100 Scientific Studies On Aspartame

Record 1 from database: MEDLINE
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Title

Results of loading doses of aspartame by two phenylketonuric (PKU) children compared with two normal children.

Author

Koch R; Schaeffler G; Shaw NF

Address

 

Source

J Toxicol Environ Health, 1976 Nov, 2:2, 459-69

Abstract

Separate tolerance tests with aspartame at 34 mg/kg-day and phenylalanine at 19 mg/kg-day were compared. The results reveal that slight serum elevation of phenylalanine and tyrosine occurred in the two PKU and the normal healthy adolescents. It would appear that the phenylalanine in the sweetener aspartame is small enough to be of little clinical significance.

Language of Publication

English

Unique Identifier

77097101

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MeSH Heading (Major)

Aspartame|*PD; Dipeptides|*PD; Phenylketonurias|BL/*UR

MeSH Heading

Adolescence; Child; Female; Glutamine|AA/UR; Human; Male; Phenylacetates|UR; Phenylalanine|BL/UR; Phenylpyruvic Acids|UR; Tyrosine|BL

Publication Type

JOURNAL ARTICLE

ISSN

0098-4108

Country of Publication

UNITED STATES

Record 2 from database: MEDLINE
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Title

Use of aspartame in phenylketonuric heteroxygous adults.

Author

Koch R; Shaw KN; Williamson M; Haber M

Address

 

Source

J Toxicol Environ Health, 1976 Nov, 2:2, 453-7

Abstract

Asparatame, a new artificial sweetener, was administered to 45 obligate phenylketonuric adults for 28 wk. This new sweetening agent was well tolerated, and no untoward medical or biochemical changes were noted.

Language of Publication

English

Unique Identifier

77097100

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MeSH Heading (Major)

Aspartame|AE/*PD; Dipeptides|*PD; Heterozygote|*; Phenylketonurias|*BL

MeSH Heading

Adult; Clinical Trials; Female; Human; Male; Middle Age; Phenylalanine|BL; Placebos; Tyrosine|BL

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0098-4108

Country of Publication

UNITED STATES

Record 3 from database: MEDLINE
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Title

Comparative metabolism of aspartame in experimental animals and humans.

Author

Ranney RE; Oppermann JA; Muldoon E; McMahon FG

Address

 

Source

J Toxicol Environ Health, 1976 Nov, 2:2, 441-51

Abstract

Aspartame [SC-18862; 3-amino-N-(alpha-carboxyphenethyl) succinamic acid, methyl ester, the methyl ester of aspartylphenylalanine] is a sweetening agent that organoleptically has about 180 times the sweetness of sugar. The metabolism of aspartame has been studied in mice, rats, rabbits, dogs, monkeys, and humans. The compound was digested in all species in the same way as are natural constituents of the diet. Hydrolysis of the methyl group by intestinal esterases yielded methanol, which was oxidized in the one-carbon metabolic pool to CO2. The resultant dipeptide was split at the mucosal surface by dipeptidases and the free amino acids were absorbed. The aspartic acid moiety was transformed in large part to CO2 through its entry into the tricarboxylic acid cycle. Phenylalanine was primarily incorporated into body protein either unchanged or as its major metabolite, tyrosine.

Language of Publication

English

Unique Identifier

77097099

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MeSH Heading (Major)

Aspartame|*ME; Dipeptides|*ME

MeSH Heading

Animal; Aspartic Acid|ME; Carbon Radioisotopes; Comparative Study; Dogs; Haplorhini; Human; Methanol|ME; Mice; Phenylalanine|ME; Rabbits; Rats

Publication Type

JOURNAL ARTICLE

ISSN

0098-4108

Country of Publication

UNITED STATES

Record 4 from database: MEDLINE
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Title

Effects of aspartame in young persons during weight reduction.

Author

Knopp RH; Brandt K; Arky RA

Address

 

Source

J Toxicol Environ Health, 1976 Nov, 2:2, 417-28

Abstract

Given the potential use of a low-calorie sweetener during weight reduction, a toxicity study of chronic aspartame ingestion was conducted. Particular attention was given to possible long-term effects of aspartame on the fuel hormonal alterations characteristically caused by weight reduction. As a group mean age was 19.3 yr, body weight was 164.6 lb, and mean height was 65.4 in. Subjects were an average of 33% in excess of ideal body weight. The aspartame dose was 2.7 g/day and was compared on a double-blind randomized basis with a lactose placebo. Both materials were given in gelatin capsules. An average of 6.9 +/- 1.5 lb was lost by the aspartame group during the 13-wk study on a calculated 1,000-calorie diet. The placebo group lost 4.5 +/- 1.2 lb (no significant difference between the two groups). After an overnight fast, reductions in glucose and immunoreactive insulin were seen in both groups, while rising trends in immunoreactive glucagon were observed. These changes are all characteristic of calorie restriction. In no instance was there a detectable effect of the ingested aspartame. No meaningful effect of weight reduction or aspartame was seen on plasma triglyceride and cholesterol, nor on any other parameter of hematologic, hepatic, or renal function that was measured. Similarly, side effects were equally distributed between asparatame and placebo.

Language of Publication

English

Unique Identifier

77097097

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MeSH Heading (Major)

Aspartame|*/AE; Diet, Reducing|*; Dipeptides|*; Obesity|BL/*DH/UR

MeSH Heading

Adolescence; Adult; Amino Acids|BL; Blood Coagulation Tests; Blood Glucose|AN; Body Weight; Child; Clinical Trials; Female; Glucagon|BL; Human; Insulin|BL; Male; Methanol|UR; Placebos; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0098-4108

Country of Publication

UNITED STATES

Record 5 from database: MEDLINE
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Title

Use of aspartame by apparently healthy children and adolescents.

Author

Frey GH

Address

 

Source

J Toxicol Environ Health, 1976 Nov, 2:2, 401-15

Abstract

This study was conducted to determine the effects and the differences, if any, resulting from the ingestion of aspartame (sweetener) versus sucrose. A 13-wk, double-blind study was conducted using 126 apparently healthy children and adolescents as panelists. Individuals were randomly assigned in a double-blind design to aspartame or sucrose in each of five age groups; dosage levels were assigned according to age and weight groups. Physical examinations and special eye examinations were performed at the beginning and end of the study. Other parameters determined including laboratory tests of liver and renal function, hematologic status, and plasma levels of phenylalanine and tyrosine. Clinically significant differences in laboratory parameters measured could not be demonstrated; all mean values were within normal limits. No unusual findings were observed in phenylalanine or tyrosine levels. All phenylpyruvic acid and methanol determinations were negative. No important physical changes occurred, and no product-related side effects were reported.

Language of Publication

English

Unique Identifier

77097096

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MeSH Heading (Major)

Aspartame|AE/*PD; Dipeptides|*PD

MeSH Heading

Acne Vulgaris; Adolescence; Adult; Body Weight; Child; Child, Preschool; Clinical Trials; Comparative Study; Female; Human; Male; Methanol|BL/UR; Middle Age; Phenylalanine|BL; Phenylpyruvic Acids|UR; Sucrose|PD; Tyrosine|BL; Visual Acuity|DE

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0098-4108

Country of Publication

UNITED STATES

Record 6 from database: MEDLINE
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Title

Effect of aspartame and aspartate loading upon plasma and erythrocyte free amino acid levels in normal adult volunteers.

Author

Stegink LD; Filer LJ Jr; Baker GL

Address

 

Source

J Nutr, 1977 Oct, 107:10, 1837-45

Abstract

Aspartame is a dipeptide (L-aspartyl-L-phenylalanyl-methyl ester) with a sweeting potential 180 to 200 times that of sucrose. Questions have been raised about potential toxic effects of its constituent amino acids, aspartate and phenylalanine when the compound is ingested in large amounts. Plasma and erythrocyte amino acid levels were measured in 12 normal subjects after administration of either Aspartame (34 mg/kg) or equimolar quantities of aspartate (13 mg/kg) in a crossover design. No changes in either plasma or erythrocyte aspartate levels were noted at any time after either Aspartame or aspartate ingestion. Plasma phenylalanine levels decrease slightly after aspartate loading, and increased from fasting levels (4.9 +/- 1 mumoles/100 ml) to 10.7 +/- 1.9 mumoles/100 ml about 45 to 60 minutes after Aspartame loading. Phenylalanine levels returned to baseline by 4 hours. Erythrocyte phenylalanine levels showed similar changes.

Language of Publication

English

Unique Identifier

78007365

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MeSH Heading (Major)

Amino Acids|*BL; Aspartame|ME/PD/*TO; Aspartic Acid|BL/PD/*TO; Dipeptides|*TO; Erythrocytes|DE/*ME

MeSH Heading

Adult; Energy Intake; Female; Human; Male; Phenylalanine|BL

Publication Type

JOURNAL ARTICLE

ISSN

0022-3166

Country of Publication

UNITED STATES

Record 7 from database: MEDLINE
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Title

A review of the metabolism of the aspartyl moiety of aspartame in experimental animals and man.

Author

Ranney RE; Oppermann JA

Address

 

Source

J Environ Pathol Toxicol, 1979 Mar, 2:4, 979-85

Abstract

Aspartame (3-amino-N-(alpha-carboxyphenethyl) succinamic acid, methyl ester; the methyl ester of aspartylphenylalanine, SC-18862) is hydrolyzed in the gut to yield aspartic acid, phenylalanine, and methanol. This review of the literature describes the metabolic paths followed by aspartate in its conversion to CO2 or its incorporation into body constituents. About 70 percent of 14C from [asp-14C]-aspartame is converted in the monkey to 14CO2. Some of the aspartate is converted at the intestinal mucosal level to alanine by decarboxylation. This amino acid may be oxidized to CO2 by entering the tricarboxylic acid cycle via pyruvate and acetyl CoA. In addition, transamination of aspartate to oxaloacetate permits this product also to enter the tricarboxylic acid cycle. Aspartate may also be incorporated into body constitutents such as other amino acids, proteins, pyrimidines, asparagine, and N-acetylaspartic acid. It is concluded that the aspartate moiety of aspartame is metabolized in a manner similar to that of dietary aspartic acid.

Language of Publication

English

Unique Identifier

79195686

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MeSH Heading (Major)

Aspartame|*ME; Aspartic Acid|BI/*ME; Dipeptides|*ME

MeSH Heading

Animal; Carbon Dioxide|ME; Diet; Human; Intestinal Absorption; Oxidation-Reduction; Tissue Distribution

Publication Type

JOURNAL ARTICLE; REVIEW

Country of Publication

UNITED STATES

Record 8 from database: MEDLINE
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Title

Administration of aspartame in non-insulin-dependent diabetics.

Author

Stern SB; Bleicher SJ; Flores A; Gombos G; Recitas D; Shu J

Address

 

Source

J Toxicol Environ Health, 1976 Nov, 2:2, 429-39

Abstract

A study was designed to determine the effect of the consumption of the nutritive sweetener aspartame on non-insulin-dependent diabetics. Forty-three adult diabetics between the ages of 21 and 70 completed a 90-day study; all were diabetics whose conditions were managed by diet and/or hypoglycemic agents. Participants in the blind study were instructed to continue their usual diet and to take two capsules of an assigned preparation three times daily with meals, either the aspartame or the placebo. The 1.8 g of aspartame administered is approximately three times the expected daily consumption of aspartame if used as a sweetener to replace sugar. Throughout the study subjects were examined for (1) symptoms of intolerance, (2) fasting plasma phenylalanine levels exceeding 4 mg/100 ml, and (3) deterioration of diabetic control. At the conclusion of the study subjects exhibited no symptoms that could be traced to the administration of aspartame or the placebo, and diabetic control was unaffected by the chronic administration of these substances. Aspartame seems to be well tolerated by non-insulin-dependent diabetics.

Language of Publication

English

Unique Identifier

77097098

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MeSH Heading (Major)

Aspartame|AE/*PD; Blood Glucose|*AN; Diabetes Mellitus|*BL; Dipeptides|*PD

MeSH Heading

Adult; Aged; Female; Human; Male; Middle Age; Phenylalanine|BL; Placebos; Tyrosine|BL

Publication Type

CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0098-4108

Country of Publication

UNITED STATES

Record 9 from database: MEDLINE
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Title

Aspartame--a sweet surprise.

Author

Mazur RH

Address

 

Source

J Toxicol Environ Health, 1976 Sep, 2:1, 243-9

Abstract

The dipeptide ester L-aspartyl-L-phenylalanine methyl ester (APM) has been found to have a remarkably clean, sucrose-like taste with no off flavor and a potency 150-200 times sucrose. Subsequent work has shown that many alpha-amides of L-aspartic acid are sweet. Some results of stability studies and a taste panel evaluation of APM are reported.

Language of Publication

English

Unique Identifier

77053927

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MeSH Heading (Major)

Aspartame|AN/*PD; Dipeptides|*PD; Sweetening Agents|*

MeSH Heading

Chemistry; Drug Stability; Human; Isomerism; Taste

Publication Type

JOURNAL ARTICLE

ISSN

0098-4108

Country of Publication

UNITED STATES

Record 10 from database: MEDLINE
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Title

Postingestive inhibition of food intake by aspartame: importance of interval between aspartame administration and subsequent eating.

Author

Rogers PJ; Burley VJ; Alikhanizadeh LA; Blundell JE

Address

Consumer Sciences Department, Institute of Food Research, Reading, United Kingdom.

