A ketogenic diet, high in fat and low in carbohydrates, could improve the mental health of people with treatment-resistant depression, a small trial has shown.
Keeping to the keto diet for six weeks had antidepressant benefits when compared with a well-matched control diet in the Dietary Interventions for Mental Health (DIME) study.
However, maintaining the eating plan—which is similar to the Atkins diet made popular in the 1970s—was challenging for participants once the provision of meals and support ended.
Indeed, less than a tenth were able to continue with the keto diet afterwards, the researchers acknowledged in JAMA Psychiatry.
Nonetheless, they added that “participants did not experience relapse to previous levels of depression, suggesting either that a short period of carefully supported dietary intervention may have enduring benefits or that the mechanism of any improvement was unrelated to ketosis and perhaps linked to study participation.”
Neurons and signals in the brain are greatly disrupted in people with severe depression, and a ketogenic diet supplies a form of energy that appears to help brain cells communicate and may affect metabolic, neurotransmitter, inflammatory and gut-brain pathways.
The high-fat, low-carbohydrate regimen shifts cellular energy metabolism from glucose to ketones and has been proposed as a novel treatment for several psychiatric disorders, including depression.
To find out more, Min Gao, PhD, from the University of Oxford, and co-workers compared the impact of a keto and a control “phytochemical” diet in 88 adults for whom traditional medication had not worked.
The participants, of whom nearly 70% were women, had all tried at least two different antidepressant medications within their current depressive episode.
Participants were randomly assigned to one of the two dietary interventions. The keto group received three prepared meals plus snacks that provided less than 30 g of carbohydrates per day with weekly nutritional counseling focused on a ketogenic diet
The control group was asked to follow the phyto diet that replaced saturated with unsaturated fats and were given a voucher to buy an extra serving of fruit or vegetables per day, together with weekly nutritional counseling.
Existing depression treatment remained for both groups. The primary outcome of change in depression symptoms at six weeks revealed a marked decrease in both groups.
The mean score on the nine-item Patient Health Questionnaire (PHQ-9) decreased by 10.5 in the keto group and 8.3 in the phyto group.
Mean between-group differences were significant at six weeks, but not at 12 weeks, and ketone concentrations were not associated with the improvement of depression.
The researchers suggest that the large reductions in PHQ-9 score “may reflect the benefit of providing hope and expectation of improvement.”
The trial suggests that keto diets may be an effective adjunct for treatment-resistant depression, they conclude.
“However, adherence to the diet required intense support, and few patients chose to continue the diet after support withdrawal,” the team adds. “Further work to develop a more comprehensive intervention is needed before further clinical testing.”
