Recent research reveals that intermittent fasting and a standard healthy diet both enhance brain function in obese adults with insulin resistance, with intermittent fasting yielding better cognitive gains.
Researchers from Johns Hopkins Medicine and the National Institute on Aging at the
Insulin resistance is a hallmark of type 2 diabetes and is common in people with obesity. Studies suggest that people with insulin resistance are at higher risk than usual for
Research Techniques and Participant Demographics
Because people with obesity and insulin resistance may be more at risk of cognitive impairment and Alzheimer’s disease than people with normal metabolism and body mass index (BMI), Dimitrios Kapogiannis, M.D., chief of the human neuroscience section at the National Institute on Aging and adjunct associate professor of neurology at the Johns Hopkins University School of Medicine, developed a method to isolate neuron-derived extracellular vesicles from blood. His laboratory found molecular evidence of insulin resistance in extracellular vesicles shed from neurons of people with diabetes and Alzheimer’s disease, and because blood samples are relatively easy to collect, they were considered good candidates for widespread use.
To test the effects of the two diets on brain function biomarkers, participants in the new study were recruited between June 2015 and December 2022, and four in-person assessments were completed at facilities run by the National Institute on Aging at MedStar Harbor Hospital in Baltimore. Among the participants, 40 completed their eight-week study. Also, 20 were assigned to an intermittent fasting diet that restricted calories to one-quarter of the recommended daily intake for two consecutive days per week, and they followed the USDA’s healthy living diet — which consists of fruits, vegetables, whole grains, lean proteins, low-fat dairy products and limited added sugars, saturated fats, and sodium — for the remaining five days. The USDA’s healthy living diet was assigned to 20 other study participants each day of the week.
The average age of participants in both groups was 63, and 25 were white, 14 were Black, and one was Hispanic. There were 24 men and 16 women. All were obese and had insulin resistance.
The researchers found that both diets had equally positive effects on reducing insulin resistance markers in extracellular vesicles, improving BrainAGE (a measurement of the brain’s biological age using structural MRI data), and lowering glucose concentration in the brain. Reduced glucose concentration is a corollary of higher glucose use.
Both diets also improved customary measurements of metabolic health, including weight, BMI, measurement of waist circumference, blood lipids such as cholesterol, and insulin resistance. Executive function and memory (which are a set of mental skills that helps with planning and achieving goals) improved approximately 20% more in the intermittent fasting group than in the healthy living diet group.
Observations and Health Cautions
A few study participants reported modest side effects including constipation loose stools, and occasional headaches.
The researchers also saw increased levels of a neurofilament protein (a structural protein in neurons) in both diet groups, but mainly in the intermittent fasting group. What that means regarding brain health is unclear.
“This is a marker to continue to evaluate in further studies,” says Mattson. “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.”
The Johns Hopkins researchers and others caution that people interested in intermittent fasting should plan carefully with a healthcare practitioner because it could be harmful to some people, including those with type 1 diabetes and eating disorders.
Reference: “Brain responses to intermittent fasting and the healthy living diet in older adults” by Dimitrios Kapogiannis, Apostolos Manolopoulos, Roger Mullins, Konstantinos Avgerinos, Francheska Delgado-Peraza, Maja Mustapic, Carlos Nogueras-Ortiz, Pamela J. Yao, Krishna A. Pucha, Janet Brooks, Qinghua Chen, Shalaila S. Haas, Ruiyang Ge, Lisa M. Hartnell, Mark R. Cookson, Josephine M. Egan, Sophia Frangou and Mark P. Mattson, 19 June 2024, Cell Metabolism.
DOI: 10.1016/j.cmet.2024.05.017
The research was supported by the National Institutes of Health’s National Institute on Aging (ZIAAG000966, ZIAAG000975).