Clinical trial NCT06382298: Cottonseed Oil Versus Matched PUFA Effects
Official title: Health Effects of Cottonseed Oil Versus Matched Composition Diets in Humans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Dyslipidemia
Overweight and Obesity
Nutrition, Healthy
Lead sponsor: University of Georgia
Sponsor class: OTHER
Collaborators: name: United States Department of Agriculture (USDA)
First posted: 2024-04-24
Enrollment: 90
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three groups of 28-day parallel feeding trials with two groups receiving 20% of energy needs from CSO, or matched PUFA diet, and one group serving as control receiving 20% of energy needs as a mixture of oils that match the fatty acid profile of the average American intake.
Primary purpose: PREVENTION

Brief summary: Cardiovascular disease risk factors, including higher BMIs and poor cholesterol profiles, are on the rise and contribute to the United States' growing disease burden. Cottonseed oil (CSO) is found readily in the food supply, and the investigator's previous studies have demonstrated that incorporating CSO into the diet is sufficient to improve fasting cholesterol profile and improve postprandial lipid and/or glycemic responses in both healthy, and at-risk populations. This study aims to compare CSO to a fatty acid composition-matched diet, on changes in fasting and postprandial lipid metabolism and markers of chronic disease risk.

The specific aims are:

* Examine the impact of CSO vs. PUFA on fasting and postprandial lipids.
* Examine the impact of CSO on other markers of chronic disease risk.

Participants will be asked to:

* Consume provided meal replacement shakes daily for 28-days.
* Attend three weekly short visits for fasting blood draws, body measurements, and collect the next week of study materials,
* Attend two longer (5.5h) testing visits which include eating a standardized breakfast meal and having blood drawn periodically before and after breakfast.

Researchers will compare CSO vs. PUFA and control groups (receiving a mixture of oils) to see if CSO is unique in imparting health benefits when compared with similar matched oil diets.

Detailed description: Accounting for nearly 1 in every 4 deaths in the U.S., cardiovascular disease (CVD) is the leading cause of death for adults. One risk factor for CVD is hypercholesterolemia which can double the risk for this disease. Cottonseed oil is a rich source of poly-unsaturated fatty acids (PUFAs). Despite having a relatively high amount of saturated fatty acids, preliminary studies demonstrate that incorporating CSO into a diet is sufficient to reduce blood lipid profiles and select postprandial measures of metabolism. These improvements in lipid metabolism may be due to the general fatty acid (FA) composition of CSO; however, evidence shows that a fatty acid unique to CSO, dihydrosterculic acid (DHSA), may be responsible for some, if not all, the positive lipid lowering effects.

This prospective clinical study is a double-blinded, randomized control trial in adults at increased risk for cardiovascular disease (poor cholesterol profiles or overweight/obesity). There are three diet interventions: CSO (20% energy needs from CSO), matched-PUFA (20% energy needs from non-CSO matched PUFA sources), and Control (20% of energy needs from control oil mixture representative of the average fatty acid composition consumed by U.S. adults). The study protocol consists of a 28-day intervention where participants are provided breakfast shakes that contain a different oil, or mixture of oils, depending on the participant's random group assignment.

There are a total of 6 testing visits: screening (v0), pre-intervention (v1), 3 weekly short visits (v2, v3, v4), and post-intervention (v5).

At screening (v0), qualification is confirmed based on anthropometrics and fasting blood draw, which is analyzed for a cholesterol panel and blood glucose. Additionally, energy requirements are estimated at this visit for use in the diet intervention.

At v1, participants will have anthropometrics measured, including body composition by dual-energy x-ray absorptiometry (DXA). Fasting and postprandial blood draws for a 5h period will occur following a high saturated-fat meal challenge which delivers 35% of the participant's estimated energy needs.

28-day dietary intervention: Participants will consume a daily shake corresponding to the participant's randomly assigned group. The ingredients for the breakfast shakes are identical between groups, the only difference being the composition of assigned oil provided. The breakfast shakes are portioned based on individual energy needs as estimated at v0.

Participants return weekly (v2, v3, v4), to return study materials and collect shakes for the next week. At these weekly visits, participants also have a fasting blood draw, body measures, and consume the daily breakfast shake in the lab.

At the end of the 28-day dietary intervention, participants return for v5, where all procedures from v1 are repeated.

The investigators hypothesize that CSO will improve the proposed overall health outcomes and markers of chronic disease risk when compared with the matched PUFA and control groups.

Eligibility criteria: Inclusion Criteria:

* 25-75 year-old men and women at increased risk for cardiovascular disease. Increased risk for cardiovascular disease will be defined by either elevated cholesterol profiles -or- overweight/obesity.
* Elevated cholesterol profiles will be defined as:

-"Borderline High" and/or "at risk" in two of more of the following variables (total cholesterol: 180-239 mg/dL, LDL cholesterol 110-159 mg/dL, triglycerides 130-199 mg/dL) --or--

* "High" in total cholesterol (240 mg/dL and higher), LDL (160 mg/dL or higher), or triglycerides (between 200-350 mg/dL).