Source

Physiol Behav, 1995 Mar, 57:3, 489-93

Abstract

Aspartame administered in capsules (i.e., without tasting) 1 h before a meal significantly reduces the amount eaten in that meal. In the present study 36 young men and women were divided into 3 groups of 12 to receive aspartame (400 mg) or placebo (400 mg starch) on separate occasions either 5 min (Group A), 30 min (Group B) or 60 min (Group C) before beginning an ad lib test meal. Compared with placebo, aspartame reduced food intake in Group C (by 18.5%, p < 0.01), but did not reliably affect intake in Groups A or B. There were, in contrast, no significant effects of aspartame on premeal ratings of hunger, desire to eat or fullness for any of the groups. These results confirm a postingestive inhibitory action of aspartame on appetite, which may involve the amplification of the satiating effects of food. The lack of effect of aspartame administered at the shorter intervals before eating suggests a postgastric or even postabsorptive mechanism of action. This observation is also important in its implications for the possible therapeutic exploitation of the anorexic effect of capsulated aspartame.

Language of Publication

English

Unique Identifier

95273450

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MeSH Heading (Major)

Aspartame|*PD; Eating|*DE

MeSH Heading

Adolescence; Adult; Appetite Depressants|PD; Diet; Feeding Behavior|DE; Female; Human; Hunger; Male; Support, Non-U.S. Gov't; Time Factors

Publication Type

CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0031-9384

Country of Publication

UNITED STATES

Record 11 from database: MEDLINE
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Title

Aspartame metabolism in normal adults, phenylketonuric heterozygotes, and diabetic subjects.

Author

Filer LJ Jr; Stegink LD

Address

Department of Pediatrics, College of Medicine, University of Iowa, Iowa City 52242.

Source

Diabetes Care, 1989 Jan, 12:1, 67-74

Abstract

This study reviews clinical studies testing the effects of various doses of aspartame on blood levels of phenylalanine, aspartate, and methanol in normal subjects and known phenylketonuric heterozygotes. The effect of aspartame on the phenylalanine-to-large neutral amino acid ratio under various feeding situations is shown. The clinical studies of aspartame in diabetic subjects are limited to observations of its effects on blood levels of glucose, lipids, insulin, and glucagon. These studies clearly demonstrate the safety of this high-intensity sweetener for use by humans.

Language of Publication

English

Unique Identifier

89231387

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MeSH Heading (Major)

Aspartame|*ME/PD; Diabetes Mellitus, Non-Insulin-Dependent|*BL; Dipeptides|*ME; Phenylalanine|*BL; Phenylketonurias|*BL/GE

MeSH Heading

Adult; Aspartic Acid|BL; Blood Glucose|ME; Erythrocytes|ME; Female; Glucagon|BL; Heterozygote; Human; Insulin|BL; Lipids|BL; Male; Methanol|BL; Reference Values

Publication Type

JOURNAL ARTICLE

ISSN

0149-5992

Country of Publication

UNITED STATES

Record 12 from database: MEDLINE
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Title

Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in individuals heterozygous for phenylketonuria.

Author

Stegink LD; Filer LJ Jr; Baker GL; Bell EF; Ziegler EE; Brummel MC; Krause WL

Address

Department of Pediatrics, University of Iowa College of Medicine, Iowa City.

Source

Metabolism, 1989 Jan, 38:1, 78-84

Abstract

It has been suggested that excessive use of aspartame (APM) (N-L-alpha-aspartyl-L-phenylalanine methyl ester) might grossly elevate plasma aspartate and phenylalanine concentrations in individuals heterozygous for phenylketonuria (PKUH). In study 1 six adult PKUH (three males; three females) ingested three successive 12-oz servings of beverage at 2-h intervals. The study was carried out in two parts in a randomized crossover design. In one arm the beverage was not sweetened. In the other the beverage provided 10 mg APM/kg body weight per serving. The addition of APM to the beverage did not significantly increase plasma aspartate concentration but did increase plasma phenylalanine levels 2.3 to 4.1 mumol/dL above baseline values 30 to 45 min after each dose. The high mean plasma phenylalanine level after repeated APM dosing (13.9 +/- 2.15 mumol/dL) was slightly, but not significantly, above the normal postprandial range for PKUH (12.6 +/- 2.11 mumol/dL). In study 2 six different adult PKUH ingested beverage providing 30 mg APM/kg body weight as a single bolus. The high mean plasma phenylalanine concentration and the phenylalanine to large neutral amino acid ratio were significantly higher when APM was ingested as a single bolus than when ingested as a divided dose.

Language of Publication

English

Unique Identifier

89082344

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MeSH Heading (Major)

Amino Acids|*BL; Aspartame|*AD/AE; Beverages|*/AE; Dipeptides|*AD; Phenylketonurias|BL/*GE

MeSH Heading

Adult; Biological Transport; Dose-Response Relationship, Drug; Female; Heterozygote; Human; Male; Phenylalanine|BL; Random Allocation; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0026-0495

Country of Publication

UNITED STATES

Record 13 from database: MEDLINE
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Title

Aspartame: review of recent experimental and observational data.

Author

Janssen PJ; van der Heijden CA

Address

National Institute of Public Health and Environmental Hygiene, Bilthoven, The Netherlands.

Source

Toxicology, 1988 Jun, 50:1, 1-26

Abstract

In this report the neurotoxicity of aspartame and its constituent amino acids aspartic acid and phenylalanine is reviewed. The adverse reactions ascribed to the consumption of aspartame-containing products, as reported in the U.S.A., are discussed and placed in perspective with the results of recent behavioural studies in humans and animals. The issue of common intake levels associated with proposed uses of aspartame is addressed. In brief, the following conclusions can be drawn: When aspartame is consumed at levels within the ADI-limit of 40 mg/kg body wt, there is no significant risk for an aspartate-induced neurotoxic effect in the brain. When aspartame is consumed at levels within the ADI-limit by normal subjects or persons heterozygous for phenylketonuria (PKU) the resultant plasma phenylalanine concentrations are practically always within the normal postprandial range; elevation to plasma concentrations commonly associated with adverse effects has not been observed. Persons suffering from phenylketonuria (PKU-homozygotes) on a phenylalanine-restricted diet should avoid consumption of aspartame. PKU-homozygotes on the (less strict) phenylalanine-liberalized diet should be made aware of the phenylalanine content of aspartame. In the available behavioural studies in humans with acute dosing, no adverse effects were observed. Long-term studies on behaviour and cognitive function in (sensitive) humans are lacking. Analyses of adverse reaction reports made by consumers in the U.S.A. have not yielded a specific constellation of symptoms clearly related to aspartame that would suggest a widespread public health hazard associated with aspartame use. Focussed clinical studies are now being carried out in the U.S.A.; the results should provide additional evidence concerning the interpretation of the reports on adverse reactions ascribed to aspartame. In the regulation of admitted uses for aspartame the possibility of intake levels exceeding the ADI-limit in some groups of consumers should be a point of attention.

Language of Publication

English

Unique Identifier

88265115

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MeSH Heading (Major)

Aspartame|*AE/ME/TO; Dipeptides|*AE; Phenylalanine|BL/*ME

MeSH Heading

Animal; Behavior, Animal|DE; Brain Chemistry|DE; Human; Phenylketonurias|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0300-483X

Country of Publication

NETHERLANDS

Record 14 from database: MEDLINE
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Title

Aspartame-sweetened beverage: effect on plasma amino acid concentrations in normal adults and adults heterozygous for phenylketonuria.

Author

Stegink LD; Wolf Novak LC; Filer LJ Jr; Bell EF; Ziegler EE; Krause WL; Brummel MC

Address

Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242.

Source

J Nutr, 1987 Nov, 117:11, 1989-95

Abstract

Twelve normal subjects ingested either unsweetened beverage (n = 6) or beverage providing 4 mg/kg body weight as aspartame (APM) (n = 6). Neither beverage had any significant effect on plasma aspartate or phenylalanine concentrations. After this study, eight normal and six obligate phenylketonuric (PKU) heterozygous adults each ingested a 354-mL (12-oz) beverage serving on two occasions in a randomized cross-over design. On one occasion the beverage was not sweetened; on the other occasion, the beverage provided 10 mg APM/kg body weight. Plasma amino acid concentrations were measured throughout the 2-h study period. The addition of 10 mg APM/kg body weight to the beverage had no significant effect on plasma aspartate concentration. APM ingestion increased plasma phenylalanine levels of normal subjects from a mean +/- SD baseline value of 5.09 +/- 0.82 mumol/dL to a high mean value of 6.73 +/- 0.75 mumol/dL. In PKU heterozygous subjects the plasma phenylalanine level increased from a mean +/- SD of 9.04 +/- 1.71 to a high mean value of 12.1 +/- 2.08 mumol/dL. The data indicate ready metabolism of the aspartate and phenylalanine portion of APM when administered at levels likely to be ingested by individuals who drink diet beverages.

Language of Publication

English

Unique Identifier

88061718

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MeSH Heading (Major)

Amino Acids|*BL; Aspartame|AD/*PD; Beverages|*; Dipeptides|*PD; Heterozygote|*; Phenylketonurias|*BL/GE

MeSH Heading

Adult; Asparagine|BL; Aspartic Acid|BL; Biological Transport; Female; Glutamates|BL; Glutamine|BL; Human; Kinetics; Male; Phenylalanine|BL; Support, Non-U.S. Gov't; Tyrosine|BL

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0022-3166

Country of Publication

UNITED STATES

Record 15 from database: MEDLINE
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Title

Intestinal hydrolysis of aspartylphenylalanine--the metabolic product of aspartame.

Author

Tobey NA; Heizer WD

Address

 

Source

Gastroenterology, 1986 Oct, 91:4, 931-7

Abstract

Aspartame [Nutrasweet, Equal (Searle Consumer Products, Chicago, Ill.)] is the methyl ester of the dipeptide aspartylphenylalanine (Asp-Phe). After hydrolysis of the ester bond in the intestinal lumen, the dipeptide is apparently absorbed and digested in the same manner as dipeptides derived from protein digestion. We observed that Asp-Phe is hydrolyzed approximately equally well by three previously reported brush border dipeptidases. However, these enzymes have very low affinity for Asp-Phe, and a substantial amount of the dipeptide may be transported intact and hydrolyzed in the cytosol. Starch gel electrophoresis and ion-exchange chromatography of the cytosol of intestinal mucosa and of red blood cell lysate revealed only one peak with Asp-Phe hydrolase activity. This activity was distinct from the seven cytosolic peptidases that have been described previously. The reduction in Asp-Phe hydrolase activity in the brush border and cytosol of diseased intestinal mucosa was similar to the reduction in levels of other brush border and cytosol enzyme activities. If double-blind studies confirm that some people have symptoms caused by aspartame ingestion, it would be appropriate to test such individuals for deficiency of cytosolic Asp-Phe hydrolase activity.

Language of Publication

English

Unique Identifier

86301726

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MeSH Heading (Major)

Aspartame|*ME; Dipeptides|*ME; Intestinal Mucosa|*ME

MeSH Heading

Chromatography, Ion Exchange; Cytosol|EN; Dipeptidases|ME; Electrophoresis, Starch Gel; Human; Hydrolases|ME; Hydrolysis; Microvilli|EN; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0016-5085

Country of Publication

UNITED STATES

Record 16 from database: MEDLINE
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Title

Evaluation of reactions to food additives: the aspartame experience.

Author

Bradstock MK; Serdula MK; Marks JS; Barnard RJ; Crane NT; Remington PL; Trowbridge FL

Address

 

Source

Am J Clin Nutr, 1986 Mar, 43:3, 464-9

Abstract

Despite the widespread use of chemical food additives, few criteria exist to evaluate consumer reports of adverse reactions. We analyzed 231 consumer complaints associated with the food additive aspartame. We developed a methodologic approach to evaluate all complaints by adapting general criteria used to investigate adverse reactions to medications. Complaints were ranked according to the effects of cessation and rechallenge. Using this method, we found no clear symptom complex that suggests a widespread public health hazard associated with aspartame use; however, we identified some case reports in which the symptoms may be attributable to aspartame in commonly-consumed amounts. The systematic application of pre-defined review criteria, such as those described here, to monitor consumer complaints related to food additives will help identify products that warrant more focused clinical studies.

Language of Publication

English

Unique Identifier

86155585

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MeSH Heading (Major)

Aspartame|*AE; Dipeptides|*AE; Food Additives|*AE

MeSH Heading

Adult; Drug Hypersensitivity|ET; Emotions|DE; Female; Gastrointestinal Diseases|CI; Headache|CI; Human; Infant; Male; Menstruation Disturbances|CI; Middle Age; Sex Factors; United States; United States Food and Drug Administration

Publication Type

JOURNAL ARTICLE

ISSN

0002-9165

Country of Publication

UNITED STATES

Record 17 from database: MEDLINE
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Title

Aspartame. Review of safety issues. Council on Scientific Affairs.

Address

 

Source

JAMA, 1985 Jul, 254:3, 400-2

Abstract

This report examines the safety issues related to the nutritive sweetener aspartame, including possible toxic effects of aspartame's component amino acids, aspartic acid and phenylalanine, and its major decomposition products, methanol and diketopiperazine, and the potential synergistic effect of aspartame and dietary carbohydrate on brain neurochemicals. Available evidence suggests that consumption of aspartame by normal humans is safe and is not associated with serious adverse health effects. Individuals who need to control their phenylalanine intake should handle aspartame like any other source of phenylalanine.

Language of Publication

English

Unique Identifier

85237822

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MeSH Heading (Major)

Aspartame|*AE/BL/TO; Dipeptides|*AE

MeSH Heading

Adolescence; Adult; Animal; Aspartic Acid|BL; Brain Chemistry|DE; Brain Diseases|CI; Brain Neoplasms|CI; Carbonated Beverages|AN; Carcinogens; Child; Dietary Carbohydrates|AE; Drug Stability; Endocrine Diseases|CI; Female; Glutamates|AE/BL; Human; Infant; Mental Retardation|CI; Methanol|AN; Mice; Neurotransmitters|ME; Phenylalanine|BL; Phenylketonurias|BL; Piperazines|AN; Pregnancy; Rats

Publication Type

JOURNAL ARTICLE

ISSN

0098-7484

Country of Publication

UNITED STATES

Record 18 from database: MEDLINE
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Title

Safety of long-term large doses of aspartame.

