Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study.

OBJECTIVE: Little is known about the transfer of essential fatty acids (FAs) across the human blood-brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF). METHODS: A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation. RESULTS: At 6 months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P < 0.01), whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and n-3 docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers. CONCLUSIONS: Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults.

Serum fatty-acid composition and the risk of Alzheimer's disease: a longitudinal population-based study.

BACKGROUND/OBJECTIVES: It is unknown if a specific fatty-acid composition influences the development of Alzheimer's disease (AD). Nutrition is a possible target for prevention of dementia and especially omega-3-based fatty acids (n-3 FAs) have previously been suggested to be beneficial for cognition. The objective was to ascertain whether serum FAs predicts the risk of incident AD and dementia in a longitudinal population-based cohort. SUBJECTS/METHODS: Uppsala Longitudinal Study of Adult Men started in 1970. The proportions of FAs in serum cholesteryl esters were estimated in men (n=2009) who were 50 years old at baseline. During a 35 year follow-up time, 213 men had developed dementia, out of which 91 AD. The associations were analyzed with Cox proportional hazards and logistic regression; adjusted for age, education and vascular risk factors. RESULTS: Subjects with a higher proportion of saturated FAs had a decreased risk of AD in crude and multi-adjusted models (hazard ratio for 1-s.d. increase in palmitic acid 0.72; 95% confidence intervals: 0.59-0.89). These associations persisted even in the group of approximately 85-year-old survivors. n-3 FAs FAs were not associated with decreased risk of AD or dementia. CONCLUSIONS: In contrast to experimental studies, saturated FAs were inversely associated with risk of AD. No evidence of a protective effect of n-3 FAs against dementia was found. The results remained essentially unchanged if competing risk from mortality was taken into account.

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.

Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome--LIPGENE: a European randomized dietary intervention study.

BACKGROUND: Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS. OBJECTIVE: This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS. DESIGN: A free-living, single-blinded dietary intervention study. SUBJECTS AND METHODS: MetS subjects (n = 417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined. RESULTS: In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P < 0.01), particularly in men. CONCLUSION: There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles.

Adipose tissue fatty acids and insulin sensitivity in elderly men.

AIMS/HYPOTHESIS: Dietary fatty acids may affect insulin sensitivity. Adipose tissue fatty acid composition partly reflects long-term dietary intake, but data from large studies regarding relationships with insulin sensitivity are lacking. We aimed to determine the association between adipose tissue fatty acids and insulin sensitivity in elderly Swedish men. METHODS: In a cross-sectional analysis of the community-based Uppsala Longitudinal Study of Adult Men (n = 795, mean age 71 years), adipose tissue biopsies were obtained and fatty acid composition was determined by gas-liquid chromatography. Insulin sensitivity was measured directly by a euglycaemic clamp. RESULTS: Palmitic acid (16:0), the major saturated fatty acid (SFA) in the diet and in adipose tissue, was negatively correlated with insulin sensitivity (r = -0.14), as were 16:1 n-7 (r = -0.15), 20:3 n-6 (r = -0.31), 20:4 n-6 (r = -0.38), 22:4 n-6 (r = -0.37) and 22:5 n-3 (r = -0.24; p < 0.001 for all). Some minor SFAs were positively correlated; 12:0 (r = 0.46), 14:0 (r = 0.32), 17:0 (r = 0.21) and 18:0 (r = 0.41; p < 0.001 for all), as were essential polyunsaturated fatty acids (PUFAs) 18:2 n-6 (r = 0.10, p < 0.01) and 18:3 n-3 (r = 0.16, p < 0.001). Docosahexaenoic acid (22:6 n-3) was negatively correlated (r = -0.11, p < 0.01), whereas eicosapentaenoic acid (20:5 n-3) was not (r = -0.02, NS). Most associations diminished or disappeared in lean individuals, indicating an effect of obesity. CONCLUSIONS/INTERPRETATION: Adipose tissue enriched with palmitic acid and depleted of essential PUFAs is associated with insulin resistance. The positive association between minor SFAs and insulin sensitivity merits further investigation.

Supplementation with trans10cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity.

