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.

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.

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.

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.

[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.

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.

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.

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.

Heart rate variability and Omega-3 Index in euthymic patients with bipolar disorders.

BACKGROUND: Affective disorders are associated with an increased risk of cardiovascular disease, which, at least partly, appears to be independent of psychopharmacological treatments used to manage these disorders. Reduced heart rate variability (SDNN) and a low Omega-3 Index have been shown to be associated with increased risk for death after myocardial infarction. Therefore, we set out to investigate heart rate variability and the Omega-3 Index in euthymic patients with bipolar disorders. METHODS: We assessed heart rate variability (SDNN) and the Omega-3 Index in 90 euthymic, mostly medicated patients with bipolar disorders (Bipolar-I, Bipolar-II) on stable psychotropic medication, free of significant medical comorbidity and in 62 healthy controls. Heart rate variability was measured from electrocardiography under a standardized 30 minutes resting state condition. Age, sex, BMI, smoking, alcohol consumption and caffeine consumption as potential confounders were also assessed. RESULTS: Heart rate variability (SDNN) was significantly lower in patients with bipolar disorders compared to healthy controls (35.4 msec versus 60.7 msec; P<0.0001), whereas the Omega-3 Index did not differ significantly between the groups (5.2% versus 5.3%). In a linear regression model, only group membership (patients with bipolar disorders versus healthy controls) and age significantly predicted heart rate variability (SDNN). CONCLUSION: Heart rate variability (SDNN) may provide a useful tool to study the impact of interventions aimed at reducing the increased risk of cardiovascular disease in euthymic patients with bipolar disorders. The difference in SDNN between cases and controls cannot be explained by a difference in the Omega-3 Index.

Optoacoustic imaging and staging of inflammation in a murine model of arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is one of the most frequent inflammatory diseases, causing pain and disability in the affected joints. Early diagnosis is essential for the efficiency of symptom-targeting treatments, but its diagnosis requires careful clinical, serologic, and imaging examinations, such as magnetic resonance imaging (MRI), which is both expensive and time consuming. In an effort to provide the biomedical community with a more accessible way to assess the advancement of arthritis, this study sought to investigate the use of multispectral optoacoustic tomography (MSOT) in a murine arthritis model, to visualize the extent of inflammation in vivo through an L-selectin/P-selectin-targeting contrast agent. METHODS: Mice with collagen-induced arthritis were studied as a model of RA. MSOT was performed using an L-selectin/P-selectin-targeting contrast agent, polyanionic dendritic polyglycerol sulfate (dPGS) labeled with a near-infrared (NIR) fluorophore, to increase the contrast of the arthritic joint. The signal intensity ratios between healthy legs and arthritic legs were calculated. Findings on contrast-enhanced MRI, clinical observations, the lymphocyte:granulocyte ratio, and histologic findings served as referents for comparison. RESULTS: MSOT using an inflammation-targeting contrast agent, dPGS-NIR, allowed for accurate diagnosis of inflammation in the mouse joints. In addition, use of this technique resulted in significant differentiation of the inflamed joints from the healthy joints (P = 0.023). The observed advancement of arthritis on the MSOT images was confirmed by clinical observation, blood analysis, contrast-enhanced MRI, and ex vivo histologic examinations. CONCLUSION: This study demonstrates that the combination of an inflammation-targeting contrast agent and optoacoustic tomographic imaging presents a promising means for the diagnosis of RA and the staging of arthritis-related inflammation.

Omega-3 Fatty acids: anti-arrhythmic, pro-arrhythmic, or both?

