Levels Of Omega-3 Polyunsaturated Fatty Acids Research Articles

Impact of erythrocyte long-chain omega-3 polyunsaturated fatty acid levels in early pregnancy on birth outcomes: findings from a Belgian cohort study.

To examine the association between maternal erythrocyte long-chain omega-3 PUFA (n-3 LCPUFA), measured in early pregnancy, and pregnancy and birth outcomes. One hundred and eight healthy women with a singleton pregnancy were included. Erythrocyte fatty acids were analyzed using gas chromatography. Gestational length, birth anthropometric measures, and pregnancy-associated complications were collected from hospital medical records. We observed significant positive associations between maternal docosahexaenoic acid (DHA) levels (p = 0.024) and omega-3 index values (p = 0.021) and gestational length in adjusted linear regression models. Each point in maternal DHA level was associated with 2.19 days longer gestational duration (β = 2.19; 95% CI 0.29-4.09). No consistent associations were found between n-3 PUFA levels and composite pregnancy outcome. These findings suggest that the gestational length is positively affected by maternal n-3 LCPUFA status as soon as the early stages of pregnancy.

Association between blood omega-3 polyunsaturated fatty acids and the gut microbiota among breast cancer survivors.

Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients demonstrated to have health benefits, such as decreasing the risk of coronary heart disease, improving parameters associated with metabolic syndrome, and decreasing anxiety symptoms and depression risk. Previous intervention studies indicated the association between blood or tissue PUFA levels and the gut microbiota; however, the details remain incompletely elucidated. We conducted a cross-sectional study to examine the association between PUFAs and the gut microbiota among breast cancer survivors. Adults who had been diagnosed with invasive breast cancer more than one year ago and were not currently undergoing chemotherapy were enrolled. Capillary blood and faecal samples were obtained to assess the blood PUFA levels and gut microbiota compositions. The mean age (n=124) was 58.7 years, and 46% of the participants had a history of chemotherapy. Multiple regression analysis controlling for possible confounders indicated that an increased relative abundance of Actinobacteria was significantly associated with increased levels of docosahexaenoic acid (DHA, beta=0.304, q<0.01). At the genus level, the abundance of Bifidobacterium was positively associated with the level of DHA (beta=0.307, q<0.01). No significant association between omega-6 PUFAs and the relative abundances of gut microbiota members was observed. In addition, analyses stratified by the history of chemotherapy indicated significant associations of PUFA levels with the abundance of some bacterial taxa, including the phylum Actinobacteria (DHA, beta=0.365, q<0.01) and Bacteroidetes (EPA, beta=-0.339, q<0.01) and the genus Bifidobacterium (DHA, beta=0.368, q<0.01) only among participants without a history of chemotherapy. These findings provide the first evidence of positive associations between the abundances of Bifidobacterium among the gut microbiota and the levels of omega-3 PUFAs in the blood. Further studies are required to gain additional insight into these associations in healthy subjects as well as into the causality of the relationship.

Dietary Habits, Fatty Acids and Carotenoid Levels Are Associated with Neovascular Age-Related Macular Degeneration in Chinese

The role of diet and circulatory carotenoids and docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are implicated in age-related macular degeneration (AMD) but not well studied in Chinese. However, other fatty acids were not comprehensively evaluated if it had additional consequence on AMD. This study investigated the relationship among dietary habits, fatty acids levels, carotenoids and AMD in Hong Kong Chinese adults. In this cross-sectional case-controlled study, plasma fatty acids including, saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), and carotenoids levels were quantified between patients with neovascular AMD (n = 99) and age-gender-matched controls (n = 198). A food frequency questionnaire was also conducted. Low blood carotenoid levels and omega-3 PUFAs namely DHA, EPA and α-linolenic acid increased the odds ratio of developing neovascular AMD. High blood omega-6 PUFAs specifically arachidonic acid and eicosadienoic acid, oleic acid (a MUFA) and SFA levels increased the odds ratio of having neovascular AMD. Neovascular AMD group had significantly less omega-3 PUFA rich food (vegetables, nuts, seafood) intake and higher SFA (meat) intake than controls. In short, neovascular AMD was associated with lower circulatory levels of carotenoids and omega-3 PUFAs, and higher level of omega-6 PUFAs, oleic acid and SFAs in the Hong Kong Chinese population. These findings enhance the understandings of dietary impacts on neovascular AMD and provide a context for future nutritional intervention studies.

