Determinants of plasma phospholipid arachidonic and docosahexaenoic acids among adolescent girls in central Mozambique - possible roles of iron and zinc.

We explored if linoleic acid (LA) and alpha-linolenic acid (ALA) will be efficiently converted to arachidonic acid (AA) and docosahexaenoic acid (DHA) in the adolescent girls (aged 15-18 years, n=145) in Mozambique consuming habitually low fat diet and if low iron and/or zinc status predicts the conversion. Total fat, LA and ALA intakes were 15-19%, 1.2-3.5% and 0.2-0.3% of energy, respectively in three areas. Iron and zinc intake varied between 9.6-12.3mg/day and 3.6-5.0mg/day. Significant negative association of plasma AA was found with plasma LA and ALA and significant positive association with serum ferritin. Plasma DHA associated, negatively with plasma LA and ALA. We showed that in a population with low intakes of LA and ALA, the proportions of phospholipid LA and ALA determines the relative proportions of AA and DHA and low iron status probably attenuates the conversion of LA to AA.

Cancer death is related to high palmitoleic acid in serum and to polymorphisms in the SCD-1 gene in healthy Swedish men.

BACKGROUND: A high proportion of monounsaturated fatty acids (MUFAs) or a high ratio of MUFAs to saturated fatty acids in plasma, reflecting a high activity of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1), has been shown to be related to cancer death and incidence in some studies. OBJECTIVES: The objective was to study whether the serum cholesteryl ester proportion of palmitoleic acid [16:1n-7 (16:1ω-3)] and the ratio of palmitoleic to palmitic acid (16:1n-7/16:0), as an estimation of the activity of SCD-1, are related to cancer death and to investigate whether polymorphisms in the SCD-1 gene are related to cancer mortality. DESIGN: A community-based cohort of 50-y-old men was followed for a maximum of >40 y. Survival analysis was used to relate fatty acid composition in serum, analyzed at baseline by gas-liquid chromatography (n = 1981), and single nucleotide polymorphisms in the SCD-1 gene (n = 986) to cancer death. A 7-d dietary record was completed at age 70 y (n = 880). RESULTS: The proportions of 16:1n-7 and the ratio of 16:1n-7 to 16:0 were associated with cancer mortality during follow-up in a comparison of the highest with the lowest quartile of 16:1n-7 (adjusted HR: 1.37; 95% CI: 1.04, 1.82). Inherited variance of the SCD-1 gene seemed to be related to cancer death, especially among men with a low proportion of PUFA in the diet in a comparison of the highest with the lowest weighted genetic risk score (HR: 2.14; 95% CI: 1.13, 4.04). CONCLUSION: The findings are compatible with the hypothesis that there is an association between endogenously synthesized MUFAs and cancer death.

Obesity modifies the relations between serum markers of dairy fats and inflammation and oxidative stress among adolescents.

Pentadecanoic acid (15:0) and heptadecanoic acid (17:0), the dairy-specific saturated fatty acids have been inversely, while inflammation and oxidative stress have been positively related to the risk of cardiovascular disease (CVD). Both fatty acid metabolism and inflammation and oxidative stress may be influenced by adiposity. In the current cross-sectional analyses among adolescents (mean age 15 years), we determined whether overweight status modified the associations between dairy fatty acids (pentadecanoic acid (15:0) and heptadecanoic acid (17:0)) represented in serum phospholipids (PL) and markers of inflammation and oxidative stress. Six biomarkers for inflammation and oxidative stress were analyzed, including circulating adiponectin, C-reactive protein (CRP), cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and urinary 15-keto-dihydro-PGF2α (15-keto) and 8-iso-PGF2α (F2-iso). Generalized linear regression analyses, adjusted for age, gender, race, tanner score, total energy intake and physical activity, revealed that PL dairy fatty acids were inversely associated with CRP, F2-iso and 15-keto in overweight, but not in normal weight adolescents (all P(interaction) < 0.05). However, higher level of PL dairy fatty acids was associated with lower IL-6 among all adolescents. Further adjustment for dietary intake of calcium, vitamin D, protein, total flavonoids, and ω-3 fatty acids did not materially change the findings. Dairy-specific saturated fats, i.e., 15:0 and 17:0 fatty acids, may contribute to the potential health benefits of dairy products, especially for overweight adolescents.

