ORIGINAL

ARTICLES

Enhoncedodrenomedullory response
ond increosedsusceptibility to
neuroglycopenio : Mechonisms
underlyingthe odverseeffects of sugor
i n g e s t i o ni n h e o l t h yc h i l d r e n
TimothyW. Jones,vo, Wolterp. Borg,vo. SusonD. Boulwore.
uo.
GregoryMcCorthy,pno.RobertS.Sherwin,vo, ond
WilliomV. Tomborlone,MD
Fromthe Deportmentsof Pediotrics,
InlernolMedicine,ond Neurosurgery
ond the Generol
centers,yole university
clinicolReseorch schoolof Medicine,New Hoven,connecticut

oblecllve: Eoling simple sugors hos been suggesled os hoving odverse behov-
lorol ond c.ognlllve ellecls in children, buf o physiologic me-chonism hos not
been esloblished. rhis srudy wos performed to oddresJ thls lssue.
Deslgn: Metobollc, hormonol, ond symptomofic responEes lo o slonctqrd orol
glucose lood (1.75 gm/kg; moxlmum, r20 gm) were compqred In 25 heolthy
children ond 23 young odults, ond lhe hypoglycemlc clomp, logether wilh
meosuremenls of p300 oudlfory evoked polenliols, wqs used fo ossesswhether
chlldren ore more vulneroble lhon odulls to neuroglycopenlo.
SettlngzChlldren's Cllnicol ReseorchCenler, Yole UniversltySchool ot Medtcine.
Pesults|Bosellne ond olol glucose-siamuloted plosmo glucose ond insulin lev_
els were simllor in bofh groups, including fhe nodir glucose level 3 to s hours of-
ler orql odmlnlslrollon ol glucose (3.4 -r 0.1 mmol/t (6,1r l.g mg/dl) in children
ond 3.5 r- 0.t mmol/t (63 -* l.E mg/dtt in odulfs). rhe lole glucose decleose
sllmuloted o lise ln plosmo epln6phrlne levets thol wos fwololJ hlgher In chlldren
lhon fn odulls (2260 t 269 vs t03t + 147 pmo'/L l4o7 -r 52 vs tg6 + 26 pg/mll, p
<0.0{) ond o slgniflconl increose in hypoglycemic symplom scores in chlldren
(p <0.0f )' bul nol ln qdulls. During conlrol experimenls, In which stx ot the heolthy
chlldren Ingesfed q sugor-tree drlnk, lhere were no slgnlficont chonges In
ploimo glucose levels, hormone concenlrollon!, or hypoglycemlc sympfom
scores. Durlng lhe hypoglycemic clomp, p300 polenilols dld not chonge In ony
ot eighl odull sublecls unlll lhe plosmo glucose concenlrollon wos lowered to
3.0 mmol/L (54 mg/dl), whereos similor chonges ln p300 polenilqls were ob-
served ln slx of seven chlldren of glucose levels 3.6 lo 4.2 mmol/l (65 fo 75
m9/dl).
concluslon: Enhonced odrenomedullory responses lo modest reducllons in
plosmo glucose concenlrolion ond Increosed suscepilblllty fo neuroglycope-
nlo moy be impoilonl conltlbuting locfors lo qdverse behqvlorol ond Jognlfive
eftecls ofler sugor ingesllon in heolthy children. (J peoren ig95;126:ll1-71

