Fatty Acid Proportions in Plasma Cholesterol Esters and Phospholipids Are Positively Correlated in Various Swedish Populations.

Background: Fatty acid (FA) proportions in cholesterol esters (CEs) and plasma phospholipids are widely used as dietary biomarkers. Information on how proportions in these fractions correlate could have implications for interpretation and use of FA biomarkers in observational and interventional studies.Objective: We investigated correlations between FA proportions in CEs and phospholipids in free-living individuals and assessed how diet-induced alterations of FA proportions correlate between fractions.Methods: Spearman's rank correlation coefficients (rs) between FA proportions (percentage of total FAs) in circulating CEs and phospholipids were calculated separately in 8 individual study populations including Swedish females and males (N = 2052; age range: 11-84 y), and pooled by inverse-variance weighted meta-analysis. In addition, study populations were stratified by age, sex, body mass index (BMI; in kg/m2), and diabetes status, and strata-specific rs were pooled by meta-analysis. In 2 randomized trials (N = 79) in which dietary saturated FAs were isocalorically replaced with unsaturated FAs, treatment-wise calculations of rs were conducted between FA changes in CEs and phospholipids.Results: Overall, FA proportions in CEs and phospholipids correlated well and especially strongly for polyunsaturated FAs (PUFAs), with pooled rs (95% CIs) ranging from 0.74 (0.72, 0.76) for α-linolenic acid to 0.92 (0.91, 0.93) for eicosapentaenoic acid. Weak correlations (pooled rs < 0.4) were observed only for palmitic acid and stearic acid, with pooled rs (95% CIs): 0.29 (0.24, 0.33) and 0.30 (0.25, 0.34), respectively. Overall, correlations were not affected by age, sex, BMI, or diabetes status. Strong correlations (rs ≥ 0.6) between diet-induced FA changes in CEs and phospholipids were observed for most PUFAs.Conclusions: Proportions of most FAs in CEs and phospholipids ranked individuals similarly, suggesting that FA proportions in these fractions can be used interchangeably in populations of diverse age, sex, body composition, and diabetes status. Caution is advised, however, when comparing results from studies assessing palmitic acid or stearic acid in different lipid fractions.

Essential fatty acid intake and serum fatty acid composition among adolescent girls in central Mozambique.

Many African diets are low in fat but are currently changing because of nutrition transition. We studied fat and fatty acid (FA) intake and the essential fatty acid (EFA) status of adolescent girls (aged 14-19 years, n 262) in Zambezia Province, central Mozambique. A cross-sectional study was carried out in a city as well as in the towns and rural villages of a coastal and an inland district. Dietary intake and FA sources were studied in a 24 h dietary recall. FA compositions of cholesteryl esters and phospholipids of non-fasting serum samples were analysed by GLC. Fat intake was low (13-18 % of energy) in all areas. Coconut and palm oil were the main sources of fat, and soyabean oil and maize were the main sources of PUFA. Compared to Food and Agriculture Organization/WHO 2010 recommendations, intake of linoleic acid (LA, 18 : 2n-6) was inadequate in the coastal district, and intakes of n-3 PUFA were inadequate in all areas. FA compositions of serum lipids differed between areas. The proportions of LA tended to be highest in the city and lowest in the rural areas. The phospholipid mead (20 : 3n-9):arachidonic acid (20 : 4n-6) ratio did not indicate EFA insufficiency. LA proportions in phospholipids were low, but those of long-chain n-6 and n-3 PUFA were high in comparison with Western adolescents. To conclude, fat sources, FA intake and EFA status differed between adolescent girls living in different types of communities. Fat intake was low, but EFA insufficiency was not indicated.

Indices of fatty acid desaturase activity in healthy human subjects: effects of different types of dietary fat.

Δ9-Desaturase (stearoyl-CoA desaturase 1, SCD-1) regulates the desaturation of SFA, mainly stearic and palmitic, to MUFA. Δ6-Desaturase (D6D) and Δ5-desaturase (D5D) are involved in the metabolism of linoleic and α-linolenic acid to polyunsaturated metabolites. The objective of the present study was to study the effects of different types of dietary fat on indices of fatty acid desaturase (FADS) activity (evaluated as product:precursor ratios) in plasma and skeletal muscle in human subjects. A high SCD-1 index has been related to obesity and metabolic disorders, while the D5D index is associated with insulin sensitivity. Fatty acid composition of serum and skeletal muscle lipids was analysed by GLC during a randomised, controlled, 3-month dietary intervention in healthy subjects. A comparison of the effects of a diet containing butter fat (SFA, n 17) with a diet containing monounsaturated fat (MUFA, n 17), keeping all other dietary components constant, showed a reduced SCD-1 activity index by 20% on the MUFA diet compared with the SFA diet assessed in serum cholesteryl esters. The D6D and D5D indices remained unaffected. Supplementation with long-chain n-3 fatty acids reduced the SCD-1 index by a similar magnitude while the D6D index decreased and the D5D index increased. It is concluded that changes in the type of fat in the diet affect the indices of FADS activity in serum and skeletal muscle in human subjects. The desaturase activity indices estimated from the serum lipid ester composition are significantly related to corresponding indices studied in skeletal muscle phospholipids.

