Scientists have discovered how a high-fat keto diet can keep your brain young

Explore the power of the ketogenic diet

At the University of Missouri, researchers are exploring how these foods affect brain function. Their work focuses on the high-fat, low-carb eating plan known as the ketogenic diet. Early results suggest that this approach can not only support long-term brain health, but can also slow or even prevent cognitive decline, especially among individuals who face a higher genetic risk of developing Alzheimer’s disease.

Inside the Roy Blunt NextGen Precision Health Building, Ai-Ling Lin, a professor in the School of Medicine, and doctoral student Kira Evanich are studying how the ketogenic diet can benefit people with the APOE4 gene, the strongest known genetic risk factor for late-onset Alzheimer’s disease.

In their recent study using mice, Lin and Ivanich found that females with the APOE4 gene developed healthier gut bacteria and showed higher levels of brain energy when on a ketogenic diet compared to those on a high-carb diet. Males did not show the same improvement, suggesting that gender may influence who benefits most from this dietary approach.

How the brain uses fuel

The key lies in how the brain produces its energy.

“When we eat carbohydrates, our brains convert glucose into fuel for our brains, but those with the APOE4 gene — especially females — struggle to convert glucose into brain energy, and this can lead to cognitive decline in the future,” Ivanich said. “By switching to the keto diet, ketones are produced and used as an alternative fuel source. This may reduce the chance of developing Alzheimer’s disease by keeping brain cells healthy.”

These findings highlight the potential of “precision nutrition,” an approach that tailors diets and interventions to fit a person’s unique biology.

“Rather than expecting a one-size-fits-all solution to work for everyone, it may be better to consider a variety of factors, including someone’s genotype, gut microbiome, gender and age,” Lin said. “Because the symptoms of Alzheimer’s disease – which tend to be incurable once they appear – typically appear after the age of 65, the time to think about preserving brain health is much earlier, so we hope our research will provide hope to many people through early interventions.”

Developing research through collaboration

Lin joined Mizzou in part because of its collaborative environment and advanced imaging facilities located in the NextGen Precision Health Building and at the University of Missouri Research Reactor.

“We can do a lot of things in-house here that in other places we have to outsource,” Lin said. “This is team science. The impact we have will be much better when we work together than by ourselves.”

With cutting-edge imaging equipment and research and clinical space under one roof, the NextGen Precision Health building allows Mizzou to quickly move from preclinical models to human trials.

For Ivanic, this real-world impact is personal.

“When my grandmother had Alzheimer’s, it sparked my interest in this topic, so being able to make an impact to help people maintain brain health is very rewarding,” she said. “With Mizzou being a leading research university and having a close-knit community, I knew I was in the right place.”

“The ketogenic diet regulates the gut-brain microbiota metabolic axis in a sex- and genotype-specific manner in APOE4 mice” was published in the Journal of Neurochemistry.