Plasma Phospholipid Docosahexaenoic Acid Research Articles

Entorhinal thickness: A marker of DHA supplementation efficacy?

AbstractBackgroundThe entorhinal cortex (ERC) area in the brain is affected early in AD, particularly among APOE4 carriers. We previously reported a positive association between plasma phospholipid docosahexaenoic acid (DHA) levels and the ERC thickness in the Aging Brain Program. We hypothesize that increases in plasma DHA after high‐dose DHA supplementation protects against thinning of the ERC when started before cognitive impairment including in APOE4 carriers, and that ERC thickness can be a useful marker for DHA supplementation efficacy.MethodWe examined the effect of DHA treatment and association of plasma DHA species on the changes in the ERC area in the DHA Brain Delivery Pilot Trial (NCT02541929). T1‐weighted MRI scans were collected at 3T and FreeSurfer software was used to segment the ERC thickness. Total DHA, DHA in phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and phosphatidylethanolamine (PE) were measured in plasma together with Red blood cell (RBC) DHA levels before and after randomization to 2 grams of triglyceride DHA per day vs placebo over 6 months (n=28). Participants were all cognitively normal, consumed less than 200 mg of DHA per day, and were stratified by APOE4 genotype before randomization.ResultDHA treatment, adjusted for APOE4, was associated with a significant increase in ERC area thickness compared with placebo (mean group difference in ERC change (95% CI) 0.161 (0.003, 0.319), p=0.046). Among DHA subspecies measured, greater increase in plasma PC DHA levels after supplementation was significantly correlated with greater ERC area (mean ERC change per SD of PC DHA=0.103, p=0.011). The association persisted after adjusting for APOE4 status (mean ERC change per SD of PC DHA=0.109, p=0.007), indicating that the effect was independent of APOE4 status.ConclusionThese preliminary findings support a protective effect of high dose DHA in preserving the ERC thickness, including among APOE4 carriers. This finding supports early intervention, before the onset of cognitive impairment, with high dose DHA supplementation in individuals at risk of cognitive decline. PREVENTE4 trial (NCT03613844) is ongoing to help understand whether high dose DHA can prevent cognitive decline in individuals at increased risk of AD.HNY is supported by AA NIRG‐15‐361854, R01AG054434, R21AG056518, ADDF GC‐201711‐2014197.

Different metabolism of EPA, DPA and DHA in humans: A double-blind cross-over study

This study aimed to compare eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) incorporated into red blood cells (RBC) phospholipids (PL), plasma PL, plasma triglyceride (TAG), and plasma cholesteryl ester (CE) fractions, and the metabolomics profiles in a double-blind cross-over study. Twelve female healthy subjects randomly consumed 1 g per day for 6 days of pure EPA, DPA, or DHA. The placebo treatment was olive oil. The fasting venous blood was taken at days 0, 3 and 6, and the RBC PL and plasma lipid fractions were separated for fatty acid determination using thin layer chromatography followed by gas chromatography. Plasma metabolites were analyzed by UHPLC-Q-Exactive Orbitrap/MS. Supplemental EPA significantly increased the concentrations of EPA in RBC PL (days 3 and 6). For subjects consuming the DPA supplement, the concentrations of both DPA and EPA were significantly increased in RBC PL over a 6-day period, respectively. For plasma PL fraction, EPA and DPA supplementation significantly increased the concentrations of EPA and DPA at both days 3 and 6, respectively. Supplemental DHA significantly increased the concentrations of DHA in plasma PL at day 6. For plasma TAG fraction, supplementation with EPA and DPA significantly increased the concentrations of EPA and DPA at both days 3 and 6, respectively. After DHA supplementation, significant increases in the concentrations of DHA were found relative to baseline at both days 3 and 6. For plasma CE fraction, EPA supplementation significantly increased the concentrations of EPA (days 3 and 6) and DPA (days 6), respectively. Supplemental DPA significantly increased the concentrations of EPA at day 6. Meanwhile, the concentrations of DHA were significantly increased over a 6-day period of intervention after subjects consuming the DHA supplements. There were a total of 922 plasma metabolites identified using metabolomics analyses. Supplementation with DPA and DHA significantly increased the levels of sphingosine 1-phosphate (P for DPA = 0.025, P for DHA = 0.029) and 15-deoxy-Δ12,14-prostaglandin A1 (P for DPA = 0.034; P for DHA = 0.021) in comparison with olive oil group. Additionally, supplementation with EPA (P = 0.007) and DHA (P = 0.005) significantly reduced the levels of linoleyl carnitine, compared with olive oil group. This study shows that DPA might act as a reservoir of n-3 LCP incorporated into blood lipid fractions, metabolized into DHA, and retro-converted back to EPA. Metabolomics analyses indicate that supplemental EPA, DPA and DHA have shared and differentiated metabolites. The differences of these metabolic biomarkers should be investigated in additional studies.

