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Food additives and hyperactive behaviour in kids, McCann D, Grimshaw K, Sonuga-Barke, Warner JO, Stevenson J, et al, The Lancet 2007.09.06 pdf 454 KB: Murray 2007.09.06



 
 
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Old September 7th 07, 02:08 AM posted to alt.support.attn-deficit,misc.kids.health,sci.med.nutrition
Rich Murray
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Default Food additives and hyperactive behaviour in kids, McCann D, Grimshaw K, Sonuga-Barke, Warner JO, Stevenson J, et al, The Lancet 2007.09.06 pdf 454 KB: Murray 2007.09.06

Food additives and hyperactive behaviour in kids, McCann D, Grimshaw
K, Sonuga-Barke, Warner JO, Stevenson J, et al, The Lancet 2007.09.06
pdf 454 KB: Murray 2007.09.06
http://groups.yahoo.com/group/aspartameNM/message/1471


"Artificial colours or a sodium benzoate preservative (or both) in the
diet result in increased hyperactivity in 3-year-old and 8/9-year-old
children in the general population."

"The study dietitian also obtained a report based on 24-h recall by
the parent of the child’s pretrial diet, which allowed an assessment
of baseline levels of the number of foods containing additives
consumed by the child in the previous 24 h."

[ Rich Murray comments: Did they collect data on the amounts of MSG,
aspartame, and sucralose consumption, which probably are significant
co-factors in neurotoxicity?

Since poor memory is a commonly reported symptom by aspartame
reactors,
could this have affected the "24-hour recall by the parent of the
child's pretrial diet"? ]

"We have completed a pilot study showing that changes in hyperactivity
in response to food additives can be produced within about 1 h."

"Doses for mixes A and B for 3-year-old children were roughly the same
as the amount of food colouring in two 56-g bags of sweets.

For 8/9-year-old children, the dose for mix A was equal to about two
bags of sweets a day and for mix B about four bags of sweets a day."

http://www.thelancet.com/journals/la...13063/fulltext

www.thelancet.com Published online September 6, 2007 DOI:10.1016/
S0140-6736(07)61306-3 1 $ 30 full text pdf 454 KB

Food additives and hyperactive behaviour in 3-year-old and
8/9-year-old children in the community: a randomised,
double-blinded, placebo-controlled trial.
Donna C McCann, ,
Angelina Barrett,
Alison Cooper,
Debbie Crumpler,
Lindy Dalen,
Kate EC Grimshaw,
,
Elizabeth Kitchin,
Kris Lok,
Lucy Porteous,
Emily Prince,
Edmund J Sonuga-Barke,
,
John O Warner,
,
Jim Stevenson.
,

Summary

Background
We undertook a randomised, double-blinded, placebo-controlled,
crossover trial to test whether intake of artificial food colour and
additives (AFCA) affected childhood behaviour.

Methods
153 3-year-old and 144 8/9-year-old children were included in the
study.

The challenge drink contained sodium benzoate and one of two AFCA
mixes (A or B) or a placebo mix.

The main outcome measure was a global hyperactivity aggregate (GHA),
based on aggregated z-scores of observed behaviours and ratings by
teachers and parents,
plus, for 8/9-year-old children, a computerised test of attention.

This clinical trial is registered with Current Controlled Trials
(registration number ISRCTN74481308).

Analysis was per protocol.

Findings
16 3-year-old children and 14 8/9-year-old children did not complete
the study, for reasons unrelated to childhood behaviour.

Mix A had a significantly adverse effect compared with placebo in GHA
for all 3-year-old children
(effect size 0â‹…20 [95% CI 0â‹…01-0â‹…39], p=0â‹…044)
but not mix B versus placebo.

This result persisted when analysis was restricted to 3-year-old
children who consumed more than 85% of juice and had no missing data
(0⋅32 [0⋅05–0⋅60], p=0⋅02).

8/9-year-old children showed a significantly adverse effect when given
mix A (0⋅12 [0⋅02–0⋅23], p=0⋅023) or
mix B (0⋅17 [0⋅07–0⋅28], p=0⋅001)
when analysis was restricted to those children consuming at least 85%
of drinks with no missing data.

Interpretation
Artificial colours or a sodium benzoate preservative (or both) in the
diet result in increased hyperactivity in 3-year-old and 8/9-year-old
children in the general population.

School of Psychology
(D McCann PhD, A Barrett BSc,A Cooper MSc, D Crumpler BSc,L Dalen PhD,
E Kitchin BSc,K Lok MSc, L Porteous BSc, E Prince MSc,
Prof EJ Sonuga-Barke PhD, Prof J Stevenson PhD)

and School of Medicine
(K Grimshaw MSc), Department of Child Health,
University of Southampton, Southampton, UK;

and Department of Paediatrics,Imperial College, London, UK
(Prof J O Warner MD)

Correspondence to:
Prof Jim Stevenson, School of Psychology, Faculty of Medicine,
Health and Life Sciences, University of Southampton,
Southampton SO17 1BJ, UK


Introduction

Artificial food colours and other food additives (AFCA) have long been
suggested to affect behaviour in children.1

Ben Feingold made his initial claims of the detrimental effect of AFCA
on childhood behaviour more than 30 years ago.2

The main putative effect of AFCA is to produce overactive, impulsive,
and inattentive behaviour -- ie, hyperactivity --
which is a pattern of behaviour that shows substantial individual
differences in the general population.

Children who show this behaviour pattern to a large degree are
probably diagnosed with attention-deficit hyperactivity disorder
(ADHD).

Despite the failure of early studies3 to identify the range of
proposed adverse affects, a recent meta-analysis4 of double-blinded,
placebo-controlled trials has shown a significant effect of AFCA on
the behaviour of children with ADHD.

The possible benefit in a reduction in the level of hyperactivity of
the general population by the removal of AFCA from the diet is less
well established.

Evidence from our previous study on the Isle of Wight has suggested
adverse effects on hyperactivity, measured by parental ratings for 3-
year-old children on a specific mix of additives.5

These findings needed replication on 3-year-old children, and to
establish whether the effects could be seen with a wider range of
measures of hyperactivity.

The present community-based, double-blinded, placebo-controlled food
challenge was designed to extend the age range studied to include
8/9-year-old children to determine whether the effects could also be
detected in middle childhood.

Methods

Participants

Figures 1 and 2 present details of recruitment and participation in
the study, for 3-year-old and 8/9-year-old children, respectively.

The study sample was drawn from a population of children aged between
3 years and 4 years, 2 months, registered in early-years settings
(nurseries, day nurseries, preschool groups, playgroups) and from
children aged between 8 and 9 years attending schools in Southampton,
UK.

To ensure that the study sample included children from the full range
of
socioeconomic backgrounds, schools were recruited based on the number
of children receiving free school meals (an index of social
disadvantage).

The distribution of the percentage of children receiving free meals in
the schools taking part indicated the proportions for the city as a
whole.

To further check on how representative the sample was, teachers
completed a hyperactivity questionnaire6 for all 3-year-old and 8/9-
year-old children.

Parents who returned an expression of interest form were contacted by
phone and a home visit arranged.

On this visit, a research assistant and the study dietitian, provided
full information about the study and its dietary implications, and
written informed consent was obtained.

The study dietitian also obtained a report based on 24-h recall by the
parent of the child’s pretrial diet, which allowed an assessment of
baseline levels of the number of foods containing additives consumed
by the child in the previous 24 h.

The study was approved by the local research ethics committee
(reference no 04/Q1702/61) and written informed consent was obtained
from parents.

Participating early-years settings received £250 and each school £500
as a contribution towards school funds for the benefit of all
children.

Study design and challenge protocols

The study design and challenge protocols for both ages were similar.

Children were entered into this study with a within-subject crossover
between two active mixes (A and B) and a placebo drink.

The two active mixes differed both in the quantities of additives and
the specific additives included.

Mix A was similar to the active challenge used in the Isle of Wight
study,5 and mix B was selected to indicate the current average daily
consumption of food additives by 3-year-old and 8/9-year-old children
in the UK.7

Both mixes included sodium benzoate, which had been included in the
challenge on the Isle of Wight study and in previous studies.8,9

Mix A for 3-year-old children included
20 mg of artificial food colourings
5 mg sunset yellow [E110],
2â‹…5 mg carmoisine [E122],
7â‹…5 mg tartrazine [E102],
and 5 mg ponceau 4R [E124, Forrester Wood, Oldham, UK])
and 45 mg of sodium benzoate [E211, Sigma Aldridge,
Gillingham, UK]).

Active mix B included
30 mg of artificial food colourings
(7â‹…5 mg sunset yellow,
7â‹…5 mg carmoisine,
7â‹…5 mg quinoline yellow [E110],
and 7â‹…5 mg allura red AC [E129])
and 45 mg of sodium benzoate.

Mix A amounts for 8/9-year-old children were multiplied by 1â‹…25 to
account for the increased amount of food consumed by children at this
age.

Therefore, mix A included
24â‹…98 mg of artificial food colourings
6â‹…25 mg sunset yellow,
3â‹…12 mg carmoisine,
9â‹…36 mg tartrazine,
and 6â‹…25 mg ponceau 4R)
and 45 mg of sodium benzoate.

Active mix B included
62â‹…4 mg of artificial food colourings
(15â‹…6 mg sunset yellow,
15â‹…6 mg carmoisine,
15â‹…6 mg quinoline yellow,
and 15â‹…6 mg allura red AC)
and 45 mg of sodium benzoate.

Doses for mixes A and B for 3-year-old children were roughly the same
as the amount of food colouring in two 56-g bags of sweets.

For 8/9-year-old children, the dose for mix A was equal to about two
bags of sweets a day and for mix B about four bags of sweets a day.

After a week on their typical diet (week 0: baseline diet),
the artificial colours to be used in the challenges and
sodium benzoate were withdrawn from their diet for 6 weeks.

Over this period when challenge with active or placebo drinks were
given, additive withdrawal continued
(week 1: withdrawal period but receiving placebo;
weeks 2, 4, and 6: challenge with randomisation to two active
periods and one placebo period;
weeks 3 and 5: washout continuing on placebo).

During this period, 3-year-old children received the challenge and
washout-placebo drinks on a weekly basis and consumed mixed fruit
juices (placebo or active) at home (300 mL/day for 3-year-old
children, 625 mL/day for 8/9-year-old children),
provided in identical sealed bottles.

At the beginning of the study, children were assigned by the study
administrator by a random-number generator to receive one of six
possible sequences of placebo, active mix A, or
active mix B challenges across weeks 2, 4, and 6.

A masked testing by two independent panels of 20 young adults showed
that the active and placebo juice drinks could not be differentiated.

When asked if the mix contained additive, 16 (40%), 21 (52%), and 26
(65%) adults responded positively for mix A, mix B, and placebo,
respectively.

We recorded no significant differences between these proportions
(Friedman test, χ²=4⋅412, df=2).

Therefore, no reliable differences were seen between the look and
taste of the drinks.

The only difference in the composition of the placebo and active
mixes was the presence of the AFCA in the active mix with some
variation in the proportions of the fruit juices to ensure matching
colour and taste for the placebo and active drinks.....

"Global hyperactivity aggregate (GHA)"

....Parents rated their child’s behaviour during the previous week for
seven items previously used
(switching activities;
interrupting or talking too much;
wriggling;
fiddling with objects or own body;
restless;
always on the go;
concentration),4
from which we obtained a total score.....

....A fourth measure for 8/9-year-old children was the Conners
continuous performance test II (CPTII),16 a [computerized] test using
visual stimuli of 14-min duration and is widely used to assess
attention and the response inhibition component of executive control.

We used four scores
(SE of reaction time,
% of commission errors,
d´ [discriminability index],
and β)
to derive a weekly aggregate score.
This subset of indicators from the CPTII has been shown to be highly
correlated with the ADHD rating scale.17.....

....128 (93%) of the 137 children who completed the study consumed more
than two-thirds of all drinks, of which 103 (80%) consumed 85% or more
(ie, at least six of seven daily drinks per week).....

....Under model 2, in which the effects of other factors were
controlled, the effect of mix A for the entire sample was not
significant (p=0·123) but mix B did have a significantly adverse
effect compared with placebo (p=0·012).

When the analyses are restricted to those children who consumed at
least 85% juice, the adverse effect of mix A on behaviour remained
non-significant (p=0·066)
but was significant for mix B (p=0·003).

The complete case groups showed significantly higher GHA scores than
placebo for mix A (p=0·023) and mix B (p=0·001).....

....Discussion

In this community-based, double-blinded, placebo-controlled
food challenge, we tested the effects of artificial food additives on
children’s behaviour and have shown that a mix of additives commonly
found in children’s food increases the mean level of hyperactivity
in children aged 3 years and 8/9 years.

Our complete case data has indicated that the effect sizes, in terms
of
the difference between the GHA under active mix and placebo
challenges, were very similar for mix B in 3-year-old and 8/9-year-old
children.

For mix A, the effect for 3-year-old children was greater than for
8/9-year-old children.

The effects for mix B were not significant for 3-year-old children
because there was greater variability in the response to the active
challenges than placebo in this age group.

Thus, we recorded substantial individual differences in the response
of children to the additives.

For both age groups, no significant effect of social and demographic
factors was seen on the initial level of GHA or in the moderation of
the challenge effects.

The moderating effects of genotype on the child’s behaviour response
to
AFCA are examined in a separate paper (unpublished data).

The effect sizes reported in this study are similar to those
calculated in the meta-analysis by Schab and Trinh.4

They estimated the effects of AFCA on hyperactivity to be
0·283 (95% CI 0·079–0·488), falling to 0·210 (0·007–0·414)
when the smallest and lowest quality trials were excluded.

It should be noted that this meta-analysis included studies of
hyperactivity in clinical samples, whereas the present study was done
on children in the general population with the full range of degrees
of
hyperactivity.

These effect sizes recorded by Schab and Trinh are smaller than those
reported for stimulant treatment for ADHD in children, for which one
meta-analysis21 reported a range of effect sizes
from 0·78 (0·64–0·91) by teacher report
to 0·54 (0·40–0·67) by parent report.

We report effect sizes that average at about 0·18.

Children with ADHD are generally about 2 SD higher on hyperactivity
measures than those without the disorder,22
thus an effect size of 0·2
is about 10% of the behavioural difference between them.

This study provides evidence of deleterious effects of AFCA on
children’s behaviour with data from a whole population sample,
using a combination of robust objective measures
with strong ecological validity,
based partly on observations in the classroom
and ratings of behaviour made independently by teachers
and by parents in the different context of the home
and applying double-blinded challenges with quantities of additives
equal to typical dietary intakes.

It also replicates the effects of mix A previously reported on a large
sample (n=277) of 3-year-old children,5 although significant effects
were only seen with parental ratings in that study.

The specific deleterious compounds in the mix cannot be determined for
the present study and need to be examined in subsequent studies.

The effect of artificial colours needs to be differentiated from the
effects of preservatives in a 2X2 design.

Further investigation would also need to establish whether the age-
related difference seen in the present study can be replicated --
ie, the effects of mix A being greater for 3-year-old children
than for 8/9-year-old children.

We examined the effects of additives on changes in behaviour during an
extended period in a community-based, double-blinded, placebo-
controlled
food challenge.

A weakness in this approach is the lack of control over when the
challenges are ingested in relation to the timing of measures of
hyperactivity.

This study design also needs extensive resources to obtain multisource
and multicontext measures of hyperactivity.

We have completed a pilot study showing that changes in hyperactivity
in response to food additives can be produced within about 1 h.

Therefore, future studies could use more feasible acute double-blinded
challenges undertaken in more controlled settings.

The present findings, in combination with the replicated evidence for
the AFCA effects on the behaviour of 3-year-old children, lend strong
support for the case that food additives exacerbate hyperactive
behaviours (inattention, impulsivity, and overactivity)
in children at least up to middle childhood.

Increased hyperactivity is associated with the development of
educational difficulties, especially in relation to reading, and
therefore these adverse effects could affect the child’s ability to
benefit from the experience of schooling.23

These findings show that adverse effects are not just seen in children
with extreme hyperactivity (ie, ADHD),4 but can also be seen in the
general population and across the range of severities of
hyperactivity.

Our results are consistent with those from previous studies and extend
the findings to show significant effects in the general population.

The effects are shown after a rigorous control of placebo effects and
for children with the full range of levels of hyperactivity.

We have found an adverse effect of food additives on the hyperactive
behaviour of 3-year-old and 8/9-year-old children.

Although the use of artificial colouring in food manufacture might
seem superfluous, the same cannot be said for sodium benzoate, which
has
an important preservative function.

The implications of these results for the regulation of food additive
use could be substantial.

Contributors

JS, JOW, and ES-B participated in the conception and design of the
study.

The Food Standards Agency assisted with the design of the study.

DMC directed the execution of the study.

AB, AC, DC, LD, EK, LP, and EP undertook assessments of the children
and helped to develop the observational methods employed in the study.

KG supervised and KL executed the nutritional aspects of the study in
relation to the preparation of suitable challenge drinks and advice on
diet for parents.

DMC and JS analysed the data and wrote the manuscript with input from
all the authors.

Conflict of interest statement

We declare that we have no conflict of interest.