Relationship of Δ(6) -desaturase and Δ(5) -desaturase activities with thyroid hormone status in adolescents with eating disorders and weight loss.

AIM: In starvation, there is down-regulation of metabolism and changes in essential fatty acid (FA) status, which could be related to alterations of desaturase activities. Presently, the relationship between thyroid hormones and desaturase activities has been investigated in adolescents with eating disorders and weight loss. METHODS: Serum triiodothyronine concentrations and proportions of polyunsaturated FA in plasma phospholipids were analysed in blood samples from 227 adolescents with ED. Δ(6) -desaturase (D6D) activity was calculated as the FA ratio 20:3ω6/18:2ω6 and Δ(5) -desaturase (D5D) activity as the ratio 20:4ω6/20:3ω6. RESULTS: Serum triiodothyronine concentrations were related to leanness and ongoing weight loss. The estimated D6D activity was positively correlated with serum triiodothyronine (R(2) = 0.232; p < 0.001). D5D activity exhibited a strong inverse correlation with serum triiodothyronine (R(2) = 0.410; p < 0.001). CONCLUSION: Changes in desaturase activities during starvation cannot be explained by inhibition/disinhibition by essential FA only. It is possible that the effects of starvation on these enzyme activities, and hence on essential FA status, are mediated by triiodothyronine.

Fatty acid composition of cholesterol esters reflects dietary fat intake after dietary interventions in a multinational population.

BACKGROUND: The effects of different dietary fatty acids (FA) on cardiovascular risk still needs clarification. Plasma lipids composition may be a biomarker of FA dietary intake. PURPOSE: To evaluate in a composite population the relationships between changes in dietary fat intake and changes in FA levels in serum cholesterol esters. METHODS: In a multinational, parallel-design, dietary intervention (KANWU study), dietary intakes (3-day food record) and FA composition of serum cholesterol esters (gas-liquid chromatography) were evaluated at baseline and after 3 months in 162 healthy individuals, randomly assigned to a diet containing a high proportion of saturated (SFA) or monounsaturated (MUFA) fat, with a second random assignment to fish oil or placebo supplements. RESULTS: Main differences in serum lipid composition after the two diets included saturated (especially myristic, C14:0, and pentadecanoic, C15:0) and monounsaturated (oleic acid, C18:1 n-9) FA. C14:0 and C15:0 were related to SFA intake, while C18:1 n-9 was associated with MUFA intake. Fish oil supplementation induced a marked increase in eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids. After the 3-month intervention, Δ-9 desaturase activity, calculated as palmitoleic acid/palmitic acid (C16:1/C16:0) ratio, was more reduced after the MUFA (0.31±0.10 vs 0.25±0.09, p<0.0001) than SFA diet (0.31±0.09 vs 0.29±0.08, p=0.006), with a statistically significant difference between the two groups (p<0.0001). CONCLUSIONS: This study shows that serum cholesterol ester FA composition can be used during randomized controlled trials as an objective indicator of adherence to experimental diets based on saturated and monounsaturated fat modifications, as well as fish oil supplementation.

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.

Omega-3 polyunsaturated essential fatty acids are associated with depression in adolescents with eating disorders and weight loss.

AIM: To study the relationship between polyunsaturated fatty acids (PUFA) status and depression in adolescents with eating disorders (ED) and weight loss. METHODS: Erythrocyte membranes from 217 adolescents (209 girls, eight boys) with ED were analysed for fatty acids (FA). ED and depression were diagnosed by clinical interviews and supported by self-report instruments. RESULTS: Adolescents with ED and depression did not differ from those with ED only in terms of age, BMI, weight loss and duration of disease. In their FA profile, depressed adolescents had lower proportions of eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), the end products of the ω3 PUFA series. The ratio of long-chain (>18 carbons) ω6/ω3 PUFA was therefore higher in depressed adolescents. Indices of desaturase activities did not differ between depressed and not depressed adolescents. CONCLUSION: Low ω3 status is related to depression in adolescents with ED. This cannot be explained by differences in weight (loss) and duration of disease, nor by differences in PUFA processing by desaturases. Data suggest a lower dietary intake of ω3 PUFA in those with depression. Further investigations should determine whether ω3 PUFA status improves by refeeding only or whether supplementation with PUFA is warranted.

