doi: 10.4414/smw.2012.13590. eCollection 2012.
  8. Lynch MA, Neuroinflammatory changes negatively impact on LTP: A focus on IL-1β.Brain Res. 2015 September 24;1621:197-204. doi: 10.1016/j.brainres.2014.08.040. Epub, 2014; September 2.
  9. Tanaka T1,2Narazaki M2Kishimoto T3.Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016 Jul;8(8):959-70. doi: 10.2217/imt-2016-0020.
  10. Singh-Manoux A1Dugravot A2Brunner E2Kumari M2Shipley M2Elbaz A2Kivimaki M,2 Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife; 2014 August 5;83(6):486-93. doi: 10.1212/WNL.0000000000000665. Epub 2014 July 2.
  11. Mundell, EJ., “In Some Cases, COVID-19 May Harm the Brain,” WebMD, https://www.webmd.com/lung/news/20200402/in-some-cases-covid-19-may-harm-the-brain#3. April 2, 2020
  12. Channappanavar R, Perlman S. Pathogenic human coronavirus infections cause and consequences of cytokine storm and immunopathology. Seminars in Immunopathology. 2017;39:529-39
  13. Brown, N. Can Supplements Help Combat COVID-19?, Psychology Today,  https://www.psychologytoday.com/us/blog/experience-engineering/202003/can-supplements-help-combat-covid-19, March 20, 2020
  14. https://medlineplus.gov/ency/article/002416.htm
  15. Kanda N1Tsuchida TTamaki K., Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells.Clin Exp Immunol. 1996 Nov;106(2):410-5.
  16. Schwartz, J., Quercetin – To Take or Not to Take? McGill University Office of Science and Society, https://www.mcgill.ca/oss/article/health/quercetin-take-or-not-take March 25, 2020.
  17. New COVID-19 HOPE Clinical Trial Recommendations Introduced Today May Reduce or Eliminate Mechanical Ventilation for Coronavirus Patients., https://www.biospace.com/article/releases/new-covid-19-hope-clinical-trial-recommendations-introduced-today-may-reduce-or-eliminate-mechanical-ventilation-for-coronavirus-patients/ March 30, 2020
  18. Pena LR1Hill DBMcClain CJ. Treatment with glutathione precursor decreases cytokine activity. JPEN J Parenter Enteral Nutr.1999 Jan-Feb;23(1):1-6.

 

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