Ultra-processed meals raise insulin despite matched nutrients, study suggests

Nutrition researchers have investigated why ultra-processed food (UPF) consumption often parallels poor health outcomes. Scientists at Virginia Tech, US, report that two meals with the same nutrition label still send the body and brain in different directions — a finding that they say may offer a “candidate mechanism” for evaluating if corresponding health problems are a result of the nutrient composition in UPFs or the processing itself.

Alexandra DiFeliceantonio, PhD, associate professor at Virginia Tech’s Fralin Biomedical Research Institute, whose lab ran the study, points out that UPFs make up more than half the calories eaten by people in the US, and says the epidemiology linking them to disease is not in question.

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

What has been missing is a clean test, according to the study. Much of the evidence comparing processed and unprocessed diets also changed the fat, sugar, fiber, and protein, which the study says left the mechanism tangled.

Higher insulin after UPF 

Published in Nature Metabolism, the study matched the two meals on calories, carbohydrate, fat, protein, fiber, sodium, water, and weight. The paper reports the match held within 1.6% on every measure, and extended to glycemic index and glycemic load.The study matches nutrients between UPF and non-UPF meals to isolate the possible effects of processing.

Zach Hutelin, the study’s first author and a researcher at the institute, says the plates were engineered to look the same on paper.

“The two meals are matched within 1% of carbs, fat, proteins, calories, water, and salt,” he says. “If these meals had a nutritional label, they would be practically identical.”

The trial enrolled 57 healthy-weight adults, 32 of whom ate both meals on separate days inside a metabolic chamber. 

However, Hutelin notes that what the meals did inside the body was not the same. After the ultra-processed meal, participants released more insulin, expended more energy, and burned more fat and less carbohydrate than they did after the non-UPF one, the study reports.

“We were shocked when every single metabolic metric differed,” Hutelin attests. “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 bit longer.”

The results show that over the three hours, total glucose exposure did not differ between the meals, and both peaked around 40 minutes. Glucose climbed faster after the non-UPF meal. The clearer split was in insulin, which ran higher after the ultra-processed meal from 40 to 120 minutes.

Building matched plates

Each meal came to 300 calories and was drawn from a set of 28 foods validated for the study. The ultra-processed plate held deli turkey, instant mashed potatoes, a chocolate chip cookie, frosted wheat cereal, veggie chips, white bread, and a bite of peanut butter and jelly.

The non-UPF plate held 30 g of a hard-boiled egg, sliced banana, cheese, and dried cranberries. To match weight and water, the team added 12 grams of water to the ultra-processed meal. The design was built to strip the familiar explanations away, explains DiFeliceantonio.

“We know that the majority of ultra-processed foods are high in fat, they’re high in sugar, they’re low in fiber, and they’re low in protein,” she says. “But if we artificially hold all of those things constant, is there something about the processing that leads to a different outcome?”

Additives under scrutiny

On a separate day, all 57 participants viewed pictures of the foods inside a functional magnetic resonance imaging (fMRI) scanner while the machine tracked blood flow. The researchers analyzed scans from 52 after excluding five for head movement, task performance, or equipment failure.

The results show that insulin runs higher and longer after the nutrient-matched ultra-processed meal.

Among the 29 participants with usable metabolic and brain data, differences in how much carbohydrate people burned after each meal tracked activity in the ventral striatum and caudate, regions tied to motivation and reward. Across the 52-person imaging group, an auction task found that participants would not pay more for UPFs than for non-UPF ones.

The study stops well short of a verdict on long-term health. Participants were healthy-weight adults between 18 and 45, every meal was a single 300-calorie pairing, and the measurements ran for hours, not years.

The authors also flag other gaps. The protein sources in the two meals differed, which can affect insulin on its own. Additionally, the ultra-processed meal carried more additives, and the team did not measure the physical or chemical structure of the foods beyond total fiber.

DiFeliceantonio says the next step is to identify which aspects of processing drive the different health effects.

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