LINUS PAULING INSTITUTE RESEARCH REPORT

The Antioxidant Function of Dietary Zinc and Protection Against Neural Disorders

Mark A. Levy, Ph.D.
OSU Research Associate

Tammy M. Bray, Ph.D.
Professor of Nutrition and Food Management
LPI Senior Scientist

Zinc, a ubiquitous trace element found throughout the plant and animal kingdoms, was first demonstrated to be an essential component of the human diet in the 1960s when it was found to reverse delayed sexual development and arrested growth. Since then, numerous syndromes associated with zinc deficiency, including immune and nervous system abnormalities, have been described in infants, adolescents, and the elderly.

Although zinc is a component of more than 70 different enzymes that function in almost every aspect of cellular metabolism, researchers have been unable to identify a specific biochemical function that can account for the many different signs and symptoms of zinc deficiency. Zinc’s function as an antioxidant was first proposed in 1990, based largely upon in vitro evidence that illuminated two distinct mechanisms. The first is the protection of proteins and enzymes against free radical attack, or oxidation. Free radicals are very unstable molecules that react quickly and deleteriously with other substances, damaging their normal functions. The zinc molecule in zinc-containing enzymes was found to act as an antioxidant and protect specific regions of the enzyme from free radical attack, thus preserving its stability and activity. Dr. Joseph Beckman of LPI has been investigating the role of zinc in Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis (ALS). He found that when superoxide dismutase, an endogenous antioxidant enzyme, loses its zinc atom, it becomes neurotoxic (see the Spring/Summer 2001 LPI Newsletter). The second mechanism by which zinc functions as an antioxidant is through the prevention of free radical formation by other metals, such as iron and copper. Unlike highly reactive iron and copper, zinc does not readily undergo oxidation and reduction, or redox, reactions. In redox reactions electrons are transferred to and from different compounds, sometimes resulting in the generation of free radicals. When zinc, instead of iron or copper, is incorporated into proteins, free radical generating reactions that may otherwise occur are inhibited.

Although the antioxidant properties of zinc were first demonstrated in vitro, there is also clear evidence that zinc functions as an antioxidant in the body. One area of growing interest is the role of zinc as an antioxidant in the central nervous system (CNS), particularly the brain. Compared to other soft tissues, the human brain contains significant amounts of zinc. Among the essential trace elements, zinc is second only to iron in total concentration in the brain. Zinc deficiency has been proposed to lead to nervous system disorders, including mental disturbances, loss of sensory acuity, and impaired cognitive and psychological function. Notably, oxidative stress is associated with the development and progression of several different neuropathologies, including Alzheimer’s disease, ALS, and Parkinson’s disease.

We recently examined the role of zinc in maintaining the integrity of the blood brain barrier (BBB), which is the highly specialized blood vessel system of the CNS that serves to protect the brain by excluding toxic agents and other foreign compounds. Alterations or dysfunction of the BBB have been observed in many brain disorders. Free radicals may play an important role in damaging the BBB because it is especially sensitive to oxidative damage. This vulnerability may be due to the high polyunsaturated fatty acid content of the BBB membrane—fatty acids that are very susceptible to free radical attack—as well as the relatively low antioxidant capacity of the BBB. Oxidation of the membrane drastically compromises its barrier properties and may lead to subsequent brain tissue damage, resulting in a host of pathologies.

Our investigations have focused on the antioxidant function of zinc that may protect the BBB against oxidative damage. Using magnetic resonance imaging, or MRI, we have demonstrated that zinc deficiency in rats dramatically increases the permeability, or leakiness, of the BBB. Additionally, we have observed that when zinc deficiency is accompanied by oxidative stress, as might occur during a bacterial or viral infection, BBB permeability increases dramatically. These observations have led us to hypothesize that under normal conditions, zinc protects the BBB against oxidative stress through its antioxidant properties and in so doing, helps to maintain homeostasis within the brain and prevent the development of neurological disorders.

In our initial work we examined the consequences of the loss of BBB integrity during zinc deficiency. First, we noted significantly increased water content, or edema, of the brain as a result of zinc deficiency. Second, we observed increased protein oxidation within the brain. And third, we documented significant changes in brain energy metabolism. These observations led us to propose that these events may be pivotal in the development and pathogenesis of many brain disorders, and our laboratory will continue to define the important roles of zinc in disease prevention.

Last updated May, 2003

Micronutrient Research for Optimum Health