The EFSA Journal (2009) 1000, 1-13
© European Food Safety Authority, 2009
SCIENTIFIC OPINION
DHA and ARA and brain development
Scientific substantiation of a health claim related to docosahexaenoic acid
(DHA) and arachidonic acid (ARA) and brain development pursuant to
Article14 of Regulation (EC) No 1924/2006
1
Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies
(Question No EFSA-Q-2008-212)
Adopted on 13 March 2009
P
ANEL
M
EMBERS
Jean-Louis Bresson, Albert Flynn, Marina Heinonen, Karin Hulshof, Hannu Korhonen, Pagona
Lagiou, Martinus Løvik, Rosangela Marchelli, Ambroise Martin, Bevan Moseley, Hildegard
Przyrembel, Seppo Salminen, Sean (J.J.) Strain, Stephan Strobel, Inge Tetens, Henk van den
Berg, Hendrik van Loveren and Hans Verhagen.
S
UMMARY
Following an application from Mead Johnson & Company submitted pursuant to Article 14 of
Regulation (EC) No 1924/2006 via the Competent Authority of France, the Panel on Dietetic
Products, Nutrition and Allergies was asked to deliver an opinion on the scientific
substantiation of a health claim related to docosahexaenoic acid and arachidonic acid and brain
development.
The scope of the application was proposed to fall under a health claim referring to children’s
development and health.
The food constituents that are the subject of the health claim are docosahexaenoic acid (DHA)
and arachidonic acid (ARA), which are well characterised fatty acids that can be quantified in
foods by established methods. The absorption of DHA and ARA is well documented. The Panel
considers that the food constituents DHA and ARA are sufficiently characterised.
The claimed effect is the contribution to the optimal brain development of infants and young
children. The target population proposed by the applicant is infants and young children (from
birth to three years of age). The Panel considers that contribution to the normal development of
the brain is beneficial for infants’ and children’s development and health.
The applicant identified a total 33 publications as being pertinent to the health claim for
humans. A total of 13 full publications which report original data from RCTs on the effects of
1
For citation purposes: Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies on a request from Mead
Johnson & Company on DHA and ARA and brain development. The EFSA Journal (2009) 1000, 1-13
DHA and ARA and brain development
The EFSA Journal (2009) 1000, 2-13
DHA supplementation (with or without ARA) on brain development in physiologic conditions
and in subjects born at term and have been presented, reporting the results from eight study
designs. All these studies were conducted in term infant populations fed different formulas
from birth through the first months of life up to 12 months at the maximum.
In two RCTs, formulas with less than 0.2% DHA (in various combinations with ARA) from
birth through six or 12 months of age had no effect on neurodevelopmental indices measured
with different methods as compared to standard, unsupplemented formulas. Two double-blind
RCTs investigated the effects of formulas supplemented with DHA around 0.3% either alone or
in combination with ARA at around the same level (ARA:DHA ratio = 1) form birth to 6-12
months of life on Bayley’s Mental and Psychomotor Developmental Indices (MDI and PDI) at
12 and 24 months or at 18 months of age as compared to unsupplemented formulas. No
differences in MDI or PDI scores were observed among the formula-fed groups. In another
double-blind RCT, term infants allocated at birth to consume a formula supplemented with
0.15-0.25% DHA and 0.30-0.40% ARA (ARA:DHA ratio = 1.7:1 to 2:1) for four months had
significantly more intentional solutions and higher intention scores at 10 months of age than
infants who received the unsupplemented formula.
In the remaining three study designs, formulas supplemented with either 0.3 % DHA alone or
in combination with ARA in higher dosages (ARA:DHA ratio from 1.4:1 to 2:1) were used in
the intervention groups. These doses of DHA and the DHA:ARA ratio are in the range of those
recommended by the applicant to obtain the claimed effect.
In the first study, term infants consuming a formula supplemented with 0.30% DHA and 0.44%
ARA for four months scored significantly higher in the Brunet-Lézine test than infants in the
control (unsupplemented) formula group at four months of age, but these differences were not
sustained at 24 months of life. In the second study, healthy term infants consuming a formula
supplemented with 0.3% DHA and 0.45% ARA (ARA:DHA ratio = 1.5) for two months had
mildly abnormal GMs significantly less often than did infants receiving the unsupplemented
formula. No differences between groups were found in clinical neurological condition,
neurological optimality score, fluency score, or the Bayley’s MDI or PDI at 18 months of life.
