Intermittent Cottonseed Oil Consumption

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 polyunsaturated fatty acids (PUFAs). Despite having a relatively high amount of saturated fatty acids, preliminary studies demonstrate that incorporating CSO into a diet at 30% and 20% of daily energy needs 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, of 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 and/or overweight/obesity). There are three diet interventions: CSO-30 (30% of energy needs from CSO), CSO-20 (20% of energy needs from CSO), and Control (not receiving CSO; will receive thickened water with yellow food coloring to mimic the appearance of oil). The study protocol consists of a 56-day intervention where participants are provided breakfast shakes and snacks that contain different amounts of oil, depending on the participant's random group assignment.

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

At screening (v0), qualification is confirmed based on anthropometrics and a 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.

56-day dietary intervention: Participants will consume a shake and snack 3 times per week, corresponding to the participant's randomly assigned group. The ingredients for the breakfast shakes and snacks are identical between groups, the only difference being the amount of assigned oil provided. The breakfast shakes and snacks are portioned based on individual energy needs as estimated at v0.

Participants return every other week (v2, v3, v4), to return study materials and collect shakes and snacks for the next two weeks. At these bi-weekly visits, participants also have a fasting blood draw and body measures taken.

At the end of the 56-day dietary intervention, participants return for v5, where all procedures from v1 are repeated.

As decided a priori, we will complete a per protocol analysis.

The investigators hypothesize that CSO-30 and CSO-20 will improve the proposed overall health outcomes and markers of chronic disease risk without changing inflammatory markers or coagulation potential compared to the control group.

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).

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 or nursing/breastfeeding
• 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, absorption, or 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 soy, dairy, gluten, Yellow No. 5, cottonseed oil, palm oil, and coconut 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)