DGA-UP study protocol: Impact of dietary guidelines diets containing mostly ultra-processed foods compared to less-processed foods on biomarkers of cardiometabolic disease, a randomized single-blind crossover study

Authors: Hess, Julie; Promschmidt, Claudia; SCHEETT, ANGELIA - University Of North Dakota; Casperson, Shanon; SLAVIN, JOANNE - University Of Minnesota; PALMER, DANIEL - University Of North Dakota

Submitted to: British Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/10/2026
Publication Date: N/A
Citation: N/A

Interpretive Summary: Ultra-processed foods (UPF) are presented in both consumer media and much of the scientific literature as detrimental to health. The study proposed in this manuscript seeks to address the accuracy of this claim that eating more UPFs leads to adverse health consequences. The Dietary Guidelines for Americans with Ultra-Processed foods (DGA-UP) study will feed generally healthy people a diet comprised of mostly less-processed foods for 4 weeks, followed by a 3-week break, and then by 4 weeks of eating a UPF-rich diet. Some participants will eat the UPF-rich diet first and the less-processed food diet after the break, but all participants will eventually eat both diets. Both will be high quality and have adequate amounts of fruits, vegetables, lean protein, healthy fats, and whole grains as well as essential vitamins and minerals. The diets will contain matching foods as well. For example, one study breakfast is pancakes with butter and syrup paired with breakfast sausage and 100% fruit juice. In the less-processed diet, these foods will be homemade pancakes, butter, maple syrup, homemade breakfast sausage, and orange juice with no additives. In the UPF-rich diet, this breakfast contains frozen pancakes, margarine, maple-flavored corn syrup, frozen premade breakfast sausage, and a 100% fruit juice blend that contains additives. Our hypothesis is that there will not be a difference in how these two diets impact health, because both study diets are nutrient-dense and nearly identical except for additive content. This manuscript contains details regarding the study methods, including the anticipated number of participants needed (95 people), the duration of the study (1/2026-10/2029), and how cardiometabolic health will be monitored (blood pressure, blood glucose and insulin levels, and blood lipids).

Technical Abstract: Ultra-processed food (UPF) consumption has generated a great deal of concern among nutrition scientists and consumers due to its potential relationship with increased risk of adverse health impacts. Evidence from intervention studies comparing UPF-rich and less-processed diets on cardiometabolic health outcomes is limited. Clinical trials that have been published to date focus on comparing more- and less-processed diets, as defined by the Nova system, and their impact on weight-related outcomes. Only one trial compares equally healthful more- and less-processed diets. The Dietary Guidelines for Americans with Ultra-Processed foods (DGA-UP) study will be the first trial to examine whether there is a differential effect to following recommendations from the 2020-2025 Dietary Guidelines for Americans (2020 DGA) including more- or less-processed foods as defined by the Nova classification system on cardiometabolic disease risk factors. A randomized controlled crossover dietary intervention study, DGA-UP will be conducted with 4 week provision of all meals to generally healthy male and female adults at eucaloric levels. The trial will consist of 2 dietary arms: 1) a less-processed 2020 DGA diet and 2) a ultra-processed 2020 DGA diet. The primary outcome is change in blood pressure on each diet from baseline to week 4. Both interventions will have excellent diet quality and contain similar amounts of macronutrients and micronutrients as well as the same types of food. DGA-UP will help to fill a significant research gap regarding potential impact of UPFs on cardiometabolic health markers independent of food type, diet quality, and micronutrient content. ClinicalTrials.gov registration: NCT07252037.