Effect of Mediterranean diet with and without weight loss on apolipoprotein B100 metabolism in men with metabolic syndrome.

OBJECTIVE: To assess the effect of a Mediterranean diet (MedDiet) with and without weight loss (WL) on apolipoprotein B100 (apoB100) metabolism in men with metabolic syndrome. APPROACH AND RESULTS: The diet of 19 men with metabolic syndrome (age, 24-62 years) was first standardized to a North American isoenergetic control diet for 5 weeks, followed by an isoenergetic MedDiet for an additional 5 weeks under full-feeding conditions (MedDiet-WL). Participants next underwent a 20-week supervised WL program under free-living conditions (-10.2 ± 2.9% body weight; P<0.01) and finally consumed the MedDiet (5 weeks) under weight-stabilizing feeding conditions (MedDiet+WL). In vivo kinetic of apoB100 was assessed in the fasted state at the end of the 3 controlled diets using a bolus of D3-leucine. Compared with the control diet, MedDiet-WL reduced low-density lipoprotein (LDL)-apoB100 pool size (-14.2%, P<0.01) primarily through an increase in LDL-apoB100 fractional catabolic rate (+30.4%, P=0.02) and increased LDL particle size (P<0.01) but had no effect on very-LDL (VLDL)-apoB100 pool size or triglyceride concentrations, despite a significant increase in VLDL-apoB100 fractional catabolic rate (+25.6%; P=0.03). MedDiet+WL had no further effect on LDL-apoB100 pool size and fractional catabolic rate but further increased LDL particle size and reduced VLDL-apoB100 pool size versus the control diet primarily through an increase in VLDL-apoB100 fractional catabolic rate (+30.7%; P<0.01). CONCLUSIONS: Consumption of MedDiet increases LDL size and reduces LDL-apoB100 concentrations primarily by increasing the catabolism of LDL even in the absence of WL in men with metabolic syndrome. MedDiet seems to have a trivial effect on VLDL concentrations and kinetics unless accompanied by significant WL. CLINICAL TRIAL REGISTRATION -URL: http://www.clinicaltrials.gov. Unique identifier: NCT00988650.

Impact of milk consumption on cardiometabolic risk in postmenopausal women with abdominal obesity.

BACKGROUND: The impact of dairy intake on cardiometabolic risk factors associated with metabolic syndrome (MetS) needs further research. OBJECTIVE: To investigate the impact of milk consumption on a wide array of cardiometabolic risk factors associated with MetS (blood lipids, cholesterol homeostasis, glucose homeostasis, systemic inflammation, blood pressure, endothelial function) in postmenopausal women with abdominal obesity. METHODS: In this randomized, crossover study, 27 women with abdominal obesity consumed two 6-week diets based on the National Cholesterol Education Program (NCEP), one with 3.2 servings/d of 2% fat milk per 2000 kcal (MILK) and one without milk or other dairy (NCEP). The macronutrient composition of both diets was comparable (55% carbohydrates, 15% proteins, 30% fat and 10% saturated fat). RESULTS: The MILK diet had no significant effect on LDL-C, triglycerides, LDL size, CRP and cell adhesion molecule concentrations and on indicators of insulin sensitivity. The MILK diet reduced HDL-C, adiponectin, endothelin and fasting glucose levels as well blood pressure (all P ≤ 0.01), but those changes were comparable to those seen with the NCEP milk-free diet (all between-diet P ≥ 0.07). Finally, the MILK diet was associated with lower VLDL apolipoprotein B fractional catabolic rate (-13.4%; P = 0.04) and plasma sterol concentrations (-12.0%; P = 0.04) compared with the control NCEP milk-free diet. CONCLUSIONS: These data suggest that short-term consumption of low fat milk in the context of a prudent NCEP diet has no favorable nor deleterious effect on cardiometabolic risk factors associated with MetS in postmenopausal women with abdominal obesity.

Substitution of dietary monounsaturated fatty acids from olive oil for saturated fatty acids from lard increases low-density lipoprotein apolipoprotein B-100 fractional catabolic rate in subjects with dyslipidemia associated with insulin resistance: a randomized controlled trial.

