Aspartame, the low-calorie sugar substitute marketed as NutraSweet, is one of the amazing success stories of the 1980s. In the four years since the artificial sweetener found its way onto grocery store shelves, more than 100 million Americans have tried it. They have tasted it in more than 90 types of products ranging from diet soft drinks to sugar-free gum. Last year, its manufacturer, G.D. Searle & Co., reported sales soaring to $535 million. By 1986, some expect it to top $1 billion.
But there is a possible dark side to all this. Aspartame contains a potentially harmful component, an amino acid called phenylalanine. Too much of it can cause brain damage, especially in fetuses and newborn of genetically susceptible women, according to studies done by Dr. Louis Elsas of Emory University in Atlanta.
"The big unanswered question," said Elsas, "is if pregnant women taking artificial sweeteners can elevate their blood level of phenylalanine to concentrations that adversely affect their fetuses. Is the damage from phenylalanine produced by a threshold effect? Or do little bits of the problem occur at lower levels? . . .
"Aspartame is being promoted as something good for you. But I don't think that it is a legitimate thing for our nation to be exposed to in large quantity."
Searle said reports about potential adverse effects of aspartame on pregnant women and infants were "misleading and do a disservice to consumers." The Chicago-based firm pointed out that in 1981, the Food and Drug Administration found the product to be safe and effective.
Searle does not dispute the contention that high levels of phenylalanine can cause damage in fetuses. But it says there is no cause for alarm because current consumption amounts are not even close to a point where they might pose a problem. Most important, it says that studies on pregnant animals show that even at "abuse levels," aspartame presents no hazard to the fetus.
Nonetheless, Elsas, director of medical genetics at the Atlanta school, said he is concerned, in part, because the sweetener's sale has been so massive and there are still some unknowns about the product. What worries him -- and this is not based on any study but his own personal thoughts as a scientist -- is the notion that aspartame's effects could be slow and subtle. They could take a generation or more to uncover.
"It's not going to be so overt an explosion," Elsas said recently on "Nightline," an ABC-TV news program. "We may not be able to see the effects for a generation. And then we'll suddenly see a lot of kids with behaviorial abnormalities -- with IQs that aren't reaching what . . . we anticipated from their educational or their genetic input."
Searle says that more than 20 years of testing in animals has shown aspartame to be safe over long periods. Elsas acknowledges there has been no documented negative side effects of aspartame. Nor has he personally conducted a study on the sweetener.
But he has done research with children and young adults with gene defects who ingested phenylalanine at high levels and found that their reaction time had slowed. That means phenylalanine can produce quantifiable changes in brain function. "I believe," he says, "the unlimited use of phenylalanine products should be moderated especially in certain groups."
A pediatrician and a biochemist, Elsas is focusing on patients with a rare genetic disorder called phenylketonuria or PKU. These individuals cannot metabolize foods containing phenylalanine. As a result, the chemical concentrates in their brains. This can cause retardation in fetuses and newborns who have this genetic disorder. Many states require tests to discover PKU babies who must then be kept on special diets.
Elsas is also concerned about parents of these children, who are normal but may carry one of the two genes needed to have PKU. "There is a genetically susceptible subpopulation of well over a million women whose fetuses may be at risk if they take indiscriminate amounts of phenylalanine," says Elsas. They, too, he says, may also have an impaired ability to metabolize phenylalanine.
Since it is not always possible to detect these single gene carriers before a PKU baby is born, the vast majority don't know who they are. About 1 percent of babies delivered each year are born to mothers who are PKU carriers.
People in whom high levels of phenylalanine may pose problems, Elsas said, are:
* Pregnant women. If blood phenylalanine rises to a level high enough to cause problems, the child's brain development could be affected.
* Children under 6 months. A high level of blood phenylalanine can produce irreversible brain damage by slowing formation of mature brain cells and by altering the formation of myelin cells that insulate parts of the brain.
* Older children and adults carrying the PKU disorder. A high blood concentration of phenylalanine will reduce the brain's ability to function as quickly and efficiently. But these changes are reversible once the level of phenylalanine returns to normal.
The flaw in Elsas' argument, says Daniel Azarnoff, president of research and development for Searle, is that he has no idea what is a dangerous level of phenylalanine concentration. Moreover, he said, Elsas' concern that people may be getting toxic amounts of phenylalanine flies in the face of scientific data. "He is saying people eat a lot of aspartame," says Azarnoff. "The evidence is they don't."
The FDA has set 50 milligrams of aspartame per kilogram (2.2 pounds) of body weight as an acceptable daily intake. To reach that amount, Searle says, a 132-pound person would have to drink 18 cans of diet soda in a day. The average 12 oz. can of diet soda contains 170 milligrams of aspartame, Searle says.
But Dr. William Patridge of the University of California at Los Angeles says the FDA has underestimated consumption of aspartame. Patridge could not be reached for comment. However, the magazine Common Cause said Patridge wrote to the FDA in 1983 citing figures showing how children eating aspartame-sweetened foods all day could be on their way to consuming the maximum amounts the FDA uses for its safety assessment. SS earle says that tests it sponsored show no harmful effects have been seen even S at levels of 200 milligrams -- four times the FDA's intake standard. However, the quality of Searle-sponsored studies has been criticized. Sen. Howard Metzenbaum (D-Ohio) has complained that the FDA overruled many scientific questions raised about the reliability of testing. A federal investigation is now under way.
Elsas also argues that the FDA's own publications show that the daily phenylalanine intake of some children ages 7 to 9 goes as high as 70 milligrams per kilogram of body weight -- exceeding the agency's acceptable daily amount of 50 milligrams. What Searle's studies do not show, he says, is long-term effects at intermediate levels. In addition, one scientist, Richard Wurtman of the Massachusetts Institute of Technology, says some foods intensify the effects of phenylalanine. "If one drinks a beverage containing aspartame at the same time one eats a carbohydrate-rich food," Wurtman says, "then aspartame's effect on brain phenylalanine is doubled."
To try to clarify the situation, Dr. Reuven Matalon of the University of Illinois has started a study funded by the National Institutes of Health to look at the effects of aspartame on PKU carriers as well as on normal individuals. The study will take about two years.
"In the meantime, I don't think it is fair to express concerns about aspartame as conclusions," he said. "There is no data to implicate it in any difficulty. At the same time, we do not know what a high level of intake will do and where the danger point comes. Until we get the data, if I were the FDA, I would recommend that pregnant women use caution. Moderation should be the key."