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Assessing the Effect of Docosahexaenoic
Acid on Cognitive Functions in Healthy,
Preschool Children: A Randomized,
Placebo-Controlled, Double-Blind Study
Alan S. Ryan, PhD, and Edward B. Nelson, MD, PhD
acids (LC-PUFA) have higher milk DHA levels com-
pared with those who consume diets low in these
fatty acids.
4
For infants who are not breastfed, com-
mercially available infant formulas are supple-
mented with DHA and arachidonic acid (ARA,
20:4n-6). For children, the typical American diet
provides relatively low levels of DHA and other LC-
PUFA compared with diets from other industrialized
nations.
5
A recent review concluded that maternal omega-
3 LC-PUFA supplementation during pregnancy and
lactation improves cognitive development of infants
and children.
6
Cohen et al
7
reported that an esti-
mated increase in maternal intake of DHA during
pregnancy of 1 g/d increases a child’s IQ by 0.8 to
1.8 points. For preterm and term infants, there is some
supportive evidence for a beneficial effect of LC-
PUFA supplementation on cognitive development.
6
Docosahexaenoic acid and ARA supplementation of
term infants improves visual development as meas-
ured by electrophysiologic tests.
6
T
here is considerable interest in the role that
docosahexaenoic acid (DHA, 22:6n-3) plays
in visual and cognitive development during
infancy and childhood. Docosahexaenoic acid is the
most abundant omega-3 fatty acid in the brain.
1-2
Humans obtain DHA either as DHA itself or from
its precursor, α-linolenic acid (18:3n-3), but the
conversion of α-linolenic acid to DHA is limited.
3
For infants, human milk is the most appropriate
means of providing optimal nutrition. The lipids in
human milk provide about half of the energy needs
of the growing infant and also provide essential fatty
acids, including DHA.
4
The level of DHA in human
milk is highly dependent on dietary intake.
4
Women
who consume fish and other foods containing high
levels of omega-3 long-chain polyunsaturated fatty
The utility of multicenter cognitive test methodology
and resultant outcomes of supplementation with
docosahexaenoic acid in healthy 4-year-old children
was evaluated in a randomized, placebo-controlled,
double-blind study. Subjects received 400-mg/d docosa-
hexaenoic acid (n = 85) or matching placebo (n = 90) in
capsules for 4 months. Cognitive tests included the
Leiter-R Test of Sustained Attention, Peabody Picture
Vocabulary Test, Day-Night Stroop Test, and Conners’
Kiddie Continuous Performance Test. The relationship
of docosahexaenoic acid levels in capillary whole blood
from a subsample (n = 93) with scores on cognitive
tests was evaluated. For each test, results indicated that
changes from baseline to end of treatment were not sta-
tistically significantly different between the docosa-
hexaenoic acid group and the placebo group.
Regression analysis, however, yielded a statistically sig-
nificant positive (P = .018) association between the
blood level of docosahexaenoic acid and higher scores
on the Peabody Picture Vocabulary Test, a test of lis-
tening comprehension and vocabulary acquisition.
Keywords: docosahexaenoic acid; cognitive functions;
omega-3 fatty acids
From Martek Biosciences Corporation, Columbia, Maryland.
Address correspondence to: Alan S. Ryan, PhD, Martek
Biosciences Corporation, 6480 Dobbin Rd, Columbia, MD
21045; e-mail: alryan@martek.com.
Clinical Pediatrics
Volume XX Number X
Month XXXX xx-xx
© 2008 Sage Publications
10.1177/0009922807311730
http://clp.sagepub.com
hosted at
http://online.sagepub.com
CLIN PEDIATR OnlineFirst, published on January 7, 2008 as doi:10.1177/0009922807311730
Copyright 2008 by SAGE Publications.
At the present time, there are no data on the
effects on cognitive performance of DHA alone
given to healthy children older than 2 years. Jensen
et al
8
considered children of breastfeeding women
who received capsules containing 200 mg of DHA
per day or a vegetable oil placebo for 4 months after
delivery. Outcome variables included measures of
cognition at 30 months of age. Docosahexaenoic acid
supplementation resulted in significantly higher
scores on the Bayley Psychomotor Development
Index but not on the Mental Development Index.