Author

Leon AS; Hunninghake DB; Bell C; Rassin DK; Tephly TR

Address

Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis.

Source

Arch Intern Med, 1989 Oct, 149:10, 2318-24

Abstract

Safety of long-term administration of 75 mg/kg of aspartame per day was evaluated with the use of a randomized, double-blind, placebo-controlled, parallel-group design in 108 male and female volunteers aged 18 to 62 years. Subjects received either aspartame or placebo in capsule form three times daily for 24 weeks. No persistent changes over time were noted in either group in vital signs; body weight; results of standard laboratory tests; fasting blood levels of aspartame's constituent amino acids (aspartic acid and phenylalanine), other amino acids, and methanol; or blood formate levels and 24-hour urinary excretion of formate. There also were no statistically significant differences between groups in the number of subjects experiencing symptoms or in the number of symptoms per subject. These results further document the safety of the long-term consumption of aspartame at doses equivalent to the amount of aspartame in approximately 10 L of beverage per day.

Language of Publication

English

Unique Identifier

90025598

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MeSH Heading (Major)

Aspartame|*AD/AE; Dipeptides|*AD

MeSH Heading

Adolescence; Adult; Amino Acids|BL; Consumer Product Safety; Double-Blind Method; Drug Administration Schedule; Female; Folic Acid|BL; Formic Acids|UR; Headache|EP; Human; Male; Methanol|BL; Middle Age; Random Allocation; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0003-9926

Country of Publication

UNITED STATES

Record 19 from database: MEDLINE
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Title

Effect of repeated ingestion of aspartame-sweetened beverage on plasma amino acid, blood methanol, and blood formate concentrations in normal adults.

Author

Stegink LD; Filer LJ Jr; Bell EF; Ziegler EE; Tephly TR

Address

Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242.

Source

Metabolism, 1989 Apr, 38:4, 357-63

Abstract

Aspartame (APM) is a widely used dipeptide sweetener (L-aspartyl-L-phenylalanine methyl ester). It has been suggested that excessive use of APM might elevate plasma aspartate, phenylalanine, and/or methanol concentrations to levels that are potentially harmful. Six normal young adults ingested eight successive servings of unsweetened and APM-sweetened beverage at one-hour intervals in a balanced crossover design. In one part, the beverage was not sweetened. In the other, each serving of beverage provided 600 mg APM, a dose equivalent to the amount provided by 36 oz of APM-sweetened diet beverage. Plasma aspartate concentration was not significantly increased after ingestion of unsweetened or APM-sweetened beverage. Similarly, ingestion of the unsweetened beverage had no significant effect on plasma phenylalanine concentration. However, ingestion of APM-sweetened beverage significantly increased plasma phenylalanine levels 1.41 to 2.35 mumol/dL above baseline 30 minutes after ingestion. Plasma phenylalanine values reached a steady state after administration of four to five servings and did not exceed normal postprandial values at any time. Blood methanol and formate concentrations remained within normal limits. The data indicate ready metabolism of APM when administered at levels that may be ingested by normal individuals who are heavy users of diet beverages.

Language of Publication

English

Unique Identifier

89261094

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MeSH Heading (Major)

Amino Acids|*BL; Aspartame|*PD; Beverages|*; Dipeptides|*PD; Formates|*BL; Methanol|*BL

MeSH Heading

Adult; Asparagine|BL; Aspartic Acid|BL; Female; Glutamates|BL; Glutamine|BL; Human; Male; Phenylalanine|BL; Support, Non-U.S. Gov't; Tryptophan|BL; Tyrosine|BL

Publication Type

JOURNAL ARTICLE

ISSN

0026-0495

Country of Publication

UNITED STATES

Record 20 from database: MEDLINE
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Title

Aspartame as a dietary trigger of headache.

Author

Lipton RB; Newman LC; Cohen JS; Solomon S

Address

 

Source

Headache, 1989 Feb, 29:2, 90-2

Abstract

Many dietary factors have been implicated as possible precipitants of headache. There have been recent differences of opinion with regard to the effect of the artificial sweetener aspartame as a precipitant of headache. To assess the importance of aspartame as a dietary factor in headache, 190 consecutive patients of the Montefiore Medical Center Headache Unit were questioned about the effect of alcohol, carbohydrates and aspartame in triggering their headaches. Of the 171 patients who fully completed the survey, 49.7 percent reported alcohol as a precipitating factor, compared to 8.2 percent reporting aspartame and 2.3 percent reporting carbohydrates. Patients with migraine were significantly more likely to report alcohol as a triggering factor and also reported aspartame as a precipitant three times more often than those having other types of headache. The conflicting results of two recent placebo-control studies of aspartame and headache are discussed. We conclude that aspartame may be an important dietary trigger of headache in some people.

Language of Publication

English

Unique Identifier

89213361

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MeSH Heading (Major)

Aspartame|*AE; Dipeptides|*AE; Headache|*CI

MeSH Heading

Adolescence; Adult; Aged; Aged, 80 and over; Child; Dietary Carbohydrates|AE; Ethanol|AE; Female; Human; Male; Middle Age; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0017-8748

Country of Publication

UNITED STATES

Record 21 from database: MEDLINE
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Title

Saccharin and aspartame. Are they safe to consume during pregnancy?

Author

London RS

Address

Division of Reproductive Medicine, North Charles Hospital, Johns Hopkins Health System Member Institution, Baltimore, Maryland 21218.

Source

J Reprod Med, 1988 Jan, 33:1, 17-21

Abstract

Saccharin and aspartame are commonly used artificial sweeteners. Some of the currently available information on their safety in pregnancy was reviewed, with recommendations formulated on their use in the periconceptional period and pregnancy.

Language of Publication

English

Unique Identifier

88172271

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MeSH Heading (Major)

Aspartame|*AE/ME/PK; Dipeptides|*AE; Pregnancy|*DE; Saccharin|*AE

MeSH Heading

Aspartic Acid|ME; Female; Human; Methanol|ME; Phenylalanine|ME

Publication Type

JOURNAL ARTICLE

ISSN

0024-7758

Country of Publication

UNITED STATES

Record 22 from database: MEDLINE
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Title

Serum methanol concentrations in rats and in men after a single dose of aspartame.

Author

Davoli E; Cappellini L; Airoldi L; Fanelli R

Address

 

Source

Food Chem Toxicol, 1986 Mar, 24:3, 187-9

Abstract

Serum methanol concentrations were measured in rats and in humans given oral aspartame. The dose given to rats was the FDA's projected 99th percentile daily intake for humans, assuming aspartame were to replace all sucrose sweeteners in the diet (34 mg/kg). Four male adult volunteers each received 500 mg, equivalent to 6-8.7 mg/kg, which is approximately the FDA's estimate of mean daily human consumption. Both treatments caused a rise in serum methanol. In rats the mean peak value was 3.1 mg/litre 1 hr after administration; serum methanol returned to endogenous values 4 hr after treatment. In the men, the mean rise over endogenous values was 1.06 mg/litre after 45 min. Two hours after treatment, serum methanol had returned to basal levels. The temporary serum methanol increase showed peak values within the range of individual basal levels.

Language of Publication

English

Unique Identifier

86166135

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MeSH Heading (Major)

Aspartame|AD/*ME; Dipeptides|*ME; Methanol|*BL

MeSH Heading

Adult; Animal; Human; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Time Factors

Publication Type

JOURNAL ARTICLE

ISSN

0278-6915

Country of Publication

ENGLAND

Record 23 from database: MEDLINE
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Title

Use of aspartame in pregnancy.

Author

Sturtevant FM

Address

 

Source

Int J Fertil, 1985, 30:1, 85-7

Abstract

The low-calorie sweetening agent, aspartame, is broken down in the small intestine into three moieties: aspartic acid, methanol and phenylalanine. Acute loading studies have been performed in human beings who received up to six times the 99th percentile of the projected daily intake (6 X 34 = 200 mg/kg). No evidence of risk to the fetus was developed. Aspartate does not readily cross the placenta. Small elevations of blood methanol following such abuse doses of aspartame did not lead to measurable increases of blood formic acid, which is the product responsible for the acidosis and ocular toxicity in methanol poisoning. Phenylalanine is concentrated on the fetal side of the placenta. Aspartame in abuse doses up to 200 mg/kg in normal subjects, or to 100 mg/kg in PKU heterozygotes, did not raise blood phenylalanine levels to the range generally accepted to be associated with mental retardation in the offspring. It is concluded that, under foreseeable conditions of use, aspartame poses no risk for use in pregnancy.

Language of Publication

English

Unique Identifier

85260289

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MeSH Heading (Major)

Aspartame|ME/*PD; Dipeptides|*PD; Fetus|*DE; Pregnancy|*DE

MeSH Heading

Aspartic Acid|ME; Digestion; Female; Human; Methanol|ME; Phenylalanine|ME

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0020-725X

Country of Publication

UNITED STATES

Record 24 from database: MEDLINE
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Title

Children's food intake following drinks sweetened with sucrose or aspartame: time course effects.

Author

Birch LL; McPhee L; Sullivan S

Address

Child Development Laboratory, University of Illinois, Urbana 61801.

Source

Physiol Behav, 1989 Feb, 45:2, 387-95

Abstract

In two experiments, 2-5-year-old children's responsiveness to caloric density cues was examined. In a preloading protocol, consumption of fixed volumes of drinks (205 ml in Experiment 1; 150 ml in Experiment 2), sweetened with sucrose, aspartame, aspartame plus low glucose maltodextrin, or a water control, was followed by ad lib consumption from among a variety of foods. Caloric drinks had about 90 kcal in Experiment 1, 65 kcal in Experiment 2. The delay interval between the preload and the ad lib consumption was 0, 30 or 60 minutes. In Experiment 1, 24 4- and 5-year-old children participated in only one delay interval, while in Experiment 2, all 20 2- and 3-year-old children were seen in all conditions. Results revealed evidence of caloric compensation, but no evidence of preload x time delay interaction. In both experiments, aspartame also produced a significant suppression of intake relative to water, primarily due to the pattern at 30 min following the preload. Across conditions, the suppression following aspartame was usually significantly less than that produced by the caloric sweet drinks, providing evidence for postingestive effects. In Experiment 1, suppression of intake was related to the children's preferences for the foods, not to macronutrient content; consumption of nonpreferred foods was most suppressed. Consumption of sweetened drinks as long as 1 hour prior to eating suppressed food intake, and this common feeding practice may also reduce dietary variety.

Language of Publication

English

Unique Identifier

89331686

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MeSH Heading (Major)

Aspartame|*PD; Dipeptides|*PD; Energy Intake|*DE; Feeding Behavior|*DE; Food Preferences|*DE; Polysaccharides|*PD; Sucrose|*PD

MeSH Heading

Child, Preschool; Female; Human; Male; Random Allocation; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors

Publication Type

CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0031-9384

Country of Publication

UNITED STATES

Record 25 from database: MEDLINE
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Title

An evaluation of the effect of aspartame on weight loss.

Author

Kanders BS; Lavin PT; Kowalchuk MB; Greenberg I; Blackburn GL

Address

Cancer Research Institute, New England Deaconess Hospital, Boston, MA 02215.

Source

Appetite, 1988, 11 Suppl 1:, 73-84

Abstract

This study explores whether the addition of aspartame-sweetened foods and beverages to a low fat, hypocaloric diet enhances compliance and resulting weight loss. Fifty-nine obese (130-225% of ideal body weight), free living men and women were randomly assigned to either a Balanced Deficit Diet (BDD) or a BDD supplemented with aspartame. Over a 12-week weight loss period, volunteers attended weekly support group meetings including behavior modification training and exercise instruction. Males achieved a clinically significant weight loss (greater than 23 lb) in both study groups, while females lost an average of 12.8 lb in the control group vs. 16.5 lb in the experimental group. In both treatment groups, sleep, general energy level, level of physical activity, and feeling of well-being showed clinically meaningful improvement. This study suggests possible advantages to supplementing a BDD with aspartame-sweetened foods as part of a multidisciplinary weight loss program. The small sample size prohibits definitive conclusions but does provide the protocol for a larger, outpatient clinical trial.

Language of Publication

English

Unique Identifier

89049115

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MeSH Heading (Major)

Aspartame|*PD; Dipeptides|*PD; Weight Loss|*DE

MeSH Heading

Adult; Blood Pressure; Diet, Reducing; Energy Intake; Female; Health Status; Human; Male; Medical Records; Middle Age; Pilot Projects; Quality of Life; Random Allocation; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0195-6663

Country of Publication

ENGLAND

Record 26 from database: MEDLINE
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Title

Aspartame use in Parkinson's disease.

Author

Karstaedt PJ; Pincus JH

Address

Department of Neurology, Georgetown University Hospital, Washington, DC 20007.

Source

Neurology, 1993 Mar, 43:3 Pt 1, 611-3

Abstract

The artificial sweetener aspartame (NutraSweet) is hydrolyzed in the gut as phenylalanine (PA), a large neutral amino acid (LNAA). LNAAs compete with levodopa for uptake into the brain. To determine the effect of aspartame on levodopa-treated Parkinson's disease (PD) patients, we studied 18 PD patients with protein-sensitive motor fluctuations by administering in a double-blind and single-crossover design, on alternate days, aspartame (600 or 1,200 mg) and placebo. Every hour, we performed a motor examination and drew blood to estimate plasma LNAA, PA, and levodopa levels. Six-hundred mg of aspartame had no effect on plasma PA or motor status. Although 1,200 mg of aspartame significantly increased plasma PA, motor performance did not deteriorate. Aspartame consumption in amounts well in excess of what would be consumed by heavy users of aspartame-sweetened products has no adverse effect on PD patients.

