Percentage Of Total Fatty Acids Research Articles

F25. NEURAPRO REVISITED: INCREASES IN LONG-CHAIN OMEGA-3 FATTY ACIDS IMPROVE FUNCTIONAL AND SYMPTOMATIC OUTCOMES IN ULTRAHIGH RISK PATIENTS

BackgroundThe NEURAPRO multicentre randomised controlled trial (RCT) of long-chain polyunsaturated omega-3 fatty acids (ω-3 PUFAs) (‘fish oil’) in combination with high-quality psychosocial intervention (cognitive behavioural case management [CBCM]) vs. placebo in combination with CBCM in young people at ultrahigh risk (UHR) of psychosis showed that the group allocated to fish oil had no clinical benefits over the placebo group. However, a limitation of the trial was that adherence with the study medication was relatively low. Furthermore, although RCTs are placed at the top of the evidence hierarchy, this methodology has limitations in fish oil RCTs, since the test agent is not only present in the intervention group, but ω-3 fats are present in the diet and in the tissues of all participants. A biomarker analysis of ω-3 changes during the trial can ultimately determine the efficacy of ω-3 supplementation in this trial.MethodsThe NEURAPRO study was conducted from March 2010 to September 2014, in 10 specialized early psychosis treatment services in Australia, Asia, and Europe. In this study of 304 young people at UHR for psychotic disorders, 153 (50.3%) were allocated to ω-3 PUFAs and 151 (49.7%) to placebo. In all, 139 (45.7%) were male; mean (SD) age was 19.1 (4.6) years. The primary outcome was transition to psychosis assessed with the Comprehensive Assessment of the At-Risk Mental State. Secondary outcomes were levels of psychopathology and functioning assessed by the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Montgomery Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), the Social and Occupational Functioning Assessment Scale (SOFAS), and the Global Functioning: Social and Role scales). Levels of ω-3 PUFAs in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (amongst other fatty acids) were measured as percentage of total fatty acids in erythrocytes at baseline and at month 6 (end-of-intervention). We examined changes in cell membrane levels of EPA and DHA, as measures of ω-3 intake independent of source. Data were analysed as a single cohort. Cox proportional hazards models and linear regression analyses were used to examine relationships between the ω-3 index (EPA+DHA) with clinical outcomes at month 6 and 12.ResultsWhen analysed as a single cohort, no association was observed between the ω-3 index and transition to psychosis at any follow-up time point but increase of the ω-3 index was found significantly related with most of the functional and symptomatic measures at month 6 and 12, in linear regression models adjusting for relevant baseline factors (i.e., functioning, psychopathology, ω-3 index and smoking). The models revealed consistent results, with low functioning or high psychopathology at baseline, low levels of ω-3s at baseline and increase of the ω-3 index independently predicting clinical improvements at in this sample.DiscussionIn contrast to our RCT analysis, this study using biomarkers shows that increase in erythrocyte ω-3 PUFAs may improve clinical outcomes of UHR patients. The results also imply that people with low DHA and EPA levels may benefit more from supplementation with fish oil. The analysis also highlights shortcomings of the RCT design in situations when the tested intervention is available outside the study.

T49. THE NEURAPRO STUDY: ADHERENCE TO STUDY MEDICATION

BackgroundAdherence to a medication is generally defined as the extent to which patients take medications as prescribed by their health care providers. Poor adherence to study medication is not uncommon posing a major challenge to treatment trails. However, poor adherence may not be randomly distributed but rather be associated with demographic or illness factors. The aim of the present study was to identify factors associated with adherence to study medication in young people at ultrahigh risk of psychosis who participated in the NEURAPRO study.MethodsSecondary analysis of data collected in a multi-centre, double-blind, placebo-controlled, randomized clinical trial to prevent or delay the onset of psychosis in participants at ultrahigh risk of psychosis testing omega-3 polyunsaturated fatty acids (omega-3 PUFAs) vs. placebo, in combination with cognitive behavioural case management (NEURAPRO) were included in this analysis. Measures included the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Montgomery Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), the Social and Occupational Functioning Assessment Scale (SOFAS), and the Global Functioning: Social and Role scales. Adherence to the study medication was assessed monthly for each participant based on capsule count. The mean adherence rating over the 6-month intervention period was then computed and categorized as either adherent (≤25% of capsules returned) or non-adherent (>25% of capsules returned). Transition to psychosis was defined on the basis of operationalized criteria and assessed with the Comprehensive Assessment of the At-Risk Mental State. Levels of ω-3 PUFAs in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (amongst other fatty acids) were measured as percentage of total fatty acids in erythrocytes at baseline and at month 6 (end-of-intervention).ResultsOf 304 randomised participants, 57.9% (N = 176) were non-adherent (>25% of capsules returned) and 128 (42.1%) were adherent (≤25% capsules returned) to the study medication.No sex differences were observed for adherence rates. At baseline the omega-3 index (EPA+DHA) was significantly lower in the non-adherent group (P = 0.018). The non-adherent group had significant lower scores on the SOFAS (P = 0.001) and the Global Functioning: Social and Role Scale at baseline assessment (P < 0.001 and P = 0.020, respectively) compared to the adherent group. No statistically significant differences were observed on symptom measures at baseline (BPRS, SANS, MADRS, YMRS). The cumulative transition to psychosis rate at month 12 was significantly higher in the non-adherent group compared to the adherent group (14.8% vs. 4.7%; Log rank test: P < 0.001).DiscussionAdherence to study medication was relatively low in NEURAPRO. Poor functioning and lower levels of ω-3 PUFAs at baseline were associated with non-adherence. Young people who were non-adherent had a significantly higher risk of progressing to first episode psychosis. Knowledge about factors associated with adherence could help to improve the delivery of interventions in young people at risk of psychosis.

T9. CROSS-SECTIONAL ASSOCIATION OF MEMBRANE FATTY ACID COMPOSITION AND PSYCHOPATHOLOGY IN THE NEURAPRO-E STUDY

BackgroundConverging evidence suggests that people at ultra-high risk (UHR) for psychosis have depleted levels of several fatty acids (FAs), and that changes in omega-3 (n-3) FA levels may indicate a higher risk for transition to psychosis. However, limited information is available on how FA deficiencies relate to psychopathology in individuals with UHR phenotypes. Here, we report the relationship between membrane FA levels and symptom severity in a study of individuals at UHR for psychosis.MethodsData from 280 of 304 (92%) of participants of the NEURAPRO study, a multi-centre randomized-controlled trial of omega-3 fatty acids versus placebo, were used for the present analysis. All participants were aged between 13 and 40 years and met criteria for UHR for psychosis. Blood samples were collected at study baseline and month 6 (end-of-intervention). Membrane fatty acids were analysed using mass spectrometry as percentage of total fatty acids in erythrocytes. Pearson correlation coefficients were calculated between baseline erythrocyte fatty acid levels and scores on the Scale for the Assessment of Negative Symptoms (SANS) and Brief Psychiatric Rating Scale (BPRS).ResultsNegative symptoms were positively correlated with one saturated FA (Tetracosanoic acid [24:0], R=0.272, p<0.0001), one n-3 FA (Eicosapentaenoic acid [20:5], R=0.142, p=0.017) and one n-9 FA (Nervonic acid [24:1], R=0.274, p<0.0001), and negatively correlated with one saturated FA (Palmitic acid [16:0], R=-0.224, p<0.0001), two n-6 FAs (Dihomo-y-linolenc acid [20:3], R=-0.201, p<0.001 and Linolelaidic acid [18:2], R=-0.333, p<0.0001), and one n-7 FA (Vaccenic acid [18:1], R=-0.172, p=0.004). BPRS scores were positively correlated with one saturated FA (Tetracosanoic acid [24:0], R=0.363, p<0.0001) and one n-9 fatty acid (Nervonic acid [24:1], R=-0.346, p<0.0001), and negatively correlated with two n-3 FAs (Dihomo-y-linolenc acid [20:3], R=-0.153, p=0.010 and Docosahexaenoic acid [22:6], R=-0.193, p<0.001), and two n-6 FAs (Arachidonic acid [20:4], R=-0.125, p=0.037 and Linoleic acid [18:2], R=-0.340, p<0.0001).DiscussionConsistent with a previous study, negative symptoms and general psychopathology were associated with levels of several classes of FAs in the present study. These findings support the relevance of membrane fatty acids for the onset of psychotic symptoms and indicate that FAs should be further evaluated as biomarkers in people at UHR for psychosis.

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.

Metabolomic Markers of Essential Fatty Acids, Carnitine, and Cholesterol Metabolism in Adults and Adolescents with Phenylketonuria

