Cottonseed Oil for High Cholesterol

Overseen By Jamie A Cooper, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Georgia

Must not be taking: Thyroid meds, Lipid-lowering, Diabetes meds, Steroid/hormone

Disqualifiers: Familial hypercholesterolemia, Pregnancy, Chronic diseases, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how cottonseed oil might help manage high cholesterol and other heart disease risk factors. Participants will consume a daily shake containing either cottonseed oil, a similar oil, or a mix of common oils for 28 days. The researchers aim to determine if cottonseed oil provides unique health benefits compared to other oils. Individuals with high cholesterol or who are overweight and concerned about heart disease may be suitable candidates. As an unphased trial, this study allows participants to contribute to early research that could inform new dietary recommendations for heart health.

Will I have to stop taking my current medications?

The trial requires that participants do not use certain medications, including those affecting digestion, metabolism, lipid-lowering medications, diabetes medications, steroid/hormone therapies, or current antibiotic cycles. If you are on any of these, you may need to stop taking them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that diets with cottonseed oil (CSO) can positively affect cholesterol levels. Studies have found that CSO can improve cholesterol in both healthy adults and those with high cholesterol in just a few weeks. This indicates that CSO is generally safe and doesn’t cause major side effects for these groups.

Evidence suggests that diets with polyunsaturated fatty acids (PUFAs) can help lower bad cholesterol, benefiting heart health. However, some studies suggest that consuming large amounts of PUFAs might increase the risk of cell damage.

Overall, both CSO and PUFAs are considered safe when consumed in recommended amounts. Various studies have used them without major safety issues, and participants have generally tolerated these treatments well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using cottonseed oil for high cholesterol because it's a natural option that might offer a new way to manage cholesterol levels. Unlike standard treatments like statins, which work by blocking cholesterol production in the liver, cottonseed oil is rich in polyunsaturated fatty acids that could help lower bad cholesterol by different means. Additionally, incorporating cottonseed oil into a daily shake is a simple dietary change, which could be easier for some people to stick with compared to taking pills. This approach could potentially provide a heart-healthy option with fewer side effects.

What evidence suggests that this trial's treatments could be effective for high cholesterol?

Research has shown that diets rich in cottonseed oil (CSO), which participants in this trial may receive, can greatly improve cholesterol levels. Studies have found that consuming CSO for just one week can lower total cholesterol and bad cholesterol (LDL) without affecting good cholesterol (HDL). Specifically, one study reported a 56% reduction in total cholesterol and a 42% drop in LDL. Meanwhile, the matched PUFA diet, another treatment arm in this trial, can also lower bad cholesterol by boosting liver activity and is associated with a reduced risk of heart disease. Both CSO and PUFA diets have strong evidence supporting their potential to improve heart health by managing cholesterol levels. ^{1 2 6 7 8}

Who Is on the Research Team?

Jamie A Cooper, Ph.D.

Principal Investigator

University of Georgia

Are You a Good Fit for This Trial?

This trial is for individuals with obesity or high cholesterol who are interested in testing the effects of cottonseed oil (CSO) on their health. Participants will use meal replacement shakes and attend regular visits for blood draws and measurements. Those with cardiovascular risk factors may benefit.

Inclusion Criteria

Overweight/obesity defined by body mass index >25 kg/m²

I am between 25-75 years old and at risk for heart disease due to high cholesterol or being overweight.

My cholesterol levels are high or borderline in two or more categories.

Exclusion Criteria

Fasting blood glucose levels >126 mg/dL

I am taking medications that affect digestion, metabolism, or hormones.

I have a chronic disease like asthma, lung, or kidney disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Pre-intervention

Participants undergo baseline measurements including anthropometrics and fasting blood draw

1 week

1 visit (in-person)

Dietary Intervention

Participants consume daily meal replacement shakes for 28 days and attend weekly visits for fasting blood draws and body measurements

4 weeks

3 weekly visits (in-person), 2 longer testing visits (in-person)

Post-intervention

Participants undergo post-intervention measurements similar to pre-intervention to assess changes

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the intervention

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cottonseed Oil
• Matched PUFA Diet

Trial Overview The study compares the impact of CSO to a matched polyunsaturated fatty acid (PUFA) diet on lipid metabolism and chronic disease markers. It involves daily shakes, weekly check-ins, and two longer visits for detailed assessments over a 28-day period.