AIMS/HYPOTHESIS: Hyperproinsulinaemia reflects both beta cell dysfunction and insulin resistance in cross-sectional studies, but it is not known whether changes in proinsulin concentrations are related to insulin resistance over time. As trans10cis12 (t10c12)-conjugated linoleic acid (CLA) supplementation induces insulin resistance in obese men, we used this fatty acid to investigate the effects on plasma proinsulin, insulin, C-peptide and adiponectin concentrations, including their associations with change in insulin sensitivity. METHODS: We randomised (double-blind) 57 non-diabetic abdominally obese men to receive either 3.4 g t10c12CLA, CLA-isomer mixture or control oil for 12 weeks. Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), intact proinsulin, insulin, the proinsulin : insulin ratio, C-peptide, glucose and adiponectin were assessed before and after supplementation. RESULTS: Supplementation with t10c12CLA increased proinsulin (p<0.01), the proinsulin : insulin ratio (p<0.05) and C-peptide concentrations (p<0.001) in comparison with control subjects. Adiponectin, however, did not change significantly. The change in proinsulin, but not the proinsulin : insulin ratio, was related to impaired insulin sensitivity (r= -0.58, p<0.0001), independently of changes in insulin, C-peptide, glucose, adiponectin and BMI. Conversely, the correlation between insulin sensitivity and specific insulin (r=-0.46, p<0.001) did not remain significant after adjustment for proinsulin. Induced hyperproinsulinaemia was also correlated to adiponectin concentrations ( r= -0.34, p<0.01). CONCLUSIONS/INTERPRETATION: In obese men, t10c12CLA induces hyperproinsulinaemia that is related to impaired insulin sensitivity, independently of changes in insulin concentrations. These results are of clinical interest, as hyperproinsulinaemia predicts diabetes and cardiovascular disease. The use of weight-loss supplements containing this fatty acid is worrying.

A programme of behaviour modification and nutrition counselling in the treatment of obesity: a randomised 2-y clinical trial.

OBJECTIVE: To compare two group treatment programmes for obese outpatients. Both programmes included behaviour modification, nutrition counselling, very-low-calorie diet (VLCD) and a continuous measuring of metabolic and anthropometrical status, but they differed regarding the treatment intensiveness. The main aim was to study whether intensive treatment gives a larger weight reduction compared with less intensive treatment and what level of input from health care personnel is needed to reach adequate treatment results. DESIGN: A 2-y randomised clinical trial. SUBJECTS: A total of 43 obese subjects aged 24-60 y, BMI 35 kg/m(2) (29-48). INTERVENTION: Two programmes were used. Both were based on group therapy and were supervised by a dietitian and a psychologist. Group 1 received a continuous intensive treatment with planned group meetings every fortnight during the first year and six group meetings the second year. Group 2 had planned group meetings every third month. Anthropometrical and metabolic data were measured every third month in both groups. The VLCD periods were the same. RESULTS: There was no evidence that a more intensive treatment promotes a larger weight reduction. Weight reduction after 1 y: group 1, -7.6 (+/-0.97) kg, BMI -2.6 (+/-0.3) kg/m(2); group 2, -6.4 (+/-1.16) kg, BMI -2.2 (+/-0.4) kg/m(2). Weight reduction after 2 y: group 1, -6.8 (+/-1.4) kg, BMI -2.4 (+/-0.3) kg/m(2); group 2, -8.6 (+/-1.6) kg, BMI -3.0 (+/-0.3) kg/m(2). The dropout rate was 26%. CONCLUSION: There were no significant differences in weight reduction, compliance or dropout rate between the groups and there was no evidence that a more intensive treatment promotes a larger weight reduction. This observation is of value when setting up treatment programmes. To measure the metabolic and anthropometrical status during the treatment and to give continuous feedback to the subjects seem to be important factors for compliance. Both treatment programmes gave highly significant weight reductions in the range of 5-10%, which has been referred to as a realistic goal for the treatment of obese patients.

Oxidative stress and antioxidant status in type 1 diabetes mellitus.

