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.

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.

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.

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.

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.

Children With Morbid Obesity Benefit Equally as Children With Overweight and Obesity From an Ongoing Care Program.

CONTEXT: Despite stabilization of childhood overweight and obesity prevalence, there is a shift toward more severe degrees of obesity, which results in an increasing prevalence of children with morbid obesity. Prior studies demonstrated that lifestyle modification without ongoing treatment has only a modest and not sustainable effect in children with morbid obesity. This suggests that a chronic care model is necessary for long-term effects on weight management and health. OBJECTIVE: This study aimed to evaluate the effect of an ongoing lifestyle intervention in children with morbid obesity in comparison with children with overweight and obesity. DESIGN AND SETTING: This was a nonrandomized prospective intervention study with 12- and 24-month followup at the Centre for Overweight Adolescent and Children's Healthcare. PATIENTS AND INTERVENTION: Children and adolescents (n = 100 females and 72 males) with overweight, obesity, or morbid obesity were given long-term, outpatient, tailored lifestyle intervention. MAIN OUTCOME MEASURE: Body mass index (BMI) z score was measured. RESULTS: In children with morbid obesity, 12- and 24-month interventions resulted in a decrease of BMI z score of -0.13 ± 0.25 (P = .001) and -0.23 ± 0.32 (P = .01) respectively, whereas weight status category improved to obese in 21% and 25% of the children. Cardiovascular risk parameters including serum total cholesterol, low-density lipoprotein cholesterol, glycosylated hemoglobin (HbA1c), and diastolic blood pressure significantly improved after 1-year intervention in the complete group. Most important, BMI z score as well as cardiovascular risk parameters improved to a similar degree in children with overweight, obesity, and morbid obesity. CONCLUSIONS: Children with overweight, obesity, and morbid obesity benefit equally from an ongoing, outpatient, tailored lifestyle intervention, and demonstrate significant weight loss and improvement of cardiovascular risk parameters.

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.

Acute effects of plant stanol esters on postprandial metabolism and its relation with changes in serum lipids after chronic intake.

BACKGROUND/OBJECTIVES: Plant stanol esters lower serum low-density lipoprotein (LDL)-cholesterol (LDL-C), but responses between individuals vary widely. As the ability of subjects to respond to acute dietary challenges may reflect the flexibility to adapt to changes on the longer term, we related subjects' acute postprandial metabolic changes to changes in serum lipoproteins after chronic intake of plant stanol esters. SUBJECTS/METHODS: In a double-blind crossover design, 20 healthy subjects received in random order a high-fat shake enriched with or without plant stanol esters (4 g). Blood samples were taken during 4 h to examine lipid, glucose and lipoprotein profiles. Two subjects dropped out. For the 3 weeks after this postprandial test, the subjects who received the shake with plant stanol esters continued the consumption of plant stanol-enriched (3g/day) margarine and subjects receiving the control shake in the postprandial test consumed for the next 3 weeks a control margarine. After the washout period, subjects received the other shake and margarines. RESULTS: The margarine enriched with plant stanol esters lowered concentrations of total cholesterol by 7.3% (P<0.01), LDL-C by 9.5% (P<0.01) and apoB100 by 8.6% (P<0.01). Furthermore, particle concentrations of total very low-density lipoprotein (VLDL), small VLDL and large LDL were reduced by 26.6% (P=0.02), 27.6% (P=0.02) and 12.3% (P=0.04), respectively. Plant stanol esters did not affect parameters related to lipid and glucose metabolism during the postprandial phase. However, the incremental area under the curve (iAUC) of the postprandial glucose concentration after consuming the control shake correlated positively with changes in fasting concentrations of total cholesterol, LDL-C, apoB100, total VLDL, small VLDL and intermediate-density lipoprotein after 3 weeks. CONCLUSIONS: A single dose of plant stanol esters does not change postprandial lipid and lipoprotein profiles. However, postprandial glucose responses may predict the effects of chronic plant stanol ester consumption.