Acknowledgments

We thank the children, families, and teachers in the participating
schools and early years settings in the Southampton area for their
help
and assistance with the study;
and Catherine Varcoe-Baylis and Jenny Scoles and the local steering
committee for their assistance,
especially Ulrike Munford and the representatives from Southampton
City Council Children’s Services and Learning
and the Southampton Early Years Development and Childcare Partnership;
and the Food Standards Agency for their significant advice and input
into the study.
This study received funding from the Food Standards Agency
(grant T07040).

References

1 Overmeyer S, Taylor E,
Annotation: principles of treatment for hyperkinetic disorder:
practice approaches for the UK.
J Child Psychol Psychiatry 1999; 40: 1147–57.

2 Feingold BF.
Hyperkinesis and learning disabilities linked to artificial food
flavors and colours.
Am J Nurs 1975; 75: 797–803.

3 Editorial. NIH consensus development conference:
defined diets and childhood hyperactivity.
Clin Pediatr 1982; 21: 627–30.

4 Schab DW, Trinh NT.
Do artificial food colours promote hyperactivity in children with
hyperactive syndromes? A meta-analysis of double-blind placebo-
controlled trials.
J Dev Behav Pediatr 2004; 25: 423–34.

5 Bateman B, Warner JO, Hutchinson E, et al.
The effects of a double blind, placebo controlled, artificial food
colourings and benzoate preservative challenge on hyperactivity in a
general population sample of preschool children.
Arch Dis Child 2004; 89: 506–11.

6 DuPaul GJ, Power TJ, Anastopoulos AD, Reid R, McGoey K, Ikeda M.
Teacher ratings of ADHD symptoms: Factor structure and normative data.
Psychol Assess 1997; 9: 436–44.

7 Gregory JR, Collins EDI Davies PSW, Hughes JM, Clarke PC.
National Diet and Nutrition Survey: children aged 1·5 to 4·5 years.
Vol 1: Report of the Diet and Nutrition Survey.
London: HM Stationery Office, 1995.

8 Egger J, Graham PJ, Carter CM, Gumley D, Soothill JF.
Controlled trial of oligoantigenic treatment in the hyperkinetic
syndrome.
Lancet 1985; 325: 540–45.

9 Carter CM, Urbanowicz M, Hemsley R, et al.
Effects of a few food diet in attention-deficit disorder.
Arch Dis Child 1993; 69: 564-68.

10 Routh D.
Hyperactivity.
In: Magrab P, ed. Psychological management of pediatric problems.
Baltimo University Park Press, 1978: 3–8.

11 Thompson MJJ, Stevenson J, Sonuga-Barke E, et al.
The mental health of preschool children and their mothers in a mixed
urban/rural population. Prevalence and ecological factors.
Br J Psychiatry 1996; 168: 16–20.

12 Hayward C, Killen J, Kraemer H, et al.
Linking self-reported childhood behavioural inhibition to adolescent
social phobia.
J Am Acad Child Adolesc Psychiatry 1998; 37: 1308–16.

13 Mash EJ, Johnston C.
Parental perceptions of child behaviour problems, parenting self-
esteem and mother’s reported stress in younger and older hyperactive
and normal children.
J Consult Clin Psychol 1983; 51: 86–99.

14 DuPaul GJ, Power TJ, Anastopoulos AD, Reid R.
AD/HD rating scale IV: checklists, norms and clinical interpretation.
New York: Guilford Press, 1998.

15 Abikoff H, Gittleman R.
Classroom observation code -- a modification of the stony-brook code.
Psychopharmacol Bull 1985; 21: 901–09.

16 Conners CK.
The Conners continuous performance test.
Toronto, ON, Canada: Multi-Health Systems, 1994.

17 Epstein N, Erkanli A, Conners CK, Klaric J, Costello JE, Angold A.
Relations between continuous performance test performance measures and
ADHD behaviours.
J Abnorm Child Psychol 2003; 31: 543–54.

18 Gueorguieva R, Krystal JH. Move over ANOVA:
Progress in analysing repeated-measures data and its reflection in
papers published in the Archives of General Psychiatry.
Arch Gen Psychiatry 2004; 61: 310–17.

19 Mallinckrodt CH, Watkin JG, Molenburghs G, et al.
Choice of the primary analysis in longitudinal clinical trials.
Pharm Stat 2004; 3: 161–69.

20 Office for National Statistics.
Standard occupational classification.
London: Stationery Office, 2000.

21 Schachter HA, King J, Langford S, Moher D.
How efficacious and safe is short-acting methylphenidate for the
treatment of attention-deficit disorder in children and adolescents?
A meta-analysis.
Can Med Assoc J 2001; 165: 1475–88.

22 Swanson JM, Sergeant J, Taylor E, Sonuga-Barke EJS, Jensen PS,
Cantwell DP.
Attention-deficit hyperactivity disorder and hyperkinetic disorder.
Lancet 1998; 351: 429–33.

23 McGee R, Prior M, Williams S, Smart D, Sanson A.
The long-term significance of teacher-rated hyperactivity and reading
ability in childhood: findings from two longitudinal studies.
J Child Psychol Psychiatry 2002; 43: 1004–17.
////////////////////////////////////////////////////////////


http://groups.yahoo.com/group/aspartameNM/message/1461
John O. Warner with U. Southampton team in 2007 finds kids hyperactive
from six food colors, confirming their report in 2004 on study in
2000: Murray 2007.08.11

" Our study has shown that the effect of food additives on behaviour
occurs independently of pre-existing hyperactive behaviour or indeed
atopic status.

This is consistent with other studies which have tended to suggest
that
if food additives have an effect at all, it is via a pharmacological
effect which is best exemplified by the non-IgE dependent histamine
release. 20,21

We believe that this suggests that benefit would accrue for all
children
if artificial food colours and benzoate preservatives were removed
from
their diet.

These findings are sufficiently strong to warrant attempts at
replication in other general population samples and to examine whether
similar benefits of the removal of artificial colourings and sodium
benzoate from the diet could be identified in community samples at
older
ages. "

[ See also: http://groups.yahoo.com/group/aspartameNM/message/1426
ASDA (unit of Wal-Mart Stores WMT.N) and Marks & Spencer
will join Tesco and also Sainsbury to ban and limit
aspartame, MSG, artificial flavors dyes preservatives additives,
trans fats, salt "nasties" to protect kids from ADHD:
leading UK media: Murray 2007.05.15

http://groups.yahoo.com/group/aspartameNM/message/1277
50% UK baby food is now organic - aspartame or MSG
with food dyes harm nerve cells, CV Howard 3 year study
funded by Lizzy Vann, CEO, Organix Brands,
Children's Food Advisory Service: Murray 2006.01.13

http://groups.yahoo.com/group/aspartameNM/message/1271
combining aspartame and quinoline yellow, or MSG and
brilliant blue, harms nerve cells, eminent
C. Vyvyan Howard et al, 2005 education.guardian.co.uk,
Felicity Lawrence: Murray 2005.12.21 ]

http://adc.bmj.com/cgi/content/full/89/6/506

Archives of Disease in Childhood 2004; 89(6): 506-511
Erratum in: Arch Dis Child. 2005 Aug; 90(8): 875.
© 2004 BMJ Publishing Group & Royal College of Paediatrics and Child
Health
The effects of a double blind, placebo controlled, artificial food
colourings and benzoate preservative challenge on hyperactivity in a
general population sample of preschool children
B Bateman 1,
J O Warner 1,
E Hutchinson 3,
T Dean 5,
,
P Rowlandson 4, Dr. Piers Rolandson, Paediatric Tutor
C Gant 5,
J Grundy 5,
C Fitzgerald 3
and J Stevenson 2
,

1 Infection, Inflammation and Repair Division, University of
Southampton, Southampton, UK
2 Department of Psychology, University of Southampton, Southampton, UK
3 Department of Clinical Psychology, St Mary’s Hospital, Isle of
Wight, UK
4 Department of Paediatrics, St Mary’s Hospital, Isle of Wight, UK
5 David Hide Asthma and Allergy Research Centre, St Mary’s Hospital,
Isle of Wight, UK
www.soton.ac.uk/

www.iow.nhs.uk/asp/homepage/index.asp
Isle of Wight NHS Primary Care Trust, St Mary's Hospital,
Parkhurst Road, Newport, Isle of Wight PO30 5TG. Tel 01983 524081


http://www.iow.nhs.uk/index.asp?record=865
David Hide Asthma and Allergy Research Centre

www.davidhideallergyresearch.co.uk/
Tel: 01983 534373 Fax: 01983 822928

Registered Charity No. 10202
"The Isle of Wight with a population of approximately 130,000 and an
annual birth-rate of approximately 1200 has proved an ideal
environment
for collecting information on the prevalence of commonly occurring
medical problems."

www.davidhideallergyresearch.co.uk/link2.htm research studies
"This study involves approximately 1400 children who were born on the
Isle of Wight from 1st January 1989 to 28th February 1990. The
majority
has been followed up at the ages of one, two, four and ten years to
enable us to follow the natural history of asthma and allergies. A
grant
is being sought to enable a follow-up of these children when they
reach
16 yrs of age in 2005/6."

"(Food Additives and Behaviour)

The study was funded by the Ministry of Agriculture, Fisheries and
Food
and was designed to assess the impact, if any, of artificial food
additives and colourings on the behaviour of three year old children.

An enormous amount of data on children's behaviour has been collected
from more than two thousand children, as well as information on
allergic
symptoms and sensitisation to allergens. Psychological testing and
dietary assessments were also carried out on a proportion of the
children."

Correspondence to:
Professor J Warner
University Child Health, Southampton General Hospital,
Tremona Road, Southampton SO16 6YD, UK; ,

Accepted for publication 14 September 2003

I have moved to a new post at Imperial College based at St. Mary's
Hospital London.
Any urgent correspondence relevant to Southampton
should be sent to Di Head
I can be contacted on my new e-mail address

Regards, John Warner

ABSTRACT

AIMS:
To determine whether artificial food colourings and a preservative in
the diet of 3 year old children in the general population influence
hyperactive behaviour.

METHODS:
A sample of 1873 children were screened in their fourth year for the
presence of hyperactivity at baseline (HA), of whom 1246 had skin
prick
tests to identify atopy (AT).
Children were selected to form the following groups:
HA/AT,
not-HA/AT,
HA/not-AT,
and not-HA/not-AT (n = 277).
After baseline assessment, children were subjected to a diet
eliminating
artificial colourings and benzoate preservatives for one week; in the
subsequent three week within subject double blind crossover study they
received, in random order, periods of dietary challenge with a drink
containing artificial colourings (20 mg daily) and sodium benzoate (45
mg daily) (active period), or a placebo mixture, supplementary to
their
diet.
Behaviour was assessed by a tester blind to dietary status and by
parents' ratings.

RESULTS:
There were significant reductions in hyperactive behaviour during the
withdrawal phase.
Furthermore, there were significantly greater increases in hyperactive
behaviour during the active than the placebo period based on parental
reports.
These effects were not influenced by the presence or absence of
hyperactivity, nor by the presence or absence of atopy.
There were no significant differences detected based on objective
testing in the clinic.

CONCLUSIONS:
There is a general adverse effect of artificial food colouring and
benzoate preservatives on the behaviour of 3 year old children which
is
detectable by parents but not by a simple clinic assessment.
Subgroups are not made more vulnerable to this effect by their prior
levels of hyperactivity or by atopy.
PMID: 15155391

Keywords: artificial food colouring; benzoate preservatives;
hyperactivity; atopy; double blind placebo controlled challenge

Abbreviations: ADHD, attention deficit-hyperactivity disorder;
APHR, aggregated parental hyperactivity ratings;
AT, atopy;
ATH, aggregated test hyperactivity;
BCL, Behaviour Checklist;
HA, hyperactivity;
WWP, Weiss–Werry–Peters Activity Scale
////////////////////////////////////////////////////////////


13 mainstream research studies in 24 months showing aspartame
toxicity, also 3 relevant studies on methanol and formaldehyde: Murray
2007.09.06
http://groups.yahoo.com/group/aspartameNM/message/1464

http://groups.yahoo.com/group/aspartameNM/message/1467
4 cases of aspartame-induced thrombocytopenia [ very low platelets in
blood ], HJ Roberts MD, Letter in Southern Medical Journal 2007 May:
100(5); 543: Murray 2007.08.25

http://groups.yahoo.com/group/aspartameNM/message/1468
Formaldehyde induced urticarial vasculitis in male medical student,
age 40, Michael Pellizzari, Gillian Marshman, Flinders U.,
Australasian J. Dermatol. 2007 Aug: Murray 2007.08.29

http://groups.yahoo.com/group/aspartameNM/message/1469
highly toxic formaldehyde, the cause of alcohol hangovers, is made by
the body from 100 mg doses of methanol from dark wines and liquors,
dimethyl dicarbonate, and aspartame: Murray 2007.08.31

http://groups.yahoo.com/group/aspartameNM/message/1470
new details on how formaldehyde and formic acid from methanol are
neurotoxic: Chun Lai Nie, Rong Giao He, et al, PLoS ONE 2(7): e629
2007.07.18 Chinese Academy of Sciences, Beijing: Murray 20097.09.01
////////////////////////////////////////////////////////////


http://groups.yahoo.com/group/aspartameNM/message/1457
aspartame bans, tis more an avalanche than a trend...: Rich Murray
2007.08.17

[ see also:
http://groups.yahoo.com/group/aspartameNM/message/1458
ASDA, Wal-Mart's UK supermarket chain, bans artificial colors, trans
fats, MSG and aspartame, Marguerite Kelly, The Washington Post: Murray
2007.08.03 ]

So far, USA print and broadcast media are deaf, blind, and dumb,
regarding recent major bans of aspartame and MSG in the UK and EU.

The EU Parliament voted July 12 to ban artificial sweeteners
in newly born and infant foods.

On May 15 four huge UK supermarket chains announced bans
of aspartame and MSG, food dyes, and many additives
to protect kids from ADHD --
Sainsbury, Tesco, Marks & Spencer, and ASDA, a unit of WalMart.

May 31: Coca-Cola and the much larger Cargill Inc.,
after years of secret development, with 24 patents,
will soon sell rebiana (stevia) in drinks and food
in the many nations where it is approved as a sweetener --
for decades a major sweetener in Japan, China, Korea, Taiwan,
Thailand, Malasia, Saint Kitts, Nevis,
Brazil, Peru, Paraguay, Uruguay, and Israel,
and an approved supplement in USA, Australia, and Canada,
according to Wikipedia.


http://groups.yahoo.com/group/aspartameNM/message/1454
recent research and news re aspartame and stevia: Murray 2007.08.16

"Of course, everyone chooses, as a natural priority,
to actively find, quickly share, and positively act
upon the facts about healthy and safe food, drink,
and environment."

Rich Murray, MA Room For All
505-501-2298 1943 Otowi Road, Santa Fe, New Mexico 87505

http://groups.yahoo.com/group/aspartameNM/messages
group with 82 members, 1,471 posts in a public,
searchable archive http://RMForAll.blogspot.com


http://groups.yahoo.com/group/aspartameNM/message/1395
Aspartame Controversy, in Wikipedia democratic
encyclopedia, 72 references (including AspartameNM # 864
and 1173 by Murray, brief fair summary of much more research:
Murray 2007.01.01

http://groups.yahoo.com/group/aspartameNM/message/1453
Souring on fake sugar (aspartame), Jennifer Couzin,
Science 2007.07.06: 4 page letter to FDA from 12 eminent
USA toxicologists re two Ramazzini Foundation
cancer studies 2007.06.25: Murray 2007.07.18

http://groups.yahoo.com/group/aspartameNMmessage/1451
Artificial sweeteners (aspartame, sucralose) and coloring
agents will be banned from use in newly-born and baby foods,
the European Parliament decided: Latvia ban in schools 2006:
Murray 2007.07.12

http://groups.yahoo.com/group/aspartameNMmessage/1437
stevia to be approved and cyclamates limited by
Food Standards Australia New Zealand:
JMC Geuns critiques of two recent stevia studies by Nunes:
Murray 2007.05.29

http://groups.yahoo.com/group/aspartameNM/message/1427
more from The Independent, UK, Martin Hickman, re ASDA
(unit of Wal-Mart Stores) and Marks & Spencer ban of
aspartame, MSG, artificial chemical additives and dyes
to prevent ADHD in kids: urray 2007.05.16
http://news.independent.co.uk/uk/hea...cle2548747.ece

http://groups.yahoo.com/group/aspartameNM/message/1426
ASDA (unit of Wal-Mart Stores WMT.N) and Marks & Spencer
will join Tesco and also Sainsbury to ban and limit
aspartame, MSG, artificial flavors dyes preservatives additives,
trans fats, salt "nasties" to protect kids from ADHD:
leading UK media: Murray 2007.05.15

http://groups.yahoo.com/group/aspartameNM/message/1438
Coca-Cola and Cargill Inc., after years of development,
with 24 patents, will soon sell rebiana (stevia)
in drinks and foods: Murray 2007.05.31

http://groups.yahoo.com/group/aspartameNM/message/1141
Nurses Health Study can quickly reveal the extent of aspartame
(methanol, formaldehyde, formic acid) toxicity: Murray 2004.11.21

The Nurses Health Study is a bonanza of information about the health
of
probably hundreds of nurses who use 6 or more cans daily of diet soft
drinks -- they have also stored blood and tissue samples from their
immense pool of subjects.
////////////////////////////////////////////////////////////

  #2  
Old September 7th 07, 08:21 AM posted to alt.support.attn-deficit,misc.kids.health,sci.med.nutrition
[email protected]
external usenet poster
 
Posts: 2
Default Food additives and hyperactive behaviour in kids, McCann D, Grimshaw K, Sonuga-Barke, Warner JO, Stevenson J, et al, The Lancet 2007.09.06 pdf 454 KB: Murray 2007.09.06

On Sep 6, 6:08Â*pm, Rich Murray wrote:
Food additives and hyperactive behaviour in kids, McCann D, Grimshaw
K, Sonuga-Barke, Warner JO, Stevenson J, et al, The Lancet 2007.09.06
pdf 454 KB: Murray 2007.09.06http://groups.yahoo.com/group/aspartameNM/message/1471

"Artificial colours or a sodium benzoate preservative (or both) in the
diet result in increased hyperactivity in 3-year-old and 8/9-year-old
children in the general population."