OBJECTIVES: To test the hypothesis that type 1 diabetes is associated with increased oxidative stress and/or antioxidant status by investigating concentrations of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) in urine and plasma and malondialdehyde (MDA) in plasma as indicators of lipid peroxidation in vivo, and antioxidant status in diabetic subjects compared with healthy control subjects. DESIGN AND SUBJECTS: Thirty-eight subjects with type 1 diabetes mellitus and 41 healthy age- and sex-matched control subjects were included in the study. Blood and urine samples were obtained and analysed for 8-iso-PGF2alpha with a newly developed radioimmunoassay, as well as for MDA, total antioxidant capacity (TAOC) and serum tocopherol levels. RESULTS: None of the variables of lipid peroxidation showed any significant difference between the two groups. Similarly, there were no significant correlations between the levels of 8-iso-PGF2alpha or MDA, and degree of glycemic control (HbA1c). Total antioxidant capacity in plasma was 16% lower amongst the subjects with type 1 diabetes than in the control group (P < 0.0005). Lipid corrected levels of alpha-tocopherol in serum were significantly increased in type 1 diabetic subjects (P < 0.05), as were gamma-tocopherol levels (P < 0.005). CONCLUSIONS: In spite of lower total antioxidant defence, our results do not support the oxidative stress hypothesis for type 1 diabetes mellitus. The higher tocopherol levels suggest that no vitamin E supplementation is necessary for subjects with type 1 diabetes mellitus.

Plasminogen activator inhibitor-1 and relations to fatty acid composition in the diet and in serum cholesterol esters.

High plasminogen activator inhibitor (PAI)-1 levels and poor dietary fat quality are potential risk factors for cardiovascular disease. The aim was to investigate the cross-sectional associations between PAI-1 activity and dietary nutrient intake, focusing on fat quality, in a population-based study of 871 men aged 70 years. The relationship between PAI-1 and the fatty acid composition in serum cholesterol esters (n=381 men) was also studied. The estimated total fat intake was positively associated with PAI-1 activity. The intake of both monounsaturated and polyunsaturated fatty acids was positively associated with PAI-1 activity, whereas the intake of saturated fatty acids was not. In serum cholesterol esters, higher proportions of palmitoleic and dihomo-gamma-linolenic acid, a lower proportion of linoleic acid, and reduced estimated Delta5-desaturase activity were associated with higher PAI-1 levels. These associations were confounded by factors representing the insulin resistance syndrome. PAI-1 activity was positively associated with gamma-linolenic and arachidonic acid, independent of potential confounders. In conclusion, this study demonstrates that dietary intake of unsaturated fatty acids is positively associated with PAI-1 activity, whereas intake of saturated fatty acids is not. The associations present between PAI-1 activity and the fatty acid proportions in serum cholesterol esters are partly influenced by metabolic syndrome-related factors.

Conjugated linoleic acid supplementation in humans--metabolic effects.

Supplementation with conjugated linoleic acid (CLA) induces a number of physiological effects in experimental animals, including reduced body fat content, decreased aortic lipid deposition, and improved serum lipid profile. Controlled trials on the effects of CLA in humans have hitherto been scarce. The aim of this study was to evaluate the effects of supplementation with CLA in healthy humans on anthropometric and metabolic variables and on the fatty acid composition of serum lipids and thrombocytes. Fifty-three healthy men and women, aged 23-63 yr, were randomly assigned to supplementation with CLA (4.2 g/d) or the same amount of olive oil during 12 wk in a double-blind fashion. The proportion of body fat decreased (-3.8%, P< 0.001) in the CLA-treated group, with a significant difference from the control group (P = 0.050). Body weight, body mass index, and sagittal abdominal diameter were unchanged. There were no major differences between the groups in serum lipoproteins, nonesterified fatty acids, plasma insulin, blood glucose, or plasminogen activator inhibitor 1 (PAI-1). In the CLA group the proportions of stearic, docosatetraenoic, and docosapentaenoic acids increased in serum lipids and thrombocytes, while proportions of palmitic, oleic, and dihomo-gamma-linolenic acids decreased, causing a decrease of the estimated delta-6 and delta-9 and an increase in the delta-5 desaturase activities. These results suggest that supplementation with CLA may reduce the proportion of body fat in humans and that CLA affects fatty acid metabolism. No effects on body weight, serum lipids, glucose metabolism, or PAI-1 were seen.

A diet containing rapeseed oil-based fats does not increase lipid peroxidation in humans when compared to a diet rich in saturated fatty acids.