BACKGROUND: The substitution of monounsaturated acids (MUFAs) for saturated fatty acids (SFAs) is recommended for cardiovascular disease prevention but its impact on lipoprotein metabolism in subjects with dyslipidemia associated with insulin resistance (IR) remains largely unknown. OBJECTIVES: This study aimed to evaluate the impact of substituting MUFAs for SFAs on the in vivo kinetics of apolipoprotein (apo)B-containing lipoproteins and on the plasma lipidomic profile in adults with IR-induced dyslipidemia. METHODS: Males and females with dyslipidemia associated with IR (n = 18) were recruited for this crossover double-blind randomized controlled trial. Subjects consumed, in random order, a diet rich in SFAs (SFAs: 13.4%E; MUFAs: 14.4%E) and a diet rich in MUFAs (SFAs: 7.1%E; MUFAs: 20.7%E) in fully controlled feeding conditions for periods of 4 wk each, separated by a 4-wk washout. At the end of each diet, fasting plasma samples were taken together with measurements of the in vivo kinetics of apoB-containing lipoproteins. RESULTS: Substituting MUFAs for SFAs had no impact on triglyceride-rich lipoprotein apoB-48 fractional catabolic rate (FCR) (Δ = -8.9%, P = 0.4) and production rate (Δ = 0.0%, P = 0.9), although it decreased very low-density lipoprotein apoB-100 pool size (PS) (Δ = -22.5%; P = 0.01). This substitution also reduced low-density lipoprotein cholesterol (LDL-C) (Δ = -7.0%; P = 0.01), non-high-density lipoprotein cholesterol (Δ = -2.5%; P = 0.04), and LDL apoB-100 PS (Δ = -6.0%; P = 0.05). These differences were partially attributed to an increase in LDL apoB-100 FCR (Δ = +1.6%; P = 0.05). The MUFA diet showed reduced sphingolipid concentrations and elevated glycerophospholipid levels compared with the SFA diet. CONCLUSIONS: This study demonstrated that substituting dietary MUFAs for SFAs decreases LDL-C levels and LDL PS by increasing LDL apoB-100 FCR and results in an overall improved plasma lipidomic profile in individuals with IR-induced lipidemia. TRIAL REGISTRATION: This trial was registered as clinicaltrials.gov as NCT03872349.

Effects of regular-fat and low-fat dairy consumption on daytime ambulatory blood pressure and other cardiometabolic risk factors: a randomized controlled feeding trial.

BACKGROUND: The extent to which dairy products and their fat content influence cardiovascular health remains uncertain. OBJECTIVE: This study aimed to assess how consumption of low-fat milk and regular-fat cheese enriched in γ-aminobutyric acid (GABA) influences daytime ambulatory blood pressure (BP) and other cardiometabolic risk factors. METHODS: In this crossover controlled feeding study, 55 healthy men and women with high-normal daytime BP were randomly assigned to sequences of three 6-wk isoenergetic diets, each comprising 1) no dairy (control diet), 2) 3 daily servings of 1% fat milk, and 3) 1 daily serving of 31% fat cheddar cheese naturally enriched in GABA. Total proteins, carbohydrates, and fats were matched across all 3 diets. The additional 2% of energy from SFAs in the cheese diet was replaced by n-6 PUFAs in the other diets. RESULTS: Comparison of postdiet ambulatory systolic BP revealed no difference (P = 0.34), which was also the case for ambulatory diastolic BP (P = 0.45). The cheese diet increased serum LDL-cholesterol concentrations compared with the control and milk diets (+5.8%, P = 0.006 and +7.0%, P = 0.0008, respectively) and increased LDL particle size compared with the milk diet (P = 0.02). HDL-cholesterol concentrations after the milk diet were lower than after the control diet (-4.1%; P = 0.009). The milk and cheese diets increased triglycerides compared with the control diet (+9.9%, P = 0.01 and +10.5%, P = 0.007, respectively). There was no significant difference between all diets for C-reactive protein concentrations and markers of glucose/insulin homeostasis. CONCLUSIONS: These results suggest that short-term consumption of dairy products, whether low or regular in fat, has no overall effect on daytime ambulatory BP compared with a dairy-free diet. Other cardiometabolic risk factors may be differently modified according to the fat content of the dairy product. This trial was registered at clinicaltrials.gov as NCT02763930.

Comparing Interviewer-Administered and Web-Based Food Frequency Questionnaires to Predict Energy Requirements in Adults.

