Cashew consumption reduces total and LDL cholesterol: a randomized, crossover, controlled-feeding trial.

Background: Cashews are the third most-consumed tree nut in the United States and are abundant with monounsaturated fatty acids and polyunsaturated fatty acids, which are associated with reduced cardiovascular disease risk. Although a qualified Food and Drug Administration health claim exists for nuts and heart health, cashews have been exempt from its use because cashews exceed the disqualifying amount of saturated fatty acids. Approximately one-third of the saturated fat in cashews is stearic acid, which is relatively neutral on blood lipids, thereby suggesting that cashews could have effects that are similar to those of other nuts. However, clinical data on cashews and blood lipids have been limited.Objective: We investigated the effect of reasonable intakes of cashews on serum lipids in adults with or at risk of high LDL cholesterol.Design: In a randomized, crossover, isocaloric, controlled-feeding study, 51 men and women (aged 21-73 y) with a median LDL-cholesterol concentration of 159 mg/dL (95% CI: 146, 165 mg/dL) at screening consumed typical American diets with cashews (28-64 g/d; 50% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 32% of kilocalories from total fat) or potato chips (control; 54% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 29% of kilocalories from total fat) for 28 d with a ≥2-wk washout period.Results: Consumption of the cashew diet resulted in a significantly greater median change from baseline (compared with the control, all P < 0.05) in total cholesterol [-3.9% (95% CI: -9.3%, 1.7%) compared with 0.8% (95% CI: -1.5%, 4.5%), respectively], LDL cholesterol [-4.8% (95% CI: -12.6%, 3.1%) compared with 1.2% (95% CI: -2.3%, 7.8%), respectively], non-HDL cholesterol [-5.3% (95% CI: -8.6%, 2.1%) compared with 1.7% (95% CI: -0.9%, 5.6%), respectively], and the total-cholesterol:HDL-cholesterol ratio [-0.0% (95% CI: -4.3%, 4.8%) compared with 3.4% (95% CI: 0.6%, 5.2%), respectively]. There were no significant differences between diets for HDL cholesterol and triglyceride.Conclusions: In comparison with a control diet, the incorporation of cashews into typical American diets decreases total cholesterol and LDL cholesterol. Results from this study provide support that the daily consumption of cashews, when substituted for a high-carbohydrate snack, may be a simple dietary strategy to help manage total cholesterol and LDL cholesterol. This study was registered at clinicaltrials.gov as NCT02769741.

A randomized, controlled, crossover trial to assess the acute appetitive and metabolic effects of sausage and egg-based convenience breakfast meals in overweight premenopausal women.

BACKGROUND: Dietary protein at breakfast has been shown to enhance satiety and reduce subsequent energy intake more so than carbohydrate or fat. However, relatively few studies have assessed substitution of protein for carbohydrate on indicators of appetite and glucose homeostasis simultaneously. METHODS: The acute appetitive and metabolic effects of commercially-prepared sausage and egg-based breakfast meals at two different protein levels (30 g and 39 g/serving), vs. a low-protein pancake breakfast (3 g protein) and no breakfast (water), were examined in premenopausal women (N = 35; age 32.5 ± 1.6 yr; BMI 24.8 ± 0.5 kg/m(2)). Test products provided ~280 kcal/serving and similar fat (12-14 g) and fiber contents (0-1 g). Visual Analog Scale ratings for appetite (hunger, fullness, prospective consumption, desire to eat) and repeated blood sampling for plasma glucose and insulin concentrations were assessed throughout each test day. Energy intake was recorded at an ad libitum lunch meal at 240 min. RESULTS: Results showed increased satiety ratings for both the 30 and 39 g protein meals vs. the low-protein and no breakfast conditions (p < 0.001 for all). Postprandial glucose and insulin excursions were lower following the 30 g and 39 g protein conditions vs. the low-protein condition, with smaller responses following the 39 g vs. 30 g protein condition (p < 0.05 for all). Energy intake at lunch was significantly less (p < 0.001) following the 39 g protein meal (692 kcal) vs. the low-protein and no breakfast conditions (789 and 810 kcal, respectively). Total energy intake from the test condition + lunch was higher (p < 0.01) for the 30 and 39 g meals (982 and 983 kcal, respectively) vs. no breakfast (810 kcal), and less than the low protein breakfast (1064 kcal; p < 0.01 vs. 39 g condition only). CONCLUSIONS: Results suggest that convenience meals providing 30 or 39 g protein/serving produce greater appetite control, lower postprandial glycemia and insulinemia, and reduced subsequent intake at lunch relative to a low-protein control, or no breakfast. TRIAL REGISTRATION: NCT01713114.

Sugar-sweetened product consumption alters glucose homeostasis compared with dairy product consumption in men and women at risk of type 2 diabetes mellitus.

BACKGROUND: Dietary patterns characterized by high intakes of fruits and vegetables, whole grains, low-fat dairy products, and low glycemic load have been associated with lower type 2 diabetes mellitus (T2DM) risk. In contrast, dietary patterns that include high intakes of refined grains, processed meats, and high amounts of added sugars have been associated with increased T2DM risk. OBJECTIVE: This randomized, 2-period crossover trial compared the effects of dairy and sugar-sweetened product (SSP) consumption on insulin sensitivity and pancreatic ß-cell function in men and women at risk of the development of T2DM who habitually consume sugar-sweetened beverages. METHODS: In a randomized, controlled crossover trial, participants consumed dairy products (474 mL/d 2% milk and 170 g/d low-fat yogurt) and SSPs (710 mL/d nondiet soda and 108 g/d nondairy pudding), each for 6 wk, with a 2-wk washout between treatments. A liquid meal tolerance test (LMTT) was administered at baseline and the end of each period. RESULTS: Participants were 50% female with a mean age and body mass index of 53.8 y and 32.2 kg/m(2), respectively. Changes from baseline were significantly different between dairy product and SSP conditions for median homeostasis model assessment 2-insulin sensitivity (HOMA2-%S) (1.3 vs. -21.3%, respectively, P = 0.009; baseline = 118%), mean LMTT disposition index (-0.03 vs. -0.36, respectively, P = 0.011; baseline = 2.59), mean HDL cholesterol (0.8 vs. -4.2%, respectively, P = 0.015; baseline = 44.3 mg/dL), and mean serum 25-hydroxyvitamin D [25(OH)D] (11.7 vs. -3.3, respectively, P = 0.022; baseline = 24.5 µg/L). Changes from baseline in LMTT Matsuda insulin sensitivity index (-0.10 vs. -0.49, respectively; baseline = 4.16) and mean HOMA2-ß-cell function (-2.0 vs. 5.3%, respectively; baseline = 72.6%) did not differ significantly between treatments. CONCLUSION: These results suggest that SSP consumption is associated with less favorable values for HOMA2-%S, LMTT disposition index, HDL cholesterol, and serum 25(OH)D in men and women at risk of T2DM vs. baseline values and values during dairy product consumption. This trial was registered at clinicaltrials.gov as NCT01936935.

Corn oil improves the plasma lipoprotein lipid profile compared with extra-virgin olive oil consumption in men and women with elevated cholesterol: results from a randomized controlled feeding trial.

BACKGROUND: Restricted intakes of saturated and trans-fatty acids is emphasized in heart-healthy diets, and replacement with poly- and monounsaturated fatty acids is encouraged. OBJECTIVE: To compare the effects of polyunsaturated fatty acid-rich corn oil (CO) and monounsaturated fatty acid-rich extra-virgin olive oil (EVOO) on plasma lipids in men and women (N = 54) with fasting low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and <200 mg/dL and triglycerides (TG) ≤350 mg/dL. METHODS: In a double-blind, randomized, crossover design (21-day treatments, 21-day washout between), 4 tablespoons/day CO or EVOO were provided in 3 servings study product/day (muffin, roll, yogurt) as part of a weight-maintenance diet (∼35% fat, <10% saturated fat, <300 mg cholesterol). Subjects ate breakfast at the clinic every weekday throughout the study. Lunches, dinners, and snacks (and breakfasts on weekends) were provided for consumption away from the clinic. RESULTS: Baseline mean (standard error) lipids in mg/dL were: LDL-C 153.3 (3.5), total cholesterol (total-C) 225.7 (3.9), non-high-density lipoprotein (non-HDL)-C 178.3 (3.7), HDL-C 47.4 (1.7), total-C/HDL-C 5.0 (0.2), and TG 124.8 (7.2). CO resulted in significantly larger least-squares mean % changes (all P < .001 vs EVOO) from baseline in LDL-C -10.9 vs -3.5, total-C -8.2 vs -1.8, non-HDL-C -9.3 vs -1.6, and total-C/HDL-C -4.4 vs 0.5. TG rose a smaller amount with CO, 3.5 vs 13.0% with EVOO (P = .007). HDL-C responses were not significantly different between conditions (-3.4 vs -1.7%). CONCLUSION: Consumption of CO in a weight-maintenance, low saturated fat and cholesterol diet resulted in more favorable changes in LDL-C and other atherogenic lipids vs EVOO.

Effects of low-fat dairy intake on blood pressure, endothelial function, and lipoprotein lipids in subjects with prehypertension or stage 1 hypertension.

OBJECTIVE: This randomized crossover trial assessed the effects of 5 weeks of consuming low-fat dairy (one serving/day each of 1% fluid milk, low-fat cheese, and low-fat yogurt) versus nondairy products (one serving/day each of apple juice, pretzels, and cereal bar) on systolic and diastolic blood pressures (SBP and DBP), vascular function (reactive hyperemia index [RHI] and augmentation index), and plasma lipids. METHODS: Patients were 62 men and women (mean age 54.5 years, body mass index 29.2 kg/m(2)) with prehypertension or stage 1 hypertension (mean resting SBP/DBP 129.8 mmHg/80.8 mmHg) while not receiving antihypertensive medications. A standard breakfast meal challenge including two servings of study products was administered at the end of each treatment period. RESULTS: Dairy and nondairy treatments did not produce significantly different mean SBP or DBP in the resting postprandial state or from premeal to 3.5 hours postmeal (SBP, 126.3 mmHg versus 124.9 mmHg; DBP, 76.5 mmHg versus 75.7 mmHg), premeal (2.35 versus 2.20) or 2 hours postmeal (2.33 versus 2.30) RHI, and premeal (22.5 versus 23.8) or 2 hours postmeal (12.4 versus 13.2) augmentation index. Among subjects with endothelial dysfunction (RHI ≤ 1.67; n = 14) during the control treatment, premeal RHI was significantly higher in the dairy versus nondairy condition (2.32 versus 1.50, P = 0.002). Fasting lipoprotein lipid values were not significantly different between treatments overall, or in subgroup analyses. CONCLUSION: No significant effects of consuming low-fat dairy products, compared with low-fat nondairy products, were observed for blood pressures, measures of vascular function, or lipid variables in the overall sample, but results from subgroup analyses were consistent with the hypothesis that dairy foods might improve RHI in those with endothelial dysfunction.

Lipid effects of a dietary supplement softgel capsule containing plant sterols/stanols in primary hypercholesterolemia.

OBJECTIVE: This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a softgel capsule dietary supplement, providing esterified plant sterols/stanols 1.8 g/d, in 28 participants (≈ 75% women) with primary hypercholesterolemia (fasting low-density lipoprotein cholesterol [LDL-C] levels ≥ 130 and <220 mg/dL), a mean age of 58.4 y, and a mean body mass index of 27.9 kg/m(2). METHODS: After a 5-wk National Cholesterol Education Program (NCEP) Therapeutic Lifestyle Changes (TLC) diet and a single-blinded placebo lead-in, subjects received double-blinded placebo or sterol/stanol softgel capsules for 6 wk and then crossed over to the opposite product for 6 wk while continuing the TLC diet. Fasting lipids were assessed in duplicate at the end of the diet lead-in (baseline) and the end of each treatment. RESULTS: The mean baseline lipid concentrations (milligrams per deciliter) were 223 for total cholesterol (TC), 179 for non-high-density lipoprotein cholesterol (non-HDL-C), 154 for low-density lipoprotein cholesterol, 44 for HDL-C, 125 for triacylglycerols, and 5.2 for TC/HDL-C. Differences from the control responses (plant sterol/stanol minus control) in the per-protocol sample were significant (P < 0.05) for LDL-C (-9.2%), non-HDL-C (-9.0%), TC (-7.4%), TC/HDL-C (-5.4%), and triacylglycerols (-9.1%). The HDL-C responses were not significantly different between treatments. CONCLUSION: The incorporation of softgel capsules providing esterified plant sterols/stanols 1.8 g/d into the NCEP TLC diet produced favorable changes in atherogenic lipoprotein cholesterol levels in these subjects with hypercholesterolemia.

Absorption of folic acid from a softgel capsule compared to a standard tablet.

