Omega-3 fatty acids in heart disease-why accurately measured levels matter.

Current guidelines barely support marine omega­3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in cardiology, mainly because results of large trials were equivocal. Most large trials have tested EPA alone or EPA + DHA combined as a drug, thereby disregarding the relevance of their blood levels. These levels are frequently assessed with the Omega­3 Index (percentage of EPA + DHA in erythrocytes), which is determined using a specific standardised analytical procedure. EPA and DHA are present in every human being at unpredictable levels (even in the absence of intake), and their bioavailability is complex. Both facts need to be incorporated into trial design and should direct clinical use of EPA and DHA. An Omega­3 Index in the target range of 8-11% is associated with lower total mortality, fewer major adverse cardiac and other cardiovascular events. Moreover, functions of organs such as the brain benefit from an Omega­3 Index in the target range, while untoward effects, such as bleeding or atrial fibrillation, are minimised. In pertinent intervention trials, several organ functions were improved, with improvements correlating with the Omega­3 Index. Thus, the Omega­3 Index is relevant in trial design and clinical medicine, which calls for a widely available standardised analytical procedure and a discussion on possible reimbursement of this test.

Chondrocalcinosis is associated with increased knee joint degeneration over 4 years: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine if presence of calcium-containing crystals (CaC) is associated with increased knee joint degeneration over 4 years and assess if total number of CaCs deposited is a useful measure of disease burden. DESIGN: Seventy subjects with CaCs in right knees at baseline were selected from the Osteoarthritis Initiative and matched to 70 subjects without evidence of CaCs. T1-weighted gradient-echo sequences were used to confirm presence of CaCs and count the numbers of distinct circumscribed CaCs. Morphological abnormalities were assessed at baseline and 4-year follow-up using the modified semi-quantitative Whole-Organ Magnetic Resonance Imaging Score (WORMS). Linear regression models were used to analyze the associations between presence of CaCs at baseline and changes in WORMS and to analyze the associations between numbers of circumscribed CaCs at baseline and changes in WORMS. RESULTS: Presence of CaCs was associated with increased cartilage degeneration in the patella (coefficient: 0.33; 95% confidence interval (CI): 0.04-0.63), the medial femur (coefficient: 0.51; 95% CI: 0.18-0.83), the lateral tibia (coefficient: 0.36; 95% CI: 0.01-0.71) as well as the medial and lateral meniscus (coefficient: 0.38; 95% CI: 0.00-0.75 and coefficient: 0.72; 95% CI: 0.12-1.32). Knees with higher numbers of CaCs had increased cartilage degeneration in the patella and medial femur (coefficient: 0.09; 95% CI: 0.05-0.14; P < 0.001 and coefficient: 0.08; 95% CI: 0.02-0.14; P = 0.005). CONCLUSIONS: CaCs were associated with increased cartilage and meniscus degeneration over a period of 4 years. Assessing the number of CaC depositions may be useful to evaluate risk of onset and worsening of degenerative disease.

Correction to: Exploring the association between whole blood Omega-3 Index, DHA, EPA, DPA, AA and n-6 DPA, and depression and self-esteem in adolescents of lower general secondary education.

The original version of this article unfortunately contained a mistake. Title was incorrect.

Exploring the association between whole blood Omega-3 Index, DHA, EPA, DHA, AA and n-6 DPA, and depression and self-esteem in adolescents of lower general secondary education.

PURPOSE: Depression is common in adolescents and long-chain polyunsaturated fatty acids (LCPUFA) are suggested to be associated with depression. However, research in adolescents is limited. Furthermore, self-esteem has never been studied in relation to LCPUFA. The objective here was to determine associations of depression and self-esteem with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), Omega-3 Index (O3I), n-6 docosapentaenoic acid (n-6 DPA, also called Osbond acid, ObA), n-3 docosapentaenoic acid (DPA), and arachidonic acid (AA) concentrations in blood of adolescents attending lower general secondary education (LGSE). METHODS: Baseline cross-sectional data from a krill oil supplementation trial in adolescents attending LGSE with an O3I ≤ 5% were analysed using regression models built with the BayesFactor package in R. Fatty acids and O3I were determined in blood. Participants filled out the Centre for Epidemiologic Studies Depression (CES-D) scale and the Rosenberg Self-Esteem scale (RSE). RESULTS: Scores indicative of depression (CES-D ≥ 16) were found in 29.4% of the respondents. Of all fatty acids, we found extreme evidence [Bayes factor (BF) > 100] for a weak negative association between ObA and depression score [- 0.16; 95% credible interval (CI) - 0.28 to - 0.04; BF10 = 245], and substantial evidence for a weak positive association between ObA and self-esteem score (0.09; 95% CI, - 0.03 to 0.20; BF10 = 4). When all fatty acids were put in one model as predictors of CES-D or RSE, all of the 95% CI contained 0, i.e., no significant association. CONCLUSION: No evidence was found for associations of DHA, EPA and O3I with depression or self-esteem scores in LGSE adolescents with O3I ≤ 5%. The associations of higher ObA status with lower depression and higher self-esteem scores warrant more research.