The third study included infants randomised at the age of five days to consume either a formula
with DHA 0.35% alone, a formula with DHA 0.36% plus ARA 0.72%, or a control formula
devoid of DHA and ARA for 17 weeks. Infants supplemented with DHA and ARA yielded
significantly higher MDI scores at 18 months than infants in the control group. No significant
differences between groups were observed among the three groups regarding the PDI or the
Behaviour Rating Scale. Infants were tested at four years of age for Intelligence Quotient (IQ).
Verbal IQ in the control and DHA-supplemented formula groups was significantly lower than
in the DHA plus ARA group. No differences were observed among groups regarding the full
scale IQ or the performance IQ.
The Panel notes that none of the studies using formulas supplemented with doses of DHA and
ARA lower than proposed in the conditions of use or 0.3% DHA and an ARA:DHA ratio of
one show an effect of DHA and ARA supplementation on neurodevelopment indices infants as
compared to unsupplemented formulas. The Panel also notes that the four studies using either
slightly lower DHA doses or about 0.3% DHA and the ARA:DHA ratio proposed in the
conditions of use (between 1.4:1 and 2:1) show a short-tem beneficial effect of DHA and ARA
supplementation on different measures of neurodevelopment. However, the different testing
ages and the use of different tests for assessment limit the comparability of the studies. Also,
the predictive value of the neurodevelopment tests used is uncertain. Indeed, only two of the
studies above show an effect beyond the supplementation period, and only one reports a
sustained effect beyond the first year of life in a limited sample of subjects. In no case the
DHA and ARA and brain development
The EFSA Journal (2009) 1000, 3-13
breastfed reference group showed lower developmental indices when compared to any formula-
fed group.
On the basis of the data presented, the Panel concludes that the data presented are insufficient
to establish a cause an effect relationship between the intake of infant and follow-on formula
supplemented with DHA at levels around 0.3% of the fatty acids and a ratio ARA:DHA
between 1.4:1 and 2:1 and the contribution to normal brain development in infants and young
children from birth to three years of age.
Key words: Docosahexaenoic acid, arachidonic acid, brain development, infants, children
DHA and ARA and brain development
The EFSA Journal (2009) 1000, 4-13
T
ABLE OF
C
ONTENTS
Panel Members ............................................................................................................................................1
Summary .....................................................................................................................................................1
Table of Contents ........................................................................................................................................4
Background .................................................................................................................................................5
Terms of reference.......................................................................................................................................5
EFSA Disclaimer.........................................................................................................................................5
Acknowledgements .....................................................................................................................................6
1.
Information provided by the applicant ................................................................................................7
1.1.
Food/constituent as stated by the applicant ...............................................................................7
1.2.
Health relationship as claimed by the applicant.........................................................................7
1.3.
Wording of the health claim as proposed by the applicant ........................................................7
1.4.
Specific conditions of use as proposed by the applicant............................................................7
2.
Assessment ..........................................................................................................................................7
2.1.
Characterisation of the food/constituent ....................................................................................7
2.2.
Relevance of the claimed effect to human health ......................................................................7
2.3.
Scientific substantiation of the claimed effect ...........................................................................8
Conclusions ...............................................................................................................................................11
Documentation provided to EFSA ............................................................................................................12
References .................................................................................................................................................12
Glossary / Abbreviations ...........................................................................................................................13
DHA and ARA and brain development
The EFSA Journal (2009) 1000, 5-13
B
ACKGROUND
Regulation (EC) No 1924/2006
2
harmonises the provisions that relate to nutrition and health
claims and establishes rules governing the Community authorisation of health claims made on
foods. As a rule, health claims are prohibited unless they comply with the general and specific
requirements of that Regulation and are authorised in accordance with this Regulation and
included in the lists of authorised claims provided for in Articles 13 and 14 thereof. In
particular, Articles 14 to 17 of that Regulation lay down provisions for the authorisation and
subsequent inclusion of reduction of disease risk claims and claims referring to children’s
development and health in a Community list of permitted claims.