Individuals with phenylketonuria (PKU) have a risk of cognitive impairment and inflammation. Many follow a low-phenylalanine (low-Phe) diet devoid of animal protein in combination with medical foods (MFs). To assess lipid metabolism in participants with PKU consuming amino acid MFs (AA-MFs) or glycomacropeptide MFs (GMP-MFs), we conducted fatty acid and metabolomics analyses. We used subsets of fasting plasma and urine samples from our randomized crossover trial in which participants with early-treated classical and variant (milder) PKU consumed a low-Phe diet combined with AA-MFs or GMP-MFs for 3 wk each. Fatty acid profiles of red blood cell (RBC) membranes were determined for 25 adults (aged 18-49 y) with PKU and 143 control participants. Metabolomics analyses of plasma and urine samples were conducted by Metabolon for 9-10 adolescent and adult participants with PKU and for 15 control participants. RBC fatty acid profiles were not significantly different with AA-MFs or GMP-MFs. PKU participants showed higher total n-6:n-3 (ω-6:ω-3) fatty acids (mean ± SD percentages of total fatty acids: AA-MF = 5.45% ± 1.07%; controls = 4.33%; P < 0.001) and lower docosahexaenoic acid (DHA; AA-MF = 3.21% ± 0.98%; controls = 3.70% ± 1.01%; P = 0.02) and eicosapentaenoic acid (AA-MF = 0.33% ± 0.12%; controls = 0.60% ± 0.43%; P < 0.001) in RBCs than did control participants. Despite higher carnitine intake from AA-MFs than GMP-MFs (mean ± SE intake: AA-MFs = 58.6 ± 5.3 mg/d; GMP-MFs = 0.3 ± 0.01 mg/d; P < 0.001), plasma concentrations of carnitine were similar and not different from those in the control group (AA-MF compared with GMP-MF, P = 0.73). AA-MFs resulted in higher urinary excretion of trimethylamine N-oxide (TMAO), which is synthesized by bacteria from carnitine, compared with GMP-MFs (mean ± SE scaled intensity-TMAO: AA-MFs = 1.2 ± 0.1, GMP-MFs = 0.9 ± 0.1; P = 0.005). Plasma deoxycarnitine was lower in PKU participants than in control participants, suggesting reduced carnitine biosynthesis in PKU (AA-MF = 0.9 ± 0.1; GMP-MF = 1.0 ± 0.1; controls = 1.3 ± 0.1; AA-MF compared with controls, P = 0.01; GMP-MF compared with controls, P = 0.04). Supplementation with DHA is needed in PKU. Carnitine supplementation of AA-MFs shows reduced bioavailability due, in part, to bacterial degradation to TMAO, whereas the bioavailability of carnitine is greater with prebiotic GMP-MFs. This trial was registered at www.clinicaltrials.gov as NCT01428258.

Adipose tissue fatty acids present in dairy fat and risk of stroke: the Danish Diet, Cancer and Health cohort.

The role of dairy fat for the risk of stroke is not yet clear. Adipose tissue reflects long-term fatty acid intake and metabolism. We, therefore, investigated associations for percentages of adipose tissue fatty acids, for which dairy products are a major source (12:0, 14:0, 14:1 cis-9, 15:0, 17:0, 18:1 trans-11 and 18:2 cis-9, trans-11), with incident total stroke and stroke subtypes. We conducted a case-cohort study within the Danish Diet, Cancer and Health cohort, including all incident stroke cases (n = 2108) and a random sample of the total cohort (n = 3186). The fatty acid composition of adipose tissue biopsies was determined by gas chromatography and specific fatty acids were expressed as percentage of total fatty acids. Stroke cases were identified in the Danish National Patient Registry and the diagnoses were individually verified. We recorded 2108 stroke cases of which 1745 were ischemic, 249 were intracerebral hemorrhages and 102 were subarachnoid hemorrhages. We observed a lower rate of ischemic stroke for a higher adipose tissue percentage of 12:0, 14:0, 15:0, 17:0, 18:1 trans-11 and 18:2 cis-9, trans-11. Adipose tissue percentages of 15:0 and 18:1 trans-11 were also inversely associated with intracerebral hemorrhage, whereas no associations between the adipose tissue fatty acids and subarachnoid hemorrhage were observed. No associations between 14:1 cis-9 and ischemic or hemorrhagic stroke were found. Our results suggest that a larger percentage in adipose tissue of fatty acids for which dairy products are a major source is associated with a lower rate of ischemic stroke.

Serum Conjugated Linoleic Acid and Risk of Incident Heart Failure in Older Men: The British Regional Heart Study.

BackgroundEvidence largely from animal studies suggests that conjugated linoleic acid (CLA) may have cardiovascular health benefits. However, few prospective studies have examined the association between CLA and cardiovascular disease. We have prospectively examined the association between serum CLA and incident coronary heart disease and heart failure (HF) in older men.Methods and ResultsProspective study of 3806 men, aged 60 to 79 years, without prevalent HF followed up for an average of 13 years, during which there were 295 incident HF cases. A high‐throughput serum nuclear magnetic resonance metabolomics platform was used to measure CLA concentration in serum, expressed as a percentage of total fatty acids (CLA%). CLA% was adversely associated with cholesterol and high‐density lipoprotein cholesterol but was inversely associated with C‐reactive protein and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; a marker of ventricular stress). No association was seen between CLA% and incident coronary heart disease. High CLA% was associated with significantly reduced risk of HF after adjustment for HF risk factors and C‐reactive protein (hazard ratio [95% confidence interval], 0.64 [0.43–0.96]; quartile 4 versus quartile 1). Elevated CLA% was associated with reduced HF risk only in those with higher dairy fat intake, a major dietary source of CLA (test for interaction P=0.03). The reduced risk of HF was partially explained by NT‐proBNP. High dairy fat intake was not associated with incident coronary heart disease but was associated with reduced risk of HF, largely because of the inverse effect of CLA.ConclusionsThe finding that high CLA% is associated with lower risk of incident HF in older men requires confirmation in larger studies.