8
Birch et al
9
followed up infants for 4 years who were
fed formula supplemented with DHA and ARA dur-
ing the first 17 weeks of life. Docosahexaenoic acid
and ARA supplementation of infant formula sup-
ported visual acuity and cognitive development sim-
ilar to that of breastfed infants.
9
Bakker et al
10
evaluated the relationship between cognitive per-
formance (Kaufman Assessment Battery for
Children) at 7 years of age and LC-PUFA levels in
umbilical venous plasma phospholipids. No signifi-
cant relationships were reported. Using cross-sec-
tional dietary intake data from the Third National
Health and Nutrition Examination Survey, 1988-
1994, Zhang et al
11
considered the association
between LC-PUFA intake and psychosocial and cog-
nitive performance of children aged 6 to 16 years.
Higher intake of LC-PUFA was associated with bet-
ter performance on the digit span test, a measure of
a child’s working memory. Specific intakes of n-3
and n-6 fatty acids were not reported, however.
There appears to be more evidence for the ben-
eficial effect of DHA supplementation in children
with diagnosed behavioral and learning problems. In
3 of 5 double-blind, randomized, controlled trials,
12-
14
LC-PUFA supplementation diminished some
behavioral and cognitive problems in school-aged
children with attention deficit/hyperactivity disorder
(ADHD) or developmental coordination disorder.
The other 2 studies reported that supplementation
with DHA alone
15
or DHA with eicosapentaenoic
acid (EPA, 20:5n-3)
16
was not effective. The study
by Voigt et al
15
included subjects who received stim-
ulant medication, whereas the study by Hirayama et
al
16
considered a small sample of 40 children sup-
plemented for only 2 months.
Given the lack of information concerning the
effect of DHA alone in healthy children, we assessed
the effects of supplementation with 400-mg/d DHA
for 4 months on measures of cognitive functions
among 4-year-olds in a multicenter, randomized,
double-blind, placebo-controlled trial. The primary
outcome measures were standardized, age-appropri-
ate measures of attention, memory, processing
speed, and error rate. Four cognitive tests were used:
Leiter-R Test of Sustained Attention, Peabody
Picture Vocabulary Test (PPVT), Day-Night Stroop
Test, and Conners’ Kiddie Continuous Performance
Test (kCPT). The hypothesis was that DHA supple-
mentation for 4 months would lead to significant
improvements compared with placebo in these key
areas of cognitive function.
Methods
Subjects
Healthy girls and boys ages 4 years 0 months to 4
years 8 months were recruited at a total of 11 sites, 1
each in California, Georgia, Kentucky, Illinois,
Nevada, Oklahoma, Tennessee, Texas, Ohio, and 2 in
Virginia. All children were screened by telephone
interview with their parents or guardians. Parents or
guardians gave written consent for their children to
participate. The study was approved by the New
England Institutional Review Board. The trial was
registered on the United States National Institutes of
Health Web site <clinicaltrials.gov> (NCT00351624).
To be eligible to participate in the study, subjects
were required to meet normal developmental mile-
stones, were able to understand instructions pro-
vided during cognitive testing (ie, English was the
primary language in the home), and were between
the 10th and 95th percentiles for weight and height
of the National Center for Health Statistics growth
curves.
17
Children were excluded from participation
if they were premature at birth (≤ 36 weeks’ gesta-
tion), had a family history of ADHD, consumed 3 oz
or more of fish more than 2 times per week, con-
sumed dietary supplements or foods containing or
fortified with omega-3 LC-PUFA, had uncorrected
vision or hearing impairment, or had ADHD or an
inborn error of metabolism or any other medical
condition that the investigator believed would pre-
clude a successful response or outcome.
At the time of enrollment, subjects were not taking
any medicine for seizure disorders, anxiety disorders,
2 Clinical Pediatrics / Vol. XX, No. X, Month XXXX
childhood psychosis, depression, or for bipolar dis-
orders. A subject was not withdrawn from the trial if
he or she needed to take one of these medications
after enrollment. Antihistamines were not adminis-
tered within 24 hours of the day of cognitive testing.