"The study dietitian also obtained a report based on 24-h recall by
the parent of the child’s pretrial diet, which allowed an assessment
of baseline levels of the number of foods containing additives
consumed by the child in the previous 24 h."

[ Rich Murray comments: Did they collect data on the amounts of MSG,
aspartame, and sucralose consumption, which probably are significant
co-factors in neurotoxicity?

Since poor memory is a commonly reported symptom by aspartame
reactors,
could this have affected the "24-hour recall by the parent of the
child's pretrial diet"? ]

"We have completed a pilot study showing that changes in hyperactivity
in response to food additives can be produced within about 1 h."

"Doses for mixes A and B for 3-year-old children were roughly the same
as the amount of food colouring in two 56-g bags of sweets.

For 8/9-year-old children, the dose for mix A was equal to about two
bags of sweets a day and for mix B about four bags of sweets a day."

http://www.thelancet.com/journals/la...40673607613063...

www.thelancet.comPublished online September 6, 2007 DOI:10.1016/
S0140-6736(07)61306-3 1 Â*$ 30 full text pdf 454 KB

Food additives and hyperactive behaviour in 3-year-old and
8/9-year-old children in the community: a randomised,
double-blinded, placebo-controlled trial.
Donna C McCann, ,
Angelina Barrett,
Alison Cooper,
Debbie Crumpler,
Lindy Dalen,
Kate EC Grimshaw, ,
Elizabeth Kitchin,
Kris Lok,
Lucy Porteous,
Emily Prince,
Edmund J Sonuga-Barke, ,
John O Warner, ,
Jim Stevenson. ,

Summary

Background
We undertook a randomised, double-blinded, placebo-controlled,
crossover trial to test whether intake of artificial food colour and
additives (AFCA) affected childhood behaviour.

Methods
153 3-year-old and 144 8/9-year-old children were included in the
study.

The challenge drink contained sodium benzoate and one of two AFCA
mixes (A or B) or a placebo mix.

The main outcome measure was a global hyperactivity aggregate (GHA),
based on aggregated z-scores of observed behaviours and ratings by
teachers and parents,
plus, for 8/9-year-old children, a computerised test of attention.

This clinical trial is registered with Current Controlled Trials
(registration number ISRCTN74481308).

Analysis was per protocol.

Findings
16 3-year-old children and 14 8/9-year-old children did not complete
the study, for reasons unrelated to childhood behaviour.

Mix A had a significantly adverse effect compared with placebo in GHA
for all 3-year-old children
(effect size 0â‹…20 [95% CI 0â‹…01-0â‹…39], p=0â‹…044)
but not mix B versus placebo.

This result persisted when analysis was restricted to 3-year-old
children who consumed more than 85% of juice and had no missing data
(0⋅32 [0⋅05–0⋅60], p=0⋅02).

8/9-year-old children showed a significantly adverse effect when given
mix A (0⋅12 [0⋅02–0⋅23], p=0⋅023) or
mix B (0⋅17 [0⋅07–0⋅28], p=0⋅001)
when analysis was restricted to those children consuming at least 85%
of drinks with no missing data.

Interpretation
Artificial colours or a sodium benzoate preservative (or both) in the
diet result in increased hyperactivity in 3-year-old and 8/9-year-old
children in the general population.

School of Psychology
(D McCann PhD, A Barrett BSc,A Cooper MSc, D Crumpler BSc,L Dalen PhD,
E Kitchin BSc,K Lok MSc, L Porteous BSc, E Prince MSc,
Prof EJ Sonuga-Barke PhD, Prof J Stevenson PhD)

and School of Medicine
(K Grimshaw MSc), Department of Child Health,
University of Southampton, Southampton, UK;

and Department of Paediatrics,Imperial College, London, UK
(Prof J O Warner MD)

Correspondence to:
Prof Jim Stevenson, School of Psychology, Faculty of Medicine,
Health and Life Sciences, University of Southampton,
Southampton SO17 1BJ, UK

Introduction

Artificial food colours and other food additives (AFCA) have long been
suggested to affect behaviour in children.1

Ben Feingold made his initial claims of the detrimental effect of AFCA
on childhood behaviour more than 30 years ago.2

The main putative effect of AFCA is to produce overactive, impulsive,
and inattentive behaviour -- ie, hyperactivity --
which is a pattern of behaviour that shows substantial individual
differences in the general population.

Children who show this behaviour pattern to a large degree are
probably diagnosed with attention-deficit hyperactivity disorder
(ADHD).

Despite the failure of early studies3 to identify the range of
proposed adverse affects, a recent meta-analysis4 of double-blinded,
placebo-controlled trials has shown a significant effect of AFCA on
the behaviour of children with ADHD.

The possible benefit in a reduction in the level of hyperactivity of
the general population by the removal of AFCA from the diet is less
well established.

Evidence from our previous study on the Isle of Wight has suggested
adverse effects on hyperactivity, measured by parental ratings for 3-
year-old children on a specific mix of additives.5

These findings needed replication on 3-year-old children, and to
establish whether the effects could be seen with a wider range of
measures of hyperactivity.

The present community-based, double-blinded, placebo-controlled food
challenge was designed to extend the age range studied to include
8/9-year-old children to determine whether the effects could also be
detected in middle childhood.

Methods

Participants

Figures 1 and 2 present details of recruitment and participation in
the study, for 3-year-old and 8/9-year-old children, respectively.

The study sample was drawn from a population of children aged between
3 years and 4 years, 2 months, registered in early-years settings
(nurseries, day nurseries, preschool groups, playgroups) and from
children aged between 8 and 9 years attending schools in Southampton,
UK.

To ensure that the study sample included children from the full range
of
socioeconomic backgrounds, schools were recruited based on the number
of children receiving free school meals (an index of social
disadvantage).

The distribution of the percentage of children receiving free meals in
the schools taking part indicated the proportions for the city as a
whole.

To further check on how representative the sample was, teachers
completed a hyperactivity questionnaire6 for all 3-year-old and 8/9-
year-old children.

Parents who returned an expression of interest form were contacted by
phone and a home visit arranged.

On this visit, a research assistant and the study dietitian, provided
full information about the study and its dietary implications, and
written informed consent was obtained.

The study dietitian also obtained a report based on 24-h recall by the
parent of the child’s pretrial diet, which allowed an assessment of
baseline levels of the number of foods containing additives consumed
by the child in the previous 24 h.

The study was approved by the local research ethics committee
(reference no 04/Q1702/61) and written informed consent was obtained
from parents.

Participating early-years settings received £250 and each school £500
as a contribution towards school funds for the benefit of all
children.

Study design and challenge protocols

The study design and challenge protocols for both ages were similar.

Children were entered into this study with a within-subject crossover
between two active mixes (A and B) and a placebo drink.

The two active mixes differed both in the quantities of additives and
the specific additives included.

Mix A was similar to the active challenge used in the Isle of Wight
study,5 and mix B was selected to indicate the current average daily
consumption of food additives by 3-year-old and 8/9-year-old children
in the UK.7

Both mixes included sodium benzoate, which had been included in the
challenge on the Isle of Wight study and in previous studies.8,9

Mix A for 3-year-old children included
20 mg of artificial food colourings
5 mg sunset yellow [E110],
2â‹…5 mg carmoisine [E122],
7â‹…5 mg tartrazine [E102],
and 5 mg ponceau 4R [E124, Forrester Wood, Oldham, UK])
and 45 mg of sodium benzoate [E211, Sigma Aldridge,
Gillingham, UK]).

Active mix B included
30 mg of artificial food colourings
(7â‹…5 mg sunset yellow,
7â‹…5 mg carmoisine,
7â‹…5 mg quinoline yellow [E110],
and 7â‹…5 mg allura red AC [E129])
and 45 mg of sodium benzoate.