1518-P: Serum Dihomo-γ-Linolenic Acid Levels Predict Glycemic Control Deterioration in Type 2 Diabetes Patients after Discharge from Admission

The measurement of serum polyunsaturated fatty acid (PUFA) levels in type 2 diabetes (T2DM) patients may be useful for evaluating not only the dietary habits, but also metabolic abnormalities, as high dihomo-γ-linolenic acid (DGLA) levels or low arachidonic acid (AA)/DGLA ratios are associated with obesity-related abnormalities. However, the impact of PUFA levels on glycemic control remains unknown. This retrospective study analyzed the association between serum PUFA levels and glycemic control one year after discharge from admission. Data from 480 T2DM patients admitted to our hospital from 2011 to 2016 were analyzed. Patients with renal dysfunction (eGFR &amp;lt; 30 mL/min/1.73 m2) or insulin deficiency [fasting C-peptide (CPR) &amp;lt; 0.5 ng/mL or two-hour postprandial CPR &amp;lt; 1.0 ng/mL] were excluded. Patients achieving &amp;lt; 7.0% glycated hemoglobin (HbA1c) at one year after discharge were defined as achievers, and the others, as non-achievers. Multiple baseline factors, including the PUFA levels between the two groups were analyzed. Of 480 patients, 206 were achievers and 274 were non-achievers. The achievers were younger (59.4±12.8 vs. 62.0±13.7 years, p = 0.0188), and had a higher two-hour postprandial CPR (4.98±2.46 vs. 4.26±2.10 ng/mL, p = 0.002), lower DGLA level (36.2±15.6 vs. 39.8±13.5 μg/mL, p = 0.002), and higher AA/DGLA ratio (6.09±2.39 vs. 5.12±1.73, p &amp;lt;0.001) than non-achievers, while the body mass index, HbA1c at admission, fasting CPR, omega-3 PUFA levels between the groups did not differ. The two-hour postprandial CPR and DGLA levels (or AA/DGLA ratios) also showed significant associations in the multivariate logistic regression model. Sensitivity analyses excluding the patients ≥ 75 years old or those treated with insulin showed similar results. Our results show that high DGLA levels and low AA/DGLA ratios, as well as decreased postprandial insulin secretion are predictors of glycemic control deterioration after discharge from admission. Disclosure T. Sunouchi: None. Y. Tsurutani: Research Support; Self; Astellas Pharma Inc. T. Takiguchi: None. J. Saito: None. T. Nishikawa: None.

Omega-3 and omega-6 polyunsaturated fatty acids and metabolic syndrome: A systematic review and meta-analysis

Previous studies suggest that polyunsaturated fatty acids (PUFAs) may reduce the risk of metabolic diseases, but some have shown ambiguous results. The aim of this study was to systematically evaluate and summarize available evidence on the association between omega-3 and omega-6 PUFA levels and risk of metabolic syndrome (MetS). A systematic literature search of articles published until December 2017 was conducted in PubMed, Web of Science, and Cochrane Library databases. Meta-analyses of the highest vs. lowest categories of omega-3 and omega-6 PUFAs were conducted using the random effects models. Thirteen studies (2 case-control, 9 cross-sectional, 1 nested case-control, and 1 prospective cohort) with 36,542 individuals were included. Higher omega-3 PUFA levels in diets or blood were associated with a 26% reduction in the risk of MetS (odds ratio (OR)/relative risk (RR) 0.74, 95% confidence interval (CI) 0.62-0.89). This inverse association was evident among studies with Asian populations (OR/RR 0.69, 95% CI 0.54-0.87), but not among those with American/European populations (OR/RR 0.84, 95% CI 0.55-1.28). Null results were found regarding the association between circulating/dietary omega-6 PUFAs and MetS. The present meta-analysis indicates that higher intakes of omega-3 PUFAs, but not omega-6 PUFAs, was associated with lower MetS risk; adding to the current body of evidence on the metabolic health effects of circulating/dietary omega-3 PUFAs.

