Association Of Polyunsaturated Fatty Acids Research Articles

Causal association of polyunsaturated fatty acids with biliary tract diseases: A Mendelian randomization study

The evidence connecting polyunsaturated fatty acids (PUFAs) to biliary problems is still highly contested and speculative despite the fact that biliary diseases are common and PUFAs have long been studied for their potential health benefits. This work used Mendelian randomization (MR) techniques in conjunction with genome-wide association study (GWAS) data to clarify the causal relationships between PUFAs and biliary tract diseases. We compiled data on PUFAs, including Omega-3 fatty acids, Omega-6 fatty acids, and the ratio of Omega-6 to Omega-3 fatty acids (Omega-6:Omega-3), using GWAS. MR was used to examine biliary tract problems (cholecystitis, cholelithiasis, gallbladder cancer, primary biliary cholangitis, primary sclerosing cholangitis, and disorders of gallbladder, biliary tract and pancreas). Single nucleotide polymorphisms significantly associated with PUFAs were selected as instrumental variables to estimate causal effects on biliary tract diseases. The final results were analyzed using five MR analysis techniques. Inverse variance weighting (IVW) was used as the primary outcome. And IVW was utilized in conjunction with the other MR analysis techniques (MR-Egger, weighted median, simple mode, and weighted mode). Additionally, we evaluated heterogeneity and horizontal multiplicity using the MR-Egger intercept test and Cochrane's Q test, respectively. Finally, to increase the accuracy and precision of the study outcomes, we carried out a number of sensitivity analyses. We found that Omega-3 fatty acids reduced the risk of cholecystitis (OR: 0.851, P=0.009), cholelithiasis (OR: 0.787, P=8.76e-5), and disorders of gallbladder, biliary tract and pancreas (OR: 0.842, P=1.828e-4) but increased the primary biliary cholangitis (OR: 2.220, P=0.004). There was no significant association between Omega-3 fatty acids and risk of gallbladder cancer (OR: 3.127, P=0.530) and primary sclerosing cholangitis (OR: 0.919, P=0.294). Omega-6 fatty acids were associated with a reduced risk of cholecystitis (OR: 0.845, P=0.040). However, they were not linked to an increased or decreased risk of cholelithiasis (OR: 0.878, P=0.14), gallbladder cancer (OR: 4.670, P=0.515), primary sclerosing cholangitis (OR: 0.993, P=0.962), primary cholestatic biliary cholangitis (OR: 1.404, P=0.509), or disorders of gallbladder, biliary tract and pancreas. Omega-6:Omega-3 fatty acids were linked to a greater risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas (OR:1.168, P=0.009, OR:1.191, P=1.60e-6, and OR:1.160, P=4.11e-6, respectively). But (OR: 0.315, P=0.010) was linked to a decreased risk of primary biliary cholangitis. Not linked to risk of primary sclerosing cholangitis (OR: 1.079, P=0.078) or gallbladder cancer (OR: 0.046, P=0.402). According to the MR-Egger intercept, our MR examination did not appear to be impacted by any pleiotropy (all P>0.05). Additionally, sensitivity studies validated the accuracy of the calculated causation. Inconsistent causative relationships between PUFAs and biliary tract diseases were revealed in our investigation. However, Omega-3 fatty acids were found to causally lower the risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas. Omega-3 fatty acids increased the risk of primary biliary cholangitis in a causative way. Omega-3 fatty acids with the risk of gallbladder cancer and primary sclerosing cholangitis did not have any statistically significant relationships. Omega-6 fatty acids were not significantly causally connected with the risk of cholelithiasis, gallbladder cancer, primary sclerosing cholangitis, or disorders of gallbladder, biliary tract and pancreas. However, they did play a causative role in lowering the risk of cholecystitis. Omega-6:Omega-3 fatty acids decreased the risk of primary biliary cholangitis but increased the risk of cholecystitis, gallstone disease, and disorders of gallbladder, biliary tract and pancreas. They had no effect on the risk of gallbladder cancer or primary sclerosing cholangitis. Therefore, additional research should be done to examine the probable processes mediating the link between polyunsaturated fatty acids and the risk of biliary tract diseases.

Causal association of polyunsaturated fatty acids with chronic pain: a two-sample Mendelian randomization study.

