University of Missouri researchers have uncovered a hidden biological superpower in bullfrogs: When their brains run low on energy, they can make their own emergency fuel supply. And that could mean good things for human health.
For decades, scientists believed most animals relied on a steady supply of glucose, the body’s primary fuel source, to power their brains. When glucose runs out, neural activity begins to fail, potentially leading to lasting brain damage.
Now, researchers at Mizzou’s College of Arts and Science have discovered that bullfrogs don’t follow that fundamental rule. Instead, when glucose becomes scarce, their brains can produce an alternative energy source known as ketone bodies, allowing critical neural functions to continue.
In most animals, ketone bodies are produced in the liver when glucose levels drop during conditions such as fasting, starvation or prolonged exercise. The liver breaks down fatty acids into these energy molecules, which then travel through the bloodstream to organs, including the brain, where they are used as fuel.
But Mizzou’s team discovered that bullfrogs can completely bypass that process. Instead of relying entirely on the liver, their brains can generate ketones locally, creating an emergency energy reserve exactly where it’s needed most.
“Scientists generally believe ketones are delivered to the brain from elsewhere in the body,” said Joseph Santin, an associate professor of biological sciences and lead author of the study. “That’s what makes this discovery so exciting. It's like finding a backup generator inside a building that everyone assumed had only one power source.”
The finding helps explain how bullfrogs survive one of the most challenging periods of their year. Each winter, they enter a hibernation-like state that slows their metabolism and depletes energy reserves.
By spring, when oxygen and energy stores are running low, the animals must immediately reactivate essential brain circuits that control bodily functions. The newly discovered metabolic backup system may be one reason why they can make that transition so quickly and successfully.
The research builds on years of work in Santin's lab exploring how frogs endure conditions that would severely damage or even kill most animals. Previous studies revealed that this hibernation-like state helps protect neural circuits during extreme oxygen deprivation. The new findings uncover another layer of that survival strategy: the ability to maintain brain activity when glucose metabolism is compromised.
The discovery also raises important questions about what triggers the switch to ketone production and how long bullfrogs can sustain it. Researchers do not believe the metabolic shift is permanent, but it appears to provide a robust backup system when the brain’s usual energy supply falls short.
While the findings offer new insight into amphibian biology, Santin believes they may also help scientists better understand the human brain because bullfrogs and humans share many of the same fundamental biological processes.
By revealing how brains adapt when energy supplies become limited, the research could open new avenues for studying neurological disorders linked to impaired energy metabolism, including Alzheimer's disease, ALS and schizophrenia.
The study, " Transforming neural activity to operate without glucose metabolism using brain-derived ketone bodies ," was published in the Proceedings of the National Academy of Sciences.
Proceedings of the National Academy of Sciences
Transforming neural activity to operate without glucose metabolism using brain-derived ketone bodies
2-Sep-2026