Research Review: Can a Ketogenic Diet Ease Psychiatric Symptoms?

This week’s research paper, Metabolic Improvements with a Ketogenic Diet Correlate with Symptom Improvement in Psychosis: A Randomized Controlled Trial,⁽¹⁾ covers a randomized controlled trial of a ketogenic diet for people with schizophrenia or bipolar 1. I will review why this is such an important study, and what key things we can learn from it.

There have been case reports, case series, and single arm studies, but this is the first randomized controlled trial of a ketogenic diet in the setting of psychoses due to schizophrenia syndrome or bipolar 1 disorder.

In psychosis, the brain struggles to use glucose for fuel. Ketones, produced during nutritional ketosis, give brain cells an alternative fuel source, which is believed to be a key reason ketogenic diets reduce positive and negative symptoms (hallucinations/delusions and flat affect/withdrawal, respectively) for people with psychoses.

The medications that are used to treat psychoses often result in weight gain and insulin resistance, and increase the risk of developing type 2 diabetes, which is one reason a metabolic intervention is worth studying.

Study Details

It was a small study. Sixty participants with schizophrenia syndrome or bipolar 1 diagnosis were enrolled. They could not be pregnant, breastfeeding, or taking a GLP-1 drug, although they could be taking metformin.

The ketogenic group received 18 microwavable ketogenic meals each week from a study-contracted meal delivery service. These meals were 70–80% fat, 10–20% protein, and no more than 10% carbohydrates. The control group was asked to continue eating their usual diet. Each week, the team contacted participants to answer questions, and a psychiatrist was available as needed.

At the end of the one-month intervention, all participants were invited into an extension study — the control group ate a ketogenic diet for four months; the intervention group continued for an additional three months. At the end of the extension period, all participants received four months of ketogenic diet therapy.

Feasibility and Tolerability

No serious adverse events were reported, and minor issues were resolved with additional electrolytes. Two people withdrew from the ketogenic arm due to difficulty adhering to the diet.

Data and Results

Positive and negative psychiatric symptoms, cognitive symptoms, and depressive symptoms were assessed through validated measures including the MATRICS Consensus Cognitive Battery, the Scale for Assessment of Positive Symptoms, the Scale for Assessment of Negative Symptoms, and the Patient Health Questionnaire 9.

Biomarkers measured included height, weight, abdominal circumference, glucose, hemoglobin A1c, insulin, C-reactive protein, and beta hydroxybutyrate.

Ketosis was achieved and sustained by most participants; only three participants did not achieve sustained ketosis (ketone level <0.5 mmol/L) during the study. Ketone levels averaged 1.38 mmol/L in the last week of the four-month extension.

Improved Metabolic Markers

In both the one-month randomized controlled period and the four-month extension, metabolic markers improved compared to the control group or baseline. Body mass index (BMI) and hemoglobin A1c decreased in the ketogenic group (but not in the control group), and they decreased further after the four-month extension.

Improved Psychiatric Symptoms

The study was unable to show a significant difference between the ketogenic intervention and the control group during the initial one-month period. The four-month ketogenic extension, however, showed improvements in cognition and positive and negative psychiatric symptoms compared to the baseline, and the team noted a trend toward mood improvements in the four-month extension.

Ketone Bodies and Their Correlation with Improvements

Investigators analyzed the relationship between the levels of ketone bodies in the blood and the improvements in participants’ metabolism and psychiatric symptoms. They found that higher levels of ketones were correlated with greater improvements in hemoglobin A1c and overall mood, but they did not report doing an analysis of whether ketone levels affected positive and negative psychiatric symptoms.

They were also not able to establish a correlation between ketone levels and weight loss.

My Take on This Study as a Researcher

Most pilot dietary studies in the setting of multiple sclerosis last for 3–6 months. A one-month study is a very short intervention period, and I am not surprised that the psychiatric symptoms did not significantly change between the two groups after one month.

However, this is the first randomized, controlled trial to show that a ketogenic diet intervention is both feasible and safe, while also reporting trends in the right direction for blood sugar metabolism and psychiatric symptoms. The improvement in psychiatric symptoms was much larger after four months, which is encouraging for people with psychiatric symptoms that have not been adequately resolved with standard therapy.

My Clinical Approach to Mental Health Support

The first thing I tell my patients with serious mental health issues is that confidential support is available through crisis lines, and the national suicide crisis line is 988.

I also advise patients to continue working with their psychiatrists and therapists as we focus on improving their brain physiology. I urge them to exercise daily, seek deeper social connections with friends and family, and engage in activities that interest them — like singing, dancing, or making crafts.

Finally, I often discuss the pros and cons of a 4–6-month trial of a ketogenic diet to see if it improves their symptoms and metabolism.

Targeted Supplements for Mental Health

Most Americans are deficient in vitamin D because we live and work inside and put on sunscreen when we go outdoors. Vitamin D functions like a hormone, and those with low vitamin D levels are more likely to have increased mental health symptoms.

I therefore suggest that my psychiatry patients take a good multivitamin/multimineral, fish oil, vitamin D + K2, and supplemental magnesium to provide greater levels of support to their mitochondria and brain cells.

There is some evidence from animal and observational studies that lithium is an essential mineral for brain function and can result in reduced severity of depression and other mental health symptoms.^(2-4) Those who are insufficient in lithium are also more likely to have cognitive impairment.

I have included all these targeted supplements in the Peace of Mind Essentials Support Kit.

Citations

1. Abram SV, Kyner JM, Vu A, Naeem Z, Sethi S, Jacob MS, et al. Metabolic Improvements with a Ketogenic Diet Correlate with Symptom Improvement in Psychosis: A Randomized Controlled Trial. Schizophr Bull. 2026;52(4).
2. Chiu CT, Chuang DM. Neuroprotective action of lithium in disorders of the central nervous system. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011;36(6):461-76.
3. Forlenza OV, Diniz BS, Radanovic M, Santos FS, Talib LL, Gattaz WF. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry. 2011;198(5):351-6.
4. Shen Y, Zhao M, Zhao P, Meng L, Zhang Y, Zhang G, et al. Molecular mechanisms and therapeutic potential of lithium in Alzheimer's disease: repurposing an old class of drugs. Front Pharmacol. 2024;15:1408462.