Can Ketones Improve Brain Health? New Study sheds light

Researchers at the Del Monte Institute for Neuroscience at the University of Rochester have identified mechanisms in the brain's hippocampal network rescued by ketones. These findings build on previous research showing that ketones can alleviate neurological and cognitive effects.

The results are published in the journal PNAS Nexus.

As we age, our brain naturally becomes more resistant to insulin, a hormone crucial for energy regulation and cellular communication. Insulin resistance in the brain disrupts the communication between neurons, leading to a cascade of negative effects. This breakdown in neuronal communication manifests in various ways, including changes in mood, such as increased anxiety or depression, and cognitive decline, where memory, attention, and problem-solving skills deteriorate. Over time, these issues can progress to more severe conditions like neurodegeneration, contributing to diseases such as Alzheimer’s and Parkinson’s.

"Once neuronal function is lost, there is no recovering the connection, so we need to identify when the function first becomes impaired," said Nathan A. Smith, the principal investigator of this research. "This study accomplishes that by bringing us closer to understanding how to rescue the function of impaired neurons and prevent or delay devastating diseases like Alzheimer's."

Using mice model, researchers studied the hippocampus, a brain region important for learning and memory. They discovered that acute insulin resistance harms several key brain functions, such as synaptic activity, axonal conduction, network synchronization, synaptic plasticity, and action potential properties, all crucial for neuron communication.

To address this, they gave the mice D-βHb (D-beta-hydroxybutyrate), a type of ketone produced when the body burns fat instead of glucose for energy. They found that D-βHb (D-beta-hydroxybutyrate) improved the previously damaged synaptic activity, increased axon conduction, resynchronized neurons, and enhanced synaptic plasticity.

“This research has implications for developing ketone-based therapies targeting specific neuronal dysfunctions in conditions involving insulin resistance/hypoglycemia like diabetes or Alzheimer's disease,” said Smith.

Reference: Bartosz Kula, Botond Antal, Corey Weistuch, Florian Gackière, Alexander Barre, Victor Velado, Jeffrey M Hubbard, Maria Kukley, Lilianne R Mujica-Parodi, Nathan A Smith, D-ꞵ-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance, PNAS Nexus, Volume 3, Issue 5, May 2024, https://doi.org/10.1093/pnasnexus/pgae196