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Food additives and hyperactivity: the University of Southampton studies. Jim Stevenson 30 March 2011 . Hyperactivity . Hyperactivity. A pattern of behaviour showing marked individual differences in the general population and comprises overactive, impulsive and inattentive behaviour.

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food additives and hyperactivity the university of southampton studies

Food additives and hyperactivity: the University of Southampton studies

Jim Stevenson30 March 2011

slide3

Hyperactivity

A pattern of behaviour showing marked individual differences in the general population and comprises overactive, impulsive and inattentive behaviour.

Children with an extreme degree of hyperactivity may be diagnosed with Attention-Deficit Hyperactivity Disorder (ADHD).

Increased hyperactivity is associated with later educational difficulties and antisocial behaviour

slide4

low

high

hyperactivity

ADHD

ADHD and hyperactivity

– disorder/normal variation.

slide5

Genetic influences

Quantitative genetic studies

twin study heritability c0.66

Molecular genetic studies

genes within dopamine system e.g. DRD4

slide6

Experiential/environmental influences

on hyperactivity

Brain damage

prematurity 2.64 relative risk for ADHD

(Bhutta et al., 2002)

hydrocephalus (Stevenson & Pit-ten Cate, 2004)

Institutional care

Tizard and Hodges (1978)

Romanian adoptees into UK (Kreppner et al., 2001)

slide7

So a wide range of contributing factors act in concert to increase the degree of hyperactivity shown by a child.

Are food colours one of these factors?

slide9

Feingold hypothesis

Pharmacological effect of artificial food colours, flavours and natural salicylates.

“No consistent evidence of effect” NIH (1983)

slide10

Schab, D.W. & Trinh, N-A. (2004). Journal of Developmental

and BehavioralPediatrics, 25, 423-434.

Meta-analysis

Do artificial food colors promote hyperactivity in children with hyperactive syndromes? A meta-analysis of double-blind placebo-controlled trials.

slide11

Schab, D.W. & Trinh, N-A. (2004). Journal of Developmental

and Behavioral Pediatrics, 25, 423-434.

“…in Sept 2002…. 15 unique double-blind placebo-controlled trials evaluating the behavioural effect of AFCs among subjects whose baseline diagnosis of hyperactivity has been graded.”

slide12

Sig. effect of additives

Schab, D.W. & Trinh, N-A. (2004). Journal of Developmental

and Behavioral Pediatrics, 25, 423-434.

slide16

Bateman et al. (2004) Archives of Disease in Childhood, 89, 506-511

Design of I.o.W. Study

All 3 year olds children on IoW

N = 2677

Screen for

HA

Screen for

Atopy

HA

Atopy

Controls

60 HA+ AT+

60 HA+ AT-

60 HA- AT+

60 HA- AT-

slide17

Bateman et al. (2004) Archives of Disease in Childhood, 89, 506-511.

On measures at home rated by parents food additives are having a detrimental effect on activity and possibly inattention.

No detectable effect on behaviour at clinics. – parallels finding by Shulte-Korne et al (1996)

The UK Food Standards Agency decided that these results needed replication and extending

slide20

McCann et al. (2007) Lancet, 370, 1560-7.

Design of Southampton Study

Randomised, double-blind, placebo controlled, crossover trial.

3-year-olds (N= 153) and 8/9-year-olds (N = 144) from the general population.

Baseline week on usual diet, then additives withdrawn.

Over subsequent 6 weeks series of placebo or additive mix drinks given daily in a randomised sequence.

Hyperactivity measured using parent and teacher ratings, observations of child in preschool setting or classroom and a computerised test of attention for 8/9-year-olds

Combined to form Global Hyperactivity Aggregate (GHA)

slide22

Test 3

Test 1

Test 0

Test 4

Test 5

Test 6

Test 2

Normal

diet

AFCPs

withdrawn

+ placebo

Active or

placebo

Washout

+ placebo

Active or

placebo

Washout

+ placebo

Active or

placebo

Week 0

Week 1

Week 2

Week 3

Week 4

Week 5

Week 6

Week 2 Week 4 Week 6

Placebo Mix A Mix B

P B A

A P B

A B P

B A P

B P A

x 20 for each age group

McCann et al. (2007) Lancet, 370, 1560-7.

slide23

McCann et al. (2007) Lancet, 370, 1560-7.

Mix contents

Mix A was the same as the active challenge employed in the Isle of Wight study published in 2004.

Mix B reflected a high average daily consumption of the additives by 3 and 8/9 year old UK children at the time the study was commissioned (2004).

slide24

McCann et al. (2007) Lancet, 370, 1560-7.

Results – 3 year olds

*

* p<.05

slide25

McCann et al. (2007) Lancet, 370, 1560-7.

Results – 3 year olds

*

* p<.05

slide26

McCann et al. (2007) Lancet, 370, 1560-7.

Results – 3 year olds

*

* p<.05

slide27

McCann et al. (2007) Lancet, 370, 1560-7.

Results – 8/9 year olds

*

* p<.05

slide28

McCann et al. (2007) Lancet, 370, 1560-7.

Results – 8/9 year olds

**

** p<.01

slide29

McCann et al. (2007) Lancet, 370, 1560-7.

Results – 8/9 year olds

*

**

* p<.05

** p<.01

slide30

The EFSA Journal (2008) 660, 1-53

European Food Standards Authority

“The Panel concludes that the McCann et al. study provides limited evidence that the two different mixtures of synthetic colours and sodium benzoate tested had a small and statistically

significant effect on activity and attention in children selected from the general population excluding children medicated for ADHD…..”

slide33

Stevenson et al. (2010) American Journal of Psychiatry, 370, 1560-7.

Possible genetic moderators

histamine

histamine N-methyltranferase gene

Thr105Ile (rs1801105) and T939C (rs1050891)

dopamine

catechol-o-methyltransferase

Val108Met (rs4680)

adrenergic

adrenergic receptor alpha 2A

ADRA2A C1291G (rs1800544).

dopamine

dopamine receptor D4 (DRD4)

DRD4 (rs7403703)

dopamine transporter gene (DAT1, 10-repeat)

slide34

Stevenson et al. (2010) American Journal of Psychiatry, 370, 1560-7.

Possible genetic moderators

Variable number tandem repeat (VNTR)

dopamine

dopamine receptor D4 (DRD4)

dopamine transporter gene (DAT1, 10-repeat))

slide36

Stevenson et al. (2007) American Journal of Psychiatry, 370, 1560-7.

Histamine may mediate the effects of food additives on ADHD symptoms, and variations in genes influencing the action of histamine may explain the inconsistency between previous studies.

slide38

Impact on mean hyperactivity scores

McCann et al. (2007), Lancet, 370, 1560-7.; Schab & Trinh (2004) J.Dev.Behav. Ped., 25, 423-434.; Kreppner et al. (2004). J Ab. Ch. Psych., 29, 513-528; Aarnoudse-Moens et al. (2009). Ped., 124,717-728; Fabiano et al. (2009). Clin. Psych. Rev., 29, 129-140.; Faraone et al. (2010) Eur.Ch.Ad. Psychiat., 19, 353-364

slide39

Changes in mean hyperactivity scores

McCann et al. (2007) food additives vs placebo

Schab & Trinh (2004) food colours vs placebo

Conners et al. (2001) MTA trial Combined treatment vs community comparison

.2

.2

Hyperactivity or ADHD symptom severity score

0

2

.7

population mean

ADHD mean

slide40

McGee (2002) J Child PsycholPsychiat, 43, 1004-1017

*

*

*

*

* p <.05 from reference category 0

“There were strong linear relationships between early hyperactivity and later adverse outcomes. Adjustment for other childhood variables suggested that early hyperactivity was associated with continuing school difficulties, problems with attention and poor reading in adolescence.”

slide41

McCann et al. (2007) Lancet, 370, 1560-7.

Conclusions

Mixtures of certain artificial colours together with a sodium benzoate preservative in the diet increased the average level of hyperactivity in 3 and 8/9 year old children in the general population.

The mean effect in these general population samples (0.18) is similar to that found by Schab and Trinh in well designed studies of clinic samples (0.21).

Although the results of the study suggest that some mixtures of certain artificial food colours and benzoate preservative may affect the level of hyperactive behaviour in children, removal of these additives from the diet would not be a panacea for ADHD.

slide42

Prof. Jim Stevenson Psychologist

Prof. John Warner Paediatrician

Prof. Edmund Sonuga-Barke Psychologist

Dr. Donna McCann Psychologist

Kate Grimshaw Dietitian

Yuet-Wan Lok Dietitian

Debbie Crumpler Secretary

Research assistant psychologists:

Angelina Barrett Alison Cooper Lyndy Dalen

Elizabeth Kitchin Lucy Porteous Emily Prince

Catherine Varcoe-Baylis