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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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Research investigating hemp protein consumption on glycemic response is limited. The effects of hemp protein consumption on blood glucose (BG), insulin, and satiety compared with soybean protein and a carbohydrate control were examined. Two acute randomized repeated-measures crossover experiments were conducted. In both, participants consumed the following isocaloric treatments: 40 g of hemp protein (hemp40), 20 g of hemp protein (hemp20), 40 g of soybean protein (soy40), 20 g of soybean protein (soy20), and a carbohydrate control. In experiments 1 ( n = 27) and 2 ( n = 16), appetite and BG were measured before (0-60 min, pre-pizza) and after a pizza meal (80-200 min, post-pizza). In experiment 1, food intake was measured at 60 min by ad libitum meal; in experiment 2 a fixed meal was provided (based on body weight) and insulin was measured pre-pizza and post-pizza. In both experiments, BG response was affected by treatment ( p < 0.01), time ( p < 0.001) and time-by-treatment ( p < 0.001) from 0-200 min. Protein treatments lowered 0-60-min BG overall mean and area under the curve compared with control ( p < 0.05) dose-dependently. In experiment 2, hemp40 and soy40 lowered ( p < 0.05) overall mean insulin concentrations compared with hemp20, soy20, and control pre-meal. Results suggest that hemp protein, like soybean, dose-dependently lowers postprandial BG and insulin concentrations compared with a carbohydrate control. Clinical trial registry: NCT02366598 (experiment 1) and NCT02458027 (experiment 2). Novelty: Hemp protein concentrate dose-dependently leads to lower postprandial BG response compared with a carbohydrate control. No differences were seen between hemp and soy protein.

The purpose of this study was to examine how using the mean of two consecutive measurements vs. one measurement post-treatment influences the sample size required to detect changes in cardiometabolic risk factors in dietary studies. For a given statistical power, using the mean of two measurements taken on consecutive days post-treatment instead of a single measurement significantly reduces the sample size required to observe changes in triglyceride, total apolipoprotein B100, and C-reactive protein concentrations in the context of a supplementation study. In the context of a controlled-feeding study, this gain is seen only in the case of change in triglyceride concentrations.

Background: Novel oils high in monounsaturated fatty acids (MUFAs) and low in saturated fatty acids (SFAs) are an alternative to partially hydrogenated oils high in trans-unsaturated fatty acids. There is widespread use of high-MUFA oils across the food industry; however, limited knowledge of their cardiovascular impact exists., Objectives: We investigated the effects of diets containing canola oil, high-oleic acid canola oil (HOCO), and a control oil blend (diet formulated to emulate a Western fat profile) on lipids, lipoproteins, and apolipoproteins (apos), as secondary outcomes of the trial., Methods: In a multi-center, double-blind, randomized, 3-period crossover, controlled feeding trial, men (n = 44) and women (n = 75) with a mean age of 44 y, mean body mass index (BMI; in kg/m2) of 31.7, and an increased waist circumference plus ≥1 metabolic syndrome criteria consumed prepared, weight-maintenance diets containing canola oil [17.5% MUFAs, 9.2% polyunsaturated fatty acids (PUFAs), 6.6% SFAs], HOCO (19.1% MUFAs, 7.0% PUFAs, 6.4% SFAs), or control oil (10.5% MUFAs, 10.0% PUFAs, 12.3% SFAs) for 6 wk with ≥4-wk washouts. Fasting serum lipids were assessed at baseline and 6 wk. Diet effects were examined using a repeated measures mixed model., Results: Compared with the control, canola and HOCO diets resulted in lower endpoint total cholesterol (TC; -4.2% and -3.4%; P < 0.0001), LDL cholesterol (-6.6% and -5.6%; P < 0.0001), apoB (-3.7% and -3.4%; P = 0.002), and non-HDL cholesterol (-4.5% and -4.0%; P = 0.001), with no differences between canola diets. The TC:HDL cholesterol and apoB:apoA1 ratios were lower after the HOCO diet than after the control diet (-3.7% and -3.4%, respectively). There were no diet effects on triglyceride, HDL cholesterol, or apoA1 concentrations., Conclusions: HOCO, with increased MUFAs at the expense of decreased PUFAs, elicited beneficial effects on lipids and lipoproteins comparable to conventional canola oil and consistent with reduced cardiovascular disease risk in adults with central adiposity. This trial was registered at www.clinicaltrials.gov as NCT02029833., (© 2019 American Society for Nutrition.)

