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.

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.

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.

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.

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.

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. MATERIAL AND METHODS: Eleven obese men (BMI: 30-35 kg m(-2)) received daily fish oil (1.35 g n-3 fatty acids) or placebo capsules in random order for 6 weeks. Eight subjects continued with a weight reduction study that lasted 8 weeks. Mean weight loss was 9.4 kg. At the end of each experimental period a postprandial study was performed. RESULTS: Relative to fasting concentrations, interleukin-6 (IL-6) levels increased by 75% 2 h and by 118% 4 h after the meal (P < 0.001), when subjects consumed the control capsules. In contrast, C-reactive protein (C-RP) concentrations decreased slightly by 0.7% and 6.6% (P = 0.046), and those of plasminogen activator inhibitor-1 (PAI-1) antigen by, respectively, 26% and 53% (P < 0.001). Tumour necrosis factor-alpha (TNF-alpha; P = 0.330) and soluble TNF-receptor concentrations (sTNF-R55 and sTNF-R75; P = 0.451 and P = 0.108, respectively) did not change. Changes relative to fasting concentrations were not significantly affected by either fish oil or weight reduction. Absolute IL-6, C-RP, sTNF-R55, sTNF-R75, and PAI-1 antigen concentrations, however, were consistently lower after weight reduction, but not after fish oil consumption. CONCLUSION: For slightly obese subjects a moderate intake of fish oil does not have the same favourable effects on markers for a low-grade inflammatory state as weight reduction.

Oxidized plant sterols in human serum and lipid infusions as measured by combined gas-liquid chromatography-mass spectrometry.

Some oxidized forms of cholesterol (oxysterols) are thought to be atherogenic and cytotoxic. Because plant sterols are structurally related to cholesterol, we examined whether oxidized plant sterols (oxyphytosterols) could be identified in human serum and soy-based lipid emulsions. We first prepared both deuterated and nondeuterated reference compounds. We then analyzed by gas-liquid chromatography-mass spectrometry the oxyphytosterol concentrations in serum from patients with phytosterolemia or cerebrotendinous xanthomatosis, in a pool serum and in two lipid emulsions. 7-Ketositosterol, 7 beta-hydroxysitosterol, 5 alpha, 6 alpha-epoxysitosterol, 3 beta,5 alpha,6 beta-sitostanetriol, and probably also 7 alpha-hydroxysitosterol were present in markedly elevated concentrations in serum from phytosterolemic patients only. Also, campesterol oxidation products such as 7 alpha-hydroxycampesterol and 7 beta-hydroxycampesterol were found. Interestingly, sitosterol was oxidized for approximately 1.4% in phytosterolemic serum, which is rather high compared with the approximate 0.01% oxidatively modified cholesterol normally seen in human serum. The same oxyphytosterols were also found in two lipid emulsions in which the ratio of oxidized sitosterol to sitosterol varied between 0.038 and 0.041. In conclusion, we have shown that oxidized forms of plant sterols are present in serum from phytosterolemic patients and two frequently used soy-based lipid emulsions. Currently, it is unknown whether oxyphytosterols affect health, as has been suggested for oxysterols. However, 7 beta-hydroxycholesterol may be one of the more harmful oxysterols, and both sitosterol and campesterol were oxidized into 7 beta-hydroxysitosterol and 7 beta-hydroxycampesterol. The relevance of these findings therefore deserves further exploration.

Dietary vegetable oil and wood derived plant stanol esters reduce atherosclerotic lesion size and severity in apoE*3-Leiden transgenic mice.

The hypolipidemic and anti-atherosclerotic effects of vegetable oil- and wood-based dietary plant stanol esters were compared in female apoE*3-Leiden transgenic mice at relevant plasma cholesterol levels. The plant stanol esters derived from vegetable oil (sitostanol 65.7%, campestanol 30.1%) had different contents of sitostanol and campestanol than the plant stanol esters derived from wood (sitostanol 87.6%, campestanol 9.5%) or from a mixture of vegetable oil and wood (sitostanol 73.0%, campestanol 24.7%). The mice (10 per group) received for 38 weeks a control diet or diets containing 1.0% (w/w) plant stanol esters derived from either vegetable oil, wood or a mixture of both. Vegetable oil (-46%), wood (-42%) and vegetable oil/wood (-51%) plant stanol esters decreased the plasma cholesterol levels (P<0.0001) by reducing the cholesterol content in plasma very low density-, intermediate density- and to a lesser extent in low density-lipoprotein. Plant stanol ester feeding did not change plasma triglyceride levels. Dietary plant stanol esters reduced the atherosclerotic lesion area by 91+/-13% (vegetable oil), 97+/-4% (wood) and 78+/-34% (vegetable oil/wood) (P<0.0001) and the severity from regular intimal fatty streaks/mild plaques (on average type 2--3 lesions) in controls to individual intimal foam cells (

Effects of diets enriched with two different plant stanol ester mixtures on plasma ubiquinol-10 and fat-soluble antioxidant concentrations.

