Ronald P. Mensink

Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials.

To calculate the effect of changes in carbohydrate and fatty acid intake on serum lipid and lipoprotein levels, we reviewed 27 controlled trials published between 1970 and 1991 that met specific inclusion criteria. These studies yielded 65 data points, which were analyzed by multiple regression analysis using isocaloric exchanges of saturated (sat), monounsaturated (mono), and polyunsaturated (poly) fatty acids versus carbohydrates (carb) as the independent variables. For high density lipoprotein (HDL) we found the following equation: delta HDL cholesterol (mmol/l) = 0.012 x (carb----sat) + 0.009 x (carb----mono) + 0.007 x (carb---- poly) or, in milligrams per deciliter, 0.47 x (carb----sat) + 0.34 x (carb----mono) + 0.28 x (carb----poly). Expressions in parentheses denote the percentage of daily energy intake from carbohydrates that is replaced by saturated, cis-monounsaturated, or polyunsaturated fatty acids. All fatty acids elevated HDL cholesterol when substituted for carbohydrates, but the effect diminished with increasing unsaturation of the fatty acids. For low density lipoprotein (LDL) the equation was delta LDL cholesterol (mmol/l) = 0.033 x (carb----sat) - 0.006 x (carb----mono) - 0.014 x (carb----poly) or, in milligrams per deciliter, 1.28 x (carb----sat) - 0.24 x (carb----mono) - 0.55 x (carb---- poly). The coefficient for polyunsaturates was significantly different from zero, but that for monounsaturates was not. For triglycerides the equation was delta triglycerides (mmol/l) = -0.025 x (carb----sat) - 0.022 x (carb----mono) - 0.028 x (carb---- poly) or, in milligrams per deciliter, -2.22 x (carb----sat) - 1.99 x (carb----mono) - 2.47 x (carb----poly).(ABSTRACT TRUNCATED AT 250 WORDS)

Water-soluble dietary fibers and cardiovascular disease

One well-established way to reduce the risk of developing cardiovascular disease (CVD) is to lower serum LDL cholesterol levels by reducing saturated fat intake. However, the importance of other dietary approaches, such as increasing the intake of water-soluble dietary fibers is increasingly recognized. Well-controlled intervention studies have now shown that four major water-soluble fiber types-beta-glucan, psyllium, pectin and guar gum-effectively lower serum LDL cholesterol concentrations, without affecting HDL cholesterol or triacylglycerol concentrations. It is estimated that for each additional gram of water-soluble fiber in the diet serum total and LDL cholesterol concentrations decrease by -0.028 mmol/L and -0.029 mmol/L, respectively. Despite large differences in molecular structure, no major differences existed between the different types of water-soluble fiber, suggesting a common underlying mechanism. In this respect, it is most likely that water-soluble fibers lower the (re)absorption of in particular bile acids. As a result hepatic conversion of cholesterol into bile acids increases, which will ultimately lead to increased LDL uptake by the liver. Additionally, epidemiological studies suggest that a diet high in water-soluble fiber is inversely associated with the risk of CVD. These findings underlie current dietary recommendations to increase water-soluble fiber intake.

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 of fats and fatty acids on blood lipids in humans: an overview

Differences in dietary fatty acid structure induce marked differences in lipid and lipoprotein concentrations in plasma from fasting subjects. Under metabolic-ward conditions, replacement of carbohydrates by lauric, myristic, and palmitic acids raise both low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) cholesterol whereas stearic acid has little effect. Oleic and linoleic acids raise HDL and slightly lower LDL; all fatty acids lower fasting triglycerides when substituted for carbohydrates. Trans monounsaturates lower HDL and raise LDL and lipoprotein(a). The fatty acids in unhydrogenated fish oil potently lower triglycerides, with variable effects on LDL. Of the commercial fats, palm-kernel and coconut oil are the most hypercholesterolemic, followed by butter and palm oil. Replacement of hard fats rich in lauric, myristic, or palmitic acids or trans fatty acids by unsaturated oils will lower LDL, but replacement by carbohydrates will in addition decrease HDL and increase triglycerides. In free-living subjects, high-oil diets could lead to obesity, undoing the favorable effects on HDL and triglycerides.

Dietary oils, serum lipoproteins, and coronary heart disease.

Variable amounts of olive oil rather than hard fats were used in classic Mediterranean diets. We review the effects of replacing hard fats with olive oils or starchy foods on blood lipoprotein concentrations. The saturated fatty acids lauric, myristic, and palmitic acids raise both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) somewhat compared with oleic acid. If any fat is replaced by carbohydrates, fasting triglyceride values rise and HDL concentrations fall; effects on LDL depend on the type of fat that is being replaced. Trans isomers of oleic acid lower HDL and raise LDL and lipoprotein(a). The fatty acids in unhydrogenated fish oil potently lower triglycerides but may raise LDL somewhat. When body weight is forcibly kept constant, substitution of unsaturated oils such as olive oil for hard fats rich in saturated or trans fatty acids will produce a more favorable lipoprotein profile than replacement of fat by carbohydrates. However, high-oil diets might lead to obesity, which would undo their favorable effects.

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.

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 β-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 β-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 β-glucans from oats or barley.Results:Compared to control, 5 g of β-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 β-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 β-glucans were found.Conclusions:A daily consumption of 5 g of oat β-glucans in a beverage improved the lipid and glucose metabolism, while barley β-glucans did not.Sponsorship:Founded by the European Commission (QLK1-CT-2000-00535).

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.