Ultraprocessed Foods Trigger Higher Insulin Response Despite Matched Nutrients
TOPLINEIn healthy adults, a meal consisting of ultraprocessed food (UPF) caused a bigger insulin response than a non-UPF meal with the same calories and nutrients. Blood glucose levels were similar, but after...
TOPLINE In healthy adults, a meal consisting of ultraprocessed food (UPF) caused a bigger insulin response than a non-UPF meal with the same calories and nutrients. Blood glucose levels were similar, but after the UPF meal the body burned less carbohydrate and more fat, and its metabolic rate was higher.
The findings suggest food processing may affect how the body handles a meal beyond calories and nutrients, though the study looked only at short-term responses. METHODOLOGY A randomized crossover study enrolled 57 healthy-weight adults (mean age 26.2 years, mean BMI 22.8 kg/m2) in Roanoke, Virginia.
Data collection ran from June 2023 to December 2025; the metabolic sessions ran from June 2023 to March 2025. A subset of 32 participants consumed nutritionally matched UPF and non-UPF meals (~300 kcal each) on separate days, in random order, while undergoing 4 hours of whole-room indirect calorimetry (a 50-minute baseline plus 3 hours post-meal) and serial blood sampling.
Meals were matched on weight, energy, macronutrients, glycemic index, fiber, sodium, and water (all ≤1.6% deviation). Spacing between sessions was not controlled, and neither data collection nor analysis was blinded. The metabolic outcomes of interest were AUC of change from baseline in blood glucose and insulin, metabolic rate, respiratory exchange ratio (RER), and carbohydrate and fat oxidation.
All 57 participants completed a functional MRI (fMRI) session, and 52 were included in the analysis. Participants bid on food pictures in a Becker–DeGroot–Marschak auction task, which measured willingness to pay (WTP) and neural responses to food cues. The metabolic–brain analyses included the 29 participants with usable data from both.
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TAKEAWAY Blood insulin AUC was significantly greater after UPF than non-UPF meals (P < .001), with insulin higher between 40 and 120 minutes post-meal. Glucose AUC did not differ (P = .92), but the curves did: glucose rose faster after the non-UPF meal (higher at 20 minutes, P = .02) and trended higher after the UPF meal at 120 and 180 minutes.
Metabolic rate AUC was higher after UPF meals (P = .02), while RER AUC was greater after non-UPF meals (P = .01). This reflected attenuated carbohydrate oxidation (P = .02) and increased fat oxidation (P = .003) after the UPF meal. A larger between-condition difference in peak carbohydrate oxidation was associated with a smaller difference in neural responses to food cues (n = 29).
The association was significant in the left superior temporal gyrus (whole-brain corrected P = .013), the right caudate (small-volume corrected P = .007), and the left ventral striatum (small-volume corrected P = .045). The authors note this direction is opposite to prior studies using oral flavor stimuli.
Willingness to pay did not differ between conditions (P = .34), after adjusting for perceived healthiness and frequency of consumption. Even so, brain activity tracking food value differed by processing level (n = 52): value was positively associated with activity for non-UPF cues and negatively for UPF cues in the left fusiform gyrus and left lingual gyrus (both whole-brain corrected P < .0001), and in the right putamen (small-volume corrected P = .017) and right caudate (small-volume corrected P = .043).
IN PRACTICE "These findings support the concept that food processing could influence physiology and brain function through mechanisms extending beyond calories and macronutrient composition alone, while identifying altered nutritional availability from altered physical structure as a plausible contributor to both their overconsumption and effects on metabolic health," wrote the study authors.
SOURCE The study was led by Zach Hutelin, Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, Virginia. It was published online in Nature Metabolism . LIMITATIONS Test meals were assembled from diverse foods, and protein sources differed between conditions, which could have influenced insulin response.
The study did not explicitly measure physical and chemical structures of the food matrix beyond total fiber. Responses may differ with larger caloric loads. Although meals were isocaloric and fully consumed, the non-UPF meal was eaten slightly faster than the UPF meal, though the 1.5-minute difference is unlikely to be physiologically meaningful.
DISCLOSURES The study was supported by grants from the National Institutes of Health and the National Science Foundation. Multiple authors reported no relevant conflicts of interest. This article was created using several editorial tools, including AI, as part of the process.
Human editors reviewed this content before publication.
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