Current evidence indicates that foods with added plant sterols or stanols can lower serum levels of low-density lipoprotein cholesterol. This review summarizes the recent findings and deliberations of 31 experts in the field who participated in a scientific meeting in Winnipeg, Canada, on the health effects of plant sterols and stanols. Participants discussed issues including, but not limited to, the health benefits of plant sterols and stanols beyond cholesterol lowering, the role of plant sterols and stanols as adjuncts to diet and drugs, and the challenges involved in measuring plant sterols and stanols in biological samples. Variations in interindividual responses to plant sterols and stanols, as well as the personalization of lipid-lowering therapies, were addressed. Finally, the clinical aspects and treatment of sitosterolemia were reviewed. Although plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management, long-term clinical trials investigating the endpoints of cardiovascular disease are still lacking.

Background: Recent evidence suggests that the association between dietary saturated fatty acids (SFAs) and coronary artery disease risk varies according to food sources. How SFAs from butter and cheese influence HDL-mediated cholesterol efflux capacity (CEC), a key process in reverse cholesterol transport, is currently unknown., Objective: In a predefined secondary analysis of a previously published trial, we have examined how diets rich in SFAs from either cheese or butter influence HDL-mediated CEC, compared with diets rich in either monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs)., Methods: In a randomized crossover controlled consumption trial, 46 men and women with abdominal obesity consumed 5 isocaloric diets, each for 4 wk. Two diets were rich in SFAs either from cheese (CHEESE) or butter (BUTTER) [12.4-12.6% of energy (%E) as SFAs, 32%E as fat, 52%E as carbohydrates]. In 2 other diets, SFAs (5.8%E) were replaced with either MUFAs from refined olive oil (MUFA) or PUFAs from corn oil (PUFA). Finally, a lower fat and carbohydrate diet was used as a control (5.8%E as SFAs, 25.0%E as fat, 59%E as carbohydrates; CHO). Post-diet HDL-mediated CEC was determined ex vivo using radiolabelled J774 macrophages incubated with apolipoprotein B-depleted serum from the participants., Results: Mean (±SD) age was 41.4 ± 14.2 y, and waist circumference was 107.6 ± 11.5 cm in men and 94.3 ± 12.4 cm in women. BUTTER and MUFA increased HDL-mediated CEC compared with CHEESE (+4.3%, P = 0.026 and +4.7%, P = 0.031, respectively). Exploring the significant diet × sex interaction (P = 0.044) revealed that the increase in HDL-mediated CEC after BUTTER compared with CHEESE was significant among men (+6.0%, P = 0.047) but not women (+2.9%, P = 0.19), whereas the increase after MUFA compared with CHEESE was significant among women (+9.1%, P = 0.008) but not men (-0.6%, P = 0.99)., Conclusion: These results provide evidence of a food matrix effect modulating the impact of dairy SFAs on HDL-mediated CEC with potential sex-related differences that deserve further investigation. This trial was registered at clinicaltrials.gov as NCT02106208.

Consumption of dietary pulses, including beans, peas and lentils, is recommended by health authorities across jurisdictions for their nutritional value and effectiveness in helping to prevent and manage major diet-related illnesses of significant socioeconomic burden. The aim of this study was to estimate the potential annual healthcare and societal cost savings relevant to rates of reduction in complications from type 2 diabetes (T2D) and incidence of cardiovascular disease (CVD) following a low glycemic index (GI) or high fiber diet that includes pulses, or 100 g/day pulse intake in Canada, respectively. A four-step cost-of-illness analysis was conducted to: (1) estimate the proportions of individuals who are likely to consume pulses; (2) evaluate the reductions in established risk factors for T2D and CVD; (3) assess the percent reduction in incidences or complications of the diseases of interest; and (4) calculate the potential annual savings in relevant healthcare and related costs. A low GI or high fiber diet that includes pulses and 100 g/day pulse intake were shown to potentially yield Can$6.2 (95% CI $2.6-$9.9) to Can$62.4 (95% CI $26-$98.8) and Can$31.6 (95% CI $11.1-$52) to Can$315.5 (95% CI $110.6-$520.4) million in savings on annual healthcare and related costs of T2D and CVD, respectively. Specific provincial/territorial analyses suggested annual T2D and CVD related cost savings that ranged from up to Can$0.2 million in some provinces to up to Can$135 million in others. In conclusion, with regular consumption of pulse crops, there is a potential opportunity to facilitate T2D and CVD related socioeconomic cost savings that could be applied to Canadian healthcare or re-assigned to other priority domains. Whether these potential cost savings will be offset by other healthcare costs associated with longevity and diseases of the elderly is to be investigated over the long term., Competing Interests: C.M. is an employee of Pulse Canada. P.J. and J.C. have received funding from Manitoba Pulse and Soybean Growers.

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.

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 β-glucan individually in managing CVD risk factors. Foods with a combination of HOCO-DHA and barley β-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 β-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 β-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 β-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.

Cholesterol metabolism is a well-defined responder to dietary intakes and a classic biomarker of cardiovascular health. For this reason, circulating cholesterol levels have become key in shaping nutritional recommendations by health authorities worldwide for better management of cardiovascular disease, a leading cause of mortality and one of the most costly health problems globally. Data from observational and dietary intervention studies, however, highlight a marked between-individual variability in the response of cholesterol metabolism to similar dietary protocols, a phenomenon linked to genetic heterogeneity. This review summarizes the postgenomic evidence of polymorphisms within cholesterol-associated genes relative to fasting circulating cholesterol levels under diverse nutritional conditions. A number of cholesterol-related gene-diet interactions are confirmed, which may have clinical importance, supporting a deeper look into the rapidly emerging field of nutrigenetics for meaningful conclusions that may eventually lead to genetically targeted dietary recommendations in the era of personalized nutrition., (© The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Dairy products are rich sources of an array of fatty acids (FA) that have been shown individually and in certain clusters to exert varying effects on cardiovascular health, for which the circulating lipid profile is a powerful biomarker. Whether the profile of these FA is reflected in blood upon short terms of intake, possibly contributing to the lipid-related health impacts of dairy products, remains to be fully established. The objectives of the present study were to assess a recommended dairy product consumption in relation to circulating FA and lipid profiles, and to evaluate certain FA in dairy fat as potential biomarkers of intake. In a free-living, multi-centre, cross-over design, 124 healthy individuals consumed 3 servings/d of commercial dairy (DAIRY; 1% fat milk, 1·5% fat yogurt and 34% fat cheese) or energy-equivalent control (CONTROL; fruit and vegetable juice, cashews and a cookie) products for 4 weeks each, separated by a 4-week washout period. Plasma FA and serum lipid profiles were assessed by standard methods at the end of each dietary phase. After 4 weeks of intake, plasma levels of FA pentadecanoic acid (15 : 0) and heptadecanoic acid (17 : 0) were higher (0·26 v. 0·22% and 0·42 v. 0·39% of the total identified FA, respectively) after the DAIRY phase than after the CONTROL phase (P< 0·0001). This was accompanied by a small but significant increase in serum LDL-cholesterol levels after the DAIRY phase compared with the CONTROL phase (+0·08 mmol/l; P= 0·04). In conclusion, intake of 3 servings/d of conventional dairy products may modify certain circulating FA and lipid profiles within 4 weeks, where 15 : 0 and 17 : 0 may be potential short-term biomarkers of intake.

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 β-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 β-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; β-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; β-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and β-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.

Background: The Canola Oil Multicenter Intervention Trial (COMIT) was a randomized controlled crossover study designed to evaluate the effects of five diets that provided different oils and/or oil blends on cardiovascular disease (CVD) risk factors in individuals with abdominal obesity. The present objective is to report preliminary findings on plasma fatty acid profiles in volunteers with abdominal obesity, following the consumption of diets enriched with n-3, n-6 and n-9 fatty acids., Methods: COMIT was conducted at three clinical sites, Winnipeg, Manitoba, Canada, Québec City, Québec, Canada and University Park, Pennsylvania, United States. Inclusion criteria were at least one of the followings: waist circumference (≥90 cm for males and ≥84 cm for females), and at least one other criterion: triglycerides ≥1.7 mmol/L, high density lipoprotein cholesterol <1 mmol/L (males) or <1.3 mmol/L (females), blood pressure ≥130 mmHg (systolic) and/or ≥85 mmHg (diastolic), and glucose ≥5.5 mmol/L. Weight-maintaining diets that included shakes with one of the dietary oil blends were provided during each of the five 30-day dietary phases. Dietary phases were separated by four-week washout periods. Treatment oils were canola oil, high oleic canola oil, high oleic canola oil enriched with docosahexaenoic acid (DHA), flax oil and safflower oil blend, and corn oil and safflower oil blend. A per protocol approach with a mixed model analysis was decided to be appropriate for data analysis., Results: One hundred and seventy volunteers were randomized and 130 completed the study with a dropout rate of 23.5%. The mean plasma total DHA concentrations, which were analyzed among all participants as a measure of adherence, increased by more than 100% in the DHA-enriched phase, compared to other phases, demonstrating excellent dietary adherence., Conclusions: Recruitment and retention strategies were effective in achieving a sufficient number of participants who completed the study protocol to enable sufficient statistical power to resolve small differences in outcome measures. It is expected that the study will generate important data thereby enhancing our understanding of the effects of n-3, n-6, and n-9 fatty acid-containing oils on CVD risks., Trial Registration: ClinicalTrials.gov NCT01351012.

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.

Pulses have been identified as important components of a healthy diet. Assessment of pulse grains' nutritional composition alongside data from available preclinical and clinical trials suggests that pulses can modulate biological processes that lead to obesity. Components of pulse grains, including pulse-derived fibre and resistant starch, have been shown to alter energy expenditure, substrate trafficking and fat oxidation as well as visceral adipose deposition. Although mechanistic studies are scarce, studies have indicated that fibres found in pulses can have an impact on the expression of genes that modulate metabolism. Arginine and glutamine may produce thermogenic effects as major components of pulse grain proteins. Finally, evidence suggests that pulse-derived fibres, trypsin inhibitors and lectins may reduce food intake by inducing satiety via facilitating and prolonging cholecystokinin secretion. Nonetheless, the aforementioned data remain controversial and associations between dietary pulse grains and energy intake require further study. Given the available evidence, it can be concluded that pulses could be useful as functional foods and food ingredients that combat obesity.

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.

Background: Information is scarce regarding the effect of dietary protein type, with specific focus on the lysine-to-arginine (Lys:Arg) ratio, on cardiovascular risk factors and vascular reactivity in humans., Objective: Determine the effect of dietary Lys:Arg ratio on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults., Design: Randomized cross-over design of two 35-day diet phases; thirty adults (21 females and 9 males, >or=50 years, LDL cholesterol>or=120 mg/dL). Diets had 20% energy (E) protein, 30%E fat, 50%E carbohydrate and were designed to have low (0.7) or high (1.4) Lys:Arg ratio. Measures included fasting and postprandial lipid, lipoprotein, apolipoprotein concentrations; fasting high sensitivity C-reactive protein (hsCRP), small dense LDL (sdLDL) cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities; cholesterol fractional synthesis rate (FSR); and flow mediated dilation (FMD) and peripheral artery tonometry (PAT)., Results: No differences were observed in fasting and/or postprandial total, LDL, HDL and sdLDL cholesterol, RemLC, Lp(a) or apo B concentrations, LCAT and CETP activities, FSR, glycated albumin, immunoreactive insulin, FMD or PAT. The low, relative to the high, Lys:Arg ratio diet resulted in lower postprandial VLDL cholesterol (-24%, P=0.001) and triglycerides (-23%, P=0.001), and small but significant differences in fasting (-3%, P=0.003) and postprandial (-3%, P=0.018) apo AI, and fasting adiponectin concentrations (+7%, P=0.035). Fasting and postprandial hsCRP concentrations were 23% lower after the low Lys:Arg ratio diet (P=0.020 for both)., Conclusions: Diets differing in Lys:Arg ratios had no or small effects on cardiovascular risk factors and vascular reactivity., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.

Recommendations for decreasing the risk of developing cardiovascular disease include increasing the intake of plant sterols and fish oil. The cholesterol-lowering action of plant sterols, when provided in a fish-oil fatty acids vehicle, remains to be investigated in humans. A randomized, crossover-feeding, single-blind trial was conducted in 30 subjects with mild-to-moderate hypercholesterolemia to study the effects on plasma lipids of 2 novel forms of plant sterols: those combined with, or esterified to, fish-oil fatty acids. The treatments were margarine (control), free plant sterols, plant sterols esterified to fatty acids from sunflower oil, plant sterols esterified to very long-chained fatty acids from fish oil, and plant sterols combined with the same amount of very long-chained fatty acids from fish oil. Each sterol-containing food (1.0-1.8 g plant sterols/d) was consumed for 29 d as a single dose with breakfast under staff supervision. Compared with the control treatment, none of the plant sterol preparations reduced plasma total cholesterol or LDL cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, lipoprotein (a), or C-reactive protein concentration. Relative to the control phase, all plant sterols treatment increased the plasma HDL cholesterol concentration (P < 0.05) by approximately 8%. In conclusion, because standard forms of plant sterols did not reduce plasma cholesterol concentrations, the efficacy of the new formulation of plant sterols cannot be confirmed from the present study design, where plant sterols were given as a single morning dose.

At present, dyslipidemia is most commonly treated with drug therapy. However, because safety concerns regarding the use of pharmaceutical agents have arisen, a need for alternative nonpharmacological therapies has become increasingly apparent. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) recommends lifestyle therapies, which include a combination of diet and exercise modifications, in place of drug treatment for patients who fall into an intermediate range of coronary heart disease (CHD) risk. This review examined the cholesterol lowering efficacy of the following 2 NCEP-recommended combination therapies: 1) low saturated fat diets combined with exercise, and 2) nutritional supplementation, i.e., fish oil, oat bran, or plant sterol supplementation, combined with exercise, in the treatment of dyslipidemia. Combination therapies are particularly advantageous because diet and exercise elicit complementary effects on lipid profiles. More specifically, diet therapies, with some exceptions, lower total (TC) and LDL cholesterol (LDL-C) concentrations, whereas exercise interventions increase HDL cholesterol (HDL-C) while decreasing triglyceride (TG) levels. With respect to specific interventions, low saturated fat diets combined with exercise lowered TC, LDL-C, and TG concentrations by 7-18, 7-15, and 4-18%, respectively, while increasing HDL-C levels by 5-14%. Alternatively, nutritional supplements combined with exercise, decreased TC, LDL-C, and TG concentrations by 8-26, 8-30, and 12-39%, respectively, while increasing HDL-C levels by 2-8%. These findings suggest that combination lifestyle therapies are an efficacious, preliminary means of improving cholesterol levels in those diagnosed with dyslipidemia, and should be implemented in place of drug therapy when cholesterol levels fall just above the normal range.

