UPDATED 4/29/2020: Functional Medicine Approach to COVID-19 Prevention and Treatment of Non-Severe Illness

Immune Boost Recommendations for Coronavirus/SARS-CoV-2/COVID-19 Prevention and Treatment

Research and knowledge about this novel coronavirus are rapidly evolving, in knowledge about transmission, infection and treatment.  I am attempting to update monthly.

General precautions:

1.     Self-quarantine, social distancing, etc.  Even as the state of Texas begins to reopen, life will not resume as usual. Please continue to take extra caution and if you are high risk, consider continued quarantine.

2.     Mask up and wear gloves if you must go out.

3.     Hand washing – frequent with soap and water.  Given the lipid envelope around the virus, soap is directly toxic to the virus and superior to hand sanitizer.  Hand sanitizer is also acceptable with 60% or higher alcohol content.  With supplies short, there are available recipes to make your own with Ethanol (vodka) or Isopropyl alcohol. Key is for 60%-70% or higher concentration of alcohol

4.     Sleep, sleep, sleep. Sleep deprivation is quickly immunosuppressive.

5.     Avoid processed sugar.

6.     Eat real food. Avoid fast/processed food

7.     Sun exposure. Moderate 20 minutes/day

8.     Get vitamin D up. (goal level 50-80, 70-100).  If you take vitamin D, continue to take it.  Their have been interesting findings regarding the ACE2 receptor in the lung and interaction with Vitamin D. It appears to be important to maintain ACE2 activity in the setting of an acute infection to avoid worse outcomes.

9.     Beware of immunosuppressive medications: corticosteroids, antihistamines, antacids. However, please do not stop treatment with any medications without discussing with your physician.  For example, if your rheumatoid arthritis is well controlled on Methotrexate or other immunosuppressive medication, there may be more risk with a flare to your immune system than the medication increases risk itself.  These cases need individual attention so please to not change without consultation with your doctor.

10.  Avoid behaviors that suppress immunity: drinking alcohol in excess, cigarette smoke, vaping

11.  Drink plenty of non -caffeinated fluids: Water, juice, decaf or herbal teas. 

Supplements to consider (Prevention/ Immune boost):

·      Vitamin C: Adults 1000mg/day. Children 200-500mg/day. See references.  IV vitamin C at high doses has been shown to be beneficial in ICU severe lung disease.  There is a current clinical trial examining effectiveness of IV vitamin C in COVID-19 pneumonia. 

·      Vitamin A: 25,000 Units/day (acute).  Chronic 10,000-15,000.  Have levels checked it taking chronically.  Children 5,000 U/day

·      Vitamin D: 2000-5,000/day of Vitamin D3 to target goal levels (50-80). Children 400 -800 IU/day. Carlson’s vitamin D drops for babies/children. There is some concern that high doses of vitamin D may upregulate the ACE2 receptor, a primary point of infection entry for coronavirus infection.  However, over the last month, more research has shown that it is important to maintain healthy ACE2 expression in an acute infection.

·      **Zinc 50-100mg/day (acute), 50mg/day (chronic). Lozenges often and early in symptomatology.  No known dosing for children, but 10-15mg/day reasonable for 3-5 days while ill.  There is evidence that zinc has activity against coronavirus. Added citations below.  There are multiple chelation forms out there including picolinate, citrate, gluconate, oxide, orotate, etc.  All forms other than oxide and methionine appear to have good absorption.

·      Probiotics boost immune system – has been shown to decrease viral infections by 10-30% in children

·      L-lysine 1-2 grams/day. Decreased viral replication

·      **Elderberry. Elderberry appears to have direct activity at the ACE2 receptor, decreasing cell susceptibility to infection via the ACE2 receptor in the lung, a major entry point of the viral infection of the cells.   Citations added below.

Adult dosing: many doses studied, experts recommending 600-1000mg/day, divided doses.  Children’s dosing not known, but I’m using 50mg twice a day.  CAUTION: there have been 2 reported cases of pancreatitis in patients using Elderberry (cause?). If you develop abdominal pain, nausea, vomiting, please stop and contact your doctor.

