•Polyunsaturated fatty acid blood levels have predictive power for disease outcomes.•Both the Omega-3 Index and the n6:n3 ratio have been used to express PUFA status.•The n6:n3 ratio has become ...scientifically out-dated.•The Omega-3 Index, because if included EPA and DHA only, is a preferred metric.
The well-known health effects of the long-chain, marine omega-3 (n-3) fatty acids (FAs) has led to a growing interest in the prognostic value that blood levels of these FAs might have vis-à-vis cardiovascular and neurocognitive diseases. The measurement and expression of n-3 FA levels is not straight-forward, however, and a wide variety of means of expression of n-3 FA status have been used in research and clinical medicine. This has led to considerable confusion as to what “optimal” n-3 FA status is. The n-6:n-3 ratio has enjoyed relatively widespread use, but this apparently simple metric has both theoretical and practical difficulties that have contributed to misunderstandings in this field. Just as the once-popular polyunsaturated:saturated FA ratio has largely disappeared from the nutritional and medical literature, it may be time to replace the n-6:n-3 ratio with a newer metric that focuses on the primary deficiency in Western diets – the lack of eicosapentaenoic and docosahexaenoic acids (EPA and DHA). The Omega-3 Index (red blood cell EPA+DHA) has much to recommend it in this regard.
Because blood concentrations of n-3 (or omega-3) fatty acids (FAs) (eicosapentaenoic and docosahexaenoic acids) are a strong reflection of dietary intake, it is proposed that a n-3 FA biomarker, the ...omega-3 index (erythrocyte eicosapentaenoic acid plus docosahexaenoic acid), be considered as a potential risk factor for coronary heart disease mortality, especially sudden cardiac death. The omega-3 index fulfills many of the requirements for a risk factor including consistent epidemiologic evidence, a plausible mechanism of action, a reproducible assay, independence from classic risk factors, modifiability, and, most important, the demonstration that raising levels will reduce risk for cardiac events. Measuring membrane concentrations of n-3 FAs is a rational approach to biostatus assessment as these FAs appear to exert their beneficial metabolic effects because of their actions in membranes. They alter membrane physical characteristics and the activity of membrane-bound proteins, and, once released by intracellular phospholipases from membrane stores, they can interact with ion channels, be converted into a wide variety of bioactive eicosanoids, and serve as ligands for several nuclear transcription factors, thereby altering gene expression. The omega-3 index compares very favorably with other risk factors for sudden cardiac death. Proposed omega-3 index risk zones are (in percentages of erythrocyte FAs): high risk, <4%; intermediate risk, 4-8%; and low risk, >8%. Before assessment of n-3 FA biostatus can be used in routine clinical evaluation of patients, standardized laboratory methods and quality control materials must become available.
Abstract Background and aims A recent 19-cohort meta-analysis examined the relationships between biomarkers of omega-3 fatty acids and risk for coronary heart disease (CHD). That study did not, ...however, report hazard ratios (HRs) specifically as a function of erythrocyte eicosapentaenoic (EPA) plus docosahexaenoic (DHA) levels, a metric called the Omega-3 Index in which EPA + DHA content is expressed as a percent of total fatty acids. The Omega-3 Index has been used in several recent studies and is a validated biomarker of omega-3 fatty acid tissue levels, but additional data are needed to confirm (or refute) the originally-proposed clinical cut-points of <4% (higher risk) and 8%–12% (lower risk). Methods The present study was therefore undertaken using published data from this meta-analysis to estimate HRs per 1-SD increase in the Omega-3 Index and median quintile values for this metric across 10 of the cohorts for which the needed data were available. Results The overall mean (SD) for the Omega-3 Index in these 10 cohort studies was 6.1% (2.1%), and the HR for a 1-SD increase was 0.85 (95% confidence interval, 0.80–0.91). Median quintile 1 and 5 levels were 4.2% vs. 8.3%, respectively. Based on these values, we estimate that risk for fatal CHD would have been reduced by about 30% moving from an Omega-3 Index of 4%–8%. Conclusions These findings support the use of <4% and >8% as reasonable therapeutic targets for the Omega-3 Index.
The REDUCE-IT study found that patients at elevated risk for cardiovascular disease (CVD) who were already taking statins obtained a marked benefit by taking 4 g/d of eicosapentaenoic acid ethyl ...esters (icosapent ethyl, IPE; Vascepa) over about 5 years. Although approved for triglyceride (TG) lowering, IPE had only a modest TG-lowering effect in REDUCE-IT, largely because median TG levels were relatively low already. Hence the question of what mechanisms IPE might be working through is of great interest. At present, it appears that the best mechanistic candidates would be anti-platelet effects and/or anti-inflammatory effects. Whatever the cause, the powerful effects of IPE on CVD risk have renewed interest in the clinical utility of omega-3 fatty acids.
Omega-3 fatty acid ethyl esters have well-known triglyceride-lowering properties and were shown >30 years ago to inhibit platelet function. With the recent US Food and Drug Administration (FDA) ...approval of these agents for treating severe triglyceride elevations, concerns about excess bleeding naturally arise. However, an objective assessment of the evidence for clinically significant bleeding reveals that such concerns are unfounded. As such, the benefits of triglyceride lowering with omega-3 fatty acids more than outweigh any theoretical risks for increased bleeding.