If a subject was taking an antihistamine on the day
of the cognitive tests, the tests were rescheduled.
Randomization
All subjects were randomly assigned in a double-
blind fashion according to a computer-generated
randomization scheme to receive 400 mg of DHA
(DHASCO-S, Martek Biosciences Corporation,
Columbia, Maryland) as a triglyceride supplied as two
200-mg bubblegum-flavored softgel chewable capsules
or placebo of high-oleic sunflower oil supplied as 2
softgel capsules for 4 months. The DHA was derived
from the microalgae Schizochytrium spp, which is
allowed for use as a dietary supplement and is generally
recognized as safe for use in foods. The placebo and
DHA capsules were provided by Martek Biosciences
Corporation and were identical in appearance.
The investigational product was dispensed at
each site according to the randomization scheme.
The computer-generated randomization numbers
were assigned sequentially through an interactive
voice response system as subjects were entered into
the study. The randomization schedule was stratified
by site and preschool experience. Preschool experi-
ence was defined as a child’s participation in an
accredited and licensed child-care center or atten-
dance at a preschool (≥ 3 days per week) within 6
months before screening.
The number of capsules dispensed was always
more than needed before the next appointment (2
months). Parents were instructed to return any
unused capsules at the time of the appointment to
determine compliance.
Polyunsaturated Fatty Acids in Capillary
Whole Blood
At the baseline visit, the parent or guardian was
asked to encourage their child to provide a sample of
blood (obtained by finger stick) to determine the
child’s PUFA levels before supplementation with the
investigational product and after the treatment
period. Willingness to provide a blood sample was
not a requirement for participation in the study.
Details of the finger stick assay have been pub-
lished elsewhere
18
and are briefly described here. A
drop of capillary blood was obtained from each sub-
ject by piercing the fingertip with a lancet device
(BD Genie, Lancet, Emergency Medical Products,
Franklin Lakes, New Jersey). Filter paper impregnated
with 2,6-di-tert-butyl-4-methylphenol (Whatman
3MM chromatography paper, Whatman Inc, Florham
Park, New Jersey) was prepared according to the
methods described by Ichihara et al
19
and applied to
the finger. The blood sample was dried overnight at
room temperature and stored at −80°C until analysis.
The filter paper samples were transferred to test
tubes with 23:0 fatty acid internal standard, directly
saponified with sodium hydroxide and methylated
with 14% boron trifluoride in methanol with no prior
extraction step. The fatty acid methyl esters were sep-
arated by capillary column gas chromatography on an
Agilent Series 6890 System (Agilent, Wilmington,
Delaware) equipped with a 30 m FAMEWAX (Restek,
State College, Pennsylvania) column. A 20:1 split
flow ratio with helium as a carrier and a programmed
temperature gradient of 130°C to 250°C was used.
Fatty acid methyl esters were identified by flame ion-
ization detection. Retention times were compared
with a mixed fatty acid methyl ester standard from
NuChek Prep, Elysian, Minnesota. Fatty acids were
quantified by comparison to the 23:0 internal stan-
dard (NuChek Prep).
Outcomes
The primary efficacy outcomes were the changes
observed from baseline to the end of the study in 4
age-standardized tests: Leiter-R Test of Sustained
Attention, PPVT, Day-Night Stroop Test, and kCPT.
The Attention Sustained, a subset of the
Attention and Memory Battery of the Leiter-R,
20
measures ability to remain attentive during repeti-
tive tasks. The PPVT measures memory and cogni-
tive function
21
and assesses the child’s level of
vocabulary acquisition as it relates to cognitive
processes. The PPVT is a test of listening compre-
hension and receptive vocabulary for the spoken
word in Standard English. The Day-Night Stroop
Test measures tendency toward impulsivity.
22
The
kCPT measures a child’s ability to sustain attention
and accuracy during a timed test.
23
This is a com-
puterized test designed to measure attention,
response time, and error rate.
Effect of DHA on Cognitive Functions / Ryan, Nelson 3
The relationship between blood DHA levels and
the efficacy end points were considered preplanned
secondary outcomes.
