A novel strategy combining high-intensity interval training and exogenous ketone supplementation for obesity treatment

High-intensity interval training (HIIT) and exogenous ketone supplementation (EKS) have individually demonstrated potential in addressing overweight and obesity, particularly through their effects on appetite regulation and dietary behavior. However, the therapeutic potential of EKS in obesity management remains underexplored, and how it interacts with HIIT remains unclear. We hypothesize that combining HIIT and EKS may have a synergistic effect through “Neurocognitive-Behavioral Mechanisms”. These mechanisms include direct effects on appetite-related brain pathways and indirect effects such as improvements in cognitive function that support healthier eating habits. Both HIIT and EKS may also increase levels of newly identified signaling compounds, such as lactate-phenylanine (Lac-Phe) and 3-β-hydroxybutyrate (BHB)-Phe, which have been linked to reduced food intake in animal studies. Importantly, the shared pathways through which HIIT and ketones enhance cognitive function suggest that future obesity treatments could focus on optimizing brain and metabolic health, rather than relying solely on calorie restriction, to improve long-term adherence. Further research should clarify the neurocognitive and metabolic pathways involved and examine the long-term impact of combined HIIT and EKS interventions. This conceptual framework offers a novel perspective on how brain and behavior interact in obesity and may guide the development of innovative lifestyle strategies.