Plasma Fatty Acid Composition in Men over 50 in the USA and Japan

Background: Coronary heart disease (CHD) rates differ markedly between the US and Japan. Fatty acid profiles have been linked to risk for CHD. Few studies have compared the plasma fatty acid composition, including trans fatty acids, in Japanese and US subjects. Methods: Fasting blood samples were taken from healthy older (>age 50) American (n = 76) and Japanese (n = 44) men, and plasma levels of 23 fatty acids were analyzed by gas chromatography and expressed as a percent of total fatty acids. Results: As expected, plasma levels of long-chain ω3 fatty acids (docosahexaenoic and eicosapentaenoic acids, DHA and EPA) were higher in Japanese men and ω6 fatty acids (e.g., arachidonic acid, AA) were lower compared with American men. Plasma levels of the major industrially-produced trans fatty acids (IP-TFAs; elaidic and linoelaidic acids) were far higher in American men, and levels of the potentially cardioprotective, primarily ruminant-derived trans fatty acid palmitoelaidic acid (POA) were higher in Japanese. Plasma levels of saturated or monounsaturated fatty acids were also higher in the American men. Conclusion: There are multiple differences in plasma fatty acid profiles between American and Japanese older men. The higher levels of DHA and EPA, along with the lower levels of the IP-TFAs, are consistent with the markedly lower risk for coronary heart disease in Japan vs. the US.

The impact of lactation and gestational age on the composition of branched-chain fatty acids in human breast milk.

Breast milk consumption reduces the incidence of necrotizing enterocolitis (NEC) in preterm infants compared to formula. Branched-chain fatty acids (BCFAs) are present in breast milk but not in most formulas intended for preterm infants. We aimed to determine the composition of BCFAs in the breast milk of mothers with preterm infants, and to understand the impact of gestational age at birth and stage of lactation on BCFA content. The main BCFAs in preterm breast milk were iso-14:0, iso-15:0, anteiso-15:0, iso-16:0, iso-17:0, and anteiso-17:0. Breast milk BCFAs as a percent of total fatty acids (g per 100 g, %) were significantly different across lactation stages, with the highest concentration in colostrum, followed by transitional and mature breast milk (median: 0.41, 0.31, and 0.28%, respectively, p < 0.05). Lower BCFAs in preterm breast milk compared to term breast milk may have been related to maternal intake, or the ability of the mammary gland to extract BCFA from plasma, or differences in mammary gland BCFA synthesis. BCFAs were mainly in the sn-2 position (52-65%), similar to palmitic acid. Overall, preterm and term breast milk BCFAs were similar and showed specific concentration patterns, resembling 16:0 with respect to sn-2 positional distribution. BCFAs were reduced with lactation stage, similar to highly unsaturated fatty acids.

Fatty acid profiles and sn-2 fatty acid distribution of γ-linolenic acid-rich Borago species

The aim of this work was to assess the seed oils of different Borago species as sources of bioavailable γ-linolenic acid (GLA) by establishing its positional distribution within the triacylglycerol (TAG) structure. To this end, seeds of wild and farmed Borago species were collected and analysed. The highest GLA percentage of total fatty acids (FA) was found in B. morisiana and B. pygmaea (23.1 and 22.9% GLA of total FA, respectively). Other endemic Borago species (B. trabutii and B. longifolia) show a lower GLA content (18.9 and 19.0% of total FA, respectively). Oil content in seeds of B. officinalis ranged from 14.4 to 20.3%, while the GLA percentage of total FA was 15.7–19.4%, which leads to a 2.3–3.7% GLA range in the whole seeds. For endemic Borago, such amounts were 5.6, 5.0, 3.9, and 3.0%, for B. morisiana, B. pygmaea, B. trabutii, and B. longifolia, respectively. The distribution of FA in the sn-2 position of TAG was assessed by enzymatic hydrolysis reaction. The best regiospecific index was found in B. longifolia (0.8) and B. officinalis (1.0). This study provides useful data on novel GLA-rich Borago seed oils, which have potential use in the food and pharmaceutical industries.