Observational studies have indicated an association between polyunsaturated fatty acids (PUFAs) and chronic pain, but the potential causal link remains controversial. Here, we aimed to investigate whether a causal relationship exists between the concentration of circulating PUFAs and chronic pain as well as the direction of this association. We collected statistical data from relevant genome-wide association studies to explore the causal link between four PUFAs, along with the ratio of omega-6 fatty acids (FAs) to omega-3 FAs (omega-6:3 ratio), and chronic pain in eight specific body parts. We used the inverse-variance weighting (IVW) method for two-sample Mendelian randomization (MR) analysis and conducted supplementary analyses using four other methods (MR-Egger, weighted median, weighted mode, and simple mode). To verify the robustness of the MR study, we performed multiple sensitivity analyses. The results revealed a negative correlation between omega-3 FAs [IVW, OR 95% CI: 0.952 (0.914, 0.991), p = 0.017] and docosahexaenoic acid (DHA) [IVW, OR 95% CI: 0.935 (0.893, 0.978), p = 0.003] with abnormal and pelvic pain. Furthermore, a positive correlation was observed between the omega-6:3 ratio [IVW, OR 95% CI: 1.057 (1.014, 1.101), p = 0.009] with abdominal and pelvic pain. Additionally, we found a negative correlation between omega-3 FAs [IVW, OR 95% CI: 0.947 (0.902, 0.994), p = 0.028] and lower back pain or sciatica. However, no causal relationship was found between the concentration of circulating PUFAs and pain in other body parts, including the face, throat and chest, joints, limbs, lower back, and gynecological parts. The robustness of these MR results was verified through multi-validity and retention method analyses. Our analysis suggests that higher circulating concentrations of omega-3 FAs and DHA and a lower omega-6:3 ratio are associated with a reduced risk of abdominal and pelvic pain. Additionally, a higher concentration of circulating omega-3 FAs is linked to a reduced risk of lower back pain and/or sciatica. These findings have major implications for the targeted prevention and treatment of chronic pain using PUFAs.

The association of polyunsaturated fatty acids and asthma: a cross-sectional study

BackgroundTo examine the relationships between polyunsaturated fatty acids (PUFAs) dietary intake and asthma in children.MethodsIn this cross-sectional study, a total of 14,727 participants from the United States National Health and Nutrition Examination Survey (NHANES) database in 1999–2018 were included, and the baseline characteristics of all participants were gathered. The description analysis was used to explore the possible covariates. Weighted multivariate logistic regression models were adopted to assessed the association between PUFAs dietary intake and asthma in children. In addition, we also performed subgroup analysis based on gender, age, and maternal smoking during pregnancy to investigate this relationship.ResultsThe prevalence of asthma approximately was 15.38% in the present study. The result of weighted multivariate logistic regression indicated that, docosahexaenoic [weighted odds ratio (OR) = 0.37, 95% confidence interval (CI) 0.19–0.74], total n − 3 PUFAs (weighted OR = 0.63, 95%CI 0.43–0.91), and eicosapentaenoic (weighted OR = 0.35, 95%CI 0.13–0.95) dietary intake were negatively associated with asthma in children. The subgroup analysis described that when children were male (weighted OR = 0.28, 95%CI 0.10–0.84), or were 5–7 years (weighted OR = 0.04, 95%CI 0.01–0.37), were 7–12 years (weighted OR = 0.46, 95%CI 0.24–0.90), or their maternal smoking during pregnancy (weighted OR = 0.16, 95%CI 0.03–0.90), docosahexaenoic dietary intake was negatively related to childhood asthma.ConclusionDocosahexaenoic dietary intake was negatively associated with the asthma in children, especially if children were male, or were 5–12 years, or their maternal smoking during pregnancy.