The association of plasma fatty acids levels with hand and knee osteoarthritis

Purpose: Obesity is one of the most important risk factors for osteoarthritis (OA). In addition to increased mechanical loading, systemic factors also likely play a role. Nutrient excess leading to obesity may result in lipotoxicity, with increased levels of circulating fatty acids. However, our knowledge about the effect of different fatty acids on OA is sparse. Therefore, we aimed to investigate the association of plasma saturated fatty acids (SFAs), monounsaturated fatty acid (MUFAs), polyunsaturated fatty acids (PUFAs), omega (n-)3 and n-6 PUFAs on clinically defined hand and knee OA. Since we are in a postprandial state most of the day, both fasting and postprandial samples after a standardized mixed meal were used for the association analyses. Methods: In the population-based Netherlands Epidemiology of Obesity (NEO) study, a total of 6,671 middle-aged participants were recruited from the greater area of Leiden. Clinical hand and knee OA were defined by the ACR clinical classification criteria. Blood samples were obtained after an overnight fast and 150 minutes after consumption of a standardized liquid mixed meal containing 600kCal, with 16% of energy (En%) derived from protein, 50 En% from carbohydrates and 34 En% from fat. EDTA-plasma samples were used for a high-throughput proton nuclear magnetic resonance (NMR) metabolomics platform (Nightingale Health Ltd., Helsinki, Finland) to quantify 159 lipid and metabolite measures. For the present analyses the concentrations of fasting and postprandial total fatty acids, SFAs, MUFAs, PUFAs, n-6 PUFAs and n-3 PUFAs in mmol/l were used. We excluded participants who reported to have inflammatory rheumatic disease or fibromyalgia, with missing physical examination, who were non-fasting at baseline, or reported using lipid-lowering medication. Logistic regression analyses were used to investigate the association between fatty acids and clinical OA phenotypes. All analyses were stratified by sex and corrected for age, education, ethnicity and total body fat percentage. Data are presented as odds ratios (OR) with 95% confidence intervals (CI). Results: In the current analysis 5,328 NEO participants were included, with a mean age of 56 years and 58% were women. Hand OA, knee OA and concurrent hand and knee OA were defined in 8%, 10% and 4%, respectively. After correction for possible confounders, SFA, total PUFA and omega-3 PUFA levels were positively associated with clinical hand OA in men, with OR (95% CI) of 1.26 (1.00 - 1.57), 1.35 (1.00 - 1.82) and 5.27 (1.07 - 25.96) respectively. In women, these associations were not found; however, although not significant, the OR of omega-3 PUFAs and hand OA was 2.49 (0.45 - 13.72). None of the postprandial fatty acid subtypes were statistically significantly associated with knee or concurrent hand and knee OA in both men and women. In comparison, although not significant, results from the analyses with fasting fatty acids showed similar albeit slightly dampened effect estimates. Conclusions: Quantitively measured plasma postprandial SFA and omega-3 PUFA levels were significantly associated with hand OA in men. In women no significant associations were found, however the estimated effect was comparable to the results in men. Intriguingly, although SFA and omega-3 PUFAs are deemed to have opposing effects on inflammation, both were positively associated with hand OA. No significant associations were found between fatty acids and knee and concurrent hand and knee OA. Future research is warranted to replicate the association and determine whether there is a causal role for plasma fatty acid levels in hand OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Omega-3 polyunsaturated fatty acids and IVF treatment.