Fish oil supplementation in chronic obstructive pulmonary disease: feasibility of conducting a randomised controlled trial

BackgroundLong-chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs) may act as an effective adjunct therapy for chronic obstructive pulmonary disease (COPD), a condition characterised by persistent airflow limitation and inflammation. However, the nature of this illness presents challenges for evaluating potential benefits. The aim of this study was to determine the feasibility of undertaking a randomised controlled trial of LCn-3PUFA supplementation in adults with COPD.MethodsA 16-week parallel, double-blind, randomised, placebo-controlled dietary supplementation trial was conducted. Participants diagnosed with COPD were randomly allocated to take six 1-g capsules of fish oil (3.6 g LCn-3PUFA) or corn oil (placebo) daily for 16 weeks. Key outcomes used to determine the feasibility of the trial included recruitment rate, participant retention rate and supplement adherence (blood biomarker and returned capsule count). An estimate of the effect size for clinical outcomes such as pulmonary function and functional exercise capacity was calculated.ResultsNone of the key feasibility criteria were met. The enrolment target was 40 participants in 52 weeks; however, only 13 were finally enrolled, with just seven in the first 52 weeks. Eight participants completed the study (retention rate 62%). Targets for compliance were not achieved; red blood cell LCn-3PUFA content (expressed as percentage of total fatty acids) did not increase by more than 2% in the fish oil group; capsule counts were unreliable. As the target sample size was not achieved and only a small number of participants completed the study, it was not possible to use the variance in clinical outcomes to estimate a sample size for a future study.ConclusionsThis study highlights major difficulties, especially with recruitment, in conducting this LCn-3PUFA supplementation trial in people with COPD, rendering the protocol unfeasible by predetermined criteria. A modified approach is needed to investigate potential health benefits of fish oil in people with COPD. A multicentre study with changes to inclusion and exclusion criteria is recommended.Trial registrationAustralia and New Zealand Clinical Trials Register (ANZCTR), ACTRN12612000158864

A Correlation Study of DHA Intake Estimated by a FFQ and Concentrations in Plasma and Erythrocytes in Mid- and Late Pregnancy

Adequate docosahexaenoic acid (DHA) is essential for the optimal growth and development of the fetus. Maternal DHA content fluctuates during pregnancy. The correlation of DHA content with dietary intake might be varied over the course of pregnancy. We aimed to compare the dietary DHA intake, estimated by a DHA-specific semiquantitative food frequency questionnaire (FFQ) against its blood content, among mid- and late-term pregnant women. A total of 804 Chinese pregnant women completed the tailored FFQ and provided fasting venous blood samples. Dietary DHA intake (mg/day) in the previous month was calculated from the FFQ using Chinese Food Composition Table. DHA concentrations (weight percent of total fatty acids) in plasma and erythrocytes were measured by capillary gas chromatography. Spearman correlation coefficients (rs) between DHA intake and its relative concentrations were calculated. After adjustment for maternal age, pre-pregnancy body mass index, stage of pregnancy, parity, education level, ethnicity, and annual family income per capita, the correlation coefficients of DHA intake with its concentrations in plasma and erythrocytes were 0.35 and 0.33, respectively (p < 0.001). The correlations were relatively stronger among women in late pregnancy (rs = 0.44 in plasma and 0.39 in erythrocytes) than those in mid-pregnancy (rs = 0.25 and 0.26). The significant correlations were consistently observed in subgroups stratified by regions, except for erythrocytes in women living in a coastland area. Multiple regression analyses also indicated significant positive linear correlations between DHA intake and its plasma or erythrocytes concentrations (p < 0.001). In conclusion, dietary DHA intake, estimated by the FFQ, was positively correlated with its concentrations in plasma and erythrocytes in Chinese pregnant women, especially for women in late pregnancy, with the exception of the erythrocytes of those living in a coastland area.

Serum omega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction.

Are serum polyunsaturated fatty acids (PUFA) concentrations, including omega-3 (ω3-PUFA) and omega-6 (ω6-PUFA), related to ART outcomes? Serum levels of long-chain ω3-PUFA were positively associated with probability of live birth among women undergoing ART. Intake of ω3-PUFA improves oocyte and embryo quality in animal and human studies. However, a recent cohort study found no relation between circulating ω3-PUFA levels and pregnancy rates after ART. This analysis included a random sample of 100 women from a prospective cohort study (EARTH) at the Massachusetts General Hospital Fertility Center who underwent 136 ART cycles within one year of blood collection. Serum fatty acids (expressed as percentage of total fatty acids) were measured by gas chromatography in samples taken between Days 3 and 9 of a stimulated cycle. Primary outcomes included the probability of implantation, clinical pregnancy and live birth per initiated cycle. Cluster-weighted generalized estimating equation (GEE) models were used to analyze the association of total and specific PUFAs with ART outcomes adjusting for age, body mass index, smoking status, physical activity, use of multivitamins and history of live birth. The median [25th, 75th percentile] serum level of ω3-PUFA was 4.7% [3.8%, 5.8%] of total fatty acids. Higher levels of serum long-chain ω3-PUFA were associated with higher probability of clinical pregnancy and live birth. Specifically, after multivariable adjustment, the probability of clinical pregnancy and live birth increased by 8% (4%, 11%) and 8% (95% CI: 1%, 16%), respectively, for every 1% increase in serum long-chain ω3-PUFA levels. Intake of long-chain ω3-PUFA was also associated with a higher probability of life birth in these women, with RR of 2.37 (95% CI: 1.02, 5.51) when replacing 1% energy of long-chain ω3-PUFA for 1% energy of saturated fatty acids. Serum ω6-PUFA, ratios of ω6 and ω3-PUFA, and total PUFA were not associated with ART outcomes. The generalizability of the findings to populations not undergoing infertility treatment may be limited. The use of a single measurement of serum fatty acids to characterize exposure may lead to potential misclassification during follow up. Serum ω3-PUFA are considered biomarkers of dietary intake. The association of higher serum long chain ω3-PUFA levels with improved ART outcomes suggests that increased intake of these fats be may be beneficial for women undergoing infertility treatment with ART. NIH grants R01-ES009718 from the National Institute of Environmental Health Sciences, P30-DK046200 and T32-DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases, and L50-HD085359 from the National Institute of Child Health and Human Development, and the Early Life Nutrition Fund from Danone Nutricia US. Dr Rueda is involved in a patent 9,295,662, methods for enhancing, improving, or increasing fertility or reproductive function (http://patents.com/us-9295662.html). This patent, however, does not lead to financial gain for Dr Rueda, or for Massachusetts General Hospital. Dr Rueda does not own any part of the company nor does he have any equity in any fertility related company. As Dr Rueda is not a physician, he does not evaluate patients or prescribe medications. All other coauthors have no conflicts of interest to declare.

Characterization of linoleic acid (C18:2) concentration in commercial corn silage and grain hybrids

Corn silage and high-moisture corn grain are commonly recognized as risk factors for biohydrogenation-induced milk fat depression and may be due to the high concentration of linoleic acid (C18:2) in corn. Corn silage and corn grain have a low concentration of fatty acids (FA), but due to their high inclusion rate in diets they contribute substantially to unsaturated FA intake. The first objective of this study was to characterize the contribution of individual plant parts to total FA in whole-plant chopped corn. The second objective was to characterize the variation in FA profile in commercial silage and grain hybrids and evaluate the relationship between FA profile and other nutrients. To determine the location of FA in the corn plant, 4 stalks from 4 different commercial hybrids were separated into stalk, husk and shank, leaves, cob, and kernels. On a dry matter basis, 80.5% of total FA were in the kernels, 11.8% in the leaves, 5.1% in the stalk, 1.7% in the cob, and 1.0% in the husk and shank. More than 96% of the oleic acid (C18:1) and 92.5% of the C18:2 was in the kernels, whereas 71.0% of the linolenic acid (C18:3) was in the leaves. Next, the FA composition of fresh whole-plant chopped corn from 124 silage hybrids and grain from 72 grain hybrids was determined over 2 yr from test plots in Pennsylvania. Last, to extend the characterization, FA composition of whole-plant corn silage from 45 hybrids grown in test plots in South Dakota were characterized. In the fresh whole-plant chopped corn from PA test plots, C18:2 as a percentage of total FA averaged from 48.7% in 2013 (percentiles: 10th = 45.2, 90th = 52.2) and 48.0% in 2014 (percentiles: 10th = 44.1, 90th = 49.4). Concentration of C18:2 in corn grain averaged 57.5% in the 2013 (percentiles: 10th = 53.4, 90th = 60.8) and 56.1% in 2014 (percentiles: 10th = 53.5, 90th = 59.4). In the corn silage from South Dakota, the concentration of C18:2 as percentage of total FA averaged 45.4% (percentiles: 10th = 39.4, 90th = 50.2) and C18:2 concentration as a percent of dry matter averaged 1.1% (percentiles: 10th = 0.76, 90th = 1.41). An increase in the concentration of C18:2 was associated with a decrease in C18:3 in fresh whole-plant chopped corn and with a decrease in C18:1 in corn grain. Total FA and C18:2 (as a percentage of dry matter) were positively correlated with starch and negatively correlated with neutral detergent fiber in both fresh whole-plant chopped corn and corn silage samples, whereas no correlation with these traits was observed for C18:2 as a percentage of total FA. In conclusion, FA concentration and profile of corn silage reflects to a great extent the FA composition of kernels and the proportion of grain in the silage. The variation in C18:2 across hybrids provides the opportunity to develop selection programs to decrease C18:2 in corn silage and grain. Selection based on C18:2 concentration as a percent of total FA is preferred as this trait did not correlate with other nutritional properties.