Evaluation of the impact of genetic polymorphisms in glutathione-related genes on the association between methylmercury or n-3 polyunsaturated long chain fatty acids and risk of myocardial infarction: a case-control study.

BACKGROUND: The n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, which are present in fish, are protective against myocardial infarction. However, fish also contains methylmercury, which influences the risk of myocardial infarction, possibly by generating oxidative stress. Methylmercury is metabolized by conjugation to glutathione, which facilitates elimination. Glutathione is also an antioxidant. Individuals with certain polymorphisms in glutathione-related genes may tolerate higher exposures to methylmercury, due to faster metabolism and elimination and/or better glutathione-associated antioxidative capacity. They would thus benefit more from the protective agents in fish, such as eicosapentaenoic+docosahexaenoic acid and selenium. The objective for this study was to elucidate whether genetic polymorphisms in glutathione-related genes modify the association between eicosapentaenoic+docosahexaenoic acid or methylmercury and risk of first ever myocardial infarction. METHODS: Polymorphisms in glutathione-synthesizing (glutamyl-cysteine ligase catalytic subunit, GCLC and glutamyl-cysteine ligase modifier subunit, GCLM) or glutathione-conjugating (glutathione S-transferase P, GSTP1) genes were genotyped in 1027 individuals from northern Sweden (458 cases of first-ever myocardial infarction and 569 matched controls). The impact of these polymorphisms on the association between erythrocyte-mercury (proxy for methylmercury) and risk of myocardial infarction, as well as between plasma eicosapentaenoic+docosahexaenoic acid and risk of myocardial infarction, was evaluated by conditional logistic regression. The effect of erythrocyte-selenium on risk of myocardial infarction was also taken into consideration. RESULTS: There were no strong genetic modifying effects on the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction risk. When eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury were divided into tertiles, individuals with GCLM-588 TT genotype displayed a lower risk relative to the CC genotype in all but one tertile; in most tertiles the odds ratio was around 0.5 for TT. However, there were few TT carriers and the results were not statistically significant. The results were similar when taking plasma eicosapentaenoic+docosahexaenoic acid, erythrocyte-selenium and erythrocyte-mercury into account simultaneously. CONCLUSIONS: No statistically significant genetic modifying effects were seen for the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction. Still, our results indicate that the relatively rare GCLM-588 TT genotype may have an impact, but a larger study is necessary for confirmation.

Randomized controlled trial of cognitive behavioral therapy vs standard treatment to prevent recurrent cardiovascular events in patients with coronary heart disease: Secondary Prevention in Uppsala Primary Health Care project (SUPRIM).

BACKGROUND: Psychosocial factors are independently associated with increased risk of cardiovascular disease (CVD) morbidity and mortality, but the effects of psychosocial factor intervention on CVD are uncertain. We performed a randomized controlled clinical trial of cognitive behavioral therapy (CBT) to measure its effects on CVD recurrence. METHODS: The study included 362 women and men 75 years or younger who were discharged from the hospital after a coronary heart disease event within the past 12 months. Patients were randomized to receive traditional care (reference group, 170 patients) or traditional care plus a CBT program (intervention group, 192 patients), focused on stress management, with 20 two-hour sessions during 1 year. Median attendance at each CBT session was 85%. Outcome variables were all-cause mortality, hospital admission for recurrent CVD, and recurrent acute myocardial infarction. RESULTS: During a mean 94 months of follow-up, the intervention group had a 41% lower rate of fatal and nonfatal first recurrent CVD events (hazard ratio [95% confidence interval], 0.59 [0.42-0.83]; P = .002), 45% fewer recurrent acute myocardial infarctions (0.55 [0.36-0.85]; P = .007), and a nonsignificant 28% lower all-cause mortality (0.72 [0.40-1.30]; P = .28) than the reference group after adjustment for other outcome-affecting variables. In the CBT group there was a strong dose-response effect between intervention group attendance and outcome. During the first 2 years of follow-up, there were no significant group differences in traditional risk factors. CONCLUSIONS: A CBT intervention program decreases the risk of recurrent CVD and recurrent acute myocardial infarction. This may have implications for secondary preventive programs in patients with coronary heart disease. Trial Registration clinicaltrials.gov Identifier: NCT00888485.