Effects of EPA and DHA Supplementation on Plasma Specialized Pro-resolving Lipid Mediators and Blood Monocyte Inflammatory Response in Subjects with Chronic Inflammation (OR29-01-19)

ObjectivesThe role of n-3 fatty acid-derived specialized pro-resolving mediators (SPMs), including the novel docosapentaenoic acid (DPA) products, in reducing inflammation in humans has not been determined. We evaluated the differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on plasma SPMs and the resulting impact on the inflammatory response of peripheral blood monocytes. MethodsIn a randomized, controlled, crossover trial, 21 subjects (9 men and 12 women, 50–75 y) with chronic inflammation (C-reactive protein > 2 μg/mL) entered a 4-week lead-in control phase (high oleic sunflower oil, 3 g/d) and then two sequential 10-week supplementation phases with pure EPA or DHA (3 g/d each), separated by a 10-week washout phase. Plasma phospholipid (PL) fatty acid composition and SPMs, including their precursors, were measured at the end of each phase. Following lipopolysaccharides (LPS) stimulation, the inflammatory response of blood monocytes was assessed by inflammatory gene expression. ResultsEPA increased PL EPA (P < 0.001) and plasma concentrations of 18-HEPE, the precursor of the E-series resolvins (RvEs) (P < 0.001). The increase in plasma 18-HEPE concentrations, was associated with the increase in PL EPA (β = 14.9 pg/ml, P < 0.01). However, RvEs were undetectable. EPA increased PL DPA (P < 0.001) but not DPA-derived SPMs. DHA increased PL DHA and plasma concentrations of 17-HDHA and 14-HDHA, the precursors of DHA-derived SPMs (P < 0.001). DHA also significantly increased PL EPA and 18-HEPE (P < 0.001), suggesting some DHA retroconversion to EPA. Interestingly, DHA lowered PL DPA (P < 0.001) but increased the DPA-derived SPMs RvD5n-3 DPA and MaR1n-3 DPA (P < 0.001). In monocytes, while both EPA and DHA lowered the LPS-induced expression of TNFA(P < 0.03 and P < 0.001, respectively), TNFA expression was inversely correlated with plasma concentrations of MaR1n-3 DPA (ρ = –0.32, P < 0.04). ConclusionsRelative to EPA, DHA supplementation increases a broader range of SPMs, with EPA and DHA differentially affecting PL DPA and DPA-derived SPMs. Plasma concentrations of MaR1n-3 DPA following EPA and DHA supplementation are associated with an attenuated inflammatory response in blood monocytes, suggesting a potential role of this SPM in reducing inflammation in humans. Funding SourcesFunded by USDA/NIFA and Cohn Student Award. Supporting Tables, Images and/or Graphs▪

Docosahexaenoic Acid Supplementation is Not Anti-Inflammatory in Adipose Tissue of Healthy Obese Postmenopausal Women.

Adipose tissue inflammation is associated with obesity comorbidities. Reducing such inflammation may ameliorate these comorbidities. n-3 fatty acids have been reported to have anti-inflammatory properties in obesity, which may modulate this inflammatory state. In the current study a 1 gram per day oral supplement of the n-3 fatty acid docosahexaenoic acid (DHA) was administered for 12 weeks to 10 grade 1-2 obese postmenopausal women and markers of adipose tissue and systemic inflammation measured and compared before and after supplementation. DHA administration resulted in approximately a doubling of plasma and red cell phospholipid and adipose tissue DHA content but no change in systemic markers of inflammation, such as circulating C-reactive protein (CRP) or interleukins (IL) 6, 8 and 10 (IL-6, IL-8, IL-10). DHA supplementation did not alter the adipose tissue marker of inflammation crown-like structure density nor did it affect any gene expression pathways, including anti-inflammatory, hypoxic and lipid metabolism pathways. The obese postmenopausal women studied were otherwise healthy, which leads us to suggest that in such women DHA supplementation is not an effective means for reducing adipose tissue or systemic inflammation. Further testing is warranted to determine if n-3 fatty acids may ameliorate inflammation in other, perhaps less healthy, populations of obese individuals.

