Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD

Lidy M Pelsser, Klaas Frankena, Jan Toorman, Rob Rodrigues Pereira, Lidy M Pelsser, Klaas Frankena, Jan Toorman, Rob Rodrigues Pereira

Abstract

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a debilitating mental health problem hampering the child's development. The underlying causes include both genetic and environmental factors and may differ between individuals. The efficacy of diet treatments in ADHD was recently evaluated in three reviews, reporting divergent and confusing conclusions based on heterogeneous studies and subjects. To address this inconsistency we conducted a systematic review of meta-analyses of double-blind placebo-controlled trials evaluating the effect of diet interventions (elimination and supplementation) on ADHD.

Methods: Our literature search resulted in 14 meta-analyses, six of which confined to double-blind placebo-controlled trials applying homogeneous diet interventions, i.e. artificial food color (AFC) elimination, a few-foods diet (FFD) and poly-unsaturated fatty acid (PUFA) supplementation. Effect sizes (ES) and Confidence intervals (CI) of study outcomes were depicted in a forest plot. I2 was calculated to assess heterogeneity if necessary and additional random effects subgroup meta-regression was conducted if substantial heterogeneity was present.

Results: The AFC ESs were 0.44 (95% CI: 0.16-0.72, I2 = 11%) and 0.21 (95% CI: -0.02-0.43, I2 = 68%) [parent ratings], 0.08 (95% CI: -0.07-0.24, I2 = 0%) [teacher ratings] and 0.11 (95% CI: -0.13-0.34, I2 = 12%) [observer ratings]. The FFD ESs were 0.80 (95% CI: 0.41-1.19, I2 = 61%) [parent ratings] and 0.51 (95% CI: -0.02-1.04, I2 = 72%) [other ratings], while the PUFA ESs were 0.17 (95% CI: -0.03-0.38, I2 = 38%) [parent ratings], -0.05 (95% CI: -0.27-0.18, I2 = 0%) [teacher ratings] and 0.16 (95% CI: 0.01-0.31, I2 = 0%) [parent and teacher ratings]. Three meta-analyses (two FFD and one AFC) resulted in high I2 without presenting subgroup results. The FFD meta-analyses provided sufficient data to perform subgroup analyses on intervention type, resulting in a decrease of heterogeneity to 0% (diet design) and 37.8% (challenge design).

Conclusion: Considering the small average ESs PUFA supplementation is unlikely to provide a tangible contribution to ADHD treatment, while further research is required for AFC elimination before advising this intervention as ADHD treatment. The average FFD ES is substantial, offering treatment opportunities in subgroups of children with ADHD not responding to or too young for medication. Further FFD research should focus on establishing the underlying mechanisms of food (e.g. incrimination of gut microbiota) to simplify the FFD approach in children with ADHD.

Conflict of interest statement

LMP is franchiser of the restricted elimination diet (RED) protocol and has received honoraria for applying the RED protocol in the Netherlands. RRP and LMP received travel grants and honoraria for speaking or participations at meetings. RRP is a board member of ADHD in Practice, Impuls & Woortblind and Dutch ADHD Quality Standard. All other authors declare to have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. PRISMA* Flow diagram for the…
Fig 1. PRISMA* Flow diagram for the meta-analyses systematically reviewed.
* PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-analyses (www.prisma-statement.org).
Fig 2. Characteristics and outcomes of the…
Fig 2. Characteristics and outcomes of the six diet meta-analyses included in this systematic review.
All meta-analyses included DBPC trials only, conducted in children meeting the criteria of ADHD.
Fig 3. Recalculation and sub-analysis of Benton’s…
Fig 3. Recalculation and sub-analysis of Benton’s FFD meta-analysis [50] (3A and 3B) based on the data derived from the original articles.
Forest plot of FFD effects and homogeneity statistics.
Fig 4. Recalculation and sub-analysis of Sonuga-Barke…
Fig 4. Recalculation and sub-analysis of Sonuga-Barke et al.’s FFD meta-analysis [24] (4A and 4B) based on the data derived from the original articles.
Forest plot of FFD effects and homogeneity statistics.
Fig 5. Risk of bias graphs: review…
Fig 5. Risk of bias graphs: review authors’ judgements about each risk of bias item.
(A) Bias presented for each individual study. (B) Bias presented as percentages across all included studies.

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