Associations of polyunsaturated fatty acids with cardiovascular disease and mortality: a study of NHANES database in 2003–2018

BackgroundThis study was to explore the association between dietary polyunsaturated fatty acids (PUFAs) consumption and cardiovascular diseases (CVDs), all-cause mortality, and CVD-specific mortality.MethodsThis retrospective cohort study extracted demographic and clinical data of 38,838 adult participants from the National Health and Nutrition Examination Survey (NHANES) database in 2003–2018. We explored the association between octadecadienoic acid (ODA), octadecatrienoic acid (ALA), octadecatetraenoic acid (ODTA), eicosatetraenoic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) and different CVDs using weighted univariate and multivariate logistic regression analyses with odds ratio (OR) and 95% confidence interval (CI). The PUFAs were divided into four levels according to the quartiles (≤ Q1, Q1 to Q2, Q1 to Q2, > Q3). Weighted univariate and multivariate COX regression analyses with hazard ratio (HR) and 95% CI were used for exploring the association between PUFAs and all-cause mortality, CVD-specific mortality and other cause-specific mortality.ResultsDuring the follow-up, a total of 4,908 (9.12%) eligible participants died. The results showed that after adjusting for covariates, ODTA intake was related to low odds of coronary heart disease (CHD) [OR = 0.75, 95%CI: (0.64–0.88)]. Q1-Q2 quartile of ALA [OR = 0.81, 95%CI: (0.66–0.99)] and Q2-Q3 quartile of DPA [OR = 0.78, 95%CI: (0.62–0.99)] intakes were linked to low odds of heart attack, and > Q3 quartile of ODA intake was associated with low odds of congestive heart failure (CHF) [OR = 0.66, 95%CI: (0.49–0.90)] and stroke [OR = 0.65, 95%CI: (0.47–0.90)]. Q2-Q3 quartile of DPA intake was linked to low odds of angina [OR = 0.76, 95%CI: (0.58–0.99)]. Higher ALA intake was associated with a lower risk of all-cause mortality [Q2-Q3: HR = 0.86, 95%CI: (0.74–0.99); > Q3: HR = 0.76, 95%CI: (0.63–0.91)]. Additionally, Q2-Q3 quartile of ALA, Q1-Q2 quartile of AA and DPA intakes were respectively related to a low risk of CVD-specific mortality, while that > Q3 quartile of ALA related to that of mortality by other causes.ConclusionOur study found that PUFAs were associated with different CVDs, and higher ALA intake was related to lower risk of all-cause mortality. Ensuring adequate intake of PUFAs was beneficial to the health and may decrease the risk of mortality.

Association of Polyunsaturated Fatty Acids and Clinical Progression in Patients With ALS: Post Hoc Analysis of the EMPOWER Trial.

Polyunsaturated fatty acids (PUFAs) have neuroprotective and anti-inflammatory effects and could be beneficial in amyotrophic lateral sclerosis (ALS). Higher dietary intake and plasma levels of PUFAs, in particular alpha-linolenic acid (ALA), have been associated with a lower risk of ALS in large epidemiologic cohort studies, but data on disease progression in patients with ALS are sparse. We examined whether plasma levels of ALA and other PUFAs contributed to predicting survival time and functional decline in patients with ALS. We conducted a study among participants in the EMPOWER clinical trial who had plasma samples collected at the time of randomization that were available for fatty acid analyses. Plasma fatty acids were measured using gas chromatography. We used Cox proportional hazards models and linear regression to evaluate the association of individual fatty acids with risk of death and joint rank test score of functional decline and survival. Fatty acid analyses were conducted in 449 participants. The mean (SD) age of these participants at baseline was 57.5 (10.7) years, and 293 (65.3%) were men; 126 (28.1%) died during follow-up. Higher ALA levels were associated with lower risk of death (age-adjusted and sex-adjusted hazard ratio comparing highest vs lowest quartile 0.50, 95% CI 0.29-0.86, p-trend = 0.041) and higher joint rank test score (difference in score according to 1 SD increase 10.7, 95% CI 0.2-21.1, p = 0.045), consistent with a slower functional decline. The estimates remained similar in analyses adjusted for body mass index, race/ethnicity, symptom duration, site of onset, riluzole use, family history of ALS, predicted upright slow vital capacity, and treatment group. Higher levels of the n-3 fatty acid eicosapentaenoic acid and the n-6 fatty acid linoleic acid were associated with a lower risk of death during follow-up. Higher levels of ALA were associated with longer survival and slower functional decline in patients with ALS. These results suggest that ALA may have a favorable effect on disease progression in patients with ALS.

Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk.