[Confusion about the effects of omega-3 fatty acids : Contemplation of study data taking the omega-3 index into consideration]. / Verwirrung um die Wirkung von Omega-3-Fettsäuren : Betrachtung von Studiendaten unter Berücksichtigung des Omega-3-Index.

BACKGROUND: Confusion reigns about omega­3 fatty acids and their effects. Scientific investigations did not appear to clarify the issue. Guidelines and regulatory authorities contradict each other. OBJECTIVE: This article provides clarity by considering not intake but levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocytes as a percentage of all fatty acids measured (omega­3 index). CURRENT DATA: The largest database of all methods of fatty acid analyses has been generated with the standardized HS-Omega­3 Index® (Omegametrix, Martinsried, Deutschland). The omega­3 index assesses the in EPA+DHA status of a person, has a minimum of 2%, a maximum of 20%, and is optimal between 8% and 11%. In many western countries but not in Japan or South Korea, mean levels are suboptimal. Suboptimal levels correlate with increased total mortality, sudden cardiac death, fatal and non-fatal myocardial infarction, other cardiovascular diseases, cognitive impairment, major depression, premature birth and other health issues. Interventional studies on surrogate and intermediary parameters demonstrated many positive effects, correlating with the omega­3 index when measured. Due to issues in methodology that became apparent from the perspective of the omega­3 index many, even large interventional trials with clinical endpoints were not positive, which is reflected in pertinent meta-analyses. In contrast, interventional trials without issues in methodology the clinical endpoints mentioned were reduced. CONCLUSION: All humans have levels of EPA+DHA that if methodologically correctly assessed in erythrocytes, are optimal between 8% and 11%. Deficits can cause serious health issues that can be prevented by optimal levels.

Nutrient reference value: non-communicable disease endpoints--a conference report.

Nutrition is complex-and seemingly getting more complicated. Most consumers are familiar with "essential nutrients," e.g., vitamins and minerals, and more recently protein and important amino acids. These essential nutrients have nutrient reference values, referred to as dietary reference intakes (DRIs) developed by consensus committees of scientific experts convened by the Institute of Medicine of the National Academy of Sciences, Engineering, and Medicine and carried out by the Food and Nutrition Board. The DRIs comprise a set of four nutrient-based reverence values, the estimated average requirements, the recommended dietary allowances (RDAs), the adequate intakes and the tolerable upper intake levels for micronutrient intakes and an acceptable macronutrient distribution range for macronutrient intakes. From the RDA, the US Food and Drug Administration (FDA) derives a labeling value called the daily value (DV), which appears on the nutrition label of all foods for sale in the US. The DRI reports do not make recommendations about whether the DV labeling values can be set only for what have been defined to date as "essential nutrients." For example, the FDA set a labeling value for "dietary fiber" without having the DV. Nutrient reference values-requirements are set by Codex Alimentarius for essential nutrients, and regulatory bodies in many countries use these Codex values in setting national policy for recommended dietary intakes. However, the focus of this conference is not on essential nutrients, but on the "nonessential nutrients," also termed dietary bioactive components. They can be defined as "Constituents in foods or dietary supplements, other than those needed to meet basic human nutritional needs, which are responsible for changes in health status (Office of Disease Prevention and Health Promotion, Office of Public Health and Science, Department of Health and Human Services in Fed Regist 69:55821-55822, 2004)." Substantial and often persuasive scientific evidence does exist to confirm a relationship between the intake of a specific bioactive constituent and enhanced health conditions or reduced risk of a chronic disease. Further, research on the putative mechanisms of action of various classes of bioactives is supported by national and pan-national government agencies, and academic institutions, as well as functional food and dietary supplement manufacturers. Consumers are becoming educated and are seeking to purchase products containing bioactives, yet there is no evaluative process in place to let the public know how strong the science is behind the benefits or the quantitative amounts needed to achieve these beneficial health effects or to avoid exceeding the upper level (UL). When one lacks an essential nutrient, overt deficiency with concomitant physiological determents and eventually death are expected. The absence of bioactive substances from the diet results in suboptimal health, e.g., poor cellular and/or physiological function, which is relative and not absolute. Regrettably at this time, there is no DRI process to evaluate bioactives, although a recent workshop convened by the National Institutes of Health (Options for Consideration of Chronic Disease Endpoints for Dietary Reference Intakes (DRIs); March 10-11, 2015; http://health.gov/dietaryguidelines/dri/ ) did explore the process to develop DVs for nutrients, the lack of which result in increased risk of chronic disease (non-communicable disease) endpoints. A final report is expected soon. This conference (CRN-International Scientific Symposium; "Nutrient Reference Value-Non-Communicable Disease (NRV-NCD) Endpoints," 20 November in Kronberg, Germany; http://www.crn-i.ch/2015symposium/ ) explores concepts related to the Codex NRV process, the public health opportunities in setting NRVs for bioactive constituents, and further research and details on the specific class of bioactives, n-3 long-chain polyunsaturated fatty acids (also termed omega-3 fatty acids) and their constituents, specifically docosahexaenoic acid and eicosapentaenoic acid.

