Effects of margarine enriched with plant sterol esters from rapeseed and tall oils on markers of endothelial function, inflammation and hemostasis.

BACKGROUND AND AIMS: The sterol profile of rapeseed oil differs from that of tall oil with higher contents of campesterol and brassicasterol. We previously found that margarines providing 2 g/day of sterols from rapeseed or tall oil resulted in similar reductions in LDL cholesterol of 8-9%. The aim of the present study was to investigate whether the consumption of these margarines affected markers of endothelial function, inflammation and hemostasis. METHODS: Blood samples were collected from 58 hypercholesterolemic volunteers who completed a double-blinded, randomized, crossover trial. Subjects consumed each of the two sterol margarines and a control non-sterol margarine for 4 weeks separated by one-week washout periods. All the margarines had the same fatty acid composition. Concentrations of vascular cell adhesion molecule-l (VCAM-1), E-selection, circulating tumor necrosis factor α (TNFα) and plasminogen activator inhibitor-1 (total, tPAI-1; active, PAI-1) were quantified. RESULTS: Rapeseed-sterol margarine reduced E-selection concentrations compared to the control margarine (p = 0.012) while tall-sterol margarine had no effect. The rapeseed-sterol margarine also reduced tPAI-1 (p = 0.008) compared to the tall-sterol margarine. No significant changes were observed in TNFα and VCAM-1. No association was found between LDL reduction and changes in E-selection and tPAI-1. CONCLUSION: Rapeseed-sterol margarine demonstrated favorable effects on vascular risk markers.

Intake of trans fatty acids from partially hydrogenated vegetable and fish oils and ruminant fat in relation to cancer risk.

Intake of trans fatty acids (TFA) may influence systemic inflammation, insulin resistance and adiposity, but whether TFA intake influences cancer risk is insufficiently studied. We examined the association between TFA intake from partially hydrogenated vegetable oils (PHVO-TFA), partially hydrogenated fish oils (PHFO-TFA), and ruminant fat (rTFA) and cancer risk in the Norwegian counties study, a large cohort study with a participation rate >80%. TFA intake was assessed three times in 1974-1988 by questionnaire. A total of 77,568 men and women were followed up through 2007, during which time 12,004 cancer cases occurred. Hazard ratios (HRs) and confidence intervals (CIs) were estimated with Cox regression for cancer sites with ≥150 cases during follow-up. Significantly increased or decreased risks were found when comparing the highest and lowest intake categories (HRs, 95% CIs) for PHVO-TFA and pancreatic cancer in men (0.52, 0.31-0.87) and non-Hodgkin lymphoma (NHL) in both genders (0.70, 0.50-0.98); PHFO-TFA and rectal cancer (1.43, 1.09-1.88), prostate cancer (0.82, 0.69-0.96), and multiple myeloma (2.02, 1.24-3.28); and rTFA and all cancers (1.09, 1.02-1.16), cancer of the mouth/pharynx (1.59, 1.08-2.35), NHL (1.47, 1.06-2.04) and multiple myeloma (0.45, 0.24-0.84). Furthermore, positive trends were found for PHFO-TFA and stomach cancer (p(trend) = 0.01) and rTFA and postmenopausal breast cancer (p(trend) = 0.03). Inverse trends were found for PHVO-TFA and all cancers (p(trend) = 0.006) and cancer of the central nervous system in women (p(trend) = 0.005). PHFO-TFA, but not PHVO-TFA, seemed to increase cancer risk. The increased risks observed for rTFA may be linked to saturated fat.

A prospective study of intake of trans-fatty acids from ruminant fat, partially hydrogenated vegetable oils, and marine oils and mortality from CVD.

