Does inflammation lower circulating zinc?

Inflammation can produce a rapid fall in circulating zinc through an acute-phase redistribution response rather than necessarily reflecting reduced total-body zinc stores. The proposed liver-centered pathway is supported with moderate confidence, particularly by experimental data.

Clinical and translational evidence

• Human experimental endotoxemia shows that serum zinc declines rapidly after rises in TNF-α and IL-6, consistent with cytokine-driven zinc redistribution during acute inflammation.
• In acutely ill older hospital populations, serum zinc was inversely associated with C-reactive protein in two groups (r = −0.33 and −0.29; both P < 0.001). Aged-care residents similarly had lower zinc concentrations alongside inflammatory markers.
• These associations vary across older populations, with some cohorts showing no zinc–CRP correlation and reports of sex-specific patterns. For a 71-year-old man, a low serum zinc result during illness or elevated CRP therefore warrants interpretation in its inflammatory context rather than being treated automatically as evidence of nutritional zinc deficiency.

Mechanistic evidence

• IL-6 promotes hepatocyte zinc uptake through induction of ZIP14, a zinc-importing transporter. In mice lacking IL-6, inflammation did not induce hepatic ZIP14 or the characteristic inflammatory hypozincemia.
• In rat hepatocytes, IL-6 increased metallothionein expression and intracellular zinc. Inflammatory animal models likewise show increased hepatic metallothionein and liver zinc.
• Metallothionein can bind intracellular zinc, providing a coherent mechanism by which cytokine-stimulated hepatic uptake retains zinc in the liver and lowers the circulating concentration.

Bottom line

• The claim is scientifically supported: inflammation-associated cytokines, particularly IL-6, can increase hepatic zinc uptake and metallothionein-mediated intracellular binding, contributing to lower circulating zinc. In clinical practice, serum zinc during active inflammation is best viewed as a marker influenced by redistribution as well as nutritional status.