Original Article
Effects of Diets High in Sucrose or Aspartame on The Behavior and Cognitive Performance of Children
N Engl J Med 1994; 330:301-307February 3, 1994
- Abstract
Background
Both dietary sucrose and the sweetener aspartame have been reported to produce hyperactivity and other behavioral problems in children.
Methods
We conducted a double-blind controlled trial with two groups of children: 25 normal preschool children (3 to 5 years of age), and 23 school-age children (6 to 10 years) described by their parents as sensitive to sugar. The children and their families followed a different diet for each of three consecutive three-week periods. One diet was high in sucrose with no artificial sweeteners, another was low in sucrose and contained aspartame as a sweetener, and the third was low in sucrose and contained saccharin (placebo) as a sweetener. All the diets were essentially free of additives, artificial food coloring, and preservatives. The children's behavior and cognitive performance were evaluated weekly.
Results
The preschool children ingested a mean (±SD) of 5600 ±2100 mg of sucrose per kilogram of body weight per day while on the sucrose diet, 38 ±13 mg of aspartame per kilogram per day while on the aspartame diet, and 12 ±4.5 mg of saccharin per kilogram per day while on the saccharin diet. The school-age children considered to be sensitive to sugar ingested 4500 ±1200 mg of sucrose per kilogram, 32 ±8.9 mg of aspartame per kilogram, and 9.9 ±3.9 mg of saccharin per kilogram, respectively. For the children described as sugar-sensitive, there were no significant differences among the three diets in any of 39 behavioral and cognitive variables. For the preschool children, only 4 of the 31 measures differed significantly among the three diets, and there was no consistent pattern in the differences that were observed.
Conclusions
Even when intake exceeds typical dietary levels, neither dietary sucrose nor aspartame affects children's behavior or cognitive function.
Media in This Article
Table 1
Diet Sequences for Two Subjects in a Latin-Square Design for Experimental Diets with a Random Distribution of Sham Diets.Table 2
Cognitive and Behavioral Measures Administered Weekly.Article Activity
- Article
Refined sugar (especially sucrose) and aspartame (α-aspartyl-l-phenylalanine-o-methyl ester) have each been considered a possible cause of hyperactivity and other behavior problems in children1,2. The presumed reaction to sucrose has been attributed to several possible causes, including a rise in blood sugar shortly after ingestion, reactive hypoglycemia several hours after ingestion, and an allergic response3. The presumed reaction to aspartame has been attributed to the possibility that its metabolism results in elevated plasma phenylalanine concentrations, which in turn may alter the transport of essential amino acids to the brain1,4,5.
Despite subjective reports about the behavioral effects of sugar and aspartame, most controlled studies have not found consistent adverse effects6,7. Previous studies with controlled designs have examined the behavior of children immediately after a dietary challenge, but these studies have been criticized for their brief duration and laboratory settings6. Some argue that preschool children may be especially sensitive to sugar8 and that its effects may vary depending on the ratio of sugar to protein and carbohydrate in food recently consumed6. Such arguments have not resolved the issue of whether dietary sweeteners have long-term behavioral effects.
Despite the lack of consistent objective data demonstrating the behavioral or cognitive effects of sugar or aspartame, subjective reports of such adverse effects continue to be widespread. Because sucrose and aspartame are common components of children's diets, any possible relation between these sweeteners and behavior is a major health concern. To test the hypothesis that sucrose or aspartame affects behavior and cognitive performance in children, we evaluated children placed on diets high in sucrose, aspartame, or saccharin (placebo) in a double-blind study with a Latin square design and a broad range of dependent measures.
Methods
Subjects
The subjects were recruited through advertisements in the popular media and presentations at preschool programs. Sugar-sensitive children were identified on the basis of reports by their parents.
Two cohorts of children were studied concurrently. One group consisted of 23 children of primary-school age (6 to 10 years) reported by their parents to respond adversely to sugar, and the other group consisted of 25 normal preschool-age children (3 to 5 years of age).
Design
The study protocol was approved by the University of Iowa Committee on Research Involving Human Subjects. The subjects and their families were placed on a different diet for each of three consecutive three-week periods. One of the three diets was high in sucrose with no artificial sweeteners, another was low in sucrose and contained aspartame, and the third was low in sucrose and contained saccharin (the placebo). All diets were essentially free of additives, artificial food coloring, and preservatives. Two of the diet sequences are shown in Table 1Table 1
Diet Sequences for Two Subjects in a Latin-Square Design for Experimental Diets with a Random Distribution of Sham Diets..The children, their families, and the research staff were kept unaware of the sequence of the diets. This blinding was reinforced by visible changes made weekly in the diets (sham diets), but the sweetener was changed only every third week. Families were informed that the diets would change weekly and were given a list of the dietary components that were either varied or controlled. The parents were asked to identify the experimental variables each week, if they could.
Provision of Diets
Immediately before the beginning of the study, a dietitian supervised the removal of food from the children's home. During the nine-week study period, all foods were provided for the subject and his or her immediate family. Family members were allowed items not included in the diet when they were out of the home and away from the subject, and coffee and alcohol were allowed to remain in the home as long as they were not consumed by the children. The food was delivered in a van equipped to serve as a mobile testing laboratory. All food was removed from the home at the end of each week, and a new supply delivered. In addition, parents kept records of all food consumed by the subjects and were encouraged to report any deviations from the specified diet.