Mix A amounts for 8/9-year-old children were multiplied by 1â‹…25 to
account for the increased amount of food consumed by children at this
age.

Therefore, mix A included
24â‹…98 mg of artificial food colourings
6â‹…25 mg sunset yellow,
3â‹…12 mg carmoisine,
9â‹…36 mg tartrazine,
and 6â‹…25 mg ponceau 4R)
and 45 mg of sodium benzoate.

Active mix B included
62â‹…4 mg of artificial food colourings
(15â‹…6 mg sunset yellow,
15â‹…6 mg carmoisine,
15â‹…6 mg quinoline yellow,
and 15â‹…6 mg allura red AC)
and 45 mg of sodium benzoate.

Doses for mixes A and B for 3-year-old children were roughly the same
as the amount of food colouring in two 56-g bags of sweets.

For 8/9-year-old children, the dose for mix A was equal to about two
bags of sweets a day and for mix B about four bags of sweets a day.

After a week on their typical diet (week 0: baseline diet),
the artificial colours to be used in the challenges and
sodium benzoate were withdrawn from their diet for 6 weeks.

Over this period when challenge with active or placebo drinks were
given, additive withdrawal continued
(week 1: withdrawal period but receiving placebo;
weeks 2, 4, and 6: challenge with randomisation to two active
periods and one placebo period;
weeks 3 and 5: washout continuing on placebo).

During this period, 3-year-old children received the challenge and
washout-placebo drinks on a weekly basis and consumed mixed fruit
juices (placebo or active) at home (300 mL/day for 3-year-old
children, 625 mL/day for 8/9-year-old children),
provided in identical sealed bottles.

At the beginning of the study, children were assigned by the study
administrator by a random-number generator to receive one of six
possible sequences of placebo, active mix A, or
active mix B challenges across weeks 2, 4, and 6.

A masked testing by two independent panels of 20 young adults showed
that the active and placebo juice drinks could not be differentiated.

When asked if the mix contained additive, 16 (40%), 21 (52%), and 26
(65%) adults responded positively for mix A, mix B, and placebo,
respectively.

We recorded no significant differences between these proportions
(Friedman test, χ²=4⋅412, df=2).

Therefore, no reliable differences were seen between the look and
taste of the drinks.

The only difference in the composition of the placebo and active
mixes was the presence of the AFCA in the active mix with some
variation in the proportions of the fruit juices to ensure matching
colour and taste for the placebo and active drinks.....

"Global hyperactivity aggregate (GHA)"

...Parents rated their child’s behaviour during the previous week for
seven items previously used
(switching activities;
interrupting or talking too much;
wriggling;
fiddling with objects or own body;
restless;
always on the go;
concentration),4
from which we obtained a total score.....

...A fourth measure for 8/9-year-old children was the Conners
continuous performance test II (CPTII),16 a [computerized] test using
visual stimuli of 14-min duration and is widely used to assess
attention and the response inhibition component of executive control.

We used four scores
(SE of reaction time,
% of commission errors,
d´ [discriminability index],
and β)
to derive a weekly aggregate score.
This subset of indicators from the CPTII has been shown to be highly
correlated with the ADHD rating scale.17.....

...128 (93%) of the 137 children who completed the study consumed more
than two-thirds of all drinks, of which 103 (80%) consumed 85% or more
(ie, at least six of seven daily drinks per week).....

...Under model 2, in which the effects of other factors were
controlled, the effect of mix A for the entire sample was not
significant (p=0·123) but mix B did have a significantly adverse
effect compared with placebo (p=0·012).

When the analyses are restricted to those children who consumed at
least 85% juice, the adverse effect of mix A on behaviour remained
non-significant (p=0·066)
but was significant for mix B (p=0·003).

The complete case groups showed significantly higher GHA scores than
placebo for mix A (p=0·023) and mix B (p=0·001).....

...Discussion

In this community-based, double-blinded, placebo-controlled
food challenge, we tested the effects of artificial food additives on
children’s behaviour and have shown that a mix of additives commonly
found in children’s food increases the mean level of hyperactivity
in children aged 3 years and 8/9 years.

Our complete case data has indicated that the effect sizes, in terms
of
the difference between the GHA under active mix and placebo
challenges, were very similar for mix B in 3-year-old and 8/9-year-old
children.

For mix A, the effect for 3-year-old children was greater than for
8/9-year-old children.

The effects for mix B were not significant for 3-year-old children
because there was greater variability in the response to the active
challenges than placebo in this age group.

Thus, we recorded substantial individual differences in the response
of children to the additives.

For both age groups, no significant effect of social and demographic
factors was seen on the initial level of GHA or in the moderation of
the challenge effects.

The moderating effects of genotype on the child’s behaviour response
to
AFCA are examined in a separate paper (unpublished data).

The effect sizes reported in this study are similar to those
calculated in the meta-analysis by Schab and Trinh.4

They estimated the effects of AFCA on hyperactivity to be
0·283 (95% CI 0·079–0·488), falling to 0·210 (0·007–0·414)
when the smallest and lowest quality trials were excluded.

It should be noted that this meta-analysis included studies of
hyperactivity in clinical samples, whereas the present study was done
on children in the general population with the full range of degrees
of
hyperactivity.

These effect sizes recorded by Schab and Trinh are smaller than those
reported for stimulant treatment for ADHD in children, for which one
meta-analysis21 reported a range of effect sizes
from 0·78 (0·64–0·91) by teacher report
to 0·54 (0·40–0·67) by parent report.

We report effect sizes that average at about 0·18.

Children with ADHD are generally about 2 SD higher on hyperactivity
measures than those without the disorder,22
thus an effect size of 0·2
is about 10% of the behavioural difference between them.

This study provides evidence of deleterious effects of AFCA on
children’s behaviour with data from a whole population sample,
using a combination of robust objective measures
with strong ecological validity,
based partly on observations in the classroom
and ratings of behaviour made independently by teachers
and by parents in the different context of the home
and applying double-blinded challenges with quantities of additives
equal to typical dietary intakes.

It also replicates the effects of mix A previously reported on a large
sample (n=277) of 3-year-old children,5 although significant effects
were only seen with parental ratings in that study.

The specific deleterious compounds in the mix cannot be determined for
the present study and need to be examined in subsequent studies.

The effect of artificial colours needs to be differentiated from the
effects of preservatives in a 2X2 design.

Further investigation would also need to establish whether the age-
related difference seen in the present study can be replicated --
ie, the effects of mix A being greater for 3-year-old children
than for 8/9-year-old children.

We examined the effects of additives on changes in behaviour during an
extended period in a community-based, double-blinded, placebo-
controlled
food challenge.

A weakness in this approach is the lack of control over when the
challenges are ingested in relation to the timing of measures of
hyperactivity.

This study design also needs extensive resources to obtain multisource
and multicontext measures of hyperactivity.

We have completed a pilot study showing that changes in hyperactivity
in response to food additives can be produced within about 1 h.

Therefore, future studies could use more feasible acute double-blinded
challenges undertaken in more controlled settings.

The present findings, in combination with the replicated evidence for
the AFCA effects on the behaviour of 3-year-old children, lend strong
support for the case that food additives exacerbate hyperactive
behaviours (inattention, impulsivity, and overactivity)
in children at least up to middle childhood.

Increased hyperactivity is associated with the development of
educational difficulties, especially in relation to reading, and
therefore these adverse effects could affect the child’s ability to
benefit from the experience of schooling.23

These findings show that adverse effects are not just seen in children
with extreme hyperactivity (ie, ADHD),4 but can also be seen in the
general population and across the range of severities of
hyperactivity.

Our results are consistent with those from previous studies and extend
the findings to show significant effects in the general population.

The effects are shown after a rigorous control of placebo effects and
for children with the full range of levels of hyperactivity.

We have found an adverse effect of food additives on the hyperactive
behaviour of 3-year-old and 8/9-year-old children.

Although the use of artificial colouring in food manufacture might
seem superfluous, the same cannot be said for sodium benzoate, which
has
an important preservative function.

The implications of these results for the regulation of food additive
use could be substantial.

Contributors

JS, JOW, and ES-B participated in the conception and design of the
study.

The Food Standards Agency assisted with the design of the study.

DMC directed the execution of the study.

AB, AC, DC, LD, EK, LP, and EP undertook assessments of the children
and helped to develop the observational methods employed in the study.

KG supervised and KL executed the nutritional aspects of the study in
relation to the preparation of suitable challenge drinks and advice on
diet for parents.

DMC and JS analysed the data and wrote the manuscript with input from
all the authors.

Conflict of interest statement

We declare that we have no conflict of interest.