Plant stanols lower intestinal cholesterol absorption. This causes a decrease in serum low-density lipoprotein (LDL)-cholesterol, despite a compensatory increase in cholesterol synthesis. We therefore hypothesized that plant stanols also change LDL-cholesterol-standardized concentrations of ubiquinol-10 (a side product of the cholesterol synthesis cascade) and of those fat-soluble antioxidants that are mainly carried by LDL. To examine this, 112 nonhypercholesterolemic subjects consumed low erucic acid rapeseed oil (LEAR)-based margarine and shortening for 4 weeks. For the next 8 weeks, 42 subjects consumed the same products, while the other subjects received products with vegetable oil-based stanols (2.6 g sitostanol plus 1.2 g campestanol daily, n = 36) or wood-based stanols (3.7 g sitostanol plus 0.3 g campestanol daily, n = 34). Consumption of both plant stanol ester mixtures increased cholesterol synthesis and lowered cholesterol absorption, as indicated by increased serum cholesterol-standardized lathosterol and decreased plant sterol concentrations, respectively. Compared with the control group, absolute plasma ubiquinol-10 concentrations were lowered by 12.3% +/- 18.9% (-0.14 microg/mL v. the control group; P =.004; 95% confidence interval [CI] for the difference in changes, -0.05 to -0.22 microg/mL) in the vegetable oil-based group and by 15.4% +/- 13.0% (-0.17 microg/mL v. the control group; P <.001; 95% CI for the difference, -0.08 to -0.27 microg/mL) in the wood-based group. Changes in LDL-cholesterol-standardized ubiquinol-10 concentrations were not significantly changed. The most lipophylic antioxidants, the hydrocarbon carotenoids (beta-carotene, alpha-carotene, and lycopene), decreased most, followed by the less lipophylic oxygenated carotenoids (lutein/zeaxanthin and beta-cryptoxanthin) and the tocopherols. These reductions were related to the reduction in LDL, which carry most of these antioxidants. The decrease in the hydrocarbon carotenoids, however, was also significantly associated with a decrease in cholesterol absorption. LDL-cholesterol-standardized antioxidant concentrations were not changed, except for beta-carotene, which was still, although not significantly, lowered by about 10%. We conclude that the increase in endogenous cholesterol synthesis during plant stanol ester consumption does not result in increased LDL-cholesterol-standardized concentrations of ubiquinol-10, a side product of the cholesterol synthesis cascade. Furthermore, decreases in absolute fat-soluble antioxidant concentrations are related to decreases in LDL-cholesterol. However, for the most lipophylic carotenoids, some of the reduction was also related to the decrease in cholesterol absorption.

Dietary trans alpha-linolenic acid from deodorised rapeseed oil and plasma lipids and lipoproteins in healthy men: the TransLinE Study.

TRANS: isomers of alpha-linolenic acid, which are formed by deodorization of refined vegetable oils, can be found in significant amounts in edible oils. Effects of trans alpha-linolenic acid on plasma lipoproteins are unknown. We therefore investigated the effects of trans alpha-linolenic acid on plasma lipids and lipoproteins in healthy European men. Eighty-eight healthy men from three European countries (France, Scotland, UK and the Netherlands) first consumed for 6 weeks a diet with experimental oils 'free' of trans fatty acids (run-in period). For the next 6 weeks, they were randomly allocated to a diet with experimental oils 'high' or 'low' in trans alpha-linolenic acid. Daily total trans alpha-linolenic acid intake in the high trans group was 1410 (range 583-2642) mg. Experimental oils were provided as such, or incorporated into margarines, cheeses, muffins and biscuits. The high trans alpha-linolenic acid diet significantly increased the plasma LDL-:HDL-cholesterol ratio by 8.1 % (95 % CI 1.4, 15.3; and the total cholesterol:HDL-cholesterol ratio by 5.1 % (95 % CI 0.4, 9.9; compared with the low-trans diet. This was largely explained by an increase in LDL-cholesterol on the high-trans diet, while no change was observed in the low-trans group (mean treatment effect of 4.7 % (95 % CI -0.8, 10.5; No effects were found on total cholesterol and HDL-cholesterol, triacylglycerols, apolipoprotein B and A-1, and lipoprotein(a) concentrations. In conclusion, trans alpha-linolenic acid may increase plasma LDL-:HDL-cholesterol and total cholesterol:HDL-cholesterol ratios. Whether diet-induced changes in these ratios truly affects the risk for CHD remains to be established.