Dietary phytosterols have been shown to reduce plasma cholesterol concentrations when consumed in different food matrices, but their effectiveness in nonfat or low-fat beverages has not been established. The objective of this study was to examine whether phytosterols alter plasma lipid levels when incorporated into nonfat or low-fat beverages. Fifteen moderately hypercholesterolemic men and women consumed three precisely controlled diets for periods of 21 days each in random order. Diets contained either a nonfat placebo beverage (NF), a beverage that is nonfat with added phytosterols (NFPS), or a beverage that is low in fat with added phytosterols (LFPS). Total cholesterol concentrations were not different between groups at endpoint, decreasing (P < 0.05) equally by 8.5%, 11.6%, and 10.1% with NF, NFPS, and LFPS consumption, respectively. There was no effect of dietary treatment on LDL cholesterol concentrations, which decreased over time (P < 0.05) by 5%, 10.4%, and 8.5% with NF, NFPS, and LFPS, respectively. HDL cholesterol and triacylglycerol concentrations were unaffected by the diets. Provision of phytosterols as part of nonfat and low-fat beverages did not exert any greater hypocholesterolemic effect than a nonfat placebo beverage. These results show that intake of phytosterols in a low-fat beverage format is not efficacious for lipid level modification.

Background: Plant sterols, in various forms, have been shown to reduce total and LDL-cholesterol concentrations. Particularly controversial at present is the effect of the degree of hydrogenation of the plant sterols on cholesterol-lowering efficacy and the responsible mechanisms., Objective: Our goal was to examine the effect of supplementation with unesterified plant sterols and stanols on plasma lipid and phytosterol concentrations and cholesterol absorption, synthesis, and turnover., Design: Fifteen otherwise healthy hypercholesterolemic subjects consumed each of 4 dietary treatments in a randomized crossover design. Unesterified sterols and stanols were blended into the butter component of the diet at a dosage of 1.8 g/d. The diets contained plant sterols (NS), plant stanols (SS), a 50:50 mixture of sterols and stanols (NSS), or cornstarch (control)., Results: Plasma total cholesterol concentrations were 7.8%, 11.9%, and 13.1% lower (P < 0.01) in the NS, SS, and NSS groups, respectively, than in the control group. LDL-cholesterol concentrations were 11.3%, 13.4%, and 16.0% lower (P < 0.03) in the NS, SS, and NSS groups, respectively, than in the control group. Plasma triacylglycerols and HDL-cholesterol concentrations did not differ significantly across diets. Cholesterol absorption efficiency was 56.0%, 34.4%, and 48.9% lower (P < 0.001) in the NS, SS, and NSS groups, respectively, than in the control group. The fractional synthesis rate was higher by 45.5% (P < 0.003) in the NSS group than in the control group. Plasma campesterol and sitosterol concentrations were higher (P < 0.01) in the NS group and sitosterol concentrations were lower (P < 0.01) in the SS group than in the control group., Conclusion: These data indicate that, in their free unesterified form, sterols and stanols lower plasma LDL cholesterol equivalently in hypercholesterolemic persons by suppressing cholesterol absorption.

Spreads enriched with plant sterol and stanol esters have been shown to possess similar cholesterol-lowering properties; however, their comparative capacity to alter circulating levels of other fat-soluble compounds has not been fully assessed. To compare actions of sterol and stanol ester consumption on serum fat-soluble vitamin and carotenoid concentrations, 15 hypercholesterolemic subjects were fed each of 3 fixed foods treatment diets over 21 days using a randomized crossover controlled design. Diets contained either (1) margarine (M), (2) margarine with sterol esters (MSE; 1.92 g/d), or (3) margarine with stanol esters (MSA; 1.76 g/d). No significant differences were found in initial or final serum fat-soluble vitamin and carotenoid concentrations among the 3 phases. Serum retinol and alpha- and gamma-tocopherol concentrations at baseline and endpoint and percentage changes relative to baseline for MSE and MSA were not significantly different from those of the M diet. After adjusting for total cholesterol reduction, no changes for alpha- and gamma-tocopherol were found. Serum vitamins D and K, lycopene, and lutein concentrations and percentage changes did not differ across diets. Serum concentrations at baseline and endpoint and percentage changes for alpha- and beta-cryptoxanthin and alpha- and gamma-carotene were not different among the diets, nor did serum alpha- and gamma-carotene concentrations to total cholesterol ratios differ. Serum lutein, beta-cryptoxanthin, and alpha-carotene concentrations increased over time. In conclusion, our results show no effect of consumption of esterified plant sterols or stanols on serum fat-soluble vitamin or carotenoid concentrations compared with a control diet., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

The article focuses on polymorphisms in the stearoyl-CoA desaturase gene modify blood glucose response to dietary oils varying in MUFA content in adults with obesity.

