Same calories, different responses: Food processing influences metabolism and brain activity
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Most nutrition science suggests that meals with the same basic nutritional profile will have the same impact on a person's blood sugar.
But is there something about food processing itself that influences how our bodies respond?
Researchers exploring that question were surprised to find that minimally and highly processed meals matched for calories, carbohydrates, fats, proteins, water, salt and weight produced distinct metabolic responses.
The ultraprocessed meals prompted the body to release more insulin and expend more energy while burning less carbohydrate for fuel. They also evoked different responses in the part of the brain involved in motivation and reward.
The results suggest that food processing may affect how the body and brain respond to food in ways that go beyond carbohydrates, fat and protein—potentially helping researchers understand why ultraprocessed foods have been associated with overconsumption and long-term health effects and pointing to new areas for research.
Virginia Tech researchers with the Fralin Biomedical Research Institute at VTC published their findings Oct. 5 in Nature Metabolism.
Ultraprocessed foods represent more than half of the average American's daily calories. Diets worldwide are also shifting to include more of these foods, which are formulated to be convenient, accessible, affordable and highly palatable, making them easy to overeat.
"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," said Alex DiFeliceantonio, a Fralin Biomedical Research Institute associate professor whose lab led the study.
While highly processed foods have been linked to disease, the mechanisms connecting processing with health outcomes and overconsumption are less understood.
What they did
"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," DiFeliceantonio said. "But if we artificially hold all of those things constant, is there something about the processing that leads to a different outcome?"
The team recruited healthy adults between 18 and 45 years old. The full study consisted of 57 adults. Of those, 32 completed both the brain functional magnetic resonance imaging (fMRI) and the metabolic sessions.
Each participant ate both types of meals in separate sessions, with three or more days between sessions. This allowed researchers to compare how the same person responded to each meal.
To examine metabolic effects, participants arrived at the testing site after fasting overnight. They climbed onto a twin-size bed in a metabolic chamber—a sealed, airtight room used to measure human energy expenditure and metabolism. Researchers then took baseline measurements.
An hour later, participants were given 10 minutes to eat either a minimally or highly processed meal, each containing 300 calories and matched for nutritional content. In selecting the meals, the study used the NOVA scale, which categorizes food in four groups based on the level of industrial processing.
The highly processed meal included a bite of a 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% 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 samples 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, brain regions 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 for 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 did not explicitly measure the 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.
Publication details
Metabolic and neural responses to ultraprocessed foods: a randomized, controlled, crossover study, Nature Metabolism (2026). DOI: 10.1038/s42255-026-01619-4
Journal information: Nature Metabolism
Key medical concepts
Food, Processedbrain activityEnergy Expenditure
Clinical categories
Nutrition & Healthy eatingEndocrinologyNeurologyHealthy living Provided by Virginia Tech Who's behind this story?
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