Add-On Supplement in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Week Randomized Double-Blind Placebo-Controlled Clinical Trial.

Chia-Jung Li, Liang-Jen Wang, Sheng-Yu Lee, Yao-Tsung Yeh, Ching-Shu Tsai, Wen-Jiun Chou, Ho-Chang Kuo, Ying-Hsien Huang, Hong-Ying Dai, Chia-Yu Yang

Journal: Nutrients 2024;16(14):

PMID: 39064703

Plain Language Summary

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This 12-week randomised, double-blinded, placebo-controlled clinical trial examined the effects of Bifidobacterium bifidum Bf-688 supplementation in children aged 6–12 with Attention-deficit/hyperactivity disorder (ADHD) who were already on stable methylphenidate (MPH) treatment. A total of 107 participants were assigned either to the probiotic group or a placebo group, with assessments conducted on ADHD symptoms, gastrointestinal (GI) side effects, cognitive performance, and gut microbiota composition. While both groups showed behavioural improvements, the Bf-688 group demonstrated superior outcomes in objective attention measures. The probiotic group also reported a reduction in gastrointestinal symptoms, unlike the placebo group where symptoms returned to baseline by week 12. Microbiome analysis revealed a significant increase in the Firmicutes to Bacteroidetes (F/B) ratio in the probiotic group. A down regulation of pathways associated with attention was also seen. These findings imply a potential gut-brain axis mechanism by which Bf-688 may enhance neurocognitive function. The study highlights the potential of Bifidobacterium bifidum Bf-688 as a complementary strategy for improving attentional performance and gastrointestinal tolerance in paediatric ADHD patients undergoing MPH treatment. Healthcare professionals may consider strain-specific probiotic supplementation as a supportive approach to inform evidence-based clinical guidelines, however, further robust, large clinical trials are warranted to confirm these findings due to the limitations of this study.

Abstract

We conducted a 12-week randomized double-blind placebo-controlled clinical trial to investigate the potential impact of () supplementation on attention-deficit/hyperactivity disorder (ADHD). Children with ADHD who were already receiving a stable dose of methylphenidate (MPH) treatment were enrolled and were randomly assigned to two groups: one receiving add-on (daily bacterial count of 5 × 10 CFUs) ( = 51) and the other receiving a placebo ( = 51). All participants underwent assessments using Conners' Continuous Performance Test (CPT) and Conners' Continuous Auditory Test of Attention (CATA). Additionally, fecal samples were collected at the beginning of the trial (week 0) and at the endpoint (week 12). Remarkably, the group receiving supplementation, but not the placebo group, exhibited significant improvements in omission errors in CPT as well as Hit reaction time in both CPT and CATA. Gut microbiome analysis revealed a significant increase in the to ratio ( ratio) only in the group. Furthermore, we identified significant negative correlations between N-Glycan biosynthesis and Hit reaction time in both CPT and CATA. Our results demonstrate that the probiotic supplement can enhance neuropsychological performance in children with ADHD, possibly by altering the composition of the gut microbiota, ultimately leading to reduced N-Glycan biosynthesis.

Address: Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.; Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.; Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.; Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.; Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.; Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.; Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.; Aging and Disease Prevention Research Center, Fooyin University, Kaohsiung 83102, Taiwan.; Department of Microbiology and Immunology/Molecular Medicine Research Center, Chang Gung University, Taoyuan 333, Taiwan.
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