New published study: Data demonstrating that, once you get to be past 85, you have three options: either you are dead, demented, or you have an omega-3-index >8%. 

Atherosclerosis. 2016 Sep;252:175-81. doi: 10.1016/j.atherosclerosis.2016.06.049. Epub 2016 Jul 1.
Omega-3 fatty acids and mortality in patients referred for coronary angiography. The Ludwigshafen Risk and Cardiovascular Health Study
Marcus E. Kleber , Graciela E. Delgado, Stefan Lorkowski , Winfried März , Clemens von Schacky  

a Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
b Competence Cluster of Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany
c Institute of Nutrition, Friedrich Schiller University Jena, Germany
d Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria
e Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany
f Omegametrix GmbH, Martinsried, Germany
g Department of Preventive Cardiology, Medizinische Klinik und Poliklinik I, Ludwig Maximilians University, Munich, Germany

Background and aims: There is an ongoing debate whether omega-3-fatty acids protect from cardio- vascular disease mortality. We examined the associations of erythrocyte omega-3 fatty acids with mortality in patients referred for coronary angiography. Methods: Erythrocyte omega-3 fatty acid proportions were measured at baseline in 3259 participants of the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) using the HS-Omega-3 Index method. Associations of omega-3 fatty acid proportions with mortality were investigated using Cox proportional hazards regression. 

Results: During a median follow-up of 9.9 years, 975 patients (29.9%) died, 614 patients (18.8%) from cardiovascular causes. Proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were inversely associated with all-cause and cardiovascular mortality in models adjusted for conventional cardiovascular risk factors. The strongest association was observed for EPA with a hazard ratio (HR) of 0.89 (0.83e0.96) per increase of one standard deviation. Furthermore, we obtained evidence for a non- linear relation between EPA and mortality. 

Conclusions: EPA and DHA were associated with reduced mortality in LURIC, independent of other risk factors, with the association of EPA with mortality being non-linear. 

Original Investigation | June 27, 2016

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease

Pooling Project of 19 Cohort Studies ONLINE FIRST

Liana C. Del Gobbo, PhD1; Fumiaki Imamura, PhD2; Stella Aslibekyan, PhD3; Matti Marklund, PhD4; Jyrki K. Virtanen, PhD5; Maria Wennberg, PhD6; Mohammad Y. Yakoob, PhD1; Stephanie E. Chiuve, ScD7,8; Luicito dela Cruz, PhD9; Alexis C. Frazier-Wood, PhD10; Amanda M. Fretts, MPH, PhD11; Eliseo Guallar, PhD12; Chisa Matsumoto, PhD, MD13,14; Kiesha Prem, MSc15; Tosh Tanaka, PhD16; Jason H. Y. Wu, PhD17; Xia Zhou, PhD18; Catherine Helmer, MD, PhD19,20; Erik Ingelsson, MD, PhD1,21; Jian-Min Yuan, MD, PhD22,23; Pascale Barberger-Gateau, PhD19,20; Hannia Campos, PhD24; Paulo H. M. Chaves, MD, PhD25; Luc Djoussé, MD, ScD14; Graham G. Giles, PhD9; Jose Gómez-Aracena, PhD26; Allison M. Hodge, PhD9; Frank B. Hu, PhD, MD, MPH8,24,27; Jan-Håkan Jansson, MD, PhD6; Ingegerd Johansson, PhD28; Kay-Tee Khaw, PhD, MD29; Woon-Puay Koh, PhD15,30; Rozenn N. Lemaitre, PhD, MPH31; Lars Lind, PhD21; Robert N. Luben, PhD29; Eric B. Rimm, ScD8,24,27; Ulf Risérus, PhD, MD4; Cecilia Samieri, PhD19,20; Paul W. Franks, PhD6,24,32; David S. Siscovick, MPH, MD33; Meir Stampfer, DrPH, MD8,24,27; Lyn M. Steffen, PhD, MPH18; Brian T. Steffen, PhD18; Michael Y. Tsai, PhD34; Rob M. van Dam, PhD15,24,35; Sari Voutilainen, PhD5; Walter C. Willett, DrPH, MD8,24,27; Mark Woodward, PhD12,17,36; Dariush Mozaffarian, MD, DrPH37 ; for the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCe)

JAMA Intern Med. Published online June 27, 2016. doi:10.1001/jamainternmed.2016.2925


Importance  The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers.

