For families with loved ones in an intensive care unit (ICU), lab reports often feature unfamiliar line items alongside standard inflammation markers like white blood cell count and C-reactive protein (CRP). Among these are trace elements such as zinc and selenium. While both micronutrients are essential for immune function and regulating inflammation, clinical evidence regarding how their levels correlate with systemic inflammation in critically ill patients has been limited.
On Aug. 18, a joint research team led by Professors Oh Hyo-seok and Lee Jae-myung of the Division of Critical Care and Trauma Surgery at Korea University Anam Hospital, along with Professor Baek Seung-min of the Division of Surgical Critical Care Medicine at Ewha Womans University Mokdong Hospital, announced that blood concentrations of zinc and selenium in ICU patients are independently associated with acute-phase inflammatory markers.
Quantifying the Impact on Inflammatory Markers
The researchers analyzed medical records from 267 adult patients admitted to the ICU at Korea University Anam Hospital between December 2016 and December 2021. They evaluated serum levels of four trace elements—zinc, selenium, copper, and manganese—against standard inflammatory indicators, including white blood cell count, neutrophil percentage, CRP, and procalcitonin.
The data revealed a consistent inverse relationship: lower concentrations of zinc and selenium were significantly tied to higher levels of CRP and procalcitonin. This association persisted even after controlling for age, disease severity, and other trace element levels. Specifically, each 1 μg/dL increase in serum zinc was associated with a 2.7% reduction in procalcitonin, while each 1 μg/L increase in selenium corresponded to an average decrease of 0.87 mg/L in CRP.
"This study is meaningful because it demonstrates the clinical necessity of evaluating trace element levels and inflammatory responses together in critically ill patients," Oh said.
Diverging Trends and Longitudinal Patterns
In contrast to zinc and selenium, serum copper levels moved in the opposite direction, increasing as systemic inflammation worsened. The researchers attributed this trend to acute-phase transport proteins like ceruloplasmin, which bind copper and naturally rise during active inflammation. Consequently, elevated copper levels should not be interpreted simply as an indicator of adequate nutrition or positive health. Manganese showed a minor association with white blood cell counts in select subgroup analyses, a finding researchers noted requires further investigation.
Importantly, the inverse correlation between zinc, selenium, and inflammation was not a temporary baseline anomaly. The pattern held firm across repeated measurements taken throughout patients' hospital stays.
"In critical care settings, trace elements are more than simple nutritional metrics—they serve as crucial indicators for assessing immune status and inflammatory dynamics," Lee said. "We will continue our research to determine how trace element status influences the clinical course and long-term prognosis of ICU patients."
Clinical Limitations and Future Directions
The authors noted several limitations, emphasizing that the retrospective, single-center observational study cannot establish direct causality. It remains unclear whether micronutrient deficiencies actively exacerbate inflammation or if severe inflammation drives down blood levels of zinc and selenium—particularly since the liver is known to sequester these elements during acute inflammatory states. Both mechanisms may operate simultaneously.
The critical question moving forward is whether targeted supplementation can yield tangible clinical benefits. The research team stressed that prospective clinical trials are necessary to verify whether replenishing deficient trace elements directly mitigates inflammation and accelerates recovery. If proven effective, monitoring these micronutrient values could transform routine blood tests into actionable therapeutic targets in critical care.
The study, titled "Serum Zinc and Selenium Are Independently Associated with Acute-Phase Inflammatory Markers in Critically Ill Patients: A Retrospective Observational Study," was published in the peer-reviewed international journal Nutrients.
