Survey of the erythrocyte EPA+DHA levels in the heart attack/stroke belt.

BACKGROUND: The Omega-3 Index (O3I; erythrocyte EPA+DHA as a percent of total fatty acids) is inversely related to risk for cardiovascular disease (CVD). The cardioprotective target O3I is 8%-12%. O3I levels in American regions with high CVD risk are poorly characterized. PURPOSE: To determine the O3I in individuals participating in a Seafood Nutrition Partnership (SNP) survey in seven US cities in the CVD "belt." METHODS: Fingerstick blood samples were analyzed for the O3I. RESULTS: The SNP cohort (n = 2177) had a mean (SD) O3I of 4.42% (1.12%). Only 1.2% were in the desirable range, whereas 42% had an undesirable (<4%) O3I. The mean (SD) O3I in a subset of 772 SNP subjects who were matched for age and sex with the Framingham study was 4.6% (1.2%) compared 5.3% (1.6%) in the Framingham cohort (p < 0.0001). CONCLUSIONS: Individuals in the CVD "belt" had relatively low O3I levels. Since in other settings, a low O3I is associated with increased risk for CVD, this may be one factor contributing to the higher risk for CVD in this region of the US.

Association of reported fish intake and supplementation status with the omega-3 index.

BACKGROUND: An Omega-3 Index (O3I; EPA+DHA as a % of erythrocyte total fatty acids) in the desirable range (8%-12%) has been associated with improved heart and brain health. OBJECTIVE: To determine the combination of fish intake and supplement use that is associated with an O3I of >8%. DESIGN: Two cross-sectional studies comparing the O3I to EPA+DHA/fish intake. PARTICIPANTS/SETTING: The first study included 28 individuals and assessed their fish and EPA+DHA intake using both a validated triple-pass 24-hr recall dietary survey and a single fish-intake question. The second study used de-identified data from 3,458 adults (84% from US) who self-tested their O3I and answered questions about their fish intake and supplement use. STATISTICAL ANALYSES PERFORMED: Study 1, chi-squared, one-way ANOVA, and Pearson correlations were computed. In Study 2, multi-variable regression models were used to predict O3I levels from reported fish/supplement intakes. RESULTS: The mean ±â€¯SD O3I was 4.87 ±â€¯1.32%, and 5.99 ±â€¯2.29% in the first and second studies, respectively. Both studies showed that for every increase in fish intake category the O3I increased by 0.50-0.65% (p < 0.0001). In the second study, about half of the population was taking omega-3 supplements, 32% reported no fish intake and 17% reported eating fish >2 times per week. Taking an EPA+DHA supplement increased the O3I by 2.2% (p < 0.0001). The odds of having an O3I of ≥8% were 44% in the highest intake group (≥3 servings/week and supplementation) and 2% in the lowest intake group (no fish intake or supplementation); and in those consuming 2 fish meals per week but not taking supplements (as per recommendations), 10%. CONCLUSIONS: Current AHA recommendations are unlikely to produce a desirable O3I. Consuming at least 3 fish servings per week plus taking an EPA+DHA supplement markedly increases the likelihood of achieving this target level.

Breast milk from women living near Lake Malawi is high in docosahexaenoic acid and arachidonic acid.

Adequate long-chain polyunsaturated fatty acid (LCPUFA) intake is critical during the fetal and infant periods. We quantified fatty acid content of breast milk (n=718) and plasma from six month old infants (n=412) in southern Malawi, and in usipa (n=3), a small dried fish from Lake Malawi. Compared to global norms, Malawian breast milk fatty acid content (% of total fatty acids) was well above average levels of arachidonic acid [ARA] (0.69% vs. 0.47%) and docosahexaenoic acid [DHA] (0.73% vs. 0.32%). Average Malawian infant plasma ARA (7.5%) and DHA (3.8%) levels were comparable to those reported in infants consuming breast milk with similar fatty acid content. The amounts (mg) of DHA, EPA and ARA provided by a 3 oz (85 g) portion of dried usipa (1439, 659 and 360, respectively) are considerably higher than those for dried salmon. Usipa may be an important source of LCPUFA for populations in this region.

Beyond building better brains: bridging the docosahexaenoic acid (DHA) gap of prematurity.

