Oleoylethanolamide: The role of a bioactive lipid amide in modulating eating behaviour.

Fatty acid ethanolamides are lipid mediators that regulate a plethora of physiological functions. One such bioactive lipid mediator, oleoylethanolamide (OEA), is a potent agonist of the peroxisome proliferator-activated receptor-alpha (PPAR-α), which modulates increased expression of the fatty acid translocase CD36 that enables the regulation of feeding behaviour. Consumption of dietary fat rich in oleic acid activates taste receptors in the gut activating specific enzymes that lead to the formation of OEA. OEA further combines with PPAR-α to enable fat oxidation in the liver, resulting in enhanced energy production. Evidence suggests that sustained ingestion of a high-fat diet abolishes the anorexic signal of OEA. Additionally, malfunction of the enterocyte that transforms oleic acid produced during fat digestion into OEA might be responsible for reduced satiety and hyperphagia, resulting in overweight and obesity. Thus, OEA anorectic signalling may be an essential element of the physiology and metabolic system regulating dietary fat intake and obesity. The evidence reviewed in this article indicates that intake of oleic acid, and thereby the resulting OEA imparting anorexic properties, is dependent on CD36, PPAR-α, enterocyte fat sensory receptors, histamine, oxytocin and dopamine; leading to increased fat oxidation and enhanced energy expenditure to induce satiety and increase feeding latency; and that a disruption in any of these systems will cease/curb fat-induced satiety.

Supplementation of krill oil with high phospholipid content increases sum of EPA and DHA in erythrocytes compared with low phospholipid krill oil.

BACKGROUND: Bioavailability of krill oil has been suggested to be higher than fish oil as much of the EPA and DHA in krill oil are bound to phospholipids (PL). Hence, PL content in krill oil might play an important role in incorporation of n-3 PUFA into the RBC, conferring properties that render it effective in reducing cardiovascular disease (CVD) risk. The objective of the present trial was to test the effect of different amounts of PL in krill oil on the bioavailability of EPA and DHA, assessed as the rate of increase of n-3 PUFA in plasma and RBC, in healthy volunteers. METHODS AND DESIGN: In a semi randomized crossover single blind design study, 20 healthy participants consumed various oils consisting of 1.5 g/day of low PL krill oil (LPL), 3 g/day of high PL krill oil (HPL) or 3 g/day of a placebo, corn oil, for 4 weeks each separated by 8 week washout periods. Both LPL and HPL delivered 600 mg of total n-3 PUFA/day along with 600 and 1200 mg/day of PL, respectively. RESULTS: Changes in plasma EPA, DPA, DHA, total n-3 PUFA, n-6:n-3 ratio and EPA + DHA concentrations between LPL and HPL krill oil supplementations were observed to be similar. Intake of both forms of krill oils increased the RBC level of EPA (p < 0.001) along with reduced n-6 PUFA (LPL: p < 0.001: HPL: p = 0.007) compared to control. HPL consumption increased (p < 0.001) RBC concentrations of EPA, DPA, total and n-3 PUFA compared with LPL. Furthermore, although LPL did not alter RBC n-6:n-3 ratio or the sum of EPA and DHA compared to control, HPL intake decreased (p < 0.001) n-6:n-3 ratio relative to control with elevated (p < 0.001) sum of EPA and DHA compared to control as well as to LPL krill oil consumption. HPL krill oil intake elevated (p < 0.005) plasma total and LDL cholesterol concentrations compared to control, while LPL krill oil did not alter total and LDL cholesterol, relative to control. CONCLUSIONS: The results indicate that krill oil with higher PL levels could lead to enhanced bioavailability of n-3 PUFA compared to krill oil with lower PL levels. TRIAL REGISTRATION: Clinicaltrials.gov# NCT01323036.

Progress and prospective of plant sterol and plant stanol research: report of the Maastricht meeting.

