Heather Bedard, C.H.E.
With fears about the COVID-19 virus monopolizing the global headlines continually, many people are searching for ways to decrease their susceptibility to the virus in ways that are natural and inexpensive. One of the treatments and preventative measures advocated by many doctors and natural health professionals is zinc.
Zinc is a chemical element that plays a part in many interrelated immune functions in the body. One of the important functions that zinc plays is cellular metabolism, which is the process by which cells grow, reproduce, and respond to the environment they are in. Furthermore, zinc has a primary role in over 300 enzymes enabling their catalytic activity. This means that zinc increases the ability of the cells to reproduce quickly or engage in the chemical reactions necessary for healthy function. This includes helping to increase the response rate of the cells as the body mounts an immune response.[1] The cells affected by the activity of zinc include macrophages and T lymphocytes and the health of these cells radically affect a strong immune response. This is because zinc plays a part in cell division and activation as mentioned above.[2],[3] Zinc also tightens and restores junctions between cells keeping pathogens out and helps to support lung function. In addition to the crucial role of serving a multitude of cell functions, zinc also plays a role in the membrane structure and the epithelial in cells giving them strength. This provides a barrier for pathogens and also plays a part in how the skin is used in immune function. This same effect is shown in the way zinc decreases the permeability of the mucosa thereby further protecting the body against pathogens.[4] Even more importantly, according to a study on how “zinc salts directly inhibit the activity of viral RNA-dependent RNA polymerase (RdRp)”, zinc salts inhibit viral replication.[5]An additional impact of zinc on immune function is how it affects the thyroid. Zinc is used in the synthesis of many different thyroid hormones and these hormones play an integral role in the body’s production and regulation of TSH (Thyroid Stimulating Hormone) and other hormones involved in the immune response.[6]
Zinc is an essential nutrient and as such is not produced or stored by the body. Therefore, ingesting it daily through a variety of foods is critical and is the primary mechanism for the body to absorb it. Zinc works with the other vitamins and minerals in the food to deliver the optimum benefit to the body as a whole. This understanding is important in determining whether or not to use a zinc supplement. Most people in the western world are not at risk of zinc deficiency due to how readily available food sources are. In the typical American diet, zinc is obtained primarily through meats like beef and chicken, while many plants are good sources as well. Although there are many plants with high levels of zinc, there are those who are concerned that vegetarians or vegans are unable to consume an adequate amount of zinc through plants alone. This is partially due to the fact that zinc is less bioavailable in plants than in meats. Concerned doctors point to the fact that many plants like grains and legumes contain phytates, which inhibit the absorption of zinc. This is, however, not as bad as it sounds. The phytates in foods play a precautionary role, inhibiting the over-consumption of zinc which could lead to toxic levels over the long-term. The body is wonderfully designed to pull out the nutrients it needs while regulating itself to short-term deficiencies if there are any. This is shown in a study of zinc absorption and intestinal losses of endogenous zinc in young Chinese women.[7] This study found that the intestines of the women who had marginal zinc intake conserved zinc and endogenous absorption did not differ from the women who consumed higher levels of zinc. While the FDA states that vegetarians should consume up to 50% more zinc than the RDA (Recommended Daily Allowance) for omnivores, studies show that vegetarians’ bodies adapt to lower levels of zinc by secreting less zinc and therefore have comparable levels of zinc as nonvegetarians.[8] Additionally, studies have not shown that vegetarians in developed countries are risk for zinc deficiency. The concerns that many health practitioners give about vegetarians and zinc are generally sourced from studies that look at vegetarians in poverty-stricken countries who don’t have access to the readily available variety of foods that developed countries have.[9] Eating zinc along with protein can increase the absorption of zinc and interestingly enough, the plants that contain the highest levels of zinc also contain relatively high levels of protein. All this being said, the line between having enough zinc and not enough is a thin one. Zinc is regulated in the cells of the body and too much zinc can cause an upset in the balance of other minerals and vitamins. A zinc deficiency, on the other hand, can be caused by malnutrition and the use of the body to combat inflammation or disease. Consequently, the body seeks to find zinc homeostasis if there is a deficiency or excess by regulating its excretion from the cells or eliminating it through fecal matter. The FDA recommends an RDA (Recommended Dietary Allowance) of 8mg for women and 11mg for men and from to 3-7mg for children ages 4 and up. They suggest the upper-level intake being up to 40mg for adults. There are currently no reliable biomarkers for the levels of zinc a person has, as plasma levels are not an accurate indicator of zinc levels.[10] This is because of how zinc is expressed in multiple types of cells and functions of the body. A more accurate indicator would be observational, such as growth patterns, immune function, etc.