OBJECTIVE: To compare the effects of a rapeseed oil-based diet containing an increased proportion of easily oxidised polyunsaturated fatty acids such as alpha-linolenic acid with a diet rich in saturated fatty acids on the degree of lipid peroxidation in the human body. DESIGN: A randomised cross-over study. SUBJECTS AND INTERVENTIONS: Nineteen healthy moderately hyperlipidemic subjects (six women and 13 men, age 50+/-8 y and body mass index (BMI) 24.5+/-2.6 kg/m(2)) were given a rapeseed oil-based diet (RO) and a control diet (SAT) rich in saturated fatty acids during two consecutive 4 week periods separated by a 4 week wash-out period. Biomarkers of lipid peroxidation and antioxidants were analysed in plasma and urine. RESULTS: No significant differences in plasma or urinary levels of free 8-iso-prostaglandin F(2alpha), plasma total 8-iso-prostaglandin F(2alpha) plasma hydroperoxides or plasma malondialdehyde were observed between the RO and SAT diets (P=0.14-0.95). A higher concentration of serum gamma-tocopherol was detected after the RO diet compared to the SAT diet (P<0.001), whereas the serum alpha-tocopherol concentration and plasma antioxidative capacity did not differ between the two test diets. The total cholesterol, LDL cholesterol and LDL/HDL ratio were lower after the RO diet compared to the SAT diet (P<0.001), while HDL cholesterol and total triglyceride levels were similar after the two diets. CONCLUSION: These results suggest that a rapeseed oil-based diet rich in alpha-linolenic acid does not seem to increase the degree of lipid peroxidation in plasma and urine compared to a diet rich in saturated fats. This is possibly due to a sufficient content of antioxidants in the rapeseed oil diet to increase circulating concentrations of antioxidants that may protect unsaturated fatty acids from oxidation. SPONSORSHIP: Swedish Council for Forestry and Agricultural Research and Foundation for Geriatric Research.

Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial.

BACKGROUND: Abdominal obesity is strongly related to metabolic disorders. Recent research suggests that dietary conjugated linoleic acid (CLA) reduces body fat and may improve metabolic variables in animals. The metabolic effects of CLA in abdominally obese humans have not yet been tested. OBJECTIVE: To investigate the short-term effect of CLA on abdominal fat and cardiovascular risk factors in middle-aged men with metabolic disorders. METHODS: Twenty-five abdominally obese men (waist-to-hip ratio (WHR), 1.05+/-0.05; body mass index (BMI), 32+/-2.7 kg/m(2) (mean+/-s.d.)) who were between 39 and 64-y-old participated in a double-blind randomised controlled trial for 4 weeks. Fourteen men received 4.2 g CLA/day and 10 men received a placebo. The main endpoints were differences between the two groups in sagittal abdominal diameter (SAD), serum cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, free fatty acids, glucose and insulin. RESULTS: At baseline, there were no significant differences between groups in anthropometric or metabolic variables. After 4 weeks there was a significant decrease in SAD (cm) in the CLA group compared to placebo (P=0.04, 95% CI; -1.12, -0.02). Other measurements of anthropometry or metabolism showed no significant differences between the groups. CONCLUSIONS: These results indicate that CLA supplementation for 4 weeks in obese men with the metabolic syndrome may decrease abdominal fat, without concomitant effects on overall obesity or other cardiovascular risk factors. Because of the limited sample size, the effects of CLA in abdominal obesity need to be further investigated in larger trials with longer duration.

Corn and sesame oils increase serum gamma-tocopherol concentrations in healthy Swedish women.

We studied the effects of dietary intervention with three vegetable oils (Linola, corn or sesame oil, all good sources of gamma-tocopherol) on absolute and relative concentrations of alpha- and gamma-tocopherol in human serum. The oils contained only small amounts of linolenic acid but varying amounts of oleic and linoleic acids, and they had different concentrations of alpha-tocopherol. Forty healthy female students (mean age 26 y) were randomly assigned to one of three groups and consumed a diet that contained one of the three oils for 4 wk. Refined oils were distributed as ingredients in specially prepared buns, in margarine or as dressing. Serum tocopherols, serum lipoproteins and plasma malondialdehyde concentrations were measured. The gamma-tocopherol concentrations normalized to serum lipids increased significantly in the corn and sesame oil groups (P < 0.01), and the alpha-/gamma-tocopherol ratios decreased significantly from baseline concentrations in all groups (P < 0.05). The alpha-tocopherol concentrations did not change during the diet period in any of the three groups. Serum cholesterol, serum apolipoprotein B and plasma malondialdehyde concentrations decreased significantly only in the Linola oil group (P < 0.05). These data show that a moderately modified natural diet that contains both alpha- and gamma-tocopherol increases the serum gamma-tocopherol concentration in healthy women without affecting the serum alpha-tocopherol concentration.