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.

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.

Stroke and plasma markers of milk fat intake--a prospective nested case-control study.

BACKGROUND: Dairy products are high in saturated fat and are traditionally a risk factor for vascular diseases. The fatty acids 15:0 and 17:0 of plasma lipids are biomarkers of milk fat intake. The aim of the present study was to evaluate the risk of a first-ever stroke in relation to the plasma milk fat biomarkers. METHODS: A prospective case-control study was nested within two population based health surveys in Northern Sweden. Among 129 stroke cases and 257 matched controls, plasma samples for fatty acid analyses were available in 108 cases and 216 control subjects. Proportions of 15:0 and 17:0 of plasma lipids, weight, height, blood lipids, blood pressures, and lifestyle data were employed in conditional logistic regression modelling. RESULTS: The proportions of fatty acids 17:0 and 15:0+17:0 of total plasma phospholipids were significantly higher in female controls than cases, but not in men. 17:0 and 15:0+17:0 were significantly and inversely related to stroke in the whole study sample as well as in women. The standardised odds ratio (95% CI) in women to have a stroke was 0.41 (0.24-0.69) for 17:0 in plasma phospholipids. Adjustment for traditional cardiovascular risk factors, physical activity and diet had marginal effects on the odds ratios. A similar, but non-significant, trend was seen in men. CONCLUSION: It is hypothesised that dairy or milk fat intake may be inversely related to the risk of a first event of stroke. The intriguing results of this study should be interpreted with caution. Follow up studies with greater power, and where intakes are monitored both by dietary recordings and fatty acid markers are needed.

Evaluation of relative intake of fatty acids according to the Northern Sweden FFQ with fatty acid levels in erythrocyte membranes as biomarkers.

OBJECTIVE: To evaluate the validity of the Northern Sweden eighty-four-item FFQ to estimate intake of fatty acids relative to 24 h diet recalls (24-HDR) and fatty acids in erythrocyte membranes. DESIGN: Participants, randomly recruited from the population-based Västerbotten Intervention Project, answered the eighty-four-item FFQ. During the following year each participant carried out ten 24-HDR. Intake of fatty acids measured by the FFQ was compared with intake by the 24-HDR and fatty acid levels in erythrocytes. SETTING: The county of Västerbotten in northern Sweden. SUBJECTS: Ninety-six men and ninety-nine women. RESULTS: Spearman correlation coefficients (rs) between intakes of the fatty acids 14 : 0, 15 : 0, 16 : 0, 17 : 0, 18 : 2n-6, 18 : 3n-3, 20 : 5n-3 and 22 : 6n-3 estimated by the FFQ and the 24-HDR were all significant and ranged from 0.29 (22 : 6n-3 in men and women) to 0.60 (16 : 0 in men), whereas significant correlations between FFQ-estimated intake and erythrocyte membrane content were only seen for milk fatty acids 14 : 0, 15 : 0 and 17 : 0 (rs = 0.23-0.34) and fish fatty acids 20 : 5n-3 and 22 : 6n-3 (rs = 0.42-0.51). CONCLUSION: The Northern Sweden eighty-four-item FFQ gives a satisfactory estimate of the intake of fish fatty acids (20 : 5n-3 and 22 : 6n-3) and milk fatty acids (15 : 0 and 17 : 0), whereas its validity for fatty acids 18 : 2n-6 and 18 : 3n-3, derived mainly from vegetable oils, cannot be shown.

Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: links to obesity and insulin resistance.

