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
http://groups.yahoo.com/group/aspartameNM/message/1461

" 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://www.ifood.tv/node/3137

Artificial Food Colors bad for Health

Experts are warning parents to avoid giving their children food
containing certain additives until results of a new study are published.

The Food Standards Agency (FSA),UK, says it will not issue formal
recommendations until the findings are made available.

A test conducted by UK researchers over effects of artificial food
coloring on children's behavior showed the results backed research made
seven years ago that linked the additives to behavioral problems such as
temper tantrums, poor concentration, hyperactivity and allergic reactions.

A team at the University of Southampton tested the additives
tartrazine (E102),
ponceau 4R (E124),
sunset yellow (E110),
carmoisine (E122),
quinoline yellow (E104)
and allura red AC (E129) on both three-year olds and eight-to-nine year
olds.

The amounts used in the study were those that an average child might
consume in a day.

The FSA's Committee of Toxicity on Chemicals looked at the original
research, known as the Isle of Wight study, which had concluded that
removal of colorings from children's diet would "significantly change"
their behavior and not just in those already showing hyperactive behavior.

But the Committee proved the research inconclusive in 2002.

At a recent closed meeting the Committee noted the "public health
importance" of the new findings but the results will not be acted upon
until published in a scientific journal.

The FSA says it would be handling the results in "a proper scientific
way" and hoped it would be published shortly.

All additives tested in the study are approved for use in the EU and are
safe but some colors are banned in Scandinavian countries and the US.

Pru Leith, chair of the School Food Trust says she hopes the findings
would be published soon. "We are keen to promote fresh healthy home
cooked food and if you get that sort of food you do not have to worry
about additives," she said.

Professor Vyvyan Howard, an expert on the FSA's Additives and Behavior
Working Group, says it was important the findings were published but
consumers could choose not to buy products containing the additives.
"These compounds have no nutritional value and I personally do not give
such foods to my 15-month-old daughter," he said.

Sainsbury's will next month become the first supermarket to ban
artificial food colors and flavorings in its own-label soft drinks.

Other major supermarkets are also reviewing their policies on additives
due to pressure from parents.

FH/AVA

Submitted by Joe Bush <http://www.ifood.tv/joe_bush> on 14 May 2007 -
1:43pm.
Posted in Health <http://www.ifood.tv/tagit/749> u.k.
<http://www.ifood.tv/tagit/928>

Joe Bush's blog <http://www.ifood.tv/ublog/joe_bush>


www.dailymail.co.uk/pages/live/articles/health/womenfamily.html?in_article_id=45\
3431&in_page_id=1799

By UK Daily Mail Newspaper
The proof food additives ARE as bad as we feared

By SEAN POULTER Last updated at 09:53am on 18th May 2007

13 Comments
Parents have been warned to avoid artificial additives used in drinks,
sweets and processed foods amid a link to behaviour problems in children.

A study funded by the government's Food Standards Agency(FSA) is
understood to have drawn a link with temper tantrums and poor concentration.

Researchers have found a definite link between additives and temper
problems with children [ photo ]

There are also concerns about allergic reactions such as asthma and rashes.

The findings are potentially explosive for the entire food industry,
which faces the need to reformulate a vast array of children's products.

Vyvyan Howard, professor of bio-imaging at Ulster University and an
adviser to the FSA, called on parents and manufacturers to protect children.
He said: "It is biologically plausible that they could be having an effect.
"Parents can protect their children by avoiding foods containing the
additives.
I personally do not feed these sorts of foods to my 15-month-old daughter."

He called on manufacturers and supermarkets to remove the additives on a
precautionary basis.

He said: "It is the right thing to do to remove these additives from
children's foods.
They have no nutritional value, so why put them in?
"There are very tight restrictions banning these additives from foods
designed for children under the age of one.
"But why stop there? Children's brains and nervous systems are
developing beyond the age of one."

Prof Howard is not a member of the FSA committee assessing the latest
research, however he did advise on how the study should be conducted.

Experts on the FSA's Committee on Toxicity(CoT) are expected to say that
parents who want to minimise any risk of an adverse reaction should
avoid these additives.

Some leading companies have already responded to mounting evidence of
harm caused by chemical additives, particularly the vivid colours used
to dress up products.

Smarties has dropped artificial colours with the result the blue variety
has been axed.

Sainsbury's recently announced a ban on artificial colours and flavours
from 120 own label soft drinks.

This follows similar moves by Marks & Spencer and the Co-op.

The research, carried out by a team from Southampton University, appears
to confirm earlier studies suggesting additives can cause reactions,
either individually or as a cocktail.

The colours, tested on groups of three-year-olds and eight-to-nine year
olds, were
tartrazine (E102),
ponceau 4R (E124),
sunset yellow (E110),
carmoisine (E122),
quinoline yellow (E104)
and allura red AC (E129).

The team also looked at the effect of the preservative sodium benzoate
(E211), which is commonly used in soft drinks.

Precise details of the research findings are being kept secret until
they can be peer reviewed and published in a scientific journal.

However, a source at Southampton University told the food industry's
magazine, The Grocer, that their results are in line with earlier
findings, published in 2004.

The original research, which took place on the Isle of Wight
[in 2000], involved giving fruit drinks to children aged three.
In some weeks, these were laced with additives.

Parents reported changed behaviour when the youngsters were given the
additives.

However, the original findings were questioned because they relied on
anecdotal reports from parents while the fact the children were so young
made it difficult to measure their behaviour in a meaningful way.

Because of these doubts, a second tranche of research was commissioned
following advice from an expert committee, which included Professor Howard.

The Founder of the Hyperactive Children Support Group, Sally Bunday,
said there is good evidence that artificial additives can have a harmful
effect.
She said: "The consequences can be very serious for both children and
adults who are sensitive to these artificial colours.
"The reaction in children can be horrendous in terms of mood swings with
crying, screaming, inability to sleep.
There can also be physical reactions such as difficulty in breathing on
skin rashes.
"For a young person there is also a risk of quite angry mood swings."

The founder of the organic brand Organix, Lizzie Vann, has been
campaigning for a ban on all artificial additives from children's food.
"The use of artificial additives in children’s foods means we are
conducting a long-term experiment on our children’s health," she said.
"If the Government is serious about improving children’s nutrition the
ban on artificial food additives must be a priority."

The Food & Drink Federation, which speaks for manufacturers, said the
colours and chemicals used by the industry are proven to be safe.
"The use of food additives is strictly regulated under European law," it
said.
"They must be approved as safe by the appropriate European scientific
committee before they can be used...Consumers' intake of food additives
is also closely monitored.