Fish consumption and myocardial infarction: a second prospective biomarker study from northern Sweden.

BACKGROUND: A beneficial role of fish consumption on the risk of myocardial infarction (MI) has been reported and is mostly ascribed to n-3 (omega-3) fatty acids. However, fish also contains methylmercury, which may increase the risk of MI. OBJECTIVE: The objective was to determine how fish consumption and erythrocyte concentrations of mercury (Ery-Hg) and selenium (Ery-Se) are related to the risk of MI and whether n-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) in plasma phospholipids (P-EPA+DHA) are protective. DESIGN: This was a case-control study nested within the northern Sweden cohort, in which data and samples were collected prospectively. The study included 431 cases with an MI after data and sample collection, including 81 sudden cardiac deaths (SCDs) and 499 matched controls. Another 69 female cases with controls from a breast cancer screening registry were included in sex-specific analyses. RESULTS: Odds ratios for the third compared with the first tertile were 0.65 (95% CI: 0.46, 0.91) for Ery-Hg, 0.75 (95% CI: 0.53, 1.06) for Ery-Se, and 0.78 (95% CI: 0.54, 1.11) for P-EPA+DHA. Ery-Hg and P-EPA+DHA were intercorrelated (Spearman's R = 0.34). No association was seen for reported fish consumption. Multivariate modeling did not change these associations significantly. Sex-specific analyses showed no differences in risk associations. High concentrations of Ery-Se were associated with an increased risk of SCD. CONCLUSIONS: The biomarker results indicate a protective effect of fish consumption. No harmful effect of mercury was indicated in this low-exposed population in whom Ery-Hg and P-EPA+DHA were intercorrelated.

Supplementation with a combination of antioxidants does not affect glycaemic control, oxidative stress or inflammation in type 2 diabetes subjects.

The present clinical trial examined the influence of a supplement, containing a combination of antioxidants extracted from fruit, berries and vegetables, on levels of plasma antioxidants (tocopherols, carotenoids and ascorbate), glycaemic control (blood glucose, HbA1c, insulin), oxidative stress biomarkers (F(2)-isoprostane, malondialdehyd, nitrotyrosine, 8-oxo-7, 8-dihydro-2'-deoxyguanosine, formamidopyrimidine glycosylase sites, frequency of micronucleated erythrocytes) and inflammatory markers (interleukin-6, C-reactive protein, prostaglandin F(2α)-metabolite) in type 2 diabetes. Forty subjects were randomly assigned to control, single or double dose group and completed the study. In summary, 12 weeks of antioxidant supplementation did neither affect glycaemic control nor the levels of biomarkers of oxidative stress or inflammation, despite substantially increased plasma concentrations of antioxidants. The absence of an effect may be explained by the selected study subjects with relatively well-controlled diabetes, a high intake of fruit and vegetable and levels of plasma antioxidants, biomarkers of oxidative stress and inflammatory markers comparable to those found in healthy subjects.

Presence of alkylresorcinols, potential whole grain biomarkers, in human adipose tissue.

Alkylresorcinols (AR) in plasma samples have been suggested to be short- to medium-term biomarkers of whole grain wheat and rye intake. In the present study, we investigated whether AR are present in human adipose tissues, and if content correlated with long-term whole grain bread intake. Furthermore, we investigated if the relative AR homologue composition reflected what has been found previously in the habitual diet of Swedes. Biopsy samples (10-25 mg) from free-living Swedish women (n 20) were analysed by GC-MS. The mean total AR concentration in the samples was 0.54 (SD 0.35) microg/g, ranging from below limit of quantification ( < 0.08 microg/g) to 1.50 microg/g. Whole grain bread intake was significantly correlated with plasma total AR content (r 0.48, P < 0.05), and the C17 : 0/C21 : 0 ratio was 0.35 (sd 0.24), which is similar to what is found in plasma among free-living subjects consuming a mixed whole grain wheat and rye diet. These results suggest that AR in the adipose tissue should be evaluated as a long-term biomarker of whole grain wheat and rye intake.