Supportedby grants RR06022, RR00125, DK20495, and Reprint requests:William V. Tamborlane,MD, Departmentof
HD3067l from the NationalInstitutesof Healthand by a grant Pediatrics,Yale University Schoolof Medicine, 333 Cedar St..
fromthe JuvenileDiabetesFoundationInternational. New Haven,CT 06510-8064.
Copyrighto 1995by Mosby-Year Book, Inc.
Submitted
for publicationSept.6, 1994;acceptedOcr,.26,1994. 0022-3476lesl$3.00
t + 0 9/2o/6rs76
I
I
I
I
t7l
172 Joneset al.
The question of whether refined sugar adverselyaffects the
behavior or cognitive functions of healthy children is a con-
tinuing source of controversy. Whereas parents and clini-
cians have frequently reported that even healthy children
are prone to the development of behavioral changes and
cognitive defectsafter eating simple sugars,the outcomesof
research studies have been complex and discrepant.l-aIn
addition, possible physiologic mechanisms for enhanced
sensitivity to dietary sugar during childhood have not been
clear. The presumed negative reactionsto sugar have been
attributed to an early rise or late fall in the plasma glucose
concentration, and to an immunologic responseto sucrose.5
Unfortunately, given the lack of consistentobjectivedata to
substantiatetheseassumptions,all thesehypothesesremain
open to questron.
The results of our previous studies of counterregulatory
respons€sto hypoglycemia in children6'7 prompted us to
propose a new hypothesis to explain the mechanisms
underlying adverseeffectsof sugar ingestionin children. We
hypothesizedthat, although the changesin plasma glucose
levels after sucrose ingestion do not differ between adults
and children, the children would show enhanced adreno-
medullary and symptomatic responsesto these changesin
comparison with those of adults. Several lines of evidence
See related article, p. l7E.
support this hypothesis.Although sugar ingestion does not
normally causeseverereductionsin plasma glucoselevelsin
the late postprandialperiod in children,s'eour previous
study showed that plasma epinephrineresponsesto identi-
cal, modest insulin-induced reductions in plasma glucose
are twofold greater in healthy children than in healthy
adults.6 In addition, the plasma glucoselevel that triggers
epinephrinereleaseand symptoms is substantiallyhigher in
children than in adults,T reaching values (plasma glucose
levels4.4 to 3.4 mmol/L [80 to 6l rng/dl]) that are com-
monly observed 3 to 5 hours after oral glucose ingestion.
To test our hypothesis,we compared the metabolic, hor-
monal, and symptomatic responsesof healthy children and
healthy young adults with a standardized, large glucose
load. In addition, the hypoglycemic clamp technique was
combined with serial measurementsof cortical auditory
evokedpotentials to assesswhether young subjectsare more
susceptibleto the adverseeffectsof reduced glucoseavail-
ability on cognitive function.
METHODS
Subjects. Forty-eight nonobesesubjects(25 children' 23
adults) were studied. To be eligible, the subjectshad to be
The Journal of Pediatrics
Februarv 1995
healthy, taking no medications, and have no history of di-
abetesor carbohydrate intolerance. The children included
eight boys and 17 girls between 8 and 16 years of age; the
adults included 9 men and 14 women between 20 and 30
years of age. Subjects with attentional, behavioral, or psy-
chiatric problems or with a history of unusual sensitivity to
sugar were excluded from the study. All subjectswere con-
suming weight-maintaining diets containing at least 115
gm/mz body surface area of carbohydratesper day before
the study. Ofthe 25 children, eight were prepubertal (Tan-
ner stage I), and the other l7 had Tanner stage II to IV de-
velopment.Bodymassindex(mean + SD)averaged18.2 +
2.2kglm2 in the children and22.6 -r 2.8 in the adults. The
study was approvedby the Yale University School of Med-
icine Human Investigation Committee, and informed writ-
ten consentwas obtained from all subjectsand their parents
(for the children).
Procedures.All subjectswere admitted to the Yale Gen-
eral Clinical ResearchCenter, where a history was obtained
and a physical examination performed. The studies were
started between8 and 8:30 epr, after the subjectshad been
fasting for l0 to 12 hours overnight. With all procedures,
an intravenouscatheter was inserted in a vein of a hand or
distal portion of a forearm for blood sampling, and that
"arterial-
hand was kept in a heated box (60o to 65" C) to
ize" the blood.
Oral glucose loading. All subjects took part in the oral
glucose loading study. They were allowed to rest for at least
30 minutes after insertion of the blood sampling catheter
before baselinemeasurementswere obtained. Glucosewas
ingestedin a dosageof 1.75 gm/kg body weight to a max-
imum of 120 gm (actual amount, I l0 + 5 gm in adults and
86 + 6 gm in children [mean + SD]) with a decaffeinated
cola preparation (General Medical Corp., Richmond, Va.).
Blood sampleswere obtained every l0 minutes from -30 to
300 minutes for measurementof the plasma glucose con-
centration, and every 30 minutes for measurement of
plasma levels of insulin, catecholamines,and other coun-
terregulatory hormones (growth hormone, cortisol, and
glucagon).
Each of the subjectsrated a list of symptoms before and
every 60 minutes after glucose ingestion, as previously de-
scribed. Symptoms (recorded on a lap-top computer) were
rated on a scale of I (not at all) to 7 (extreme). The eight
hypoglycemic symptoms included pounding heart, feeling
shaky, feeling weak, having difficulty concentrating, head-
aches,feeling anxious, slowed thinking, and feeling sweaty.
The sum of these symptoms at each observation point con-