Language of Publication

English

Unique Identifier

93196900

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MeSH Heading (Major)

Aspartame|*AE; Parkinson Disease, Secondary|BL/*CI

MeSH Heading

Aged; Human; Levodopa|BL; Middle Age; Phenylalanine|BL; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0028-3878

Country of Publication

UNITED STATES

Record 27 from database: MEDLINE
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Title

Biochemical and clinical effects of aspartame in patients with chronic, stable alcoholic liver disease.

Author

Hertelendy ZI; Mendenhall CL; Rouster SD; Marshall L; Weesner R

Address

Division of Hepatic Research, Department of Veterans Affairs Medical Center, Cincinnati, Ohio.

Source

Am J Gastroenterol, 1993 May, 88:5, 737-43

Abstract

Aspartame is an artificial sweetener completely metabolized in the gut and absorbed as aspartate, phenylalanine, and methanol. Phenylalanine is thought to mediate or exacerbate hepatic encephalopathy, and an impaired liver may not be able to cope with the ammoniagenic properties of the amino acid constituents, or adequately metabolize methanol. Thus, we compared the clinical and biochemical effects of a single ingestion of aspartame (15 mg/kg) to skim milk (phenylalanine content equimolar to aspartame) and placebo in patients with chronic, alcoholic liver disease in a randomized, crossover study. Aspartame produced an elevation of plasma phenylalanine significantly greater than milk and placebo (Cmax 14.55 +/- 7.38, 10.95 +/- 4.95, 8.84 +/- 4.55 mumol/dl, respectively; p < 0.01). However, quantified encephalopathic changes were observed only with milk (p < 0.05). Plasma aspartate, methanol, formate, and ammonia levels remained unchanged after all treatments. The lack of clinical derangements in encephalopathic indices, methanol accumulation, or biochemical changes in liver status suggests that a single large dose of aspartame (representing 5 times the average daily intake of adults) may be used safely by patients with chronic, stable liver disease.

Language of Publication

English

Unique Identifier

93243368

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MeSH Heading (Major)

Aspartame|*PD/TO; Liver|*ME; Liver Diseases, Alcoholic|*ME; Phenylalanine|*ME

MeSH Heading

Amino Acids|BL; Animal; Comparative Study; Drug Evaluation; Hepatic Encephalopathy|CI; Human; Male; Methanol|BL; Middle Age; Milk; Risk Factors; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0002-9270

Country of Publication

UNITED STATES

Record 28 from database: MEDLINE
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Title

Can aspartame meet our expectations?

Author

Horwitz DL; Bauer Nehrling JK

Address

 

Source

J Am Diet Assoc, 1983 Aug, 83:2, 142-6

Abstract

Aspartame is a dipeptide containing aspartic acid and phenylalanine methyl ester. It is a nutritive sweetener with a caloric value equivalent to that of other proteins and with sweetness approximately 180 times that of sucrose. Thus, for equivalent sweetening power, it contributes only 0.5% of the kilocalories of sugar. Numerous studies have shown no potential toxicity of amounts of aspartame likely to be ingested, or even of abuse doses. Although aspartame cannot fully replace sugar, it appears to be a safe and acceptable sweetener for those who must, or desire to, reduce their intake of sucrose.

Language of Publication

English

Unique Identifier

83266622

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MeSH Heading (Major)

Aspartame|AE/*ME; Dipeptides|*ME

MeSH Heading

Diet, Reducing; Drug Evaluation; Human; Phenylketonurias|ME; Structure-Activity Relationship; Sweetening Agents|AE

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0002-8223

Country of Publication

UNITED STATES

Record 29 from database: MEDLINE
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Title

Aspartame's effects on behavioral thermoregulation in albino rats.

Author

Vitulli WF; McAleer JE; Rockwell AC; Granade CR; Parman DL; Benoit C; Quinn JM

Address

Department of Psychology, University of South Alabama, Mobile 36688, USA.

Source

Percept Mot Skills, 1996 Aug, 83:1, 15-20

Abstract

Aspartame (L-aspartyl-L-phenylalanine methyl ester) was administered intraperitoneally to 9 Sprague-Dawley rats partitioned into 2 studies (4 in Study 1 and 5 for a replication in Study 2) over a two-year period using a within-subjects, repeated-measures reversal design. Behavioral thermoregulation was assessed in a cold Skinner Box using 5-sec. exposures of microwave radiation [Specific Absorption Rate = 0.34 Watts/kg/(mW/cm2)] as reinforcing stimuli under a fixed-interval 2-min. schedule of positive reinforcement. Two factorial analyses of variance [5 (doses) x 8 (hours)] indicated that the main effect for the doses of aspartame (2, 4, 8, 16 mg/kg, and saline control) was not significant; yet, the interaction (dose x hours) was significant (p < .05). Tentatively, aspartame should not cause an uncomfortable rise in body temperature (as sugar can do) when consumed in common substances such as soft drinks, yogurt, tea, coffee, etc., in doses commensurate with "hedonic" sweetness.

Language of Publication

English

Unique Identifier

97026998

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MeSH Heading (Major)

Appetitive Behavior|*DE; Aspartame|*PD; Body Temperature Regulation|*DE

MeSH Heading

Animal; Dose-Response Relationship, Drug; Female; Human; Injections, Intraperitoneal; Male; Rats; Rats, Sprague-Dawley; Reinforcement Schedule

Publication Type

JOURNAL ARTICLE

ISSN

0031-5125

Country of Publication

UNITED STATES

Record 30 from database: MEDLINE
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Title

Plasma phenylalanine levels in phenylketonuric heterozygous and normal adults administered aspartame at 34 mg/kg body weight.

Author

Stegink LD; Koch R; Blaskovics ME; Filer LJ Jr; Baker GL; McDonnell JE

Address

 

Source

Toxicology, 1981, 20:1, 81-90

Abstract

Following administration of aspartame (34 mg/kg body wt) in orange juice, plasma concentrations of free amino acids were measured in 12 female subjects known to be heterozygous for phenylketonuria and 22 normal subjects (12 male, 10 female). No change in fasting plasma aspartate concentrations were noted after aspartame loading in either group. In normal male subjects, the mean (+/-S.D.) plasma phenylalanine concentration increased from a fasting value of 5.86 +/- 1.25 mumol/dl. Plasma phenylalanine levels in normal female subjects increased from a mean fasting concentration of 4.83 +/- 0.84 mumol/dl to a men peak value of 8.95 +/- 1.49 mumol/dl suggesting a more rapid absorption, metabolism, and/or clearance of phenylalanine by females. In female heterozygous subjects, the mean peak plasma phenylalanine concentration was significantly higher than in normal females. Plasma phenylalanine values increased from a mean fasting value of 5.92 +/- 1.51 mumol/dl to a mean peak value of 15.1 +/- 4.76 mumol/dl. Similarly, the area under the plasma phenylalanine concentration-time curve was significantly greater in heterozygous female subjects (21.36 +/- 5.10 IU) than in normal female subjects (10.84 +/- 2.32 IU). However, peak plasma phenylalanine levels were well below those associated with toxic effects in all cases.

Language of Publication

English

Unique Identifier

81275617

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MeSH Heading (Major)

Aspartame|*ME; Dipeptides|*ME; Phenylalanine|*BL; Phenylketonurias|DH/*ME

MeSH Heading

Adult; Aspartic Acid|BL; Female; Heterozygote; Human; Male; Sex Factors; Support, Non-U.S. Gov't; Tyrosine|BL

Publication Type

JOURNAL ARTICLE

ISSN

0300-483X

Country of Publication

NETHERLANDS

Record 31 from database: MEDLINE
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Title

Effect of an abuse dose of aspartame upon plasma and erythrocyte levels of amino acids in phenylketonuric heterozygous and normal adults.

Author

Stegink LD; Filer LJ Jr; Baker GL; McDonnell JE

Address

 

Source

J Nutr, 1980 Nov, 110:11, 2216-24

Abstract

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.

Language of Publication

English

Unique Identifier

81048888

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MeSH Heading (Major)

Amino Acids|*BL; Aspartame|*TO; Dipeptides|*TO; Erythrocytes|DE/*ME; Phenylketonurias|*BL

MeSH Heading

Aspartic Acid|BL; Dose-Response Relationship, Drug; Female; Heterozygote; Human; Kinetics; Male; Phenylalanine|BL; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0022-3166

Country of Publication

UNITED STATES

Record 32 from database: MEDLINE
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Title

Increasing brain tumor rates: is there a link to aspartame? [see comments]

Author

Olney JW; Farber NB; Spitznagel E; Robins LN

Address

Department of Psychiatry, Washington University Medical School, St. Louis, MO 63110, USA.

Source

J Neuropathol Exp Neurol, 1996 Nov, 55:11, 1115-23

Abstract

In the past two decades brain tumor rates have risen in several industrialized countries, including the United States. During this time, brain tumor data have been gathered by the National Cancer Institute from catchment areas representing 10% of the United States population. In the present study, we analyzed these data from 1975 to 1992 and found that the brain tumor increases in the United States occurred in two distinct phases, an early modest increase that may primarily reflect improved diagnostic technology, and a more recent sustained increase in the incidence and shift toward greater malignancy that must be explained by some other factor(s). Compared to other environmental factors putatively linked to brain tumors, the artificial sweetener aspartame is a promising candidate to explain the recent increase in incidence and degree of malignancy of brain tumors. Evidence potentially implicating aspartame includes an early animal study revealing an exceedingly high incidence of brain tumors in aspartame-fed rats compared to no brain tumors in concurrent controls, the recent finding that the aspartame molecule has mutagenic potential, and the close temporal association (aspartame was introduced into US food and beverage markets several years prior to the sharp increase in brain tumor incidence and malignancy). We conclude that there is need for reassessing the carcinogenic potential of aspartame.

Language of Publication

English

Unique Identifier

97093657

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MeSH Heading (Major)

Aspartame|*AE; Brain Neoplasms|*CI/*EP/PA; Sweetening Agents|*AE

MeSH Heading

Animal; Human; Incidence; Mortality; Support, U.S. Gov't, P.H.S.; United States

Publication Type

JOURNAL ARTICLE

ISSN

0022-3069

Country of Publication

UNITED STATES

Record 33 from database: MEDLINE
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Title

Interference of rheumatoid factor activity by aspartame, a dipeptide methyl ester [corrected and republished with original paging, article originally printed in J Mol Recognit 1999 Jul-Aug;12(4):249-57]

Author

Ramsland PA; Movafagh BF; Reichlin M; Edmundson AB

Address

Crystallography Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.

Source

J Mol Recognit, 1999 Sep, 12:5, 249-57

Abstract

Circulating autoimmune complexes of IgM rheumatoid factors (RF) bound to the Fc portions of normal, polyclonal IgG antibodies are frequently present in humans with rheumatoid arthritis (RA). The sweet tasting methyl ester of L-Asp-L-Phe (aspartame or APM) was found to relieve pain and improve joint mobility in subjects with osteo- and mixed osteo/rheumatoid arthritis [Edmundson, A. B. and Manion, C. V. (1998). Clin. Pharmac. Ther. 63, 580-593]. These clinical observations prompted the testing of the inhibition by APM of the binding interactions of human IgM RFs with IgG Fc regions. The propensity of APM to inhibit IgM RF binding was assessed by competitive enzyme immunoassays with solid-phase human IgG. Ten RA serum samples and three purified monoclonal cryoglobulins, all of which had RF activity, were tested in this system. We found that the presence of APM significantly reduced the binding of IgM RFs. The inhibitory propensity of APM with monoclonal RF cryoglobulins was increased by the addition of CaCl(2) to the binding buffer. Similar inhibition of the binding of RA derived RFs to IgG was observed for Asp-Phe and its amidated derivative, indicating that the methyl ester is not required for APM's interaction with IgM antibodies. A human (Mez) IgM known to bind octameric peptides derived from the Fc portion of a human IgG(1) antibody was tested for binding of dipeptides by the Pepscan method of combinatorial chemistry. The relative binding constants of Asp-Phe and Phe-Asp were ranked among the highest values for 400 possible combinations of the 20 most common amino acids. Possible blocking interactions of APM were explored by computer-assisted docking studies with the model of a complex of an RF Fab with the Fc of a human IgG(4) antibody. Modeling of ternary immune complexes revealed a few key residues, which could act as molecular recognition sites for APM. A structural hypothesis is presented to explain the observed interference with RF reactivity by APM. Extrapolations of the current results suggest that APM may inhibit the binding of IgG in a substantial proportion of IgM RFs. Interference of RF reactivity, especially in RA patients, may alleviate the pain and immobility resulting from chronic inflammation of the joints. Copyright 1999 John Wiley & Sons, Ltd.

Language of Publication

English

Unique Identifier

20228737

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MeSH Heading (Major)

Antirheumatic Agents|*PD/TU; Arthritis, Rheumatoid|BL/DT/*IM; Aspartame|*PD/TU; Rheumatoid Factor|*IM

MeSH Heading

Adult; Aged; Aged, 80 and over; Antigen-Antibody Complex|DE; Calcium|PD; Cations, Divalent; Computer Simulation; Dipeptides|PD; Female; Human; IgG|IM; IgM|IM; Male; Middle Age; Models, Molecular; Support, U.S. Gov't, P.H.S.; Sweetening Agents|PD/TU

Publication Type

CORRECTED AND REPUBLISHED ARTICLE; JOURNAL ARTICLE

ISSN

0952-3499

Country of Publication

ENGLAND

Record 34 from database: MEDLINE
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Title

Blood methanol concentrations in one-year-old infants administered graded doses of aspartame.