Omega-3 fatty acids vs. cardiac disease--the contribution of the omega-3 index.

Although statistically and clinically significant, reductions of clinical events seen in large scale intervention studies with omega-3 fatty acids in the cardiovascular field were smaller than would have been predicted from the results of epidemiologic studies. In epidemiologic studies, assessment of intake of fish or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) predicted clinical events less well than assessing blood levels of EPA and DHA, e.g. by the Omega-3 Index. The Omega-3 Index is the percentage of EPA+DHA in red cell lipids, determined with a highly standardized methodology. Using the perspective of the Omega-3 Index facilitates reconciling discrepancies in results from intervention studies and from epidemiologic studies. Moreover, a low Omega-3 Index can be considered a risk factor for sudden cardiac death and for non-fatal cardiovascular events, whereas a high Omega-3 Index can be used as a therapeutic target. Currently ongoing and future scientific work on the basis of the Omega-3 Index will further define its value.

Effect of one year krill oil supplementation on depressive symptoms and self-esteem of Dutch adolescents: A randomized controlled trial.

INTRODUCTION: Observational studies have shown a relationship between omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) and depression in adolescents. However, n-3 LCPUFA supplementation studies investigating the potential improvement in depressive feelings in adolescents from the general population are missing. METHODS: A one-year double-blind, randomized, placebo controlled krill oil supplementation trial was conducted in two cohorts. Cohort I started with 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or placebo, after three months this increased to 800 mg EPA and DHA per day, whilst cohort II started with this higher dose. Omega-3 Index (O3I) was monitored via finger-prick blood measurements. At baseline, six and 12 months participants completed the Centre for Epidemiologic Studies Depression Scale (CES-D) and the Rosenberg Self Esteem questionnaire (RSE). Adjusted mixed models were run with treatment allocation/O3I as predictor of CES-D and RSE scores. RESULTS: Both intention-to-treat and assessing the change in O3I analyses did not show significant effects on CES-D or RSE scores. CONCLUSION: There is no evidence for less depressive feelings, or higher self-esteem after one year of krill oil supplementation. However, due to a lack of adherence and drop-out issues, these results should be interpreted with caution.

Metabolism and effects on platelet function of the purified eicosapentaenoic and docosahexaenoic acids in humans.

