Effects of an 8-week aerobic exercise program on plasma markers for cholesterol absorption and synthesis in older overweight and obese men.

BACKGROUND: Increased physical activity is inversely related to the risk to develop cardiovascular disease (CVD). In a recent systematic review, it was reported that CVD patients had an increased cholesterol absorption and a decreased synthesis as compared with control participants. As increased physical activity levels reduce CVD risk, we hypothesized that exercise training will reduce cholesterol absorption and increase endogenous cholesterol synthesis in older overweight and obese men. METHODS: A randomized, controlled, crossover trial was performed. Seventeen apparently healthy older overweight and obese men were randomized to start with an aerobic exercise or no-exercise control period for 8 weeks, separated by 12 weeks washout. Fasting serum total cholesterol (TC) and non-cholesterol sterol concentrations were measured at baseline, and after 4 and 8 weeks. RESULTS: The aerobic exercise program did not affect serum TC concentrations. In addition, exercise did not affect TC-standardized serum concentrations of sitosterol and cholestanol that are markers for cholesterol absorption. However, a trend for reduced TC-standardized campesterol concentrations, which is another validated marker for cholesterol absorption, was observed as compared with control. Lathosterol concentrations, reflecting cholesterol synthesis, did not differ between both periods. CONCLUSIONS: Aerobic exercise training for 8 weeks did not lower serum TC concentrations in older overweight and obese men, but a trend towards a decrease in the cholesterol absorption marker campesterol was found. The cholesterol synthesis marker lathosterol did not change. TRIAL REGISTRATION: posted on www.clinicaltrials.gov as NCT03272061 on 7 September 2017.

Effects of lutein-enriched egg yolk in buttermilk or skimmed milk on serum lipids & lipoproteins of mildly hypercholesterolemic subjects.

BACKGROUND AND AIMS: Earlier studies in our group suggested that traditionally prepared buttermilk influences cholesterol metabolism. We therefore designed a study to evaluate whether traditionally prepared buttermilk lowers serum low-density lipoprotein cholesterol (LDL-C) and/or prevents the LDL-C raising effect of egg yolks. METHODS AND RESULTS: Mildly hypercholesterolemic subjects were randomly allocated to one of four diet groups consuming daily at lunch 80 ml skimmed milk with (n = 23) or without (n = 25) lutein-enriched egg yolk (28 g from 1.5 eggs providing 323 mg cholesterol) or traditionally prepared buttermilk with (n = 23) or without (n = 21) lutein-enriched egg yolk during a 12 week period. Fasting blood samples were taken to measure concentrations of serum lipids, (apo)lipoproteins, liver and kidney function markers, and plasma lutein, zeaxanthin and high-sensitive C-reactive protein (hsCRP). Egg yolk consumption significantly increased serum total cholesterol (total-C) (p = 0.035) and LDL-C concentrations (p = 0.022). Buttermilk did not change the effects of egg yolk on serum lipids and (apo)lipoproteins. There was a trend towards significant lower total-C (p = 0.077), but not LDL-C (p = 0.204) concentrations in the buttermilk groups. Plasma lutein and zeaxanthin concentrations increased significantly (p < 0.001) in the egg yolk groups. CONCLUSION: In mildly hypercholesterolemic subjects, daily consumption of traditionally prepared buttermilk for 12 weeks did not lower serum total-C or LDL-C concentrations, nor did it prevent the serum total-C and LDL-C raising effect of daily egg yolk consumption. REGISTRATION NUMBER: This study is registered at www.clinicaltrials.gov as NCT01566305.

Prolonged fasting and the effects on biomarkers of inflammation and on adipokines in healthy lean men.