Traditional food frequency questionnaires (FFQs) are influenced by systematic error, but web-based FFQ (WEB-FFQs) may mitigate this source of error. The objective of this study was to compare the accuracy of interview-based and web-based FFQs to assess energy requirements (mERs). The mER was measured in a series of controlled feeding trials in which participants daily received all foods and caloric drinks to maintain stable body weight over 4 to 6 weeks. FFQs assessing dietary intakes and hence mean energy intake were either interviewer-administered by a registered dietitian (IA-FFQ, n = 127; control method) or self-administered using a web-based platform (WEB-FFQ, n = 200; test method), on a single occasion. Comparison between self-reported energy intake and mER revealed significant under-reporting with the IA-FFQ (-9.5%; 95% CI, -12.7 to -6.1) and with the WEB-FFQ (-11.0%; 95% CI, -15.4 to -6.4), but to a similar extent between FFQs (p = 0.62). However, a greater proportion of individuals were considered as accurate reporters of energy intake using the IA-FFQ compared with the WEB-FFQ (67.7% vs. 48.0%, respectively), while the prevalence of over-reporting was lower with the IA-FFQ than with the WEB-FFQ (6.3% vs. 17.5%, respectively). These results suggest less accurate prediction of true energy intake by a self-administered WEB-FFQ than with an IA-FFQ.

High-Dose DHA Has More Profound Effects on LDL-Related Features Than High-Dose EPA: The ComparED Study.

Context: Supplementation with high-dose docosahexaenoic acid (DHA) increases serum low-density lipoprotein (LDL) cholesterol (LDL-C) concentrations more than high-dose eicosapentaenoic acid (EPA). The mechanisms underlying this difference are unknown. Objective: To examine the phenotypic change in LDL and mechanisms responsible for the differential LDL-C response to EPA and DHA supplementation in men and women at risk of cardiovascular disease. Design, Setting, Participants, and Intervention: In a double-blind, controlled, crossover study, 48 men and 106 women with abdominal obesity and subclinical inflammation were randomized to a sequence of three treatment phases: phase 1, 2.7 g/d of EPA; phase 2, 2.7 g/d of DHA; and phase 3, 3 g/d of corn oil. All supplements were provided as three 1-g capsules for a total of 3 g/d. The 10-week treatment phases were separated by a 9-week washout period. Main Outcome Measure: In vivo kinetics of apolipoprotein (apo)B100-containing lipoproteins were assessed using primed-constant infusion of deuterated leucine at the end of each treatment in a subset of participants (n = 19). Results: Compared with EPA, DHA increased LDL-C concentrations (+3.3%; P = 0.038) and mean LDL particle size (+0.7 Å; P < 0.001) and reduced the proportion of small LDL (-3.2%; P < 0.01). Both EPA and DHA decreased proprotein convertase subtilisin/kexin type 9 concentrations similarly (-18.2% vs -25.0%; P < 0.0001 vs control). Compared with EPA, DHA supplementation increased both the LDL apoB100 fractional catabolic rate (+11.4%; P = 0.008) and the production rate (+9.4%; P = 0.03). Conclusions: The results of the present study have shown that supplementation with high-dose DHA increases LDL turnover and contributes to larger LDL particles compared with EPA.

Inflammatory gene expression in whole blood cells after EPA vs. DHA supplementation: Results from the ComparED study.

BACKGROUND AND AIMS: Whether EPA and DHA exert similar anti-inflammatory effects through modulation of gene expression in immune cells remains unclear. The aim of the study was to compare the impact of EPA and DHA supplementation on inflammatory gene expression in subjects at risk for cardiometabolic diseases. METHODS: In this randomized double-blind crossover trial, 154 men and women with abdominal obesity and low-grade inflammation were subjected to three 10-wk supplementation phases: 1) EPA (2.7 g/d); 2) DHA (2.7 g/d); 3) corn oil (3 g/d), separated by a 9-wk washout. Pro- and anti-inflammatory gene expression was assessed in whole blood cells by RT-qPCR after each treatment in a representative sample of 44 participants. RESULTS: No significant difference was observed between EPA and DHA in the expression of any of the genes investigated. Compared with control, EPA enhanced TRAF3 and PPARA expression and lowered CD14 expression (p < 0.01) whereas DHA increased expression of PPARA and TNFA and decreased CD14 expression (p < 0.05). Variations in gene expression after EPA and after DHA were strongly correlated for PPARA (r = 0.73, p < 0.0001) and TRAF3 (r = 0.66, p < 0.0001) and less for TNFA (r = 0.46, p < 0.005) and CD14 (r = 0.16, p = 0.30). CONCLUSIONS: High-dose supplementation with either EPA or DHA has similar effects on the expression of many inflammation-related genes in immune cells of men and women at risk for cardiometabolic diseases. The effects of EPA and of DHA on anti-inflammatory gene expression may be more consistent than their effects on expression of pro-inflammatory genes in whole blood cells.