Author

Stegink LD; Brummel MC; Filer LJ Jr; Baker GL

Address

 

Source

J Nutr, 1983 Aug, 113:8, 1600-6

Abstract

Blood methanol concentrations were measured in 24 1-year-old infants administered aspartame, a dipeptide methyl ester sweetener. The doses studied included a dose projected to be the 99th percentile of daily ingestion for adults (34 mg/kg body weight), a very high use dose (50 mg/kg body weight) and a dose considered to be in the abuse range (100 mg/kg body weight). Blood methanol values in infants were compared to values observed previously in adults administered equivalent doses of aspartame. Methanol concentrations were below the level of detection (0.35 mg/dl) in the blood of 10 infants administered aspartame at 34 mg/kg body weight, but were significantly elevated (P less than or equal to 0.05) after ingestion of aspartame at 50 and 100 mg/kg body weight. At the latter doses, mean peak blood methanol concentrations and the area under the blood methanol concentration-time curve increased in proportion to dose. Mean (+/- SEM) peak blood methanol concentration was 0.30 +/- 0.10 mg/100 ml at a 50 mg/kg body weight aspartame dose (n = 6) and 1.02 +/- 0.28 mg/ml at the 100 mg/kg body weight dose (n = 8). Blood methanol values in infants were similar to those observed in normal adults.

Language of Publication

English

Unique Identifier

83267838

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MeSH Heading (Major)

Aspartame|*AD/ME/TO; Dipeptides|*AD; Methanol|*BL

MeSH Heading

Age Factors; Dose-Response Relationship, Drug; Human; Infant; Support, Non-U.S. Gov't; Time Factors

Publication Type

JOURNAL ARTICLE

ISSN

0022-3166

Country of Publication

UNITED STATES

Record 35 from database: MEDLINE
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Title

Blood glucose and meal patterns in time-blinded males, after aspartame, carbohydrate, and fat consumption, in relation to sweetness perception [see comments]

Author

Melanson KJ; Westerterp Plantenga MS; Campfield LA; Saris WH

Address

Department of Human Biology, Maastricht University, The Netherlands.

Source

Br J Nutr, 1999 Dec, 82:6, 437-46

Abstract

In a study of the impact of aspartame, fat, and carbohydrate on appetite, we monitored blood glucose continuously for 431 (SE 16) min. Ten healthy males (19-31 years) participated in three time-blinded visits. As blood glucose was monitored, appetite ratings were scored at randomized times. On the first meal initiation, volunteers consumed one of three isovolumetric drinks (aspartame, 1 MJ simple carbohydrate, and 1 MJ high-fat; randomized order). High-fat and high-carbohydrate foods were available ad libitum subsequently. Blood glucose patterns following the carbohydrate drink (+1.78 (SE 0.28) mmol/l in 38 (SE 3) min) and high-fat drink (+0.83 (SE 0.28) mmol/l in 49 (SE 6) min) were predictive of the next intermeal interval (R 0.64 and R 0.97 respectively). Aspartame ingestion was followed by blood glucose declines (40% of subjects), increases (20%), or stability (40%). These patterns were related to the volunteers' perception of sweetness of the drink (R 0.81, P = 0.014), and were predictive of subsequent intakes (R -0.71, P = 0.048). For all drinks combined, declines in blood glucose and meal initiation were significantly associated (chi 2 16.8, P < 0.001), the duration of blood glucose responses and intermeal intervals correlated significantly (R 0.715, P = 0.0001), and sweetness perception correlated negatively with hunger suppression (R -0.471, P = 0.015). Effects of fat, carbohydrate, and aspartame on meal initiation, meal size, and intermeal interval relate to blood glucose patterns. Varied blood glucose responses after aspartame support the controversy over its effects, and may relate to sweetness perception.

Language of Publication

English

Unique Identifier

20154749

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MeSH Heading (Major)

Appetite Regulation|*; Aspartame|*AD; Blood Glucose|*ME; Dietary Carbohydrates|*AD; Dietary Fats|*AD; Taste|*

MeSH Heading

Adult; Eating; Human; Male; Support, Non-U.S. Gov't; Time Factors

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0007-1145

Country of Publication

ENGLAND

Record 36 from database: MEDLINE
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Title

Interference of rheumatoid factor activity by aspartame, a dipeptide methyl ester.

Author

Ramsland PA; Movafagh BF; Reichlin M; Edmundson AB

Address

Crystallography Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.

Source

J Mol Recognit, 1999 Jul, 12:4, 249-57

Abstract

Circulating autoimmune complexes of IgM rheumatoid factors (RF) bound to the Fc portions of normal, polyclonal IgG antibodies are frequently present in humans with rheumatoid arthritis (RA). The sweet tasting methyl ester of L-Asp-L-Phe (aspartame or APM) was found to relieve pain and improve joint mobility in subjects with osteo- and mixed osteo/rheumatoid arthritis [Edmundson, A. B. and Manion, C. V. (1998). Clin. Pharmac. Ther. 63, 580-593]. These clinical observations prompted the testing of the inhibition by APM of the binding interactions of human IgM RFs with IgG Fc regions. The propensity of APM to inhibit IgM RF binding was assessed by competitive enzyme immunoassays with solid-phase human IgG. Ten RA serum samples and three purified monoclonal cryoglobulins, all of which had RF activity, were tested in this system. We found that the presence of APM significantly reduced the binding of IgM RFs. The inhibitory propensity of APM with monoclonal RF cryoglobulins was increased by the addition of CaCl(2) to the binding buffer. Similar inhibition of the binding of RA derived RFs to IgG was observed for Asp-Phe and its amidated derivative, indicating that the methyl ester is not required for APM's interaction with IgM antibodies. A human (Mez) IgM known to bind octameric peptides derived from the Fc portion of a human IgG(1) antibody was tested for binding of dipeptides by the Pepscan method of combinatorial chemistry. The relative binding constants of Asp-Phe and Phe-Asp were ranked among the highest values for 400 possible combinations of the 20 most common amino acids. Possible blocking interactions of APM were explored by computer-assisted docking studies with the model of a complex of an RF Fab with the Fc of a human IgG(4) antibody. Modeling of ternary immune complexes revealed a few key residues, which could act as molecular recognition sites for APM. A structural hypothesis is presented to explain the observed interference with RF reactivity by APM. Extrapolations of the current results suggest that APM may inhibit the binding of IgG in a substantial proportion of IgM RFs. Interference of RF reactivity, especially in RA patients, may alleviate the pain and immobility resulting from chronic inflammation of the joints. Copyright 1999 John Wiley & Sons, Ltd.

Language of Publication

English

Unique Identifier

99369710

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MeSH Heading (Major)

Analgesics|ME/*PD; Antigen-Antibody Complex|*DE/ME; Arthritis, Rheumatoid|*DT/IM; Aspartame|ME/*PD; Autoimmune Diseases|*DT/IM; Rheumatoid Factor|*DE/ME

MeSH Heading

Antibodies, Monoclonal|DE/ME; Binding Sites; Calcium|PD; Combinatorial Chemistry Techniques; Comparative Study; Computer Simulation; Cryoglobulins|DE/ME; Dipeptides|ME; Human; IgG|IM/ME; IgM|IM/ME; Immunoglobulins, Fc|IM/ME; Macromolecular Systems; Models, Immunological; Models, Molecular; Peptide Fragments|DE/ME; Peptide Library; Protein Binding; Protein Conformation; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0952-3499

Country of Publication

ENGLAND

Record 37 from database: MEDLINE
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Title

Measurement of the relative sweetness of stevia extract, aspartame and cyclamate/saccharin blend as compared to sucrose at different concentrations.

Author

Cardello HM; Da Silva MA; Damasio MH

Address

Department of Food and Nutrition, FCF-UNESP, Araraquara, SP, Brazil. cardhel@fcfar.unesp.br

Source

Plant Foods Hum Nutr, 1999, 54:2, 119-30

Abstract

Special diets are used to mitigate many human diseases. When these diets require changes in carbohydrate content, then sweetness becomes an important characteristic. The range of low-calorie sweeteners available to the food industry is expanding. It is essential to have an exact knowledge of the relative sweetness of various sweeteners in relation to different sucrose concentrations. The objective of this study was to determine the variation on the relative sweetness of aspartame (APM), stevia [Stevia rebaudiana (Bert.) Bertoni] leaf extract (SrB) and the mixture cyclamate/saccharin--two parts of cyclamate and one part of saccharin--(C/S) with the increase in their concentrations, and in neutral and acid pH in equisweet concentration to 10% sucrose, using magnitude estimation. Sweetness equivalence of SrB in relation to sucrose concentrations of 20% or higher and of APM and C/S to sucrose concentrations of 40% or higher could not be determined, because a bitter taste predominated. The potency of all sweeteners decreased as the level of sweetner increased. In equi-sweet concentration of sucrose at 10%, with pH 7.0 and pH 3.0, the potency was practically the same for all sweeteners evaluated.

Language of Publication

English

Unique Identifier

20110479

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MeSH Heading (Major)

Sweetening Agents|*; Taste Threshold|*

MeSH Heading

Aspartame; Comparative Study; Cyclamates; Dose-Response Relationship, Drug; Glucosides; Human; Hydrogen-Ion Concentration; Saccharin; Sucrose; Support, Non-U.S. Gov't; Terpenes

Publication Type

JOURNAL ARTICLE

ISSN

0921-9668

Country of Publication

NETHERLANDS

Record 38 from database: MEDLINE
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Title

Plasma and erythrocyte concentrations of free amino acids in adult humans administered abuse doses of aspartame.

Author

Stegink LD; Filer LJ Jr; Baker GL

Address

 

Source

J Toxicol Environ Health, 1981 Feb, 7:2, 291-305

Abstract

Plasma and erythrocyte concentrations of amino acids were measured in 18 fasting adult subjects (9 male, 9 female) administered abuse doses of aspartame (100, 150, and 200 mg/kg body weight) dissolved in 500 ml orange juice. Six subjects were studied at each dose. Plasma aspartate concentrations increased significantly (p less than or equal to 0.05) over baseline values after ingestion of each dose. However, the increase was small in each case, and maximal levels observed were below those noted postprandially in formula-fed infants. No significant changes (p greater than 0.05) were noted in erythrocyte glutamate, or erythrocyte aspartate concentrations after any dose. Plasma phenylalanine concentrations increased significantly over fasting concentrations (p less than 0.01) from 15 min to 6 h after each dose, and the increase was proportional to dose. Mean (+/- SD) peak plasma phenylalanine concentrations were 20.3 +/- 2.03, 35.1 +/- 11.3, and 48.7 +/- 15.5 mumol/dl, respectively, after aspartame doses of 100, 150, and 200 mg/kg. Erythrocyte phenylalanine concentrations showed similar changes. Although these phenylalanine concentrations are considerably above the normal postprandial range (12 +/- 3 mumol/dl), they are below values associated with toxic findings. These data indicate little risk to normal subjects from excessive aspartate or phenylalanine levels after ingestion of single abuse loads of aspartame.

Language of Publication

English

Unique Identifier

81194838

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MeSH Heading (Major)

Amino Acids|*BL; Aspartame|*ME/PO; Dipeptides|*ME

MeSH Heading

Adult; Alanine|BL; Alanine Transaminase|BL; Aspartate Transaminase|BL; Erythrocytes|ME; Female; Human; Male; Phenylalanine|BL; Plasma|ME; Support, Non-U.S. Gov't; Tyrosine|BL

Publication Type

JOURNAL ARTICLE

ISSN

0098-4108

Country of Publication

UNITED STATES

Record 39 from database: MEDLINE
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Title

Blood methanol concentrations in normal adult subjects administered abuse doses of aspartame.

Author

Stegink LD; Brummel MC; McMartin K; Martin Amat G; Filer LJ Jr; Baker GL; Tephly TR

Address

 

Source

J Toxicol Environ Health, 1981 Feb, 7:2, 281-90

Abstract

Blood methanol concentrations were measured in 30 normal adult subjects administered aspartame, a dipeptide methyl ester. The doses studied included the 99th percentile of projected daily ingestion (34 mg/kg body weight) and three doses considered to be in the abuse range (100, 150, and 200 mg/kg body weight). Methanol concentrations were below the level of detection (0.4 mg/dl) in the blood of the 12 normal subjects who ingested aspartame at 34 mg/kg. They were significantly elevated (p less than or equal to 0 .001) after ingestion of each abuse dose, with the mean peak blood methanol concentrations and the areas under the blood methanol concentration-time curve increasing in proportion to dose. Mean (+/- SD) peak blood methanol concentrations were 1.27 +/- 0.48 mg/dl at the 100 mg/kg dose, 2.14 +/- 0.35 mg/dl at the 150 mg/kg dose, and 2.58 +/- 0.78 mg/dl at the 200 mg/kg dose. Blood methanol concentrations returned to predosing levels by 8 h after administration of the 100 mg/kg dose. Methanol was still detected in the blood 8 h after the subjects had ingested aspartame at 150 or 200 mg/kg. Blood formate analyses were carried out in the 6 subjects who ingested aspartame at 200 mg/kg, since recent studies indicate that the toxic effects of methanol are due to formate accumulation. No significant increase in blood formate concentrations over predosing concentrations was noted. No changes were noted in any of the blood chemistry profile parameters measured 24 h after aspartame ingestion, compared to values noted before administration. Similarly, no differences were noted in ophthalmologic examinations carried out before and after aspartame loading.

Language of Publication

English

Unique Identifier

81194837

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MeSH Heading (Major)

Aspartame|*ME/PO; Dipeptides|*ME; Methanol|*BL

MeSH Heading

Adult; Female; Human; Male; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0098-4108

Country of Publication

UNITED STATES

Record 40 from database: MEDLINE
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Title

Aspartame intolerance.

Author

Garriga MM; Metcalfe DD

Address

Mast Cell Physiology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.