stituted the total hypoglycemic symptom score at that time.
In addition, four filler items (earache, pain in joints, watery
eyes,and ringing in ears) were included to account for non-
The Journal of pediatrics
Volume126,Number 2
specificeffects not referable to glucoseand antiinsulin hor-
mones.
Control experiments were also performed in three boys
and three girls, aged 10 + 3 years (mean r- SD), who had
participated in the oral glucoseloading studies.These con_
trol experiments were performed as describedabove; how_
ever, the oral glucoseload was replacedby an equal volume
of sugar-free decaffeinatedcola drink (Coca-Cola Co., At_
lanta. Ga.).
Hypoglycemic clamping. Eight of the children, aged
ll + 2 years (mean + SD), and eight of the adults,aged
24 -t 2 years, who had taken part in oral glucose loading
experiments participated in the clamp protocol. However,
the cortical evoked potentials of one of children could not
be analyzed becauseof technical problems and was not rn-
cluded in the analysis of electrophysiologicdata.
The methods used for the hypoglycemicclamp have been
describedin detail elsewhere.l0For this procedure,a second
cathcter was inserted in an antecubital vein in the arm op-
posite to the blood-sampling hand for administration of ex-
ogenous glucose and insulin.
After a 30-minute rest period, three blood sampleswere
obtained during a 40-minute interval for measurementof
baselinc glucose and hormone levels.A primed continuous
infusion of rapid-acting human insulin (Novolin; Novo
Nordisk, Princeton, N.J.) was then begun at a continuous
rate of 480 pmol . m-2 . min-I.
After the insulin infusion was begun, the desired plasma
glucose level was achieved by varying the rate of 20Vogltt-
cose infusion on the basis of measurementsof plasma glu-
cose obtained at S-minute intervals. Blood samples for
measurementof insulin and epinephrinewere taken at 20-
minute intervals throughout the study. In all subjects,
plasma glucosewas initially maintained at fasting euglyce-
mic levelsfor 60 minutes and then reducedin hourly -Q.J6
mmol/L (10 mg/dl) steps to a nadir of 3.0 mmol/L (54
mg/dl). The subjectswere masked to plasma glucoselevels
during the study.
Electrophysiologic recordings were obtained during the
last l0 to 15 minutes of each glycemicplateau.Scalp elec-
trodes were placed at the C, and P, positions,with a refer-
ence electrode placed on one ear and the ground electrode
placed on the opposite ear. A bipolar pair of electrodeswas
placed above and below the right eye to monitor for ocular
artifacts. The P300 evokedpotentialswere obtained with an
auditory categorization ("oddball") task in which subjects
were required to count silently the number of soft clicks de-
livered in a train consistingof a random mix of frequent loud
and infrequent soft clicks. The loud clicks were presentedto
the ear ipsilateral to the reference electrode, and the soft
clicks wcre deliveredto the ear contralateral to the reference
Joneset al. 173
electrode.The proportion ofsoft clicks varied between l0Zo
aad 20Vaof 200 clicks, and subjectsreported their count of
soft clicks at the end of each run. Two replicationswere ob-
tained at each baseline(before insulin infusion) and at each
plasma glucose plateau.
f)eterminations.Plasma glucose was measuredin dupli_
cate at the bedsidewith a glucose analyzer (Beckman In_
struments Inc., Fullerton, Calif.). Epinephrine and norepi_
nephrine were measured with a radioenzymatic assay
(Amersham Corp., Arlington Heights, Ill.), glucagon (ICN
Biomedicals,Inc., Costa Mesa, Calif.), cortisol (Diagnostic
Products Corp., Los Angeles, Calif.), and growth hormone
(Kallestad Diagnostic Inc., Chaska, Minn.) were deter_
mined by radioimmunoassay.The intraassaycoefficientsof
variation for these assayswere as follows: for epinephrine,
20.2Voat 175 pmol/L (31.5 pg/ml) and 6.j%oat l168
pmol/L (210 pg/ml); for growth hormone, 6.2Voat 3.5
pg/L (3.5 nglml); for glucagon,9Vaat t22 ng/L (t22 pgl
ml); and for cortisol, l2go.Plasma insulin was measuredby
double-antibody radioimmunoassay (Binax Inc., South
Portland, Maine).
Statistical methods and analyses. Glucose and hormone
responsesto orally administered glucoseand during clamp
studies were compared betweon groups by analysis of var!
ance with repeated measures design. Other comparisons
were made by analysisof variance,unpaired Student , test,
and chi-square analysis where appropriate. The p values
(0.05 are reported as significant.
Group differencesin symptom scores after glucose in-
gestion were examined with time and at the plasma glu-
cosenadir. For the latter comparison,the symptom assess-
ment that occurred at or immediately after the nadir
plasma glucoselevel in each subject was used. During the
hypoglycemicclamp procedure,the plasma glucosethresh-
old for epinephrine releasein each individual subject was
defined as the glucoselevel at which a sustainedelevation
of >410 pmol/L Qa pg/ml\ above basal values was ob-
served, as previously described.TThe glycemic threshold
for changesin P300 potentials in individual subjectsduring
the clamp procedure was defined as the plateau plasma
glucoselevel at which a 30Voor greater reduction in p300
amplitude was observed.Demographic data are presented
as mean + SD, whereas other data are presented as
mean + sEM.
RESULTS
Glucose ingestion. Basal plasma glucose levels and plas-
ma insulin levels (55 + 5 pmol/L [8.8 t 0.8 pUlm|
in children;60 {- 5 pmol/L [9.6 + 0.E pUlm[ in adults)
were similar in both groups, and the glucose and insu-
lin profiles were similar in children and adults after glucose
,,,t,rRU
11 4 Jones et al The Journal of Pediatrics
Februarv 1995

