The highly processed meal included a bite of peanut butter and jelly sandwich, deli turkey, veggie chips, a cookie, cereal, instant mashed potatoes, and a little bit of water. The minimally processed meal included a sliced banana, dried cranberries, cheese, and egg.
“The two meals are matched within 1 percent of carbs, fat, proteins, calories, water, and salt,” said Zach Hutelin, a researcher at the institute and the study’s first author. The study was part of his doctoral research through Virginia Tech’s Translational Biology, Medicine, and Health Graduate Program. “If these meals had a nutritional label, they would be practically identical.”
Blood draws were again taken immediately after the meal, then six more times over the next three hours. Researchers measured post-meal metabolism, including insulin response, energy expenditure, and carbohydrate oxidation.
“We were shocked when every single metabolic metric differed,” Hutelin said. “What we noticed with the ultraprocessed food is that insulin response was much higher and blood sugar stays a little bit higher for a little bit longer.”
Chronically elevated blood sugar increases the risk of conditions like diabetes.
The brain’s reward system
DiFeliceantonio is a neuroscientist who works to understand the basic mechanisms of food choice — why we eat what we eat. She wanted to see if the metabolic response to the meals connected to the brain's response to food cues.
On a separate day, participants viewed pictures of nutritionally matched highly and minimally processed foods while undergoing functional MRI. The scan measures brain activity by tracking changes in blood flow across different regions of the brain. The foods served during the metabolic tests were among those shown in the pictures.
While viewing each food, participants reported how much they would be willing to pay for it. This let researchers compare how participants’ subjective value of the foods corresponded with their brain activity.
One notable result involved the ventral striatum and nucleus accumbens, part of the brain involved in learning, motivation, and reward. Differences in how participants burned carbohydrates for energy after each type of meal were linked to differences in how their brains responded to pictures of food.
Participants did not say they were willing to pay more for the ultraprocessed or minimally processed foods, but the results suggested that metabolic differences produced by food processing are related to differences in how the brain responds to food cues.
“A key debate in the literature is whether [ultraprocessed food] associations with poor health outcomes are driven by nutrient composition rather than processing,” Carlos A. Monteiro of the University of São Paulo told Nature Metabolism. Monteiro is a Brazilian epidemiologist whose research into obesity led to the development of the international NOVA classification of food processing used in nutrition and public health studies. He noted that beyond metabolic response, the Roanoke team looked at brain activity. “This is a novel and important contribution, as the brain ultimately regulates eating behavior.”
What comes next
This study looked at one set of matched 300-calorie meals, and study subjects were young and healthy. DiFeliceantonio, who also holds an appointment in the Department of Human Nutrition, Foods, and Exercise in Virginia Tech’s College of Agriculture and Life Sciences, would like to examine different populations, longer time periods, bigger meals, and more pairings of minimally and highly processed foods. While the meals served were matched on protein, for example, protein sources were different and could have influenced the outcome.
The ultraprocessed meal also contained more additives, and while the study did measure total fiber, it not explicitly measure physical and chemical structures of the food studied.
“We want to examine specific factors, such as commercial additives or specific processing steps, that might lead to different metabolic responses,” DiFeliceantonio said.
The research was funded by a National Institutes of Health research grant through the National Institute of Diabetes and Digestive and Kidney Diseases and a National Science Foundation graduate research fellowship.
Original study DOI: 10.1038/s42255-026-01619-4