Objective  To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD.

Data Sources  A global consortium of 19 studies identified by November 2014.

Study Selection  Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD.

Data Extraction and Synthesis  Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes.

Main Outcomes and Measures  Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI).

Results  The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses.

Conclusions and Relevance  On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD. 
Eur Psychiatry. 2012 Jul;27(5):335-42. doi: 10.1016/j.eurpsy.2011.05.004. Epub 2011 Jul 31.

The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension.
Manor I1, Magen A, Keidar D, Rosen S, Tasker H, Cohen T, Richter Y, Zaaroor-Regev D, Manor Y, Weizman 


To study the efficacy and safety of phosphatidylserine (PS) containing Omega3 long-chain polyunsaturated fatty acids attached to its backbone (PS-Omega3) in reducing attention-deficit/ hyperactivity disorder (ADHD) symptoms in children.


A 15-week, double-blind, placebo-controlled phase followed by an open-label extension of additional 15 weeks. Two hundred ADHD children were randomized to receive either PS-Omega3 or placebo, out of them, 150 children continued into the extension. Efficacy was assessed using Conners' parent and teacher rating scales (CRS-P,T), Strengths and Difficulties Questionnaire (SDQ), and Child Health Questionnaire (CHQ). Safety evaluation included adverse events monitoring.


The key finding of the double-blind phase was the significant reduction in the Global:Restless/impulsive subscale of CRS-P and the significant improvement in Parent impact-emotional (PE) subscale of the CHQ, both in the PS-Omega3 group. Exploratory subgroup analysis of children with a more pronounced hyperactive/impulsive behavior, as well as mood and behavior-dysregulation, revealed a significant reduction in the ADHD-Index and hyperactive components. Data from the open-label extension indicated sustained efficacy for children who continued to receive PS-Omega3. Children that switched to PS-Omega3 treatment from placebo showed a significant reduction in subscales scores of both CRS-P and the CRS-T, as compare to baseline scores. The treatment was well tolerated.


The results of this 30-week study suggest that PS-Omega3 may reduce ADHD symptoms in children. Preliminary analysis suggests that this treatment may be especially effective in a subgroup of hyperactive-impulsive, emotionally and behaviorally-dysregulated ADHD children.
Omega-3 in the press

A flurry of national and international media articles was based on an epidemiologic, i.e. observatory study, stating that the higher eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in plasma phospholipd fatty acids, the higher the risk to develop prostate cancer (Brasky TM et al, J Natl Cancer Inst. 2013 Aug 7;105:1132). It was suggested that this was due to high intake of EPA and DHA, which might also have other risks.

The levels of EPA and DHA measured by Brasky et al in plasma were very low, basically excluding high intake of EPA and DHA. Moreover, differences between groups were very small: differences were within the large variability when measuring fatty acids in plasma. In other words: Brasky et al heard a signal, when there was only noise. And then they falsely interpreted their data. This was uncritically repeated by the media.

In Japan and Korea, we measured the HS-Omega-3 Index in many healthy populations in the suggested target range of 8 -11 %. In these countries, the incidence of prostate cancer is 10 per 100.000 men, while in the USA, it is 63 per 100.000 white men, and 102 per 100.000 black men. (source: World Foundation of Urology, Prostate Cancer Prevention). In the USA, we found a mean HS-Omega-3 Index of 4.5% in 160.000 measurements (Harris et al, PLEFA 2013;88:257). Our figures indicate that facts are the reverse of what the media reported: A high HS-Omega-3 Index correlates with a low risk for prostate cancer.

Even if the figures of Brasky et al were true: A HS-Omega-3 Index of 8 - 11% means a longer life than a lower HS-Omega-3 Index, prostate cancer included.

A recent meta-analysis found omega-3 fatty acids to be associated with a low risk for breast cancer (Zheng et al, Br Med J 2013; 346:f3706, e-pub 27.06.13).