To determine the role that zinc could possibly play in the treatment or prevention of the COVID-19 virus, we need to first understand what COVID-19 is and the mechanisms by which it attacks the body. COVID-19 is the name for the disease caused by a coronavirus known as SARS-CoV-2. Coronaviruses affect the respiratory system and are the cause of the common cold. Symptoms of COVID-19 vary from person to person, but generally include fever, aches, shortness of breath, dry cough, chills, sore throat, and a loss of taste and smell. Currently, there is no reliable test to differentiate COVID-19 from any other coronavirus. Due to this fact, and because the symptoms are similar to other coronaviruses and the flu, we will use colds, the flu, and other coronaviruses to establish probable efficacy and mechanism of action to treat or prevent COVID-19.
Coronaviruses typically enter the body through the eyes, nose, or mouth and then get trapped in the mucosal linings of the throat or nose. From this point the immune system launches an attack. As the virus travels through the body it attaches itself to ACE2 (angiotensin-converting enzyme 2) receptors using a spike protein. ACE2 mRNA is highly expressed in the cardiovascular system and is found in the epithelium of the lungs as well as many other organs in the body. Specifically, SARS-CoV-2 (COVID-19) attacks the cells in the lungs called the alveoli and this is one of the reasons why the immune response is typically characterized by shortness of breath, pneumonia, lung damage, and cough.
When it comes to zinc, there are multiple ways that its effect on the body could play a part in the prevention or treatment of the COVID-19 virus. To begin with, Zinc is known to hinder rhinovirus binding and replication in nasal passageways.[11] Because many coronaviruses enter through the nasal passages, this is a potential mechanism for preventing the COVID-19 virus replicating before it gets very far. Furthermore, the way that zinc contributes to cell strength and replication ensures that the cells are stronger and able to withstand the virus’ attempts at penetration more effectively. This function of zinc includes strengthening natural killer cells, which are sensitive to decreased levels of zinc.[12] Furthermore, ACE2 receptors (the receptors the COVID-19 spike protein attaches to) are a zinc-metalloenzyme meaning that zinc is crucial for its enzymatic ability. Lastly, one primary effect of zinc is its integral role on inflammation and infection as it relates to regulating inflammatory cytokines and protecting tissues during cell apoptosis.[13]
The fact that zinc plays a critical role in the strength of the immune system and how the cells of the body respond to pathogens is well established. However, we are still left wondering whether or not supplementing with zinc is useful for the prevention of COVID-19 specifically. The answer to this question is multi-faceted. While zinc itself is useful for the individual processes of the body that would make someone less likely to have serious side effects or mortality from an infectious disease, studies do not support the idea that supplementation is beneficial for people who are not zinc deficient. This is exemplified in a study on zinc as an adjunct therapy in the management of severe pneumonia among Gambian children.[14] This study found that using zinc against a placebo in adjunct therapy did not result in any statistically meaningful benefits. Furthermore, if you are eating a well-rounded plant-based diet or even a diet high in animal foods as most Americans are, you are less likely to be zinc deficient to begin with. The importance of this is that if you are not deficient, supplementing will not help you due to the fact that the body does not store excess zinc. However, once the body has contracted COVID-19, zinc support and supplementation could be critical to mounting a successful immune response. At the onset of inflammation, zinc stores are depleted as the body uses the zinc to modulate the immune response. In this scenario, zinc would be supplemented at the onset of symptoms to support the body as disease and lack of homeostasis causes zinc to be depleted. This depletion is characteristic of what is called the triage theory, which postulates that in the event of a nutrient deficiency, the nutrient is allocated primarily to functions related to immediate survival while long-term functions are impaired.[15] More studies need to be done on this expression of zinc deficiency as it relates to COVID-19 symptoms. Chloroquine is another highly recommended protocol for COVID-19 in addition to zinc and there is good reason for that. Chloroquine is a zinc ionophore, meaning it helps to transport zinc into a cell.[16] This greatly increases the amount of zinc in the cells which, as stated earlier, contributes to the cells strength and ability to ward off pathogens. More studies need to be done in the area of pairing zinc with an ionophore for efficacy in treatment protocols. One important consideration on zinc supplementation would be that COVID-19 is known to have a worse effect on the elderly. It is possible that the elderly is more at risk because they are commonly more zinc deficient due to the typical increase in medication with age, reduced food intake, and the quality of foods typically consumed. If a person is considered zinc deficient, preliminary research seems to show that supplementation could be helpful. However, more research needs to be done to prove this is an effective option long-term. All-in-all, the most beneficial action would be to ingest zinc naturally as a part of a healthy diet.