Differential impact of the cheese matrix on the postprandial lipid response: a randomized, crossover, controlled trial.

Background: In a simulated gastrointestinal environment, the cheese matrix modulates dairy fat digestion. However, to our knowledge, the impact of the cheese matrix on postprandial lipemia in humans has not yet been evaluated.Objective: In healthy subjects, we compared the impact of dairy fat provided from firm cheese, soft cream cheese, and butter on the postprandial response at 4 h and on the incremental area under the curve (iAUC) of plasma triglycerides.Design: Forty-three healthy subjects were recruited to this randomized, crossover, controlled trial. In random order at intervals of 14 d and after a 12-h fast, subjects ingested 33 g fat from a firm cheese (young cheddar), a soft cream cheese (cream cheese), or butter (control) incorporated into standardized meals that were matched for macronutrient content. Plasma concentrations of triglycerides were measured immediately before the meal and 2, 4, 6, and 8 h after the meal.Results: Cheddar cheese, cream cheese, and butter induced similar increases in triglyceride concentrations at 4 h (change from baseline: +59%, +59%, and +62%, respectively; P = 0.9). No difference in the triglyceride iAUC0-8 h (P-meal = 0.9) was observed between the 3 meals. However, at 2 h, the triglyceride response caused by the cream cheese (change from baseline: +44%) was significantly greater than that induced by butter (change from baseline: +24%; P = 0.002) and cheddar cheese (change from baseline: +16%; P = 0.0004). At 6 h, the triglyceride response induced by cream cheese was significantly attenuated compared with that induced by cheddar cheese (change from baseline: +14% compared with +42%; P = 0.0004).Conclusion: This study demonstrates that the cheese matrix modulates the impact of dairy fat on postprandial lipemia in healthy subjects. This trial was registered at clinicaltrials.gov as NCT02623790.

Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index more than high-dose eicosapentaenoic acid.

BACKGROUND: Recent studies suggest that eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have distinct effects on cardiometabolic risk factors. The Omega-3 Index (O3I), which is calculated as the proportion of EPA and DHA in red blood cell (RBC) membranes, has been inversely associated with the risk of coronary heart diseases and coronary mortality. The objective of this study was to compare the effects of EPA and DHA supplementation on the O3I in men and women with abdominal obesity and subclinical inflammation. METHODS: In a double-blind controlled crossover study, 48 men and 106 women with abdominal obesity and subclinical inflammation were randomized to a sequence of three treatment phases: 1-2.7g/d of EPA, 2-2.7g/d of DHA, and 3-3g/d of corn oil (0g of EPA+DHA). All supplements were provided as 3×1g capsules for a total of 3g/d. The 10-week treatment phases were separated by nine-week washouts. RBC membrane fatty acid composition and O3I were assessed at baseline and the end of each phase. Differences in O3I between treatments were assessed using mixed models for repeated measures. RESULTS: The increase in the O3I after supplementation with DHA (+5.6% compared with control, P<0.0001) was significantly greater than after EPA (+3.3% compared with control, P<0.0001; DHA vs. EPA, P<0.0001). Compared to control, DHA supplementation decreased (-0.8%, P<0.0001) while EPA increased (+2.5%, P<0.0001) proportion of docosapentaenoic acid (DPA) in RBCs (DHA vs. EPA, P<0.0001). The baseline O3I was higher in women than in men (6.3% vs. 5.8%, P=0.011). The difference between DHA and EPA in increasing the O3I tended to be higher in men than in women (+2.6% vs. +2.2% respectively, P for the treatment by sex interaction=0.0537). CONCLUSIONS: The increase in the O3I is greater with high dose DHA supplementation than with high dose EPA, which is consistent with the greater potency of DHA to modulate cardiometabolic risk factors. The extent to which such differences between EPA and DHA in increasing the O3I relates to long-term cardiovascular risk needs to be investigated in the future.

