Transl Psychiatry. 2025 Sep 10;15(1):322. doi: 10.1038/s41398-025-03544-8.

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.

PMID:40925905 | PMC:PMC12420795 | DOI:10.1038/s41398-025-03544-8

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