Zinc in Human Health and Infectious Diseases Original paper

What was reviewed?

This review explains zinc in human health and infectious diseases and shows how zinc status shapes immune defense and pathogen control. The review describes zinc transport and storage, the ZIP and ZnT transporter families, metallothioneins, and S100 proteins such as calprotectin. It links zinc deficiency to a higher risk of respiratory infections, diarrhea, malaria, HIV, tuberculosis, and worse outcomes in sepsis, while zinc support can shorten common cold illness and some pneumonias. It also shows how illness shifts serum zinc into the liver via IL-6–driven ZIP14, lowering circulating zinc to starve microbes. The paper connects these host moves to pathogen countermeasures and to trial data on zinc supplements across infections.

Who was reviewed?

The review draws on adult and child populations from diverse regions, including elders in high-income countries and children in low-income settings where diet limits zinc. It summarizes human trials on colds, pneumonias, diarrhea, malaria, HIV, tuberculosis, and COVID-19, and adds cell and animal data that explain zinc signals in neutrophils, monocytes, and T cells. It also covers pathogens such as Candida albicans, Staphylococcus aureus, Escherichia coli, Helicobacter pylori, Neisseria species, and Mycobacterium tuberculosis to show how host zinc withholding or overload pressures shape survival.

Most important findings

Zinc sits at the center of nutritional immunity. Neutrophils release calprotectin, which binds zinc and limits the growth of Candida albicans and major bacteria; neutrophil traps carry calprotectin to infection sites and add killing power. During acute infection, IL-6 induces ZIP14, serum zinc falls, and the liver sequesters zinc, which denies microbes a key nutrient. Pathogens respond with high-affinity importers such as ZnuABC and surface proteins like ZnuD or TdfH that strip zinc from host proteins, yet many still exhibit slow growth under zinc restriction. In trials, zinc lozenges can shorten common cold duration, and zinc helps some childhood pneumonias and diarrheal disease, though results vary by dose, timing, and baseline status. The review warns that excess zinc can block copper uptake and disturb the copper–zinc balance, which links to poor outcomes in several diseases.

Key implications

Clinicians should check diet risk and disease context when they consider zinc. In patients with frequent viral colds or acute childhood diarrhea, short courses of oral zinc can aid recovery, while severe sepsis does not show clear benefit and may worsen with untargeted dosing. During acute inflammation, falling serum zinc reflects a host strategy, not simple deficiency, so replacement should match clinical goals. Because zinc and copper compete, long high-dose zinc can trigger copper lack, anemia, and immune harm; balance matters. For microbiome reporting, record zinc exposure, the copper–zinc ratio, and gene reads for znuA/B/C or znuD in pathogens, and calprotectin or ZIP14 in host samples. These markers explain shifts in pathogen load and can enrich a microbiome signatures database with metal-stress features that track response to care.