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

17 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Age is the primary risk factor for cardiovascular disease (CVD) and age-related vascular dysfunction is considered the key process linking the two. Middle age is a particularly vulnerable period when risk factors exceed diagnostic thresholds and clinical expression of CVD first becomes evident. Ultra-processed foods (UPF) comprise almost 60% of total energy in the standard American diet. The results of observational studies suggest that UPF consumption increases CVD risk, independent of overall diet quality (i.e., saturated fat, sodium, sugar, and dietary fiber intake). The "industrialized microbiota" may link diet, particularly UPF, to increased inflammation and CVD in middle-aged adults. High intake of UPF increases the likelihood of an excess heart age \>10 years and doubles the risk of subclinical coronary atherosclerosis in middle-aged adults. However, the impact of reducing UPF consumption on vascular function in middle-aged adults is unknown. The overall objective of this study is to establish proof-of-concept for an improvement in vascular function following reductions in UPF consumption in mid-life adults, in order to conduct a larger, more comprehensive and mechanistic trial in the future. In addition, changes in gut microbial composition and function, intestinal inflammation and permeability, serum endotoxin concentrations, and inflammatory cytokines as potential mechanisms by which UPF consumption influences vascular function will be investigated.

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 a diet low in ultra-processed foods safe for humans?

Research suggests that reducing ultra-processed foods in the diet is generally safe and may lower the risk of various health issues like obesity, diabetes, and heart disease. ^{1 2 3 4 5}

How does the No UPF controlled diet treatment differ from other treatments for cardiovascular health?

The No UPF controlled diet treatment is unique because it focuses on reducing the intake of ultra-processed foods, which are linked to higher risks of cardiovascular disease and poor metabolic health. Unlike other treatments that may involve medication, this approach emphasizes dietary changes to improve heart health. ^{2 3 6 7 8}

What data supports the effectiveness of the treatment 'No UPF controlled diet, Low Ultra-Processed Food Diet, Whole Food Diet, Minimally Processed Food Diet, Standard UPF controlled diet, Ultra-processed foods controlled diet, Standard American diet modification' for cardiovascular health?

Research shows that high consumption of ultra-processed foods (UPF) is linked to increased risk of heart disease and other health issues. Reducing UPF intake, as in the proposed diets, may improve heart health by lowering risks associated with poor diet quality and metabolic problems. ^{2 7 9 10 11}

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% energy) for 6 weeks. The controlled diet is eucaloric (50% carbohydrate, 35% fat,15% protein) matched for dietary soluble and insoluble fiber, added sugar, mono- and polyunsaturated fat, saturated fat, antioxidant nutrients, sodium, pre- and probiotics, and overall diet quality. Participants will consume a diet containing 0% total energy from UPF 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 59% UPF for 6 weeks. The controlled diet is eucaloric (50% carbohydrate, 35% fat,15% protein) matched for dietary soluble and insoluble fiber, added sugar, mono- and polyunsaturated fat, saturated fat, antioxidant nutrients, sodium, pre- and probiotics, and overall diet quality.

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

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 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]

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]

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]

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 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 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]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Impact of ultra-processed food consumption on metabolic health. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The relationship between ultra processed food consumption and premature coronary artery disease: Iran premature coronary artery disease study (IPAD). [2023]

3. England pubmed.ncbi.nlm.nih.gov

Consumption of ultra-processed foods and health status: a systematic review and meta-analysis. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Ultra-processed foods and mortality: analysis from the Prospective Urban and Rural Epidemiology study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Ultra-processed foods consumption is associated with cardiovascular disease and cardiometabolic risk factors in Brazilians with established cardiovascular events. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Ultra-processed Foods, Weight Gain, and Co-morbidity Risk. [2022]

7. United States 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. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

[What is ultra-processed food and how is it related to diet-related diseases?] [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Ultra-Processed Foods and Health Outcomes: A Narrative Review. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

High Consumption of Ultra-Processed Food is Associated with Incident Dyslipidemia: A Prospective Study of Older Adults. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Ultra-processed Foods and Cardiometabolic Health Outcomes: from Evidence to Practice. [2022]