Vitamin E reduces lipid peroxidation in experimental hepatotoxicity in rats.

BACKGROUND AND AIMS: Lipid peroxidation is believed to be involved in the pathophysiology of a number of diseases and in the process of aging. This study investigates the effects of dietary supplementation with vitamin E (20 g/kg diet of all-rac-alpha-tocopheryl succinate for 3 weeks) on both non-enzymatic and enzymatic lipid peroxidation in experimental rats with carbon tetrachloride (CCl4)-induced hepatotoxicity (2.5 mL/kg body). METHODS: Plasma, urine and liver samples from control rats (n = 6), CCl4-treated rats (n = 6), and rats supplemented with vitamin E prior to CCl4 treatment (n = 8) were collected. Non-enzymatic lipid peroxidation induced by free radicals was investigated by measurement of a major F2-iso-prostane, 8-iso-prostaglandin F2 alpha (8-iso-PGF2 alpha). Cyclooxygenase-catalyzed enzymatic lipid peroxidation was measured with a major PGF2 alpha metabolite, 15-keto-13,14-dihydro-prostaglandin F2 alpha (15-K-DH-PGF2 alpha). Malondialdehyde and antioxidants in plasma were also quantified. RESULTS: CCl4 treatment alone resulted in significantly higher levels of plasma, urinary and liver 8-iso-PGF2 alpha, and of plasma and urinary 15-K-DH-PGF2 alpha compared to controls. Rats supplemented with vitamin E prior to CCl4 treatment had significantly lower levels of urinary and liver 8-iso-PGF2 alpha, urinary 15-K-DH-PGF2 alpha, and plasma malondialdehyde than rats treated with CCl4 alone. However, plasma 8-iso-PGF2 alpha and plasma 15-K-DH-PGF2 alpha were not affected by vitamin E supplementation. CONCLUSION: Thus, both non-enzymatic and enzymatic lipid peroxidation during experimental hepatic oxidative injury were suppressed by dietary vitamin E supplementation in rats.

Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study.

AIMS/HYPOTHESIS: The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. METHODS: The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. RESULTS: Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10%, p = 0.03) but did not change on the monounsaturated fatty acid diet (+2%, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E%). Here, insulin sensitivity was 12.5% lower and 8.8% higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet (+4.1%, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (-5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12% (p < 0.001). CONCLUSIONS/INTERPRETATION: A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake (> 37E%).

The alpha and gamma tocopherol levels in serum are influenced by the dietary fat quality.

BACKGROUND: Alpha tocopherol in serum is thought to be of importance in protecting lipids against oxidation and low serum levels of alpha tocopherol has been suggested to increase the risk for coronary heart disease. However, low levels of gamma, rather than alpha, tocopherol have been found in patients with manifest coronary heart disease and in populations with a high incidence of coronary heart disease. AIM: The aim of this study was to determine the tocopherol concentrations in serum after two diets with identical nutrient content but with different fat quality, enriched in butter and rapeseed oil-based fats, respectively. METHOD: Twenty moderately hyperlipidemic, healthy subjects (six females and 14 males) participated in this double-blind cross-over study, where two isoenergetic diets were given in a randomized order during two 3-week periods, interrupted by a wash-out period of 3-4 weeks. RESULTS: The lipid-corrected serum concentrations of alpha and gamma tocopherol increased during the diet rich in rapeseed oil (by 7 and 23%, respectively) compared with on the baseline diet (P < 0.001), while these concentrations decreased (by 5 and 37%, respectively, P < 0.01) during the diet rich in saturated fat. The ratio between alpha and gamma tocopherol decreased significantly during the rapeseed oil diet (-23%, P < 0.01) and increased (+46%, P < 0.001) during the butter diet. CONCLUSION: Alpha and gamma tocopherol levels in serum are influenced by the type of fat used in the diet. The most unexpected finding is that the lipid-adjusted gamma tocopherol concentration significantly decreased by 37% during a diet rich in saturated fat with an increased ratio between alpha and gamma tocopherol, similar to the situation found in CHD patients.

