Pilot study provides ‘blueprint’ for evaluating the effect of diet on brain health

Researchers from Johns Hopkins Medicine and the National Institute on Aging of the National Institutes of Health say their study of 40 older adults with obesity and insulin resistance who were randomly assigned to an intermittent fasting diet or a standard healthy diet approved by the U.S. Department of Agriculture . USDA) provides important clues about the potential benefits of both eating plans for brain health.

The paper is published in the news Cell metabolism.

Insulin resistance is a hallmark of type 2 diabetes and is common in obese people. Studies suggest that people with insulin resistance are at higher than normal risk for Alzheimer’s disease and other cognitive disorders. As a result, various weight loss regimens are widely used as ways to reduce the risk of these metabolic and brain disorders.

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 tested the effects of intermittent fasting on women and men at risk for cognitive impairment. It provides a “blueprint,” the authors write, for using a broad panel of biomarkers to assess the impact of diet, including analysis of extracellular vesicles — small packets of material released by neurons, types of brain cells that send messages. Such neuron-derived extracellular vesicles are shed into the circulating blood and were collected from the participants in the new study over a period of eight weeks, while each person followed one of two diets.

The results revealed that both types of diet plans had benefits in reducing insulin resistance and improving cognition, with improvements in memory and executive function on both diets, but stronger on the intermittent fasting diet, according to Mark Mattson, Ph.D. ., adjunct professor of neuroscience at Johns Hopkins University School of Medicine and former head of the neuroscience laboratory at the National Institute on Aging in Baltimore.

“Other scientists may want to include the (brain) markers (we used) in additional, larger studies of diet and brain health,” Mattson says.

Because people with obesity and insulin resistance may be at greater risk for cognitive impairment and Alzheimer’s disease than people with normal metabolism and body mass index (BMI), says Dimitrios Kapogiannis, MD, chief of the National Department of Human Neurosciences. 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 secreted by neurons from 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 biomarkers of brain function, participants in the new study were recruited in June 2015 and December 2022, and four in-person assessments were conducted at National Institute on Aging facilities at MedStar Harbor Hospital in Baltimore . .

Of the participants, 40 completed their eight-week study. Also, 20 were assigned to an intermittent fasting diet that limited calories to a quarter of the recommended daily allowance for two consecutive days per week, and they followed the USDA Healthy Diet – which consists of fruits, vegetables, whole grains and lean proteins . , low-fat dairy products and limited added sugars, saturated fats and sodium – for the remaining five days. The USDA Healthy Eating Plan was assigned to 20 different 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 biological age of the brain using structural MRI data) and lowering glucose concentration in the brain . A reduced glucose concentration is a consequence of a higher glucose use.

Both diets also improved common measures of metabolic health, including weight, BMI, waist circumference measurement, blood lipids such as cholesterol and insulin resistance.

Executive function and memory (a set of mental skills that help with planning and achieving goals) improved about 20% more in the intermittent fasting group than in the healthy living diet group.

A few study participants reported modest side effects, including constipation and 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 especially in the intermittent fasting group. What that means for brain health is unclear.

“This is a marker that we need to continue to evaluate in further studies,” says Mattson. “Neurons release a lot of proteins, and one idea is that intermittent fasting may induce a 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 it carefully with a healthcare practitioner because it can be harmful for some people, including people with type 1 diabetes and eating disorders.