Jogchum Plat

Dietary modulation of immune function by β-glucans

The immune response can be modulated by nutrients like beta-glucans, which are glucose polymers that are major structural components of the cell wall of yeast, fungi, and bacteria, but also of cereals like oat and barley. There is a lot of structural variation in the beta-glucans from these different sources, which may influence their physiological functions. In this review the current status concerning possibilities to modulate immune function by beta-glucans is discussed. In vitro as well as in vivo studies in animals and humans show that especially beta-glucans derived from fungi and yeast have immune modulating properties. Most frequently evaluated are effects on leukocyte activity, which has been suggested to contribute to the increased resistance against infections observed after beta-glucan interventions. Although most studies supply the beta-glucans parenteral (e.g. intravenous or subcutaneous), also enteral administrated (dietary) beta-glucan influence the immune response. Although more human studies are needed, it is tempting to suggest that dietary beta-glucans may be a useful tool to prime the host immune system and increase resistance against invading pathogens.

Metabolic effects of plant sterols and stanols (Review)

High serum LDL cholesterol concentration is a major risk factor for cardiovascular complications. This risk can be lowered by diet. In this respect foods containing plant sterol or stanol esters can be useful for mildly- and hypercholesteraemic subjects. Plant sterols and stanols, which are structurally related to cholesterol, decrease the incorporation of dietary and biliary cholesterol into micelles. This lowers cholesterol absorption. Furthermore, these components increase ABC-transporter expression, which may also contribute to the decreased cholesterol absorption. Consequently, cholesterol synthesis and LDL receptor activity increase, which ultimately leads to decreased serum LDL cholesterol concentrations. Animal studies have further shown that these dietary components may also lower atherosclerotic lesion development. Plant sterols and stanols also lower plasma lipid-standardized concentrations of the hydrocarbon carotenoids, but not those of the oxygenated cartenoids and tocopherols. Also, vitamin A and D concentrations are not affected. Although absorption of plant sterols and stanols (0.02-3.5%) is low compared to cholesterol (35-70%), small amounts are found in the circulation and may influence other physiological functions. However, there is no consistent evidence that plant sterols or stanols can change the risk of colon or prostate cancer, or immune status. In conclusion, plant sterols and stanols effectively reduce serum LDL cholesterol and atherosclerotic risk. In addition potential effects of plant sterols and stanols on other metabolic processes remain to be elucidated.

Effects on serum lipids, lipoproteins and fat soluble antioxidant concentrations of consumption frequency of margarines and shortenings enriched with plant stanol esters.

Objective: To examine in humans the effects on serum lipids, lipoproteins and fat-soluble antioxidants of a daily consumption of 2.5 g plant stanols, consumed either once per day at lunch or divided over the three meals.Design: A randomized, double-blind, placebo-controlled, cross-over design.Subjects: Thirty-nine healthy normocholesterolemic or mildly hypercholesterolemic subjects participated.Interventions: Each subject consumed in random order; no plant stanols; 2.5 g plant stanols at lunch; and 2.5 g plant stanols divided over the three meals (0.42 g at breakfast, 0.84 g at lunch and 1.25 g at dinner, which is proportional to dietary cholesterol intake). Each period lasted 4 weeks. Plant stanols were esterified with fatty acids from low erucic rapeseed oil (LEAR) and incorporated into margarines or shortenings.Results: Consumption of 2.5 g plant stanols at lunch results in a similar low-density lipoprotein (LDL)-cholesterol-lowering efficacy compared to consumption of 2.5 g plant stanols divided over the three meals (−0.29 mmol/l compared with the control period (P<0.001; 95% CI, −0.19 to −0.39 mmol/l) for the once per day diet and −0.31 mmol/l (P<0.001; 95% CI, −0.20 to −0.41 mmol/l)) for the three times per day period). High-density Lipoprotein (HDL) cholesterol and triacylglycerol concentrations did not change. After standardization for LDL cholesterol, the sum of the most lipophylic hydrocarbon carotenoids (ie α-carotene, β-carotene and lycopene) in particular was slightly, though not significantly, lowered by −0.017±0.018 μmol/mmol LDL cholesterol (P=0.307) after the once per day period and by −0.032±0.016 μmol/mmol LDL cholesterol (P=0.049) after the three times per day period.Conclusions: Our findings suggest that for lowering LDL cholesterol concentrations it is not necessary to consume products rich in plant stanol ester at each meal or simultaneously with dietary cholesterol.Sponsorship: Raisio Group, Raisio, Finland.European Journal of Clinical Nutrition (2000) 54, 671–677

Increased intestinal ABCA1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption

The hypocholesterolemic effect of plant stanols is explained by a decreased intestinal cholesterol absorption due to a competition between plant stanols and cholesterol for incorporation into mixed micelles. Earlier we had suggested that plant stanols have a so far unknown action inside the enterocytes. The recent discovery of the involvement of ATP binding cassette (ABC) transporters in cholesterol absorption was a lead to further explore the hypocholesterolemic mechanism of plant stanols. We found that mixed micelles enriched with sitostanol or with cholesterol plus sitostanol were potent inducers of ABCA1 expression in caco‐2 cells, an accepted model to study human intestinal lipoprotein metabolism. Based on these findings, we now hypothesize that plant stanols– and possibly plant sterols–increase ABCA1‐mediated cholesterol efflux back into the intestinal lumen. We further hypothesize that intracellular levels of plant stanols are monitored by the same sensors (SREBP‐2 and LXR) as those that monitor cholesterol. Consequently, increased plant stanol levels within the enterocyte activate cholesterol efflux through ABCA1‐but not SREBP‐2‐mediated endogenous cholesterol synthesis even if intracellular cholesterol concentrations are lowered through consumption of plant stanols. If our hypothesis is correct, then the LXR pathway may be a target for dietary regulation of intestinal lipid metabolism.—Plat, J., Mensink, R. P. Increased intestinal ABCA1 expression contributes to the decrease in cholesterol absorption after plant stanol consumption. FASEB J. 16, 1248–1253 (2002)

Effects of plant stanol esters supplied in low-fat yoghurt on serum lipids and lipoproteins, non-cholesterol sterols and fat soluble antioxidant concentrations

Oil-based products enriched with plant stanol esters can lower low-density lipoprotein (LDL) cholesterol concentrations by 10-14%. Effectiveness of low-fat products, however, has never been evaluated, although such products fit into a healthy diet. We therefore examined the effects of plant stanol esters emulsified into low-fat yoghurt (0.7% fat) on fasting concentrations of plasma lipids and lipid-soluble antioxidants, which may also change by plant stanol consumption. Sixty non-hypercholesterolemic subjects first consumed daily three cups (3 x 150 ml) of placebo yoghurt for 3 weeks. For the next 4 weeks, 30 subjects continued with the placebo yoghurt, while the other 30 subjects received three cups of experimental yoghurt. Each cup provided 1 g of plant stanols (0.71 g sitostanol plus 0.29 g campestanol) as its fatty acid ester. LDL cholesterol (mean+/-S.D.) increased by 0.06+/-0.21 mmol/l in the placebo group, but decreased by -0.34+/-0.30 mmol/l in the experimental group. The difference in changes between the two groups of 0.40 mmol or 13.7% was highly significant (P<0.001; 95% confidence interval for the difference, (-)0.26 -(-)0.53 mmol/l). Effects were already maximal after 1 week. HDL cholesterol and triacylglycerol concentrations did not change. Total tocopherol levels increased by 1.43 micromol/mmol LDL cholesterol (14.0%, P=0.015). beta-carotene levels, however, decreased by -0.02 micromol/mmol LDL cholesterol (-14.4%, P=0.038). Decreases in absolute beta-carotene concentrations were found in all apoB-containing lipoproteins. LDL-cholesterol standardised phytofluene levels decreased by 21.4+/-25.7% (P<0.001), while other plasma carotenoid (lutein/zeaxanthin, beta-cryptoxanthin, lycopene and alpha-carotene) levels did not change significantly. We conclude that low-fat yoghurt enriched with plant stanol esters lowers within 1 week LDL cholesterol to the same extent as oil-based products. LDL-cholesterol standardised concentrations of tocopherol increased. The observed decrease in beta-carotene levels, as found in many other studies, appears not to be limited to the LDL fraction.

Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease

OBJECTIVE This EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added plant sterols and/or plant stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk. METHODS AND RESULTS Plant sterols/stanols (when taken at 2 g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/stanols being 500-/10,000-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of plant sterols/stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of plant sterols/stanols associated with intakes of 2 g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6-9% lowering of plasma triglyceride by 2 g/day in hypertriglyceridaemic patients warrants further evaluation. CONCLUSION Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with plant sterols/stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of plant sterols or plant stanols.

Weight reduction, but not a moderate intake of fish oil, lowers concentrations of inflammatory markers and PAI-1 antigen in obese men during the fasting and postprandial state.

Background  In obese subjects, chronic low‐grade inflammation contributes to an increased risk of metabolic abnormalities, which are reversed by weight loss. Sustained weight loss, however, is difficult to achieve and more insight into dietary approaches on anti‐inflammatory responses in obese subjects is needed. In this respect, fish oil deserves attention.