Statistical Analyses
All data were encoded and analyzed by an independ-
ent contract research organization (Premier
Research, Horsham, Pennsylvania). Statistical
analyses were performed using SAS 8.2 software
(SAS Institute, Cary, North Carolina). National data
from the Leiter-R Test of Sustained Attention
20
were
used to design the study to detect an effect size of
0.5 using a 2-group t test with a .05 significance
level. With an expected dropout rate of 20%, a sam-
ple size of 86 subjects in each group had 90% power
to detect the effect. A total of 202 subjects were ran-
domized to achieve 86 subjects per treatment group
completing the study.
Three populations were defined a priori for sta-
tistical analyses:
1. The per protocol analysis population included
subjects who were compliant and completed the
protocol, with the exception of the voluntary
blood draw.
2. The intent-to-treat (ITT) analysis population
included all randomized subjects with at least 1
postbaseline cognitive test. The analyses per-
formed for the ITT population were considered
primary.
3. The DHA blood analysis population included all
subjects with blood PUFA levels measured at
baseline and at the end of the study.
A safety population, which was not considered
for statistical analyses, included all subjects who
were randomized into the study and who received at
least 1 dose of the investigational product.
Change from baseline to the end of the study for
each variable was analyzed using an analysis of
covariance with treatment, site, sex, preschool expe-
rience, and median age as factors and the baseline
value of the variable being analyzed as a covariate.
All statistical tests were performed as 2-tailed tests,
and all effects were considered to be statistically
significant if P ≤ .05. Regression analysis was used
to determine whether blood DHA level (continuous
variable) was a significant predictor for each of the
4 outcomes. Change from baseline to the end of the
study for blood LC-PUFA levels was analyzed using
a paired t test to determine whether the change was
statistically significant within each treatment group.
The 2-sample t test was used to determine signifi-
cant differences between the treatment groups.
Results
Subjects
The study screened 405 subjects by telephone, and
202 were randomized into the study. Of these, 27
children did not complete the study: 11 in the DHA
group and 5 in the placebo group were lost to follow-
up (n = 16), 4 parents in the DHA group and 3 in
the placebo group withdrew their children from the
study (n = 7), 2 children in the DHA group and 1 in
the placebo group were noncompliant based on cap-
sule count (n = 3), and 1 subject in the placebo
group was discontinued prematurely owing to a mild
adverse event of ocular icterus that was not consid-
ered to be related to the investigational product.
Thus, 175 subjects completed the study with at least
1 postbaseline cognitive test (ITT population, Table 1).
The per protocol analysis population included 163
subjects, 77 subjects in the DHA group, and 86 in
the placebo group, who were compliant and com-
pleted the protocol, with the exception of the volun-
tary blood draw (Table 1). The DHA blood analysis
population included 93 subjects, 46 in the DHA
group and 47 in the placebo group, whose blood
PUFA levels were measured at baseline and at the
end of the study. The safety population included 202
subjects, 102 in the DHA group and 100 in the
placebo group.
The investigational product was well tolerated.
No subject in either treatment group experienced a
serious adverse event. The compliance rate, deter-
mined from capsule count, was nearly 100% (Table
1). However, 4 subjects in the DHA group and 2 in
the placebo group were considered to be noncom-
pliant because their blood DHA levels at the final
visit were inconsistent with their assigned treat-
ment; that is, no change in the level of DHA in the
blood of subjects in the DHA group and a 2-fold
increase in the level of DHA in the blood of subjects
in the placebo group. These 6 subjects were
excluded from the regression analyses that were
used to determine whether blood DHA level was sig-
nificantly associated with each of the 4 outcomes.
4 Clinical Pediatrics / Vol. XX, No. X, Month XXXX
None of the baseline values were significantly
different between the 2 treatment groups (Table 1).
A minor difference, however, was found between
groups in ethnicity: The DHA group had twice
as many Hispanic or Latino subjects than the
placebo group.