Biomarkers of oxidative stress in overweight men are not influenced by a combination of antioxidants.

The effect of antioxidant supplementation on biomarkers of oxidative stress was investigated in a 6-week intervention study in 60 overweight men. The supplement contained a combination of antioxidants aiming to correspond to the antioxidant content found in a diet rich in fruit and vegetables. Placebo, single or double dose of antioxidants was provided to the subjects. Metabolic variables, plasma antioxidants and biomarkers of oxidative stress (lipid peroxidation and DNA damage) were measured. No effect of supplementation on biomarkers of oxidative stress was observed. Both intervention groups showed substantial increases of plasma antioxidants. This study demonstrated that supplementation with a combination of antioxidants did not affect lipid peroxidation and DNA damage in overweight men, despite increased concentrations of plasma antioxidants. The absence of antioxidant supplement effect might possibly be explained by the chosen study group having a normal level of oxidative stress, duration of the intervention and/or doses of antioxidants.

Glycaemic status in relation to oxidative stress and inflammation in well-controlled type 2 diabetes subjects.

The aim of the present observational study was to investigate the relationships between glycaemic status and levels of oxidative stress and inflammation in well-controlled type 2 diabetes subjects. Metabolic variables (weight, BMI, waist circumference (waist), blood glucose, glycated Hb (HbA(1c)), insulin, blood lipids), biomarkers of oxidative stress (8-iso-PGF(2alpha), malondialdehyde, 8-oxo-7,8-dihydro-2'-deoxyguanosine, formamido pyrimidine glycosylase-sites, frequency of micronucleated erythrocytes, nitrotyrosine) and inflammatory markers (high sensitivity C-reactive protein (hsCRP), IL-6, cyclo-oxygenase-catalyzed PGF(2alpha)-metabolite) were measured. Fifty-six patients (thirty women and twenty-six men, age 62.3 (SD 7.0) years, HbA(1c) 6.1 (SD 0.9) %, BMI 28.3 (SD 3.8) kg/m(2), waist 99.6 (SD 11.1) cm) were included in the study. HbA(1c) (r 0.29, P=0.03) and blood glucose (r 0.33, P=0.01) correlated positively with 8-iso-PGF(2alpha). Positive correlations were also observed between HbA(1c) and nitrotyrosine (r 0.42, P=0.01), waist and hsCRP (r 0.37, P=0.005), hsCRP and IL-6 (r 0.61, P<0.0001) and between PGF(2alpha)-metabolite and 8-iso-PGF(2alpha) (r 0.27, P=0.048). The present study indicates that glycaemic status is associated with oxidative stress even in subjects with well-controlled type 2 diabetes. Furthermore, inflammation was more related to abdominal obesity than to glycaemic control. A large number of biomarkers of oxidative stress and inflammation were investigated, but only a few associations were found between the markers. This could be due to the fact that none of these biomarkers biosynthesises via similar pathways or simultaneously owing to their diverse nature and origin.

Markers of dietary fat quality and fatty acid desaturation as predictors of total and cardiovascular mortality: a population-based prospective study.

BACKGROUND: Desaturase indexes, as markers of endogenous fatty acid desaturation, and a characteristic serum fatty acid (FA) composition are related to cardiovascular and metabolic diseases, but the relation to mortality is poorly investigated. OBJECTIVE: The objective was to evaluate the relation between dietary fat biomarkers, desaturase indexes, and mortality. DESIGN: In this community-based prospective sample, 50-y-old men were followed for a maximum of 33.7 y. Cox proportional hazard analysis was conducted to investigate desaturase indexes (stearoyl-CoA-desaturase and Delta(6)- and Delta(5)-desaturase) and the relation of individual serum esterified fatty acids (FAs) in relation to total and cardiovascular mortality in the total study sample (n = 2009) and in a healthy subsample (n = 1885). Desaturase indexes were estimated as product-to-precursor FA ratios. RESULTS: During follow-up, 1012 men in the total sample died and 931 men in the healthy subsample died. Desaturase indexes predicted both total and cardiovascular mortality. The relations were independent of smoking status, physical activity, BMI, total cholesterol, and hypertension. The adjusted and standardized (per SD) hazard ratios (HRs) and 95% CIs for cardiovascular mortality were 1.15 (1.04, 1.27) for stearoyl-CoA-desaturase, 1.12 (1.0, 1.24) for Delta(6)-desaturase, and 0.88 (0.80, 0.98) for Delta(5)-desaturase, respectively. The proportion of serum linoleic acid was inversely related, whereas serum FAs associated with saturated fat intake (palmitic, palmitoleic, and dihomo-gamma-linolenic acids) were directly related to total and cardiovascular mortality. CONCLUSIONS: Altered endogenous FA desaturation might contribute to mortality risk because we observed independent associations between desaturase activity indexes and mortality. The proportion of linoleic acid was inversely related, and FAs reflecting saturated fat intake were directly related to mortality.