According to Article 15 of that Regulation, an application for authorisation shall be submitted
by the applicant to the national competent authority of a Member State, who will make the
application and any supplementary information supplied by the applicant available to European
Food Safety Authority (EFSA).
Steps taken by EFSA:
•
The application was received on 14/02/2008.
•
The scope of the application was proposed to fall under a health claim referring to
children’s development and health.
•
During the check for completeness
3
of the application, the applicant was requested to
provide missing information on 21/03/2008 and on 23/09/2008.
•
The applicant provided the missing information on 31/08/2008 and on 06/10/2008.
•
The scientific evaluation procedure started on 15/10/2008.
•
During the meeting on 13/03/2009, the NDA Panel, after having evaluated the overall
data submitted, adopted an opinion on the scientific substantiation of a health claim
related to docosahexaenoic acid and arachidonic acid and brain development.
T
ERMS OF REFERENCE
EFSA is requested to evaluate the scientific data submitted by the applicant in accordance with
Article 16 of Regulation (EC) No 1924/2006. On the basis of that evaluation, EFSA will issue
an opinion on the scientific substantiation of a health claim related to: docosahexaenoic acid
and arachidonic acid and brain development.
EFSA
D
ISCLAIMER
The present opinion does not constitute, and cannot be construed as, an authorisation to the
marketing of docosahexaenoic acid and arachidonic acid, a positive assessment of its safety,
nor a decision on whether docosahexaenoic acid and arachidonic acid are, or are not, classified
as a foodstuff. It should be noted that such an assessment is not foreseen in the framework of
Regulation (EC) No 1924/2006.
2
European Parliament and Council (2006). Regulation (EC) No 1924/2006 of the European Parliament and of the Council of
20 December 2006 on nutrition and health claims made on foods. Official Journal of the European Union OJ L 404,
30.12.2006. Corrigendum OJ L 12, 18.1.2007, p. 3–18.
3
In accordance with EFSA “Scientific and Technical guidance for the Preparation and Presentation of the Application for
Authorisation of a Health Claim”
DHA and ARA and brain development
The EFSA Journal (2009) 1000, 6-13
It should also be highlighted that the scope, the proposed wording of the claim and the
conditions of use as proposed by the applicant may be subject to changes, pending the outcome
of the authorisation procedure foreseen in Article 17 of Regulation (EC) No 1924/2006.
A
CKNOWLEDGEMENTS
The European Food Safety Authority wishes to thank Carlo Agostoni and the members of the
Working Group for the preparation of this opinion: Jean-Louis Bresson, Albert Flynn, Marina
Heinonen, Hannu Korhonen, Ambroise Martin, Andreu Palou, Hildegard Przyrembel, Seppo
Salminen, Sean (J.J.) Strain, Inge Tetens, Henk van den Berg, Hendrik van Loveren and Hans
Verhagen.
DHA and ARA and brain development
The EFSA Journal (2009) 1000, 7-13
1.
Information provided by the applicant
Applicant’s name and address: Mead Johnson & Company 3 rue Joseph Monier-BP 325,
92506 Rueil-Malmaison Cedex, France.
The application includes a request for the protection of proprietary data.
1.1. Food/constituent
as
stated by the applicant
Docosahexaenoic acid (DHA) and arachidonic acid (ARA)
1.2. Health
relationship
as claimed by the applicant
Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are important for brain
development.
1.3.
Wording of the health claim as proposed by the applicant
DHA and ARA contribute to the optimal brain development of infants and young children.
1.4.
Specific conditions of use as proposed by the applicant
Condition of use for the claim: the formula contains at least 0.3% of the fatty acids as DHA and
the ratio ARA: DHA is between 1.4:1 and 2.0:1.
2. Assessment
2.1. Characterisation
of the food/constituent
The food constituents that are the subject of the health claim are docosahexaenoic acid (DHA)
and arachidonic acid (ARA) derived from single cell oils for which complete specifications,
manufacturing process, bioavailability and stability information have been provided. DHA is
derived from the alga Crypthecodinium cohnii and ARA from the fungus Mortierella alpina.
