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.

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.

Calcium from salmon and cod bone is well absorbed in young healthy men: a double-blinded randomised crossover design.

BACKGROUND: Calcium (Ca) - fortified foods are likely to play an important role in helping the consumer achieve an adequate Ca intake, especially for persons with a low intake of dairy products. Fish bones have a high Ca content, and huge quantities of this raw material are available as a by-product from the fish industry. Previously, emphasis has been on producing high quality products from fish by-products by use of bacterial proteases. However, documentation of the nutritional value of the enzymatically rinsed Ca-rich bone fraction remains unexplored. The objective of the present study was to assess the bioavailability of calcium in bones of Atlantic salmon (oily fish) and Atlantic cod (lean fish) in a double-blinded randomised crossover design. METHODS: Ca absorption was measured in 10 healthy young men using 47Ca whole body counting after ingestion of a test meal extrinsically labelled with the 47Ca isotope. The three test meals contained 800 mg of Ca from three different calcium sources: cod bones, salmon bones and control (CaCO3). RESULTS: Mean Ca absorption (+/- SEE) from the three different Ca sources were 21.9 +/- 1.7%, 22.5 +/- 1.7% and 27.4 +/- 1.8% for cod bones, salmon bones, and control (CaCO3), respectively. CONCLUSION: We conclude that bones from Atlantic salmon and Atlantic cod are suitable as natural Ca sources in e.g. functional foods or as supplements.

Vitamin D requirement and setting recommendation levels - current Nordic view.

At the latitude of the Nordic countries, where there is almost no dermal formation of vitamin D during winter, dietary intake is required to avoid deficiency. Dietary intake is of the order of 4-5 microg/day but varies widely. The lowest intake is seen among adolescents. Low levels of serum 25(OH)D have been found in population groups in all Nordic countries. The drop in 25(OH)D during the winter months may be considerable, falling below acceptable levels (50 nmol/L) in one half of the population. To ensure an acceptable vitamin D status is maintained in the population and to diminish the seasonal drop in 25(OH)D, the Nordic Nutrition Recommendations 2004 increased the vitamin D recommendation for the age group 2-60 years by 50% from 5 microg/day to 7.5 microg/day. To attain such an intake at the population level, public health actions, including information dissemination and increased fortification of foods, are necessary.

Dietary patterns, food groups and myocardial infarction: a case-control study.

Certain dietary patterns may be related to the risk of CVD. We hypothesised that a plant-centred dietary pattern would be associated with a reduced risk of first myocardial infarction (MI). A case-control study of Norwegian men and postmenopausal women (age 45-75 years) was performed. A FFQ was administered, generally within 3 d after incident MI (n 106 cases). Controls (n 105) were frequency matched on sex, age and geographic location. On the FFQ, 190 items were categorised into thirty-five food groups and an a priori healthy diet pattern score was created. We estimated OR using logistic regression with adjustment for energy intake, family history of heart disease, marital status, current smoking, education and age. Among food groups, the risk of MI was significantly higher per SD of butter and margarine (OR 1.66 (95 % CI 1.12, 2.46)), and lower per SD of tomatoes (OR 0.53 (95 % CI 0.35, 0.79)), high-fat fish (OR 0.57 (95 % CI 0.38, 0.86)), wine (OR 0.58 (95 % CI 0.41, 0.83)), salad (OR 0.59 (95 % CI 0.40, 0.87)), whole grain breakfast cereals (OR 0.64 (95 % CI 0.45, 0.90)), cruciferous vegetables (OR 0.66 (95 % CI 0.47, 0.93)) and non-hydrogenated vegetable oil (OR 0.68 (95 % CI 0.49, 0.95)). An abundance of cases were found to have a low a priori healthy diet pattern score. A dietary pattern emphasising nutrient-rich plant foods and high-fat fish and low in trans fatty acids was associated with decreased risk of MI among Norwegians.

Palm oil versus hydrogenated soybean oil: effects on serum lipids and plasma haemostatic variables.

