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Zinc: The Gatekeeper of Immune Function

By Dr. Michael Murray

In this article:


Deficiency of the essential trace mineral zinc offers insight into how a single nutrient can impact immune function. Without adequate zinc intake, we may lose the ability to fight off viruses as well as regulate overactive immune responses that lead to inflammation.1 Low zinc levels are common, especially in children and the elderly. Even in developed countries, nearly 30% of the elderly population is considered to be zinc deficient. Vegetarians or vegans, people with kidney disorders or chronic diarrhea are also often zinc deficient. For general health benefits of zinc and benefits to specific health conditions see my Quick Guide to Zinc. In this article, the focus will be on the key roles of zinc in immunity.

NOTE: There are no current studies in relation to zinc and COVID-19 or the SARs-CoV2 virus. The below discussion reflects the effects of zinc in general as it relates to viruses and viral infections. If you are experiencing any symptoms suggestive of COVID-19 or other infections, please consult a healthcare provider immediately.

Zinc and 3 Important Immune Processes

Zinc serves a vital role in many immune system reactions. It is involved in virtually every aspect of immunity, but is most important in the following three processes: 

  • Thymus function and hormones
  • White blood cell function and signaling
  • “Innate immunity”2

There is one important consideration when talking about any single nutrient and immune function. Our immune system relies on a complex interplay of many different factors. A deficiency of any single nutrient can disrupt the entire system. For example, zinc functions in close companionship with vitamin A and Dselenium, and many other nutrients. A deficiency of any of these other nutrients will undermine the benefits of zinc.

Zinc and the Thymus Gland

One of the main ways that zinc promotes a healthy immune system is through its role in thymus function. The thymus is the major gland of our immune system. It is composed of two soft pinkish-gray lobes lying in a bib-like fashion just below the thyroid gland and above the heart. To a very large extent, the health of the thymus determines the health of the immune system.

The thymus is responsible for many immune system functions including the production of T lymphocytes, a type of white blood cell responsible for "cell-mediated immunity". Cell-mediated immunity refers to immune mechanisms not controlled or mediated by antibodies. Cell-mediated immunity is extremely important in the resistance to infection by mold-like bacteria, yeast (including Candida albicans), fungi, parasites, and viruses (including Herpes simplex, Epstein-Barr, and viruses that cause hepatitis). Low levels of zinc lead to impaired cell-mediated immunity for several reasons including the effect on the thymus overall as well as within the white blood cells. And it not only increases the risk for infections, but also allergies, autoimmune conditions, and inflammation. Fortunately, several studies have shown that zinc supplementation has been shown to reverse issues caused by inadequate zinc levels on cell-mediated immunity even in elderly subjects.3,4

The thymus gland also releases several hormones that are critically dependent on zinc, so without adequate levels of zinc, these hormones are not active. Thymus derived hormones are powerful enhancers of white blood cell function throughout the body. Not surprisingly, low levels of these hormones in the blood are associated with depressed immunity and increased susceptibility to infection. 

Zinc and White Blood Cell Function

All white blood cells utilize zinc extensively for their specialized functions. In addition to the T cells involved in cell-mediated immunity, white blood cells known as monocytes are particularly sensitive to low zinc levels as well. Monocytes are the “garbage collectors” of the body. Monocytes located in specific tissues like the liver, spleen, and lymph nodes are termed macrophages. Monocytes and macrophages phagocytize or engulf foreign particles including bacteria, viruses, and cellular debris and destroy them. Macrophages are essential in protecting against invasion by microorganisms as well as processing what the danger is so that they can send out messages to other cells of the immune system. All of these very important processes of monocytes and macrophages are zinc-dependent. Anything less than optimal levels of zinc means these processes are not functioning optimally.5

Another type of white blood cell is the natural killer cell or NK cell. These cells received their name because of their ability to destroy cells that have become cancerous or infected with viruses. Zinc is involved in the signaling of the NK cell to perform its function. Therefore, when zinc levels are low, the NK cell does not get the signal to perform its function.3 This failure could be a very bad situation during an active viral infection and is another reason why it is so important to ensure adequate zinc levels in one’s diet at all times.

