Cottonseed Oil Dose Response

NCT05686954 | Completed

• 1 other identifier: PROJECT00006633
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

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.

Conditions

Dyslipidemias; Overweight and Obesity; Nutrition, Healthy

Outcome Measures

Primary Outcomes (14)

• Change in fasting serum lipoprotein and cholesterol concentrations

  The concentration of fasting serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein B (mg/dl)

  baseline, 4 weeks

• Change in fasting serum lipoprotein particle numbers

  Number of particles of low density lipoproteins (LDL), LDL small, HDL large, LDL medium, lipoprotein (a) (nmol/L)

  baseline, 4 weeks

• Change in fasting and postprandial plasma triglyceride concentrations

  The concentration of plasma triglycerides before and after the high saturated fat meal challenge at both pre- and post-intervention visits (mg/dL)

  baseline, 4 weeks

• Change in fasting and postprandial plasma non-esterified fatty acid (NEFA) concentrations

  The concentration of plasma NEFAs before and after the high saturated fat meal challenge at both pre- and post-intervention visits (mEq/L)

  baseline, 4 weeks

• Change in fasting and postprandial plasma glucose concentrations

  The concentration of plasma glucose before and after the high saturated fat meal challenge at both pre- and post-intervention visits (mg/dL)

  baseline, 4 weeks

• Change in fasting and postprandial plasma insulin concentrations

  The concentration of plasma insulin before and after the high saturated fat meal challenge at both pre- and post-intervention visits (uU/mL)

  baseline, 4 weeks

• Change in fasting and postprandial plasma appetite control hormones concentrations

  The concentration of plasma appetite control hormones before and after the high saturated fat meal challenge at both pre- and post-intervention visits. Appetite control hormones include Cholecystokinin (CCK), Peptide YY (PYY), Ghrelin (pg/mL)

  baseline, 4 weeks

• Change in fasting and postprandial subjective feelings related to appetite

  Visual analog scale ratings of feelings related to appetite before and after the high saturated fat meal challenge at both pre- and post-intervention visits. Subjective feelings of hunger, fullness, desire to eat, prospective consumption, and a composite appetite score are measured by visual analog scales (mm).

  baseline, 4 weeks

• Change in fasting and postprandial plasma Malondialdehyde (MDA)

  The concentration of MDA before and after the high saturated fat meal challenge at both pre- and post-intervention visits (nmol/mL).

  baseline, 4 weeks

• Change in fasting and postprandial plasma total antioxidant capacity

  Total antioxidant capacity before and after the high saturated fat meal challenge at both pre- and post-intervention visits (U/mL).

  baseline, 4 weeks

• Change in fasting and postprandial plasma inflammatory cytokine concentrations

  The concentration of interleukin-1 beta, C reactive protein, tumor-necrosis factor-alpha, and interleukin-6 before and after the high saturated fat meal challenge at both pre- and post-intervention visits (pg/mL).

  baseline, 4 weeks

• Change in fasting and postprandial plasma markers of coagulation potential

  The concentration of plasminogen activator inhibitor-1, and tissue factor before and after the high saturated fat meal challenge at both pre- and post-intervention visits (pg/mL).

  baseline, 4 weeks

• Change in fasting and postprandial plasma angiopoietin-like (ANGPTL) proteins

  The concentration of ANGPTL 3, ANGPTL 4, and ANGPTL 8 before and after the high saturated fat meal challenge at both pre- and post-intervention visits (ng/mL).

  baseline, 4 weeks

• Change in fasting insulin resistance metrics

  Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Homeostatic Model Assessment for β-cell function (HOMA-B) will be calculated from fasting insulin and glucose measures before and after the 28-day intervention.

  baseline, 4 weeks

Secondary Outcomes (8)

• Change in fasting serum hepatic enzymes

  Baseline, 4 weeks

• Change in fasting serum hepatic proteins

  Baseline, 4 weeks

• Change in fasting serum bilirubin

  Baseline, 4 weeks

• Change in additional fasting and postprandial plasma appetite control hormones concentrations

  baseline, 4 weeks

• Change in fasting and postprandial plasma antioxidant parameters

  baseline, 4 weeks

Other Outcomes (12)

• Change in blood pressure

  baseline, 4 weeks

• Change in body weight

  baseline, 4 weeks

• Change in body composition

  baseline, 4 weeks

Study Arms (4)

CSO LOW

EXPERIMENTAL

Participants are given foods enriched with cottonseed oil and instructed on how to substitute study foods into their diet to maintain caloric balance.

Other: CSO LOW

CSO MID

EXPERIMENTAL

Participants are given foods enriched with cottonseed oil and instructed on how to substitute study foods into their diet to maintain caloric balance.

Other: CSO MID

CSO HIGH

EXPERIMENTAL

Participants are given foods enriched with cottonseed oil and instructed on how to substitute study foods into their diet to maintain caloric balance.

Other: CSO HIGH

CONTROL

ACTIVE COMPARATOR

Participants are given foods enriched with a mixture of oils and instructed on how to substitute study foods into their diet to maintain caloric balance.

Other: CONTROL

Interventions

CSO LOW OTHER

Participants are provided a breakfast shake and a snack daily that delivers 10% of the participant's estimated energy needs as cottonseed oil for 28 days.

CSO LOW

CSO MID OTHER

Participants are provided a breakfast shake and a snack daily that delivers 20% of the participant's estimated energy needs as cottonseed oil for 28 days.

CSO MID

CSO HIGH OTHER

Participants are provided a breakfast shake and a snack daily that delivers 30% of the participant's estimated energy needs as cottonseed oil for 28 days.

CSO HIGH

CONTROL OTHER

Participants are provided a breakfast shake and a snack daily that delivers 10% of the participant's estimated energy needs as a mixture of oils that match the average American fat intake for 28 days.

CONTROL

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Georgia: lead
• Cotton Incorporated: collaborator

Study Sites (1)

University of Georgia

Athens, Georgia, 30602, United States

Location

Related Publications (1)

• Hawkins CD, Prater MC, Ward CA, Paton CM, Cooper JA. Dose-Response Effects of Cottonseed Oil on Blood Lipid Responses in Adults at Risk of Cardiovascular Disease: A Randomized Controlled Trial. J Nutr. 2026 Feb;156(2):101236. doi: 10.1016/j.tjnut.2025.11.006. Epub 2025 Nov 12.

  PMID: 41238122 DERIVED

MeSH Terms

Conditions

Dyslipidemias; Overweight; Obesity

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jamie A Cooper, Ph.D.

  University of Georgia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants are blinded to which group they are in and what oil they are receiving.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Director of UGA Obesity Initiative

Model Details: 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.

Study Record Dates

• First Submitted: January 5, 2023
• First Posted: January 17, 2023
• Study Start: March 1, 2023
• Primary Completion: May 2, 2024
• Study Completion: May 2, 2024
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (1)