Long-chain polyunsaturated fatty acids (LCPUFA) including docosahexaenoic acid (DHA) are essential for normal vision and neurodevelopment. DHA accretion in utero occurs primarily in the last trimester of pregnancy to support rapid growth and brain development. Premature infants, born before this process is complete, are relatively deficient in this essential fatty acid. Very low birth weight (VLBW) infants remain deficient for a long period of time due to ineffective conversion from precursor fatty acids, lower fat stores and a limited nutritional provision of DHA after birth. In addition to long-term visual and neurodevelopmental risks, VLBW infants have significant morbidity and mortality from diseases specific to premature birth, including bronchopulmonary dysplasia, necrotizing enterocolitis, and retinopathy of prematurity. There is increasing evidence that DHA has protective benefits against these disease states. The aim of this article is to identify the unique needs of premature infants, review the current recommendations for LCPUFA provision in infants and discuss the caveats and innovative new ways to overcome the DHA deficiency through postnatal supplementation, with the long-term goal of improving morbidity and mortality in this at-risk population.

Omega-3 fatty acid therapy reduces triglycerides and interleukin-6 in hypertriglyeridemic HIV patients.

OBJECTIVES: Cardiovascular disease and osteoporosis are common in HIV-infected patients and residual systemic inflammation is thought to contribute to both of these disorders. We performed a randomized placebo-controlled trial of omega-3-acid (O3A) ethyl esters in HIV-infected patients with hypertriglyceridaemia, hypothesizing that O3A would decrease serum levels of triglycerides, markers of systemic inflammation, and markers of bone turnover. METHODS: HIV-infected patients (n = 48 recruited at three sites) with CD4 count >200 cells/µL, suppressed viral load, and triglycerides >200 mg/dL were randomized to placebo or 3.6 g/d of O3A. Fasting lipid profiles and markers of inflammation and bone turnover were assessed at baseline and after 8 weeks of treatment. RESULTS: Baseline HIV status, lipid profile, bone metabolism and cardiovascular risk factors were similar between the groups. Inflammatory markers were similar between the treatment groups at baseline, except for interleukin (IL)-6 and tumour necrosis factor (TNF)-α, which were higher in the O3A group. The concentration of triglycerides in patients receiving O3A decreased by a median (interquartile range (IQR)) of -34 (-149, 9.5) mg/dL vs. a median increase of 46.5 (-51, 123) mg/dL in the placebo group (P = 0.01). The median percentage change in IL-6 was greater in the O3A group compared with the placebo group [-39% (-63, 12%) vs. 29% (10, 177%), respectively; P = 0.006]. Similar results were observed for TNF-α, but not other inflammatory or bone turnover markers. CONCLUSIONS: O3A ethyl esters decreased the concentrations of triglycerides, IL-6 and TNF-α in patients with well-controlled HIV infection and hypertriglyceridaemia. Larger studies are required to confirm these findings and investigate their clinical significance.

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

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

Red blood cell ω-3 fatty acid levels and markers of accelerated brain aging.

OBJECTIVE: Higher dietary intake and circulating levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been related to a reduced risk for dementia, but the pathways underlying this association remain unclear. We examined the cross-sectional relation of red blood cell (RBC) fatty acid levels to subclinical imaging and cognitive markers of dementia risk in a middle-aged to elderly community-based cohort. METHODS: We related RBC DHA and EPA levels in dementia-free Framingham Study participants (n = 1575; 854 women, age 67 ± 9 years) to performance on cognitive tests and to volumetric brain MRI, with serial adjustments for age, sex, and education (model A, primary model), additionally for APOE ε4 and plasma homocysteine (model B), and also for physical activity and body mass index (model C), or for traditional vascular risk factors (model D). RESULTS: Participants with RBC DHA levels in the lowest quartile (Q1) when compared to others (Q2-4) had lower total brain and greater white matter hyperintensity volumes (for model A: ß ± SE = -0.49 ± 0.19; p = 0.009, and 0.12 ± 0.06; p = 0.049, respectively) with persistence of the association with total brain volume in multivariable analyses. Participants with lower DHA and ω-3 index (RBC DHA+EPA) levels (Q1 vs. Q2-4) also had lower scores on tests of visual memory (ß ± SE = -0.47 ± 0.18; p = 0.008), executive function (ß ± SE = -0.07 ± 0.03; p = 0.004), and abstract thinking (ß ± SE = -0.52 ± 0.18; p = 0.004) in model A, the results remaining significant in all models. CONCLUSION: Lower RBC DHA levels are associated with smaller brain volumes and a "vascular" pattern of cognitive impairment even in persons free of clinical dementia.

Effects of duration of treatment and dosage of eicosapentaenoic acid and stearidonic acid on red blood cell eicosapentaenoic acid content.