DHA and ARA from single cell oils are intended to be added to food for particular nutritional
uses for infants and young children from birth to 3 years of age according to
Directive
89/398/EEC at the concentration of at least 0.3% of the fatty acids as DHA and a ratio
ARA:DHA between 1.4:1 and 2:1. This evaluation will apply to DHA and ARA from all
sources with appropriate bioavailability in the specified amounts.
DHA and ARA are well characterised fatty acids the absorption of which is well documented
and can be quantified in foods by established methods.
The Panel considers that the food constituents DHA and ARA are sufficiently characterised.
2.2.
Relevance of the claimed effect to human health
The claimed effect is the contribution to the optimal brain development of infants and young
children. The target population proposed by the applicant is infants and young children (from
birth to three years of age).
The Panel considers that contribution to the normal development of the brain is beneficial for
infants’ and children’s development and health.
DHA and ARA and brain development
The EFSA Journal (2009) 1000, 8-13
2.3.
Scientific substantiation of the claimed effect
The applicant performed a literature search in PubMed and Scopus to identify randomised
controlled trials (RCTs) on the effects of formulae intended for infants and young children
(from birth to 36 months) containing DHA and ARA on brain and cognitive development (as
primary or secondary outcome) with the following search terms: DHA, ARA, infant, brain,
cognitive, mental, long-chain polyunsaturated fatty acids, fatty acids, omega 3, omega 6,
toddler milk and all combinations of terms. The snow ball method (search for additional
references in the papers identified through the search) was used for hand searching.
The applicant identified a total 33 publications as being pertinent to the health claim for
humans (13 RCTs, one meta-analysis of RCTs, one observational cohort study, three
postmortem studies, six reviews, seven expert recommendations and two abstracts containing
unpublished data).
The Panel considers that publications/reports presented in summary form only and/or
investigating the effects of DHA and ARA in pre-term infants and/or addressing clinical
outcomes other than brain development in physiologic conditions are not suitable sources of
data to support the claimed effect. The Panel also considers that the results of the meta-analysis
presented assessing the effects of long-chain polyunsaturated fatty acid supplementation on
developmental outcomes in term infants cannot be directly extrapolated for the substantiation
of the claimed effect as the inclusion criteria used for trial selection do not match the conditions
of use proposed by the applicant in the present application (Simmer et al., 2008).
A total of 13 full publications (Agostoni et al, 1995; Agostoni et al. 1997; Auestad et al., 2001;
Auestad et al., 2003; Ben et al., 2004; Birch et al., 2000, proprietary data; Birch et al., 2007,
proprietary data; Bouwstra et al., 2003; Bouwstra et al., 2005; Lucas et al., 1999 ; Makrides et
al., 2000; Willatts et al. 1998a and 1998b) which report original data from RCTs on the effects
of DHA supplementation (with or without ARA) on brain development in physiologic
conditions and in subjects born at term and have been presented by the applicant.
The 13 publications above include long term observations on subjects supplemented in the first
months of life (Agostoni et al., 1997; Auestad et al., 2003; Bouwstra et al., 2005; Birch et al.,
2007) while one publication reports complementary observations on neurodevelopmental
outcomes (Willatts et al., 1998b). Therefore, the results from eight original study designs are
available. All these studies were conducted in term infant populations fed different formulas
from birth through the first months of life up to 12 months at the maximum (Agostoni et al.,
1995; Auestad et al., 2001; Ben et al., 2004; Birch et al., 2000; Bouwstra et al., 2003; Lucas et
al., 1999; Makrides et al., 2000; Willatts et al., 1998a).
In two RCTs (Auestad et al, 2001; Ben et al, 2004), formulas with less than 0.2% DHA (in
various combinations with ARA) from birth through six (Ben et al., 2004) or 12 months of age
(Auestad et al., 2001; Auestad et al., 2003, follow-up) had no effect on neurodevelopmental
indices measured with different methods as compared to standard, unsupplemented formulas.