During each three-week diet period, foods were sweetened with sucrose, aspartame, or saccharin, depending on which diet was assigned for that period. Care was taken to keep the appearance of the sweetened products identical, regardless of the sweetener used. Sweetened foods included pure fruit juice, fruit, cereals, pudding, flavored yogurt, cookies, fruit toppings, and bottled carbonated soft drinks. The soft drinks were supplied by three national bottlers in unmarked but coded bottles; unsweetened fruit juice and unsweetened cereal were provided by two national distributors. Small amounts of saccharin were used to sweeten items, such as condiments, that were consumed in small amounts by the subjects during all nine weeks. The use of various food components popularly believed to influence behavior was kept to a minimum. These included artificial colors, artificial flavors, additives, monosodium l-glutamate, chocolate, and caffeine. Shortenings and oils used in the diets did not contain butylated hydroxyanisole or butylated hydroxytoluene, and the use of frozen meats and baked products treated with these antioxidants was kept to a minimum. The three sham diets consisted of abundant quantities of red and orange foods (diet A); beef and pork, with only raw fruits and vegetables (diet B); and chicken and fish, with only cooked fruits and vegetables (diet C) (Table 1).
Dietary Intake
Dietary intake was documented in diaries by the parents and reviewed weekly with the dietitian. Parents were taught how to estimate the amounts of food consumed, and each week they received seven diary sheets listing the daily menus. The study design imposed no restrictions on the quantity of each food consumed, and parents were asked not to restrict access to any food.
Compliance
To determine dietary compliance, 1 mg of ascorbic acid per milligram of aspartame was added to foods sweetened with aspartame, and 1 mg of riboflavin per 5 g of sucrose was added to foods sweetened with sucrose. These concentrations provide at least 10 times the recommended dietary allowances,9 with the amount excreted roughly proportional to the amount of sweetener ingested. Urine samples were obtained weekly and tested for ascorbate, riboflavin, and creatinine10-12.
Behavioral and Cognitive Measures
The children were initially evaluated by means of a structured psychiatric interview with the parent (Diagnostic Interview Schedule for Children -- Parent Version),13 the Wechsler Intelligence Scale for Children -- Revised14 or the Wechsler Preschool and Primary Scale of Intelligence,15 and the Wide Range Achievement Test -- Revised16 (for school-age children only). At base line and during each of the nine weeks of the study, the subjects were evaluated with behavioral and cognitive measures hypothesized to be sensitive to the effects of sweetener (Table 2Table 2
Cognitive and Behavioral Measures Administered Weekly.). During base-line testing, children were oriented to the tests, and appropriate levels of difficulty were determined for the learning and academic tasks. This served to minimize the effects of practice during the study period. Motor activity was assessed with a solid-state device for measuring motion28. Five-second time sampling was used to assess behavior and activity levels during the performance of a writing or drawing task29. Several tasks (e.g., card sorting and academic tests) were too difficult to be administered to the preschool children. Children rated their mood and physical state on a visual-analogue scale20 adapted from a self-report measure used to assess the effects of stimulants in previous studies30. Measures were administered in the mobile laboratory each week on the same day of the week and at the same time of day. In addition, structured ratings of specific types of behavior were completed by the children's parents, the children's teachers, and research assistants (Table 2). For the preschool-age children, the teacher's rating was completed by a preschool teacher or a care giver other than the mother.Biochemical Tests
Base-line biochemical tests included a fasting sucrose-tolerance test and fasting plasma amino acid analyses. Sucrose tolerance was calculated by determining blood glucose concentrations in samples drawn at 0, 0.5, 1, 2, 3, and 4.5 hours after a sucrose drink (1.75 g per kilogram of body weight). On the third, sixth, and ninth weeks of the study, postprandial blood samples for plasma glucose and amino acid analyses were drawn 2 to 3 hours after a meal and 30 to 60 minutes after the subject had drunk 250 ml (8 oz) of an uncarbonated beverage (providing 170 mg of aspartame, 30 g of sucrose, or 40 mg of saccharin). Plasma glucose concentrations were assessed by the glucose-6-phosphate dehydrogenase method. Plasma amino acid levels were determined with automated amino acid analyzers (Beckman 121 MB; Beckman Instruments, Palo Alto, Calif.),31 and these calculations included the molar ratio of the plasma phenylalanine concentration to the sum of the concentrations of the other large neutral amino acids32 sharing its transport to the brain.
Statistical Analysis
The analysis was designed to evaluate a large number of possible effects. At the same time, it was important that significance levels not be set so conservatively that we would incorrectly accept the null hypothesis despite clinically important differences; for this reason, Bonferroni corrections were not applied. Similarly, multivariate analyses were not used because of concern about a reduction in the degrees of freedom and difficulty in handling selective missing data in such analyses. Separate repeated-measures analyses of variance were carried out for each dependent variable, and individual comparisons among the three treatments were made with Tukey's test, each at the 0.05 level of significance. Although this approach increased the chance of a type I error, it maximized our ability to detect any differences attributable to the sweeteners. The use of a counterbalanced Latin square design33 eliminated the possibility that practice or the sequence of the diets would account for differences in the cognitive or behavioral variables.