Omega-3 polyunsaturated fatty acids (PUFAs) are essential fatty acids, derived mostly from fish oil, that have a significant anti-inflammatory effect. Data from animal studies support their role in the reproductive mechanism, and recent human studies suggest a positive effect on sperm quality and natural conception. Their general role in human fertility, and specifically in IVF treatment, however, is not clear. A few small, prospective cohort studies have examined the relationship between serum PUFAs and outcome measures and success in IVF, with conflicting results. Some have demonstrated a better chance of live birth with increased levels of serum omega-3 PUFAs, whereas others have failed to show such a correlation, and the reasons for such differences are not clear. Moreover, no well-designed, published studies have assessing whether the administration of omega-3 PUFAs before IVF treatment can improve clinical pregnancy and live birth rates. The development of safe and well-tolerated pharmaceutical forms of the active omega-3 PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), mean that assessment of this question is now possible and future studies are warranted.

Fish Oil and Perioperative Bleeding.

Background Fish oil is among the most common natural supplements for treatment of hypertriglyceridemia or prevention of cardiovascular disease. However, concerns about theoretical bleeding risk have led to recommendations that patients should stop taking fish oil before surgery or delay in elective procedures for patients taking fish oil by some health care professionals. Methods and Results We tested the effect of fish oil supplementation on perioperative bleeding in a multinational, placebo-controlled trial involving 1516 patients who were randomized to perioperative fish oil (eicosapentaenoic acid+docosahexaenoic acid; 8-10 g for 2-5 days preoperatively, and then 2 g/d postoperatively) or placebo. Primary outcome was major perioperative bleeding as defined by the Bleeding Academic Research Consortium. Secondary outcomes include perioperative bleeding per thrombolysis in myocardial infarction and International Society on Thrombosis and Hemostasis definitions, chest tube output, and total units of blood transfused. Participants' mean (SD) age was 63 (13) years, and planned surgery included coronary artery bypass graft (52%) and valve surgery (50%). The primary outcome occurred in 92 patients (6.1%). Compared with placebo, risk of Bleeding Academic Research Consortium bleeding was not higher in the fish oil group: odds ratio, 0.81; 95% CI, 0.53-1.24; absolute risk difference, 1.1% lower (95% CI, -3.0% to 1.8%). Similar findings were seen for secondary bleeding definitions. The total units of blood transfused were significantly lower in the fish oil group compared with placebo (mean, 1.61 versus 1.92; P<0.001). Evaluating achieved plasma phospholipid omega-3 polyunsaturated fatty acids levels with supplementation (on the morning of surgery), higher levels were associated with lower risk of Bleeding Academic Research Consortium bleeding, with substantially lower risk in the third (odds ratio, 0.30 [95% CI, 0.11-0.78]) and fourth (0.36 [95% CI, 0.15-0.87]) quartiles, compared with the lowest quartile. Conclusions Fish oil supplementation did not increase perioperative bleeding and reduced the number of blood transfusions. Higher achieved n-3-PUFA levels were associated with lower risk of bleeding. These novel findings support the need for reconsideration of current recommendations to stop fish oil or delay procedures before cardiac surgery. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00970489.

Lower Circulating Omega-3 Polyunsaturated Fatty Acids Are Associated with Coronary Microvascular Dysfunction Evaluated by Hyperemic Microvascular Resistance in Patients with Stable Coronary Artery Disease.

The consumption of omega-3 polyunsaturated fatty acids (PUFAs) reduces the incidence of cardiovascular events and sudden cardiac death. Coronary microvascular dysfunction (CMD) is a predictor of cardiac mortality, but little information is known on the relationship between CMD and omega-3 PUFAs. This study aimed to identify the relationship between the serum levels of omega-3 PUFAs and the CMD evaluated by the hyperemic microvascular resistance index (hMVRI) to assess coronary microvascular function in patients with stable coronary artery disease (CAD).Intracoronary physiological variables (fractional flow reserve (FFR), hMVRI, mean distal coronary pressure (Pd), and average peak velocity (APV)) were measured in 108 patients. These parameters were evaluated in 150 coronary arteries with stenosis of intermediate severity and without significant ischemia (FFR > 0.80). The PUFA levels and atherosclerotic risk factors were also measured. Univariate analysis shows that hMVRI was negatively correlated with eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio (β = -0.31, P = 0.001) and EPA (β = -0.25, P = 0.009) and was positively correlated with dihomo-γ-linolenic acid (β = 0.26, P = 0.006). Multivariate regression analysis shows that the EPA/AA ratio was the only independent determinant of hMVRI (β = -0.234, SE = 0.231, P = 0.024). Furthermore, hMVRI decreased significantly from the lowest to highest tertiles of the EPA/AA ratio (P = 0.007). The EPA/AA ratio was positively correlated with APV at hyperemia (β = 0.26, P = 0.008) but not with Pd at hyperemia.A lower serum EPA/AA ratio may cause CMD in patients with stable CAD.

