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The Omega-3 Index: Clinical Utility for Therapeutic Intervention
Abstract
Red blood cell levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are a reflection of tissue levels and are determined by a complex interplay of metabolism and nutrition. Low levels of EPA+DHA in erythrocytes are associated with increased risk for sudden cardiac death. If levels of EPA+DHA in erythrocytes are determined using a strictly defined and standardized method, then the clinical significance of differing levels (previously defined in major research studies using this methodology) may be understood and applied in patient care. The Omega-3 Index, which is the EPA+DHA content of erythrocytes expressed as a percent of total identified fatty acids, was originally suggested as a marker of increased risk for death from coronary heart disease, but it can also be viewed as an actual risk factor, playing a pathophysiologic role in the disease. Optimal levels appear to be 8% or greater. At this stage of its development, the Omega-3 Index appears to fulfill many of the requirements for both a risk marker and a risk factor. Using the Omega-3 Index in the design of clinical studies might allow for a more efficient use of research resources.
... The Omega-3 Index, proposed by Harris and von Schacky in 2004, is the percentage of EPA+DHA content in erythrocytes out of a total fatty acids identified 31 . This index serves as a biomarker of cardiovascular disease, vascular pathology, and later for obesity, insulin resistance, and mood disorders 32 . ...
... Their analysis found that 30 of the 36 studies "found either significant differences in omega-3 indexes between patients and controls or an inverse relationship between omega-3 indexes and disease severity" 33 . The optimal levels of omega-3 fatty are 8% or greater 31 . ...
... For analysis of fatty acid composition, 2.0 mL aliquots of frozen (− 80 °C) EDTA-blood were sent to Omegametrix (Martinsried, Germany). At Omegametrix, a reference laboratory for fatty acid analyses, whole blood fatty acid composition was analyzed according to the HS-Omega-3 Index ® methodology [26]. Fatty acid methyl esters were generated by acid transesterification and were analyzed by gas chromatography using a GC2010 Gas Chromatograph (Shimadzu, Duisburg, Germany) equipped with a SP2560, 100-m column (Supelco, Bellefonte, Pennsylvania, United States) using hydrogen as carrier gas. ...
... Fatty acids were identified by comparison with a standard mixture of fatty acids characteristic of erythrocytes. Results for EPA&DHA from whole blood aliquots were recalculated into the erythrocyte O3I by the use of a validated correction factor, [26] while individual fatty acid results are given as relative amounts of ALA (C18:3n3), EPA (C20:5n3) and DHA (C22:6n3) expressed as a percentage of a total of 26 identified FAs in whole blood. Analyses were quality-controlled according to DIN ISO 15189. ...
Objectives
To evaluate associations of omega-3 fatty acid (O3-FA) blood levels with cardiometabolic risk markers, functional capacity and cardiac function/morphology in patients with heart failure with preserved ejection fraction (HFpEF).
Background
O3-FA have been linked to reduced risk for HF and associated phenotypic traits in experimental/clinical studies.
Methods
This is a cross-sectional analysis of data from the Aldo-DHF-RCT. From 422 patients, the omega-3-index (O3I = EPA + DHA) was analyzed at baseline in n = 404 using the HS-Omega-3-Index ® methodology. Patient characteristics were; 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E / e ′ 7.1 ± 1.5; median NT-proBNP 158 ng/L (IQR 82–298). Pearson’s correlation coefficient and multiple linear regression analyses, using sex and age as covariates, were used to describe associations of the O3I with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline/12 months.
Results
The O3I was below (< 8%), within (8–11%), and higher (> 11%) than the target range in 374 (93%), 29 (7%), and 1 (0.2%) patients, respectively. Mean O3I was 5.7 ± 1.7%. The O3I was inversely associated with HbA1c ( r = − 0.139, p = 0.006), triglycerides-to-HDL-C ratio ( r = − 0.12, p = 0.017), triglycerides ( r = − 0.117, p = 0.02), non-HDL-C ( r = − 0.101, p = 0.044), body-mass-index ( r = − 0.149, p = 0.003), waist circumference ( r = − 0.121, p = 0.015), waist-to-height ratio ( r = − 0.141, p = 0.005), and positively associated with submaximal aerobic capacity ( r = 0.113, p = 0.023) and LVEF ( r = 0.211, p < 0.001) at baseline. Higher O3I at baseline was predictive of submaximal aerobic capacity ( β = 15.614, p < 0,001), maximal aerobic capacity ( β = 0.399, p = 0.005) and LVEF ( β = 0.698, p = 0.007) at 12 months.
Conclusions
Higher O3I was associated with a more favorable cardiometabolic risk profile and predictive of higher submaximal/maximal aerobic capacity and lower BMI/truncal adiposity in HFpEF patients.
Graphic abstract
Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients. Higher O3I was associated with a more favorable cardiometabolic risk profile and aerobic capacity (left) but did not correlate with echocardiographic markers for left ventricular diastolic function or neurohumoral activation (right). An O3I-driven intervention trial might be warranted to answer the question whether O3-FA in therapeutic doses (with the target O3I 8–11%) impact on echocardiographic markers for left ventricular diastolic function and neurohumoral activation in patients with HFpEF. This figure contains modified images from Servier Medical Art ( https://smart.servier.com ) licensed by a Creative Commons Attribution 3.0 Unported License.
... At Omegametrix, a reference laboratory for fatty acid analyses, whole blood fatty acid composition was analyzed according to the HS-Omega-3 Index ® methodology. [25] Fatty acid methyl esters were generated by acid transesterification and were analyzed by gas chromatography using a GC2010 Gas Chromatograph (Shimadzu, Duisburg, Germany) equipped with a SP2560, 100-m column (Supelco, Bellefonte, Pennsylvania, United States) using hydrogen as carrier gas. Fatty acids were identified by comparison with a standard mixture of fatty acids characteristic of erythrocytes. ...
... Fatty acids were identified by comparison with a standard mixture of fatty acids characteristic of erythrocytes. Results for EPA&DHA from whole blood aliquots were recalculated into the erythrocyte O3I by the use of a validated correction factor, [25] while individual fatty acid results are given as relative amounts of ALA (C18:3n3), EPA (C20:5n3) and DHA (C22:6n3) expressed as a percentage of a total of 26 identified FAs in whole blood. Analyses were quality-controlled according to DIN ISO 15189. ...
Objectives:
To evaluate the association of Omega-3 fatty-acid (O3-FA) blood levels with cardiometabolic risk markers, functional capacity and cardiac function/morphology in HFpEF patients.
Background:
O3-FA demonstrated favorable effects on heart failure and associated phenotypic traits in experimental/clinical studies. In patients with heart failure with preserved ejection fraction (HFpEF), the association of O3-FA status with patient characteristics is unknown.
Methods:
This is a cross-sectional analysis of baseline data from the Aldo-DHF-RCT. From 422 patients, the omega-3-index (O3I=EPA+DHA) was analyzed in n=404 using the HS-Omega-3-Index® methodology. Patient characteristics were; 67±8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥50%, E/e´ 7.1±1.5; median NT-proBNP 158 ng/L (IQR 82-298). Pearson's correlation coefficient was used to describe associations of the O3I with metabolic phenotype, exercise capacity, echocardiographic markers for LVDF, and neurohumoral activation.
Results:
The O3I was below(<8%)/within(8-11%)/higher >11%) than the target range in 374 (93%)/29 (7%)/1 (0.2%) patients respectively. Mean O3I was 5.7±1.7%. The O3I was inversely associated with HbA1c (r=-0.139, p=0.006), triglycerides-to-HDL-C ratio (r=-0.12, p=0.017), triglycerides (r=-0.117, p=0.02), non-HDL-C (r=-0.101, p=0.044), body-mass-index (r=-0.149, p=0.003), waist circumference (r=-0.121, p=0.015), waist-to-height ratio (r=-0.141, p=0.005), and positively associated with submaximal aerobic capacity (r=0.113, p=0.023) and LVEF (r=0.211, p<0.001). We did not observe an association between the =3I and maximal functional capacity, echocardiographic markers of LVDF or NT-proBNP.
Conclusions:
Higher O3I was associated with a more favorable cardiometabolic risk profile and better submaximal aerobic capacity in HFpEF patients but did not correlate with echocardiographic markers for left ventricular filling pressures, left ventricular relaxation or neurohumoral activation.
... Results are given as relative amounts of EPA (C20:5n3) and DHA (C22:6n3), expressed as a percentage of a total of 26 identified FAs, referred to as Omega-3 Index. A validated correction factor was applied for whole blood aliquots (14,15). Where mentioned, ALA (C18:3n3) is given as percentage of a total of 26 identified FAs. ...
... The decreased risk of ischemic events through n-3 PUFA mediated triglyceride level modification was impressively demonstrated in the REDUCE-IT trial, where very high dosages of n-3 PUFAS were administrated (34). In contrast, the median Omega-3 Index of 4.6% in our population is highly comparable to data from other Western countries with an average Index of 4-5% (35-37), but still well-below the 8% recommended for optimal cardioprotection (14) or countries with high fish consumption like Japan (Omega-3 Index between 8 and 10%) (38). This suggests, that in the measured range of our population, no specific lower n-3 threshold exists. ...
Background: Omega-3 fatty acids are associated with a lower risk of cardiovascular disease (CVD) and with beneficial effects on CV risk factors. The albumin-creatinine ratio (ACR) is a risk factor for CVD, all-cause mortality and accelerated glomerular filtration rate (GFR) decline in the general population. We aimed to investigate the association between n-3 PUFAS and ACR in heathy individuals with preserved GFR.
Design and Methods: The present cross-sectional analysis is part of the GAPP study, a population-based cohort of healthy adults aged 25–41 years. Individuals with known CVD, diabetes, or a BMI >35 kg/m ² were excluded. eGFR was calculated according to the combined Creatinine/Cystatin C CKD-EPI formula. ACR was obtained from a fasting morning urine sample. The Omega-3 Index (relative amount of EPA and DHA of total fatty acids in %) was obtained from whole blood aliquots.
Results: Overall, 2001 participants (median age 37 years IQR 31; 40, 53% female) were included in this analysis. Median Omega-3 Index was 4.59 (IQR 4.06; 5.25) and median eGFR 111 ml/min/1.73 m ² (IQR 103; 118). Median ACR was 0.14 mg/mmol (IQR 0; 0.43). We found a significant inverse association of the Omega-3 Index with ACR (ratio 0.84, 95%CI 0.73–0.96; p = 0.011) which remained after comprehensive adjustment (ratio 0.86, 95%CI 0.74–1.00; p = 0.048). No association of the Omega-3 Index with eGFR was found. The adjusted difference in eGFR per 1-unit increase in Omega3-Index was −0.21 (95%CI −0.76; 0.35; p = 0.47).
Conclusions: A higher Omega-3 Index was significantly associated with lower ACR in this young and healthy population with preserved eGFR. Omega-3 fatty acids may exhibit cardio- and nephroprotective effects in healthy individuals through modulation of ACR.
... Ten healthy male and ten healthy female participants aged 50-70 years were enrolled into the study. Inclusion criteria for participation were as follows: age between 50 and 75 years, BMI (kg/m 2 ) 20-35, self-reported oily fish intake of <1 portion/week and an omega-3 index (erythrocyte EPA þ DHA (26) ) determined from a screening blood sample of ≤6·5. Exclusion criteria were any chronic medical condition, cancer within the last 2 years, gastrointestinal problems, allergy to fish, smoking, pregnancy or lactation, or consumption of any n-3 FA or other lipid supplements. ...
... The first was a screening visit during which participants provided written informed consent prior to having their weight and height measured and providing a non-fasting blood sample. This sample was used to determine erythrocyte omega-3 index (EPA þ DHA as a % of total erythrocyte FA (26) ), with a value of ≤6·5 required for study enrolment. Participants who met all inclusion and exclusion criteria were enrolled into the study and randomly assigned. ...
A glyceride mix of mono, di, and triglycerides increases solubilisation and enhances emulsification of omega-3 (ω-3) fatty acid (FA) containing lipids in the stomach. This allows for better access of digestive enzymes, pivotal for the release of bioactive ω-3 FA.
The objective was to compare the effect of a glyceride formulation and an ethyl ester (EE) formulation of EPA+DHA on concentrations of EPA and DHA in plasma following single dosing.
We conducted a double-blind crossover trial in which twenty healthy adults aged 50-70 y consumed a single dose (2.8 g EPA+DHA) of each EPA+DHA formulation without a meal in random order separated by a two-week wash out period. EPA and DHA were measured in plasma total lipid over the following 12 h.
EPA and DHA in plasma total lipid increased over 12 h with both formulations. A 10 x greater Δ concentration of EPA, 3 x greater Δ concentration of DHA, and 5 x greater Δ concentration of EPA+DHA was seen with the glyceride-EPA+DHA. The time at which the maximal concentrations of ω-3 FA occurred was 4 h earlier for EPA, 1 h earlier for DHA, and 2 h earlier for EPA+DHA when consuming glyceride-EPA+DHA.
A mix of mono, di, and triglycerides results in greater and faster incorporation of EPA and DHA into blood plasma lipid in the absence of a fatty meal. This may provide benefit to individuals on a low fat diet or with digestive impairments and could result in greater efficacy in clinical trials using ω-3 FA.
... Packed RBCs were stored at −80°C until batch assayed for n-3 PUFA content of EPA and DHA, the n-3 index (OmegaQuant). 25,26 This analysis was blinded to patient type (healthy versus PAD) and visit number. ...
... The n-3 index is a validated biomarker used to define the RBC content of EPA and DHA, thus it reflects the interplay between oral intake and metabolism of n-3 and omega-6 PUFA. 25,26 Identifying the percentage contribution of EPA and DHA to total RBC fatty acids accurately reflects plasma and tissue levels of EPA and DHA, and may be considered a measure of compliance with the study protocol. At baseline, the n-3 index was significantly lower among patients with PAD compared with healthy volunteers (PAD 4.9±0.3 ...
Background
Peripheral artery disease (PAD) is an advanced form of atherosclerosis characterized by chronic inflammation. Resolution of inflammation is a highly coordinated process driven by specialized pro‐resolving lipid mediators endogenously derived from omega‐3 fatty acids. We investigated the impact of a short‐course, oral, enriched marine oil supplement on leukocyte phenotype and biochemical mediators in patients with symptomatic PAD and healthy volunteers.