Acknowledgments

We thank the children, families, and teachers in the participating
schools and early years settings in the Southampton area for their
help
and assistance with the study;
and Catherine Varcoe-Baylis and Jenny Scoles and the local steering
committee for their assistance,
especially Ulrike Munford and the representatives from Southampton
City Council Children’s Services and Learning
and the Southampton Early Years Development and Childcare Partnership;
and the Food Standards Agency for their significant advice and input
into the study.
This study received funding from the Food Standards Agency
(grant T07040).

References

1 Overmeyer S, Taylor E,
Annotation: principles of treatment for hyperkinetic disorder:
practice approaches for the UK.
J Child Psychol Psychiatry 1999; 40: 1147–57.

2 Feingold BF.
Hyperkinesis and learning disabilities linked to artificial food
flavors and colours.
Am J Nurs 1975; 75: 797–803.

3 Editorial. NIH consensus development conference:
defined diets and childhood hyperactivity.
Clin Pediatr 1982; 21: 627–30.

4 Schab DW, Trinh NT.
Do artificial food colours promote hyperactivity in children with
hyperactive syndromes? A meta-analysis of double-blind placebo-
controlled trials.
J Dev Behav Pediatr 2004; 25: 423–34.

5 Bateman B, Warner JO, Hutchinson E, et al.
The effects of a double blind, placebo controlled, artificial food
colourings and benzoate preservative challenge on hyperactivity in a
general population sample of preschool children.
Arch Dis Child 2004; 89: 506–11.

6 DuPaul GJ, Power TJ, Anastopoulos AD, Reid R, McGoey K, Ikeda M.
Teacher ratings of ADHD symptoms: Factor structure and normative data.
Psychol Assess 1997; 9: 436–44.

7 Gregory JR, Collins EDI Davies PSW, Hughes JM, Clarke PC.
National Diet and Nutrition Survey: children aged 1·5 to 4·5 years.
Vol 1: Report of the Diet and Nutrition Survey.
London: HM Stationery Office, 1995.

8 Egger J, Graham PJ, Carter CM, Gumley D, Soothill JF.
Controlled trial of oligoantigenic treatment in the hyperkinetic
syndrome.
Lancet 1985; 325: 540–45.

9 Carter CM, Urbanowicz M, Hemsley R, et al.
Effects of a few food diet in attention-deficit disorder.
Arch Dis Child 1993; 69: 564-68.

10 Routh D.
Hyperactivity.
In: Magrab P, ed. Psychological management of pediatric problems.
Baltimo University Park Press, 1978: 3–8.

11 Thompson MJJ, Stevenson J, Sonuga-Barke E, et al.
The mental health of preschool children and their mothers in a mixed
urban/rural population. Prevalence and ecological factors.
Br J Psychiatry 1996; 168: 16–20.

12 Hayward C, Killen J, Kraemer H, et al.
Linking self-reported childhood behavioural inhibition to adolescent
social phobia.
J Am Acad Child Adolesc Psychiatry 1998; 37: 1308–16.

13 Mash EJ, Johnston C.
Parental perceptions of child behaviour problems, parenting self-
esteem and mother’s reported stress in younger and older hyperactive
and normal children.
J Consult Clin Psychol 1983; 51: 86–99.

14 DuPaul GJ, Power TJ, Anastopoulos AD, Reid R.
AD/HD rating scale IV: checklists, norms and clinical interpretation.
New York: Guilford Press, 1998.

15 Abikoff H, Gittleman R.
Classroom observation code -- a modification of the stony-brook code.
Psychopharmacol Bull 1985; 21: 901–09.

16 Conners CK.
The Conners continuous performance test.
Toronto, ON, Canada: Multi-Health Systems, 1994.

17 Epstein N, Erkanli A, Conners CK, Klaric J, Costello JE, Angold A.
Relations between continuous performance test performance measures and
ADHD behaviours.
J Abnorm Child Psychol 2003; 31: 543–54.

18 Gueorguieva R, Krystal JH. Move over ANOVA:
Progress in analysing repeated-measures data and its reflection in
papers published in the Archives of General Psychiatry.
Arch Gen Psychiatry 2004; 61: 310–17.

19 Mallinckrodt CH, Watkin JG, Molenburghs G, et al.
Choice of the primary analysis in longitudinal clinical trials.
Pharm Stat 2004; 3: 161–69.

20 Office for National Statistics.
Standard occupational classification.
London: Stationery Office, 2000.

21 Schachter HA, King J, Langford S, Moher D.
How efficacious and safe is short-acting methylphenidate for the
treatment of attention-deficit disorder in children and adolescents?
A meta-analysis.
Can Med Assoc J 2001; 165: 1475–88.

22 Swanson JM, Sergeant J, Taylor E, Sonuga-Barke EJS, Jensen PS,
Cantwell DP.
Attention-deficit hyperactivity disorder and hyperkinetic disorder.
Lancet 1998; 351: 429–33.

23 McGee R, Prior M, Williams S, Smart D, Sanson A.
The long-term significance of teacher-rated hyperactivity and reading
ability in childhood: findings from two longitudinal studies.
J Child Psychol Psychiatry 2002; 43: 1004–17.
////////////////////////////////////////////////////////////

http://groups.yahoo.com/group/aspartameNM/message/1461
John O. Warner with U. Southampton team in 2007 finds kids hyperactive
from six food colors, confirming their report in 2004 on study in
2000: Murray 2007.08.11

" Our study has shown that the effect of food additives on behaviour
occurs independently of pre-existing hyperactive behaviour or indeed
atopic status.

This is consistent with other studies which have tended to suggest
that
if food additives have an effect at all, it is via a pharmacological
effect which is best exemplified by the non-IgE dependent histamine
release. 20,21

We believe that this suggests that benefit would accrue for all
children
if artificial food colours and benzoate preservatives were removed
from
their diet.

These findings are sufficiently strong to warrant attempts at
replication in other general population samples and to examine whether
similar benefits of the removal of artificial colourings and sodium
benzoate from the diet could be identified in community samples at
older
ages. "

[ See also:http://groups.yahoo.com/group/aspartameNM/message/1426
ASDA (unit of Wal-Mart Stores WMT.N) and Marks & Spencer
will join Tesco and also Sainsbury to ban and limit
aspartame, MSG, artificial flavors dyes preservatives additives,
trans fats, salt "nasties" to protect kids from ADHD:
leading UK media: Murray 2007.05.15

http://groups.yahoo.com/group/aspartameNM/message/1277
50% UK baby food is now organic - aspartame or MSG
with food dyes harm nerve cells, CV Howard 3 year study
funded by Lizzy Vann, CEO, Organix Brands,
Children's Food Advisory Service: Murray 2006.01.13

http://groups.yahoo.com/group/aspartameNM/message/1271
combining aspartame and quinoline yellow, or MSG and
brilliant blue, harms nerve cells, eminent
C. Vyvyan Howard et al, 2005 education.guardian.co.uk,
Felicity Lawrence: Murray 2005.12.21 ]

http://adc.bmj.com/cgi/content/full/89/6/506

Archives of Disease in Childhood 2004; 89(6): 506-511
Erratum in: Arch Dis Child. 2005 Aug; 90(8): 875.
© 2004 BMJ Publishing Group & Royal College of Paediatrics and Child
Health
The effects of a double blind, placebo controlled, artificial food
colourings and benzoate preservative challenge on hyperactivity in a
general population sample of preschool children
B Bateman 1,
J O Warner 1,
E Hutchinson 3,
T Dean 5, ,
P Rowlandson 4, Dr. Piers Rolandson, Paediatric Tutor
C Gant 5,
J Grundy 5,
C Fitzgerald 3
and J Stevenson 2 ,

1 Infection, Inflammation and Repair Division, University of
Southampton, Southampton, UK
2 Department of Psychology, University of Southampton, Southampton, UK
3 Department of Clinical Psychology, St Mary’s Hospital, Isle of
Wight, UK
4 Department of Paediatrics, St Mary’s Hospital, Isle of Wight, UK
5 David Hide Asthma and Allergy Research Centre, St Mary’s Hospital,
Isle of Wight, UKwww.soton.ac.uk/

www.iow.nhs.uk/asp/homepage/index.asp
Isle of Wight NHS Primary Care Trust, St Mary's Hospital,
Parkhurst Road, Newport, Isle of Wight PO30 5TG. Tel 01983 524081


http://www.iow.nhs.uk/index.asp?record=865
David Hide Asthma and Allergy Research Centre

www.davidhideallergyresearch.co.uk/
Tel: 01983 534373 Fax: 01983 822928

Registered Charity No. 10202
"The Isle of Wight with a population of approximately 130,000 and an
annual birth-rate of approximately 1200 has proved an ideal
environment
for collecting information on the prevalence of commonly occurring
medical problems."

http://www.davidhideallergyresearch....k2.htmresearch studies
"This study involves approximately 1400 children who were born on the
Isle of Wight from 1st January 1989 to 28th February 1990. The
majority
has been followed up at the ages of one, two, four and ten years to
enable us to follow the natural history of asthma and allergies. A
grant
is being sought to enable a follow-up of these children when they
reach
16 yrs of age in 2005/6."