To increase the reliability of the cognitive and behavioral assessments, the three scores obtained for each dietary period were averaged, and these mean scores were compared by a repeated-measures analysis of variance. To detect possible cumulative effects, the results from the final week of each period were also compared. In addition, analyses of variance were performed to determine whether the sham diets had any influence on the cognitive and behavioral variables. Dietary intake was calculated for each treatment period and for each sham diet during that period. The intake of macronutrients, sweeteners, and vitamin markers was tabulated, and differences were evaluated with an analysis of variance.
To identify individual subjects who may have responded adversely to sugar or aspartame, the weekly scores for each of nine core neurobehavioral measures were ranked and examined to determine whether the poorest scores were clustered during a particular dietary period. This approach was considered preferable to setting a fixed cutoff point for differences (e.g., a 25 percent change) because of the wide variation in raw scores among the variables studied and in score levels at different ages.
Results
Subjects
Fifty-eight subjects were recruited for the study. Pilot studies of the first three subjects were used to refine the protocol; these children were therefore eliminated from the final analysis. Three subjects were eliminated because of poor compliance, as confirmed by the weekly urine tests for ascorbate and riboflavin; three withdrew before completing the study; and one (the youngest) was unable to complete the cognitive and behavioral assessments.
The 48 remaining subjects (25 normal preschool children and 23 school-age children thought to be sensitive to sugar) tended to have average academic skills and above-average intellectual ability, with a mean IQ (±SD) of 125 ±11 and 117 ±10, respectively (range, 95 to 144). The mean number of years of maternal education was 15.5 and 14.7, respectively (range, 12 to 20). The mean age was 4.7 years (range, 3 to 5) in the preschool group and 8.1 years (range, 6 to 10) in the school-age group; 48 percent of the younger children and 78 percent of the older children were boys. No psychiatric disorders were identified in the preschool group. Five of the presumably sugar-sensitive children met the criteria for attention-deficit disorder with hyperactivity, and two of the five also met the criteria for oppositional defiant disorder; two other children met the criteria for oppositional defiant disorder alone.
Dietary Consumption
The preschool children ingested a mean of 5600 ±2100 mg of sucrose per kilogram per day while on the sucrose diet, 38 ±13 mg of aspartame per kilogram per day while on the aspartame diet, and 12 ±4.5 mg of saccharin per kilogram per day while on the saccharin diet. The respective values for the school-age children thought to be sensitive to sugar were 4500 ±1200 mg of sucrose per kilogram, 32 ±8.9 mg of aspartame per kilogram, and 9.9 ±3.9 mg of saccharin per kilogram. The mean daily intake of energy and macronutrients (protein, fat, total carbohydrate, and sucrose), as well as saccharin, aspartame, riboflavin, and ascorbate, is shown in Table 3Table 3
Mean Daily Intake of Energy and Nutrients during the Three-Week Diet Periods.. The intake values were calculated from the dietary records, summarized separately for each experimental period and for each sham diet. The mean daily intake of total carbohydrate and sucrose was approximately 65 g and 82 g higher, respectively, during the sucrose diet than during the other two diets. The daily intake of sucrose, carbohydrate, and energy differed significantly between the sucrose diet and the other two diets. Some small but significant differences among the sham diets were also found for certain variables. The parents of children completing the study reported only a small number of dietary infractions, which were included in the dietary analysis. Only one parent correctly identified the sequence of diets.Behavioral and Cognitive Measures
The mean behavioral and cognitive variables are summarized in Table 4Table 4
Cognitive and Behavioral Variables during the Three Diet Periods.. Two analyses were performed: one compared the mean values for the three-week dietary periods, and the other compared the mean values for the third week alone. The differences were identical in the two analyses, except for differences in pegboard performance, which were evident only in the analysis of the three-week means. Because the analyses were so similar, only the three-week means are presented.In the group of school-age children thought to be sensitive to sugar, none of the 39 behavioral and cognitive variables differed among the three dietary periods. In the normal preschool group, there were no significant differences in the 31 variables, with two exceptions. Parents' ratings on the cognition subscale of the Pediatric Behavior Scale were significantly better during the sucrose diet than during the aspartame and saccharin diets (P<0.008). Pegboard performance was significantly slower during the sucrose diet (Table 4), although it was still faster than average. No child in either group had an adverse response to sucrose or aspartame.
Biochemical Tests
The results of the base-line fasting sucrose-tolerance test were reviewed by a pediatric endocrinologist who was not one of the investigators. All the profiles were within normal limits, except that four subjects had slightly elevated glucose levels (173 to 187 mg per deciliter [9.61 to 10.4 mmol per liter]) one half-hour after the sucrose drink, and four subjects had low levels: three at two hours (55 to 59 mg per deciliter [3.06 to 3.28 mmol per liter]) and one at one hour (50 mg per deciliter [2.78 mmol per liter]). Postprandial glucose concentrations in the two groups of subjects did not differ significantly among the three diets.
Base-line plasma phenylalanine concentrations were similar in the two groups (Table 5Table 5
Postprandial Plasma Phenylalanine and Glucose Concentrations and the Ratio of Phenylalanine to Large Neutral Amino Acids, According to Diet.) and within the normal fasting range (mean of upper and lower limits, 0.81 ±0.13 mg per deciliter [49.0 ±8.0 μmol per liter])34. Postprandial plasma phenylalanine concentrations and the ratio of phenylalanine concentrations to the sum of the values for the other large neutral amino acids were significantly higher than base-line values in both groups during all three diets and were also significantly higher in both groups during the aspartame diet than during the sucrose and saccharine diet. Postprandial plasma phenylalanine values were within the normal range (mean of upper and lower limits, 1.29 ±0.19 mg per deciliter [78.1 ±11.8 μmol per liter]) in both groups during all three diets34.To evaluate the suggestion that people who are allergic to sucrose may need to be free of the nutrient before they respond to a challenge, we examined the data for all the children who were on the sucrose diet during the third dietary period. For each variable, the mean value for this period was subtracted from the mean value for the placebo (saccharin) period and the difference was compared with zero to determine whether there were any significant differences. None were found.