Effects of docosahexaenoic acid-rich n-3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes: the OmegAD study.

BACKGROUND: Dietary fish or fish oil rich in n-3 fatty acids (n-3 FAs), eg, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), ameliorate inflammatory reactions by various mechanisms. Whereas most studies have explored the effects of predominantly EPA-based n-3 FAs preparations, few have addressed the effects of n-3 FAs preparations with DHA as the main FA. OBJECTIVE: The objective was to determine the effects of 6 mo of dietary supplementation with an n-3 FAs preparation rich in DHA on release of cytokines and growth factors from peripheral blood mononuclear cells (PBMCs). DESIGN: In a randomized, double-blind, placebo-controlled trial, 174 Alzheimer disease (AD) patients received daily either 1.7 g DHA and 0.6 g EPA (n-3 FAs group) or placebo for 6 mo. In the present study blood samples were obtained from the 23 first randomized patients, and PBMCs were isolated before and after 6 mo of treatment. RESULTS: Plasma concentrations of DHA and EPA were significantly increased at 6 mo in the n-3 FAs group. This group also showed significant decreases of interleukin (IL)-6, IL-1beta, and granulocyte colony-stimulating factor secretion after stimulation of PBMCs with lipopolysaccharide. Changes in the DHA and EPA concentrations were negatively associated with changes in IL-1beta and IL-6 release for all subjects. Reductions of IL-1beta and IL-6 were also significantly correlated with each other. In contrast, this n-3 FA treatment for 6 mo did not decrease tumor necrosis factor-alpha, IotaL-8, IL-10, and granulocyte-macrophage colony-stimulating factor secretion. CONCLUSION: AD patients treated with DHA-rich n-3 FAs supplementation increased their plasma concentrations of DHA (and EPA), which were associated with reduced release of IL-1beta, IL-6, and granulocyte colony-stimulating factor from PBMCs. This trial was registered at clinicaltrials.gov as NCT00211159.

Genetic variation in glutathione-related genes and body burden of methylmercury.

BACKGROUND: Exposure to toxic methylmercury (MeHg) through fish consumption is a large problem worldwide, and it has led to governmental recommendations of reduced fish consumption and blacklisting of mercury-contaminated fish. The elimination kinetics of MeHg varies greatly among individuals. Knowledge about the reasons for such variation is of importance for improving the risk assessment for MeHg. One possible explanation is hereditary differences in MeHg metabolism. MeHg is eliminated from the body as a glutathione (GSH) conjugate. OBJECTIVES: We conducted this study to assess the influence of polymorphisms in GSH-synthesizing [glutamyl-cysteine ligase modifier subunit (GCLM-588) and glutamyl-cysteine ligase catalytic subunit (GCLC-129)] or GSH-conjugating [glutathione S-transferase pi 1 (GSTP1-105 and GSTP1-114)] genes on MeHg retention. METHODS: Based on information obtained from questionnaires, 292 subjects from northern Sweden had a high consumption of fish (lean/fat fish two to three times per week or more). We measured total Hg in erythrocytes (Ery-Hg) and long-chain n-3 polyunsaturated fatty acids in plasma (P-PUFA; an exposure marker for fish intake). RESULTS: The GSTP1 genotype modified Ery-Hg; effects were seen for GSTP1-105 and -114 separately, and combining them resulted in stronger effects. We found evidence of effect modification: individuals with zero or one variant allele demonstrated a steeper regression slope for Ery-Hg (p=0.038) compared with individuals with two or more variant alleles. The GCLM-588 genotype also influenced Ery-Hg (p=0.035): Individuals with the GCLM-588 TT genotype demonstrated the highest Ery-Hg, but we saw no evidence of effect modification with increasing P-PUFA. CONCLUSIONS: These results suggest a role of GSH-related polymorphisms in MeHg metabolism.