Fatty acid composition of serum lipids and adipose tissue triacylglycerols (AT-TAG) partly reflect dietary fatty acid intake. The fatty acid composition is, besides the diet, also influenced by desaturating enzymes that can be estimated using product-to-precursor fatty acid ratios. The interrelationships between desaturase indices derived from different serum lipid fractions and adipose tissue are unclear, as well as their associations with obesity and insulin resistance. We aimed to investigate cross-sectional correlations between desaturase indices as measured in serum lipid fractions (phospholipids; PL and free fatty acids; FFA) and in adipose tissue (AT-TAG). In a population-based sample of 301 healthy 60-year-old men various desaturase indices were assessed: stearoyl-CoA-desaturase (16:1n-7/16:0; SCD-16 and 18:1n-9/18:0; SCD-18, respectively), delta-6-desaturase (20:3n-6/18:2n-6; D6D) and delta-5-desaturase (20:4n-6/20:3n-6; D5D). Correlations with BMI and insulin resistance (HOMA-IR) were also examined. SCD-16 and D5D were significantly correlated between fractions and tissues (all r > 0.30), whereas SCD-18 and D6D were not. Desaturase indices in serum FFA and AT-TAG were significantly correlated; SCD-16 (r = 0.63), SCD-18 (r = 0.37), and D5D (r = 0.43). In phospholipids, SCD-16 was positively correlated to BMI (r = 0.15), while D5D negatively to both BMI (r = -0.30) and HOMA-IR (r = -0.31), all p < 0.01. D6D in both phospholipids and AT-TAG was positively correlated to HOMA-IR and BMI (all p < 0.01). In conclusion, SCD-1 and D5D activity indices showed overall strong correlations between lipid pools. SCD-1 activity index in adipose tissue is best reflected by 16:1/16:0-ratio in serum FFA, but associations with obesity and insulin resistance differ between these pools. D5D in PL was inversely related to obesity and insulin resistance, whereas D6D index showed positive associations.

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.

Effects of saturated and unsaturated fatty acids on estimated desaturase activities during a controlled dietary intervention.

BACKGROUND AND AIMS: Direct measurement of desaturase activities are difficult to obtain in humans. Consequently, surrogate measures of desaturase activity (estimated desaturase activities) have been frequently used in observational studies, and estimated Delta(9)- (or stearoyl-CoA-desaturase (SCD)), Delta(6)- and Delta(5)-desaturase activities have been associated with cardiometabolic disease. Data on how the markers of desaturase activities are modified by changes in dietary fat quality are lacking and therefore warrant examination. METHODS AND RESULTS: In a two-period (three weeks) strictly controlled cross-over study, 20 subjects (six women and 14 men) consumed a diet high in saturated fat (SAT-diet) and a rapeseed oil diet (RO-diet), rich in oleic acid (OA), linoleic acid (LA) and alpha-linolenic acid (ALA). Estimated desaturase activities were calculated as precursor to product FA ratios in serum cholesteryl esters and phospholipids. The estimated SCD [16:1 n-7/16:0] and Delta(6)-desaturase [20:3 n-6/18:2 n-6] was significantly higher while Delta(5)-desaturase [20:4 n-6/20:3 n-6] was significantly lower in the SAT-diet (P<0.001 for all), compared to the RO-diet. The serum proportions of palmitic, stearic, palmitoleic and dihomo-gamma-linolenic acids were significantly higher in the SAT-diet while the proportions of LA and ALA were significantly higher in the RO-diet. CONCLUSION: This is the first study to demonstrate that surrogate measures of desaturase activities change as a consequence of an alteration in dietary fat quality. Both the [16:1/16:0]-ratio and 16:1 seem to reflect changes in saturated fat intake and may be useful markers of saturated fat intake in Western countries.

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.

The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study.

BACKGROUND AND AIMS: Hepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of lipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study the effects of the G-250A polymorphism on HL activity, serum lipid profile and insulin sensitivity. METHODS AND RESULTS: Altogether 151 healthy subjects (age 49+/-8 years, BMI 26.5+/-3.0kg/m(2)) were randomly assigned for 3 months to an isoenergetic diet containing either a high proportion of saturated fatty acids (SFA diet) or monounsaturated fatty acids (MUFA diet). Within groups there was a second random assignment to supplements with fish oil (3.6g n-3 FA/day) or placebo. At baseline, the A-250A genotype was associated with high serum LDL cholesterol concentration (P=0.030 among three genotypes). On the MUFA diet carriers of the A-250A genotype presented a greater decrease in LDL cholesterol concentration than subjects with other genotypes (P=0.007 among three genotypes). The rare -250A allele was related to low HL activity (P<0.001 among three genotypes). The diet did not affect the levels of HL activity among the genotypes. CONCLUSION: The A-250A genotype of the LIPC gene was associated with high LDL cholesterol concentration, but the MUFA-enriched diet reduced serum LDL cholesterol concentration especially in subjects with the A-250A genotype.

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.

Leisure physical activity and the risk of fracture in men.