Metabolism and effects on platelet function of 6 g/d for 6 d of either eicosapentaenoic acid (EPA, C20:5 omega-3) or docosahexaenoic acid (DCHA, C22:6 omega-3) in volunteers were compared in a randomized crossover study. Incorporation kinetics revealed that EPA appeared in plasma free fatty acids and plasma phospholipids after 4 h, but was not incorporated into platelet phosphatidylcholine and -ethanolamine until day 6. This indicates that platelet fatty acid composition does not immediately reflect that of the surrounding plasma milieu, but rather may be determined during megakaryocyte maturation. Importantly, EPA was not incorporated into platelet phosphatidylinositol or -serine in vivo, thus reflecting selective biosynthesis of platelet phospholipids. After dietary EPA, C22:5 omega-3 increased in plasma and platelet phospholipids. In contrast, DCHA-levels were unaltered. After DCHA-ingestion, C20:5 omega-3 concentrations rose in plasma phospholipids, implying that retroconversion took place. These findings indicate that dietary DCHA can serve as a source of EPA. During this short-term study, ingestion of both EPA and DCHA resulted in reduced platelet aggregation in response to collagen. The response to ADP was lowered significantly only by DCHA. After either EPA or DCHA, thromboxane formation was unchanged in serum derived from clotted whole blood as was total in vivo synthesis measured by excretion of immunoreactive 2,3-dinor thromboxane B2/3. We conclude that DCHA reduces platelet responsiveness, contributing to the antithrombotic effects of omega-3 fatty acid-rich fish oil ingestion, of which DCHA is a major component.

Long-term effects of dietary marine omega-3 fatty acids upon plasma and cellular lipids, platelet function, and eicosanoid formation in humans.

We studied the incorporation and metabolism of eicosapentanoic (EPA) and docosahexaenoic acid in six human volunteers who supplemented their normal Western diet for 5 mo daily with 10-40 ml of cod liver oil, rich in omega-3 polyunsaturated fatty acids. EPA and docosahexaenoic acid were incorporated into the total phospholipids of plasma, platelets, and erythrocytes in a dose- and time-dependent manner. During omega-3 fatty acid ingestion serum triacylglycerols were lowered and platelet aggregation upon low doses of collagen was reduced. Concomitantly, formation and excretion of prostanoids showed a characteristic change. As measured in serum from whole clotted blood, thromboxane A3 was formed in small amounts, whereas thromboxane A2 formation was reduced to 50% of control values. Excretion of the main urinary thromboxane A metabolites was unaltered in subjects with low basal excretion rates, but decreased markedly in two subjects with high control values. As determined from the main urinary metabolite, prostaglandin I3 was formed from EPA at rates up to 50% of unaltered prostaglandin I2 formation. The biochemical and functional changes observed lasted for the entire supplementation period of 5 mo and were reversible within 12 wk after cessation of cod liver oil intake. Favorable changes induced by long-chain omega-3 fatty acids include a dose-related and sustained shift of the prostaglandin I/thromboxane A balance to a more antiaggregatory and vasodilatory state.

Studies on the mechanism of omega-hydroxylation of platelet 12-hydroxyeicosatetraenoic acid (12-HETE) by unstimulated neutrophils.

Stimulated platelets, in the presence or absence of aspirin, synthesize significant quantities of 12-hydroxyeicosatetraenoic acid (12-HETE), which is chemotactic and chemokinetic, and enhances mononuclear cell procoagulant activity. During a cell-cell interaction between stimulated platelets and unstimulated neutrophils, platelet 12-HETE is metabolized to 12,20-dihydroxyeicosatetraenoic acid (12,20-DiHETE) by neutrophils. Characteristics of the enzyme system in unstimulated neutrophils responsible for this omega-hydroxylation were investigated. A broad range of cytochrome P-450 inhibitors, as well as leukotriene B4, blocked formation of 12,20-DiHETE. Owing largely to released proteases, neutrophil homogenization abolished activity. Pretreatment with diisopropylfluorophosphate preserved activity in neutrophil homogenates. omega-Hydroxylation of 12-HETE was confined solely to the microsomal fraction. Specific activity increased 6.6-fold compared with neutrophil sonicates. The electron donor NADPH was a required cofactor. These results indicate that the enzyme in unstimulated human neutrophils, which metabolizes 12-HETE from stimulated platelets to 12,20-DiHETE in this cell-cell interaction, is a cytochrome P-450 monooxygenase.

Omega-3 fatty acids predict recurrent venous thromboembolism or total mortality in elderly patients with acute venous thromboembolism.