"A recent European Commission report on 'Dietary Food Additive Intake'
indicated that consumption of all types of additives was within the
strict safety limits set by the legislation.
Particular attention was given to consumption by children."

The FSA and Southampton University refused to comment until the research
has been officially published.

14 May 2007 -- 2:23pm

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, j.o.warner@...
E Hutchinson 3,
T Dean 5, tara.dean@...,
P Rowlandson 4, Dr. Piers Rolandson, Paediatric Tutor
C Gant 5,
J Grundy 5,
C Fitzgerald 3
and J Stevenson 2 jsteven@...,

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
general@...

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
ha@...
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; jow@...,

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 <deh@...>
I can be contacted on my new e-mail address <j.o.warner@...>
Regards, John Warner

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

There have been no population based studies examining the prevalence of
hyperactivity related to intolerance to food additives following the
initial claims of the detrimental effect of artificial additives on
children’s behaviour. 1
Subsequent studies, despite improved methodology, have failed to
substantiate this claim 2–7 or have only shown a small effect. 8–18

A double blind placebo controlled high dose azo dye challenge in a
highly selected group of children with behaviour disturbance suggested a
small adverse effect on the children’s behaviour based on ratings on the
Connor scale. 16
There was no association between response and atopy, leading the authors
to conclude that any effect was pharmacological rather than IgE mediated.

Further clinical evidence from research on urticaria linked artificial
food additive responses to IgE independent histamine (and other
mediator) release. 19

An in vitro study showed that circulating basophils released histamine
in a non-IgE dependent response on exposure to azo dyes, 20
and in an in vivo study in which high doses of tartrazine were
administered to normal subjects induced significant histamine release. 21

Despite this suggested mechanism of action there continues to persist,
particularly in the public mind, links between "allergy" to artificial
food additives and behaviour disturbance.

The generalisability of findings from previous studies is limited by
samples which are small,
depend on an attention deficit-hyperactivity disorder (ADHD) diagnosis, 9
are in patients already thought to show adverse behaviour triggered by
artificial additives, 16
or are recruited from specialist clinics. 11

Some studies have identified a higher than expected proportion of atopic
children within those whose behaviour appeared to be affected, 13 but
this has never been systematically examined.

The present study used population based screening to identify children
with or without hyperactivity (HA) and with and without atopy (AT).

Children were selected from this population for the dietary challenge
phase of a within subject double blind placebo controlled study
examining the impact of artificial colourings and benzoate preservatives
on hyperactive behaviour.

The study was designed to test the hypothesis that food additives have a
pharmacological effect on behaviour irrespective of other
characteristics of the child. 16

METHODS

Study population

Figure 1 presents details of the children in the study.
The study population comprised 2878 children (dates of birth 1 September
1994 to 31 August 1996), resident and registered with general
practitioners on the Isle of Wight (IOW), UK on their third birthday.
This includes all children living on the IOW.
The study was approved by the local Research Ethics Committee (Reference
Number 40/96) and written informed consent was obtained from the
parents. Screening with the behaviour questionnaires (phase I) was
completed on 1873 children;
of these, 1246 subsequently underwent skin prick testing for atopy
(phase II).

Therefore, of the 2731 children resident on the IOW, 1246 (46%) were
potentially available for entry to the food challenge (phase III).

One hundred and eighty two did not consent to take part in the challenge
and a total of 397 children were selected to enter phase III.

Figure 1 Number of children completing each phase of the study.

Study design and treatment protocols

The children were initially assessed for hyperactivity, using two scales.
Those who scored at least a mean of 4 on the EAS activity scale 22 and
20 on the Weiss–Werry–Peters Activity Scale (WWP) 23 were designated
hyperactive. This definition has been shown in a previous
epidemiological study to identify a distinct group of hyperactive 3 year
olds. 24,25
These two measures appraise hyperactivity in terms of the degree to
which the child shows inattention, overactivity, fidgetiness, and
impulsivity.
The ratings are made by parents on the basis of the child’s usual
current behaviour.
The children were also assessed for a wider range of behaviour problems
using the Behaviour Checklist (BCL). 26

Children were defined as atopic if on skin prick testing
(Dermatophagoides pteronyssinus, grass pollen, cat allergens, cows’
milk, egg, and peanut) (ALK, Hørsholm, Denmark) they had one or more
reactions with a mean wheal diameter 2 mm in the presence of a positive
histamine control and negative saline control. 27

Children were entered into the four group randomised, placebo
controlled, double blind, crossover challenge study.
The four groups were in a 2x2 between group design with the following
groups:
HA/AT, non-HA/AT, HA/non-AT, and non-HA/non-AT.

For the four week study period the child followed an artificial
colouring and sodium benzoate free diet.
During the second and fourth week they received, daily, and to be taken
at home over the course of the day, 300 ml of mixed fruit juices
(placebo or active randomly assigned) in identical, sealed bottles, of
the same appearance.
The active drink included 20 mg in total of artificial food colourings
(sunset yellow, tartrazine, carmoisine, and ponceau 4R; 5 mg of each)
(Forrester Wood, Oldham, UK) and 45 mg of sodium benzoate (J Loveridge,
Southampton, UK).

The washout periods used in other studies have varied from days 17 to
weeks. 11,16
There was no carry over effect noted by Rowe and Rowe despite repeated
challenges with tartrazine with only two day long placebo periods. 17
A period of one week was felt to be both suitable and practical for both
the challenge and the washout periods.

A preliminary test showed that the drinks could not be accurately
differentiated on blind testing.
Preliminary blind tasting of the placebo and active drinks by 34 adults
had shown that they were no more likely to identify content of the drink
than expected by chance.

Fifteen of the 59 parents who withdrew their child from the study did so
due to perceived adverse behavioural changes.

Nine of these withdrawals occurred during an active week and six during
a placebo week.

At the end of the study period the parents were equally divided into
those who did or did not correctly identify the drink order.

All the study team and the family were blind, apart from the dietician
who prepared the drinks and randomly allocated each child using a random
number table to receive either active or placebo drinks first.

The child’s behaviour was assessed weekly in the clinic by research
psychologists, using validated tests.

There was a baseline assessment at the beginning of the challenge month,
then four subsequent weekly assessments (time 1 to time 4).

The parents also rated changes within their child’s behaviour daily,
using behaviours from the WWP: 23
(1) switching activities;
(2) interrupting or talking too much;
(3) wriggling;
(4) fiddling with objects or own body;
(5) restless;
(6) always on the go;
(7) concentration.
Parents kept a daily "snack" diary to allow an estimate of their
compliance with the consumption of the challenge drinks as well as with
the diet over the four week study period.

