Processed vs Unprocessed Diet for Obesity

Overseen By Valerie L Darcey

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must not be taking: Diet medications, others

Disqualifiers: Diabetes, Cancer, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the impact of diets with processed foods versus unprocessed foods on health and metabolism. Researchers aim to understand how these diets affect weight and energy usage in the body. Ideal participants have a stable weight, no diabetes, and can engage in daily exercise like moderate cycling. Participants will stay at the research facility for four weeks, receive meals, and undergo various tests to measure the diets' effects. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research on diet and health.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescription medications or drugs that may influence appetite, as these are part of the exclusion criteria for the study.

What prior data suggests that this protocol is safe for participants?

Research has shown that consuming a lot of ultra-processed foods links to health problems. People who eat more of these foods face a higher risk of heart disease and obesity. For instance, one study found that those who consumed the most ultra-processed foods had a 31% higher chance of dying earlier than those who ate the least.

In contrast, unprocessed foods appear to aid in weight control. Research indicates that when people switch to unprocessed foods, they tend to consume fewer calories and lose weight. This suggests that unprocessed foods are generally better for maintaining a healthy weight and reducing the risk of certain health issues.

While these studies highlight some risks and benefits, this trial aims to explore these effects further. Researchers will closely monitor participants to ensure safety throughout the study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different types of diets, specifically ultra-processed versus unprocessed foods, impact obesity. Unlike standard obesity treatments that often focus on calorie restriction or medication, this trial examines the quality and processing level of the food itself. The unique feature of this trial is its focus on the degree of food processing and energy density, which could reveal new insights into how diet composition affects weight management. By understanding these dietary impacts, researchers hope to discover more effective, sustainable ways to address obesity beyond traditional methods.

What evidence suggests that this trial's diets could be effective for obesity?

Research has shown that consuming a lot of ultra-processed foods links to higher risks of obesity and other health issues. People who eat more of these foods often have higher body weights and are more likely to be obese. This trial will compare different dietary patterns, including ultra-processed and unprocessed food diets. Studies have found that switching to a diet with unprocessed foods can aid weight loss and improve health indicators like cholesterol levels. In one study, participants lost about twice as much weight on unprocessed diets compared to those eating ultra-processed foods. Overall, reducing ultra-processed foods can help manage weight and improve health. ^{1 6 7 8 9}

Who Is on the Research Team?

Valerie L Darcey

Principal Investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Are You a Good Fit for This Trial?

Adults aged 18-60 without diabetes, stable weight, and able to exercise can join this study. They must be willing to follow the study's lifestyle guidelines for 4 weeks at NIH, including daily cycling and various health tests. Those with appetite-affecting conditions or on certain medications cannot participate.

Inclusion Criteria

Provision of signed and dated informed consent form

Body mass index (BMI) > =20 kg/m2

My weight has been stable, with less than a 5% change in the past 6 months.

Exclusion Criteria

I have a condition like cancer, diabetes, or changes in smell/taste after COVID-19 that affects my appetite.

My hematocrit level is below 40%.

I am not on medications that affect my appetite, including weight-loss drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants will stay at NIH for 4 weeks, receiving different diets each week to study their effects on health and metabolism

4 weeks

Daily monitoring and activities

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ultra-processed food, both high
• Ultra-processed food, both low
• Ultra-processed food, high energy density
• Unprocessed food diet

Trial Overview The trial is testing how different diets (ultra-processed vs unprocessed foods) impact energy metabolism over a period of four weeks. Participants will eat provided meals in controlled amounts and undergo regular health assessments to measure the effects.

How Is the Trial Designed?

Group I: 4/ UNF LL, UPF HH, UPF LL, UPF HL Experimental Treatment 4 Interventions

Four diets in the order specified

Group II: 3/ UPF LL, UNF LL, UPF HL, UPF HH Experimental Treatment 4 Interventions

Four diets in the order specified

Group III: 2/ UPF HL, UPF LL, UPF HH, UNF LL Experimental Treatment 4 Interventions

Four diets in the order specified

Group IV: 1/UPF HH, UPF HL, UNF LL, UPF LL Experimental Treatment 4 Interventions

Four diets in the order specified

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Ultra-processed foods, which are heavily modified and often contain additives, have been linked to lower nutritional quality and increased risks of chronic diseases such as cancer, cardiovascular disease, and obesity, based on numerous global studies.

Public health authorities are now recommending a reduction in the consumption of ultra-processed foods, but more research is needed to understand the mechanisms behind their health impacts and to inform regulations on food additives and processing methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ultra-processed food : from research to guidelines]. Srour, B., Chazelas, E., Touvier, M.[2022]

The rise in consumption of ultra-processed foods (UPF) is linked to a growing prevalence of obesity and non-communicable diseases worldwide, indicating potential health risks associated with these products.

This correlation suggests that the increasing volume of industrially processed foods in the global food supply may negatively impact human health, warranting further investigation into dietary choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-Processed Foods, Diet Quality and Human Health. Dinu, M., Martini, D.[2023]

Ultra-processed foods make up 57.9% of energy intake in the USA and contribute a staggering 89.7% of the total energy intake from added sugars, indicating a strong link between these foods and high sugar consumption.

Individuals consuming the highest amounts of ultra-processed foods are significantly more likely to exceed the recommended limit of 10% of total energy from added sugars, with 82.1% in the highest consumption group surpassing this limit compared to only 26.4% in the lowest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study. Martínez Steele, E., Baraldi, LG., Louzada, ML., et al.[2022]

High consumption of ultra-processed foods (UPF) is linked to a significant increase in the risk of overweight/obesity (39%), high waist circumference (39%), and metabolic syndrome (79%) based on a systematic review of 23 studies.