Effect of weight loss resulting from a combined low-fat diet/exercise regimen on low-density lipoprotein particle size and distribution in obese women.

Weight loss resulting from diet interventions has been shown to favorably affect low-density lipoprotein (LDL) particle size and distribution, and, hence, decrease cardiovascular disease risk. However, the effect of a dietary weight loss strategy when combined with exercise, on LDL electrophoretic characteristics, has yet to be tested. This study examined the effect of a weight loss intervention that combined a low-fat diet with moderate endurance training, on LDL particle size and distribution in obese women. Thirty obese, hypercholesterolemic women participated in a controlled longitudinal weight loss trial, which consisted of (1) a 2-week pre-stabilization phase, (2) a 20-week weight loss phase, and (3) a 2-week post-stabilization phase. Weight reduction resulted from a low-fat diet (<30% fat, 50%-60% carbohydrate, 20% protein) combined with an endurance training program (>40 minutes moderate training, 3 times per week). Mean weight loss was 14.8% (P < .01) of initial body weight. Total, LDL cholesterol, and triacylglycerol concentrations decreased (P < .01) by 8.9%, 7.5%, and 27.1%, respectively, whereas high-density lipoprotein cholesterol concentrations increased (P < .01) by 9.9%. No significant differences were noted for LDL peak or integrated particle size. The relative proportion of small, medium, and large particles was not significantly different posttreatment. Estimated cholesterol concentrations in large- and medium-sized LDL particles decreased (P < .05) by 15.3% and 5.9%, respectively, as a result of weight loss. No effect was noted for estimated cholesterol concentrations in small size LDL particles. In conclusion, these findings suggest that weight loss, resulting from a low-fat diet/exercise program, has only a minimal effect on LDL particle size and distribution.

A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA (ComparED) Study.

BACKGROUND: To date, most studies on the anti-inflammatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans have used a mixture of the 2 fatty acids in various forms and proportions. OBJECTIVES: We compared the effects of EPA supplementation with those of DHA supplementation (re-esterified triacylglycerol; 90% pure) on inflammation markers (primary outcome) and blood lipids (secondary outcome) in men and women at risk of cardiovascular disease. DESIGN: In a double-blind, randomized, crossover, controlled study, healthy men (n = 48) and women (n = 106) with abdominal obesity and low-grade systemic inflammation consumed 3 g/d of the following supplements for periods of 10 wk: 1) EPA (2.7 g/d), 2) DHA (2.7 g/d), and 3) corn oil as a control with each supplementation separated by a 9-wk washout period. Primary analyses assessed the difference in cardiometabolic outcomes between EPA and DHA. RESULTS: Supplementation with DHA compared with supplementation with EPA led to a greater reduction in interleukin-18 (IL-18) (-7.0% ± 2.8% compared with -0.5% ± 3.0%, respectively; P = 0.01) and a greater increase in adiponectin (3.1% ± 1.6% compared with -1.2% ± 1.7%, respectively; P < 0.001). Between DHA and EPA, changes in CRP (-7.9% ± 5.0% compared with -1.8% ± 6.5%, respectively; P = 0.25), IL-6 (-12.0% ± 7.0% compared with -13.4% ± 7.0%, respectively; P = 0.86), and tumor necrosis factor-α (-14.8% ± 5.1% compared with -7.6% ± 10.2%, respectively; P = 0.63) were NS. DHA compared with EPA led to more pronounced reductions in triglycerides (-13.3% ± 2.3% compared with -11.9% ± 2.2%, respectively; P = 0.005) and the cholesterol:HDL-cholesterol ratio (-2.5% ± 1.3% compared with 0.3% ± 1.1%, respectively; P = 0.006) and greater increases in HDL cholesterol (7.6% ± 1.4% compared with -0.7% ± 1.1%, respectively; P < 0.0001) and LDL cholesterol (6.9% ± 1.8% compared with 2.2% ± 1.6%, respectively; P = 0.04). The increase in LDL-cholesterol concentrations for DHA compared with EPA was significant in men but not in women (P-treatment × sex interaction = 0.046). CONCLUSIONS: DHA is more effective than EPA in modulating specific markers of inflammation as well as blood lipids. Additional studies are needed to determine the effect of a long-term DHA supplementation per se on cardiovascular disease risk. This trial was registered at clinicaltrials.gov as NCT01810003.

