Aspartame

Serendipity, the act of making a useful discovery of something for which one is not actually searching, seems to be an inherent part of the discovery of nearly all artificial sweeteners. Like Remsen and Fahlberg's discovery of saccharin, the discovery of aspartame was accidental. James Schlatter, a chemist at the G. D. Searle pharma­ceutical company, was involved in research on new drugs that might be used to treat ulcers. One day in December 1965, a small amount of one of the compounds with which he was working inadvertently got on his fingers. He did not notice what had happened until later, when he licked his finger to pick up a piece of paper. Immediately he noticed a strong, sweet taste. He eventually realized that the taste must have come from the compound he was working with that day, L-aspartylphenylalanine methyl ester. Abandoning normal labora­tory safety procedures, he added some of the compound to a cup of black coffee. He drank it and found that the chemical did, indeed, have a very strong sweet flavor with none of the bitter aftertaste associated with saccharin. Schlatter's research team immediately grasped the compound's commercial potential and convinced Searle to begin developing the new product for FDA approval. Within a short time, aspartame became a widely popular consumer product, surpassing the use of any other artificial sweetener then available.

Aspartame is the generic name for the chemical whose systematic name is a-L-aspartyl-L-phenylalanine methyl ester or 3-amino-N-(a-carboxyphenethyl)-succinamic acid N-methyl ester. Aspartame is marketed commercially under a variety of brand names, includ­ing Canderel, Equal, and NutraSweet. The chemical structure of aspartame is shown below.

As the formula shows, aspartame is a dipeptide, a molecule con­sisting of two amino acids—aspartic acid and phenylalanine—joined to each other by a peptide bond. When aspartame is metabolized, it forms three products: the two amino acids and methanol (methyl alcohol). Aspartic acid is a nonessential amino acid, that is, one that the human body can manufacture from metabolites obtained from other foods, while phenylalanine is an essential amino acid, that is, one that the body cannot make and must be obtained from foods. Aspartic acid plays a number of important roles in the body, including the synthesis of nucleic acids (DNA and RNA) and urea

COOH CH2

Aspartic acid

\

CH2

I

Phenylalanine

H2N — CH — CONH — CH — COOCH3

Peptide bond

Aspartame

© Infobase Publishing

Chemical structure of aspartame

and the transmission of nerve messages in the brain. Phenylalanine plays a key role in the biosynthesis of other amino acids and some neurotransmitters. Both substances are totally natural components of the human body. Methanol by contrast, is highly toxic, but the amount produced during the metabolism of aspartame is so small as to be considered harmless.

The biochemistry of aspartame is different from that of saccha­rin. Saccharin passes through the digestive system without being di­gested at all. Since it undergoes no changes in the digestive system, saccharin produces no calories and is a truly "calorie-free" artificial sweetener.

By contrast, aspartame is digested and metabolized in the body. Like other amino acids, it provides 4 calories of energy per gram when metabolized. This production of energy is considered insig­nificant, however. The reason is that aspartame is so sweet that only very small amounts of the sweetener are needed to produce the same level of sweetness as a much larger amount of sugar. When aspartame is used to replace sugar, about 99.4 percent of the calories that would have been obtained from sugar are eliminated. Thus, while aspartame cannot be considered a "zero calorie" sweetener, it certainly qualifies as a very, very low calorie sweetener.

Controversy over the safety of aspartame began almost as soon as the FDA first granted approval for its use in certain types of foods (July 26, 1974). Less than a month later two concerned citizens, James Turner and Dr. John Olney, filed a petition objecting to the FDA's decision, citing possible errors in Searle's testing procedures. After continued studies, extending over a seven-year period, the FDA reiterated its original decision to approve aspartame for use in dry foods.

A year later, Searle requested FDA approval for the use of aspar-tame in carbonated beverages and certain other liquids. This time, the National Soft Drink Association (NSDA) raised objections with the FDA in spite of its potentially lucrative value to the association. The NSDA expressed concerns about the stability of aspartame in liquid solution under extremes of temperature and asked for further studies on aspartame's safety as an additive in carbonated bever­ages. The FDA was unconvinced by the NSDA's concerns and, in the fall of 1983, the first carbonated beverages containing aspartame went on the market.

NSDA's early concerns notwithstanding, aspartame has become an essential ingredient of many soft drinks. Since its introduction in 1981, aspartame has become by far the most popular sweetener in virtually all canned and bottled diet soft drinks in the United States. Carbonated soft drinks now account for an estimated 85 percent of all aspartame consumed in the United States.

Still, complaints about aspartame continue to pour in. A number of Internet Web sites are devoted to having the product banned by the FDA in connection with various reported adverse reactions to aspartame. The health problems ascribed to aspartame range from neurological and behavioral symptoms, such as headaches, dizziness, and mood alterations, to gastrointestinal symptoms, alterations in menstrual patterns, and allergic and/or dermatologic symptoms.

The Centers for Disease Control and Prevention (CDC) conducted an intensive study of some of these symptoms in 1984 and reported that the vast majority were mild and did not represent a serious long-term threat to human health. Everyone agrees, however, that aspartame does pose a health risk for individuals who have a ge­netic disorder known as phenylketonuria (PKU). People with PKU lack the enzyme needed to convert phenylalanine to tyrosine. As a consequence, any phenylalanine that they ingest is not metabolized but builds up in the bloodstream. Excessive amounts of the amino acid can damage the brain, leading to mental retardation. Because phenylalanine is a metabolic product of aspartame, all food products that contain aspartame are required to carry a warning that people with PKU should avoid the product.