Aspartame is a methyl ester of a dipeptide used as a synthetic nonnutritive sweetener in over 90 countries worldwide in over 6000 products. The purpose of this investigation was to review the scientific literature on the absorption and metabolism, the current consumption levels worldwide, the toxicology, and recent epidemiological studies on aspartame. Current use levels of aspartame, even by high users in special subgroups, remains well below the U.S. Food and Drug Administration and European Food Safety Authority established acceptable daily intake levels of 50 and 40 mg/kg bw/day, respectively. Consumption of large doses of aspartame in a single bolus dose will have an effect on some biochemical parameters, including plasma amino acid levels and brain neurotransmitter levels. The rise in plasma levels of phenylalanine and aspartic acid following administration of aspartame at doses less than or equal to 50 mg/kg bw do not exceed those observed postprandially. Acute, subacute and chronic toxicity studies with aspartame, and its decomposition products, conducted in mice, rats, hamsters and dogs have consistently found no adverse effect of aspartame with doses up to at least 4000 mg/kg bw/day. Critical review of all carcinogenicity studies conducted on aspartame found no credible evidence that aspartame is carcinogenic. The data from the extensive investigations into the possibility of neurotoxic effects of aspartame, in general, do not support the hypothesis that aspartame in the human diet will affect nervous system function, learning or behavior. Epidemiological studies on aspartame include several case-control studies and one well-conducted prospective epidemiological study with a large cohort, in which the consumption of aspartame was measured. The studies provide no evidence to support an association between aspartame and cancer in any tissue. The weight of existing evidence is that aspartame is safe at current levels of consumption as a nonnutritive sweetener.

Intestinal adaptation after massive bowel resection in animal models is characterized by increased gut-mucosal growth and expression of nutrient transporters. Few data about these indexes exist in humans with short-bowel syndrome (SBS).

The objective was to compare small-bowel and colonic mucosal growth and expression of the peptide transporter PepT1 in adults with or without SBS.

Mucosal biopsy specimens were obtained from the small bowel and colon of 33 control subjects with intact intestine and from 13 SBS patients dependent on parenteral nutrition because of chronic malabsorption. Gut-mucosal crypt depth, villus height, and villus width were measured, and expression of PepT1 was determined by Northern blotting, in situ hybridization, and immunohistochemistry.

The indexes of small-bowel and colonic mucosal growth were not significantly different between the 2 groups. PepT1 expression was high in the apical region of duodenal, jejunal, and ileal villus epithelial cells; low in absorptive colonocytes; and not significantly different in the distal small intestine of the 2 groups. However, the abundance of PepT1 mRNA in the colon of SBS patients was more than 5-fold that in control subjects (P < 0.01).

Gut adaptation in SBS patients does not appear to involve an increase in gut-mucosal crypt depth or villus size. PepT1 is abundant along the small-bowel brush border in humans; expression in the colon indicates that the large intestine has a mechanism for luminal di- and tripeptide transport. Up-regulation of colonic PepT1 in SBS may adaptively improve accrual of malabsorbed di- and tripeptides, independent of changes in the mucosal surface area.

Sepsis has been shown to cause a decrease in mesenteric blood flow in association with ultrastructural changes in the small intestine and impaired immune, barrier, and metabolic functions of the gut. These impairments in the structure and function of the gastrointestinal tract may have a detrimental effect on the morbidity and mortality of sepsis. Two recent studies have shown that the ability of the small intestine to absorb amino acids is also impaired during sepsis, but the systemic and cellular mechanisms of this impairment are not known. Release of cytokines induced by systemic bacteria or endotoxin may lead to a reduction in the synthesis of transporter proteins by the enterocyte at a time when there is reduced availability of both luminal (because of anorexia) and circulating (because of reduced mesenteric blood flow) substrates. Future research needs to investigate the systemic and local mediation of the sepsis-induced reduction in intestinal amino acid absorption and the possibility of correcting the defect by the administration of enteral nutrients, hormones, or drugs.

We have investigated rates of dipeptide disappearance during jejunal perfusion with an equimolar mixture of 12 glycyl-dipeptides and compared amino acid absorption rates from this mixture with those from the corresponding free amino acid mixture in healthy volunteers. All dipeptides contained glycine in the N-terminal position, which was designed to favor peptide absorption rather than hydrolysis. At 2 mM concentration there was little difference in disappearance among dipeptides, but at 6 mM there was some selectivity: Gly-Phe and Gly-Met exhibited the fastest, and Gly-Arg and Gly-His the slowest rates of disappearance. However, between these ends of the spectrum there were only modest differences in disappearance among dipeptides (Gly-Ala, Gly-Thr, Gly-Leu, Gly-Ile, Gly-Val, Gly-Lys, Gly-Pro, Gly-Trp). The amino acid absorption rates were generally smaller but more selective from the free amino acid than from the dipeptide mixture. We conclude that (a) the C-terminal amino acid residue influences intestinal assimilation of glycyl-dipeptides and (b) the considerably greater absorption rate of amino acids from the dipeptide than from the amino acid mixture appears to be the result of uptake by a system that has a greater transport capacity than amino acid carrier systems, thus minimizing competition among its substrates.

When baboons, while consuming an adequate diet, were infused continuously for 3 days with parenteral solutions (1I/day) containing either triglycine (50 mM) or trileucine (5 mM) there was either no or very little accumulation of these peptides either in plasma or urine. The increases in plasma concentrations of glycine or leucine and urinary excretion rates of these amino acids during the infusion of the above tripeptides were similar to those found when baboons were infused with parenteral solutions containing either glycine (150 mM) or leucine (15 mM). These data show efficient utilization of tripeptides under the condition of continuous infusion and encourage further investigation of tripeptides as substrates for parenteral nutrition.