Zinc for Immune Health

The function and integrity of the immune system depends on multiple nutrients and can be adversely affected during states of malnutrition. Unfortunately, suboptimal intake of any one nutrient can inhibit the full potential for fighting bacteria, viruses, and other invaders. Zinc is one of the nutrients involved in almost every aspect of immune function, playing both direct and indirect roles in protecting and defending against pathogens.

Zinc’s Role in Innate Immunity

Physical barrier

Zinc is an important player in maintaining the integrity of the physical barriers in the human body. The skin, mucus membranes, and epithelial linings are dependent on zinc for repair and maintenance through both structural and functional mechanisms. Zinc deficiency has been shown to cause degradation of the tight junction complexes that make connections between cells that line the gut and respiratory tissues.₁ This breakdown disrupts the physical barriers that prevents pathogens and toxins from invading. Invasion induces the migration of white blood cells to the site, initiating an inflammatory response. If not controlled, the inflammatory response will lead to further damage to epithelial cells.  Zinc supplementation has been shown to reverse membrane damage and restore function, including preservation of the mucosal secretions.₁

Structurally, zinc is embedded in the cell membranes of these barrier tissues and plays a role in stabilization. Zinc’s ability to act as an antioxidant protects cell membranes from reactive oxygen species and prevents damage. It competes with oxidative metals (iron and copper), displacing them in the cell membranes. Zinc also exerts indirect antioxidant effects through binding to and protecting sulfur-containing proteins (such as glutathione) and inducing expression of the protein metallothionein – an excellent scavenger of hydroxyl radicals.₂

Cellular immunity

Another immune function of zinc is its role in the innate immune response. The innate immune response is the first line of defense following a breach of the physical barriers. The innate immune system is responsible for recruiting white blood cells to the site of infection, identification and removal of foreign substances by phagocytic cells, and the presentation of antigens required for a T cell immune response. Zinc deficiency has been shown to reduce the effectiveness of each of these actions, resulting in diminished phagocytosis and reduced pathogen destruction.₃

Inhibition of viral replication

Viruses are microscopic packages of genetic material and come wrapped in a protein coating. They don’t contain the components required for translating their own genetic code into proteins, thus they require a host in order to replicate. The ability of zinc to inhibit viral replication has long been studied in cell culture and is now widely accepted to do the same in vivo. The mechanism of action may be virus specific, but in single-stranded RNA viruses such as rhinovirus (common cold) and influenza, zinc has been shown to inhibit the enzyme required for translating the virus’ genetic material.₄

Adaptive Immunity

Along with the ability of zinc to prevent viral replication, zinc plays a role in the output of T and B lymphocytes.₅ T lymphocytes originate in the bone marrow and develop in the thymus gland. B lymphocytes also originate in the bone marrow but develop in the spleen and lymph. Various forms of T cells perform different functions, including direct destruction of infected cells by cytotoxic T cells, and the release of cytokines to activate and differentiate different types of immune cells by T helper cells.

Certain T helper cells are considered essential for inducing B cells to produce antibodies. Zinc deficiency impacts the output and function of T helper cells and tips the scales away from the activation of cellular immunity (e.g. macrophages, cytotoxic T cells) and toward humoral immunity (e.g. B cell proliferation, antibody production and B cell class switching – such as from IgG to IgM type, etc.).₅ This downregulation of cellular immunity can lead to increased susceptibility to infection. Zinc supplementation restores normal immune response, although optimal dosing is still under investigation.

Zinc Supplementation

In 2012, researchers estimated that inadequate zinc intake affects between 15 and 25 percent of the world population. Deficiency is especially prevalent among poorer populations and in those who consume a diet high in phytates (particularly cereal grains) and low in animal foods.₆  Normal serum zinc levels are key for supporting a healthy immune response; however, excessive zinc supplementation can lead to a suppression of T and B cells.

It is important to balance zinc and copper intake in higher doses of zinc. Long-term use of doses higher than 40 mg per day (the upper limit for zinc) can lead to a copper deficiency, but short-term studies using doses at higher levels showed no serious adverse effects (though bad taste and nausea were quite common).₆ A 2011 meta-analysis looking at 13 placebo-controlled trials assessing zinc lozenges for common cold symptoms found that only higher dose studies (75 mg and more) resulted in reduction and duration of symptoms. And studies using anywhere from 50 to 180 mg per day for one to two weeks resulted in no serious side effects.₇

The complex nature of the immune system – and its reliance on zinc – reveals just a glimpse into the intricacies of the human body. Maintaining the integrity of the immune system requires attention to one’s intake of micronutrients such as zinc.

References

1. Gammoh NZ, Rink L. Zinc in Infection and Inflammation. Nutrients. 2017;9(6):624. Published 2017 Jun 17. doi:10.3390/nu9060624
2. Gombart AF, Pierre A, Maggini S. A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection. Nutrients. 2020;12(1):236. Published 2020 Jan 16. doi:10.3390/nu12010236
3. Barati F, Pouresmaieli M, Ekrami E, Asghari S, Ziarani FR, Mamoudifard M. Potential Drugs and Remedies for the Treatment of COVID-19: a Critical Review. Biol Proced Online. 2020;22:15. Published 2020 Jul 23. doi:10.1186/s12575-020-00129-1
4. Calder PC. Nutrition, immunity and COVID-19. BMJ Nutrition, Prevention & Health. 2020;bmjnph-2020-000085. doi:10.1136/bmjnph-2020-000085
5. Djoko KY, Ong CL, Walker MJ, McEwan AG. The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens. J Biol Chem. 2015 Jul 31;290(31):18954-61. doi: 10.1074/jbc.R115.647099. Epub 2015 Jun 8. PMID: 26055706; PMCID: PMC4521016.
6. Wessells KR, Brown KH. Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting. PLoS One. 2012;7(11):e50568. doi:10.1371/journal.pone.0050568
7. 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