Ketogenic Therapy Shows Promise for Anorexia Nervosa Treatment in UC San Diego Clinical Trial
Key Insights
A 14-week ketogenic therapy (search) trial at UC San Diego demonstrated high tolerability and safety in 22 women with anorexia nervosa (search), with 82% completing the study and no significant weight loss observed.
Seventy-two percent of study completers achieved eating disorder symptom scores in the recovered range by study end, while all participants showed improvements in depression (search) scores.
The high-fat, low-carbohydrate intervention targets underlying neurometabolic dysfunction in anorexia nervosa (search), offering a novel approach beyond traditional weight restoration therapies.
A groundbreaking clinical trial from UC San Diego School of Medicine (search) has demonstrated that ketogenic therapy (search)—a high-fat, low-carbohydrate nutritional intervention—shows significant promise as a treatment for anorexia nervosa (search), a psychiatric disorder with one of the highest mortality rates among mental illnesses.
The single-arm feasibility study, published in Communications Medicine, enrolled 22 women with anorexia nervosa (search) who were either weight-restored or mildly underweight (BMI > 17.5 kg/m²). Participants underwent a supervised 14-week ketogenic intervention with macronutrient targets of 70% fat, 20% protein, and 10% carbohydrates.
High Completion Rates and Safety Profile
The study achieved an 82% completion rate, with 18 of 22 participants finishing the full 14-week program. Importantly, no significant weight loss was observed throughout the intervention period, addressing a key concern about dietary interventions in this vulnerable population. The mean BMI change was a slight increase of 0.2, and no participant's BMI fell below the 17.5 threshold.
"We urgently need new approaches to anorexia nervosa (search). Our work with ketogenic therapy (search) looks beyond standard therapies and potentially at the underlying physiology of the disorder," said study lead Guido Frank, MD, Professor of Psychiatry at UC San Diego School of Medicine (search), who has been studying and treating anorexia patients for over 25 years.
Side effects were generally mild and transient, initially reported by 40% of participants but decreasing to 0% by study end. The most common adverse effects included nausea, constipation, and dehydration, with no serious adverse events reported.
Significant Symptom Improvements
The results showed remarkable improvements in eating disorder symptoms. Using the Eating Disorder Examination Questionnaire (EDE-Q), researchers found that 72% of study completers achieved scores in the recovered range by study end—meaning they no longer met criteria for anorexia nervosa (search) diagnosis. The mean baseline EDE-Q Global score of 4.11 decreased to 1.72 at study completion, representing a clinically meaningful improvement.
All participants demonstrated improvements in depression (search) scores as measured by the Beck Depression Inventory (BDI), with 72% achieving scores within the normal range. Additional assessments showed significant improvements in eating disorder-specific measures (EDI-3), clinical impairment (CIA), anxiety (search) levels (STAI), and harm avoidance behaviors.
Targeting Neurometabolic Dysfunction
The ketogenic approach represents a paradigm shift from traditional anorexia nervosa (search) treatments, which primarily focus on weight restoration through structured meal plans. The intervention targets what researchers believe may be underlying neurometabolic dysfunction in the disorder.
"Growing evidence links anorexia nervosa (search) to neurometabolic dysfunction, and we are hopeful that direct metabolic intervention can regulate neural function and address the psychological symptoms patients experience," Frank explained.
The study monitored nutritional ketosis through daily blood β-hydroxybutyrate (search) (BHB) measurements during the initial 14-day induction period, then weekly thereafter, targeting levels of 0.5-3.0 mmol/L. Participants achieved ketosis within two weeks and maintained this metabolic state throughout the study duration.
Sustained Benefits and Predictive Factors
At a three-month follow-up assessment, symptom improvements were largely maintained regardless of whether participants continued the ketogenic diet. Thirty-nine percent of study completers continued ketogenic therapy (search) independently after the study concluded.
The research identified low self-esteem as a key predictor of treatment response. Participants whose eating disorder symptoms did not normalize by study end had significantly higher baseline low self-esteem scores, suggesting this factor may influence treatment outcomes.
Exploratory genetic analysis revealed that variations in genes involved in carnitine metabolism—specifically CPT2 (search) and SLC22A5 (search)—were associated with different carnitine levels, potentially affecting the ability to achieve and maintain ketosis.
Clinical Implications and Future Directions
The study builds on preliminary case series evidence and addresses longstanding challenges in anorexia nervosa (search) treatment. Even after successful weight restoration, patients often struggle with persistent psychological symptoms including body dissatisfaction, intense fear of eating, and preoccupation with body shape—factors that contribute to high relapse rates.
For co-author Barbara Scolnick, MD, an internal medicine physician in Massachusetts, the research represents the culmination of a personal journey. "The scientific inquiry that led to this research began in search of answers for my niece, Caroline Beckwith," Dr. Scolnick shared. "Ketogenic therapy (search), a standard in epilepsy care, was the major catalyst, when combined with other interventions, that allowed Caroline to achieve remission after a 15-year struggle with anorexia nervosa (search)."
Study Limitations and Next Steps
The researchers acknowledge several limitations, including the small sample size limited to females and predominantly White, non-Hispanic participants, which restricts generalizability. The single-arm design without a placebo control also limits conclusions about specific treatment effects.
A current extension study for patients with both anorexia nervosa (search) and bulimia nervosa (search) diagnoses is underway and recruiting participants nationally. Future research will need to replicate these findings in more diverse populations and incorporate objective assessments of brain function to better understand the neurobiological mechanisms of action.
The findings suggest that ketogenic therapy (search), when delivered with specialized medical supervision and trained support, may provide a promising treatment option for patients who have not responded to traditional approaches, potentially offering new hope for individuals and families affected by this devastating disorder.