Long-chain Polyunsaturated Fatty Acid Supplementation Improves Mood in Elderly Japanese Men.

Although several studies have reported the effects of long-chain polyunsaturated fatty acid (LCPUFA) supplementation on the mood in healthy adults, the effects of LCPUFA on elderly individuals remain unclear. Thus, we hypothesized that LCPUFA supplementation improves mood in the elderly. To address this hypothesis, 115 elderly Japanese men aged 55-64 years were assigned and randomly allocated to the LCPUFA or placebo group. Participants received 4 weeks of supplementation with LCPUFA-containing oil (docosahexaenoic acid (DHA) 300 mg/day, eicosapentaenoic acid (EPA) 100 mg/day, arachidonic acid (ARA) 120 mg/day) or a placebo oil. Mood was assessed using the Profile of Mood States (POMS) before and after supplementation as the secondary outcome in a previously performed randomized controlled trial on cognitive function. A total of 113 participants completed the supplementation period. One hundred participants (LCPUFA, n = 51; placebo, n = 49) who were eligible for evaluation of mood were analyzed. Increases in vigor scores on POMS, reflecting a positive mood, were significantly larger in the LCPUFA group than in the placebo group (LCPUFA, +1.8; placebo, -0.5). No significant differences were observed in changes in other negative mood scores between groups. DHA and ARA content in plasma phospholipids were increased by 0.8% and 0.7%, respectively, in the LCPUFA group, and were significantly larger than those in the placebo group. Dietary DHA, EPA, and ARA intake was unchanged during the study. These results suggest that LCPUFA supplementation may improve vigor (positive mood) in elderly Japanese men.

The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease.

BackgroundApolipoprotein E (APOE) ɛ4 and low cerebrospinal fluid (CSF) amyloid-β42 (Aβ42) levels are predictors for developing Alzheimer’s disease (AD). The results of several studies indicate an interaction between docosahexaenoic acid (DHA) consumption and cognitive outcomes by APOE genotype. Our objective in the present study was to examine whether APOE ɛ4 genotype and low CSF Aβ42 levels were associated with reduced delivery of DHA to CSF in the Alzheimer’s Disease Cooperative Study-sponsored DHA clinical trial.MethodsPhospholipid DHA was assayed in the plasma of 384 participants and CSF of 70 participants at baseline. Forty-four of the 70 participants completed the 18-month follow-up visit after allocation to placebo (n = 15) or DHA (n = 29). Plasma and CSF DHA levels, CSF Aβ42, Tau, and phosphorylated Tau were measured at baseline and after the 18-month intervention. Participants were divided into tertiles based on baseline Aβ42 CSF levels. To assess DHA delivery across the blood-brain barrier, the ratio of CSF to plasma DHA levels was calculated.ResultsAt baseline, there were no significant differences between CSF or plasma phospholipid DHA levels by CSF Aβ42 tertiles or ɛ4 status. After 18 months of DHA supplementation, participants at the lowest Aβ42 tertile had significantly lower CSF DHA levels (p = 0.01) and lower CSF-to-plasma DHA ratios (p = 0.05) compared to the other tertiles. Baseline CSF Aβ42 levels were significantly lower in ɛ4 carriers than in ɛ4 noncarriers (p = 0.01). Participants carrying the ɛ4 allele (n = 25) demonstrated a less pronounced increase in CSF DHA level compared with noncarriers (n = 4), with a possible interaction effect between treatment and APOE genotype (p = 0.07).ConclusionsAPOE ɛ4 allele and lower CSF Aβ42 levels were associated with less transport of DHA to CSF. Brain amyloid pathology may limit the delivery of DHA to the brain in AD.Trial RegistrationClinicaltrials.gov identifier: NCT00440050. Registered on 22 Feb 2007.

Omega-3 polyunsaturated fatty acid supplementation and white matter changes in major depression

White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = −1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity.

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.

Docosahexaenoic Acid Alleviates Atopic Dermatitis in Mice by Generating T Regulatory Cells and M2 Macrophages

Han et al. (this issue) describe a novel mechanism by which docosahexaenoic acid (DHA) may suppress atopic dermatitis symptoms in mice. They find that DHA induces FoxP3 T regulatory cells in vivo, M2 macrophages drive transforming growth factor-β and IL-10 conversion of CD4 T cells to CD4 FoxP3 T regulatory cells in vitro, and DHA-treated M2 macrophages suppress atopic dermatitis in mice.

