Researchers from the Johns Hopkins University School of Medicine and the National Institute on Aging at the National Institutes of Health say a study in which 40 older adults with obesity and insulin resistance were randomly assigned to either an intermittent fasting diet or a standard health diet approved by the U.S. Department of Agriculture (USDA) offers important clues about the potential benefits of both eating plans for brain health.
Insulin resistance is a hallmark of type 2 diabetes and is common in obese people. Research suggests that people with insulin resistance are at higher risk for Alzheimer's disease and other cognitive disorders. Therefore, various weight loss therapies are widely considered as a way to reduce the risk of these metabolic and brain disorders.
Previous studies conducted by Johns Hopkins in animal models of diabetes and Alzheimer's disease have shown that intermittent fasting can improve cognitive function and insulin sensitivity. The new study, published June 19 in the journal Cell Metabolism, tested the effects of intermittent fasting on women and men at risk for cognitive impairment and provides a “blueprint” for using a broad panel of biomarkers to evaluate the diet's impact, including analysis of extracellular vesicles, the authors write. Extracellular vesicles are tiny chunks of material released by neurons, a type of brain cell that transmits messages. These neuron-derived extracellular vesicles are released into the circulating blood and were collected over an eight-week period from participants in the new study, each of whom followed one of two diets.
According to Dr. Mark Mattson, an adjunct professor of neuroscience at the Johns Hopkins University School of Medicine and former director of the Neuroscience Laboratory at the National Institute on Aging in Baltimore, the results showed that both types of eating plans had benefits in terms of lowering insulin resistance and improving cognition, and that improvements in memory and executive function were seen with both diets, but the effects were more pronounced with the intermittent fasting diet. “Other scientists may want to incorporate the[brain]markers[we used]into larger studies of diet and brain health,” Dr. Mattson says.
Because people with obesity and insulin resistance may be at higher risk for cognitive impairment and Alzheimer's disease than those with normal metabolism and BMI, Dimitrios Kapogiannis, MD, PhD, chief of the Division of Human Neuroscience 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 lab has found molecular evidence of insulin resistance in extracellular vesicles shed from neurons in patients with diabetes and Alzheimer's disease, and because blood samples are relatively easy to obtain, they seemed like a good candidate for widespread use.
To test the effects of the two diets on biomarkers of brain function, participants in the new study were recruited from June 2015 to December 2022 and underwent four in-person assessments at a facility run by the National Institute on Aging at MedStar Harbor Hospital in Baltimore. Forty of the participants completed the eight-week study. Twenty were also assigned to an intermittent fasting diet that restricted calories to one-quarter of the daily recommended intake for two consecutive days a week, while the remaining five days followed the USDA Healthy Living diet (consisting of fruits, vegetables, whole grains, lean protein, low-fat dairy, limited added sugars, saturated fats, and sodium). The USDA Healthy Living diet was assigned to the other 20 study participants for each day of the week.
The average age of participants in both groups was 63 years old. There were 25 white, 14 black, and one Hispanic. There were 24 men and 16 women. All were obese and insulin resistant.
The researchers found that both diets had similarly positive effects on reducing insulin resistance markers in extracellular vesicles, improving BrainAGE (a measure of the brain's biological age using structural MRI data), and reducing glucose concentrations in the brain, which is a corollary of increased glucose usage.
Both diets improved the usual measures of metabolic health, including weight, BMI, waist circumference, blood lipids like cholesterol, and insulin resistance. Executive function and memory (a set of mental skills that help you plan and achieve your goals) improved by about 20% in the intermittent fasting group compared to the healthy living diet group.
Some study participants reported mild side effects, including constipation, loose stools, and occasional headaches.
The researchers also found elevated levels of neurofilament proteins (structural proteins in neurons) in both diet groups, but mainly in the intermittent fasting group. What this means in terms of brain health is unclear.
“This is an indicator that we should continue to evaluate in future studies. Neurons release many proteins, and the idea is that intermittent fasting may be causing some kind of neuroplasticity (changes in structure) in neurons, which causes the release of neurofilament proteins.”
Dr. Mark Mattson, adjunct professor of neuroscience at the Johns Hopkins University School of Medicine
Johns Hopkins University researchers caution that intermittent fasting can be harmful for some people, such as those with type 1 diabetes or eating disorders, so people interested in trying it should plan carefully with their health care provider.
The research reported in Cell Metabolism was supported by the National Institute on Aging at the National Institutes of Health (ZIAAG000966, ZIAAG000975).
Other researchers who contributed to the study include Apostolos Manolopoulos, Francesca Delgado Peraza, Maya Mustapic, Carlos Nogueras Ortiz, Pamela Yao, Krishna Pucha, Janet Brooks, Qinghua Chen, Lisa Hartnell, Mark Cookson and Josephine Egan of the National Institute on Aging, Roger Mullins of Morgan State University, Konstantinos Avgerinos of Wayne State University, Shalayla Haas and Sophia Frangou of the Mount Sinai School of Medicine, and Ruiyan Ge of the University of British Columbia.
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Journal References:
Kapogiannis, D., et al. (2024). Brain Responses to Intermittent Fasting and Healthy Diet in Older Adults. Cell Metabolism. doi.org/10.1016/j.cmet.2024.05.017.
