Brain disorders like Alzheimer’s pose some of the biggest challenges in today’s medical research, with few treatment options and urgently needed new solutions. Scientists have long studied how the process of metabolism converting food into energy affects brain health. New research now shows that natural compounds produced by the body may play a key role in protecting the brain.
Scientists led by Dr. John Newman of the Buck Newman Institute of Aging, as well as researchers at the University of Southern California, Leonard Davis School of Geriatric Medicine and the University of California, San Francisco, have identified beta-hydroxybutyrate, a ketone body produced in the body that produces a ketone body when the body burns fat. They found this to be a key factor in maintaining protein balance in the aging brain and Alzheimer’s disease. Their findings, published in the journal Cytochemistry Biology, highlight how the molecule can help prevent the accumulation of harmful proteins associated with brain decline.
Dr. Newman’s team found that beta-hydroxybutyrate affects how proteins perform in the brain, especially those that are often mismatched, meaning they fold into the wrong shape and become dysfunctional. These misfolded proteins accumulate in Alzheimer’s disease. Experiments show that β-hydroxybutyrate reduces the toxic effect of amyloid proteins, which form plaques in the brains of patients with Alzheimer’s disease. This is observed in lab-grown cells and in tiny worm models that are often used in scientific research. Even more impressively, their brains showed a decrease in harmful protein clusters when older mice were given ketone supplements to increase their beta-hydroxybutyric acid levels. This suggests that β-hydroxybutyric acid can help remove these destructive proteins through natural biological processes that do not rely on changes in acidity, chemical changes or other factors.
“Our research shows that beta-hydroxybutyric acid interacts with misfolded proteins and helps clear the brain,” Dr. Newman said. “This could be a natural way to happen during periods of metabolic stress, when cells have difficulty getting enough energy.”
Scientists have long known that ketone bodies including beta-hydroxybutyric acid, including beta-hydroxybutyric acid, when the body’s glucose levels are low, such as on fasting or ketogenic diets, high-fat, low-fat, low-carb diet plans. The study shows that the body can also use beta-hydroxybutadiene to check for the accumulation of harmful proteins, which could explain why the ketogenic diet is associated with improving brain function and longer life spans in animals.
These findings open the door to new therapeutic possibilities for brain disease. Researchers believe that drugs or supplements can be developed to mimic the effects of ketosis, which is the body burns fat rather than carbohydrates. This may offer new options for older people and older people with Alzheimer’s disease.
“Exploring how metabolism affects protein stability, or proteins maintain the right structure and function is an important step towards better treatment of brain diseases,” said Dr. Newman. “Our results show that beta-hydroxybutyric acid is more than just providing energy, it can actively help protect the brain from the accumulation of harmful proteins.”
The role of β-hydroxybutyric acid in controlling protein behavior may pave the way for new approaches to treat Alzheimer’s disease and age-related slowdown in cognitive decline. Future research will focus on translating these findings into treatments that can be tested in clinical settings to determine their effectiveness in humans.
Journal Reference
Madhavan SS, Roa Diaz S., Peralta S. et al. “β-hydroxybutyric acid is a metabolic regulator of proteins in the brain of elderly and Alzheimer’s disease.” Cell Chemical Biology, 2025. DOI: https://doi.org/10.1016/j.chembiol.2024.11.001
About the Author
Dr. John Newman He is a physician and scientist specializing in aging and metabolism research. He is a faculty member of the Buck Institute for Aging and an elderly doctor at the University of California, San Francisco. His research focuses on metabolic processes, especially how ketone bodies such as beta-hydroxybutyric acid affect aging and neurodegenerative diseases, such as Alzheimer’s. Dr. Newman explores the potential of dietary and pharmacological approaches to improve brain health and longevity. His work combines laboratory research with clinical applications to develop treatments that support healthy aging. As a dedicated advocate for the transformation of scientific discoveries into real-world health solutions, he contributes to numerous peer-reviewed publications and actively participates in guiding the next generation of researchers. His groundbreaking research continues to shape the future of aging science and metabolic health.