Obesity and insulin resistance are associated with low-grade systemic inflammation, which is related to increased concentrations of plasma FFAs, glucose, or insulin. Prolonged fasting induces insulin resistance due to elevated plasma FFAs, but is not accompanied by hyperinsulinemia or hyperglycemia. This makes it possible to study effects of physiologically increased FFA concentrations on inflammatory markers, when insulin and glucose concentrations are not increased. In random order, 10 healthy young lean men (mean BMI: 22.8 kg/m2) were fasted or fed in energy balance for 60 h with a 2-week wash-out period. Subjects stayed in a respiration chamber during the 60-h periods. Blood samples were taken after 12, 36, and 60 h. Then, a hyperinsulinemic-euglycemic clamp was performed.Fasting decreased insulin sensitivity by 45% and increased FFA concentrations 5-fold. Fasting did not change concentrations of the inflammatory cytokines TNF-α, IL-1ß, IL-6 and IL-8, or of hs-CRP. Effects on vascular endothelial growth factor (VEGF)--which may positively relate to insulin resistance, and on chemerin and leptin--adipokines related to obesity, and obesity-related pathologies, were also studied. At t=60 h, VEGF concentrations were significantly increased during the fasted period (p<0.05). At the same time point, chemerin (p<0.01) and leptin (p<0.01) were significantly decreased after fasting. For leptin, this decrease was also significant after 36 h (p<0.01). Adiponectin levels remained unchanged. In healthy young lean men, fasting-induced increases in FFAs leading to insulin resistance do not cause changes in concentrations of the inflammatory cytokines. VEGF concentrations increased and those of chemerin decreased.

Comparison of the effects of n-3 long chain polyunsaturated fatty acids and fenofibrate on markers of inflammation and vascular function, and on the serum lipoprotein profile in overweight and obese subjects.

BACKGROUND AND AIMS: To compare the effects of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA), with those of fenofibrate, on markers of inflammation and vascular function, and on the serum lipoprotein profile in overweight and obese subjects. METHODS AND RESULTS: Twenty overweight and obese subjects participated in a randomized, double-blind, placebo-controlled intervention trial and received 3.7 g/d n-3 fatty acids (providing 1.7 g/d EPA and 1.2 g/d DHA), 200 mg fenofibrate or placebo treatment for 6 weeks separated by a 2 weeks wash-out period. Fish oil and fenofibrate treatment reduced triglyceride (-0.61 ± 0.81 mmol/L, P < 0.001, and -0.34 ± 0.85 mmol/L, P = 0.048, respectively) and increased HDL cholesterol concentrations (0.13 ± 0.21 mmol/L, P = 0.013, and 0.10 ± 0.18 mmol/L, P = 0.076), as reflected by a decrease of large very VLDL particles and increases of large HDL particles and medium size HDL particles. Fish oil increased serum LDL cholesterol concentrations (0.34 ± 0.59 mmol/L, P = 0.013). Fenofibrate reduced concentrations of soluble endothelial selectin (sE-selectin) (-4.1 ± 7.5 ng/mL, P = 0.032), but increased those of macrophage chemoattractant protein 1 (MCP1) (28 ± 55 ng/mL, P = 0.034). Fish oil had no effects on these markers. CONCLUSION: Although n-3 LCPUFA and fenofibrate can both activate PPARα, they have differential effects on cardiovascular risk markers. In overweight and obese subjects fenofibrate (200 mg/d) or n-3 LCPUFA (3.7 g/d) treatment for 6 weeks did not improve markers for low-grade systemic inflammation, while fenofibrate had more profound effects on plasma lipids and markers for vascular activity compared to fish oil. Registration number clinical trials EudraCT 2006-005743-28.

Plasma oxyphytosterols most likely originate from hepatic oxidation and subsequent spill-over in the circulation.

We evaluated oxyphytosterol (OPS) concentrations in plasma and various tissues of two genetically modified mouse models with either increased cholesterol (apoE KO mice) or increased cholesterol and plant sterol (PS) concentrations (apoExABCG8 dKO mice). Sixteen female apoE KO and 16 dKO mice followed the same standard, low OPS-chow diet. Animals were euthanized at 36 weeks to measure PS and OPS concentrations in plasma, brain, liver and aortic tissue. Cholesterol and oxysterol (OS) concentrations were analyzed as reference for sterol oxidation in general. Plasma campesterol (24.1 ± 4.3 vs. 11.8 ± 3.0 mg/dL) and sitosterol (67.4 ± 12.7 vs. 4.9 ± 1.1 mg/dL) concentrations were severely elevated in the dKO compared to the apoE KO mice (p < 0.001). Also, in aortic and brain tissue, PS levels were significantly elevated in dKO. However, plasma, aortic and brain OPS concentrations were comparable or even lower in the dKO mice. In contrast, in liver tissue, both PS and OPS concentrations were severely elevated in the dKO compared to apoE KO mice (sum OPS: 7.4 ± 1.6 vs. 4.1 ± 0.8 ng/mg, p < 0.001). OS concentrations followed cholesterol concentrations in plasma and all tissues suggesting ubiquitous oxidation. Despite severely elevated PS concentrations, OPS concentrations were only elevated in liver tissue, suggesting that OPS are primarily formed in the liver and plasma concentrations originate from hepatic spill-over into the circulation.