Abundant evidence over past decades shows that foods with added plant sterols and plant stanols lower serum LDL cholesterol concentrations. However, despite the overwhelming data, numerous scientific questions still remain. The objective of this paper is to summarize the considerations of 60 academic and industrial experts who participated in the scientific meeting in Maastricht, the Netherlands, on issues related to the health effects of plant sterols and plant stanols. The meeting participants discussed issues including efficacy profiling, heterogeneity in responsiveness, effects beyond LDL-C lowering, and food formulation aspects of plant sterol and stanol consumption. Furthermore, aspects related to the potential atherogenicity of elevated circulatory plant sterol concentrations were discussed. Until the potential atherogenicity of plant sterols is resolved, based on the results >200 clinical trials, the risk to benefit of plant sterol use is favorable. Evidence on these topics in plant sterol and plant stanol research was presented and used to reach consensus where possible. It was concluded that endpoint studies looking at plant sterol and plant stanol efficacy are needed, however, there was no clear opinion on the best marker and best design for such a study. Based on the current scientific evidence, plant sterols and plant stanols are recommended for use as dietary options to lower serum cholesterol.

Anti-atherogenic effects of resveratrol.

Resveratrol (RS), a polyphenol compound found in grapes and grape products, including wine, peanuts and berries, exists in cis- and trans-isomeric forms. RS is believed to decrease circulating low-density lipoprotein cholesterol levels and reduce cardiovascular disease (CVD) risk. However, it is possible that RS has other mechanisms to reduce the risk of CVD without altering lipid levels. The objective of this review is to critically examine results from recent research concerning potential effects of RS on CVD. RS exerts several health benefits including anti-atherogenic, anti-inflammatory and anti-cancer effects. RS may also prevent lipid oxidation, platelet aggregation, arterial vasodilation and modulates the levels of lipids and lipoproteins. As a potent, anti-oxidant RS reduces oxidative stress and regenerates alpha-tocopherol, which further strengthens the anti-oxidant defense mechanism. RS has been considered safe as no significant toxic effects have been identified, even when consumed at higher concentrations. This evidence identified RS as an effective anti-atherogenic agent, which could be used in the prevention and treatment of CVD.

Effect of plant sterol-enriched diets on plasma and egg yolk cholesterol concentrations and cholesterol metabolism in laying hens.

Egg exists as a major dietary source of cholesterol in Western diets. In North America, laying hen diets are usually devoid of cholesterol when diets are formulated to exclude animal-based products. Hence, laying hens meet their physiological cholesterol requirement through de novo synthesis. Plant sterols exert a cholesterol-lowering effect in humans by interfering with intestinal sterol absorption. However, it is unknown whether plant sterol supplementation could be effective in reducing intestinal reabsorption of biliary cholesterol in laying hens, thus modulating whole body cholesterol in favor of lower plasma and yolk cholesterol content. The current study was designed to investigate the effect of diets enriched with 0, 0.5, 1, and 2% plant sterols on cholesterol absorption, synthesis, as well as plasma, liver, and egg yolk cholesterol concentrations in laying hens. After 8 wk of plant sterol intervention (first 2 wk were acclimatization), feed intake, BW, egg weight, egg yolk weight, egg production, Haugh units, liver mass, plasma, and hepatic cholesterol concentrations did not differ as a function of plant sterol supplementation. Egg cholesterol concentrations (mg/g) fluctuated during the 6-wk experimental period. At wk 6, a minor reduction in egg yolk cholesterol concentration (mg per g of yolk, P<0.05, vs. control) was observed in hens fed 1 and 2% cholesterol-enriched diets, respectively. However, such result failed to affect total egg cholesterol content. No statistical difference was observed across treatments over 6 wk. Neither cholesterol absorption rates nor synthesis differed as a function of treatment. Results suggested that overall cholesterol content in egg yolk was not affected by feeding hens plant sterol-enriched diets over 6 wk.

Dietary cholesterol and the risk of cardiovascular disease in patients: a review of the Harvard Egg Study and other data.

