A combination of single nucleotide polymorphisms is associated with the interindividual variability in the blood lipid response to dietary fatty acid consumption in a randomized clinical trial.

BACKGROUND: Blood lipid concentrations display high interindividual variability in response to dietary interventions, partly due to genetic factors. Existing studies have focused on single nucleotide polymorphisms (SNPs) analyzed individually, which only explain a limited fraction of the variability of these complex phenotypes. OBJECTIVE: We aimed to identify combinations of SNPs associated with the variability in LDL cholesterol and triglyceride (TG) concentration changes following 5 dietary interventions. DESIGN: In a multicenter randomized crossover trial, 92 participants with elevated waist circumference and low HDL cholesterol concentrations consumed 5 isoenergetic diets for 4 wk: a diet rich in saturated fatty acids (SFAs) from cheese, SFA from butter, monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs), and a diet higher in carbohydrates (CHO). The association between 22 candidate SNPs in genes involved in lipid and bile acid metabolism and transport and changes in LDL cholesterol and TG concentrations was assessed with univariate statistics followed by partial least squares regression. RESULTS: Endpoint LDL cholesterol concentrations were significantly different (cheese: 3.18 ± 0.04, butter: 3.31 ± 0.04, MUFA: 3.00 ± 0.04, PUFA: 2.81 ± 0.04, CHO: 3.11 ± 0.04 mmol/L; P < 0.001) while endpoint TG concentrations were not (P = 0.117). Both displayed consistently elevated interindividual variability following the dietary interventions (CVs of 34.5 ± 2.2% and 55.8 ± 1.8%, respectively). Among the 22 candidate SNPs, only ABCA1-rs2066714 and apolipoprotein E (APOE) isoforms exhibited consistent significant effects, namely on LDL cholesterol concentrations. However, several SNPs were significantly associated with changes in LDL cholesterol and TG concentrations in a diet-specific fashion. Generated multivariate models explained from 16.0 to 33.6% of the interindividual variability in LDL cholesterol concentration changes and from 17.5 to 32.0% of that in TG concentration changes. CONCLUSIONS: We report combinations of SNPs associated with a significant part of the variability in LDL cholesterol and TG concentrations following dietary interventions differing in their fatty acid profiles.

Understanding connections and roles of gut microbiome in cardiovascular diseases.

The gut microbiome encompasses trillions of residing microbes, mainly bacteria, which play a crucial role in maintaining the physiological and metabolic health of the host. The gut microbiome has been associated with several diseases, including cardiovascular disease (CVD). A growing body of evidence suggests that an altered gut environment and gut-microbiome-derived metabolites are associated with CVD events. The gut microbiome communicates with host physiology through different mechanisms, including trimethylamine N-oxide generation, primary and secondary bile acid metabolism pathways, and short-chain fatty acids production. The main focus of this review is to understand the association of the gut microbiome with CVD and its implications on the interactions between the gut microbiome and the host. Manipulation of the gut microbiome through specific dietary intervention is a simple approach to identifying novel targets for therapy or better dietary recommendations, and new preventive measures for screening biomarkers to reduce CVD risk in humans.

Comparison of the impact of SFAs from cheese and butter on cardiometabolic risk factors: a randomized controlled trial.

