Zinc Ionophore Activity of Quercitin and EGCG

As ways to boost immunity and protect against infection continue to be front and center issues in our world, research focused on nutritional support for the immune system continues to progress.

Zinc has become a major topic of interest of late, since this tried-and-true mineral has been in the news for its ability to prevent viral replication and its role in regulating the inflammasome response that leads to cytokine storms.  

Zinc alone is effective depending on the form.  Not all zincs are created equal, however, and forms such as glycinate and arginate appear to be the most bioavailable.  That said, there may be ways to enhance the bioavailability of zinc, thus providing an even greater impact on immunity and viral load.

Getting zinc into the cell is obviously dependent on having adequate levels of zinc outside the cell. With most of us, this is usually not a problem. However, zinc absorption does vary by individual. Physiological stressors, such as infection and inflammation, tend to deplete zinc pretty fast.

Zinc is a decidedly anti-viral mineral. High intracellular concentrations inhibit the replication of RNA type viruses, such as SARS-CoV-2. Zinc does this by blocking RNA-dependent RNA polymerase (RdRp), the core enzyme of the multiprotein replication and transcription complex critical for the copying of viral RNA. 

That’s the conundrum. In high concentrations, zinc can block coronavirus reproduction, but the cell typically does not tolerate high levels of zinc due to its other actions.

Enter the zinc ionophores.

An ionophore is any substance which is able to transport particular ions across a lipid membrane in a cell. In the case of zinc, there are molecules that can act as facilitators and enhance the entry of zinc into the cell. These are known as zinc ionophores. 

Quercetin and EGCG from green tea are zinc ionophores.  These plant polyphenols  act as antioxidants and as signaling molecules.1

Quercetin plus zinc is being tested as an antiviral in human clinical trials for the treatment of Covid-19. The combination had already made it through animal trials for use against Ebola and SARS-CoV1, and was approved by the FDA for human clinical trials. Plans are underway for a large scale trial in China for patients with Covid-19.

Using these compounds in combination can be a very powerful option against viral infections.  

1. Zinc inophore Activity of Quercetin and Epigallocatechin gallate: From Hepa 1-6 Cells to Liposome Model, July 2014, Journal of Agriculture and Food Chemistry, 62(32), PubMed)

VITAMIN C: Still a Superstar and Growing in Fame Even More

Since the 1970s, Vitamin C has enjoyed superstar status, partly due to Dr. Linus Pauling's Nobel Prize winning work.  But for the past several years, good ole' ascorbic acid has been making a rebound in the research, as this "old news" vitamin has been showing great promise for a number of health applications other than just immunity.  

For example, research has shown that vitamin C protects against endothelial dysfunction, high blood pressure, and the blood vessel changes that precede heart disease.1-3 Additional research is discovering that vitamin C can be helpful in preventing asthma,4 protecting against cancer,5 and supporting healthy blood sugar levels in diabetics.6

While often taken for granted, vitamin C is a critical supplement in improving cardiac health and avoid degenerative diseases.  

British researchers, for example, studied the effects of vitamin C supplementation (250 mg/day) on atherosclerosis in 40 healthy adults.7 Before the study, subjects with low pre-supplementation levels of vitamin C had 30% greater monocyte adhesion than normal, putting them at higher risk for atherosclerosis. Impressively, after six weeks of supplementation, the rate of this dangerous monocyte adhesion actually fell by 37%!  

OTHER HEALTH BENEFITS OF VITAMIN C IN THE RESEARCH

• Ascorbic acid, or vitamin C, is a potent antioxidant with increasingly diverse uses in health promotion and disease prevention. 
• Every step in the progression of atherosclerosis can benefit from the antioxidant power of vitamin C, from preventing endothelial dysfunction and altering lipid profiles and coagulation factors to preventing blood vessel changes that can lead to strokes and other vascular catastrophes. 
• Vitamin C supplements reduce cellular DNA damage that is the vital first step in cancer initiation and also reduce the inflammatory changes that allow a malignant cell to grow into a dangerous tumor.  Additionally, vitamin C has been shown to be chemoprotective, showing protection from both the toxic effects of chemotherapy drugs, but also increasing the anti-tumor activity of chemotherapy, while perhaps reducing the risk of getting cancer in the first place.  8,9,10,11,12,13,14
• Vitamin C supplements enhance the health-promoting effects of exercise and reduce exercise-induced oxidative damage. 15
• Vitamin C supplements also dramatically combat the oxidative damage caused by smoking and exposure to tobacco smoke. 16
• In respiratory conditions, vitamin C supplements help avert or shorten the duration of common colds and may mitigate the risk of serious respiratory conditions like asthma.17, 18,19
• Vitamin C supplements can speed the clearance of the stomach disease-causing bacterium Helicobacter pylori and cut the risk of gastric cancer it causes.  20,21

While all the above benefits can be obtained by taking basic ascorbic acid, the effects may be enhanced by either adding other antioxidants to the mix, or providing a buffered and better absorbed forms.  Vojdani et al at Drew Medical College showed in 1993 that an admixture of vitamin C metabolites, presursors, and asorbates, along with a more bioavailable form of vitamin C, ascorbyl palmitate, was able to not only provide better uptake into the white blood cell, but the effect on leukocyte activity and overall immunity was profoundly better than ascorbic acid alone.22  This exact formula used in the Drew Medical College study is patented and available commercially in only one place.  Ascorbic acid products are typically not patented and are bountiful on the market.  