Only in one study the power calculations were reported (Auestad et al., 2001). The Panel notes
that the doses of DHA (and ARA) used in these studies were lower than those proposed by the
applicant to obtain the claimed effect.
Two publications report the results of double-blind RCTs investigating the effects of formulas
supplemented with DHA around 0.3% either alone or in combination with ARA at around the
same level (ARA:DHA ratio = 1) form birth to 6-12 months of life as compared to
unsupplemented formulas (Lucas et al., 1999; Makrides et al., 2000). In the study by Lucas et
al. (1999), 309 healthy term infants were randomly allocated at birth to receive either a DHA
and ARA supplemented formula (n = 154) or a control (unsupplemented) formula (n = 155) for
DHA and ARA and brain development
The EFSA Journal (2009) 1000, 9-13
six months. Breastfed infants for at least six weeks served as reference group (n = 138). Sample
sizes were based on power calculations considering the Bayley’s Mental and Psychomotor
Developmental Indices (MDI, PDI) of infant development as primary outcomes. A total of 125,
125, and 104 infants in the intervention, control and reference groups were evaluated at 18
months for Bayley’s MDI and PDI. No significant differences were observed at 18 months
between the intervention and the control group, or between the formula-fed vs the breastfed
groups, on either cognitive or motor development after adjustment for confunders. In the study
by Makrides et al. (2000), 83 healthy full-term infants were randomly allocated at the age of
one week to receive one of three formulae (placebo formula, formula with 0.35 % of total fatty
acids as DHA or formula with both DHA 0.34 % and ARA 0.34 %) to be consumed throughout
the first year of life. A total of 61 infants could be investigated at 1 and 2 years of age. From a
control group of 63 breast-fed infants, 46 completed the trial until two years of age. Sample
sizes were based on power calculations considering sweep VEP acuity (and not Bayley’s MDI
and/or PDI scales) as primary outcome. No differences were observed between the three
formula-fed groups at one or two years of age on Bayley’s MDI or PDI. Breastfed infants had
higher MDI scores than formula-fed infants at two years of age even after adjusting for
environmental variables. The Panel notes that doses of DHA in these studies (but not the
DHA:ARA ratio) are in the range of those recommended by the applicant to obtain the claimed
effect.
In the double-blind RCT by Willatts et al. (1998a), 44 term infants were randomly allocated at
birth to consume either a formula supplemented with 0.15-0.25% DHA and 0.30-0.40% ARA
(ARA:DHA ratio = 1.7:1 to 2:1, n = 21) or a standard (control, n = 23) unsupplemented
formula for four months in order to investigate the effects of DHA and ARA supplementation
on infant cognitive behaviour at 10 months of age by a means-end problem-solving test. A
sample size of 24 subjects per group was calculated as being required to detect a difference of
one intentional solution on the entire three-step problem with a power of 90% at P=0.05.
Infants who received the DHA and ARA supplemented formula had significantly more
intentional solutions and higher intention scores than infants who received the unsupplemented
formula. The means-end problem-solving test is currently used to explore the function of
specific associative areas in the prefrontal lobes, which are particularly rich in DHA.
Significantly higher DHA content in these brain areas has been observed in breastfed infants vs
(unsupplemented) formula-fed infants at four months of life in autoptic studies (“cot” death)
presented by the applicant in the section of biological plausibility (Farquharson et al., 1993;
Makrides et al., 1994). In anoher publication on the same infant population (Willatts et al.,
1998b), a post-hoc analysis comparing infants with evidence of reduced growth parameters at
birth and impaired attention control as manifested by a late peak fixation during infant
habituation assessment at three months versus infants with early peak fixation within the
supplemented (n = 11 vs n = 9, respectively) and the unsupplemented (n = 10 n = 10,
respectively) formula groups showed that the number of solutions in the means-end problem-
solving ability at nine months was significantly reduced in the late peak-fixation infants
receiving the unsupplemented formula as compared to the other three groups. The Panel notes
the small sample size on each of the groups and that the hypothesis tested in this post-hoc
analysis falls beyond the primary outcome (number of solutions at the means-end problem
solving test) for which the sample size required was initially identified (Willatts et al., 1998a).
