A pilot study in college students with major depressive disorder found that adding a well-formulated ketogenic diet to usual care was associated with large reductions in depressive symptoms, improvements in well-being, and favorable changes in body composition and biomarkers.
Depression scores fell 69% on the Patient Health Questionnaire-9 and 71% on the Hamilton Rating Scale for Depression. Improvements appeared within 2 to 6 weeks. More specifically, patient-reported scores decreased by 37% as early as week 2, and were sustained through the study. Global well-being scores increased nearly threefold, while cognitive performance improved in multiple domains. Episodic memory rose 10%, and processing speed increased 4% to 5% on standardized assessments. Executive function showed trends toward improvement, and no measures declined.
Patients remained in nutritional ketosis 73% of the time, with mean blood beta-hydroxybutyrate levels of 0.7 mmol/L. Body weight decreased 6%, or about 5 kg, during the study. Fat mass declined 13%, while lean mass decreased slightly. Serum leptin fell 52%, and brain-derived neurotrophic factor rose 32%. Insulin resistance, measured by HOMA-IR, decreased 28% but was not statistically significant. Lipid profiles, including cholesterol and triglycerides, did not change.
Adherence was high. Patients logged ketone and glucose values on 77% of study days. The authors noted that coaching and feedback through a mobile application, some supplementary food items, extensive diet coaching and education before starting the diet, and regular monitoring of blood ketone and glucose values likely contributed to adherence.
Sixteen of 24 patients completed the 10- to 12-week intervention, though 36 were originally screened. Participants were included if they were students aged 18 to 30 years with clinician-confirmed mild to moderate major depressive disorder (MDD), and they could be receiving counseling, psychiatric medication, or both at the time of the trial. Seven patients were on medication at baseline, with minimal changes during the study. The researchers reported no interaction between depression outcomes and medication use. Exclusion criteria were severe MDD, active suicidal ideation, pregnancy, and history of bipolar, psychotic, or eating disorders. Attrition was 33%, and 7 of 8 withdrawals were unrelated to diet. One patient discontinued because of difficulty with adherence, two patients reported transient headaches and cramps in the first week that resolved with electrolyte supplementation, and three patients developed unrelated viral illnesses.
Jeff S. Volek, PhD, RD, of The Ohio State University and corresponding author of the study, explained that “This pilot study provides preliminary evidence that a well-formulated ketogenic diet is a feasible and synergistic strategy adjunctive to a counseling and consultation treatment program for young adults with MDD.” He also noted that ketogenic therapies are increasingly being studied in this field for their potential to attenuate mental health symptoms.
The study had several limitations. Its single-arm design made it impossible to separate the effects of diet from those of counseling, medication, or time. The sample size was small, and the intervention period was short, which prevented conclusions about remission or long-term sustainability. The authors also emphasized challenges in scaling this intervention to a broader and more diverse population. They noted that "college students may have specific advantages in terms of adherence, such as greater access to resources and support, but they also face unique stressors related to academic life that could affect consistent engagement with treatment." As a result, the generalizability of these findings to populations outside this demographic remains limited. Attrition was relatively high, and selection bias or demand effects may have influenced results.
The study was supported by the Baszucki Brain Research Fund. Dr. Volek reported a conflict of interest as cofounder and shareholder of Virta Health and author of books recommending a ketogenic diet. The other authors reported no conflicts of interest.
Source: Translational Psychiatry