Despite numerous observational studies reporting a positive correlation between polyunsaturated fatty acids (PUFAs) and the risk of sepsis and mortality, the causation of such an association has yet to be firmly established. Thus, our study aimed to undertake the Mendelian randomization (MR) approach to scrutinize the potential causalities of PUFAs with sepsis and mortality risk. We conducted the MR investigation using genome-wide association study (GWAS) summary statistics of PUFAs [including omega-3 fatty acids (omega-3), omega-6 fatty acids (omega-6), the ratio of omega-6 to omega-3 fatty acids (omega-6:3), docosahexaenoic acid (DHA), linoleic acid (LA)], sepsis, and sepsis mortality. We utilized the GWAS summary data from the UK Biobank. To establish reliable causality, we employed the inverse-variance weighted (IVW) method as the primary analytical approach, together with four additional MR methods. In addition, we performed heterogeneity and horizontal pleiotropy assessments using Cochrane's Qtest and MR-Egger intercept test, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings. The IVW method showed that genetically predicted omega-3 [odd ratio (OR) 0.914, 95% confidence interval (CI) 0.845-0.987, P = 0.023] and DHA (OR 0.893, 95%CI 0.815-0.979, P = 0.015) were suggestively linked to a decreased risk of sepsis. Furthermore, genetically predicted DHA (OR 0.819, 95%CI 0.681-0.986, P = 0.035) was suggestively associated with a reduced risk of sepsis-related death. Conversely, the omega-6:3 ratio (OR 1.177, 95%CI 1.011-1.371, P = 0.036) was suggestively linked to an increased risk of sepsis-induced mortality. On the basis of the MR-Egger intercept assessment, it appears that our MR examination was not influenced by any horizontal pleiotropy (all P > 0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses. Our study supported the casual effect between PUFAs and susceptibility to sepsis and sepsis-related death. Our findings underline the importance of specific PUFAs levels, particularly for individuals with a genetic susceptibility to sepsis. Further research is needed to confirm these findings and investigate the underlying mechanisms.

Association of Polyunsaturated Fatty Acid Intake on Inflammatory Gene Expression and Multiple Sclerosis: A Systematic Review and Meta-Analysis.

The health benefits of omega-3 fatty acid (FA) supplementation on inflammatory gene expression (IGE) and multiple sclerosis (MS) are becoming more evident. However, an overview of the results from randomized controlled trials is lacking. This study aimed to conduct a meta-analysis to evaluate the effect of omega-3 fatty acid intake on MS (based on the criteria of the Expanded Disability Status Scale (EDSS)) and inflammatory gene expression (IGE). A search was conducted of PubMed, EMBASE, and Web of Science for cohort studies published from the inception of the database up to May 2022 that assessed the associations of omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA), α-linolenic acid (ALA), and eicosapentaenoic acid (EPA) with EDSS and inflammatory gene expression (peroxisome proliferator-activated receptor gamma (PPAR-γ), tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8)) outcomes. For the highest vs. lowest comparison, the relative risk (RR) estimates with a 95% confidence interval (CI) were pooled using the random-effect model. In total, 13 cohort studies with 1353 participants were included in the meta-analysis during periods of 3 to 144 weeks. A significant inverse relationship was found between DHA and EDSS scores (RR: 1.05; 95% CI: 0.62, 1.48; p < 0.00001). Our results also showed that omega-3 FAs significantly upregulated the gene expression of PPAR-γ (RR: 0.95; 95% CI: 0.52, 1.38; p < 0.03) and downregulated the expression of TNF-α (RR: -0.15; 95% CI: -0.99, 0.70; p < 0.00001) and IL-1 (RR: -0.60; 95% CI: -1.02, -0.18; p < 0.003). There was no clear evidence of publication bias with Egger's tests for inflammatory gene expression (p = 0.266). Moreover, n-3 PUFAs and EPA were not significantly associated with EDSS scores (p > 0.05). In this meta-analysis of cohort studies, blood omega-3 FA concentrations were inversely related to inflammatory gene expression (IGE) and EDSS score, which indicates that they may hold great potential markers for the diagnosis, prognosis, and management of MS. However, further clinical trials are required to confirm the potential effects of the omega-3 FAs on MS disease management.

A prospective analysis of red blood cell membrane polyunsaturated fatty acid levels and risk of non-Hodgkin lymphoma

Published studies report inconsistent associations of polyunsaturated fatty acid (PUFA) intake with non-Hodgkin lymphoma (NHL) risk. We conducted a nested case-control study in Nurses’ Health Study and Health Professionals Follow-Up Study participants to evaluate a hypothesis of inverse association of pre-diagnosis red blood cell (RBC) membrane PUFA levels with risk of NHL endpoints. We confirmed 583 NHL cases and matched 583 controls by cohort/sex, age, race and blood draw date/time. We estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL endpoints using logistic regression. RBC PUFA levels were not associated with all NHL risk; cis 20:2n-6 was associated with follicular lymphoma risk (OR [95% CI] per one standard deviation increase: 1.35 [1.03–1.77]), and the omega-6/omega-3 PUFA ratio was associated with diffuse large B-cell lymphoma risk (2.33 [1.23–4.43]). Overall, PUFA did not demonstrate a role in NHL etiology; the two unexpected positive associations lack clear biologic explanations.

The causal association of polyunsaturated fatty acids with allergic disease: A two-sample Mendelian randomization study.

ObjectivesPrevious studies have reported a potential association of polyunsaturated fatty acids (PUFAs) levels with allergic disease risk and the possible benefit of PUFAs supplementation on allergic disease prevention. This study was performed to estimate the genetic association between PUFAs and allergic diseases using the method of both univariable and multivariable two-sample Mendelian randomization (MR).MethodsAs indicators of the PUFAs levels, we included the omega-3, omega-6, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), linoleic acid (LA), and the ratio of omega-6 to omega-3 (omega-6:3). Summarized statistics of genome-wide association studies (GWASs) for these PUFAs were obtained from the United Kingdom Biobank and the Twins United Kingdom cohort. Genetic data relating to allergic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), allergic conjunctivitis (AC), allergic urticaria (AU) and asthma, were accessed from the FinnGen biobank analysis. Odds ratios and 95% CIs were used to express the impact.ResultsThe MR results denoted a genetic association between the genetically determined increase in omega-3 levels and the decreased risk of some allergic diseases including AD (OR: 0.863; 95% CI: 0.785 to 0.949; p = 3.86E-03), AC (OR:0.720; 95% CI: 0.547 to 0.947; p = 1.87E-02) and AU (OR:0.821; 95% CI: 0.684 to 0.985; p = 3.42E-02), while omega-6 and DHA level was only found to have negatively correlation with risk of AC with ORs of 0.655 (95% CI: 0.445 to 0.964; p = 3.18E-02) and 0.671 (95% CI 0.490 to 0.918; p = 1.25E-02), respectively. Omega-6:3 were causally significantly associated with the increased risk of AD (OR:1.171; 95% CI: 1.045 to 1.312; p = 6.46E-03) and AC (IVW: OR:1.341; 95% CI: 1.032 to 1.743; p = 2.83E-02). After adjustment of age, economic level, BMI, smoking and alcohol behaviors in the multivariable MR analysis, a direct causal protective effect of omega-3 on AD and AC, as well as a direct causal association between DHA and AD were observed. Omega-6:3 was also found to be directly associated with an increased risk of AD and AC. No association was found of EPA or LA with allergic diseases.ConclusionHigher PUFA concentrations (omega-3, omega-6, DHA) and lower omega-6:3 ratios were genetically associated with a lower risk of some allergic diseases.

Association of Lipid Mediators With Development of Future Incident Inflammatory Arthritis in an Anti–Citrullinated Protein Antibody–Positive Population

To determine the association of polyunsaturated fatty acid (PUFA)-derived lipid mediators with progression from rheumatoid arthritis (RA)-related autoimmunity to inflammatory arthritis (IA). We conducted a prospective cohort study using data from the Studies of the Etiology of Rheumatoid Arthritis (SERA). SERA enrolled first-degree relatives (FDRs) of individuals with RA (FDR cohort) and individuals who screened positive for RA-related autoantibodies at health fairs (screened cohort). We followed up 133 anti-cyclic citrullinated peptide 3.1 (anti-CCP3.1)-positive participants, 29 of whom developed IA. Lipid mediators selected a priori were quantified from stored plasma samples using liquid chromatography tandem mass spectrometry. We fit multivariable Cox proportional hazards models for each lipid mediator as a time-varying variable. For lipid mediators found to be significantly associated with IA, we then examined interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor (TNF) as potential statistical mediators. For every 1 natural log pg/ml increase in the circulating plasma levels of proinflammatory 5-HETE, the risk of developing IA increased by 241% (hazard ratio 2.41 [95% confidence interval 1.43-4.07]) after adjusting for age at baseline, cohort (FDR or screened), and shared epitope status. The models examining 15-HETE and 17-HDHA had the same trend but did not reach significance. We did not find evidence that the association between 5-HETE and IA risk was influenced by the proinflammatory cytokines tested. In a prospective cohort of anti-CCP-positive individuals, higher levels of 5-HETE, an important precursor to proinflammatory leukotrienes, is associated with subsequent IA. Our findings highlight the potential significance of these PUFA metabolites in pre-RA populations.

The Role of CaMKII and ERK Signaling in Addiction.

Nicotine is the predominant addictive compound of tobacco and causes the acquisition of dependence through its interactions with nicotinic acetylcholine receptors and various neurotransmitter releases in the central nervous system. The Ca2+/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) play a pivotal role in synaptic plasticity in the hippocampus. CaMKII is involved in long-term potentiation induction, which underlies the consolidation of learning and memory; however, the roles of CaMKII in nicotine and other psychostimulant-induced addiction still require further investigation. This article reviews the molecular mechanisms and crucial roles of CaMKII and ERK in nicotine and other stimulant drug-induced addiction. We also discuss dopamine (DA) receptor signaling involved in nicotine-induced addiction in the brain reward circuitry. In the last section, we introduce the association of polyunsaturated fatty acids and cellular chaperones of fatty acid-binding protein 3 in the context of nicotine-induced addiction in the mouse nucleus accumbens and provide a novel target for the treatment of drug abuse affecting dopaminergic systems.

Association of polyunsaturated fatty acids with improved heart rate variability and cardiovascular events in patients with end-stage renal disease receiving maintenance dialysis: a systematic review and meta-analysis of randomized controlled trials.

Apart from dietary restriction and medical therapy, the benefits of cardiovascular protection offered by polyunsaturated fatty acid (PUFA) supplements in patients with ESRD receiving maintenance dialysis remain unclear. This systematic review and meta-analysis examined the effects of PUFAs on blood pressure, heart rate (HR), HR variability (HRV), and cardiovascular disease (CVD) prognosis. We identified randomized controlled trials (RCTs) from Embase, PubMed (including MEDLINE), and Web of Science. We included seven RCTs that involved 724 patients with ESRD receiving dialysis and PUFA supplements. The data indicated that compared with the control group, the PUFA group demonstrated decreased cardiovascular events (Peto odds ratio = 0.52, 95% confidence interval [CI] = 0.32 to 0.85, P = 0.009) and HRV (changes in the mean HR [mean difference = -2.59, 95% CI = -4.91 to -0.26, P = 0.03, I2 = 0%]; mean RR interval [MD = 29.03, 95% CI = 5.43 to 52.63, P = 0.02, I2 = 0%]; mean of the standard deviation of all normal RR intervals for all 5 min segments [MD = 2.73, 95% CI = 0.48 to 4.99, P = 0.02, I2 = 0%], and square root of the mean of the sum of the squares of differences between adjacent intervals [MD = 2.03, 95% CI = 0.04 to 4.03, P = 0.05, I2 = 0%]). PUFA supplements appeared to improve CVD prognosis in patients receiving dialysis. Additional RCTs with longer follow-up periods need to clarify the benefits of PUFA supplements in this patient population.

Association of Polyunsaturated Fatty Acids and Vitamin B6 with Inflammation in Adults from the National Health and Nutrition Examination Survey (NHANES) 2003–2004

Abstract Objectives Polyunsaturated fatty acids (PUFA) such as n-3 PUFA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and n-6 PUFA, arachidonic acid (AA) may mediate inflammatory responses. Vitamin B6 deficiency has been shown to alter plasma PUFA levels. This perturbation of PUFA metabolism in vitamin B6 deficiency measured by pyridoxal-5’-phosphate (PLP) may contribute to inflammation. Thus, we aimed to examine the associations of 1) dietary EPA + DHA, and vitamin B6 with plasma ratio of AA/(EPA + DHA) by PLP level, 2) plasma AA/(EPA + DHA) and PLP with C-reactive protein (CRP), a marker for inflammation, and 3) dietary EPA + DHA, and vitamin B6 with CRP level, using NHANES. Methods NHANES datasets (2003–2004) with subjects ≥20 years were analyzed, accounting for survey design and sample weights (n = 4486). The significance level was P < 0.05. Covariates were age, gender, ethnicity, BMI, smoking, alcohol, total energy, dietary supplements, physical activity, and NSAIDs, depending on analyses. Multiple linear regression assessed the association of dietary EPA + DHA, and vitamin B6 with plasma ratio of AA/(EPA + DHA) by PLP level (Low: < 20 nmol/L, High: ≥20 nmol/L). Next, multivariate logistic regression predicted the associations of plasma AA/(EPA + DHA) and PLP with CRP level (Low: ≤3 mg/L, Moderate to High: > 3 mg/L); then, dietary EPA + DHA, and B6 with CRP level. Results In the low PLP level, dietary EPA + DHA was negatively associated with plasma ratio of AA/(EPA + DHA) (B = ─5.29, SE = 0.84, P = < .0001), but B6 intake was not, whereas, in the high PLP level, both dietary EPA + DHA (B = ─2.99, SE = 0.53, P = < .0001) and dietary vitamin B6 (B = ─0.21, SE = 0.04, P = 0.0001) were inversely associated with plasma AA/(EPA + DHA). Further, low PLP level was associated with greater odds of moderate to high CRP level compared to high PLP level (adjusted OR (aOR): 2.8, 95% CI: 1.93–4.04, P = < .0001), but plasma AA/(EPA + DHA) was not. In addition, both dietary EPA + DHA (aOR: 0.5, 95% CI: 0.23–0.98, P = 0.04) and vitamin B6 (aOR: 0.8, 95% CI: 0.68–0.95, P = 0.009) were inversely associated with moderate to high CRP level. Conclusions Our findings show that low plasma PLP level and low vitamin B6 intake are associated with inflammation, and the relationship may be through their effect on PUFA metabolism, suggesting that increased intake of vitamin B6 and EPA and DHA may protect against inflammation. Funding Sources N/A.

The Association of Polyunsaturated Fatty Acid δ-5-Desaturase Activity with Risk Factors for Type 2 Diabetes Is Dependent on Plasma ApoB-Lipoproteins in Overweight and Obese Adults

δ-5 and δ-6 desaturases (D5D and D6D) catalyze the endogenous conversion of n-3 (ω-3) and n-6 (ω-6) polyunsaturated fatty acids (PUFAs). Their activities are negatively and positively associated with type 2 diabetes (T2D), respectively, by unclear mechanisms. Elevated plasma apoB-lipoproteins (measured as plasma apoB), which can be reduced by n-3 PUFA intake, promote T2D risk factors. The aim of this study was to test the hypothesis that the association of D5D and D6D activities with T2D risk factors is dependent on plasma apoB. This is a pooled analysis of 2 populations recruited for 2 different metabolic studies. It is a post hoc analysis of baseline data of these subjects [n=98; 60% women (postmenopausal); mean ± SD body mass index (in kg/m2): 32.8±4.7; mean ± SD age: 57.6±6.3 y]. Glucose-induced insulin secretion (GIIS) and insulin sensitivity (IS) were measured using Botnia clamps. Plasma clearance of a high-fat meal (600 kcal/m2, 66% fat) and white adipose tissue (WAT) function (storage of 3H-triolein-labeled substrate) were assessed in a subpopulation (n=47). Desaturase activities were estimated from plasma phospholipid fatty acids. Associations were examined using Pearson and partial correlations. While both desaturase activities were positively associated with percentage of eicosapentaenoic acid, only D5D was negatively associated with plasma apoB (r=-0.30, P=0.003). Association of D5D activity with second-phase GIIS (r=-0.23, P=0.029), IS (r=0.33, P=0.015, in women) and 6-h area-under-the-curve (AUC6h) of plasma chylomicrons (apoB48, r=-0.47, P=0.020, in women) was independent of age and adiposity, but was eliminated after adjustment for plasma apoB. D6D activity was associated in the opposite direction with GIIS (r=0.24, P=0.049), IS (r=-0.36, P=0.004) and AUC6h chylomicrons (r=0.52, P=0.004), independent of plasma apoB. Both desaturases were associated with plasma interleukin-1-receptor antagonist (D5D: r=-0.45, P<0.001 in women; D6D: r=-0.33, P=0.007) and WAT function (trend for D5D: r=0.30, P=0.05; D6D: r=0.39, P=0.027) independent of any adjustment. Association of D5D activity with IS, lower GIIS, and plasma chylomicron clearance is dependent on plasma apoB in overweight and obese adults.

