Diet Modification for Cardiovascular Health

Overseen By Elaina Marinik, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Must not be taking: Diabetes medications, Antibiotics

Disqualifiers: Diabetes, Heart diseases, Stroke, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether reducing ultra-processed foods (UPF) can improve heart and blood vessel health in middle-aged adults. Participants will follow either a diet with no UPF (No UPF controlled diet) or a diet high in UPF (Standard UPF controlled diet) to assess the impact on vascular function and gut health. Ideal participants consume an average amount of UPF, similar to most Americans, and have maintained a stable weight for the past six months. As an unphased trial, this study allows participants to contribute to groundbreaking research on diet and health.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications if you are on a stable dose of estrogen, testosterone, or lipid-lowering medication for more than 6 months. However, if you are taking diabetes medication or have used antibiotics, prebiotics, or probiotics in the last 3 months, you would not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that consuming a lot of ultra-processed foods (UPFs) links to higher risks of health issues like heart disease and stroke. Many people derive a significant portion of their daily calories from UPFs, which has been associated with an increased risk of heart problems.

Conversely, reducing or avoiding UPFs may benefit heart health. Although direct studies on the effects of eliminating UPFs are lacking, research suggests that consuming fewer UPFs could enhance heart health. Some studies have found that individuals who eat fewer UPFs tend to lose more weight and have lower levels of unhealthy fats in their blood.

Overall, diets both high and low in UPFs are generally well-tolerated. However, based on current research, consuming fewer UPFs could potentially improve heart health. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the impact of ultra-processed foods (UPF) on cardiovascular health, offering insights that could revolutionize dietary recommendations. Unlike traditional treatments that often rely on medication to manage cardiovascular issues, this trial examines the effects of dietary changes alone, specifically the elimination or significant reduction of UPF. The trial is investigating two distinct dietary approaches: one completely eliminates UPF, while the other comprises 81% UPF. This could provide groundbreaking evidence on how diet modifications alone, without medication, might improve heart health, potentially leading to new, non-pharmacological strategies for preventing and managing cardiovascular diseases.

What evidence suggests that this trial's diet modifications could be effective for cardiovascular health?

Research has shown that consuming many ultra-processed foods (UPFs) can increase the risk of heart problems and lead to more inflammation and digestive issues. Studies have found that reducing UPF intake can lower these risks and improve heart health. In this trial, participants will be assigned to one of two diet groups: one will follow a diet without UPFs, while the other will follow a diet high in UPFs. Specifically, individuals who consumed mostly natural foods lost twice as much weight as those who consumed many UPFs. Additionally, diets high in UPFs are linked to a greater risk of heart disease. These findings suggest that reducing UPFs might improve heart health by decreasing inflammation and other harmful effects. ^{2 5 6 7 8}

Who Is on the Research Team?

Kevin Davy, PhD

Principal Investigator

Virginia Polytechnic Institute and State University

Are You a Good Fit for This Trial?

This trial is for middle-aged adults who are sedentary to moderately active, have a stable weight, and consume a diet with ultra-processed foods close to the US average. They must not plan on changing their diet or exercise routine and should be willing to eat provided food for 8 weeks. Exclusions include those with high cholesterol/triglycerides, BMI over 35, vegetarians/vegans, certain diseases, allergies or aversions to food, irregular bowel movements/laxative use, recent antibiotic/prebiotic/probiotic use.

Inclusion Criteria

Usual UPF intake +/-15% of US average of 60% total energy

Sedentary to recreationally active

Weight stable for previous 6 months (<2 kg change)

Exclusion Criteria

I have diabetes or am taking medication for it.

I have been diagnosed with inflammatory bowel disease.

