Effectiveness And Safety Of Dietary Interventions Across ADHD Subgroups Defined By Baseline Nutrient Deficiency, Gastrointestinal Symptoms, And Medication Status: A Protocol For A Systematic Review

Abstract

Background; Dietary interventions for attention-deficit/hyperactivity disorder (ADHD) have attracted increasing interest as potentially modifiable adjuncts to standard care. However, the evidence base remains fragmented, methodologically heterogeneous, and clinically difficult to interpret. Existing narrative evidence suggests that unhealthy dietary patterns may be associated with worse ADHD outcomes, whereas selected nutritional approaches, including supplementation and restrictive diets, may offer benefit in some patients. At the same time, restrictive approaches may carry meaningful harms, including nutritional deficiency and poor growth, and available evidence indicates that such interventions do not work uniformly across all patients. The literature therefore points toward a subgroup-sensitive, precision-oriented approach rather than broad claims of benefit for all individuals with ADHD. Yet no systematic review has specifically synthesized treatment effects according to baseline nutrient deficiency, gastrointestinal symptoms, and medication status. Objective; To systematically evaluate whether the effectiveness and safety of dietary interventions in children, adolescents, and adults with ADHD differ according to baseline nutrient deficiency, gastrointestinal symptom status, and medication status. Methods; This review will be conducted as a systematic review of intervention effectiveness with planned subgroup synthesis. Randomized controlled trials will form the core evidence base, and comparative nonrandomized studies of interventions will also be considered where they contribute clinically relevant evidence on effectiveness, subgroup response, or harms not adequately captured by randomized designs. Eligible interventions will include nutrient supplementation, restrictive or elimination diets, whole-diet interventions, and microbiome-targeted nutritional interventions. Primary outcomes will be change in core ADHD symptoms and functional impairment. Secondary outcomes will include executive function, emotional and behavioral symptoms, sleep outcomes, gastrointestinal symptoms, biomarkers relevant to nutrient status or inflammation, adverse events, nutritional deficiencies, growth outcomes, and treatment adherence or acceptability. Searches will be conducted in MEDLINE via PubMed, Embase via Elsevier, PsycINFO via EBSCOhost, Cochrane CENTRAL via the Cochrane Library, Web of Science Core Collection via Clarivate, and Scopus via Elsevier, supplemented by trial registries, backward and forward citation searching, reference list screening, and contact with corresponding authors when needed. Search reporting will follow PRISMA-S. Two reviewers will independently screen studies, assess full texts, conduct risk-of-bias appraisal, and oversee data extraction. RoB 2 will be used for randomized trials and ROBINS-I for comparative nonrandomized studies. Structured narrative synthesis will be the primary synthesis method, with random-effects meta-analysis undertaken only where clinical and methodological homogeneity permits. Certainty of evidence will be assessed using GRADE. Registration; The protocol will be registered prospectively in PROSPERO before full-text screening begins.