Potential role of Zinc in prevention or treatment of COVID-19


Greta Goldshtein, PharmD, APh

January 10, 2021




Essential nutrient functions


Zinc is an essential trace element that is involved in numerous biological processes including metabolism of lipids and carbohydrates, maintenance of proper function of the nervous and cardiovascular systems, facilitation of gene expression, growth and tissue repair. It is also essential in the function of the innate and adaptive immune system, where it acts as an important modulator with anti-inflammatory and antioxidant properties.


Proposed role in COVID-19*


Zinc deficiency increases susceptibility to infections, particularly in populations vulnerable to deficiency states. Several studies have supported the benefits of zinc in mitigating infections, though best use protocols and doses have not been fully described. The benefit of zinc supplementation has been demonstrated by a well-designed 12-month long study that found 55-85-year-old patients experienced fewer infections when given zinc supplementation. It has also been demonstrated to decrease the duration of the common cold when used in higher doses (>75 mg/day).


There are several possible immune-related mechanisms by which zinc may be helpful in mitigating infection with SARS-CoV-2 virus that causes COVID-19. Specifically, zinc is thought to decrease the replication of respiratory viruses and to up-regulate immune components that increase their destruction. It may also improve the barrier function by strengthening tight junctions between cells and thus help maintain clearance of mucous from respiratory passages.


Dietary sources


Dietary sources of zinc include meat, dairy, and some seafood (oysters); nuts and legumes are also a source but provide smaller amounts. The amount of zinc found in plant-based foods is highly dependent on zinc concentration in the soil and its biological availability is further hindered by presence of phytic acid, which binds with zinc in the digestive tract and decreases its absorption.


Risk of inadequate intake in an American diet is moderate, and many individuals may not consume sufficient amounts of zinc even with additional supplementation. National Health and Nutritional Examination Survey (NHANES) from 2009-2012 found that 15.8% of Americans consume less than the Estimated Average Requirement of zinc from food alone.


Deficiency


Dietary deficiency manifests as delayed growth, poor wound healing, various skin and hair changes, impaired taste, and others. Such findings have been described in chronic conditions involving poor dietary intake (malnutrition, alcoholism, older age, parenteral nutrition), impaired absorption from the small intestine (inflammatory bowel disease, gastric bypass surgery, diarrhea, drug interactions), and increased metabolic needs (pregnancy, breastfeeding, wound healing) and increased urinary losses (diabetes). Drug interaction mechanisms include binding in the digestive tract and impaired dietary absorption (antibiotics such as quinolones and tetracyclines) and increased urinary excretion (thiazide and loop diuretics, angiotensin receptor blockers).


Supplementation


Recommended dietary intake is 8 mg per day in women and 11 mg per day in men, however larger doses are likely to be beneficial, particularly in individuals in high-risk groups (high metabolic needs; poor dietary intake, absorption, or increased losses; as well as infants and people over the age of 70 years). Side effects are dose related and include bad taste, nausea, vomiting, abdominal cramps, diarrhea, and headache. Permanent loss of smell has also been described with nasal zinc preparations, which have since been removed from the market.


The usual therapeutic dose recommendations (as elemental zinc content) are zinc lozenges 13.3 mg per dose every 2 to 3 hours while awake for viral upper respiratory tract infections and 50 mg per day as an oral supplement. Though humans can tolerate high dose intake of up to 100 mg per day, long term supplementation with doses above 40 mg per day is not recommended outside of medical supervision since high dose zinc intake can interfere with copper and iron absorption. Interestingly, the “eye health” vitamin formulations such as AREDS2 contain 80 mg of zinc per day have added copper content to guard against development of copper deficiency with long-term administration.


Zinc supplements come in different forms: gluconate, sulfate, acetate, oxide, bisglycinate, and others. Since the elemental zinc content differs widely by formulation, it is recommended to follow the dosing recommendations using the elemental zinc content of the supplement. While it is generally believed that absorption and utilization of zinc is the same from the different formulations, some studies have demonstrated that the amino acid chelated forms (e.g. bisglycinate) may be superior and may also have decreased interaction potential with copper and iron.



* To date, there are no rigorous scientific studies affirming the role or defining best treatment protocols of any vitamins or supplements for prevention or treatment of COVID-19. The information in this section is based on expert opinion and data available to date. Best protection against COVID-19 is socially distancing, wearing a mask, and avoiding congregating indoors with people outside of immediate household members, practicing good hygiene, and receiving vaccination when available.



References:


Bauer SR, Kapoor A, Rath M, Thomas SA. COVID-19 Curbside Consults: What is the role of supplementation with ascorbic acid, zinc, vitamin D, N-acetylcysteine for prevention or treatment of COVID-19? Cleveland Clinic Journal of Medicine, June 2020 https://doi:10.3949/ccjm/87a.ccc046


Guilliams TG. Supplementing Dietary Nutrients: A Guide for Healthcare Professionals, 2nd Edition. Point Institute, 2020


Louca, Panayiotis (2020). Dietary supplements during the COVID-19 pandemic: insights from 1.4M users of the COVID symptom study app – longitudinal app-based community survey. medRxiv preprint server. Doi: https://doi.org.10.1101/2020/2020.11.27.20239087, https://www.medrxiv.org/content/10/1101.2020.11.27.20239087v1


Sahebnasagh A, Saghafi F, et al. The prophylaxis and treatment potential of supplements for COVID-19. European Journal of Pharmacology, September 2020. https://doi.rog/10.1016/j.ejphar.2020.173530


UpToDate: Overview of dietary trace elements. Online version, accessed on 01/04/2021


Zinc Fact Sheet for Health Professionals. National Institutes of Health. Accessed on 01/09/2021. https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional

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