Ioble l. Basal and nadir plasma glucoseand basal and Toble ll. Total hypoglycemic and filler (control)
peak hormone concentrations (mean -r SEM) after symptom scoresat baselineand at the postprandial
glucose load glucose nadir

Chlldren Adults Children Adulfs

P l a s m a / g l u c o s e( m m o l / L ) Glucose Glucose
Basal 4.6 + 0.1 4.8+ 0.1 Boseline nodir Soieline nodll
Peak ?.5 + 0.3 8.1 + 0.4
Nadir 3.4 + 0.1 3.5+ 0.1 Total hypoglycemic scores
P l a s m a e p i n e p h r i n e( p m o l / L ) Mean 12.8 22.O' l0.o l 3.o
Basal 229 + 27 I9l + 27 sE 1.0 3.0 0.5 1.7
Peak 2260 + 289* l03l + 147 Filler (control) scores
Plasma growth hormone (pg/L) Mean 5.0 5.5 5.0 5.2
Basal 1.7+ 0.3 l.l + 0.2 sE 0.5 0.6 0.4 0.5
Peak 1 9 . 5+ 2 . 5 1 8 . 3+ 2 . 8 tp <0.01 versus baseline.

Plasma glucagon (ng/L)

Basal 94+12 1 2 0+ l 8
Peak 2 0 1+ 3 l 180 + 25
To convert to metric units: multiply glucosevalue by 18. epinephrinevalue
by 0.I8. growth hormone value by 1.0, and glucagon value by L0.
tp <0.01 versus adults.
ingestion (data not shown). Peak and nadir plasma glu-
cose levels observed in the postprandial period in individ-
ual subjects determined by frequent sampling (every 10
minutes) were virtually identical in children and adults
(Table I).
Baseline plasma epinephrine levels were similar, and
mean epinephrine concentrationsrose in both groups in re-
sponseto the late postprandial fall in plasma glucose (Ta-
ble I). However, the rise in the plasma concentration of
epinephrinewas significantly greater in the children, reach-
ing peak values that were nearly twofold higher in the chil-
dren than in the adults (p <0.01) (Table I). On the oth-er
hand, peak postprandial plasma growth hormone and glu-
cagon levelsdid not differ betweenthe groups.Basal plasma
concentrationsof cortisol and norepinephrinewere similar
in healthy children and adults, and levelsof thesehormones
did not change significantly in either group after oral glu-
cose (data not shown). Results of subgroup analysesfailed
to demonstrate a significant effect of gender or pubertal
stageon the rise in epinephrinelevelsafter glucoseingestion
by the 25 healthy children.
Total hypoglycemic and filler (control) symptom scores
were similar in both groups at baseline(Table II), and the
symptom scores remained unchanged in the adults after
glucoseingestion. In contrast, total hypoglycemicsymptom
scoresrose sharply in the children in associationwith the
late fall in plasma glucoseconcentration (p <0.01 vs base-
line). As in the adults, filler (control) symptom scoresdid
not changein the children throughout the study. The change
in hypoglycemic symptom scoresin the children was mainly
due to significantly increased reporting of feeling shaky
(from 1.7 + 0.2 to 3.2 + 0.6), sweaty(1.5 + 0.2 to 2.8 +
0.5), or weak (1.9 + 0.3 to 3.8 + 0.5), or having a
pounding heart I ."7+ 0.2 to 2.5 + 0.5) (p (0.05 vs base-
line).
ln contrast to the response to glucose ingestion, no
changesin plasma epinephrine levels were observedafter
the sugar-free cola drink. As a result, plasma epinephrine