Trans-fatty acids (TFA) have adverse effects on blood lipids, but whether TFA from different sources are associated with risk of CVD remains unresolved. The objective of the present study was to evaluate the association between TFA intake from partially hydrogenated vegetable oils (PHVO), partially hydrogenated fish oils (PHFO) and ruminant fat (rTFA) and risks of death of CVD, CHD, cerebrovascular diseases and sudden death in the Norwegian Counties Study, a population-based cohort study. Between 1974 and 1988, participants were examined for up to three times. Fat intake was assessed with a semi-quantitative FFQ. A total of 71,464 men and women were followed up through 2007. Hazard ratios (HR) and 95 % CI were estimated with Cox regression. Energy from TFA was compared to energy from all other sources, carbohydrates or unsaturated cis-fatty acids with different multivariable models. During follow-up, 3870 subjects died of CVD, 2383 of CHD, 732 of cerebrovascular diseases and 243 of sudden death. Significant risks, comparing highest to lowest intake category, were found for: TFA from PHVO and CHD (HR 1.23 (95 % CI 1.00, 1.50)) and cerebrovascular diseases (HR 0.65 (95 % CI 0.45, 0.94)); TFA from PHFO and CVD (HR 1.14 (95 % CI 1.03, 1.26)) and cerebrovascular diseases (HR 1.32 (95 % CI 1.04, 1.69)); and rTFA intake and CVD (HR 1.30 (95 % CI 1.05, 1.61)), CHD (HR 1.50 (95 % CI 1.11, 2.03)) and sudden death (HR 2.73 (95 % CI 1.19, 6.25)) in women. These associations with rTFA intake were not significant in men (P interaction ≥ 0.01). The present study supports that TFA intake, irrespective of source, increases CVD risk. Whether TFA from PHVO decreases risk of cerebrovascular diseases warrants further investigation.

[Model for estimation of cardiovascular risk in Norway]. / Modell for estimering av kardiovaskulaer risiko i Norge.

BACKGROUND: Guidelines for prevention of cardiovascular disease (CVD) include calculation of total risk. A new risk model based on updated Norwegian data is needed, as the European SCORE function overestimates the risk of fatal CVD in Norway. NORRISK for 10-year CVD mortality is presented. It includes gender, age and smoking and levels of systolic blood pressure and serumtotal cholesterol. MATERIAL AND METHODS: NORRISK is based on national age- and sex specific mortality rates from Statistics Norway (1999-2003), mean levels of risk factors from Norwegian Health Surveys (2000-03) and relative risks from mortality follow-up of Norwegian Cardiovascular Screenings (1985-2002). The model is adjusted to the mortality level in the period 1999-2003 and is compared with the SCORE model. RESULTS: 10-year risk estimates calculated from NORRISK fall between SCORE high- and low-risk estimates and increase strongly with age. Very few persons below 50 years of age have a 10-year risk above 5% (European limit for high risk). More than half of men aged 60 years have estimated risks above this limit, while only 7% of 60-year-old women exceed the limit. Even if the risk limit is reduced to 1% for younger age groups, very few women below 50 years of age have risks above the limit. INTERPRETATION: NORRISK is more adapted to the current situation in Norway than the SCORE model and may be a useful and relevant tool in Norwegian clinical practice.

Impaired lipid accumulation by trans10, cis12 CLA during adipocyte differentiation is dependent on timing and length of treatment.

