Healthy adults released substantially more insulin after consuming an ultraprocessed 300-calorie meal than a whole-food meal matched for identical nutrients and calories, according to a randomized crossover study published October 5, 2026, in Nature Metabolism by researchers at Virginia Tech.
How Virginia Tech Researchers Matched the Test Meals
To test whether industrial manufacturing alters how the body handles food independent of basic nutrient content, the research team recruited 57 healthy-weight adults aged 18 to 45 according to a controlled feeding and neuroimaging study. The study participants entered a whole-room indirect calorimeter in randomized order across separate days to consume a roughly 300-kilocalorie meal composed entirely of either ultraprocessed items or minimally processed alternatives. The two meals were algorithmically matched on weight, energy density, total and available carbohydrate, fat, protein, fiber, sodium, and water with deviations of no more than 1 percent between conditions.
Zach Hutelin, Monica Ahrens, Mary Elizabeth Baugh, Emmanuel Nartey, Delbert L. Herald III, Andrea L. Hanlon, and Alexandra G. DiFeliceantonio authored the work titled Metabolic and neural responses to ultraprocessed foods: a randomized, controlled, crossover study.
The research protocol received approval from the Virginia Tech Institutional Review Board under protocol 21-1052 and was registered at ClinicalTrials.gov with the identifier NCT06017986. Financial support for the investigation came from the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases, alongside backing from a National Science Foundation graduate research fellowship.
Insulin Spikes and Energy Expenditure Changes in Metabolic Trials
Although overall glucose exposure across the session remained similar between the two meals, the ultraprocessed meal triggered significantly greater insulin release. Blood sugar levels rose more rapidly after the non-ultraprocessed meal during the opening 20 minutes, but the ultraprocessed meal kept blood sugar elevated for a longer duration while prompting a much higher insulin response.
“What we noticed with the ultra-processed food is that insulin response was much higher and blood sugar stays a little bit higher for a little longer.”
Zach Hutelin, study’s first author
Furthermore, the ultraprocessed meals prompted participants’ bodies to expend more energy while burning less carbohydrate for fuel as detailed in the findings. Researchers interpreted this transition from fat to carbohydrate oxidation as resembling what is seen during early insulin resistance according to the research team. Blood samples were drawn immediately following consumption and across six subsequent time points over a three-hour window using custom ports to preserve whole-room indirect calorimetry accuracy.
Brain Reward Circuitry Activation During Functional MRI Scans
Participants completed functional magnetic resonance imaging sessions where they viewed pictures of the 28 tested food items while evaluating their willingness to pay during BDM auction tasks.
While participants did not report valuing one food category higher than the other in subjective pricing, the neuroimaging revealed distinct activity shifts in the ventral striatum and nucleus accumbens, which serve as core motivation and reward hubs.
Scientific Context and Open Questions on Long-Term Health Outcomes
Lu Qi noted that the work brings new experimental evidence to explain adverse health effects, while nutrition epidemiologist Lindsey Smith Taillie pointed out that the trial helps answer questions regarding underlying biological mechanisms.
Alex DiFeliceantonio noted that population data consistently tie high consumption of manufactured foods to elevated rates of obesity, cardiac events, and type 2 diabetes in findings highlighted by the research team. Readers reviewing these findings should note that the investigation evaluated a single 300-calorie meal in a controlled laboratory setting, meaning larger and longer-term studies are necessary to establish direct clinical consequences. Individuals managing specific conditions such as diabetes or prediabetes should consult qualified medical professionals or registered dietitians prior to implementing major dietary modifications.
Whether these short-term physiological changes contribute to longer-term metabolic dysfunction is not yet known, and further studies will be required to separate industrial processing steps from specific ingredient structures.