levelswere significantly higher after glucoseingestion ver-
suscontrol valuesat 240 minutes and 270 minutes (p <0.05)
in these subjects (Fig. l). Total hypoglycemic symptom
scoresalso did not change from baseline values (ll + 2)
during the control study, in contrast to the increasein hy-
poglycemicsymptomsin thesesubjects( I I -r 2 to 25 + 4)
after glucoseingestion.
Hypoglycemic clamp studies. As shown in Fig. 2, the
plasma glucose concentration was gradually reduced in
nearly identical 0.56 mmol/L (10 mg/dl) stepsfrom 4.8 to
3.0 mmol/L (86 mg/dl to 54 mgldl) in both children and
adults during the 240-minute hypoglycemic clamp proce-
dure. As expected,Tthis controlled reduction in the plasma
glucoseconcentrationstimulated an exaggeratedrise in the
plasma epinephrineconcentration in children, in compari-
son with that in adults (e.9.,4830 -t 334 vs 2365 t 3ll
pmol/L [870 -r 60 vs 426 -r- 56 pg/ml] at 240 minutes; p
<0.011. The plasma glucoselevel that stimulated a rise in
epinephrinewas also significantly higher in children than in
adults (3.6 + 0.1 vs 3.0 -r 0.1 mmol/L [65 + 1.8 vs 54 +
1.8 mg/dll; p <0.01), even though steady-stateplasma in-
sulin levelsachievedduring the insulin infusion were sim-
ilar in both groups (903 + 48 pmol/L [144.5 t 7.6 pU/
mll in childrenvs 857 * 42pmollL [137 + 6.7 pUlml] in
adults).
At baseline(before the start of the insulin infusion) the
P300 amplitude was not significantly greater in the children
than in the adults (l 1.7 t 1.5 vs 9.7 + 1.4, respcctively),
and no change in either group was observed at thc cnd of
the initial euglycemic period (plasma glucose level, 4.E
mmol/L [86 mgi dl]) (Fig. 3). Most important, no change
 The Journal of Pediatrics
volume 126,Number Z Jones et al. I 75

2 10 0

18 0 0

15 0 0
Plasma
12 0 0
Ep r n e p n n n e
(mmo/L) eoo
500

300

0 60 120 180 240 300

TIME (minutes)
Flg' {. Plasma epinephrinelevels(mean + SEM) in six of the healthy children
before and after ingestionof oral glucose
(a) and a sugar-free cola drink (L). Asterisk indicates
significant difference in values between oral glucoseand control
e x p e r i m e n t sI < 0 . 0 5 ) . T o c o n v e r t t o m e t r i c u n i t s , m u l t i p l y e p i n e p h r i n e
value by 0.1g.

Plasma
Glucose
(mmol/L)

Plasma
Epinephrine
(pmol/L)

o 50 240 3oo
,,i? ,-,",,:::
Fig. 2. Plasma glucoseand epinephrinelevels (mean + SEM) during hypoglycemic
clamp studies in children (tr) and
adults (I). Asrerisk indicates significant difference (p <0.01) versuscorrespondingvalue
in adults. To convert to metric
units, multiply glucosevalue by 18, and e p i n e p h r i n ev a l u e b y 0 . 1 8 .

in P300 potentials was observedin any of the adults until glucoseconcentrationwas lowered to 4.2 mmol/L (75 mg/
the plasma glucose concentration was lowered to the last dl) (p <0.05 vs baseline)and the p300 amplitude remained
step (3.0 mmol/L [5a mg/dl]). In contrast,in the children significantly reduced throughout the remainder of the
the P300 amplitude was significantly reduced when the study. All but one of the children had alterations in cortical