Background: Cholesterol efflux plays an important role in preventing atherosclerosis progression. Vegetable oils with varying unsaturated fatty acid profiles favorably affect multiple cardiovascular disease risk factors; however, their effects on cholesterol efflux remain unclear.Objective: The objectives of this study were to examine the effects of diets low in saturated fatty acids (SFAs) with varying unsaturated fatty acid profiles on serum-mediated cholesterol efflux and its association with the plasma lipophilic index and central obesity.Methods: The present study is a randomized, crossover, controlled-feeding study. Participants [men: n = 50; women: n = 51; mean ± SE age: 49.5 ± 1.2 y; body mass index (in kg/m2): 29.4 ± 0.4] at risk for or with metabolic syndrome (MetS) were randomly assigned to 5 isocaloric diets containing the treatment oils: canola oil, high oleic acid-canola oil, DHA-enriched high oleic acid-canola oil, corn oil and safflower oil blend, and flax oil and safflower oil blend. These treatment oils were incorporated into smoothies that participants consumed 2 times/d. For a 3000-kcal diet, 60 g of treatment oil was required to provide 18% of total energy per day. Each diet period was 4 wk followed by a 2- to 4-wk washout period. We quantified cholesterol efflux capacity with a validated ex vivo high-throughput cholesterol efflux assay. Statistical analyses were performed with the use of the SAS mixed-model procedure.Results: The 5 diets increased serum-mediated cholesterol efflux capacity from THP-1 macrophages similarly by 39%, 34%, 55%, 49% and 51%, respectively, compared with baseline (P < 0.05 for all). Waist circumference and abdominal adiposity were negatively correlated with serum-mediated cholesterol efflux capacity (r = -0.25, P = 0.01, r = -0.33, P = 0.02, respectively).Conclusion: Diets low in SFAs with different monounsaturated fatty acid and polyunsaturated fatty acid profiles improved serum-mediated cholesterol efflux capacity in individuals with or at risk for MetS. This mechanism may account, in part, for the cardiovascular disease benefits of diets low in SFAs and high in unsaturated fatty acids. Importantly, central obesity is inversely associated with cholesterol efflux capacity. This trial was registered at www.clinicaltrials.gov as NCT01351012. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Dairy intake has been associated with varying impacts on circulating cholesterol concentrations across nutritional epidemiology and intervention studies, with findings attributed mainly to differences in the nature of dairy products consumed or study designs. The contribution of the genomic architecture to such observations has yet to be revealed.Objective: We assessed the impact of multiple common genetic variations in cholesterol-related genes on responses of serum cholesterol to the recommended amount of dairy product intake in Canada.Methods: In a multicenter, randomized crossover design, 101 normolipidemic adults (n = 29 men and 72 women), with a mean ± SD age of 41.7 ± 16.7 y and a body mass index (BMI, in kg/m(2)) of 25.9 ± 4.3 consumed 3 servings/d of dairy [375 mL 1% milk-fat (MF) milk, 175 g 1.5% MF yogurt, and 30 g of 34% MF cheese] or energy-matched control products (juice, cashews, and cookies) provided within a prudent background diet for 4 wk each, separated by a 4- to 8-wk washout period. Serum lipid variables were determined by standard enzymatic methods by using an autoanalyzer. Candidate single nucleotide polymorphisms were assessed by TaqMan genotyping assay.Results: The responsiveness of serum total cholesterol (TC) and LDL cholesterol to the dairy compared with the control diet was associated with individuals' genotypes. The cholesterol transport gene ATP-binding cassette subfamily G, member 5 (ABCG5) rs6720173-GG homozygotes had higher concentrations of TC (+0.18 mmol/L; P = 0.0118) and LDL cholesterol (+0.17 mmol/L; P = 0.0056) relative to C-allele carriers (-0.07 and -0.06 mmol/L, respectively). The bile acid synthesis gene cholesterol 7α-hydroxylase (CYP7A1) rs3808607-G-allele carriers had higher TC (+0.20 to +0.28 mmol/L; P = 0.0026) and LDL cholesterol (+0.19 mmol/L for GT genotype; P = 0.0260) relative to TT homozygotes (-0.11 and -0.03 mmol/L, respectively). In addition, the cholesterol synthesis gene 7-dehydrocholesterol reductase (DHCR7) rs760241-A-allele carriers had higher LDL cholesterol (+0.26 mmol/L; P = 0.0399) relative to GG homozygotes (+0.06 mmol/L).Conclusion: Genetic variations in ABCG5, CYP7A1, and DHCR7 may contribute to differing responses of serum cholesterol to dairy intake among healthy adults. This trial was registered at clinicaltrials.gov as NCT01444326. [ABSTRACT FROM AUTHOR]

