Study Title:

Zinc Deficiency, Organ Damage, and Sepsis

Study Abstract

Objective: Zinc deficiency is common among populations at high risk for sepsis mortality, including elderly, alcoholic, and hospitalized patients. Zinc deficiency causes exaggerated inflammatory responses to endotoxin but has not been evaluated during bacterial sepsis. We hypothesized that subacute zinc deficiency would amplify immune responses and oxidant stress during bacterial sepsis {lsqb;i.e., cecal ligation and puncture (CLP){rsqb; resulting in increased mortality and that acute nutritional repletion of zinc would be beneficial.

Design: Prospective, randomized, controlled animal study.

Setting: University medical center research laboratory.

Subjects: Adult male C57BL/6 mice.

Interventions: Ten-week-old, male, C57BL/6 mice were randomized into three dietary groups: 1) control diet, 2) zinc-deficient diet for 3 weeks, and 3) zinc-deficient diet for 3 weeks followed by oral zinc supplementation for 3 days (n = 35 per diet). Mice were then assigned to receive either CLP or sham operation (n = 15 each per diet). CLP and sham-operated treatment groups were further assigned to a 7-day survival study (n = 10 per treatment per diet) or were evaluated at 24 hours (n = 5 per treatment per diet) for signs of vital organ damage.

Measurements and Main Results: Sepsis mortality was significantly increased with zinc deficiency (90% vs. 30% on control diet). Zinc-deficient animals subject to CLP had higher plasma cytokines, more severe organ injury, including increased oxidative tissue damage and cell death, particularly in the lungs and spleen. None of the sham-operated animals died or developed signs of organ damage. Zinc supplementation normalized the inflammatory response, greatly diminished tissue damage, and significantly reduced mortality.

Conclusions: Subacute zinc deficiency significantly increases systemic inflammation, organ damage, and mortality in a murine polymicrobial sepsis model. Short-term zinc repletion provides significant, but incomplete protection despite normalization of inflammatory and organ damage indices.

From press release:

COLUMBUS, Ohio – Nutrition plays a vital role in how humans handle serious infection. Eating foods high in zinc may influence the difference between life and death for some patients, according to a new study.
Critical care researchers at Ohio State University Medical Center found that correcting zinc deficiency may also significantly enhance a critically ill patient’s chance of surviving sepsis, a deadly blood infection that can lead to organ failure and death.

“Zinc deficiency is common in patients in intensive care units and in those at risk for developing sepsis,” says Dr. Elliott Crouser, a critical care specialist at Ohio State’s Medical Center and senior author of the study.

The findings are published online in the journal Critical Care Medicine and will appear in the journal’s April issue.

Data suggests that many more individuals have zinc deficiency than originally predicted, and it is especially prevalent in elderly populations and people suffering from chronic diseases where zinc deficiency is prevalent, such as diabetes and alcoholism.

Zinc deficiency increases the likelihood of organ damage and amplifies the immune response, also preventing the clearance of infection, according to Daren Knoell, an investigator at Ohio State’s Dorothy M. Davis Heart and Lung Research Institute and first author of the study.

Researchers randomized mice into three different dietary groups: a normal control diet; a zinc-deficient diet; and, a zinc-deficient diet followed by zinc supplements for three additional days. The zinc-deficient mice experienced an exaggerated immune response, increased tissue damage and organ failure. Ninety-percent of the zinc-deficient septic mice were dead within two days, compared to the control group where 30 percent died over the course of a week. The mice that had zinc added to their diets significantly improved their chances of survival, reporting a normalized inflammatory response and greatly diminished tissue damage.

Crouser and Knoell say future studies will be conducted at Ohio State to determine if correcting zinc deficiency in patients in the intensive care unit reduces the risk of dying from sepsis.

“Although zinc deficiency is common globally, it is fixable. If we could identify zinc deficient patients upon admittance to the hospital, we could very likely prevent them from contracting sepsis and death by providing supplementation and improved care,” Knoell adds.

Foods high in zinc include beef, lamb, pork, crabmeat, turkey, chicken, lobster, clams and salmon. Additional good zinc food sources include dairy products such as milk and cheese, peanuts, beans, wholegrain cereals, brown rice, whole wheat bread, potatoes and yogurt.

Sepsis, the leading cause of hospital death, is .a systemic response to infection affecting more than 750,000 Americans annually, killing more people than strokes, breast cancer and lung cancer combined.

Funding from the National Institutes of Health supported this research.

Study Information

Daren L. Knoell; Mark W. Julian; Shengying Bao; Beth Besecker; Jennifer E. Macre; George D. Leikauf; Robert A. DiSilvestro; Elliott D. Crouser.
Zinc deficiency increases organ damage and mortality in a murine model of polymicrobial sepsis.
Critical Care Medicine.
2009 March
Ohio State University Medical Center

Full Study