Phospholipid Eicosapentaenoic Acid Research Articles

Sex, Body Mass Index, and APOE4 Increase Plasma Phospholipid–Eicosapentaenoic Acid Response During an ω-3 Fatty Acid Supplementation: A Secondary Analysis

BackgroundThe brain is concentrated with omega (ω)-3 (n–3) fatty acids (FAs), and these FAs must come from the plasma pool. The 2 main ω-3 FAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), must be in the form of nonesterified fatty acid (NEFA) or esterified within phospholipids (PLs) to reach the brain. We hypothesized that the plasma concentrations of these ω-3 FAs can be modulated by sex, body mass index (BMI, kg/m2), age, and the presence of the apolipoprotein (APO) E-ε4 allele in response to the supplementation. ObjectivesThis secondary analysis aimed to determine the concentration of EPA and DHA within plasma PL and in the NEFA form after an ω-3 FA or a placebo supplementation and to investigate whether the factors change the response to the supplement. MethodsA randomized, double-blind, placebo-controlled trial was conducted. Participants were randomly assigned to either an ω-3 FA supplement (DHA 0.8 g and EPA 1.7 g daily) or to a placebo for 6 mo. FAs from fasting plasma samples were extracted and subsequently separated into PLs with esterified FAs and NEFAs using solid-phase extraction. DHA and EPA concentrations in plasma PLs and as NEFAs were quantified using gas chromatography. ResultsEPA and DHA concentrations in the NEFA pool significantly increased by 31%−71% and 42%−82%, respectively, after 1 and 6 mo of ω-3 FA supplementation. No factors influenced plasma DHA and EPA responses in the NEFA pool. In the plasma PL pool, DHA increased by 83%−109% and EPA by 387%−463% after 1 and 6 mo of ω-3 FA supplementation. APOE4 carriers, females, and individuals with a BMI of ≤25 had higher EPA concentrations than noncarriers, males, and those with a BMI of >25, respectively. ConclusionsThe concentration of EPA in plasma PLs are modulated by APOE4, sex, and BMI. These factors should be considered when designing clinical trials involving ω-3 FA supplementation.This trial was registered at clinicaltrials.gov as NCT01625195.

Effect of fatty acid profiles in varying recipes of ready-to-use therapeutic foods on neurodevelopmental and clinical outcomes of children (6-59 months) with severe wasting: a systematic review.

In 2020, 13.6 million children under 5 years suffered from severe acute malnutrition (SAM)/wasting. Standard ready-to-use therapeutic foods (RUTFs) improve polyunsaturated fatty acid (PUFA) status but contain suboptimal amounts of omega-3 (n-3) PUFAs with unbalanced n-6-to-n-3 PUFA ratios. The aim was to compare the effects of RUTFs with different essential fatty acid contents on PUFA status, neurodevelopmental, and clinical outcomes (mortality, comorbidities, and recovery) of children with severe wasting. Twelve databases, trial repositories, and article references with no publication limitations. Ten studies from randomized, quasi, and cluster-randomized controlled trials providing RUTFs as home treatment to children 6-59 months with SAM/wasting were included. Plasma phospholipid eicosapentaenoic acid content was higher in children receiving RUTF with altered essential fatty acid contents compared with standard RUTF (0.20 [0.15-0.25], P < 0.00001). Docosahexaenoic acid (DHA) status only improved in children receiving RUTF with added fish oil (0.33 [0.15-0.50], P = 0.0003). The Malawi Developmental Assessment tool (MDAT) global development and problem-solving assessment scores were higher in global assessment and gross motor domains in children receiving added fish oil compared with standard formulation (0.19 [0.0-0.38] and 0.29 [0.03-0.55], respectively). Children receiving high-oleic-acid RUTF (lowering the n-6:n-3 PUFA ratio of the RUTF) with or without fish oil had significantly higher scores in social domains compared with those receiving the standard formulation (0.16 [0.00-0.31] and 0.24 [0.09-0.40]). Significantly higher mortality risk was found in children receiving a standard formulation compared with RUTF with a lower n-6:n-3 PUFA ratio (0.79 [0.67-0.94], P = 0.008). Although lowering n-6:n-3 PUFA ratios did not increase plasma DHA, it improved specific neurodevelopmental scores and mortality due to lower linoleic acid (high-oleic-acid peanuts), higher alpha-linolenic acid (altered oil), or both. Additional preformed n-3 long-chain PUFAs (fish oil) with RUTF improved the children's DHA status, neurodevelopmental outcomes, and weight-for-height z score. More research is needed regarding cost, availability, stability, acceptability, and the appropriate amount of n-3 long-chain PUFAs required in RUTFs for the best clinical outcomes. PROSPERO registration no. CRD42022303694.

