Consuming a ketogenic diet along with medication and/or psychotherapy was associated with a nearly 70% decrease in symptoms of major depressive disorder (MDD), a small pilot study showed.
After 10-12 weeks of following a keto diet, investigators found that depressive symptoms improved significantly based on self-reported surveys by college students and clinician assessments.
Participants also performed better on cognitive tests that measure episodic memory, processing speed, and executive function.
While urging caution in interpreting the results given its small design and college-aged cohort, investigators said the results of the proof-of-concept study are encouraging.
“Everybody across the board improved their scores of depression. It’s showing that a [keto diet] is feasible, that it’s not going to negatively impact individuals that are suffering and that we could potentially see improvements by adding this onto standard of care treatment,” lead author Drew Decker, MS, graduate research associate at The Ohio State University, Columbus, Ohio, told Medscape Medical News.
The study was published online on September 10 in Nature Translational Psychiatry.
Metabolic Health and Depression
MDD affects an estimated 8% of adults and roughly a third of college-aged students in the US.
While the treatment of MDD typically relies on talk therapy or psychiatric drugs, the researchers noted that these interventions don’t take the metabolic contributors of depression into account, despite growing evidence that poor metabolic health is associated with a greater risk for anxiety and depression.
The investigators analyzed data on 16 students (10 women; mean age, 24 years) who were already in counseling or receiving treatment for depression, had a confirmed MDD diagnosis and were willing to eat a well-formulated keto diet for 10-12 weeks.
The students received training on how to follow the diet, which consisted of a daily intake of < 50 g of carbohydrates and a moderate protein intake of 1.2-1.5 g per kg of body weight and fat, with a focus on monounsaturated and saturated fats from whole foods. Typical recommended foods included meats, cheese, eggs, nonstarchy vegetables and low-glycemic fruits.
Investigators measured students’ symptoms of depression and well-being at baseline using the Patient Health Questionnaire-Nine and the World Health Organization-Five Well-Being Index, respectively.
Nutritional ketosis was assessed daily by measuring blood ketone values before students ate their first meal of the day. Biochemical markers including brain-derived neurotrophic factor (BDNF) were also measured. Cognitive function was evaluated using the National Institutes of Health Toolbox that test episodic and working memory, processing speed, executive function, and attention.
Cognitive Improvements and Weight Loss
Ketosis was achieved 73% of the time based on blood ketone measurements. At the end of the dietary period, self-reported symptoms of depression fell by 69% (P < .001) and clinician assessments of depression reduced by 71% (P < .001).
By week 2, students reported a twofold increase in well-being, with a threefold increase by the end of the study period. All but one student lost weight, with an average weight loss of 11 pounds.
Of note, they measured a 32% increase in BDNF, which they suggested could be “a potential neurobiological mechanism underlying an antidepressant effect.”
Researchers also noted significant improvements in scores for episodic memory, processing speed, and executive function following the dietary intervention.
Students improved on the auditory verbal learning test (10%; P = .032) and could recall more words across three trials. They also showed improved processing speed on the oral symbol digit test (5%; P = .046) and pattern comparison test (4%; P = .021).
Regression analyses did not find a significant correlation of weight loss affecting depression scores independent of ketosis, meaning that symptom improvements were likely not due to just losing weight. However, Decker highlighted that the scope of this study could not definitively conclude that improvements were due to ketosis.
More Research Needed
Although the underlying mechanisms were outside the scope of the study, potential reasons for the observed benefits of a keto diet could be increased energy supply to the brain or increased BDNF, Decker said. The next step would be a randomized controlled trial with multiple dietary arms, he said.
“We haven’t teased out those mechanisms here because this is a proof-of-concept study for an adjunctive therapy,” principal investigator Jeff Volek, PhD and professor of human sciences at The Ohio State University, said in a news release. “This is one of the first really well-controlled studies and it has limitations, but the results encourage us to want to keep pursuing it.”
The study was limited by the fact that it had a small sample size, single-arm design, no control group and a high attrition rate, Uma Naidoo, MD, nutritional psychiatrist, director of nutritional and lifestyle psychiatry at Massachusetts General Hospital, Boston, told Medscape Medical News.
“Selection bias is possible because participants volunteered for dietary intervention and they may not represent the broader population of individuals who have MDD, and this was restricted to college students so that all limits external validity,” said Naidoo, who was not part of the study.
In addition, the foods in the diet might not agree or be sustainable for everyone, noted Naidoo, author of “This is Your Brain on Food.”
“I don’t think we can consider it a form of treatment yet. I think we can consider it an intervention that might work with the right patient,” she said.
Although the study showed some positive preliminary results, Naidoo urged caution. “We want to be very careful with dietary interventions and make sure the person is stable enough to tolerate [it].”
Key findings included the potential antidepressant effect of increased BDNF and clinically significant weight loss that also affected participant’s serum leptin levels, she said. But randomized controlled trials are needed to test the diet in broader populations, Naidoo added.
Naidoo and Decker reported no disclosures. The research was supported by a grant to The Ohio State University from the Baszucki Brain Research Fund.