A recent study published in Frontiers in Nutrition introduces a neurobiological model suggesting that a therapeutic ketogenic diet (TKD) could be effective in treating anorexia nervosa (AN). This model combines insights into behavioral traits, brain energy metabolism, and neurotransmitter function, offering a comprehensive approach to understanding how TKD might address AN’s underlying neurobiological mechanisms.
Understanding Anorexia Nervosa
Anorexia nervosa is a severe psychiatric disorder marked by extreme weight loss, food avoidance, and a distorted perception of body image. The condition poses significant health risks, with a high treatment cost and frequent relapses. It also has a notably high mortality rate—12 times greater for females aged 15 to 24 compared to other causes of death.
Even after weight recovery, individuals with AN often continue to experience heightened fears of body dissatisfaction and weight gain, which can persist for years. The neural mechanisms behind self-starvation remain unclear, highlighting the need for effective therapies. The new study proposes that TKD could address both the metabolic and psychological factors contributing to AN’s persistence.
The Neurobiological Model
The model suggests that stress and anxiety, coupled with perfectionistic traits, disrupt normal brain glucose metabolism in those predisposed to AN. This disruption triggers a shift to ketone bodies for energy, reinforcing the cycle of self-starvation and temporary anxiety relief.
Research has shown that individuals with AN have altered brain structure and neurotransmitter systems, impacting reward processing and motivation. Environmental factors, such as social media, can exacerbate these issues by conditioning fear responses. Difficulties in emotion regulation and negative affect often persist into recovery, potentially increasing the risk of relapse.
Metabolic Abnormalities in AN
Metabolic abnormalities are common in AN, with genetic studies linking metabolic traits to the disorder. Stress increases glucose demand in the brain, but utilization does not match this increased need, potentially leading to overeating. Individuals with AN often display high anxiety and perfectionistic traits, which can interfere with glucose utilization.
The researchers propose that reduced glucose utilization, despite high demand, contributes to the disorder’s development and maintenance. Individuals with AN enter a state of ketosis, using ketones as an alternative energy source. The study suggests that providing ketone bodies could help eliminate self-starvation and support weight maintenance.
Ketogenic Diet and Its Effects
A ketogenic diet, similar to fasting, involves a reduction in glucose and insulin levels, leading to increased fat metabolism. This diet shifts energy production from glucose to ketone bodies. Studies indicate that TKD changes brain glucose metabolism, with higher ketone levels correlating with lower glucose uptake in the brain.
TKD could potentially be an effective treatment for AN by normalizing energy homeostasis and reducing anxiety. The model proposes that ketosis increases the synthesis of gamma-aminobutyric acid (GABA), which may help regulate emotion and reduce anxiety, supporting the use of TKD as a therapeutic approach.
Pilot Study Results
A preliminary case study showed that TKD, combined with ketamine infusion, successfully treated a patient with AN. Building on this, researchers conducted an open-label trial with five adults who had persistent eating disorder symptoms. Participants followed TKD for at least eight weeks and received ketamine infusions after 4–8 weeks of stable ketosis.
The results indicated significant improvements in various assessments, including the Eating Disorder Examination Questionnaire (EDEQ) and the Eating Disorders Recovery Questionnaire (EDRQ). Body weight remained stable throughout the trial. Although four participants maintained recovery for at least a year, one relapse occurred after discontinuing TKD.
Future Directions
These findings are preliminary and based on a small sample. Further research with larger, more diverse populations is needed to confirm the efficacy and safety of TKD for AN. The study highlights the potential of targeting brain metabolism as a novel treatment approach and underscores the need for more comprehensive trials.
The integration of metabolic and psychological factors in the proposed model reflects the complexity of AN and the need for multifaceted treatment strategies.