For many years, both the medical community and the general public have incorrectly associated eggs with high serum cholesterol and being deleterious to health, even though cholesterol is an essential component of cells and organisms. It is now acknowledged that the original studies purporting to show a linear relation between cholesterol intake and coronary heart disease (CHD) may have contained fundamental study design flaws, including conflated cholesterol and saturated fat consumption rates and inaccurately assessed actual dietary intake of fats by study subjects. Newer and more accurate trials, such as that conducted by Frank B. Hu of the Harvard School of Public Health (1999), have shown that consumption of up to seven eggs per week is harmonious with a healthful diet, except in male patients with diabetes for whom an association in higher egg intake and CHD was shown. The degree to which serum cholesterol is increased by dietary cholesterol depends upon whether the individual's cholesterol synthesis is stimulated or down-regulated by such increased intake, and the extent to which each of these phenomena occurs varies from person to person. Several recent studies have shed additional light on the specific interplay between dietary cholesterol and cardiovascular health risk. It is evident that the dynamics of cholesterol homeostasis, and of development of CHD, are extremely complex and multifactorial. In summary, the earlier purported adverse relationship between dietary cholesterol and heart disease risk was likely largely over-exaggerated.

Anti-inflammatory effect of Inonotus obliquus, Polygala senega L., and Viburnum trilobum in a cell screening assay.

AIM OF THE STUDY: The purpose of the study was to assess the anti-inflammatory effects of the mushroom Inonotus obliquus (Chaga), Polygala senega (Senega) and Viburnum trilobum (Cranberry) bark extract fractions from locally produced materials in lipopolysaccharide (LPS) induced murine macrophage RAW 164.7 cells. MATERIALS AND METHODS: Four fractions from each of the three extracts were obtained: (80% ethanol extracted; Fa), (water-soluble polysaccharide fraction; Fb), (Polyphenolic fraction; Fc) and (ETOAc/H(2)O extracted fraction; Fd). These extract fractions were tested in the cell screening system at 50,100 and 500 microg/ml for their ability to inhibit LPS induced inflammatory cytokines IL-1beta, TNFalpha and IL-6. Supernatants from LPS alone treated cells were used as control. The cytokines in the cell culture supernatants following treatments with extract fractions were quantified by ELISA method, using 96 well ELISA plates. RESULTS: All fractions of the extracts significantly inhibited (p<0.05) the levels of IL-1beta, IL-6 and TNFalpha except the polyphenolic Fc fraction of Senega which showed an increased production of IL-6. Furthermore, each fraction showed a dose-dependant anti-inflammatory effect. Nitric oxide production was not affected by cranberry and senega, while Chaga significantly reduced NO production in murine macrophage cell assay. CONCLUSIONS: These results demonstrate that the extracts obtained from the root of Polygala senega L., bark of Viburnum trilobum, and the mushroom Inonotus obliquus possess anti-inflammatory properties when tested in a RAW 264.7 macrophage cell system.

Anticancer effects of phytosterols.

Phytosterol and stanol (or phytosterols) consumption reduces intestinal cholesterol absorption, leading to decreased blood LDL-cholesterol levels and lowered cardiovascular disease risk. However, other biological roles for plant sterols and stanols have also been proposed. The objective of this review is to critically examine results from recent research regarding the potential effects and mechanisms of action of phytosterols on forms of cancer. Considerable emerging evidence supports the inhibitory actions of phytosterols on lung, stomach, as well as ovarian and breast cancer. Phytosterols seem to act through multiple mechanisms of action, including inhibition of carcinogen production, cancer-cell growth, angiogenesis, invasion and metastasis, and through the promotion of apoptosis of cancerous cells. Phytosterol consumption may also increase the activity of antioxidant enzymes and thereby reduce oxidative stress. In addition to altering cell-membrane structure and function, phytosterols probably promote apoptosis by lowering blood cholesterol levels. Moreover, consumption of phytosterols by healthy humans at the recommended level of 2 g per day does not cause any major health risks. In summary, mounting evidence supports a role for phytosterols in protecting against cancer development. Hence, phytosterols could be incorporated in diet not only to lower the cardiovascular disease risk, but also to potentially prevent cancer development.

