Beyond handwashing, surface cleaning, and social distancing
I’ve been browsing the internet looking for some additional things that one might do to minimize the chance of contracting COVID 19 or to take care of the illness if infected. As with any current topic, the internet is loaded with fact and fiction. After spending considerable time sorting through this, I found some things to do that may be worth considering. In a nutshell, they involve the usual common sense things for staying healthy like ensuring a good diet, getting enough sleep, exercise, and sunshine. However, based on the results of some coronavirus studies, there are some particular combinations of vitamins, minerals, and food ingredients (or supplements) that could be very helpful. A list of some of these and the rationale for them is discussed below. Of particular interest is the combination of zinc and zinc ionophores like quercetin and EGCG. Also, the article https://www.drfabio.com/healthblog/integrative-considerations-during-the-covid-19-pandemic-march-19-2020 from the University of Arizona Medical School is very good.
A promising treatment for COVID-19
Note: At the urging of doctors, a journal article discussed below (and others), and President Trump, the FDA just approved (3/30/2020) hydroxychloroquine and chloroquine phosphate to treat hospitalized patients for COVID-19. One may wonder why this took so long since CDC has known about this activity since 2005 (See BREAKING: New evidence shows CDC knew since at least 2005 that chloroquine is effective against coronaviruses)HHS has accepted 30 million doses of hydroxychloroquine sulfate donated by Novartis and one million doses of chloroquine phosphate from Bayer. Novartis intends to donate up to 130 million 200 mg doses by the end of May. Additional sources for manufacturing these are being sought. These drugs are currently used for malaria, lupus, and rheumatoid arthritis and these patients are facing shortages. HHS reiterated that the drug still only has anecdotal evidence for its efficacy because rigorous, randomized clinical trials have not been completed. However, the Novartis CEO has indicated that the drug is effective based on pre-clinical studies in animals as well as clinical studies which show that hydroxychloroquine kills the corona virus.
The coronavirus COVID-19 is rapidly spreading around the USA and the world. Unprecedented measures are being taken to reduce the rate of infection and there are widespread efforts to find a treatment. This is a challenge because any new treatment requires drug development and testing. COVID-19 is a new strain, but other coronaviruses (e.g., SARS) have been known for some time. So, there are some rational approaches that are being taken to develop treatments. There are some recent reports with promising results for hydroxychloroquine (Plaquenil and other trade names)1 in combination with the antibiotic azithromycin (Brand name Zithromax Z-Pak). Hydroxychloroquine was approved for medical use in the USA in 1955. It has been used to treat malaria, lupus, and rheumatoid arthritis. Azithromycin is a type of macrolide antibiotic that is used for a variety of infections. It was discovered in 1980 and approved for medical use in 1988.
For example, a research group in France reported exceptionally good results with this combination.2 The study was on a relatively small group of patients and further testing is needed to prove its effectiveness. Following this, a Wall Street Journal article3 (3/22) reported that Dr Joe Brewer in Kansas City, MO was using hydroxychloroquine as a treatment and as prophylaxis to protect health care workers from infection. They had been using an approach from research in China, but when they switched to the combination from the French study, the patients showed fewer symptoms. They urged using this approach as a first line treatment. However, there is a shortage of hydroxychloroquine, so steps should be taken to increase the supply. Although, further study may reveal less effective results, they argue that it is better to act now to use this approach to save lives and prevent others from becoming infected rather than wait several weeks for confirming test results and realize that an opportunity to end the pandemic more quickly was missed. Also in this regard, there is a letter from the Association of American Physicians and Surgeons to President Donald Trump.4 Among other things, it is very critical of the roadblocks to innovation and testing that are imposed by the FDA and CDC because of the Clinical Laboratory Improvement Act (CLIA). Also, the letter thanks President Trump for his help in making the “long established anti-malarial drugs chloroquine and hydroxychloroquine available for testing”. Also of interest is a paper by the New York State Bar Association Environmental Law Section.5 It outlines legal issues related to using the treatments discussed above.
