Ketone supplement may improve brain function in obesity

• People with obesity may have a higher risk of cognitive impairment, such as difficulty making decisions or remembering.
• A small study involving oral ketone supplementation for 14 days suggests an improvement in brain blood flow and function in people with obesity.
• Scientists will need to carry out larger studies with a more diverse population to understand the underlying mechanism and confirm whether this approach could have real-world application.

Obesity is a common condition. The Centers for Disease Control and Prevention (CDC) estimate that in 2017–2018, obesity affected around 50% of non-Hispanic Black adults, 45% of Hispanic adults, 42% of non-Hispanic white adults, and 17% of non-Hispanic Asian adults in the United States.

Health experts define obesity as a body mass index (BMI) over 30 kilograms per square meter of height (kg/m2).

Obesity may increase the risk of developing type 2 diabetes, stroke, heart disease, metabolic syndrome, cancer, osteoarthritis, and cognitive decline.

People with obesity or impaired glucose tolerance may have reduced levels of brain-derived neurotrophic factor (BDNF). BDNF is an active protein in the synapses — junctions between nerve cells — in the brain that regulates synaptic plasticity.

Synaptic plasticity refers to the way in which synapses change over time in response to experience. This plays a critical role in learning and memory.

BDNF concentrates in areas of the brain that control body weight, eating, and drinking.

Ketone-brain connection

Treatments that can alleviate impaired glucose tolerance and lower high blood glucose levels may play an essential role in improving brain health in people with obesity.

The ketone body, β-hydroxybutyrate (β OHB), is synthesized in the liver and is a vital energy source when the body’s energy needs exceed glucose supply. This occurs, for instance, during starvation, absence of carbohydrate intake, or extended exercise.

Results of animal studies suggest that β OHB may also have signaling functions that could influence health conditions such as type 2 diabetes and Alzheimer’s disease.

This led researchers at the University of British Columbia Okanagan in Canada to study the effects of ketone supplementation on brain function in people with obesity.

Dr. Jeremy Walsh, Ph.D., lead author of the study and an assistant professor in the Department of Kinesiology at McMaster University Ontario, Canada, spoke with Medical News Today. He explained:

“Experimental trials that infuse ketone bodies, like [β OHB], have shown […] rapid increases in brain blood flow and alterations in brain metabolism. [These results suggest] that ketones may have therapeutic benefits for people who are at an elevated risk of problems with cognitive function.”

“The recent development of supplements that contain the β OHB that are safe for human consumption prompted our group to investigate the potential therapeutic effects of ketone supplementation on aspects of brain health in people with obesity,” he added.

The study enrolled 15 participants aged 30–69 years, between March 2019 and January 2020 with at least one of the following:

• an increased waist circumference — over 102 centimeters (cm) (40 inches [in]) for males and over 88 cm (35 in) for females
• obesity — BMI over 30 kg/m2
• a diagnosis of prediabetes

The scientists randomly assigned the participants to take either an oral ketone supplement or a similarly tasting placebo supplement before breakfast, lunch, and dinner for 14 days.

The participants then received no treatment for the next 14 days and switched to the opposite treatment for the next 14 days.

The researchers provided the participants with all meals and prepackaged snacks during both 14-day treatment periods. The study measured cognitive function on a tablet using three validated tests: digit symbol substitution task, the Stroop test, and the task-switching test.

The researchers also measured BDNF levels and blood flow in the brain. Only 14 participants completed the study — 10 females and four males.

The results of the study appear in The Journal of Physiology.

Inconsistent findings

Ketone supplementation improved the number of correct items processed in 90 seconds in the digit symbol substitution task, compared with placebo. However, there was no significant difference between the groups in the Stroop test or task-switching test.

Also, there was a significant increase in cerebral blood flow but no difference in BDNF levels in the group receiving ketones versus placebo.

Dr. Walsh commented: “It was interesting and exciting to see that improvements in cognitive function were positively associated with increases in brain blood flow. This provides insight into brain blood flow being a potential mechanism for improved cognitive function with ketone supplementation.”

The study’s strength includes the participants’ diet control and randomized placebo-controlled crossover design, allowing for a direct comparison of responses to both the ketone and placebo in the same study participant.

MNT also spoke with Dr. Rose Lin, an endocrinologist at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the study.

Dr. Lin pointed out some major limitations: “It was a pretty short study […], and the population size […] was 14 individuals only. The paper was based on secondary outcomes […] and so […] potentially not powered to really see a true difference in the study versus placebo arms.”

The data for this study come from an earlier one. In the original study, the researchers were measuring glucose levels following a meal; this was the primary outcome. However, the current study focused on secondary outcomes. In other words, the authors analyzed other data that the original researchers collected.

Dr. Lin also spoke about the need for more research: “I don’t know how [the study results] translate […] into [the] everyday real world. Additional studies should [include] a larger, more diverse population [with a] longer treatment and observation period.”

Dr. Walsh agreed: “We need to conduct follow-up studies with a larger sample size [to] confirm our findings and to look closer at the potential mechanisms by which ketone supplementation improves cognitive function in people with obesity. Our study provides an important foundation for future follow-up work to confirm these findings and explore this relationship.”

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