Baseline plasma plant sterol concentrations do not predict changes in serum lipids, C-reactive protein (CRP) and plasma plant sterols following intake of a plant sterol-enriched food.

BACKGROUND/OBJECTIVES: Plant sterol (PS) consumption lowers serum cholesterol levels, while modestly increasing plasma PS concentrations. Plasma PS concentrations may reflect sterol absorption, thus individuals with high plasma plant sterol (HPS) concentrations may show greater changes in circulating cholesterol and PS than individuals with low plasma plant sterol (LPS) concentrations. The objective of this study was to examine whether HPS and LPS concentrations are related to subsequent changes in plasma PS, serum lipid and C-reactive protein (CRP) concentrations, following dietary PS intake in otherwise healthy hypercholesterolemic men. SUBJECTS/METHODS: This single-blinded, randomized, diet-controlled study consisted of two 4-week phases, separated by a 4-week washout, where a diet with a placebo or the 2.0 g per day PS-enriched spread was consumed during the phases. RESULTS: At baseline, men with HPS possessed higher (P<0.01) mean serum cholesterol concentration, while those with LPS had higher (P<0.05) body mass index. Following PS intake, plasma sum of campesterol plus sitosterol concentrations were elevated from 34.6+/-4.2 to 46.2+/-3.3 micromol l(-1) (mean+/-SE) and 16.5+/-0.9 to 20.8+/-1.2 micromol l(-1) after PS intake in men with HPS and LPS, respectively. Changes in plasma PS concentrations, however, were not different between individuals with either HPS or LPS baseline concentrations. Total cholesterol and low-density lipoprotein cholesterol levels were decreased (P<0.0001) by 6.3 and 7.8%, respectively, with PS consumption for all individuals. Changes in lipid parameters were not different between individuals with HPS or LPS baseline concentrations. No changes in CRP were apparent subsequent to PS intervention. CONCLUSIONS: Baseline plasma PS concentrations are not associated or predictive of changes in serum cholesterol or plasma PS concentrations after PS intervention. Thus, individuals with HPS show similar increases in PS concentrations as individuals with LPS following PS supplementation. Plasma PS remained in the range of previously reported concentrations.

Plant sterol consumption frequency affects plasma lipid levels and cholesterol kinetics in humans.

BACKGROUND/OBJECTIVES: To compare the efficacy of single versus multiple doses of plant sterols on circulating lipid level and cholesterol trafficking. SUBJECTS/METHODS: A randomized, placebo-controlled, three-phase (6 days/phase) crossover, supervised feeding trial was conducted in 19 subjects. Subjects were provided (i) control margarine with each meal; (ii) 1.8 g/day plant sterols in margarine with breakfast (single-BF) and control margarine with lunch and supper or (iii) 1.8 g/day plant sterols in margarine divided equally at each of the three daily meals (three times per day). RESULTS: Relative to control, end point plasma low-density lipoprotein (LDL) cholesterol concentrations were lower (P<0.05) after consuming plant sterols three times per day but were not different when consumed once per day (3.43+/-0.62, 3.22+/-0.58 and 3.30+/-0.65 mmol/l, control, three times per day and single-BF, respectively). Relative to the control, end point LDL level was 0.21+/-0.27 mmol/l (6%) lower (P<0.05) at the end of the three times per day phase. Cholesterol fractional synthesis rate was highest (P<0.05) after the three times per day phase (0.0827+/-0.0278, 0.0834+/-0.0245 and 0.0913+/-0.0221 pool/day, control, single-BF and three times per day, respectively). Cholesterol-absorption efficiency decreased (P<0.05) by 36 and 39% after the three times per day and single-BF phase, respectively, relative to control. CONCLUSIONS: Present data indicate that to obtain optimal cholesterol-lowering impact, plant sterols should be consumed as smaller doses given more often, rather than one large dose.

Hypocholesterolemic and anti-obesity effects of saponins from Platycodon grandiflorum in hamsters fed atherogenic diets.