How Is the Trial Designed?

Group I: MATCHED PUFA DIET Experimental Treatment 1 Intervention

Participants are given a daily shake enriched with a mixture of oils with a similar fatty acid profile to CSO and instructed on how to substitute provided study shake into usual diet to maintain caloric balance.

Group II: COTTONSEED OIL Experimental Treatment 1 Intervention

Participants are given a daily shake enriched with cottonseed oil and instructed on how to substitute provided study shake into usual diet to maintain caloric balance.

Group III: CONTROL Active Control 1 Intervention

Participants are given a daily shake enriched with a mixture of oils that match the fatty acid profile of the average American diet, and instructed on how to substitute provided study shake into usual diet to maintain caloric balance.

Who Is Running the Clinical Trial?

University of Georgia

Lead Sponsor

Trials

109

Recruited

43,500+

United States Department of Agriculture (USDA)

Collaborator

Trials

103

Recruited

287,000+

Published Research Related to This Trial

A 5-day high-fat diet rich in cottonseed oil (CSO) significantly improved lipid profiles in normal-weight men, lowering total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, while increasing high-density lipoprotein (HDL) cholesterol.

In contrast, a diet rich in olive oil (OO) did not result in any significant changes in blood lipid levels, highlighting the potential cardiovascular benefits of CSO over OO in a short-term dietary intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 5-day high-fat diet rich in cottonseed oil improves cholesterol profiles and triglycerides compared to olive oil in healthy men. Polley, KR., Oswell, NJ., Pegg, RB., et al.[2019]

Cottonseed oil (CS-O) is a valuable source of vitamin E and has a unique fatty acid profile, making it beneficial for antioxidant activities, anti-inflammatory effects, and cardiovascular protection.

CS-O can be extracted using various methods, and despite some loss of tocopherols during processing, it remains a versatile oil with applications in cooking, biofuels, cosmetics, and agriculture.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cottonseed oil: A review of extraction techniques, physicochemical, functional, and nutritional properties. Riaz, T., Iqbal, MW., Mahmood, S., et al.[2023]

Cottonseed oil (CSO) may improve lipid profiles by significantly lowering fasting low-density lipoprotein cholesterol (LDL-C) and triglycerides compared to olive oil, based on a systematic review of 2 trials with 58 participants.

Incorporating CSO into a healthy dietary pattern is predicted to lower total cholesterol and LDL-C levels without significantly affecting high-density lipoprotein cholesterol, suggesting it can be a beneficial addition to diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of cottonseed oil on lipids/lipoproteins: a systematic review and plasma cholesterol predictive equations estimations. Hart, TL., Petersen, KS., Kris-Etherton, PM.[2023]

An 8-week diet intervention with either cottonseed oil (CSO) or olive oil (OO) in 42 adults with untreated hypercholesterolemia showed no significant differences in inflammatory and coagulation markers, suggesting that both types of dietary fat do not promote inflammation.

This study provides further evidence that n-6 polyunsaturated fats, like those in CSO, may not be pro-inflammatory compared to monounsaturated fats, even in individuals at higher risk for cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No Observed Difference in Inflammatory and Coagulation Markers Following Diets Rich in n-6 Polyunsaturated Fat vs Monounsaturated Fat in Adults With Untreated Hypercholesterolemia: A Randomized Trial. Prater, MC., Scheurell, AR., Paton, CM., et al.[2023]

Cottonseed Oil and its derivatives, including Hydrogenated Cottonseed Oil, are generally safe for use in cosmetics, showing no significant toxicity in animal studies and no irritation in clinical formulations.