Low-fat dairy consumption reduces systolic blood pressure, but does not improve other metabolic risk parameters in overweight and obese subjects.

BACKGROUND AND AIMS: Epidemiological studies have indicated a negative relation between low-fat dairy consumption and the metabolic syndrome. However, evidence from intervention studies is scarce. Our aim was to investigate the effects of daily consumption of low-fat dairy products on metabolic risk parameters in overweight and obese men and women. METHODS AND RESULTS: Thirty-five healthy subjects (BMI>27 kg/m(2)) consumed low-fat dairy products (500 mL low-fat milk and 150 g low-fat yogurt) or carbohydrate-rich control products (600 mL fruit juice and 3 fruit biscuits) daily for 8 weeks in random order. Compared with the control period, systolic blood pressure was decreased by 2.9 mm Hg (95% confidence interval (CI), -5.5 to -0.3 mm Hg; P=0.027), while the difference in diastolic blood pressure did not reach statistical significance (95% CI, -3.4 to 0.3 mm Hg; P=0.090). Low-fat dairy consumption decreased HDL-cholesterol concentrations by 0.04 mmol/L (95% CI, -0.07 to -0.01 mmol/L; P=0.021) and apo A-1 concentrations by 0.04 g/L (95% CI, -0.07 to -0.01 g/L; P=0.016) compared with control. Serum total cholesterol, LDL-cholesterol, apo B, triacylglycerols, non-esterified fatty acids, glucose, insulin, C-reactive protein and plasminogen activator inhibitor-1 were unchanged. CONCLUSION: We conclude that in overweight and obese subjects, daily intake of low-fat dairy products for 8 weeks decreased systolic blood pressure, but did not improve other metabolic risk factors related to the metabolic syndrome.

Comparing patterns of volatile organic compounds exhaled in breath after consumption of two infant formulae with a different lipid structure: a randomized trial.

Infant formulae have been used since decades as an alternative to or a complement to human milk. Human milk, the "gold standard" of infant nutrition, has been studied for its properties in order to create infant formulae that bring similar benefits to the infant. One of the characteristics of milk is the size of the lipid droplets which is known to affect the digestion, gastric emptying and triglyceride metabolism. In the current study a concept infant milk formula with large, phospholipid coating of lipid droplets (mode diameter 3-5 µm; NUTURIS, further described as "active"), was compared to a commercially available formula milk characterised by smaller lipid droplets, further described as "control" (both products derived from Nutricia). We investigated whether we could find an effect of lipid droplet size on volatile compounds in exhaled air upon ingestion of either product. For that purpose, exhaled breath was collected from a group of 29 healthy, non-smoking adult males before ingestion of a study product (baseline measurements, T0) and at the following time points after the test meal: 30, 60, 120, 180 and 240 min. Volatile organic compounds (VOCs) in breath were detected by gas chromatography-time-of-flight-mass spectrometry. Any differences in the time course of VOCs patterns upon intake of active and control products were investigated by regularised multivariate analysis of variance (rMANOVA). The rMANOVA analysis revealed statistically significant differences in the exhaled breath composition 240 min after ingestion of the active formula compared to control product (p-value < 0.0001), but did not show significant changes between active and control product at any earlier time points. A set of eight VOCs in exhaled breath had the highest contribution to the difference found at 240 minutes between the two formulas. A set of ten VOCs was different between baseline and the two formulae at T240 with p-value < 0.0001. To our knowledge this is the first study that shows the ability of VOCs in exhaled breath to monitor metabolic effects after ingestion of infant formulae with different lipid structure. The statistically significant differences in compound abundance found between active and control formula milk may be related to: (i) specific differences in the digestion, (ii) absorption of lipids and proteins and (iii) assimilation of the products in the gut.

Plant-based sterols and stanols in health & disease: "Consequences of human development in a plant-based environment?"