Background: Controversies persist concerning the association between intake of dietary saturated fatty acids (SFAs) and cardiovascular disease risk.Objective: We compared the impact of consuming equal amounts of SFAs from cheese and butter on cardiometabolic risk factors.Design: In a multicenter, crossover, randomized controlled trial, 92 men and women with abdominal obesity and relatively low HDL-cholesterol concentrations were assigned to sequences of 5 predetermined isoenergetic diets of 4 wk each separated by 4-wk washouts: 2 diets rich in SFAs (12.4-12.6% of calories) from either cheese or butter; a monounsaturated fatty acid (MUFA)-rich diet (SFAs: 5.8%, MUFAs: 19.6%); a polyunsaturated fatty acid (PUFA)-rich diet (SFAs: 5.8%, PUFAs: 11.5%); and a low-fat, high-carbohydrate diet (fat: 25%, SFAs: 5.8%).Results: Serum HDL-cholesterol concentrations were similar after the cheese and butter diets but were significantly higher than after the carbohydrate diet (+3.8% and +4.7%, respectively; P < 0.05 for both). LDL-cholesterol concentrations after the cheese diet were lower than after the butter diet (-3.3%, P < 0.05) but were higher than after the carbohydrate (+2.6%), MUFA (+5.3%), and PUFA (+12.3%) diets (P < 0.05 for all). LDL-cholesterol concentrations after the butter diet also increased significantly (from +6.1% to +16.2%, P < 0.05) compared with the carbohydrate, MUFA, and PUFA diets. The LDL-cholesterol response to treatment was significantly modified by baseline values (P-interaction = 0.02), with the increase in LDL cholesterol being significantly greater with butter than with cheese only among individuals with high baseline LDL-cholesterol concentrations. There was no significant difference between all diets on inflammation markers, blood pressure, and insulin-glucose homeostasis.Conclusions: The results of our study suggest that the consumption of SFAs from cheese and butter has similar effects on HDL cholesterol but differentially modifies LDL-cholesterol concentrations compared with the effects of carbohydrates, MUFAs, and PUFAs, particularly in individuals with high LDL cholesterol. In contrast, SFAs from either cheese or butter have no significant effects on several other nonlipid cardiometabolic risk factors. This trial was registered at clinicaltrials.gov as NCT02106208.

Effect of dietary cholesterol and plant sterol consumption on plasma lipid responsiveness and cholesterol trafficking in healthy individuals.

Dietary cholesterol and plant sterols differentially modulate cholesterol kinetics and circulating cholesterol. Understanding how healthy individuals with their inherent variabilities in cholesterol trafficking respond to such dietary sterols will aid in improving strategies for effective cholesterol lowering and alleviation of CVD risk. The objectives of this study were to assess plasma lipid responsiveness to dietary cholesterol v. plant sterol consumption, and to determine the response in rates of cholesterol absorption and synthesis to each sterol using stable isotope approaches in healthy individuals. A randomised, double-blinded, crossover, placebo-controlled clinical trial (n 49) with three treatment phases of 4-week duration were conducted in a Manitoba Hutterite population. During each phase, participants consumed one of the three treatments as a milkshake containing 600 mg/d dietary cholesterol, 2 g/d plant sterols or a control after breakfast meal. Plasma lipid profile was determined and cholesterol absorption and synthesis were measured by oral administration of [3, 4-13C] cholesterol and 2H-labelled water, respectively. Dietary cholesterol consumption increased total (0·16 (sem 0·06) mmol/l, P=0·0179) and HDL-cholesterol (0·08 (sem 0·03) mmol/l, P=0·0216) concentrations with no changes in cholesterol absorption or synthesis. Plant sterol consumption failed to reduce LDL-cholesterol concentrations despite showing a reduction (6 %, P=0·0004) in cholesterol absorption. An over-compensatory reciprocal increase in cholesterol synthesis (36 %, P=0·0026) corresponding to a small reduction in absorption was observed with plant sterol consumption, possibly resulting in reduced LDL-cholesterol lowering efficacy of plant sterols. These data suggest that inter-individual variability in cholesterol trafficking mechanisms may profoundly impact plasma lipid responses to dietary sterols in healthy individuals.