Essentials The role of omega-3 fatty acids (n-3 FAs) in recurrent venous thromboembolism (VTE) is unknown. Association of n-3 FAs with recurrent VTE or total mortality was investigated in 826 patients. Whole blood n-3 FAs were inversely correlated with recurrent VTE or total mortality. Major and non-major bleeding was not increased in patients with higher levels of n-3 FAs. SUMMARY: Background The role of omega-3 fatty acids (n-3 FAs) in recurrent venous thromboembolism (VTE) remains unknown. Objectives To investigate the association of n-3 FAs with recurrent VTE or total mortality at 6 months and 3 years. Methods N-3 FAs were assessed in 826 patients aged ≥ 65 years, categorized into low, medium and high based on the 25th and 75th percentile. Mean follow-up was 29 months. Results At 6 months, subjects with medium (adjusted hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22-0.62) and high n-3 FA levels (adjusted HR, 0.36; 95% CI, 0.20-0.67) were less likely to develop recurrent VTE or total mortality, compared with those with low n-3 FAs. At 3 years, medium levels (adjusted HR, 0.67; 95% CI, 0.47-0.96) were associated with lower risk of recurrent VTE or total mortality. As compared with low n-3 FAs, the adjusted sub-hazard ratio [SHR] of recurrent VTE was 0.39 (95% CI, 0.15-0.99) in patients with medium and 0.17 (95% CI, 0.03-0.82) in patients with high n-3 FAs. The cumulative incidence of recurrent VTE was lower in the medium and high n-3 FA groups as compared with the low n-3 FA groups, but seems to have worn off after 3 years. The incidence of major and non-major bleeding was not greater in the high n-3 FA group. Conclusion Higher levels of n-3 FAs were associated with a lower risk of recurrent VTE or total mortality in elderly patients with VTE, but not with greater bleeding risk.

A protocol for a randomised controlled trial investigating the effect of increasing Omega-3 index with krill oil supplementation on learning, cognition, behaviour and visual processing in typically developing adolescents.

INTRODUCTION: The influence of n-3 long-chain polyunsaturated fatty acids (LCPUFA) supplementation on brain functioning is debated. Some studies have found positive effects on cognition in children with learning difficulties, elderly people with cognitive impairment and depression scores in depressed individuals. Other studies have found null or negative effects. Observational studies in adolescents have found positive associations between fish consumption (containing n-3 LCPUFAs) and academic achievement. However, intervention studies in typically developing adolescents are missing. OBJECTIVE: The goal of this study is to determine the influence of increasing Omega-3 Index on cognitive functioning, academic achievement and mental well-being of typically developing adolescents. METHODS AND DATA ANALYSIS: Double-blind, randomised, placebo controlled intervention; 264 adolescents (age 13-15 years) attending lower general secondary education started daily supplementation of 400 mg eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA) in cohort I (n=130) and 800 mg EPA+DHA in cohort II (n=134) or a placebo for 52 weeks. Recruitment took place according to a low Omega-3 Index (<5%). The Omega-3 Index was monitored via a finger prick at baseline and after 3, 6 and 12 months. The supplement dose was adjusted after 3 months (placebo analogously) to reach an Omega-3 Index of 8-11%. At baseline, 6 and 12 months, a neuropsychological test battery, a number of questionnaires and a standardised math test (baseline and 12 months) were administered. School grades were collected. In a subsample, sleep quality and quantity data (n=64) and/or eye-tracking data (n=33) were collected. ETHICS AND DISSEMINATION: Food2Learn is performed according to Good Clinical Practice. All data collected are linked to participant number only. The results will be disseminated on group level to participants and schools. The results will be presented at conferences and published in peer-reviewed journals. The study is approved by the Medical Ethical Committee of Atrium-Orbis-Zuyd Hospital and is registered at the Netherlands Trial Register (NTR4082). TRIAL REGISTRATION NUMBERS: NTR4082 and NCT02240264; Pre-results.

Prostaglandins E3 and F3 alpha are excreted in human urine after ingestion of n - 3 polyunsaturated fatty acids.

Prostaglandins E3 and F3 alpha, presumably of renal origin, were characterized for the first time in urine of volunteers after ingestion of n - 3 polyunsaturated fatty acids by combined gas chromatography-mass spectrometry. Quantitation of prostaglandins E3, E2, F3 alpha and F2 alpha using deuterated internal standards showed low levels of the 3 series prostaglandins in the control period. Levels of prostaglandins E3 and F3 alpha rose about 10-fold by the 12th week of the dietary trial and were still elevated 4-fold after a wash-out period of 20 weeks. Excretion of prostaglandins E2 and F2 alpha tended to be depressed in the 12th week of the dietary trial and rose again to control values after the wash-out period. Our data indicate that n - 3 polyunsaturated fatty acids are incorporated into the human kidney and are retained there for a long time. Prostaglandins E3 and F3 alpha may contribute to the observed favorable effects of marine oils rich in n - 3 polyunsaturated fatty acids on certain renal diseases.