Consumption of 400 µg folic acid per day from fortified foods and/or supplements, plus food folate from a varied diet is recommended for women of childbearing potential to reduce the risk for neural tube defects during fetal development. This randomized crossover study was designed to evaluate the bioavailability of folic acid from a multivitamin softgel capsule vs a folic acid tablet in 16 premenopausal women (18 to 45 years of age). Participants were randomly assigned to receive a single dose of ∼1,000 µg folic acid in two tablets or ∼1,000 µg folic acid in a multivitamin softgel capsule, and then crossed over to receive the other study product ∼1 week later. Products were administered with a low-folate breakfast. Blood samples were collected predose (0 hour) and 1, 2, 3, 4, 6, and 8 hours post-dose for serum folate analysis. Repeated measures analysis of variance was used to compare responses between treatments. Data from the two sequence groups (n=8 per sequence) were pooled. Mean serum folate total and net incremental areas under the curve (AUC(0-8 hours)) were not significantly different between tablets and softgel capsule (AUC(0-8 hours) 214.9±11.2 hours×ng/mL [487±25.4 hours×nmol/L] and 191.6±13.3 hours×ng/mL [434.2±30.1 hours×nmol/L]; net incremental AUC(0-8 hours) 117.3±8.5 hours×ng/mL [265.8±19.3 hours×nmol/L] and 105.8±12.5 hours×ng/mL [239.7±28.3 hours×nmol/L], respectively), nor was maximum folate concentration (45.1±2.5 ng/mL [102.2±5.7 nmol/L] and 42.5±3.8 ng/mL [96.3±8.6 nmol/L], respectively). Time to peak folate concentration was significantly (P<0.001) delayed for the softgel capsule vs tablet (3.9±0.3 vs 1.7±0.2 hours, respectively). In conclusion, apparent bioavailability of folic acid was similar for the folic acid tablets and a multivitamin softgel capsule.

Resistant starch from high-amylose maize increases insulin sensitivity in overweight and obese men.

This study evaluated the effects of 2 levels of intake of high-amylose maize type 2 resistant starch (HAM-RS2) on insulin sensitivity (S(I)) in participants with waist circumference ≥89 (women) or ≥102 cm (men). Participants received 0 (control starch), 15, or 30 g/d (double-blind) of HAM-RS2 in random order for 4-wk periods separated by 3-wk washouts. Minimal model S(I) was assessed at the end of each period using the insulin-modified i.v. glucose tolerance test. The efficacy evaluable sample included 11 men and 22 women (mean ± SEM) age 49.5 ± 1.6 y, with a BMI of 30.6 ± 0.5 kg/m2 and waist circumference 105.3 ± 1.3 cm. A treatment main effect (P = 0.018) and a treatment × sex interaction (P = 0.033) were present. In men, least squares geometric mean analysis for S(I) did not differ after intake of 15 g/d HAM-RS2 (6.90 × 10⁻5 pmol⁻¹ · L⁻¹ × min⁻¹) and 30 g/d HAM-RS2 (7.13 × 10⁻5 pmol⁻¹ · L⁻¹ × min⁻¹), but both were higher than after the control treatment (4.66 × 10⁻5 pmol⁻¹ · L⁻¹ × min⁻¹) (P < 0.05). In women, there was no difference among the treatments (overall least squares ln-transformed mean ± pooled SEM = 1.80 ± 0.08; geometric mean = 6.05 × 10⁻5 pmol⁻¹ · L⁻¹ × min⁻¹). These results suggest that consumption of 15-30 g/d of HAM-RS2 improves S(I) in men. Additional research is needed to understand the mechanisms that might account for the treatment × sex interaction observed.

Lipid-altering effects of a dietary supplement tablet containing free plant sterols and stanols in men and women with primary hypercholesterolaemia: a randomized, placebo-controlled crossover trial.

This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a dietary supplement (tablet form) providing 1.8 g/day free (non-esterified) plant sterols and stanols versus placebo for 6 weeks as part of a therapeutic lifestyle changes (TLC) diet in 32 men and women with primary hypercholesterolaemia. Mean ± SE baseline (end of a 5-week TLC diet lead-in) lipid concentrations (mmol/l) were total cholesterol (TC), 5.88 ± 0.08; non-high-density lipoprotein cholesterol (non-HDL-C), 4.71 ± 0.09; low-density lipoprotein cholesterol (LDL-C), 4.02 ± 0.08; HDL-C, 1.17 ± 0.06 and triglycerides (TGs), 1.51 ± 0.12. Differences from control in responses (plant sterol/stanol - control) were significant (p < 0.05) for LDL-C ( - 4.9%), non-HDL-C ( - 3.6%) and TC ( - 2.8%). HDL-C and TG responses were not significantly different between treatment conditions. These results indicate that 1.8 g/day free plant sterols/stanols administered in a tablet produced favourable lipoprotein lipid changes in men and women with hypercholesterolaemia.