Low Doses of Long-chain Polyunsaturated Fatty Acids Affect Cognitive Function in Elderly Japanese Men: A Randomized Controlled Trial.

Several studies have reported that the supplementation of long-chain polyunsaturated fatty acids (LCPUFA), such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) improve cognitive function in the elderly. However, the doses used in these studies were higher than general dietary LCPUFA intake levels. This randomized, double-blind, placebo-controlled trial evaluated the effects of low doses of LCPUFA supplementation corresponding to general dietary intake on cognitive function in non-demented elderly Japanese participants. Japanese men aged 55-64 years were enrolled and randomly allocated to the placebo or LCPUFA group. Participants received 4 weeks of supplementation with LCPUFA-containing oil (DHA, 300 mg/day; EPA, 100 mg/day; and ARA, 120 mg/day) or purified olive oil as placebo. Event-related potential P300, reflecting cognitive processes, was measured before and after supplementation. A total of 113 participants completed the supplementation period, and the per-protocol analysis included 69 participants. Changes in P300 latency were significantly different between the placebo group (+13.6 msec) and the LCPUFA group (-1.8 msec) after supplementation. Significant increases in DHA (+0.9%) and ARA (+0.6%) contents in plasma phospholipids were observed in the LCPUFA group; no changes were observed in the placebo group. Dietary DHA, EPA, and ARA intake were in the normal range for Japan participants and remained unchanged during the study. These results suggest that low doses of LCPUFA supplementation have the potential to improve cognitive function in elderly Japanese men.

Higher Docosahexaenoic acid, lower Arachidonic acid and reduced lipid tolerance with high doses of a lipid emulsion containing 15% fish oil: A randomized clinical trial

Lipid emulsions containing fish oil, as source of long chain omega 3 fatty acids, have recently became available for parenteral nutrition in infants, but scanty data exist in extremely low birth weight preterms. The objective of this study was to compare plasma fatty acids and lipid tolerance in preterm infants receiving different doses of a 15% fish oil vs. a soybean oil based lipid emulsion. Preterm infants (birth weight 500-1249g) were randomized to receive parenteral nutrition with MOSF (30% Medium-chain triglycerides, 25% Olive oil, 30% Soybean oil, 15% Fish oil) or S (S, 100% Soybean oil) both at two levels of fat intake: 2.5 or 3.5gkg(-1)d(-1), named 2.5Fat and 3.5Fat respectively. Plasma lipid classes and their fatty acid composition were determined on postnatal day 7 and 14 by gas chromatography together with routine biochemistry. We studied 80 infants. MOSF infants had significantly higher plasma phospholipid Docosahexaenoic acid and Eicosapentaenoic and lower Arachidonic acid. Plasma phospholipids, triglycerides and free cholesterol were all significantly higher in the MOSF-3.5Fat group, while cholesterol esters were lower with MOSF than with S. The area under the curve of total bilirubin was significantly lower with MOSF than with S. The use of a lipid emulsion with 15% FO resulted in marked changes of plasma long-chain fatty acids. Whether the benefits of increasing Docosahexaenoic acid outweigh the potential negative effect of reduced Arachidonic acid should be further studied. MOSF patients exhibited reduced lipid tolerance at 3.5gkg(-1)d(-1) fat intake. The trial was conducted between January 2008 and December 2012 so we had not registered it in a public trials registry as it is now required for trials that started after July 2008.

Inflammatory response following heart surgery and association with n−3 and n−6 long-chain polyunsaturated fatty acids in plasma and red blood cell membrane lipids

BackgroundOpen heart surgery is associated with a systemic inflammatory response. The n−3 long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the n−6 LC-PUFA arachidonic acid (AA) may contribute to modulation of the inflammatory response. ObjectiveWe investigated whether the preoperative levels of EPA, DHA and AA in plasma phospholipids (PL) and red blood cell (RBC) membrane lipids in patients (n=168) undergoing open heart surgery were associated with changes in the plasma concentration of selected inflammatory mediators in the immediate postoperative period. Results and conclusionsThe postoperative concentration of TNF-β was lower (P<0.05) and those of hs-CRP, IL-6, IL-8, IL-18 and IL-10 higher (P<0.05) than the respective preoperative concentrations. We observed that the preoperative levels of EPA and AA in plasma PL and RBC membrane lipids were associated with changes in the concentration of pro-inflammatory and anti-inflammatory mediators, suggesting a complex role in the postoperative inflammatory process.

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.