IGF-1, PDGF and CD18 are adherence-responsive genes: regulation during monocyte differentiation.

Unstimulated mononuclear cells express IGF-1, PDGF-A and PDGF-B mRNA, but not a number of other genes coding for growth factors or cytokines, as we demonstrated previously. The main focus of the present investigation was to compare gene expression of mononuclear cells unstimulated in suspension with gene expression of monocytes stimulated by adherence. mRNA levels of IGF-1-A and -B, PDGF-A, -B, PD-ECGF, basic FGF, acidic FGF, TGF-alpha, TGF-beta 1, and IGF-2 were sought for and quantified with our sensitive RT-PCR method (3n-PCR). The respective mRNAs of basic FGF, acidic FGF, TGF-alpha and IGF-2 were not detected, independent of the culture conditions. In suspension culture, mRNA levels of IGF-1A and -B, PDGF-A, -B, and CD18 remained unchanged. Monocyte adherence regulated IGF-1A, PDGF-A, and -B mRNA levels. In parallel, mRNA levels of the monocyte adhesion molecule CD18 increased rapidly (4.5-fold). In contrast, independent of the presence of an adherence stimulus, the mRNAs for the cytoskeletal structure protein beta-actin and PD-ECGF remained constant, whereas mRNA for growth factors TGF-beta 1 and IGF-1B, respectively, was increased. Thus, monocyte adherence selectively regulates IGF-1, PDGF-A, PDGF-B and CD18 mRNAs (adherence-responsive genes) in a coordinated manner. This led us to identify two novel consensus elements within their respective functional promoters. Both motifs, an 11 bp purine-rich sequence and a 13 bp pyrimidine-rich segment, respectively, are absent from the genes that were not specifically activated by adherence. The identified elements are potential binding sites for transcription factors that may define a common basis for the regulation of the adherence-responsive genes IGF-1A, PDGF-A, PDGF-B and CD18.

Dietary n-3 fatty acids accelerate catabolism of leukotriene B4 in human granulocytes.

Addition of n-3 fatty acids to a human diet for more than 3 weeks lowers levels of the powerful proinflammatory compound, leukotriene (LT) B4. This can be shown ex vivo after stimulation of human granulocytes with ionophore A23187. In a controlled, randomized, observer-blind study in 14 human volunteers, we investigated the effect of adding 7 g/day of a 85% n-3 fatty acid concentrate to the diet of 7 volunteers (7 served as controls). Levels of LTB4, 20-OH-LTB4, 20-COOH-LTB4 as well as LTB5, 20-OH-LTB5 and 20-COOH-LTB5 were measured by high-pressure liquid chromatography (HPLC) after stimulation and extraction of a platelet-free granulocyte preparation (92% neutrophils). LTB5 and 20-COOH-LTB5 were only detected during n-3 fatty acids, when 20-OH-LTB5 increased from trace amounts to substantial quantities. Importantly, levels of catabolites of LTB4, i.e., 20-OH-LTB4 and 20-COOH-LTB4 were not significantly altered throughout the study. However, the level of LTB4 itself was reduced dramatically after 6 weeks (less so after 1 week) of dietary n-3 fatty acid administration. These data demonstrate that during dietary n-3 fatty acids levels of LTB4 are lowered by a combination of accelerated catabolism and diminished LTB4 generation. This newly observed mechanism of increased LT catabolism may be mediated via induction of peroxisomal enzymes catabolizing leukotrienes B.

Pilot study on omega-3 fatty acids in type I diabetes mellitus.