.,*--
I 76 Jones et al
- l
-2
A of P3O0
Amplitude -3
@v) -4
-5
-6
-7
8
6A5AL
Fig.3. Deltaof P300amplitudeduringeachglycemicplateauinchildren(O)andadults(I).
icant differences versus euglycemia in the children (rp <0.05). Dagger (l\
cemia in adults (p <0.01).
evoked potentials at glycemic levels greater than 3.0
mmol/L (5a mg/dl) (p <0.002 vs adult values).
DISCUSSION
Our findings indicate that the late postprandialrise in the
plasma epinephrineconcentration was markedly greater in
children than in adults, whereasthe responsesof other an-
tiinsulin, counterregulatory hormones were not different.
Epinephrine r€sponseswere exaggeratedin children, even
though a glucoseload larger than the standard 75 to I 00 gm
was given to adults and, more important, the peak and na-
dir plasma glucose levels were nearly identical in the two
groups.
Enhanced adrenomedullary responsesin the children
were associatedwith an increasein symptoms,such as feel-
ing shaky and sweaty, that are commonly attributed to
stimulation of th€ sympatheticnervoussystem,lI' l2 whereas
the scoreson filler items included to control for nonspecific
fatigue effects did not change. Moreover, adults who had
blunted epinephrine responsesremained free of symptoms
throughout the study, even though the lowest plasma glu-
cose level in the postprandial period, as determined by fre-
quent measurements,was nearly identical in the two groups.
These data suggestthat discrepanciesin symptom aware-
nessof the late fall in the plasma glucoseconcentrationaf-
ter an oral glucoseload are more likely related to differences
in epinephrine responses than to the absolute plasma
glucose level achieved. The plasma glucose concentration
fell to only 3.4 + 0.1 mmol/L (61 + 1.8 mg/dl) in the
children, so "enhanced adrenomedullary responsiveness,"
rather than "reactive hypoglycemia," might be a more ap-
The Journal of Pediatrics
February 1995
4.E 4.2 3.0 3.0
cLyCEutCLEVEL (mmal/L)
Asterisksindicatesignif-
indicates significant difference versus eugly-
propriate term to describethesephenomena.To excludethe
possibility that the findings reported above might have been
caused by nonspecific effects not connected with the oral
glucose load, we performed control experiments with a sug-
ar-free drink on a subgroup of the healthy childrcn wbose
responses to glucose ingestion were typical of the cntire
group of children studied, and no changes in plasma
hormone concentrations or hypoglycemic symptom scores
were noted.
The P300 evoked potential is a neuroelectrophysiologic
measureof cognitive function produced when a subject at-
tends to and discriminates a given stimulus.l3 The cortical
auditory evoked potential has been shown to be adversely
affected by modest reductions in plasma glucose levelsl4 and
may therefore provide a sensitiveindex of neuroglycopenia.
During controlled reductionsin the plasma glucoseconcen-
tration, cortical potentials are normally maintained until a
critical threshold glucosevalue is reduced.r5In this study,
P300 potentials were markedly altered in almost all the
children when the plasma glucose concentration was low-
ered to values that were equal to or higher than the nadir
plasma glucose level seen after glucose ingestion in this
group. On the other hand, in adults P300 potentials were
preserved until the plasma glucose concentration was low-
ered to 3.0 mmol/L (5a mg/dl), values rarely observedin
either group after glucose ingestion. These data suggestthat
healthy children are more vulnerable to the effects of hypo-
glycemia on cognitive function than are adults. Becausere-
lease of epinephrine in responseto a fall in the plasma glu-
cose concentration appears to be mediated through the
central nervous system,l6' l7 increased susceptibility to neu-
ril
 The Journal of Pediatrics
Volume 126, Number 2
roglycopenia may, in turn, account for the higher plasma
glucose level that triggered release of epinephrine in the
children.
The putative adverseeffectsofdietary sugar on behavior
and cognitive function in children have been the subject of
marked controversy.lE-20 Previous studies in this area that
have been focused on children with attention deficit disor-
der have tended to make exaggeratedclaims regarding the
global effectsof sugar and other food additives on their be-
havioral problems. Kinsbourne2l noted that the problems
caused by dietary sugar appear to be much less severeor
prevalent than some studiessuggest.On the other hand, we
have shown in this study that consumption of glucosein an
amount roughly equivalent in carbohydrate content to two
l2-ounce cans of Coca-Cola is followed by a fall in the
plasmaglucoseconcentrationsufficient to induce hormonal,
symptomatic, and neurophysiologic changes in healthy
children. However, the rise in the plasma epinephrinecon-
centration and in associated adrenergic symptoms was
acute and self-limited, and occurred only in the late post-
prandial period. These data do not indicate that dietary
sugar is the cause of hyperactivity problems, but they em-
phasizethat most children could benefit from eating mixed
1 nitive function and later activation of glucose counterregula-
mealsthat include protein, fat, complex carbohydrate,and
fiber to limit postprandial reductions in plasma glucose lev-
cls and increasesin plasma epinephrine levels. [n keeping
I with this conclusion,Wolraich et al.l were unableto dem-
I onstrate any effects on behavior and cognitive function in
I preschooland school-agechildren by adding or subtracting
Ii sucrosefrom a balanced diet.
I vest 1994;93:1677-82.
i 17. Biggers DW, Myers SR, Neal D, et al. Role of brain in coun-
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L WolraichML, LindgrenSD, StumboPJ,SteginkLD, Appel-
baum MI, Kiritsy MC. Effect of diets high in sucroseor
aspartame
on the behaviorand cognitiveperformanceof chil-
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:. Milich R, Wolraich M, Lindgren SD. Sugar and hyperactiv-
rty: a critical review of empirical findings.Clinical Psychology
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L Crook WG. Food allergy: the great masquerader.Pediatr Clin
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i Wcnder E. Review of researchof the relationship of nutritive
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 Yolume126 FEBRITARY1995 Number 2