Long-Chain Polyunsaturated Fatty Acids n-3 (n-3 LC-PUFA) as Phospholipids or Triglycerides Influence on Epinephelus marginatus Juvenile Fatty Acid Profile and Liver Morphophysiology.

Simple SummaryFish feeding is responsible for almost 60% of the total cost of marine fish production, so nutritional studies are always in demand. Dusky grouper is a promising species for aquaculture, but studies of the species’ nutrition are still lacking. The present study investigated the effects of fatty acids, provided as different lipid classes in four different diets, for Epinephelus marginatus fingerlings and evaluated their physiological and morphological responses in order to provide new insights about grouper nutrition. The fatty acids, provided as different lipid classes, modified the physiological and morphological responses of E. marginatus, showing that the inclusion of these lipids as different classes should be considered in order to obtain better results in terms of fish fillet quality. These results provided valuable insights into the nutrition and physiology of dusky groupers, helping to pave the way for the establishment of this fish species as a produced species worldwide.Phospholipids (PL) are membrane components composed of fatty acids (FA), while triglycerides (TG) are a main source of energy and essential FA. Polyunsaturated FA (PUFA), such as docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), are essential for marine carnivorous fish; thus, an 8-week experiment was performed to evaluate the influence of DHA and EPA, provided as PL and TG, on the morphophysiology of Epinephelus marginatus juveniles. A basal diet was manufactured, and DHA and EPA in PL form (PL1—low amount PL2—high amount) and TG form (TG1—low amount; TG2—high amount) were added. Dusky grouper juveniles were equally distributed in 12 tanks of 20 animals each, and liver and muscle were sampled for metabolic analysis. The total hepatic lipids in PL1 and PL2 were higher when compared to the initial, TG1 and TG2 groups. Total lipids in muscle were higher in PL2 and TG1 than PL1 and TG2, respectively. Diets rich in DHA and EPA in PL and TG resulted in higher deposition of these FA in the muscle polar fraction. However, fish fed diets containing lower amounts of DHA and EPA in PL and TG stored those in the muscle neutral fraction and liver, centralizing the storage of DHA and EPA.

Application of genetic disruption of a Nannochloropsis oceanica cell wall synthesizing gene to n-3 HUFA enrichment of Brachionus plicatilis

It is believed that microalgae of the genus Nannochloropsis can replace fish oil as an n-3 highly unsaturated fatty acid (n-3 HUFA) source in live feed for sustainable marine fish larviculture. This is due to the fact that these microalgae are rich in eicosapentaenoic acid (EPA). On the other hand, the cell wall of microalgae is an obstacle to enriching live feed with n-3 HUFA. Manipulation of the cellulose synthase gene has the potential to facilitate degradation of the cell wall structure, although little is known how effective the genetically modified microalga would be in n-3 HUFA enrichment of live feed. This study aimed to evaluate the significance of the cellulose synthase gene-knockout strain (ΔCESA) of N. oceanica as an EPA enrichment diet for Brachionus plicatilis. The transgenic microalga was established via homologous recombination, and cultured under the same conditions as the wild-type strain (WT). According to the cellular ultrastructure, ΔCESA had a thinner cell wall than WT and its outer layer was unnaturally peeled back. Biochemical analysis revealed that with the exception of carbohydrates, WT and ΔCESA had comparable levels of proteins, lipids, and EPA. Carbohydrates were lower in ΔCESA than WT, which can cause changes in the cell wall structure. Digestive enzymatic and mechanical treatments of microalga showed ΔCESA to have higher accessibility of intracellular fatty acids. When microalga was used as the diet in the long-term cultivation of rotifers (1 week), rotifers fed ΔCESA presented higher growth rates than those fed WT. In short-term cultivation for rotifer EPA enrichment (≤24 h), the percentage of EPA in neutral lipids and phospholipids increased more rapidly in rotifers fed ΔCESA than those fed WT. As a result, rotifers fed ΔCESA for only 12 h exhibited comparable EPA levels to those fed WT for 24 h. The results of this study suggest that the efficiency of n-3 HUFA enrichment of rotifers is enhanced by feeding cellulose synthase gene-disrupted N. oceanica, due to the high vulnerability of its cell wall and unchanged nutritional value. Our findings provide evidence that gene modification technology can be applied to improve the targeted biological characteristics of microalgae used as the source of n-3 HUFA in marine larviculture.