Down-regulation of oxidative DNA lesions in human mononuclear cells after antioxidant supplementation correlates to increase of gamma-tocopherol.

The protective effect of vitamin E supplements has been questioned, possibly because they often contain only alpha-tocopherol, and recent studies indicate that gamma-tocopherol also has important properties. The aim of this study was to investigate whether the levels of DNA lesions in middle-aged, overweight males could be reduced by consumption of low doses of an antioxidant supplement for six weeks, designed to imitate a balanced diet. The participants (n=60) were randomly divided into: placebo, single-, and double-dose groups. Genotoxic and oxidative DNA lesions in mononuclear cells were measured with the Comet assay, before and after supplement administration. Furthermore, a cell study was performed to investigate if pre-incubation of a human lung cell line (A549) with alpha- and gamma-tocopherol (5 and 50 microM for 23 hours) could protect against induced oxidative DNA lesions as measured by the Comet assay. The level of oxidative DNA lesions in the double-dose group was significantly lower than in the control group. Oxidative DNA lesions correlated only to changes in serum gamma-tocopherol, and not alpha-tocopherol. In the cell study, only gamma-tocopherol protected cells against induced oxidative DNA lesions. We therefore hypothesize that gamma-tocopheol rather than alpha-tocopherol is involved in reducing oxidative DNA lesions.

Fatty acid profile of the erythrocyte membrane preceding development of Type 2 diabetes mellitus.

BACKGROUND AND AIMS: The respective roles of dietary fatty acids in the pathogenesis of diabetes are as yet unclear. Erythrocyte membrane fatty acid (EMFA) composition may provide an estimate of dietary fatty acid intake. This study investigates the relation between EMFA composition and development of Type 2 diabetes mellitus. METHODS AND RESULTS: In a nested case-referent design we studied 159 individuals tested as non-diabetic at baseline who after a mean observation time of 5.4+/-2.6years were diagnosed with Type 2 diabetes mellitus and 291 sex- and age-matched referents. Higher proportions of pentadecanoic acid (15:0) and heptadecanoic acid (17:0) were associated with a lower risk of diabetes. In accordance with earlier findings, higher proportions of palmitoleic (16:1 n-7), dihomo-gamma-linolenic (20:3 n-6) and adrenic (22:4 n-6) acids were associated with increased risk, whereas linoleic (18:2 n-6) and clupanodonic (22:5 n-3) acids were inversely associated with diabetes. After adjustment for BMI, HbA1c, alcohol intake, smoking and physical activity the only significant predictors were 15:0 and 17:0 as protective factors and 22:4 n6 as risk factor. CONCLUSION: In accordance with previous studies, our results indicate that EMFA-patterns predict development of Type 2 diabetes mellitus. The inverse association with two saturated fatty acids, previously shown to reflect consumption of dairy products, is a new finding.

Whole-grain foods do not affect insulin sensitivity or markers of lipid peroxidation and inflammation in healthy, moderately overweight subjects.