Omega-3 Fatty Acid Intakes Are Inversely Related to Elevated Depressive Symptoms among United States Women
May A. Beydoun5,*, Marie T. Fanelli Kuczmarski6, Hind A. Beydoun7,Joseph R. Hibbeln8, Michele K. Evans5, and Alan B. Zonderman 

Evidence that depressive symptoms are inversely related to n–3 (ω3) fatty acids is growing among United States adults. We assessed whether self-reported depressive symptoms were inversely associated with n–3 fatty acid intakes by using a cross-sectional study in 1746 adults (aged 30–65 y) in Baltimore City, MD (2004–2009). The 20-item Center for Epidemiologic Studies–Depression Scale (CES-D) was used, with a CES-D score ≥16 suggestive of elevated depressive symptoms (EDS). By using the mean of two 24-h dietary recalls, n–3 highly unsaturated fatty acids (HUFAs; ≥20 carbons), n–3 polyunsaturated fatty acids (PUFAs; ≥18 carbons), and plausible ratios with n–6 (ω6) fatty acids were estimated. EDS prevalence was 18.1% among men and 25.6% among women. In women, the uppermost tertile (tertile 3) of n–3 PUFAs (compared with tertile 1) was associated with reduced odds of EDS by 49%, with a substantial sex differential. The n–3 PUFA:n–6:PUFA ratio was inversely related to EDS among women (tertile 2 vs. tertile 1, OR: 0.74; 95% CI: 0.41, 1.32; tertile 3 vs. tertile 1, OR: 0.47; 95% CI: 0.27, 0.83). A similar pattern was noted for n–3 HUFA:n–6 HUFA among women. For CES-D subscales, n–3 PUFA (% of energy) was inversely related to somatic complaints, whereas positive affect was directly related to n–3 HUFA (% of energy; total population and among women), n–3 HUFA:n–6 HUFA (women), and n–3 HUFA:n–6 PUFA (total population and among women). In sum, among United States women, higher intakes of n–3 fatty acids [absolute (n–3) and relative to n–6 fatty acids (n–3:n–6)] were associated with lower risk of elevated depressive symptoms, specifically in domains of somatic complaints (mainly n–3 PUFAs) and positive affect (mainly n–3 HUFAs). 

The Omega-3 Index: a new risk factor for death from coronary heart disease?
Harris WS, Von Schacky C. 

Lipid and Diabetes Research Center, Mid America Heart Institute of Saint Luke's Hospital, University of Missouri-KC School of Medicine, Kansas City, MO 64111, USA. vharris@saint-lukes.org
BACKGROUND:Low intakes or blood levels of eicosapentaenoic and docosahexaenoic acids (EPA + DHA) are independently associated with increased risk of death from coronary heart disease (CHD). In randomized secondary prevention trials, fish or fish oil have been demonstrated to reduce total and CHD mortality at intakes of about 1 g/day. Red blood cell (RBC) fatty acid (FA) composition reflects long-term intake of EPA + DHA. We propose that the RBC EPA + DHA (hereafter called the Omega-3 Index) be considered a new risk factor for death from CHD.
METHODS:We conducted clinical and laboratory experiments to generate data necessary for the validation of the Omega-3 Index as a CHD risk predictor. The relationship between this putative marker and risk for CHD death, especially sudden cardiac death (SCD), was then evaluated in several published primary and secondary prevention studies.
RESULTS:The Omega-3 Index was inversely associated with risk for CHD mortality. An Omega-3 Index of > or = 8% was associated with the greatest cardioprotection, whereas an index of < or = 4% was associated with the least.
CONCLUSION:The Omega-3 Index may represent a novel, physiologically relevant, easily modified, independent, and graded risk factor for death from CHD that could have significant clinical utility.
Copyright 2004 The Institute for Cancer Prevention and Elsevier Inc. 

Dietary intake and food sources of total and individual polyunsaturated fatty acids in the Belgian population over 15 years old. 

Sioen I, Vyncke K, De Maeyer M, Gerichhausen M, De Henauw S.

Department of Public Health, Ghent University, Ghent, Belgium. 

