Common sense and knowledge tell us that whole food is healthier than processed food. It is nice to now have a rigorous randomized clinical trial proving this concept.
The NIH study shows that even when food calories, energy density, macronutrients, sugar, sodium, and fiber were matched, individuals consuming ultra-processed food gained weight compared to those on unprocessed meals.
This is a landmark study as it can influence guidelines/advice at the national level.
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Cell Metabolism
Randomized
July 2019
We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults, mean age 31 years and BMI = 27 kg/m2 .
Subjects were admitted to the NIH Clinical Center and randomized to receive either ultra-processed or unprocessed diets for 2 weeks immediately followed by the alternate diet for 2 weeks.
Meals were designed to be matched for their calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired.
Energy intake was greater during the ultra-processed diet (~508 kcal/day; p = 0.0001), with:
- Increased consumption of carbohydrate (~280 kcal/day; p < 0.0001),
- Increased consumption of fat (~230 kcal/day; p = 0.0004),
- but not increased consumption of protein (-2 ± 12 kcal/day; p = 0.85).
Weight changes were highly correlated with energy intake (r = 0.8, p <0.0001), with participants gaining 0.9 kg (p = 0.009) during the ultra-processed diet and losing 0.9 kg (p = 0.007) during the unprocessed diet.
Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment.
More from the publication
The perpetual diet wars between factions promoting low-carbohydrate, keto, paleo, high-protein, low-fat, plant-based, vegan, and a seemingly endless list of other diets have led to substantial public confusion and mistrust in nutrition science.
While debate rages about the relative merits and demerits of various so-called healthy diets, less attention is paid to the fact that otherwise diverse diet recommendations often share a common piece of advice: avoid ultra-processed foods.
Ultra-processed foods have been described as ‘‘formulations mostly of cheap industrial sources of dietary energy and nutrients plus additives, using a series of processes’’ and containing minimal whole foods.
As an alternative to traditional approaches that focus on nutrient composition of the diet, the NOVA diet classification system considers the nature, extent, and purpose of processing when categorizing foods and beverages into four groups:
- Unprocessed or minimally processed foods,
- Processed culinary ingredients,
- Processed foods, and
- Ultra-processed foods
While the NOVA system has been criticized as being too imprecise and incomplete to form an adequate basis for making diet recommendations, Brazil’s national dietary guidelines use the NOVA system and recommend that ultra-processed foods should be avoided.
However, several attributes of ultra-processed foods make them difficult to replace: they are inexpensive, have long shelf-life, are relatively safe from the microbiological perspective, provide important nutrients, and are highly convenient—often being either ready-to-eat or ready-to heat.
The rise in obesity and type 2 diabetes prevalence occurred in parallel with an increasingly industrialized food system characterized by large-scale production of high-yield, inexpensive, agricultural ‘‘inputs’’ (primarily corn, soy, and wheat) that are refined and processed to generate an abundance of ‘‘added value’’ foods.
Ultra-processed foods have become more common worldwide, now constitute the majority of calories consumed in America, and have been associated with a variety of poor health outcomes, including death.
Ultra-processed foods may facilitate overeating and the development of obesity because they are typically high in calories, salt, sugar, and fat and have been suggested to be engineered to have supernormal appetitive properties that may result in pathological eating behavior.
Furthermore, ultra-processed foods are theorized to disrupt gut-brain signaling and may influence food reinforcement and overall intake via mechanisms distinct from the palatability or energy density of the food.
As compelling as such theories may be, it is important to emphasize that no causal relationship between ultra-processed food consumption and human obesity HAS YET been established. In fact, there has never been a RCT demonstrating any beneficial effects of reducing ultra-processed foods or deleterious effects of increasing ultra-processed foods in the diet.
Therefore, to address the causal role of ultra-processed foods on energy intake and body weight change, we conducted a RCT examining the effects of ultra-processed versus unprocessed diets on ad libitum energy intake.

In conclusion, our data suggest that eliminating ultra-processed foods from the diet decreases energy intake and results in weight loss, whereas a diet with a large proportion of ultra-processed food increases energy intake and leads to weight gain.
Whether reformulation of ultra-processed foods could eliminate their deleterious effects while retaining their palatability and convenience is unclear. Until such reformulated products are widespread, limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment.
Such a recommendation could potentially be embraced across a wide variety of healthy dietary approaches including lowcarb, low-fat, plant-based, or animal-based diets. However, policies that discourage consumption of ultra-processed foods should be sensitive to the time, skill, expense, and effort required to prepare meals from minimally processed foods—resources that are often in short supply for those who are not members of the upper socioeconomic classes.
Limitations of Study Ultra-processed foods are less expensive and more convenient than preparing meals using unprocessed whole foods and culinary ingredients. Because the meals were prepared and presented at no cost to our subjects, and they could not choose their meals or their mode of presentation, our study did not address how consumer choices between ultra-processed versus unprocessed meals may be influenced by cost and convenience.
Our study was not designed to identify the cause of the observed differences in energy intake. Many of the potential negative effects of ultra-processed foods have been hypothesized to relate to their elevated sugar, fat, and sodium content while being low in protein and fiber.
However, we attempted to match these nutritional variables in the presented meals to investigate whether other aspects of ultra-processed diets contribute to excess energy intake. Had the experimental diets used in our study allowed for greater differences in sugar, fat, and sodium content more typical of differences between ultra-processed vs. unprocessed diets, we may have observed larger differences in energy intake.
Our study did not include a weight-maintenance run-in period or a washout period between test diets. These design choices were made to lessen the burden to the subjects and reduce the likelihood of dropouts, which was successful because all 20 subjects who successfully screened for the study also completed.
Finally, the inpatient environment of the metabolic ward makes it difficult to generalize our results to free-living conditions. However, current dietary assessment methods are insufficient to accurately or precisely measure energy intake outside the laboratory, and adherence to study diets cannot be guaranteed in free-living subjects.
While the 28-day duration of our study was relatively modest, most laboratory-based studies of food intake are typically much shorter in duration, often occurring within a single day of testing with one or two meals.