Abstract
BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic mental health condition, and standard treatment often results in incomplete symptom relief. Growing evidence suggests that nutritional supplements, including vitamins, minerals, and amino acids, may serve as potential adjunctive treatments for OCD by influencing neurotransmitter regulation and inflammation. OBJECTIVE: Our systematic review aims to assess the comparative efficacy of nutritional supplements on relevant clinical outcomes in individuals with OCD. METHODS: A protocol was developed and registered for this systematic review. Randomized controlled trials assessing the efficacy of nutritional supplementation compared with standard treatments (pharmacological and psychological interventions) will be included. Primary outcomes are changes in cognitive performance, quality of life, and psychiatric symptoms. Secondary outcomes include the presence of comorbidities or multimorbidities (eg, metabolic syndrome). Systematic searches will be conducted in MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov from their inception onward. Two independent researchers will screen the citations and full-text studies. The risk of bias and study quality will be evaluated using validated tools, and association measures with 95% CIs will be calculated. Potential sources of heterogeneity will also be analyzed. RESULTS: The search commenced in January 2025. Between June and August 2025, studies were identified and the full texts reviewed. Data extraction is anticipated to be completed in September 2025. The final synthesis is scheduled for December 2025. CONCLUSIONS: We aim to address the gaps in the current treatment paradigm for OCD by evaluating the efficacy of nutritional supplementation as an adjunctive therapy. These findings may provide insights into the potential of these supplements to improve cognitive and psychiatric outcomes. This protocol establishes a foundation for the rigorous synthesis of available evidence, which may inform future clinical practices and support the integration of nutritional strategies in OCD management. TRIAL REGISTRATION: OSF Registries 10.17605/OSF.IO/NZ5MU; https://osf.io/NZ5MU. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/80240.