Long Chain Polyunsaturated
Fatty Acid Levels in Capillary
Whole Blood
Mean levels of DHA, ARA, and EPA in capillary
whole blood were similar at baseline (Table 2). After
4 months, the mean capillary whole blood content of
DHA in the placebo group remained low, whereas
the mean content in the DHA group increased by
more than 300% (P < .0001). This increase in capil-
lary whole blood content of DHA was accompanied
by a 9% decline in the mean capillary whole blood
content of ARA. After 4 months of treatment, an
approximate 2-fold increase in the mean level of
EPA in capillary whole blood occurred in the DHA
group, whereas in the placebo group the mean level
of EPA remained the same.
Measures of Cognitive Functions
The results did not demonstrate statistically significant
improvements in cognitive measures on the Leiter-R
Test of Sustained Attention, PPVT, Day-Night Stroop
Test, or kCPT after 4 months of DHA supplementation.
The primary end points may have been compromised
by the following:
• A large, unexpected ceiling effect was observed on
the Leiter-R Test of Sustained Attention that was
designed for children aged 4 to 5 years old. A rel-
ative high percentage of subjects in the ITT popu-
lation⎯36% in the DHA group (n = 31) and 19%
in the placebo group (n = 17)⎯scored 100% at
baseline and at the end of the study. A ceiling
effect was also observed, to a lesser extent, on the
Day-Night Stroop Test, with 2% in the DHA group
(n = 2) and 10% in the placebo group (n = 9).
• The PPVT is dependent on fluency in English.
Although the protocol stipulated that only sub-
jects who spoke English in the home were eligi-
ble to participate, a relatively large number of
Hispanic and Latino subjects⎯11 in the DHA
group (13%) and 5 in the placebo group (6%)⎯
were randomized into the study.
Effect of DHA on Cognitive Functions / Ryan, Nelson 5
Table 1. Description of Study Subjects
ITT Population PP Population DHA Blood Population
Characteristic DHA Placebo DHA Placebo DHA Placebo
Subjects, No. 85 90 77 86 46 47
Sex, No. (%)
Male 45 (53) 47 (52) 39 (51) 43 (50) 28 (61) 25 (53)
Female 40 (47) 43 (48) 38 (49) 43 (50) 18 (39) 22 (47)
Age, mean (SD) mon 51.9 (2.3) 51.6 (2.4) 52.0 (2.3) 51.4 (2.4) 51.7 (2.4) 51.3 (2.4)
Ancestry, No. (%)
Asian 0 (0) 4 (4) 0 (0) 3 (3) 0 (0) 0 (0)
Black 7 (8) 14 (16) 6 (8) 13 (15) 5 (11) 9 (19)
White 78 (92) 72 (80) 71 (92) 70 (82) 41 (89) 38 (81)
Hispanic/Latino descent
Hispanic or Latino 11 (13) 5 (6) 10 (13) 4 (5) 8 (17) 3 (6)
Not Hispanic or Latino 74 (87) 85 (94) 67 (87) 82 (95) 38 (83) 44 (94)
Height, mean (SD) cm 104.6 (3.8) 104.0 (7.7) 104.7 (3.8) 104.0 (7.8) 103.9 (4.1) 102.7 (10.0)
NCHS height percentile, mean (SD) 55.3 (26.1) 56.8 (24.3) 56.6 (26.1) 57.5 (24.0) 50.3 (26.6) 54.0 (23.9)
Weight, mean (SD) kg 17.7 (2.9) 17.7 (2.2) 17.7 (2.9) 17.7 (2.2) 17.8 (3.6) 17.5 (2.6)
NCHS weight percentile, mean (SD) 59.0 (22.6) 60.1 (22.3) 59.2 (22.2) 59.8 (21.6) 54.4 (22.2) 57.2 (23.9)
Preschool experience, No. %
Stay at home 22 (26) 23 (26) 21 (27) 22 (26) 11 (24) 13 (28)
Institutional setting 63 (74) 67 (74) 56 (73) 64 (74) 35 (76) 34 (72)
Compliance, %
a
98 99 99 99 96 99
Note: DHA = docosahexaenoic acid; ITT = intention to treat; PP = per protocol.
a. Compliance (number of capsules consumed/number of days × 2 × 100%, for baseline to final visit).