Advances in our knowledge of the physiological functions of dietary polyunsaturated fatty acids (PUFAs) have led to an increased interest in food sources and the level of dietary intake of these nutrients. Up to now, no representative data was available for the Belgian adult population. This study aimed to describe data on the intake and food sources of total and individual omega-6 and omega-3 PUFA for the Belgian population over 15 years old. PUFA intakes were assessed for 3,043 Belgian adults, based on two non-consecutive 24 h recalls. Usual intakes were calculated using the multiple source method. The results showed that the intake of linoleic acid (LA) is in accordance with the recommendation for almost all Belgianadults. However, the intake of omega-3 PUFA is suboptimal for a large part of the studied population and also the intake of total PUFA should be increased for a part of the population. The main food source of LA and α-linolenic acid (ALA) was the group of fats and oils (60.6 % for LA and 53.1 % for ALA). Fish and fish products were the most important sources of long chain omega-3 PUFA. Age influenced fatty acids intake, with higher intake of omega-3 PUFA in the older age groups. To fill the gap between the intake and recommendation of total PUFA, and in particular omega-3PUFA, sustainable strategies and efficient consumer communication strategies will be needed. 

The influence of n-3 PUFA supplements and n-3 PUFA enriched foods on the n-3 LC PUFA intake of Flemish women. 

Sioen I, Devroe J, Inghels D, Terwecoren R, De Henauw S.

Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, UZ-2 Blok A, De Pintelaan 185, 9000 Ghent, Belgium.
Food consumption data of Flemish women of reproductive age collected in 2002 showed a large deficit for ALA and n-3 LC PUFA compared to the recommendations (mean ALA and EPA + DHA intake 1.4 g/day and 209 mg/day, respectively) and indicated a need to tackle the problem of low n-3 PUFA intake. Another recent Belgian study demonstrated that enrichment of commonly eaten food items with n-3 PUFA provides the opportunity to increase the n-3 PUFA intake up to 6.5 g/day and decrease the n-6/n-3 ratio. Since a large supply of n-3 PUFA supplements and n-3 PUFA enriched foods exists on the Belgian market, this study aimed at assessing the influence of these products on the n-3 LC PUFA intake for Flemish women of reproductive age. It was found that n-3 supplements are consumed by 5% of the Flemish women. Of all the n-3 PUFA enriched foods on the Flemish market, margarines and cooking fat are most frequently consumed by young women. The results indicated that a big gap remains between the EPA&DHA intake (mean = 276 mg/day) and the recommendation. Seafood remains the most important source of EPA&DHA. Only 11.6% of the population sample reached an intake level of 500 mg EPA&DHA per day. The study showed that other strategies will be needed to increase the EPA&DHA intake in the long term.Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters 

J Neubronner1, JP Schuchardt1, G Kressel1, M Merkel2, C von Schacky3 and A Hahn1 
1Institute of Food Science and Human Nutrition, Leibniz Universita¨t Hannover, Am Kleinen Felde 30, Hannover, Germany; 2Asklepios 
Klinik St. Georg, 1. Medizinische Abteilung, Haus O, Lohmu¨hlenstra_e 5, Hamburg, Germany and 3Preventive Cardiology, 
Medizinische Klinik und Poliklinik Innenstadt, Ludwig Maximilians University, Munich, Ziemssenstr. 1, Mu¨nchen, Germany 

Url : http://www.ncbi.nlm.nih.gov/pubmed/21063431 

Bioavailability of marinen-3 fatty acid formulations 

J. Dyerberg a,n, P.Madsen b, J.M.Møller c, I.Aardestrup b, E.B.Schmidt d a Department ofHumanNutrition,FacultyofLifeSciences,UniversityofCopenhagen,Copenhagen,Denmark b Department ofClinicalBiochemistry,CenterforCardiovascularResearchAalborgHospital,Aalborg,Denmark c Department ofGastroenterology,AalborgHospital,Aalborg,Denmark d Department ofCardiology,CenterforCardiovascularResearchAalborgHospital,Aalborg,Denmark 

Url : http://www.ncbi.nlm.nih.gov/pubmed/20638827 


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