Ketogenic diet associated with 70% decrease in depression symptoms in new pilot study

A new study suggests that a well-formulated ketogenic diet, followed for at least 10 weeks, is associated with a significant reduction in depression symptoms among a small group of college students. Published in the journal Translational Psychiatry, the research also documented notable improvements in the participants’ overall well-being and their performance on several cognitive tests.

The research was prompted by the rising prevalence of major depression, particularly on college campuses. Existing treatments, such as psychotherapy and medication, are effective for many but do not help everyone and can come with unwanted side effects. Researchers led by Drew D. Decker at The Ohio State University sought to explore a different approach, one that addresses the potential link between metabolic health and depression.

A growing body of evidence connects issues like insulin resistance and excess body fat to an increased risk of depression, possibly through inflammatory pathways. The team hypothesized that a dietary intervention known to improve metabolic health, the very low-carbohydrate ketogenic diet, might serve as a beneficial add-on therapy for students already receiving treatment for depression.

The study was designed as a single-arm prospective trial, meaning all participants received the same dietary intervention without a comparison control group. Researchers recruited students from The Ohio State University who had been formally diagnosed with Major Depressive Disorder and were currently engaged in counseling or taking medication for their condition. After an extensive screening process to confirm eligibility and rule out conditions like eating disorders, 24 students began the study, with 16 completing the full 10 to 12 week intervention.

“One of the things we really wanted to make sure of is that we were providing a treatment for people who met the diagnostic criteria for having major depressive disorder,” said co-author Jennifer Cheavens, a professor of clinical psychology at Ohio State who oversaw the clinical assessments. “Each participant had about a 2 1/2-hour interview at the beginning, and then weekly assessments of their symptoms.”

Before starting the diet, each participant received a detailed educational session. The well-formulated ketogenic diet required them to limit carbohydrate intake to less than 50 grams per day, consume a moderate amount of protein, and get the rest of their calories from fat, with an emphasis on whole food sources like olive oil, nuts, and fatty fish. To help with adherence and offset costs, the research team provided some staple ketogenic foods and ongoing support from dietitians through a secure messaging application.

“It was very important to make sure participants knew what they were getting themselves into,” said Drew Decker, the study’s first author. “And a big part of increasing chances for adherence to the diet was talking to each individual about what they like and don’t like to eat so we could tailor some suggestions for how they could structure their diet.”

Throughout the study, researchers tracked several outcomes. Participants self-reported their depressive symptoms bi-weekly using the Patient Health Questionnaire-9. A qualified clinician also rated their depression at the start, midpoint, and end of the study using the Hamilton Rating Scale of Depression. To confirm they were following the diet, students measured their morning blood ketone and glucose levels daily. Researchers also assessed body composition using scans, collected blood samples to analyze for markers related to metabolism and inflammation, and administered a battery of cognitive tests on an iPad.

The results showed a robust and sustained decrease in depression symptoms. Among the 16 students who completed the study, self-reported depression scores dropped by an average of 69 percent from the beginning to the end of the intervention. Clinician-rated scores showed a similar 71 percent reduction. Every participant who completed the study showed an improvement in their depression scores, and by the end, no one met the criteria for moderate or severe depression.

Ryan Patel, a psychiatrist at Ohio State who met with the students during the trial, noted the significance of these changes. “The average effect size for medications and counseling after 12 weeks is about 50%, and we saw a substantially greater result,” he said. “That is an impressive finding, that across the board, in this real-world setting, everybody got better, and across the board, our participants did not need more treatment or emergency intervention.”

Alongside the mental health improvements, participants experienced physical changes. Fifteen of the 16 students lost a clinically significant amount of weight, with an average loss of five kilograms, or about 11 pounds. This weight loss was predominantly from body fat. Blood analysis revealed a 32 percent increase in brain-derived neurotrophic factor, a protein important for neuron health, and a 52 percent decrease in leptin, a hormone related to body fat and appetite.

The diet was also associated with better cognitive function. Participants showed significant improvements on tests measuring episodic memory, processing speed, and executive functions. For example, they were able to recall more words from a list and complete symbol-matching tasks more quickly at the end of the study compared to the beginning. Their self-reported global well-being also increased nearly threefold over the course of the intervention.

The researchers explored whether the improvements in depression were simply a result of weight loss or the presence of ketones in the blood. They found no significant statistical correlation, suggesting the diet’s positive effects on mood may stem from more complex biological changes rather than weight loss alone.

“The idea is that the ketogenic diet is working through a variety of potentially different mechanisms, there’s a whole range of physiological metabolic adaptations to the diet that could overlap with some of the pathophysiology of depression,” explained Jeff Volek, the study’s senior author and a professor of human sciences at The Ohio State University.

The study authors acknowledge several limitations. The single-arm design means it is not possible to definitively separate the effects of the diet from the participants’ ongoing counseling and medication, or from the simple passage of time. The small sample size and the fact that participants volunteered for a diet study could also influence the results. Additionally, repeated cognitive testing can sometimes lead to better scores due to practice, an effect that could not be ruled out without a control group.

Future research is needed to confirm these findings in larger, randomized controlled trials that can more clearly isolate the diet’s impact. Such studies could also help identify the specific biological mechanisms responsible for the observed benefits.

Despite these limitations, the researchers see the results as a promising step toward new treatment options. “We have a treatment gap in that we have more students suffering from mental health concerns than can feasibly receive professional treatment,” Patel said. “There is a need for finding ways of helping students on a large scale. And nutrition is one way we can do that.”

Volek added that the study provides a solid foundation for further investigation. “So many people are suffering right now, so it’s rewarding to potentially bring forward a solution,” he said. “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, “A pilot study examining a ketogenic diet as an adjunct therapy in college students with major depressive disorder,” was authored by Drew D. Decker, Ryan Patel, Jennifer Cheavens, Scott M. Hayes, Whitney Whitted, Ann J. Lee, Alex Buga, Bradley T. Robinson, Christopher D. Crabtree, Madison L. Kackley, Justen T. Stoner, Teryn N. Sapper, Ashwini Chebbi, and Jeff S. Volek.