Scientists will probe whether processing itself makes ultra-processed foods harmful

A controlled-feeding trial aims to untangle one of nutrition science’s biggest questions: are UPFs harmful because of how they are made, or because of what they contain?

UPFs have increasingly become prevalent in diets worldwide. Meta-analytical evidence suggests that high UPF intake is associated with an elevated risk of cancers, cardiovascular disease (CVD), diabetes, and mortality. Despite increasing research on UPFs, the features underlying their unfavorable health effects remain unclear. Some suggest that food transformations and industrial processes are responsible for the hazardous effects of UPFs.

The poor nutrient profile of UPFs may explain their adverse impact on cardiometabolic risk. A 2025 scientific advisory noted the lack of consensus regarding whether all UPFs constitute a cardiovascular health concern. It also underscored the need to independently assess distinct UPF dimensions, such as industrial processing and nutrient content. Therefore, identifying the factors underlying the adverse effects of UPFs is crucial to informing public health policies.

UPF Trial Design and Participant Criteria

In the present study, researchers presented a protocol for a 2 × 2 factorial RCT to investigate how UPFs modulate cardiometabolic risk. The first factor is the degree of industrial processing of UPFs according to NOVA definitions, and the second is the nutrient composition. The primary objective of the trial is to dissect the individual effects of industrial processing of UPFs on their nutrient content on cardiometabolic risk in healthy adults. The authors hypothesize that the high saturated fat, added sugar, and sodium content of some UPFs will increase cardiometabolic risk factors, while the degree of industrial food processing itself will not.

Participants will be recruited through social media advertisements and electronic newsletters from the research center. Eligible participants will be those aged 18–75 years, with a body mass index (BMI) between 18 kg/m2 and 35 kg/m2, stable weight, low-density lipoprotein cholesterol (LDL-C) < 5 mmol/L, blood pressure (BP) < 150/90 mmHg, and glycated hemoglobin (HbA1c) < 6.5%.

Individuals with diabetes, CVD, hypertension, or cancer, and those taking medications for BP lowering, lipid lowering, or diabetes, will be excluded. Those who are pregnant or lactating, consume more than seven servings of alcohol per week, have relevant food allergies or aversions, or follow diets that could limit compliance will also be excluded. Participants will be randomized to consume a low UPF diet low in saturated fats, added sugars, and sodium (SFSS), a low UPF diet high in SFSS, a high UPF diet low in SFSS, or a high UPF diet high in SFSS for six weeks.

Controlled Feeding Diets and Outcome Measures

A cyclic seven-day daily menu standardized at 2,500 kcal was developed for each diet, with protein (15% kcal), carbohydrates (50% kcal), and fats (35% kcal) matched. Each item in the menu was classified into one of four groups of the NOVA classification: group 1–minimally processed or unprocessed foods; group 2–processed culinary ingredients; group 3–processed foods; group 4–UPFs.

The high UPF diets predominantly include commercial foods classified as NOVA group 4, such as flavored yogurt, oatmeal raisin cookies, waffles, spaghetti with pre-packaged sauce, and ready-to-eat coleslaw. The low UPF diets mainly include custom-prepared recipes and foods classified as NOVA groups 1–3, such as plain yogurt with maple syrup and frozen fruit, spaghetti with homemade sauce, homemade oatmeal raisin cookies, and pancakes.

Participants will visit the study’s cafeteria on two or three weekdays for supervised meal intake and to collect meals/snacks for the rest of the day and the next day. They will abstain from consuming alcohol, probiotics, natural health products, artificially sweetened beverages, and fiber supplements throughout the study period. Dietary compliance will be assessed daily using self-reported checklists. Blood lipids, glucose, and insulin will be measured at baseline and post-intervention.

The primary outcomes include changes from baseline in LDL-C, daytime ambulatory systolic BP (dtSBP), and homeostatic assessment model of insulin resistance (HOMA-IR) at the end of the intervention. Secondary outcomes include changes from baseline in triglycerides, ApoB-100, high-density lipoprotein cholesterol (HDL-C), 24-hour ambulatory systolic BP, 24-hour ambulatory diastolic BP, daytime ambulatory diastolic BP, insulin, and glucose.

In addition, questionnaires will be administered to examine perceived meal healthiness, diet palatability, perceived hunger and fullness, eating pleasure dimensions, and physical activity. Dual-energy x-ray absorptiometry scanning will be performed to assess body composition and fat at the start and end of the intervention. Mixed models will be used to analyze data, following an intention-to-treat approach.

Implications for UPF Nutrition Policy

In summary, the proposed RCT will help unravel which features of UPFs account for their unfavorable health effects, advancing current knowledge and helping inform policymakers in better incorporating UPFs into future guidelines. The RCT has several strengths: its factorial design, sample size, and controlled feeding conditions enable disentangling the individual effects of UPFs from their industrial processing on cardiometabolic risks. However, because the diets are provided under isocaloric conditions to maintain body weight, the trial will not directly test whether UPFs promote excess calorie intake or weight gain under ad libitum eating conditions.

Journal reference:

• Rochette M, Charest A, Gigleux I, Couture P, Provencher V, Lamarche B (2026). How ultra-processed foods modulate cardiometabolic risk: A 2 × 2 factorial randomized controlled trial protocol in healthy adults. Contemporary Clinical Trials, 165, 108323. DOI: 10.1016/j.cct.2026.108323, https://www.sciencedirect.com/science/article/pii/S1551714426001096