Protective Effects of Eicosapentaenoic Acid Plus Hydroxytyrosol Supplementation Against White Adipose Tissue Abnormalities in Mice Fed a High-Fat Diet.

Objective: Obesity induced by high-fat diet (HFD) elicits white adipose tissue dysfunction. In this study, we have hypothesized that the metabolic modulator eicosapentaenoic acid (EPA) combined with the antioxidant hydroxytyrosol (HT) attenuates HFD-induced white adipose tissue (WAT) alterations. Methods: C57BL/6J mice were administered with a HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg/kg/day), HT (5 mg/kg/day), or both for 12 weeks. Determinations in WAT include morphological parameters, EPA and docosahexaenoic acid content in phospholipids (gas chromatography), lipogenesis, oxidative stress (OS) and inflammation markers, and gene expression and activities of transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma (PPAR-γ), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65 subunit) and nuclear factor erythroid 2-related factor 2 (Nrf2) (quantitative polymerase chain reaction and enzyme linked immunosorbent assay). Results: HFD led to WAT hypertrophy in relation to PPAR-γ downregulation. WAT metabolic dysfunction was characterized by upregulation of lipogenic SREBP-1c system, mitochondrial energy metabolism depression, loss of the antioxidant Nrf2 signaling with OS enhancement, n-3 long-chain polyunsaturated fatty acids depletion and activation of the pro-inflammatory NF-κB system. EPA and HT co-supplementation diminished HFD-dependent effects additively, reaching values close or similar to controls. Conclusion: Data presented strengthen the importance of combined protocols such as EPA plus HT to attenuate metabolic-inflammatory states triggered by obesity.

Predicting Risk for Incident Heart Failure With Omega-3 Fatty Acids: From MESA

ObjectivesThe 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. BackgroundClinical 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. MethodsIn 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. ResultsA 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. ConclusionsHigher plasma EPA was significantly associated with reduced risk for HF, with both reduced and preserved EF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487)

Omega-3 Index in Division I Collegiate American FootballAthletes

American football athletes are exposed to repetitive head impacts (RHI) that, even in the absence of a clinically discernible head injury, result in quantifiable neurological damage. Pre-clinical studies utilizing rodent models indicate that traumatic brain injuries (TBI) can cause a reduction in neuronal omega-3 fatty acids (n-3FAs), specifically docosahexaenoic acid (DHA). Pre-injury administration of n-3FAs, however, has shown to effectively allay the pathological response to TBI. Furthermore, one study has demonstrated the potential neuroprotective effect of DHA supplementation in American football athletes evidenced by a marked reduction in blood biomarkers of axonal injury. Given that the American diet is scarce in the n-3FAs DHA and eicosapentaenoic acid (EPA), the potential neuroprotective effect of n-3FA supplementation may uniquely benefit American football athletes. PURPOSE: This descriptive study sought to examine the omega-3 index, an indicator of n-3FA status, in American collegiate football athletes not supplementing with n-3FAs. METHODS: One hundred twelve (n = 112) athletes participated in this study. Blood was obtained via finger stick and collected on blood spot cards pre-treated with an antioxidant cocktail. The dried blood samples were analyzed by gas chromatography for fatty acid (FA) levels (expressed as a % of total blood FAs). A regression formula (r = 0.98) was used to estimate the percentage of DHA and EPA in red blood cell phospholipids (omega-3 index). RESULTS: Levels of DHA, EPA, and alpha-linolenic acid (ALA) were (mean ± SD) 2.27% ± 0.01% (range = 1.1% - 5.2%), 0.39% ± 0.00% (range = 0.2% - 1.2%) and 0.39% ± 0.00% (range = 0.1% - 1.0%), respectively. Mean omega-6 levels were 9.55 ± 1.72 (range = 4.5 - 13.9) times higher than n-3FAs levels. The mean omega-3 index was 4.35% ± 0.01% (range = 2.8% - 8.0%). Sub-optimal n-3FA levels (i.e., an index < 8.0%) were observed in 99.12% of participants. CONCLUSION: These data suggest that dietary intake of the n-3FAs DHA and EPA may not be adequate in American collegiate football athletes. Though the current evidence relates n-3FA deficiency to an increased risk for cardiovascular risk, American football athletes may derive neuroprotective benefit from n-3FA supplementation with little to no risk.