Dietary plant sterols and stanols as present in our diet and in functional foods are well-known for their inhibitory effects on intestinal cholesterol absorption, which translates into lower low-density lipoprotein cholesterol concentrations. However, emerging evidence suggests that plant sterols and stanols have numerous additional health effects, which are largely unnoticed in the current scientific literature. Therefore, in this review we pose the intriguing question "What would have occurred if plant sterols and stanols had been discovered and embraced by disciplines such as immunology, hepatology, pulmonology or gastroenterology before being positioned as cholesterol-lowering molecules?" What would then have been the main benefits and fields of application of plant sterols and stanols today? We here discuss potential effects ranging from its presence and function intrauterine and in breast milk towards a potential role in the development of non-alcoholic steatohepatitis (NASH), cardiovascular disease (CVD), inflammatory bowel diseases (IBD) and allergic asthma. Interestingly, effects clearly depend on the route of entrance as observed in intestinal-failure associated liver disease (IFALD) during parenteral nutrition regimens. It is only until recently that effects beyond lowering of cholesterol concentrations are being explored systematically. Thus, there is a clear need to understand the full health effects of plant sterols and stanols.

Role of stearoyl-CoA desaturases in obesity and the metabolic syndrome.

The prevalence of obesity and related metabolic disorders increases rapidly in western societies. A proper choice of foods may now prevent or delay many of the health consequences related to these disorders. In this respect, replacing dietary saturated fatty acids (SFAs) by cis-monounsaturated fatty acids (cis-MUFAs) has beneficial effects. In addition to diet-derived cis-MUFAs, the human body can also generate cis-MUFAsfrom SFAs through the action of stearoyl-CoA desaturases (SCDs). SCDs may play an adverse role in obesity and obesity-related insulin resistance. Here, we review the current knowledge on the molecular aspects and the role of SCD1 in obesity and the metabolic syndrome (MS). In mice, many studies have suggested a negative role for SCD1 in the development of obesity and insulin resistance. In humans, however, evidence is less convincing. If anything, increased, rather than decreased, levels of SCD1 mRNA levels are negatively associated with MS-related diseases such as insulin resistance. However, an unequivocal conclusion is currently not possible as the number of human studies is limited. Therefore, more human studies are needed at the molecular as well as at the physiological level to understand the true role of SCD1 during the development of obesity and the MS.

The metabolic syndrome in relation with the glycemic index and the glycemic load.

The metabolic syndrome (MS) is a clustering of metabolic abnormalities that increases the risk to develop chronic diseases such as cardiovascular disease and type 2 diabetes mellitus. Although its precise aetiology is unknown, dietary habits play a major role. Nowadays, more and more attention is paid to the glycemic index (GI) and the glycemic load (GL) of a diet. The GI of a food is a value based on the average increase in blood glucose levels occurring when a 50 g carbohydrate portion of that food is consumed. The GL accounts for the amount of carbohydrate per serving. From reviewing the current literature, we conclude that for healthy and/or overweight subjects the importance of low GI or GL diets in relation to the metabolic syndrome has not been established. One of the reasons is that the diets used in the intervention studies frequently not only differed in GI or GL, but also in fibre, protein and/or fat content. In some of the prospective cohort studies, effects of GI or GL attenuated or even disappeared after correcting for fibre intake. This makes it impossible to ascribe the possible beneficial metabolic effects of low GI or GL diets unequivocally to the GI or GL. The question, therefore, remains open on to what components of the metabolic syndrome are specifically affected by the GI per se. To answer this question, controlled longer-term intervention studies are needed to monitor the effects of the GI on the various components of the metabolic syndrome.

Effects of products made from a high-palmitic acid, trans-free semiliquid fat or a high-oleic acid, low-trans semiliquid fat on the serum lipoprotein profile and on C-reactive protein concentrations in humans.

