Effect of an abuse dose of aspartame upon plasma and erythrocyte levels of amino acids in phenylketonuric heterozygous and normal adults.
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Plasma and erythrocyte levels of free amino acids were measured in five female subjects known to be heterozygous for phenylketonuria and six subjects assumed to be normal (three male, three female) who were administered an abuse dose of aspartame (100 mg/kg) in orange juice. Small increases in plasma aspartate levels were noted 30 minutes after aspartame loading in both groups, with mean (+/- SD) levels increasing from 0.15 +/- 0.05 mumoles/100 ml to 0.43 +/- 0.23 mumoles/100 ml in normal subjects (P = 0.02), and from 0.49 +/- 0.23 mumoles/100 ml to 0.80 +/- 0.56 mumoles/100 ml in heterozygous subjects (P > 0.05). However, plasma aspartate levels remained within normal postprandial levels in each case. Erythrocyte aspartate levels were unchanged in both groups. In normal subjects, plasma phenylalanine levels (mean +/- SD) increased from fasting levels (5.40 +/- 1.05 mumoles/100 ml) to mean peak values of 20.2 +/- 6.77 mumoles/100 ml. In heterozygous subjects, mean peak plasma phenylalanine levels were approximately twice as high (41.7 +/- 2.33 mumoles/100 ml), and the area under the plasma concentration-time curve twice as large. Peak plasma phenylalanine levels, however, were below those associated with toxic effects. The data indicate slower, but adequate metabolism and clearance of an abuse dose of aspartame by the phenylketonuric heterozygote. (+info)
Erythrocyte L-aspartyl-L-phenylalanine hydrolase activity and plasma phenylalanine and aspartate concentrations in children consuming diets high in aspartame.
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A deficit of alpha-aspartyl-phenylalanine (alpha-Asp-Phe) hydrolase activity has been suggested as a cause of possible adverse effects of aspartame ingestion. Twenty-five normal preschool children and 23 school-age children described by their parents as sensitive to sugar were fed diets high in sucrose, aspartame, or saccharin for three successive 3-wk periods. Blood samples were obtained at baseline (fasting) and within the last 3 d of each dietary period (postprandial). alpha-Asp-Phe concentrations were below detection limits (0.5 mumol/L) in all plasma samples and Phe and Asp concentrations remained within normal limits, alpha-Asp-Phe hydrolase activities in baseline hemolysate samples did not differ between groups. One subject had a plasma alpha-Asp-Phe hydrolase activity > 2 SD below the mean. Despite this low activity, this subject did not show consistent cognitive or behavioral anomalies that could be linked to low hydrolase activity. (+info)
Metabolism of aspartame by human and pig intestinal microvillar peptidases.
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The artificial sweetener aspartame (N-L-alpha-aspartyl-L-phenyl-alanine-1-methyl ester; Nutrasweet), its decomposition product alpha Asp-Phe and the related peptide alpha Asp-PheNH2 were rapidly hydrolysed by microvillar membranes prepared from human duodenum, jejunum and ileum, and from pig duodenum and kidney. The metabolism of aspartame by the human and pig intestinal microvillar membrane preparations was inhibited significantly (> 78%) by amastatin or 1,10-phenanthroline, and partially (> 38%) by actinonin or bestatin, and was activated 2.9-4.5-fold by CaCl2. The inhibition by amastatin and 1,10-phenanthroline, and the activation by CaCl2 are characteristic of the cell-surface ectoenzyme aminopeptidase A (EC 3.4.11.7) and a purified preparation of this enzyme hydrolysed aspartame with a Km of 0.25 mM and a Vmax of 126 mumol/min per mg. A purified preparation of aminopeptidase W (EC 3.4.11.16) also hydrolysed aspartame but with a Km of 4.96 mM and a Vmax of 110 mumol/min per mg. However, rentiapril, an inhibitor of aminopeptidase W, caused only slight inhibition (maximally 19%) of the hydrolysis of aspartame by the microvillar membrane preparations. Similar patterns of inhibition and kinetic parameters were observed for alpha Asp-Phe and alpha Asp-PheNH2. Two other decomposition products of aspartame, beta Asp-PheMe and cyclo-Asp-Phe, were essentially resistant to hydrolysis by both the human and pig intestinal microvillar membrane preparations and the purified preparations of aminopeptidases A and W. Although the relatively selective inhibitor of aminopeptidase N (EC 3.4.11.2), actinonin, partially inhibited the metabolism of aspartame, alpha Asp-Phe and alpha Asp-PheNH2 by the human and pig intestinal microvillar membrane preparations, these peptides were not hydrolysed by a purified preparation of aminopeptidase N. Membrane dipeptidase (EC 3.4.13.19) only hydrolysed the unblocked dipeptide, alpha Asp-Phe, but the selective inhibitor of this enzyme, cilastatin, did not block the metabolism of alpha Asp-Phe by the microvillar membrane preparations. (+info)
Effects of diets high in sucrose or aspartame on the behavior and cognitive performance of children.