Discussion
The results of this study do not support the hypothesis that a diet high in either sucrose or aspartame adversely affects the behavior or cognitive functioning of children. There were few sweetener-related effects in either the preschool-age or the school-age children, and none of the children in either group had a consistently adverse response to either sucrose or aspartame. The findings were negative even though the older children were selected because their parents believed them to be sensitive to sugar and even though the children in both groups ingested substantial amounts of the sweeteners. Cognitive or behavioral differences were as likely to be found between sham diets as they were between experimental diets, and the few differences associated with the ingestion of sucrose were more consistent with a slight calming effect than with hyperactivity.
The absence of effects in our study could have resulted from the use of insensitive measures or an inadequate statistical power to detect small differences, but neither explanation seems likely. The measures we used have proved to be sensitive to hyperactivity, attention deficits, and the effects of medications and foods in earlier research21,35. In addition, the study design provided sufficient statistical power to detect potential differences if they were present. On the basis of a calculation of power that used three core measures from the three primary sources of data (parents, teachers, and children), the study would have been able to detect an effect with an average size of 0.4 SD with a probability of approximately 0.55 or an effect with a size of 0.6 SD with a probability of 0.9. Given the large number of analyses, the number of differences found is no higher than the number that would be anticipated by chance alone.
Despite the generally negative findings of this study, it is possible that there are some children who respond adversely to sugar or aspartame. Our subjects had average or above-average intelligence, and children with less intellectual ability may respond differently. However, the groups of children we studied should have maximized the likelihood of finding dietary effects. One group was composed of children whose parents considered them sensitive to sugar, and the other consisted of preschoolers, a population reported to be sensitive to dietary effects8.
It could be argued that all three sweeteners had adverse effects. This possibility seems unlikely because behavior ratings and test scores generally improved during the dietary periods, as compared with the base-line values. Also, it is improbable that all three sweeteners could have had equally adverse effects on each of the diverse variables studied. It is particularly unlikely that our failure to observe any effects of aspartame or sucrose ingestion on behavior reflects an insufficient consumption of aspartame or sucrose. Calculations by the Market Research Corporation of America36,37 indicate that the highest daily aspartame intake under normal conditions ranges from 22 to 34 mg per kilogram, with a calculated 99th percentile of 34 mg per kilogram37 -- a value close to that observed in our study (32 mg per kilogram in the school-age subjects and 38 mg per kilogram in the preschool subjects). Data on sucrose intake in children are scarce, and comparisons require calculations. If the energy requirements of a 20-kg 4-to-6-year-old child range from 1300 to 2300 kcal per day, with 17 percent of the energy provided by sugar,9 the sucrose intake ranges from 2800 to 4900 mg per kilogram; similar calculations for a 28-kg 7-to-10-year-old child indicate an intake of 2500 to 5300 mg of sucrose per kilogram. In our study, the sucrose intake was 5600 ±2100 and 4500 ±1200 mg per kilogram in the preschool and school-age children, respectively -- values clearly at the upper end of the normal range.
Large increases in the plasma phenylalanine concentrations (24.78 ±3.80 mg per deciliter [1500 ±230 μmol per liter]) and in the ratio of phenylalanine to the sum of the other large neutral amino acids (4.17 ±1.42; normal value, 0.11 ±0.01) are associated with adverse effects in children with phenylketonuria38. By comparison, these values were much lower in our subjects (Table 5). The slight increases noted in the children in our study while they were on the aspartame diet would be unlikely to produce adverse effects, particularly when these values are evaluated in the light of the data of Waisbren and Levy and colleagues. Their data indicate that untreated mild hyperphenylalaninemia (6.8 mg per deciliter [410 μmol per liter]) in women was associated with a normal outcome in their offspring, including a normal IQ39,40.
We conclude from this carefully controlled nine-week study that neither sucrose nor aspartame produces discernible cognitive or behavioral effects in normal preschool children or in school-age children believed to be sensitive to sugar.
Supported by grants from the National Institute of Child Health and Human Development (HD24751) and the Clinical Research Centers Branch (RR59), National Institutes of Health, and the Nutrition Foundation-International Life Sciences Institute.
We are indebted to Dan Medenblik, Greg Peak, Lisa Marchman, Bridget Zimmerman, Robert Woolson, and Helen DeEmden for assistance with this research, and to General Mills, Libby's NutraSweet, Coca-Cola, PepsiCo, and Royal Crown for supplying products for the study.
Source Information
From the Departments of Pediatrics (M.L.W.) and Psychology and Human Development (M.I.A.), Vanderbilt University, Nashville, and the Department of Pediatrics (S.D.L., L.D.S.) and the Clinical Research Center (P.J.S., M.C.K.), University of Iowa College of Medicine, Iowa City.
Address reprint requests to Dr. Wolraich at the Child Development Center, 2100 Pierce Ave., Nashville, TN 37232-3573.