Methods and Results
This was a prospective, open‐label study of 5‐day oral administration of an enriched marine oil supplement, assessing 3 escalating doses in 10 healthy volunteers and 10 patients with PAD. Over the course of the study, there was a significant increase in the plasma level of several lipid mediator families, total specialized pro‐resolving lipid mediators, and specialized pro‐resolving lipid mediator:prostaglandin ratio. Supplementation was associated with an increase in phagocytic activity of peripheral blood monocytes and neutrophils. Circulating monocyte phenotyping demonstrated reduced expression of multiple proinflammatory markers (cluster of differentiation 18, 163, 54, and 36, and chemokine receptor 2). Similarly, transcriptional profiling of monocyte‐derived macrophages displayed polarization toward a reparative phenotype postsupplementation. The most notable cellular and biochemical changes over the study occurred in patients with PAD. There were strong correlations between integrated biochemical measures of lipid mediators (specialized pro‐resolving lipid mediators:prostaglandin ratio) and phenotypic changes in circulating leukocytes in both healthy individuals and patients with PAD.
Conclusions
These data suggest that short‐term enriched marine oil supplementation dramatically remodels downstream lipid mediator pathways and induces a less inflammatory and more pro‐resolution phenotype in circulating leukocytes and monocyte‐derived macrophages. Further studies are required to determine the potential clinical relevance of these findings in patients with PAD.
Registration
URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02719665.
... A low Omega-3 Index is associated with high proinflammatory activity, and increasing the Omega-3 Index decreases elevated pro-inflammatory cytokines, like IL-1, IL-6, TNF-alpha [11][12][13][14]. Moreover, an Omega-3 Index below the optimal range of 8-11% is associated with and predicts cardiac and neurological diseases [15][16][17][18][19][20][21][22]. However, the Omega-3 Index is variable across the globe, with most of the countries and regions of the world having levels that are considered low (4-6%) to very low (<4%) [23]. ...
... In all participants blood samples were collected from an anti-cubital vein into EDTA buffered containers and immediately sent to Omegametrix GmbH, Martinsried, Germany. The containers were sent at ambient temperature to the laboratory with no further processing, reached the laboratory within a maximum of 4 days, and were processed on the day of arrival, while stability at ambient temperature has been demonstrated for 7-10 days [15]. Erythrocyte fatty acid composition was analyzed according to the HS-Omega-3 Index ® methodology as previously described [30]. ...
Background
The etiology of degenerative rotator cuff tears is multifactorial but chronic inflammation plays an important role in the pathogenesis. Some polyunsaturated fatty acids (PUFA) can modulate inflammation and marine n-3 (Omega-3) PUFA have anti- inflammatory effects. We hypothesized that the Omega-3 Index is lower in patients with degenerative rotator cuff tears when compared to controls without rotator cuff tendinopathy.
Methods
From 684 consecutive patients with full thickness rotator cuff tears 655 were excluded because of possible bias. In the remaining 29 patients (22 m, 7 f; 53,9 y) with degenerative full thickness rotator-cuff tears, erythrocyte fatty acids were analyzed using the HS-Omega-3 Index® methodology. 15 healthy volunteers (10 m, 5 f; 52.5y) served as a control.
Results
The Omega-3 Index (% EPA + DHA) was 5.01% (95% CI: 3.81–4.66) in patients and 6.01% (95% CI: 4.48–5.72) in controls (p = 0.028) Conclusions
Patients with full thickness degenerative rotator cuff tears had a significantly lower Omega-3 Index than controls without rotator cuff tendinopathy. Whether a lower Omega-3 Index represents an independent risk factor for degenerative rotator cuff tears should be further investigated, e.g. in a longitudinal study.
... Although there is a limitation regarding the difference in the proportion of patients with RRMS and PMS, this study enrolled a considerable total number of participants, in comparison to most previous studies, which mainly investigated the fatty acid profiles between MS patients and controls and in relatively small sample groups, lacking the associations according to the defined clinical course of disease, which we revealed here [7,55,63,66]. The advantage of using erythrocytes as a source of fatty acids lies in the fact that the biological variability in the fatty acid levels in erythrocytes is several times lower than that of plasma [67], thus reflecting a relatively long-term tissue fatty acid status and avoiding the concern that some true associations may be missed [68]. Another strength is that we established course-specific associations of the fatty acid levels with the levels of the molecular indicator of fatty acid peroxidation (4-HNE), as well as the values of relevant clinical parameters (EDSS and MSSS), thus linking the fatty acid changes with the oxidative stress, disability, and severity of the disease. ...
Background/Objectives: Dietary lifestyle, particularly the intake of fatty acids (FAs), may be useful in alleviating the key pathogenic processes in multiple sclerosis (MS); however, the data are still scarce, particularly with regard to the course of disease. Therefore, the objectives of this study were to investigate the erythrocyte profile of FAs in patients with relapsing-remitting (RR)MS and progressive (P)MS, and to examine whether dietary supplementation with n-3 PUFAs could influence the FA profile, according to the course of disease. Methods: The FA profile was determined in erythrocytes by gas–liquid chromatography, in 153 patients with RRMS and 69 with PMS, whereas the group on dietary supplementation with n-3 PUFAs consisted of 36 RRMS and 17 PMS patients. Individual FAs were quantified as a percentage of the total identified FAs and analyzed in relation to the demographic and clinical parameters. Results: Compared to RRMS, the PMS patients had higher saturated (S)FAs, n-7 mono-unsaturated (MU)FAs, and n-3 polyunsaturated (PU)FAs, and lower n-6 PUFAs. In the group on omega-3 supplementation, the only difference in FA profile was higher MUFA 16:1n-7 (POA) in PMS than RRMS patients. In PMS patients, there was a positive correlation of disability (EDSS) with the total SFA levels, whereby 16:0 (PA) correlated positively with EDSS and MS severity (MSSS). Also, in PMS, the MSSS correlated negatively with the total and individual n-6, and positively with the total and individual n-3 PUFAs. In PMS patients on n-3 supplementation, there was a negative correlation between MSSS and total n-6/n-3 ratio, and a positive one between MSSS and 22:6n-3 (DHA). The observed decrease in levels of circulating lipid peroxidation product 4-HNE in PMS patients was not found in the n-3 PUFA supplementation group. Conclusions: The present findings suggest that the changes in the levels of FAs and their correlations are specific for the course of MS. Detected FA profile differences can be influenced by n-3 supplementation, primarily in regard to SFAs and PUFAs, supporting an option for the use of dietary supplements in managing the clinical course and progression of MS.
... 14,15 An ideal target range of 8-11% has been identified for omega-3 index for its protective status. 36,37 Our sample averaged well below this recommendation (PL = 4.70 ± 0.11, FO = 3.90 ± 0.88). Following supplementation, the FO group had a significant 46.92% increase in omega-3 index (5.73 ± 0.16, p = 0.004), but was still far below the recommended guideline of 8%. ...
Introduction: NCAA track and field (T&F) athletes hold one of the longest competitive seasons, making adequate nutrition and supplementation critical. Studies suggest that omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation may benefit athletic performance, strength, and body composition. This study examined the effects of n-3 PUFA supplementation on sport performance, hand grip strength, and body composition in NCAA Division I T&F athletes. Methods: Twenty-five NCAA Division I T&F athletes (14 females, 11 males) were recruited. In a single-blind randomized controlled trial, participants consumed either: 4.0 grams of fish oil (FO) or 4.0 grams of placebo (i.e., coconut oil) daily for eight weeks, starting at the beginning of their outdoor season competitions. Body composition, hand grip strength, sport performance, and omega-3 indexes were sampled prior to in-season competition and following the 8-week supplementation. Data were analyzed using a two-way repeated measures ANOVA (p < 0.05). Results: FO group saw a significant increase in omega-3 index (p = 0.004, but no significant differences in body composition, hand grip strength, or performance. Despite improvement in omega-3 index, all participants still possessed levels below current recommendations. Conclusions: No changes in body composition, hand grip strength, or sport performance were found, despite improvements in omega-3 status with supplementation.
... The study participants' baseline and week-12 blood omega-3 index values [14] and AA:EPA ratios [6] were assessed separately. A lower AA:EPA ratio represents higher inflammatory levels and is used as a marker of chronic inflammation [6]. ...
Background: COVID-19 is known to cause significant multisystem inflammatory responses, leading to symptoms beyond the acute phase of illness. These “long COVID" symptoms affect quality of life and interfere with daily activities. This pilot study looks at the feasibility, tolerability, and safety of omega-3 (docosahexaenoic acid+eicosapentaenoic acid, EPA) among healthcare workers with long COVID symptoms in New Jersey.
Methods: This double-blind, randomized-controlled pilot trial used self-administered omega-3 vs. placebo for 12 weeks in healthcare workers. The enrollment period was from October 2021 to March 2023. Participants were monitored weekly for compliance and adverse effects. They completed the Symptoms and Quality of Life survey biweekly. Baseline and week-12 blood test for omega-3 levels and arachidonic acid (AA):EPA ratio was also measured and analyzed. Descriptive statistics were calculated for all variables at 12 weeks. An independent sample t-test was conducted to compare the ages of the treatment groups. Fisher's exact tests were conducted on each outcome by the treatment arm. No adjustments for multiple testing were included; therefore, significance was set at p ≤ 0.05. Analyses were conducted using R version 4.3.3 (R Core Team, Vienna, Austria).
Results: Thirty-two healthcare workers were recruited, and 18 completed the study. Feasibility was assessed based on enrollment and compliance with the study protocol. There was no significant difference in age between the placebo and treatment groups. The intervention group did not show significant improvement in the long COVID symptoms: shortness of breath (p = 0.39), cough (p = 0.76), fatigue (p = 0.57), lack of taste (p = 0.10), and lack of smell (p = 0.10). In the placebo group, baseline average omega-3 and AA:EPA ratio were 4.09 (standard deviation, SD = 0.85) and 23.9 (SD = 13.4), respectively, and week-12 omega-3 and AA:EPA ratio were 4.46 (SD = 0.95) and 20.8 (SD = 6.0), respectively. For the supplement group, baseline average omega 3 and AA:EPA ratio were 3.75 (SD = 0.48) and 23.1 (SD = 8.3), respectively, and week-12 omega-3 and AA:EPA ratio were 5.97 (SD = 1.93) and 11.8 (SD = 14.0), respectively. One supplement-treated participant and five placebo-treated participants experienced adverse events. No serious adverse events were reported.
Conclusions: This pilot study successfully demonstrated the feasibility, safety, and tolerability of using omega-3 supplements for the treatment of long COVID syndrome. The study results did not show statistically significant improvement in the long COVID symptoms. The mean difference in the AA:EPA ratio in the placebo vs. supplement group showed a pronounced decline in inflammatory markers in the supplement group. However, our study did not show a connection between the decreased inflammatory markers and clinical symptoms. We may need a longer follow-up to understand the possible clinical benefits of the decreased AA:EPA ratio.
... Lipidomic analyses revealed that lipid classes distribution in plasma and erythrocytes of volunteers was not affected by the consumption of MFGM-M (Table 3), with both groups exhibiting a similar evolution after 14 weeks of intervention. Plasma lipids are used as short-term indicators of dietary intake whereas erythrocyte lipids are a reliable indicator of overall FA status (Harris, 2010). The FA composition of plasma and erythrocytes from volunteers are shown in Table 4 and Table 5, respectively. ...
... In order to maintain stable FA levels, samples were immediately cooled, centrifugated, and processed for storage at −80 • C (−112 • F). 2.0 mL aliquots of frozen (−80 • C) EDTA blood taken at baseline were transported to Omegametrix (Martinsried, Germany) and analysed according to the HS-Omega-3 Index ® methodology, which recalculates the longchain omega-3 fatty acid content EPA&DHA into the erythrocyte Omega-3 Index. MUFAs are given as relative amounts of palmitoleic acid (C16:1n7), oleic acid (C18:1n9), eicosenoic acid (C20:1n9), and nervonic acid (C24:1n9) expressed as a percentage of 26 fatty acids in the blood [17]. Acid transesterification generated fatty acid methyl esters. ...
De novo lipogenesis (DNL)-related monounsaturated fatty acids (MUFAs) in the blood are associated with incident heart failure (HF). This observation’s biological plausibility may be due to the potential of these MUFAs to induce proinflammatory pathways, endoplasmic reticulum stress, and insulin resistance, which are pathophysiologically relevant in HF. The associations of circulating MUFAs with cardiometabolic phenotypes in patients with heart failure with a preserved ejection fraction (HFpEF) are unknown. In this secondary analysis of the Aldosterone in Diastolic Heart Failure trial, circulating MUFAs were analysed in 404 patients using the HS-Omega-3-Index® methodology. Patients were 67 ± 8 years old, 53% female, NYHA II/III (87/13%). The ejection fraction was ≥50%, E/e′ 7.1 ± 1.5, and the median NT-proBNP 158 ng/L (IQR 82-298). Associations of MUFAs with metabolic, functional, and echocardiographic patient characteristics at baseline/12 months follow-up (12 mFU) were analysed using Spearman’s correlation coefficients and linear regression analyses, using sex/age as covariates. Circulating levels of C16:1n7 and C18:1n9 were positively associated with BMI/truncal adiposity and associated traits (dysglycemia, atherogenic dyslipidemia, and biomarkers suggestive of non-alcoholic-fatty liver disease). They were furthermore inversely associated with functional capacity at baseline/12 mFU. In contrast, higher levels of C20:1n9 and C24:1n9 were associated with lower cardiometabolic risk and higher exercise capacity at baseline/12 mFU. In patients with HFpEF, circulating levels of individual MUFAs were differentially associated with cardiovascular risk factors. Our findings speak against categorizing FA based on physicochemical properties. Circulating MUFAs may warrant further investigation as prognostic markers in HFpEF.
... La maggior parte della letteratura scientifica relativa agli effetti benefici di questi acidi grassi sullo stato di salute, ed in particolare sul rischio cardiovascolare, è andata ad analizzare prevalentemente il consumo di pesce riferito dalla popolazione in esame piuttosto che utilizzare dei biomarcatori specifici per tale scopo; per questa ragione l'assunzione di omega-3 mediante la dieta, attraverso alimenti o integratori, potrebbe non sempre essere correlata all'effettivo stato degli omega-3 presenti nell'organismo [3]. Nel tentativo di superare questo limite, al fine di misurare l'assorbimento a lungo termine e la deposizione tissutale di questi acidi grassi, alcuni ricercatori si sono quindi concentrati sull'incorporazione di EPA e di DHA all'interno dei lipidi che costituiscono le membrane cellulari degli eritrociti; in particolare si definisce come indice omega-3 (O3I, Omega-3 Index) la percentuale combinata di EPA e di DHA in rapporto agli acidi grassi totali che caratterizzano le membrane dei globuli rossi, determinata con una precisa metodica analitica, ben definita e standardizzata [4]. Si è scelto di valutare le membrane cellulari delle emazie principalmente per la loro semplicità di analisi e per il legame biologicamente stabile a queste strutture da parte di EPA e di DHA, andando quindi a rappresentare l'assunzione a lungo termine di queste molecole ed indicando il loro reale stato di incorporazione tissutale. ...