BACKGROUND: Many studies have shown that trans fatty acids have unfavorable effects on the serum lipoprotein profile. In general, however, fats were compared with different functional characteristics, which lower the practical applications of the results. OBJECTIVE: The major aim of this study was to compare the effects of a high-palmitic acid, trans-free semiliquid fat with those of a high-oleic acid, low-trans semiliquid fat on the serum lipoprotein profile of healthy subjects. SUBJECTS AND DESIGN: Forty-four subjects (33 women and 11 men) consumed, in random order, two experimental diets, each for 3 weeks. Diets provided 40 energy percent (En%) from fat, while 15 En% was supplied by the experimental fats. At the end of each intervention period, concentrations of serum lipoproteins, C-reactive protein, glucose and insulin were measured. RESULTS: When subjects consumed the high-oleic acid, low-trans semiliquid fat, intakes of stearic acid (+1.3 En%), oleic acid (+2.9 En%), alpha-linolenic acid (+0.1 En%) and trans fatty acids (+0.6 En%) were higher and that of palmitic acid (-4.2 En%) lower. Serum concentration of low-density lipoprotein cholesterol decreased by 0.34+/-0.39 mmol/l (mean+/-s.d.; 95% confidence interval (CI), -0.46 to -0.23 mmol/l; P<0.001) and high-density lipoprotein (HDL) cholesterol by -0.06+/-0.17 mmol/l (95% CI, -0.11 to -0.01 mmol/l; P=0.021). Also, the total to HDL cholesterol ratio was lower (-0.15+/-0.34; 95% CI, -0.25 to -0.05; P=0.006). Other parameters did not change. CONCLUSIONS: A high-oleic acid, low-trans semiliquid fat has a more favorable effect on the serum lipoprotein profile than a trans-free semiliquid fat with comparable functional characteristics, but high in palmitic acid.

Effects of plant sterol and stanol ester consumption on lipid metabolism, antioxidant status and markers of oxidative stress, endothelial function and low-grade inflammation in patients on current statin treatment.

OBJECTIVE: The present study was designed to examine for the first time, side-by-side, the effects of plant sterol and stanol consumption on lipid metabolism and markers of antioxidant status, oxidative stress, endothelial dysfunction and low-grade inflammation in subjects on stable statin-treatment. DESIGN: Double-blind, randomized, placebo-controlled, intervention trial. SETTING: University. SUBJECTS: Forty-five patients on current statin treatment were recruited via newspaper advertisements. Data of 41 patients were used in statistical analysis. INTERVENTION: Subjects consumed margarine with no added plant sterols or stanols for 4 weeks and were then divided into three groups of 15 subjects. For the next 16 weeks, one group continued with the control margarine and the other two groups with either a plant sterol- or stanol (2.5 g/day)-enriched margarine. Blood was sampled at the end of the run-in and intervention periods. RESULTS: Plant sterol and stanol consumption significantly (P=0.026) reduced low-density lipoprotein (LDL) cholesterol by 0.34 mmol/l (95% confidence interval (CI), -0.67 to -0.04 mmol/l). No effects were shown on enzymatic and non-enzymatic antioxidants and markers of oxidative modification of lipids and DNA. In addition, no effect was found on soluble adhesion molecules, C-reactive protein and monocyte chemotactic protein-1 concentrations. CONCLUSIONS: We conclude that 16 weeks of plant sterol or stanol consumption did not affect markers of antioxidant status, oxidative stress, endothelial dysfunction and low-grade inflammation in patients on stable statin treatment, despite a significant reduction of LDL cholesterol.

Infant milk fat droplet size and coating affect postprandial responses in healthy adult men: a proof-of-concept study.

BACKGROUND/OBJECTIVES: Fat droplets in human milk (HM) are larger and surrounded by a phospholipid membrane compared with infant milk formulas (IMF). Since the physical structure of fat droplets might affect digestion and postprandial metabolism, an IMF was developed more mimicking HM lipid structure than current IMF. SUBJECTS/METHODS: A randomised, double-blind, crossover study was performed in 29 fasted healthy men (aged 18-25 years, BMI: 18-25 kg/m2) to compare 5-hour postprandial responses after consumption of an experimental IMF (Concept, Nuturis) with a current IMF (Control). RESULTS: Postprandial triacylglycerol (TAG) concentrations tended to increase faster after intake of Concept IMF (P=0.054), but peaked 3 h after intakes at similar concentrations. ApoB48 increased steadily and peaked 3 h after consumption. Increases in plasma glucose concentrations were comparable, but peak concentrations were reached faster after consumption of Concept IMF (P<0.05). Peak insulin concentrations were higher and reached earlier after intake of Concept IMF, causing a sharper decremental glucose rebound (P<0.05) and an earlier time to nadir in non-esterified fatty acid (NEFA) concentrations (P<0.01). Changes in plasma amino acids (AA), apoB100 and apoA1 were comparable. The incremental or decremental areas under-the-curve did not differ between Concept and Control IMF. Satiety scores and changes in the satiety hormones ghrelin and peptide YY were comparable, while cholecystokinin responses were earlier and higher after consumption of Control IMF (P<0.05). CONCLUSIONS: This proof-of-concept study suggests that fats and carbohydrates from the Concept IMF with larger and phospholipid-coated fat droplets are more rapidly absorbed than those from the current IMF.