This review focuses on developments after 2008, when the topic was last reviewed by the author. Pertinent publications were found by medline searches and in the author's personal data base. Prevention of atrial fibrillation (AF) was investigated in a number of trials, sparked by one positive report on the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), considerations of upstream therapy, data from electrophysiologic laboratories and animal experiments. If EPA + DHA prevent postoperative AF, the effect is probably smaller than initially expected. The same is probably true for maintenance of sinus rhythm after cardioversion and for new-onset AF. Larger trials are currently ongoing. Prevention of ventricular arrhythmias was studied in carriers of an implanted cardioverter-defibrillator, with no clear results. This might have been due to a broad definition of the primary endpoint, including any ventricular arrhythmia and any action of the device. Epidemiologic studies support the contention that high levels of EPA + DHA prevent sudden cardiac death (SCD). However, since SCD is a rare occurrence, it is difficult to conduct an adequately powered trial. In patients with congestive heart failure, EPA + DHA reduced total mortality and rehospitalizations, but not SCD or presumed arrhythmic death. Of three trials in patients after a myocardial infarction, two were inadequately powered, and in one, the dose might have been too low. Taken together, while epidemiologic studies support an inverse relation between EPA + DHA and occurrence of SCD or arrhythmic death, demonstrating this effect in intervention trials remained elusive so far. A pro-arrhythmic effect of EPA + DHA has not been seen in intervention studies, and results of epidemiologic and animal studies also rather argue against such an effect. A different, and probably more productive, perspective is provided by a standardized analytical assessment of a person's status in EPA + DHA by use of the omega-3 index, EPA + DHA in red cell fatty acids. In populations with a high omega-3 index, SCD is rare. Intervention trials can become more effective by including a low omega-3 index into the inclusion criteria, thus creating a study population more likely to demonstrate an effect of EPA + DHA. This is especially relevant in case of rare endpoints, like new-onset AF or SCD.

Red blood cell fatty acids are associated with depression in a case-control study of adolescents.

INTRODUCTION: Epidemiological studies suggest that reduced intakes and/or blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with increased risk for depression in adults, but data on adolescents are scarce. The objective of this study was to determine whether red blood cell (RBC) levels of EPA+DHA (the omega-3 index) and/or the overall RBC fatty acid profile differ between depressed adolescents (cases) and non-depressed adolescents (controls). PATIENTS AND METHODS: We measured the RBC fatty acid composition of cases admitted to the hospital for depression (n=150) and compared it to that of controls (n=161). RESULTS: Cases and controls had similar ages, gender proportions, and body mass index (BMI) distributions, but there was a significant difference in racial/ethnic composition due to differences in recruitment sites. The unadjusted odds ratio for case status was 0.72 (95% CI; 0.55-0.95) for a 1% absolute increase in the omega-3 index. A multivariable logistic regression model was used to determine which fatty acids were useful in classifying cases and controls; BMI, age, gender, and race/ethnicity were forced into the model. Seven fatty acids were selected (DHA, myristic, stearic, oleic, trans linoleic, trans palmitoleic, and alpha-linolenic acids) to optimize the model fit to the data. In the adjusted model, the odds ratio was 0.67 (95% CI; 0.49-0.93) for a 1 SD increase in DHA. Adding the seven fatty acid profile to the basic model increased the area under the ROC curve by 12.6% (7.5%-17.6%). DISCUSSION AND CONCLUSION: These findings support the hypothesis that adolescent depression is associated with a perturbed RBC fatty acid pattern which includes a reduced omega-3 index. Intervention studies with EPA and DHA should be conducted in this vulnerable population for which few, safe therapeutic options currently exist.

Moderate doses of EPA and DHA from re-esterified triacylglycerols but not from ethyl-esters lower fasting serum triacylglycerols in statin-treated dyslipidemic subjects: Results from a six month randomized controlled trial.

Recently, in a supplementation study over six months, it has been demonstrated that re-esterified omega-3 fatty acid triacylglycerols (n3-FA-rTAGs) led to a higher increase in omega-3-index compared to identical doses of n3-FA ethyl-esters (n3-FA-EEs), suggesting a better long-term bioavailability. The aim of this study was to examine whether differences occur between the two forms in affecting fasting serum lipid levels. 150 dyslipidemic statin-treated participants were randomized to corn oil as a placebo or fish oil either as rTAG or EE in identical doses (1.01g EPA+0.67g DHA). No changes in total cholesterol, HDL or LDL levels were observed. In the rTAG-group, but not in the EE-group, fasting serum TAG levels were significantly reduced from baseline after three and six months. There was no significant difference between the two n3-FA-groups. However, serum TAG levels were significantly lowered after six months in the rTAG-group compared to the placebo-group in contrast to the EE-group.

Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters.

BACKGROUND: There is a debate currently about whether different chemical forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are absorbed in an identical way. The objective of this study was to investigate the response of the omega-3 index, the percentage of EPA+DHA in red blood cell membranes, to supplementation with two different omega-3 fatty acid (n-3 FA) formulations in humans. DESIGN: The study was conducted as a double-blinded placebo-controlled trial. A total of 150 volunteers was randomly assigned to one of the three groups: (1) fish oil concentrate with EPA+DHA (1.01 g+0.67 g) given as reesterified triacylglycerides (rTAG group); (2) corn oil (placebo group) or (3) fish oil concentrate with EPA+DHA (1.01 g+0.67 g) given as ethyl ester (EE group). Volunteers consumed four gelatine-coated soft capsules daily over a period of six months. The omega-3 index was determined at baseline (t(0)) after three months (t(3)) and at the end of the intervention period (t(6)). RESULTS: The omega-3 index increased significantly in both groups treated with n-3 FAs from baseline to t(3) and t(6) (P<0.001). The omega-3 index increased to a greater extent in the rTAG group than in the EE group (t(3): 186 versus 161% (P<0.001); t(6): 197 versus 171% (P<0.01)). CONCLUSION: A six-month supplementation of identical doses of EPA+DHA led to a faster and higher increase in the omega-3 index when consumed as triacylglycerides than when consumed as ethyl esters.

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.

n-3 PUFA in CVD: influence of cytokine polymorphism.

In their current guidelines cardiac societies recommend the consumption of the two n-3 fatty acids EPA and DHA to prevent cardiovascular complications. Cardiovascular events are reduced by EPA and DHA, because they are antiarrhythmic, mitigate the course of atherosclerosis and stabilise plaque. As atherosclerosis is considered an inflammatory disorder a number of studies have investigated the anti-inflammatory mechanisms of EPA and DHA in a cardiovascular context in human dietary intervention studies. Pro-inflammatory cytokines, or cytokines reflecting inflammatory processes, e.g. IL-1beta, IL-2, IL-6, TNFalpha, platelet-derived growth factor (PDGF)-A and -B and monocyte chemoattractant protein-1 (MCP-1), are reduced by ingestion of EPA and DHA by human subjects. Interestingly, C-reactive protein remains largely unaltered. However, in in vitro and animal models, but less so in human subjects, soluble cytokines reflecting interactions between blood cells and the vessel wall, such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, are reduced. Moreover, in contrast to common expectations, oxidative stress seems to be reduced after ingestion of EPA and DHA, at least as indicated by measurement of urinary F(2) isoprostane excretion. Notably, for PDGF-A and -B and for MCP-1 the reduction has been demonstrated to occur at the gene expression level, which indicates that a deliberate change in diet can alter gene expression quantitatively. The precise underlying mechanism, however, remains to be clarified, but might involve PPAR, NF-kappaB and/or the eicosanoid system. The same holds true for the mechanisms by which levels of other cytokines are altered by EPA and DHA.

[Total risk for cardiovascular disease. At what point is medical prophylactic medication useful?]. / Gesamtrisiko für kardiovaskuläre Erkrankungen Ab wann ist eine medikamentöse Prophylaxe sinnvoll?

Despite the epidemiological importance of coronary artery disease: cardiovascular events are rare from the individual viewpoint. There is considerable uncertainty when to start medical treatment. A given risk factor modification results in a relative risk reduction independent of the global risk. Therefore the global risk determines the absolute benefit of a preventive measure. The global risk can be estimated using different scoring systems. Using the global risk and the expected relative risk reduction, the number needed to treat (NNT) to avoid one event or cardiac death can be calculated. The NNT is a measure for the usefulness of a preventive intervention. A NNT of <200 appears acceptable for primary prevention. This can be achieved with pharmacological preventive strategies if the global risk of 10 years is > or =20%. As age is one of the most important risk predictors the need for treatment at comparable risk factor constellations is age dependent. Risk stratification with estimation of the NNT is therefore important for the decision to treat or not to treat.