Platycodins, a group of saponin glycosides from Platycodon grandiflorum, are believed to possess anti-obesity and cholesterol-lowering properties. The aim of the present study was to investigate whether dietary platycodins affect plasma, hepatic, or fecal cholesterol concentrations, as well as cholesterol absorption and fractional synthesis rates in a dose-dependent manner. Golden Syrian hamsters (n= 45) were fed atherogenic (0.25% cholesterol) diets enriched with platycodins in the forms of either aqueous extracts (containing 0.3% to 0.5% of platycodins of diet mass) or crude saponins fractions (containing 0.9% to 1.0% of platycodins of diet mass) for 28 d. [3, 4](-13)C-cholesterol and (2)H2O tracers were administered on days 26 and 28 to assess cholesterol absorption and biosynthesis, respectively. After platycodin intervention, total cholesterol concentrations in plasma and liver were reduced (P < 0.05) by 13% to 28% and 41% to 79%, respectively, whereas cholesterol concentrations in feces were increased (P < 0.05) up to 2.5-fold compared to controls. Platycodin feeding increased (P < 0.001) cholesterol absorption up to 60%, but not cholesterol synthesis. These results suggest that platycodin-enriched diets can lower circulating and whole body cholesterol contents, and thus reduce the risk of cardiovascular diseases through mechanisms independent from cholesterol absorption or synthesis.

Cholesterol metabolism and body composition in women: the effects of moderate weight loss.

OBJECTIVE: To determine how moderate weight loss protocol through diet and exercise may affect changes in body composition, to determine the effects of weight loss on cholesterol metabolism and to examine the relationship between cholesterol metabolism and changes in body composition. DESIGN: Thirty-five otherwise healthy, hypercholesterolemic women completed a 24-week weight loss study. A 20% decrease in energy intake through diet and a 10% increase in energy expenditure by exercise were combined with motivational strategies to encourage weight loss. The diet was self-selected and comprised of 50-60% carbohydrates, 20% protein and <30% fat. RESULTS: Participants lost an average of 11.7+/-2.5 kg (P<0.001). Whole body and regional losses in tissue mass occurred after weight loss. After weight loss, cholesterol fractional synthesis rate (FSR) decreased (P=0.003) 3.86+/-9.33%, whereas rates of cholesterol absorption and turnover did not change (3.31+/-19.4%, P=0.32 and -0.01+/-6.20%, P=0.75, respectively). Changes in cholesterol turnover were positively correlated (r=0.44, P=0.01) with changes in FSR. Reductions in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were predictive (beta=-5.04, r=0.38; P=0.03, and beta=-147, r=0.40; P=0.03, respectively) of increases in cholesterol turnover. Losses in skeletal muscle (SM) and upper-body SM predicted (beta=6.82, r=0.36; P=0.04 and beta=14.7, r=0.41; P=0.01, respectively) decreases in cholesterol absorption. CONCLUSIONS: Decreases in cholesterol synthesis after moderate weight loss are not compensated for by changes in cholesterol absorption or turnover. Changes in regional body composition were associated with variations in cholesterol metabolism. Understanding how weight loss affects cholesterol metabolism will help identify more effective treatment routes for overweight individuals undergoing weight loss resulting in earlier and more intensive therapy for the associated dyslipidemia.

Effect of plant sterols and glucomannan on lipids in individuals with and without type II diabetes.

