Targeting Antioxidant Status Could Help Victims of Malnutrition

Correcting a critical shortage of glutathione, the body's most potent antioxidant, could be the key to reversing life-threatening complications that kill millions of malnourished Third-World children each year, according to a study published this month in the American Journal of Physiology.

The study's findings could also help answer a question that for more than 30 years has troubled researchers working with malnourished children: Why do two very different malnutrition syndromes - one often lethal, the other very easy to treat - develop among children living in the same famine-stricken area?

"About half of all malnourished children develop the more serious syndrome called kwashiorkor, which is characterized by edema, an enlarged liver and other systemic symptoms," says Dr. Farook Jahoor, an associate professor of pediatrics at the USDA/ARS Children's Nutrition Research Center at Baylor College of Medicine. "Although these children might not appear very wasted, they are very difficult to treat, slow to recover and suffer death rates as high as 25 percent."

This is in sharp contrast to the fate of children with marasmus, the stick-thin-but-big-bellied syndrome that most people associate with malnourished children. "Marasmic children are more wasted, but they actually respond very quickly to treatment and nearly always survive," Dr. Jahoor says.

He suspected that many of the symptoms of kwashiorkor, such as edema, fatty deposits in the liver, poor immune function and congestive heart failure, stemmed from oxidative cell damage caused by a shortage of glutathione. "Without enough glutathione, the body can't adequately protect cell membranes, the immune system can't function properly and damaging toxins build up," he says.

The study, conducted at the Tropical Metabolism Research Unit, University of the West Indies, Jamaica, confirmed an antioxidant shortage.

Children admitted to the hospital with kwashiorkor had much lower glutathione levels and synthesis rates and higher levels of compounds that signal oxidative cell damage than those admitted with marasmus. Dr. Jahoor traced the problem to a critical shortage of two amino acids: cysteine, which is required for glutathione synthesis, and methionine, which the body can convert into cysteine.

The reason for the amino-acid shortage is unknown. However, once the children were fully recovered and ready for discharge, their cysteine, methionine and glutathione levels were comparable whether their initial diagnosis had been kwashiorkor or marasmus.

The next phase of the study, in which children diagnosed with kwashiorkor are given cysteine supplements, is already yielding positive results. "We are seeing glutathione synthesis rates and blood levels restored within one week," Dr. Jahoor says. Yet he cautions that the real test will be whether cysteine supplementation improves the children's recovery and survival rates.

"More than 200 million malnourished young children live in developing nations plagued by natural disasters, political conflict and famine. Until we can end food shortages, finding therapeutic regimes that reduce malnutrition-related deaths is essential," Dr. Jahoor says.

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©2006 Texas Medical Center

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