Two hundred and twenty four (81%) of children drank all or nearly all of
the active and placebo drinks;
only 14 (5%) children drank less than two thirds of the active and
placebo drinks.

Dietary infractions were estimated from the "snack diary".

Each time a portion of drink or food was recorded containing sodium
benzoate or an artificial colour this was counted as one "mistake".

Over the study month 34% of children recorded no "mistakes",
58% recorded 1–6,
and 8% more than 6 total "mistakes".

There was no difference in infractions during active or placebo weeks.

Attrition

Of the 397 selected for phase III,
120 (30%) failed to complete all four weeks of the study.
There was no effect of order (children were no more likely to drop out
on active than placebo).

Gender, hyperactivity, or atopy were also not related to the failure to
complete the study.

Clinic tests

Children were observed during a period of free play, 28
then assessed with three structured tasks:
the "bear and dragon" task, 29
a delay-aversion "hiding stickers" task, 29
and "draw-a-line slowly and walk-a-line-slowly". 30

The clinic based tests produced 12 measures for each visit based on task
performance and tester recordings of behaviour:
three of inattention, three of activity, and six of impulsivity
(for further details of these measures, please contact the authors).

The three attention and three activity measures were aggregated into a
single index since these aspects of behaviour were so highly correlated.

The six impulsivity measures were also aggregated.
These summary measures were calculated as a mean of the available
constituent measures.
An overall aggregate test hyperactivity (ATH) index was also calculated
using the same methodology.

The weekly mean of the daily parental behaviour ratings was calculated.
Three parental ratings were calculated from the seven item weekly
behaviour questionnaire,
measuring activity (items 1, 3, 4, 5, and 6), attention (item 7), and
impulsivity (item 2).

There were 277 children who completed the trial and for whom test data
was available at all five measurement time points (see fig 1).

Inevitably with studies on children as young as 3 years, there were
missing data in the testing.

To deal with this, two procedures were adopted.

If the scores were aggregated across a number of measures the mean score
was taken for those measures on which the participants had data.

If a child had sporadic missing data this was replaced by the modal
value for that variable.

By this means it was possible to achieve an n of 277 for each of the
three measures
(aggregated test hyperactivity, test impulsivity, and test activity and
attention)
at each of the five time points (baseline, pre 1, post 2, pre 3, post 4).

Each of the measures was based on a different scaling and therefore had
different mean values and variances.
To facilitate interpretation of the data analysis, all measures were
standardised as follows.
Each score was expressed as deviation from the baseline mean for that
measure divided by the standard deviation at baseline.
The test-retest reliabilities for all measures were established
(please contact the authors for details).

To avoid inflating type I errors two primary outcome variables were
identified:
aggregated test hyperactivity (ATH)
and aggregated parental hyperactivity ratings (APHR).
This aggregation was made after standardisation and resulted in the
standard deviations of the aggregated measures being less than unity.

Statistical analysis

The initial analysis was based on the pooled data for all subjects.
The effect of the order with which the active and placebo supplements
were administered was tested in an analysis of variance (ANOVA) by the
interaction of the between subject factor of order and the within
subject five-level factor of time of measurement.
Subsequent analyses pooled subjects across order and were concerned with
detecting a difference between the changes in scores in the placebo and
active periods.
This was tested using a repeated measures ANOVA and shown by the
interaction between the two within subject two-level factors of period
(active/placebo) and time (pre and post).

The initial sample selection was designed to allow a mixed ANOVA
analysis with 2 two-level between subject factors:
hyperactive/non-hyperactive and atopic/non-atopic.
The interaction of these between subject factors and the within subject
factors of period (active/placebo) x time (pre/post) interaction effect
was tested. These analyses were based on the total sample of 277 subjects.
To take advantage of the matching of cases it was possible to repeat the
analysis using 35 matched quartets in the 2x2 design with n = 140.

There were pre-period inequalities in APHR for the active and placebo
periods.
The analysis was repeated casting the active and placebo periods as a
between subject factor.
The post-period scores were the dependent variable and the pre-period
scores a covariate.
The main effect of period in this analysis of covariance indicates
differential change in behaviour in the active and placebo periods with
initial level of hyperactivity controlled.

Treating the study as a crossover challenge with two treatments with a
total of 240 children, the probability is 94% that the study will detect
a challenge difference at = 0.05, if the true difference between the
treatments is 0.3 standard deviation units of pre- to post-treatment
change scores.
As a 2x2 design with 30 subjects per cell the main effects of each
factor of 0.35 could be detected with power greater than 0.80 and p = 0.05.

RESULTS

Study population

Table 1 presents the characteristics of the children entering the
crossover challenge phase of the study.
There were no significant differences between the four groups in terms
of gender and mother’s age at leaving full time education.
As would be expected the children in the HA/AT and HA/not-AT groups had
a significantly higher rate of behaviour problems than the other two
groups (2 (3, n = 277) = 67.8, p < 0.001).

Table 1 Characteristics of the sample entering the double blind, placebo
controlled, crossover challenge

Validation of the tests

To establish that the tests administered to the children were sensitive
to cognitive and behavioural differences between hyperactive and
non-hyperactive preschoolers a preliminary analysis was conducted to
compare the scores at baseline for these two groups.
It was found that on the test measures of impulsivity (t (275) = 3.0, p
< 0.004) and attention and activity (t (275) = 3.0, p < 0.004) as well
as the ATH measure (t (275) = 3.9, p < 0.001), the hyperactive children
had significantly worse scores.

Mean scores on testing and parent ratings from baseline to time 4

Figures 2 and 3 show the pattern of mean scores for children in the
active-then-placebo and placebo-then-active groups.
There is no evidence for any changes across time for the ATH score.
For the parent ratings by contrast there is a pattern indicating a
reduction in hyperactivity (an increase in APHR) between baseline and
time 1; a period over which food additives were removed from the diet.
In the active-then-placebo and the placebo-then-active groups there were
increases in hyperactivity for both the placebo and active challenge
periods.

However in both groups the slope of the lines indicates a greater
increase in hyperactivity during the active periods.

Figure 2 Mean and 95% CI for standardised aggregated test hyperactivity
(ATH) scores at five time points for the active-then-placebo and
placebo-then-active groups; change during additive diet, change during
placebo diet, change during active diet.