Source

Ann Allergy, 1988 Dec, 61:6 Pt 2, 63-9

Abstract

Aspartame is a food additive marketed under the brand name Nutrasweet. Aspartame is a white, odorless, crystalline powder and consists of two amino acids, L-aspartic acid and L-phenylalanine. It is 180 times as sweet as sugar. The Food and Drug Administration (FDA) first allowed its use in dry foods in July 1981 and then approved its use in carbonated beverages in July 1983. It has subsequently been approved for use in a number of materials including multivitamins, fruit juices, stick-type confections, breath mints, and iced tea. The FDA requires the statement "phenylketonurics: contains phenylalanine" on labels of food products containing aspartame because individuals with phenylketonuria (PKU) must restrict their intake of phenylalanine. Aspartame is judged to be free of long-term cancer risks. Aspartame is not stable under certain conditions including baking and cooking, and prolonged exposure to acid conditions. In such situations it loses its sweetness. Products formed from aspartame include its component amino acids (phenylalanine and aspartic acid), methanol, and diketopiperazine (DKP). Animal studies show DKP to be nontoxic. Methanol occurs in small amounts and does not exceed that formed during consumption of many foods including fresh fruits and vegetables. FDA's Center for Food Safety and Applied Nutrition (CFSAN) monitors aspartame's safety in part through reports of adverse reactions. After aspartame was approved for use in carbonated beverages, the FDA received an increased number of reports concerning adverse reactions related to aspartame. The Centers for Disease Control (CDC) reviewed these reports, which included complaints of neurologic, gastrointestinal, andallergic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

89086740

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MeSH Heading (Major)

Aspartame|*AE; Dipeptides|*AE; Product Surveillance, Postmarketing|*

MeSH Heading

Behavior; Female; Headache|ET; Human; Hypersensitivity|ET; Male

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0003-4738

Country of Publication

UNITED STATES

Record 41 from database: MEDLINE
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Title

Aspartame pharmacokinetics - the effect of ageing [see comments]

Author

Puthrasingam S; Heybroek WM; Johnston A; Maskrey V; Swift CG; Turner P; Abrams SM; Jackson SH

Address

Department of Health Care of the Elderly, King's College School of Medicine and Dentistry, Dulwich Hospital, E. Dulwich Grove, London E22 8PT, UK.

Source

Age Ageing, 1996 May, 25:3, 217-20

Abstract

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.

Language of Publication

English

Unique Identifier

96324224

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MeSH Heading (Major)

Aging|*BL; Aspartame|AD/*PK

MeSH Heading

Adult; Aged; Aged, 80 and over; Female; Human; Male; Metabolic Clearance Rate|PH; Phenylalanine|BL; Pilot Projects; Reference Values; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0002-0729

Country of Publication

ENGLAND

Record 42 from database: MEDLINE
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Title

Effects of aspartame and phenylalanine on meal-time food intake of humans.

Author

Anderson GH; Leiter LA

Address

Department of Nutritional Sciences, University of Toronto, Ontario, Canada.

Source

Appetite, 1988, 11 Suppl 1:, 48-53

Abstract

This article reviews data relevant to the hypothesis that aspartame may have a unique effect on meal-time food intake regulation due to its amino acid composition and in addition to its effects as a high intensity sweetener. It is concluded that future studies involving aspartame should be directed towards developing a fundamental understanding of the effects of high intensity sweeteners on food intake, and not give undue attention to putative actions based on its amino acid constituents.

Language of Publication

English

Unique Identifier

89049110

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MeSH Heading (Major)

Aspartame|AD/*PD; Dipeptides|*PD; Eating|*DE; Phenylalanine|AD/BL/*PD

MeSH Heading

Amino Acids|ME/PD; Human; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0195-6663

Country of Publication

ENGLAND

Record 43 from database: MEDLINE
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Title

Aspartame is no more likely than placebo to cause urticaria/angioedema: results of a multicenter, randomized, double-blind, placebo-controlled, crossover study [see comments]

Author

Geha R; Buckley CE; Greenberger P; Patterson R; Polmar S; Saxon A; Rohr A; Yang W; Drouin M

Address

Harvard Medical School, Boston, MA.

Source

J Allergy Clin Immunol, 1993 Oct, 92:4, 513-20

Abstract

BACKGROUND: Anecdotes and single case reports have suggested that the high-intensity sweetener, aspartame, may be associated with allergic/hypersensitivity-type reactions. METHODS: We conducted a multicenter, placebo-controlled clinical study to evaluate individuals who had experienced urticaria and/or angioedema allegedly associated with ingestion of an aspartame-containing product. Despite extensive recruiting efforts over 4 years, only 21 subjects could be enrolled. After admission to clinical research units, subjects were given aspartame and placebo in a randomized, double-blind, crossover fashion. Subjects received, on different days, increasing doses (50, 300, 600 mg) of aspartame and placebo at 8:00 AM, 10:00 AM, and noon. Subjects who weighed less than 40 kg received one half of these doses. Conversion products of aspartame, aspartyl-phenylalanine diketopiperazine and beta-aspartame, were also included in the aspartame arm of the study. Positive reactions were defined as urticaria (hives with wheals 4 mm or more in diameter with a collective diameter of at least 15 mm or one or more hives with a wheal of 4 mm or greater with a flare of 8 mm or greater) or as angioedema. RESULTS: According to these criteria, four reactions were observed; two followed aspartame ingestion and two followed placebo ingestion (p = 1.00). The incidence of other adverse experiences was no different after aspartame versus placebo ingestion (p = 0.289). CONCLUSION: These results indicate that aspartame and its conversion products are no more likely than placebo to cause urticaria and/or angioedema reactions in subjects with a history consistent with hypersensitivity to aspartame.

Language of Publication

English

Unique Identifier

94014012

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MeSH Heading (Major)

Angioneurotic Edema|*CI; Aspartame|AD/*AE; Drug Hypersensitivity|*ET; Urticaria|*CI

MeSH Heading

Administration, Oral; Adolescence; Adult; Capsules; Child; Double-Blind Method; Female; Human; Incidence; Male; Middle Age; Placebos; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL

ISSN

0091-6749

Country of Publication

UNITED STATES

Record 44 from database: MEDLINE
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Title

Response to single dose of aspartame or saccharin by NIDDM patients.

Author

Horwitz DL; McLane M; Kobe P

Address

Department of Medicine, University of Illinois, Chicago 60680.

Source

Diabetes Care, 1988 Mar, 11:3, 230-4

Abstract

Twelve normal subjects and 10 subjects with non-insulin-dependent diabetes mellitus were given, in random order at intervals of greater than or equal to 1 wk, three drinks of the same beverage: one unsweetened, one sweetened with 400 mg aspartame, and one sweetened with 135 mg saccharin. The amount of sweetener approximated that in 1 L of sugar-free soft drink. Plasma glucose, insulin, and glucagon were measured for 3 h after ingestion of the test beverage. Plasma glucose declined slightly throughout the test period, probably due to fasting, with no differences between the three treatments. Neither sweetener affected peak insulin levels in subjects with or without diabetes. Analysis of area under the curve showed that mean insulin levels were statistically significantly higher after aspartame than after saccharin or unsweetened beverage in normal subjects only, but the magnitude of the difference was small and unlikely to be of physiological importance in the absence of differences in glucose levels. Furthermore, the differences could largely be accounted for by a decrease in insulin values after both unsweetened beverage and saccharin, with no change from baseline after aspartame. Glucagon levels showed time-to-time variation but no overall differences. We conclude that ingestion of aspartame- or saccharin-sweetened beverages by fasting subjects, with or without diabetes, did not affect blood glucose homeostasis.

Language of Publication

English

Unique Identifier

88328598

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MeSH Heading (Major)

Aspartame|*PD; Blood Glucose|*ME; Diabetes Mellitus, Non-Insulin-Dependent|*BL; Dipeptides|*PD; Insulin|*BL; Saccharin|*PD

MeSH Heading

Adult; Female; Glucagon|BL; Human; Kinetics; Male; Middle Age; Reference Values; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0149-5992

Country of Publication

UNITED STATES

Record 45 from database: MEDLINE
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Title

Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population.

Author

Walton RG; Hudak R; Green Waite RJ

Address

Department of Psychiatry, Northeastern Ohio Universities College of Medicine, Youngstown.

Source

Biol Psychiatry, 1993 Jul, 34:1-2, 13-7

Abstract

This study was designed to ascertain whether individuals with mood disorders are particularly vulnerable to adverse effects of aspartame. Although the protocol required the recruitment of 40 patients with unipolar depression and a similar number of individuals without a psychiatric history, the project was halted by the Institutional Review Board after a total of 13 individuals had completed the study because of the severity of reactions within the group of patients with a history of depression. In a crossover design, subjects received aspartame 30 mg/kg/day or placebo for 7 days. Despite the small n, there was a significant difference between aspartame and placebo in number and severity of symptoms for patients with a history of depression, whereas for individuals without such a history there was not. We conclude that individuals with mood disorders are particularly sensitive to this artificial sweetener and its use in this population should be discouraged.

Language of Publication

English

Unique Identifier

93385314

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MeSH Heading (Major)

Aspartame|*AE/*TU; Depressive Disorder|DI/*DT/PX

MeSH Heading

Adult; Comparative Study; Cross-Sectional Studies; Double-Blind Method; Eye Diseases|ET/PP; Female; Headache|ET; Human; Male; Middle Age; Placebos; Psychiatric Status Rating Scales; Vision Disorders|ET/PP

Publication Type

CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0006-3223

Country of Publication

UNITED STATES

Record 46 from database: MEDLINE
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Title

Aspartame as a source of essential phenylalanine for the growth of oral anaerobes.

Author

Wyss C

Address

Department of Oral Microbiology and General Immunology, University of ZÂurich, Switzerland.

Source

FEMS Microbiol Lett, 1993 Apr, 108:3, 255-8

Abstract

Phenylalanine and aspartic acid requirements were determined for 13 species of oral bacteria using the chemically defined medium OMIZ-W1. None of Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Eikenella corrodens, Selenomonas sputigena, Treponema pectinovorum, T. socranskii, or Wolinella recta required either of these amino acid constituents of aspartame (L-aspartyl-L-phenylalanine methylester). Phenylalanine was essential for the growth of Capnocytophaga gingivalis, Eubacterium timidum, Fusobacterium nucleatum, Porphyromonas gingivalis, T. denticola, and T. vincentii, while aspartic acid was not required. With the exception of E. timidum, all phenylalanine-dependent strains could grow when the free amino acid was replaced by aspartame at concentrations at least 10-fold lower than those used for aspartame as an artificial sweetener.

Language of Publication

English

Unique Identifier

93292902

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MeSH Heading (Major)

Aspartame|*ME; Bacteria, Anaerobic|GD/*ME; Dental Plaque|*MI; Phenylalanine|*ME

MeSH Heading

Comparative Study; Human; Species Specificity

Publication Type

JOURNAL ARTICLE

ISSN

0378-1097

Country of Publication

NETHERLANDS

Record 47 from database: MEDLINE
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Title

Mutagenic activity of peptides and the artificial sweetener aspartame after nitrosation.

Author

Shephard SE; Wakabayashi K; Nagao M

Address

Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.

Source

Food Chem Toxicol, 1993 May, 31:5, 323-9

Abstract

Naturally occurring dipeptides, cholecystokinine (CCK, a tetrapeptide hormone) and the artificial sweetener aspartame were nitrosated for 10-30 min with 40 mM-nitrite (pH 3.5, 37 degrees C), and the resultant products examined for mutagenicity in Salmonella typhimurium TA100. Specific mutagenicities (net revertants per mumol precursor) spanned four orders of magnitude, with CCK being the most potent precursor (4700 revertants/mumol) followed by tryptophyl-tryptophan (Trp-Trp; 1000 revertants/mumol). Aspartame and glycyl-Trp (Gly-Trp) had intermediate activity (300 revertants/mumol), while Gly-Gly and methionyl-methionine were only weakly mutagenic (20 and 12 revertants/mumol, respectively). The dipeptides of aspartic acid, phenylalanine and tyrosine had no detectable mutagenicity (limits of detection 0.5, 40 and 5 revertants/mumol, respectively). Kinetic studies with aspartame and Gly-Trp suggested that the mutagenic products arose primarily from nitrosation of the primary amine rather than the amide or indole group. The mutagenicities of nitrosated aspartame and Gly-Trp were higher in TA100 than in TA98, and higher without than with enzymatic activation (S-9 mix) in both strains. The time-course study of Trp-Trp nitrosation showed the production of at least two mutagens: a potent but unstable mutagenicity was seen at very short nitrosation times and a more stable but weaker effect was obtained after more than 60 min of nitrosation. Not only the absolute specific mutagenicity but also the nitrite dependence of the nitrosation reaction and the stability of the nitroso product must be taken into account in determining the risk posed by endogenous nitrosation of foods in the human stomach. Under stomach conditions, nitrosation of the side-chains of certain Trp peptides would be expected to contribute more to the endogenous burden of nitrosated products than nitrosation of aspartame or Gly peptides.

Language of Publication

English

Unique Identifier

93279602

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MeSH Heading (Major)

Aspartame|*TO; Dipeptides|*TO

MeSH Heading

Animal; Comparative Study; Human; Mutagenicity Tests; Nitrosation; Salmonella typhimurium|DE; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0278-6915

Country of Publication

ENGLAND

Record 48 from database: MEDLINE
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Title

An Equiratio Mixture Model for non-additive components: a case study for aspartame/acesulfame-K mixtures.

Author

Schifferstein HN

Address

Department of Marketing and Marketing Research, Agricultural University, Wageningen, The Netherlands.

Source

Chem Senses, 1996 Feb, 21:1, 1-11

Abstract

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.