As mentioned above, due to the fact that there is no reliable test for proof of infection, we will look here at the common cold which has similar symptoms and effects, to establish the efficacy or not of zinc supplementation at the onset of disease. There are multiple strains of viruses that cause the common cold and some of them are caused by coronaviruses. While none of the studies I found specified what type of strain was being tested against, zinc has been proven as beneficial for treating colds in general when used at early onset.[17],[18] While exact dosages need to be studied further, a meta-analysis of seven studies of 575 participants with naturally occurring colds found that zinc supplementation greater than 75mg a day reduced cold duration by an estimated 33%. Zinc supplementation greater than 100mg was not seen to make a difference.[19] Despite the fact that many studies show that zinc plays an integral role in immune function, a structured review of the treatment of naturally occurring colds with zinc showed little to no effect of zinc on healing colds or relief of symptoms in other well-structured studies based on strict criteria.[20] Conversely, this review specifies that the different studies contain varying levels of adherence to good study practices which makes it difficult to judge.
While zinc supplementation will not reduce the risk of contracting COVID-19 unless you are deficient, once a person has contracted COVID-19 there are certain protocols for zinc supplementation that will produce better results than others. Many varieties of supplements contain different compounds of zinc like zinc gluconate, zinc sulfate, and zinc acetate. These are all pairings of zinc with other minerals and each compound reacts differently in the body. Zinc sulfate is the least expensive form of zinc, but it is not absorbed easily. The forms of zinc most easily absorbed would be zinc picolinate, zinc citrate, zinc acetate, zinc glycerate, and zinc monomethine. The actual amount of elemental zinc available in these compounds vary. Approximately 23% of zinc sulfate is composed of elemental zinc and the rest is sulfate. In other words, 220mg of zinc sulfate contains 50mg of elemental zinc.
If one is concerned about being zinc deficient due to chronic disease or decides to supplement due to COVID-19 infection, there are limitations on safety and the length of time one should supplement with zinc. One of the side effects of too much zinc is zinc toxicity resulting in copper deficiency and neurologic disease. However, this would typically only occur with long-term use and high dosage. If given in appropriate ratios, zinc and copper should have no detrimental effects.[21]If one is taking a multi-vitamin containing iron or an iron specific supplement it is important to remember that large doses of iron may prevent some zinc absorption and zinc may also inhibit the absorption of copper resulting in anemia.[22] A general rule of thumb would be to supplement during the course of the disease and not long term. Many people report bad taste, nausea, and diarrhea when consuming zinc supplements in various forms. Consumers should also be aware that not all supplements are created equal. Some brands contain additives, and those additives can negate the effects of the zinc that is contained within.[23]This is further expressed in a review of randomized control trials (RCT) on zinc gluconate and the common cold.[24] The author found in her review of seven double blind RCT’s, that citric acid, sorbital, and mannitol can bind the free zinc ions and potentially make the therapy less effective.
When it comes to the prevention of COVID-19 as it relates to zinc, the best prevention is a healthy diet which will provide the optimal combination of zinc and other healthy minerals and vitamins to support the immune system. In regard to treatment, one could supplement safely with up to 25mg of zinc over the duration of the disease to help support the immune system and potentially reduce disease term by 2 days or 33%, but not necessarily symptoms as shown in the studies of the reduction of the common cold duration.[25] Zinc is a crucial element in the body, but the preponderance of evidence does not support its use prophylactically and studies are mixed on the statistical benefits during disease.