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.

Palmitic acid in the sn-2 position decreases glucose-dependent insulinotropic polypeptide secretion in healthy adults.

BACKGROUND/OBJECTIVES: Dietary triacylglycerols (TAGs) containing palmitic acid in the sn-2 position might impair insulin release and increase plasma glucose. We tested this hypothesis by comparing postprandial responses to fats with varying proportions of palmitic acid in the sn-2 position. SUBJECTS/METHODS: Using a crossover-designed randomized controlled trial in healthy men (n=25) and women (n=25), we compared four meals on postprandial changes in glucose (primary outcome), insulin, C-peptide, glucose, glucose-dependent insulinotropic polypeptide (GIP) and polypeptide YY (PYY) concentrations. The meals provided 14 g protein, 85 g carbohydrate and 50 g test fat, supplied as high oleic sunflower (HOS) oil (control), palm olein (PO), interesterified palm olein (IPO) and lard containing 0.6, 9.2, 39.1 and 70.5 mol% palmitic acid at sn-2, respectively. RESULTS: No differences in plasma glucose, insulin and C-peptide response between meals were found. GIP release was lower (P<0.001) for IPO and lard compared with HOS and PO meals; the maximal increments (geometric mean and 95% confidence interval) for HOS, PO, IPO and lard were 515 (468, 569), 492 (448, 540), 398 (350, 452) and 395 (364, 429) ng/l, respectively. There was a trend for the postprandial increase in PYY to be lower in women on the IPO and lard meals than those on the HOS and PO meals. CONCLUSIONS: Dietary TAGs with an increased proportion of palmitic acid in the sn-2 position do not have acute adverse effects on the insulin and glucose response to meals in healthy men and women, but they decrease GIP release.

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.

Cholesterol-lowering properties of different pectin types in mildly hyper-cholesterolemic men and women.

BACKGROUND/OBJECTIVES: Viscous fibers typically reduce total cholesterol (TC) by 3-7% in humans. The cholesterol-lowering properties of the viscous fiber pectin may depend on its physico-chemical properties (viscosity, molecular weight (MW) and degree of esterification (DE)), but these are not typically described in publications, nor required by European Food Safety Authority (EFSA) with respect to its generic pectin cholesterol-lowering claim. SUBJECTS/METHODS: Here, different sources and types of well-characterized pectin were evaluated in humans. Cross-over studies were completed in mildly hyper-cholesterolemic persons receiving either 15 g/day pectin or cellulose with food for 4 weeks. RESULTS: Relative low-density lipoprotein (LDL) cholesterol (LDL-C) lowering was as follows: citrus pectin DE-70=apple pectin DE-70 (7-10% reduction versus control)>apple pectin DE-35=citrus pectin DE-35>OPF (orange pulp fiber) DE-70 and low-MW pectin DE-70>citrus DE-0. In a subsequent 3-week trial with 6 g/day pectin, citrus DE-70 and high MW pectin DE-70 reduced LDL-C 6-7% versus control (without changes in TC). In both studies, high DE and high MW were important for cholesterol lowering. Source may also be important as citrus and apple DE-70 pectin were more effective than OPF DE-70 pectin. Pectin did not affect inflammatory markers high-sensitivity C-reactive protein (hsCRP) nor plasma homocysteine. CONCLUSIONS: Pectin source and type (DE and MW) affect cholesterol lowering. The EFSA pectin cholesterol-lowering claim should require a minimum level of characterization, including DE and MW.

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.

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.

Effects of alpha-glucans from Agaricus bisporus on ex vivo cytokine production by LPS and PHA-stimulated PBMCs; a placebo-controlled study in slightly hypercholesterolemic subjects.

INTRODUCTION: Mushrooms are known for their immune modulating effect for which the polysaccharide fraction, mainly glucans, seem to be responsible. Fungal beta-glucans have been studied extensively, whereas little is known about mushroom alpha-glucans. We have earlier shown that the polysaccharide fraction from the mushroom A. bisporus, consisting 90% of alpha-glucans, induced in vitro tumor necrosis factor (TNF)alpha and nitric oxide production. The purpose of this study was to evaluate the effects of consuming. METHOD: A. bisporus alpha-glucan on ex vivo cytokine production by human peripheral mononuclear blood cells (PBMCs). A double-blind randomized trial was designed in which 56 mildly hypercholesterolemic subjects consumed a control fruit juice with no added alpha-glucans (200 ml/day) for a 2-week run-in period. For the next 5 weeks, the control group (N=30) continued consumption of the control fruit juice, whereas the intervention group (N=26) consumed the same fruit juice enriched with alpha-glucans from A. bisporus (5 g glucans/day). Changes in interleukin (IL)-1beta, IL-6 and TNFalpha cytokine production by lipopolysaccharide (LPS)-stimulated PBMCs were evaluated, as well as changes in T-helper (Th)1/Th2 cytokines by phytohemaggutinin (PHA)-stimulated PBMCs. RESULTS: Consumption of A. bisporus alpha-glucans lower LPS-induced TNFalpha production by 69% (P=0.017) as compared with the control group, whereas no effect on IL-1beta and IL-6 was observed. No obvious Th1-Th2 skewing by PHA-stimulated PBMCs was observed. However, we observed a trend towards a decreased production of IL-12 and IL-10. CONCLUSION: Our current finding suggests that in vivo, alpha-glucans have lost their efficacy to stimulate the immune response as observed in our in vitro mouse model.

Which are the greatest recent discoveries and the greatest future challenges in nutrition?

BACKGROUND: Nutrition science aims to create new knowledge, but scientists rarely sit back to reflect on what nutrition research has achieved in recent decades. METHODS: We report the outcome of a 1-day symposium at which the audience was asked to vote on the greatest discoveries in nutrition since 1976 and on the greatest challenges for the coming 30 years. Most of the 128 participants were Dutch scientists working in nutrition or related biomedical and public health fields. Candidate discoveries and challenges were nominated by five invited speakers and by members of the audience. Ballot forms were then prepared on which participants selected one discovery and one challenge. RESULTS: A total of 15 discoveries and 14 challenges were nominated. The audience elected Folic acid prevents birth defects as the greatest discovery in nutrition science since 1976. Controlling obesity and insulin resistance through activity and diet was elected as the greatest challenge for the coming 30 years. This selection was probably biased by the interests and knowledge of the speakers and the audience. For the present review, we therefore added 12 discoveries from the period 1976 to 2006 that we judged worthy of consideration, but that had not been nominated at the meeting. CONCLUSIONS: The meeting did not represent an objective selection process, but it did demonstrate that the past 30 years have yielded major new discoveries in nutrition and health.

Validating nutrient-related gene expression changes from microarrays using RT(2) PCR-arrays.

Microarray technology allows us to perform high-throughput screening of changes in gene expression. The outcome of microarray experiments largely depends on the applied analysis methods and cut-off values chosen. Results are often required to be verified using a more sensitive detection technique, such as quantitative real-time PCR (qPCR or RT-PCR). Throughout the years, this technique has become a de facto golden standard. Individual qPCRs are time-consuming, but the technology to perform high-throughput qPCR reactions has become available through PCR-arrays that allow up to 384 PCR reactions simultaneously. Our current aim was to investigate the usability of a RT(2) Profilertrade mark PCR-array as validation in a nutritional intervention study, where the measured changes in gene expression were low. For some differentially expressed genes, the PCR-array confirmed the microarray prediction, though not for all. Furthermore, the PCR-array allowed picking up the expression of genes that were not measurable on the microarray platform but also vice versa. We conclude that both techniques have their own (dis)advantages and specificities, and for less pronounced changes using both technologies may be useful as complementation rather than validation.

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.