Language of Publication

English

Unique Identifier

96233838

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MeSH Heading (Major)

Aspartame|AD/*CH/PD; Sweetening Agents|AD/*CH/PD; Taste|*DE; Thiazines|AD/*CH/PD

MeSH Heading

Adolescence; Adult; Female; Human; Hydrogen-Ion Concentration; Male; Models, Chemical; Taste Threshold

Publication Type

JOURNAL ARTICLE

ISSN

0379-864X

Country of Publication

ENGLAND

Record 49 from database: MEDLINE
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Title

Effect of aspartame loading on plasma and erythrocyte free amino acid concentrations in one-year-old infants.

Author

Filer LJ Jr; Baker GL; Stegink LD

Address

 

Source

J Nutr, 1983 Aug, 113:8, 1591-9

Abstract

Aspartame is a new dipeptide sweetener. It has been suggested that infants metabolize its constituent amino acids (aspartate and phenylalanine) less well than adults. To test this hypothesis, 24 1-year-old infants were administered 34, 50 and 100 mg/kg body weight aspartame in cherry-flavored beverage mix. Plasma amino acid concentrations and the areas under the plasma concentration-time curves (AUC) were determined and were compared with values in adults administered equivalent doses. The doses studied include the 99th percentile of projected ingestion for adults (34 mg/kg), a very high use dose (50 mg/kg body weight), and a potentially abusive dose (100 mg/kg body weight). Plasma aspartate concentrations did not change significantly (P greater than 0.05) at aspartame doses of 34 and 50 mg/kg body weight, but did increase significantly at the 100 mg/kg body weight dose. The change over base line was similar in infants and adults. Aspartame dosing significantly increased both the mean peak plasma phenylalanine concentration and the plasma phenylalanine AUC value in proportion to dose. Mean (+/- SD) peak plasma phenylalanine concentrations in infants were 9.37 +/- 1.44, 11.6 +/- 4.44 and 22.3 +/- 11.5 mumol/100 ml at aspartame doses of 34, 50 and 100 mg/kg body weight, respectively. Values in infants were similar to those noted in adults. The data do not support the suggestion that infants metabolize the amino acids of aspartame less well than adults.

Language of Publication

English

Unique Identifier

83267837

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MeSH Heading (Major)

Amino Acids|*BL; Aspartame|*AD/ME/TO; Dipeptides|*AD; Erythrocytes|*ME

MeSH Heading

Adult; Age Factors; Aspartic Acid|BL; Dose-Response Relationship, Drug; Glutamates|BL; Human; Infant; Phenylalanine|BL; Support, Non-U.S. Gov't; Tyrosine|BL

Publication Type

JOURNAL ARTICLE

ISSN

0022-3166

Country of Publication

UNITED STATES

Record 50 from database: MEDLINE
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Title

The effects of aspartame on mast cells and basophils.

Author

Szucs EF; Barrett KE; Metcalfe DD

Address

 

Source

Food Chem Toxicol, 1986 Feb, 24:2, 171-4

Abstract

The artificial sweetener aspartame was studied to determine whether it had any direct effects on mast cells and basophils. Aspartame was not shown to be a direct mast cell or basophil secretagogue in vitro, or in vivo as assessed by skin testing. During an acute incubation, aspartame did not affect IgE-mediated histamine release from mast cells. However, mast cells cultured in aspartame for periods of up to 9 days showed enhanced rates of proliferation and decreased responsiveness to releasing stimuli. The effect of aspartame on proliferation of cells in culture could be ascribed to a non-specific enhancing effect of its constituent amino acids.

Language of Publication

English

Unique Identifier

86166129

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MeSH Heading (Major)

Aspartame|*PD; Basophils|*DE; Dipeptides|*PD; Mast Cells|*DE

MeSH Heading

Animal; Cell Division|DE; Cell Line; Histamine Release|DE; Human; IgE|PD; Mice; Skin Tests; Support, Non-U.S. Gov't; Time Factors

Publication Type

JOURNAL ARTICLE

ISSN

0278-6915

Country of Publication

ENGLAND

Record 51 from database: MEDLINE
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Title

Consuming aspartame with and without taste: differential effects on appetite and food intake of young adult males.

Author

Black RM; Leiter LA; Anderson GH

Address

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Canada.

Source

Physiol Behav, 1993 Mar, 53:3, 459-66

Abstract

Despite some reports that aspartame (APM)-sweetened beverages may increase subjective appetite, previously we demonstrated that drinking 280 ml of an APM-sweetened soft drink (170 mg APM) had no effect on appetite, and 560 ml of the same soft drink (340 mg APM) reduced appetite. The present study examined this appetite reduction to determine its cause. Eighteen normal weight young adult males received five treatments (beverage preloads) at 1100 h in a randomized order, one per week: 280 ml of carbonated mineral water (CMW) (control), 560 ml of CMW, 280 ml of CMW with 340 mg of encapsulated APM, 280 ml of CMW sweetened with 340 mg APM, 560 ml of an APM-sweetened soft drink (340 mg APM). Subjective hunger and food appeal were measured from 0930 a.m. to 1230 h, and food intake from a buffet lunch offered at 1205 h was measured. Treatment had no effect on food intake or macronutrient selection. Both 560 ml of CMW or soft drink suppressed appetite, although 280 ml of APM-sweetened mineral water significantly increased subjective appetite relative to the control. Encapsulated APM had no effect on appetite. Therefore, appetite reduction following consumption of an APM-sweetened drink is likely due to drink volume and not the APM content. In addition, consuming APM-sweetened CMW produces a short-term increase in subjective appetite.

Language of Publication

English

Unique Identifier

93197378

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MeSH Heading (Major)

Appetite|*DE; Aspartame|*PD; Eating|*DE; Taste|*DE

MeSH Heading

Adult; Food Preferences|DE; Human; Hunger|DE; Male; Satiety Response|DE; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0031-9384

Country of Publication

UNITED STATES

Record 52 from database: MEDLINE
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Title

Effect of dietary aspartame on plasma concentrations of phenylalanine and tyrosine in normal and homozygous phenylketonuric patients.

Author

Mackey SA; Berlin CM Jr

Address

Department of Pediatrics, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.

Source

Clin Pediatr (Phila), 1992 Jul, 31:7, 394-9

Abstract

Six normal subjects each ingested a single 12-oz can of a diet cola (Diet Coke) providing 184 mg aspartame (APM), of which 104 mg is phenylalanine (Phe), and, on another occasion, a single 12-oz can of regular cola (Coke Classic). Neither cola significantly affected plasma concentrations of Phe or tyrosine over the three-hour postingestion study period. Each of five homozygous phenylketonuric (PKU) subjects (ages 11, 16, 17, 21, and 23 years) ingested a single 12-oz can of the same diet cola. In these five subjects (three with classic PKU and two with hyperphenylalinemia), the increase in plasma Phe concentrations varied from 0.26 mg/dL to 1.77 mg/dL two or three hours after ingestion (baseline levels, 5.04 to 17.2 mg/dL). Tyrosine concentrations did not differ significantly from baseline levels. The data indicate that ingestion of dietary Phe, as supplied in a single can of diet cola, is readily handled in both normal and PKU subjects. The small increases in plasma Phe concentrations in the homozygous PKU patients are not considered clinically significant.

Language of Publication

English

Unique Identifier

92315540

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MeSH Heading (Major)

Aspartame|AD/*PD; Phenylalanine|*BL/DE; Phenylketonurias|BL/*DH/GE; Sweetening Agents|AD/*PD; Tyrosine|*BL/DE

MeSH Heading

Adolescence; Adult; Body Weight; Child; Female; Homozygote; Human; Male; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0009-9228

Country of Publication

UNITED STATES

Record 53 from database: MEDLINE
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Title

Intake of saccharin, aspartame, acesulfame K and cyclamate in Italian teenagers: present levels and projections.

Author

Leclercq C; Berardi D; Sorbillo MR; Lambe J

Address

National Institute of Nutrition, Rome, Italy.

Source

Food Addit Contam, 1999 Mar, 16:3, 99-109

Abstract

The intake of saccharin, aspartame, acesulfame K and cyclamate was assessed in 212 Italian teenagers aged 13-19 in 1996. Total daily intake of intense sweeteners was assessed on the basis of dietary records (14 consecutive days). The sweetener content of sugar-free products (soft drinks, candies, chewing gums, yoghurts, jam and table-top sweeteners) was provided by manufacturers. Sugar-free products were consumed by 77% of the subjects. Mean daily intake among consumers was 0.24 mg/kg body weight (bw) for cyclamate (13 subjects), 0.21 mg/kg bw for saccharin (9 subjects), 0.03 mg/kg bw for aspartame (162 subjects), and 0.02 mg/kg bw for acesulfame K (56 subjects). No subject exceeded the ADI (Acceptable Daily Intake) of an intense sweetener. Projections based on the present levels of use of intense sweeteners in sugar-free products and on the dietary pattern observed in the sample suggest that approaching the ADI could be possible only if subjects with high intakes of both soft drinks and table-top sugar substituted these items with respectively sugar-free beverages and table-top sweeteners containing either saccharin or cyclamate.

Language of Publication

English

Unique Identifier

99422370

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MeSH Heading (Major)

Sweetening Agents|*AD

MeSH Heading

Adolescence; Adult; Aspartame|AD; Cyclamates|AD; Diet Surveys; Human; Italy; Maximum Allowable Concentration; Saccharin|AD; Sex Factors; Thiazines|AD

Publication Type

JOURNAL ARTICLE

ISSN

0265-203X

Country of Publication

ENGLAND

Record 54 from database: MEDLINE
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Title

Repeated ingestion of aspartame-sweetened beverages: further observations in individuals heterozygous for phenylketonuria.

Author

Stegink LD; Filer LJ Jr; Bell EF; Ziegler EE; Tephly TR; Krause WL

Address

Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242.

Source

Metabolism, 1990 Oct, 39:10, 1076-81

Abstract

Six adults heterozygous for phenylketonuria (PKU) ingested eight successive servings of unsweetened and aspartame (APM)-sweetened beverage at 1-hour intervals in a randomized, balanced, crossover design. In one part, the eight beverage servings were not sweetened. In the other, each of the eight beverage servings provided 600 mg of APM, a dose equivalent to the amount provided by 36 oz of an APM-sweetened diet beverage. Plasma aspartate concentration was not significantly increased after ingestion of unsweetened or APM-sweetened beverage. Similarly, ingestion of the unsweetened beverage had no significant effect on plasma phenylalanine concentration. However, ingestion of APM-sweetened beverage significantly increased plasma phenylalanine concentrations 2.35 to 4.03 mumol/dL above baseline 30 minutes after ingestion. Plasma phenylalanine values reached a steady-state after administration of five servings of APM-sweetened beverage and were slightly, but significantly higher than usual postprandial values for adults heterozygous for PKU. Similarly, the ratio of the plasma phenylalanine concentration to the sum of the concentration of the large neutral amino acids was significantly higher than usual postprandial values. Blood methanol and formate concentrations remained within normal limits. These data indicate that a fasting adult heterozygous for PKU could consume the equivalent of 24 12-oz servings of APM-sweetened beverage over an 8-hour period and only increase plasma phenylalanine concentration to a modest degree.

Language of Publication

English

Unique Identifier

91014744

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MeSH Heading (Major)

Aspartame|*AD/AE/ME; Heterozygote|*; Phenylketonurias|GE/*ME

MeSH Heading

Adult; Amino Acids|BL; Aspartic Acid|BL; Beverages; Female; Human; Male; Methanol|BL; Phenylalanine|BL; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0026-0495

Country of Publication

UNITED STATES

Record 55 from database: MEDLINE
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Title

Aspartame ingestion with and without carbohydrate in phenylketonuric and normal subjects: effect on plasma concentrations of amino acids, glucose, and insulin.

Author

Wolf Novak LC; Stegink LD; Brummel MC; Persoon TJ; Filer LJ Jr; Bell EF; Ziegler EE; Krause WL

Address

Department of Pediatrics, University of Iowa College of Medicine, Iowa City.

Source

Metabolism, 1990 Apr, 39:4, 391-6

Abstract

Seven subjects homozygous for phenylketonuria (PKU) and seven normal subjects were administered four beverage regimens after an overnight fast: unsweetened beverage, beverage providing carbohydrate (CHO), beverage providing aspartame (APM), and beverage providing APM plus CHO. The APM dose (200 mg) was the amount provided in 12 oz of diet beverage; the CHO was partially hydrolyzed starch (60 g). Plasma amino acid concentrations were determined after dosing and the molar plasma phenylalanine (Phe) to large neutral amino acid (LNAA) ratio calculated. APM administration without CHO did not increase plasma Phe concentrations over baseline values in either normal or PKU subjects (5.48 +/- 0.85 and 150 +/- 23.0 mumols/dL, respectively). Similarly, the Phe/LNAA did not increase significantly. Ingestion of beverage providing APM and CHO did not significantly increase plasma Phe concentrations over baseline values in either normal or PKU subjects. However, ingestion of beverage providing CHO (with or without APM) significantly decreased plasma levels of valine, isoleucine, and leucine 1.5 to 4 hours after dosing in both normal and PKU subjects, thereby increasing the Phe/LNAA ratio significantly. These data indicate that changes noted in Phe/LNAA values after ingestion of beverage providing APM plus CHO were due to CHO. The plasma insulin response to beverage providing CHO (with or without APM) was significantly higher in PKU subjects than in normals.

Language of Publication

English

Unique Identifier

90220328

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MeSH Heading (Major)

Amino Acids|*BL; Aspartame|AD/*PD; Blood Glucose|*ME; Dipeptides|*PD; Insulin|*BL; Phenylketonurias|*BL

MeSH Heading

Adolescence; Beverages; Comparative Study; Diet; Female; Human; Kinetics; Male; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors

Publication Type

JOURNAL ARTICLE

ISSN

0026-0495

Country of Publication

UNITED STATES

Record 56 from database: MEDLINE
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Title

Sweet and bitter taste: structure and conformations of two aspartame dipeptide analogues.