Conjugated linoleic acids (CLAs) are a group of polyunsaturated fatty acids found in ruminant products, where the predominant isomers are cis9, trans11 (c9,t11) and trans10, cis12 (t10,c12) CLA. We have previously shown that t10,c12 CLA prevents lipid accumulation in mature adipocytes in part by acting as a peroxisome proliferator-activated receptor gamma (PPAR gamma) modulator. The objective of this study was to further establish the molecular mechanisms underlying the attenuating effect on lipid accumulation by t10,c12 CLA, with focus on time point and duration of treatment during adipogenesis. We have shown that t10,c12 CLA treatment has its most attenuating effect early (day (D) 0-6) during differentiation. Treatment during this period is sufficient to prevent lipid accumulation in mature adipocytes. The adipogenic marker genes PPAR gamma and CCAAT/enhancer binding protein alpha (C/EBP alpha) are both down-regulated after treatment within the period from D0-6, while additional treatment also down-regulates the expression of sterol regulatory element binding protein-1c (SREBP-1c), liver X receptor alpha (LXR alpha), fatty acid binding protein (aP2), fatty acid translocase (CD36) and insulin-sensitive glucose transporter 4 (GLUT4). These effects of t10,c12 CLA reflect the subsequent attenuation of lipid accumulation observed in mature adipocytes. Interestingly, the early B-cell factor (O/E-1), which is known to promote adipogenesis and to be involved in control of genes important for terminal adipocyte differentiation, is unaffected by treatment of t10,c12 CLA. Taken together, our data indicate that inhibition of lipid accumulation induced by t10,c12 CLA treatment during adipocyte differentiation is associated with a tight regulatory cross-talk between early (PPAR gamma and C/EBP alpha) and late (LXR alpha, aP2 and CD36) adipogenic marker genes.

Effects of structural changes of fatty acids on lipid accumulation in adipocytes and primary hepatocytes.

Conjugated linoleic acids (CLAs), tetradecylthioacetic acid (TTA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are all shown to differently affect lipid homeostasis. Additionally, previous studies have shown that introducing a methyl group in the molecule potentiates the hypolipidemic effect of EPA. The objective of this study was to determine how cis9,trans11 CLA, trans10,cis12 CLA, TTA, EPA and DHA affect lipid accumulation in 3T3-L1 adipocytes and in cultured primary rat hepatocytes, and to what extent changes in cis/trans configuration or introducing a methyl group in the molecules influence their way of affecting lipid accumulation in these cells. Our results show that trans10,cis12 CLA is highly specific in preventing lipid accumulation in adipocytes, and that small structural changes in the molecule (changing to trans/trans or introducing an alpha-methyl group) totally abolish this effect and up-regulate the expression levels of adipogenic marker genes towards control levels. Furthermore, all the fatty acids increased hepatic lipid accumulation, whereas the lipid content was normalized after adding an alpha-methyl group into the molecules. Taken together, our data demonstrate that the various fatty acids are highly specialized molecules, and that small structural changes markedly alter their way of affecting lipid accumulation in adipocytes and hepatocytes.

[Trans fatty acids in the Norwegian diet]. / Transfettsyrer i norsk kosthold.

BACKGROUND: Intake of trans fatty acids and saturated fatty acids should be limited, as high intakes may increase the risk of coronary heart disease. There is no up-to-date information on intake of trans fatty acids in the Norwegian population. MATERIAL AND METHODS: Information on trans fatty acid content in foods in 2003 from a survey among Norwegian food manufacturers and importers, together with data from the Norwegian Food Composition data base, is used to estimate the content of trans fatty acids in food groups. Intake of trans fatty acids is calculated on the basis of food intake reported in a national dietary survey among adults in 1997. RESULTS: Mean intake of trans fatty acids was 1.6 gram/person/day, corresponding to 0.6 percent of total energy intake. Trans fatty acids contributed with less than 1% of energy intake among 97 percent of the participants; differences in intake related to gender, age and length of education were small. Main contributors of trans fatty acids were dairy products 50%, meat products 18%, buns and cakes 8% and bread products 7%. Food groups containing partially hydrogenated fats contributed totally approximately 30%. For several food groups the content has been reduced since 2003. INTERPRETATION: The calculated intake of trans fatty acids among Norwegians in 2003 was lower than earlier estimates based on household consumption surveys in 2001, and at the same level as reported for Mediterranean countries in the 1990s. Mean intake is now in accordance with the recommendation from World Health Organization: intake should be limited to less than 1 % total energy intake. Our calculations imply that intake of trans fatty acids no longer represents a public health concern in Norway.

Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial.