Patients with diabetes mellitus are prone to develop vascular complications. Because omega-3 polyunsaturated fatty acid (omega 3FA) intake has a potential protective effect on cardiovascular disease, we studied the influence of omega 3FA supplementation (5.4 g eicosapentaenoic acid and 2.3 g docosahexaenoic acid daily) for 4 wk in 13 well-controlled type I (insulin-dependent) diabetic subjects on a vascular risk profile. Each subject served as his/her own control in a pre- and post-omega 3FA-intake phase. In plasma and platelets, phospholipids eicosapentaenoic acid and docosahexaenoic acid increased at the expense of arachidonic acid and linoleic acid. There was no significant change in blood pressure and glycosylated proteins. Only small changes were noted in blood glucose levels and insulin dose. Side effects were not noted. Triglycerides decreased significantly in the first 14 days, and total cholesterol increased slightly, probably because of an elevation of high-density lipoprotein cholesterol, although low-density lipoprotein cholesterol remained unchanged. Platelet aggregation induced by low doses of ADP and collagen, which was higher in diabetic than nondiabetic subjects, decreased during omega 3FA intake to levels of healthy control subjects. Thromboxane production after ADP- and collagen-induced platelet aggregation decreased significantly. Thromboxane liberation during clotting of whole blood and urinary excretion of thromboxane were markedly lowered during omega 3FA supplementation. The results show that even short-term intake of omega 3FAs leads to beneficial changes of vascular risk factors without significant changes in glucose homeostasis.

Hormone replacement therapy and distensibility of carotid arteries in postmenopausal women: a randomized, controlled trial.

OBJECTIVES: The study objective was to clarify in a randomized, controlled, observer-blind trial whether hormone replacement therapy (HRT) improves elastic properties of the common carotid artery in women with signs of subclinical atherosclerosis, especially in subgroups with increased risk, and whether less progestin enhances the effect. BACKGROUND: Previous observational studies have yielded conflicting results on the influence of HRT on central arteries. Some studies reported improvement of distensibility by estrogen alone or in the subgroup of smokers. METHODS: A total of 321 postmenopausal women were randomized to 1 mg 17beta-estradiol plus 0.025 mg gestodene for 12 days every month (HRT 1), or 1 mg 17beta-estradiol plus 0.025 mg gestodene for 12 days every third month (HRT 2), or no-HRT, during 48 weeks. In 173 women, distensibility of the common carotid artery was determined before and after therapy by M-mode ultrasound and brachial blood pressure measurement. RESULTS: Change of distensibility was small and similar in the three treatment groups. In the subgroup of current smokers, HRT 2 (low progestin) increased distensibility by 32% (HRT 2: 8.2+/-11.7; HRT 1:0.6+/-6.0; no HRT: -1.8+/-6.8 x 10(-3)/kPa, p = 0.025 for no-HRT vs. HRT 2). In the subgroups with elevated blood pressure, high low density lipoprotein (LDL) cholesterol, or high age, no effect of HRT was detected. CONCLUSIONS: This randomized intervention study demonstrates that long-term HRT with estrogen and progestin does not substantially influence distensibility of central arteries. Yet, in currently smoking postmenopausal women, HRT with low progestin seems to improve distensibility; this merits further study in a specifically designed trial.

Impact of social support, cynical hostility and anger expression on progression of coronary atherosclerosis.

OBJECTIVES: This prospective cohort study of patients with coronary artery disease (CAD) sought to determine the impact of social support, anger expression and cynical hostility on progression of coronary atherosclerosis as shown by angiography. BACKGROUND: Low social support, high levels of expressed anger and cynical hostility are correlated to increased CAD morbidity and mortality. However, the impact of these factors, alone or together, on progression of human coronary atherosclerosis is unknown. METHODS: Of 223 patients with CAD documented by standardized angiography at baseline, 162 had a second angiogram after two years. An expert panel who had no knowledge of the patients' characteristics evaluated the films pairwise to determine disease progression. At baseline, all patients were asked to answer three self-report questionnaires: questions concerning emotional social support, the State-Trait-Anger-Expression Inventory (STAXI) and the Cook-Medley cynical hostility scale. Each patient's clinical and laboratory status was followed. RESULTS: Questionnaires and angiographic follow-up data were available for 150 patients. Bivariate analysis of the psychological variables showed a higher risk of progression only for patients who scored high on STAXI anger-out or low on social support. In the multivariate analysis, when adjusting for confounding variables and examining the interaction between psychological variables, only patients with both high anger-out and low social support were at highly increased risk for progression (odds ratio 30, confidence interval [CI] 5.5 to 165.1; RR 3.19). CONCLUSIONS: Patients with CAD and low emotional social support who express anger outwardly are at a highly increased risk of disease progression, independent of medication or other risk factors.