Figure 3 Mean and 95% CI standardised aggregated parental hyperactivity
rating (APHR) scores at five time points for the active-then-placebo and
placebo-then-active groups; change during additive diet, change during
placebo diet, change during active diet.

Effects of withdrawal of food colourings and additives

There is a similar APHR increase for both groups between time 2 and time
3 -- that is, the wash out period between challenges.
This indicates that the removal of food additives and colourings from
the diet may have a beneficial effect detected by parental ratings (fig
3) but not by formal clinic testing (fig 2).
These changes in APHR between baseline and time 1 (t (274) = 6.0, p <
0.001) and time 2 and time 3 are significant (t (275) = 7.4, p < 0.001).
There were no significant interactions of order with the effects of
active and placebo on the mean scores for either ATH scores (F(1,275) =
1.3, NS) or APHR (F(1,274) = 1.4, NS); subsequent analyses are based on
the pooled scores for the active and placebo periods ignoring the order.
Table 2 presents the means for the five time points.

Table 2 Mean scores at the five time points on test and parental ratings
of hyperactivity

Effects of challenges

A repeated measures analysis of variance showed that there were no
significant changes in the test scores in either the active or placebo
periods for the impulsivity (F(1,276) = 1.1, NS), activity and
inattention (F(1,275) = 0.3, NS), or ATH (F(1,276) = 1.1, NS) measures.

There were, however, significant changes in parental ratings that were
shown to interact with type of dietary supplement indicating
significantly greater increase in hyperactive behaviour during the
active period.
These significant interactions were found for activity (F(1,275) = 7.7,
p < 0.007) as well as for the APHR (F(1,275) = 6.2, p < 0.02), but not
for impulsivity (F(1,266) = 0.2.8, NS (p < 0.10)) or inattention
(F(1,271) = 3.5, NS (p < 0.07)).

To reduce the risk of type I errors, the remaining analyses will be
conducted only on the ATH scores and the APHR.

To test whether the child’s initial hyperactivity level or atopy status
influenced these changes in hyperactivity under dietary challenge, a set
of 2x2 analyses of variance were conducted to detect interactions
between these between subject factors and the interaction between time
and challenge type.

With the ATH score as the dependent variable there was no significant
effect of challenge (F(1,273) = 0.2, NS) nor any evidence of
interactions between challenge type and atopy or initial hyperactivity.

With the APHR there was a significant effect of challenge type (F(1,272)
= 6.5, p < 0.02) but this effect did not interact with either initial
hyperactivity status (F(1,272) = 0.0, NS) or atopy (F(1,272) = 0.5, NS),
nor was there a joint interaction between these two factors and
challenge type (F(1,272) = 0.5, NS).

It can be seen in table 2 that by chance the mean scores on the APHR
pre-placebo were lower than pre-active (t (275) = 2.5, p < 0.02).

It is necessary to establish whether the significant differences in
changes in behaviour under the placebo and active challenges remain when
the initial scores differences are controlled.
An analysis of covariance was conducted on the post-period scores with
placebo/active as a between group factor and the pre-period scores as
covariates. There was a significant effect of the covariate (F(1,550) =
43.1, p < 0.001) and the effect of type of challenge type remained
significant (F(1,550) = 3.9, p < 0.05).

DISCUSSION

The observed effect of food additives and colourings on hyperactivity in
this community sample is substantial, at least for parental ratings.

The change in aggregated hyperactivity as rated by parents while the
child was on placebo was 0.38 and for the active supplement was 0.77.

The difference between these changes is 0.39 and represents an effect
size of 0.51 in relation to the baseline standard deviation of 0.76.

The standard deviation at baseline was chosen for this comparison since
it represents the extent of variance in hyperactive behaviour in this
general population sample before any intervention or dietary manipulations.

The change effect size of removing additives and colourings is shown in
the increase from baseline to the time 1 scores and was approximately
0.5; a value slightly higher that the 0.39 estimate above.

This would be expected given that the parents were not blind to the
removal of additives/colourings from their children’s diets and
expectancy effects would therefore inflate this change estimate.

Nevertheless these two estimates of the impact of food
additives/colourings on 3 year old children’s hyperactive behaviour both
indicate a statistically substantial effect detectable by parents.

The effect size is less than that obtained for methylphenidate (0.82)31
but similar to that for clonidine (0.58)32 in the treatment of children
with ADHD.

These results are based on a sample constituting 10% (277/2731) of a
general population of 3 year olds.

The starting point of the study were all the 3 year old children living
on the IOW.

There may have been some self-selection of families to take part in the
food challenge phase of the study.

However, where checks were made on broad sociodemographic factors,
selective attrition for the various stages of the study was not detected.

The loss of families during the challenge phase was low considering that
these families were not ones that entered the study because of a referral.

From this general population sample. 70% (277/397) of those invited to
take part in the food challenge completed all phases.

It was not possible in the present study to obtain parallel evidence for
changes in hyperactivity on the basis of psychologist administered tests.

This has proved difficult to obtain in previous studies of dietary
changes in selected hyperactive samples. 33

Parents’ reports have also been found to show the largest effects in
drug trials of treatment for ADHD. 32

One possible explanation of this is that the tests are not sensitive to
hyperactivity in this age group.
This was shown not to be the case since the hyperactive children did
show significantly worse scores on these tests at baseline.

Parental ratings might be more sensitive to changes in behaviour in that
parents experience their child’s behaviour over a longer period of time,
in more varied settings and under less optimal conditions.

The tests conducted in clinic are liked by the majority of children who
see them as an entertaining game; they are given when the children are
optimally alert and engaged.

In contrast, parents will observe the child’s behaviour when they are
competing with siblings for attention; at times when the child is hungry
or tired; when the child has less devoted attention from one adult; when
the child is interacting with other children; or in a constraining
setting such as on public transport or in a supermarket queue.

This range of disparate settings will provide the parent with a greater
opportunity to observe the child’s hyperactive behaviour.

An additional possibility is that the test-retest reliability of the
tests being used was simply insufficient to detect systematic effects of
dietary supplements.

The reliabilities of the test scores were only modest (0.24–0.72) but
comparable with a number of physiological measures at this age
(0.25–0.50). 34,35

These findings therefore suggest that significant changes in children’s
hyperactive behaviour could be produced by the removal of artificial
colourings and sodium benzoate from their diet.

The results were obtained in a general population sample with only a
modest degree of self-selection.

A total of 397 families were invited to enter the double blind food
challenge phase.

Although approximately one sixth of families did not complete the
challenge phase, the completers were no different from the
non-completers on any of our baseline measures.

