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Finding the Simple Solutions
New CHORI Study Finds First Time Association between Zinc Deficiency and Critical Illness in Children

"What is surprising was that even in this small group of 20 kids, low levels of zinc were associated with the degree of organ failure. In other words, the kids with the lowest zinc levels had the most organ failure."

In the January issue of Pediatric Critical Care Medicine, CHORI scientists Natalie Cvijanovich, MD, Janet King, PhD, Heidi Flori, MD, and their colleague at the Cincinnati Children’s Hospital Medical Center, Hector Wong, MD, report the intriguing results of a new study linking low levels of zinc with critical illness in children.

“We found that critically ill kids in fact do have abnormally low zinc levels, which in some ways isn’t surprising if the zinc is going into the cells,” says Dr. Cvijanovich.

“What is surprising was that even in this small group of 20 kids, low levels of zinc were associated with the degree of organ failure. In other words, the kids with the lowest zinc levels had the most organ failure.”

Zinc is an essential nutrient for the human body, contributing to normal functioning of the immune system, controlling glucose levels, formation of insulin, as well as a lot of other different kinds of functions in the body, like DNA signaling to turn genes on or off. Recent data from a large investigation undertaken by Dr. Wong to investigate gene expression patterns in kids with septic shock suggested a potential role for zinc in critically ill children as well.

"The data from Dr. Wong's study showed that a lot of proteins that were involved with zinc regulation, or that required zinc for function, were regulated very differently in kids with septic shock as compared to healthy kids. In particular, in the kids who didn't survive, there were very big differences. This led us to take a closer look at zinc in critically ill children," explains Dr. Cvijanovich of what brought her and her colleagues to the latest study.

"We don't actually know a lot about zinc levels in critically ill children," said Dr. Cvijanovich. "We know zinc has a lot of functions in the body, and that zinc blood levels become low probably because the zinc is going into the cell to do its jobs. So we wanted to see if there was an association with zinc levels and how sick kids were, and if so, would giving kids zinc supplements in the future help."

In addition to finding the surprising correlation between low levels of zinc and increased organ failure, Dr. Cvijanovich and her colleagues also discovered that lower levels of zinc were associated with higher levels of inflammation.
"We only looked at 20 patients, but our inflammation markers did yield results, even in this small a number of patients, which suggests that in a larger study, there could be even more significant differences."
The study was as small as it was because it was only intended as a pilot study to provide more information about how zinc levels behave in critically ill children for the first time; however, the results suggest very exciting potential for zinc supplementation in larger studies.

"Our data on inflammation and organ failure and low zinc levels makes us think that manipulating zinc levels, which would be a cheap and safe and fairly simple thing to do, could make a difference in the degree of illness," says Dr. Cvijanovich.

As a result, an in-depth study looking at which doses of zinc are safe for kids is already getting underway, with the goal of eventually being able to establish a much larger, randomized blinded trial to test the effects of zinc supplementation in critically ill kids.

"Sepsis and infection is a fairly common thing in kids in the intensive care unit, with as many as 40 thousand kids admitted each year and a mortality rate of about 10 percent. It's not a small problem," says Dr. Cvijanovich.
"This of course is just kids with septic shock, whereas we hope zinc supplementation could be helpful in an even larger population."

While Dr. Cvijanovich and her colleagues can't yet be sure that the low zinc levels are the problem, and not just reflective of the general degree of illness, they hold high hopes for the long term.

"It's very preliminary data," Dr. Cvijanovich acknowledges, "but our hope is that something as benign and simple as giving critically ill children extra zinc could help them get better faster and survive their critical illness."

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Tuesday, May 17, 2011 8:19 AM

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