Plant sterol or stanol consumption does not affect erythrocyte osmotic fragility in patients on statin treatment.

OBJECTIVE: To assess the effects of plant sterol or stanol ester consumption on their incorporation into erythrocytes and their effects on osmotic fragility of red blood cells. DESIGN: Double-blind, randomized, placebo-controlled intervention trial. SUBJECTS AND INTERVENTION: Forty-one subjects on stable statin treatment - who already have increased serum plant sterol and stanol concentrations - first received for 4 weeks a control margarine. For the next 16 weeks, subjects were randomly assigned to one of three possible interventions. Eleven subjects continued with control margarine, 15 subjects with plant sterol ester enriched and 15 subjects with plant stanol ester-enriched margarine. Daily plant sterol or stanol intake was 2.5 g. Erythrocyte haemolysis was measured spectrophotometrically at five different saline concentrations. RESULTS: Despite significant (P = 0.004) increases of, respectively, 42 and 59% in cholesterol-standardized serum sitosterol and campesterol concentrations in the plant sterol group as compared to the control group, campesterol levels in the red blood cells did not change (P = 0.196). Osmotic fragility did not change significantly (P = 0.757) in the plant sterol and plant stanol groups as compared to the control group. CONCLUSION: We conclude that plant sterol and stanol ester consumption for 16 weeks does not change osmotic fragility of erythrocytes in statin-treated patients. SPONSORSHIP: Netherlands Organisation for Health Research and Development (Program Nutrition: Health, Safety and Sustainability, Grant 014-12-010).

Effects of alpha-linolenic acid versus those of EPA/DHA on cardiovascular risk markers in healthy elderly subjects.

OBJECTIVE: To compare the effects of alpha-linolenic acid (ALA, C18:3n-3) to those of eicosapentaenoic acid (EPA, C20:5n-3) plus docosahexaenoic acid (DHA, C22:6n-3) on cardiovascular risk markers in healthy elderly subjects. DESIGN: A randomized double-blind nutritional intervention study. SETTING: Department of Human Biology, Maastricht University, the Netherlands. SUBJECTS: Thirty-seven mildly hypercholesterolemic subjects, 14 men and 23 women aged between 60 and 78 years. INTERVENTIONS: During a run-in period of 3 weeks, subjects consumed an oleic acid-rich diet. The following 6 weeks, 10 subjects remained on the control diet, 13 subjects consumed an ALA-rich diet (6.8 g/day) and 14 subjects an EPA/DHA-rich diet (1.05 g EPA/day + 0.55 g DHA/day). RESULTS: Both n-3 fatty acid diets did not change concentrations of total-cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerol and apoA-1 when compared with the oleic acid-rich diet. However, after the EPA/DHA-rich diet, LDL-cholesterol increased by 0.39 mmol/l (P = 0.0323, 95% CI (0.030, 0.780 mmol/l)) when compared with the ALA-rich diet. Intake of EPA/DHA also increased apoB concentrations by 14 mg/dl (P = 0.0031, 95% CI (4, 23 mg/dl)) and 12 mg/dl (P = 0.005, 95% CI (3, 21 mg/dl)) versus the oleic acid and ALA-rich diet, respectively. Except for an EPA/DHA-induced increase in tissue factor pathway inhibitor (TFPI) of 14.6% (P = 0.0184 versus ALA diet, 95% CI (1.5, 18.3%)), changes in markers of hemostasis and endothelial integrity did not reach statistical significance following consumption of the two n-3 fatty acid diets. CONCLUSIONS: In healthy elderly subjects, ALA might affect concentrations of LDL-cholesterol and apoB more favorably than EPA/DHA, whereas EPA/DHA seems to affect TFPI more beneficially.