In a large cohort of 183,491 participants followed for 3.5 to 19 years, high UPF consumption was associated with a 25% increased risk of all-cause mortality and a 29% increased risk of cardiovascular disease, indicating serious long-term health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consumption of ultra-processed foods and health status: a systematic review and meta-analysis. Pagliai, G., Dinu, M., Madarena, MP., et al.[2023]

Research identified 25 policy actions related to ultraprocessed foods in the U.S. from 1983 to 2022, with a focus on children's nutrition and food pricing, indicating a growing awareness of the issue.

Only one policy specifically defined ultraprocessed food, highlighting a gap in clear regulatory frameworks compared to other countries that have integrated ultraprocessed food considerations into their dietary guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Policies Addressing Ultraprocessed Foods, 1980-2022. Pomeranz, JL., Mande, JR., Mozaffarian, D.[2023]

From 1988 to 2018, a significant portion of the US food supply consisted of ultraprocessed foods (58%-65%), hyper-palatable foods (55%-69%), and high energy density foods (37%-47%), indicating a trend towards more processed and calorie-dense options.

The study found that while the overall availability of these food categories increased, hyper-palatable foods saw the largest rise (14%), suggesting a growing concern for obesity risk associated with these types of foods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultraprocessed, hyper-palatable, and high energy density foods: Prevalence and distinction across 30 years in the United States. Sutton, CA., Stratton, M., L'Insalata, AM., et al.[2023]

Higher intake of unprocessed and minimally processed foods (UMP) is linked to improved diet quality metrics over 3 decades in two large cohorts of health professionals, with significant increases in scores for healthy eating indices.

In contrast, higher consumption of ultraprocessed foods (UPF) is associated with lower diet quality, indicating that UMP consumption promotes healthier eating patterns while UPF consumption detracts from them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intakes of Unprocessed and Minimally Processed and Ultraprocessed Food Are Associated with Diet Quality in Female and Male Health Professionals in the United States: A Prospective Analysis. Rossato, SL., Khandpur, N., Lo, CH., et al.[2023]

The semi-quantitative food frequency questionnaire (SFFQ) demonstrated acceptable validity in estimating energy intake from both unprocessed/minimally processed foods and ultra-processed foods among 226 Mexican adults, regardless of age group.

Correlation coefficients indicated a stronger relationship for ultra-processed foods (0.67 for adults <60 years and 0.48 for adults ≥60 years) compared to unprocessed/minimally processed foods, suggesting that the SFFQ is particularly effective for assessing intake of ultra-processed foods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Semi-quantitative Food Frequency Questionnaire Has Relative Validity to Identify Groups of NOVA Food Classification System Among Mexican Adults. Oviedo-Solís, CI., Monterrubio-Flores, EA., Rodríguez-Ramírez, S., et al.[2022]

This systematic review and meta-analysis of 12 observational studies found that higher consumption of ultra-processed foods (UPF) is significantly associated with an increased risk of obesity (odds ratio of 1.55) and overweight (odds ratio of 1.36) in the general population.

Every 10% increase in UPF consumption in daily calorie intake correlates with a 7% higher risk of overweight, a 6% higher risk of obesity, and a 5% higher risk of abdominal obesity, indicating a clear link between UPF intake and excess weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-processed food consumption and adult obesity risk: a systematic review and dose-response meta-analysis. Moradi, S., Entezari, MH., Mohammadi, H., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5787353/

Ultra-processed Food Intake and Obesity Being in the highest compared to lowest quintile of ultra-processed food consumption was associated with significantly higher BMI and odds of being obese [55].

2. bmj.com bmj.com/content/384/bmj-2023-077310

Ultra-processed food exposure and adverse health outcomes Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2667268525000245

Review The impact of ultra-processed foods on obesity risk This study aims to analyze the research landscape pertaining to the impact of ultra-processed foods and their potential association with the risk of obesity.

4. eatrightpro.org eatrightpro.org/news-center/practice-trends/nutrition-fact-check-ultra-processed-foods

Nutrition Fact Check: Ultra-Processed Foods Current evidence shows that diets high in UPFs are associated with a higher risk of obesity, Type 2 diabetes, cardiovascular disease and overall mortality.

5. nature.com nature.com/articles/s41591-025-03842-0

Ultraprocessed or minimally processed diets following ... To date, two RCTs demonstrate unfavorable weight changes on UPF compared with MPF diets matched for presented energy and nutrients, but no RCTs ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10924027/

Ultra-processed Food and Obesity: What Is the Evidence? - PMC Ultra-processed starchy foods and breakfast cereals were associated with increased risks of overweight, but not obesity [35]. These food groups ...

7. med.stanford.edu med.stanford.edu/news/insights/2025/07/ultra-processed-food--five-things-to-know.html

Ultra-processed food: Five things to know - Stanford Medicine It found “highly suggestive” evidence that greater consumption of these foods increases the risk of death from heart disease by 66%, the risk of ...

8. fda.gov fda.gov/food/nutrition-food-labeling-and-critical-foods/ultra-processed-foods

Ultra-Processed Foods ... highly processed foods (commonly called ultra-processed foods ... outcomes, including cardiovascular disease, obesity and certain cancers.

9. ama-assn.org ama-assn.org/public-health/prevention-wellness/what-doctors-wish-patients-knew-about-ultraprocessed-foods

What doctors wish patients knew about ultraprocessed foods A large study conducted over 19 years showed a 31% higher mortality for the highest versus lowest consumers of ultraprocessed foods,” Dr. Devries explained.