The purpose of this study was to test if replacement of trans fatty acids by palmitic acid in an experimental margarine results in unfavourable effects on serum lipids and haemostatic factors. We have compared the effects of three different margarines, one based on palm oil (PALM-margarine), one based on partially hydrogenated soybean oil (TRANS- margarine) and one with a high content of polyunsaturated fatty acids (PUFA-margarine), on serum lipids in 27 young women. In nine of the participants fasting levels and diurnal postprandial levels of haemostatic variables on the 3 diets were compared. The sum of 12:0, 14:0, 16:0 provided 11% of energy (E%) in the PALM diet, the same as the sum of 12:0, 14:0, 16:0 and trans fatty acids in the TRANS-diet. Oleic acid provided 10-11E% in all three diets, while PUFA provided 5.7, 5.5 and 10.2 E%, respectively. Total fat provided 30-31% and the test margarines 26% of total energy in all three diets. Each of the diets was consumed for 17 days in a crossover design. There were no significant differences in total cholesterol, LDL-cholesterol and apoB between the TRANS- and the PALM-diet. HDL-cholesterol and apoA-I were significantly higher on the PALM-diet compared to the TRANS-diet while the ratio of LDL- to HDL-cholesterol was lower, although not significantly (P = 0.077) on the PALM-diet. Total cholesterol, LDL-cholesterol and apoB were significantly lower on the PUFA-diet compared to the two other diets. HDL-cholesterol was not different on the PALM- and the PUFA-diet while it was significantly lower on the TRANS-diet compared to the PUFA-diet. Triglycerides and Lp(a) were not different among the three diets. The diurnal postprandial state level of tissue plasminogen activator (t-PA) activity was significantly decreased on the TRANS-diet compared to the PALM-diet. t-PA activity was also decreased on the PUFA-diet compared to PALM-diet although not significantly (P=0.07). There were no significant differences in neither fasting levels or in circadian variation of t-PA antigen, PAI-1 activity, PAI-1 antigen, factor VII coagulant activity or fibrinogen between the three diets. Our results suggest that dietary palm oil may have a more favourable effect on the fibrinolytic system compared to partially hydrogenated soybean oil. We conclude that from a nutritional point of view, palmitic acid from palm oil may be a reasonable alternative to trans fatty acids from partially hydrogenated soybean oil in margarine if the aim is to avoid trans fatty acids. A palm oil based margarine is, however, less favourable than one based on a more polyunsaturated vegetable oil.

[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.

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.

A diet rich in coconut oil reduces diurnal postprandial variations in circulating tissue plasminogen activator antigen and fasting lipoprotein (a) compared with a diet rich in unsaturated fat in women.

The effects of high and low fat diets with identical polyunsaturated/saturated fatty acid (P/S) ratios on plasma postprandial levels of some hemostatic variables and on fasting lipoprotein (a) [Lp(a)] are not known. This controlled crossover study compared the effects of a high fat diet [38.4% of energy (E%) from fat; HSAFA-diet, P/S ratio 0.14], a low fat diet (19.7 E% from fat; LSAFA-diet, P/S ratio 0.17), both based on coconut oil, and a diet with a high content of monounsaturated fatty acids (MUFA) and PUFA (38.2 E% from fat; HUFA-diet, P/S ratio 1.9) on diurnal postprandial levels of some hemostatic variables (n = 11) and fasting levels of Lp(a) (n = 25). The postprandial plasma concentration of tissue plasminogen activator antigen (t-PA antigen) was decreased when the women consumed the HSAFA-diet compared with the HUFA-diet (P = 0.02). Plasma t-PA antigen was correlated with plasminogen activator inhibitor type 1 (PAI-1) activity when the participants consumed all three diets (Rs = 0.78, P < 0.01; Rs = 0.76, P < 0.01; Rs = 0.66, P = 0.03; on the HSAFA-, the LSAFA- and the HUFA-diet, respectively), although the diets did not affect the PAI-1 levels. There were no significant differences in postprandial variations in t-PA activity, factor VII coagulant activity or fibrinogen levels due to the diets. Serum fasting Lp(a) levels were lower when women consumed the HSAFA-diet (13%, P < 0.001) and tended to be lower when they consumed the LSAFA-diet (5.3%, P = 0.052) than when they consumed the HUFA-diet. Serum Lp(a) concentrations did not differ when the women consumed the HSAFA- and LSAFA-diets. In conclusion, our results indicate that a coconut oil-based diet (HSAFA-diet) lowers postprandial t-PA antigen concentration, and this may favorably affect the fibrinolytic system and the Lp(a) concentration compared with the HUFA-diet. The proportions of dietary saturated fatty acids more than the percentage of saturated fat energy seem to have a beneficial influence on Lp(a) levels.

Effects of dietary fat quantity and composition on fasting and postprandial levels of coagulation factor VII and serum choline-containing phospholipids.