DHA-enriched high-oleic acid canola oil improves lipid profile and lowers predicted cardiovascular disease risk in the canola oil multicenter randomized controlled trial.

BACKGROUND: It is well recognized that amounts of trans and saturated fats should be minimized in Western diets; however, considerable debate remains regarding optimal amounts of dietary n-9, n-6, and n-3 fatty acids. OBJECTIVE: The objective was to examine the effects of varying n-9, n-6, and longer-chain n-3 fatty acid composition on markers of coronary heart disease (CHD) risk. DESIGN: A randomized, double-blind, 5-period, crossover design was used. Each 4-wk treatment period was separated by 4-wk washout intervals. Volunteers with abdominal obesity consumed each of 5 identical weight-maintaining, fixed-composition diets with one of the following treatment oils (60 g/3000 kcal) in beverages: 1) conventional canola oil (Canola; n-9 rich), 2) high-oleic acid canola oil with docosahexaenoic acid (CanolaDHA; n-9 and n-3 rich), 3) a blend of corn and safflower oil (25:75) (CornSaff; n-6 rich), 4) a blend of flax and safflower oils (60:40) (FlaxSaff; n-6 and short-chain n-3 rich), or 5) high-oleic acid canola oil (CanolaOleic; highest in n-9). RESULTS: One hundred thirty individuals completed the trial. At endpoint, total cholesterol (TC) was lowest after the FlaxSaff phase (P < 0.05 compared with Canola and CanolaDHA) and highest after the CanolaDHA phase (P < 0.05 compared with CornSaff, FlaxSaff, and CanolaOleic). Low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were highest, and triglycerides were lowest, after CanolaDHA (P < 0.05 compared with the other diets). All diets decreased TC and LDL cholesterol from baseline to treatment endpoint (P < 0.05). CanolaDHA was the only diet that increased HDL cholesterol from baseline (3.5 ± 1.8%; P < 0.05) and produced the greatest reduction in triglycerides (-20.7 ± 3.8%; P < 0.001) and in systolic blood pressure (-3.3 ± 0.8%; P < 0.001) compared with the other diets (P < 0.05). Percentage reductions in Framingham 10-y CHD risk scores (FRS) from baseline were greatest after CanolaDHA (-19.0 ± 3.1%; P < 0.001) than after other treatments (P < 0.05). CONCLUSION: Consumption of CanolaDHA, a novel DHA-rich canola oil, improves HDL cholesterol, triglycerides, and blood pressure, thereby reducing FRS compared with other oils varying in unsaturated fatty acid composition. This trial was registered at www.clinicaltrials.gov as NCT01351012.

Short-term, high-fat diet increases the expression of key intestinal genes involved in lipoprotein metabolism in healthy men.

BACKGROUND: The modulation of cholesterol and fatty acid homeostasis by dietary fatty acids is thought to be mediated by changes in the expression of key intestinal genes involved in lipoprotein metabolism. However, the short-term effect of dietary fat intake on the expression of these genes has not been fully investigated in humans. OBJECTIVE: To test whether short-term changes in dietary fatty acid intake affect the expression of key intestinal genes involved in lipoprotein metabolism, we conducted a randomized, double-blind, crossover study in 12 nonobese, healthy men with normal plasma lipid profiles. DESIGN: Participants were subjected to the following 2 intensive 3-d dietary interventions under isocaloric conditions: 1) a high-fat diet (37% of energy from fat and 50% of energy from carbohydrates) and 2) a low-fat diet (25% of energy from fat and 62% of energy from carbohydrates). Expressions of key genes involved in lipoprotein metabolism were compared by using real-time polymerase chain reaction quantification on duodenal biopsy specimens obtained in a fasting state after each diet. RESULTS: After the 3-d high-fat diet, plasma cholesterol, LDL cholesterol, and HDL cholesterol concentrations were significantly higher than concentrations observed after the low-fat diet was consumed. The high-fat diet also resulted in significant increases in the intestinal messenger RNA expression of several key genes involved in lipoprotein metabolism. Plasma triglycerides and apolipoprotein B-48 concentrations were significantly lower after the high-fat diet than after the low-fat diet. CONCLUSION: These findings suggest that short-term exposure to a high-fat diet upregulates the expression of key genes involved in lipid and lipoprotein metabolism at the enterocyte level. This trial was registered at clinicaltrials.gov as NCT01806441.