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.

Circulating fatty acids in relation to alcohol consumption: Cross-sectional results from a cohort of 60-year-old men and women

Alcohol consumption is considered to affect circulating fatty acids (FAs) but knowledge about specific associations is limited. We aimed to assess the relation between alcohol consumption and serum FAs in 60-year-old Swedish men and women. In a random sample of 1917 men and 2058 women residing in Stockholm county, cross-sectional associations between different categories of alcohol consumption and FAs were assessed using linear regression; β1 coefficients with 95% confidence interval (CI) were calculated. Self-reported alcohol consumption was categorized as none, low (≤9.9g/day) (reference), moderate (10-29.9g/day) and high (≥30g/day). Moderate alcohol consumption was further subdivided into consumption of beer, wine, liquor and their combinations. Thirteen serum cholesterol ester FAs were measured by gas chromatography and individual FAs were expressed as percentage of total FAs. Increasing alcohol consumption was associated to linear increase of saturated myristic acid, monounsaturated FAs and n-6 polyunsaturated (PUFA) arachidonic acid, whereas linear decrease was noted for saturated pentadecanoic acid and for n-6 PUFA linoleic acid. With non-linear associations, increasing alcohol consumption also associated to decreased saturated stearic acid, n-6 PUFA dihomo-gamma-linolenic acid, and n-3 PUFA docosahexaenoic acid and increased saturated palmitic acid, n-6 PUFA gamma-linolenic acid and n-3 PUFA eicosapentaenoic acid. Among types of beverages, wine consumption was associated with n-6 PUFA arachidonic acid (β1 0.59; 95% CI: 0.30;0.88) and the n-3 PUFAs eicosapentaenoic acid (β1 0.54; 95% CI: 0.30;0.78), and docosahexaenoic acid (β1 0.06; 95% CI: 0.00;0.12). These findings may give important basis for further investigations to better understand biological mechanisms behind the dose-dependent associations between alcohol consumption and health outcomes observed in many previous studies.

The association between fatty acid index and in vitro fertilization outcomes

Fatty acids have been shown to play an important role in oocyte competence and early implantation of the embryo. Our hypothesis-generating study sought to determine if individual fatty acids expressed as a percentage of total erythrocyte fatty acids are associated with embryo quality and other in vitro fertilization (IVF) outcomes. This was a prospective cohort study at an academic fertility center. Sixty women undergoing their first IVF cycle were recruited. Serum measurements of 22 fatty acids were obtained. We calculated each fatty acid as a percentage of total fatty acids, defined as the index for that individual fatty acid. Omega-3 index had no correlation with IVF outcomes. A negative correlation was found between the trans fatty acid index, elaidic acid (EA), and IVF outcomes, including fertilization rate (r=-0.261, p=0.04), blastocyst conversion rate (r=-0.41, p=0.001), and number of usable blastocysts and embryos (r=-0.411, p=0.001). There was no correlation between EA index and number of oocytes retrieved, embryo grade, or clinical pregnancy. No consistent correlations were observed with the additional fatty acids analyzed. No correlation was observed between omega-3 index and IVF outcomes. Elevated erythrocyte EA index, the major trans fatty acid commonly consumed in hydrogenated oils, margarine, and fried foods, was negatively correlated with number of usable blastocysts and embryos, blastocyst conversion, and fertilization rate. Our findings suggest preliminary evidence that trans fat may be negatively associated with IVF outcomes.

Comparison of Body Composition and Fatty Acid Profiles between Wild and Cultured Rio Grande Silvery Minnows

