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Food additives and hyperactivity: the University of Southampton studies

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

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  1. Food additives and hyperactivity: the University of Southampton studies Jim Stevenson30 March 2011

  2. Hyperactivity

  3. 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

  4. low high hyperactivity ADHD ADHD and hyperactivity – disorder/normal variation.

  5. Genetic influences Quantitative genetic studies twin study heritability c0.66 Molecular genetic studies genes within dopamine system e.g. DRD4

  6. 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)

  7. 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?

  8. Previous work on food colours and hyperactivity

  9. Feingold hypothesis Pharmacological effect of artificial food colours, flavours and natural salicylates. “No consistent evidence of effect” NIH (1983)

  10. 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.

  11. 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.”

  12. Sig. effect of additives Schab, D.W. & Trinh, N-A. (2004). Journal of Developmental and Behavioral Pediatrics, 25, 423-434.

  13. University of Southampton studies

  14. Isle of Wight study

  15. 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-

  16. 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

  17. Southampton study

  18. 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)

  19. Distribution of the Global Hyperactivity Aggregate at baseline for 8/9 year olds

  20. 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.

  21. 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).

  22. McCann et al. (2007) Lancet, 370, 1560-7. Results – 3 year olds * * p<.05

  23. McCann et al. (2007) Lancet, 370, 1560-7. Results – 3 year olds * * p<.05

  24. McCann et al. (2007) Lancet, 370, 1560-7. Results – 3 year olds * * p<.05

  25. McCann et al. (2007) Lancet, 370, 1560-7. Results – 8/9 year olds * * p<.05

  26. McCann et al. (2007) Lancet, 370, 1560-7. Results – 8/9 year olds ** ** p<.01

  27. McCann et al. (2007) Lancet, 370, 1560-7. Results – 8/9 year olds * ** * p<.05 ** p<.01

  28. 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…..”

  29. What might be the mechanisms underlying these effects of food additives on behaviour?

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

  31. 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)

  32. 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))

  33. Stevenson et al. (2010) American Journal of Psychiatry, 370, 1560-7. 3 year olds 8/9 year olds

  34. 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.

  35. How important are these effects?

  36. 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

  37. 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

  38. 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.”

  39. 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.

  40. 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

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