The study, published in Nature Medicine, is the first interventional study comparing ultra-processed food (UPF) and minimally processed food (MPF) diets in ‘real world’ conditions, as well as being the longest experimental study of a UPF diet to date¹.

The trial split 55 adults into two groups. One group started with an eight-week diet of MPF, such as overnight oats or homemade spaghetti Bolognese. After a four-week ‘washout’ period during which participants went back to their normal diet, they switched to a diet of UPF, such as breakfast oat bars or a lasagna ready meal. The other group completed the diets in the opposite order. In total, 50 participants completed at least one diet.

The provided diets were nutritionally matched in accordance with the Eatwell Guide, the UK’s official government advice on how to eat a healthy, balanced diet. This included levels of fat, saturated fat, protein, carbohydrate, salt and fiber, as well as providing recommended intakes of fruits and vegetables. Participants had plenty of food (i.e. more calories than they needed) delivered to their home and were told to eat as much or as little as they wanted, as they would normally. They were not told to limit their intake.

After eight weeks on each diet, both groups lost weight, likely as a result of the improved nutritional profile of what they were eating compared to their normal diet. However, this effect was higher (2.06% reduction) on the MPF diet compared to the UPF diet (1.05% reduction)².

These changes corresponded to an estimated calorie deficit of 290 kilocalories (kcal) per day on the MPF diet, compared to 120 kcal per day on the UPF diet. To put this in context, the Eatwell Guide recommends a daily energy intake of 2,000 kcal for women and 2,500 kcal for men.

The greater weight loss experienced on the MPF diet came from reductions in fat mass and total body water, with no change in muscle or fat-free mass, indicating a healthier body composition overall.

The findings suggest that, when observing recommended dietary guidelines, choosing minimally processed foods may be more effective for losing weight.

Dr Samuel Dicken, first author of the study from the UCL Centre for Obesity Research and UCL Department of Behavioural Science & Health, said: “Previous research has linked ultra-processed foods with poor health outcomes. But not all ultra-processed foods are inherently unhealthy based on their nutritional profile. The main aim of this trial was to fill crucial gaps in our knowledge about the role of food processing in the context of existing dietary guidance, and how it affects health outcomes such as weight, blood pressure and body composition, as well as experiential factors like food cravings.

“The primary outcome of the trial was to assess percentage changes in weight and on both diets we saw a significant reduction, but the effect was nearly double on the minimally processed diet. Though a 2% reduction may not seem very big, that is only over eight weeks and without people trying to actively reduce their intake. If we scaled these results up over the course of a year, we’d expect to see a 13% weight reduction in men and a 9% reduction in women on the minimally processed diet, but only a 4% weight reduction in men and 5% in women after the ultra-processed diet. Over time this would start to become a big difference.”

Participants completed several questionnaires to assess their food cravings before starting the diets, and at weeks four and eight during the diets³.

There were significantly greater improvements in the number of cravings and ability to resist them (craving control) on the MPF diet compared to the UPF diet, despite greater weight loss on the MPF diet that might ordinarily be expected to lead to stronger cravings.

On the MPF diet compared to the UPF diet, participants reported a two-fold greater improvement in overall craving control, a four-fold greater improvement in craving control for savoury food, and an almost two-fold greater improvement in resisting whichever food they most craved.

Professor Chris van Tulleken, an author of the study from UCL Division of Infection & Immunity and UCLH, said: “The global food system at the moment drives diet-related poor health and obesity, particularly because of the wide availability of cheap, unhealthy food. This study highlights the importance of ultra-processing in driving health outcomes in addition to the role of nutrients like fat, salt and sugar. It underlines the need to shift the policy focus away from individual responsibility and on to the environmental drivers of obesity, such as the influence of multinational food companies in shaping unhealthy food environments.

“Stakeholders across disciplines and organisations must work together and focus on wider policy actions that improve our food environment, such as warning labels, marketing restrictions, progressive taxation and subsidies, to ensure that healthy diets are affordable, available and desirable for all.”

The trial also measured secondary health markers, such as blood pressure and heart rate, as well as blood markers such as liver function, glucose, cholesterol and inflammation. Across these markers, there were no significant negative impacts of the UPF diet, with either no change, or a significant improvement from baseline.

Generally, there weren’t significant differences in these markers between the diets, and the researchers caution that longer studies would be needed to investigate these measures properly in relation to the changes in weight and fat mass.

Professor Rachel Batterham, senior author of the study from the UCL Centre for Obesity Research, said: “Despite being widely promoted, less than 1% of the UK population follows all of the recommendations in the Eatwell Guide, and most people stick to fewer than half.

“The normal diets of the trial participants tended to be outside national nutritional guidelines and included an above average proportion of UPF, which may help to explain why switching to a trial diet consisting entirely of UPF, but that was nutritionally balanced, resulted in neutral or slightly favourable changes to some secondary health markers.

“The best advice to people would be to stick as closely to nutritional guidelines as they can by moderating overall energy intake, limiting intake of salt, sugar and saturated fat, and prioritizing high-fiber foods such as fruits, vegetables, pulses and nuts. Choosing less processed options such as whole foods and cooking from scratch, rather than ultra-processed, packaged foods or ready meals, is likely to offer additional benefits in terms of body weight, body composition and overall health.”

This research was supported by the National Institute for Health and Care Research UCLH Biomedical Research Centre and the Rosetrees Trust.