Randomized controlled trials have shown that a combination of vitamin D and calcium can prevent fragility fractures in the elderly. Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known. We studied if an intervention with 10 microg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double-blinded randomized controlled trial. Residents from 51 nursing homes were allocated randomly to receive 5 ml of ordinary cod liver oil (n = 569) or 5 ml of cod liver oil where vitamin D was removed (n = 575). During the study period of 2 years, fractures and deaths were registered, and the principal analysis was performed on the intention-to-treat basis. Biochemical markers were measured at baseline and after 1 year in a subsample. Forty-seven persons in the control group and 50 persons in the vitamin D group suffered a hip fracture. The corresponding figures for all nonvertebral fractures were 76 persons (control group) and 69 persons (vitamin D group). There was no difference in the incidence of hip fracture (p = 0.66, log-rank test), or in the incidence of all nonvertebral fractures (p = 0.60, log-rank test) in the vitamin D group compared with the control group. Compared with the control group, persons in the vitamin D group increased their serum 25-hydroxyvitamin D concentration with 22 nmol/liter (p = 0.001). In conclusion, we found that an intervention with 10 microg of vitamin D3 alone produced no fracture-preventing effect in a nursing home population of frail elderly people.

Serum non-esterified very long-chain PUFA are associated with markers of endothelial dysfunction.

The objective of this study was to investigate the pattern of serum non-esterified fatty acid (NEFA) fraction in association with atherosclerosis development. We have studied possible relationships between eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) in the NEFA fraction and biochemical markers of endothelial activation or dysfunction. The study population consisted of 152 elderly men with high risk for coronary heart disease. The composition of fasting serum NEFA was analysed by gas-liquid chromatography. Endothelial activation was evaluated using biochemical analyses of some markers of endothelial function. A significant inverse linear association was found between serum non-esterified EPA and DHA, and soluble vascular cell adhesion molecule-1 (sVCAM-1) (P=0.02 and 0.001, respectively). An inverse linear association was found between serum non-esterified AA and sVCAM-1 (P=0.001) and von Willebrand Factor (P=0.005). The significant inverse associations for DHA and AA were independent from the serum content of other NEFAs. Taken together, negative associations were found between sVCAM-1 and the serum levels of non-esterified DHA, EPA and AA. The inverse relation between the levels of sVCAM-1 and very long-chain n-3 fatty acids might indicate an anti-inflammatory effect of the latter.

The effects of long-term diet and omega-3 fatty acid supplementation on coagulation factor VII and serum phospholipids with special emphasis on the R353Q polymorphism of the FVII gene.

The aim of the present study was to investigate the effect of long-term diet and very long chain n-3 fatty acids (VLC n-3) intervention on plasma coagulation factor VII (FVII), choline-containing phospholipids (PC) and triglycerides (TG), especially related to the R353Q polymorphism of the FVII gene. The present investigation included 219 subjects from the Diet and Omega-3 Intervention Trial on atherosclerosis (DOIT), a 2x2 factorial designed study in elderly men with long-standing hypercholesterolemia. The subjects were randomly allocated to receive placebo capsules (corn oil) (control), placebo capsules and dietary advice ("Mediterranean type" diet), VLC n-3 capsules, or VLC n-3 capsules and dietary advice combined. The R353Q genotype and the levels of FVIIc, FVIIag, FVIIa, PC, and TG at baseline and after 6 months were determined. Diet intervention was followed by a significant reduction of 5.1% in the levels of FVIIag and 2.4 mU/ml in FVIIa (95% CI -7.4, -2.9, and -3.8, -1.1, respectively) (both p<0.001) compared to the no diet group, independent of genotype. No effects of diet intervention on FVIIc, PC or TG were observed. After VLC n-3 supplementation the TG levels were significantly reduced compared to placebo (p=0.01), whereas all FVII levels and PC remained unchanged. Dietary advice towards a "Mediterranean type" diet, but not VLC n-3 supplementation, was shown to reduce the levels of FVIIag and FVIIa after 6 months, independent of genotype. The results indicate the dietary advice to be more favourable in reducing this risk factor for CVD as compared to specific VLC n-3 supplementation.

