Quantitative Erythrocyte Omega-3 EPA Plus DHA Levels are
Related to Higher Regional Cerebral Blood Flow on Brain SPECT.

Neuroimaging shows increased blood flow in regions of the brain associated with memory and learning for people with higher omega-3 levels, according to a new report in the  Journal of Alzheimer’s Disease:
“This study is a major advance in demonstrating the value of nutritional intervention for brain health by using the latest brain imaging,” commented George Perry, PhD, Dean and Professor of Biology, The University of Texas at San Antonio, and Editor-in-Chief of the Journal of Alzheimer’s Disease
J Alzheimers Dis. 2017 May 18. doi: 10.3233/JAD-170281.
Amen DG1, Harris WS2, Kidd PM1, Meysami S3, Raji CA
The interrelationships between omega-3 fatty acids status, brain perfusion, and cognition are not well understood.
To evaluate if SPECT brain imaging of cerebral perfusion and cognition varies as a function of omega-3 fatty acid levels.
A random sample of 166 study participants was drawn from a psychiatric referral clinical for which erythrocyte quantification of omega-3 eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (the Omega-3 Index) was available. Quantitative brainSPECT was done on 128 regions based on a standard anatomical Atlas Persons with erythrocyte EPA+DHA concentrations were dichotomized based on membership in top 50th percentile versus bottom 50th percentile categories. Two-sample t-tests were done to identify statistically significant differences in perfusion between the percentile groups. Partial correlations were modeled between EPA+DHA concentration and SPECT regions. Neurocognitive status was assessed using computerized testing (WebNeuro) and was separately correlated to cerebral perfusion on brain SPECT imaging and omega-3 EPA+DHA levels.

Partial correlation analyses showed statistically significant relationships between higher omega-3 levels and cerebralperfusion were in the right parahippocampal gyrus (r=0.20, p=0.03), right precuneus (r=0.20, p=0.03), and vermis subregion 6 (p=0.21, p=0.03). Omega-3 Index levels separately correlated to the feeling subsection of the WebNeuro (r=0.25, p=0.01).
Quantitative omega-3 EPA+DHA erythrocyte concentrations are independently correlated with brain perfusion on SPECTimaging and neurocognitive tests. These results have implications for the role of omega-3 fatty acids toward contributing to cognitive reserve

Association of Marine Omega-3 Fatty Acid Levels With Telomeric Aging in Patients With Coronary Heart Disease

Ramin Farzaneh-Far, MD; Jue Lin, PhD; Elissa S. Epel, PhD; William S. Harris, PhD; Elizabeth H. Blackburn, PhD; Mary A. Whooley, MD
JAMA. 2010;303(3):250-257.