Effect of short-term low- and high-fat diets on low-density lipoprotein particle size in normolipidemic subjects.

High-fat, low-carbohydrate diets have been shown to raise plasma cholesterol levels, an effect associated with the formation of large low-density lipoprotein (LDL) particles. However, the impact of dietary intervention on time-course changes in LDL particle size has not been investigated. To test whether a short-term dietary intervention affects LDL particle size, we conducted a randomized, double-blind, crossover study using an intensive dietary modification in 12 nonobese healthy men with normal plasma lipid profile. Participants were subjected to 2 isocaloric 3-day diets: high-fat diet (37% energy from fat and 50% from carbohydrates) and low-fat diet (25% energy from fat and 62% from carbohydrates). Plasma lipid levels and LDL particle size were assessed on fasting blood samples after 3 days of feeding on each diet. The LDL particles were characterized by polyacrylamide gradient gel electrophoresis. Compared with the low-fat diet, plasma cholesterol, LDL cholesterol, and high-density lipoprotein cholesterol were significantly increased (4.45 vs 4.78 mmol/L, P = .04; 2.48 vs 2.90 mmol/L, P = .005; and 1.29 vs 1.41 mmol/L, P = .005, respectively) following the 3-day high-fat diet. Plasma triglycerides and fasting apolipoprotein B-48 levels were significantly decreased after the high-fat diet compared with the low-fat diet (1.48 vs 1.01 mmol/L, P = .0003 and 9.6 vs 5.5 mg/L, P = .008, respectively). The high-fat diet was also associated with a significant increase in LDL particle size (255.0 vs 255.9 Å;P = .01) and a significant decrease in the proportion of small LDL particle (<255.0 Å) (50.7% vs 44.6%, P = .01). As compared with a low-fat diet, the cholesterol-raising effect of a high-fat diet is associated with the formation of large LDL particles after only 3 days of feeding.

Randomized controlled study of the effect of a butter naturally enriched in trans fatty acids on blood lipids in healthy women.

BACKGROUND: Whereas the negative effect of consuming trans fatty acids found in partially hydrogenated vegetable oils on cardiovascular disease (CVD) risk is well established, the effect of trans fatty acids from ruminant sources (rTFAs) on CVD risk factors has not yet been established, particularly among women. OBJECTIVE: We investigated the effects of a butter naturally enriched in rTFAs, of which vaccenic acid is the predominant isomer, on plasma lipid concentrations among healthy women. DESIGN: In a double-blind, randomized, crossover controlled study, 61 healthy women aged 19-70 y were fed 2 isoenergetic diets lasting 4 wk each. The 2 diets were defined as moderately high in rTFAs (3.7 g/d, 1.5% of daily energy) and control (0.9 g/d, 0.3% of daily energy). RESULTS: No significant effect of the rTFA diet was found on total plasma cholesterol, LDL cholesterol, apolipoprotein B, apolipoprotein A-I, and triglyceride concentrations compared with the control diet. There was a small yet statistically significant reduction in plasma HDL-cholesterol concentrations with the rTFA diet (-2.8%; P = 0.004), which was significant (P for the BMI × treatment interaction = 0.006) among women with a BMI (in kg/m(2)) ≥25 (-5.2%; P = 0.004; n = 18) but not among women with a BMI <25 (-1.2%; P = 0.13; n = 43). CONCLUSIONS: These results suggest that an increase in dietary rTFAs equivalent to ∼1% of daily energy has no significant effect on LDL but may be associated with a reduction in plasma HDL-cholesterol concentrations, particularly in overweight women. This trial is registered at clinicaltrials.gov as NCT00930137.

Study of the effect of trans fatty acids from ruminants on blood lipids and other risk factors for cardiovascular disease.

BACKGROUND: The intake of trans fatty acids (TFA) from industrially hydrogenated vegetable oils (iTFA) is known to have a deleterious effect on cardiovascular health, the effects of TFA from ruminants (rTFA) are virtually unknown. OBJECTIVE: The purpose of the present study was to compare the effects of rTFA and iTFA on plasma LDL concentrations and other cardiovascular disease risk factors in healthy subjects. DESIGN: In a double-blind, randomized crossover controlled study, 38 healthy men were fed each of 4 experimental isoenergetic diets lasting 4 wk each. The 4 diets were high in rTFA (10.2 g/2500 kcal), moderate in rTFA (4.2 g/2500 kcal), high in iTFA (10.2 g/2500 kcal), and low in TFA from any source (2.2 g/2500 kcal) (control diet). RESULTS: Plasma LDL-cholesterol concentrations were significantly higher after the high- rTFA diet than after the control (P = 0.03) or the moderate- rTFA (P = 0.002) diet. Plasma LDL-cholesterol concentrations also were significantly (P = 0.02) higher after the iTFA diet than after the moderate-rTFA diet. Plasma HDL-cholesterol concentrations were significantly (P = 0.02) lower after the high-rTFA diet than after the moderate-rTFA diet. Finally, all risk factors were comparable between the control and the moderate-rTFA diets. CONCLUSIONS: These results suggest that, whereas a high dietary intake of TFA from ruminants may adversely affect cholesterol homeostasis, moderate intakes of rTFA that are well above the upper limit of current human consumption have neutral effects on plasma lipids and other cardiovascular disease risk factors.

Unesterified plant sterols and stanols do not affect LDL electrophoretic characteristics in hypercholesterolemic subjects.

The extent to which sterols and stanols modulate LDL particle size is unknown. We examined the effects of supplementation with unesterified plant sterols and stanols on several LDL electrophoretic characteristics. Healthy hypercholesterolemic subjects (n = 14) consumed each of four experimental diets contained plant sterols (S), plant stanols (SN), a 50:50 mixture of sterols and stanols (SSN), or cornstarch (control) in a randomized crossover design. The butter component of the diet was blended with unesterified sterols and stanols at a dose of 1.8 g/d. The LDL particles were characterized by polyacrylamide gradient gel electrophoresis of whole plasma. LDL cholesterol (LDL-C) concentrations decreased by 8.8, 13.6, and 13.1% in the S, SN, and SSN groups, respectively (P < 0.01) with a significant increase of 4.3% in the control group. None of the treatments with sterols and stanols induced significant changes in LDL peak particle diameter or in the cholesterol levels of the small LDL subfraction (<25.5 nm). The reduction in plasma LDL-C levels with SN consumption was due mainly to a decrease (P < 0.05) in the concentration of cholesterol in the large subfraction (>26.0 nm). The significant reduction in plasma LDL-C concentrations by sterol and stanol consumption in subjects was not paralleled by any beneficial changes in LDL electrophoretic characteristics.

Effect of a nutritional intervention promoting the Mediterranean food pattern on electrophoretic characteristics of low-density lipoprotein particles in healthy women from the Québec City metropolitan area.

The objective of the present study was to evaluate the effect of a nutritional intervention promoting the Mediterranean food pattern in free-living conditions on LDL electrophoretic characteristics in a group of seventy-one healthy women, aged between 30 and 65 years. The 12-week nutritional intervention consisted of two courses on nutrition and seven individual sessions with a dietitian. The first course provided information on the Mediterranean food pattern and the second was a cooking lesson. LDL peak particle diameter (LDL-PPD) and cholesterol levels in small (LDL-cholesterol<255 A) and large LDL fractions (LDL-cholesterol>260 A) were obtained by 2-16 % polyacrylamide gel electrophoresis of whole plasma. The sample was divided on the basis of baseline LDL-PPD using tertiles of the distribution (258.4 A and 260.0 A). Among the total sample of women, no significant change in LDL-PPD was observed in response to the nutritional intervention. However, subjects who at baseline were in the first tertile of the LDL-PPD distribution (<258.4 A) showed a significant increase in LDL-PPD and in the proportion of LDL %>260 A in response to the 12-week nutritional intervention (P<0.05). In contrast, LDL-PPD decreased significantly (P=0.007) among women with large LDL particles at baseline (LDL-PPD >260 A) while the proportion of LDL %<255 A and of LDL %>260 A remained unchanged. To conclude, changes in the food pattern, in response to a nutritional intervention promoting the Mediterranean food pattern, were accompanied by beneficial modifications in LDL electrophoretic characteristics in women who were characterised at baseline by smaller LDL particles.