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 alpha-carotene, beta-carotene and lycopene) in particular was slightly, though not significantly, lowered by -0. 017+/-0.018 micromol/mmol LDL cholesterol (P=0.307) after the once per day period and by -0.032+/-0.016 micromol/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.

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.

A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations.

BACKGROUND: Tocotrienols, lipid-soluble antioxidants with vitamin E activity, have been reported to lower LDL-cholesterol concentrations and platelet aggregation in men, but results are contradictory. OBJECTIVE: To examine in detail the effects of a vitamin E concentrate rich in tocotrienols on serum lipoproteins and on platelet function in men at risk for cardiovascular disease. DESIGN: In this randomized, double-blind, placebo-controlled parallel trial, 20 men received daily for 6 wk 4 capsules, each containing 35 mg tocotrienols and 20 mg alpha-tocopherol; 20 other men received 4 capsules daily, each providing 20 mg alpha-tocopherol. All men had concentrations of serum total cholesterol between 6.5 and 8.0 mmol/L or lipoprotein(a) concentrations > 150 mg/L. RESULTS: Compliance was confirmed by changes in serum tocopherol and tocotrienol concentrations. Serum LDL cholesterol in the tocotrienol group was 4.80 mmol/L before and 4.79 mmol/L after intervention, and increased from 4.70 to 4.86 mmol/L in the placebo group (95% CI for the difference: -0.54, 0.19 mmol/L; P = 0.333). Also, changes in HDL cholesterol, triacylglycerol, lipoprotein(a), and lipid peroxide concentrations did not differ between the groups. After adjustment for differences in initial values, no effects were found on collagen-induced platelet aggregation velocity, maximum aggregation, or thromboxane B2 formation in citrated whole blood. ATP release, however, was lower in the tocotrienol group. Urinary thromboxane B2 and 11-keto-thromboxane B2 concentrations and coagulation and fibrinolytic measures did not change. CONCLUSION: The tocotrienol supplements used had no marked favorable effects on the serum lipoprotein profile or on platelet function in men with slightly elevated lipid concentrations.

Individual saturated fatty acids and effects on whole blood aggregation in vitro.

OBJECTIVES: In two studies we have compared the effects of four different saturated fat diets (medium chain fatty acids (MCFA), and lauric, myristic and palmitic acids) with those of a monounsaturated oleic acid diet on in-vitro whole blood aggregation in healthy women and men. DESIGN: Study 1 had a cross-over design with three diet periods of each six weeks, and studied the effects of diets enriched in lauric, palmitic or oleic acids. Study 2 had a parallel design. After a three week oleic acid run-in diet, three groups of subjects were formed which consumed either an MCFA, myristic acid or oleic acid rich diet for six weeks. SUBJECTS: Eighteen women and 14 men in Study 1 and 37 women and 23 men in Study 2. All subjects were healthy and were aged 20-60 y. INTERVENTIONS: The experimental diets were the same in nutrient composition except for on average 8 En% (Study 1) or 10 En% (Study 2) which was provided by either MCFA, lauric acid, myristic acid, palmitic acid or oleic acid. Blood samples were taken at the end of each dietary period. Whole blood platelet aggregation, anticoagulated with recombinant hirudin was assessed after administration of collagen (final concentration (fc): 0.38 microgram/mL) in Study 1 and collagen (fc: 0.22 microgram/mL) or ADP (fc: 1.25 mumol/L) in Study 2. Collagen-induced formation of thromboxane (Tx)A2, measured as thromboxane (Tx)B2, was evaluated in Study 1 only. RESULTS: The aggregation velocity between the saturated fatty acid diets and the monounsaturated fatty acid diet did not differ. TxB2 concentrations measured in collagen activated blood samples, which correlated significantly with aggregation velocity, did not differ between the lauric or the palmitic compared with the oleic acid diet. A stepwise regression analysis indicated that collagen-induced aggregation was negatively correlated with the number of red blood cells. ADP-induced aggregation also correlated negatively with red blood cell count, and positively with platelet count. CONCLUSIONS: The exchange of 7-10 En% from oleic acid for MCFA, lauric, myristic or palmitic acid does not affect in-vitro whole blood aggregation induced by collagen. ADP-induced aggregation is not affected when 10 En% from oleic acid is exchanged for MCFA or myristic acid.

Pregnancy-induced hypertension: maternal and neonatal plasma lipid-soluble antioxidant levels and its relationship with fatty acid unsaturation.

OBJECTIVE: Our purpose was to investigate whether plasma lipid-soluble antioxidant levels during the third trimester of pregnancy and immediately after birth are altered in women with pregnancy-induced hypertension. DESIGN: Nested case-control study of women with pregnancy-induced hypertension. SUBJECTS: A group of 23 women with (mild) pregnancy-induced hypertension and their neonates, were compared with 23 matched controls with uncomplicated pregnancies. METHODS: Concentrations of vitamin E isomers, several carotenoids, and retinol were determined by HPLC in venous plasma which had been stored for 2-5 y. Antioxidant levels were adjusted for the degree of fatty acid unsaturation in plasma phospholipids as analysed 2-5 y before. RESULTS: In the third trimester of pregnancy, lipid-soluble antioxidant levels were similar in women with pregnancy-induced hypertension and controls. From the third trimester to postpartum, mean (+/- s.e.m.) beta + gamma-tocopherol levels decreased by 0.38 +/- 0.17 mumol/l or 5% (P = 0.038) in the control group. In the pregnancy-induced hypertension group, however, plasma levels of most antioxidants decreased from the third trimester to postpartum, but only the decreases in plasma levels of beta + gamma-tocopherol of 1.08 +/- 0.27 mumol/l or 26% (P = 0.042), of alpha-tocopherol of 2.51 +/- 1.58 mumol/l or 6% (P = 0.024), and of lutein of 0.13 +/- 0.04 mumol/l or 15% (P = 0.013) reached statistical significance as compared with the changes in the control group. At the same time, the polyunsaturated fatty acid unsaturation index of plasma phospholipids (UI) decreased in the pregnancy-induced hypertension group as well. Consequently, antioxidant levels, adjusted for UI, changed similarly in both groups. Umbilical vein plasma antioxidant levels were also similar after complicated and uncomplicated pregnancies. CONCLUSION: Plasma lipid-soluble antioxidant levels in mother and child are affected by mild pregnancy-induced hypertension, but this effect disappears after adjustment for fatty acid unsaturation.

Maternal and neonatal plasma antioxidant levels in normal pregnancy, and the relationship with fatty acid unsaturation.

During pregnancy, maternal plasma concentrations of the peroxidation-susceptible polyunsaturated fatty acids (polyenes) increase. In addition, the proportion of polyenes is higher in neonatal plasma than in maternal plasma. To study whether these increased amounts of polyenes affect antioxidant levels, we measured lipid-soluble antioxidants in maternal and neonatal plasmas obtained during thirty-five normal pregnancies. These values were then related to the degree of phospholipid-fatty acid unsaturation. Maternal plasma levels of tocopherols and lutein increased during pregnancy, as assessed at 14, 22, and 32 weeks of gestation. However beta-carotene levels decreased, and levels of other carotenoids remained unchanged. Retinol levels were only decreased at 32 weeks of gestation. The value for alpha-tocopherol: phospholipid-polyene unsaturation index (UI) also increased during pregnancy, despite the observed increase in UI. Corresponding ratios for several carotenoids and retinol, however, decreased during pregnancy. After delivery, maternal plasma levels of delta-tocopherol and beta + gamma-tocopherol, as well as beta + gamma-tocopherol: UI values, were lower than values at 32 weeks of gestation. Umbilical-cord plasma antioxidant levels and antioxidant: UI values, except retinol: UI, were significantly lower than maternal values. Significant and consistent cord v. maternal correlations were observed for plasma levels of beta + gamma-tocopherol, lutein and beta-carotene, but not for delta-tocopherol, alpha-tocopherol, lycopene, alpha-carotene, and retinol. In conclusion, although during pregnancy maternal plasma tocopherol levels increased concurrently with, or more than, fatty acid unsaturation in plasma phospholipids, the decrease in carotenoid: UI values during gestation, the decrease in maternal plasma levels of delta-tocopherol and beta + gamma-tocopherol after delivery, and the low neonatal antioxidant levels merit further investigation.

Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice.

Studying the effects of dietary fish oil on VLDL metabolism in humans is subject to both large intra- and interindividual variability. In the present study we therefore used hyperlipidemic apolipoprotein (APO) E*3-Leiden mice, which have impaired chylomicron and very low density lipoprotein (VLDL) remnant metabolism, to study the effects of dietary fish oil on serum lipids and VLDL kinetics under highly standardized conditions. For this, female APOE*3-Leiden mice were fed a fat- and cholesterol-containing diet supplemented with either 0, 3 or 6% w/w (i.e. 0, 6, or 12% of total energy) of fish oil. Fish oil-fed mice showed a significant dose-dependent decrease in serum cholesterol (up to -43%) and triglyceride levels (up to -60%), mainly due to a reduction of VLDL (-80%). LDL and HDL cholesterol levels were not affected by fish oil feeding. VLDL-apoB kinetic studies showed that fish oil feeding resulted in a significant 2-fold increase in VLDL-apoB fractional catabolic rate (FCR). Hepatic VLDL-apoB production was, however, not affected by fish oil feeding. VLDL-triglyceride turnover studies revealed that fish oil significantly decreased hepatic VLDL-triglyceride production rate (-60%). A significant increase in VLDL-triglyceride FCR was observed (+70%), which was not related to increased lipolytic activity. We conclude that APOE*3-Leiden mice are highly responsive to dietary fish oil. The observed strong reduction in serum very low density lipoprotein (VLDL) is primarily due to an effect of fish oil to decrease hepatic VLDL triglyceride production rate and to increase VLDL-apoB fractional catabolic rate.

Exercise performance, red blood cell deformability, and lipid peroxidation: effects of fish oil and vitamin E.

Previous studies have indicated that fish oil supplementation increases red blood cell (RBC) deformability, which may improve exercise performance. Exercise alone, or in combination with an increase in fatty acid unsaturation, however, may enhance lipid peroxidation. Effects of a bicycle time trial of approximately 1 h on RBC characteristics and lipid peroxidation were, therefore, studied in 24 trained cyclists. After 3 wk of fish oil supplementation (6 g/day), without or with vitamin E (300 IU/day), trial performance, RBC characteristics, and lipid peroxidation were measured again. RBC deformability appeared to decrease during endurance exercise. After correction for hemoconcentration, plasma total tocopherol concentrations decreased by 0.77 micromol/l (P = 0. 012) or 2.9% and carotenoid concentrations by 0.08 micromol/l (P = 0. 0008) or 4.5%. Endurance exercise did not affect the lag time and rate of in vitro oxidation of low-density lipoproteins (LDLs), but the maximum amount of conjugated dienes formed decreased by 2.1 +/- 1.0 micromol/mmol LDL cholesterol (P = 0.042) or 1.2%. Fish oil supplementation with and without vitamin E did not affect RBC characteristics or exercise performance. Both supplements decreased the rate of LDL oxidation, and fish oil supplementation with vitamin E delayed oxidation. The amount of dienes, however, was not affected. The supplements also did not change effects of exercise. We conclude that the changes observed during endurance exercise may indicate increased oxidative stress, but further research is necessary to confirm this. Fish oil supplementation does not improve endurance performance, but it also does not cause or augment changes in antioxidant levels or LDL oxidation during exercise.

Effects of fish oil and vitamin E supplementation on copper-catalysed oxidation of human low density lipoprotein in vitro.

Eleven men received a fish oil (2.4 g n-3 fatty acids), fish oil plus vitamin E (300 IU) or no supplement for 3 weeks. Dietary fish oil increased the maximum amount of conjugated dienes formed during copper-catalysed oxidation of LDL in vitro by 18-20%. Fish oil also tended to decrease the lagtime before onset of oxidation, but this effect was counteracted by vitamin E. We conclude that fish oil supplementation increases the oxidizability of LDL in vitro, and vitamin E increases its oxidation resistance.