Comment on "Impact of AOC1 and HNMT Variants on the Therapeutic Outcomes of a Histamine Reducing Diet in Autism Spectrum Disorder".

Kadiyska et al. recently investigated the impact of a histamine-reducing diet in children with autism spectrum disorder (ASD), with attention to potential modifying effects of AOC1 and HNMT gene variants. Although the study poses an important question, several design limitations may affect the certainty of its conclusions. The dietary intervention removed not only foods high in histamine but also gluten, dairy, sugar, and other items. Such broad restrictions can influence health and behavior on their own. This makes it difficult to determine whether the reported improvements were specifically the result of reduced histamine. The histamine cut-off chosen for participant selection was not explained or tied to clinical standards, which makes reproducibility less clear. In addition, some of the genetic results rested on very small numbers, at times a single child, reducing confidence in their reliability. Finally, histamine levels were not re-measured after the intervention, and the developmental outcomes were not fully explained in terms of clinical significance. Stronger evidence will require controlled diets, standardized thresholds, larger cohorts, and outcomes relevant to daily life.