Dietary supplements for aggressive behaviour in people with intellectual disabilities: A randomised controlled crossover trial

**Background:** Aggressive behaviour is common in people with intellectual disabilities, with prevalence rates ranging from 10% to over 45%. Existing treatments include behavioural therapies, contextual approaches, sedatives, and off-label antipsychotics, but additional evidence-based and safe options are needed. Previous research has suggested that micronutrients may influence the central nervous system through neurotransmitter synthesis, energy production, and neuroprotective properties. Several randomized trials in inmates and children found that multivitamin and mineral supplementation reduced antisocial and externalizing behaviour, though results have been mixed.

**Methods:** This pragmatic, randomized, triple-blind, placebo-controlled, multicentre crossover trial was conducted at six care organizations in the Netherlands between 11 April 2018 and 1 February 2021. Participants (n = 113; 57 active, 56 placebo) were aged 12–40 years, had an IQ < 85, received care from an intellectual disabilities organization, and scored ≥5 on the Social Dysfunction and Aggression Scale (SDAS-11). After a 2-week run-in phase with placebo, participants were randomized to receive either active supplements (multivitamins, minerals, and omega-3 FA: 200 mg DHA and 300 mg EPA daily) or placebo for 16 weeks. After completion, 24 participants (14 active, 10 placebo) entered the crossover phase following a washout period of at least 2 weeks. The primary outcome was the number of aggressive incidents per day measured by the Modified Overt Aggression Scale (MOAS), completed daily by support staff. Secondary outcomes included quality of life (IDQOL-16) and change in aggressive behaviour (SDAS-11). Statistical analysis used generalized linear mixed models with negative binomial distribution.

**Key Results:** A total of 13,432 aggressive incidents were registered. There was no significant difference in mean number of incidents per day between the supplement group (0.94; 95% CI: 0.69–1.29) and placebo group (1.02; 95% CI: 0.73–1.41), with a rate ratio of 0.93 (95% CI: 0.59–1.46; p = 0.74). No significant differences were found for any subtype of aggression (verbal, against objects, physical, self-harm). Quality of life changes did not differ significantly between groups (active: mean change 0.61; 95% CI: −10.48 to 11.71; placebo: mean change 3.0; 95% CI: −8.09 to 14.13). Adherence was 83.8% overall (84.4% active, 83.2% placebo). Blinding was successful, with 81.2% of participants and 61.6% of support staff unable to correctly guess group assignment. Adverse events did not differ between groups (29.6% active vs. 31.8% placebo). During the COVID-19 pandemic (affecting 40 trajectories, 29.2%), aggressive incidents doubled (IRR 1.99; 95% CI: 1.30–3.01), and the direction of the treatment effect reversed (pre-COVID IRR 0.62 favouring supplements; during COVID IRR 1.44 favouring placebo), though the interaction was not statistically significant (p = 0.067).

**Clinical Implications:** This trial found no evidence that dietary supplementation with multivitamins, minerals, and omega-3 fatty acids reduces aggressive incidents in people with intellectual disabilities. The null result contrasts with several previous positive trials in other populations, possibly due to differences in participant age, high rates of psychotropic medication use (58.4%), or the disruptive impact of the COVID-19 pandemic. The authors recommend replication of the study, noting that the pandemic may have obscured a modest treatment effect. Clinicians should not recommend these supplements for aggression management in this population based on current evidence.