Trans monounsaturated fatty acids in nutrition and their impact on serum lipoprotein levels in man.

Trans-C18:1 in the diet originate predominantly from partially hydrogenated oils, with beef, mutton and dairy products being an additional source. These fatty acids are absorbed and incorporated into lipids. Their estimated consumption is about 5-7% of total fatty acids, although reliable data are lacking. In addition, large variations between individuals exist. There is no evidence that trans fatty acids accumulate in human tissues. Elaidic acid and its positional isomers do, however, raise LDL cholesterol and apoprotein B and Lp(a) and probably depress HDL cholesterol and apoprotein A-I, compared with the cis isomer, oleic acid. In view of these adverse effects, patients at high risk for atherosclerosis, in addition to reducing their intake of saturated fatty acids and of cholesterol might also do well to avoid excessive intakes of trans fatty acids. Still, trans fatty acids form only a minor component of the diets of most patients and therefore even marked relative reductions in intake will probably have less of an impact on LDL cholesterol than a sizeable reduction in saturated fatty acids and cholesterol will produce.

Dietary plant stanol esters reduce VLDL cholesterol secretion and bile saturation in apolipoprotein E*3-Leiden transgenic mice.

Dietary plant stanols lower serum cholesterol levels in humans and in hyperlipidemic rodents, mainly by inhibition of the intestinal cholesterol absorption. We used female apolipoprotein E*3-Leiden transgenic mice to investigate the consequences of this effect on serum lipid levels and hepatic lipid metabolism. Five groups of 6 or 7 mice received for 9 weeks a diet containing 0.25% cholesterol and 0.0%, 0.25%, 0.5%, 0.75%, or 1.0% (wt/wt) plant stanols (sitostanol 88% [wt/wt], campestanol 10% [wt/wt]) esterified to fatty acids. Compared with the control diet, plant stanol ester treatment dose-dependently reduced serum cholesterol levels by 10% to 33% (P<0.05), mainly in very low density lipoproteins (VLDLs), intermediate density lipoproteins, and low density lipoproteins. Furthermore, 1.0% of the dietary plant stanols significantly decreased the liver contents of cholesteryl esters (-62%), free cholesterol (-31%), and triglycerides (-38%) but did not change the hepatic VLDL-triglyceride and VLDL-apolipoprotein B production rates. However, plant stanol ester feeding significantly decreased the amounts of cholesteryl esters and free cholesterol incorporated in nascent VLDLs by 72% and 30%, respectively, resulting in a net 2-fold decreased VLDL cholesterol output. Liver mRNA levels of low density lipoprotein receptors, 3-hydroxy-3-methylglutaryl coenzyme A synthase, cholesterol 7alpha-hydroxylase, and sterol 27-hydroxylase were not changed by plant stanol ester feeding. Nevertheless, the serum lathosterol-to-cholesterol ratio was significantly increased by 23%, indicating that dietary plant stanol esters increased whole-body cholesterol synthesis. Plant stanol esters also significantly decreased the cholesterol saturation index in bile by 55%. In conclusion, in apolipoprotein E*3-Leiden transgenic mice, plant stanol ester feeding dose-dependently lowered serum cholesterol levels as a result of a reduced secretion of VLDL cholesterol. This was caused by a decreased hepatic cholesterol content that also resulted in a lowered biliary cholesterol output, indicative of a reduced lithogenicity of bile in these mice.

Changes in serum lipids and postprandial glucose and insulin concentrations after consumption of beverages with beta-glucans from oats or barley: a randomised dose-controlled trial.