BMI >35 kg/m2

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Diet

Participants follow a 2-week eucaloric lead-in diet to standardize conditions before the main intervention

2 weeks

1 visit (in-person)

Treatment

Participants consume either a high UPF diet or a no UPF diet for 6 weeks

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in vascular function and other health markers after the diet intervention

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• No UPF controlled diet
• Standard UPF controlled diet

Trial Overview The study tests how cutting down on ultra-processed foods affects vascular health in middle-aged adults. Participants will follow either no UPF controlled diet or a standard UPF controlled diet for eight weeks while researchers monitor changes in vascular function and potential mechanisms like gut microbiota composition and inflammation.

How Is the Trial Designed?

Group I: No UPF (Ultra-processed foods) Experimental Treatment 1 Intervention

Following a 2-week eucaloric lead-in diet, participants will be provided and consume a diet without UPF (0% total energy) for 6 weeks.

Group II: High UPF Experimental Treatment 1 Intervention

Following a 2-week eucaloric lead-in diet, participants will be provided and consume a diet composed of 81% UPF for 6 weeks.

Who Is Running the Clinical Trial?

Virginia Polytechnic Institute and State University

Lead Sponsor

Trials

162

Recruited

26,900+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

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]

Ultra-processed food (UPF) consumption is linked to a higher risk of weight gain and related health issues in both adults and children, based on observational studies.

A mechanistic study indicates that UPFs lead to greater energy intake and weight gain compared to whole foods, suggesting that reducing UPF consumption could improve health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-processed Foods, Weight Gain, and Co-morbidity Risk. Crimarco, A., Landry, MJ., Gardner, CD.[2022]

In a study of 2,357 patients with established cardiovascular diseases, higher consumption of ultra-processed foods (UPF) was linked to increased cardiometabolic risk factors, such as high waist circumference and overweight.

Interestingly, while higher UPF intake was associated with certain risks, it also showed a decreased likelihood of having multiple cardiovascular conditions like coronary artery disease and stroke, particularly in women, suggesting a complex relationship that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-processed foods consumption is associated with cardiovascular disease and cardiometabolic risk factors in Brazilians with established cardiovascular events. da Silva, A., Brum Felício, M., Caldas, APS., et al.[2021]

Ultra-processed foods make up about 46% of daily energy intake in Germany and are linked to various non-communicable diseases such as obesity, diabetes, and cardiovascular disease.

The study highlights the need for intervention studies to better understand the mechanisms behind these associations and to improve dietary assessments in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What is ultra-processed food and how is it related to diet-related diseases?] Fedde, S., Rimbach, G., Schwarz, K., et al.[2022]

A review of 43 studies found that 37 studies linked ultra-processed food (UPF) consumption to various adverse health outcomes, including obesity, type-2 diabetes, and cardiovascular diseases in adults, and cardio-metabolic risks in children.

No studies reported any beneficial health outcomes associated with UPF consumption, highlighting the need for dietary guidelines that consider the health risks of these foods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-Processed Foods and Health Outcomes: A Narrative Review. Elizabeth, L., Machado, P., Zinöcker, M., et al.[2021]

In a study of 1082 older adults in Spain, higher consumption of ultra-processed foods (UPFs) was linked to a greater risk of developing dyslipidemia, specifically hypertriglyceridemia and low HDL cholesterol, over a follow-up period of 5 to 7 years.

Participants in the highest tertile of UPF consumption had more than double the odds of developing hypertriglyceridemia and low HDL cholesterol compared to those in the lowest tertile, suggesting that UPF intake may contribute to cardiovascular disease risk through these lipid abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Consumption of Ultra-Processed Food is Associated with Incident Dyslipidemia: A Prospective Study of Older Adults. Donat-Vargas, C., Sandoval-Insausti, H., Rey-García, J., et al.[2023]

Ultra-processed foods are strongly linked to an increased risk of various cardiometabolic issues, including obesity, type 2 diabetes, and cardiovascular disease, based on high-quality epidemiological and experimental studies.