Vegetable oil based versus wood based stanol ester mixtures: effects on serum lipids and hemostatic factors in non-hypercholesterolemic subjects

A pine wood based stanol ester mixture-composed of sitostanol (92%) and campestanol (8%) effectively lowers cholesterol absorption and consequently LDL-cholesterol concentrations. It has been postulated that the less absorbable plant sterols reduce cholesterol absorption more effectively. As sitostanol is absorbed less than campestanol, we decided to examine if a vegetable oil based stanol ester mixture with 68% sitostanol and 32% campestanol is less effective than the wood based stanol ester mixture. For this, 112 non-hypercholesterolemic men and women consumed for 4 weeks a rapeseed oil (LEAR) based margarine and shortening. For the next 8 weeks, 42 subjects continued with these products, while the other subjects received products with a vegetable oil (n=36) or a pine wood based stanol ester mixture (n=34). Consumption of 3.8 g vegetable oil based stanols (2.6 g sitostanol plus 1.2 g campestanol) lowered LDL cholesterol 14.6+/-8.0% (-0.37 mmol/l; vs. the control group; P<0.001; 95% CI for the difference, -0.22 to -0. 51 mmol/l). Four grams pine wood based stanols (3.7 g sitostanol plus 0.3 g campestanol) showed a comparable decrease of 12.8+/-11.2% (-0.34 mmol/l; P<0.001; 95% CI-0.18 to-0.51 mmol/l). Decreases in LDL cholesterol were not different between the two experimental groups (P=0.793), while apoE genotype did not have a major impact on this hypocholesterolemic response. Serum HDL cholesterol and triacylglycerol concentrations were not changed. The decreases in apo B in both experimental groups differed significantly (P<0.001) from changes in the control group. Coagulation and fibrinolytic parameters were not affected. We therefore conclude that vegetable oil and wood based stanol ester mixtures, with a different sitostanol/campestanol ratio, have similar LDL cholesterol lowering effects in a non-hypercholesterolemic population.

Effects of plant sterols and stanols on intestinal cholesterol metabolism: suggested mechanisms from past to present.

Plant sterols and stanols are natural food ingredients found in plants. It was already shown in 1950 that they lower serum low-density lipoprotein cholesterol (LDL-C) concentrations. Meta-analysis has reported that a daily intake of 2.5 g plant sterols/stanols reduced serum LDL-C concentrations up to 10%. Despite many studies, the underlying mechanism remains to be elucidated. Therefore, the proposed mechanisms that have been presented over the past decades will be described and discussed in the context of the current knowledge. In the early days, it was suggested that plant sterols/stanols compete with intestinal cholesterol for incorporation into mixed micelles as well as into chylomicrons. Next, the focus shifted toward cellular processes. In particular, a role for sterol transporters localized in the membranes of enterocytes was suggested. All these processes ultimately lowered intestinal cholesterol absorption. More recently, the existence of a direct secretion of cholesterol from the circulation into the intestinal lumen was described. First results in animal studies suggested that plant sterols/stanols activate this pathway, which also explains the increased fecal neutral sterol content and as such could explain the cholesterol-lowering activity of plant sterols/stanols.

FADS1 FADS2 gene variants modify the association between fish intake and the docosahexaenoic acid proportions in human milk

BACKGROUND The genes encoding Delta(5)- and Delta(6)-desaturases (FADS1 FADS2 gene cluster) were reported to be associated with n-3 (omega-3) and n-6 (omega-6) fatty acid proportions in human plasma, tissues, and milk. Docosahexaenoic acid (DHA) can be supplied especially by dietary fish or fish oil and synthesized from alpha-linolenic acid through a pathway involving these desaturases. OBJECTIVE We evaluated whether FADS gene variants modify the effect of maternal fish and fish-oil intake on plasma and milk DHA proportions. DESIGN FADS1 rs174561, FADS2 rs174575, and intergenic rs3834458 single nucleotide polymorphisms were genotyped in 309 women from the KOALA Birth Cohort Study in The Netherlands. Plasma was collected at 36 wk of pregnancy, and milk was collected at 1 mo postpartum. Fish and fish-oil intake was assessed by using a food-frequency questionnaire at 34 wk of pregnancy and updated for the week of milk collection. Gene-diet interactions were tested by linear regression analysis. RESULTS DHA proportions were lower in women homozygous for the minor allele than in women who were homozygous for the major allele (DHA proportions in plasma phospholipids: P < 0.01; DHA proportions in milk: P < 0.05). Fish intake ranged from 0 to 2.5 portions of fatty fish/wk, and 12 women took fish-oil supplements during pregnancy. DHA proportions in plasma phospholipids increased with increasing fish and fish-oil intake, irrespective of the genotype. DHA proportions in milk increased only with fish and fish-oil intake in the major-allele carriers. CONCLUSION Lower proportions of DHA in milk from women who were homozygous for the minor allele could not be compensated for by increasing fish and fish-oil intake, possibly because of limited incorporation into milk.