Dietary high oleic canola oil supplemented with docosahexaenoic acid attenuates plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels in participants with cardiovascular disease risk: A randomized control trial.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel circulating protein which plays an important role in regulation of cholesterol metabolism by promoting hepatic LDL receptor degradation. However, the action of dietary fat composition on PCSK9 levels remains to be fully elucidated. The objective was to investigate the action of different dietary oils on circulating PCSK9 levels in the Canola Oil Multicenter Intervention Trial (COMIT). COMIT employed a double-blinded crossover randomized control design, consisting of five 30-d treatment periods. Diets were provided based on a 3000Kcal/d intake, including a 60g/d treatment of conventional canola oil (Canola), a high oleic canola/DHA oil blend (CanolaDHA), a corn/safflower oil blend (CornSaff), a flax/safflower oil blend (FlaxSaff) or a high oleic canola oil (CanolaOleic). Plasma PCSK9 levels were assessed using ELISA at the end of each phase. Lipid profiles (n=84) showed that CanolaDHA feeding resulted in the highest (P<0.05) serum total cholesterol (TC, 5.06±0.09mmol/L) and LDL-cholesterol levels (3.15±0.08mmol/L) across all five treatments. CanolaDHA feeding also produced the lowest (P<0.05) plasma PCSK9 concentrations (216.42±8.77ng/mL) compared to other dietary oil treatments. Plasma PCSK9 levels positively correlated (P<0.05) with serum TC, LDL-cholesterol, apolipoprotein A, and apolipoprotein B levels but did not correlate to HDL-cholesterol levels. Results indicate that post-treatment response in PCSK9 may be altered with the CanolaDHA diet. In conclusion, the elevated LDL-C levels from a DHA oil treatment may not be relevant for the observed decline in PCSK9 levels.

Safety and Health Benefits of Novel Dietary Supplements Consisting Multiple Phytochemicals, Vitamins, Minerals and Essential Fatty Acids in High Fat Diet Fed Rats.

The objective was to determine safety and efficacy of health supplements "Beyond Tangy Tangerine," a multivitamin/mineral complex and combination of multivitamin/mineral complex, "Osteofx," a bone healthy supplement and "Ultimate Essential Fatty Acids" in Sprague Dawley rats consuming high-fat diets. Initially a pilot study was conducted which confirmed palatability and acceptability of supplements. In a second study, rats (n = 15/group) were randomized to Control; Multivitamin/mineral complex (2 g/kg BW) or Combination (2 g Multivitamin/mineral complex, 1.5 g Bone healthy supplement and 0.34 g Essential fatty acids/kg BW). No differences were observed in BW change, feed intake, organ weights or bone mineral composition with supplementations compared to control. Multivitamin/mineral complex supplementation decreased abdominal white adipose tissue weights (WAT) (p = .005), total (p = .033) and fat mass (p = .040), plasma IL-6 (p = .016) and ALKP (p = .038) and elevated plasma calcium (p < .001), phosphorus (p = .038), total protein (p = .002), albumin (p = .014) and globulin (p = .018), compared to control. Similarly, combination supplementation reduced WAT (p < .001), total (p = .023) and fat mass (p = .045), plasma triglycerides (p = .018), IL-6 (p = .002) and ALKP (p < .001) with increases in plasma calcium (p = .031), phosphorus (p < .001) compared to control. Results indicate that consuming either supplement can be considered safe and improves overall health by reducing inflammation, abdominal fat mass and plasma triglycerides, as well as promote bone health.

Docosahexaenoic Acid Attenuates Cardiovascular Risk Factors via a Decline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Plasma Levels.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that regulates cholesterol metabolism by promoting LDL receptor degradation in the liver and has recently been proposed as a therapeutic target in the management of hyperlipidaemia. We investigated the impact of dietary fat on the metabolism of sterols and on plasma PCSK9 concentrations to explore likely clinical usefulness. In a post hoc analysis of a double-blind randomised crossover controlled feeding trial, the Canola Oil Multicenter Intervention Trial (COMIT), volunteers (n = 54) with at least one condition related to metabolic syndrome consumed diets with one of the following treatment oils in beverages: (1) conventional canola oil (Canola); (2) canola oil rich in docosahexanoic acid (DHA) (CanolaDHA); and (3) high-oleic acid canola oil (CanolaOleic). The enrichment in oleic acid resulted in lower plasma cholesterol concentration compared with diets enriched in DHA. Contrarily, DHA-enriched oil significantly decreased plasma PCSK9 and triacylglycerols levels, but increased circulating levels of sterols. The variations in lathosterol, sitosterol, and campesterol indicate that plasma PCSK9 levels are sensitive to changes in cholesterol synthesis and/or absorption. There was a significant correlation between plasma PCSK9 levels and plasma triacylglicerol and apolipoprotein B levels, which was not affected by dietary fat. Therefore, our results suggest that the impact of dietary fats should not be discarded as complementary treatment in the management of patients with hyperlipidaemia. These findings should be considered in the analysis of ongoing studies and may represent a cautionary note in the treatment of patients with cardiovascular risk.

