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High-protein diets have been advocated for weight loss and the treatment of diabetes. Yet animal protein sources are often high in saturated fat and cholesterol. Vegetable protein sources, by contrast, are low in saturated fat and without associated cholesterol. We have therefore assessed the effect on serum lipids of raising the protein intake by 5% using a cereal protein, barley protein, as part of a standard therapeutic diet. Twenty-three hypercholesterolemic men and postmenopausal women completed a randomized crossover study comparing a bread enriched with either barley protein or calcium caseinate [30 g protein, 8374 kJ (2000 kcal)] taken separately as two 1-mo treatment phases with a minimum 2-wk washout. Body weight and diet history were collected weekly during each treatment. Fasting blood samples were obtained at wk 0, 2, and 4. Palatability, satiety, and compliance were similar for both the barley protein- and casein- enriched breads, with no differences between the treatments in effects on serum LDL cholesterol or C-reactive protein, measures of oxidative stress, or blood pressure. Nevertheless, because no adverse effects were observed on cardiovascular risk factors, barley protein remains an additional option for raising the protein content of the diet. J. Nutr. 140: 1633-1637, 2010. doi: 10.3945/jn.110.123224.

The effect of dietary plant sterols on cholesterol homeostasis has been well characterized in the intestine, but how plant sterols affect lipid metabolism in other lipid-rich tissues is not known. Changes in hepatic cholesterol homeostasis in response to high dietary intakes of plant sterols were determined in male golden Syrian hamsters fed hypercholester-olemia-inducing diets with and without 2% plant sterols (wt:wt; Reducol, Forbes Meditech) for 28 d. Plasma and hepatic cholesterol concentrations, cholesterol biosynthesis and absorption, and changes in the expression of sterol response element binding protein 2 (SREBP2) and liver X receptor-/3 (LXR/3) and their target genes were measured. Plant sterol feeding reduced plasma total cholesterol, non-HDL cholesterol, and HDL cholesterol concentrations 43% (P < 0.0001), 60% (P < 0.0001), and 21% (P = 0.001), respectively, compared with controls. Furthermore, there was a 93% reduction (P < 0.0001) in hepatic total cholesterol and >6-fold (P= 0.029) and >2-fold (P < 0.0001)increases in hepatic/3-sitosterol and campesteroi concentrations, respectively, in plant sterol-fed hamsters compared with controls. Plant sterol feeding also increased fractional cholesterol synthesis >2-fold (P < 0.03) and decreased cholesterol absorption 83% (P < 0.0001) compared with controls. Plant sterol feeding increased hepatic protein expression of cytosolic (inactive) SREBP2, decreased nuclear (active) SREBP2, and tended to increase LXR/3 (P = 0.06) and ATP binding cassette transporter G5, indicating a differential modulation of the expression of proteins central to cholesterol metabolism. In conclusion, high-dose plant sterol feeding of hamsters changes hepatic protein abundance in favor of cholesterol excretion despite lower hepatic cholesterol concentrations and higher cholesterol fractional synthesis. doi: 10.3945/jn.109.120311

Diacylglycerol (DAG) may undergo differential metabolism compared with triacylglycerol (TAG) in humans, possibly resulting in decreased serum TAG concentration and TAG synthesis and increased energy expenditure (EE), thus reducing fat accumulation. Our objective was to examine the efficacy of DAG oil (Enova oil) consumption on serum lipid profiles, hepatic lipogenesis, EE, and body weight and composition compared with a control oil-blend composed of sunflower, safflower, and rapeseed oils at a 1:1:1 ratio. Twenty-six overweight (78.3 [+ or -] 3.6 kg body weight and BMI 30.0 [+ or -] 0.7 kg/[m.sup.2]) mildly hypertriglyceridemic (1.81 [+ or -] 0.66 mmol/L) women underwent 2 treatment phases of 28 d separated by a 4-wk washout period using a randomized crossover design. They consumed 40 g/d of either DAG or control oil during treatment phases. The baseline, EE, fat oxidation, body composition, and lipid profiles did not differ between the DAG and control oil intervention periods. Relative to control oil, DAG oil did not alter endpoint postprandial EE, fat oxidation, serum lipid profiles, or hepatic lipogenesis. However, DAG oil consumption reduced (P < 0.05) accumulation of body fat within trunk, android, and gynoid regions at the endpoint compared with control oil, although neither DAG nor control oil altered any of these variables during the 4-wk intervention period compared with their respective baseline levels. We conclude that although DAG oil is not effective in lowing serum lipids over a 4-wk intervention, it may be useful for reducing adiposity. J. Nutr. 140: 1122-1126, 2010. doi: 10.3945/jn.110.121665

Worldwide consumer interest in functional foods and their potential health benefits has been increasing over the past 10 y. To respond to this interest, regulatory bodies have developed guidelines for assessing health claims on functional foods. The objective of this article is to investigate the type and amount of evidence needed in various jurisdictions on a worldwide basis to substantiate both generic and product-specific health claims. Two types of health claims were examined using separate case studies. Analysis of generic health claims was highlighted by (n-3) fatty acids and their relation to heart health; whereas examination of product-specific health claims was conducted using probiotics and their association with gastrointestinal well-being. Results showed a common core for use of convincing high-quality human data, especially in the form of randomized controlled trials (RCT), but there was significant variability in the type and amount of scientific evidence needed to substantiate health claims, both generic and product specific, across different jurisdictions. Product-specific claims tended to use human RCT as the main basis for claims, whereas generic claims tended to base their statements on a wider spectrum of literature.

Colonic short-chain fatty acids (SCFA) may affect hepatic lipid metabolism. Lactulose increases colonic acetate production, whereas L-rhamnose increases propionate. To test the effects of oral L-rhamnose and lactulose for 28 d on fasting concentrations and hepatic synthesis of lipids in humans, 18 men were administered 25 g/d of L-rhamnose, lactulose, or D-glucose for 4 wk in a partially randomized crossover design, with blood collected from fasting subjects on the first and last day of each period. Cholesterol and triacylglycerol (TG) synthesis rates were determined using deuterated water uptake rate over the last 24 h of each period. Postprandial blood lipids, and glucose and insulin were assessed in 11 subjects on d 28. Fasting serum cholesterol was unchanged; however, when expressed as a percentage change, TG were decreased, relative to baseline (P < 0.04), by L-rhamnose (-10%) and lactulose (-10%), compared with D-glucose, which increased serum TG (+11%). Net TG-fatty acid (TGFA) synthesis on d 28 was lower with L-rhamnose (2.42 [+ or -] 0.38 g/d) and lactulose (2.62 [+ or -] 0.35 g/d) than with D-glucose (2.96 [+ or -] 0.31 g/d, P< 0.01). We conclude that these results do not support a primary role for propionate in the cholesterol-lowering effect of soluble fiber. However, both lactulose and L-rhamnose lowered serum TG (expressed as a percentage change) and TGFA synthesis, compared with D-glucose, which increased them. Although these data are consistent with inhibition of TGFA synthesis by SCFA, other aspects of the metabolism of these sugars cannot be ruled out as putative agents of their TG-lowering effects.

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 sterolcontaining 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 ~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 3resent study design, where plant sterols were given as a single morning dose. KEY WORDS: * plant sterols * fish oil * plant sterol--fish-oil ester * single 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. J. Nutr. 135: 1829-1835, 2005. KEY WORDS: * dyslipidemia * diet * exercise * cholesterol * coronary heartdisease

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

[alpha]-Lipoic acid (ALA) has been identified as a powerful antioxidant found naturally in our diets, but appears to have increased functional capacity when given as a supplement in the form of a natural or synthetic isolate. ALA and its active reduced counterpart, dihydrolipoic acid (DHLA), have been shown to combat oxidative stress by quenching a variety of reactive oxygen species (ROS). Because this molecule is soluble in both aqueous and lipid portions of the cell, its biological functions are not limited solely to one environment. In addition to ROS scavenging, ALA has been shown to be involved in the recycling of other antioxidants in the body including vitamins C and E and glutathione. Not only have the antioxidant qualities of this molecule been studied, but there are also several reports pertaining to its blood lipid modulating characteristics, protection against LDL oxidation and modulation of hypertension. Therefore, ALA represents a possible protective agent against risk factors of cardiovascular disease (CVD). The objective of this review is to examine the literature pertaining to ALA in relation to CVD and describe the most powerful actions and potential uses of this naturally occurring antioxidant. Despite the numerous studies on ALA, many questions remain relating to the use of ALA as a supplement. There is no consensus on dosage, dose frequency, form of administration, and/or preferred form of ALA. However, collectively the literature increases our understanding of the potential uses for supplementation with ALA and identifies key areas for future research. KEY WORDS: * [alpha]-lipoic acid * antioxidant * cardiovascular disease

Medium-chain triglycerides (MCT) have been proposed as weight-lowering agents, although there is some concern regarding their hyperlipidemic effect. This study evaluates the effects of a combination of MCT oil, phytosterols and flaxseed oil [functional oil (FctO)] on plasma lipid concentrations and LDL particle size. Twenty-four healthy overweight men (body mass index 28.2 [+ or -] 0.4 kg/[m.sup.2]) consumed controlled diets designed to maintain weight for two periods of 29 d each. Diets contained 40% of energy as fat, 75% of which was added fat, either FctO or olive oil (OL). Body composition and blood samples were analyzed at the baseline and the endpoint of each period. Total cholesterol concentration decreased 12.5% (-0.68 mmol/L; P < 0.05) when subjects consumed FctO and 4.7% when they consumed OL. Similarly, FctO consumption lowered LDL cholesterol concentrations by 13.9%, whereas OL consumption did not. There was no difference in absolute change in LDL-cholesterol between FctO and OL consumption. Peak LDL particle size was greater in those who consumed FctO than in those who consumed OL (P < 0.05), with no effect of diet on proportion of large, medium or small particles. We conclude that those who consume a diet containing FctO have a better lipid profile than those who consume a diet rich in OL, which also leads to a larger lipoprotein particle size. Functional oil consumption can therefore help reduce the risk of cardiovascular disease. J. Nutr. 133: 1815-1820, 2003. KEY WORDS: * cholesterol * lipoproteins * low-density lipoprotein cholesterol * medium-chain triglycerides * phytosterols

