Post traumatic stress disorder (PTSD) is a mental disorder arising from a threatening event(s) that may cause physical harm, intense fear, feeling of helplessness, and/or horror (1). PTSD is often accompanied by poor physical health and is prevalent in veterans as well as the general population (2, 3). Although the data is limited, previous studies have supported the notion that PTSD-related impairments in physical health may result from a disrupted gut-brain axis (4, 5, 6,7).
The brain and gastrointestinal system are extensively connected complex systems with similar pathways and neurotransmitters (8,9). Generally, a stressed brain leads to a dysfunctional gut, and a dysfunctional gut affects the brain – it is a viscous cycle (8, 10). Mediators interlinking the brain and gut include the immune system, colon-dwelling microbiome, and circulating inflammation and hormones (9,10). In regards to the gut side of the gut-brain axis, individuals with PTSD commonly exhibit gastrointestinal dysfunction via irritable bowel syndrome, increased intestinal permeability, altered gut microbiota, altered stress hormone levels (i.e., cortisol), and increased systemic inflammation (i.e., C-reactive protein and lipopolysaccharides) (7, 11,12, 13, 14). The brain side of the axis is also impaired with PTSD, demonstrated by signs of compromised cognitive performance (i.e., short-term memory and attention span) and emotional health (i.e., hostility levels, alcohol dependency, and domestic violence tendencies) (7,15).
Physiologic dysregulation that occurs with PTSD streams through the blood vessels of these diagnosed patients. Characteristically, PTSD is associated with elevated blood glucose levels as well as dyslipidemia defined as increases in triglyceride and low density lipoprotein cholesterol (LDL-c) levels with decreases in high density lipoprotein cholesterol (HDL-c) levels (16, 17). The combination of dyslipidemia and elevated glucose levels places individuals with PTSD at an increased risk for developing type 2 diabetes (18,19). Furthermore, individuals diagnosed with PTSD demonstrate elevated basal heart rates and blood pressure, which contribute to the possible development of cardiovascular disease (20, 21).
Effective therapies in the treatment of PTSD are lacking. A plausible holistic therapy, due to its efficacy in improving PTSD-associated health deficiencies, is the incorporation of a ketogenic diet. The ketogenic diet is a high fat, low carbohydrate, moderate protein dietary regimen that has successfully treated numerous chronic diseases. Unlike a regular mixed diet which promotes only glucose as the primary fuel source for the brain, the ketogenic diet provides two primary energy sources for the brain: 1) glucose, derived from glycogen and gluconeogenesis in the liver, and 2) ketone bodies, synthesized from fatty acids in the liver (22). On a molecule by molecule basis, the ketone body beta-hydroxybutyrate (β-HB) provides more energy than glucose, and has been shown to be a beneficial fuel for the brain, especially in a damaged brain cell (23). Neurological diseases and symptoms improved by a ketogenic diet include epilepsy, headaches, neurotrauma, Alzheimer’s disease, Parkinson’s disease, sleep disorders, brain cancer, autism, and multiple sclerosis (24, 25, 26).
Cognitive performance and emotional health impairments often associated with PTSD may be improved by the ketogenic diet. The mechanisms and outcomes of a ketogenic diet are similar to fasting as both lack dietary glucose and subsequently produce ketone bodies to supply energy-requirements. Improved mood and cognitive function often accompany use of the ketogenic diet or long periods of fasting (< 7days) possibly due to increased β-HB levels and/or decreased glucose levels (27, 28). β-HB is an isomer of γ-hydroxybutyrate (GHB), a euphoric drug that may be used as treatment for alcohol and opiate dependency and narcolepsy-associated cataplexy (sudden loss of control over muscles) (27). Similar to the actions of its isomer GHB, β-HB may also cause a mild euphoric state which subsequently improves mood and cognitive function (27). Also, reduced cerebral glucose levels resulting from low carbohydrate consumption may promote neurogenesis and the synthesis of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) that is associated with improved cognition, serotonin metabolism, and reduced aging of the brain (29). The repeated success that the ketogenic diet has shown with treating dyslipidemia and systemic inflammation makes it an excellent therapeutic candidate for PTDS. The ketogenic diet’s management of dyslipidemia occurs via a decrease in liver triglyceride synthesis (due to fewer carbohydrates consumed) (30,31), a reduction of circulating triglyceride levels, and an elevation of HDL-c levels; these alterations decrease the risk for type 2 diabetes and cardiovascular disease (32, 33, 34, 35). Additionally, the ketogenic diet has been associated with obesity prevention/reduction via reduced adiposity (specifically, reduced visceral adipose tissue) and reduced inflammation (35, 36, 37).
In addition to the brain, ketone bodies fuel other tissues including skeletal muscle, heart, and intestinal tissues (38). Intestinal cells are called enterocytes; the luminal membranes of the large intestine enterocytes are laden with a layer of microorganisms that contribute to enhancing the immune system. Typically, this colon-dwelling microbiome consumes carbohydrates (i.e., fiber) and releases short chain fatty acids (SCFAs) as a by-product that subsequently fuels the enterocytes (9,10). Accordingly, with appropriate levels of fiber, the ketogenic diet may improve the health of the intestines by supplying enterocytes with two forms of energy: 1) SCFAs produced by the microbiome, and 2) ketone bodies synthesized by the liver (9, 38).
The compilation of the previous studies support the postulation that the ketogenic diet may ultimately improve gut, immune, and brain health to reestablish a well-functioning gut-brain axis. The efficacy of a ketogenic diet as a health intervention for those suffering from PTSD has not been studied in any major context. PTSD negatively affects many veterans as well as individuals of the general population, but the treatment for this diagnosis is lacking. Therefore, research studies that examine the effectiveness of dietary-based treatments for PTSD, such as the ketogenic diet, are of great importance.