Secondary Preplanned Analyses
Regression analysis yielded a statistically significant
positive association between the level of DHA in cap-
illary whole blood with higher scores on the PPVT for
the ITT population (R
2
= 0.14, P = .018, Figure 1).
The association was stronger when Hispanic/Latino
subjects were deleted from the analyses: higher levels
of DHA in the blood were associated with higher
scores on the PPVT for the ITT (R
2
= 0.21, P = .008)
and per protocol (R
2
= 0.16, P = .04) populations.
These data suggest that for each increase in the level
of DHA in the blood by weight 1% of total fatty acids,
the PPVT percentile rank improves by 6 to 9 points.
Discussion
Although the primary end points of the study were
not met, the results demonstrated that higher levels
of DHA in capillary whole blood resulting from sup-
plementation with DHA at 400 mg/d were signifi-
cantly and positively associated with improved
scores on the PPVT. The results also indicated that
DHA supplementation of 400 mg/d for 4 months in
preschool children was safe and well tolerated.
The PPVT is a test of listening comprehension for
the spoken word in standard English.
21
It is designed
as a measure of a subject’s receptive (hearing)
vocabulary and is considered to be a screening test
for memory and cognitive function.
21
With respect
to other tests of cognitive function such as the
Wechsler Intelligence Scale for Children−Revised,
Wechsler noted that the vocabulary subtest scores
correlated more highly with Full Scale IQ scores
than did any other subtest scores.
24
According to
Roid and Miller,
20
who designed the current version
of the PPVT, there is substantial evidence that the
PPVT may predict school success and verbal ability.
21
A 4-month period of supplementation with 400-
mg/d DHA increased mean capillary whole blood
levels of DHA by more than 300%, whereas the
mean blood level of DHA in the placebo group
remained nearly unchanged. The increase in capil-
lary whole blood content of DHA was accompanied
by a decline in the mean capillary whole blood con-
tent of ARA and an increase in the mean level of
EPA. It is not surprising that an increase in the level
of DHA in blood is accompanied by a decrease in
ARA and a modest increase in EPA.
25
This finding is
consistent with other clinical studies that indicated
both DHA and EPA reduce ARA blood concentra-
tion whereas DHA increases EPA concentration.
25
Docosahexaenoic acid, EPA, ARA, and α-linolenic
6 Clinical Pediatrics / Vol. XX, No. X, Month XXXX
Table 2. Polyunsaturated Fatty Acid Levels in Capillary Whole Blood
DHA (n = 42
b
), weight % fatty acids Placebo (n = 45
b
), weight % fatty acids
Fatty Acid
a
Baseline 4 Months Change Baseline 4 Months Change
DHA (22:6n-3) 1.0 (0.34) 3.3 (1.54)
c
2.4 (1.46)
d
1.0 (0.34) 1.1 (0.40)
c
0.1 (0.37)
ARA (20:4n-6) 7.5 (1.89) 6.9 (2.14) −0.6 (1.90) 7.9 (1.69) 7.8 (2.23) −0.1 (2.17)
EPA (20:5n-3) 0.3 (0.39) 0.5 (0.70) 0.2 (0.86) 0.3 (0.40) 0.3 (0.20) 0.0 (0.47)
Note: ARA = arachidonic acid; EPA = eicosapentaenoic acid; DHA = docosahexaenoic acid.
a . Data are expressed as mean (SD).
b. Six subjects (DHA group, n = 4; placebo group, n = 2) were considered to be noncompliers because their blood DHA levels at the
final visit were inconsistent with their assigned treatment.
c. Difference between DHA group and placebo group, P < .0001.
d. Change from baseline to 4 months, P < .0001.
Figure 1. Regression analysis of Peabody Picture Vocabulary
Test (PPVT) percentile rank scores vs docosahexaenoic acid
(DHA) levels in whole capillary blood at end of treatment
(4 months) in the intention to treat population.
acid (18:3n-3) compete for the sn-2 position on
membrane phospholipids.
25
Docosahexaenoic acid
itself also serves as a substrate for metabolic retro-
conversion to EPA through β-oxidation reaction.
Clinical data have shown that the retroconversion
rate of DHA to EPA may be as high as 12%.
