Megadosing A

Vitamin A megadoses questioned as Ômagic bullet'

Using vitamin A supplements to dramatically reduce child mortality in poor nations is "one of the most important public health advances in the last century," says Dr. Jeffrey Griffiths, director of Tufts' graduate programs in public health. But he cautions the strategy may not be a simple "magic bullet" and may, when used as a blanket strategy, be hurting the health of some children.

Photomicrograph of vitamin A © Dennis Kunkel

Large doses of vitamin A given to malnourished children have resulted in pediatric death rate declines of 23 percent or more, according to the World Health Organization (WHO). The vitamin megadoses seem to help protect children from diarrheal infections and death from measles, two significant causes of pediatric death in underdeveloped nations.

But paradoxically, children who are not malnourished are more susceptible to pneumonia when given megadoses of vitamin A, according to a study by Griffiths that was later confirmed by another, independent investigator. Griffiths, associate professor of family medicine and community health, is now directing a five-year, $2.6 million study in Quito, Ecuador, that will closely monitor supplements of vitamin A and zinc to 2,400 infants and toddlers.

Zinc is another micronutrient that has shown great promise in combating diarrheal and respiratory infections and is of special interest to Dr. Davidson Hamer, assistant professor of medicine, and one of Griffiths' co-investigators. Other Tufts faculty working on the study are Dr. Simin Meydani, Dr. Christine Wanke and Elena Naumova.

Micronutrient supplementsÑespecially vitamin A and zincÑcurrently are the most promising and least expensive strategies available for helping protect malnourished children from potentially fatal infections. International organizations, including WHO, recommend poor children in underdeveloped nations receive vitamin A megadoses (200,000 international units) every four to six months.

After the first dramatic results of vitamin A for malnourished children were reported, Griffiths and his Ecuadorian colleagues noted an interesting paradox: While mortality rates decreased, the incidence of pneumonia remained the same. In fact, a 1995 WHO review noted vitamin A supplementation "has no consistent overall protective or detrimental effect on pneumonia-specific mortality in children."

Griffiths does not completely agree with that conclusion. A study he conducted in Ecuador in 1988 showed that among children given vitamin A supplements, those who were malnourished had a 60 percent decline in pneumonia rates. But children with adequate nourishment receiving the supplement had rates of pneumonia 2.5 times greater than normal.

"One theory of what might be happening," says Griffiths, "is that A is an immunosuppressant in big doses, something that has been indicated in a couple of studies with adults and rats."

The current Quito study seeks to confirm the results of Griffiths' earlier research and also determine the impact of zincÑalone and in combination with AÑas a supplement. "We suspect the study will confirm what we and others have learned beforeÑthat A is not beneficial to all children and that zinc is," Griffiths says. "But we also suspect we may find that zinc ameliorates A's downside."