Still another study showed that a buffered admixture vitamin C supplement increased the natural killer (NK) cell activity 10-FOLD in 78% of patients who had decreased NK, T and B cell function due to chemical exposure!  T and B cells also returned to normal.23  

Yes, while vitamin C is sort of yesterday's news in a market of trendy supplements now too long to list, it remains one of the most powerful and effective vitamins in the world for overall health. 

References

1. Rossig L, Hoffmann J, Hugel B, et al. Vitamin C inhibits endothelial cell apoptosis in congestive heart failure. Circulation. 2001 Oct 30;104(18):2182-7. 2. Fotherby MD, Williams JC, Forster LA, Craner P, Ferns GA. Effect of vitamin C on ambulatory blood pressure and plasma lipids in older persons. J Hypertens. 2000 Apr;18(4):411-5. 3. Salonen RM, Nyyssonen K, Kaikkonen J, et al. Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study. Circulation. 2003 Feb 25;107(7):947-53. 4. Romieu I, Sienra-Monge JJ, Ramirez-Aguilar M, et al. Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. Am J Respir Crit Care Med. 2002 Sep 1;166(5):703-9. 5. Guz J, Dziaman T, Szpila A. Do antioxidant vitamins influence carcinogenesis?. Postepy Hig Med Dosw.(Online.). 2007;61:185-98. 6. Afkhami-Ardekani M, Shojaoddiny-Ardekani A. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. Indian J Med Res. 2007 Nov;126(5):471-4.  7. Woollard KJ, Loryman CJ, Meredith E, et al. Effects of oral vitamin C on monocyte: endothelial cell adhesion in healthy subjects. Biochem Biophys Res Commun. 2002 Jun 28;294(5):1161-8. 8. Bast A, Haenen GR, Bruynzeel AM, Van d, V. Protection by flavonoids against anthracycline cardiotoxicity: from chemistry to clinical trials. Cardiovasc Toxicol. 2007;7(2):154-9. 9. bdel-Latif MM, Raouf AA, Sabra K, Kelleher D, Reynolds JV. Vitamin C enhances chemosensitization of esophageal cancer cells in vitro. J Chemother. 2005 Oct;17(5):539-49. 10. Chen J, Kang J, Da W, Ou Y. Combination with water-soluble antioxidants increases the anticancer activity of quercetin in human leukemia cells. Pharmazie. 2004 Nov;59(11):859-63. 11. Chen J, Wanming D, Zhang D, Liu Q, Kang J. Water-soluble antioxidants improve the antioxidant and anticancer activity of low concentrations of curcumin in human leukemia cells. Pharmazie. 2005 Jan;60(1):57-61. 12. Correa P, Fontham ET, Bravo JC, et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. J Natl Cancer Inst. 2000 Dec 6;92(23):1881-8. 13. Maramag C, Menon M, Balaji KC, Reddy PG, Laxmanan S. Effect of vitamin C on prostate cancer cells in vitro: effect on cell number, viability, and DNA synthesis. Prostate. 1997 Aug 1;32(3):188-95. 14. Wei DZ, Yang JY, Liu JW, Tong WY. Inhibition of liver cancer cell proliferation and migration by a combination of (-)-epigallocatechin-3-gallate and ascorbic acid. J Chemother. 2003 Dec;15(6):591-5. 15. Thompson D, Williams C, McGregor SJ, et al. Prolonged vitamin C supplementation and recovery from demanding exercise. Int J Sport Nutr Exerc Metab. 2001 Dec;11(4):466-81. 16. Block G, Jensen C, Dietrich M, et al. Plasma C-reactive protein concentrations in active and passive smokers: influence of antioxidant supplementation. J Am Coll Nutr. 2004 Apr;23(2):141-7. 17. Romieu I, Trenga C. Diet and obstructive lung diseases. Epidemiol Rev. 2001;23(2):268-87. 18. Trenga CA, Koenig JQ, Williams PV. Dietary antioxidants and ozone-induced bronchial hyperresponsiveness in adults with asthma. Arch Environ Health. 2001 May;56(3):242-9. 19. Tecklenburg SL, Mickleborough TD, Fly AD, Bai Y, Stager JM. Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Respir Med. 2007 Aug;101(8):1770-8. 20. Correa P, Fontham ET, Bravo JC, et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. J Natl Cancer Inst. 2000 Dec 6;92(23):1881-8. 21. Chuang CH, Sheu BS, Kao AW, et al. Adjuvant effect of vitamin C on omeprazole-amoxicillin-clarithromycin triple therapy for Helicobacter pylori eradication. Hepatogastroenterology. 2007 Jan;54(73):320-4. 22.  Vajdoni, A, et al.  In Vivo Effect of Ascrobic Acid on Enhancement of Human Natural Killer Cell Activity.  Drew University of Medicine and Science, Published in Nutritiona Research, Vol. 13, pp. 753-764, 1993. 23. Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals: Immunopharmacol Immunotoxicol. 1997 Aug;19(3):291-312