Eight weeks of daily cottonseed oil intake attenuates postprandial angiopoietin-like proteins 3 and 4 responses compared to olive oil in adults with hypercholesterolemia: A secondary analysis of a randomized clinical trial.

Angiopoietin-like proteins (ANGPTLs) -3, -4, and -8 are regulators of lipid metabolism and have been shown to respond to changes in dietary fats. It is unknown how ANGPTLs respond to cottonseed oil (CSO) and olive oil (OO) consumption in a population with hypercholesterolemia. The purpose of this study was to determine the impact of CSO vs. OO consumption on fasting and postprandial ANGPTL responses in adults with hypercholesterolemia. We hypothesized that CSO would have lower fasting and postprandial ANGPTL responses compared with OO. Forty-two adults with high cholesterol completed a single-blind, randomized trial comparing CSO (n = 21) vs. OO (n = 21) diet enrichment. An 8-week partial outpatient feeding intervention provided ∼60% of the volunteers' total energy expenditure (∼30% of total energy expenditure as CSO or OO). The remaining 40% was not controlled. Fasting blood draws were taken at pre-, mid-, and postintervention visits. Volunteers consumed a high saturated fat meal followed by 5 hours of blood draws pre- and postvisits. Fasting ANGPTL3 had a marginally significant treatment by visit interaction (P = .06) showing an increase from pre- to postintervention in CSO vs. OO (CSO: 385.1 ± 27.7 to 440.3 ± 33.9 ng/mL; OO: 468.2 ± 38.3 to 449.2 ± 49.5 ng/mL). Both postprandial ANGPTL3 (P = .02) and ANGPTL4 (P < .01) had treatment by visit interactions suggesting increases from pre- to postintervention in OO vs. CSO with no differences between groups in ANGPTL8. These data show a worsening (increase) of postprandial ANGPTLs after the OO, but not CSO, intervention. This aligns with previously reported data in which postprandial triglycerides were protected from increases compared with OO. ANGPTLs may mediate protective effects of CSO consumption on lipid control. This trial was registered at clinicaltrials.gov (NCT04397055).

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.

BACKGROUND: Inflammatory and prothrombotic responses are hallmark to the progression of cardiovascular disease and may be influenced by the type of dietary fat. Cottonseed oil (CSO) is rich in n-6 polyunsaturated fats and improves traditional cardiovascular disease risk factors such as cholesterol profiles. However, some clinicians are still hesitant to promote n-6 polyunsaturated fats consumption despite growing evidence suggesting they may not be independently pro-inflammatory. OBJECTIVE: To investigate the inflammatory and coagulation marker responses to an 8-week diet intervention rich in either CSO or olive oil (OO) (OO is rich in monounsaturated fat) in adults with untreated hypercholesterolemia. DESIGN: This was a secondary analysis of a parallel-arm randomized clinical trial with the main outcome of cholesterol measures. PARTICIPANTS/SETTING: Participants included in this analysis were 42 sedentary adults aged 30 to 75 years (62% women) in the Athens, GA, area, between May 2018 and June 2021, with untreated hypercholesterolemia or elevated blood lipids and body mass index >18.5. Hypercholesterolemia was defined as at least two blood lipid levels in a borderline undesirable/at risk range (total cholesterol level ≥180 mg/dL, low-density lipoprotein cholesterol level ≥110 mg/dL, high-density lipoprotein cholesterol level <50 mg/dL, or triglyceride level ≥130 mg/dL), or at least one in an undesirable range (total cholesterol level ≥240 mg/dL, low-density lipoprotein cholesterol level ≥160 mg/dL, high-density lipoprotein cholesterol level <40 mg/dL, or triglyceride level ≥200 mg/dL). INTERVENTION: Participants were randomly assigned to either the CSO or OO group in a partial outpatient feeding trial. Meals from the study provided approximately 60% of their energy needs with 30% of energy needs from either CSO or OO for 8 weeks. Participants fulfilled their remaining energy needs with meals of their choosing. MAIN OUTCOME MEASURES: Fasting plasma concentrations of inflammatory markers, including C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-1ß were measured at baseline and 8 weeks. Markers of coagulation potential, including plasminogen activator inhibitor-1, and tissue factor were measured at the same time points. STATISTICAL ANALYSES PERFORMED: Repeated measures linear mixed models were used with treatment and visit in the model for analyses of all biochemical markers. RESULTS: There were no significant differences in fasting C-reactive protein (P = 0.70), tumor necrosis factor-α (P = 0.98), interleukin-6 (P = 0.21), interleukin-1ß (P = 0.13), plasminogen activator inhibitor-1 (P = 0.29), or tissue factor (P = 0.29) between groups across the intervention. CONCLUSIONS: Inflammation and coagulation marker responses to diets rich in CSO vs OO were not significantly different between groups, and neither group showed changes in these markers in adults with untreated hypercholesterolemia. This provides additional evidence suggesting that dietary n-6 polyunsaturated fats may not promote inflammation compared with monounsaturated fatty acids, even in adults at increased risk for cardiovascular disease.

Dietary Nitrate from Plant Foods: A Conditionally Essential Nutrient for Cardiovascular Health.

Under specific conditions, such as catabolic stress or systemic inflammation, endogenous nutrient production becomes insufficient and exogenous supplementation (for example, through dietary intake) is required. Herein, we propose consideration of a dietary nitrate from plant foods as a conditionally essential nutrient for cardiovascular health based on its role in nitric oxide homeostasis. Nitrate derived from plant foods may function as a conditionally essential nutrient, whereas nitrate obtained from other dietary sources, such as drinking water and cured/processed meats, warrants separate consideration because of the associated health risks. We have surveyed the literature and summarized epidemiological evidence regarding the effect of dietary nitrate on cardiovascular disease and risk factors. Meta-analyses and population-based observational studies have consistently demonstrated an inverse association of dietary nitrate with blood pressure and cardiovascular disease outcomes. Considering the available evidence, we suggest 2 different approaches to providing dietary guidance on nitrate from plant-based dietary sources as a nutrient: the Dietary Reference Intakes developed by the National Academies of Sciences, Engineering, and Medicine, and the dietary guidelines evaluated by the Academy of Nutrition and Dietetics. Ultimately, this proposal underscores the need for food-based dietary guidelines to capture the complex and context-dependent relationships between nutrients, particularly dietary nitrate, and health.

Hunger and satiety responses to diets enriched with cottonseed oil vs. olive oil.

Studies suggest that the type of dietary fat consumed habitually may modulate appetite and further influence weight management. The purpose of this study was to evaluate the impact of an 8-week diet intervention enriched with either cottonseed oil (CSO; polyunsaturated fat-rich) or olive oil (OO; monounsaturated fat-rich) on appetite responses in adults with high cholesterol. This was a parallel design, randomized partial outpatient feeding trial designed to provide approximately 60% of participants daily energy needs with ∼30% of energy needs as CSO (n = 21, BMI 27.3 ± 0.92 kg/m2, age 53 ± 2y) or OO (n = 21, BMI 27.6 ± 1.20 kg/m2, age 54 ± 2y). A high saturated fat meal challenge was completed at pre- and post-intervention visits with 5 h postprandial blood draws and visual analog scales (VAS) for cholecystokinin (CCK), peptide YY (PYY), ghrelin, and subjective appetite, respectively. Participants also completed VAS questionnaires hourly and recorded dietary intake after leaving the lab for the remainder of the day. There was a greater increase in fasting CCK (CSO: 0.54 ± 0.03 to 0.56 ± 0.04; OO: 0.63 ± 0.07 to 0.60 ± 0.06 ng/ml p = 0.05), a greater suppression of postprandial ghrelin (p < 0.01), and a greater increase in postprandial VAS fullness (p = 0.04) in CSO compared to OO. Additionally, there was a greater decrease in self-reported energy intake in CSO compared to OO (CSO: 2464 ± 123 to 2115 ± 123; OO: 2263 ± 147 to 2,434 ± 184 kcal/d p = 0.02). Only postprandial VAS prospective consumption showed greater suppression (p = 0.03) in OO vs. CSO. Altogether, these data show that CSO has a greater effect on appetite suppression than OO diet enrichment and may be beneficial for weight maintenance, especially in a population at-risk for chronic disease. Registered at clinicaltrials.gov: NCT04397055.

Blood Lipid Responses to Diets Enriched with Cottonseed Oil Compared With Olive Oil in Adults with High Cholesterol in a Randomized Trial.

BACKGROUND: Increasing unsaturated fat intake is beneficial for cardiovascular health, but the type of unsaturated fat to recommend remains equivocal. OBJECTIVES: We investigated the effects of an 8-week diet intervention that was rich in either cottonseed oil (CSO; PUFA rich) or olive oil (OO; MUFA rich) on blood lipids in hypercholesterolemic adults. METHODS: Forty-three men and women with hypercholesterolemia (53 ± 10 years; BMI, 27.6 ± 4.8 kg/m2) completed this randomized parallel clinical trial consisting of an 8-week partial outpatient feeding intervention. 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 postdiet intervention visits, participants consumed a high-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 5-hour period. RESULTS: There were greater reductions from baseline to week 8 in fasting serum total cholesterol (TC; -17.0 ± 3.94 mg/dL compared with -2.18 ± 3.72 mg/dL, respectively; P = 0.008), LDL cholesterol (-19.7 ± 3.94 mg/dL compared with -5.72 ± 4.23 mg/dL, respectively; P = 0.018), non-HDL cholesterol (-20.8 mg/dL ± 4.00 compared with -6.61 ± 4.01 mg/dL, respectively; P = 0.014), and apoB (-11.8 mg/dL ± 2.37 compared with -3.10 ± 2.99 mg/dL, respectively; P = 0.05), in CSO compared with OO. There were also visit effects from baseline to week 8 for increases in HDL cholesterol (CSO, 56.5 ± 2.79 mg/dL to 60.2 ± 3.35 mg/dL, respectively; OO: 59.7 ± 2.63 mg/dL to 64.1 ± 2.24 mg/dL, respectively; P < 0.001), and decreases in the TC:HDL-cholesterol ratio (CSO, 4.30 ± 0.27 mg/dL to 3.78 ± 0.27 mg/dL, respectively; OO, 3.94 ± 0.16 mg/dL to 3.57 ± 0.11 mg/dL, respectively; 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 nonesterified 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. This trial was registered at clinicaltrials.gov as NCT04397055.