The relationship between nutrition and health-economic outcomes is important at both the individual and the societal level. While personal nutritional choices affect an individual's health condition, thus influencing productivity and economic contribution to society, nutrition interventions carried out by the state also have the potential to affect economic output in significant ways. This review summarizes studies of nutrition interventions in which health-related economic implications of the intervention have been addressed. Results of the search strategy have been categorized into three areas: economic studies of micronutrient deficiencies and malnutrition; economic studies of dietary improvements; and economic studies of functional foods. The findings show that a significant number of studies have calculated the health-economic impacts of nutrition interventions, but approaches and methodologies are sometimes ad hoc in nature and vary widely in quality. Development of an encompassing economic framework to evaluate costs and benefits from such interventions is a potentially fruitful area for future research. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a major cause of death and disability in many developed countries. The purpose of this literature review is to establish a recommendation for the intake of functional food ingredients in a healthy diet - such as plant sterols (PSs) in low-fat and functional matrices, fatty acid composition and other nutrients of tree nuts and flavonoids in dark chocolate - for the prevention and treatment of CVD. These three specific functional foods are explored in this review, since there is a higher potential for their increased consumption by the population to prevent CVD. First, PS have been added to various nontraditional matrices, such as low-fat products and functional oils, which have shown cholesterol-lowering effects in most clinical trials. Secondly, a growing number of clinical studies indicate that the beneficial effect of tree nuts may not only be due to their fatty acid composition but to other key nutrients, which may provide supplementary health benefits, such as endothelial cell function, as well as decreasing total cholesterol and lowdensity lipoprotein cholesterol (LDL-C). Lastly, flavonoids in dark chocolate may protect LDL-C particles from undergoing oxidative modification. However, some gaps in our knowledge need to be filled before firm recommendations can be made for habitual dark chocolate consumption. Overall, these functional foods should be considered as an addition to current lipid-lowering recommendations for improving CVD risk. [ABSTRACT FROM AUTHOR]

Background. The endogenous cholesterol fractional synthesis rate (FSR) is related inversely to infant dietary cholesterol at 4 months of age; however, it remains to be established whether this effect is permanent, possibly contributing to later hypercholesterolemia. Objective. To determine whether levels of dietary cholesterol in infancy induced changes in FSR and plasma lipid levels that persisted at 18 months. Methods. A prospective clinical trial was conducted with 47 infants, from their first week of life until 18 months of age, who received human milk (HM)until weaned (n = 15)or were randomized to receive modified cow's milk formula (MCF)with added cholesterol (n = 15)or cow's milk formula (CF)(n = 17)for 12 months. Cholesterol contents of HM, MCF, and CF were 120, 80, and 40 mg/L, respectively. FSR and plasma lipid levels were measured at 4 and 18 months. Results. At 4 months, total cholesterol and low-density lipoprotein cholesterol levels were higher for infants fed HM and MCF, compared with CF. High-density lipoprotein cholesterol levels were higher in the MCF group than in the HM and CF groups. FSR in the HM group (0.034 ± 0.005 pools per day) was lower than that in the CF group (0.052 ± 0.005 pools per day). There was no difference between the HM and MCF (0.047 ± 0.005 pools per day) groups or between the MCF and CF groups. At 18 months, there were no differences in FSRs or plasma lipid profiles between the groups. Conclusion. Although cholesterol intake before weaning affects FSRs and plasma lipid profiles at 4 months, these differences do not persist after weaning to an unrestricted diet at 18 months. This provides additional evidence that there is no imprinting of FSR in infancy with differing dietary levels of cholesterol. [ABSTRACT FROM AUTHOR]

Discusses functional foods, in light of the controversy over the nature of the relation between diet and disease. Definition of functional foods; Impetus behind their evolution; Examples of functional foods, including oat bran fiber, soy protein, fish oil fatty acids, probiotics and prebiotics, and plant sterols and stanols; Factors influencing the future viability and success of functional foods; Outlook for global acceptance.

The article presents the authors' views on the impact of Maasai gummivory on human diet and public health in Africa during the Paleolithic period. The consumption of myrrhs and other gums and resins influences the health of Maasai pastoralists. It also has implications for general human ecological significance. The consumption of plant chemical constituents or phytochemicals has an impact on public health.