Coagulation factor VII, R353Q polymorphism, and serum choline-containing phospholipids in males at high risk for coronary heart disease.

INTRODUCTION: Elevated levels of coagulation factor VII (FVII) have been associated with increased risk for myocardial infarction (MI). The R353Q polymorphism of the FVII gene has been shown to modify plasma levels of FVII, and has in some studies also been associated with reduced risk for MI. OBJECTIVES: To examine the R353Q polymorphism of the FVII gene and the relation to myocardial infarction (MI), cardiovascular disease (CVD), and diabetes, and furthermore, to elucidate the association between the polymorphism and plasma levels of FVII coagulant activity (FVIIc), FVII antigen (FVIIag), activated FVII (FVIIa), and serum choline-containing phospholipids (PC). METHODS: In 560 elderly men characterised as hypercholesterolemic in 1972, we examined the R353Q polymorphism by melting curve analysis after real-time PCR. In a subgroup of 205 individuals, FVIIc, FVIIag, FVIIa, and PC were analysed. RESULTS: There were no significant associations between genotype and the disease states, although we observed a lower number of MI cases among subjects with the Q allele, compared to the RR individuals (14% vs. 19%). FVIIag and FVIIc levels were lower in RQ compared to RR subjects, whereas for FVIIa the opposite was observed (p<0.001 for all). PC correlated positively with FVIIag (r=0.24, p<0.001), but negatively with FVIIa (r=-0.25, p<0.001). No genotype specific interactions were found for the association between FVII and PC. CONCLUSION: No significant associations between the R353Q polymorphism and MI, CVD, or diabetes were observed, although the polymorphism strongly influenced plasma levels of FVII. Serum PC correlated significantly with FVIIag and inversely with FVIIa, independently of genotype.

Vitamins A and E in serum in relation to weight and lung function in patients with advanced pulmonary disease.

The objective of the study was to examine whether serum concentrations of retinol (vitamin A) and alpha-, beta-, and gamma-tocopherols (vitamin E) are affected by underweight and weight gain. The analysis was carried out in underweight (n = 42, of whom 24 had chronic obstructive pulmonary disease) and normal-weight (n = 29, of whom 16 had chronic obstructive pulmonary disease) candidates for lung transplantation before and after dietary intervention for weight gain. In all the patients, serum concentrations of retinol at baseline and changes in retinol were positively associated with body mass index (unstandardized regression coefficient, b = 0.03; p = 0.05) and an increase in weight (b = 0.09, p = 0.02) after dietary intervention, respectively. At baseline, serum retinol concentrations were positively correlated with forced vital capacity (b = 0.24, p < 0.05) and forced expiratory volume in one second (b = 0.17, p < 0.05). In patients with chronic obstructive pulmonary disease (COPD), tocopherols were higher in the underweight patients than in the normal-weight ones, while it was an opposite tendency in patients with other lung diseases. Only in patients with lung diseases other than COPD was there found a positive association between tocopherols and lung gas diffusion. In patients with other diagnoses compared with patients with COPD, a positive change in serum tocopherol status after weight gain was suggested.

[Diet changes and the rise and fall of cardiovascular disease mortality in Norway]. / Kostendringer og dødelighetsutvikling av hjerte- og karsykdommer i Norge.

