Research & Education

The Biochemistry of Zinc and the Immune Response

Zinc has been referred to as the “gatekeeper of the immune system” for solid reasons. This essential mineral, with its critical roles in over 300 enzymes within the body, has been recognized for its vital function in promoting proper immune health since the 1960s

Zinc is required for the optimal development and function of both arms of the immune system – the innate and adaptive immune responses. It affects immune signaling cascades by binding directly to signaling proteins or indirectly by influencing enzymes that complement and regulate signaling pathways. 

A zinc deficiency, whether severe or marginal, is associated with immune dysfunction, increased oxidative stress, and an unbalanced inflammatory response, which may be associated with allergic reactions and autoimmune diseases. A systematic review and meta-analysis of 62 case-control studies observed that zinc concentrations in serum and plasma were significantly lower in patients with autoimmune diseases compared to controls. 

Patients with severe zinc deficiency (typically due to malabsorption of zinc resulting from a mutation of zinc-importing proteins) present with lymphopenia, a decreased ratio of T helper (Th) cells to cytotoxic T cells, decreased natural killer cell activity, and increased monocyte activity. Patients with marginal zinc deficiency (often seen in vegetarians, vegans, or the elderly) also exhibit impaired immune function. Suboptimal zinc status may adversely affect the maturation and function of T and B cells, imbalance the ratio of Th1 and Th2 cells in favor of the Th2-driven allergic reactions, lead to thymus atrophy, and may also increase production of pro-inflammatory Th17 and Th9 cells. 

Zinc deficiencies were once rare, but according to the World Health Organization, zinc deficiency is now the fifth largest health risk factor in developing countries and eleventh globally. Approximately 20% of the global population is zinc deficient, and nearly 30% of elderly adults are affected. The recommended daily zinc intake for adults 19 or older is 11 mg for males and 8 mg for females. 

Suboptimal zinc status can be due to insufficient dietary intake or compromised zinc uptake. Rich dietary sources of zinc include animal products, such as red meat, poultry, and seafood. Although plant-based foods like cereals or legumes contain zinc, their zinc bioavailability is decreased due to the zinc-chelating agents of lignans and phytates that counteract zinc absorption. 

A crucial aspect of zinc’s role in the immune system is its balance with copper, another essential mineral. An elevated copper/zinc ratio has also been associated with dysregulated immune function. As zinc concentration tends to fall with age, copper concentration tends to increase. Furthermore, an increased copper/zinc ratio can be associated with chronic exposure to cadmium, especially in smokers

Zinc homeostasis promotes a healthy and balanced immune system. Beyond immune function, zinc is necessary to support proper RNA transcription, DNA synthesis, and cell survival. Maintaining optimal zinc status through diet or supplementation is critical to promoting optimal immune function. 

By Danielle Moyer Male, MS, CNS, LDN