De novo lipogenesis plays a key role in the hypertriglyceridemia associated with type-2 diabetes. Kinetic approaches are needed to study the effectiveness of potential treatment interventions for this aspect of the disease. Therefore, the objective of this study was to evaluate the effects of dietary sugar on synthesis and desaturation of palmitic, stearic and oleic acids in dogs using stable isotope techniques. Twelve dogs were randomized to a high sugar or low sugar diet and orally administered deuterated water (DzO) following consumption of the treatment diet. Blood samples were taken 1 hour before and 1, 2, 4, 6, 8 hours post D20 administration. Deuterium incorporation into newly synthesized fatty acids was assessed using GC/TC/IRMS. Plasma concentrations of palmitic, stearic and oleic acids in both groups remained similar over the 8 hours while deuterium enrichment of fatty acids increased linearly. Deuterium enrichment in the high sugar group was 3, 4 and 10-fold higher for palmitic, stearic and oleic acids, respectively, compared to controls (P < 0.05). The palmitic and stearic acid plasma pools (enrichment/µg) reached plateau enrichment after 6 hours however enrichment of the oleate pool continued in increase at 8 hours. These findings demonstrate the usefulness of this model for the study of both perturbations and therapeutic interventions in de novo synthesis of fatty acids. [ABSTRACT FROM AUTHOR]

N-acylethanolamines (NAEs) are lipid signaling mediators, which can be synthesized from dietary fatty acids via n-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD) and in turn influence physiological outcomes; however, the roles of NAPE-PLD upon dietary fatty acid modulation are not fully understood. Presently, we examine if NAPE-PLD is necessary to increase NAEs in response to dietary fatty acid manipulation. Post-weaning male wild-type (C57Bl/6), NAPE-PLD (-/+) and NAPE-PLD (-/-) mice received isocaloric fat diets containing either beef tallow, corn oil, canola oil or fish oil (10% wt/wt from fat) for 9 weeks. Brain docosahexaenoic acid (DHA) levels were higher (P<.01) in NAPE-PLD (-/+) (10.01±0.31 μmol/g) and NAPE-PLD (-/-) (10.89±0.61 μmol/g) than wild-type (7.72±0.61 μmol/g) consuming fish oil. In NAPE-PLD (-/-) mice, brain docosahexaenoylethanolamide (DHEA) levels were higher (P<.01) after fish oil feeding suggesting that NAPE-PLD was not necessary for DHEA synthesis. Liver and jejunum arachidonoylethanolamide, 1,2-arachidonoylglycerol and DHEA levels reflected their corresponding fatty acid precursors suggesting that alternate pathways are involved in NAE synthesis. NAPE-PLD (-/-) mice had lower oleoylethanolamide levels in the jejunum and a leaner phenotype compared to wild-type mice. Overall, these results demonstrate that dietary fatty acid can augment tissue NAEs in the absence of NAPE-PLD. [ABSTRACT FROM AUTHOR]

Introduction: Up to 20% of outpatients receiving HMG-CoA reductase inhibitors (statins) experience treatment reluctance on the basis of side effects, leaving a large population at increased risk of CVD. We hypothesized that a practical food-based approach can be utilized to lower LDL-C in statin reluctant patients and that the lipid response can be predicted based upon CYP7A1-rs3808607 (CYP7A1) and APOE genetic isoforms. Methods: This was a multicenter, randomized, double-blind, free-living cross-over study composed of 2 phases of 4 wk each, separated by a 4 wk washout. Participants (n=54) received an assortment of individually packaged, shelf stable snacks along with printed instructions to ingest 2 servings of the foods per day as a substitute for similar items they were eating already. No other dietary or behavior adjustments were requested. Treatment products supplied at least 1800 mg alpha-linoleic acid (ALA), 5 g of fiber and 1g of phytosterols per serving. Control products were calorie-matched like items drawn from the general grocery marketplace. Lipid parameters were measured and averaged over 2 d at baseline and at 4 wk of each phase. Ingestion of study foods was confirmed by C18:3n3 serum level assessment. Single nucleotide polymorphisms and APOE isoform were assessed by Taqman genotyping assay. Results: As compared to control, LDL-C decreased 8.8% in the treatment arm (p<0.0001, range -37.6% to +20.5%) and total cholesterol fell 5.1% (p<0.004). No significant change was seen in HDL-C, TG or fasting glucose levels. LDL-C was reduced by diet in CYP7A1 T/T homozygotes (-0.3924+0.1271mmol/l, p = 0.0033) and APOE4 carriers (-0.3808+0.098 mmol/l, p = 0.0003). Conclusions: Significant LDL-C reductions can be affected through a simple food intervention supplying high levels of phytosterols, fiber and ALA. CYP7A1 and APOE isoforms influence the variability in LDL-C response and can help identify individual patients especially appropriate for a food-based LDL-C lowering approach. Given the large number of patients unable/unwilling to take statins, our findings have significant impact for management of this challenging population. [ABSTRACT FROM AUTHOR]