OBJECTIVE: The purpose of this study was to determine whether supplements of plant sterols and/or glucomannan improve lipid profile and cholesterol biosynthesis in mildly hypercholesterolemic type II diabetic and non-diabetic subjects and to compare the response of these two subject groups to the treatments. DESIGN: A randomized, crossover study consisting of four phases of 21 days, with each phase separated by a 28-day washout. SETTING: The Mary Emily Clinical Nutrition Research Unit of McGill University. SUBJECTS: Eighteen non-diabetic individuals and 16 type II diabetic individuals aged 38-74 years. INTERVENTIONS: Subjects were supplemented with plant sterols (1.8 g/day), glucomannan (10 g/day), a combination of glucomannan and plant sterols, and a placebo, provided in the form of bars. RESULTS: Overall plasma cholesterol concentrations were lowered (P<0.05) after combination treatment (4.72+/-0.20 mmol/l) compared to control (5.47+/-0.18 mmol/l). Plasma low-density lipoprotein (LDL) cholesterol concentrations were decreased (P<0.05) after glucomannan (3.16+/-0.14 mmol/l) and combination treatments (2.95+/-0.16 mmol/l) compared to control (3.60+/-0.16 mmol/l). The results of lipid profiles did not differ between subject groups. Overall plasma lathosterol concentrations, an index of cholesterol biosynthesis, were lowered (P<0.05) after the combination treatment compared to the plant sterol treatment. CONCLUSIONS: The results suggest that glucomannan and a combination of glucomannan and plant sterols substantially improves plasma LDL cholesterol concentrations. SPONSORSHIP: Forbes Medi-Tech Inc., Vancouver, British Columbia, Canada.

Micellar solubilisation of cholesterol is essential for absorption in humans.

BACKGROUND AND AIMS: Intralumenal bile acid (BA) concentrations have a profound effect on cholesterol absorption. We performed studies to assess the effects of markedly reduced lumenal BA on cholesterol absorption in children with inborn errors in BA synthesis and the role of micellar solubilisation of cholesterol on its absorption in an animal model using human intestinal contents. METHODS: We studied five subjects: two with 3beta hydroxy-C27 steroid dehydrogenase isomerase deficiency (3-HSD), two with Delta(4)-3-oxosteroid 5beta reductase deficiency (5beta reductase), and one with 2-methylacyl CoA racemase deficiency (racemase). Subjects were studied on supplemental BA therapy and three weeks after withdrawal of supplements. During each treatment period a liquid meal was consumed. Duodenal samples were collected and analysed, and cholesterol absorption and cholesterol fractional synthetic rates were measured. Human intralumenal contents were infused in a bile diverted rat lymph fistula model to assess micellar versus vesicular absorption of cholesterol. RESULTS: Without BA supplementation, intralumenal BA concentrations were below the critical micellar concentration (CMC) whereas intralumenal BAs increased to above the CMC in all subjects on BA supplementation. Lumenal cholesterol was carried primarily as vesicles in untreated subjects whereas it was carried as both micelles and vesicles in treated subjects. Cholesterol absorption increased approximately 55% in treated compared with untreated subjects (p=0.041), with a simultaneous 70% decrease in synthesis rates (p=0.029). In the rat lymph fistula model, minimal vesicular cholesterol was absorbed whereas vesicular and micellar fatty acid and phospholipid were comparably absorbed. CONCLUSIONS: Increasing micellar cholesterol solubilisation by supplemental BA in subjects with inborn errors of BA synthesis leads to an improvement in cholesterol absorption and reduction in cholesterol synthesis due to improved micellar solubilisation of cholesterol.

Plant stanol ascorbate esters reduce body weight gain through decreased energy absorption in hamsters.

