Researchers Explore Connections Between Diet, Treatment-Resistant Depression

Investigators are attempting to broaden their understanding of the connection between diet and treatment resistant depression (TRD). The findings are preliminary. but they could provide useful evidende for how well-managed diets could supplement or even head off the need for pharmacological care of TRD.

An independent study examined nutritionally poor changes in diet apparently induced by or related to treatment with ketamine, which was first authorized for treatment of TRD by the FDA in 2019.

Separately, in a first-time study just getting underway, investigators are exploring the value of a ketogenic diet, which is rich in fatty foods such as meat and fish and low in carbohydrate, for moderating the symptoms of TRD.

Lastly, investigators have long known that antioxidants might play a role in moderating symptoms of TRD. A recent review sought to summarize the evidence in support of a diet rich in antioxidants for combating TRD.

In the ketamine study, which included 30 participants, investigators observed a significant decline in the quality of diet among patients taking ketamine versus controls. Significantly lower consumption of whole grains, natural milk drinks, and vegetables containing anti-inflammatories and neuroprotective compounds was noted.

Although the study group’s nutritional intake was already inferior to the controls’ prior to receiving ketamine, “The results showed a significant reduction in vitamins in the patients’ diet after the treatment with ketamine,” the authors wrote.

They hypothesized that ketamine may suppress the natural appetite or intensify weak dietary practices that patients may have had before treatment.

For example, statistically significant lower levels of tryptophan, magnesium, and vitamin C were consumed by the study group following ketamine administration. Deficiencies of tryptophan (an amino acid), magnesium, and vitamin C are associated with depression.

“Lower consumption of macronutrients, minerals, vitamins, and energy in many patients and not meeting the daily requirements, which increase after treatment with ketamine, pose a significant risk of developing malnutrition among patients with TRD, which may have a more negative impact on depression symptoms and achieving remission of the disease,” wrote lead author Agnieszka Mechlinska, of the Department of Psychiatry, Medical University of Gdansk, Poland, and her co-authors.

Investigators at the University of Oxford in England have announced enrollment for a study of the value of ketogenic diet (high fat, moderate protein, and very low carbohydrates) to reduce the severity of TRD and improve patients’ quality of life.

In the notice published in June in the Journal of Psychiatric Research, the investigators explained they want to probe the use of a ketogenic diet as an adjunctive treatment for TRD.

The theory is that by training the body to draw its energy from fats, glucose consumption in the brain can be reduced and the functioning of neurotransmitters in the brain can be improved.

Min Gao, Ph.D.

“Ketogenic diets enhance cellular bioenergetics, reduce oxidative stress, and promote vascular brain changes,” wrote lead author Min Gao, Ph.D., an epidemiologist the Nuffield Department of Primary Care Health Sciences, University of Oxford, and her colleagues. “Moreover, ketogenic diets may also improve cognitive function,” they wrote.

Ketogenic diets are associated with changes in neurotransmitters and neuromodulators such as dopamine, noradrenaline, and serotonin. They offer the body “an alternative energy source to maintain normal brain cell metabolism” and may even be a “more efficient fuel than glucose,” the authors said.

The antidepressant value of diets high in antioxidants and anti-inflammatories has gained emphasis in TRD because roughly 50% of patients with a major depressive disorder do not respond to first-line pharmacological treatments.

“It has been consistently reported that antioxidant capacity is reduced in depressed patients," wrote Maria Eugenia Riveros, of the Center for Cellular and Integrative Physiology at German Clinic University of Development, and her co-authors. This may contribute to oxidative stress, resulting in poor response to antidepressant medications, they said.

“Oxidative stress can damage mitochondria, and … mitochondrial damage promotes oxidative stress and is involved in depressive pathology.” This is “generally a vicious cycle that is maintained for a long time,” they wrote.

Their study evaluated the potential for antioxidant biomolecules to aid in the treatment of TRD.

They noted that tea, vitamin C, and common spices such as turmeric and saffron help to support oxidative balance in the body. But there was also a note of caution: “More evidence is needed to endorse their antidepressant actions,” they wrote.