Such losses from the study would be expected given the heavy demands
placed on these general population families to modify their children’s
diet over a five week period.

The reduction in hyperactive behaviour that would arise from removal of
the additives used in this study from the diet of preschool children are
ones that are not related to initial levels of hyperactivity in the child.

The child with more extreme hyperactivity showed changes no greater but
also no less than other children.

The potential long term public health benefit that might arise is
indicated by the follow up studies which have shown that the young
hyperactive child is at risk of continuing behavioural difficulties,
including the transition to conduct disorder and educational
difficulties. 36,37

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.

ACKNOWLEDGEMENTS

The authors would like to acknowledge the contribution to the study from
Dave Pearson, Hasan Arshad, Sharon Matthews, Brenda Fishwick, Karen
Simms, and Sophie Dodswell.

FOOTNOTES

The research reported in this paper was funded by research grants from
the Food Standards Agency, UK (Grant: FS 3015) and the South West
Regional Research and Development Directorate. Smith Kline Beecham
contributed to the challenge materials.

REFERENCES

1. Feingold BF. Hyperkinesis and learning disabilities linked to
artificial food flavors and colors. Am J Nurs 1975;75:797–803.[Medline]

2. Levy F, Dumbrell S, Hobbes G, et al. Hyperkinesis and diet: a double
blind crossover trial with tartrazine challenge. Med J Aust
1978;1:61–8.[Medline]

3. Goyette CH, Conners CK, Petti TA, et al. Effects of artificial colors
on hyperkinetic children: a double-blind challenge study.
Psychopharmacol Bull 1978;14:39–40.

4. Harley JP, Ray RS, Tomasi L, et al. Hyperkinesis and food additives:
testing the Feingold hypothesis. Pediatrics
1978;61:818–28.[Abstract/Free Full Text]

5. Mattes JM, Gittelman R. Effects of artificial food colorings in
children with hyperactive symptoms. Arch Gen Psychiatry
1981;38:714–18.[Abstract]

6. David TJ. Reactions to dietary tartrazine. Arch Dis Child
1987;62:119–22.[Abstract]

7. Gross MD, Tofanelli PA, Butzirus MS, et al. The effects of diets rich
in and free from additives on the behaviour of children with
hyperkinetic and learning disorders. J Am Acad Child Adol Psychiatry
1987;26:53–5.[CrossRef][Medline]

8. Weiss BW, Williams JH, Margen S, et al. Behavioural responses to
artificial food colors. Science 1980;207:1487–9.[Abstract/Free Full Text]

9. Conners CK, Goyette CH, Southwick DA, et al. Food additives and
hyperkinesis: a controlled double-blind experiment. Pediatrics
1976;58:154–66.[Abstract/Free Full Text]

10. Williams JI, Cram DM, Tausig FT, et al. Relative effects of drugs
and diet on hyperactive behaviours: an experimental study. Pediatrics
1978;61:811–17.[Abstract/Free Full Text]

11. Harley JP, Matthews CG, Eichman P. Synthetic food colors and
hyperactivity in children: a double-blind experiment. Pediatrics
1978;62:975–83.[Abstract/Free Full Text]

12. Swanson JM, Kinsbourne M. Food dyes impair performance of
hyperactive children on a laboratory learning task. Science
1980;207:1485–6.[Abstract/Free Full Text]

13. Carter CM, Urbanowicz M, Hemsley R, et al. Effects of a few food
diet in attention deficit disorder. Arch Dis Child 1993;69:564–8.[Abstract]

14. Rowe KS. Synthetic food colorings and "hyperactivity": a double
blind crossover study. Aust Paediatr J 1988;24:143–7.[Medline]

15. Kaplan BJ, McHicol J, Conte RA, et al. Dietary replacement in
preschool-aged hyperactive boys. Pediatrics 1989;83:7–17.[Abstract/Free
Full Text]

16. Pollock I, Warner JO. Effect of artificial food colours on childhood
behaviour. Arch Dis Child 1990;65:74–7.[Abstract]

17. Rowe KS, Rowe KJ. Synthetic food colouring and behavior: a dose
response effect in a double-blind, placebo-controlled, repeated measures
study. J Pediatr 1994;125:691–8.[CrossRef][Medline]

18. Boris M, Mandel FS. Foods and additives are common causes of the
attention deficit hyperactive disorder in children. Ann Allergy
1994;72:462–8.[Medline]

19. Supramaniam G, Warner JO. Artificial food additive intolerance in
patients with angio-oedema and urticaria. Lancet 1986;2:907–9.[Medline]

20. Murdoch RD, Lessof MH, Pollock I, et al. The effects of food
additives on leukocyte histamine release in normal and urticarial
subjects. J R Coll Physicians Lond 1987;4:251–6.

21. Murdock RD, Plooock I, Naeem S. Tartrazine induced histamine release
in vivo in normal subjects. J R Coll Physicians Lond
1987;21:257–61.[Medline]

22. Buss AR, Plomin R. Temperament: early developing personality traits.
Hillsdale, NJ: Erlbaum, 1984.

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

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

25. Sonuga-Barke E, Stevenson J, Thompson MJJ. Mental health of
preschool children and their mothers in a mixed urban/rural population:
II. Family and maternal factors and child behaviour. Br J Psychiatry
1996;168:21–5.[Abstract]

26. Hogg C, Rutter M, Richman N. Emotional and behavioural problems in
children. In: Sclare I, ed. Child psychology portfolio. Windsor:
NFER-Nelson).

27. Dreborg S, Frew A. Position paper—allergen standardization and
skin-tests. Allergy 1993; (suppl 48):49–82.

28. Taylor E. Preschool behaviour observation schedule (PS-BOS). London:
Dept of Child and Adolescent Psychiatry, Institute of Psychiatry, 1997.

29. Reed MA, Pien DL, Rothbart MK. Inhibitory self-control in pre-school
children. Merrill Palmer Quart 1984;30:131–47.

30. Maccoby EE, Dowley EM, Hagen JW, et al. Activity level and
intellectual functioning in normal preschool children. Child Dev
1965;36:761–70.[CrossRef]

31. Swanson JM, McBurnett K, Christian DL, et al. Stimulant medications
and the treatment of children with ADHD. Adv Clin Child Psychol
1995;17:265–32.