While Cottonseed Oil can have some adverse effects, such as increased mammary tumors in certain studies, it also demonstrated protective effects against tumor incidence when compared to sunflower oil, suggesting a complex safety profile that requires careful monitoring of contaminants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final report on the safety assessment of Hydrogenated Cottonseed Oil, Cottonseed (Gossypium) Oil, Cottonseed Acid, Cottonseed Glyceride, and Hydrogenated Cottonseed Glyceride. [2019]

In a study using mice on a high-fat diet, those fed cottonseed oil (CSO) showed significantly lower levels of total cholesterol, free cholesterol, triglycerides, and LDL compared to the high-fat control group, indicating CSO's potential to improve lipid profiles in fatty liver disease.

When both CSO and olive oil (OO) diets were reduced in calories, both groups lost weight, but CSO was more effective in reducing liver and plasma lipids, suggesting that CSO may be a better dietary option for managing lipid levels in obesity-related fatty liver conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cottonseed oil-enriched diet improves liver and plasma lipid levels in a male mouse model of fatty liver. Son, Y., Shockey, J., Dowd, MK., et al.[2023]

In a study involving 38 healthy adults consuming a cottonseed oil-rich diet for one week, total cholesterol and LDL levels were significantly reduced, indicating potential cholesterol-lowering effects of dietary cottonseed oil.

The reduction in total cholesterol was particularly notable in female participants, while levels of HDL and triglycerides remained unchanged, suggesting that cottonseed oil may be a safe dietary option for lowering cholesterol without negatively impacting beneficial HDL levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consumption of a diet rich in cottonseed oil (CSO) lowers total and LDL cholesterol in normo-cholesterolemic subjects. Davis, KE., Prasad, C., Imrhan, V.[2021]

Dietary cottonseed protein has been shown to effectively lower plasma cholesterol levels in rabbits and rats compared to casein, suggesting it may be beneficial for cholesterol metabolism.

In humans, replacing animal proteins with cottonseed protein may lead to a small decrease in serum cholesterol levels, although more research is needed to confirm this effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary cottonseed protein and cholesterol metabolism. Beynen, AC., Liepa, GU.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9449680/

Blood Lipid Responses to Diets Enriched with Cottonseed ... Previous studies have shown that CSO-rich diets can improve cholesterol profiles in healthy, young adults (11, 12).

2. nutrition.org nutrition.org/cottonseed-oil-a-possible-nutritional-therapeutic-for-adults-with-hypercholesterolemia/

Cottonseed oil: A possible nutritional therapeutic for adults ... Study results showed that consumption of a diet enriched with cottonseed oil for 8 weeks resulted in significant improvements in blood lipids ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3407983/

Consumption of a Diet Rich in Cottonseed Oil (CSO) ... Consumption of a high fat, CSO-rich diet for one week reduced total cholesterol in female participants without reducing HDL.

4. withpower.com withpower.com/trial/phase-overweight-7-2024-109ed

Cottonseed Oil for High Cholesterol A 5-day high-fat diet rich in cottonseed oil (CSO) significantly improved lipid profiles in normal-weight men, lowering total cholesterol, low-density ...

5. journals.physiology.org journals.physiology.org/doi/full/10.1152/ajpregu.00052.2022?doi=10.1152/ajpregu.00052.2022

A cottonseed oil-enriched diet improves liver and plasma ... The CSO group had lower plasma total cholesterol (−56 ± 6%, P < 0.01), free cholesterol (−53 ± 7%, P < 0.01), triglycerides (−61 ± 14%, P < 0.01), and LDL (−42 ...

6. liebertpub.com liebertpub.com/doi/full/10.1089/jmf.2024.0114

Is Cottonseed Oil the Next Healthy Oil? A 5-day high-fat diet rich in cottonseed oil improves cholesterol profiles and triglycerides compared to olive oil in healthy men. Nutr Res 2018 ...

7. academic.oup.com academic.oup.com/nutritionreviews/article/82/8/1079/7268824

The effect of cottonseed oil on lipids/lipoproteins: a systematic ... Compared with the healthy eating pattern, incorporating 27 g of CSO was predicted to increase TC and LDL-C levels by 2.4 mg/dL. Conclusion.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2212267223014909

No Observed Difference in Inflammatory and Coagulation ... Neither cottonseed oil nor olive oil diets resulted in significant changes in circulating markers of inflammation or coagulation potential after 8 weeks.