Johns Hopkins scientists discover surprising benefits for brain health

Recent research suggests that both intermittent fasting and a standard healthy diet enhance brain function in obese adults with insulin resistance, and that intermittent fasting leads to better cognitive benefits.

This is the conclusion reached by researchers at Johns Hopkins Medicine and the National Institute on Aging. National Institutes of Health report the findings of their study involving 40 older adults with obesity Insulin resistance. Participants were randomly assigned to follow either an intermittent fasting diet or a standard healthy diet approved by the US Department of Agriculture (USDA). The study provides important insights into the potential brain health benefits of both dietary approaches.

Insulin resistance is a hallmark of type 2 diabetes and is common in people with obesity. Studies show that people with insulin resistance have a higher than normal risk Alzheimer’s diseases and other cognitive impairments. As a result, various weight loss regimens are widely touted as ways to reduce the risk of these metabolic and brain disorders.

Study findings and methodology

Previous research from Johns Hopkins on animal models of diabetes and Alzheimer’s disease has shown that intermittent fasting can improve cognition and insulin sensitivity. The new study, published June 19 in Cell metabolismtested the effects of intermittent fasting on women and men at risk for cognitive impairment, and it provides a “blueprint” for using a broad panel of biomarkers to assess dietary effects, including analysis of extracellular vesicles — tiny packets of material released from neurons, which are the type of brain cells that send messages. Such neuron-derived extracellular vesicles are shed into the circulating blood and were collected from the new study participants during an eight-week period while each person followed one of two diets.

According to Mark Mattson, PhD, assistant professor of neuroscience at the Johns Hopkins University School of Medicine and former chief of the Laboratory of Neuroscience at the National Institute on Aging in Baltimore, the results showed that both types of diet plans had benefits with regard to decreased insulin resistance and improved cognition, with improvements in memory and executive function seen with both diets, but stronger with the intermittent fasting diet. “Other scientists may want to incorporate the (brain) markers we used in additional, larger studies of diet and brain health,” Mattson says.

Research techniques and participant demographics

Because people with obesity and insulin resistance may have a higher risk of cognitive impairment and Alzheimer’s disease than people with normal metabolism and body mass index (BMI), Dimitrios Kapogiannis, MD, chief of the Human Neurology Section at the National Institute on Aging and adjunct associate professor of neurology at Johns Hopkins University School of Medicine, developed a method to isolate neuron-derived extracellular vesicles from blood. His lab found molecular evidence of insulin resistance in extracellular vesicles released 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 completed four in-person assessments at facilities run by the National Institute on Aging at MedStar Harbor Hospital in Baltimore. Of the participants, 40 completed their eight-week study. In addition, 20 were given an intermittent fasting diet, which limits calories to one-quarter of the recommended daily intake, for two consecutive days per week, and they followed the USDA’s Healthy Living diet for the remaining five days — which includes fruits, vegetables, whole grains, lean proteins, low-fat dairy products and limited added sugars, saturated fats and sodium.

The average age of participants in both groups was 63 years, 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 measure of the biological age of the brain using structural MRI data), and reducing glucose concentrations in the brain. Lower glucose concentrations are a result of higher glucose utilization.

Both diets also improved traditional measurements of metabolic health, including weight, BMI, waist circumference measurement, blood lipids such as cholesterol, and insulin resistance. Executive function and memory (which is a set of mental skills that help make plans and achieve goals) improved about 20% more in the intermittent fasting group than in the healthy lifestyle diet group.

Observations and health precautions

Some study participants reported they experienced minor side effects, such as constipation, diarrhea, and occasional headaches.

The researchers found increased levels of neurofilament protein (a structural protein in neurons) in both diet groups, but primarily in the intermittent fasting group. What this means in relation to brain health is unclear.

“This is a marker that should be evaluated in further studies,” Mattson says. “Neurons release a lot of proteins, and one idea is that intermittent fasting might cause some kind of neuroplasticity (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 health care professional, as it may be harmful for some people, including those with type 1 diabetes and eating disorders.

Reference: “Brain responses to intermittent fasting and healthy lifestyle in the elderly” 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, Shailaila S. Haas, Ruiyang Ji, Lisa M. Hartnell, Mark R. Cookson, Josephine M. Egan, Sophia Frango and Mark P. Mattson, June 19, 2024, Cell metabolism,
DOI: 10.1016/j.cmet.2024.05.017

This research was supported by the National Institute on Aging (ZIAAG000966, ZIAAG000975) of the National Institutes of Health.