Sex-specific differences in essential fatty acid metabolism

Sex hormones may influence the enzymatic synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), which may lead to sex-specific differences in LC-PUFA status. Isotope studies with U-(13)C α-linolenic acid (ALA) have shown a considerably higher conversion rate of ALA to n-3 (omega-3) LC-PUFAs in women than in men. A review of the literature generally suggested that there was a higher contribution of arachidonic acid (AA) and docosahexaenoic acid (DHA) in blood lipids in women than in men; however, sex-specific differences were not seen in every study. The fatty acid composition of plasma phospholipids was recently reported separately for a large group of women and men (n > 3000) living in 15 regions of Europe. The contributions of saturated and monounsaturated fatty acids were higher, whereas those of AA and DHA were lower in men than in women; however, sex explained only ≈ 2% of the variability of plasma phospholipid DHA values. Results reported from a limited number of randomized controlled trials of perinatal LC-PUFA supplementation have, on occasion, shown sex-specific differences in some outcomes; however, the heterogeneity both in the interventions and outcomes measured made it difficult to draw conclusions on the direction or the extent of the effects. Data summarized in the current review highlight the importance of planning a subgroup analysis by sex in perinatal LC-PUFA supplementation trials.

Allergic disease in infants up to 2 years of age in relation to plasma omega‐3 fatty acids and maternal fish oil supplementation in pregnancy and lactation

We have previously reported a protective effect of maternal omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) supplementation in pregnancy and lactation on IgE-associated eczema and food allergy in the infant during the first year of life. Here we investigate whether the effects of the LCPUFA supplementation on IgE-associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of ω-3 PUFAs and the frequency and severity of infant allergic disease. 145 pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid (EPA) and 1.1 g docosahexaenoic acid (DHA) or placebo starting in the 25th gestational week and continuing through 3.5 months of breastfeeding. Clinical examinations, skin prick tests and analysis of maternal and infant plasma phospholipid fatty acids and infant specific IgE were performed. No difference in the prevalence of allergic symptoms was found between the intervention groups. The cumulative incidence of IgE-associated disease was lower in the ω-3-supplemented group (6/54, 13%) compared with the placebo group (19/62, 30%, p=0.01). Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease (p=0.01-0.05) in a dose-dependent manner. Higher maternal and infant proportions of DHA and EPA were found if the infants presented none, when compared with multiple allergic symptoms, (p<0.05) regardless of sensitization. In summary, the ω-3 supplementation offered no obvious preventive effect on the prevalence of clinical symptoms of allergic disease, but the decrease in cumulative incidence of IgE-associated disease seen during the first year still remained until 2 yr of age. Furthermore, high proportions of DHA and EPA in maternal and infant plasma phospholipids were associated with less IgE-associated disease and a reduced severity of the allergic phenotype.

Effects of Docosahexaenoic Acid Supplementation on Blood Pressure, Heart Rate, and Serum Lipids in Scottish Men with Hypertension and Hypercholesterolemia

To investigate the effects of daily supplementation with docosahexaenoic acid (DHA) on coronary heart disease risks in 38 middle-aged men with hypertension and/or hypercholesterolemia in Scotland, a five-week double-blind placebo-controlled dietary supplementation with either 2 g of DHA or active placebo (1 g of olive oil) was conducted. Percent composition of DHA in plasma phospholipids increased significantly in DHA group. Systolic and diastolic blood pressure and heart rate decreased significantly in DHA group, but not in placebo group. High-density lipoprotein cholesterol (HDL-C) increased significantly, and total cholesterol (TC)/HDL-C and non-HDL-C/HDL-C ratios decreased significantly in both groups. There was no change in TC and non-HDL-C. We conclude that 2 g/day of DHA supplementation reduced coronary heart disease risk factor level improving blood pressure, heart rate, and lipid profiles in hypertensive, hypercholesterolemic Scottish men who do not eat fish on a regular basis.

A Simple Method of Supplementation of Omega‐3 Polyunsaturated Fatty Acids

A relative dietary ω-3 fatty acid deficiency exists in Western diets, and this deficiency may be associated with some chronic diseases. The aim of the present study was to supplement yogurt with docosahexaenoic acid and assess whether this fatty acid could be incorporated into plasma lipids. We developed a stable emulsion of docosahexaenoic acid that was incorporated into yogurt. Twelve healthy volunteers agreed to consume 1 serving daily that contained 600 mg of docosahexaenoic acid. After 3 weeks of supplementation, plasma phospholipid docosahexaenoic acid content increased significantly, by 32%, in parallel with a 16% rise in total ω-3 fatty acids. This result was associated with a significant 7% decline in phospholipid arachidonic acid. Fortification of ordinary foods with docosahexaenoic acid is a potentially attractive method of increasing ω-3 fatty acid content of plasma lipids, and might even lower arachidonic acid concentrations.