STUDY OF THE LEVEL OF FATTY ACIDS IN ERYTHROCYTE MEMBRANES AND SERUM OF PATIENTS WITH COLORECTAL CANCER IN NOVOSIBIRSK

The objectiveis to measure the level of fatty acids in erythrocyte membranes and serum of patients with colorectal cancer.Materials and methods.The study group included 100 patients with diagnosed colorectal cancer (57 men and 43 women). The control group included 24 reasonably healthy people (14 men and 10 women) matched for age and sex, without malignant cancers or manifested pathology of the internal organs.Results.Decreased levels of saturated, monounsaturated fatty acids and increased levels of polyunsaturated fatty acids (PUFAs) in erythrocyte membranes and serum (p &lt;0.0001–0.05) were observed. The levels of omega-3 PUFAs in colorectal cancer exceeded the levels in healthy individuals both in erythrocyte membranes and in serum; for omega-6 PUFAs only a trend was observed. At the same time, the ratio of omega-6/omega-3 PUFAs in colorectal cancer was lower than in control (p &lt;0.0001–0.002). The state of erythrocyte membranes more significantly and for more parameters characterized differences between the groups than serum. The most discriminating parameters between patients with colorectal cancer and healthy individuals both in erythrocyte membranes and serum were the levels of C20:2;11,14 (eicosadienoic), C20:3;8,11,14 (dihomo-γ-linolenic), C20:4;5,8,11,14 (eicosatetraenoic, arachidonic), C22:5;7,10,13,16,19 (docosapentaenoic), and C22:6;4,7,10,13,16,19 (docosahexaenoic) PUFAs.

Omega-3 polyunsaturated fatty acid levels and dysregulations in biological stress systems

BackgroundStudies have shown that omega-3 (n-3) Polyunsaturated Fatty Acids (PUFAs), including docosahexaenoic acid (DHA), might have beneficial effects on somatic and mental health, potentially partly due to their mitigating effects on three major biological stress systems: the immune-inflammatory system, the hypothalamic-pituitary-adrenal-axis (HPA-axis) and the autonomic nervous system (ANS). ObjectiveTo examine the association between (cumulative measures of) markers of three biological stress systems and n-3 PUFA and DHA plasma levels. DesignPlasma n-3 PUFA and DHA were measured using Nuclear Magnetic Resonance in 2724 participants from the Netherlands Study of Depression and Anxiety. Linear regression analyses (adjusted for sociodemographic, sampling, lifestyle and somatic disease variables) associated inflammation (C-reactive protein, interleukin-6, tumor necrosis factor alpha), HPA-axis (cortisol awakening response and evening cortisol) and ANS (heart rate, respiratory sinus arrhythmia and pre-ejection period) markers and cumulative indices within and across stress systems as independent variables with n-3 PUFA and DHA levels as dependent variables. ResultsParticipants had a mean age of 41.8 (SD = 13.1) and 65.7% were female. Higher levels of all three inflammation markers (Beta=−.146 to −.073, all p-values<.001), evening cortisol (Beta=−.045, p = .033) and heart rate (Beta=−.080, p < 0.001) were significantly negatively associated with n-3 PUFA. Suggesting an exposure-response relationship, a higher number of markers indicative of inflammation and hyperactive HPA-axis (p < .001 and p = .003, respectively), but not of ANS dysregulation, was found in persons with lower n-3 PUFA levels. An exposure-response relationship was also found for having a higher number of different stress system dysregulations with lower n-3 PUFA levels (p < .001). For DHA, results were in line with those for n-3 PUFA, although with slightly smaller effect sizes. ConclusionsOur study confirmed that having various (cumulative) indicators of dysregulation of three biological stress systems was significantly associated with lower n-3 PUFA and DHA plasma levels. If low n-3 PUFA levels are the cause of dysregulated stress systems, then n-3 PUFA supplementation might reduce biological stress and thereby improve somatic and mental health.

