A pilot study examining a ketogenic diet as an adjunct therapy in college students with major depressive disorder

Abstract

A ketogenic diet (KD) has shown promise as an adjunctive therapy for neurological and neuropsychiatric disorders, including bipolar disorder and major depressive disorder (MDD). We examined tolerance for a KD in young adults with MDD and assessed symptoms of depression and metabolic health. Students (n = 24) with a confirmed diagnosis of MDD at baseline receiving standard of care counseling and/or medication treatment were enrolled in a 10-12 week KD intervention that included partial provision of ketogenic-appropriate food items, frequent dietary counseling, and daily morning tracking of capillary R-beta-hydroxybutyrate (R-BHB). Primary outcome measures for mood symptoms included the Patient Health Questionnaire (PHQ-9) and Hamilton Rating Scale for Depression (HRSD). Additional outcomes included body composition, neurocognitive function, and blood hormonal and inflammatory markers. Sixteen students (10 women, 6 men, mean age 24 yr) completed the intervention. Nutritional ketosis (R-BHB > 0.5 mM) was achieved 73% of the time. Depressive symptoms decreased by 69% (PHQ-9) and 71% (HRSD) post-intervention (p < 0.001), with improvement occurring within 2-6 weeks. Global well-being increased nearly 3-fold (p < 0.001). Participants lost body mass (-6.2%; p = 0.002) and fat mass (-13.0%; p < 0.001). Serum leptin decreased (-52%; p = 0.009) and brain-derived neurotropic factor increased (+32%; p = 0.029). Performance improved on several cognitive tasks. In students with mild to moderate depression based on PHQ-9 and HRSD, implementation of a WFKD for 10-12 weeks is a feasible adjunctive therapy and may be associated with improvements in depression symptoms, well-being, body composition, and cognition.

Fig. 1

Consort Diagram.

Fig. 2. Ketone Responses.

Individual variability in daily morning fasted capillary (A) R- BHB and 7-day moving average of R-BHB (B). Values ≥ 0.5 mM denote ketosis. The numbers below the dotted line reflect the n- size. All values are mean ± SEM.

Fig. 3. Survey Responses.

Mean and individual survey responses for PHQ-9 (A), (B), HRSD (C), (D), and WHO-5 (E), (F). Lower scores denote improvement in PHQ-9 and HRSD. The numbers below the dotted line reflect the n-size. The HRSD scale is divided into quadrants indicating no depression (0–7), mild depression (8–16), moderate depression (17–24), and severe (>25). All values are mean ± SEM. * = p < 0.05 compared to baseline. ** = p < 0.01 compared to baseline. *** = p < 0.001 compared to baseline.

Fig. 4. Individual body weight and body composition responses.

* = p < 0.05 compared to baseline. ** = p < 0.01 compared to baseline. *** = p < 0.001 compared to baseline. # = p < 0.05 compared to midpoint ## = p < 0.01 compared to midpoint.