Absorption, distribution, metabolism and excretion
The metabolism of aspartame and its metabolic breakdown products in animals, healthy individuals and in PKU subjects has been comprehensively reviewed by Lajtha et al. (1994). Aspartame is metabolised by gut esterases and peptidases to three common dietary components - two amino acids (aspartic acid and Phe) and methanol.
Animal studies have demonstrated that the metabolic breakdown products of aspartame are absorbed and metabolised similarly whether they are given alone or derived from aspartame. The extensive presystemic metabolism of aspartame results in little or no parent compound reaching the general circulation.
Initial studies focused on the effects of ingesting single bolus doses of aspartame on plasma aspartate and Phe levels and blood methanol concentrations in normal adults. These studies were done with doses of aspartame approximating current levels of dietary exposure (4 and 10 mg/kg bw), doses representative of premarketing projections of the high level intake and the ADI (34 and 40 mg/kg bw respectively), and ‘abuse’ doses of 100, 150 and 200 mg/kg bw (Stegink and Filer 1996).
The plasma Phe concentrations in healthy adults administered various doses of aspartame have been compared to values obtained: (1) in the fasting and postprandial state; (2) in individuals who are heterozygous for PKU; and (3) in subjects with various forms of hyperphenylalaninaemia other than PKU (Stegink et al 1990; Stegink and Filer, 1996). The data indicated that the plasma Phe concentrations after single bolus doses (ranging between 4 and 50 mg/kg bw) and repeated doses (30 and 69 mg/kg bw given as 3 and 8 divided doses respectively) of aspartame were generally within the normal postprandial range for this amino acid and well below those measured in subjects homozygous for PKU after ingestion of aspartame.
The aspartate component is rapidly metabolised and thus the plasma aspartate concentrations are not significantly elevated following aspartame doses of 34 to 50 mg/kg bw, whereas plasma Phe concentrations may increase depending on dose (Stegink, 1984). Methanol is also rapidly metabolised and blood levels are usually not detectable unless large bolus doses of aspartame (>50 mg/kg bw) are administered.