Cardiometabolic risks and omega-3 index in recent-onset bipolar I disorder.

The aims of the present study were to characterize cardiometabolic risk factors in a cohort of bipolar disorder patients with limited exposure to psychotropic medications, and to evaluate their associations with mood symptoms and omega-3 polyunsaturated fatty acid (PUFA) blood levels. Cardiometabolic risk assessments were compared in individuals with bipolar I disorder experiencing a first manic or mixed episode or an early depressive episode (n=117) and healthy subjects (n=56). Patients were medication free at assessment and had no or limited exposure to mood-stabilizer or antipsychotic medications prior to the current admission. Associations among cardiometabolic parameters and Clinical Global Impression-Severity scale (CGI-S), manic (Young Mania Rating Scale [YMRS]), and depressive (Hamilton Depression Rating Scale [HDRS]) symptom ratings were evaluated within the bipolar group. Following adjustment for demographic variables (i.e., age, gender, and parental education), significantly higher fasting triglyceride levels were observed in the bipolar group compared to the healthy group (121.7mg/dL vs 87.0mg/dL; P<.01). There were no clear trends for other metabolic indicators, including blood pressure, body mass index, and fasting glucose. Nineteen percent of the bipolar group and 6% of the healthy group met the criteria for metabolic syndrome (P=.23). The omega-3 index was lower in the bipolar group (3.4% vs 3.9%; P<.01). Within the bipolar group, no associations were found between the cardiometabolic parameters and CGI-S, YMRS, and HDRS symptom ratings. Recent-onset medication-free bipolar disorder is associated with higher triglyceride levels. These findings are suggestive of early metabolic dysregulation prior to long-term psychotropic medication exposure. Lower omega-3 PUFA levels in individuals with bipolar I disorder represent a potential therapeutic target for additional investigation.

Association between Red Blood Cells Omega-3 Polyunsaturated Fatty Acids and White Matter Hyperintensities: The MAPT Study.

The association between circulating biomarkers of red blood cells (RBC) omega-3 polyunsaturated fatty acids (PUFAs) and cerebral white matter hyperintensities (WMH) on the brain MRI remains yet unclear. We investigated the cross-sectional and prospective associations of RBC omega-3 PUFAs with WMH in dementia-free older adults with subjective memory complaints. Participants were 234 older adults with assessments for both PUFA and MRI near to baseline; among them, 79 also had an MRI assessment at 3-year follow-up. The measurement of WMH volume was obtained by an automated segmentation algorithm. We related individual or combinational baseline RBC omega-3 PUFAs levels with baseline WMH volumes and WMH evolution over 3 years. We carried out multiple (cross-sectional) and mixed-effect (prospective analysis, with random effects at participant's level) linear regressions with adjustment for age, sex, time interval between date of blood draw for measurement of fatty acids and date of brain MRI, the status of APOE e4 carrier, body mass index, and vascular risk factors. Associations were considered significant at p ≤ 0.006 to take into account multiplicity (8 comparisons). None of the eight RBC omega-3 PUFAs tested was significantly associated with WMH at both cross-sectional and prospective analyses. We did not find any association between omega-3 PUFAs and WMH in non-demented older adults with memory complaints. A longer longitudinal study with data on omega-3 PUFAs and WMH would contribute important information to this field.

Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies

The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes. We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis. Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m2, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I2=53·9%, pheterogeneity=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88-1·05; p=0·38; I2=63·0%, pheterogeneity<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all pheterogeneity≥0·13). Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful. Funders are shown in the appendix.

Omega-3 fatty acid levels in red blood cell membranes and physical decline over 3years: longitudinal data from the MAPT study.