The Panel also notes that doses of DHA (but not the DHA:ARA ratio) reported in these studies
were lower than those recommended by the applicant to obtain the claimed effect.
In the remaining three study designs (Agostoni et al, 1995; Bouwstra et al., 2003; Birch et al.,
2000) formulas supplemented with either 0.3 % DHA alone or in combination with ARA in
higher dosages (ARA:DHA ratio from 1.4:1 to 2:1) were used in the intervention groups. The
DHA and ARA and brain development
The EFSA Journal (2009) 1000, 10-13
Panel also notes these doses of DHA and the DHA:ARA ratio are in the range of those
recommended by the applicant to obtain the claimed effect.
In the double-blind RCT by Agostoni et al. (1995), healthy term infants were randomised at
birth to consume either a formula supplemented with 0.30% DHA and 0.44% ARA
(ARA:DHA ratio = 1.4:1, n = 29) or a control (unsupplemented) formula (n = 31) for four
months. An exclusively breastfed group (n = 31) served as reference. Global
neurodevelopmental performance was assessed by means of the Brunet-Lézine test as
Developmental Quotient (DQ) at 4 months. A sample size of 24 subjects per group was
calculated as being required to detect a clinically significant difference on DQ (10%) between
groups with a power of 90% at P=0.05. Infants in the supplemented formula and in the
breastfed groups scored significantly higher in the Brunet-Lézine test than infants in the control
group at four months of age. No differences were observed between the supplemented formula
and the breastfed groups. Differences between the formula-fed groups were not sustained when
infants were re-evaluated with the Brunet-Lézine test at 24 months of life (Agostoni et al.,
1997). The Panel notes that the Brunet-Lézine test (as well as the Griffith’s scale and the
Bayley’s indices) ultimately derives from the Gesell’s developmental schedules published in
1947 (Gesell and Amatruda, 1947), which were originary developed for the definition of mental
handicap and not for the scoring of attitudes generally indicated as “intelligence” within the
“normal” population of infants and children, in which their predictive value is doubtful.
In the double-blind RCT by Bouwstra et al. (2003), healthy term infants were randomised at
birth to consume either a formula supplemented with 0.3% DHA and 0.45% ARA (ARA:DHA
ratio = 1.5:1, n = 119) or a control (unsupplemented) formula (n = 131) for two months. A
breastfed group (n = 147), of which 73 infants stopped breasfeeding before the 2-month
intervention and were subsequently assigned to the supplemented formula, served as reference.
The quality of general movements (GMs) based on the observations of videotapes recording the
infants’ movements was assessed 3 months of age. The quality of GMs was classified as
normal-optimal, normal-suboptimal and midly abnormal. This test appears to have a predictive
value for the neurological development (not intelligence) later in life. No power calculations
are reported. Infants in the control group had mildly abnormal GMs significantly more often
than did infants in the supplemented formula and breastfed groups (31% compared with 19%
and 20%, respectively). Infants in the breastfed group had normal-optimal GMs more
frequently than did infants in the supplemented formula and control groups (34% compared
with 18% and 21%, respectively). No differences between the supplemented formula, the
control formula and the breastfeed groups were found in clinical neurological condition,
neurological optimality score, fluency score, or the Bayley’s MDI or PDI when the infants were
re-tested at 18 months of life (Bouwstra et al., 2005).
