Is there a future for restricted elimination diets

Authors: Nanda Rommelse Jan Buitelaar

Publish Date: 2013/02/27

Volume: 22, Issue: 4, Pages: 199-202

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Abstract

Attention deficit hyperactivity disorder ADHD is a neuropsychiatric disorder characterized by symptoms of inattention impulsive behavior and hyperactivity 1 The disorder affects about 5  of all children and adolescents 2 and generally manifests itself before the age of seven years Children and adolescents with ADHD often have other psychiatric and developmental problems such as oppositional defiant disorder ODD conduct disorder CD autism spectrum disorder ASD specific learning disorders like dyslexia and dyscalculia developmental motor coordination disorder DCD and anxiety and mood disorders Though ADHD is classified as a childhood disorder a large proportion of individuals will continue to exhibit symptoms into adolescence and adulthood 3 This places them at high risk of social and economic disadvantage in the course of the lifespan and puts a large strain on social and healthcare servicesStudies in twins and adopted children indicate that genetic factors play an important role in the etiology of ADHD 4 However the role of environmental factors contributing to childrens’ vulnerability to develop ADHD should not be ignored 5 One of the relevant environmental factors seems to be food There is a growing awareness that food may play a role in determining not only our physical wellbeing but also our behaviour and cognitive functioning 6 7 8 The role of food in ADHD has been investigated since 1985 in several restricted elimination diet RED studies A restricted elimination diet is commonly used to identify food intolerance and involves a temporary 2–5 weeks total change of diet in which the patient is only allowed to eat a few different hypoallergenic foods including rice turkey lettuce pears and water 9 10 11 12 13 14 15 16 17 The rationale for this diet is that a patient may show adverse reactions to any foods Although various forms of restricted elimination diets have been designed and applied in ADHD patients and modest to substantial behavioural improvements have been observed Further research into the relationship between food and behaviour is therefore recommended by the National Institutes of Health in the USA 18In the Netherlands three randomized controlled trials RCTs have been conducted over the last 10 years 13 14 15 The elimination diet applied in these studies is based on the few foods diet but is somewhat more extensive rice turkey lamb a range of vegetables pear rice milk with added calcium and water This basis is complemented with potatoes fruits corn some sweets and wheat allowed in limited doses twice a week Vegetables fruits rice and meat are allowed every day in normal doses Occasionally the diet will be varied to avoid foods for which the child has a particular craving or dislike The first phase elimination phase covers 5 weeks the second phase reintroduction phase may last up to 15 years and only includes children who respond to the first phase with a significant 40  reduction in ADHD symptoms During the reintroduction phase parents see a dietician every 1–2 weeks to identify foods that trigger ADHD symptoms in their child Eventually this phase leads to a consolidated dietary advice about the specific foods to be avoided On average this concerns three to five foods These studies showed that this elimination diet may be effective in about 60  of the children and may also significantly reduce comorbid oppositional defiant disorder symptoms as well as physical complaints such as abdominal pain diarrhoea headaches eczema or asthmaThe latest conducted Dutch RCT applying a RED was published in The Lancet 15 and was both applauded as well as criticized in scientific and public media 19 20 21 It is thus far the largest study conducted of this kind in ADHD patients not selected for an atopic constitution or presence/absence of comorbidities and with a rigorous attempt to investigate possible immunological mechanisms underlying response to RED Results indicated that 64  of the children responded with at least 40  ADHD symptom reduction in the first phase of the diet according to both pediatrician/parent and teacher ratings A large effect on ODD symptom reduction was found as well The dietresponders continued with a 4week challenge phase in which from a list of 270 different foods randomly during 2 weeks three foods were added to which the participant showed high IgG blood levels at baseline and during the other 2 weeks three foods to which the participant showed low IgG blood levels Over 60  of the children showed a behavioral relapse during this challenge phase which was not specifically related to high or low IgG foodsThe main point of criticism raised regarding the study is the unsatisfactory blinding with primary outcome measurements based on a blinded pediatrician’s clinical judgement who based his judgement on the nonblinded information provided to him by parents Expectation bias originating from parents and/or pediatrician may have potentially influenced the outcomes A second point of criticism was the nature of the control group receiving nonobligatory healthy food advice It cannot be ruled out for certain that nondietary factors such as increased positive attention towards the child and/or increased structure in the household may have contributed to the positive outcomes in the dietary group although no change in family structure was observed in these already highly organized households 22In addition some other issues are still open and need to be resolved before more final conclusions can be drawn on the utility and place of RED in treatment guidelines of ADHD Among these is the unknown longterm effectiveness of RED ie are treatment effects maintained over time and how many children do have a consolidated diet from which the incriminated foods only are eliminated 2 years after startying with RED Further what is the effectivness and costeffectiveness of dietary interventions compared