Clinical trial NCT05686954: Cottonseed Oil Dose Response
Official title: Nutritional Effects of Different Doses of Cottonseed Oil in Humans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Dyslipidemias
Overweight and Obesity
Nutrition, Healthy
Lead sponsor: University of Georgia
Sponsor class: OTHER
Collaborators: name: Cotton Incorporated
First posted: 2023-01-17
Enrollment: 80
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: Four groups of 28-day parallel feeding trials with three groups receiving different amounts of cottonseed oil (low, mid, high) and one group serving as control receiving a mixture of oils that match the fatty acid profile of the average American diet.
Primary purpose: PREVENTION

Brief summary: Adding cottonseed oil to the diet has been shown to improve cholesterol profiles and other markers of chronic disease risk in both healthy and at-risk adults. However, CSO has only been tested in the context of high-fat diets. The goal of this clinical trial is to learn about the health effects of lower amounts of cottonseed oil (CSO) added to the diet in adults at increased risk for cardiovascular disease.

The main questions it aims to answer are:

* How do different amounts of CSO in the diet affect fasting cholesterol profiles and markers of liver function?
* How do different amounts of CSO in the diet affect fasting and post-meal markers of lipid metabolism (i.e. triglycerides) and glycemic control (i.e. blood sugar and insulin)?
* How do different amounts of CSO in the diet affect fasting and post-meal markers of chronic disease risk factors such as oxidative stress, inflammation, coagulation potential, and appetite control?

Participants will be asked to:

* Consume provided breakfast shakes and snacks 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 (5.5 h) testing visits which include eating a standardized breakfast meal and having blood drawn periodically before and after breakfast.

Researchers will compare CSO LOW, CSO MID, CSO HIGH, and Control groups (receiving a mixture of oils) to see if lower doses of CSO in the diet impart the same health benefits as previously shown with high doses of CSO.

Detailed description: 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 our food supply. Our previous studies have demonstrated that incorporating CSO into the diet is sufficient to reduce fasting total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c), increase high-density lipoprotein cholesterol (HDL-c), and improve postprandial lipid and/or glycemic responses in both healthy and at-risk populations. However, in these human studies, diets provided 30-44% of total energy from CSO, which corresponded to high-fat (HF) diet intake (40-50% of energy). The impact of lower doses of CSO on human health has yet to be tested. Therefore, this study aims to investigate whether lower doses of CSO are equally effective as previously proven high doses for improving fasting and postprandial lipid metabolism and markers of chronic disease risk. If lower doses of CSO in the diet are found to improve these markers, these study findings could lead to improvements in health.

This prospective clinical study is a single-blinded, randomized control trial in adults at increased risk for cardiovascular disease (poor cholesterol profiles or overweight/obesity). There are four diet interventions: CSO LOW (10% energy from CSO), CSO MID (20% energy from CSO), CSO HIGH (30% energy from CSO), and CON (10% energy from control oil mix). The study protocol consists of a 28-day intervention where participants are provided breakfast shakes and snacks that contain different amounts of cooking oil depending on their 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 BodPod. Next, a certified phlebotomist places an IV catheter and takes the fasting blood sample. Then the participant consumes a high-saturated-fat meal challenge which delivers 35% of their estimated energy needs (from v0). Then the participant has blood drawn 8 times using the IV catheter over the next 5 hours.

28-day dietary intervention: Before leaving v1, participants are sent home with their first week's supply of daily shakes and snacks corresponding to their randomly assigned group. The ingredients for the breakfast shakes and snacks are identical between groups, the only difference being the amount of the assigned oil incorporated into the foods. All foods are portioned based on individual energy needs as estimated at v0.

Participants return weekly (v2, v3, v4) to return study materials and collect food for the next week. At these weekly visits, participants also have a fasting blood draw, body measures and consume their first breakfast shake of the week 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 LOW, CSO MID, and CSO HIGH will improve the proposed overall health outcomes and markers of chronic disease risk without changing inflammatory markers compared to the control group.

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 or 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 (overweight 25-29.9 kg/m2 or obesity 30 kg/m2 or greater).

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 for less than 2 years
* women who are pregnant
* individuals who regularly exercise more than 3 h/w
* weight gain or loss of more than 5% of their 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 diseases
* 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 and 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/d for men; greater than 2 drinks/d 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 and postprandial plasma inflammatory cytokine concentrations
timeFrame: baseline, 4 weeks
measure: Change in fasting and postprandial 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
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 and postprandial plasma appetite control hormones concentrations
timeFrame: baseline, 4 weeks
measure: Change in fasting and postprandial plasma antioxidant parameters
timeFrame: baseline, 4 weeks
measure: Change in additional fasting and postprandial plasma inflammatory cytokine concentrations
timeFrame: baseline, 4 weeks
measure: Change in additional fasting and postprandial 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 and postprandial fatty acid composition
timeFrame: baseline, 4 weeks
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 A Cooper, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: