Blood Levels Of Fatty Acids Research Articles

Association of maternal blood and umbilical cord blood plasma fatty acid levels with the body size at birth of Japanese infants

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mainly obtained from fish, have been implicated in fetal development. Because few studies have examined maternal and umbilical cord blood fatty acid levels and infant body size in Japan with a fish-eating culture, we examined differences in plasma fatty acid levels in pregnant women and infant size at birth. This study is a large birth cohort study of 1476 pairs of Japanese pregnant women and their infants. Maternal blood DHA levels and infant birth weight showed a positive relationship. However, analysis adjusted for gestational age did not reveal correlations. Negative relationships were found between cord blood DHA levels and infant body size, and between the difference in mother-to-child DHA levels and infant body size. Thus, the smaller the birth size, the higher the differences in umbilical cord blood DHA levels and mother-to-child DHA levels when considering gestational age.

Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation

BackgroundThe relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial. ObjectivesThis study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF. MethodsWe used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. ResultsAmong 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively. ConclusionsIn vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.

Fish Oil in Glaucoma Treatment: From Biological Functions to Clinical Potential.

Glaucoma is the leading cause of irreversible vision loss worldwide, and multiple risk factors influence its pathogenesis and progression, including age, increased intraocular pressure (IOP), low-grade inflammation, oxidative stress, and ocular blood flow deficits. IOP-lowering therapy is currently the most effective way to control glaucoma progression; however, due to insufficient response and persistent retinal neural degeneration, the result may not always be satisfactory. In recent decades, fish oil, an omega-3 dietary supplement, is reported to be beneficial to glaucoma patients, but its efficiency and underlying mechanisms remain unclear. Intriguingly, glaucoma patients have lower omega-3 fatty acid blood levels, especially docosahexaenoic acid and eicosapentaenoic acid. Dietary omega-3 supplementation in patients may normalize levels of fatty acid and, thereby, enhance their effects. Therefore, fish oil may serve as an area of new focus for glaucoma treatment studies. In this review, the study summarizes the roles of active ingredients in fish oil in delaying glaucoma development, including lowering IOP, regulating blood supply, alleviating inflammation, and diminishing oxidative stress, with a view to promoting the development of the clinical management of glaucoma.

Maternal Blood Fatty Acid Levels in Fetal Growth Restriction.

To assess the maternal blood levels of fatty acids (FAs) in pregnancies with fetal growth restriction (FGR). This prospective cross-sectional study included pregnant women with gestational age between 26 and 37 + 6 weeks with FGR and appropriate for gestational age (AGA) fetuses. The levels of saturated, trans, monounsaturated, and polyunsaturated FAs were measured using centrifugation and liquid chromatography. The Student's t-test, Mann-Whitney test, and general linear model, with gestational age and maternal weight as covariants, were used to compare FA levels and the FGR and AGA groups. The Chi-square was used to evaluate the association between groups and studied variables. Maternal blood sample was collected from 64 pregnant women, being 24 FGR and 40 AGA. A weak positive correlation was found between the palmitoleic acid level and maternal weight (r = 0.285, p = 0.036). A weak negative correlation was found between the gamma-linoleic acid level and gestational age (r = - 0.277, p = 0.026). The median of the elaidic acid level (2.3 vs. 4.7 ng/ml, p = 0.045) and gamma-linoleic acid (6.3 vs. 6.6 ng/ml, p = 0.024) was significantly lower in the FGR than the AGA group. The palmitoleic acid level was significantly higher in the FGR than AGA group (50.5 vs. 47.6 ng/ml, p = 0.033). Pregnant women with FGR had lower elaidic acid and gamma-linoleic acid levels and higher palmitoleic acid levels than AGA fetuses.

Trans fatty acid blood levels and HFpEF phenotype: from the Aldo-DHF RCT

Abstract Background Prognosis in HFpEF is determined by risk factor control and treatment of comorbidities. Industrially processed TFA (IP-TFA) from partially hydrogenated oils have been linked to altered lipoprotein metabolism, endothelial dysfunction, increased biomarkers of inflammation and increased NTproBNP. In patients with heart failure with preserved ejection fraction (HFpEF), associations of TFA blood levels with patient characteristics are unknown. Purpose To evaluate associations of blood TFA with cardiovascular risk factors, aerobic capacity and cardiac function in patients with HFpEF. Methods This is a secondary analysis from the Aldo-DHF-RCT. From 422 patients, individual blood TFA were analyzed at baseline in n=404 using the HS-Omega-3-Index® methodology. Patient characteristics were; 67±8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥50%, E/e' 7.1±1.5; median NT-proBNP 158 ng/L (IQR 82–298). Multiple linear regression analyses, using sex and age as covariates, were used to describe associations of TFA with metabolic phenotype, functional capacity, echocardiographic markers for left ventricular diastolic function (LVDF), and neurohumoral activation at baseline and after 12-months-follow-up (12mFU). To account for randomization group, all analyses were repeated as sensitivity analysis with group as covariate. A significance level of α=5% was used for all tests. As all tests were hypothesis generating without confirmatory interpretation, no correction was applied to counteract the problem of multiple comparisons. Results Higher blood levels of the naturally occurring TFA C16:1n-7t were broadly associated with a more favorable lipid profile, lower body weight/central adiposity, lower white blood cell count and lower biochemical markers of non-alcoholic fatty liver disease at baseline/12mFU. Conversely, blood levels of the IP-TFA C18:1n9t were directly associated with lipid risk markers [triglycerides (β=19.7, p<0,001), non-HDL-C (β=7.9, p=0,001), and LDL-C (β=5.4, p=0,011)]. The two IP-TFA C18:2n6 isomers C18:2n6tt and C18:2n6ct were positively associated with HbA1c [(β=14.6, p=0,003) and (β=4.2, p=0,014) respectively]. The IP-TFA C18:2n6tt/-ct isomers were associated with lower submaximal aerobic capacity (distance covered in the 6MWT) at baseline/12mFU. No significant association was found between TFA blood levels and left ventricular filling pressures, left ventricular relaxation or neurohumoral activation. Significant effects of group allocation (spironolactone +/−) were found for the 12mFU outcomes systolic/diastolic blood pressure (all p<0.001), heart rate, E/e$'$ and HbA1c. Conclusions In HFpEF patients, higher blood levels of industrially processed TFA, but not of the TFA C16:1n-7t in full fat dairy and meat, were associated with a higher risk phenotype and lower aerobic capacity. Our findings support efforts to remove IP-TFA from the food supply for improving risk factor control in HFpEF patients. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Foundation of Heart Research

Saturated Fatty Acid Blood Levels and Cardiometabolic Phenotype in Patients with HFpEF: A Secondary Analysis of the Aldo-DHF Trial.

Background: Circulating long-chain (LCSFAs) and very long-chain saturated fatty acids (VLSFAs) have been differentially linked to risk of incident heart failure (HF). In patients with heart failure with preserved ejection fraction (HFpEF), associations of blood SFA levels with patient characteristics are unknown. Methods: From the Aldo-DHF-RCT, whole blood SFAs were analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were 67 ± 8 years, 53% female, NYHA II/III (87%/13%), ejection fraction ≥50%, E/e’ 7.1 ± 1.5; and median NT-proBNP 158 ng/L (IQR 82–298). Spearman´s correlation coefficients and linear regression analyses, using sex and age as covariates, were used to describe associations of blood SFAs with metabolic phenotype, functional capacity, cardiac function, and neurohumoral activation at baseline and after 12-month follow-up (12 mFU). Results: In line with prior data supporting a potential role of de novo lipogenesis-related LCSFAs in the development of HF, we showed that baseline blood levels of C14:0 and C16:0 were associated with cardiovascular risk factors and/or lower exercise capacity in patients with HFpEF at baseline/12 mFU. Contrarily, the three major circulating VLSFAs, lignoceric acid (C24:0), behenic acid (C22:0), and arachidic acid (C20:0), as well as the LCSFA C18:0, were broadly associated with a lower risk phenotype, particularly a lower risk lipid profile. No associations were found between cardiac function and blood SFAs. Conclusions: Blood SFAs were differentially linked to biomarkers and anthropometric markers indicative of a higher-/lower-risk cardiometabolic phenotype in HFpEF patients. Blood SFA warrant further investigation as prognostic markers in HFpEF. One Sentence Summary: In patients with HFpEF, individual circulating blood SFAs were differentially associated with cardiometabolic phenotype and aerobic capacity.

Targeted dietary interventions to reduce pain in persistent post-traumatic headache among service members: Protocol for a randomized, controlled parallel-group trial

IntroductionPost-traumatic headache (PTH) is common after traumatic brain injury (TBI), especially among active-duty service members (SMs), affecting up to 35% of patients with chronic TBI. Persistent PTH is disabling and frequently unresponsive to treatment and is often migrainous. Here, we describe a trial assessing whether dietary modifications to increase n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and reduce n-6 linoleic acid (LA), will alter nociceptive lipid mediators and result in clinical improvements in persistent PTH. MethodsThis prospective, randomized, controlled trial tests the efficacy, safety, and biochemical effects of targeted, controlled alterations in dietary n-3 and n-6 fatty acids in 122 adult SMs and military healthcare beneficiaries with diagnosed TBI associated with actively managed persistent frequent (>8 /month) PTH with migraine. Following a 4-week baseline, participants are randomized to one of two equally intensive dietary regimens for 12 additional weeks: 1) increased n-3 EPA + DHA with low n-6 LA (H3L6); 2) usual US dietary content of n-3 and n-6 fatty acids (Control). During the intervention, participants receive diet arm-specific study oils and foods sufficient for 75% of caloric needs and comprehensive dietary counseling. Participants complete daily headache diaries throughout the intervention. Clinical outcomes, including the Headache Impact Test (HIT-6), headache hours per day, circulating blood fatty acid levels, and bioactive metabolites, are measured pre-randomization and at 6 and 12 weeks. Planned primary analyses include pre-post comparisons of treatment groups on clinical measures using ANCOVA and mixed-effects models. Similar approaches to explore biochemical and exploratory clinical outcomes are planned.ClinicalTrials.gov registration: NCT03272399

Fish intake, n-3 fatty acid body status, and risk of cognitive decline: a systematic review and a dose-response meta-analysis of observational and experimental studies.

Randomized controlled trials (RCTs) testing supplementation with eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids have failed to provide evidence supporting a suggested inverse association between fish intake and dementia risk. Dose-response analyses were conducted to evaluate associations between fish intake, all-cause dementia or Alzheimer's Disease (AD), and the effect of EPA/DHA supplementation on cognitive performance. PubMed, Scopus and Web of Science databases were searched for original research evaluating either associations between fish intake and dementia or AD, or the impact of EPA and/or DHA supplementation on the risk of cognitive decline. Data were collected on study characteristics and methods; number of cases/deaths (for observational studies); categories of exposure; model covariates; risk estimates from the most-adjusted model; type and dosage of supplementation (from RCTs); fatty acid levels in blood; and differences in cognition test results before and after supplementation. Risk of bias was assessed through the ROBINS-E and RoB2.0 tools for observational and experimental studies, respectively. Weighted mixed-effects models were applied, allowing for the inclusion of studies with 2 levels of exposure. Based on findings with low/moderate risk of bias, fish intake of up to 2 portions (250 g) per week was associated with a 10% reduction (95% confidence interval [CI]: 0.79, 1.02, Ν = 5) in all-cause dementia and a 30% reduction (95% CI: 0.54, 0.89, Ν = 3) in AD risk. Changes in EPA and DHA body status had a positive impact on participants' executive functions, but not on their overall cognitive performance. The protection offered by fish intake against cognitive decline levels off at intakes higher than 2 portions/week and likely relates to the impact of EPA and DHA on the individual's executive functions, although there remain questions about the mechanisms linking the short- and long-term effects. PROSPERO registration no. CRD42019139528.

The Omega-3 Index is higher in people from a coastal town versus 5 inland US cities: An observational study

Higher omega-3 fatty acid blood levels, as assessed by the Omega-3 Index (O3I, erythrocyte eicosapentaenoic [EPA] + docosahexaenoic [DHA] percentage), have been linked with lower risk for cardiovascular disease and total mortality. Because seafood is an excellent source of EPA and DHA, we reasoned that people living on the coast with direct access to fresh seafood might have higher O3I levels than people living inland. Using O3I data originally collected for other purposes and an observational design, we compared the mean O3I from people in Newport, RI, with that of people living from 5 inland US cities (Indianapolis, IN; Charleston, WV; Lexington, KY; Oklahoma City, OK; and Memphis, TN). The Newport samples were collected at free, industry-sponsored health fairs, whereas the inland city samples were collected at free public health screenings sponsored by the Seafood Nutrition Partnership in 2014 through 2015. The mean (standard deviation) O3I in the Newport sample (n = 226) was 5.13% (1.34%) and the mean of the 5 cities (n = 1109) was 4.48% (1.08%) (P < .001). An O3I of ≥8% (considered optimal) was found in 3% of the Newport sample and in 1% of the pooled inland cities (P < .05). An O3I of ≤4% (considered low) was found in 22% of the Newport sample and in 41% of the pooled inland cities (P < .001). These data support our hypothesis, but because only 3% of those in the Newport sample had an O3I >8%, even greater seafood intake (or the use of fortified foods or dietary supplements) is needed to attain optimal omega-3 status.

Maternal Blood Fatty Acid Levels in Small and Adequate for Gestational Age Pregnancies.

The aim is to assess the levels of fatty acids (FAs) in pregnancies with small for gestational age (SGA) and adequate for gestational age (AGA) fetuses, constituting an association between FAs and fetal growth; according to the role of FA, lower levels were expected in SGA. This was an analytical cross-sectional study including pregnant women with gestational ages of 26-36weeks with AGA and constitutionally SGA fetuses diagnosed by ultrasonography. The levels of saturated, trans, monounsaturated, and polyunsaturated fatty acids were measured using centrifugation and liquid chromatography. Student's t test and general linear model using gestational age as covariant were used to compare the levels of FAs and the groups (AGA and SGA). Chi-square was used to evaluate the association between groups and studied variables. Pearson correlation coefficient and linear regression were used to evaluate the correlation between the levels of FAs and gestational age. Peripheral blood was collected from 67 pregnant women, 3 of whom were excluded from the study. No significant statistical differences were observed between SGA (n = 40) and AGA (n = 24) in relation to saturated, trans, monounsaturated, and polyunsaturated fatty acids (p > 0.05). There was not significant correlation between saturated, trans, monounsaturated, and polyunsaturated FAs and gestational age (p > 0.05). The levels of saturated, trans, monounsaturated, and polyunsaturated FAs were similar in constitutionally SGA and AGA fetuses.

Omega-3 fatty acids promote neuroprotection, decreased apoptosis and reduced glial cell activation in the retina of a mouse model of OPA1-related autosomal dominant optic atrophy

The purpose of this study was to evaluate the neuroprotective effects of omega-3 polyunsaturated fatty acid (ω3-PUFA) supplementation in a mouse model of OPA1-associated autosomal dominant optic atrophy (ADOA). The blood level of arachidonic acid (AA) and eicosapentaenoic acid (EPA) served to adjust the treatment dosage (AA/EPA = 1.0–1.5). Eight-month-old mice were allocated to four groups (n = 20/group): the ω3-PUFA-treated Opa1enu/+, untreated Opa1enu/+, ω3-PUFA-treated wild-type and untreated wild-type groups. Treated mice received the ω3-PUFAs, EPA and docosahexaenoic acid (DHA; 5:1 ratio) by daily gavage for 4 months based on the measured AA/EPA ratio. Blood, retina and optic nerve (ON) fatty acid levels were determined by gas chromatography, and the retina and ON were histologically examined. Western blotting and/or immunohistochemistry was performed to analyse retinal mediators involved in Opa1-mutation-mediated apoptosis, inflammation and oxidative stress. Increased EPA and reduced AA levels were primarily observed predominantly in the blood and retinal tissues, and a similarly high EPA level tended to be observed in the ONs of ω3-PUFA-treated mice. Retinal ganglion cell and ON axonal densities were higher in both mouse strains upon ω3-PUFA treatment than in the corresponding untreated groups. Caspase-3 expression analysis showed fewer apoptotic retinal cells in both groups of treated mice. Decreases in inflammatory microglia and astrocytes activation and proapoptotic Bcl-2-associated X protein (Bax) expression were noted in the treated groups, with no difference in the antioxidant superoxide dismutase-2 expression. ω3-PUFA supplementation had neuroprotective effects on the retinas of Opa1enu/+ and wild-type mice via blockade of microglia and astrocytes activation and suppression of Bax and caspase-3. Our findings indicated that inhibition of oxidative stress may not be involved in ω3-PUFA-mediated neuroprotection. These novel findings support the use of ω3-PUFAs as a beneficial therapy in the occurrence of ADOA, posing the basis for future clinical trials to confirm these observations.

Omega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients: the Aldo-DHF randomized controlled trial

ObjectivesTo evaluate associations of omega-3 fatty acid (O3-FA) blood levels with cardiometabolic risk markers, functional capacity and cardiac function/morphology in patients with heart failure with preserved ejection fraction (HFpEF).BackgroundO3-FA have been linked to reduced risk for HF and associated phenotypic traits in experimental/clinical studies.MethodsThis is a cross-sectional analysis of data from the Aldo-DHF-RCT. From 422 patients, the omega-3-index (O3I = EPA + DHA) was analyzed at baseline in n = 404 using the HS-Omega-3-Index® methodology. Patient characteristics were; 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e′ 7.1 ± 1.5; median NT-proBNP 158 ng/L (IQR 82–298). Pearson’s correlation coefficient and multiple linear regression analyses, using sex and age as covariates, were used to describe associations of the O3I with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline/12 months.ResultsThe O3I was below (< 8%), within (8–11%), and higher (> 11%) than the target range in 374 (93%), 29 (7%), and 1 (0.2%) patients, respectively. Mean O3I was 5.7 ± 1.7%. The O3I was inversely associated with HbA1c (r = − 0.139, p = 0.006), triglycerides-to-HDL-C ratio (r = − 0.12, p = 0.017), triglycerides (r = − 0.117, p = 0.02), non-HDL-C (r = − 0.101, p = 0.044), body-mass-index (r = − 0.149, p = 0.003), waist circumference (r = − 0.121, p = 0.015), waist-to-height ratio (r = − 0.141, p = 0.005), and positively associated with submaximal aerobic capacity (r = 0.113, p = 0.023) and LVEF (r = 0.211, p < 0.001) at baseline. Higher O3I at baseline was predictive of submaximal aerobic capacity (β = 15.614, p < 0,001), maximal aerobic capacity (β = 0.399, p = 0.005) and LVEF (β = 0.698, p = 0.007) at 12 months.ConclusionsHigher O3I was associated with a more favorable cardiometabolic risk profile and predictive of higher submaximal/maximal aerobic capacity and lower BMI/truncal adiposity in HFpEF patients.Graphic abstractOmega-3 fatty acid blood levels are inversely associated with cardiometabolic risk factors in HFpEF patients. Higher O3I was associated with a more favorable cardiometabolic risk profile and aerobic capacity (left) but did not correlate with echocardiographic markers for left ventricular diastolic function or neurohumoral activation (right). An O3I-driven intervention trial might be warranted to answer the question whether O3-FA in therapeutic doses (with the target O3I 8–11%) impact on echocardiographic markers for left ventricular diastolic function and neurohumoral activation in patients with HFpEF. This figure contains modified images from Servier Medical Art (https://smart.servier.com) licensed by a Creative Commons Attribution 3.0 Unported License.

Is the Omega-3 Index Higher in Coastal Than Inland US Cities?

ObjectivesHigher omega-3 fatty acid blood levels, as assessed by the Omega-3 Index (O3I, erythrocyte EPA + DHA expressed as a % of total fatty acids), have been linked with lower risk for cardiovascular disease and total mortality. Seafood is an excellent source of EPA and DHA. The purpose of this study was to determine if individuals living in a coastal US city (Newport, RI) with direct access to fresh seafood have higher O3I levels than people living in inland cities. MethodsDried blood spot samples were collected from a convenience sample of people attending a sponsored health fair on the boardwalk in Newport, RI between July and August 2019. Attendees interested in obtaining their O3I signed a consent form before testing and then provided a drop of blood for testing. As a comparator inland group, we used published data (Harris et al. PLEFA 2019;148:30–34) from 7 US cities in the “stroke belt” (note, only one of the 7 cities was coastal, Jacksonville, FL). Dried blood samples were analyzed for the O3I by gas chromatography in both settings. ResultsThe Newport sample included 234 individuals, 50/50 male/female, with a mean (SD) age of 46 (16) years. The 7 cities comparator cohort contained 2177 subjects, with a mean age of 48 (16) years and of those reporting gender, 78% were female. The mean (SD) O3I in Newport was 5.15% (1.37%), whereas in the 7 cities study it was 4.42% (1.12%; P < 0.0001). An O3I of ≤4% (considered low) was found in 21% of the Newport subjects compared to 42% in comparator cohort (P < 0.0001). Relatedly, an O3I of >8% (considered optimal) was found in 3% of the Newport sample compared to 1.2% in the 7 cities study (P = 0.19). ConclusionsThese data support our hypothesis that the O3I is higher in populations living in a coastal city than those living inland. Still, only 3% of individuals with immediate access to fresh seafood had O3I levels in the optimal zone. Given the documented health benefits of having an optimal O3I, increased intakes of EPA and DHA from fish and other dietary sources or supplementation should be recommended. Funding SourcesRB Health (US) LLC.

Safety and Efficacy of Sodium and Potassium Arachidonic Acid Salts in the Young Pig.

Arachidonic acid (ARA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n3) are polyunsaturated fatty acids (FA) naturally present in breast milk and added to most North American infant formulas (IF). We investigated the safety and efficacy of novel sodium and potassium salts of arachidonic acid as bioequivalent to support tissue levels of ARA comparable to the parent oil; M. alpina oil (Na-ARA and K-ARA) and including a Na-DHA group. Pigs of both sexes were randomized to one of five dietary treatments (n = 16 per treatment; 8 male and 8 female) from postnatal day 2 to 23. ARA and DHA were included as either triglyceride (TG) or salt. Target dietary ARA/DHA concentrations as percent of total FA by weight were as follows: TT (0.47 TG/0.32 TG), NaT (0.47 Na-salt/0.32 TG), KT (0.47 K-salt/0.32 TG), and Na0 (0.47 Na-salt/0.00), NaNa (0.47 Na-salt/0.32 Na-salt). The primary outcome in this study was bioequivalence of ARA brain accretion. Growth performance; blood and tissue fatty acid levels; liver histology; complete blood cell counts; and serum chemistries were all evaluated. Overall, diets containing test sources of ARA and DHA did not affect growth performance; liver histology; or substantially influence hematological outcomes as compared with TT. The results confirm that the use of Na and K salt forms of ARA yield bioequivalent ARA accretion in the cerebral cortex and retinal tissue compared to TG-ARA. These findings confirm that use of Na-ARA and K-ARA salts in the young pig was safe and nutritionally bioequivalent to TG-ARA for critical neural tissues.

DNA methylation of tumour necrosis factor (TNF) alpha gene is associated with specific blood fatty acid levels in a gender-specific manner.

BackgroundFatty acids, specifically polyunsaturated fatty acids (PUFAs) play an important role in inflammation and its resolution, however, their interaction with the epigenome is relatively unexplored. Here we investigate the relationship between circulating blood fatty acids and the DNA methylation of the cytokine encoding gene tumour necrosis factor (TNF, OMIM 191160).MethodsUsing a cross‐sectional study approach, we collected blood samples from adults (N=88 (30 males, 58 females); 18–74 years old) for DNA methylation pyrosequencing analysis at four sites in TNF exon 1 and gas‐chromatography mass‐spectrometry analysis of the fatty acid profile of dried blood spots (DBS).ResultsMethylation levels of TNF exon 1 are significantly correlated with specific fatty acids in a gender‐specific manner. In the males the PUFAs Docosahexaenoic Acid (DHA) and Arachidonic Acid (AA) were positively associated with TNF methylation, as was the saturated fatty acid (SFA) Stearic Acid; in contrast, mono‐unsaturated fatty acids (MUFAs) had a negative association. In the females, omega‐6 PUFA γ‐Linolenic acid (GLA) was negatively correlated with TNF methylation; Adrenic acid and Eicosadienoic Acid were positively correlated with TNF methylation.ConclusionThese results suggest that one way that fatty acids interact with the inflammation is through altered methylation profiles of cytokine genes; thus, providing potential therapeutic targets for nutritional and health interventions.

Fatty acids and osteoarthritis: the MOST study

Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Saturated and n-6 fatty acids (FAs) increase, whereas n-3 FAs reduce inflammation. We examined whether FA levels affected the development of OA. We studied participants from the Multicenter Osteoarthritis study (MOST) at risk of developing knee OA. After baseline, repeated knee x-rays and MRIs were obtained and knee symptoms queried through 60 month follow-up. Using baseline fasting samples, serum FAs were analyzed with standard assays. After excluding participants with baseline OA, we defined two sets of cases: those developing radiographic OA and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage loss and synovitis and of knee pain using WOMAC and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of saturated, n-3 and n-6 FAs adjusting for age, sex, BMI, education, race, baseline pain and depressive symptoms. We studied 260 cases with incident symptomatic and 259 with incident radiographic OA. Mean age was 61 years (61% women). We found no signficant nor suggestive associations of FA levels with incident OA (e.g., for incident symptomatic OA, OR per s.d. increase in n-3 FA 1.00 (0.85, 1.18) nor with any OA outcome in knee or hand. Despite previously described effects on systemic inflammation, blood levels of FAs were not associated with risk of later knee OA or other OA outcomes.

Functionally Relevant Differences in Plasma Fatty Acid Composition and Expression of Cytotoxic and Inhibitory NK Cell Receptors between Healthy Young and Healthy Elder Adults.

(1) Background: In the healthy ageing, NK cell number is not modified; however, their spontaneous cytotoxicity decreases. We postulated that the age-dependent decline in metabolic activities might be responsible for this effect. (2) Methods: The fatty acid profile of 30 healthy young males (23 ± 4 years old, BMI 22.1 ± 1.3) and 30 older males (63 ± 5 years old, BMI 22.9 ± 2.5) donors were evaluated along with the expression of killing (KR) and inhibitory NK receptors (KIR) at basal level and after cultivation with fatty acids for 24 h. (3) Results: Significantly higher levels of oleic (p < 0.01), arachidonic (p < 0.001), lignoceric (p < 0.001), and nervonic acids (p < 0.0001) and significantly lower levels of docosapentaenoic and docosahexaenoic acids (p < 0.01) were found in elders as compared to young adults. At basal levels, significant (p < 0.005) differences in KR and KIR expression were encountered; 12/16 antigens. Treatment of cells with saturated fatty acids or arachidonic acid (AA) significantly enhanced KR expressions (p < 0.001). AA treatment decreased inhibitory KIR expression while docosahexaenoic, and eicosapentaenoic acid increased them. (4) Conclusions: Changes in fatty acids blood levels, and KR and KIR expression in NK cell, are age-dependent. Supplementation of NK cells with eicosapentaenoic or docosahexaenoic acid enhanced inhibitory KIR receptors’ expression which may improve their cell function.

Urinary concentrations of phthalates in relation to circulating fatty acid profile in National Health and Nutrition Examination Survey, 2003–2004 and 2011–2012

Animal studies have suggested that phthalate exposure alters the fatty acid composition of blood plasma. Therefore, we conducted an epidemiological study to examine whether urinary concentrations of phthalates are correlated with circulating fatty acids in the general US population. The 2003–2004 and 2011–2012 National Health and Nutrition Examination Survey were used in this study. Ten urinary phthalate metabolites and 23 fatty acids were measured. Fatty acid patterns were identified using principal component analysis (PCA) with an eigenvalue greater than 1. A two-step analysis was performed. We first performed multivariable linear regressions to evaluate whether urinary phthalate metabolites were related to the PCA-derived components of blood fatty acid levels. Then we performed multivariable linear regressions to investigate each of the fatty acids that were suggestively correlated with some of the phthalates in PCA. There were 994 participants (51.91% women). As for men, after adjustments for potential confounding factors, MECPP, MEHHP, and ∑DEHP were all positively correlated with gamma-linolenic, myristoleic, and myristic acids; both MEHHP and ∑DEHP were positively correlated with stearic acid; MMP was positively correlated with docosahexaenoic acid. As for women, MMP was negatively correlated with docosanoic, lignoceric, and arachidic acids; MBzP was negatively correlated with docosahexaenoic acid; both MEHP and MCPP were negatively correlated with docosatetraenoic acid; MEHP was negatively correlated with arachidonic acid, and MCPP was negatively correlated with docosapentaenoic-6 acid. Our findings support that phthalates may be correlated with circulating fatty acids.

Microencapsulated Tuna Oil Results in Higher Absorption of DHA in Toddlers.

Docosahexaenoic acid (DHA) is an essential component for brain and visual acuity development during foetal and early postnatal life. A newly released directive under the European Commission stipulates DHA as a mandatory ingredient in infant formula. This poses challenges to manufacturers in preserving the stability and bioavailability of DHA at levels akin to human breast milk. The aims of this study were (a) to investigate the bioavailability of microencapsulated omega-3 DHA formulations in healthy toddlers compared with high DHA fish oil for a one-month period and (b) to assess the effect of DHA supplementation on children’s sleep and cry patterns. Sixty toddlers were randomly allocated to four groups: 1. unfortified formula, 2. unfortified formula plus high DHA tuna oil, 3. fortified formula with dairy-based microencapsulated high DHA tuna oil powder, and 4. fortified formula with allergenic-free microencapsulated high DHA tuna oil powder. Bioavailability was assessed from both blood and faecal fatty acid levels. The results showed an enhanced bioavailability with significantly greater concentrations of blood DHA levels in formulas with microencapsulated powders. There were no significant effects of treatment on sleep and cry patterns. Application and delivery of microencapsulated DHA tuna oil powder in toddlers’ formula provided better bioavailability of the active DHA.

Proopiomelanocortin Processing in the Hypothalamus Is Directly Regulated by Saturated Fat: Implications for the Development of Obesity

In outbred mice, susceptibility or resistance to diet-induced obesity is associated with rapid changes in hypothalamic proopiomelanocortin (POMC) levels. Here, we evaluated 3 hypotheses that potentially explain the development of the different obesity phenotypes in outbred Swiss mice. First, rapid and differential changes in the gut microbiota in obesity-prone (OP) and obesity-resistant (OR) mice fed on a high-fat diet (HFD) might cause differential efficiencies in fatty acid harvesting leading to changes in systemic fatty acid concentrations that in turn affect POMC expression and processing. Second, independently of the gut microbiota, OP mice might have increased blood fatty acid levels after the introduction of a HFD, which could affect POMC expression and processing. Third, fatty acids might act directly in the hypothalamus to differentially regulate POMC expression and/or processing in OP and OR mice. We evaluated OP and OR male Swiss mice using 16S rRNA sequencing for the determination of gut microbiota; gas chromatography for blood lipid determination; and immunoblot and real-time polymerase chain reaction for protein and transcript determination and indirect calorimetry. Some experiments were performed with human pluripotent stem cells differentiated into hypothalamic neurons. We did not find evidence supporting the first 2 hypotheses. However, we found that in OP but not in OR mice, palmitate induces a rapid increase in hypothalamic POMC, which is followed by increased expression of proprotein convertase subtilisin/kexin type 1 PC1/3. Lentiviral inhibition of hypothalamic PC1/3 increased caloric intake and body mass in both OP and OR mice. In human stem cell-derived hypothalamic cells, we found that palmitate potently suppressed the production of POMC-derived peptides. Palmitate directly regulates PC1/3 in OP mice and likely has a functional impact on POMC processing.