BACKGROUND: Cardiovascular disease mortality in Norway during the last 50 years has been analysed and related to changes in dietary habits and serum cholesterol in the population. MATERIAL AND METHODS: Mortality and dietary data have been collected from official statistics. Changes in serum cholesterol have been estimated from changes in intake of fatty acids based on published regression equations. Data on changes in serum cholesterol and blood pressure are from the former National Health Screening Service. RESULTS: Mortality from ischemic heart disease (IHD) peaked in 1966-70 when it was 100% higher than in 1951-55 for men and 50% higher for women. For age group 40-69 years mortality has been reduced by more than one half during the last 30 years. For the period 1996-2000 and for all age groups, 30,903 fewer deaths occurred than expected, had the mortality remained the same as during 1971-75, that is 6180 per year. Mortality from sudden death has followed the same pattern as for IHD. Cerebrovascular disease mortality has shown a declining tendency during the entire period. Since 1960 the proportion of total fat in the diet has been reduced from 41 to 34% of energy and the proportion of unsaturated to saturated plus trans fatty acids has increased. Cholesterol in the diet has been reduced by almost one half. Based on changes in consumption in milk fat, fat from meat and margarine, and taken into consideration the change from boiled to filtered coffee the estimated reduction in serum cholesterol in the population is in the order of 0.8 mmol/l. This corresponds closely to the observed 0.5 to 1 mmol/l. Most of the reduction is due to changes in milk fat and margarine consumption and composition. INTERPRETATION: Based on the established relation between serum cholesterol and risk of IHD we conclude that reduction in serum cholesterol may explain most of the decline in mortality since 1970. Other factors that may have contributed are reduced smoking (in men), a small reduction in blood pressure, increased consumption of fruit, vegetables, cod liver - and fish oil and better means of treatment.

[Vitamin and minerals supplements--required for good health?]. / Vitamin- og mineraltilskudd--nødvendig for god helse?

Both laymen and the learned are discussing the need for vitamin and minerals supplements and their eventual preventive and therapeutic potential. Documentation is needed, but this word is most of the time used without clarifying the criteria it is based on. In this article we use vitamin E in order to illustrate that there is generally a long way to go from initial hypothesis to eventual practical advice and recommendations. Promising cell and animal studies combined with epidemiological observation studies are not sufficient as evidence; randomised intervention studies are required before conclusions can be drawn. Because high intakes of vitamins and minerals can have negative health effects, we also present the work carried out to decide upper safe intake levels in the Nordic countries, the EU and the USA. Women of fertile age should under certain circumstance take iron and folate supplements, and everyone in Scandinavia should take a supplement with vitamin D. It is sensible and harmless to take a multivitamin and mineral pill for people in risk groups, e.g. people eating very little or have an unbalanced diet (children, old people, patients). Except for these groups it is poorly documented that vitamins and minerals in large doses have a preventive or therapeutic potential. The largest health potential lies in a healthy diet.

Metabolic effects of krill oil are essentially similar to those of fish oil but at lower dose of EPA and DHA, in healthy volunteers.

The purpose of the present study is to investigate the effects of krill oil and fish oil on serum lipids and markers of oxidative stress and inflammation and to evaluate if different molecular forms, triacylglycerol and phospholipids, of omega-3 polyunsaturated fatty acids (PUFAs) influence the plasma level of EPA and DHA differently. One hundred thirteen subjects with normal or slightly elevated total blood cholesterol and/or triglyceride levels were randomized into three groups and given either six capsules of krill oil (N = 36; 3.0 g/day, EPA + DHA = 543 mg) or three capsules of fish oil (N = 40; 1.8 g/day, EPA + DHA = 864 mg) daily for 7 weeks. A third group did not receive any supplementation and served as controls (N = 37). A significant increase in plasma EPA, DHA, and DPA was observed in the subjects supplemented with n-3 PUFAs as compared with the controls, but there were no significant differences in the changes in any of the n-3 PUFAs between the fish oil and the krill oil groups. No statistically significant differences in changes in any of the serum lipids or the markers of oxidative stress and inflammation between the study groups were observed. Krill oil and fish oil thus represent comparable dietary sources of n-3 PUFAs, even if the EPA + DHA dose in the krill oil was 62.8% of that in the fish oil.