High intakes of whole grain foods are inversely related to the incidence of coronary heart diseases and type 2 diabetes, but the mechanisms remain unclear. Our study aimed to evaluate the effects of a diet rich in whole grains compared with a diet containing the same amount of refined grains on insulin sensitivity and markers of lipid peroxidation and inflammation. In a randomized crossover study, 22 women and 8 men (BMI 28 +/- 2) were given either whole-grain or refined-grain products (3 bread slices, 2 crisp bread slices, 1 portion muesli, and 1 portion pasta) to include in their habitual daily diet for two 6-wk periods. Peripheral insulin sensitivity was determined by euglycemic hyperinsulinemic clamp tests. 8-Iso-prostaglandin F(2alpha) (8-iso PGF(2alpha)), an F(2)-isoprostane, was measured in the urine as a marker of lipid peroxidation, and highly sensitive C-reactive protein and IL-6 were analyzed in plasma as markers of inflammation. Peripheral insulin sensitivity [mg glucose . kg body wt(-1) . min(-1) per unit plasma insulin (mU/L) x 100] did not improve when subjects consumed whole-grain products (6.8 +/- 3.0 at baseline and 6.5 +/- 2.7 after 6 wk) or refined products (6.4 +/- 2.9 and 6.9 +/- 3.2, respectively) and there were no differences between the 2 periods. Whole-grain consumption also did not affect 8-iso-PGF(2alpha) in urine, IL-6 and C-reactive protein in plasma, blood pressure, or serum lipid concentrations. In conclusion, substitution of whole grains (mainly based on milled wheat) for refined-grain products in the habitual daily diet of healthy moderately overweight adults for 6-wk did not affect insulin sensitivity or markers of lipid peroxidation and inflammation.

Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids?

AIM: To evaluate whether a moderate supplementation of long-chain n-3 fatty acids is able to modulate insulin sensitivity, insulin secretion, beta-cell function and glucose tolerance in healthy individuals consuming a diet rich in either saturated or monounsaturated fat, also in relation to their habitual dietary intake of n-6 and n-3 fatty acid. METHODS AND RESULTS: One hundred and sixty-two healthy individuals were randomly assigned to follow either one of two isoenergetic diets for 3 months, one rich in monounsaturated fats and the other rich in saturated fats. Within each group there was a second randomisation to fish oil (n-3 fatty acids 3.6 g/day) or placebo. At the beginning and at the end of the treatment periods insulin sensitivity (SI), first phase insulin response (FPIR) and glucose tolerance (K(G)-value) were evaluated by the intravenous glucose tolerance test (IVGTT). Fish oil did not have any effect on SI, FPIR, K(G)-value and disposition index in either diet. Even after dividing subjects according to the median value of n-6/n-3 ratio of serum phospholipids at baseline, there was no change in SI (Delta SI 0.42+/-0.34 on fish oil vs 0.14+/-0.23 on placebo for those with n-6/n-3 <4.85; -1.03+/-0.47 on fish oil vs -0.27+/-0.32 on placebo for those with n-6/n-3 >4.85) (M+/-SE), FPIR (Delta FPIR 135.9+/-78.9 vs 157.2+/-157.5 pmol/L; 38.8+/-181.7 vs 357.1+/-181.7 pmol/L), K(G)-value (Delta K(G) 0.14+/-0.15 vs 0.12+/-0.11; -0.32+/-0.16 vs 0.15+/-0.15) or disposition index (Delta disposition index 1465.4+/-830.4 vs 953.8+/-690.0; -1641.6+/-1034.3 vs 446.6+/-905.1). Considering the 75th percentile of n-6/n-3 ratio (5.82) the results on insulin sensitivity, insulin secretion and disposition index were confirmed, while, in this more extreme situation, n-3 fatty acid supplementation induced a significant deterioration of K(G)-value (p=0.02). CONCLUSIONS: In healthy individuals a moderate supplementation of fish oil does not affect insulin sensitivity, insulin secretion, beta-cell function or glucose tolerance. The same is true even when the habitual dietary intake of n-6 and n-3 fatty acids is taken into account.

Metabolic risk factors for stroke and transient ischemic attacks in middle-aged men: a community-based study with long-term follow-up.

BACKGROUND AND PURPOSE: The impact of lipometabolic and glucometabolic disturbances on stroke incidence remains to be characterized in detail. We investigated relations of a comprehensive panel of baseline lipometabolic and glucometabolic variables to incident fatal and nonfatal stroke or transient ischemic attack (TIA), and stroke subtypes. METHODS: A community-based prospective study of 2313 middle-aged men invited to a health survey at age 50. RESULTS: During a follow-up of up to 32 years, 421 developed stroke or TIA. In Cox proportional hazards analyses adjusting for treatment with cardiovascular drugs at baseline, 1-standard deviation increases in body mass index, systolic and diastolic blood pressures, serum proinsulin, and lipoprotein(a) were associated with 11 to 35% increased risk for subsequent stroke/TIA. Electrocardiographic left ventricular hypertrophy and smoking were also associated with a higher risk for stroke/TIA. Essentially the same variables were related to brain infarction/TIA. Higher proportions of palmitic (16:0), palmitoleic (16:1), and oleic acid (18:1) in cholesterol esters were associated with an increased risk, whereas a higher proportion of linoleic acid (18:2 n-6) was protective against stroke/TIA. Further adjusting all models also for hypertension, diabetes, the metabolic syndrome, serum cholesterol, atrial fibrillation, cardiovascular disease, smoking, and physical activity, essentially the same pattern was observed. CONCLUSIONS: Indices of an unhealthy dietary fat intake and a high serum lipoprotein (a) level predicted fatal and nonfatal stroke/TIA independently of established risk factors in a community-based sample of middle-aged men followed for 32 years.

Factor analysis of fatty acids in serum lipids as a measure of dietary fat quality in relation to the metabolic syndrome in men.

BACKGROUND: A specific fatty acid (FA) composition in plasma lipid esters is related to the metabolic syndrome (MetS) and may influence the development of the MetS. OBJECTIVE: The objective was to define and study FA factors as measures of dietary fat quality and endogenous FA metabolism in relation to MetS. DESIGN: Principal factor analysis was performed to define specific FA factors in men participating in a population-based cohort study-the Uppsala Longitudinal Study of Adult Men. The factors were generated at ages 50 (n = 2009) and 70 (n = 576) y, and relations between FA factors and MetS (National Cholesterol Education Program) were studied in cross-sectional and prospective (20 y) analyses. RESULTS: The factor analysis generated 3 major FA factors: a low-linoleic acid (LA) factor, a dietary saturated FA factor, and an n-3 polyunsaturated FA (PUFA) factor. All factors differed between those subjects with MetS (n = 281 of 2009) and those without MetS at age 50 y; only the low-LA factor differed at age 70 y, which suggests an association between MetS and fat quality. The low-LA factor (odds ratio: 1.51; 95% CI: 1.28, 1.79; P < 0.0001) and the n-3 PUFA factor (0.76; 0.64, 0.90; P < 0.001) predicted MetS development over 20 y, independent of smoking habits, physical activity, and BMI. CONCLUSIONS: The generated FA factors, which presumably represent dietary fat quality and endogenous FA metabolism, may be important in the development of MetS. This finding supports current dietary recommendations to increase PUFA intakes and restrict saturated FA intakes.

Fatty acid composition and estimated desaturase activities are associated with obesity and lifestyle variables in men and women.

It is known that the fatty acid (FA) composition in serum cholesteryl esters to a certain extent mirrors not only the FA composition of dietary fat, but also the endogenous FA synthesis, where desaturases play an important part. A surrogate measure of delta9-, delta6- and delta5-desaturase activity can be calculated as a [product:precursor] fatty acid ratio. Delta9-desaturase activity is known to be high in conditions like diabetes, atherosclerosis and obesity. The aim of the present study was to relate the proportions of individual fatty acids in serum cholesteryl esters, as well as estimated desaturase ratios to markers of obesity and lifestyle variables (smoking, physical activity and dietary fat). We also studied gender differences. These relationships were studied in a reference population consisting of men (n=554) and women (n=295) who took part in a health survey concerning coronary heart disease in Sweden. We found positive and significant correlations between markers of obesity and the proportions of 16:0, 16:1 (n-7), 18:0, 18:3 (n-6), 20:3 (n-6), 20:4 (n-6), 20:5 (n-3), delta9 and delta6 activities, and an inverse correlation to delta5 activity and 18:2 (n-6). These relationships were independent of age and physical activity and in some cases of body mass index (BMI). For each standard deviation (SD) increase of delta9 and delta6 activities, the risk of being overweight was increased by about 60%, whereas the risk was reduced to about 30% for every SD increase of delta5 activity. Women were found to have significantly higher levels of delta9 and lower levels of delta6 desaturase activities than men. In conclusion, this study shows that a changed FA profile in serum cholesteryl esters and estimated desaturase activities are associated with obesity and lifestyle factors in men and women.