Effect of consuming novel foods consisting high oleic canola oil, barley ß-glucan, and DHA on cardiovascular disease risk in humans: the CONFIDENCE (Canola Oil and Fibre with DHA Enhanced) study - protocol for a randomized controlled trial.

BACKGROUND: Metabolic syndrome (MetS) has been identified as a major contributor to the development of cardiovascular disease (CVD). Current recommendations for dietary management of people with MetS involve quantitative and qualitative modifications of food intake, such as high consumption of vegetables, fruits, and whole grain foods. The results from our previous human trials revealed the potential of the dietary components high-oleic acid canola oil (HOCO)-docosahexaenoic acid (DHA) and high molecular weight barley ß-glucan individually in managing CVD risk factors. Foods with a combination of HOCO-DHA and barley ß-glucan have never been tested for their effects on CVD risk. The objective is to determine the effects of consuming novel foods HOCO-DHA, and barley ß-glucan on managing CVD risk factors in people with MetS. METHODS/DESIGN: We are conducting a randomized, single-blind crossover trial with four treatment phases of 28 days each separated by a 4-week washout interval. Participants (n=35) will be provided with weight-maintaining, healthy balanced diet recommendations according to their energy requirements during the intervention periods. Participants will receive muffins and cookies as treatment foods in a random order and will consume at least one meal per day at the research center under supervision. The four treatments include muffins and cookies consisting of (1) all-purpose flour and HOCO-DHA (50 g/day); (2) barley flour (4.36 g/day of ß-glucan) and a blend of sunflower oil, safflower oil, and butter as control oil (50 g/day); (3) barley flour (4.36 g/day of ß-glucan) and HOCO-DHA (50 g/day; dosage of DHA would be 3 g/day); and (4) all-purpose flour and control oil (50 g/day). At the beginning and end of each phase, we will evaluate anthropometrics; systolic and diastolic blood pressure; blood lipid profile; low-density lipoprotein subfractions and particle size; 10-year Framingham CVD risk score; inflammatory status; and plasma and red blood cell fatty acid profiles, fecal microbiome, and body composition by dual-energy X-ray absorptiometry. CONCLUSION: Cholesterol synthesis will also be studied, using a stable isotope approach. The proposed study will lead to innovation of novel food products, which may result in improvement in the overall cardiovascular health of humans. TRIAL REGISTRATION: Clinical trials.gov identifier: NCT02091583 . Date of registration: 12 March 2014.

Role of Phytosterols in Cancer Prevention and Treatment.

Plant sterols or phytosterols have been shown to be effective in improving blood lipid profile and thereby protective against cardiovascular disease. In addition to their cardioprotective effects, phytosterols have gained more insight for their protective effect against various forms of cancer. Phytosterols have been reported to alleviate cancers of breast, prostate, lung, liver, stomach and ovary. Reductions in growth of various cancer cells including liver, prostate and breast by phytosterols treatment have been demonstrated. Although exact mechanisms of phytosterols for their anticancer effects are not very well delineated, there have been several mechanisms proposed such as inhibition of carcinogen production, cancer cell growth and multiplication, invasion and metastasis and induction of cell cycle arrest and apoptosis. Other mechanisms including reduction of angiogenesis, invasion and adhesion of cancer cells and production of reactive oxygen species have also been suggested. However, cancer therapy using phytosterol formulations have yet to be designed, largely due to the gap in the literature with regards to mode of action. Furthermore, most of the studies on anticancer effects of phytosterols were conducted in vitro and animal studies and need to be confirmed in humans.

Fish oil for the reduction of atrial fibrillation recurrence, inflammation, and oxidative stress.