·      Echinacea (Avoid if. you have an autoimmune disease)

·      Pre-biotic: Larch Arabinogalactan.  Has been shown to reduce viral infections in children and boost vaccine responses in children and adults. Likely affective by augmenting the healthy microbiome, which plays an essential role in immune health.  Very safe for children and adults. 1-2 teaspoons/day

·      NAC (N-acetylcysteine) 1200-2000mg/day (low protein meal or empty stomach).  Pediatric dose – 100mg/kg body weight. Safe for pregnancy and breast feeding

·      L-glutamine 2-5g/day (low protein meal or empty stomach). Glutamine is an Amino acid that feeds lymphocytes and repairs damaged mucosa.  Children’s dose 500 -1000mg/day (bulk supplements)

·      Astragalus

·      Garlic – 1 clove per day or Garlic extract supplement. The best way to consume garlic cloves directly is to crush or mince and allow to be exposed to ambient air for 10 minutes before swallowing (or Chewing if tolerated), to increase Allicin activity, active enzyme which is antimicrobial.

·      Selenium: data coming out of China is suggesting those low in selenium (a common nutritional deficiency there) are at highest risk of severe disease from coronavirus.  Selenium deficiency is less common in the US, but a potential target for antiviral therapy.  You can consider having levels checked (elderly patients have highest selenium deficiency rates), but I recommend 4-8 Brazil nuts weekly to optimize levels. Do not exceed on average 4 nuts/day as the selenium content is so high, you risk toxicity. Given the high levels of selenium in brazil nuts and other nutritional benefit, I do not use selenium supplements outside a multivitamin.

Adults: If infected with COVID-19, Flu or other significant viral illness:

·      NAC (N-acetylcysteine) 2000mg-4000mg/day.  Nausea/upset stomach may limit high dose, vitamin C 1000mg-5000mg /day (dose limited by lose bowels), vitamin A 25,000 Units/day, Vitamin D –continue dose recommended by your doctor 400-5000 U/day, zinc lozenges, Elderberry 600-1000mg/day, Echinacea tea/supplement (avoid in autoimmune disease), Larch arabinogalactan 1-2 teaspoons/day, L-glutamine 2-5grams/day.  Consider Umcka cold care three times per day. Consider Astragalus drops.  Avoid any NSAIDS (aspirin, ibuprofen, aleve, motrin, naproxen, etc) if you have a fever.  If you need a fever reducing medication, would stick with Acetaminophen or Tylenol.  NSAIDS may allow increased viral replication.  The current recommendations, however, is that NSAIDS may be used in the short term to reduce very high fevers.

Children: acute infection with flu or COVID-19:

·      Vitamin C 200-500mg/day, Vitamin A 5000 U/d, Vitamin D- continue low dose 400-800 IU /day for immune upregulation, Elderberry gummy 1/day (50mg/day), Larch arabinogalactan 1 teaspoon/day, NAC 100mg/kg body weight. Consider Umcka cold care (approved for age 6 and older, but I use in my 4 year old), zinc 10-15mg/day. Avoid any NSAIDS (aspirin, ibuprofen, aleve, motrin, naproxen, etc) if you have a fever.  If you need a fever reducing medication, would stick with Acetaminophen or Tylenol.

If severely ill (short of breath, in distress with high fevers), go to the nearest Emergency room with mouth and nose covered.  If not severely ill, stay home, isolated for 14 days.

Other issues:

·      Protein levels – have to have adequate dietary protein to make body’s antibodies/immunoglobulins.  Need enough stomach acid to digest protein

• Quercetin - a polyphenol, used for asthma, allergies, and various cancers, has potential role in reducing lung inflammation through regulation of the NLRP3 inflammasome, and has preliminary data in benefits for active COVID infection. It is a naturally occurring compound in grape skins, apples, capers, and other plant foods and has a long-standing safety profile. I have started 500mg/day in my daughter with asthma.

·      Get the flu vaccine. Influenza vaccines are still available and recommended currently for the 2019-2020 season.  This of course has to be balanced with efforts to self-quarantine. COVID is here for a while. When Sept-Oct 2020 comes around, would recommend the influenza vaccine if not contraindicated.