- References
References
1
Wurtman RJ . Neurochemical changes following high-dose aspartame with dietary carbohydrates. N Engl J Med 1983;309:429-430
Full Text | Web of Science | Medline2
Crook WG . Food allergy -- the great masquerader. Pediatr Clin North Am 1975;22:227-238
Web of Science | Medline3
Wender E. Review of research on the relationship of nutritive sweeteners and behavior. In: Diet and behavior. Washington, D.C.: National Center for Nutrition and Dietetics, 1991:65-80.
4
Pardridge WM . The safety of aspartame. JAMA 1986;256:2678-2678
CrossRef | Web of Science | Medline5
Elsas LJ II, Trotter JF. Changes in physiological concentrations of blood phenylalanine produce changes in sensitive parameters of human brain function. In: Wurtman RJ, Ritter-Walker E, eds. Dietary phenylalanine and brain function. Boston: Birkhauser, 1988:187-95.
6
Milich R ,Wolraich M ,Lindgren S . Sugar and hyperactivity: a critical review of empirical findings. Clin Psychol Rev 1986;6:493-513
CrossRef | Web of Science7
Wolraich ML. Aspartame and behavior in children. In: Wurtman RJ, Ritter-Walker E, eds. Dietary phenylalanine and brain function. Boston: Birkhauser, 1988:201-6.
8
Goldman JA ,Lerman RH ,Contois JH ,Udall JN Jr . Behavioral effects of sucrose on preschool children. J Abnorm Child Psychol 1986;14:565-577
CrossRef | Web of Science | Medline9
National Research Council. Recommended dietary allowances. 10th rev. ed. Washington, D.C.: National Academy Press, 1989.
10
Roe JH ,Kuether CA . The determination of ascorbic acid in whole blood and urine through the 2,4-dinitrophenylhydrazine derivative of dehydroascorbic acid. J Biol Chem 1943;147:399-407
Web of Science11
Baker H, Frank O. Analysis of riboflavin and its derivatives in biologic fluids and tissues. In: Rivlin RS, ed. Riboflavin. New York: Plenum Press, 1975:49-79.
12
O'Brien D, Ibbott FA, Rodgerson DO. Laboratory manual of pediatric micro-biochemical techniques. 4th ed. New York: Harper & Row, 1968:114-6.
13
Costello A, Edelbrock C, Dulcan M, Kalas R, Conover N. Testing of the NIMH diagnostic interview schedule for children (DISC) in a clinical population: final report. Bethesda, Md.: National Institute of Mental Health, 1985.
14
Wechsler Intelligence Scale for Children -- Revised (WISC-R). New York: Psychological Corporation, 1974.
15
Wechsler Preschool and Primary Scale of Intelligence (WPPSI). New York: Psychological Corporation, 1967.
16
Wide Range Achievement Test -- Revised (WRAT-R). Wilmington, Del.: Jastak Associates, 1984.
17
Lindgren SD, Koeppl GK. Assessing child behavior problems in a medical setting: development of the pediatric behavior scale. In: Prinz RJ, ed. Advances in behavioral assessment of children and families. Vol. 3. Greenwich, Conn.: JAI Press, 1987:57-90.
18
Ullmann RK ,Sleator EK ,Sprague RL . A new rating scale for diagnosis and monitoring of ADD children. Psychopharmacol Bull 1984;20:160-164
Medline19
Roberts MA ,Milich R ,Loney J ,Caputo J . A multitrait-multimethod analysis of teachers' ratings of aggression, hyperactivity, and inattention. J Abnorm Child Psychol 1981;9:371-380
CrossRef | Web of Science | Medline20
Lindgren SD. Pediatric assessment of mood. Iowa City: University of Iowa, Department of Pediatrics, 1991.
21
Swanson J, Kinsbourne M. Artificial color and hyperactivity behavior. In: Knights R, Bakker D, eds. Treatment of hyperactive and learning disorders of children. Baltimore: University Park Press, 1980:131-49.
22
Grant DA ,Berg EA . A behavioral analysis of degree of reinforcement and ease of shifting to new responses in a Weigl-type card-sorting problem. J Exp Psychol 1948;38:404-411
CrossRef | Web of Science | Medline23
Lindgren SD, Lyons D. Pediatric assessment of cognitive efficiency (PACE). Iowa City: University of Iowa, Department of Pediatrics, 1984.
24
Pliszka SR . Comorbidity of attention-deficit hyperactivity disorder and overanxious disorder. J Am Acad Child Adolesc Psychiatry 1992;31:197-203
CrossRef | Web of Science | Medline25
Rourke BP ,Yanni DW ,MacDonald GW ,Young GC . Neuropsychological significance of lateralized deficits on the Grooved Pegboard test for older children with learning disabilities. J Consult Clin Psychol 1973;41:128-134
CrossRef | Web of Science | Medline26
Knights RM ,Moule AD . Normative data on the motor steadiness battery for children. Percept Mot Skills 1968;26:643-650
CrossRef | Web of Science | Medline27
Pelham WE, Hoza J. Behavioral assessment of psychostimulant effects on ADD children in a summer day treatment program. In: Prinz RJ, ed. Advances in behavioral assessment of children and families. Vol. 3. Greenwich, Conn.: JAI Press, 1987:3-34.