Prospective cohort study of 608 ambulatory outpatients in California with stable coronary artery disease recruited from the Heart and Soul Study between September 2000 and December 2002 and followed up to January 2009 (median, 6.0 years; range, 5.0-8.1 years).
Design, Setting, and Participants:
We measured the content of EPA+DHA in 768 ACS patients and 768 age-, sex- and race-matched controls. The association with ACS case status of blood cell EPA+DHA [both by a 1 unit change and by category (low, <4%; intermediate 4.1-7.9%; and high, > or =8%)] was assessed using multivariate conditional logistic regression models adjusting for matching variables and smoking status, alcohol use, diabetes, body mass index, serum lipids, education, family history of coronary artery disease, personal histories of myocardial infarction and hypertension, and statin, aspirin, and other antiplatelet drug use.
Main Outcome Measures:
We measured leukocyte telomere length at baseline and again after 5 years of follow-up. Multivariable linear and logistic regression models were used to investigate the association of baseline levels of omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) with subsequent change in telomere length.
Individuals in the lowest quartile of DHA+EPA experienced the fastest rate of telomere shortening (0.13 telomere-to-single-copy gene ratio [T/S] units over 5 years; 95% confidence interval [CI], 0.09-0.17), whereas those in the highest quartile experienced the slowest rate of telomere shortening (0.05 T/S units over 5 years; 95% CI, 0.02-0.08; P < .001 for linear trend across quartiles). Levels of DHA+EPA were associated with less telomere shortening before (unadjusted β coefficient x 10–3 = 0.06; 95% CI, 0.02-0.10) and after (adjusted β coefficient x 10–3 = 0.05; 95% CI, 0.01-0.08) sequential adjustment for established risk factors and potential confounders. Each 1-SD increase in DHA+EPA levels was associated with a 32% reduction in the odds of telomere shortening (adjusted odds ratio, 0.68; 95% CI, 0.47-0.98).
Among this cohort of patients with coronary artery disease, there was an inverse relationship between baseline blood levels of marine omega-3 fatty acids and the rate of telomere shortening over 5 years.
Author Affiliations:
Division of Cardiology, San Francisco General Hospital (Dr Farzaneh-Far), Departments of Medicine (Drs Farzaneh-Far and Whooley), Biochemistry and Biophysics (Drs Lin and Blackburn), Psychiatry (Dr Epel), and Epidemiology and Biostatistics (Dr Whooley), University of California, San Francisco, and Veterans Affairs Medical Center (Dr Whooley), San Francisco; and Sanford Research/USD and Sanford School of Medicine, University of South Dakota, Sioux Falls (Dr Harris).

Use of red blood cell fatty-acid profiles as biomarkers in cardiac disease

Prof. Dr. med. Clemens von Schacky
The Omega-3 Index is defined as the percentage of eicosapentaenoic acid plus docosahexaenoic acid in red blood cell fatty acids, assessed by a standardized methodology. Better than fatty-acid compositions in other compartments, the Omega-3 Index Index represents a person’s status in eicosapentaenoic acid plus docosahexaenoic acid. An Omega-3 Index Index less than 4% is associated with a tenfold risk for sudden cardiac death in comparison to an Omega-3 Index Index greater than 8%. Mechanisms of action are plausible and large-scale intervention studies in humans support causality. A low Omega-3 Index Index may also be a risk factor for coronary artery disease and for complications of congestive heart failure. Ongoing research will define the value of the Omega-3 Index Index as a risk factor and treatment parameter more precisely.

EPA and DHA in blood cell membranes from acute coronary syndrome patients and controls. Atherosclerosis. 2008;197:821-8

Block RC, Harris WS, Reid KJ, Sands SA and Spertus JA
Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, Rochester, Box 644, 601 Elmwood Avenue, NY 14642, United States. robert block@urmc.rochester.edu
Increased blood levels of the omega-3 fatty acids (FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been inversely associated with risk for sudden cardiac death, but their relationship with acute coronary syndromes (ACS) is unclear. OBJECTIVE: We hypothesized that the EPA+DHA content of blood cell membranes, as a percent of total FAs, is reduced in ACS patients relative to matched controls.
We measured the content of EPA+DHA in 768 ACS patients and 768 age-, sex- and race-matched controls. The association with ACS case status of blood cell EPA+DHA [both by a 1 unit change and by category (low, <4%; intermediate 4.1-7.9%; and high, > or =8%)] was assessed using multivariate conditional logistic regression models adjusting for matching variables and smoking status, alcohol use, diabetes, body mass index, serum lipids, education, family history of coronary artery disease, personal histories of myocardial infarction and hypertension, and statin, aspirin, and other antiplatelet drug use.
The combined groups had a mean age of 61+/-12 years, 66% were male, and 92% were Caucasian. The EPA+DHA content was 20% lower in cases than controls (3.4+/-1.6 vs. 4.25+/-2.0%, p<0.001). The multivariable-adjusted odds for case status was 0.77 (95% CI 0.70 to 0.85, p<0.001) for a 1 unit increase in EPA+DHA content. Compared with the lowest EPA+DHA group, the odds ratio for an ACS event was 0.58 (95% CI 0.42-0.80), in the intermediate EPA+DHA group and was 0.31 (95% CI 0.14-0.67; p for trend <0.0001) in the highest EPA+DHA group.
Odds for ACS case status increased incrementally as the EPA+DHA content decreased suggesting that low EPA+DHA may be associated with increased risk for ACS.