AbstractFederally endangered Rio Grande Silvery Minnows (RGSM; Hybognathus amarus) were raised in one of three culture regimes: intensively, with only a hatchery diet; semi-intensively with access to natural food and hatchery diet supplementation; and with only natural food available at the Los Lunas Silvery Minnow Refugium (Los Lunas, New Mexico), a naturalized conservation refugium designed to mimic the natural environment of the RGSM in the Rio Grande. The project compared each culture regime and assessed differences and similarities in lipid and fatty acid content between feeding an artificial diet and consumption of natural food items in this species. After 117 d, whole-body lipid levels and fatty acid profiles were measured in each group and compared with values for wild RGSM. Fish fed the hatchery diet exclusively or as supplementary feed had significantly higher percent lipid (15.5% ± 0.5% and 10.6% ± 0.1%, respectively) than fish raised without access to the diet. Both groups had significantly higher percent lipid than fish raised in the refugium or wild fish (8.3% ± 0.1% and 7.8% ± 0.2%, respectively). Condition factor differed among groups and was highest in fish fed the hatchery diet (1.00) followed by fish supplemented with the hatchery diet (0.93), refugium fish (0.91), and wild fish (0.90). In this respect, refugium fish appeared more similar to wild fish than fish fed the hatchery diet or offered the diet as a supplement. Comparison of fatty acid profiles among groups showed marked differences among wild fish, refugium fish, and those fed the hatchery diet, either exclusively or as supplementary feed. Total omega-3 fatty acids, expressed as percentage of total fatty acids, were highest in wild fish but similar among other groups. Total omega-6 fatty acids showed an opposite trend, with five to nine times higher percentages of linoleic acid observed among fish from the three culture regimes compared with wild fish. Significant differences in lipid content and fatty acid composition between wild RGSM and cultured silvery minnows reflected their respective diets and culture regimes. Given similarities in fat content and condition factor with wild RGSM, we conclude that fish in the refugium do not require supplemental feeding with an artificial diet for this type of naturalized conservation management. Results from this study show that RGSM readily forage on natural food items present and also artificial feed when available, indicating dietary plasticity, which is advantageous for fish culture and future recovery.

The Omega-3 Index and relative risk for coronary heart disease mortality: Estimation from 10 cohort studies

Background and aimsA recent 19-cohort meta-analysis examined the relationships between biomarkers of omega-3 fatty acids and risk for coronary heart disease (CHD). That study did not, however, report hazard ratios (HRs) specifically as a function of erythrocyte eicosapentaenoic (EPA) plus docosahexaenoic (DHA) levels, a metric called the Omega-3 Index in which EPA + DHA content is expressed as a percent of total fatty acids. The Omega-3 Index has been used in several recent studies and is a validated biomarker of omega-3 fatty acid tissue levels, but additional data are needed to confirm (or refute) the originally-proposed clinical cut-points of <4% (higher risk) and 8%–12% (lower risk). MethodsThe present study was therefore undertaken using published data from this meta-analysis to estimate HRs per 1-SD increase in the Omega-3 Index and median quintile values for this metric across 10 of the cohorts for which the needed data were available. ResultsThe overall mean (SD) for the Omega-3 Index in these 10 cohort studies was 6.1% (2.1%), and the HR for a 1-SD increase was 0.85 (95% confidence interval, 0.80–0.91). Median quintile 1 and 5 levels were 4.2% vs. 8.3%, respectively. Based on these values, we estimate that risk for fatal CHD would have been reduced by about 30% moving from an Omega-3 Index of 4%–8%. ConclusionsThese findings support the use of <4% and >8% as reasonable therapeutic targets for the Omega-3 Index.

Plasma ω-3 fatty acids in pregnancy are inversely associated with postpartum weight retention in a multiethnic Asian cohort ,

Background: Studies have demonstrated associations between polyunsaturated fatty acids (PUFAs) and adiposity. It is unclear whether PUFAs in pregnancy have an effect on maternal weight retention after childbirth, which can contribute to long-term obesity.Objective: We examined the association of maternal plasma PUFAs in pregnancy with 18-mo postpartum weight retention (PPWR) in a multiethnic Asian cohort.Design: We studied pregnant women (n = 653) recruited between June 2009 and September 2010 from a prospective cohort. At 26–28 wk of gestation, plasma phosphatidylcholine PUFA concentrations were measured and determined as percentages of total fatty acids (FAs). PPWR was calculated based on the difference between measured weight at the first antenatal clinic visit and at 18 mo postpartum.Results: The median retained weight of women was 0.90 kg (IQR: −1.40, 3.25) at 18 mo postpartum. Of 653 women, 544 women (83.3%) had PPWR of <5 kg and 109 (16.7%) had PPWR of ≥5 kg. In adjusted linear regression models, higher plasma eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total ω-3 (n–3) PUFA concentrations were associated with lower PPWR [EPA: β = −0.62 kg/1% increase of total FAs (95% CI: −1.18, −0.05); DHA: β = −0.24 kg/1% increase (95% CI: −0.45, −0.02); total ω-3 PUFAs: β = −0.20 kg/1% increase (95% CI: −0.36, −0.03)], whereas a higher ratio of plasma ω-6-to-ω-3 PUFAs was associated with a higher PPWR [β = 0.21 kg/unit increase (95% CI: 0.05, 0.36)].Conclusions: Higher plasma percentages of ω-3 PUFAs and a lower ratio of ω-6-to-ω-3 PUFAs in the late-second trimester of pregnancy are associated with less weight retention at 18 mo postpartum. This may offer an alternative strategy to assist postpartum weight reduction by increasing EPA and DHA status together with a decreased ratio of ω-6-to-ω-3 PUFA through diet or fish-oil supplementation during pregnancy. This study was registered at clinicaltrials.gov as NCT01174875.