28
Porrino LJ ,Rapoport JL ,Behar D ,Sceery B ,Ismond DR ,Bynney WE Jr . A naturalistic assessment of the motor activity of hyperactive boys. I. Comparison with normal controls. Arch Gen Psychiatry 1983;40:681-687
Web of Science | Medline29
Roberts MA . A behavioral observation method for differentiating hyperactive and aggressive boys. J Abnorm Child Psychol 1990;18:131-142
CrossRef | Web of Science | Medline30
Rapoport JL ,Buchsbaum MS ,Weingartner H ,Zahn TP ,Ludlow C ,Mikkelsen EJ . Dextroamphetamine: its cognitive and behavioral effects in normal and hyperactive boys and normal men. Arch Gen Psychiatry 1980;37:933-943
Web of Science | Medline31
Stegink LD ,Filer LJ Jr ,Baker GL . Plasma glutamate concentrations in adult subjects ingesting monosodium L-glutamate in consomme. Am J Clin Nutr 1985;42:220-225
Web of Science | Medline32
Fernstrom JD ,Faller DV . Neutral amino acids in the brain: changes in response to food ingestion. J Neurochem 1978;30:1531-1538
CrossRef | Web of Science | Medline33
Winer BJ, Brown DR, Michels KM. Statistical principles in experimental design. 3rd ed. New York: McGraw-Hill, 1991.
34
Stegink LD ,Filer LJ Jr ,Brummel MC , et al. Plasma amino acid concentrations and amino acid ratios in normal adults and adults heterozygous for phenylketonuria ingesting a hamburger and milk shake meal. Am J Clin Nutr 1991;53:670-675
Web of Science | Medline35
Barkley RA. Attention deficit hyperactivity disorder: a handbook for diagnosis and treatment. New York: Guilford Press, 1990.
36
Abrams IJ. Using the menu census survey to estimate dietary intake -- post market surveillance of aspartame. In: Proceedings of the International Aspartame Workshop, Marbella, Spain, November 17-21, 1986. Washington, D.C.: International Life Sciences Institute, Nutrition Foundation, 1986: Session 2, Paper 2.
37
General Foods, Market Research Department. Potential aspartame consumption estimation: research summary. Washington, D.C.: Food and Drug Administration, 1976. (Administrative record no. (Aspartame) 75F-0355.) File volume 103.
38
Wolf-Novak LC ,Stegink LD ,Brummel MC , et al. Aspartame ingestion with and without carbohydrate in phenylketonuric and normal subjects: effect on plasma concentrations of amino acids, glucose, and insulin. Metabolism 1990;39:391-396
CrossRef | Web of Science | Medline39
Waisbren SE ,Schnell R ,Levy HL . Intelligence and personality characteristics in adults with untreated atypical phenylketonuria and mild hyperphenylalaninemia. J Pediatr 1984;105:955-958
CrossRef | Web of Science | Medline40
Levy HL ,Waisbren SE ,Lobbregt D ,Leviton A . Offspring outcome in untreated maternal mild hyperphenylalaninemia (MHP). Pediatr Res 1993;33:Suppl:130A-130A abstract.
CrossRef
- Citing Articles (59)
Citing Articles
1
Susan Dickerson Mayes, Susan L. Calhoun, Rebecca D. Mayes, Sarah Molitoris. (2012) Autism and ADHD: Overlapping and discriminating symptoms. Research in Autism Spectrum Disorders 6:1, 277-285
CrossRef2
Susan Dickerson Mayes, Susan L. Calhoun, Richa Aggarwal, Courtney Baker, Santoshkumar Mathapati, Robert Anderson, Christopher Petersen. (2012) Explosive, oppositional, and aggressive behavior in children with autism compared to other clinical disorders and typical children. Research in Autism Spectrum Disorders 6:1, 1-10
CrossRef3
J. K. Buitelaar. (2011) Understanding comorbidity: from epidemiological designs and model-fitting approaches to systems biology as a new tool. European Child & Adolescent Psychiatry
CrossRef4
Elizabeth A. Hurt, L. Eugene Arnold, Nicholas Lofthouse. (2011) Dietary and Nutritional Treatments for Attention-Deficit/Hyperactivity Disorder: Current Research Support and Recommendations for Practitioners. Current Psychiatry Reports 13:5, 323-332
CrossRef5
Eyassu Abegaz, Dale Mayhew, Harriett Butchko, W Stargel, C Comer. 2011. Aspartame. , 57-76.
CrossRef6
Susan Dickerson Mayes, Susan L. Calhoun, Michael J. Murray, Jahanara Zahid. (2011) Variables Associated with Anxiety and Depression in Children with Autism. Journal of Developmental and Physical Disabilities 23:4, 325-337
CrossRef7
H C Storey, J Pearce, P A L Ashfield-Watt, L Wood, E Baines, M Nelson. (2011) A randomized controlled trial of the effect of school food and dining room modifications on classroom behaviour in secondary school children. European Journal of Clinical Nutrition 65:1, 32-38
CrossRef8
Susan Dickerson Mayes, Susan L. Calhoun, Michael J. Murray, Meesha Ahuja, Laura A. Smith. (2011) Anxiety, depression, and irritability in children with autism relative to other neuropsychiatric disorders and typical development. Research in Autism Spectrum Disorders 5:1, 474-485