Given the widespread consumption of ultra-processed foods and their associated health risks, they should be a primary focus for public health initiatives and clinical interventions aimed at improving diet quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-processed Foods and Cardiometabolic Health Outcomes: from Evidence to Practice. Juul, F., Deierlein, AL., Vaidean, G., et al.[2022]

Recent research, including 30 studies, indicates that high consumption of ultra-processed foods (UPF) is linked to negative effects on metabolic health, such as increased risk of metabolic syndrome, obesity, and cardiovascular diseases.

The evidence suggests a strong need to reduce UPF consumption globally, especially among adults, although further studies are required to establish clear causal relationships and understand the underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of ultra-processed food consumption on metabolic health. Costa de Miranda, R., Rauber, F., Levy, RB.[2021]

In a study of 5,565 U.S. adolescents aged 12-19, it was found that 65.7% of their daily calories came from ultraprocessed foods (UPF), which is concerning for their cardiovascular health.

Every 5% increase in calories from UPF was linked to a decrease in cardiovascular health scores, indicating that higher UPF consumption is associated with poorer cardiovascular health outcomes among adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship Between Ultraprocessed Food Intake and Cardiovascular Health Among U.S. Adolescents: Results From the National Health and Nutrition Examination Survey 2007-2018. Zhang, Z., Jackson, SL., Steele, EM., et al.[2023]

In a study of 2,354 Iranian adults, those consuming the highest amounts of ultra-processed foods (UPFs) were found to be more than twice as likely to develop premature coronary artery disease (PCAD) compared to those with the lowest consumption levels.

The risk of severe PCAD also increased significantly with higher UPF consumption, indicating a strong association between UPF intake and both the likelihood and severity of coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between ultra processed food consumption and premature coronary artery disease: Iran premature coronary artery disease study (IPAD). Ansari, S., Mohammadifard, N., Haghighatdoost, F., et al.[2023]

In a study of 138,076 participants from various regions over a median follow-up of 10.2 years, a high intake of ultra-processed foods (UPFs) was linked to a 28% increased risk of total mortality and a 32% increased risk of non-cardiovascular mortality.

While UPF consumption was associated with higher mortality rates, it did not show a significant link to the risk of major cardiovascular events, suggesting that the impact of UPFs may be more pronounced on overall health rather than specific cardiovascular outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-processed foods and mortality: analysis from the Prospective Urban and Rural Epidemiology study. Dehghan, M., Mente, A., Rangarajan, S., et al.[2023]

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/CIR.0000000000001365

Ultraprocessed Foods and Their Association With ... Certain ingredients, additives, and processing methods used in UPFs may pose long-term health risks through both direct and indirect mechanisms.

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

Ultra-processed food exposure and adverse health outcomes Highly suggestive (class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2949688825000103

The impact of ultra-processed foods on cardiovascular ... Ultra-processed foods (UPFs) are associated with increased risks of cardiovascular diseases and cancer. •. Systemic inflammation and gut dysbiosis are key ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11233771/

Ultra-processed foods consumption and health-related ... Prospective observational studies have reported significant associations between higher intake of UPFs and adverse health outcomes.

5. news-medical.net news-medical.net/news/20250804/Weight-loss-doubles-when-eating-minimally-processed-foods-over-ultra-processed-alternatives.aspx

Weight loss doubles when eating minimally processed ... When given nutritionally matched diets, participants lost twice as much weight eating minimally processed foods compared to ultra-processed ...

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

Ultraprocessed or minimally processed diets following ... Ultraprocessed food (UPF) consumption is associated with noncommunicable disease risk, yet no trial has assessed its health impact within ...

7. thelancet.com thelancet.com/journals/lanepe/article/PIIS2666-7762(24)00115-7/fulltext

Implications of food ultra-processing on cardiovascular risk ... This study aims to assess CVD risk associated with the dietary contribution of food groups that consider both plant or animal origin and food processing ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7399967/

Ultra-Processed Foods and Health Outcomes: A Narrative ... 37 found dietary UPF exposure associated with at least one adverse health outcome. Among adults, these included overweight, obesity and cardio-metabolic risks.