OBJECTIVE: The purpose of this randomized, controlled, parallel group study was to characterize the relationships between dosages of stearidonic acid (SDA) and eicosapentaenoic acid (EPA), and incorporation of EPA into red blood cell (RBC) membranes over time. METHODS: Healthy subjects (n=131) received capsules with placebo (safflower oil), SDA (0.43, 1.3, 2.6, or 5.2 g/d) or EPA (0.44, 1.3, or 2.7 g/d) for 12 weeks. RBC fatty acids were analyzed biweekly. RESULTS: RBC %EPA increased in all EPA and SDA groups (p<0.02 vs. control) except the 0.43 g/d SDA group (p=0.187). For theoretical intakes of EPA of 0.25, 0.5, and 0.89 g/d, the amounts of SDA needed to achieve equivalent RBC EPA enrichment were 0.61, 1.89, and 5.32 g/d (conversion efficiencies of 41%, 26%, and 17%), respectively. CONCLUSIONS: SDA increased RBC %EPA in a dosage and time-dependent manner at intakes as low as 1.3 g/d.

Omega-3 fatty acids modulate collagen signaling in human platelets.

Dietary intake of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) results in cardioprotective benefits. However, the cellular and physiological bases for these benefits remain unclear. We hypothesized that EPA and DHA treatments would interfere with collagen-mediated platelet signaling. Thirty healthy volunteers received 28 days of 3.4 g/d EPA+DHA with and without a single dose of aspirin. Clinical hematologic parameters were then measured along with assays of collagen-stimulated platelet activation and protein phosphorylation. Omega-3 therapy led to a small but significant reduction in platelets (6.3%) and red blood cells (1.7%), but did not impair clinical time-to-closure assays. However, collagen-mediated platelet signaling events of integrin activation, α-granule secretion, and phosphatidylserine exposure were all reduced by roughly 50% after omega-3 incorporation, and collagen-induced tyrosine phosphorylation was significantly impaired. The diminished platelet response to collagen may account for some of the cardioprotective benefits provided by DHA and EPA.

Initial operation of a pulse-burst laser system for high-repetition-rate Thomson scattering.

A pulse-burst laser has been installed for Thomson scattering measurements on the Madison Symmetric Torus reversed-field pinch. The laser design is a master-oscillator power-amplifier. The master oscillator is a commercial Nd:YVO(4) laser (1064 nm) which is capable of Q-switching at frequencies between 5 and 250 kHz. Four Nd:YAG (yttrium aluminum garnet) amplifier stages are in place to amplify the Nd:YVO(4) emission. Single pulses through the Nd:YAG amplifier stages gives energies up to 1.5 J and the gain for each stage has been measured. Repetitive pulsing at 10 kHz has also been performed for 2 ms bursts, giving average pulse energies of 0.53 J with ΔE/E of 4.6%, where ΔE is the standard deviation between pulses. The next step will be to add one of two Nd:glass (silicate) amplifier stages to produce final pulse energies of 1-2 J for bursts up to 250 kHz.

Pulse-burst laser systems for fast Thomson scattering (invited).

Two standard commercial flashlamp-pumped Nd:YAG (YAG denotes yttrium aluminum garnet) lasers have been upgraded to "pulse-burst" capability. Each laser produces a burst of up to 15 2 J Q-switched pulses (1064 nm) at repetition rates of 1-12.5 kHz. Variable pulse-width drive (0.15-0.39 ms) of the flashlamps is accomplished by insulated gate bipolar transistor (IGBT) switching of electrolytic capacitor banks. Direct control of the laser Pockels cell drive enables optimal pulse energy extraction, and up to four 2 J laser pulses during one flashlamp pulse. These lasers are used in the Thomson scattering plasma diagnostic system on the MST reversed-field pinch to record the dynamic evolution of the electron temperature profile and temperature fluctuations. To further these investigations, a custom pulse-burst laser system with a maximum pulse repetition rate of 250 kHz is now being commissioned.

The effects of EPA, DHA, and aspirin ingestion on plasma lysophospholipids and autotaxin.

Lysophophatidylcholine (LPC) and lysophosphatidic acid (LPA) are potent lysolipid mediators increasingly linked with atherosclerosis and inflammation. A current model proposing that plasma LPA is produced when LPC is hydrolyzed by the enzyme autotaxin has not been rigorously investigated in human subjects. We conducted a clinical trial of eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) and aspirin ingestion in normal volunteers. Fasting blood samples were drawn at baseline and after 4-week supplementation with EPA/DHA (3.4 g/d) with and without aspirin (650 mg). Plasma LPC and LPA species and autotaxin activity were measured. EPA-LPC and DHA-LPC concentrations increased significantly with EPA/DHA supplementation whereas EPA- and DHA-LPA did not. Autotaxin activity was unaffected by any treatment, and aspirin had no effect on any endpoint. Taken together, our data demonstrate that plasma LPC, but not LPA, species can be dynamically regulated by dietary supplementation, and argue against a simple model of LPA generation via LPC hydrolysis.