·      These recommendations do not take precedence over any of your doctors’ recommendations.  I if you want to a personalized approach to address immune optimization, consider consultation with a functional or integrative medicine practitioner.  Knowing your vitamin D levels, vitamin A levels, zinc levels, etc. can really improve dosing recommendations.  Unfortunately, the recommendations above are broad and may not apply to everyone.  For example, if your vitamin A level is 110 (above reference range), I would not recommend you take any vitamin A due to concern for toxicity. Same applies for vitamin D, zinc, etc.  Vitamin C has little toxicity.

·      High fever: There is concern that using NSAIDS (Ibuprofen, motrin, naproxen, Aleve, etc) upregulates the ACE2 receptor and increases replication of Coronavirus.  Fever is a natural, protective way for your body to manage infection, and is probably beneficial. Consider letting fevers ride. However, if the fever is reaching very high temperatures (>103 F), then the metabolic implications may be harmful.  Tylenol is a non-NSAID fever reducer which might be safer than NSAIDS. However, Tylenol depletes Glutathione stores (the most potent antioxidant in your body) and should not be used at high doses for lengths of time.   If you are running a high fever, consult with your medical expert on what to do.

References:

Vitamin D

Gruber-Bzura BM. Vitamin D and Influenza-Prevention or Therapy?. Int J Mol Sci. 2018;19(8):2419. Published 2018 Aug 16. doi:10.3390/ijms19082419

Urashima M, et al.  Am J Clin Nutr. 2010 May;91(5):1255-60. doi: 10.3945/ajcn.2009.29094. Epub 2010 Mar 10

Zhou J, et al. The Pediatric Infectious Disease Journal: August 2018 - Volume 37 - Issue 8 - p 749-754

Vitamin A

Huang Z, Liu Y, Qi G, Brand D, Zheng SG. Role of Vitamin A in the Immune System. J Clin Med. 2018;7(9):258. Published 2018 Sep 6. doi:10.3390/jcm7090258

Committee on Infectious Diseases. Vitamin A Treatment of Measles.  Pediatrics May 1993, 91 (5) 1014-1015

Vitamin C

Landmark ICU trial:

Fowler AA, Truwit JD, Hite RD, et al. Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial. JAMA. 2019;322(13):1261–1270. doi:10.1001/jama.2019.11825

Zhang M, Jativa DF. Vitamin C supplementation in the critically ill: A systematic review and meta-analysis. SAGE Open Med. 2018;6:2050312118807615. Published 2018 Oct 19. doi:10.1177/2050312118807615

NAC/ N acetylcysteine

De Flora, Silvio & Grassi, C & Carati, Livio. (1997). Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 10. 1535-41. 10.1183/09031936.97.10071535.

Sharafkhah M, Abdolrazaghnejad A, Zarinfar N, Mohammadbeigi A, Massoudifar A, Abaszadeh S. Safety and efficacy of N-acetyl-cysteine for prophylaxis of ventilator-associated pneumonia: a randomized, double blind, placebo-controlled clinical trial. Med Gas Res. 2018;8(1):19–23. Published 2018 Apr 18. doi:10.4103/2045-9912.229599

F.S. De, C. Grassi, L. Carat Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment
Eur Respir J, 10 (7) (1997 July), pp. 1535-1541

Larch Arabinogalactan

Dion C, Chappuis E, Ripoll C. Does larch arabinogalactan enhance immune function? A review of mechanistic and clinical trials. Nutr Metab (Lond). 2016;13:28. Published 2016 Apr 12. doi:10.1186/s12986-016-0086-x

L. Riede, B. Grube & J. Gruenwald (2013) Larch arabinogalactan effects on reducing incidence of upper respiratory infections, Current Medical Research and Opinion, 29:3, 251-258

Udani JK, Singh BB, Barrett ML, Singh VJ. Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers. Nutr J. 2010;9:32. Published 2010 Aug 26. doi:10.1186/1475-2891-9-32

Zinc

Eby GA. Reduction in Duration of Common Colds by Zinc Gluconate Lozenges in a Double-Blind Study Antimicrobial Agents and Chemotherapy, Jan. 1984, p. 20-24 0066-4804/84/010020-05$02.