Overweight/obesity will be defined by body mass index \>25 kg/m².

Exclusion Criteria:

* Probable familial hypercholesterolemia, defined by: total cholesterol greater than 290 mg/dL or LDL levels greater than 190 mg/dL plus a family history of myocardial infarction (MI) before 50 years of age in a 2nd-degree relative or below age 60 in a 1st-degree relative.
* Women on hormone replacement therapy less than 2 years.
* Women who are pregnant
* individuals who regularly exercise more than 3h/w
* weight gain or loss of more than 5% body weight in the past 3 months
* plans to begin a weight loss/exercise regimen during the trial
* history of medical or surgical events that could affect digestion or swallowing
* gastrointestinal surgeries, conditions, or disorders
* any chronic diseases (including moderate to severe asthma, chronic lung disease, and kidney disease),
* metabolic disease
* atherosclerosis
* previous MI or stroke
* cancer
* fasting blood glucose levels greater than 126 mg/dL
* blood pressure greater than 180/120 mmHg
* medication use affecting digestion an absorption, metabolism (e.g. thyroid meds), lipid-lowering medications, medications for diabetes, steroid/hormone therapies, or current antibiotic cycles
* medically prescribed or special diets
* Food allergies (specific to the foods in the study, including wheat, dairy, and cottonseed oil)
* fish oil supplements
* excessive alcohol use (greater than 3 drinks/day for men; greater than 2 drinks/day for women)
* tobacco or nicotine use
* underweight BMI (\<18.5 kg/m²)

Primary outcomes:
measure: Change in fasting serum lipoprotein and cholesterol concentrations
timeFrame: baseline, 4 weeks
measure: Change in fasting serum lipoprotein particle numbers
timeFrame: baseline, 4 weeks
measure: Change in fasting and postprandial plasma triglyceride concentrations
timeFrame: baseline, 4 weeks
measure: Change in fasting and postprandial plasma non-esterified fatty acid (NEFA) concentrations
timeFrame: baseline, 4 weeks
measure: Change in fasting and postprandial plasma glucose concentrations
timeFrame: Baseline, 4 weeks
measure: Change in fasting and postprandial plasma insulin concentrations
timeFrame: baseline, 4 weeks
measure: Change in fasting and postprandial plasma appetite control hormones concentrations
timeFrame: baseline, 4 weeks
measure: Change in fasting and postprandial subjective feelings related to appetite
timeFrame: baseline, 4 weeks
measure: Change in fasting and postprandial plasma Malondialdehyde (MDA)
timeFrame: baseline, 4 weeks
measure: Change in fasting and postprandial plasma total antioxidant capacity
timeFrame: baseline, 4 weeks
measure: Change in fasting inflammatory cytokine concentrations
timeFrame: baseline, 4 weeks
measure: Change in fasting plasma markers of coagulation potential
timeFrame: baseline, 4 weeks
measure: Change in fasting and postprandial plasma angiopoietin-like (ANGPTL) proteins
timeFrame: baseline, 4 weeks
measure: Change in fasting insulin resistance metrics
timeFrame: baseline, 4 weeks
measure: Desaturation index
timeFrame: baseline, 4 weeks
Secondary outcomes:
measure: Change in fasting serum hepatic enzymes
timeFrame: Baseline, 4 weeks
measure: Change in fasting serum hepatic proteins
timeFrame: Baseline, 4 weeks
measure: Change in fasting serum bilirubin
timeFrame: Baseline, 4 weeks
measure: Change in additional fasting plasma inflammatory cytokine concentrations
timeFrame: baseline, 4 weeks
measure: Change in additional fasting plasma markers of coagulation potential
timeFrame: baseline, 4 weeks
measure: Change in acute dietary intake
timeFrame: baseline, 4 weeks
Other outcomes:
measure: Change in blood pressure
timeFrame: baseline, 4 weeks
measure: Change in body weight
timeFrame: baseline, 4 weeks
measure: Change in body composition
timeFrame: baseline, 4 weeks
measure: Change in diet composition
timeFrame: baseline, week 2, week 4
measure: Change in fasting tocopherol concentrations
timeFrame: baseline, 4 weeks
measure: Change in anthropometric circumferences
timeFrame: baseline, 4 weeks
measure: Change in resting metabolic rate
timeFrame: Screening
measure: Change in Perceived Stress
timeFrame: baseline, 4 weeks
measure: Change in anxiety
timeFrame: baseline, 4 weeks
measure: Change in self reported physical activity levels
timeFrame: baseline, 2 weeks, 4 weeks
measure: Change in Body Mass Index (BMI)
timeFrame: baseline, 4 weeks
Locations:
city: Athens
country: United States
facility: University of Georgia
state: Georgia
Study officials:
affiliation: University of Georgia
name: Jamie Cooper, PhD
role: PRINCIPAL_INVESTIGATOR
References: