Replacing dairy fat with rapeseed oil causes rapid improvement of hyperlipidaemia: a randomized controlled study.

BACKGROUND: Rapeseed oil (RO), also known as canola oil, principally contains the unsaturated fatty acids 18:1n-9, 18:2n-6 and 18:3n-3 and may promote cardiometabolic health. OBJECTIVE: To investigate the effects on lipoprotein profile, factors of coagulation and insulin sensitivity of replacing a diet rich in saturated fat from dairy foods (DF diet) with a diet including RO-based fat (RO diet). DESIGN: During a 2×3-week randomized, controlled, cross-over trial, 20 free-living hyperlipidaemic subjects were provided with isocaloric test diets that differed in fat composition alone. Blood lipoprotein profile, coagulation and fibrinolytic factors and insulin sensitivity (euglycaemic clamp) were determined before and after the dietary intervention. RESULTS: All subjects completed the study, and compliance was high according to changes in serum fatty acids. The RO diet, but not the DF diet, reduced the levels of serum cholesterol (-17%), triglycerides (-20%) and low-density lipoprotein cholesterol (-17%), cholesterol/high-density lipoprotein (HDL) cholesterol ratio (-21%), apolipoprotein (apo) B/apo A-I ratio (-4%) and factor VII coagulant activity (FVIIc) (-5%) from baseline. These changes were significantly different between the diets (P=0.05 to P<0.0001), except for FVIIc (P=0.1). The RO diet, but not the DF diet, modestly increased serum lipoprotein(a) (+6%) and tended to increase the glucose disappearance rate (K-value, +33%). HDL cholesterol, insulin sensitivity, fibrinogen and tissue plasminogen activator inhibitor-1 levels did not change from baseline or differ between the two diets. CONCLUSIONS: In a diet moderately high in total fat, replacing dairy fat with RO causes a rapid and clinically relevant improvement in serum lipoprotein profile including lowering of triglycerides in hyperlipidaemic individuals.

Clinical manifestation of gadodiamide-related nephrogenic systemic fibrosis.

AIMS: To further characterize the clinical signs and symptoms of nephrogenic systemic fibrosis, a new and serious disease affecting renal failure patients and caused by some Gd-containing contrast agents, including gadodiamide. MATERIAL: 22 cases of gadodiamide-related nephrogenic systemic fibrosis followed at the nephrology department of Copenhagen University Hospital Herlev. METHOD: Retrospective cohort study based on medical records, personal interviews and physical examinations. RESULTS: Typical first signs of the disease were skin discoloration, induration and warmth, itching, constant pain and other neuropathic symptoms localized to the lower legs. First sign appeared in a median of 14 days (range 0 â 53 days) after gadodiamide exposure. Associated early symptoms included sleeplessness and transient, diffuse hair loss. The predominant late symptom was symmetrical skin stiffness of extremities with or without restricted joint motion. Ten of 22 patients (45, 95% CI: 27 â 66%) were severely disabled due to contractures on the average of 29 months after being exposed to gadodiamide. Four patients died (18, 95% CI: 6 â 41). Patients perceived that intensive physiotherapy was effective in limiting disabling contractures. CONCLUSIONS: Signs and symptoms of nephrogenic systemic fibrosis vary over time and between patients. The disease leads to severe disability in a significant proportion of affected patients. Intensive physiotherapy may limit the development of contractures.

Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis.

BACKGROUND: Gadolinium (Gd)-based magnetic resonance contrast agents (GBMCA), including gadodiamide, have been identified as the probable causative agents of the serious disease, nephrogenic systemic fibrosis (NSF). OBJECTIVES: To investigate retained Gd-containing deposits in skin biopsies from patients with NSF and to determine their relative concentrations over time from administration of GBMCA. METHODS: An investigator-blinded retrospective study, analysing 43 skin biopsies from 20 patients with gadodiamide-related NSF and one NSF-negative gadodiamide-exposed dialysis patient, ranging from 16 days to 1991 days after Gd contrast dose. Utilizing automated quantitative scanning electron microscopy/energy-dispersive X-ray spectroscopy we determined the concentration of Gd and associated elements present as insoluble deposits in situ in the tissues. RESULTS: We detected Gd in skin lesions of all 20 patients with NSF, whereas Gd was undetectable in the NSF-negative patient. Gd concentration increased over time in 60% of patients with multiple sequential biopsies (n=10), decreasing only when the initial sampling time was >23 months after first gadodiamide dose. All Gd-containing deposits contained phosphorus, calcium and sodium. The ratio of Gd to calcium in tissue deposits correlated positively with the gadodiamide dose and with serum ionized calcium at the time of Gd exposure. CONCLUSIONS: These findings demonstrate the in vivo release (through transmetallation) of the toxic free Gd3+ from gadodiamide, and its retention in apatite-like deposits. We suggest that Gd may be mobilized over time from bone stores, explaining variably delayed onset of NSF and increasing skin concentration over time in patients with NSF.

Effect of red wine and red grape extract on blood lipids, haemostatic factors, and other risk factors for cardiovascular disease.

OBJECTIVE: Some epidemiological studies found a lower risk of cardiovascular disease among wine drinkers than among drinkers of other types of ethanol. This difference might be due to an effect of nonalcohol compounds in wine on important cardiovascular risk factors. The objective of this study was to compare the effect of red wine, nonalcohol compounds of red wine and placebo on established cardiovascular risk factors. DESIGN: A parallel, four-armed intervention study. SUBJECTS: A total of 69 healthy 38-74-y-old men and women. INTERVENTIONS: Subjects were randomised to either 1: red wine (males: 300 ml/day, 38.3 g alcohol/day, female subjects: 200 ml/day, 25.5 g alcohol/day), 2: water + red grape extract tablets (wine-equivalent dose), 3: water + red grape extract tablets (half dose), or 4: water + placebo tablets for a period of 4 weeks. No other sources of alcohol or anthocyanin were allowed. Plasma high-density lipoprotein (HDL)-cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol (LDL-C), HDL-C/LDL-C-ratio, very-low-density lipoprotein (VLDL)-triacylglycerol, total cholesterol, fibrinogen, factor VII coagulant activity (FVIIc), blood pressure, and body weight were determined before and after intervention. RESULTS: Wine consumption was associated with a significant 11-16% increase in fasting HDL-C and 8-15% decrease in fasting fibrinogen relative to not drinking wine. There were no significant treatment effects on fasting LDL-C, HDL-C/LDL-C-ratio, VLDL-triacylglycerol, total cholesterol, FVIIc, or blood pressure. Drinking wine was associated with relative body weight increments closely corresponding to the energy contributed by the alcohol component. CONCLUSION: Moderate red wine consumption for 4 weeks is associated with desirable changes in HDL-C and fibrinogen compared with drinking water with or without red grape extract. The impact of wine on the measured cardiovascular risk factors thus seems primarily explained by an alcohol effect. Our finding suggests that the putative difference in cardiac risk associated with wine vs other alcoholic beverages might be rather explained by other life-style confounders than by red wine contents of nonalcohol components.

Fish oil feeding is associated with an increased accumulation of dietary lipids in enterocytes: results from an in vivo study in rats.

BACKGROUND: Chronic fish oil consumption is associated with reduced postprandial lipaemia, but the mechanism behind this effect is not fully understood. We studied whether lipid absorption might be altered in rats fed fish oil. METHODS: Male Wistar rats were fed fish oil enriched chow (n = 6) or control oil enriched chow (n = 6). After 4 weeks, 61 mg 3H-triolein was instilled into duodenal tied-off loops. Intestinal segments were removed after 15, 30, 45, 60 and 90 min. Enterocytes were then isolated by calcium chelation and quantified by DNA determination. Non-absorbed 3H-lipid and 3H-lipid contents of enterocytes were determined by liquid scintillation counting. Two other groups of rats (2 x 6) fed the experimental diets were given an oral fat load and fasting and postprandial blood samples were taken. RESULTS: The accumulation of 3H-lipids in enterocytes was higher in rats fed fish oil than in controls (area under the 3H-lipid time curve: 1041.3 versus 670.3 nmol oleic acid x min/microg DNA, P < 0.05). Separation of lipids showed that an accumulation of triglycerides and free fatty acids occurred in rats fed fish oil. The amount of non-absorbed 3H-lipid tended to be higher in the fish oil fed rats (P > 0.1). It was confirmed that the fish oil enriched chow caused lower postprandial lipaemia (34% reduction in serum triglyceride concentrations, P < 0.05). CONCLUSION: Attenuated postprandial lipaemia following fish oil feeding is explained, at least partly, by a transient lipid accumulation in enterocytes which may result in a delayed triglyceride efflux from the enterocytes into the circulation.

Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes.

OBJECTIVE: Fish oil supplement has been proposed as a non-pharmacological strategy to correct the atherogenic lipid profile associated with type 2 diabetes mellitus. However, fish oil may have deleterious effects on lipid peroxidation and glycemic control. DESIGN: In this study, 44 type 2 diabetic patients were randomized to vitamin E standardized (53.6 mg/day) supplementation (capsules) with 4 g daily of either fish oil (n=23) or corn oil (n=21) for 8 weeks preceded by a 4 week run-in period of corn oil supplementation. LDL was isolated by density gradient ultracentrifugation and oxidized in vitro with Cu(2+). As a marker of in vivo oxidation malondialdehyde concentration in LDL (LDL-MDA) was measured. RESULTS: Fish oil reduced both mean lag time (before, 57.8; after, 48.8 min, P<0.001) and mean propagation rate (before, 0.018 DeltaOD/min; after, 0.015 DeltaOD/min, P<0.001), whereas corn oil had no influence on lag time and propagation rate. The changes in lag time and propagation rate differed significantly between fish oil and corn oil treatment. LDL-MDA changes differed borderline significantly between groups (FO, 110.4 pmol/mg protein; CO, 6.7 pmol/mg protein; P=0.057). Fish oil supplementation had no influence on glycemic control as assessed from HbA(1c) and fasting blood glucose. CONCLUSION: According to our findings, fish oil supplementation leads to increased in vivo oxidation and increased in vitro oxidation susceptibility of LDL particles. More studies are needed to clarify the clinical importance of this finding.

The Göttingen minipig as a model for postprandial hyperlipidaemia in man: experimental observations.

Postprandial hyperlipidaemia is believed to be atherogenic. This study aimed to establish a minipig model to investigate determinants of postprandial lipid metabolism. In a randomized cross-over design seven minipigs were subjected to six different feeding regimens: intragastric fat loads of 1, 2, and 4 g fat (Intralipid, 20%) kg(-1) in two fractions 1.5 h apart (1/3 first, 2/3 second), 2 g fat (Intralipid kg(-1) in one fraction, and 2 g olive oil kg(-1) in two fractions, all after pre-feeding with standard diet, and finally 2 g fat (Intralipid kg(-1) in two fractions without pre-feeding. Blood was sampled before and hourly for 7 h after gavaging, and plasma triglycerides were measured. Triglycerides increased significantly in all the feeding regimens (P < 0.001), except when olive oil was used as the fat source. A borderline significant dose-response effect of the Intralipid dose on the triglyceride response was observed. We found no significant differences in triglyceride response whether 2 g fat (Intralipid kg(-1) was given in one or two fractions, with or without pre-feeding. We conclude that postprandial hyperlipidaemia in minipigs can be induced by gavaging an emulgated lipid solution (1-4 g fat/kg, Intralipid, while olive oil is not applicable. There is no need to administer the fat fractionated or to withhold food prior to administration.

[The effect of dietary oils on blood lipids and the risk of ischemic heart disease with special emphasis on olive oil. A literature review]. / Spiseoliers effekt på blodlipider og risiko for iskaemisk hjertesygdom med saerlig fokus på olivenolie. En litteraturgennemgang.

INTRODUCTION: The European Union is financing a large-scale campaign, in which olive oil is represented as the optimal fat for dietetic prevention of coronary heart disease. METHOD: We reviewed all controlled dietary studies comparing the effect on blood lipids of olive oil and alternative vegetable oils. Fifteen studies were identified. RESULTS: Consumption of olive oil was associated with significantly raised plasma concentrations of low density lipoprotein cholesterol (+6.5%), high density lipoprotein cholesterol (), and triglycerides (+7%) as compared with an average of the alternative oils. In the light of these differences in blood lipids and the risk coefficients published earlier, we calculated that the consumption of olive oil was associated with a 7% increase in the risk of coronary heart disease. CONCLUSION: We conclude that olive oil cannot be considered more cardioprotective than other unsaturated vegetable oils as judged from its effects on blood lipids.

A high-fat meal does not activate blood coagulation factor VII in minipigs.

It is a matter of debate whether postprandial activation of blood coagulation factor VII (FVII) is associated with an increased risk of thrombosis. To clarify this question, an animal model in which consequences of dietary FVII activation can be studied in a more detailed way would be an important tool. We studied postprandial FVII activation in seven non-fasting Göttingen minipigs. Intralipid (4 g/kg) was administered through a gastric tube in two fractions at 9.00 a.m. (one-third of total dose) and 10.30 a.m. (two-thirds of total dose). Blood samples were drawn 0.5 h before (baseline) and 2, 3, 3.5, 4, 5, and 6 h after the first fat load. Triglycerides, activated FVII (FVIIa), FVII coagulant activity (FVIIc), FVII amidolytic activity (FVIIam) and prothrombin fragment I + 2 (F1 + 2) were analysed in plasma samples. Median plasma triglycerides were significantly raised from 0.67 mmol/l (baseline) to 2.56 mmol/l 5 h postprandially (P < 0.001). There were no significant changes in FVIIa (9.6 U/l at baseline), FVIIam (142% at baseline) and F1 + 2 (0.13 nmol/l at baseline). FVIIc decreased from 141% at baseline to 114% 6 h postprandially (P < 0.001). As a high-fat meal does not seem to activate blood coagulation FVII in minipigs, the pig is apparently not a relevant model for the study of dietary FVII activation and thrombin generation.

An olive oil-rich diet results in higher concentrations of LDL cholesterol and a higher number of LDL subfraction particles than rapeseed oil and sunflower oil diets.

We investigated the effect of olive oil, rapeseed oil, and sunflower oil on blood lipids and lipoproteins including number and lipid composition of lipoprotein subclasses. Eighteen young, healthy men participated in a double-blinded randomized cross-over study (3-week intervention period) with 50 g of oil per 10 MJ incorporated into a constant diet. Plasma cholesterol, triacylglycerol, apolipoprotein B, and very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) cholesterol concentrations were 10;-20% higher after consumption of the olive oil diet compared with the rapeseed oil and sunflower oil diets [analysis of variance (ANOVA), P < 0.05]. The size of IDL, VLDL, and LDL subfractions did not differ between the diets, whereas a significantly higher number (apolipoprotein B concentration) and lipid content of the larger and medium-sized LDL subfractions were observed after the olive oil diet compared with the rapeseed oil and sunflower oil diets (ANOVA, P < 0.05). Total HDL cholesterol concentration did not differ significantly, but HDL(2a) cholesterol was higher after olive oil and rapeseed oil compared with sunflower oil (ANOVA, P < 0.05).In conclusion, rapeseed oil and sunflower oil had more favorable effects on blood lipids and plasma apolipoproteins as well as on the number and lipid content of LDL subfractions compared with olive oil. Some of the differences may be attributed to differences in the squalene and phytosterol contents of the oils.

Dietary factor VII activation does not increase plasma concentrations of prothrombin fragment 1+2 in patients with stable angina pectoris and coronary atherosclerosis.

Studies in healthy subjects showed that blood coagulation factor VII (FVII) is activated postprandially after consumption of high-fat meals, but accompanying thrombin formation has not been demonstrated. In patients with coronary atherosclerosis, the arterial intima is supposed to present more tissue factor, the cofactor of FVII, to circulating blood; therefore, thrombin formation in response to FVII activation is more likely to occur in such patients. This hypothesis was tested in a randomized crossover study of 30 patients (aged 43 to 70 years) with stable angina pectoris and angiographically verified coronary atherosclerosis. They were served a low-fat (5% of energy from fat) breakfast and lunch and a high-fat (40% of energy from fat) breakfast and lunch on 2 different days. Venous blood samples were collected at 8:15 AM (fasting), 12:30 PM, 2:00 PM, 3:30 PM, and 4:45 PM and analyzed for triglycerides, activated FVII (FVIIa), FVII protein concentration (FVII:Ag), prothrombin fragment 1+2 (F1+2), and soluble fibrin. Triglyceride levels increased from fasting levels on both diets, but they increased most markedly on the high-fat diet. FVIIa and FVIIa/FVII:Ag increased with the high-fat diet and decreased with the low-fat diet. For both diets, FVII:Ag and F1+2 decreased slightly. No postprandial changes were observed for soluble fibrin. Postprandial mean values of triglycerides, FVIIa, FVII:Ag, and FVIIa/FVII:Ag were significantly higher for the high-fat diet than for the low-fat diet. Our findings confirm that high-fat meals cause immediate activation of FVII. The clinical implication is debatable because FVII activation was not accompanied by an increase in plasma F1+2 concentrations in patients with severe atherosclerosis. However, a local thrombin generation on the plaque surface cannot be excluded.

[A quantitative assessment of the impact of diet on the mortality of heart disease in Denmark. Estimation of etiologic fraction]. / En kvantitativ vurdering af kostens betydning for dødeligheden af hjertesygdomme i Danmark. Beregning af aetiologisk fraktion.

INTRODUCTION: The aim of the present study was to quantify the impact of different dietary factors on the mortality from ischaemic heart disease in Denmark. METHODS: Relative risks and knowledge on the distribution of different dietary factors were used to estimate etiological fractions. RESULTS: It is estimated that an intake of fruit and vegetables and saturated fat as recommended would prevent 12 and 22%, respectively, of deaths from ischaemic heart disease in Denmark. An intake of fish among those at high risk for ischaemic heart disease, would lead to a 26% lower mortality, while alcohol intake among abstainers would have no significant quantitative effect. DISCUSSION: These results suggest that changes in dietary habits according to current recommendations would have an impact on public health in Denmark.