Micronutrient Therapy for Violent and Aggressive Male Youth: An Open-Label Trial

Objectives: Pharmacotherapy for problematic aggressive and violent behavior disorders in male children and adolescents is associated with significant adverse events. Treatments with more acceptable risk-benefit ratios are critically needed. Micronutrient intervention will be investigated as an alternative to bridge the therapeutic gap in the management of these behaviors. Methods: Males aged 4-14 who displayed ongoing violent and aggressive behaviors received micronutrient intervention containing alpha-tocopherol (vitamin E), ascorbic acid (vitamin C), biotin, chromium, pyridoxal-5-phosphate (P5P), pyridoxine (vitamins B6), selenium, and zinc, in a 16-week open-label trial. Plasma zinc, plasma copper, copper/zinc ratio, and urinary hydroxyhemopyrroline-2-one (HPL) tests were conducted at baseline and endpoint. Participants were examined for changes in aggressive and violent behaviors measured using the Children's Aggression Scale (CAS) and the Modified Overt Aggression Scale (MOAS), improvements in family functioning measured using the Family Functioning Style Scale, improvements in health-related quality of life (HRQoL) measured using the Pediatric Quality of Life Inventory (PedsQL) at baseline, 8 weeks, endpoint, and at 4-6-month follow-up. Results: Thirty-two male children and adolescents met inclusion criteria. Thirty-one (mean 8.35standard deviation 2.93 years) completed the study, with one participant lost to follow-up. Micronutrient therapy significantly improved parent-reported aggressive and violent behaviors measured using the CAS for all domains except the use of weapons (p<0.001 to p=0.02) with medium to large effect size (Cohen's d=0.72-1.43) and the MOAS (p<0.001) with large effect size (Cohen's d=1.26). Parent-reported HRQoL (p<0.001; Cohen's d=-1.69) and family functioning (p=0.03; Cohen's d=-0.41) also significantly improved. Conclusion: Micronutrient therapy appeared well tolerated, with a favorable side effect profile. It appeared effective in the reduction of parent-reported aggressive and violent behaviors, and showed improvement in family functioning and HRQoL in male youth after 16 weeks. Further research in the form of a double-blinded, randomized controlled trial is required to verify these initial positive observations.