The objective of this article is to review the existing literature concerning the effects and mechanisms of action of red wine consumption vs. other alcoholic beverages on the risk of cardiovascular disease (CVD). Of particular interest is the form and quantity of alcohol consumed. This relationship between alcohol consumption and mortality is well supported by epidemiologic studies, which have suggested that different forms of alcohol alter the relative risk values for mortality from CVD. Although not without exception, current evidence from epidemiologic and experimental studies suggests a protective effect against the development of CVD with moderate consumption of red wine. The exact nature of the protective effect remains to be established. However, mechanisms including LDL oxidation and alterations in hemostatic variables are being increasingly recognized as contributory. Key components of red wine thought to be responsible for the protective effects include phenolic compounds and alcohol content. Despite the research presented, some questions relating to the current recommendations regarding moderate alcohol consumption and cardiovascular health remain. However, collectively, the literature aids in understanding some of the ways in which alcoholic beverages and their components affect the health of our population. J. Nutr. 131: 1401-1404, 2001. KEY WORDS: * cardiovascular disease * phenolic compounds * red wine * alcohol

Medium chain fatty acids (MCFA) are readily oxidized in the liver. Animal and human studies have shown that the fast rate of oxidation of MCFA leads to greater energy expenditure (EE). Most animal studies have also demonstrated that the greater EE with MCFA relative to long-chain fatty acids (LCFA) results in less body weight gain and decreased size of fat depots after several months of consumption. Furthermore, both animal and human trials suggest a greater satiating effect of medium-chain triglycelides (MCT) compared with long-chain triglycerides (LCT). The aim of this review is to evaluate existing data describing the effects of MCT on EE and satiety and determine their potential efficacy as agents in the treatment of human obesity. Animal studies are summarized and human trials more systematically evaluated because the primary focus of this article is to examine the effects of MCT on human energy metabolism and satiety. Hormones including cholescytokinin, peptide YY, gastric inhibitory peptide, neurotensin and pancreatic polypeptide have been proposed to be involved in the mechanism by which MCT may induce satiety; however, the exact mechanisms have not been established. From the literature reviewed, we conclude that MCT increase energy expenditure, may result in faster satiety and facilitate weight control when included in the diet as a replacement for fats containing LCT. J. Nutr. 132: 329-332, 2002. KEY WORDS: * medium-chain triglycerides * satiety * energy expenditure * obesity

Mechanisms explaining the decrease in circulatory cholesterol levels after weight loss remain ill defined. The objective was to examine effects of weight loss as achieved through energy restriction upon human in vivo cholesterol biosynthesis. Six subjects (64-77 y, body mass index, 30.3 [+ or -] 3.8 kg/[m.sup.2]) were recruited into a two-phase prospective clinical trial. In the first phase, subjects complied with American Heart Association (AHA) Step I diets for 3 mo with no change in their usual energy intake. After this weight-stable phase, subjects consumed an AHA Step I diet with a targeted reduction in energy intake of [approximately]1000 kJ/d for 6 mo to achieve negative energy balance leading to weight loss. The incorporation rate of deuterium from body water into erythrocyte membrane free cholesterol over 24 h was utilized as an index of cholesterogenesis at the end of both phases. Subjects' mean weights decreased (P < 0.05) from 89.3 [+ or -] 12.5 kg to 83.2 [+ or -] 11.5 kg (6.8 [+ or -] 2.6% of initial body weight) across phases. Circulating concentrations of total and LDL-cholesterol, and triglycerides also decreased (P < 0.05) across phases. HDL-cholesterol concentrations were unchanged (P > 0.05). Cholesterol fractional synthetic rate (FSR) after phase 2 (3.04 [+ or -] 1.90%/d) was lower (P < 0.05) than that after phase 1 (8.42 [+ or -] 3.90%/d). Absolute synthesis rate (ASR) after phase 2 [0.59 [+ or -] 0.38 g/(kg [multiplied by] d)] also was lower (P < 0.05) than that after phase 1 [1.66 [+ or -] 0.84 g/(kg [multiplied by] d)]. These data suggest that, in obese men, energy restriction resulting in even modest weight loss suppresses endogenous cholesterol synthesis, which contributes to a decline in circulating lipid concentrations. KEY WORDS: weight loss; energy restriction; cholesterol; deuterium; humans