Author

Benedetti E; Gavuzzo E; Santini A; Kent DR; Zhu YF; Zhu Q; Mahr C; Goodman M

Address

Biocrystallography Research Center, CNR, University of Naples Federico II, Italy.

Source

J Pept Sci, 1995 Nov, 1:6, 349-59

Abstract

The synthesis and X-ray diffraction analysis of two dipeptide taste ligands have been carried out as part of our study of the molecular basis of taste. The compounds L-aspartyl-D-alpha-methylphenylalanine methyl ester [L-Asp-D-(alpha Me)Phe-OMe] and L-aspartyl-D-alanyl-2,2,5, 5-tetramethylcyclopentanyl ester [L-Asp-D-Ala-OTMCP] elicit bitter and sweet taste, respectively. The C-terminal residues of the two analogues adopt distinctly different conformations in the solid state. The aspartyl moiety assumes the same conformation found in other dipeptide taste ligands with the side-chain carboxylate and the amino groups forming a zwitterionic ring with a conformation defined by psi, chi 1 = 157.7 degrees, -61.5 degrees for L-Asp-D-Ala-OTMCP and 151.0 degrees, -68.8 degrees for L-Asp-D-(alpha Me)Phe-OMe. In the second residue, a left-handed helical conformation is observed for the (alpha Me)Phe residue of L-Asp-D-(alpha Me)Phe-OMe with phi 2 = 49.0 degrees and psi 2 = 47.9 degrees, while the Ala residue of L-Asp-D-Ala-OTMCP adopts a semi-extended conformation characterized by dihedral angles phi 2 = 62.8 degrees and psi 2 = -139.9 degrees. The solid-state structure of the bitter L-Asp-D-(alpha Me)Phe-OMe is extended: while the crystal structure of the sweet L-Asp-D-OTMCP roughly adopts the typical L-shaped structure shown by other sweeteners. The data of L-Asp-D-(alpha Me)Phe-OMe are compared with those of its diastereoisomer L-Asp-L-(alpha Me)Phe-OMe. Conformational analysis of the two taste ligands in solution by NMR and computer simulations agrees well with our model for sweet and bitter tastes.

Language of Publication

English

Unique Identifier

97366204

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MeSH Heading (Major)

Aspartame|*AA/CH/CS; Taste|*PH

MeSH Heading

Comparative Study; Computer Simulation; Crystallography, X-Ray; Human; Ligands; Models, Molecular; Molecular Structure; Nuclear Magnetic Resonance; Protein Conformation; Solutions; Stereoisomerism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

1075-2617

Country of Publication

ENGLAND

Record 57 from database: MEDLINE
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Title

Metabolic effects of adding sucrose and aspartame to the diet of subjects with noninsulin-dependent diabetes mellitus.

Author

Colagiuri S; Miller JJ; Edwards RA

Address

Department of Endocrinology and Metabolism, Prince of Wales Hospital, Randwick, NSW, Australia.

Source

Am J Clin Nutr, 1989 Sep, 50:3, 474-8

Abstract

This study compared the effects of adding sucrose and aspartame to the usual diet of individuals with well-controlled noninsulin-dependent diabetes mellitus (NIDDM). A double-blind, cross-over design was used with each 6-wk study period. During the sucrose period, 45 g sucrose (9% of total daily energy) was added, 10 g with each main meal and 5 g with each between-meal beverage. An equivalent sweetening quantity of aspartame (162 mg) was ingested during the aspartame period. The addition of sucrose did not have a deleterious effect on glycemic control, lipids, glucose tolerance, or insulin action. No differences were observed between sucrose and aspartame. Sucrose added as an integral part of the diabetic diet does not adversely affect metabolic control in well-controlled NIDDM subjects. Aspartame is an acceptable sugar substitute for diabetic individuals but no specific advantage over sucrose was demonstrated.

Language of Publication

English

Unique Identifier

89371567

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MeSH Heading (Major)

Aspartame|*PD; Diabetes Mellitus, Non-Insulin-Dependent|DH/*ME; Diabetic Diet|*; Dipeptides|*PD; Sucrose|*PD

MeSH Heading

Aged; Blood Chemical Analysis; Blood Glucose|ME; Female; Glucose Clamp Technique; Human; Insulin|ME; Male; Middle Age; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0002-9165

Country of Publication

UNITED STATES

Record 58 from database: MEDLINE
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Title

Aspartame: clinical update [see comments]

Author

Potenza DP; el Mallakh RS

Address

 

Source

Conn Med, 1989 Jul, 53:7, 395-400

Abstract

Since the introduction of aspartame into the American food supply in 1981, it has grown to become the most widely used and accepted artificial sweetener. However, recent published and unpublished reports of headaches, seizures, blindness, and cognitive and behavioral changes with long-term, high-dose aspartame may be cause for concern. Physician awareness of the present clinical and research status of aspartame is important.

Language of Publication

English

Unique Identifier

89337714

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MeSH Heading (Major)

Aspartame|*/AE/AN/ME; Dipeptides|*/AE/AN/ME

MeSH Heading

Human; Phenylalanine|AE/AN/ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0010-6178

Country of Publication

UNITED STATES

Record 59 from database: MEDLINE
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Title

Evaluation of an aspartame loading test for the detection of heterozygotes for classical phenylketonuria.

Author

Silva LC; Pires RF; Coelho JC; Jardim LB; Giugliani R

Address

Department of Biochemistry, Federal University of Rio Grande do Sul, and Clinical Hospital of Porto Alegre, RS, Brazil.

Source

Clin Genet, 1997 Apr, 51:4, 231-5

Abstract

Classical phenylketonuria (PKU) is an inborn error of metabolism of autosomal recessive inheritance characterized by the accumulation of phenylalanine (Phe) in tissues due to Phe-4-hydroxylase deficiency. Several methods have been developed for the detection of PKU heterozygotes based on the determination of plasma Phe and tyrosine (Tyr) levels, on the analysis of the Phe/Tyr and Phe2/Tyr ratios and on the use of discriminant functions. The objective of the present study was to test the value of loading with aspartame (a sweetener consisting of Phe, aspartate and methanol) for the identification of PKU carriers. The study was conducted on 22 obligate heterozygotes and 27 controls. Two blood samples were collected (under fasting conditions and 30 min after the loading) for fluorometric determination of Phe and Tyr. Phe, Phe/Tyr and Phe2/Tyr values were higher in heterozygotes, whereas Tyr was higher in controls in both situations investigated. Linear discriminant function was considered to be the best parameter for differentiation of the individuals in the two groups. Under the conditions employed in the present study, aspartame loading did not show any advantages in discriminating between PKU carriers and normal individuals when compared to the same analysis performed under fasting conditions.

Language of Publication

English

Unique Identifier

97327576

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MeSH Heading (Major)

Aspartame|*AD; Heterozygote Detection|*MT; Phenylketonurias|*GE

MeSH Heading

Evaluation Studies; Female; Human; Male; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0009-9163

Country of Publication

DENMARK

Record 60 from database: MEDLINE
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Title

Effects of acute aspartame and acute alcohol ingestion upon the cognitive performance of pilots.

Author

Stokes AF; Belger A; Banich MT; Taylor H

Address

University of Illinois, Institute of Aviation, Savoy 61874.

Source

Aviat Space Environ Med, 1991 Jul, 62:7, 648-53

Abstract

Anecdotal evidence has associated the artificial sweetener aspartame with a number of symptoms of central nervous system (CNS) dysfunction. There are, however, little scientific data concerning the effect of aspartame upon complex mental operations such as those necessary for flying an aircraft. Thirteen pilots were tested in a double-blind study using the SPARTANS cognitive test battery of aviation-relevant information-processing tasks. These tasks relate to perceptual-motor abilities, spatial abilities, working memory, attentional performance, risk taking, processing flexibility, planning and sequencing ability. Subjects were tested over five sessions consisting of pretest and posttest controls and three randomly ordered treatment sessions. The treatment conditions involved an aspartame dose of 50 mg/kg body weight, a placebo condition, and an ethyl alcohol (0.1% BAL) condition as the positive control. No detectable performance decrements were associated with the aspartame condition, although decrements in psychomotor and spatial abilities were detected in the ethanol condition. Results were found to be consistent with prior flight-simulator studies of alcohol, but do not appear to support the concerns expressed in anecdotal testimony regarding the deleterious effects of aspartame upon cognitive performance.

Language of Publication

English

Unique Identifier

91378842

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MeSH Heading (Major)

Aerospace Medicine|*; Aspartame|*PD; Cognition|*DE; Ethanol|*PD

MeSH Heading

Central Nervous System|DE; Double-Blind Method; Female; Human; Male; Psychomotor Performance|DE; Random Allocation; Space Perception|DE/PH; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0095-6562

Country of Publication

UNITED STATES

Record 61 from database: MEDLINE
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Title

Clinical safety of aspartame.

Author

Yost DA

Address

University of Arizona College of Medicine, Tucson.

Source

Am Fam Physician, 1989 Feb, 39:2, 201-6

Abstract

Aspartame is a synthetic sweetener commonly used in soft drinks and many foods. Even with high doses, the metabolites of this sweetener do not accumulate in toxic amounts. To date, no definite symptom complex has been connected with aspartame, and it is considered safe for use in all populations, including diabetics, phenylketonuric heterozygotes and pregnant women.

Language of Publication

English

Unique Identifier

89132285

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MeSH Heading (Major)

Aspartame|*/AD/AE/ME; Dipeptides|*/AD/AE/ME

MeSH Heading

Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0002-838X

Country of Publication

UNITED STATES

Record 62 from database: MEDLINE
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Title

Evolution of the sweetness receptor in primates. I. Why does alitame taste sweet in all prosimians and simians, and aspartame only in Old World simians?

Author

Glaser D; Tinti JM; Nofre C

Address

Anthropological Institute, University of ZÂurich-Irchel, Switzerland.

Source

Chem Senses, 1995 Oct, 20:5, 573-84

Abstract

In the order Primates the responses to sucrose, alitame and aspartame were ascertained. All primates tested to date like sucrose and prefer this sweet substance to tap water. The artificial dipeptide aspartame was found to be not sweet in Prosimii and Platyrrhini (New World monkeys). Only the Cercopithecoidea (Old World monkeys) and Hominoidea (apes and humans) show the same response to aspartame and to sucrose. In contrast, all primates tested so far prefer alitame, another artificial dipeptide sweetener, which is structurally closely related to aspartame. This phylogenetic difference is consistent with the existence in catarrhine primates of a sweetness receptor containing two differently located hydrophobic recognition sites, one for the hydrophobic binding site of alitame, the other for the hydrophobic binding site of aspartame. On the basis of these results, it is suggested that the alitame-related hydrophobic recognition site, which is found in the sweetness receptor of all primates, could be a requisite for the interaction of the receptor with sucrose, while the aspartame-related hydrophobic recognition site, which is found exclusively in the sweetness receptor of Old World simians, could have been a crucial factor in the improvement in detection or selection of sucrose in foods, so favouring the mental development of these simians and maybe the emergence of humans.

Language of Publication

English

Unique Identifier

96127274

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MeSH Heading (Major)

Aspartame|*PD; Chemoreceptors|DE/*PH; Dipeptides|*PD; Evolution|*; Primates|*PH; Sweetening Agents|*PD

MeSH Heading

Animal; Cebidae; Cercopithecidae; Comparative Study; Human; Pongidae; Species Specificity; Sucrose|PD; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE

ISSN

0379-864X

Country of Publication

ENGLAND

Record 63 from database: MEDLINE
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Title

Soft drinks with aspartame: effect on subjective hunger, food selection, and food intake of young adult males.

Author

Black RM; Tanaka P; Leiter LA; Anderson GH

Address

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Canada.

Source

Physiol Behav, 1991 Apr, 49:4, 803-10

Abstract

Ingestion of aspartame-sweetened beverages has been reported to increase subjective measures of appetite. This study examined the effects of familiar carbonated soft drinks sweetened with aspartame on subjective hunger, energy intake and macronutrient selection at a lunch-time meal. Subjects were 20 normal weight young adult males, classified as either restrained or nonrestrained eaters. Four treatments of carbonated beverages included 280 ml of mineral water, one can of a soft drink (280 ml) consumed in either 2 or 10 minutes, or two cans of a soft drink (560 ml) consumed in 10 minutes, administered at 11:00 a.m. Subjective hunger and food appeal were measured from 9:30 a.m. to 12:30 p.m., and food intake data were obtained from a buffet lunch given at 12:00 noon. There were no treatment effects on energy intake, macronutrient selection or food choice at the lunch-time meal, or food appeal, though restrained eaters consumed more than nonrestrained eaters in all four treatment conditions. Consumption of two soft drinks (560 ml, 320 mg aspartame) significantly reduced subjective hunger from 11:05 a.m. to 11:30 a.m. compared to one soft drink (280 ml, 160 mg aspartame) or 280 ml of mineral water. Thus ingestion of soft drinks containing aspartame did not increase short-term subjective hunger or food intake.

Language of Publication

English

Unique Identifier

91352174

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MeSH Heading (Major)

Aspartame|*PD; Beverages|*/AN; Feeding Behavior|*DE; Food Preferences|*DE; Hunger|*DE

MeSH Heading

Adult; Appetite|DE; Dose-Response Relationship, Drug; Energy Intake|DE; Human; Male; Motivation; Satiety Response|DE; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0031-9384

Country of Publication

UNITED STATES

Record 64 from database: MEDLINE
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Title

Effects of drinks sweetened with sucrose or aspartame on hunger, thirst and food intake in men.