Rao G, Rowland K. PURLs: Zinc for the common cold--not if, but when. J Fam Pract. 2011;60(11):669–671.

Hemilä, H., Chalker, E. The effectiveness of high dose zinc acetate lozenges on various common cold symptoms: a meta-analysis. BMC Fam Pract 16, 24 (2015). https://doi.org/10.1186/s12875-015-0237-6

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. Published 2010 Nov 4. doi:10.1371/journal.ppat.1001176

Zhang, L, Liu, Y. Potential interventions for novel coronavirus in China: A systematic review. J Med Virol. 2020; 92: 479– 490. https://doi.org/10.1002/jmv.25707

Probiotics

Tapiovaara L, Pitkaranta A, Korpela R (2016) Probiotics and the Upper Respiratory Tract - A Review. Pediatric Infect Dis 1:19. doi: 10.21767/2573-0282.100019

Lehtoranta, Liisa & Pitkäranta, A & Korpela, Riitta. (2014). Probiotics in respiratory virus infections. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 33. 10.1007/s10096-014-2086-y.

Zolnikova, O., Komkova, I., Potskherashvili, N., Trukhmanov, A., & Ivashkin, V. (2018). Application of probiotics for acute respiratory tract infections. Italian Journal of Medicine, 12(1), 32-38. 

Elderberry

Torabian G, Valtchev P, Adil Q, Dehghani F. Anti-influenza activity of elderberry (Sambucus nigra). Journal of Functional Foods. 2019;54:353-360. doi:10.1016/j.jff.2019.01.031

Roschek B, Fink RC, McMichael MD, Li D, Alberte RS. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry. 2009;70:1255-1261.

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. Complementary Therapies in Medicine. 2019; 42:361–365.

Weng J. Antiviral activity of Sambucus Formosana Nakai ethanol extract and related phenolic acid constituents against human coronavirus NL63. Virus Research. 2019; 273: 197767

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. Published 2014 Jan 16. doi:10.1186/1746-6148-10-24

Glutamine (L-Glutamine)

Zhang, Y., Zhao, L., Zhou, Y., Diao, C., Han, L., Yinjie, N., … Chen, H. (2017). Glutamine Ameliorates Mucosal Damage Caused by Immune Responses to Duck Plague Virus. Dose-Response. https://doi.org/10.1177/1559325817708674

Cruzat V, Macedo Rogero M, Noel Keane K, Curi R, Newsholme P. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients. 2018;10(11):1564. Published 2018 Oct 23. doi:10.3390/nu10111564

Echinacea

Hudson J, Vimalanathan S. Echinacea—A Source of Potent Antivirals for Respiratory Virus Infections. Pharmaceuticals (Basel). 2011;4(7):1019–1031. Published 2011 Jul 13. doi:10.3390/ph4071019

Quercetin

Polansky H, Lori G. Coronavirus disease 2019 (COVID-19): first indication of efficacy of Gene-Eden-VIR/Novirin in SARS-CoV-2 infection [published online ahead of print, 2020 Apr 10]. Int J Antimicrob Agents. 2020;105971. doi:10.1016/j.ijantimicag.2020.105971

TY - JOUR AU - Perdigão Domiciano, Talita AU - Wakita, Daiko AU - Jones, Heather AU - Crother, Timothy AU - Verri, Waldiceu AU - Arditi, Moshe AU - Shimada, Kenichi PY - 2017/02/02 SP - 41539 T1 - Quercetin Inhibits Inflammasome Activation by Interfering with ASC Oligomerization and Prevents Interleukin-1 Mediated Mouse Vasculitis VL - 7 DO - 10.1038/srep41539 JO - Scientific Reports ER -

 Domiciano TP, Wakita D, Jones HD, et al. Quercetin Inhibits Inflammasome Activation by Interfering with ASC Oligomerization and Prevents Interleukin-1 Mediated Mouse Vasculitis. Sci Rep. 2017;7:41539. Published 2017 Feb 2. doi:10.1038/srep41539

-Written by Leann Silhan, MD

Contact information:

Diamond Physicians

214-974-4852

drsilhan@diamondphysicians.com