Conjugated linoleic acid induces lipid peroxidation in men with abdominal obesity.

Conjugated linoleic acid (CLA) has been shown in experimental studies to have chemoprotective properties, and may decrease the deposition of body fat. CLA is prone to oxidation, and it has been suggested that increased lipid oxidation may contribute to the anti-tumorigenic effects of this agent. The present study investigates the urinary levels of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)), a major isoprostane, and of 15-oxo-dihydro-PGF(2alpha), a major metabolite of PGF(2alpha), as indicators of non-enzymic and enzymic arachidonic acid oxidation respectively after dietary supplementation with CLA in middle-aged men (mean age 53 years) with abdominal obesity for 1 month in a randomized controlled trial. Significant increases in the levels of both 8-iso-PGF(2alpha) and 15-oxo-dihydro-PGF(2alpha) in urine (P<0. 0001 and P=0.0013 respectively) were observed after 1 month of daily CLA intake (4.2 g/day) as compared with the control group. The lipid peroxidation parameters had returned to their basal levels at 2 weeks after the cessation of CLA intake, and remained at the same levels for a further 2 weeks until the end of the study. CLA had no effect on serum alpha-tocopherol and gamma-tocopherol levels, or on the urinary levels of 2,3-dinor-thromboxane B(2). Thus CLA may induce both non-enzymic and enzymic lipid peroxidation in vivo in middle-aged men with abdominal obesity, without any side effects. The consequences of the increased lipid peroxidation after CLA supplementation are unknown.

Dietary fat and insulin action in humans.

A high intake of fat may increase the risk of obesity. Obesity, especially abdominal obesity, is an important determinant of the risk of developing insulin resistance and non-insulin-dependent diabetes mellitus. It is suggested that a high proportion of fat in the diet is associated with impaired insulin sensitivity and an increased risk of developing diabetes, independent of obesity and body fat localization, and that this risk may be influenced by the type of fatty acids in the diet. Cross-sectional studies show significant relationships between the serum lipid fatty acid composition, which at least partly mirrors the quality of the fatty acids in the diet, and insulin sensitivity. Insulin resistance, and disorders characterized by insulin resistance, are associated with a specific fatty acid pattern of the serum lipids with increased proportions of palmitic (16:0) and palmitoleic acids (16:1 n-7) and reduced levels of linoleic acid (18:2 n-6). The metabolism of linoleic acid seems to be disturbed with increased proportions of dihomo-gamma linolenic acid (20:3 n-6) and a reduced activity of the delta 5 desaturase, while the activities of the delta 9 and delta 6 desaturases appear to be increased. The skeletal muscle is the main determinant of insulin sensitivity. Several studies have shown that the fatty acid composition of the phosholipids of the skeletal muscle cell membranes is closely related to insulin sensitivity. An increased saturation of the membrane fatty acids and a reduced activity of delta 5 desaturase have been associated with insulin resistance. There are several possible mechanisms which could explain this relationship. The fatty acid composition of the lipids in serum and muscle is influenced by diet, but also by the degree of physical activity, genetic disposition, and possibly fetal undernutrition. However, controlled dietary intervention studies in humans investigating the effects of different types of fatty acids on insulin sensitivity have so far been negative.

Conjugated linoleic acid induces lipid peroxidation in humans.

Conjugated linoleic acid (CLA) is shown to have chemoprotective properties in various experimental cancer models. CLA is easily oxidised and it has been suggested that an increased lipid oxidation may contribute to the antitumorigenic effects. This report investigates the urinary levels of 8-iso-PGF(2alpha), a major isoprostane and 15-keto-dihydro-PGF(2alpha), a major metabolite of PGF(2alpha), as indicators of non-enzymatic and enzymatic lipid peroxidation after dietary supplementation of CLA in healthy human subjects for 3 months. A significant increase of both 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) in urine was observed after 3 months of daily CLA intake (4.2 g/day) as compared to the control group (P<0.0001). Conjugated linoleic acid had no effect on the serum alpha-tocopherol levels. However, gamma-tocopherol levels in the serum increased significantly (P=0. 015) in the CLA-treated group. Thus, CLA may induce both non-enzymatic and enzymatic lipid peroxidation in vivo. Further studies of the mechanism behind, and the possible consequences of, the increased lipid peroxidation after CLA supplementation are urgently needed.