OBJECTIVE: The objective of this study was to determine the effects of disodium ascorbyl phytostanyl phosphate (DAPP), a novel hydrophilic phytostanol analogue, on energy homeostasis, including body weight and intestinal energy absorption, and plasma triglyceride concentrations, in hamsters. METHODS: Male Golden Syrian hamsters (n = 50) were fed for 5 weeks with experimental diets varying in cholesterol and phytostanol content. Diets included (i) non-cholesterol (semipurified diet without added cholesterol), (ii) cholesterol-control (semipurified diet with 0.25% cholesterol), (iii) stanol (cholesterol-control with 1% free phytostanols), (iv) DAPP 0.7% (cholesterol-control with 0.71% DAPP) or (v) DAPP 1.4% (cholesterol-control with 1.43% DAPP). Fecal samples were collected continuously for 3 days on week 3, and fecal energy output was measured by bomb calorimetry. RESULTS: Hamsters fed 1.4% DAPP gained less (P<0.05) weight than hamsters fed non-cholesterol and stanol diets. Diets had no effect on total food consumption or gross energy intake after 5 weeks, but lower (P<0.05) weekly food consumptions in hamsters fed 1.4% DAPP were observed at weeks 1 and 2 of the experiment in comparison to animals fed the non-cholesterol diet. In comparison to non-cholesterol and cholesterol-control diets, DAPP 1.4% increased (P<0.01) fecal energy output by 47 and 46%, respectively. In hamsters supplemented with 1.4% DAPP, plasma triglyceride concentrations were 45% lower (P<0.05) than in cholesterol-control fed hamsters. Furthermore, plasma triglyceride levels in the DAPP 1.4% group was 49% lower (P<0.01) than in the stanol group, despite the fact that both diets contained equivalent amounts of phytostanols. The lower concentration of DAPP (0.7%) also reduced plasma triglycerides (P<0.05) compared with the stanol diet. CONCLUSION: Stanol-ascorbate decreases body weight gain in hamsters, likely due to lower energy absorption at the intestinal level. In addition to its previously observed powerful cholesterol-lowering effect, DAPP has a hypotriglyceridemic function in hamsters.

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

OBJECTIVE: To examine the impact of nonfat and low-fat phytosterol-enriched beverages on low-density lipoprotein (LDL) electrophoretic characteristics. DESIGN: Double-blind, randomized, crossover, placebo-controlled dietary trial. SETTING: Diets were prepared and consumed at the Mary Emily Clinical Nutrition Research Unit of McGill University. Analyses were performed at the Institute on Nutraceuticals and Functional Foods of Laval University. SUBJECTS AND INTERVENTION: In total, 15 moderately hypercholesterolemic persons consumed each of three experimental diets that each comprised a different beverage: nonfat placebo (NF control), nonfat with phytosterols (NFPS) or low-fat with phytosterols (LFPS). Participants consumed three beverages daily at meal time for a total of 1.8 g of phytosterols per day. Nondenaturing 2-16% polyacrylamide gradient gel electrophoreses were used to characterize LDL size characteristics. RESULTS: The NFPS and LFPS beverage induced no significant changes in several features of the LDL size phenotype compared to the control diet. CONCLUSION: The consumption of phytosterol-supplemented nonfat and low-fat beverages is not associated with clinically meaningful changes in the LDL particle size phenotype.

Effect of plant sterols and endurance training on LDL particle size and distribution in previously sedentary hypercholesterolemic adults.

BACKGROUND: Plant sterols and exercise favourably alter lipid profiles in a way that protect against future coronary heart disease (CHD). However, their effects on other indicators of CHD risk, such as LDL particle size, still need further clarification. OBJECTIVE: This study examined the effect of plant sterols, exercise, and the combination of plant sterols and exercise, on LDL particle size and distribution in previously sedentary, hypercholesterolemic adults. DESIGN: In an 8-week, placebo-controlled, parallel-arm clinical trial, 84 subjects were randomized to one of four intervention groups: (1) combination of sterols and exercise, (2) exercise, (3) sterol, or (4) control. RESULTS: Exercise significantly (P < 0.05) reduced post-treatment LDL peak particle size from 255 to 253 A. Additionally, exercise significantly (P < 0.05) decreased the proportion of large LDL particles within plasma. Sterol supplementation significantly (P < 0.05) decreased the estimated cholesterol concentrations within small, medium, and large LDL particles by 13.4, 13.5, and 14.4%, respectively, yet had no effect on the distribution of cholesterol among various LDL particle sizes. Furthermore, decreased body weight post-training was associated with increased cholesterol in small LDL particles (r = -0.52, P < 0.0001). Decrease in body fat percent (BF%) post-training was associated with increased cholesterol concentrations in small LDL particles (r = -0.29, P < 0.01). CONCLUSION: On the basis of modulating LDL electrophoretic characteristics, the present study demonstrates that plant sterols have no effect on CHD risk, while short-term exercise may potentially increase CHD risk by decreasing LDL peak particle size. SPONSORSHIP: This study was sponsored by The Heart and Stroke Foundation of Canada.