Gli omega-3 rappresentano una famiglia di acidi grassi di fondamentale importanza per il nostro organismo e la loro carenza può influenzare il nostro stato di salute sotto numerosi aspetti. Secondo i più recenti rapporti relativi al consumo di omega-3 si stima che oltre l'80% della popolazione mondiale, specialmente quella che vive nei paesi occidentali, non assuma una quantità adeguata di questi acidi grassi essenziali attraverso la dieta. La maggior parte della letteratura scientifica relativa agli effetti benefici di questi acidi grassi sullo stato di salute, ed in particolare sul rischio cardiovascolare, è andata ad analizzare prevalentemente il consumo di pesce riferito dalla popolazione in esame piuttosto che utilizzare dei biomarcatori specifici per tale scopo; per questa ragione l' assunzione di omega-3 mediante la dieta, attraverso alimenti o integratori, potrebbe non sempre essere correlata all'effettivo stato degli omega-3 presenti nell' organismo. Nel tentativo di superare questo limite, al fine di misurare l'assorbimento a lungo termine e la deposizione tissutale di questi acidi grassi, alcuni ricercatori si sono quindi concentrati sull'incorporazione di EPA e di DHA all'interno dei lipidi che costituiscono le membrane cellulari degli eritrociti; in particolare si definisce come indice omega-3 (O3I, Omega-3 Index) la percentuale combinata di EPA e di DHA in rapporto agli acidi grassi totali che caratterizzano le membrane dei globuli rossi, determinata con una precisa metodica analitica, ben definita e standardizzata.
... RBC cell membranes consist almost exclusively of phospholipids esterified with EPA and DHA and are pre-analytically stable. In addition, the O3I reflects the EPA + DHA composition of other peripheral tissues (gastrointestinal tract, liver, myocardium, and kidney; Cholewski et al., 2018;Harris, 2010;von Schacky, 2014). ...
The bioavailability of long-chain omega-3 polyunsaturated fatty acids (n3 PUFA) can be affected by the form in which they are bound. An alternative source of n3 PUFA is Calanus finmarchicus oil (CO), which, unlike fish oil (FO) and krill oil (KO), contains fatty acids primarily bound as wax esters. Recent studies have shown that n3 PUFA from CO are bioavailable to humans, but CO has not been compared to other marine oils such as FO or KO. Therefore, the aim of this study was to investigate the influence of 12 weeks supplementation with CO, FO and KO on the long-term n3 PUFA status in healthy volunteers. The Omega-3 Index (O3I), defined as red blood cell EPA + DHA content as a percentage of total identified fatty acids, was used as a measure to assess n3 PUFA status. Sixty-two participants (mean ± standard deviation [SD] age: 29.7 ± 8.43 years) completed the randomized parallel group study (CO group: n = 21, 4 capsules/day, EPA + DHA dose: 242 mg/day; FO group: n = 22, 1 capsule/day, EPA + DHA dose: 248 mg/day; KO group: n = 19, 2 capsules/day, EPA + DHA dose: 286 mg/day). At baseline, the three groups showed comparable (mean ± SD) O3I values (CO: 5.13 ± 1.12%, FO: 4.90 ± 0.57%, KO: 4.87 ± 0.77%). The post-interventional (mean ± SD) O3I increase was comparable between the three groups (CO: 1.09 ± 0.55%; FO: 1.0 ± 0.53%; KO: 1.15 ± 0.65%, all p < 0.001). The study confirms that CO can increase the n3 PUFA status comparable to FO and KO and is therefore an alternative marine source of bioavailable n3 PUFA, especially with regard to sustainability.
... The EPA and DHA content of RBC membranes, i.e., the Omega-3 Index (O3I) [23], reflects long-term dietary omega-3 intake [24] and the EPA+DHA composition of major organs [25]. Optimal O3I levels for cardiovascular health appear to be >8% [26]. O3I is predictive of risk of total mortality in individuals without prevalent cardiovascular disease [27] and associated with mortality risk before and after adjustment for individual n-6 fatty acids, whether in aggregate, by carbon-chain groups, or individually [28]. ...
High red blood distribution width (RDW) is associated with decreased red blood cell deformability, and high neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and innate-adaptive immune system imbalance. Both RDW and NLR are predictors of chronic disease risk and mortality. Omega-3 index (O3I) values have previously been shown to be inversely associated with RDW and NLR levels. Our objective was to determine if total plasma long chain omega-3 fatty acids (Omega3%) measured in the UK Biobank cohort were associated with RDW and NLR values. RDW- and NLR- relationships with Omega3% were characterized in 109,191 adults (58.4% female). RDW- and NLR-Omega3% relationships were inversely associated with Omega3% (both p < 0.0001). These cross-sectional associations confirm previous findings that increasing RDW and NLR values are associated with low O3I. The hypothesis that RDW and/or NLR values can be reduced in individuals with less-than optimal long chain omega 3 values need to be tested in randomized controlled intervention trials using EPA and/or DHA.
... Red blood cells (RBCs) from all timepoints (i.e., baseline, 30 wk of pregnancy, cord blood, and at 3-mo of age) were analyzed to measure the omega-3 index [38], as markers of compliance with the study protocol and absorption of the active treatment. Fatty acid profiles were analyzed via direct transesterification of the washed RBC fraction of blood, followed by gas chromatography [39]. ...
Background:
Maternal obesity during pregnancy is associated with increased risk of obesity and metabolic disease in the offspring. Supplementation with fish oil (FO), which is insulin-sensitizing, during pregnancy in mothers with overweight or obesity may prevent the development of greater adiposity and metabolic dysfunction in their children.
Objective:
To determine the effects of FO supplementation throughout the second half of pregnancy and lactation in mothers with overweight or obesity on infant body composition and metabolism.
Design:
A double-blind randomized controlled trial of 6g FO (3.55 g/day of n-3 PUFAs) versus olive oil (control) from mid-pregnancy until 3 months postpartum. Eligible females had singleton pregnancies at 12-20 weeks of gestation, and BMI ≥25 kg/m2. The primary outcome was infant body fat percentage (DXA scans) at 2 weeks of age. Secondary outcomes included maternal metabolic markers during pregnancy, infant anthropometry at 2 weeks and 3 months of age, and metabolic markers at 3 months.
Results:
129 mothers were randomized, and 98 infants had a DXA scan at 2 weeks.
Primary outcome:
Imputed and non-imputed analyses showed no effects of FO supplementation on infant body fat percentage at age 2 weeks.
Secondary outcomes:
There were no treatment effects on infant outcomes at 2 weeks, but FO infants had higher BMI z-score (p=0.025) and ponderal index (p=0.017) at age 3 months. FO supplementation lowered maternal triglycerides by 17% at 30 weeks of pregnancy (p=0.0002) and infant triglycerides by 21% at 3 months of age (p=0.016), but did not affect maternal or infant insulin resistance (HOMA-IR). The rate of emergency caesarean section was lower with FO supplementation [aRR=0.38 (95%CI 0.16, 0.90); p=0.027].
Conclusions:
FO supplementation of mothers with overweight or obesity during pregnancy did not impact infant body composition. There is a need to follow-up the offspring to determine whether observed metabolic effects persist.
Clinical trial registry:
NumberThis study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617001078347p). In addition, the Universal Trial Number, WHO, has been obtained (U1111-1199-5860).
... For the analysis of fatty acid composition, 2.0 mL aliquots of frozen (− 80 °C) EDTA blood was sent to Omegametrix (Martinsried, Germany). At Omegametrix, a reference laboratory for fatty acid analyses, whole blood fatty acid composition was analyzed according to the HS-Omega-3 Index ® methodology [26]. Fatty acid methyl esters were generated by acid transesterification and were analyzed by gas chromatography using a GC2010 Gas Chromatograph (Shimadzu, Duisburg, Germany) equipped with a SP2560, 100-m column (Supelco, Bellefonte, Pennsylvania, USA) using hydrogen as carrier gas. ...
Background
Industrially processed trans-fatty acids (IP-TFA) have been linked to altered lipoprotein metabolism, inflammation and increased NT-proBNP. In patients with heart failure with preserved ejection fraction (HFpEF), associations of TFA blood levels with patient characteristics are unknown.
Methods
This is a secondary analysis of the Aldo-DHF-RCT. From 422 patients, individual blood TFA were analyzed at baseline in n = 404 using the HS-Omega-3-Index ® methodology. Patient characteristics were: 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E / e ′ 7.1 ± 1.5; NT-proBNP 158 ng/L (IQR 82–298). A principal component analysis was conducted but not used for further analysis as cumulative variance for the first two PCs was low. Spearman’s correlation coefficients as well as linear regression analyses, using sex and age as covariates, were used to describe associations of whole blood TFA with metabolic phenotype, functional capacity, echocardiographic markers for LVDF and neurohumoral activation at baseline and after 12 months.
Results
Blood levels of the naturally occurring TFA C16:1n-7t were inversely associated with dyslipidemia, body mass index/truncal adiposity, surrogate markers for non-alcoholic fatty liver disease and inflammation at baseline/12 months. Conversely, IP-TFA C18:1n9t, C18:2n6tt and C18:2n6tc were positively associated with dyslipidemia and isomer C18:2n6ct with dysglycemia. C18:2n6tt and C18:2n6ct were inversely associated with submaximal aerobic capacity at baseline/12 months. No significant association was found between TFA and cardiac function.
Conclusions
In HFpEF patients, higher blood levels of IP-TFA, but not naturally occurring TFA, were associated with dyslipidemia, dysglycemia and lower functional capacity. Blood TFAs, in particular C16:1n-7t, warrant further investigation as prognostic markers in HFpEF.
Graphical abstract
Higher blood levels of industrially processed TFA, but not of the naturally occurring TFA C16:1n-7t, are associated with a higher risk cardiometabolic phenotype and prognostic of lower aerobic capacity in patients with HFpEF.
... According to the American Heart Association, the general public should aim to consume two servings of fatty fish per week, equal to 0.5 grams per day, to reduce the risk of developing coronary heart disease. 2 Recommendations are increased to one gram per day for those diagnosed with coronary heart disease. 2 Dietary consumption of EPA and DHA is positively associated with the percent of long chain fatty acids found in the erythrocytes, known as the Omega-3 Index. [3][4][5] The Omega-3 Index has been validated for use as a risk factor for cardiovascular health, specifically mortality risk from cardiac arrhythmias. 5 According to Harris, 6 the Omega-3 Index can be utilized as a risk factor, an indicator of intake of omega-3 fatty acids, and a goal for nutrition interventions related to coronary heart disease. ...
Background: A newly developed omega-3 questionnaire (O3Q) designed to capture habitual intakes of omega-3 fatty acids was previously validated based on the whole blood levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and Omega-3 Index, but lacks comparison with existing “gold standard” dietary tools.
Objective: To compare the estimated habitual intakes of omega-3 fatty acids from three dietary assessment tools including O3Q and two other commonly used methods (24-hour recall and Diet History Questionnaire).
Methods: A correlational study of estimated omega-3 intakes from the O3Q, multiple 24-hour recalls, and Diet History Questionnaire collected from an observational study (n = 49) were compared to corresponding whole blood levels of EPA, DHA, and Omega-3 Index. The 49 participants included in this study completed the O3Q, Diet History Questionnaire, and at least one 24-hour recall during the observational study. Any incomplete data sets (missing one of the three kinds of dietary assessments) were excluded. Spearman’s correlation evaluated the relationship between estimated omega-3 intake from each diet assessment method and biomarkers. Stepwise multiple linear regression examined associations of estimated dietary intakes of EPA+DHA from the three intake methods and the Omega-3 Index level.
Results: The estimated intakes from the O3Q had higher correlation coefficients with the corresponding blood biomarkers (EPA, rs=0.75; DHA, rs=0.74; Omega-3 Index, rs=0.77; p<0.001 for all) compared to the DHQ (EPA, rs=0.53; DHA, rs=0.41; Omega-3 Index, rs=0.45; p<0.001 for all) and 24 hr diet recall (EPA, rs=0.61; DHA, rs=0.45; Omega-3 Index, rs=0.55; p<0.001 for all). The regression analysis only demonstrated the O3Q as the significant dietary assessment predictor of the Omega 3-Index level (β = 0.66, p<0.001).
Conclusions: The O3Q is the preferred tool to evaluate habitual Omega-3 fatty acids intake and estimate Omega-3 index and outperforms using multiple 24-hour recalls or the Diet History Questionnaire for these specific dietary variables.
... NLR continued to decrease with increasing O3I until O3I > 8.5%, similar to the target proposed for cardiovascular health, i.e. O3I > 8% [46,81]. Clearly additional evidence, including intervention studies, is needed to determine whether the NLR-O3I relationship is causal or coincidental. ...
The neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and measures innate-adaptive immune system balance. The omega-3-index (O3I) measures the amount of EPA+DHA in blood. Both a low O3I and an elevated NLR are associated with increased risk for chronic disease and mortality, including cardiovascular diseases and cancer. Hypothesizing that low O3I may partly contribute to systemic chronic inflammation, we asked if a relationship existed between O3I and NLR in healthy adults (≥18y, n=28,871, 51% female) without inflammation [C-reactive protein (CRP) <3mg/mL)] who underwent a routine clinical assessment. NLR was inversely associated with O3I before (p<0.0001) and after adjusting for age, sex, BMI, and CRP (p<0.0001). Pearson correlations of other variables with NLR were r=0.06 (CRP), r=0.14 (age), and r=0.01(BMI). In this healthy population, an O3I <6.6% was associated with increasing NLR whereas NLR remained relatively constant (low) when O3I >6.6%, suggestive of a quiescent, balanced immune system.
... We propose that achieving an O3I >5.6% could help maintain a normal RBC size distribution. Our finding complements evidence that a higher O3I is linearly and inversely associated with risk for death from any cause [30], with values of >8% characterizing the lowest risk population [74]. Numerous researchers have called for the establishment of Dietary Reference Intake (DRI) for EPA+DHA [63][64][65]. ...