The double-blind RCT by Birch et al. (2000) included 112 infants randomised at the age of five
days to consume either a formula with DHA 0.35% alone, a formula with DHA 0.36% plus
ARA 0.72%, or a control formula devoid of DHA and ARA for 17 weeks. An additional group
of term infants (n = 29) exclusively breastfed for at least the first 17 weeks of life served as
non-randomised control group. A sample size of 16 subjects per group was calculated as being
required to detect mean differences in the MDI of the Bayley scales of 1SD or greater at 18
months between groups. At that age, 20 subjects in the control formula group, 17 in the DHA-
supplemented formula group and 19 in the DHA plus ARA formula groups were tested with the
Bayley scales of infant development. Infants supplemented with DHA and ARA yielded
significantly higher MDI scores (mean = 7 points) than infants in the control group. Both the
cognitive and motor subscales of the MDI showed a significant developmental age advantage
for the groups supplemented with DHA and with DHA plus ARA as compared to controls. No
significant differences between groups were observed among the three groups regarding the
PDI or the Behaviour Rating Scale. Significant correlations were observed between DHA
DHA and ARA and brain development
The EFSA Journal (2009) 1000, 11-13
concentrations in red blood cells (but not between ARA, linoleic acid,
α-linolenic acid or
eicosapentaenoic acid) at four months (but not at 12 months) and the MDI scores at 18 months
of age. Infants in the formula-fed and breastfed groups were tested at four years of age for
Intelligence Quotient (IQ). Verbal IQ in the control and DHA-supplemented formula groups
was significantly lower than in the DHA plus ARA and the breastfed groups. No differences
were observed among all four groups regarding the full scale IQ or the performance IQ (Birch
et al., 2007).
The Panel notes that none of the studies using formulas supplemented with doses of DHA and
ARA lower than proposed in the conditions of use or 0.3% DHA and an ARA:DHA ratio of
one show an effect of DHA and ARA supplementation on neurodevelopment indices infants as
compared to unsupplemented formulas (Auestad et al., 2001; Auestad et al., 2003; Ben et al.,
2004; Lucas et al., 1999; Makrides et al., 2000). The Panel also notes that the four studies using
either slightly lower DHA doses (Willatts et al., 1998a) or about 0.3% DHA (Agostoni et al,
1995; Birch et al, 2000; Bouwstra et al., 2003) and the ARA:DHA ratio proposed in the
conditions of use (between 1.4:1 and 2:1) show a short-tem beneficial effect of DHA and ARA
supplementation on different measures of neurodevelopment. However, the different testing
ages and the use of different tests for assessment limit the comparability of the studies. Also,
the predictive value of the neurodevelopment tests used is uncertain. Indeed, only two of the
studies above show an effect beyond the supplementation period (Willatts et al., 1998a; Birch
et al., 2007), and only one reports a sustained effect beyond the first year of life in a limited
sample of subjects (Birch et al., 2007). In no case the breastfed reference group showed lower
developmental indices when compared to any formula-fed group.
Although the Panel acknowledges that there is some evidence supporting a short-tem effect of
DHA and ARA supplementation starting at birth on brain development in non-breastfed infants,
the Panel considers that the data available is inconsistent and does not support an effect beyond
the supplementation period or beyond the first year of life.
The Panel concludes that the data presented are insufficient to establish a cause an effect
relationship between the intake of infant and follow-on formula supplemented with DHA at
levels around 0.3% of the fatty acids and a ratio ARA:DHA between 1.4:1 and 2:1 and the
contribution to normal brain development in infants and young children from birth to three
years of age.
C
ONCLUSIONS
On the basis of the data presented, the Panel concludes the following:
•
The food constituents DHA and ARA are sufficiently characterised.
•
The claimed effects is the contribution to the optimal brain development of infants and
young children.
The target population proposed by the applicant is infants and young
children (from birth to three years of age). Contribution to the normal development of
the brain is beneficial for infants’ and children’s development and health.
•
The data presented are insufficient to establish a cause an effect relationship between
the intake of infant and follow-on formula supplemented with DHA at levels around
0.3% of the fatty acids and a ratio ARA:DHA between 1.4:1 and 2:1 and the
contribution to normal brain development in infants and young children (from birth to
three years of age).
DHA and ARA and brain development
The EFSA Journal (2009) 1000, 12-13
D
OCUMENTATION PROVIDED TO
EFSA
Health claim application on DHA and ARA and brain development pursuant to Article 14 of
Regulation (EC) No 1924/2006 (Claim serial No:0131a-FR). October 2008. Submitted by
Mead Johnson & Company.
R
EFERENCES
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G
LOSSARY
/
A
BBREVIATIONS
ARA Arachidonic
acid
DHA Docosahexaenoic
acid
GMs General
movements
DQ Developmental
Quotient
IQ Intelligence
Quotient
MDI Mental
Developmental
Index
PDI Psychomotor
Developmental Index
RCTs
Randomised controlled trials
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