Effects of Pglucans on lipid metabolism

Cardiovascular diseases, such as myocardial infarction (MI), angina and stroke, are major contributors to the global burden of disease. The diseases are caused by the development of atherosclerosis in the blood vessels and one factor that may influence the atherosclerotic process is the dietary fibre content in the diet. The intake of dietary fibre and risk of coronary heart disease were followed for 10 years among women in the Nurses' Health Study.48 In total, 68 782 women were included in the analysis and the age-adjusted relative risk for major cardiovascular events was 0.53 for women in the highest quintile of total dietary fibre intake (median 22.9 g/day) compared with women in the lowest quintile (median 11.5 g/day). Among different sources of dietary fibre, only cereal fibre was strongly associated with a reduced risk of cardiovascular events. Male health professionals have been followed in a similar study.49 Their food habits were assessed using a 131-item food frequency questionnaire. During 6 years of follow-up there were 511 non-fatal cases of MI and 229 coronary deaths. The age-adjusted relative risk of MI for the top quintile of total dietary fibre intake was 0.64 (median intake 28.9 g/day) compared with men in the lowest quintile (median intake 12.4 g/day). Cereal fibre was most strongly associated with a reduced risk of MI compared with other fibre sources like vegetables and fruits. Thus, the same associations were found for male health professionals as for female health professionals. In the study on female health professionals, an inverse relation between both soluble and insoluble fibre and the risk of cardiovascular diseases and MI was also found, but after multivariate adjustments the associations were no longer significant.50

More data on the effect of dietary fibre on cardiovascular diseases have been gained from intervention trials. Over 50 studies have investigated the effect of P-glucans on blood cholesterol levels. Some investigators have also addressed the task to make overall evaluations on the relation between oat P-glucan intake and its cholesterol-lowering effects. A large meta-analysis of oat products and their lowering effects on plasma cholesterol was made by Ripsin et al.51 The included studies presented differences in study designs, oat products, doses of oats and control products, and subjects with different initial cholesterol levels, gender and age; the influence of these parameters was assessed in the meta-analysis. To be included in the meta-analysis, studies had to be controlled and randomized and the control product had to have a low soluble fibre content. Moreover, the trial should also have included a dietary assessment and measurement of body weight. Twelve trials were included in the calculation of the summary effect size.51 Most of the trials used a parallel design and the length of the treatment phase varied between 18 days and 12 weeks. The summary effect size for change in total cholesterol was -0.13 mmol/l. The initial cholesterol level was highly predictive of the reduction in total cholesterol level while age and gender could not predict the response to oats. The dose-response effect was also evaluated and, after dividing the material into intakes of <3 g and >3 g of soluble fibre, the interaction was statistically significant. Malkki52 also evaluated the dose-response effect of oats. She identified 53 clinical trials, and 37 of them showed significant reductions in blood cholesterol levels after consumption of oat products while in 10 studies no significant effects were detected. The dose-response effect was not very obvious. The Food and Drug Administration (FDA) reviewed 37 oat trials and 17 studies showed a positive effect of oat bran and oat meal on total and LDL cholesterol.53 The amount of oat bran or oat meal given in the studies ranged from 34 g (2.5 g soluble fibre) to 123 g (10.3 g soluble fibre). Five studies showed equivocal results in reducing serum cholesterol, 4 had too short a study period and 11 showed no effect on serum lipid levels. However, the overall conclusion was that oats could lower serum cholesterol levels, specifically LDL cholesterol, without any significant change in the high-density lipoprotein (HDL) fraction. The FDA thus authorized a health claim stating: 'Diets high in oat bran or oat meal and low in saturated fat and cholesterol may reduce the risk of heart disease.' To be able to use the health claim a product must contain at least 0.75 g p-glucan soluble fibre per serving and the recommended daily intake is 3 g.53 It is known that the cholesterol-lowering effect is larger in subjects with increased cholesterol levels. Ripsin et al.51 indicated that if the initial cholesterol levels were over 5.9 mmol/l the reduction was larger. The molecular weight of the p-glucans may also be of importance for the cholesterol-lowering effects. In one study an intake of 5.9 g p-glucan from oat bran incorporated into bread and cookies did not have any significant effect on blood lipids while an intake of 5 g p-glucans mixed in orange juice significantly lowered LDL cholesterol compared with a control group.54 The molecular weight of the p-glucans was lower in the bread compared with the muffins and the preparation mixed with orange juice. However, the molecular weight is probably not the only important factor for the cholesterol-reducing potential. In another trial an oat drink containing p-glucans of rather low molecular weight (peak molecular weight 82 400) was compared with a control drink with low p-glucans content.55 The intake of oat drink (3.8 g p-glucan/day) resulted in significantly lower cholesterol (6%) and LDL cholesterol (6%) levels compared with the control drink and, thus, the oat drink had the expected quantitative cholesterol-lowering effects as in products containing p-glucans with a higher molecular weight. One explanation for the results could be that the p-glucans were in a soluble form. Onning56 compared the method for administration of p-glucans in 17 human studies that included hyperlipidaemic subjects. The total cholesterol level at the end of the intervention period in the control group was between 5.9 and 7.4 mmol/l. The change in total cholesterol in the oat group in comparison with the control group varied from 0 to -13% while the change in LDL cholesterol varied from 0 to -16.5%. The studies with the largest reductions incorporated the oats in crisps, hot cereals, muffins and beverages while in the studies with small reductions the oats were given in cold cereals and also in bread. Inclusion of the p-glucans in liquid foods and also using some heat treatment seemed to increase the lipid-lowering effect probably by increasing the solubility of the p-glucans. The fact that the solubility of the p-glucans varies a lot in foods was confirmed in a study by Lia Amundsen et al.57 Products like bread, teacakes, muesli, muffins, macaroni, pasta and apple drinks were supplemented with an oat bran concentrate and the solubility of the p-glucans varied from 22% in pasta to 70% in the apple drink. Thus, the solubility of the p-glucans in the products was rather low (mean value of about 50%) but the daily dose of soluble p-glucans consumed by hypercholesterolaemic subjects (2.7 g) was still high enough to significantly decrease blood cholesterol levels compared with a control diet. The molecular weight and the solubility of the p-glucans used in human studies have seldom been documented and this makes it difficult to compare results from different studies in relation to the doses used.

Several mechanisms have been proposed for the cholesterol-lowering effects of p-glucans. The main hypothesis is that they decrease the intestinal uptake of bile acids. In subjects with ileostomy, intake of oat bran bread lead to an increased excretion of chenodeoxycholic acid and total bile acids in comparison with intake of wheat flour bread.58 A recent study focused on the effects of oat P-glucans incorporated into a drink on cholesterol absorption (measurement of plant sterols) and cholesterol synthesis (analysis of lathosterol) in humans.59 Intake of 5 g P-glucan daily led to a significant decrease in serum total and LDL cholesterol levels and, at the same time, the concentration of lathosterol was increased and that of sitosterol was decreased. This indicates that P-glucans reduce cholesterol absorption in the intestine.

Furthermore, P-glucans are fermented in the colon and the short-chain fatty acids produced may influence cholesterol metabolism in the liver. However, only a few human studies exist on this subject and more studies are needed to evaluate this effect. Soluble fibre can also decrease gastric emptying, prolong glucose absorption and increase insulin sensitivity. These changes can also have an effect on lipid metabolism in the liver. In animals the main outcome of the action of fibre is a lowering of hepatic cholesterol pools as a result of more cholesterol being diverted to bile acid synthesis and lower cholesterol delivery to the liver through chylomicron remnants.60

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