TFIE JOLIRNAL OF
PEDIffiRICS Medlcol progress 261 Sweat chlorides in Mauriac syndrome polack er al.

163 Allergic colitis in inltnts Odze et al.

263 Transformation of neutropenia into leukemia in child treated
with G-CSF Weinblatt et al.
Orlglnot orilctes
l7l Adrenomedullery responseand susceptibility to neuroglvcopenia 266 Keratoderma and photophobia in tyrosinemia type II
efter suglr ingestion Jones et al. Rabinowitz et al.

178 Effects of hyperglycemig on mental efficiency in adolescentswith 269 Loss of antibody to hepatitis B in immunized patients with
diebetes Gschwend et al. hemophilia Maris, Butler, and Cohen

lE5 Subsequentinsect stings in Hymenoptera hypersensitivity-

Felol oncl neonolql medlclne
Hauk et al.

l9l Relotion between infent feeding and infections 212 EfIect of maternal glucocorticoids on intraventricular
Eeaudry, Dufour, and Marcoux hemorrhage in preterr4 infa.nts Garland, Buck, and ltviton

l9E Effect of neonetel immunization with DT toxoids on responsesto 2E0 Reducing blood donor exposures by use of older red blood cells
Haemophilus conjugete vlccines Lieberntan et al. Lee et al.

20,6 Antibody responses after different sequencesof Haemophilus 2E7 Effects of L-carnitine on fat metabolism in premrture neonates
conjugate vaccinesGreenberget al. Bonner et al.

212 Risk fectors and outcomes in patients hospitalizedwith RSV

infection l|/ang et al. 293 Congenital CMV infection causedby nonprimary diseasein
mother with AIDS Sclueb&e el a/.

220 Hmpitelizrtion rNtes for lower respirrtory tract illness in infants

McConnochre, Roghmann, and Liptak Phormqcology ond lheropeullct

230 Binding oI Pseudomonosto respiratory cells in cystic fibrosis

297 Growth and growth holmone axis in children treated for asthma
Zar et al.
Crowley et al.

23.f Spectrum of herpes simplex encephalitisSthlesinger et al.

304 Corticosteroid therapy for ventricular tachycardia in lymphocytic
myocarditis Ino et al.
242 Lipid rbnormelities in Turner syndrome Ross et al.

246 Lysinuric protein intolennce with bone marrow abnormalities 309 Granisetron vs chlorpromazine plus dexametha$ne to prevent
Parenti et al. ifosfamide-inducedemcsis Hiihlen et al.

252 Reduction in bone mess after severe bttns Klein et al. 313 Amoxicillin-clavulanatcduring URI for preventionof otitis media
Heikkinen et al.
Edllor'r column
Currenl lllelqlule ond cllnlcol lrsues
257 Venom immunotherapy Eierman

317 Antenatal corticosteroid therapy to prevent RDS Ryan and Finer

llons

*"5l,gPlls,*k*"o."9M 327 Acknowledgmenl ol reylewe]3

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