BACKGROUND: Recent trials of fish oil for the prevention of atrial fibrillation (AF) recurrence have provided mixed results. Notable uncertainties in the existing evidence base include the roles of high-dose fish oil, inflammation, and oxidative stress in patients with paroxysmal or persistent AF not receiving conventional antiarrhythmic (AA) therapy. OBJECTIVES: The aim of this study was to evaluate the influence of high-dose fish oil on AF recurrence, inflammation, and oxidative stress parameters. METHODS: We performed a double-blind, randomized, placebo-controlled, parallel-arm study in 337 patients with symptomatic paroxysmal or persistent AF within 6 months of enrollment. Patients were randomized to fish oil (4 g/day) or placebo and followed, on average, for 271 ± 129 days. RESULTS: The primary endpoint was time to first symptomatic or asymptomatic AF recurrence lasting >30 s. Secondary endpoints were high-sensitivity C-reactive protein (hs-CRP) and myeloperoxidase (MPO). The primary endpoint occurred in 64.1% of patients in the fish oil arm and 63.2% of patients in the placebo arm (hazard ratio: 1.10; 95% confidence interval: 0.84 to 1.45; p = 0.48). hs-CRP and MPO were within normal limits at baseline and decreased to a similar degree at 6 months (Δhs-CRP, 11% vs. -11%; ΔMPO, -5% vs. -9% for fish oil vs. placebo, respectively; p value for interaction = NS). CONCLUSIONS: High-dose fish oil does not reduce AF recurrence in patients with a history of AF not receiving conventional AA therapy. Furthermore, fish oil does not reduce inflammation or oxidative stress markers in this population, which may explain its lack of efficacy. (Multi-center Study to Evaluate the Effect of N-3 Fatty Acids [OMEGA-3] on Arrhythmia Recurrence in Atrial Fibrillation [AFFORD]; NCT01235130).

Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds.

BACKGROUND: Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption. OBJECTIVE: The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins. METHODS: Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months. RESULTS: No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased ß-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted ß-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; ß-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; ß-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and ß-sitosterol concentrations were negatively correlated (p < 0.001) with total and LDL-C levels. CONCLUSION: Results demonstrate that consuming a portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.

Response to commentary on a trial comparing krill oil versus fish oil.

Nichols et al. (Lipids Health Dis13:2, 2014) raised concern about the higher n-6 concentration in fish oil used in our recent study which is different from typical commercial fish oils (Ramprasath et al. Lipids Health Dis12:178, 2013). The aim of our study was to compare the effect of consumption of similar amount of n-3 PUFA from krill and fish oil with placebo on plasma and RBC fatty acids. As the concentration of n-3 PUFA in the fish oil utilised was higher than that in krill oil, we deemed it important to keep consistent the concentration of n-3 PUFA and volumes to be administered to participants between krill versus fish oils. As such, the fish oil used in the study was diluted with corn oil. Although the n-6 PUFA concentration in fish oil was higher compared to traditionally used fish oil, consumption of the fish oil used in our study actually reduced the total n-6 PUFA in plasma and RBC to a similar extent as did krill oil. Overall, our conclusion was that the increases in plasma and RBC concentrations of EPA and DHA along with improvement in the omega-3 index observed with consumption of krill oil compared with fish oil are due to differences in absorption and bioavailability based on the structural difference of the two oils rather than their n-6 PUFA content.

Phytosterols protect against diet-induced hypertriglyceridemia in Syrian golden hamsters.

BACKGROUND: In addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), however, the underlying mechanisms are not known. METHODS: We examined the TG-lowering mechanisms of dietary PS in Syrian golden hamsters randomly assigned to a high fat (HF) diet or the HF diet supplemented with PS (2%) for 6 weeks (n = 12/group). An additional subset of animals (n = 12) was provided the HF diet supplemented with ezetimibe (EZ, 0.002%) as a positive control as it is a cholesterol-lowering agent with known TG-lowering properties. RESULTS: In confirmation of diet formulation and compound delivery, both the PS and EZ treatments lowered (p < 0.05) intestinal cholesterol absorption (24 and 31%, respectively), blood non-HDL cholesterol (61 and 66%, respectively), and hepatic cholesterol (45 and 55%, respectively) compared with the HF-fed animals. Blood TG concentrations were lower (p < 0.05) in the PS (49%) and EZ (68%)-treated animals compared with the HF group. The TG-lowering response in the PS-supplemented group was associated with reduced (p < 0.05) intestinal SREBP1c mRNA (0.45 fold of HF), hepatic PPARα mRNA (0.73 fold of HF), hepatic FAS protein abundance (0.68 fold of HD), and de novo lipogenesis (44%) compared with the HF group. Similarly, lipogenesis was lower in the EZ-treated animals, albeit through a reduction in the hepatic protein abundance of ACC (0.47 fold of HF). CONCLUSIONS: Study results suggest that dietary PS are protective against diet-induced hypertriglyceridemia, likely through multiple mechanisms that involve modulation of intestinal fatty acid metabolism and a reduction in hepatic lipogenesis.