Conjugated linoleic acid and obesity control: efficacy and mechanisms.

Obesity is associated with high blood cholesterol and high risk for developing diabetes and cardiovascular disease. Therefore, management of body weight and obesity are increasingly considered as an important approach to maintaining healthy cholesterol profiles and reducing cardiovascular risk. The present review addresses the effects of conjugated linoleic acid (CLA) on fat deposition, body weight and composition, safety, as well as mechanisms involved in animals and humans. Animal studies have shown promising effects of CLA on body weight and fat deposition. The majority of the animal studies have been conducted using CLA mixtures that contained approximately equal amounts of trans-10, cis-12 (t10c12) and cis-9, trans-11 (c9t11) isomers. Results of a few studies in mice fed CLA mixtures with different ratios of c9t11 and t10c12 isomers have indicated that the t10c12 isomer CLA may be the active form of CLA affecting weight gain and fat deposition. Inductions of leptin reduction and insulin resistance are the adverse effects of CLA observed in only mice. In pigs, the effects of CLA on weight gain and fat deposition are inconsistent, and no adverse effects of CLA have been reported. A number of human studies suggest that CLA supplementation has no effect on body weight and insulin sensitivity. Although it is suggested that the t10c12 CLA is the antiadipogenic isomer of CLA in humans, the effects of CLA on fat deposition are marginal and more equivocal as compared to results observed in animal studies. Mechanisms through which CLA reduces body weight and fat deposition remain to be fully understood. Proposed antiobesity mechanisms of CLA include decreased energy/food intake and increased energy expenditure, decreased preadipocyte differentiation and proliferation, decreased lipogenesis, and increased lipolysis and fat oxidation. In summary, CLA reduces weight gain and fat deposition in rodents, while produces less significant and inconsistent effects on body weight and composition in pigs and humans. New studies are required to examine isomer-specific effects and mechanisms of CLA in animals and humans using purified individual CLA isomers.

Greater rise in fat oxidation with medium-chain triglyceride consumption relative to long-chain triglyceride is associated with lower initial body weight and greater loss of subcutaneous adipose tissue.

OBJECTIVE: Medium-chain triglyceride (MCT) consumption has been shown to increase energy expenditure (EE) and lead to greater losses of the adipose tissue in animals and humans. The objective of this research was to examine the relationship between body composition and thermogenic responsiveness to MCT treatment. DESIGN: Randomized, crossover, controlled feeding trial, with diets rich in either MCT or long-chain triglyceride (LCT) (as olive oil) for periods of 4 weeks each. SUBJECTS: A total of 19 healthy overweight men aged (x+/-s.e.m.) 44.5+/-2.5 y with a body mass index of 27.8+/-0.5 kg/m(2). MEASUREMENTS: EE and body composition were measured using indirect calorimetry and magnetic resonance imaging, respectively, at the baseline and end point of each feeding period. EE was measured for 30 min before consumption of a standard meal and for 5.5 h following the meal. RESULTS: Body weight (BW) decreased (P<0.05) by 1.03+/-0.25 kg with MCT consumption compared to 0.62+/-0.29 kg with LCT consumption. The difference in average EE between MCT and LCT consumptions was related to initial BW, such that men with lower initial BW had a greater rise in EE with MCT consumption relative to LCT on day 28 (r=-0.472, P=0.04) but not day 2 (r=-0.368, P=0.12). Similar results were obtained with fat oxidation on day 28 (r=-0.553, P=0.01). The greater rise in fat oxidation with MCT compared to LCT consumption on day 2 tended to be related to greater loss of BW after MCT vs LCT consumption (r=-0.4075, P=0.08). CONCLUSION: These data suggest that shunting of dietary fat towards oxidation results in diminished fat storage, as reflected by the loss of BW and subcutaneous adipose tissue. Furthermore, MCT consumption may stimulate EE and fat oxidation to a lower extent in men of greater BW compared to men of lower BW, indicative of the lower responsiveness to a rapidly oxidized fat by overweight men.International