Just very recently, additional support for the French Group’s approach has come from a doctor in New York. Dr. Vladimir Zelenko’s team has treated 500 patients with hydroxychloroquine, azithromycin and zinc sulfate. So far, there have been no deaths, hospitalizations, or intubations and the only side effects have been temporary nausea and diarrhea in 10% of the patients6. He describes his rationale as follows:
I combined the data available from China and South Korea with the recent study published from France (sites available on request). We know that hydroxychloroquine helps Zinc enter the cell. We know that Zinc slows viral replication within the cell. Regarding the use of azithromycin, I postulate it prevents secondary bacterial infections. These three drugs are well known and usually well tolerated, hence the risk to the patient is low.
Dr Zenlenko’s addition of zinc to the treatment is of interest. As he mentioned, zinc slows viral replication within a cell. It has been postulated that one mechanism for the activity of chloroquine and hydroxychloroquine against viruses is related to its ability to act as a zinc ionophore.7 Ionophore means “ion carrier”. These chemicals reversibly bind ions and they can catalyze ion transport across hydrophobic membranes. Notably, some macrolide antibiotics are ionophores. There are naturally occurring ionophores that have drawn some recent interest. The flavonoids quercetin (QCT) and epigallocatechin-gallate ( EGCG) have been shown to be zinc ionophores in vitro.8 This has led to speculation that these in combination with zinc could be a treatment for coronavirus. The McGill Tribune reported on 3/17/2020: “Doctors Michel Chrétien and Majambu Mbikay, senior researchers at the Montreal Clinical Research Institute (IRCM), have proposed the use of a plant-based compound called quercetin to treat COVID-19. Clinical trials to test its effectiveness are scheduled to start in China within the next few weeks.”9 Also, Quercetin, epigallocatechin gallate and gallocatechin gallate (GCG) have displayed good inhibition toward 3CLpro which is vital for SARS-CoV replication.10 It would be great if these natural compounds would be effective, because they are available and relatively inexpensive. Also, they are found in a variety of foods such as in grapes, raspberries, broccoli, onions, tomatoes, cooked asparagus, and matcha green tea.11,12 However, most of the reports have been in vitro studies, and the bioavailabilty of these substances in vivo is questionable because quercetin is metabolized in the digestive process. Still, there is some indication that quercetin metabolites may have some positive effects.13
The current status (March 30, 2020) is that there are some promising strategies for treatment of COVID-19 such as the approach mentioned above and some others. They are in test and being used to some extent in other countries. But, as the AAPS letter points out, the Federal regulations and bureaucracy not only stand in the way of innovation but also have made it so difficult to manufacture in the US that “our capacity to manufacture antibiotics, vitamin, C, protective gear, and most other drugs was outsourced overseas decades ago.”4 Since other countries are struggling with COVID-19 as much or more than we are, where will we be able to procure what we need for this crisis? Getting these things has been slow so far and the situation is likely to get worse. So, what can we do to help ourselves as much as we can?
One possibility is to consider including more fruits and vegetables with flavonoids in our diet. This along with trying to ensure that we are not zinc deficient may be worthwhile. Some multivitamin formulations have zinc. Also, zinc lozenges for treating colds are available. However, excess zinc can be very harmful, so care must be taken to not overdue the use of zinc supplements. Zinc is available from meat, shellfish, legumes (however phytates in these inhibit zinc absorption), cashews, and dairy products. Most people will get enough zinc in their diet, but young children, teenagers, the elderly, women who are pregnant, and people on certain diets, may have some risk. 14 Zinc deficiency can be caused by a diet high in phytate containing whole grains, foods grown in zinc deficient soil, or processed foods low in zinc. Wikepedia has a table with the zinc content in a variety of foods.15
There is a good article with a list of steps we can take for possibly reducing the risk or severity of COVID-19 infection. There is no clinical evidence for any prevention or treatment of COVID-19, but here are some things to consider based on what is known about coronavirus infections. 16
- Get adequate sleep: Insufficient sleep increases the risk of infectious illness. Adequate sleep ensures the secretion of melatonin which may help reduce coronavirus virulence.