OBJECTIVES: To investigate side by side the effects on serum lipoproteins and postprandial glucose and insulin concentrations of beverages enriched with 5 or 10 g of beta-glucans from oats or barley. DESIGN AND SETTING: An 8-week single blind, controlled study with five parallel groups carried out at two centres under identical conditions. SUBJECTS: A total of 100 free-living hypercholesterolaemic subjects were recruited locally and 89 completed the study. INTERVENTIONS: During a 3-week run-in period all subjects consumed a control beverage. For the following 5-week period four groups received a beverage with 5 or 10 g beta-glucans from oats or barley and one group continued with the control beverage. Blood samples in weeks 0, 2, 3, 7 and 8 were analysed for serum lipids, lipoproteins, glucose and insulin. Postprandial concentrations of glucose and insulin were compared between control and the beverage with 5 g of beta-glucans from oats or barley. RESULTS: Compared to control, 5 g of beta-glucans from oats significantly lowered total-cholesterol by 7.4% (P<0.01), and postprandial concentrations of glucose (30 min, P=0.005) and insulin (30 min, P=0.025). The beverage with 10 g of beta-glucans from oats did not affect serum lipids significantly in comparison with control. No statistically significant effects compared to control of the beverages with barley beta-glucans were found. CONCLUSIONS: A daily consumption of 5 g of oat beta-glucans in a beverage improved the lipid and glucose metabolism, while barley beta-glucans did not.

Fatty acids and atherosclerotic risk.

Most research concerning the effects of dietary fatty acids on atherosclerotic risk has focused on their effects on lipid and lipoprotein metabolism. However, it is known that fatty acids also influence a number of other relevant mechanisms involved in atherosclerosis such as lipid peroxidation, inflammation and haemostasis. The most favourable distribution of cholesterol over the various lipoproteins is achieved when saturated and trans fatty acids are replaced by a mixture of cis-unsaturated fatty acids. Furthermore, fatty acids from fish oil lower triacylglycerol concentrations. Effects on other atherosclerotic risk markers are less evident. Monounsaturated fatty acids maybe preferable above other fatty acids with respect to low-density lipoprotein oxidation as measured by indirect in vitro assays. The relevance of these assays for the in vivo situation is, however, limited. With respect to inflammation, mainly the effects of n-3 polyunsaturated fatty acids from fish oil have been studied, but results were inconsistent. Also results from studies evaluating the effects of fatty acids on haemostatic risk markers were inconsistent, which may be partly related to the use of different analytical methods. The most consistent finding however is the potential beneficial effect of moderate intakes of fish oil on platelet aggregation. Furthermore, reducing total fat intake rather than changing the fatty acid composition of the diet may beneficially affect the coagulation system. In conclusion, while beneficial effects on atherosclerotic risk are mainly ascribed to cis-unsaturated fatty acids, it remains debateable whether trans and saturated fatty acids in the diet have to be replaced by cis-unsaturated fatty acids or by carbohydrates. To answer this question adequately more validated methods are needed that reflect in vivo lipid peroxidation, inflammation and haemostasis.

Effects of stearidonic acid on serum triacylglycerol concentrations in overweight and obese subjects: a randomized controlled trial.

BACKGROUND/OBJECTIVES: Eicosapentaenoic acid (EPA), which may reduce the risk for coronary heart disease (CHD), can be synthesized at low rates from α-linolenic acid (ALA). The rate-limiting step for this conversion is the Δ6-desaturation of ALA into stearidonic acid (SDA). Thus providing oils rich in SDA may increase endogenous synthesis of EPA, which may subsequently lower serum triacylglycerol concentrations, an effect frequently observed after EPA supplementation. We therefore studied the effects of Echium oil on serum triacylglycerol concentrations and the omega-3 index, which correlate negatively with the risk for CHD. SUBJECTS/METHODS: A randomized, double-blind, placebo-controlled crossover trial was conducted, in which 36 healthy overweight and slightly obese subjects daily received 10 g of Echium oil (providing 1.2 g of SDA) or a high oleic acid sunflower oil (HOSO) as control for 6 weeks, with a washout period of at least 14 days. Four subjects dropped out. Differences between periods were tested for statistical significance (P<0.05) using a paired t-test. RESULTS: Serum triacylglycerol and other lipid concentrations were not significantly affected by consumption of Echium oil compared with HOSO. Echium oil significantly increased percentage of EPA in red blood cell (RBC) membranes with 0.14 ± 0.25% (mean ± s.d.) compared with HOSO (P=0.02). No significant effects on docosahexaenoic acid in RBC membranes or on the omega-3 index were found. CONCLUSIONS: In healthy overweight and slightly obese subjects, an increased intake of SDA from Echium oil does not lower serum triacylglycerol concentrations. Despite an increase in the percentage of EPA in RBC membranes, the omega-3 index was not changed.