Oxidative Stress, Antioxidant Cofactor Micronutrients, and Cognitive Outcomes in Childhood Obesity: Mechanisms, Evidence, and Therapeutic Opportunities

Overweight and obesity are major public health concerns among children and adolescents worldwide. The most prevalent form is exogenous-constitutional obesity, which is driven by a sedentary lifestyle and an unhealthy diet in which caloric intake exceeds energy expenditure. Beyond their association with chronic disease, these factors are closely linked to deficits in cognitive development and executive functions essential for learning (including working memory, sustained attention, planning, behavioral self-regulation, and cognitive flexibility). Oxidative stress (OS), characterized by the accumulation of reactive oxygen species (ROS) in cells and extracellular fluids, is a significant potential mediator in childhood obesity and an important contributor to its comorbidities. The antioxidant defense system (AOD)'s activity largely depends on levels of trace element cofactors, which determine the body's resistance to adverse environmental factors (the "maladaptation phenomenon"). OS and trace element deficiencies contribute to the development of morphological changes in the brain, thus serving as a critical connecting link between childhood obesity and cognitive impairment. Non-pharmacological interventions are the most accessible and effective approach for prevention and treatment. Bioactive compounds derived from food and natural plants, classified as antioxidants and phytopreparations, may represent a promising complementary approach. These compounds are most effective when used in combination with sustained lifestyle modifications in children. Research in this area can help define future directions for study and develop targeted intervention strategies in the pediatric population. The aim of this review is to examine the relationship between OS, antioxidant cofactor micronutrients, and cognitive outcomes in childhood obesity and to explore mechanisms, evidence, and therapeutic opportunities.