Abstract 026: Eicosapentaenoic Acid is a Strong Predictor of Risk for Heart Failure in the Multi-ethnic Study of Atherosclerosis

Introduction: In animal models of afterload stress, eicosapentaenoic acid (EPA) prevents interstitial myocardial fibrosis and preserves diastolic dysfunction. Hypothesis: We hypothesized that EPA is similarly protective in humans. Methods: In the Multi-Ethnic Study of Atherosclerosis, we tested for an effect of plasma phospholipid EPA percent of total fatty acids on primary heart failure incidence across heart failure types including, heart failure with reduced ejection fraction (HFrEF; &lt;45% EF), and with preserved ejection fraction (HFpEF) using Cox proportional hazards modeling in 6566 subjects. Results are mean [95% CI]. Results: A total of 6566 subjects had measured baseline EPA, including 1797 black, 794 Chinese, 1444 Hispanic, and 2531 white participants; 52% were female. Over a median follow-up of 13.0 years, 293 heart failure events occurred in subjects with measured EPA: 129 had HFrEF, 110 had HFpEF, and the remaining 54 had unknown ejection fraction status. Mean EPA in HF-free subjects was 0.77% (0.76 - 0.79), and was lower in heart failure subjects 0.70% (0.65 - 0.74), p=0.002. EPA was associated with lower incidence of HF, having a hazard ratio of 0.73 (0.60 - 0.89) per unit change in percentage of total fatty acids, p=0.001. Adjusting for age, sex, race, BMI, smoking, diabetes mellitus, blood pressure, lipids and lipid-lowering drugs, and albuminuria did not change this relationship. Sensitivity analysis showed no dependence on heart failure type. Adjusting for other fatty acids with clustering did not change hazards. In animals, &gt;2.5% EPA is required for prevention of HF, between 2.5% and 1% is marginal, and &lt;1% EPA is insufficient. Most subjects had insufficient EPA levels (n=4794), fewer had marginal levels (n=1471), and fewer still had sufficient levels (n=301). Subjects with sufficient EPA levels were at 0.40 (0.15 - 0.81) fold risk compared to insufficient EPA (p=0.008). Conclusion: High abundance of EPA is robustly associated with reduced risk for heart failure, independent of established risk factors and regardless of ejection fraction status.

Effects of a hypoenergetic diet rich in α-linolenic acid on fatty acid composition of serum phospholipids in overweight and obese patients with metabolic syndrome.

Plant-derived α-linolenic acid (ALA) may exert cardioprotective effects. Dietary ALA can undergo desaturation and elongation to form long-chain ω-3 polyunsaturated fatty acids, but the extent to which this occurs in humans is unclear. The aim of the study was to examine the effects of an energy-restricted diet enriched with ALA on fatty acid composition of serum phospholipids in patients with metabolic syndrome. The present analysis compared the effects of a hypoenergetic diet high in ALA (3.4 g/d) with a control diet low in ALA (0.9 g/d) on fatty acid composition of serum phospholipids in 81 overweight or obese patients with features of metabolic syndrome. After a 26-wk intervention, concentration of ALA in serum phospholipids remained constant in both diet groups. The control group had a significant decrease in serum phospholipid eicosapentaenoic acid concentration, although no significant intergroup difference was observed. Serum phospholipid docosahexaenoic acid concentration significantly decreased to a similar extent with both interventions. Additionally, both interventions significantly decreased serum phospholipid concentrations of palmitic acid, stearic acid, total saturated fatty acids, linoleic acid, total ω-6 and ω-3 polyunsaturated fatty acids, with no effect of diet group on these changes. Compared with the ALA diet, the control diet led to a significant increase in serum phospholipid oleic acid concentration. Daily intake of 3.4 g of ALA during a 26-wk energy-restricted diet did not lead to an enrichment of serum phospholipids with ALA and did not increase eicosapentaenoic acid due to conversion. Additionally, dietary ALA was unable to compensate for a decrease in serum phospholipid docosahexaenoic acid.