Low red blood cell (RBC) membrane content of EPA and DHA, i.e., the omega-3 index (O3I), and elevated RBC distribution width (RDW) are risk factors for all-cause mortality. O3I and RDW are related with membrane fluidity and deformability. Our objective was to determine if there is a relationship between O3I and RDW in healthy adults. Subjects without inflammation or anemia, and with values for O3I, RDW, high-sensitivity C-reactive protein (CRP), body mass index (BMI), age and sex were identified (n=25,485) from a clinical laboratory dataset of >45,000 individuals. RDW was inversely associated with O3I in both sexes before and after (both p<0.00001) adjusting models for sex, age, BMI and CRP. Stratification by sex revealed a sex-O3I interaction with the RDW-O3I slope (p<0.00066) being especially steep in females with O3I ≤5.6%. In healthy adults of both sexes, the data suggested that an O3I of >5.6% may help maintain normal RBC structural and functional integrity.
... The Omega-3 Index (O3I) represents the percentage of DHA and EPA making up total erythrocyte fatty acids, with cut-off points of 4% or less, between 4 and 8% and greater than 8% defined as high, moderate, or low coronary heart disease (CHD) risk, respectively [18,19]. In the general Canadian population, mean O3I levels were 4.5%, with less than 3% of Canadians between 20 and 79 years old having levels with low risk for CHD [20]. ...
Background:
EPA and DHA n-3 FA play crucial roles in both neurological and cardiovascular health and high dietary intakes along with supplementation suggest potential neuroprotection and concussion recovery support. Rugby athletes have a high risk of repetitive sub-concussive head impacts which may lead to long-term neurological deficits, but there is a lack of research looking into n-3 FA status in rugby players. We examined the dietary n-3 FA intake through a FFQ and n-3 FA status by measuring the percentage of n-3 FA and O3I in elite Canadian Rugby 7s players to show distribution across O3I risk zones; high risk, <4%; intermediate risk, 4 to 8%; and low risk, >8%.
Methods:
n-3 FA profile and dietary intake as per FFQ were collected at the beginning of the 2017-2018 Rugby 7s season in male (n = 19; 24.84 ± 2.32 years; 95.23 ± 6.93 kg) and female (n = 15; 23.45 ± 3.10 years; 71.21 ± 5.79 kg) athletes.
Results:
O3I averaged 4.54% ± 1.77, with female athlete scores slightly higher, and higher O3I scores in supplemented athletes (4.82% vs. 3.94%, p = 0.183), with a greater proportion of non-supplemented athletes in the high-risk category (45.5% vs. 39.1%). Dietary intake in non-supplemented athletes did not meet daily dietary recommendations for ALA or EPA + DHA compared to supplemented athletes.
Conclusions:
Overall, despite supplementation, O3I score remained in the high-risk category in a proportion of athletes who met recommended n-3 FA dietary intakes, and non-supplemented athletes had a higher proportion of O3I scores in the high-risk category, suggesting that dietary intake alone may not be enough and athletes may require additional dietary and n-3 FA supplementation to reduce neurological and cardiovascular risk.
... The ω-3 HUFA score is the sum of EPA (C20:5ω3), DPA (C22:5ω3), and DHA (C22:6ω3) as a percentage of the most abundant HUFAs (C20:5ω3, C22:5ω3, C22:6ω3, C20:3ω6, C20:4ω6, C22:4ω6, C22:5ω6, C20:3ω9) (35). The %EPA+DHA was calculated by taking the sum of EPA and DHA as a percent of total fatty acids (36). In red blood cells, this value is referred to as Omega 3 Index. ...
Workplace exposure to respirable crystalline silica dust (cSiO2) has been etiologically linked to the development of lupus and other human autoimmune diseases. Lupus triggering can be recapitulated in female NZBWF1 mice by four weekly intranasal instillations with 1 mg cSiO2. This elicits inflammatory/autoimmune gene expression and ectopic lymphoid structure (ELS) development in the lung within 1 week, ultimately driving early onset of systemic autoimmunity and glomerulonephritis. Intriguingly, dietary supplementation with docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid (PUFA) found in fish oil, beginning 2 week prior to cSiO2 challenge, prevented inflammation and autoimmune flaring in this novel model. However, it is not yet known how ω-3 PUFA intervention influences established autoimmunity in this murine model of toxicant-triggered lupus. Here we tested the hypothesis that DHA intervention after cSiO2-initiated intrapulmonary autoimmunity will suppress lupus progression in the NZBWF1 mouse. Six-week old NZWBF1 female mice were fed purified isocaloric diet for 2 weeks and then intranasally instilled with 1 mg cSiO2 or saline vehicle weekly for 4 consecutive weeks. One week after the final instillation, which marks onset of ELS formation, mice were fed diets supplemented with 0, 4, or 10 g/kg DHA. One cohort of mice (n = 8/group) was terminated 13 weeks after the last cSiO2 instillation and assessed for autoimmune hallmarks. A second cohort of mice (n = 8/group) remained on experimental diets and was monitored for proteinuria and moribund criteria to ascertain progression of glomerulonephritis and survival, respectively. DHA consumption dose-dependently increased ω-3 PUFA content in the plasma, lung, and kidney at the expense of the ω-6 PUFA arachidonic acid. Dietary intervention with high but not low DHA after cSiO2 treatment suppressed or delayed: (i) recruitment of T cells and B cells to the lung, (ii) development of pulmonary ELS, (iii) elevation of a wide spectrum of plasma autoantibodies associated with lupus and other autoimmune diseases, (iv) initiation and progression of glomerulonephritis, and (v) onset of the moribund state. Taken together, these preclinical findings suggest that DHA supplementation at a human caloric equivalent of 5 g/d was an effective therapeutic regimen for slowing progression of established autoimmunity triggered by the environmental toxicant cSiO2.
... Unexpectedly, male desaturase-transgenic channel catfish had a 42.8% reduction in total fat compared to controls. The mechanism of converting precursors to longer chain fatty acids is perhaps inefficient, leading to a reduction of total fat (Das 2006;Harris 2010;Jones et al. 2014). This is the likely the reason that the desaturase transgenesis resulted in muscle with a healthier n-3 fatty acid profile, but an overall reduction in n-3 fatty acids. ...
Channel catfish (Ictalurus punctatus) is the primary culture species in the US along with its hybrid made with male blue catfish, I. furcatus. In an effort to improve the nutritional value of channel catfish, the masou salmon Δ5-desaturase like gene (D5D) driven by the common carp beta-actin promoter (βactin) was inserted into channel catfish. The objectives of this study were to determine the effectiveness of βactin-D5D for improving n-3 fatty acid production in F1 transgenic channel catfish, as well as examine pleiotropic effects on growth, proximate analysis, disease resistance, and other performance traits. Transgenic F1 channel catfish showed a 33% increase in the relative proportion of n-3 fatty acids coupled with a 15% decrease in n-6 fatty acids and a 17% decrease in n-9 fatty acids when compared to non-transgenic full-siblings (P < 0.01, P < 0.01, P < 0.01). However, while the relative proportion of n-3 fatty acids was achieved, the total amount of fatty acids in the transgenic fish decreased resulting in a reduction of all fatty acids. Insertion of the βactin-D5D transgene into channel catfish also had large effects on the body composition, and growth of channel catfish. Transgenic channel catfish grew faster, were more disease resistant, had higher protein and moisture percentage, but lower fat percentage than full-sib controls. There were sex effects as performance changes were more dramatic and significant in males. The βactin-D5D transgenic channel catfish were also more uniform in their fatty acid composition, growth and other traits.
... EPA and DHA) in the setting of this study. As a consequence of increased EPA and DHA content in erythrocyte membranes, the O3-I (an important marker for the EPA and DHA status of a person and assumed to be optimal between 8% and 11% [19,20]) was significantly increased in the omega-3 group compared to the control group. However, O3-I until D6 was well below the range assumed to be optimal suggesting that the omega-3 PUFA dose administered in the setting of this study was not high enough to substantially improve EPA and DHA status and in further consequence to induce beneficial effects on lung function [21]. ...
Background and Aims
Enteral nutrition (EN) and parenteral nutrition (PN) enriched with omega-3 polyunsaturated fatty acids (PUFA) have beneficial effects in critical illness. This study aimed to assess the combined effect of EN and supplemental PN enriched with omega-3 PUFA on blood oxygenation in intensive care unit (ICU) patients.
Methods
Single-center, prospective, randomized, controlled, double-blind, phase III trial conducted from 10/2013 to 11/2017. A total of 100 ICU patients (18-85 years, APACHE II score>15) requiring mechanical ventilation were randomly assigned to received combined EN and PN either with omega-3 PUFA (omega-3 group) or without (control group) for up to 28 days. Primary endpoint: ‘change of PaO2/FiO2 from day (D) 1 to D4’. Secondary endpoints: lung function parameters, ICU complications, length of hospital stay, days free of ICU care/ventilation/sedation/catecholamine treatment, mortality, erythrocyte fatty acid composition, inflammatory parameters. Safety parameters: standard laboratory assessment, vital signs, physical examination, SOFA score, adverse events.
Results
Combined EN and PN covered energy requirements to more than 80 %. Blood oxygenation (ΔPaO2/FiO2 from D1 to D4: -1.3 ± 83.7, n=42, and 13.3 ± 86.1, n=39, in omega-3 and control group, respectively, p=0.7795) and other lung function parameters did not differ between groups but days free of catecholamine treatment were significantly higher in the omega-3 group (∼4 days, p=0.0481). On D6, significantly more patients in the omega-3 group tolerated EN alone (51.0 % vs. 29.8 %, p=0.0342).. Eicosapentaenoic acid (EPA) content in erythrocytes was significantly increased in the omega-3 group at last observation compared with the control group (ΔEPA: 0.928 ± 0.808 % vs -0.024 ± 0.190 %, p<0.0001). No further significant group differences were detected.
Conclusions
Enteral and supplemental PN both enriched with omega-3 PUFA did not improve lung function but allowed earlier weaning from catecholamine treatment and PN. Supplemental PN succeeded to adequately cover energy requirements in critically ill patients.
Trial registration
www.clinicaltrials.gov, registration number: NCT01162928.
... The increased of membrane erythrocytes omega-3 FA and decreased omega-6 FA in the erythrocytes membrane result in a decrease in the omega-6/omega-3 FA ratio, which has been associated with a decreased risk of developing T2D by [44]. In other words, considering that the omega-3 index has been proposed as the dietary intake of omega-3 FA [45] from fish consumption [46] and, in particular, from a sardine-enriched diet [20], we can consider it a biomarker of a correct adherence to the nutrition intervention carried out in SG. Also, as demonstrated previously [47], an increase in this index is related with a protective effect against CVD, which would suggest a reduced risk of developing cardiovascular complications in subjects with preDM [48]. ...
Background
Fish could play a role in preventing type 2 diabetes (T2D) but there has been little specification about the type of fish and the preventive mechanism involved in its health claim. The sardine is a source of omega-3 and taurine that, in isolation or in synergy, would produce T2D-delaying through different molecular mechanism.
Hypothesis
The consumption of twice a week of sardine, during one year would reduce T2D-developing risk in a population with prediabetes (preDM) and old age.
Design
152 subjects with fasting glucose between 100-124 mg/dL aged ≥65 yo were recruited from three primary care centers in Barcelona and were randomly distributed among two interventional groups: control group (CG) and sardine group (SG). Both groups received same T2D-prevention nutritional during a year but only SG had to add 200 g of sardine per week. All variables were collected before to start and at the end of the diet. (ClinicalTrials.gov: NCT03557541).
Results
152 people were randomized into CG (n=77) and SG (n=75) with 18 and 12 drop outs respectively. Subjects in SG, significantly compared to CG, decreased percentage classified-individuals in a very high risk group to develop T2D according to FINDRISC (p=0.035). In addition to increasing HDL-cholesterol and adiponectin and decreasing triglycerides (p<0.05) and blood pressure (<0.05), SG showed a lower HOMA-IR (p=0.032). The consumption of sardine characteristics nutrients as omega-3, EPA and DHA, vitamin D, fluorine and taurine were higher for SG (p<0.05). These results agreed with the increased of taurine, fatty acid (FA) omega-3 and bile acids circulating metabolites (p<0.05). Changes erythrocyte membrane FA were detected only in SG with a decrease of 5 omega-6 FA (p<0.001) and an increase of 3 omega-3 FA types (p<0.001).
Conclusion
We conclude that a year T2D-prevention diet with sardine supplementation has a greater protective effect against developing T2D and CV events.
... This change reduced the ω-6/ω-3 ratio to 4% (q < 0.0001), considering that the optimal range is between 3.5 and 5.5%. Moreover, the ω-3 index, considered an independent cardiovascular risk marker in primary prevention [80], significantly increased after the intervention from 5.6 up to 7.3% (q < 0.0001), getting very close to the level suggested for a good cardioprotective effect (≥8%), while an index ≤ 4% has been associated with a high cardiovascular risk [81,82]. Importantly, the literature suggests the relevance of the ω-6/ω-3 ratio in correlation with human health status. ...
Background and aim:
A state of chronic, subclinical inflammation known as inflammaging is present in elderly people and represents a risk factor for all age-related diseases. Dietary supplementation with ad hoc fortified foods seems an appealing strategy to counteract inflammaging. The purpose of this study was to test the efficacy of elderly-tailored fortified milk on inflammaging and different health parameters.
Methods:
A double-blind randomized cross-over study was performed on forty-eight volunteers aged 63-80 years. The fortified milk was enriched with ω-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA), vitamins (25-hydroxyvitamin D, E, C, B6, B9, B12), and trace elements (zinc, selenium). The two intervention periods lasted for 12 weeks, with a 16-week washout intermission.
Results:
Compared to placebo, the consumption of fortified milk increased the circulating levels of different micronutrients, including vitamins and the ω-3 index of erythrocyte membranes. Conversely, it reduced the amount of arachidonic acid, homocysteine, and ω-6/ω-3 ratio.
Conclusion:
Twelve-week daily consumption of adhoc fortified milk has an overall positive impact on different health parameters related to inflammaging in the elderly.
... In the present research, 42% of the pregnant women had an omega-3 index above 8%. It was mentioned that this index plays a pathophysiologic role in depressive symptoms [45,49,50]. The International Society for Nutritional Psychiatry Research Practice Guidelines for ω-3 fatty acids has recently recommended therapeutic dosages of pure EPA or a combination of EPA and DHA (with net EPA starting from at least 1 up to 2 g/day) for at least eight weeks as a potential treatment for major depressive disorders [51]. ...
There is a growing interest in determining fatty acid reference intervals from pregnancy cohort, especially considering the lack of reference values for pregnant women in the literature and the generalized misconception of equating reference intervals for nonpregnant women as equivalent to pregnant women. Seafood and supplements are important dietary sources for the omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA), such as eicosapentaenoic acid (EPA, 20:5ω-3), docosapentaenoic acid (DPA, 22:55ω-3), and docosahexaenoic acid (DHA, 22:6ω-3). Sufficient intake of EPA and DHA is vital during pregnancy for the development of the fetus, as well as for maintaining adequate levels for the mother. This study describes the fatty acid status and suggests reference values and cutoffs for fatty acids in red blood cells (RBC) from pregnant women (n = 247). An electronic food frequency questionnaire (e-FFQ) mapped the dietary habits of the participants, and gas chromatography was used to determine the fatty acid levels in RBC. The association between e-FFQ variables and fatty acid concentrations was established using a principal component analysis (PCA). Twenty-nine-point-one percent (29.1%) of the participants reported eating seafood as dinner according to the Norwegian recommendations, and they added in their diet as well a high percentage (76.9%) intake of ω-3 supplements. The concentration levels of fatty acids in RBC were in agreement with those reported in similar populations from different countries. The reference interval 2.5/97.5 percentiles for EPA, DPA, DHA were 0.23/2.12, 0.56/2.80, 3.76/10.12 in relative concentration units (%), and 5.99/51.25, 11.08/61.97, 64.25/218.08 in absolute concentration units (µg/g), respectively. The number of participants and their selection from all over Norway vouch for the representativeness of the study and the validity of the proposed reference values, and therefore, the study may be a useful tool when studying associations between fatty acid status and health outcome in future studies. To the best of our knowledge, this is the first PCA study reporting a direct association between ω-3 LCPUFA and intake of seafood and ω-3 supplements in a pregnancy cohort.
... The O3I was calculated by taking the sum of EPA and DHA as a percent of total fatty acids (40). In tissues, this value is referred to as EPA + DHA. ...
Lupus is a systemic autoimmune disease typified by uncontrolled inflammation, disruption of immune tolerance, and intermittent flaring – events triggerable by environmental factors. Preclinical and clinical studies reveal that consumption of the marine ω-3 highly unsaturated fatty acids (HUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) might be used as a precision nutrition intervention to lessen lupus symptoms. The anti-inflammatory and pro-resolving effects of ω-3 HUFAs are inextricably linked to their presence in membrane phospholipids. The ω-3 HUFA score, calculated as [100 × (ω-3 HUFAs/(ω-3 HUFAs + ω-6 HUFAs))] in red blood cells (RBCs), and the Omega-3 Index (O3I), calculated as [100 × ((DHA+EPA)/total fatty acids)] in RBCs, are two biomarkers potentially amenable to relating tissue HUFA balance to clinical outcomes in individuals with lupus. Using data from three prior preclinical DHA supplementation studies, we tested the hypothesis that the ω-3 HUFA score and the O3I inversely correlate with indicators of autoimmune pathogenesis in the cSiO2-triggered lupus flaring model. The three studies employed both low and high fat rodent diets, as well as more complex diets emulating the U.S. dietary pattern. The ω-3 HUFA scores in RBCs were comparatively more robust than the O3I at predicting HUFA balances in the kidney, liver, spleen, and lung. Importantly, increases in both the ω-3 HUFA score (>40%) and the O3I (>10%) were strongly associated with suppression of cSiO2-triggered (1) expression of interferon-regulated genes, proinflammatory cytokine production, leukocyte infiltration, and ectopic lymphoid structure development in the lung, (2) pulmonary and systemic autoantibody production, and (3) glomerulonephritis. Collectively, these findings identify achievable ω-3 HUFA scores and O3I thresholds that could be targeted in future human intervention studies querying how ω-3 HUFA consumption influences lupus and other autoimmune diseases.
... Likewise, other authors have reported increased SFA plasma levels in aged individuals [38], with this fact being negatively related to insulin sensitivity and positively related to metabolic syndrome and arterial stiffness [39]. In addition, treatment with the oil mixture significantly increased the % of the ω-3 PUFA EPA and DHA [40,41] which serum levels negatively correlate with cardio-metabolic risk [42]. Therefore, it is likely that most of the beneficial effects could be due, at least in part, to both the decrease in the % of SFA and the increase in the % of both MUFA and PUFA. ...
Aging is one of the major risk factors for suffering cardiovascular and metabolic diseases. Due to the increase in life expectancy, there is a strong interest in the search for anti-aging strategies to treat and prevent these aging-induced disorders. Both omega 3 polyunsaturated fatty acids (ω-3 PUFA) and extra virgin olive oil (EVOO) exert numerous metabolic and cardiovascular benefits in the elderly. In addition, EVOO constitutes an interesting ingredient to stabilize ω-3 PUFA and decrease their oxidation process due to its high content in antioxidant compounds. ω-3 PUFA are commonly obtained from fish. However, more ecological and sustainable sources, such as algae oil (AO) can also be used. In this study, we aimed to study the possible beneficial effect of an oil mixture composed by EVOO (75%) and AO (25%) rich in ω-3 PUFA (35% docosahexaenoic acid (DHA) and 20% eicosapentaenoic acid (EPA)) on the cardiometabolic alterations associated with aging. For this purpose; young (three months old) and old (24 months old) male Wistar rats were treated with vehicle or with the oil mixture (2.5 mL/kg) for 21 days. Treatment with the oil mixture prevented the aging-induced increase in the serum levels of saturated fatty acids (SFA) and the aging-induced decrease in the serum concentrations of mono-unsaturated fatty acids (MUFA). Old treated rats showed increased serum concentrations of EPA and DHA and decreased HOMA-IR index and circulating levels of total cholesterol, insulin and IL-6. Treatment with the oil mixture increased the mRNA levels of antioxidant and insulin sensitivity-related enzymes, as well as reduced the gene expression of pro-inflammatory markers in the liver and in cardiac and aortic tissues. In addition, the treatment also prevented the aging-induced endothelial dysfunction and vascular insulin resistance through activation of the PI3K/Akt pathway. Moreover, aortic rings from old rats treated with the oil mixture showed a decreased response to the vasoconstrictor AngII. In conclusion, treatment with a mixture of EVOO and AO improves the lipid profile, insulin sensitivity and vascular function in aged rats and decreases aging-induced inflammation and oxidative stress in the liver, and in the cardiovascular system. Thus, it could be an interesting strategy to deal with cardiometabolic alterations associated with aging
... However, there is still large interperson variability in tissue incorporation as it relates to intake (8). The O3I was first proposed as a potential risk factor for coronary heart disease (CHD) death in 2004 (6), and subsequent cross-sectional as well as prospective studies have supported its clinical utility for that purpose (9,10). Analysis of these studies shows that an O3I of 8% or more is protective against fatal CHD (11). ...
Background:
Supplemental long-chain omega-3 (n-3) fatty acids (EPA and DHA) raise erythrocyte EPA + DHA [omega-3 index (O3I)] concentrations, but the magnitude or variability of this effect is unclear.
Objective:
The purpose of this study was to model the effects of supplemental EPA + DHA on the O3I.
Methods:
Deidentified data from 1422 individuals from 14 published n-3 intervention trials were included. Variables considered included dose, baseline O3I, sex, age, weight, height, chemical form [ethyl ester (EE) compared with triglyceride (TG)], and duration of treatment. The O3I was measured by the same method in all included studies. Variables were selected by stepwise regression using the Bayesian information criterion.
Results:
Individuals supplemented with EPA + DHA (n = 846) took a mean ± SD of 1983 ± 1297 mg/d, and the placebo controls (n = 576) took none. The mean duration of supplementation was 13.6 ± 6.0 wk. The O3I increased from 4.9% ± 1.7% to 8.1% ± 2.7% in the supplemented individuals ( P < 0.0001). The final model included dose, baseline O3I, and chemical formulation type (EE or TG), and these explained 62% of the variance in response (P < 0.0001). The model predicted that the final O3I (and 95% CI) for a population like this, with a baseline concentration of 4.9%, given 850 mg/d of EPA + DHA EE would be ∼6.5% (95% CI: 6.3%, 6.7%). Gram for gram, TG-based supplements increased the O3I by about 1 percentage point more than EE products.
Conclusions:
Of the factors tested, only baseline O3I, dose, and chemical formulation were significant predictors of O3I response to supplementation. The model developed here can be used by researchers to help estimate the O3I response to a given EPA + DHA dose and chemical form.
... For fish oil supplementation, the intake duration of 16 weeks was long enough to reach a steady state condition [88][89][90] and the intake amount was high enough to trigger a significant increase of the omega-3 FAs values in the blood. For the omega-3 index, all the participants within the fish oil group adapted from a undesirable level of less than 4% or an intermediate-risk zone of 4-8% to a cardio protective level of 8% or higher [91] after 16 weeks. We concluded that all the participants responded well to the fish oil supplementation. ...
Abstract Background Older adults often suffer from age- and behavior-related brain changes affecting neuronal functioning and, therefore, cognitive and motor functions. The improvement of these functions might decrease falls and improve mobility. Previous studies indicate that video game-based physical exercise, so-called exergames, or omega-3 fatty acids (FAs) improve motor and cognitive functioning through brain adaptations. The aim of this study was to assess the effects of exergame training combined with fish oil supplementation on neuronal system levels in the brain and behavioral measurements in older adults. We hypothesized that the combination would differently affect these factors compared to the sole administration of exergame. Methods Fifty-eight participants were randomly assigned to one of two groups (N = 29 each group) in a parallel, double-blind, randomized controlled trial lasting 26 weeks. The experimental group received daily fish oil, whereas the control group received daily olive oil. After 16 weeks, both groups started with an exergame training. Measurements were performed pre, during, and post intervention. Primary outcomes were recruitment curves using transcranial magnetic stimulation and response-locked potentials using electroencephalography. Secondary outcomes included executive functions and gait parameters. Blood samples were taken to control for FAs. Results Forty-three individuals (mean age 69.4 ± 4.6 years) completed the study (Nexperimental = 22, Ncontrol = 21). The results showed no significant time × group interaction effects for any parameters. Blood samples demonstrated significant time × group interaction effects. Post-hoc tests showed a significant increase of omega-3 FAs (p
... The O3-I has been demonstrated to have a good dose-response relationship with dietary intakes of O3-FAs, and the O3-I has been a validated surrogate biomarker of dietary intakes [21,[36][37][38]. Omega-3 status has been related to a wide range of health outcomes. ...
Vitamin D plays an important role in bone health, but dietary intakes are below recommendations. The purpose of this cross-sectional study was to compare perceptions of dietary vitamin adequacy with the biomarker of vitamin D exposure [25(OH)D] in two populations with (USA) and without (Germany) fortification among adults not using dietary supplements (n = 200). US adults were more racially diverse and younger, but did not differ with regard to educational attainment, income, UV exposure, or BMI. Mean concentrations were lower, and the prevalence of inadequacy (<20 ng/mL) and suboptimal (<30 ng/mL) 25(OH)D was higher in Germany (23 ng/mL; 70%; 82%) than in the USA (28 ng/mL; 17%; 36%), respectively. Most adults rated vitamin D as important for bone health; but, fewer Germans (22%) than US adults (50%) perceived their diet as adequate. Mean 25(OH)D concentrations and risk of vitamin D inadequacy did not differ by perceptions of dietary adequacy, ratings of a balanced diet, knowledge of vitamin D food sources, or by rankings of importance of vitamin D for health. Fortification with vitamin D in the USA may explain the higher 25(OH) concentrations as UV exposure, and BMI did not differ. Perceptions and knowledge of vitamin D were not related to status in either group.
... The omega-3 index which corresponds to the percentage of EPA and DHA in RBC membranes was formally developed and used as a biomarker for cardiovascular health [40,41]. Although an omega-3 index of >8% has been set as a target for good cardiovascular health, it has been observed that an omega-3 index >10% is associated with better insulin sensitivity among overweight males [42]. ...
Three recent studies revealed synergy between immune-checkpoint inhibitors and the microbiome as a new approach in the treatment of cancer. Incidentally, there has been significant progress in understanding the role of polyunsaturated fatty acids (PUFAs) in modulating cancer and the immune system, as well as in regulating the microbiome. Inflammation seems to be the common denominator among these seemingly unrelated biological entities-immune system, the microbiome, and long-chain polyunsaturated fatty acids (LC-PUFAs). This commentary presents a hypothesis proposing the existence of an optimal level of LC-PUFAs that nurtures the suitable gut microbiota preventing dysbiosis. This synergy between optimal LC-PUFAs and gut microbiota helps the immune system overcome the immunosuppressive tumour microenvironment including enhancing the efficacy of immune checkpoint inhibitors. A model on how LC-PUFAs (such as omega(n)-3 and n-6 fatty acids) forms a synergistic triad with the immune system and the microbiome in regulating inflammation to maintain homeostasis is presented. The principles underlying the hypothesis provide a basis in managing and even preventing cancer and other chronic diseases associated with inflammation.
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) from fish and fish oils can protect against cardiovascular disease (CVD), which is still the most common cause of mortality and morbidity worldwide. To reduce CVD risk, integral lifestyle modifications, such as smoking cessation, moderate alcohol consumption, exercise, stress reduction, weight control, and diet, are needed. Evidence indicates that consuming fatty fish and n-3 PUFAs reduces the risk of CVD and mortality. Extensive randomized trials and meta-analyses have shown that high doses (1.8–4.0 g/day) of n-3 PUFAs are associated with a modest reduction in risk of myocardial infarction (MI) (−25%) as a secondary prevention, but not in the risk of all-cause mortality. However, the clinical outcomes of n-3 PUFAs are unequivocal, because their effects appear to depend on optimal background treatments (such as statins or antiplatelet agents) and specific patient groups. The optimal cutoff dose has not been established for the protective effects of n-3 PUFAs against CVD.
Background/Objectives: Traumatic brain injury (TBI) can lead to substantial disability and health loss. Despite its importance and impact worldwide, no treatment options are currently available to help protect or preserve brain structure and function following injury. In this review, we discuss the potential benefits of using omega-3 polyunsaturated fatty acids (O3 PUFAs) as therapeutic agents in the context of TBI in the paediatric and adult populations. Methods: Preclinical and clinical research reports investigating the effects of O3 PUFA-based interventions on the consequences of TBI were retrieved and reviewed, and the evidence presented and discussed. Results: A range of animal models of TBI, types of injury, and O3 PUFA dosing regimens and administration protocols have been used in different strategies to investigate the effects of O3 PUFAs in TBI. Most evidence comes from preclinical studies, with limited clinical data available thus far. Overall, research indicates that high O3 PUFA levels help lessen the harmful effects of TBI by reducing tissue damage and cell loss, decreasing associated neuroinflammation and the immune response, which in turn moderates the severity of the associated neurological dysfunction. Conclusions: Data from the studies reviewed here indicate that O3 PUFAs could substantially alleviate the impact of traumatic injuries in the central nervous system, protect structure and help restore function in both the immature and adult brains.
Microalgae are being recognized as valuable sources of bioactive chemicals with important medical properties, attracting interest from multiple industries, such as food, feed, cosmetics, and medicines. This review study explores the extensive research on identifying important bioactive chemicals from microalgae, and choosing the best strains for nutraceutical manufacturing. It explores the most recent developments in recovery and formulation strategies for creating stable, high-purity, and quality end products for various industrial uses. This paper stresses the significance of using Life Cycle Analysis (LCA) as a strategic tool with which to improve the entire process. By incorporating LCA into decision-making processes, researchers and industry stakeholders can assess the environmental impact, cost-effectiveness, and sustainability of raw materials of several approaches. This comprehensive strategy will allow for the choosing of the most effective techniques, which in turn will promote sustainable practices for developing microalgae-based products. This review offers a detailed analysis of the bioactive compounds, strain selection methods, advanced processing techniques, and the incorporation of LCA. It will serve as a valuable resource for researchers and industry experts interested in utilizing microalgae for producing bioactive products with medicinal properties.
Background:
Industrially processed trans-fatty acids (IP-TFA) have been linked to altered lipoprotein metabolism, inflammation and increased NTproBNP. In patients with heart failure with preserved ejection fraction (HFpEF), associations of TFA blood levels with patient characteristics are unknown.
Methods:
This is a secondary analysis of the Aldo-DHF-RCT. From 422 patients, individual blood TFA were analyzed at baseline in n=404 using the HS-Omega-3-Index® methodology. Patient characteristics were; 67±8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥50%, E/e´ 7.1±1.5; NT-proBNP 158 ng/L (IQR 82-298). A principal component analysis was conducted but not used for further analysis as cumulative variance for the first two PCs was low. Spearman´s correlation coefficients as well as linear regression analyses, using sex and age as covariates, were used to describe associations of whole blood TFA with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline and after 12 months.
Results:
Blood levels of the naturally occurring TFA C16:1n-7t were inversely associated with dyslipidemia, body-mass-index/truncal adiposity, surrogate markers for non-alcoholic fatty liver disease and inflammation at baseline/12 months. Conversely, IP-TFA C18:1n9t, C18:2n6tt and C18:2n6tc were positively associated with dyslipidemia and isomer C18:2n6ct with dysglycemia. C18:2n6tt and C18:2n6ct were inversely associated with submaximal aerobic capacity at baseline/12 months. No significant association was found between TFA and cardiac function.
Conclusions:
In HFpEF patients, higher blood levels of IP-TFA, but not naturally occurring TFA, were associated with dyslipidemia, dysglycemia and lower functional capacity. Blood TFAs, in particular C16:1n-7t, warrant further investigation as prognostic markers in HFpEF.
The EPA+DHA content of red blood cell membranes, i.e., the omega-3 index (O3I), reflects omega-3 fatty acid status. EPA and DHA modulate inflammation via effects on cell signaling and the synthesis of pro-resolving lipid mediators. The neutrophil-lymphocyte ratio (NLR) is a measure of innate-adaptive immune system balance and is a biomarker of systemic inflammation. Both a low O3I and an elevated NLR are associated with increased risk for chronic disease and mortality, including cardiovascular diseases and cancer. Our objective was to determine if a relationship existed between O3I and NLR in healthy adults. A healthy cohort of 28,871 non-inflamed individuals [C-reactive protein (CRP) <3 mg/L] was identified from a clinical laboratory dataset. NLR was inversely associated with O3I (p<0.0001) after adjusting for age, sex, body mass index, and CRP. In this healthy population, an O3I >6.6% was associated with a low NLR, reflective of a quiescent, balanced immune system.
Background
The effects of fish oil products containing docosahexaenoic acid (DHA) on LDL-C levels are controversial.
Objective
To determine if changes in erythrocyte DHA are associated with changes in LDL-C levels.
Methods
In this prospective observational study, erythrocyte DHA levels and LDL-C levels were measured in 9253 individuals who presented for at least two examinations at a medical clinic. Changes in DHA levels and the reported use of omega-3 dietary supplements were correlated with changes in LDL-C in multi-variable adjusted models including the use of LDL-C-lowering drugs.
Results
Mean (standard deviation) age at baseline was 52.6 (10.6) years, and the time between exams averaged 1.9 (1.4) years. As a group, erythrocyte DHA increased from 5.0% (1.3) to 5.3% (1.3) (p < 0.001), and LDL-C was not significantly changed (109 (33) to 108 (33) mg/dL, p = 0.875). However, in multivariable-adjusted models of within-participant changes, a 1% increase in erythrocyte DHA was associated with a 1.9 mg/dL reduction in LDL-C (95% confidence interval (1.6, 2.2), p < 0.001). Similar relationships were seen with changes in erythrocyte EPA and EPA + DHA. In adjusted analyses, an increased use of omega-3 supplements was associated with a significant increase in erythrocyte DHA and a decrease in LDL-C in both users and non-users of lipid-lowering drugs.
Conclusions
In a predominantly male, normolipidemic, middle-aged cohort, increases in erythrocyte DHA were associated with decreases in LDL-C, and initiating fish oil supplement use did not increase LDL-C. These findings may serve to reassure individuals who, in adopting a more heart-healthy lifestyle, want to increase their omega-3 fatty acid intake.
Introduction
Maternal obesity during pregnancy is associated with adverse changes in body composition and metabolism in the offspring. We hypothesise that supplementation during pregnancy of overweight and obese women may help prevent the development of greater adiposity and metabolic dysfunction in children. Previous clinical trials investigating fish oil supplementation in pregnancy on metabolic outcomes and body composition of the children have not focused on the pregnancies of overweight or obese women.
Methods and analysis
A double-blind randomised controlled trial of fish oil (providing 3 g/day of n-3 polyunsaturated fatty acids) versus an equal volume of olive oil (control) taken daily from recruitment until birth, and in breastfeeding mothers, further continued for 3 months post partum. Eligible women will have a singleton pregnancy at 12–20 weeks’ gestation and be aged 18–40 years with body mass index ≥25 kg/m2 at baseline. We aim to recruit a minimum of 128 participants to be randomised 1:1. Clinical assessments will be performed at baseline and 30 weeks of pregnancy, including anthropometric measurements, fasting metabolic markers, measures of anxiety, physical activity, quality of life and dietary intake. Subsequent assessments will be performed when the infant is 2 weeks, 3 months and 12 months of age for anthropometry, body composition (dual-energy X-ray absorptiometry (DXA)) and blood sampling. The primary outcome of the study is a between-group difference in infant percentage body fatness, assessed by DXA, at 2 weeks of age. Secondary outcomes will include differences in anthropometric measures at each time point, percentage body fat at 3 and 12 months and homeostatic model assessment of insulin resistance at 3 months. Statistical analysis will be carried out on the principle of intention to treat.
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 long chain polyunsaturated fatty acids (n-3 LCPUFA) are necessary for optimum mental health, with recent studies showing low n-3 LCPUFA in people at ultra-high risk (UHR) of developing psychosis. Furthermore, people at UHR of psychosis had increased erythrocyte sphingomyelin (SM) and reduced phosphatidylethanolamine (PE) concentrations as well as 27 erythrocyte phospholipid species that differed when compared to erythrocytes from age matched people not at UHR of psychosis. The aim of this analysis was to evaluate the effect of n-3 supplementation on the different erythrocyte lipid species (including SM and PE concentrations) in people at UHR of psychosis. Participants were randomly assigned to fish oil (containing 840mg EPA and 560mg DHA per day) or placebo (paraffin oil) for 6 months. Fasted blood samples were taken at baseline and post intervention. Mass spectrometry was used to analyse the molecular phospholipids and fatty acid composition of erythrocytes for both groups. The n-3 index was significantly increased from 3.0% to 4.12% after 6 months of receiving n-3 capsules. Fish oil capsules increased the phospholipid molecular species containing n-3 LCPUFA, and concomitant decreases in n-6 LCPUFA species. SM species did not show any significant changes in n-3 LCPUFA group however, three SM species (SM 16:0, SM 18:0, SM 18:1) significantly increased after 6 months of supplementation with placebo. N-3 supplementation for 6 months led to higher n-3 incorporation into erythrocytes, at the expense of n-6 PUFA across all phospholipid classes analysed and may have prevented the increase in SM seen in the placebo group.
Objectives:
The aim of this study was to determine if plasma eicosapentaenoic acid (EPA) abundance (%EPA) is associated with reduced hazard for primary heart failure (HF) events in the MESA (Multi-Ethnic Study of Atherosclerosis) trial.
Background:
Clinical trials suggest that omega-3 polyunsaturated fatty acids (ω3 PUFAs) prevent sudden death in coronary heart disease and HF, but this is controversial. In mice, the authors demonstrated that the ω3 PUFA EPA prevents contractile dysfunction and fibrosis in an HF model, but whether this extends to humans is unclear.
Methods:
In the MESA cohort, the authors tested if plasma phospholipid EPA predicts primary HF incidence, including HF with reduced ejection fraction (EF) (EF <45%) and HF with preserved EF (EF ≥45%) using Cox proportional hazards modeling.
Results:
A total of 6,562 participants 45 to 84 years of age had EPA measured at baseline (1,794 black, 794 Chinese, 1,442 Hispanic, and 2,532 white; 52% women). Over a median follow-up period of 13.0 years, 292 HF events occurred: 128 HF with reduced EF, 110 HF with preserved EF, and 54 with unknown EF status. %EPA in HF-free participants was 0.76% (0.75% to 0.77%) but was lower in participants with HF at 0.69% (0.64% to 0.74%) (p = 0.005). Log %EPA was associated with lower HF incidence (hazard ratio: 0.73 [95% confidence interval: 0.60 to 0.91] per log-unit difference in %EPA; p = 0.001). Adjusting for age, sex, race, body mass index, smoking, diabetes mellitus, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid for each cluster did not change this relationship. Sensitivity analyses showed no dependence on HF type.
Conclusions:
Higher plasma EPA was significantly associated with reduced risk for HF, with both reduced and preserved EF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).
The objective of the study is to compare the fatty acid pattern in different blood components to find the simplest and most appropriate method for the rapid validation of the essential fatty acids in humans. Comparing the different blood components can lead to a specifying the preferred component for easy and rapid analysis of fatty acids
while giving valid information about the status of essential fatty acids.
Ischemic heart disease is very uncommon in Greenland Eskimos (Harvald, 1974). In his extensive nosography of Greenland, Berthelsen (1940) does not even mention this disease, although he gives some information on atherosclerosis in Greenlanders. Other thrombotic diseases, in both the arterial and the venous systems, are mentioned either very infrequently by him or not at all. In the annual report on the state of health in Greenland (Bøggild et al., 1978) covering the years 1973–1976, death from ischemic heart diseases constitutes an average of 3.5% of all causes of death. In this and in other official medical statistics, no distinction is made between true Greenlanders and Danish workers who spend various amounts of time in Greenland, but who almost invariably carry their Western way of life with them. However, this fraction of the total population of nearly 50,000 inhabitants on this huge island of 2,175,000 km2 is small. Life expectancy rapidly increased in the more than 60 years since tuberculosis was successfully defeated. The most common cause of death is still accidents, amounting to about one-third of all deaths. The same statistical source reports an annual average of 9 1/2 cases of myocardial infarction among hospitalized patients in Greenland. The majority of these, as well as of the deaths reportedly caused by ischemic heart diseases, is from the southern and most “Westernized” part of Greenland, whereas from 1968 to 1978, not a single death from ischemic heart disease or case of myocardial infarction was reported from the UmanaK district (population of about 2600) where the present investigations were carried out.
Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease. We aimed to test the hypothesis that long-term use of eicosapentaenoic acid (EPA) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish.
18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999. Patients were randomly assigned to receive either 1800 mg of EPA daily with statin (EPA group; n=9326) or statin only (controls; n=9319) with a 5-year follow-up. The primary endpoint was any major coronary event, including sudden cardiac death, fatal and non-fatal myocardial infarction, and other non-fatal events including unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting. Analysis was by intention-to-treat. The study was registered at ClinicalTrials.gov, number NCT00231738.
At mean follow-up of 4.6 years, we detected the primary endpoint in 262 (2.8%) patients in the EPA group and 324 (3.5%) in controls-a 19% relative reduction in major coronary events (p=0.011). Post-treatment LDL cholesterol concentrations decreased 25%, from 4.7 mmol/L in both groups. Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events. Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group. Sudden cardiac death and coronary death did not differ between groups. In patients with a history of coronary artery disease who were given EPA treatment, major coronary events were reduced by 19% (secondary prevention subgroup: 158 [8.7%] in the EPA group vs 197 [10.7%] in the control group; p=0.048). In patients with no history of coronary artery disease, EPA treatment reduced major coronary events by 18%, but this finding was not significant (104 [1.4%] in the EPA group vs 127 [1.7%] in the control group; p=0.132).
EPA is a promising treatment for prevention of major coronary events, and especially non-fatal coronary events, in Japanese hypercholesterolaemic patients.
There is strong evidence that the intake of EPA and DHA reduces the risk of adverse cardiac events. Fish and fish oil capsules are not necessarily an ideal source of EPA and DHA for every individual. The aim of the present study was to evaluate the effect of a convenience drink enriched with 500 mg EPA and DHA on the n-3 index, a biomarker of EPA and DHA status in an individual. Of the 190 subjects with atherosclerotic disease screened between February and June 2009, 50 were recruited based on an n-3 index < 5 %. Participants were randomly assigned to receive a convenience drink supplemented either with n-3 fatty acids (n 40, 200 mg EPA and 300 mg DHA) or placebo (n 10, 1.1 g linoleic acid, C18 : 2n-6, from maize oil) daily for 8 weeks. The primary end point was a change in the n-3 index. Intention-to-treat analysis was done. After 8 weeks of daily intake of 200 mg EPA+300 mg DHA, the mean n-3 index increased from 4.37 (sd 0.51) to 6.80 (sd 1.45) % (P < 0.001). Interindividual variability in response was high (CV of the Delta, cv = 0.21). The control group showed no change in the n-3 index. The results showed that daily intake of a convenience drink supplemented with n-3 fatty acids leads to a significant increase of the n-3 index with high interindividual variability in response. Dose and preparation used were safe, well tolerated and highly palatable.
Background
Although red blood cell eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) content (the Omega-3 Index) predicts cardiovascular death, the factors determining the Index are unknown.
Methods
In 704 outpatients, we undertook an investigation of the clinical determinants of the Index.
Results
Factors associated with the Index in decreasing order were: EPA+DHA supplement use, fish consumption frequency, triglyceride level, age, high cholesterol history, and smoking. These factors explained 59% of Index variability, with capsules/fish intake together accounting for 47%. The Index increased by 13% ( p < 0.0001) for each serving level increase in fish intake and EPA+DHA supplementation correlated with a 58% increase ( p < 0.0001) regardless of background fish intake ( p =0.25; test for interaction). A 100 mg/dL decrease in serum triglycerides was associated with a 15% higher (p<0.0001) Index.
Conclusions
The intake of EPA+DHA-rich foods and supplements principally determined the Omega-3 Index, but explained only about half of the variability.
Studies of depressed psychiatric patients have shown that antidepressant efficacy can be increased by augmentation with omega-3 fatty acids.
To determine whether omega-3 improves the response to sertraline in patients with major depression and coronary heart disease (CHD).
Randomized controlled trial. Between May 2005 and December 2008, 122 patients in St Louis, Missouri, with major depression and CHD were randomized.
After a 2-week run-in period, all patients were given 50 mg/d of sertraline and randomized in double-blind fashion to receive 2 g/d of omega-3 acid ethyl esters (930 mg of eicosapentaenoic acid [EPA] and 750 mg of docosahexaenoic acid [DHA]) (n=62) or to corn oil placebo capsules (n=60) for 10 weeks.
Scores on the Beck Depression Inventory (BDI-II) and the Hamilton Rating Scale for Depression (HAM-D).
Adherence to the medication regimen was 97% or more in both groups for both medications. There were no differences in weekly BDI-II scores (treatment x time interaction = 0.02; 95% confidence interval [CI], -0.33 to 0.36; t(112) = 0.11; P = .91), pre-post BDI-II scores (placebo, 14.8 vs omega-3, 16.1; 95% difference-in-means CI, -4.5 to 2.0; t(116) = -0.77; P = .44), or HAM-D scores (placebo, 9.4 vs omega-3, 9.3; 95% difference-in-means CI, -2.2 to 2.4; t(115) = 0.12; P = .90). The groups did not differ on predefined indicators of depression remission (BDI-II < or = 8: placebo, 27.4% vs omega-3, 28.3%; odds ratio [OR], 0.96; 95% CI, 0.43-2.15; t(113) = -0.11; P = .91) or response (> 50% reduction in BDI-II from baseline: placebo, 49.0% vs omega-3, 47.7%; OR, 1.06; 95% CI, 0.51-2.19; t(112) = 0.15; P = .88).
Treatment of patients with CHD and major depression with sertraline and omega-3 fatty acids did not result in superior depression outcomes at 10 weeks, compared with sertraline and placebo. Whether higher doses of omega-3 or sertraline, a different ratio of EPA to DHA, longer treatment, or omega-3 monotherapy can improve depression in patients with CHD remains to be determined.
clinicaltrials.gov Identifier: NCT00116857.
The risk of CHD has been linked to n-3 and trans-fatty acids. The purpose of the present study was to evaluate the hypothesis that lower n-3 fatty acids and higher trans-fatty acids in erythrocytes are associated with an increased risk of acute non-fatal myocardial infarction (MI), and that fatty acid profiles can discriminate MI cases from controls. Fifty cases with acute non-fatal MI and fifty age- and sex-matched controls without MI were recruited. The Omega-3 Index (the sum of EPA and DHA in erythrocytes) was significantly lower in cases than controls (9.57 (SEM 0.28) v. 11.81 (SEM 0.35) %; P < 0.001), while total trans-fatty acids were significantly higher (1.01 (SEM 0.04) v. 0.56 (SEM 0.03) %; P < 0.001). The Omega-3 Index was associated with decreased risk of MI (OR 0.08 (95 % CI 0.02, 0.38); P = 0.001), while total trans-fatty acids were associated with an increased risk of MI (OR 72.67 (95 % CI 6.68, 790.74); P < 0.001). The area under the receiver operating characteristic curve of fatty acid profiles was larger than that for traditional risk factors, suggesting that fatty acid profiles make a higher contribution to the discrimination of MI cases from controls compared with modified Framingham risk factors. In conclusion, a higher Omega-3 Index and lower trans-fatty acids in erythrocytes are associated with a decreased risk of MI. Furthermore, fatty acid profiles improve discrimination of acute non-fatal MI compared with established risk factors.
Diabetes mellitus (DM) and deficiency in n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) are known to increase the incidence of cardiovascular disease (CVD). However, it has not yet been reported whether n-3 LCPUFAs are related to arteriosclerosis in patients under long-term hemodialysis (HD).
Pulse wave velocity from the brachium to the ankle (baPWV) was measured as a marker of arteriosclerosis with a volume-plethysmographic apparatus in 147 long-term HD patients (non-diabetic (non-DM): 51 males/42 females, 62 +/- 14 y; and DM: 33 males/21 females, 67 +/- 9 y). The fatty acid composition of the total phospholipid fraction from washed RBCs was analyzed by gas chromatography. Analyses were adjusted for age, sex, diastolic blood pressure, pulse, body mass index, duration of HD treatment, smoking status, LDL/HDL-cholesterol ratios and diabetes mellitus (DM).
The mean baPWV was 18.9 +/- 5.2 and 23.7 +/- 6.3 m/s in non-DM and DM patients, respectively. The mean baPWV in DM patients was significantly higher than that of non-DM patients after adjustment (p = 0.0002). Multiple regression analysis showed that there was a significant inverse association between baPWV and docosahexaenoic acid (DHA) levels (p = 0.017) and DHA/arachidonic acid (AA) ratios (p = 0.012) in RBC in non-DM patients after adjustment but not in DM patients.
We suggest that n-3 LCPUFAs may be a negative risk factor of CVD also in non-DM HD patients. In DM patients the effects of n-3 PUFAs on the vascular system became undetectable probably because DM overwhelmingly affected PWV. Further studies in a prospective manner are necessary.
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Tissue levels of n-3 fatty acids reflect dietary intake, but quantitative data about rate of incorporation and levels as a function of intake are scarce. We fed 58 men 0, 3, 6, or 9 g/d of fish oil for 12 months and monitored fatty acids in serum cholesteryl esters, erythrocytes, and subcutaneous fat during and after supplementation. Eicosapentaenoic acid (EPA) in cholesteryl esters plateaued after 4-8 weeks; the incorporation half-life was 4.8 days. Steady-state levels increased by 3.9 +/- 0.3 mass % points (+/- SE) for each extra gram of EPA eaten per day. Incorporation of docosahexaenoic acid (DHA) was erratic; plateau values were 1.1 +/- 0.1 mass % higher for every g/d ingested. Incorporation of EPA into erythrocyte membranes showed a half-life of 28 days; a steady state was reached after 180 days. Each g/d increased levels by 2.1 +/- 0.1 mass %. C22:5n-3 levels increased markedly. Changes in DHA were erratic and smaller. EPA levels in adipose tissue rose also; the change after 6 months was 67% of that after 12 months in gluteal and 75% in abdominal fat. After 12 months each gram per day caused an 0.11 +/- 0.01 mass % rise in gluteal fat for EPA, 0.53 +/- 0.07 for C22:5n-3, and 0.14 +/- 0.03 for DHA. Thus, different (n-3) fatty acids were incorporated with different efficiencies, possibly because of interconversions or different affinities of the enzymatic pathways involved. EPA levels in cholesteryl esters reflect intake over the past week or two, erythrocytes over the past month or two, and adipose tissue over a period of years. These findings may help in assessing the intake of (n-3) fatty acids in epidemiological studies.
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.
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.
The blood eicosapentaenoic and docosahexaenoic acid (EPA+DHA) concentration is an important inverse risk factor for sudden cardiac death. However, it is not known what kinds of factors influence the EPA+DHA levels in the total phospholipid fraction in red blood cells (RBC EPA+DHA) in Japan, who regularly eat more fish with increasing age. Four hundred and fifty-six healthy individuals (320 men and 136 women, 18 to 70 years old) were recruited between 2002 and 2005. RBC EPA+DHA were measured by gas chromatography and questionnaires were administered. Multivariate analysis indicated that there were significant correlations between RBC EPA+DHA and (i) dietary EPA+DHA (beta=0.31), (ii) age (beta=0.33), (iii) gender (beta=-0.15) and (iv) physical activity (beta=-0.11) but not with body mass index or smoking.
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.
Background-Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction. Methods and Results-In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths. Conclusions-The early effect of low-dose ( I g/d) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies.
Background
Several epidemiological and experimental studies suggest that n-3 polyunsaturated fatty acids (PUFA) can exert favourable effects on atherothrombotic cardiovascular disease, including arrhythmias. We investigated whether n-3 PUFA could improve morbidity and mortality in a large population of patients with symptomatic heart failure of any cause.
Methods
We undertook a randomised, double-blind, placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy. We enrolled patients with chronic heart failure of New York Heart Association class II–IV, irrespective of cause and left ventricular ejection fraction, and randomly assigned them to n-3 PUFA 1 g daily (n=3494) or placebo (n=3481) by a concealed, computerised telephone randomisation system. Patients were followed up for a median of 3·9 years (IQR 3·0–4·5). Primary endpoints were time to death, and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00336336.
Findings
We analysed all randomised patients. 955 (27%) patients died from any cause in the n-3 PUFA group and 1014 (29%) in the placebo group (adjusted hazard ratio [HR] 0·91 [95·5% CI 0·833–0·998], p=0·041). 1981 (57%) patients in the n-3 PUFA group and 2053 (59%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 0·92 [99% CI 0·849–0·999], p=0·009). In absolute terms, 56 patients needed to be treated for a median duration of 3·9 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons. In both groups, gastrointestinal disorders were the most frequent adverse reaction (96 [3%] n-3 PUFA group vs 92 [3%] placebo group).
Interpretation
A simple and safe treatment with n-3 PUFA can provide a small beneficial advantage in terms of mortality and admission to hospital for cardiovascular reasons in patients with heart failure in a context of usual care.
Funding
Società Prodotti Antibiotici (SPA; Italy), Pfizer, Sigma Tau, and AstraZeneca.
Objective.
—To assess whether the dietary intake of long-chain n-3 polyunsaturated fatty acids from seafood, assessed both directly and indirectly through a biomarker, is associated with a reduced risk of primary cardiac arrest.
The composition of fatty acids in abdominal subcutaneous adipose tissue and the correlation of fatty acid values of plasma and erythrocytes had not been reported in Japan. The aim of the present study was to investigate the fatty acid composition and correlation of plasma and erythrocyte phospholipids (PL) and adipose triacylglycerols (TG) in 75 adult patients admitted for non-malignant diseases. We also examined the relationship of n-3 and n-6 polyunsaturated fatty acid (PUFA) with patients' characteristics. The total n-3 PUFA were 11.2, 11.8 and 1.9%, and the ratios of n-6/n-3 were 2.41, 1.87 and 8.20 in plasma and erythrocyte PL and adipose TG, respectively. There were the highest correlations for total n-3 PUFA and the n-6/n-3 ratio between plasma and erythrocyte PL and adipose TG. There was a positive correlation between n-3 PUFAs and age, but a negative correlation was found between n-6 PUFAs and age. There was no significant difference in the values of PUFAs in plasma and erythrocyte PL and adipose TG between men and women. The patients with cholesterol cholecystolithiasis showed a significantly lower proportion of eicosapentaenoic acid in plasma and erythrocyte PL than those of the other patients. Our findings suggest that PUFA in plasma and erythrocyte PL may be good biomarkers and more acceptable for studying participants than adipose TG.
Studies relating cardiovascular outcomes to dietary or blood measures of various fatty acids rely on the implicit assumptions that dietary change results in changes in blood fatty acids that, in turn, alter cardiac fatty acids. Although dietary intakes of n-3 (omega-3), n-6 (omega-6), and trans fatty acids are reflected in their concentrations in blood, there are few human data on the relation between blood and cardiac concentrations of fatty acids.
The objective was to explore relations between blood and myocardial n-3, n-6, trans, monosaturated, and saturated fatty acids over a range of community intakes to evaluate whether blood fatty acids are useful surrogate markers of their cardiac counterparts.
Patients undergoing on-pump coronary bypass surgery were recruited. Right atrial appendages and blood were collected at surgery for fatty acid analysis.
Atrial appendages and matching blood samples were collected from 61 patients. Highly significant correlations were identified between atrial and erythrocyte or plasma n-3 [eg, eicosapentaenoic acid (erythrocytes: r = 0.93, P < 0.0001; plasma: r = 0.87, P < 0.0001)], some n-6 [eg, arachidonic acid (erythrocytes: r = 0.45, P = 0.0003; plasma: r = 0.39, P = 0.002)], trans [eg, total trans 18:1 (erythrocytes: r = 0.89, P < 0.0001; plasma: r = 0.74, P < 0.0001)], and monounsaturated [eg, oleic acid (erythrocytes: r = 0.37, P = 0.003)] fatty acids. There were no statistical associations between blood and cardiac saturated fatty acids.
Erythrocyte- and plasma phospholipid-derived fatty acids can be used to estimate cardiac fatty acid status in humans.
Increased dietary intake of marine omega-3 fatty acids is associated with prolonged survival in patients with coronary heart disease. However, the mechanisms underlying this protective effect are poorly understood.
To investigate the association of omega-3 fatty acid blood levels with temporal changes in telomere length, an emerging marker of biological age.
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).
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 beta coefficient x 10(-3) = 0.06; 95% CI, 0.02-0.10) and after (adjusted beta 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.
Blood levels of omega-3 fatty acids reflect the interplay of metabolism and the intake of omega-3-rich foods (eg, oily fish). Multiple lines of evidence link reduced tissue and/or blood levels of omega-3 fatty acids, as reflected in the erythrocyte eicosapentaenoic acid plus docosahexaenoic acid level (ie, the omega-3 index), with increased risk for coronary heart disease, especially sudden cardiac death. The purpose of this review is to examine the extent to which biomarkers like the omega-3 index qualify as coronary heart disease risk markers and/or risk factors based on new criteria from the American Heart Association and older guidelines proposed in 1965 by Sir Austin Bradford Hill. These standards include consistency, strength of association, biological plausibility, coherence, dose-response relationship, clinical utility, cost effectiveness, and prospective validation. The omega-3 index appears to fulfill many of the requirements for a risk marker and, more importantly, for a risk factor.
We conducted a pilot study to estimate the biological variability and effects of a prior meal on the omega-3 fatty acid (FA) content of 3 blood FA pools.
We measured FA levels in red blood cells (RBCs), plasma and plasma phospholipids (PL) obtained from 20 healthy volunteers tested weekly over 6 weeks.
The within-subject coefficients of variation were 4.1%+/-1.9%, 15.9%+/-6.4%, and 14.5%+/-8.4%, respectively (RBC vs. others, p<0.001). RBC omega-3 FA content had the lowest biological variability and was not altered in the fed state.
From the perspective of variability and of the sample types tested, RBCs may be the preferred sample type for assessing omega-3 FA status.
There is increasing interest in utilizing novel markers of cardiovascular disease risk, and consequently, there is a need to assess the value of their use. This scientific statement reviews current concepts of risk evaluation and proposes standards for the critical appraisal of risk assessment methods. An adequate evaluation of a novel risk marker requires a sound research design, a representative at-risk population, and an adequate number of outcome events. Studies of a novel marker should report the degree to which it adds to the prognostic information provided by standard risk markers. No single statistical measure provides all the information needed to assess a novel marker, so measures of both discrimination and accuracy should be reported. The clinical value of a marker should be assessed by its effect on patient management and outcomes. In general, a novel risk marker should be evaluated in several phases, including initial proof of concept, prospective validation in independent populations, documentation of incremental information when added to standard risk markers, assessment of effects on patient management and outcomes, and ultimately, cost-effectiveness.
Omega-3 fatty acids (n-3 FA) from oily fish are clinically useful for lowering triglycerides and reducing risk of heart attacks. Accordingly, patients at risk are often advised to take both aspirin and n-3 FA. However, both of these agents can increase bleeding times, and the extent to which the combination inhibits platelet function is unknown. The purpose of this pilot study was to determine the effects of a prescription omega-3 FA product (P-OM3) and aspirin, alone and in combination, on platelet aggregation assessed by whole blood impedance aggregometry (WBA). Ten healthy volunteers provided blood samples on four separate occasions: Day 1, baseline; Day 2, one day after taking aspirin (2 x 325 mg tablets); Day 29, after 28 days of P-OM3 (4 capsules/day); and Day 30, after one day of combined P-OM3 and aspirin. WBA was tested with two concentrations of collagen, with ADP and with a thrombin receptor activating peptide (TRAP). Compared to baseline, aspirin alone inhibited aggregation only with low-dose collagen stimulation; P-OM3 alone did not inhibit aggregation with any agonist; and combined therapy inhibited aggregation with all agonists but TRAP. Significant interactions between interventions were not observed in response to any agonist. In conclusion, P-OM3 alone did not inhibit platelet aggregation, but did (with two agonists) when combined with aspirin. Since previous studies have not reported a clinically significant risk for bleeding in subjects on combined therapy, P-OM3 may safely enhance the anti-platelet effect of aspirin.
Several epidemiological and experimental studies suggest that n-3 polyunsaturated fatty acids (PUFA) can exert favourable effects on atherothrombotic cardiovascular disease, including arrhythmias. We investigated whether n-3 PUFA could improve morbidity and mortality in a large population of patients with symptomatic heart failure of any cause.
We undertook a randomised, double-blind, placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy. We enrolled patients with chronic heart failure of New York Heart Association class II-IV, irrespective of cause and left ventricular ejection fraction, and randomly assigned them to n-3 PUFA 1 g daily (n=3494) or placebo (n=3481) by a concealed, computerised telephone randomisation system. Patients were followed up for a median of 3.9 years (IQR 3.0-4.5). Primary endpoints were time to death, and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00336336.
We analysed all randomised patients. 955 (27%) patients died from any cause in the n-3 PUFA group and 1014 (29%) in the placebo group (adjusted hazard ratio [HR] 0.91 [95.5% CI 0.833-0.998], p=0.041). 1981 (57%) patients in the n-3 PUFA group and 2053 (59%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 0.92 [99% CI 0.849-0.999], p=0.009). In absolute terms, 56 patients needed to be treated for a median duration of 3.9 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons. In both groups, gastrointestinal disorders were the most frequent adverse reaction (96 [3%] n-3 PUFA group vs 92 [3%] placebo group).
A simple and safe treatment with n-3 PUFA can provide a small beneficial advantage in terms of mortality and admission to hospital for cardiovascular reasons in patients with heart failure in a context of usual care.
A plant source of omega-3 fatty acid (FA) that can raise tissue eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) is needed. A soybean oil (SBO) containing approximately 20% stearidonic acid [SDA; the delta-6 desaturase product of alpha-linolenic acid (ALA)] derived from genetically modified soybeans is under development. This study compared the effects of EPA to SDA-SBO on erythrocyte EPA+DHA levels (the omega-3 index). Overweight healthy volunteers (n=45) were randomized to SDA-SBO (24 ml/day providing approximately 3.7 g SDA) or to regular SBO (control group) without or with EPA ethyl esters (approximately 1 g/day) for 16 weeks. Serum lipids, blood pressure, heart rate, platelet function and safety laboratory tests were measured along with the omega-3 index. A per-protocol analysis was conducted on 33 subjects (11 per group). Compared to baseline, average omega-3 index levels increased 19.5% in the SDA group and 25.4% in the EPA group (p<0.05 for both, vs. control). DHA did not change in any group. Relative to EPA, SDA increased RBC EPA with about 17% efficiency. No other clinical endpoints were affected by SDA or EPA treatment (vs. control). In conclusion, SDA-enriched SBO significantly raised the omega-3 index. Since EPA supplementation has been shown to raise the omega-3 index and to lower risk for cardiac events, SDA-SBO may be a viable plant-based alternative for providing meaningful intakes of cardioprotective omega-3 FAs.
We sought to examine whether marine-derived n-3 fatty acids are associated with less atherosclerosis in Japanese versus white populations in the U.S.
Marine-derived n-3 fatty acids at low levels are cardioprotective through their antiarrhythmic effect.
A population-based cross-sectional study in 281 Japanese (defined as born and living in Japan), 306 white (defined as white men born and living in the U.S.), and 281 Japanese-American men (defined as Japanese men born and living in the U.S.) ages 40 to 49 years was conducted to assess intima-media thickness (IMT) of the carotid artery, coronary artery calcification (CAC), and serum fatty acids.
Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar levels. Japanese had 2-fold higher levels of marine-derived n-3 fatty acids than whites and Japanese Americans in the U.S. Japanese had significant and nonsignificant inverse associations of marine-derived n-3 fatty acids with IMT and CAC prevalence, respectively. The significant inverse association with IMT remained after adjusting for traditional cardiovascular risk factors. Neither whites nor Japanese Americans had such associations. Significant differences between Japanese and whites in multivariable-adjusted IMT (mean difference 39 mum, 95% confidence interval [CI]: 21 to 57mum, p < 0.001) and CAC prevalence (mean difference 10.7%, 95% CI: 2.9% to 18.4%, p = 0.007) became nonsignificant after we adjusted further for marine-derived n-3 fatty acids (22 mum, 95% CI: -1 to 46 mum, p = 0.065 and 5.0%, 95% CI: -5.3% to 15.4%, p = 0.341, respectively).
Very high levels of marine-derived n-3 fatty acids have antiatherogenic properties that are independent of traditional cardiovascular risk factors and may contribute to lower the burden of atherosclerosis in Japanese, a lower burden that is unlikely the result of genetic factors.
To assess whether the dietary intake of long-chain n-3 polyunsaturated fatty acids from seafood, assessed both directly and indirectly through a biomarker, is associated with a reduced risk of primary cardiac arrest.
Population-based case-control study.
Seattle and suburban King County, Washington.
A total of 334 case patients with primary cardiac arrest, aged 25 to 74 years, attended by paramedics during 1988 to 1994 and 493 population-based control cases and controls, matched for age and sex, randomly identified from the community. All cases and controls were free of prior clinical heart disease, major comorbidity, and use of fish oil supplements. MEASURES OF EXPOSURE: Spouses of case patients and control subjects were interviewed to quantify dietary n-3 polyunsaturated fatty acid intake from seafood during the prior month and other clinical characteristics. Blood specimens from 82 cases (collected in the field) and 108 controls were analyzed to determine red blood cell membrane fatty acid composition, a biomarker of dietary n-3 polyunsaturated fatty acid intake.
Compared with no dietary intake of eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3), an intake of 5.5 g of n-3 fatty acids per month (the mean of the third quartile and the equivalent of one fatty fish meal per week) was associated with a 50% reduction in the risk of primary cardiac arrest (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4 to 0.8), after adjustment for potential confounding factors. Compared with a red blood cell membrane n-3 polyunsaturated fatty acid level of 3.3% of total fatty acids (the mean of the lowest quartile), a red blood cell n-3 polyunsaturated fatty acid level of 5.0% of total fatty acids (the mean of the third quartile) was associated with a 70% reduction in the risk of primary cardiac arrest (OR, 0.3; 95% CI, 0.2 to 0.6).
Dietary intake of n-3 polyunsaturated fatty acids from seafood is associated with a reduced risk of primary cardiac arrest.
Experimental data suggest that long-chain n-3 polyunsaturated fatty acids found in fish have antiarrhythmic properties, and a randomized trial suggested that dietary supplements of n-3 fatty acids may reduce the risk of sudden death among survivors of myocardial infarction. Whether long-chain n-3 fatty acids are also associated with the risk of sudden death in those without a history of cardiovascular disease is unknown.
We conducted a prospective, nested case-control analysis among apparently healthy men who were followed for up to 17 years in the Physicians' Health Study. The fatty-acid composition of previously collected blood was analyzed by gas-liquid chromatography for 94 men in whom sudden death occurred as the first manifestation of cardiovascular disease and for 184 controls matched with them for age and smoking status.
Base-line blood levels of long-chain n-3 fatty acids were inversely related to the risk of sudden death both before adjustment for potential confounders (P for trend = 0.004) and after such adjustment (P for trend = 0.007). As compared with men whose blood levels of long-chain n-3 fatty acids were in the lowest quartile, the relative risk of sudden death was significantly lower among men with levels in the third quartile (adjusted relative risk, 0.28; 95 percent confidence interval, 0.09 to 0.87) and the fourth quartile (adjusted relative risk, 0.19; 95 percent confidence interval, 0.05 to 0.71).
The n-3 fatty acids found in fish are strongly associated with a reduced risk of sudden death among men without evidence of prior cardiovascular disease.
Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction.
In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths.
The early effect of low-dose (1 g/d) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies.
Although previous data suggested that only doses of 4 g/day or higher of n-3 polyunsaturated fatty acids (PUFA) have had a beneficial effect in the prevention of atherosclerosis and cardiovascular diseases, the GISSI-Prevenzione Study in a 3-year trial showed that 1 g/day reduced total and cardiovascular mortality in over 11,000 post-infarction patients. The aim of this study was to investigate the time course and the extent of incorporation of n-3 fatty acids in plasma and blood cells after 1 g/day of n-3 PUFA, the dose effective in the GISSI-Prevenzione in comparison with higher doses.
Thirty-six healthy volunteers were given 1, 2 and 4 g/day of n-3 PUFA ethyl esters for 12 weeks, followed by a 4-week washout. Blood was collected at weeks 0, 1, 2, 4, 8, 12 and 16 and used for lipid profile analysis and measurement of fatty acid composition in plasma phospholipids, platelets and mononucleates.
Total n-3 PUFA increased by 2.0-, 2.2- and 2.9-fold versus baseline after 12-week treatment with 1, 2 and 4 g respectively. A statistically significant raise of total n-3 PUFA was seen in platelets and mononucleates. Among individual n-3 PUFA, 22:5 n-3 was enriched early and dose dependently in plasma phospholipids, platelets and mononucleates; the raise of 22:6 n-3 was less marked especially in platelets and mononucleates.
One gram per day of n-3 PUFA induces fast (within 1 week) and striking changes in blood composition of PUFA that may well explain their beneficial effects against cardiovascular diseases.
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.
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.
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.
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.
Animal studies have demonstrated evidence of an anti-arrhythmic effect of marine n-3 fatty acids (FAs). In humans the same mechanism may explain the observed reduction in sudden cardiac death (SCD) associated with intake of fish. Whether high levels of n-3 FAs could protect against ventricular fibrillation (VF) during the acute ischaemic phase of a myocardial infarction (MI) is, however, not known.
We measured red blood cell content of eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) expressed as a percentage of total FAs (the omega-3 index) at admission in 460 patients hospitalised with an acute coronary syndrome. Out of 265 patients suffering their first MI, 10 (cases) experienced an episode of VF during the initial 6h of symptom onset. The omega-3 index of these patients was compared to that of 185 first-MI patients (controls) free of VF for at least 30 days post-admission.
The median value of the omega-3 index in the VF cases was 4.88% as compared to 6.08% in the controls (p=0.013). After adjustment for age, sex, ejection fraction, high-sensitivity C-reactive protein, use of beta-blocker, differences of infarct characteristics and previous angina pectoris, a 1% increase of the omega-3 index was associated with a 48% reduction in risk of VF (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.28-0.96; p=0.037).
Our study supports an anti-arrhythmic effect of n-3 FAs through their incorporation into myocardial cell membranes, reducing the risk of VF during ischaemia.
Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association This important paper provides a roadmap and rationale for the evaluation and validation of new markers for CHD
- bullet Hlatky Ma
- P Greenland
- Arnett
- Dk
@BULLET Hlatky MA, Greenland P, Arnett DK, et al.: Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association. Circulation 2009, 119: 2408–2416. This important paper provides a roadmap and rationale for the evaluation and validation of new markers for CHD.
EPA and DHA in blood cell membranes from acute coronary syndrome patients and controls
- R C Block
- W S Harris
- K J Reid
- RC Block
Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study
- M B Katan
- J P Deslypere
- A P Van Birgelen
- MB Katan