Prescription omega-3-acid ethyl esters reduce fasting and postprandial triglycerides and modestly reduce pancreatic ß-cell response in subjects with primary hypertriglyceridemia.

Treatment with prescription omega-3-acid ethyl esters (POM3) reduces triglycerides (TG) and TG-rich lipoprotein particles, but has been associated with increased fasting glucose (2-6mg/dL). This double-blind, randomized, controlled crossover trial in 19 men and women with hypertriglyceridemia (fasting TG ≥150 and ≤499mg/dL) examined lipid responses and indices of insulin sensitivity and secretion following a liquid meal tolerance test. Six weeks treatment with POM3 vs. corn oil resulted in significant lower mean fasting (-50.1mg/dL, p<0.001) and postprandial TG (-76.1mg/dL, p<0.001), higher mean fasting glucose (2.8mg/dL, p=0.062), reduced mean disposition index (2.1 vs. 2.4, p=0.037), and no change in the median Matsuda composite insulin sensitivity index (3.3 vs. 3.2, p=0.959). These results suggest that POM3 slightly reduces pancreatic ß-cell responsiveness to plasma glucose elevation, which may contribute to the rise in fasting glucose sometimes observed with POM3.

Validation of insulin sensitivity and secretion indices derived from the liquid meal tolerance test.

BACKGROUND: A liquid meal tolerance test (LMTT) has been proposed as a useful alternative to more labor-intensive methods of assessing insulin sensitivity and secretion. OBJECTIVE: This substudy, conducted at the conclusion of a randomized, double-blind crossover trial, compared insulin sensitivity indices from a LMTT (Matsuda insulin sensitivity index [MISI] and LMTT disposition index [LMTT-DI]) with indices derived from minimal model analysis of results from the insulin-modified intravenous glucose tolerance test (IVGTT) (insulin sensitivity index [S(I)] and disposition index [DI]). RESULTS: Participants included men (n = 16) and women (n = 8) without diabetes but with increased abdominal adiposity (waist circumference ≥102 cm and ≥89 cm, respectively) and mean age of 48.9 years. The correlation between S(I) and the MISI was 0.776 (P < 0.0001). The respective associations between S(I) and MISI with waist circumference (r = -0.445 and -0.554, both P < 0.05) and body mass index were similar (r = -0.500 and -0.539, P < 0.05). The correlation between DI and LMTT-DI was 0.604 (P = 0.002). CONCLUSIONS: These results indicate that indices of insulin sensitivity and secretion derived from the LMTT correlate well with those from the insulin-modified IVGTT with minimal model analysis, suggesting that they may be useful for application in clinical and population studies of glucose homeostasis.

Effects of prescription omega-3-acid ethyl esters on fasting lipid profile in subjects with primary hypercholesterolemia.

This double-blind, randomized crossover study investigated the effects of 6 weeks of treatment with prescription omega-3-acid ethyl esters (POM3, 4 g/day) versus placebo (soy oil) on low-density lipoprotein cholesterol (LDL-C) and other aspects of the fasting lipid profile in 31 men and women with primary, isolated hypercholesterolemia (LDL-C 130-220 mg/dL and triglycerides less than 150 mg/dL while free of lipid-altering therapies). Mean ± standard error of the mean baseline concentrations of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein cholesterol, and triglycerides were 229 ± 3, 146 ± 3, 60 ± 2, 23 ± 2, and 113 ± 8 mg/dL, respectively. POM3 produced a modest increase from baseline in LDL-C (3.4%) versus the placebo response (-0.7%, P = 0.010). Significant changes (P < 0.05) for POM3 (placebo-corrected) were observed for very-low-density lipoprotein cholesterol (-18.8%), triglycerides (-18.7%), and HDL-C (3.3%). Nuclear magnetic resonance-determined very-low-density lipoprotein particle concentration and size and HDL particle concentration decreased significantly more with POM3 versus placebo, whereas LDL and HDL particle sizes increased significantly more with POM3 versus placebo. Total cholesterol, non-HDL-C, apolipoproteins A1 and B, and LDL particle concentration responses did not differ between treatments. These results did not confirm the hypothesis that POM3 treatment would lower LDL-C in primary, isolated hypercholesterolemia. Effects on other variables were consistent with prior results in mixed dyslipidemia.