Dietary fat influences plasma levels of coagulation factor VII (FVII) and serum phospholipids (PL). It is, however, unknown if the fat-mediated changes in FVII are linked to PL. The present study aimed to investigate the effects of dietary fat on fasting and postprandial levels of activated FVII (FVIIa), FVII coagulant activity (FVIIc), FVII protein (FVIIag) and choline-containing PL (PC). In a randomized single-blinded crossover-designed study a high-fat diet (HSAFA), a low-fat diet (LSAFA), both rich in saturated fatty acids, and a high-fat diet rich in unsaturated fatty acids (HUFA) were consumed for 3 weeks. Twenty-five healthy females, in which postprandial responses were studied in a subset of twelve, were included. The HSAFA diet resulted in higher levels of fasting FVIIa and PC compared with the LSAFA and the HUFA diets (all comparisons P< or =0.01). The fasting PC levels after the LSAFA diet were also higher than after the HUFA diet (P<0.001). Postprandial levels of FVIIa and PC were highest on the HSAFA diet and different from LSAFA and HUFA (all comparisons P< or =0.05). Postprandial FVIIa was higher on the HUFA compared with the LSAFA diet (P<0.03), whereas the HUFA diet resulted in lower postprandial levels of PC than the LSAFA diet (P<0.001). Significant correlations between fasting levels of PC and FVIIc were found on all diets, whereas FVIIag was correlated to PC on the HSAFA and HUFA diet. The present results indicate that dietary fat, both quality and quantity, influences fasting and postprandial levels of FVIIa and PC. Although significant associations between fasting FVII and PC levels were found, our results do not support the assumption that postprandial FVII activation is linked to serum PC.

Supplementation with fish oil affects the association between very long-chain n-3 polyunsaturated fatty acids in serum non-esterified fatty acids and soluble vascular cell adhesion molecule-1.

We have investigated the effect of fish oil supplementation on the association between serum non-esterified fatty acid (NEFA) pattern and atherosclerotic activity. We studied correlations between serum non-esterified very long-chain eicosapentaenoic (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) and biochemical markers of endothelial activation before and after 18-months intervention with fish oil supplementation. The fish oil supplementation consisted of 2.4 g of EPA and DHA per day, with corn oil as placebo. Elderly men ( n =171) with high risk for coronary heart disease were divided into four intervention groups in a factorial design: fish oil supplementation ( n =44), dietary intervention ( n =42), fish oil supplementation+dietary intervention ( n =47) or placebo ( n =38). The composition of fasting NEFA was analysed before and after intervention by GLC. Circulating endothelial markers were analysed by ELISA. A statistically significant positive correlation between the change in serum non-esterified DHA and soluble vascular cell adhesion molecule-1 (sVCAM-1) was found in the pooled group that received fish oil supplementation ( n =91; Spearman's correlation coefficient r =0.24, P =0.02). No such correlation was found in the pooled group without fish oil supplementation ( n =80). Furthermore, there was a significant negative correlation between the change in serum non-esterified EPA and the relative change in sVCAM-1 in the group that did not receive fish oil supplementation ( r =-0.34, P =0.002). No such correlation was found in the group with fish oil supplementation. We conclude that large increase in serum non-esterified EPA and DHA, which can only be attained by supplementation, might increase inflammation in vascular endothelium. A moderate dietary increase in fish oil intake may, however, have an effect on decreasing inflammatory markers.

The serum LDL/HDL cholesterol ratio is influenced more favorably by exchanging saturated with unsaturated fat than by reducing saturated fat in the diet of women.

We compared the effects of a high fat diet [38.4% of energy (E%) from fat; HSAFA diet, polyunsaturated/saturated fatty acid (P/S) ratio = 0.14], a low fat diet (19.7 E% from fat; LSAFA diet, P/S = 0.17), both based on coconut oil, and a diet with a high content of mono- and polyunsaturated fatty acids (PUFA; 38.2 E% from fat; HUFA diet, P/S = 1.9) on serum lipoproteins. The 25 women studied consumed each diet for 3-wk periods in a crossover design. The two high fat diets were identical except for the quality of the test fat. The LSAFA diet was identical to the HSAFA diet except that half the fat was replaced by carbohydrates. Serum total cholesterol, LDL cholesterol and apoB concentrations did not differ between the HSAFA and the LSAFA diet periods. Total cholesterol, LDL cholesterol and apoB were lower when women consumed the HUFA diet than when they consumed the other two diets. HDL cholesterol and apoA-I were 15 and 11%, respectively, higher when women consumed the HSAFA diet than when they consumed the LSAFA diet; HDL cholesterol and apoA-I were lower when women consumed the HUFA diet than when they consumed the HSAFA diet, but not the LSAFA diet. The LDL cholesterol/HDL cholesterol and apoB/apoA-I ratios were higher when women consumed the LSAFA diet than when they consumed the HSAFA diet. The LDL/HDL cholesterol ratio was higher when women consumed either the LSAFA or the HSAFA diet than when they consumed the HUFA diet, whereas apoB/apoA-I was higher when women consumed the LSAFA diet than when they consumed the HUFA diet. Triacylglycerol and VLDL cholesterol were higher when women consumed the LSAFA diet than when they consumed either the HSAFA or the HUFA diet. We conclude that, to influence the LDL/HDL cholesterol ratio, changing the proportions of dietary fatty acids may be more important than restricting the percentage of total or saturated fat energy, at least when derived mainly from lauric and myristic acids, both of which increase HDL cholesterol.

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.