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BACKGROUND: Both dietary sucrose and the sweetener aspartame have been reported to produce hyperactivity and other behavioral problems in children. METHODS: We conducted a double-blind controlled trial with two groups of children: 25 normal preschool children (3 to 5 years of age), and 23 school-age children (6 to 10 years) described by their parents as sensitive to sugar. The children and their families followed a different diet for each of three consecutive three-week periods. One diet was high in sucrose with no artificial sweeteners, another was low in sucrose and contained aspartame as a sweetener, and the third was low in sucrose and contained saccharin (placebo) as a sweetener. All the diets were essentially free of additives, artificial food coloring, and preservatives. The children's behavior and cognitive performance were evaluated weekly. RESULTS: The preschool children ingested a mean (+/- SD) of 5600 +/- 2100 mg of sucrose per kilogram of body weight per day while on the sucrose diet, 38 +/- 13 mg of aspartame per kilogram per day while on the aspartame diet, and 12 +/- 4.5 mg of saccharin per kilogram per day while on the saccharin diet. The school-age children considered to be sensitive to sugar ingested 4500 +/- 1200 mg of sucrose per kilogram, 32 +/- 8.9 mg of aspartame per kilogram, and 9.9 +/- 3.9 mg of saccharin per kilogram, respectively. For the children described as sugar-sensitive, there were no significant differences among the three diets in any of 39 behavioral and cognitive variables. For the preschool children, only 4 of the 31 measures differed significantly among the three diets, and there was no consistent pattern in the differences that were observed. CONCLUSIONS: Even when intake exceeds typical dietary levels, neither dietary sucrose nor aspartame affects children's behavior or cognitive function. (+info)
Comparing the effects of aspartame and sucrose on motivational ratings, taste preferences, and energy intakes in humans.
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This study compared the effects of four breakfast preloads on motivational ratings, taste preferences, and energy intakes of 24 normal-weight nondieting young men and women. The preloads, composed of creamy white cheese (fromage blanc), were either plain or sweetened with aspartame or sucrose. Their energy value was either 1255 or 2929 kJ (300 or 700 kcal). Taste preferences were measured before and 150 min after breakfast. Motivational ratings were obtained at 30-min intervals. The subjects ate lunch, snack, and dinner meals in the laboratory. The consumption of low-energy as opposed to high-energy breakfasts, regardless of sweetness, led to elevated motivational ratings and increased energy intakes at lunch. However, intakes at subsequent meals were the same for all preloads, and no overall compensation in energy was observed. Aspartame did not promote hunger or lead to increased energy intakes in normal-weight subjects. (+info)
An Equiratio Mixture Model for non-additive components: a case study for aspartame/acesulfame-K mixtures.
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The Equiratio Mixture Model predicts the psychophysical function for an equiratio mixture type on the basis of the psychophysical functions for the unmixed components. The model reliably estimates the sweetness of mixtures of sugars and sugar-alcohols, but is unable to predict intensity for aspartame/sucrose mixtures. In this paper, the sweetness of aspartame/acesulfame-K mixtures in aqueous and acidic solutions is investigated. These two intensive sweeteners probably do not comply with the model's original assumption of sensory dependency among components. However, they reveal how the Equiratio Mixture Model could be modified to describe and predict mixture functions for non-additive substances. To predict equiratio functions for all similar tasting substances, a new Equiratio Mixture Model should yield accurate predictions for components eliciting similar intensities at widely differing concentration levels, and for substances exhibiting hypo- or hyperadditivity. In addition, it should be able to correct violations of Stevens's power law. These three problems are resolved in a model that uses equi-intense units as the measure of physical concentration. An interaction index in the formula for the constant accounts for the degree of interaction between mixture components. Deviations from the power law are corrected by a nonlinear response output transformation, assuming a two-stage model of psychophysical judgment. (+info)
Aspartame pharmacokinetics - the effect of ageing.
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Aspartame is an intense sweetener which is increasingly used in the UK. It is registered at an acceptable daily intake (ADI) of 40 mg/kg, although there are no previous data relating to the metabolism of aspartame in older people. Twelve young and 12 elderly volunteers each received a single dose of approximately 40 mg/kg of aspartame. Baseline concentrations of phenylalanine (the main metabolite of aspartame) rose after ingestion with a significantly higher maximum concentration (Cmax) (81.3 vs. 63.3 micromol/1, p<0.01) and area under the plasma concentration-time curve extrapolated to infinity AUC 9(0-infinity)(518.7 vs. 353.5 micromol . h/l, p<0.01) in the elderly group. The higher concentrations reflected a significant fall in volume of distribution (V) from 2.03 to 1.59 1/kg (p <0.05) and clearance (CL) from 7.3 to 4.9 ml/min/kg (p <0.005) in the elderly group. The greater effect on CL than on V resulted in a small but non-significant rise in elimination half life (3.5 to 3.9 hours). The sizes of the differences were modest implying that there is no need on pharmacokinetic grounds for a change in the ADI for older people. (+info)
The effect of aspartame as part of a multidisciplinary weight-control program on short- and long-term control of body weight.
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This study investigated whether the addition of the high-intensity sweetener aspartame to a multidisciplinary weight-control program would improve weight loss and long-term control of body weight. One hundred sixty-three obese women were randomly assigned to consume or to abstain from aspartame-sweetened foods and beverages during 16 wk of a 19-wk weight-reduction program (active weight loss), a 1-y maintenance program, and a 2-y follow-up period. Women in both treatment groups lost approximately 10% of initial body weight (10 kg) during active weight loss. Among women assigned to the aspartame-treatment group, aspartame intake was positively correlated with percentage weight loss during active weight loss (r = 0.32, P < 0.01). During maintenance and follow-up, participants in the aspartame group experienced a 2.6% (2.6 kg) and 4.6% (4.6 kg) regain of initial body weight after 71 and 175 wk, respectively, whereas those in the no-aspartame group gained an average of 5.4% (5.4 kg) and 9.4% (9.4 kg), respectively. The aspartame group lost significantly more weight overall (P = 0.028) and regained significantly less weight during maintenance and follow-up (P = 0.046) than did the no-aspartame group. Percentage weight losses at 71 and 175 wk were also positively correlated with exercise (r = 0.32, P < 0.001; and r = 0.34, P < 0.01, respectively) and self-reported eating control (r = 0.37, P < 0.001; and r = 0.33, P < 0.01, respectively). These data suggest that participation in a multidisciplinary weight-control program that includes aspartame may facilitate the long-term maintenance of reduced body weight. (+info)