Plasma phospholipid pentadecanoic acid, EPA, and DHA, and the frequency of dairy and fish product intake in young children

BackgroundThere is a lack of studies comparing dietary assessment methods with the biomarkers of fatty acids in children.ObjectiveThe objective was to evaluate the suitability of a food frequency questionnaire (FFQ) to rank young children according to their intake of dairy and fish products by comparing food frequency estimates to the plasma phospholipid fatty acids pentadecanoic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).DesignCross-sectional data for the present study were derived from the prospective cohort ‘Environmental Triggers of Type 1 Diabetes Study’. Infants were recruited from the Norwegian general population during 2001–2007. One hundred and ten (age 3–10 years) children had sufficient volumes of plasma and FFQ filled in within 2 months from blood sampling and were included in this evaluation study. The quantitative determination of plasma phospholipid fatty acids was done by fatty acid methyl ester analysis. The association between the frequency of dairy and fish product intake and the plasma phospholipid fatty acids was assessed by a Spearman correlation analysis and by investigating whether participants were classified into the same quartiles of distribution.ResultsSignificant correlations were found between pentadecanoic acid and the intake frequency of total dairy products (r=0.29), total fat dairy products (r=0.39), and cheese products (r=0.36). EPA and DHA were significantly correlated with the intake frequency of oily fish (r=0.26 and 0.37, respectively) and cod liver/fish oil supplements (r=0.47 for EPA and r=0.50 DHA). To a large extent, the FFQ was able to classify individuals into the same quartile as the relevant fatty acid biomarker.ConclusionsThe present study suggests that, when using the plasma phospholipid fatty acids pentadecanoic acid, EPA, and DHA as biomarkers, the FFQ used in young children showed a moderate capability to rank the intake frequency of dairy products with a high-fat content and cod liver/fish oil supplements.

Integrated process of two stage cultivation of Nannochloropsis sp. for nutraceutically valuable eicosapentaenoic acid along with biodiesel

The marine eustigmatophyte Nannochloropsis is one of the potential producers of eicosapentaenoic acid (EPA), a valued nutraceutical. Nannochloropsis sp. was cultivated under photoautotrophic condition utilizing CO2 in a two phase cultivation process in order to enhance the eicosapentaenoic acid (EPA) productivity. It was cultivated in a photobioreactor up to late log phase for cell growth (phase I). Then, the culture was harvested and confronted to relatively low temperature (10°C) and low light (30μmolphotonsm−2s−1) in both photobioreactor and Erlenmeyer flask (phase II), thus augmenting EPA% by 3.4 fold. Lower temperature with low light favored the synthesis of EPA although, biomass productivity, lipid content and lipid productivity were slightly decreased relative to phase I. The total lipids extracted from Nannochloropsis sp. fractionated into neutral lipids (NLs), glycolipids (GLs) and phospholipids (PLs) and a major proportion of EPA was found in phospholipids. Results suggested that low temperature and low light may ameliorate partitioning towards EPA in phospholipids.

Pretreatment With an Intravenous Lipid Emulsion Increases Plasma Eicosapentanoic Acid and Downregulates Leukotriene B4, Procalcitonin, and Lymphocyte Concentrations After Open Heart Surgery in Infants

The effect of providing a lipid emulsion containing medium-chain triglyceride (MCT), soybean oil, and fish oil in critically ill infants is not widely studied. This study investigated lipid emulsion effects on plasma phospholipids and immune biomarkers. Thirty-two infants undergoing cardiopulmonary bypass (CPB) and dependent on parenteral nutrition (PN) were randomized to receive either soybean oil (control, n = 16) or a 50:40:10 mixture of MCT, soybean oil, and fish oil (treatment, n = 16). PN was administered for 3 days preoperatively and 10 days postoperatively. Fatty acids, procalcitonin (PCT), leukotriene B4 (LTB4), and lymphocytes were quantified at baseline, before surgery, and days 1, 7 and 10 after surgery. PCT was significantly lower in the treatment vs control group 1 day postoperatively (P = .01). The treatment group exhibited a lower ω-6 to ω-3 ratio (P = .0001) and a higher ω-3 concentration at all postoperative study periods (P = .001). Treatment resulted in higher (P < .05) plasma phospholipid eicosapentaenoic acid (EPA) on days 7 and 10, while α-linolenic acid, arachidonic acid, and docosahexaenoic acid remained constant. An increase in plasma phospholipid EPA concentration was associated with a decrease in plasma phospholipid LTB4 concentration (P < .05). On postoperative day 10, treatment infants with high Pediatric Risk of Mortality III scores exhibited a 45% lower lymphocyte concentration (P < .05). These findings suggest that treating infants undergoing CPB with a lipid emulsion containing ω-3 improves fatty acid status and results in a lower inflammatory response after surgery. Overall, this alternative ω-3-enriched lipid emulsion may benefit clinical outcomes of critically ill infants after cardiac surgery.

A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats

This study investigated the efficacy of the plant-based n−3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n−3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n−6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n−3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile.

Concurrent Physical Activity Modifies the Association between n3 Long-Chain Fatty Acids and Cardiometabolic Risk in Midlife Adults

Greater consumption of n3 (ω3) polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce risk for cardiovascular disease events, yet their effects on metabolic risk factors and diabetes remain unclear. This cross-sectional study used a community volunteer sample to test whether the associations between n3 fatty acids and cardiometabolic risk vary as a function of physical activity. Participants were 344 generally healthy adults, 30–54 y of age, not taking fish oil supplements or confounding medications. Serum phospholipid EPA and DHA were used together (EPA+DHA) as a biomarker of n3 fatty acid exposure. Cardiometabolic risk was calculated as a continuous measure based on standardized distributions of blood pressure, waist circumference, HDL cholesterol, triglycerides, glucose, and a simple count of risk factors. Insulin resistance was estimated from the homeostatic model assessment. Physical activity was found to predict cardiometabolic risk (P ≤ 0.02) and insulin resistance (P ≤ 0.02) and to moderate the association between EPA+DHA and both cardiometabolic risk (P-interaction ≤ 0.02) and insulin resistance (P-interaction ≤ 0.02). Specifically, higher EPA+DHA was associated with lower cardiometabolic risk and insulin resistance in persons engaged in regular physical activity but not in relatively inactive individuals. These findings were noted in several components of cardiometabolic risk, in men and women separately, and in models adjusted for overall diet quality. In midlife adults, habitual physical activity may be necessary to unmask the salutary effects of n3 fatty acids on cardiometabolic risk and insulin resistance.

Plasma oxylipin profiling identifies polyunsaturated vicinal diols as responsive to arachidonic acid and docosahexaenoic acid intake in growing piglets

The dose-responsiveness of plasma oxylipins to incremental dietary intake of arachidonic acid (20:4n-6; ARA) and docosahexaenoic acid (22:6n-3; DHA) was determined in piglets. Piglets randomly received one of six formulas (n = 8 per group) from days 3 to 27 postnatally. Diets contained incremental ARA or incremental DHA levels as follows (% fatty acid, ARA/DHA): (A1) 0.1/1.0; (A2) 0.53/1.0; (A3-D3) 0.69/1.0; (A4) 1.1/1.0; (D1) 0.66/0.33; and (D2) 0.67/0.62, resulting in incremental intake (g/kg BW/day) of ARA: 0.07 ± 0.01, 0.43 ± 0.03, 0.55 ± 0.03, and 0.82 ± 0.05 at constant DHA intake (0.82 ± 0.05), or incremental intake of DHA: 0.27 ± 0.02, 0.49 ± 0.03, and 0.81 ± 0.05 at constant ARA intake (0.54 ± 0.04). Plasma oxylipin concentrations and free plasma PUFA levels were determined at day 28 using LC-MS/MS. Incremental dietary ARA intake dose-dependently increased plasma ARA levels. In parallel, ARA intake dose-dependently increased ARA-derived diols 5,6- and 14,15-dihydroxyeicosatrienoic acid (DiHETrE) and linoleic acid-derived 12,13-dihydroxyoctadecenoic acid (DiHOME), downstream metabolites of cytochrome P450 expoxygenase (CYP). The ARA epoxide products from CYP are important in vascular homeostatic maintenance. Incremental DHA intake increased plasma DHA and most markedly raised the eicosapentaenoic acid (EPA) metabolite 17,18-dihydroxyeicosatetraenoic acid (DiHETE) and the DHA metabolite 19,20-dihydroxydocosapentaenoic acid (DiHDPE). In conclusion, increasing ARA and DHA intake dose-dependently influenced endogenous n-6 and n-3 oxylipin plasma concentrations in growing piglets, although the biological relevance of these findings remains to be determined.

A randomized trial of fish oil omega-3 fatty acids on arterial health, inflammation, and metabolic syndrome in a young healthy population

BackgroundLong chain omega-3 fatty acids from fish oils (O3) are known to have beneficial effects on a number of vascular risk factors in at-risk populations. The effects of a highly bioavailable emulsified preparation on an overweight young adult population are less well known.MethodsYoung adults, age 18–30, with body mass indices (BMIs) greater than 23 (average = 28.1) were administered 1.7 g of O3 per day (N = 30) or safflower oil placebo (N = 27) in an emulsified preparation (Coromega, Inc.) for 4 weeks in a double-blind randomized design. Blood was drawn and anthropometric measurements taken before and after dosing. Hemodynamic measures (central pulse wave velocity, augmentation index, and aortic systolic blood pressure), inflammatory cytokines (IL-6, IL-8, IL-10, and tumor necrosis factor-α), red blood cell and plasma phospholipid fatty acid profiles, fasting serum lipids, glucose, and C-reactive protein were measured.ResultsRed cell and plasma phospholipid eicosapentaenoic acid and docosahexaenoic acid concentrations increased over the four weeks of dosing in the O3 group. Dosing with O3 did not affect central pulse wave velocity, augmentation index, or aortic systolic blood pressure. None of the five American Heart Association metabolic syndrome components improved over the dosing period. None of the inflammatory cytokines, C-reactive protein, or lipids (total or LDL cholesterol) improved over the dosing period.ConclusionsNo salutary effects of O3 were observed in hemodynamic, metabolic syndrome criteria or inflammatory markers as a result of this relatively short period of administration in this relatively overweight, but healthy young adult cohort.

Plasma Phospholipid Long-Chain ω-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults

Long-chain ω-3 polyunsaturated fatty acids (ω3-PUFAs), including eicosapentaenoic acid (EPA) (20:5ω-3), docosapentaenoic acid (DPA) (22:5ω-3), and docosahexaenoic acid (DHA) (22:6ω-3), have been shown to reduce cardiovascular risk, but effects on cause-specific and total mortality and potential dose-responses remain controversial. Most observational studies have assessed self-reported dietary intake and most randomized trials have tested effects of adding supplements to dietary intake and evaluated secondary prevention, thus limiting inference for dietary ω3-PUFAs or primary prevention.To investigate associations of plasma phospholipid EPA, DPA, DHA, and total ω3-PUFA levels with total and cause-specific mortality among healthy older adults not receiving supplements.Prospective cohort study.4 U.S. communities.2692 U.S. adults aged 74 years (±5 years) without prevalent coronary heart disease (CHD), stroke, or heart failure at baseline.Phospholipid fatty acid levels and cardiovascular risk factors were measured in 1992. Relationships with total and cause-specific mortality and incident fatal or nonfatal CHD and stroke through 2008 were assessed.During 30 829 person-years, 1625 deaths (including 570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal and 276 nonfatal strokes occurred. After adjustment, higher plasma levels of ω3-PUFA biomarkers were associated with lower total mortality, with extreme-quintile hazard ratios of 0.83 for EPA (95% CI, 0.71 to 0.98; P for trend = 0.005), 0.77 for DPA (CI, 0.66 to 0.90; P for trend = 0.008), 0.80 for DHA (CI, 0.67 to 0.94; P for trend = 0.006), and 0.73 for total ω3-PUFAs (CI, 0.61 to 0.86; P for trend < 0.001). Lower risk was largely attributable to fewer cardiovascular than noncardiovascular deaths. Individuals in the highest quintile of phospholipid ω3-PUFA level lived an average of 2.22 more years (CI, 0.75 to 3.13 years) after age 65 years than did those in the lowest quintile.Temporal changes in fatty acid levels and misclassification of causes of death may have resulted in underestimated associations, and unmeasured or imperfectly measured covariates may have caused residual confounding.Higher circulating individual and total ω3-PUFA levels are associated with lower total mortality, especially CHD death, in older adults.National Institutes of Health.

Association of marine-origin N-3 polyunsaturated fatty acids consumption and functional mobility in the community-dwelling oldest old

To examine whether habitual dietary intake of marine-origin n-3 polyunsaturated fatty acids (MOPUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with functional mobility in the community-dwelling oldest old, 85 years or older, who are at high risk for physical disability. A cross-sectional study. A community-based survey conducted at university research center or home-based. Four hundred seventeen (189 men, 228 women) out of 542 participants in the baseline examination of the Tokyo Oldest Old Survey on Total Health, a community-based ongoing longitudinal study among the oldest old living in the center of Japan. Habitual dietary intake of MOPUFA was assessed by the brief-type self-administered diet history questionnaire (BDHQ), and functional mobility was assessed by the timed up and go test. Plasma inflammatory biomarkers (C-reactive protein, interleukin-6 and tumor necrosis factor-α) were measured. We evaluated the cross-sectional association between habitual intake of MOPUFA and functional mobility using multivariate logistic regression analysis. Prior to the analysis, validation of BDHQ in this study was confirmed among 190 participants (96 men, 94 women) based on the EPA and DHA concentrations in the erythrocyte membrane phospholipids as reference. Moderate correlation between estimated dietary intake of EPA/DHA and concentration of EPA/DHA in the erythrocyte membrane phospholipids was obtained (Spearman's r=0.29-0.58, p<0.01). Multivariate logistic regression analysis revealed that a lower habitual intake of EPA+DHA was significantly associated with poor functional mobility in men but not in women (OR (95% CI) per 1 SD increase of EPA+DHA intake; 0.55 (0.33-0.91), 0.88 (0.59-1.32), men and women respectively). Habitual intake of MOPUFA was associated with functional mobility in community-dwelling oldest old men.