to care as usual CAU Next how effective and feasible is RED when it is administered by health care professionals working in clinical practice rather than by a single private ADHD research center How effective and feasible is the long and burdensome reintroduction phase of RED when offered to “normal” unselective ADHD families that were not a priori highly motivated for diet interventions In other words can the results of RED be generalized to the more broader population of ADHD patients Finally what are the effects of RED on childrens’ selfesteem and social status Do they feel stigmatized and isolated since they have to obey strict rules and regulations about diet habits that will likely differ from those observed by their peers A recent metaanalysis excluded the Dutch studies because the effect sizes were significanty larger than the other studies of this kind 21 Excluding outliers in metaanalyses is not generally considered to be the standard approach as outliers may actually “reveal patterns that may lead to new insights about study characteristics that could be acting as potential moderators ie characteristics of treatment” 23 However despite the limitations of the study a substantial percentage of children improved significantly according to multiple raters It is unlikely that only expectation bias can explain such drastic behavioral improvements in so many children If so this is perhaps the largest and most dramatic placeboeffect documented thus far in ADHD research and it is certainly worthwhile pursuing this matter furtherNevertheless the raised critique should be taken very seriously since it is both valid as well as indicative of reluctance in scientific and public circles to move forward with applying dietary interventions in clinical practice We would recommend to followup on the promising results trying to incorporate the critique into a better designed study that is more able to convince criticasters than the existing studies Therefore we would like to make the following specific recommendations for future studies examining the effects of dietary interventions in ADHD A longitudinal at least 2 years threearmed RCT including a restricted elimination diet and two control arms CAU and a control diet is perhaps most optimal in addressing the criticism regarding nondietary factors explaining the reduction of symptoms in the elimination diet arm The control diet can be a normal diet satisfying the World Health Organization Guidelines for a healthy diet but offered in a strict manner In this way it will affect the household the positive attention that the child receives and the structure to their daily diet as the elimination diet does without affecting the allergen content of the diet Importantly parents and child must have the expectancy that both diets will be equally effective Even if this control diet is offered for only 6 months it is a useful control as to whether prescribing a strict diet is the most powerful and effective behavioural intervention in ADHD Furthermore comparison with CAU will allow to examine the effectiveness and costeffectiveness compared to treatments currently available for ADHD medication and behavioural therapy Measurements should include not only parental and teacher ADHD rating scales but also observations made by a blinded clinician and preferably objective cognitive and motoractivity ie actigraph measures and when feasible blood urine and bowel samples The latter might point into the direction of possible biological working mechanisms underlying the effect of RED If possible the study should be carried out in health care centers that are independent from the private ADHD research center and include all new referrals to examine generalizability of the findings Information regarding number and characteristics of dropouts are highly relevant before implementation of dietary interventions for ADHD in clinical practice can occur In addition every effort should be made to find a method to lighten the reintroduction phase and thus alleviate the burden of the second phase of dietary research for the child and family membersBut why go through all this trouble when CAU mainly psychoeducation medication and/or behaviour therapy offers significant benefits to about 80  of patients such as substantial reduction of symptoms and better psychosocial adaptation and functioning The main reason for doing so is that there is growing concern among parents health care professionals and politicians about overprescription of medication particularly psychostimulants and about potential longterm sideeffects 24 In addition there is no conclusive evidence that any of these treatments improve the longterm prognosis 25 There is a demand for dietary interventions as an alternative treatment for ADHD illustrated by the fact that on average children wait 6 months before they can start with an elimination diet diagnostic trajectory at one of the four private ADHD research centers in The Netherlands despite the fact that it is not reimbursed Furthermore the RED intervention eliminating the trigger for ADHD symptoms may be a very costeffective approach since treatment expenses are almost limited to onceonly costs for a complete diagnostic trajectory In contrast CAU and especially the use of methylphenidate will pose continuous burdens on the public health care Nationwide implementability of RED is probably feasible given that RED is widely used to identify food intolerance Therefore dieticians in cooperation with child psychiatrists psychologists and/or pediatricians can administer RED intervention for ADHD relatively easily nationwide If proven longterm cost effective RED may provide an alternative treatment which is likely to be recommended in guidelines for ADHD treatment and is likely to qualify for reimbursement under public health insurance So yes we believe there is a future for dietary interventions in ADHD clinical practice but valid and important points of criticism should be tackled first before implementation in clinical practice can be considered

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