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Randomized controlled trials (RCTs) provide “weak support” for the idea that ultraprocessed foods (UPFs) are “inherently harmful,” a new analysis suggests.

“Much of the public and policy debate assumes that UPFs exert unique, processing-specific harms, yet the RCTs often cited in support of this idea were not designed to isolate ‘ultraprocessing’ from well-known nutritional factors,” Faidon Magkos, PhD, professor of obesity and metabolism at the University of Copenhagen, Copenhagen, Denmark, told Medscape Medical News. Magkos is co-author of a commentary, published online in Science that dissects five RCTs of UPFs’ health effects.

“We wanted to re-examine these trials carefully and show that differences in energy density, texture, fiber, sodium (salt), and saturated fat — not processing per se — can fully explain the observed effects on energy intake, weight, and metabolic markers,” he said.

‘UPF Effect Disappeared’

Magkos and co-authors described the five clinical trials conducted on UPFs in the US, UK, Denmark, and Japan, all of which had a crossover design. In three trials, participants consumed the diets ad libitum until comfortably full, and in two trials, they received a fixed amount of calories. The duration of each diet arm of the study was 1-3 weeks in four trials; the longest lasted 8 weeks.

After outlining the trials’ methods, variable findings, and limitations, the authors suggested that the studies don’t show that ultraprocessing is inherently harmful. Instead, they proposed, the effects seen in the studies are likely due to differences in nutritional properties that UPFs frequently exhibit, including soft textures that can lead people to eat more and faster, high calorie density, high amounts of saturated fat and salt, and low fiber and protein content.

“What stood out was how consistently the apparent UPF effect disappeared once traditional nutritional variables were accounted for,” Magkos said. “For example, the much-publicized weight gain in ad libitum trials aligned almost perfectly with differences in calorie density and texture, and the cholesterol increases tracked with higher saturated fat content. It was also striking that when diets were matched for fiber and sodium contents, the so-called calorie-independent effects of UPFs disappeared, strongly suggesting no unique metabolic effects.”

“UPF classifications capture many unhealthy foods, but they also sweep in items that are nutritionally sound or even beneficial,” he continued. “The randomized trials do not show a consistent adverse effect of UPFs on glucose, insulin, triglycerides, blood pressure, or insulin resistance. The current evidence base simply does not support the idea that ‘ultraprocessing’ itself is a meaningful biological exposure.”

“The evidence shows that calorie density, texture, fiber, protein content, sodium and saturated fat drive energy intake, weight change, and changes in lipid profile,” he said, “regardless of whether a food is classified as ultraprocessed or minimally processed.”

To determine if ultraprocessing itself is harmful, he added, researchers would need to manipulate specific processing-related attributes, such as fractionation, extrusion, and emulsifier content, while holding nutritional composition constant, which would be difficult to do.

‘Hard to Mass Market Broccoli’

Luc Hagenaars, PhD, Department of Public and Occupational Health, Amsterdam University Medical Center, Amsterdam, Netherlands, doesn’t disagree with the issues raised in the editorial, but thinks “the authors are not asking a question that matters more, but that is unanswerable with RCTs” — ie, “‘How did food supplies become so unhealthy in Western countries, and in the US in particular, in the last couple of decades?’”

“Ultraprocessing techniques made UPFs profitable by enabling the usage of cheap, unhealthy bulk ingredients (sugar, refined carbs) in many products, and long shelf lives (eg, by stripping out the fiber),” explained Hagenaars, who was the co-author of an essay and poster presented at the 33rd European Congress on Obesity (ECO) 2026 highlighting the food industry’s role in the obesity epidemic. 

“Both reduced costs, but at the expense of nutrient quality,” he told Medscape Medical News. “Ultraprocessing techniques also enabled food companies to tap into habit-forming psychological and physiological pathways that make people overeat certain foods and thus drive sales — eg, through formulating foods so they conform with the ‘bliss point’, with flavorants, and soft textures etc,” as suggested in a recent Lancet article.

The commentary authors aren’t wrong, he affirmed, but their perspective neglects the economic mechanisms that explain why the food industry has become so invested in nutritionally poor, calorie-dense, and rapidly consumed foods. “It is really hard to mass market broccoli.”

What to Tell Patients

Clinicians should focus on nutritional quality and eating behaviors, not processing labels, Magkos said. “Encouraging patients to prioritize higher-fiber, lower-energy-density foods, and avoid soft, rapidly consumed foods will have far greater health impact than telling them to avoid UPFs as a category.”

Hagenaars added, “I’d advise patients not to stock up on foods that are easy (or engineered) to overeat. But that is really hard when the food environment is loaded with those exact foods! I cannot wish away that situation, unfortunately, but fortunately doctors can contribute to local action to improve the food environment in their own hospitals or city.”

Seamus Higgins, associate professor in Food Process Engineering, University of Nottingham, Nottingham, England, noted that the debate around UPFs “risks overlooking something the food industry has understood for decades: Consumers rarely choose foods according to scientific classifications. Their choices are driven primarily by price, taste, and convenience, all of which interact with biological instincts shaped during millions of years of food scarcity. The modern food system has become exceptionally effective at satisfying these ancient drivers, helping explain consumption patterns far more effectively than food classifications alone.”

Magkos acknowledged receiving support from the Novo Nordisk Foundation, Arla Food for Health, the Independent Research Fund Denmark, and the Sino-Danish Center for Education and Research; he reported serving on the advisory board for AstraZeneca in 2025. Hagenaars reported having no relevant conflicts of interest. Higgins disclosed that he authored “Food and Us, The Incredible Story of How Food Shapes Humanity” and declared that he “does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article and has disclosed no relevant affiliations beyond their academic appointment.” 

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.