Amélie Charest

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.

Effect of the Mediterranean diet with and without weight loss on cardiovascular risk factors in men with the metabolic syndrome

BACKGROUND AND AIMS No study has yet examined how weight loss modifies the impact of the Mediterranean diet (MedDiet) on cardiovascular risk factors in men with the metabolic syndrome (MetS). The objective of the study was to assess the efficacy of MedDiet, with and without weight loss, to modify the cardiometabolic risk profile of male patients with MetS. METHODS AND RESULTS Twenty-six men aged between 24 and 62 years with the MetS consumed a North American control diet for 5 weeks followed by a 5-week MedDiet, both under weight-maintaining conditions. Participants then underwent a 20-week weight loss period, after which they consumed the MedDiet for five weeks under weight stable conditions. Body weight was reduced by 10.2% ± 2.9% after the weight loss period (p < 0.001). All foods were provided to participants during the weight stable phases of the study. The MedDiet in the absence of weight loss decreased total plasma cholesterol (C) (-7.1%), LDL-C (-9.3%) and the total/HDL-C ratio (-6.5%) compared to the control diet (all p < 0.04). The MedDiet combined with weight loss led to reductions in systolic blood pressure (-4.7%), diastolic blood pressure (-7.7%), triglycerides (-18.2%), ApoB (-10.7%), fasting glucose (-4.2%) and insulin (-29.9%) compared to the control diet (all p < 0.001). CONCLUSION The MedDiet in the absence of weight loss leads to significant changes in plasma cholesterol concentrations but has little effects on other cardiometabolic risk factors associated with the MetS in men.

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.

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/m2) ≥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.

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.

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.

Phytosterols in nonfat and low-fat beverages have no impact on the LDL size phenotype

Objective:To examine the impact of nonfat and low-fat phytosterol-enriched beverages on low-density lipoprotein (LDL) electrophoretic characteristics.Design:Double-blind, randomized, crossover, placebo-controlled dietary trial.Setting:Diets were prepared and consumed at the Mary Emily Clinical Nutrition Research Unit of McGill University. Analyses were performed at the Institute on Nutraceuticals and Functional Foods of Laval University.Subjects and intervention:In total, 15 moderately hypercholesterolemic persons consumed each of three experimental diets that each comprised a different beverage: nonfat placebo (NF control), nonfat with phytosterols (NFPS) or low-fat with phytosterols (LFPS). Participants consumed three beverages daily at meal time for a total of 1.8 g of phytosterols per day. Nondenaturing 2–16% polyacrylamide gradient gel electrophoreses were used to characterize LDL size characteristics.Results:The NFPS and LFPS beverage induced no significant changes in several features of the LDL size phenotype compared to the control diet.Conclusion:The consumption of phytosterol-supplemented nonfat and low-fat beverages is not associated with clinically meaningful changes in the LDL particle size phenotype.Sponsorship:This study was supported partly by the Canada Research Chair in Nutrition, Functional Foods and Cardiovascular Health (B Lamarche) and by the Dairy Farmers of Canada.

Effect of sitagliptin therapy on triglyceride-rich lipoprotein kinetics in patients with type 2 diabetes

To investigate the effects of sitagliptin therapy on the kinetics of triglyceride‐rich lipoprotein (TRL) apolipoprotein (apo)B‐48, VLDL apoB‐100, apoE and apoC‐III in patients with type 2 diabetes.

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.

Docosahexaenoic acid-enriched canola oil increases adiponectin concentrations: A randomized crossover controlled intervention trial

BACKGROUND AND AIMS Little is known about the effect of various dietary fatty acids on pro- and anti-inflammatory processes. We investigated the effect of 5 oils containing various amounts of alpha-linolenic acid (ALA), linoleic acid (LA), oleic acid (OA) and docosahexaenoic acid (DHA) on plasma inflammatory biomarkers and expression levels of key inflammatory genes and transcription factors in whole blood cells. METHODS AND RESULTS In a randomized, crossover controlled nutrition intervention, 114 adult men and women with abdominal obesity and at least one other criterion for the metabolic syndrome consumed 5 experimental isoenergetic diets for 4 weeks each, separated by 4-week washout periods. Each diet provided 60 g/3000 kcal of different oils: 1) control corn/safflower oil blend (CornSaff; LA-rich), 2) flax/safflower oil blend (FlaxSaff; ALA-rich), 3) conventional canola oil (Canola; OA-rich), 4) high oleic canola oil (CanolaOleic; highest OA content), 5) DHA-enriched high oleic canola oil (CanolaDHA; OA- and DHA-rich). Gene expression in whole blood cells was assessed in a subset of 62 subjects. CanolaDHA increased plasma adiponectin concentrations compared with the control CornSaff oil treatment (+4.5%, P = 0.04) and FlaxSaff (+6.9%, P = 0.0008). CanolaDHA also reduced relative expression levels of interleukin (IL)1B compared with CornSaff and Canola (-11% and -13%, respectively, both P = 0.03). High-sensitivity C-reactive protein concentrations were lower after Canola than after FlaxSaff (-17.8%, P = 0.047). CONCLUSION DHA-enriched canola oil exerts anti-inflammatory effects compared with polyunsaturated fatty acids from plant sources.