Omega-3-Fettsäuren in der Kardiologie - Neueste Entwicklungen

Prof. Dr. med. Clemens von Schacky, Medizinische Klinik und Poliklinik der Ludwig-Maximilians-Universität München und Omegametrix, Martinsried

Die wesentlichen kardiologischen Fachgesellschaften auf der Welt empfehlen die beiden Omega-3 Fettsäuren Eicosapentaensäure (EPA) und Docosahexaensäure (DHA) zur Nachbehandlung nach Myokardinfarkt, zur Prävention des plötzlichen Herztodes und zur Prävention kardiovaskulärer Ereignisse. Die Empfehlungen beruhen auf einer umfassenden Datenlage, die in systematischen Reviews und Metaanalysen aufgearbeitet wurden. In epidemiologischen Arbeiten korrelierte der Gehalt eines Menschen an diesen beiden Omega-3 Fettsäuren invers mit der Wahrscheinlichkeit, den plötzlichen Herztod zu erleiden. Dieser Gehalt wird am besten durch den Omega-3 Index ausgedrückt, der den Gehalt der Erythrozyten an EPA und DHA erfasst. Der Omega-3 Index stellt sich so als Risikofaktor für den plötzlichen Herztod dar. Dies wird durch statistische Daten zum plötzlichen Herztod und durch die Ergebnisse von Interventionsstudien mit Omega-3-Fettsäuren gestützt. Der Omega-3 Index kann durch Aufnahme von Omega-3 Fettsäuren in einen Bereich steigen (> 8%), der den plötzlichen Herztod um 90% unwahrscheinlicher macht als der bei uns gängige Bereich (< 4%). Methodische Aspekte und analytische Probleme legen es nahe, den Omega-3 Index in einem hierfür ausgewiesenen Labor zu bestimmen.
Myokardinfarkt, Omega-3 Fettsäuren, Plötzlicher Herztod, Prävention, Omega-3 Index
MMW-Fortschritte der Medizin Originalien Nr. III/2007 (149. Jg.), S. 97-101
Die beiden Omega-3-Fettsäuren EPA+DHA sind sicher und effektiv in der Prophylaxe des plötzlichen Herztodes, in der Nachbehandlung nach Myokardinfarkt oder in der kardiovaskulären Prävention. Die Gesamtmortalität wird um 17% gesenkt, was den Effekt der Statine übersteigt [13, 14]. Dies gilt insbesondere für die Verwendung von Quellen der Omega-3 Fettsäuren, die frei von Kontaminanten sind, wie hochwertige Fischöle. Der Omega-3 Index stellt sich als Risikofaktor für den plötzlichen Herztod dar und scheint bisher bekannten Risikofaktoren überlegen. Eine Therapie mit Omega-3-Fettsäuren kann mit dem Omega-3-Index kontrolliert und gesteuert werden.
Omega-3-Fettsäuren in der Kardiologie – Neueste Entwicklungen

Omega-3 Fatty Acids and Cardiac Arrhythmias: Prior Studies and Recommendations for Future Research: A Report from the National Heart, Lung, and Blood Institute and Office of Dietary Supplements Omega-3 Fatty Acids and Their Role in Cardiac Arrhythmogenesis Workshop

Barry London, Christine Albert, Mark E. Anderson, Wayne R. Giles, David R. Van Wagoner, Ethan Balk, George E. Billman, Mei Chung, William Lands, Alexander Leaf, John McAnulty, Jeffrey R. Martens, Rebecca B. Costello and David A. Lathrop
Future randomized trials should feature the following: Patient selection and follow-up should include clinically relevant biological parameters and markers (eg, plasma and cellular n-3 fatty acid levels and markers of systemic inflammation, redox state, or oxidative stress).
Circulation 2007;116;e320-e335 DOI: 10.1161/CIRCULATIONAHA.107.712984
Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514
Copyright © 2007 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/cgi/content/full/116/10/e320

Comparison between plasma and erythrocyte fatty acid content as biomarkers of fatty acid intake in US women.

