Background Increasing unsaturated fat intake is beneficial for cardiovascular health but the type of unsaturated fat to recommend remains equivocal. Objective To investigate the effects of an 8-week diet-intervention that was rich in either cottonseed oil (CSO; polyunsaturated fat-rich) or olive oil (OO; monounsaturated fat-rich) on blood lipids in hypercholesterolemic adults. Methods 43 men and women with hypercholesterolemia (53±10y, BMI 27.6±4.8kg/m2) completed this randomized parallel clinical trial consisting of an 8-week partial outpatient feeding intervention. This trial was registered at clinicaltrials.gov (NCT04397055). Participants were given meals and snacks accounting for ∼60% of their daily energy needs, with 30% of energy needs from either CSO (n = 21) or OO (n = 22). At pre- and post-diet intervention visits, participants consumed a high saturated fat (SFA) meal (35% of total energy needs; 70% of energy from fat). The primary outcomes of fasting cholesterol profiles and secondary outcomes of postprandial blood lipids and glycemic markers were assessed over a 5h period. Results There were greater reductions from baseline in fasting serum total cholesterol (TC) (-17.0±3.94 vs.-2.18±3.72mg/dL; p = 0.008), LDL cholesterol (-19.7±3.94 vs.-5.72±4.23mg/dL; p = 0.018), Non-HDL cholesterol (non-HDL-c) (-20.8±4.00 vs. -6.61±4.01mg/dL;p = 0.014), and apolipoprotein B (-11.8±2.37 vs.-3.10±2.99mg/dL; p = 0.05), in CSO vs. OO. There were also visit effects for increases in HDL cholesterol (CSO: 56.5±2.79 to 60.2±3.35mg/dL; OO: 59.7±2.63 to 64.1±2.24mg/dL; p<0.001), and decreases in TC/HDL ratio (CSO: 4.30±0.27 to 3.78±0.27; OO: 3.94±0.16 to 3.57±0.11; p<0.001) regardless of group assignment. In response to the high SFA meal, there were differences in postprandial plasma glucose (p = 0.003) and triglyceride (p = 0.004) responses, and a trend in non-esterified fatty acids (p = 0.11), between groups showing protection in the postprandial state from an occasional high SFA fat meal with CSO, but not OO, diet enrichment. Conclusions CSO, but not OO, diet enrichment caused substantial improvements in fasting and postprandial blood lipids, and postprandial glycemia, in hypercholesterolemic adults. Clinical Trial #: NCT04397055

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Background Differences in metabolic responses between diets rich in monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) could affect energy balance and weight maintenance. The present study was a secondary analysis to investigate 8‐week diet interventions rich in either PUFA (cottonseed oil [CSO]) or MUFA (olive oil [OO]) on metabolic responses in adults with dyslipidaemia. Methods Forty‐one adults with dyslipidaemia completed this randomised trial consisting of an 8‐week partial‐outpatient feeding trial. Provided foods accounted for about 60% of their daily energy needs, with about 30% of energy needs provided by CSO (n = 20) or OO (n = 21). At pre‐ and postdiet intervention visits, participants consumed a high saturated fatty acid (SFA) meal (35% daily energy needs, 47.9% from SFA), and fasting and 3.5‐h postprandial indirect calorimetry were used to measure energy expenditure (EE) and substrate oxidation. Results No changes were observed in fasting measures. The OO group had greater increases in postprandial EE (p = 0.002); however, there were no differences in substrate oxidation between groups. A lack of metabolic flexibility was found in both groups, which was partially explained by changes in insulin sensitivity (homeostasis model assessment of insulin resistance). Conclusions The results of the present study show that OO, but not CSO, diet enrichment improves EE after an occasional high SFA meal, which may improve weight maintenance over time. This study is registered at https://clinicaltrials.gov (NCT04397055).