Ketogenic therapy as a potential novel treatment approach for PTSD: an integrative review and proposed mechanistic model.

BACKGROUND: Brain and body metabolic disruptions have been suggested in several studies as a mechanism underlying posttraumatic stress disorder (PTSD). Therapies targeting metabolic pathways might provide new treatment options. This review explores the potential of ketogenic therapies, such as the ketogenic diet and ketone supplementation, as novel metabolic treatments for PTSD. METHODS: An integrative review was conducted. We searched PubMed, Scopus, PsycINFO, PsycArticles, PSYNDEX, MEDLINE, ClinicalTrials.gov, International Clinical Trials Registry Platform, and EU Clinical Trials Register for clinical, preclinical, observational, mechanistic, and review studies that reported outcomes or mechanisms on the intersection of ketogenic therapy and PTSD. Methodological quality of included studies was assessed independently by two reviewers based on predefined criteria. RESULTS: Sixteen articles (9 human, 4 animal studies, 3 reviews) were eligible and included in the present review. Several metabolic and signaling pathways through which ketogenic therapies could impact PTSD pathophysiology were identified. Preclinical data suggestive of potential efficacy were identified, while only minimal reliable information is available from human studies. DISCUSSION: Importantly, the absence of larger clinical trials and the reliance on low-level evidence substantially limit current interpretations. High-quality randomized and adequately powered clinical trials are required to examine the potential role of ketogenic therapies in treating PTSD.