Electron density measurements of a field-reversed configuration plasma using a novel compact ultrastable second-harmonic interferometer.

A compact high-sensitivity second-harmonic interferometer for line-integrated electron density measurements on a large plasma machine is presented. The device is based on a fiber coupled near-infrared continuous-wave Nd:YAG laser and is remotely controlled. The performances of the instrument are tested on the Irvine field-reversed configuration machine, and a sensitivity of few 10(14) cm(-2) in measuring line integrated electron density is demonstrated with a time resolution of a few microseconds. The interferometer is self calibrated, has an impressive stability, and it does not require any further alignment after proper installation. These features make this device a real turn-key system suitable for electron density measurement in large plasma machines.

Time-of-flight neutral particle analyzer and calibration.

A time-of-flight diagnostic has been implemented on the Irvine field reversed configuration (IFRC) to obtain an energy distribution function from charge-exchanged neutral hydrogen. The diagnostic includes a 13 cm radius slotted disk rotating at 165 Hz in vacuum which chops the emitted neutrals at a rate of 26 kHz. In situ timing verification was performed with a dc xenon discharge lamp with an uncertainty less than 100 ns for a 38 micros chopping period. Energy calibration was accomplished with a singly ionized lithium source in the range of 300-1500 eV, achieving an average energy uncertainty, DeltaE/E, of 0.11. The diagnostic has measured neutrals in the range of 20-80 eV from the IFRC and the corresponding energy distribution function has been obtained.

Clinical trial evidence for the cardioprotective effects of omega-3 fatty acids.

The notion that marine omega (w)-3 fatty acids might have beneficial cardiovascular effects was first suggested by epidemiologic studies in Greenland Inuits published in the late 1970s. These simple observations spawned hundreds of other studies, the confluence of which strongly suggests a true cardioprotective effect of w-3 fatty acids. The strongest confirmation has come from the publication of three randomized clinical trials, all of which reported benefits to patients with preexisting coronary artery disease. The most convincing of these was the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico (GISSI)-Prevezione study, in which 5654 patients with coronary artery disease were randomized to either w-3 fatty acids (850 mg/d) or usual care. After 3.5 years, those taking the w-3 fatty acids had experienced a 20% reduction in overall mortality and a 45% decrease in risk for sudden cardiac death. These findings support the view that relatively small intakes of w-3 fatty acids are indeed cardioprotective, and suggest that they may operate by stabilizing the myocardium itself.

Measurement of human chylomicron triglyceride clearance with a labeled commercial lipid emulsion.

Human chylomicron triglyceride (TG) kinetics has been difficult to determine directly owing to technical limitations. This report describes a new method for studying chylomicron metabolism. Healthy volunteers (n = 10) sipped a drink providing 175 mg fat x kg(-1) h(-1) for 7.5 h to produce a steady-state chylomicronemia. A commercial 10% intravenous lipid emulsion was labeled with [3H]triolein, purified by high-performance liquid chromatography, and sterilized. A trace amount of labeled emulsion was injected intravenously 30 min before (i.e., in the fasting state) and 5, 6, and 7 h after sipping began (i.e., triplicate determinations in the fed state). Chylomicron half-lives were calculated from the monoexponential decay curves, and apparent distribution volumes were estimated by back-extrapolation to time zero. Plasma and estimated chylomicron TG concentrations increased from 89+/-13 and 0.8+/-0.3 to 263+/-43 and 91+/-39 mg/dL (mean +/- SEM), respectively, with feeding. Tracer-determined chylomicron TG half-lives were 5.34+/-0.58 and 6.51+/-0.58 min during the fasting and fed states, respectively (P < 0.01). The apparent distribution volume during the fasting state was 24% greater than plasma volume (4515+/-308 vs. 3630+/-78 mL, P < 0.02), consistent with significant margination of lipid emulsion particles to endothelial binding sites. Margination was reduced during the fed state, suggesting that native chylomicrons competed with lipid emulsion particles for endothelial lipoprotein lipase. The results indicate that a radiolabeled commercial lipid emulsion is metabolized in a fashion similar to native chylomicron TG, and thus can be used to study chylomicron TG kinetics.

A new method for the study of chylomicron kinetics in vivo.

Our understanding of the metabolism of chylomicrons, the lipoprotein that transports dietary fat from the intestine to peripheral tissues, is incomplete. The present studies were conducted to determine whether a labeled intravenous lipid emulsion could be used to estimate chylomicron triglyceride (TG) rate of appearance (R(a)) and thereby quantify the rate of intestinal fat absorption. After an overnight fast, healthy volunteers (n = 6) sipped a (3)H-labeled drink over 6.5 h at a rate of 175 mg fat. kg(-1). h(-1). Beginning at hour 5, an HPLC-purified, (14)C-labeled lipid emulsion was infused intravenously for 90 min. During the study, plasma total and chylomicron TG concentrations increased from 100 +/- 21 to 237 +/- 40 mg/dl and from undetectable to steady-state levels of 35 +/- 13 mg/dl, respectively. After a minor correction for VLDL contamination, tracer-determined chylomicron TG R(a) was 175 +/- 30 mg. kg(-1). h(-1), equal to the presumed ingestion rate. In summary, a radiolabeled intravenous lipid emulsion is able to accurately estimate chylomicron TG R(a) and therefore can be used to measure in vivo fat absorption rates.

Effect of atorvastatin on hemorheologic-hemostatic parameters and serum fibrinogen levels in hyperlipidemic patients.

Plasma fibrinogen and hemorheologic-hemostatic factors contribute to dyslipidemia-induced morbidity. Some of these parameters can be favorably affected when abnormal serum lipoprotein levels are corrected. Thus, we investigated whether treatment with atorvastatin would result in changes in plasma viscosity and other hemorheologic and hemostatic parameters. Twenty-two hyperlipidemic men at a university lipid clinic were treated single-blinded with atorvastatin 80 mg/day for 12 weeks to determine hemostatic-hemorheologic parameters including blood viscosity, fibrinogen levels, whole blood platelet aggregation, tissue plasminogen activator antigen, hematocrit, plasminogen activator inhibitor activity, factor VII activity, red blood cell (RBC) deformity and lipid ratio, sedimentation rate, and fasting serum lipoprotein levels. Atorvastatin treatment provided significant lowering of serum lipoprotein levels: low-density lipoprotein -53% (p = 0.0001), very low density lipoprotein -43% (p = 0.0001), and triglycerides -35% (p < 0.0001). These effects were accompanied by changes in plasma viscosity -10% (p = 0.0007), arachidonic acid-induced whole blood platelet aggregation -11% (p = 0.006), factor VII -8% (p = 0.001), RBC lipid composition +5% (p = 0.0003), and RBC sedimentation -33% (p = 0.0002). Plasma fibrinogen levels were not affected. Thus, atorvastatin 80 mg/day produced marked reductions in serum low-density lipoprotein cholesterol (-53%), very low density lipoprotein cholesterol (-43%), and triglycerides levels (-35%), and significant changes in plasma viscosity as well as other hemorheologic-hemostatic parameters, but no changes in plasma fibrinogen levels.

From Inuit to implementation: omega-3 fatty acids come of age.

During the past 25 years, the cardiovascular effects of marine omega-3 (omega-3) fatty acids have been the subject of increasing investigation. In the late 1970s, epidemiological studies revealed that Greenland Inuits had substantially reduced rates of acute myocardial infarction compared with Western control subjects. These observations generated more than 4,500 studies to explore this and other effects of omega-3 fatty acids on human metabolism and health. From epidemiology to cell culture and animal studies to randomized controlled trials, the cardioprotective effects of omega-3 fatty acids are becoming recognized. These fatty acids, when incorporated into the diet at levels of about 1 g/d, seem to be able to stabilize myocardial membranes electrically, resulting in reduced susceptibility to ventricular dysrhythmias, thereby reducing the risk of sudden death. The recent GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico)-Prevention study of 11,324 patients showed a 45% decrease in risk of sudden cardiac death and a 20% reduction in all-cause mortality in the group taking 850 mg/d of omega-3 fatty acids. These fatty acids have potent anti-inflammatory effects and may also be antiatherogenic. Higher doses of omega-3 fatty acids can lower elevated serum triglyceride levels; 3 to 5 g/ d can reduce triglyceride levels by 30% to 50%, minimizing the risk of both coronary heart disease and acute pancreatitis. This review summarizes the emerging evidence of the use of omega-3 fatty acids in the prevention of coronary heart disease.