Enhanced increase of omega-3 index in healthy individuals with response to 4-week n-3 fatty acid supplementation from krill oil versus fish oil.

BACKGROUND: Due to structural differences, bioavailability of krill oil, a phospholipid based oil, could be higher than fish oil, a triglyceride-based oil, conferring properties that render it more effective than fish oil in increasing omega-3 index and thereby, reducing cardiovascular disease (CVD) risk. OBJECTIVE: The objective was to assess the effects of krill oil compared with fish oil or a placebo control on plasma and red blood cell (RBC) fatty acid profile in healthy volunteers. PARTICIPANTS AND METHODS: Twenty four healthy volunteers were recruited for a double blinded, randomized, placebo-controlled, crossover trial. The study consisted of three treatment phases including krill or fish oil each providing 600 mg of n-3 polyunsaturated fatty acids (PUFA) or placebo control, corn oil in capsule form. Each treatment lasted 4 wk and was separated by 8 wk washout phases. RESULTS: Krill oil consumption increased plasma (p = 0.0043) and RBC (p = 0.0011) n-3 PUFA concentrations, including EPA and DHA, and reduced n-6:n-3 PUFA ratios (plasma: p = 0.0043, RBC: p = 0.0143) compared with fish oil consumption. Sum of EPA and DHA concentrations in RBC, the omega-3 index, was increased following krill oil supplementation compared with fish oil (p = 0.0143) and control (p < 0.0001). Serum triglycerides and HDL cholesterol concentrations did not change with any of the treatments. However, total and LDL cholesterol concentrations were increased following krill (TC: p = 0.0067, LDL: p = 0.0143) and fish oil supplementation (TC: p = 0.0028, LDL: p = 0.0143) compared with control. CONCLUSIONS: Consumption of krill oil was well tolerated with no adverse events. Results indicate that krill oil could be more effective than fish oil in increasing n-3 PUFA, reducing n-6:n-3 PUFA ratio, and improving the omega-3 index. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01323036.

Correlates of reactive hyperemic index in men and postmenopausal women.

The aim of the present study was to investigate the differences in digital reactive hyperemic index (RHI) in men and postmenopausal women. We investigated the differences in and correlates of RHI, measured by peripheral artery tonometry (PAT), in a group of 82 men (mean age ± SD: 55.6 ± 8.2 years; body mass index: 29.0 ± 4.2 kg/m(2)) and 125 postmenopausal women (58.9 ± 5.2 years; 27.7 ± 4.1 kg/m(2)). We also examined fRHI values (natural log of the PAT ratio of the 90-120 seconds post-occlusion interval) and augmentation index (AIx) as a measure of arterial stiffness. We found that RHI, fRHI and AIx were significantly lower in men compared to postmenopausal women (p<0.0001). We also found that fRHI values were significantly lower in individuals with (MetS+) versus without (MetS-) the metabolic syndrome (MetS). Endothelial inflammation was present in MetS+ subjects as indicated by increased plasma soluble intercellular adhesion molecule-1 (sICAM-1) (p<0.001) and E-selectin (p=0.0519) concentrations compared to MetS- individuals. No significant difference was found in RHI or AIx between MetS+ versus MetS- individuals. In summary, our study reveals that men have an impairment of endothelial function, assessed by digital PAT, compared to postmenopausal women. Furthermore, we show that the presence of the MetS is characterized by endothelial dysfunction, as suggested by lower fRHI, as well as by endothelial inflammation, which likely contributes to the increased cardiovascular disease risk associated with the MetS. ClinicalTrials.gov Identifier: NCT01085019.