26
Some issues were identified while the statistical
analysis was completed that may have decreased the
likelihood of attaining statistically significant end
points. The large ceiling effect observed for the
Leiter-R Test of Sustained Attention and to a lesser
extent for the Day-Night Stroop Test not only
decreased the sample size but also indicated that the
level of difficulty of the tests used in the study was
inadequate for the study subjects. The use of differ-
ent or more challenging tests might have avoided the
ceiling effect and provided statistically analyzable
data for a greater number of subjects.
The difficulty in identifying subtle effects of cog-
nitive development during childhood may be related
to slight differences in techniques of cognitive test-
ing between study sites and psychologists. For exam-
ple, a study conducted in a clinical setting at a single
site reported statistically significant results on the
Leiter-R Test of Sustained Attention.
27
This study
considered former breastfed infants with cognitive
assessments made at 4 months to 5 years of age.
Mothers of these infants were administered 200-mg/d
DHA or a placebo during the first 4 months of
breastfeeding. Compared with infants of mothers
who received placebo, those of mothers who received
DHA supplementation performed significantly better
(P < .008) on the Leiter-R Test of Sustained Attention
at 5 years.
27
This one-site study may have increased
the likelihood of finding a statistically significant
effect by limiting the possibility of a high variance of
measurement.
The potential for detection of a beneficial effect
of DHA supplementation on cognition in older chil-
dren may be more difficult than is detection in
infants because brain development, and thus the
potential incorporation of DHA, slows considerably
after the age of 2 years.
28
However, it remains possi-
ble than an increased supply of DHA to the brain in
this period results in changes of fatty acid composition
of brain tissue or that the DHA has other metabolic
effects that can affect brain function.
29
Administration
of a larger dose of DHA or the same dose for a
longer period of time may improve the chances of
detecting subtle cognitive effects during childhood.
Also, new technologies such as brain imaging and
functional magnetic resonance imaging could help
detect slight effects of DHA on brain structure and
as well as on function.
30
Conclusion
There is supportive evidence for a significant associ-
ation between higher DHA levels in blood and
improved scores on a test of listening comprehension
and vocabulary in healthy preschool children. That
healthy young children may benefit from DHA sup-
plementation is promising. Future studies are needed
to further elucidate the effects of DHA supplemen-
tation on cognitive function in healthy children.
Acknowledgments
We gratefully acknowledge the following princi-
pal investigators and clinical research centers who
contributed to enrollment and cognitive testing:
Barney Blue, DO, Eminence Research, LLC, 305
Northwest Eubanks, Oklahoma City, Oklahoma;
Umesh P. Goswami, MD, Northern Illinois
Research Associates, 625 E Bethany Rd, Ste 3,
DeKalb, Illinois; Lydie L. Hazan, MD, Impact
Clinical Trials, 8500 Wilshire Blvd, Ste 700, Beverly
Hills, California; Carroll E. Howard, MD, Pedia
Research, LLC, 920 Frederica St, Ste 1010,
Owensboro, Kentucky; Michael L. Levin, MD,
MPH, Henderson Pediatrics, 220 E Horizon Dr, Ste
A, Henderson, Nevada; David Matson, MD, PhD,
Center for Pediatric Research, 855 W Brambleton
Ave, Norfolk, Virginia; Lewis M. Purnell, MD,
Southwest Children’s Research Associates, PA, 5282
Medical Dr, Ste 311, San Antonio, Texas; Nathan
Segall, MD, Clinical Research Atlanta, 175 Country
Club Dr, Ste 100-A, Stockbridge, Georgia; Mark A.
Smikle, PhD, Prevention & Strengthening Solutions
Inc, 1803 E Main St, Humboldt, Tennessee; Paul P.
Wisman, MD, Pediatric Associates of Charlottesville,
PLC, 1011 E Jefferson St, Charlottesville, Virginia;
Julie S. Shepard, MD, MPH, Ohio Pediatrics, 7371
Brandt Pike, Huber Heights, Ohio.
We also thank Eileen Bailey-Hall for the analy-
ses of the blood samples.
Effect of DHA on Cognitive Functions / Ryan, Nelson 7
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