CrossRef9
D. Benton. 2011. Carbohydrate consumption, mood and anti-social behaviour. , 160-179.
CrossRef10
Nathaniel Riggs, Chih-Ping Chou, Donna Spruijt-Metz, Mary Ann Pentz. (2010) Executive Cognitive Function as a Correlate and Predictor of Child Food Intake and Physical Activity. Child Neuropsychology 16:3, 279-292
CrossRef11
Fabienne Klaus, Thomas Hauser, Lutz Slomianka, Hans-Peter Lipp, Irmgard Amrein. (2009) A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice. Behavioural Brain Research 204:1, 175-181
CrossRef12
Susan Dickerson Mayes, Susan L. Calhoun. (2009) Variables related to sleep problems in children with autism. Research in Autism Spectrum Disorders 3:4, 931-941
CrossRef13
Nerissa L Soh, Garry Walter, Louise Baur, Clare Collins. (2009) Nutrition, mood and behaviour: a review. Acta Neuropsychiatrica 21:5, 214-227
CrossRef14
Marianne M. Glanzman. (2009) ADHD and nutritional supplements. Current Attention Disorders Reports 1:2, 75-81
CrossRef15
Louisa J. Ells, Frances C. Hillier, Janet Shucksmith, Helen Crawley, Laurence Harbige, Julian Shield, Andy Wiggins, Carolyn D. Summerbell. (2008) A systematic review of the effect of dietary exposure that could be achieved through normal dietary intake on learning and performance of school-aged children of relevance to UK schools. British Journal of Nutrition 100:05, 927
CrossRef16
Jaswinder K. Ghuman, L. Eugene Arnold, Bruno J. Anthony. (2008) Psychopharmacological and Other Treatments in Preschool Children with Attention-Deficit/Hyperactivity Disorder: Current Evidence and Practice. Journal of Child and Adolescent Psychopharmacology 18:5, 413-447
CrossRef17
David Benton, . (2008) The influence of children’s diet on their cognition and behavior. European Journal of Nutrition 47:S3, 25-37
CrossRef18
Susan Dickerson Mayes, Susan L. Calhoun, Edward O. Bixler, Alexandros N. Vgontzas. (2008) Nonsignificance of Sleep Relative to IQ and Neuropsychological Scores in Predicting Academic Achievement. Journal of Developmental & Behavioral Pediatrics 29:3, 206-212
CrossRef19
S. D. Mayes, S. L. Calhoun, E. O. Bixler, A. N. Vgontzas, F. Mahr, J. Hillwig-Garcia, B. Elamir, L. Edhere-Ekezie, M. Parvin. (2008) ADHD Subtypes and Comorbid Anxiety, Depression, and Oppositional-Defiant Disorder: Differences in Sleep Problems. Journal of Pediatric Psychology 34:3, 328-337
CrossRef20
David Benton. (2008) Sucrose and Behavioral Problems. Critical Reviews in Food Science and Nutrition 48:5, 385-401
CrossRef21
Wee Bin Lian, Selina Ho Kah Ying, Sylvia Choo Henn Tean, Daisy Chan Kwai Lin, Yeo Cheo Lian, Ho Lai Yun. (2008) Pre-school teachers' knowledge, attitudes and practices on childhood developmental and behavioural disorders in Singapore. Journal of Paediatrics and Child Health 44:4, 187-194
CrossRef22
Wendy Weber, Sanford Newmark. (2007) Complementary and Alternative Medical Therapies for Attention-Deficit/Hyperactivity Disorder and Autism. Pediatric Clinics of North America 54:6, 983-1006
CrossRef23
Scott Sicherer. 2007. Food Allergy. , 1111-1123.
CrossRef24
Suzanne Domel Baxter. 2007. Nutrition for Healthy Children and Adolescents Aged 2 to 18 Years. , 285-344.
CrossRef25
Terry B. Ernest, David P. Elder, Luigi G. Martini, Matthew Roberts, James L. Ford. (2007) Developing paediatric medicines: identifying the needs and recognizing the challenges. Journal of Pharmacy and Pharmacology 59:8, 1043-1055
CrossRef26
C. Hausteiner, S. Bornschein, T. Zilker, H. Förstl, J. Graßmann. (2007) Über den möglichen Einfluss der Ernährung auf die psychische Gesundheit. Der Nervenarzt 78:6, 696-705
CrossRef27
R. Hammersley, M. Reid, M. Duffy. (2007) How may refined carbohydrates affect satiety and mood?. Nutrition Bulletin 32:s1, 61-70
CrossRef28
David Benton. (2007) The impact of diet on anti-social, violent and criminal behaviour. Neuroscience & Biobehavioral Reviews 31:5, 752-774
CrossRef29
Manfred Kroger, Kathleen Meister, Ruth Kava. (2006) Low-calorie Sweeteners and Other Sugar Substitutes: A Review of the Safety Issues. Comprehensive Reviews in Food Science and Food Safety 5:2, 35-47
CrossRef30
Shahid A. Bangash, Sami L. Bahna. (2005) Pediatric food allergy update. Current Allergy and Asthma Reports 5:6, 437-444
CrossRef31
Neal L. Rojas, Eugenia Chan. (2005) Old and new controversies in the alternative treatment of attention-deficit hyperactivity disorder. Mental Retardation and Developmental Disabilities Research Reviews 11:2, 116-130
CrossRef32
Robin Kanarek, Caroline Mahoney, Holly Taylor. 2005. The Acute Effects of Meals on Cognitive Performance. .
CrossRef33
PATRICIA MURPHY, SERGEI S. LIKHODII, MOHAMMAD HATAMIAN, W MCINTYRE BURNHAM. (2005) Effect of the Ketogenic Diet on the Activity Level of Wistar Rats. Pediatric Research 57:3, 353-357
CrossRef34
Djin Gie Liem, Monica Mars, Cees De Graaf. (2004) Sweet preferences and sugar consumption of 4- and 5-year-old children: role of parents. Appetite 43:3, 235-245
CrossRef35
Brandon Christian, Kenneth McConnaughey, Elena Bethea, Scott Brantley, Amy Coffey, Leigha Hammond, Shelly Harrell, Kasee Metcalf, Danielle Muehlenbein, Willie Spruill, Leslie Brinson, Mona McConnaughey. (2004) Chronic aspartame affects T-maze performance, brain cholinergic receptors and Na+,K+-ATPase in rats. Pharmacology Biochemistry and Behavior 78:1, 121-127
CrossRef36
(2004) Position of the American Dietetic Association: Use of Nutritive and Nonnutritive Sweeteners. Journal of the American Dietetic Association 104:2, 255-275
CrossRef37
Edward A. Neuwelt. (2004) Mechanisms of Disease: The Blood-Brain Barrier. Neurosurgery 54:1, 131-142
CrossRef38
Alexander Lucas, Diane Olson, F Karen Olson. 2002. Food Intake Management in Patients with Psychiatric Disorders. , 291-306.
CrossRef39
EUGENIA CHAN. (2002) The Role of Complementary and Alternative Medicine in Attention-Deficit Hyperactivity Disorder. Journal of Developmental and Behavioral Pediatrics 23:Supplement, S37-S45
CrossRef40
H Butchko. (2001) Aspartame: Scientific Evaluation in the Postmarketing Period. Regulatory Toxicology and Pharmacology 34:3, 221-233
CrossRef41
Victor Herbert, Stephen Barrett. 2001. Questionable Practices in Foods and Nutrition. .
CrossRef42
Suzanne Domel Baxter. 2001. Nutrition for Healthy Children and Adolescents Ages 2 to 18 Years. .
CrossRef43
L. EUGENE ARNOLD. (2001) Alternative Treatments for Adults with Attention-Deficit Hyperactivity Disorder (ADHD). Annals of the New York Academy of Sciences 931:1, 310-341
CrossRef44
C. Keith Haddock, Patricia L. Dill. (2000) The Effects of Food on Mood and Behavior: Implications for the Addictions Model of Obesity and Eating Disorders. Drugs & Society 15:1-2, 17-47
CrossRef45
Christopher J LaBuda, Robert L Hale. (2000) Anxiety in mice following acute aspartame and ethanol exposure. Alcohol 20:1, 69-74
CrossRef46
Mark L Wahlqvist, Bridget H-H Hsu-Hage, Widjaja Lukito. (1999) Clinical trials in nutrition. Asia Pacific Journal of Clinical Nutrition 8:3, 231-241
CrossRef47
(1998) Position of the American Dietetic Association. Journal of the American Dietetic Association 98:5, 580-587
CrossRef48
M. Wolraich. 1998. HYPERACTIVITY. , 475-479.
CrossRef49
Richard Hammersley, Marie Reid. (1997) Are Simple Carbohydrates Physiologically Addictive?. Addiction Research & Theory 5:2, 145-160
CrossRef50
Brenda S. Brownlow, Anne Petro, Mark N. Feinglos, Richard S. Surwit. (1996) The role of motor activity in diet-induced obesity in C57BL/6J mice. Physiology & Behavior 60:1, 37-41
CrossRef51
CHARLES W. POPPER, BRIAN ZIMNITZKY. (1996) Child and Adolescent Psychopharmacology Update: January 1994–December 1994. Journal of Child and Adolescent Psychopharmacology 6:1, 1-40
CrossRef52
Joseph Levine, Aliza Ring, Yoram Barak, Avner Elizur, R. H. Belmaker. (1995) Inositol may worsin attention deficit disorder with hyperactivity. Human Psychopharmacology: Clinical and Experimental 10:6, 481-484
CrossRef53
J. O. WARNER. (1995) Food and behaviour. Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy 25:s1, 23-26
CrossRef54
A. R. P. Walker. (1995) Nutritional and dental implications of high and low intakes of sugar. International Journal of Food Sciences and Nutrition 46:2, 161-169
CrossRef55
Jo-Anne Bachorowski, Joseph P. Newman, Dian A. Gans, Alfred E. Harper, Sharon L. Nichols, Steven L. Taylor. (1994) Effects of sucrose ingestion on juvenile offenders with low, borderline, and normal nadir serum glucose values. Personality and Individual Differences 17:6, 833-843
CrossRef56
JWS. (1994) Food and attention deficit hyperactivity disorder. European Journal of Pediatrics 153:8, 611-612
CrossRef57
(1994) Sugar and Children's Behavior. New England Journal of Medicine 330:26, 1901-1904
Full Text58
Robin B. Kanarek. (1994) Does Sucrose or Aspartame Cause Hyperactivity in Children?. Nutrition Reviews 52:5, 173-175
CrossRef59
Kinsbourne, Marcel, . (1994) Sugar and the Hyperactive Child. New England Journal of Medicine 330:5, 355-356
Full Text
- Letters