The effect of dietary walnuts compared to fatty fish on eicosanoids, cytokines, soluble endothelial adhesion molecules and lymphocyte subsets: a randomized, controlled crossover trial

We tested the hypothesis that walnut consumption can exert effects on markers of inflammation and endothelial activation similar to those produced by fish consumption. In a crossover dietary intervention trial, 25 normal to mildly hyperlipidemic men and women were randomly assigned to one of three isoenergetic diets: a walnut diet incorporating 42.5g of walnuts per 10.1mJ 6 times per week (1.8% of energy n-3 fat); a fish diet providing 113g of fatty fish per 10.1mJ 2 times per week (0.8% of energy n-3 fat), or a control diet (no nuts or fish, 0.4% of energy n−3 fat) for 4 weeks on each diet. Both the walnut and fish diets inhibited circulating concentrations of prostaglandin E metabolite (PGEM) and 11-dehydro thromboxane B2, but demonstrated no effect on blood interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α¯ (TNF-α¯), and C-reactive protein (CRP) or the number of circulating lymphocyte subsets. On the walnut diet the proportion of plasma phospholipid α¯-linolenic acid (ALA) increased 140% and arachidonic acid (AA) decreased 7% compared to both the control and fish diets. The proportion of plasma phospholipid eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increased about 200% and 900% respectively on the fish diet relative to either the control or walnut diet. The walnut diet inhibited E-selectin by 12.7% relative to the fish diet, and the fish diet inhibited secretory intercellular adhesion molecule-1 (s-ICAM-1) by 4.5% relative to the control diet. Both walnuts and fish in commonly consumed amounts may have modest albeit distinct effects on circulating adhesion molecules.

Circulating Long-Chain ω-3 Fatty Acids and Incidence of Congestive Heart Failure in Older Adults: The Cardiovascular Health Study

Few previous studies have evaluated associations between long-chain ω-3 fatty acids and incidence of congestive heart failure (CHF), and those that have are typically based on diet questionnaires and yield conflicting results. Circulating fatty acid concentrations provide objective biomarkers of exposure. To determine whether plasma phospholipid concentrations of long-chain ω-3 fatty acids, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), were associated with incident CHF. Prospective cohort study. 4 U.S. communities. 2735 U.S. adults without prevalent heart disease who were enrolled in the Cardiovascular Health Study from 1992 to 2006. Plasma phospholipid fatty acid concentrations and other cardiovascular risk factors were measured in 1992 by using standardized methods. Relationships with incident CHF (555 cases during 26 490 person-years, adjudicated by using medical records) were assessed by using Cox proportional hazards models. After multivariate adjustment, plasma phospholipid EPA concentration was inversely associated with incident CHF; risk was approximately 50% lower in the highest versus the lowest quartile (hazard ratio [HR], 0.52 [95% CI, 0.38 to 0.72]; P for trend = 0.001). In similar analyses, trends toward lower risk were seen for DPA (HR, 0.76 [CI, 0.56 to 1.04]; P for trend = 0.057) and total long-chain ω-3 fatty acids (HR, 0.70 [CI, 0.49 to 0.99]; P for trend = 0.062) but not for DHA (HR, 0.84 [CI, 0.58 to 1.21]; P for trend = 0.38). In analyses censored to the middle of follow-up (7 years) to minimize exposure misclassification over time, multivariate-adjusted HRs were 0.48 for EPA (CI, 0.32 to 0.71; P for trend = 0.005), 0.61 for DPA (CI, 0.39 to 0.95; P for trend = 0.033), 0.64 for DHA (CI, 0.40 to 1.04; P for trend = 0.057), and 0.51 for total ω-3 fatty acids (CI, 0.32 to 0.80; P for trend = 0.003). Temporal changes in fatty acid concentrations over time may have caused underestimation of associations. Unmeasured or imperfectly measured covariates may have caused residual confounding. Circulating individual and total ω-3 fatty acid concentrations are associated with lower incidence of CHF in older adults. National Institutes of Health.