Effect of dietary sphingomyelin on absorption and fractional synthetic rate of cholesterol and serum lipid profile in humans.

BACKGROUND: Diets enriched with sphingolipids may improve blood lipid profiles. Studies in animals have shown reductions in cholesterol absorption and alterations in blood lipids after treatment with sphingomyelin (SM). However, minimal information exists on effect of SM on cholesterol absorption and metabolism in humans. The objective was to assess the effect of SM consumption on serum lipid concentrations and cholesterol metabolism in healthy humans. METHODS: Ten healthy adult males and females completed a randomized crossover study. Subjects consumed controlled diets with or without 1 g/day SM for 14 days separated by at least 4 week washout period. Serum lipid profile and markers of cholesterol metabolism including cholesterol absorption and synthesis were analyzed. RESULTS: Serum triglycerides, total, LDL- and VLDL- cholesterol were not affected while HDL cholesterol concentrations were increased (p = 0.043) by SM diet consumption. No change in cholesterol absorption and cholesterol fractional synthesis rate was observed with supplementation of SM compared to control. Intraluminal cholesterol solubilization was also not affected by consumption of SM enriched diet. CONCLUSIONS: In humans, 1 g/day of dietary SM does not alter the blood lipid profile except for an increased HDL-cholesterol concentration and has no effect on cholesterol absorption, synthesis and intraluminal solubilization compared to control. TRIAL REGISTRATION: Clinicaltrials.gov # NCT00328211.

Decreased plasma cholesterol concentrations after PUFA-rich diets are not due to reduced cholesterol absorption/synthesis.

Plasma cholesterol concentrations increase with consumption of high saturated fatty acid (SFA) and decrease with high polyunsaturated fatty acid (PUFA) diets, leading to shifts in lipid levels consistent with reduction in heart disease risk. Direct measurements of cholesterol absorption, one of the key regulators of plasma cholesterol levels, have not been performed in humans after consumption of high PUFA diets. Thus, cholesterol absorption and fractional synthesis rates (FSRs) were measured in 16 healthy adults (8 males and 9 females) using a randomized cross-over study with a diet containing high (PUFA/SFA) P/S ratio (2:1) and a low P/S ratio (0.5:1). Cholesterol absorption and fractional cholesterol synthetic rates were measured using stable isotopes after 20 days of dietary intervention. Diet did not affect cholesterol absorption or synthesis. There was a significant decrease in plasma cholesterol concentrations (P < 0.02), specifically LDL-cholesterol (P < 0.02), without a change in HDL-cholesterol or triacylglycerol concentrations. Intraluminal cholesterol solubilization and plasma sterol (cholesterol biosynthetic intermediates and plant sterols) levels were not affected by diet. Thus, consumption of diets with a high P/S ratio reduces plasma total and LDL-cholesterol concentrations independent of shifts in cholesterol absorption or synthesis.

Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a randomized controlled trial.