BACKGROUND: Data from previous studies are inconsistent, and it is therefore uncertain whether, to what extent, and at what level leisure physical activity influences the risk of osteoporotic fractures in men. METHODS AND FINDINGS: A cohort of 2,205 men, 49-51 y of age, was enrolled in a longitudinal, population-based study. Leisure physical activity and other lifestyle habits were established at baseline and at ages 60, 70, 77, and 82 y. During 35 y of follow-up, 482 men had at least one fracture. Cox's proportional hazards regression was used to determine hazard ratios (HRs) of fracture associated with time-dependent physical activity habits and covariates. Men with a sedentary lifestyle (HR 2.56, 95% confidence interval 1.55-4.24) or men who walked or bicycled only for pleasure (HR 1.61, 95% confidence interval 1.10-2.36) had an increased adjusted risk of hip fracture compared with men who participated in regular sports activities for at least 3 h/wk. At the end of follow-up, 8.4% of the men with a high physical activity, 13.3% of the men with a medium physical activity, and 20.5% of the men with a low physical activity had suffered a hip fracture. According to the estimation of population-attributable risk, one third of all hip fractures could be prevented by participation in regular sports activities. High activity also conferred a reduced overall fracture risk. CONCLUSIONS: Our data indicate that regular sports activities can reduce the risk of fractures in older men.

Serum retinol levels and the risk of fracture.

BACKGROUND: Although studies in animals and epidemiologic studies have indicated that a high vitamin A intake is associated with increased bone fragility, no biologic marker of vitamin A status has thus far been used to assess the risk of fractures in humans. METHODS: We enrolled 2322 men, 49 to 51 years of age, in a population-based, longitudinal cohort study. Serum retinol and beta carotene were analyzed in samples obtained at enrollment. Fractures were documented in 266 men during 30 years of follow-up. Cox regression analysis was used to determine the risk of fracture according to the serum retinol level. RESULTS: The risk of fracture was highest among men with the highest levels of serum retinol. Multivariate analysis of the risk of fracture in the highest quintile for serum retinol (>75.62 microg per deciliter [2.64 micromol per liter]) as compared with the middle quintile (62.16 to 67.60 microg per deciliter [2.17 to 2.36 micromol per liter]) showed that the rate ratio was 1.64 (95 percent confidence interval, 1.12 to 2.41) for any fracture and 2.47 (95 percent confidence interval, 1.15 to 5.28) for hip fracture. The risk of fracture was further increased within the highest quintile for serum retinol. Men with retinol levels in the 99th percentile (>103.12 microg per deciliter [3.60 micromol per liter]) had an overall risk of fracture that exceeded the risk among men with lower levels by a factor of seven (P<0.001). The level of serum beta carotene was not associated with the risk of fracture. CONCLUSIONS: Our findings, which are consistent with the results of studies in animals, as well as in vitro and epidemiologic dietary studies, suggest that current levels of vitamin A supplementation and food fortification in many Western countries may need to be reassessed.

The apolipoprotein B/AI ratio and the metabolic syndrome independently predict risk for myocardial infarction in middle-aged men.

BACKGROUND: Both the metabolic syndrome and an increased apolipoprotein B/AI (apoB/AI) ratio are powerful risk factors for cardiovascular events. We hypothesized that the apoB/AI ratio well-characterizes the dyslipidemia associated with insulin resistance and the metabolic syndrome and investigated those relations and if the apoB/AI ratio and the metabolic syndrome independently predicted subsequent myocardial infarction (MI). METHODS AND RESULTS: A community-based sample of 1826 men aged 50 was investigated at baseline and again at age 70. ApoB/AI ratio and the metabolic syndrome (National Cholesterol Education Program definition) were evaluated, and the incidence of fatal and nonfatal MI was followed for a median of 26.8 years from the age 50 baseline. ApoB/AI ratio was significantly higher in men with versus without the metabolic syndrome (P<0.0001), and increased with the number of components defining the syndrome (P<0.0001). ApoB/AI ratio was inversely related to euglycemic insulin clamp glucose disposal rate at age 70 (r=-0.34, P<0.0001). During follow-up from age 50, 462 subjects developed an MI. An apoB/AI ratio > or =0.9 (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.15 to 1.91) and presence of the metabolic syndrome (HR, 1.69; 95% CI, 1.30 to 2.21) at baseline were independent predictors for MI, adjusting for low-density lipoprotein cholesterol and smoking. CONCLUSIONS: The apoB/AI ratio was related to the metabolic syndrome, as well as to a direct measurement of insulin resistance. Despite this, the apoB/AI ratio and the metabolic syndrome were both independent long-term predictors of MI in a community-based sample of middle-aged men.