"(Food Additives and Behaviour)

The study was funded by the Ministry of Agriculture, Fisheries and
Food
and was designed to assess the impact, if any, of artificial food
additives and colourings on the behaviour of three year old children.

An enormous amount of data on children's behaviour has been collected
from more than two thousand children, as well as information on
allergic
symptoms and sensitisation to allergens. Psychological testing and
dietary assessments were also carried out on a proportion of the
children."

Correspondence to:
Professor J Warner
University Child Health, Southampton General Hospital,
Tremona Road, Southampton SO16 6YD, UK; ,

Accepted for publication 14 September 2003

I have moved to a new post at Imperial College based at St. Mary's
Hospital London.
Any urgent correspondence relevant to Southampton
should be sent to Di Head
I can be contacted on my new e-mail address

Regards, John Warner

ABSTRACT

AIMS:
To determine whether artificial food colourings and a preservative in
the diet of 3 year old children in the general population influence
hyperactive behaviour.

METHODS:
A sample of 1873 children were screened in their fourth year for the
presence of hyperactivity at baseline (HA), of whom 1246 had skin
prick
tests to identify atopy (AT).
Children were selected to form the following groups:
HA/AT,
not-HA/AT,
HA/not-AT,
and not-HA/not-AT (n = 277).
After baseline assessment, children were subjected to a diet
eliminating
artificial colourings and benzoate preservatives for one week; in the
subsequent three week within subject double blind crossover study they
received, in random order, periods of dietary challenge with a drink
containing artificial colourings (20 mg daily) and sodium benzoate (45
mg daily) (active period), or a placebo mixture, supplementary to
their
diet.
Behaviour was assessed by a tester blind to dietary status and by
parents' ratings.

RESULTS:
There were significant reductions in hyperactive behaviour during the
withdrawal phase.
Furthermore, there were significantly greater increases in hyperactive
behaviour during the active than the placebo period based on parental
reports.
These effects were not influenced by the presence or absence of
hyperactivity, nor by the presence or absence of atopy.
There were no significant differences detected based on objective
testing in the clinic.

CONCLUSIONS:
There is a general adverse effect of artificial food colouring and
benzoate preservatives on the behaviour of 3 year old children which
is
detectable by parents but not by a simple clinic assessment.
Subgroups are not made more vulnerable to this effect by their prior
levels of hyperactivity or by atopy.
PMID: 15155391

Keywords: artificial food colouring; benzoate preservatives;
hyperactivity; atopy; double blind placebo controlled challenge

Abbreviations: ADHD, attention deficit-hyperactivity disorder;
APHR, aggregated parental hyperactivity ratings;
AT, atopy;
ATH, aggregated test hyperactivity;
BCL, Behaviour Checklist;
HA, hyperactivity;
WWP, Weiss–Werry–Peters Activity Scale
////////////////////////////////////////////////////////////

13 mainstream research studies in 24 months showing aspartame
toxicity, also 3 relevant studies on methanol and formaldehyde: Murray
2007.09.06http://groups.yahoo.com/group/aspartameNM/message/1464

http://groups.yahoo.com/group/aspartameNM/message/1467
4 cases of aspartame-induced thrombocytopenia [ very low platelets in
blood ], HJ Roberts MD, Letter in Southern Medical Journal 2007 May:
100(5); 543: Murray 2007.08.25

http://groups.yahoo.com/group/aspartameNM/message/1468
Formaldehyde induced urticarial vasculitis in male medical student,
age 40, Michael Pellizzari, Gillian Marshman, Flinders U.,
Australasian J. Dermatol. 2007 Aug: Murray 2007.08.29

http://groups.yahoo.com/group/aspartameNM/message/1469
highly toxic formaldehyde, the cause of alcohol hangovers, is made by
the body from 100 mg doses of methanol from dark wines and liquors,
dimethyl dicarbonate, and aspartame: Murray 2007.08.31

http://groups.yahoo.com/group/aspartameNM/message/1470
new details on how formaldehyde and formic acid from methanol are
neurotoxic: Â*Chun Lai Nie, Rong Giao He, et al, PLoS ONE 2(7): e629
2007.07.18 Chinese Academy of Sciences, Beijing: Murray 20097.09.01
////////////////////////////////////////////////////////////

http://groups.yahoo.com/group/aspartameNM/message/1457
aspartame bans, tis more an avalanche than a trend...: Rich Murray
2007.08.17

[ see also:http://groups.yahoo.com/group/aspartameNM/message/1458
ASDA, Wal-Mart's UK supermarket chain, bans artificial colors, trans
fats, MSG and aspartame, Marguerite Kelly, The Washington Post: Murray
2007.08.03 ]

So far, USA print and broadcast media are deaf, blind, and dumb,
regarding recent major bans of aspartame and MSG in the UK and EU.

The EU Parliament voted July 12 to ban artificial sweeteners
in newly born and infant foods.

On May 15 four huge UK supermarket chains announced bans
of aspartame and MSG, food dyes, and many additives
to protect kids from ADHD --
Sainsbury, Tesco, Marks & Spencer, and ASDA, a unit of WalMart.

May 31: Coca-Cola and the much larger Cargill Inc.,
after years of secret development, with 24 patents,
will soon sell rebiana (stevia) in drinks and food
in the many nations where it is approved as a sweetener --
for decades a major sweetener in Japan, China, Korea, Taiwan,
Thailand, Malasia, Saint Kitts, Nevis,
Brazil, Peru, Paraguay, Uruguay, and Israel,
and an approved supplement in USA, Australia, and Canada,
according to Wikipedia.

http://groups.yahoo.com/group/aspartameNM/message/1454
recent research and news re aspartame and stevia: Murray 2007.08.16

"Of course, everyone chooses, as a natural priority,
to actively find, quickly share, and positively act
upon the facts about healthy and safe food, drink,
and environment."

Rich Murray, MA Room For All
505-501-2298 1943 Otowi Road, Santa Fe, New Mexico 87505

http://groups.yahoo.com/group/aspartameNM/messages
group with 82 members, 1,471 posts in a public,
searchable archivehttp://RMForAll.blogspot.com

http://groups.yahoo.com/group/aspartameNM/message/1395
Aspartame Controversy, in Wikipedia democratic
encyclopedia, 72 references (including AspartameNM # 864
and 1173 by Murray, brief fair summary of much more research:
Murray 2007.01.01

http://groups.yahoo.com/group/aspartameNM/message/1453
Souring on fake sugar (aspartame), Jennifer Couzin,
Science 2007.07.06: 4 page letter to FDA from 12 eminent
USA toxicologists re two Ramazzini Foundation
cancer studies 2007.06.25: Murray 2007.07.18

http://groups.yahoo.com/group/aspartameNMmessage/1451
Artificial sweeteners (aspartame, sucralose) and coloring
agents will be banned from use in newly-born and baby foods,
the European Parliament decided: Latvia ban in schools 2006:
Murray 2007.07.12

http://groups.yahoo.com/group/aspartameNMmessage/1437
stevia to be approved and cyclamates limited by
Food Standards Australia New Zealand:
JMC Geuns critiques of two recent stevia studies by Nunes:
Murray 2007.05.29

http://groups.yahoo.com/group/aspartameNM/message/1427
more from The Independent, UK, Martin Hickman, re ASDA
(unit of Wal-Mart Stores) and Marks & Spencer ban of
aspartame, MSG, artificial chemical additives and dyes
to prevent ADHD in kids: urray 2007.05.16http://news.independent.co.uk/uk/health_medical/article2548747.ece

http://groups.yahoo.com/group/aspartameNM/message/1426
ASDA (unit of Wal-Mart Stores WMT.N) and Marks & Spencer
will join Tesco and also Sainsbury to ban and limit
aspartame, MSG, artificial flavors dyes preservatives additives,
trans fats, salt "nasties" to protect kids from ADHD:
leading UK media: Murray 2007.05.15

http://groups.yahoo.com/group/aspartameNM/message/1438
Coca-Cola and Cargill Inc., after years of development,
with 24 patents, will soon sell rebiana (stevia)
in drinks and foods: Murray 2007.05.31

http://groups.yahoo.com/group/aspartameNM/message/1141
Nurses Health Study can quickly reveal the extent of aspartame
(methanol, formaldehyde, formic acid) toxicity: Murray 2004.11.21

The Nurses Health Study is a bonanza of information about the health
of
probably hundreds of nurses who use 6 or more cans daily of diet soft
drinks -- they have also stored blood and tissue samples from their
immense pool of subjects.
////////////////////////////////////////////////////////////


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