Context: Cottonseed oil (CSO) is higher in polyunsaturated fatty acids (PUFA) and saturated fatty acids (SFAs) than many liquid plant oils.

Objectives: To conduct a systematic review of randomized controlled trials (RCTs) examining effects of CSO on markers of lipid metabolism and evaluate lipid and lipoprotein effects of incorporating CSO into a healthy dietary pattern using regression equations.

Data sources: A systematic search was conducted for RCTs comparing CSO with a non-CSO comparator in any population.

Data analyses: The Katan regression equation was used to predict lipid/lipoprotein changes when incorporating CSO into a US-style healthy eating pattern at 25 to 100% of the total oil allowance (ie, 27 g/2000 kcal) compared with average American intake (NHANES 2017 to 2020 pre-COVID pandemic).

Results: In total, 3 eligible publications (n = 2 trials), with 58 participants that provided 44% and 30% of total energy as CSO, were included. Fasting low-density lipoprotein cholesterol (LDL-C; ≈ -7.7 mg/dL) and triglycerides (≈ -7.5 mg/dL) were lower after 5 days of a CSO-enriched diet vs olive oil (OO). In a 56-day trial, CSO lowered total cholesterol (TC; ≈ -14.8 mg/dL), LDL-C (≈ -14.0 mg/dL), and non-high-density lipoprotein cholesterol (≈ -14.2 mg/dL) vs OO. Postprandially, angiopoietin-like protein-3, -4, and -8 concentrations decreased with CSO and increased with OO intake. Compared with average American intake, a healthy eating pattern with 27 g of CSO was estimated to lower TC (-8.1 mg/dL) and LDL-C (-7.3 mg/dL) levels, with minimal reduction in high-density lipoprotein cholesterol (-1.1 mg/dL). 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: Limited high-quality research suggests CSO may improve lipid/lipoprotein levels compared with OO. Cholesterol predictive equations suggest CSO can be incorporated into a healthy dietary pattern without significantly affecting lipids/lipoproteins.