Studies have shown that omega-3 polyunsaturated fatty acids (PUFAs) are associated with brain, cardiovascular, and immune function, as well as physical performance and bone health in older adults. So far, few studies have investigated the associations between PUFA status and performance-based tests of physical function. The objective of this study was to investigate the associations between the omega-3 PUFA levels (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)) in red blood cell (RBC) membranes and physical performance, in a sample of community-dwelling older adults. This is a longitudinal observational study using data from the Multidomain Alzheimer's Disease Trial (MAPT), a randomized, placebo-controlled trial. Four hundred participants from MAPT placebo group with available PUFA data were included. Omega-3 PUFA levels in RBC membranes were measured at baseline, and their percentage of total RBC membrane fatty acid content was calculated. We dichotomized the standardized omega-3 PUFA levels in RBC membranes as low (lowest quartile) vs. high (three upper quartiles). Gait speed (in m/s) and short physical performance battery (SPPB) score (range from 0 to 12, higher is better) were used to assess physical performance at baseline and after 6, 12, 24, and 36months. Participants were 75.2 (±4.3) years old and 68% were female. Bivariate analyses found that the characteristic of the participants in the lowest quartile of omega-3 PUFA levels (Q1) and those in the three upper quartiles (Q2-Q4) was not different at baseline; only those in Q1 were slightly older. In an unadjusted model, the difference in gait speed after 3years of follow-up was significant (-0.09±0.03m/s; p=0.008) between participants in Q1 and those in Q2-Q4. In a model adjusted for age, gender, educational level, cognitive function, depressive status, body mass index, physical activity, grip strength, and their time interaction, this difference remained clinically relevant (-0.07±0.04m/s; p=0.075). No difference between the two groups was found for the SPPB score development over 3years. Older adults with subjective memory complaints and in the lower quartile of omega-3 have a faster decline on gait speed compared to people in the three upper quartiles. Other longitudinal studies are needed to explore this association and to examine mechanisms.

Dietary choline and phospholipid supplementation enhanced docosahexaenoic acid enrichment in egg yolk of laying hens fed a 2% Schizochytrium powder-added diet

The aim of this study was to evaluate the effect of dietary phospholipid supplementation on laying hen performance, egg quality, and the fatty acid profile of egg yolks from hens fed a 2% Schizochytrium powder diet. Three-hundred-sixty 28-wk-old Hy-line W-36 laying hens were randomly allocated to one of the 5 dietary treatments, each treatment with 6 replicates of 12 birds each. All diets included 2% Schizochytrium powder (docosahexaenoic acid [DHA], 137.09 mg/g). The control group was not supplemented with any additional phospholipids, whereas the other 4 experimental diets were supplemented with 1,000 mg/kg choline (CHO), 1,000 mg/kg monoethanolamine (MEA), 1,000 mg/kg lysophosphatidylcholine (LPC), or 500 mg/kg LPC + 500 mg/kg MEA (LPC + MEA). The experimental diets were isocaloric (metabolizable energy, 11.15 MJ/kg) and isonitrogenous (crude protein, 16.60%). The feeding trial lasted 28 days. Laying hen performance and egg quality were not affected (P>0.05) by the diets used. The monounsaturated fatty acid (MUFA) level was reduced in the LPC group at d 28 (P < 0.01), whereas the polyunsaturated fatty acid (PUFA) level was increased (P < 0.05). The omega-6 (n-6) PUFA level of the egg yolks in the LPC group had a trend to increase in comparison to the control (P = 0.07). The CHO and LPC groups had higher omega-3 (n-3) PUFA and DHA levels and lower n-6/n-3 ratios than the other groups at d 28 (P < 0.01). The DHA content in egg yolk reached a plateau after the laying hens consumed the experimental diets for 14 days, and higher yolk DHA contents were observed in the CHO and LPC groups as compared with the other groups at d 14. It was concluded that dietary choline supplementation for more than 14 d enhanced egg yolk enrichment with n-3 PUFA and DHA when laying hen diets were supplemented with 2% Schizochytrium powder. All the diets had no adverse effect on hen performance, egg quality, or egg components under the experimental condition.