[1] MacIver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013;31:259-283. doi:10.1146/annurev-immunol-032712-095956 [2] Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68(2 Suppl):447S-463S. doi:10.1093/ajcn/68.2.447S [3] Ananda S. Prasad, Zinc: Mechanisms of Host Defense, The Journal of Nutrition, Volume 137, Issue 5, May 2007, Pages 1345–1349, https://doi.org/10.1093/jn/137.5.1345 [4] Maares M, Haase H. Zinc and immunity: An essential interrelation. Arch Biochem Biophys. 2016;611:58-65. doi:10.1016/j.abb.2016.03.022 [5] Kaushik N, Subramani C, Anang S, et al. Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase. J Virol. 2017;91(21):e00754-17. Published 2017 Oct 13. doi:10.1128/JVI.00754-17 [6] Severo JS, Morais JBS, de Freitas TEC, et al. The Role of Zinc in Thyroid Hormones Metabolism. Int J Vitam Nutr Res. 2019;89(1-2):80-88. doi:10.1024/0300-9831/a000262 [7] Sian L, Mingyan X, Miller LV, Tong L, Krebs NF, Hambidge KM. Zinc absorption and intestinal losses of endogenous zinc in young Chinese women with marginal zinc intakes. Am J Clin Nutr. 1996;63(3):348-353. doi:10.1093/ajcn/63.3.348 [8] Saunders AV, Craig WJ, Baines SK. Zinc and vegetarian diets. Med J Aust. 2013;199(S4):S17-S21. doi:10.5694/mja11.11493 [9] Janet R Hunt, Bioavailability of iron, zinc, and other trace minerals from vegetarian diets, The American Journal of Clinical Nutrition, Volume 78, Issue 3, September 2003, Pages 633S–639S, https://doi.org/10.1093/ajcn/78.3.633S [10] Gibson RS, Hess SY, Hotz C, Brown KH. Indicators of zinc status at the population level: a review of the evidence. Br J Nutr. 2008;99 Suppl 3:S14-S23. doi:10.1017/S0007114508006818 [11] Novick SG, Godfrey JC, Godfrey NJ, Wilder HR. How does zinc modify the common cold? Clinical observations and implications regarding mechanisms of action. Med Hypotheses. 1996;46(3):295-302. doi:10.1016/s0306-9877(96)90259-5 [12] Tapazoglou E, Prasad AS, Hill G, Brewer GJ, Kaplan J. Decreased natural killer cell activity in patients with zinc deficiency with sickle cell disease. J Lab Clin Med. 1985;105(1):19-22. [13] Gammoh NZ, Rink L. Zinc in Infection and Inflammation. Nutrients. 2017;9(6):624. Published 2017 Jun 17. doi:10.3390/nu9060624 [14] Howie S, Bottomley C, Chimah O, et al. Zinc as an adjunct therapy in the management of severe pneumonia among Gambian children: randomized controlled trial. J Glob Health. 2018;8(1):010418. doi:10.7189/jogh.08.010418 [15] Ames BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci U S A. 2006;103(47):17589-17594. doi:10.1073/pnas.0608757103 [16] Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ. Chloroquine is a zinc ionophore. PLoS One. 2014;9(10):e109180. Published 2014 Oct 1. doi:10.1371/journal.pone.0109180 [17]Science M, Johnstone J, Roth DE, Guyatt G, Loeb M. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ. 2012;184(10):E551-E561. doi:10.1503/cmaj.111990 [18] Ananda S. Prasad, James T. Fitzgerald, Bin Bao, et al. Duration of Symptoms and Plasma Cytokine Levels in Patients with the Common Cold Treated with Zinc Acetate: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Intern Med.2000;133:245-252. [Epub ahead of print 15 August 2000]. doi:10.7326/0003-4819-133-4-200008150-00006 [19] Hemilä H. Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage. JRSM Open. 2017;8(5):2054270417694291. Published 2017 May 2. doi:10.1177/2054270417694291 [20] Caruso TJ, Prober CG, Gwaltney JM Jr. Treatment of naturally acquired common colds with zinc: a structured review. Clin Infect Dis. 2007;45(5):569-574. doi:10.1086/520031 [21] Plum LM, Rink L, Haase H. The essential toxin: impact of zinc on human health. Int J Environ Res Public Health. 2010;7(4):1342-1365. doi:10.3390/ijerph7041342 [22] G J Fosmire, Zinc toxicity, The American Journal of Clinical Nutrition, Volume 51, Issue 2, February 1990, Pages 225–227, https://doi.org/10.1093/ajcn/51.2.225 [23] Eby GA 3rd. Zinc lozenges as cure for the common cold--a review and hypothesis. Med Hypotheses. 2010;74(3):482-492. doi:10.1016/j.mehy.2009.10.017 [24] Marshall S. Zinc gluconate and the common cold. Review of randomized controlled trials. Can Fam Physician. 1998;44:1037-1042. [25]Hemilä H. Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage. JRSM Open. 2017;8(5):2054270417694291. Published 2017 May 2. doi:10.1177/2054270417694291