A study recently published in Cell Metabolism examines the effects of intermittent fasting (IF) on neuronal insulin resistance (IR) and cognitive function in older adults with IR. With increasing evidence linking metabolic conditions such as IR to neurodegenerative diseases like Alzheimer’s, the study aimed to explore how IF might influence key biomarkers associated with neuronal health. The goal was to see whether IF could have an impact on neuronal IR and, by extension, possibly protect against cognitive decline.
The study employed a range of assessments, from advanced biomarker analysis to brain imaging, to track the effects of IF. Participants were assigned to an IF diet or a healthy living (HL) control diet, with both groups undergoing extensive monitoring over an eight-week period. Plasma, cerebrospinal fluid (CSF), and brain scans were used to track changes in biomarkers related to neuronal IR, neuroplasticity, and cognitive function.
One of the central features of this study was the measurement of neuronal-derived extracellular vesicles (NDEVs) from plasma samples taken at baseline, week 4, and week 8. NDEVs are known to carry important proteins and molecular signals from neurons, allowing researchers to assess changes in brain function through minimally invasive blood tests. A two-step process was used to isolate these vesicles: size exclusion chromatography (SEC) to purify them, followed by immunoaffinity capture targeting neuron-specific proteins such as L1CAM, GAP43, and NLGN3.
The study also collected cerebrospinal fluid (CSF) from participants via lumbar puncture. This allowed for direct measurement of brain health-related biomarkers such as amyloid-beta (Aβ), total Tau, and phosphorylated Tau, which are strongly linked to Alzheimer’s disease. CSF is often considered a “window into the brain,” making these measurements highly valuable for assessing early signs of neurodegeneration.
One of the significant findings was the potential impact of IF on neuroplasticity. As the researchers pointed out, IF might promote structural changes in neurons that lead to the release of certain proteins associated with neuronal damage or repair. Specifically, the study’s authors suggest that “neurons release a lot of proteins, and one idea is that intermittent fasting may be causing some kind of neuroplasticity (a change in structure) in neurons, causing the release of neurofilament proteins.” This points to the possibility that IF could trigger beneficial adaptations in the brain that help preserve or enhance cognitive function, especially in people at risk for neurodegenerative diseases.
The study’s findings suggest that intermittent fasting may have a positive impact on neuronal insulin resistance and cognitive health. Through the release of neurofilament proteins and other biomarkers, IF may be triggering neuroplasticity, potentially reducing the risk of neurodegenerative diseases. The combination of plasma-based NDEV biomarkers, CSF analysis, and brain imaging offered a comprehensive view of how IF can affect brain health at a molecular level, particularly in individuals with IR, a condition closely linked to cognitive decline.
Sources: Cell Metabolism, Scitech Daily