32. Connor DF, Fletcher KE, Swanson JM. A meta-analysis of clonidine for
symptoms of attention-deficit hyperactivity disorder. J Am Acad Child
Adolesc Psychiatry 1999;38:1551–9.[CrossRef][Medline]

33. Schulte-Korne G, Deimel W, Gutenbrunner C, et al. The influence of
an oligoantigenic diet on the behavior of children with
attention-deficit hyperactivity disorders. Z Kinder Jugendpsychiatr
Psychother 1996;24:176–83.[Medline]

34. Boyce WT, Tschann JM, Chesney MA, et al. Dimensions of
psychobiologic reactivity: cardiovascular responses to laboratory
stresses in preschool children. Ann Behav Med 1995;17:315–23.

35. Taras HL, Sallis JF. Blood-pressure reactivity in young
children—comparing three stressors. J Dev Behav Pediatr
1992;13:41–5.[Medline]

36. Sonuga-Barke EJS, Thomson M, Stevenson J, et al. Patterns of
behaviour problems among pre-school children. Psychol Med
1997;27:909–18.[CrossRef][Medline]

37. Taylor E. Developmental neuropsychopathology of attention deficit
and impulsiveness. Dev Psychopathol 1999;11:607–28.[CrossRef][Medline]

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eLetters:

Feingold revisited and acknowledged
Dr. Herbert H. Nehrlich
ADC Online, 30 Jun 2004

Where's the effect?
Richard B. Mailman
ADC Online, 12 Jul 2004

http://adc.bmj.com/cgi/eletters/89/6/506#927

Feingold revisited and acknowledged 30 June 2004

Dr. Herbert H. Nehrlich, drhhnehrlich@...,
Private Practice

Send letter to journal:
Re: Feingold revisited and acknowledged

Dear Editor

I remember the days of cramming for exams, working part-time and
checking off the remaining days to the end of the torture in my diary.

I am talking about the seventies, when petrol crises alternated with
political disasters like the Nixon Gate.
It was then that we first heard of Dr Feingold's revolutionary findings:
Apparently, colourings and other chemicals in food and environment could
cause behaviour problems and learning difficulties.
A very sexy and down to earth psychology professor persuaded many of us
to forego the Hostess Twinkies, the Hot Dogs and the beautifully
coloured licorice twists, fig Newtons and Oreo cookies.
Of course, being mature beyond our years, we aimed to please and soon
found other staples.
And there was no doubt about it, the therapy was effective.
Having only read the abstract I can't say whether credit was given where
credit is due but suffice it to say that Feingold was ahead of his time.
May he rest snugly.


Where's the effect? 12 July 2004

Richard B. Mailman, richard_mailman@...,
Professor
University of North Carolina School of Medicine

Send letter to journal:
Re: Where's the effect?

Dear Editor

Having been an interested observer to the Feingold Hypothesis many years
ago, I was startled to see it rise from the dead (highlighted in many
medical excerpting services).

I eagerly downloaded this article, and shortly thereafter, my thoughts
could be paraphrased in a well-done American advertisement: "Where's the
meat?"

Figure 3 screamed at me one obvious conclusion: "Parents are sensitive
to knowing something was to be changed in their child's environment."
The withdrawal phase, placebo phase, and challenge phase ALL seemed to
cause identical responses in both experimental orders.
Imagine if the two groups (e.g., placebo-challenge vs challenge-placebo)
had instead been a repeat experiment done at a different time.
For a clinical study, the obvious conclusion was "wow, really tight,
repetable findings."

Instead, some manner of statistics has overwhelmed common sense, leading
to wide publicity of a "toxic effect."
Most people will never read this manuscript, and the reivewers and
editors owed us careful thought before opening up this Pandora's Box.
The field will not Find-Gold with Feingold.


Proc Nutr Soc. 2006 Nov; 65(4): 361-5.
Dietary influences on cognitive development and behaviour in children.
Stevenson J.
Developmental Brain Behaviour Unit, School of Psychology, University of
Southampton, Southampton SO17 1BJ, UK. jsteven@...

There are a number of ways in which food can influence behaviour,
including malnutrition, types of diet, eating habits, pharmacological
effects, food allergy, fatty acid deficiency and possibly food additives.
The range of behaviour affected is also wide, and includes attention,
conduct disorder and mood.
A particular focus of interest has been the effects of food on
hyperactivity in children.
There is some initial evidence that fatty acids may influence
hyperactivity in children with specific learning disabilities.
The findings also suggest that some food additives (colourings,
flavourings and preservatives) may increase hyperactivity in children
with behaviour problems.
For children showing behaviour problems such as hyperactivity the use of
dietary manipulation tends to be a more acceptable approach to treatment
than the use of drugs.
However, there needs to be awareness of the dangers of the use of
unsupervised restriction diets with children, and the use of dietary
treatments alone is not likely to be sufficient treatment for many
children with attention-deficit hyperactivity disorder.
A study is currently underway to investigate the possible effects of
additives on behaviour in the general population of children.
PMID: 17181902


J Allergy Clin Immunol. 2007 Feb; 119(2): 307-13.
Prevention of allergic disease during childhood by allergen avoidance:
the Isle of Wight prevention study.
Arshad SH, Bateman B, Sadeghnejad A, Gant C, Matthews SM.
David Hide Asthma and Allergy Research Center, St Mary's Hospital,
Newport, Isle of Wight, UK. sha@... <sha@...>

BACKGROUND:
Early life allergen exposure may increase the risk of childhood allergy,
but the protective effect of reduction in allergen exposure remains
uncertain. OBJECTIVE:
To evaluate the effect of reduction in food and house dust mite (HDM)
allergen exposure in infancy in preventing asthma and allergy.
METHODS: Infants, at higher risk because of family predisposition, were
recruited prenatally and randomized to prophylactic (n = 58) and control
(n = 62) groups.
Prophylactic group infants were either breast-fed with mother on a low
allergen diet or given an extensively hydrolyzed formula.
Exposure to HDM was reduced by the use of an acaricide and mattress covers.
The control group followed standard advice.
Development of allergic diseases and sensitization to common allergens
(atopy) was assessed blindly at ages 1, 2, 4, and 8 years in all 120
children. RESULTS:
Repeated measurement analysis, adjusted for all relevant confounding
variables, confirmed a preventive effect on asthma: adjusted odds ratio
(OR), 0.24; 95% CI, 0.09-0.66; P = .005; atopic dermatitis, OR, 0.23;
CI, 0.08-0.64; P = .005; rhinitis, OR, 0.42; CI, 0.19-0.92; P = .03; and
atopy, OR, 0.13; CI, 0.05-0.32; P < .001. The protective effect was
primarily observed in the subgroup of children with persistent disease
(symptoms at all visits) and in those with evidence of allergic
sensitization.
CONCLUSION:
Allergic diseases can be reduced, for at least the first 8 years of
life, by combined food and HDM allergen avoidance in infancy.
CLINICAL IMPLICATIONS:
Strict food and HDM allergen avoidance should be considered for
prevention of allergy in high-risk infants.
PMID: 17291851


" 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.

We are now conducting just such a replication. "

http://adc.bmj.com/cgi/content/full/90/8/875

Archives of Disease in Childhood 2005; 90: 875; doi:10.1136/adc.2005.072157
Copyright © 2005 BMJ Publishing Group Ltd & Royal College of Paediatrics
and Child Health

LETTER

Rejoinder to Eigenmann PA, Haengelli CA, Food colourings and
preservatives—allergy and hyperactivity (Lancet 2004; 364: 823–4) and an
erratum
J Stevenson, B Bateman and J O Warner
School of Psychology, University of Southampton, UK

Correspondence to:
Prof. J O Warner
School of Psychology, University of Southampton, Southampton SO17 1 BJ,
UK; jow@...
[ now j.o.warner@..., ]

Keywords: allergy; behaviour; food additives

Eigenmann and Haenggeli have commented1 on a paper we recently published
on food additives and hyperactivity in children. 2
This commentary gives a seriously misleading account of the findings of
the study.
Eigenmann and Haenggeli claim that "the term hyperactivity seems to be
used as synonymous to ADHD".
We deliberately did not use the term ADHD as a criterion for recruitment
into the study.
This is a diagnostic term requiring a set of explicit criteria to be met
and is of doubtful validity when applied to 3 year olds.
The definition of hyperactivity we used for this study was one based on
the risk of subsequent behavioural difficulties in middle childhood
which we had established previously in a longitudinal study of an
epidemiologically ascertained sample of 3 years olds. 3,4

The study used screens for atopy (AT) and for hyperactivity (HA) applied
to a total population sample to identify cases for the following design:
"Children were entered into the four group randomised, placebo
controlled, double blind, crossover challenge study.
The four groups were in a 2x2 between group design with the following
groups: HA/AT, non-HA/AT, HA/non-AT, and non-HA/non-AT." 2
Eigenmann and Haenggeli observe that "...families interested in
hyperactivity seem to be over-represented" and on this basis conclude
that "...results from this study should not lead to recommendations for
the general population".
The presence of hyperactivity was one of the inclusion criteria of the
food challenge phase of the study and consequently occurs in about half
of the cases.
A substantial proportion of children were included in the food challenge
phase by design.
Full details of participant flow were given in a diagram (fig 1 in our
paper) as recommended in the CONSORT statement for reporting randomised
trials. 5

The separate issue of sample attrition through each of the stages of the
study was considered carefully and we concluded that the findings from
the group completing the food challenge phase would indeed hold for the
general population.

The study found significantly greater increases in hyperactive behaviour
reported by parents when the children were given the active compared to
the placebo challenge.
The statement by Eigenmann and Haenggeli that "parents’ observations can
be easily explained by their expectations" is puzzling.
The parents, children, and the person collecting the behaviour ratings
were blind as to the food challenge being taken by the child over these
periods.
Consequently "expectations" cannot account for the effects we identified
based on changes during the active and placebo periods.
This does not hold for the reduction in hyperactivity we observed during
the withdrawal phase which, as we discussed in the paper, was not
blinded and was greater than that for the placebo versus active periods.
This would be expected if the withdrawal effect alone was influenced by
parental expectations.

The final part of the Eigenmann and Haenggeli commentary is concerned
with the use of diet changes as treatments for hyperactivity.
Our study showed that the effects of food colourings and the benzoate
preservative were not restricted to or more strongly present for
children with atopy or hyperactivity.
Consequently our conclusions did not relate to the treatment of children
with hyperactivity but rather to the preventive public health issue of
whether food additives are having a general detrimental effect on
children’s behaviour.
The final conclusion from the paper was "...if additives have an effect
at all, it is via a pharmacological effect which is best exemplified by
the non-IgE dependent histamine release. 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." We are now
conducting just such a replication.

Erratum

While preparing this rejoinder, we have discovered an error in the
reporting of the composition of the above mix in the paper. The sentence
that reads:

"The active drink included 20 mg in total of artificial food colourings
(sunset yellow, tartrazine, carmoisine, and ponceau 4R; 5 mg of each)
(Forrester Wood, Oldham, UK) and 45 mg of sodium benzoate (J Loveridge,
Southampton, UK)."

should have read:
"The active drink included 20 mg in total of artificial food colourings
(sunset yellow 5 mg, tartrazine 7.5 mg, carmoisine 2.5 mg, and ponceau
4R 5 mg) (Forrester Wood, Oldham, UK) and 45 mg of sodium benzoate (J
Loveridge, Southampton, UK)."

FOOTNOTES

Funding: Jim Stevenson and John Warner are funded to conduct studies on
children’s food by the Food Standards Agency, UK

Competing interests: none declared

References

1. Eigenmann PA, Haengelli CA. Food colourings and preservatives—allergy
and hyperactivity. Lancet 2004;364:823–4.[CrossRef][Medline]

2. 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.[Abstract/Free Full
Text]

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

4. Sonuga-Barke EJS, Thompson M, Stevenson J,et al. Patterns of
behaviour problems among pre-school children. Psychol Med
1997;27:909–18.[CrossRef][Medline]

5. Moher D, Schulz KF, Altman G, for the CONSORT Group. The CONSORT
statement: revised recommendations for improving the quality of reports
of parallel-group randomised trials. Lancet
2001;357:1191–4.[CrossRef][Medline]


Child Care Health Dev. 2001 May; 27(3): 241-50.
Can parents accurately perceive hyperactivity in their child?
Hutchinson E, Pearson D, Fitzgerald C, Bateman B, Gant C, Grundy J,
Stevenson J, Warner J, Dean T, Matthews S, Arshad H, Rowlandson P.
David Hide Asthma and Allergy Centre, St. Mary's Hospital, Newport, Isle
of Wight andUniversity of Southampton, Southampton, UK.

In all, 1872 children were recruited as part of a larger study
concerning food additives and behaviours in preschool children.
This figure represented 70% of the whole population of 3 1/4 -year-old
children resident on the Isle of Wight, UK.
Parents completed an assessment concerning their perceptions of their
child's behaviour.
The results of this assessment were compared with scores on two
validated parental questionnaires, the Weiss Werry Peters (WWP)
hyperactivity scale and the Emotionality, Activity and Sociability
Temperament Questionnaire (EAS), which were used to assess hyperactivity.
The accuracy of parents in perceiving hyperactivity in their children
was found to be around 50% if the child was hyperactive, and 89% if the
child was not hyperactive.
The implications of these findings for services are discussed.
Frequencies of potential risk groups for future Attention Deficit
Hyperactivity Disorder (ADHD) and Conduct Disorder were also suggested.
PMID: 11350452

Altern Med Rev. 2003 Aug; 8(3): 319-30.
Outcome-based comparison of Ritalin versus food-supplement treated
children with AD/HD.
Harding KL, Judah RD, Gant C.
McLean Hospital, Belmont, Massachusetts, USA.

Twenty children with attention deficit/hyperactivity disorder (AD/HD)
were treated with either Ritalin (10 children) or dietary supplements
(10 children), and outcomes were compared using the Intermediate Visual
and Auditory/Continuous Performance Test (IVA/CPT) and the WINKS two-way
analysis of variance with repeated measures and with Tukey multiple
comparisons.
Subjects in both groups showed significant gains (p less than 0.01) on
the IVA/CPT's Full Scale Response Control Quotient and Full Scale
Attention Control Quotient (p less than 0.001).
Improvements in the four sub-quotients of the IVA/CPT were also found to
be significant and essentially identical in both groups:
Auditory Response Control Quotient (p less than 0.001),
Visual Response Control Quotient (p less than 0.05),
Auditory Attention Quotient (p less than 0.001),
and Visual Attention Quotient (p less than 0.001).
Numerous studies suggest that biochemical heterogeneous etiologies for
AD/HD cluster around at least eight risk factors:
food and additive allergies,
heavy metal toxicity and other environmental toxins,
low-protein/high-carbohydrate diets,
mineral imbalances,
essential fatty acid and phospholipid deficiencies,
amino acid deficiencies,
thyroid disorders,
and B-vitamin deficiencies.
The dietary supplements used were a mix of vitamins, minerals,
phytonutrients, amino acids, essential fatty acids, phospholipids, and
probiotics that attempted to address the AD/HD biochemical risk factors.
These findings support the effectiveness of food supplement treatment in
improving attention and self-control in children with AD/HD and suggest
food supplement treatment of AD/HD may be of equal efficacy to Ritalin
treatment.
PMID: 12946241
////////////////////////////////////////////////////////////


http://groups.yahoo.com/group/aspartameNM/message/1457
aspartame bans, tis more an avalanche than a trend...: Rich Murray
2007.08.11

[ 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 2007.08.11

"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 rmforall@...
505-501-2298 1943 Otowi Road, Santa Fe, New Mexico 87505

http://groups.yahoo.com/group/aspartameNM/messages
group with 81 members, 1,461 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/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/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://groups.yahoo.com/group/aspartameNM/message/1417
formaldehyde as a potent unexamined cofactor in cancer research --
sources include methanol, dark wines and liquors,
aspartame, wood and tobacco smoke: IARC Monographs on the Evaluation
of Carcinogenic Risks to Humans implicate formaldehyde
in #88 and alcohol drinks in #96: some related abstracts:
Murray 2007.05.15

http://groups.yahoo.com/group/aspartameNM/message/1286
methanol products (formaldehyde and formic acid)
are main cause of alcohol hangover symptoms
[same as from similar amounts of methanol, the 11% part of aspartame]:
YS Woo et al, 2005 Dec: Murray 2006.01.20

http://groups.yahoo.com/group/aspartameNM/message/1143
methanol (formaldehyde, formic acid) disposition:
Bouchard M et al, full plain text, 2001: substantial sources
are degradation of fruit pectins, liquors, aspartame, smoke:
Murray 2005.04.02

http://groups.yahoo.com/group/aspartameNM/message/1455
FEMA slow to safety test Katrina toxic trailers,
Charles Babington, Associated Press -- 1 ppm formaldehyde in air
is about half the daily dose from 3 cans aspartame diet soda
and ten times the 1999 EPA alarm level for drinking water:
Murray 2007.07.23

http://groups.yahoo.com/group/aspartameNM/message/1459
third study by expert Greek team of neurotoxicity
in infant rats by aspartame (or its parts, methanol,
phenylalanine, aspartic acid), KH Schulpis et al,
Food Chem Toxicol 2007.06.16: Murray 2007.08.05

http://groups.yahoo.com/group/aspartameNMmessage/1447
second study by expert Greek team of neurotoxicity
in infant rats by aspartame (or its parts, methanol,
phenylalanine, aspartic acid), KH Schulpis et al,
Toxicology 2007.05.18: Murray 2007.07.04

http://groups.yahoo.com/group/aspartameNMmessage/1444
expert Greek group finds aspartame (or its parts,
methanol, phenylalanine, aspartic acid) harm infant rat
brain enzyme activity, KH Schulpis et al,
Pharmacol. Res. 2007.05.13: Murray 2007.06.23

http://groups.yahoo.com/group/aspartameNM/message/1414
effect of aspartame on oncogene and suppressor gene
expressions in mice, Katalin Gambos, Istvan Ember, et al,
University of Pecs, Hungary, In Vivo 2007 Jan;
scores of their relevant past studies since 1977: Murray 2007.04.14

http://groups.yahoo.com/group/aspartameNM/message/1373
aspartame rat brain toxicity re cytochrome P450 enzymes,
especially CYP2E1, Vences-Mejia A, Espinosa-Aguirre JJ et al,
2006 Aug, Hum Exp Toxicol: relevant abstracts re formaldehyde
from methanol in alcohol drinks: Murray 2006.09.29

http://groups.yahoo.com/group/aspartameNM/message/1340
aspartame groups and books:
updated research review of 2004.07.16: Murray 2006.05.11

Dark wines and liquors, as well as aspartame,
provide similar levels of methanol,
above 120 mg daily, for long-term heavy users,
2 L daily, about 6 cans.

Within hours, methanol is inevitably largely turned into formaldehyde,
and thence largely into formic acid -- the major causes
of the dreaded symptoms of "next morning" hangover.

Fully 11% of aspartame is methanol -- 1,120 mg aspartame
in 2 L diet soda,
almost six 12-oz cans, gives 123 mg methanol (wood alcohol).
If 30% of the methanol is turned into formaldehyde,
the amount of formaldehyde, 37 mg, is 18.5 times the
USA EPA limit for daily formaldehyde in drinking water,
2.0 mg in 2 L average daily drinking water.
////////////////////////////////////////////////////////////