Marine phospholipids—a promising new dietary approach to tumor-associated weight loss

Advanced tumor disease very often evokes excessive loss of body weight. Among others, fish oil or marine fatty acid ethyl esters were investigated for treatment of cancer cachexia with controversial results. In this study, a new formulation of marine fatty acids was investigated, the marine phospholipids, with more than 50% of phospholipid-bound fatty acids being eicosapentaenoic and docosahexaenoic acid. Thirty-one tumor patients with various tumor entities suffering from weight loss were asked to take marine phospholipids (1.5 g/day) as softgel capsules for a period of 6 weeks. Compliance, body weight, appetite, and quality of life as well as the fatty acid profile in plasma and blood cells were monitored; 17 patients could be analyzed. Marine phospholipids were very well accepted; low-dose supplementation resulted in a significant increase of eicosapentaenoic and docosahexaenoic acid in plasma phospholipids; therefore, significantly reducing the n-6 to n-3 fatty acid ratio. A stabilization of body weight was achieved (median weight change of +0.6% after 6 weeks), while appetite and quality of life improved. These promising first results encourage further investigation of marine phospholipids in cancer care.

Docosahexaenoic Acid (DHA) Supplementation of Orange Juice Increases Plasma Phospholipid DHA Content of Children

The major dietary source of docosahexaenoic acid (DHA) is fish, which is not widely consumed by children. There is concern, therefore, that children may not receive adequate DHA and so might benefit from dietary supplementation. The aim of the present study was to evaluate the effects of providing a supplement of microencapsulated algal DHA in juice. We assessed the effects of two levels of DHA supplementation on the plasma phospholipid DHA content of healthy 4- to 6-year-old and 7- to 12-year-old children who were randomly assigned to consume 180 mL juice containing either 50 mg (lower dose) or 100 mg (higher dose) DHA daily for 6 weeks. Plasma phospholipid DHA content (mole % of total fatty acids) was measured before and after 6 weeks of daily juice consumption. Because there are no data for plasma phospholipid DHA content in healthy children, data were compared to that of breastfed infants. At baseline, plasma phospholipid DHA content was lower in both age groups and dose groups than observed in breastfed infants. It increased significantly in both dose groups, but more so in the higher dose group of both age groups ( P<0.05, overall mean±standard deviation: 3.72±0.66 vs 4.64±0.77); reaching levels similar to or greater than content of breastfed infants. Thus, DHA supplementation of juice at either 50 mg/day or 100 mg/day for 6 weeks was effective in increasing plasma phospholipid DHA contents of children.

Plasma phospholipid EPA and DHA in relation to atherosclerosis in 61-year-old men

Introduction Increased intake of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to decrease the risk for cardiovascular death and to reduce CVD risk factors. It has also been suggested that EPA and DHA reduce atherosclerosis progression, but data are inconclusive. Carotid intima-media thickness (IMT) is a well-established surrogate measure for sub-clinical atherosclerosis. Our aim was to examine if plasma phospholipid EPA and DHA are associated with IMT and plaque occurrence and size in the carotid and femoral arteries. Methods IMT and plaque occurrence in carotid and femoral arteries was measured by ultrasound in 487 sixty-one-year-old men in this cross-sectional study. Plasma phospholipid levels of EPA and DHA, serum lipids, cell adhesion molecules, and blood pressure were measured, and occurrence of diabetes and socioeconomic factors were assessed. Results Plasma phospholipid EPA was negatively associated with IMT in carotid and femoral arteries, and with cigarette years and cell adhesion proteins. EPA was positively associated with HDL, total cholesterol, blood pressure, plasma insulin and years of education. The association between EPA and carotid IMT remained after adjustment for blood pressure, but not for other covariates. Plasma phospholipid DHA was negatively associated with cigarette years and several endothelial markers, and positively associated with years of education and systolic blood pressure. In contrast to other studies, EPA content was higher in diabetic patients compared with patients without diabetes. Conclusion Plasma phospholipid EPA, but not DHA, was inversely associated with carotid and femoral IMT, as well as several endothelial markers supporting the concept of an effect of EPA on the vascular wall. This association was independent of blood pressure, but not for other covariates. There was no association between plasma phospholipid EPA or DHA and plaque occurrence in the carotid and femoral arteries.