Metabolomics Identifies Distinctive Metabolite Signatures for Measures of Glucose Homeostasis: The Insulin Resistance Atherosclerosis Family Study (IRAS-FS).

Metabolomics provides a biochemical fingerprint that, when coupled with clinical phenotypes, can provide insight into physiological processes. Survey metabolites associated with dynamic and basal measures of glucose homeostasis. Analysis of 733 plasma metabolites from the Insulin Resistance Atherosclerosis Family Study. Community based. One thousand one hundred eleven Mexican Americans. Dynamic measures were obtained from the frequently sampled intravenous glucose tolerance test and included insulin sensitivity and acute insulin response to glucose. Basal measures included homeostatic model assessment of insulin resistance and β-cell function. Insulin sensitivity was associated with 99 metabolites (P < 6.82 × 10-5) explaining 28% of the variance (R2adj) beyond 28% by body mass index. Beyond branched chain amino acids (BCAAs; P = 1.85 × 10-18 to 1.70 × 10-5, R2adj = 8.1%) and phospholipids (P = 3.51 × 10-17 to 3.00 × 10-5, R2adj = 14%), novel signatures of long-chain fatty acids (LCFAs; P = 4.49 × 10-23 to 4.14 × 10-7, R2adj = 11%) were observed. Conditional analysis suggested that BCAA and LCFA signatures were independent. LCFAs were not associated with homeostatic model assessment of insulin resistance (P > 0.024). Acute insulin response to glucose was associated with six metabolites; glucose had the strongest association (P = 5.68 × 10-16). Homeostatic model assessment of β-cell function had significant signatures from the urea cycle (P = 9.64 × 10-14 to 7.27 × 10-6, R2adj = 11%). Novel associations of polyunsaturated fatty acids (P = 2.58 × 10-13 to 6.70 × 10-5, R2adj = 10%) and LCFAs (P = 9.06 × 10-15 to 3.93 × 10-7, R2adj = 10%) were observed with glucose effectiveness. Assessment of the hyperbolic relationship between insulin sensitivity and secretion through the disposition index revealed a distinctive signature of polyunsaturated fatty acids (P = 1.55 × 10-12 to 5.81 × 10-6; R2adj = 3.8%) beyond that of its component measures. Metabolomics reveals distinct signatures that differentiate dynamic and basal measures of glucose homeostasis and further identifies new metabolite classes associated with dynamic measures, providing expanded insight into the metabolic basis of insulin resistance.

Association of polyunsaturated fatty acids in breast milk with fatty acid desaturase gene polymorphisms among Chinese lactating mothers

BackgroundThe fatty acid desaturase (FADS) controls polyunsaturated fatty acid (PUFA) synthesis in human tissues and breast milk. DesignEvaluate the influence of 10 single nucleotide polymorphisms (SNPs) and various haplotypes in the FADS gene cluster (FADS1, FADS2, FADS3) on PUFA concentration in the breast milk of 209 healthy Chinese women. PUFA concentrations were measured in breast milk using gas chromatography and genotyping was performed using the Sequenom Mass Array system. ResultsA SNP (rs1535) and 2-locus haplotypes (rs3834458-rs1535, rs1535-rs174575) in the FADS2 gene were associated with concentrations of γ-linoleic acid (GLA) and arachidonic acid (AA) in breast milk. Likewise, in the FADS1 gene, a 2-locus constructed haplotype (rs174547-rs174553) also affected GLA and AA concentration (P<0.05 for all). