Professor Patrick Holford of Teesside University (and also Head of Science and Education at Biocare) and Drew Fobbester are joint researchers and authors of the Food for the Brain Child Survey, September 2007 (pdf). This is the third of three Holford Watch posts in which we explain why the literature overview in the FFTB Child Survey is inadequate: some of the claims made in the review are not supported by relevant references or studies of sufficient quality. Part 1 discusses the claims relating to supplements and children’s diet. Part 2 examines the claims made for the benefit of a balanced glycaemic load diet for children. For Part 3, we discuss the claims for the alleged incidence of food sensitivities and gluten sensitivity.
A brief summary of the detail for Part 3. Holford and Fobbester refer to the truism that children’s nutrition affects their learning and behaviour. The FFTB authors draw our attention to studies that involve children with clinical disorders or do not fully address the topic: e.g., the references for “a significant proportion of children with ADHD may have unidentified food and chemical sensitivities” do not comment on the relative numbers of those with/out these “sensitivities” in such a way as to quantify what Holford and Fobbester understand to be a “significant proportion”. The results or observations from such studies are not generalisable to a wider population of children. In a refreshing change from the other sections, 2 out of the 3 references have some relevance; sadly, however, reference 3 does not exist. So, again, this looks like a list of assertions for which the authors feel the truthiness, and attempt to create the necessary scienciness through referenciness.
Section 3.1 (pg 6) offers a short introduction and overview of the literature in this field:
A substantial and convincing body of scientific evidence, including many randomised-controlled trials, shows that a child’s nutrition has a profound effect on their learning and behaviour:
- Ten out of twelve randomised controlled trials (RCTs) assessing the impact of vitamin and mineral supplementation have illustrated significant improvement in non verbal IQ and concentration
- A diet high in essential fats, especially omega 3 essential fats, as well as supplementation improves attention and reading, and reduces anxiety and aggression. Numerous studies have been conducted in this area including two recent randomised controlled trials[3,4]
- A diet with a balanced glycemic load, incorporating more whole foods and slow-releasing sugars and less refined foods and fast-releasing sugars, eaten at regular intervals, may improve learning, attention and reduce anxiety and aggressive behaviour[5, 6, 7]
- A significant proportion of children with ADHD may have unidentified food and chemical sensitivities[8,9] Gluten sensitivity, for example, is far more common in children with behavioural problems than in those without
The evidence from what is now a large and growing body of broadly consistent research links sub-optimum nutrition with poor cognition and behaviour. While much is known about the kind of diet that provides Recommended Daily Allowances, little is known about the kind of diet that equates to optimal mental health, learning and behaviour. Since RDAs largely do not take into account recent research on nutrition and mental health there is no good reason to assume that these kinds of levels, if eaten, are optimal for mental health. [Too many errors to sic.]
Holford and Fobbester do provide references for ‘sensitivities’ among an unquantified “significant proportion of children with ADHD”; as such, this is already an improvement on other references that they provide. Holford Watch must report, however, that one of the references doesn’t exist: we have called Holford’s attention to this matter on an earlier occasion.
Food and Chemical Sensitivities
In a refreshing change from Part 1 and Part 2, 2[8,9] of the 3 references have some relevance to the topic of food and chemical sensitivities. The difficulty lies in the use of these references to comment on children who meet the current diagnostic criteria for ADHD when the children involved in one of these studies were judged to be hyperkinetic – they were not formally diagnosed with ADHD which is unsurprising given the 1985 publication date. It is inappropriate to accept the use of the term hyperkinesis syndrome as if it is synonymous to ADHD when ADHD is a clinical diagnosis with a set of explicit criteria. Carter et al involved children who met DSM III criteria for attention deficit disorder with hyperactivity.
It is true that there have been several studies that suggest that, for some children, some form of food intolerance may produce behaviour that may be interpreted as hyperactivity and both the Carter et al and Egger et al[8,9] papers are among those studies.
Egger et al investigated a selected sample of children with high Conners’ scores (n=76) who had been referred to Great Ormond Street Hospital with hyperkinesis syndrome while often displaying signs of other neurological disabilities or associated allergic problems. The researchers investigated a few-foods diet: this is a way of eating that is constructed around foods that people are allowed to eat and, as such, differs from the typical elimination diet which emphasises foods that are to be avoided. E.g., two meats, two carbohydrate sources, two fruits, vegetables and water to drink. A substantial number of the children improved with this diet; 62/76, and the authors report that 21 of these children achieved a “normal range of behaviour”.
Egger et al also recorded improvement in other symptoms such as headaches, abdominal pain and fits. 28 of the children who had improved participated in a double-blind, crossover, placebo-controlled trial. The food challenges elicited increases or return of symptoms more frequently when the children were on active material than placebo but it is apparent that there is a strong order effect and the difference between the single active and placebo challenge is not striking.
Although food additives such as artificial colorants and preservatives were the commonest provoking substances, the researchers reported that “no child was sensitive to these alone”. However, it is notable that the challenges included very high doses of tartrazine and benzoic acid: this might indicate that the challenges provoked a pharmacological effect rather than demonstrating a physiological sensitivity.
Carter et al replicated these findings in a similar study. 78 children who had been referred to a specialist diet clinic because of hyperactive behaviour were placed on a few-foods diet. The authors report that 59/78 children improved in their behaviour during this open trial. For 19 of the children who had improved, it was possible to design a double-blind challenge protocol to reintroduce the culprit foodstuff. The provoking foodstuff was associated with a deterioration in behaviour ratings and psychological test performance.
Carter et al’s results are interesting, but the authors acknowledge that (as for Egger et al) a high proportion of the children had other physical symptoms and the parents were interested in pursuing a dietary approach for the management of their children’s symptoms.
Although these references have some relevance, Holford and Fobbester have not made a case as to why these studies should be considered pertinent to the wider population of children. We discuss these issues further in the conclusion.
Holford and Fobbester state:
Gluten sensitivity, for example, is far more common in children with behavioural problems than in those without
Undoubtedly, there are papers that explore this issue but this is not one of them because it does not exist. Holford Watch can hazard a guess as to which paper is intended but this is not the way that the review process should work. We wonder if we are observing a self-replicating bibliographic virus in action which continues to propagate through Holford’s writings although we have mentioned the problem with this reference on previous occasions. Even if Holford and Fobbester intended to reference the paper that we have in mind, it does not support their assertion (see below). It is possible that although this paper has a title that resembles the reference, it is still not the reference that Holford and Fobbester intended to use.
It is regrettable that the authors further confound the issue by their reference to a (non-existent) paper about Coeliac Disease when the assertion concerns “gluten sensitivity”. It is unfortunate that Holford has a record of using the terms ‘wheat/gluten sensitivity’, ‘wheat/gluten allergy’ and Coeliac Disease almost interchangeably which must influence the interpretation of this assertion in default of sufficient detail in the FFTB report.
We stand to be corrected on this point, but, at present, the paper that most resembles the Holford and Fobbester reference is Fasano et al. Fasano et al. conducted:
a large multicenter screening study to determine the prevalence of CD in the United States in at-risk groups (first- and second-degree relatives of patients with biopsy-proven CD and children and adults with symptoms frequently associated with CD) and in not-at-risk groups (blood donors, schoolchildren, and subjects seen in outpatient clinics for routine checkups).
Fasano et al. do not identify or discuss a group of children with behavioural problems. If Holford and Fobbester intended to use this reference, it does not support their assertion.
Holford and Fobbester offer a very slight literature overview that relies upon references that can not support their assertions.
Holford Watch has extended a good deal of cooperation towards Holford and Fobbester in attempting to identify the reference that they intended but the authors have not made any case for their assertion that gluten sensitivity is more common in children with behavioural problems.
Both of the studies that Holford and Fobbester reference to support their argument for food and chemical sensitivities[8,9] demonstrate that foodstuffs may be linked to the provocation of hyperactivity. However, it is important to note that these studies were with children who had complex behavioural difficulties that had attracted sufficient concern such that they were referred to specialist units. It is true that a substantial number of the children in these studies had undiagnosed food and chemical sensitivities but it does not follow that this would be true even of a wider population of children with hyperactive syndromes. It would be unwise to extrapolate from these findings to claim that food and chemical sensitivities underlie or exacerbate levels of hyperactivity in the more general population of children.
Egger et al explicitly comment that their study and results are not generalisable:
Many of the children were referred for dietary treatment because parents were keen on this form of treatment or because physicians treating the children were aware of our work. A high proportion of the sample had neurological disorders, allergic conditions, or other associated physical symptoms…The children were therefore probably not typical of overactive children in the general population…(pg. 541)
The children in our study were selected for severe overactivity and so were not representative of hyperkinetic children in the general population…
This trial clearly need replication before results are widely applied to children with the hyperkinetic syndrome. The results may not be fully applicable to children without associated symptoms. [pg. 544] [Emphasis added]
Similarly, Carter et al make several comments that do not support the generalisability of their results:
The important conclusion is that the parents’ reports of a behaviour change with diet can, in a selected group of children, be confirmed…[pg. 567]
It is not possible to conclude that diet is a satisfactory treatment for all hyperactive children. Although efforts were made to recruit an unbiased sample…this was only partially successful. Our group still included a high proportion of children with physical symptoms and of parents who were particularly interested in following a dietary approach…
The ways in which diet worked remain unclear. Toxic, pharmacological, or allergic mechanisms could be involved, and the physiological effects of different foods may vary…
It is still not clear how generally applicable such a treatment might be within a general group of hyperactive children. [pg. 568] [Emphasis added.]
Holford Watch has an observation that may seem a little anachronistic given the differences in diagnostic practice between the date of the FFTB report (2007) and the date of these studies.[8,9] For many years it was received wisdom that ADHD affects boys more than girls however it now seems as if it fails to respect gender lines. More comprehensive diagnostic criteria and an adjustment for social mores mean that although ADHD is still predominantly a diagnosis for boys, more girls are being categorised in this way.[16,17] In the light of this readjustment, it is more difficult to extrapolate the findings from these studies or to have confidence that there are no gender differences in response. E.g., Carter et al state that 69/78 of the children in their study were boys; Egger et al report participation rates for boys of 60/76. However, neither study discusses gender differences albeit it is possible that none were apparent because of the small numbers of girls. As such, it is difficult to argue that the results from these studies apply to children other than boys who match the specified criteria.
The FFTB Child Survey was published at the same time as a large and detailed re-examination of the impact of food additives and children and so suffers from being unable to reference those findings in this report. Nonetheless, there are several reviews, studies and meta-analyses that the Holford and Fobbester might have included to provide a better context for their survey. E.g., Schab and Trinh conducted a meta-analysis of double blind placebo-controlled trials that investigated the impact of artificial food colorants on hyperactivity in children with hyperactivity syndromes; Warner et al discuss possible mechanisms whereby adverse reactions to foodstuffs might influence children’s behaviour.
Schab and Trinh identified 15 appropriate trials for their meta-analysis. They reported that there is a significant effect for artificial food colorants (effect size 0.283 with a 95% CI 0.079, 0.488). However, a secondary analysis of the impact of artificial food colorants for children who did not have a diagnosis for hyperactivity revealed that the effect size is lower at 0.117 (95% CI 0.113, 0.347). Although Holford and Fobbester did not cite appropriate references, there is a strong case to argue that dietary manipulations that avoid some food additives such as artificial colorants may result in a decrease in hyperactivity for children with hyperactivity syndromes. However, a cautious researcher would note that there was a total of only 219 children with hyperactivity in the 15 trials assessed by Schab and Trinh and that when the smallest and lowest quality trials were excluded, the effect size fell to 0.210 (95% CI 0.007, 0.414). Schab and Trinh’s secondary analysis indicates that these beneficial effects are less marked in the more general population of children: furthermore, for this meta-analysis, the effect size was not significant for the wider population of children.
Holford Watch accepts that there are several plausible mechanisms by which adverse reactions to foodstuffs might be associated with behavioural or cognitive difficulties in children. Warner et al provide a fine overview of these possible mechanisms.
There are three potential mechanisms by which food ingestion and behavior disturbance might be linked…The first is that the discomfort of symptoms associated with allergic disease causes secondary emotional reactions. This is clearly a mechanism common to many chronic illnesses and is not specific to allergic disease. Second, psychological problems may either directly cause or exacerbate allergic symptoms. This could be a common phenomenon among food allergy sufferers, whereby the onset of symptoms following exposure to a food allergen leads to intense anxiety and signficant worsening of the symptoms. Finally, there could be a common causal mechanism-genetic, neuroendocrine, immunologic, or environmental-behind both psychological problems and allergic disease. [pg. 523]
Bateman et al’s Isle of Wight Study in 2004 explored the effects of artificial food colorants and benzoate preservative for 3-year-old children. Bateman et al report that the adverse effects were not restricted to or more strongly present for children with atopy or hyperactivity. The authors offer this observation as their conclusion:
…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. [pp. 510-11]
It would have been helpful to the reader if Holford and Fobbester had acknowledged the body of research that indicates that although there is a high rate of parentally-reported perception of food hypersensitivities among children, the confirmed prevalence is substantially lower. One useful example of this is Venter et al’s population-based study of 6-year-olds on the Isle of Wight. For this population of 6-year-olds, 11.8% presented with a reported problem with a food or food ingredient. However, when the children were assessed using double-blind challenges, a clinical diagnosis or suggestive history and positive skin tests, the confirmed prevalence was 1.6% (95% CI 0.9-2.7).
Holford Watch does not consider that Holford and Fobbester have made their case with this literature overview; in Part 1, Part 2 and 3, the references are mostly irrelevant or refer to such a specialised population that the results should not be readily generalised to a wider population of schoolchildren.
It is premature, at best, to attempt to use the results of this FFTB report or its literature overview to argue that there is a robust scientific case for a change in public policy or dietary recommendations that affects the general population of children. The results are not even sufficient to sustain the authors’ animadversions about the current recommended RDAs. Ironically, when so few children in this survey of children (albeit, it is not a representative sample) adhere to the dietary recommendations that already exist (see, e.g., the publications of the Caroline Walker Trust), it would seem that this sample can not be used to comment on the adequacy or otherwise of RDAs.
Holford Watch has heard a surprising rumour that this report is being proposed as the scientific foundation for a project to validate a ‘psychonutrimetric’ questionnaire. After Holford Watch has finished publishing this multi-part exploration of the report, including the data and statistical analyses, it should be readily apparent that this report can not serve as the scientific foundation or justification for a diagnostic or descriptive tool. We shall update this section when we learn whether or not there is truth to this rumour.
To reiterate our position, in its present form, this report should not be promoted as the scientific foundation or justification for a diagnostic or descriptive tool based on its contents or findings, far less the basis for a change in public policy.
 Benton D, Micro-nutrient supplementation and the intelligence of children. Neurosci Biobehav Rev. 2001 Jun;25(4):297-309.
 Richardson AJ, Long-chain polyunsaturated fatty acids in childhood developmental and psychiatric disorders. Lipids. 2004 Dec;39(12):1215-22.
 Richardson AJ, Montgomery P. The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder. Pediatrics. 2005 May;115(5):1360-6. [The authors misquote the name in the FFTB Survey.]
 Sinn N, Bryan J. Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD. J Dev Behav Pediatr. 2007 Apr;28(2):82-91.
 Haapalahti M, Mykkänen H, Tikkanen S, Kokkonen J. Food habits in 10-11-year-old children with functional gastrointestinal disorders. Eur J Clin Nutr. 2004 Jul;58(7):1016-21.
 Benton D. The impact of the supply of glucose to the brain on mood and memory. Nutr Rev. 2001 Jan;59(1 Pt 2):S20-1
 Lien L, Lien N, Heyerdahl S, Thoresen M, Bjertness E. Consumption of soft drinks and hyperactivity, mental distress, and conduct problems among adolescents in Oslo, Norway. Am J Public Health. 2006 Oct;96(10):1815-20.
 Carter CM, Urbanowicz M, Hemsley R, Mantilla L, Strobel S, Graham PJ, Taylor E. Effects of a few food diet in attention deficit disorder. Arch Dis Child. 1993 Nov;69(5):564-8.
 Egger J, Carter CM, Graham PJ, Gumley D, Soothill JF. Controlled trial of oligoantigenic treatment in the hyperkinetic syndrome. Lancet. 1985 Mar 9;1(8428):540-5.
 The FFTB Child Survey cites: Gerarduzzi T et al. Celiac disease in USA among risk groups and general population in USA. Journal of Pediatric Gastroenterology and Nutrition. Vol 31 (suppl) 2000: pp S29, Abst 104. [Having searched Jnl of Ped Gastro and Nutr, this paper doesn’t seem to exist as per this reference. It appears in Google Scholar as a citation only which might indicate an error.] Holford Watch has previously mentioned our difficulty with this reference: Running out of tolerance.
 Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, Elitsur Y, Green PH, Guandalini S, Hill ID, Pietzak M, Ventura A, Thorpe M, Kryszak D, Fornaroli F, Wasserman SS, Murray JA, Horvath K. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med. 2003 Feb 10;163(3):286-92.
 Schab DW, Trinh NH. Do artificial food colors promote hyperactivity in children with hyperactive syndromes? A meta-analysis of double-blind placebo-controlled trials. J Dev Behav Pediatr. 2004 Dec;25(6):423-34.
 Warner JO, Bateman BM, Stevenson J. Behaviour and adverse food reactions. In: Food Allergy: Adverse Reactions to Food and Food Allergies, 2004: pp. 522-531 (eds) DD Metcalfe, HA Sampson, RA Simon. Oxford: Blackwell.
 Bateman B, Warner JO, Hutchinson E, Dean T, Rowlandson P, Gant C, Grundy J, Fitzgerald C, Stevenson J. 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 Jun;89(6):506-11.
 Venter C, Pereira B, Grundy J, Clayton CB, Arshad SH, Dean T. Prevalence of sensitization reported and objectively assessed food hypersensitivity amongst six-year-old children: a population-based study. Pediatr Allergy Immunol. 2006 Aug;17(5):356-63.
 Maitre, S. Attention Deficit Hyperactivity Disorder in Childhood; Overview, Diagnosis and Treatment. Virtual Mentor. 2007 June;9(6):433-436
 Froehlich TE, Lanphear BP, Epstein JN, Barbaresi WJ, Katusic SK, Kahn RS. Prevalence, recognition, and treatment of attention-deficit/hyperactivity disorder in a national sample of US children. Arch Pediatr Adolesc Med. 2007 Sep;161(9):857-64.
 McCann D, Barrett A, Cooper A, Crumpler D, Dalen L, Grimshaw K, Kitchin E, Lok K, Porteous L, Prince E, Sonuga-Barke E, Warner JO, Stevenson J. 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. Lancet. 2007 Nov 3;370(9598):1560-7.
Food for the Brain Child Survey 2007: The Promotion
Holford Watch looks at the literature review:
Food for the Brain Child Survey 2007: Review Part 1
Food for the Brain Child Survey 2007: Review Part 2
Food for the Brain Child Survey 2007: Review Part 3
Food for the Brain Child Survey 2007: Review Part 4
Food for the Brain Child Survey 2007: Review Part 5
Holford Watch appeals for help to Professor Holford and two members of the Scientific Advisory Board who approved this report and then looks at the data and analyses:
Food for the Brain Child Survey 2007: Review Part 7
Food for the Brain Child Survey 2007: Review Part 8
Why Don’t Food for the Brain Report Their Survey Results on Supplement Pills Survey: Review Part 9
Food for the Brain Child Survey 2007: Review Part 10