•Nutrition-based interventions to reduce COVID-19 morbidity/mortality are needed.•The Omega-3 Index (O3I) was measured in banked blood from 100 COVID-19 patients.•Risk for death was analyzed as a ...function of quartiles (Q) of the O3I.•Patients in Q4 (O3I ≥ 5.7%) vs. Q1–3 were 75% less likely to die (p = 0.07).•These pilot data suggest that a higher O3I may lower risk for death from COVID-19.
Very-long chain omega-3 fatty acids (EPA and DHA) have anti-inflammatory properties that may help reduce morbidity and mortality from COVID-19 infection. We conducted a pilot study in 100 patients to test the hypothesis that RBC EPA+DHA levels (the Omega-3 Index, O3I) would be inversely associated with risk for death by analyzing the O3I in banked blood samples drawn at hospital admission. Fourteen patients died, one of 25 in quartile 4 (Q4) (O3I ≥5.7%) and 13 of 75 in Q1–3. After adjusting for age and sex, the odds ratio for death in patients with an O3I in Q4 vs Q1–3 was 0.25, p = 0.07. Although not meeting the classical criteria for statistical significance, this strong trend suggests that a relationship may indeed exist, but more well-powered studies are clearly needed.
•Pregnant women with ‘low’ omega-3 blood levels have higher risk for early preterm birth.•DHA supplementation during pregnancy can reduce premature birth rates in higher risk individuals.•There is no ...agreed upon blood DHA level that would define what ‘low’ omega-3 status is.•Blood DHA levels from 6 pregnancy studies were converted to a common DHA metric for comparison.•Having a standardized metric for ‘low’ DHA status is needed for use in clinical practice.
Recent trials in pregnant women on the effects of supplemental DHA on early preterm birth (ePTB) risk have shown that there is a maternal blood docosahexaenoic acid (DHA) level below which risk for ePTB was increased and supplemental DHA was effective at reducing risk. However, DHA levels were expressed in different terms across these trials making cross study comparisons impossible. The purposes of this study were 1) to report interlaboratory conversion factors from study-specific metrics to a common metric, red blood cell (RBC) DHA measured by OmegaQuant Analytics (OQA), and 2) to translate reported pre- and post-treatment DHA levels from these trials into a RBC DHA for comparison. Data from five published and one unpublished study are included. Across these studies, the effects on RBC DHA levels after supplementation with 0, 200, 600, 800 and 1000 mg of DHA were (as a% change from baseline): 0 mg, no change; 200 mg, 15–20% increase; 600 mg, 55–60% increase; 800 mg, 13–65% increase; and 1000 mg, 51% increase. Standardization of fatty acid analysis and reporting and a target omega-3 or DHA level for identifying those for which higher dose DHA supplementation is indicated to prevent ePTB are needed for clinical use.
Several recent randomized trials and subsequent meta-analyses have questioned the value of n-3 fatty acid supplementation in cardiovascular disease risk reduction.
This report focuses on four ...clinical trials published between 2010 and 2012 that have failed to show benefits of n-3 fatty acids, and on one meta-analysis from 2012 that used a controversial statistical approach in reaching a conclusion of no effect.
The question of the extent to which n-3 fatty acid supplementation reduces risk for cardiovascular disease remains open. Future studies must be properly powered, use doses of n-3 fatty acids significantly higher than those provided in background diets, focus on patient populations with low n-3 fatty acid tissue levels, treat for longer periods of time, and consider the effects of these agents in the great majority of patients who are not on guideline-directed therapeutic regimens. The strong evidence-base from prospective cohort studies and the ever-deepening understanding of the cellular effects of long-chain n-3 fatty acids together support the need for these nutrients in reducing cardiovascular risk. Short-term findings from randomized controlled trials need to be interpreted in the light of all the evidence.
Information on the Omega-3 Index (O3I) in the United Kingdom (UK) is scarce. The UK-Biobank (UKBB) contains data on total plasma n3-PUFA% and DHA% measured by NMR. The aim of our study was to create ...an equation to estimate the O3I (eO3I) from these data. We first performed an inter-laboratory experiment with 250 random blood samples in which the O3I was measured in erythrocytes by GC, and total n3 % and DHA% were measured in plasma by NMR. The best predictor of eO3I included both DHA% and a derived metric, the total n3 %–DHA%. Together these explained 65 % of the variability (r = 0·832, P < 0·0001). We then estimated the O3I in 117 108 UKBB subjects and correlated it with demographic and lifestyle variables in multivariable-adjusted models. The mean eO3I was 5·58 % (sd 2·35 %) in this UKBB cohort. Several predictors were significantly correlated with eO3I (all P < 0·0001). In general order of impact and with directionality (–, inverse and +, direct): oily-fish consumption (+), fish oil supplement use (+), female sex (+), older age (+), alcohol use (+), smoking (–), higher waist circumference and BMI (–), lower socioeconomic status and less education (–). Only 20·5 % of eO3I variability could be explained by predictors investigated, and oily fish consumption accounted for 7·0 % of that. With the availability of the eO3I in the UKBB cohort, we will be in a position to link risk for a variety of diseases with this commonly used and well-documented marker of n3-PUFA biostatus.
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