Omega-6 to omega-3 polyunsaturated fatty acid ratio and subsequent mood disorders in young people with at-risk mental states: a 7-year longitudinal study

While cross-sectional studies suggest that patients with mood disorders have a higher ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) and lower levels of omega-3 PUFAs, it is unknown if a high n-6/3 ratio indicates vulnerability for depression. We tested this hypothesis in a 7-year follow-up study of young individuals with an ultra-high risk (UHR) phenotype. We conducted a secondary analysis of the Vienna omega-3 study, a longitudinal study of omega-3 PUFAs in individuals at UHR for psychosis (n=69). Levels of n-6 and n-3 PUFAs were measured in the phosphatidylethanolamine fraction of erythrocyte membranes at intake into the study. Mood disorder diagnosis was ascertained with the Structured Clinical Interview for DSM-IV-TR and confirmed by review of medical records and interviews of caregivers. A higher n-6/3 PUFA ratio at baseline predicted mood disorders in UHR individuals over a 7-year (median) follow-up (odds ratio=1.89, 95% CI=1.075–3.338, P=0.03). This association remained significant after adjustment for age, gender, smoking, severity of depressive symptoms at baseline and n-3 supplementation. Consistent results were obtained for individual PUFAs, including lower levels of eicosapentaenoic acid and docosahexaenoic acid. The predictive capacity of these findings was specific to mood disorders as no associations were found for any other psychiatric disorder. To our knowledge, our data provide the first prospective evidence that the n-6/3 PUFA ratio is associated with an increased risk for mood disorders in young people exhibiting an UHR phenotype. These findings may have important implications for treatment and risk stratification beyond clinical characteristics.

High Omega-3 Polyunsaturated Fatty Acids in fat-1 Mice Reduce Inflammatory Pain.

Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs), such as α-linolenic and linoleic acids, are essential fatty acids in mammals, because they cannot be synthesized de novo. However, fat-1 transgenic mice can synthesize omega-3 PUFAs from omega-6 PUFAs without dietary supplementation of omega-3, leading to abundant omega-3 PUFA accumulation in various tissues. In this study, we used fat-1 transgenic mice to investigate the role of omega-3 PUFAs in response to inflammatory pain. A high omega-3 PUFA tissue content attenuated formalin-induced pain sensitivity, microglial activation, inducible nitric oxide synthase expression, and the phosphorylation of NR2B, a subunit of the N-methyl-d-aspartate (NMDA) receptor. Our findings suggest that elevated omega-3 PUFA levels inhibit NMDA receptor activity in the spinal dorsal horn and modulate inflammatory pain transmission by regulating signal transmission at the spinal dorsal horn, leading to the attenuation of chemically induced inflammatory pain.

ω３脂肪酸の代謝と抗炎症作用に関する研究

Dietary supplementation of omega-3 polyunsaturated fatty acid（PUFA）includingeicosapentaenoic acid（EPA）and docosahexaenoic acid（DHA）is widely held to be beneficial in human health. Also, elevation in omega-3 PUFA levels in omega-3desaturase（ fat-1）transgenic mice that endogenously biosynthesize omega-3 PUFA from omega-6 PUFA exhibits resistance to inflammatory disease models. To elucidate the molecular mechanisms underlying the beneficial effects of omega-3 PUFAs, we developed a comprehensive LC-MS/MS-based lipidomics method that can detect and quantify more than 500 of PUFA metabolites simultaneously. Using this lipidomics system, and genetically modified animals or nutritional control to manipulate fatty acid balance in the body, we try to understand how different balance of omega-3/omega-6 fatty acids and their unique metabolites function in vivo that could explain the biological significance of omega-3 PUFAs in controlling inflammation and related diseases.

The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

BackgroundMaternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here.MethodsThe Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks’ follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018.DiscussionThe trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations.Trial registrationClinicaltrials.gov: NCT02166424. Registered 15 June 2014; University Hospital Medical Information Network (UMIN) Center: UMIN000017979. Registered 20 May 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-1031-2) contains supplementary material, which is available to authorized users.