Qi Sun, Jing Ma, Hannia Campos, Susan E Hankinson, and Frank B Hu
Erythrocyte fatty acids may be superior to plasma fatty acids for reflecting long-term fatty acid intake because of less sensitivity to recent intake and a slower turnover rate.
The objective was to compare the fatty acid content of erythrocytes with that of plasma with respect to their abilities to reflect usual fatty acid intake.
Fatty acids in plasma and erythrocytes were measured by capillary gas-liquid chromatography in 306 US women aged 43-69y. Fatty acid intake was assessed with a food-frequency question- naire, which was validated for measuring intakes of various fatty acids.
Docosahexaenoic acid (DHA, 22:6n 3) in erythrocytes and plasma provided the strongest correlations with its intake, but erythrocyte DHA concentrations [Spearman’s partial correlation co- efficient (rs) 0.56] were better than plasma DHA concentrations (rs 0.48) as a biomarker. Total trans fatty acids (rs 0.43) and total 18:1 trans isomers (rs 0.42) in erythrocytes were also more strongly correlated with intake than were those in plasma (rs 0.30 and rs 0.29, respectively). Moderate correlations were observed for linoleic acid (18:2n 6; erythrocytes, rs 0.24; plasma, rs 0.25), -linolenic acid (18:3n 3; erythrocytes, rs 0.18; plasma, rs 0.23), and eicosapentaenoic acid (20:5n 3; erythrocytes, rs 0.38; plasma, rs 0.21). For polyunsaturated and trans fatty acids, correlations between intakes and biomarkers improved moderately when average intakes over previous years were used.
Erythrocyte n 3 fatty acids of marine origin and trans fatty acid content are suitable biomarkers for long-term intake.
Am J Clin Nutr 2007;86:74-81.
Fatty acids, erythrocytes, plasma, biological markers, food-frequency questionnaires, US women
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://www.ajcn.org/cgi/content/abstract/86/1/74

Low long chain omega-3 fatty acid status in middle-aged women.Authors: Gellert S1, Schuchardt JP2, Hahn

INTRODUCTION: Long-chain (LC) omega-3 fatty acids (n-3 PUFAs) have beneficial effects on cardiovascular health and cognitive decline. Several studies have shown that the LC n-3 PUFA status in women in western countries is low. The aim of this study was to assess the LC n-3 PUFA status in middle-aged German women and to identify variables that might affect the status.
MATERIAL AND METHODS: From the nationwide and cross-sectional German VitaMinFemin study, fatty acid levels in the erythrocyte membrane (% of total erythrocyte fatty acids) were ascertained for 446 women (40-60 years).
RESULTS: The average omega-3 index (% of eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) of the total study population was 5.49±1.17%. A total of 62.8% of women had a low omega-3 index (>4-6%). The omega-3 index was affected by age and smoking, with slightly higher values in women ≥50 years (p=0.032) and non-smokers (p=0.002). Women taking hormonal contraceptives showed a lower EPA level (p<0.001), a lower ratio of EPA/alpha-linoleic acid (p<0.001) and a higher ratio of DHA/EPA (p<0.001) than women without hormonal contraception.
CONCLUSION: The low LC n-3 PUFA status in middle-aged German women (40-60 years) is related to an increased risk of cardiovascular diseases and possibly other diseases and should therefore be improved. Further studies are needed to determine the influence of estrogen on the effect on LC n-3 PUFA status.

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