Researchers at Virginia Tech’s Fralin Biomedical Research Institute at VTC found that two meals with the same carbohydrates, fats, proteins, water, calories, salt, and weight — but that differed in their level of processing — produced different metabolic responses. Credit: Zach Hutelin/Virginia Tech

Two meals looked nearly identical nutritionally, yet the ultraprocessed option triggered more insulin release in healthy adults, hinting at differences nutrition labels may miss.

Ultraprocessed foods supply more than half of the average American’s daily calories, and their place in diets worldwide is growing. Formulated to be convenient, accessible, affordable, and highly palatable, they can be easy to overeat. Understanding their effects on health, however, requires untangling the influence of processing from that of the nutrients they contain.

Meals with the same basic nutritional profile are generally expected to affect blood sugar in similar ways. Yet in a Virginia Tech study, healthy adults expended more energy and burned less carbohydrate after eating an ultraprocessed meal than after a minimally processed one. Both meals contained 300 calories and were closely matched for carbohydrates, fat, protein, water, salt, and weight. The findings appeared in Nature Metabolism.

“We know that the majority of ultraprocessed foods are high in fat, they’re high in sugar, they’re low in fiber, and they’re low in protein,” said Alex DiFeliceantonio, an associate professor at Virginia Tech’s Fralin Biomedical Research Institute at VTC whose lab led the study. “But if we artificially hold all of those things constant, is there something about the processing that leads to a different outcome?”

Neuroscientist Alex DiFeliceantonio (left) and researcher Zach Hutelin at Virginia Tech’s Fralin Biomedical Research Institute at VTC unexpectedly found that two meals with the same carbohydrates, fats, proteins, water, calories, salt, and weight — but that differed in their level of processing — produced different brain and metabolic responses. Credit: Stephanie Klein-Davis for Virginia Tech

Matched nutrients, a stronger insulin response

The researchers selected foods using NOVA, a classification system that divides foods into four groups according to their level of industrial processing. Their ultraprocessed meal included a bite of a peanut butter and jelly sandwich, deli turkey, veggie chips, a cookie, cereal, instant mashed potatoes, and a little water. The minimally processed meal consisted of sliced banana, dried cranberries, cheese, and egg.

“The two meals are matched within 1 percent of carbs, fat, protein, calories, water, and salt,” said Zach Hutelin, a researcher at the institute and the study’s first author. “If these meals had a nutritional label, they would be practically identical.” The study formed part of his doctoral research through Virginia Tech’s Translational Biology, Medicine, and Health Graduate Program.

The full study involved 57 healthy adults ages 18 to 45, including 32 who completed both the metabolic testing and brain imaging sessions. Participants ate the two types of meals in separate sessions at least three days apart, allowing the researchers to compare each person’s responses.

Alexandra DiFeliceantonio is a neuroscientist who works to understand the basic mechanisms of food choice — why we eat what we eat. Credit: Virginia Tech

For the metabolic tests, participants arrived after fasting overnight and settled onto a twin-size bed inside a metabolic chamber, a sealed, airtight room used to measure energy expenditure and metabolism. Researchers took baseline measurements, then waited an hour before giving participants 10 minutes to eat one of the meals. Blood samples were collected immediately afterward and six more times over the next three hours. The team tracked energy expenditure, carbohydrate oxidation, or the burning of carbohydrates for fuel, and the response of insulin, a hormone that helps cells take up glucose from the blood.

“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.”

Matching the amounts of nutrients did leave some differences unresolved. The meals contained different protein sources, which could have influenced the results, and the ultraprocessed meal contained more additives. Although the researchers measured total fiber, they did not explicitly measure the foods’ physical and chemical structures.

Carbohydrate burning linked to brain responses

DiFeliceantonio, a neuroscientist who studies the basic mechanisms behind food choice, also wanted to know whether the metabolic responses were connected to how the brain responded to food cues. On a separate day, participants underwent functional magnetic resonance imaging, or fMRI, while viewing pictures of nutritionally matched highly and minimally processed foods. These included the foods served during the metabolic tests. The scans measured brain activity by tracking changes in blood flow across different regions.

For each food pictured, participants reported how much they would be willing to pay for it. Their answers gave researchers a measure of subjective value to compare with brain activity. Participants did not report being willing to pay more for either the ultraprocessed or minimally processed foods.

Zach Hutelin, a researcher conducting experiments at the metabolic kitchen at the Fralin Biomedical Research Institute and the study’s first author, said the two meals are matched within 1 percent of carbs, fat, protein, calories, water, and salt. Credit: Virginia Tech

Differences in how participants burned carbohydrates after the two meals were nevertheless linked to differences in their brain responses to food pictures. One notable result involved the ventral striatum and nucleus accumbens, brain structures involved in learning, motivation, and reward. The association suggests a connection between the body’s response to the meals and the brain’s response to food cues, although it does not establish that those differences cause people to eat more.

“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 obesity research led to the development of the international NOVA classification used in nutrition and public health studies. He highlighted the Roanoke team’s examination of brain activity alongside metabolism. “This is a novel and important contribution, as the brain ultimately regulates eating behavior.”

Untangling the health risks of ultraprocessed foods

Whether these short-term responses help explain the health effects associated with ultraprocessed foods remains unresolved. Chronically elevated blood sugar increases the risk of conditions such as diabetes, but measurements taken over three hours after a meal cannot establish long-term consequences.

“If you look at that population-level data, people who consume large amounts of ultraprocessed foods have higher rates of poor health outcomes — obesity, cardiac events, type 2 diabetes, and even some metrics of mental health,” DiFeliceantonio said.

The experiment tested only one pair of matched 300-calorie meals in young, healthy adults. 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 other populations, follow responses over longer periods, and test larger meals and more pairings of minimally and highly processed foods.

“We want to examine specific factors, such as commercial additives or specific processing steps, that might lead to different metabolic responses,” DiFeliceantonio said.

Reference: “Metabolic and neural responses to ultraprocessed foods: a randomized, controlled, crossover study” by Zach Hutelin, Monica Ahrens, Mary Elizabeth Baugh, Emmanuel Nartey, Delbert L. Herald III, Alexandra L. Hanlon and Alexandra G. DiFeliceantonio, 5 October 2026, Nature Metabolism.
DOI: 10.1038/s42255-026-01619-4

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.

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