- Stress management: Stress disrupts immune regulation.
- Get vegetables and fruits with flavonoids in your diet.
- liquiritigenin from licorice
- dihydroquercetin and quercetin: onions and apples
- myricetin: tomatoes, oranges, nuts and berries
- apigenin: parsley and celery
- curcumin: turmeric root
- epigallocatechine gallate (EGCG): green tea
- vitamin C
- Vitamin D
- If infected, avoid the following immunostimulatory agents which may increase inflammatory cytokines that appear to be involved in the pathogenicity of COVID-19
- medicinal mushrooms
- Vitamin D
1. Hydroxychloroquine. Wikepedia. https://en.wikipedia.org/wiki/Hydroxychloroquine.
2. Gautret P, Lagier J-C, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. March 2020:105949. doi:10.1016/j.ijantimicag.2020.105949
3. Jeff Colyer and Daniel Hinthorn. These Drugs Are Helping Our Coronavirus Patients The evidence is preliminary on repurposing two treatments. But we don’t have the luxury of time. Wall Street Journal. https://www.wsj.com/articles/these-drugs-are-helping-our-coronavirus-patients-11584899438.
4. M.D. JO. Letter to Donald Trump outlining roadblocks to innovation in addressing COVID-19. Letter from Association of American Physicians and Surgeons, Inc. to Donald Trump. https://drive.google.com/file/d/15TwCtLCyP8ptFlQAK_0N_gxINUOHbHxn/view.
5. James P. Rigano, Esq. and Alyse Delle Fave E. Coronavirus: The End of the Crisis? Webinar on Coronavirus: Treatment and Legal Solutions, March 202. https://docs.google.com/document/u/1/d/e/2PACX-1vTjQcABGPeyoIPkGd5in2tG5q7smXLAjD7chxjlAWk7y__IH0htH4V4VS14yRQqbQ/pub.
6. Zelenko V. Letter to Trump re: chloroquine zinc andazithromycin. https://docs.google.com/document/d/1SesxgaPnpT6OfCYuaFSwXzDK4cDKMbivoALprcVFj48/preview.
7. te Velthuis AJW, van den Worm SHE, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture. Andino R, ed. PLoS Pathog. 2010;6(11):e1001176. doi:10.1371/journal.ppat.1001176
8. Dabbagh-Bazarbachi H, Clergeaud G, Quesada IM, Ortiz M, O’Sullivan CK, Fernández-Larrea JB. Zinc Ionophore Activity of Quercetin and Epigallocatechin-gallate: From Hepa 1-6 Cells to a Liposome Model. J Agric Food Chem. 2014;62(32):8085-8093. doi:10.1021/jf5014633
9. Abbas Mehrabian and Sepideh Mikaeeli. Montreal researchers propose a treatment for COVID-19. The McGill Tribune. https://www.mcgilltribune.com/sci-tech/montreal-researchers-propose-a-treatment-for-covid-19-170320/.
10. Nguyen TTH, Woo H-J, Kang H-K, et al. Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris. Biotechnol Lett. 2012;34(5):831-838. doi:10.1007/s10529-011-0845-8
11. Nicolas Noble. Quercetin: A Safe, Natural Antiviral? https://matcha.com/blogs/news/quercetin-a-safe-natural-antiviral-covid19-2020.
12. dahlman. Chloroquine and Natural Solutions for Coronavirus. http://drdahlman.com/chloroquine-and-natural-solutions-for-coronavirus/.
13. Bioavailability of Quercetin. https://www.quercetin.com/overview/bioavailability-of-quercetin.
14. West H. The 10 Best Foods That Are High in Zinc. Healthline. https://www.healthline.com/nutrition/best-foods-high-in-zinc.
15. Zinc deficiency. Wikepedia. https://en.wikipedia.org/wiki/Zinc_deficiency.
16. Alschuler L, Weil A, Horwitz R, et al. Integrative considerations during the COVID-19 pandemic. EXPLORE. March 2020. doi:10.1016/J.EXPLORE.2020.03.007