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Deep Dive: Zinc and immunity

One big reason people take zinc is to boost immunity. This meta-analysis looked at the details of how supplementation impacted specific immune and inflammation markers.

Study under review: Zinc supplementation and immune factors in adults: a systematic review and meta-analysis of randomized clinical trials

Introduction

Zinc is essential for adequate development and functioning of the immune system. Inadequate intake can lead to a compromised[1] immune response. The immunological outcomes associated with zinc deficiency are well known. Some evidence suggests[2][3] that zinc supplementation may help prevent or treat certain specific diseases involving the immune system. However, studies evaluating the general immunoregulatory effect of zinc supplementation have arrived at different results[4][5]. The variety of results plus the sheer number of immune markers which zinc can affect makes it difficult to say what effects zinc supplementation could have on immune function. That’s where the study under review comes in. This is a meta-analysis that combines the results of 35 studies to evaluate the effect of zinc supplementation on markers of immune system function.

As this study looked at changes in select markers of the immune response associated with zinc supplementation, it is important to have a basic understanding of the immune system and how the measured markers fit in. Immunity is a response our body has to foreign agents. It occurs through a complex system of cellular mechanisms, such as through T cells and B cells, and humoral mechanisms.

Immune mechanisms fall into two main categories: innate and adaptive. Innate immunity is the body’s first line of defense and is activated in case of exposure to foreign agents like bacteria and viruses. It is not specific to a particular foreign agent. The innate response involves white blood cells (also known as leukocytes, a term that uses Greek roots to say “white cell”) called neutrophils, basophils, eosinophils, monocytes (which turn into macrophages at the site of damage or infection), dendritic cells, and natural killer cells. Neutrophils and macrophages engulf and destroy foreign invaders. Eosinophils fight parasitic infections. Basophils release histamine. Dendritic cells can be found on the skin and linings of the nose, lung and stomach. Once activated, they interact with T and B cells. Natural killer cells limit the spread of tumor cells and infections. Innate immunity also includes groups of chemicals that band together to destroy pathogens, called the complement system.

Adaptive immunity happens after a period of time and is a process in which the immune system learns to combat specific pathogens. It involves white blood cells called T lymphocytes (T cells) and B lymphocytes (B cells). Macrophages that have been activated during the innate response act to turn on a specific kind of T cell called T helper cells. The T helper cells activate another specific kind of T cell called cytotoxic T cells along with B cells. The cytotoxic T cells divide to make an army and directly attack pathogens. The B cells turn into plasma cells that make antibodies (Y-shaped proteins that recognize foreign pathogens, also called immunoglobulins) which stick to pathogens to take them out of commission.

Figure 1 details an index of the factors measured in this meta-analysis, what the factors indicate, and whether the factors are part of the innate or adaptive immune response. This table can be used as a guide to understand the methodology and outcomes of this study.

Figure 1: Factors measured in the meta-analysis
Factor MeasuredInnate or AdaptiveDefinition

CD3

Adaptive

A marker for all types of T cells.

CD4

Adaptive

A marker for T helper cells. These cells help lead the fight against infections.

CD4/CD8

Adaptive

Ratio of T helper cells (CD4) to cytotoxic T cells (CD8). A normal ratio is between 1 and 4. Outside of this range could indicate infection or other disease.

WBC

Innate and adaptive

White blood cells, also called leukocytes, include neutrophils, monocytes/macrophages, eosinophils, basophils, lymphocytes, T cells, B cells and plasma cells. An increase in the WBC number in the blood is used as a marker of an ongoing or recently resolved infection.

Lymphocytes

Adaptive

T and B cells.

Monocytes

Innate

Monocytes are a type of white blood cell (leukocyte). They are the largest type of leukocyte and can differentiate into macrophages and dendritic cells. Although they are considered a part of the innate immune system, monocytes also influence the process of adaptive immunity.

Neutrophils

Innate

Type of white blood cell (leukocyte) that helps heal damaged tissues and resolve infections. Neutrophils help prevent infections by blocking, disabling, digesting, or warding off invading particles and microorganisms. They also communicate with other cells to help them repair cells and mount a proper immune response.

CRP / hs-CRP

Innate and adaptive

C-reactive protein (CRP) is a protein found in blood plasma. Circulating concentrations of CRP rise in response to inflammation. It originates in the liver and increases following interleukin-6 (IL-6) secretion by macrophages and T cells. The high-sensitivity C-reactive protein (hs-CRP) test is a blood test that finds lower levels of CRP.

TNFα

Innate

Tumour Necrosis Factor-alpha (TNF-α), is an inflammatory cytokine produced by macrophages/monocytes during acute inflammation and is responsible for signaling events within cells that lead to necrosis or apoptosis. The protein is also important for resistance to infection and cancers.

IL-6

Innate and adaptive

Interleukin-6 is active in inflammation and B-cell maturation. It is produced in response to inflammation, usually in conjunction with other cytokines. Cytokines are small proteins released by cells that have a specific effect on the interactions and communications between cells.

The association between zinc deficiency and decreased immunity is well known. There are several studies that have evaluated the effects of zinc supplementation on altering immune function. However, outcomes have varied. Immunity is accomplished through the innate and adaptive immune systems and each system involves different types of cells and signaling molecules components released from cells. These signaling molecules are markers scientists use to indicate what the immune system is doing. This study was designed to evaluate the non-disease-specific effect of zinc supplementation on certain markers of immune function.

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