Racemization of aspartic acid and phenylalanine in the sweetener aspartame at 100 degrees C.

Abstract

The racemization half-lives (i.e., the time required to reach a D/L = 0.33) at pH 6.8 for aspartic acid and phenylalanine in the sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester) were determined to be 13 and 23 hours, respectively, at 100'C. Racemization at this pH does not occur in aspartame but rather in its diketopiperazine decomposition product. Our results indicate that the use of aspartame to sweeten neutral pH foods and beverages that are then heated at elevated temperature could generate D-aspartic acid and Dphenylalanine. The nutritive consequences of these D-amino acids in the human diet are not well established, and thus aspartame should probably not be used as a sweetener when the exposure of neutral pH foods and beverages to elevated temperatures is required. At pH 4, a typical pH of most foods and beverages that might be sweetened with aspartame, the half-lives are 47 hours for aspartic acid and 1200 hours for phenylalanine at 100'C. Racemization at pH 4 takes place in aspartame itself. Although the racemization rates at pH 4 are slow and no appreciable racemization of aspartic acid and phenylalanine should occur during the normal use of aspartame, some food and beverage components could conceivably act as catalysts. Additional studies are required to evaluate whether the use of aspartame as a sugar substitute might not in turn result in an increased human consumption of D-aspartic acid and D-phenylalanine.A reduction in human sugar consumption is advocated for numerous reasons, with the prevention of dental caries and obesity probably being the most compelling. However, efforts to find a sugar substitute have not been generally successful. Recently, a new sweetener, aspartame, the methyl ester of the dipeptide L-aspartyl-L-phenylalanine, has been approved by the Food and Drug Administration as a sugar substitute in certain foods and beverages. Aspartame has a sweetness factor nearly 200 times that of sucrose (1, 2). Moreover, since aspartame is composed of amino acids it is classified as a "natural" sweetener in contrast to saccharin, which is considered artificial (1). Whether aspartame is a safe alternative to sugar in the human diet, however, remains controversial (3, 4). Several potential problems exist. For example, some individuals (phenylketonurics) are highly susceptible to excess phenylalanine in their diet and thus are cautioned on the package of the commercially available product about using aspartame.In aqueous solution, aspartame decomposes (1, 5, 6) via a series of reactions that include ester and peptide-bond hydrolysis and cyclization to the diketopiperazine, 3-carboxymethyl-6-benzyl-2,5-piperazinedione. We were particularly interested in the diketopiperazine pathway since results obtained in this laboratory (7) and in earlier work (8-10) had demonstrated that amino acid residues in diketopiperazines are highly susceptible to racemization at both neutral and basic pH values. Since the presence of D amino acids in the human diet may have a variety of consequences...

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