CONTEXT: Combining foods with recognized cholesterol-lowering properties (dietary portfolio) has proven highly effective in lowering serum cholesterol under metabolically controlled conditions. OBJECTIVE: To assess the effect of a dietary portfolio administered at 2 levels of intensity on percentage change in low-density lipoprotein cholesterol (LDL-C) among participants following self-selected diets. DESIGN, SETTING, AND PARTICIPANTS: A parallel-design study of 351 participants with hyperlipidemia from 4 participating academic centers across Canada (Quebec City, Toronto, Winnipeg, and Vancouver) randomized between June 25, 2007, and February 19, 2009, to 1 of 3 treatments lasting 6 months. INTERVENTION: Participants received dietary advice for 6 months on either a low-saturated fat therapeutic diet (control) or a dietary portfolio, for which counseling was delivered at different frequencies, that emphasized dietary incorporation of plant sterols, soy protein, viscous fibers, and nuts. Routine dietary portfolio involved 2 clinic visits over 6 months and intensive dietary portfolio involved 7 clinic visits over 6 months. MAIN OUTCOME MEASURES: Percentage change in serum LDL-C. RESULTS: In the modified intention-to-treat analysis of 345 participants, the overall attrition rate was not significantly different between treatments (18% for intensive dietary portfolio, 23% for routine dietary portfolio, and 26% for control; Fisher exact test, P = .33). The LDL-C reductions from an overall mean of 171 mg/dL (95% confidence interval [CI], 168-174 mg/dL) were -13.8% (95% CI, -17.2% to -10.3%; P < .001) or -26 mg/dL (95% CI, -31 to -21 mg/dL; P < .001) for the intensive dietary portfolio; -13.1% (95% CI, -16.7% to -9.5%; P < .001) or -24 mg/dL (95% CI, -30 to -19 mg/dL; P < .001) for the routine dietary portfolio; and -3.0% (95% CI, -6.1% to 0.1%; P = .06) or -8 mg/dL (95% CI, -13 to -3 mg/dL; P = .002) for the control diet. Percentage LDL-C reductions for each dietary portfolio were significantly more than the control diet (P < .001, respectively). The 2 dietary portfolio interventions did not differ significantly (P = .66). Among participants randomized to one of the dietary portfolio interventions, percentage reduction in LDL-C on the dietary portfolio was associated with dietary adherence (r = -0.34, n = 157, P < .001). CONCLUSION: Use of a dietary portfolio compared with the low-saturated fat dietary advice resulted in greater LDL-C lowering during 6 months of follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00438425.

Diacylglycerol oil reduces body fat but does not alter energy or lipid metabolism in overweight, hypertriglyceridemic women.

Diacylglycerol (DAG) may undergo differential metabolism compared with triacylglycerol (TAG) in humans, possibly resulting in decreased serum TAG concentration and TAG synthesis and increased energy expenditure (EE), thus reducing fat accumulation. Our objective was to examine the efficacy of DAG oil (Enova oil) consumption on serum lipid profiles, hepatic lipogenesis, EE, and body weight and composition compared with a control oil-blend composed of sunflower, safflower, and rapeseed oils at a 1:1:1 ratio. Twenty-six overweight (78.3 +/- 3.6 kg body weight and BMI 30.0 +/- 0.7 kg/m(2)) mildly hypertriglyceridemic (1.81 +/- 0.66 mmol/L) women underwent 2 treatment phases of 28 d separated by a 4-wk washout period using a randomized crossover design. They consumed 40 g/d of either DAG or control oil during treatment phases. The baseline, EE, fat oxidation, body composition, and lipid profiles did not differ between the DAG and control oil intervention periods. Relative to control oil, DAG oil did not alter endpoint postprandial EE, fat oxidation, serum lipid profiles, or hepatic lipogenesis. However, DAG oil consumption reduced (P < 0.05) accumulation of body fat within trunk, android, and gynoid regions at the endpoint compared with control oil, although neither DAG nor control oil altered any of these variables during the 4-wk intervention period compared with their respective baseline levels. We conclude that although DAG oil is not effective in lowing serum lipids over a 4-wk intervention, it may be useful for reducing adiposity.

Potential of resveratrol in anticancer and anti-inflammatory therapy.

Phytochemicals present in food have shown significant prospects in the treatment and management of a vast array of human diseases. Resveratrol is a stilbene-type aromatic phytoalexin predominantly found in grapes, peanuts, berries, turmeric, and other food products. Resveratrol has been reported to exhibit several physiological activities including anticancer and anti-inflammatory activities in vitro and in experimental animal models, as well as in humans. Anticancer activity of this compound is mainly due to induction of apoptosis via several pathways, as well as alteration of gene expressions, all leading to a decrease in tumor initiation, promotion, and progression. Resveratrol exhibits anti-inflammatory activity through modulation of enzymes and pathways that produce mediators of inflammation and also induction of programmed cell death in activated immune cells. Resveratrol has been shown to produce no adverse effects, even when consumed at high concentrations. Hence, resveratrol possesses good potential to be used as an adjunctive or alternative therapy for cancer and inflammatory diseases.