Notes

1. MPF have undergone very little alteration from their natural state, such as fruits, vegetables, whole grains, meat, fish and dairy products like natural yoghurt. UPF have been significantly altered from their original form through processing, and typically contain ingredients not commonly used in home cooking, such as artificial flavours, preservatives and emulsifiers.
2. Not all participants lost weight, with 10 individuals in each group gaining weight. This is thought to be due to a lack of adherence to the diet, particularly on the second diet that they undertook. When the unadjusted results from the first round of diets (either MPF or UPF) were considered in isolation, the weight loss was greater than when the average across both rounds of diets (4.09% reduction for MPF and 2.12% reduction for UPF).
3. The Control of Eating Questionnaire (CoEQ) assesses overall craving control, craving for sweet foods, craving for savoury foods, positive mood, and the perceived ability to resist eating foods that are craved. The Power of Food Scale (PFS) assesses the appetite for and motivation to consume palatable foods when that food is available (but not physically present), when it is present (but not tasted), and when the food has been tasted (but not yet consumed).

“Carnivorous dinosaurs took very different paths as they evolved into giants in terms of feeding biomechanics and possible behaviors,” said Andrew Rowe of the University of Bristol, UK.

“Tyrannosaurs evolved skulls built for strength and crushing bites, while other lineages had comparatively weaker but more specialized skulls, suggesting a diversity of feeding strategies even at massive sizes. In other words, there wasn’t one ‘best’ skull design for being a predatory giant; several designs functioned perfectly well.”

Rowe has always been fascinated by big carnivorous dinosaurs, and he considers them interesting subjects for exploring basic questions in organismal biology. In this study, he and co-author Emily Rayfield wanted to know how bipedalism — or walking on two legs — influenced skull biomechanics and feeding techniques.

It was previously known that despite reaching similar sizes, predatory dinosaurs evolved in very different parts of the world at different times and had very different skull shapes. For Rowe and Rayfield, those facts raised questions about whether their skulls were functionally similar under the surface or if there were notable differences in their predatory lifestyles. As there are no massive, bipedal carnivores alive today — ever since the end-Cretaceous mass extinction event — the authors note that studying these animals offers intriguing insights into a way of life which has since disappeared.

To examine the relationship between body size and skull biomechanics, the authors used 3D technologies including CT scans and surface scans analyze the skull mechanics, quantify the feeding performance, and measure the bite strength across 18 species of therapod, a group of carnivorous dinosaurs ranging from small to giant. While they expected some differences between species, they were surprised when their analyses showed clear biomechanical divergence.

“Tyrannosaurids like T. rex had skulls that were optimized for high bite forces at the cost of higher skull stress,” Rowe says. “But in some other giants, like Giganotosaurus, we calculated stress patterns suggesting a relatively lighter bite. It drove home how evolution can produce multiple ‘solutions’ to life as a large, carnivorous biped.”

Skull stress didn’t show a pattern of increase with size. Some smaller therapods experienced greater stress than some larger species due to increased muscle volume and bite forces. The findings show that being a predatory biped didn’t always equate to being a bone-crushing giant. Unlike T. rex, some dinosaurs, including the spinosaurs and allosaurs, became giants while maintaining weaker bites more suited for slashing at prey and stripping flesh.

“I tend to compare Allosaurus to a modern Komodo dragon in terms of feeding style,” Rowe says. “Large tyrannosaur skulls were instead optimized like modern crocodiles with high bite forces that crushed prey. This biomechanical diversity suggests that dinosaur ecosystems supported a wider range of giant carnivore ecologies than we often assume, with less competition and more specialization.”

This research was supported by funding from the Biotechnology and Biological Sciences Research Council.

The study, published online in Cell on August 4, achieves multiple types of precise DNA manipulations ranging from kilobase to megabase scale in higher organisms, especially plants.

Extensive research has demonstrated the immense potential of the site-specific recombinase Cre-Lox system for precise chromosomal manipulation. However, its broader application has been hindered by three critical limitations:

1. Reversible recombination reactions — stemming from the inherent symmetry of Lox sites — can negate desired edits.
2. The tetrameric nature of Cre recombinase complicates engineering efforts, hindering activity optimization.
3. Residual Lox sites after recombination may compromise editing precision.

The research team addressed each of these challenges and developed novel methods to advance the state of this technology. First, they built a high-throughput platform for rapid recombination site modification and proposed an asymmetric Lox site design. This led to the development of novel Lox variants that reduce reversible recombination activity by over 10-fold (approaching the background level of negative controls) while retaining high-efficiency forward recombination.

They then leveraged their recently developed AiCE (AI-informed Constraints for protein Engineering), model — a protein-directed evolution system integrating general inverse folding models with structural and evolutionary constraints — to develop AiCErec, a recombinase engineering method. This approach enabled precise optimization of Cre’s multimerization interface, yielding an engineered variant with a recombination efficiency 3.5 times that of wild-type Cre.

Lastly, they designed and refined a scarless editing strategy for recombinases. By harnessing the high editing efficiency of prime editors, they developed Re-pegRNA, a method that uses specifically designed pegRNAs to perform re-prime editing on residual Lox sites, precisely replacing them with the original genomic sequence, thereby ensuring seamless genome modifications.

The integration of these three innovations led to the creation of two programmable platforms, PCE and RePCE. These platforms allow flexible programming of insertion positions and orientations for different Lox sites, enabling precise, scarless manipulation of DNA fragments ranging from kilobase to megabase scale in both plant and animal cells. Key achievements include: targeted integration of large DNA fragments up to 18.8 kb, complete replacement of 5-kb DNA sequences, chromosomal inversions spanning 12 Mb, chromosomal deletions of 4 Mb, and whole-chromosome translocations.

As a proof of concept, the researchers used this technology to create herbicide-resistant rice germplasm with a 315-kb precise inversion, showcasing its transformative potential for genetic engineering and crop improvement.

This pioneering work not only overcomes the historical limitations of the Cre-Lox system but also opens new avenues for precise genome engineering in a variety of organisms.