Enhanced adrenomedullary response and increased susceptibility to neuroglycopenia: Mechanisms underlying the adverse effects of sugar ingestion in healthy children


      Objective: Eating simple sugars has been suggested as having adverse behavioral and cognitive effects in children, but a physiologic mechanism has not been established. This study was performed to address this issue. Design: Metabolic, hormonal, and symptomatic responses to a standard oral glucose load (1.75 gm/kg; maximum, 120 gm) were compared in 25 healthy children and 23 young adults, and the hypoglycemic clamp, together with measurements of P300 auditory evoked potentials, was used to assess whether children are more vulnerable than adults to neuroglycopenia. Setting: Children's Clinical Research Center, Yale University School of Medicine. Results: Baseline and oral glucose-stimulated plasma glucose and insulin levels were similar in both groups, including the nadir glucose level 3 to 5 hours after oral administration of glucose (3.4 ± 0.1 mmol/L [61 ± 1.8 mg/dl] in children and 3.5 ± 0.1 mmol/L [63 ± 1.8 mg/dl] in adults). The late glucose decrease stimulated a rise in plasma epinephrine levels that was twofold higher in children than in adults (2260 ± 289 vs 1031 ± 147 pmol/L [407 ± 52 vs 186 ± 26 pg/ml], p < 0.01) and a significant increase in hypoglycemic symptom scores in children ( p < 0.01), but not in adults. During control experiments, in which six of the healthy children ingested a sugar-free drink, there were no significant changes in plasma glucose levels, hormone concentrations, or hypoglycemic symptom scores. During the hypoglycemic clamp, P300 potentials did not change in any of eight adult subjects until the plasma glucose concentration was lowered to 3.0 mmol/L (54 mg/dl), whereas similar changes in P300 potentials were ob-served in six of seven children at glucose levels 3.6 to 4.2 mmol/L (65 to 75 mg/dl). Conclusion: Enhanced adrenomedullary responses to modest reductions in plasma glucose concentration and increased susceptibility to neuroglycopenia may be important contributing factors to adverse behavioral and cognitive effects after sugar ingestion in healthy children. (J P EDIATR 1995;126:171-7)
      To read this article in full you will need to make a payment


        • Wolraich ML
        • Lindgren SD
        • Stumbo PJ
        • Stegink LD
        • Appelbaum MI
        • Kiritsy MC.
        Effect of diets high in sucrose or aspartame on the behavior and cognitive performance of children.
        N Engl J Med. 1994; 330: 301-307
        • Milich R
        • Wolraich M
        • Lindgren SD.
        Sugar and hyperactivity: a critical review of empirical findings.
        Clinical Psychology Review. 1986; 6: 493-513
        • Crook WG.
        Food allergy: the great masquerader.
        Pediatr Clin North Am. 1957; 22: 227-238
        • Rapp DJ.
        Does diet affect hyperactivity?.
        Journal of Learning Disabilities. 1978; 11: 383-389
        • Wender E.
        Review of research of the relationship of nutritive sweeteners and behavior.
        in: Diet and behavior. National Center for Nutrition and Dietetics, Washington, D.C1991: 65-80
        • Amiel SA
        • Simonson DC
        • Sherwin RS
        • Lauritano AA
        • Tamborlane WV
        Exaggerated epinephrine responses to hypoglycemia in normal and insulin dependent diabetic children.
        J PEDIATR. 1987; 110: 832-837
        • Jones TW
        • Boulware SD
        • Kraemer DT
        • Caprio S
        • Sherwin RS
        • Tamborlane WV.
        Independent effects of youth and poor diabetes control on responses to hypoglycemia in children.
        Diabetes. 1991; 40: 358-363
        • Rosenbloom AL
        • Wheeler L
        • Bianchi R
        • Chin FT
        • Tiwary CM
        • Gorgic A.
        Age-adjusted analysis of insulin responses during normal and abnormal glucose tests in normal children and adolescents.
        Diabetes. 1975; 24: 820-828
        • Grant DB.
        Serum-insulin levels in children during glucose tolerance tests.
        Acta Paediatr Scand. 1968; 57: 297-299
        • Amiel SA
        • Simonson DC
        • Tamborlane WV
        • DeFronzo RA
        • Sherwin RS.
        Rate of glucose fall does not affect counterregulatory hormone responses to hypoglycemia in normal and diabetic humans.
        Diabetes. 1987; 36: 518-522
        • Cryer PE
        • Binder C
        • Bolli GB
        • et al.
        Hypoglycemia in IDDM.
        Diabetes. 1989; 38: 1193-1199
        • Heller SR
        • Herbert M
        • MacDonald IA
        • Tattersall RB.
        Influence of sympathetic nervous system on hypoglycemic warning symptoms.
        Lancet. 1987; 2: 359-363
        • Sutton S
        • Tueting P
        • Zubin J
        • John ER.
        Information delivery and the sensing evoked potential.
        Science. 1976; 155: 1436-1439
        • DeFeo P
        • Gallai V
        • Mazzotta G
        • et al.
        Modest decrements in plasma glucose concentrations cause early impairment in cognitive function and later activation of glucose counterregulation in the absence of hypoglycemic symptoms in normal man.
        J Clin Invest. 1988; 82: 436-444
        • Jones TW
        • McCarthy G
        • Tamborlane WV
        • et al.
        Mild hypoglycemia and impairment of brain stem and cortical evoked potentials in healthy subjects.
        Diabetes. 1990; 39: 1550-1555
        • Borg WP
        • During MJ
        • Sherwin RS
        • Borg MA
        • Brines ML
        • Shulman GI.
        Ventromedial hypothalamic lesions in rats suppress counterregulatory responses to hypoglycemia.
        J Clin Invest. 1994; 93: 1677-1682
        • Biggers DW
        • Myers SR
        • Neal D
        • et al.
        Role of brain in counterregulation of insulin-induced hypoglycemia.
        Diabetes. 1989; 38: 7-16
        • Rosen LA
        • Booth SR
        • Bender ME
        • McGrath ML
        • Sorrel S
        • Drabman RS.
        Effects of sugar (sucrose) on children's behavior.
        J Consult Clin Psychol. 1988; 57: 583-589
        • Goldman JA
        • Lerman RH
        • Contois JM
        • Udall JN.
        Behavioral effects of sucrose on preschool children.
        J Abnorm Child Psychol. 1986; 14: 565-577
        • Wender EH
        • Solanto MV.
        Effects of sugar on aggressive and inattentive behavior in children with attention deficit disorder with hyperactivity and normal children.
        Pediatrics. 1991; 88: 960-966
        • Kinsbourne M.
        Sugar and the hyperactive child.
        N Engl J Med. 1994; 330: 355-356