Zinc and Innate Immunity

In addition to its effects on the immune system offering protection against infection, zinc alone in its ionic state exerts activity against viral infection. Zinc is not an antibiotic or antiviral drug, rather it is a nutrient that is part of the body’s fight against organisms. Zinc is a valuable component of our “innate immunity.” This term is used to describe defense mechanisms in the body that are naturally present and are not due to activation of the immune system. The importance of zinc to our innate immunity is another reason why it is referred to as the “gatekeeper of immune function.” Zinc, along with many other nutrients like vitamins A and D, is especially important in the function of our barriers to infection in our skin and the linings of our respiratory and gastrointestinal tract.

In its free, ionic state zinc is a powerful component of our innate immune system's fight against infection by directly inhibiting the growth of many viruses.6 When a virus infects a cell, it inserts a piece of its genetic code and often an enzyme called replicase to allow the virus to replicate. Zinc, as part of our innate immunity, is able to block the replicase enzyme and, therefore, block the replication or spread of the virus. In order for zinc to have this effect, however, it seems that it is dependent upon an open “ionophore” - a special cell membrane portal (door) that allows for an ion to enter the cell. There are a number of natural compounds that can act as zinc ionophores to aid the intracellular levels of ionic zinc, most notable are flavonoids like quercetin and those found in green tea.7 These compounds might assist in increasing intracellular zinc levels.

Recommended Dosage of Zinc

In adults, the dosage range for zinc supplementation for general health support and during pregnancy or lactation is 15 to 20 mg. For children, the dosage range is 5 to 10 mg. When zinc supplementation is being used to address an increased need or bolster host defense mechanisms, the dosage range for men is 30 to 45 mg; for women 20 to 30 mg. 

Zinc lozenges are often recommended to boost zinc levels during the common cold. Typically the dosage recommended for lozenges that supply 15 to 25 mg of elemental zinc is to dissolve them in the mouth every two waking hours after an initial double dose. This dosage can be continued for up to seven days. 

Available Forms of Zinc

There are many forms of zinc to choose from as a dietary supplement. While many clinical studies have utilized zinc sulfate, this form is not as well absorbed. Better forms include zinc picolinate, acetate, citrate, bisglycinate, oxide, or monomethionine. There is data to support each of these forms as being very well-absorbed and able to produce health benefits. Most zinc lozenges are made with zinc gluconate, which appears to be an effective form for this application.

Possible Side Effects of Zinc

If taken on an empty stomach (particularly if taking zinc sulfate), zinc supplementation can result in gastrointestinal upset and nausea. Prolonged intake at levels greater than 150 mg per day may lead to anemia, reduced HDL-cholesterol levels, and depressed immune function through interference in the absorption of copper.

Drug Interactions: Zinc may decrease the absorption of tetracycline and ciprofloxacin. Take any zinc supplement at least 2 hours before or after taking these antibiotics.

Use of the following drugs increases the loss of zinc from the body or interferes with absorption: aspirin; AZT (azidothymidine); captopril; enalapril; estrogens (oral contraceptives and Premarin®); penicillamine; and the thiazide class of diuretics. Supplementation may be required to maintain zinc status in people taking these drugs.

References:

  1. Gammoh NZ, Rink L. Zinc in Infection and Inflammation. Nutrients. 2017 Jun 17;9(6). pii: E624
  2. Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients. 2017 Nov 25;9(12). pii: E1286. 
  3. Mocchegiani E, Romeo J, Malavolta M, et al. Zinc: dietary intake and impact of supplementation on immune function in elderly. Age (Dordr). 2013 Jun;35(3):839-60. 
  4. Barnett JB, Dao MC, Hamer DH, et al. Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2016 Mar;103(3):942-51.
  5. Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med. 2008 May-Jun;14(5-6):353-7. 
  6. Hulisz D. Efficacy of zinc against common cold viruses: an overview. J Am Pharm Assoc (2003). 2004 Sep-Oct;44(5):594-603.
  7. Dabbagh-Bazarbachi H, et al. Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1-6 cells to a liposome model. J Agric Food Chem. 2014 Aug 13;62(32):8085-93.

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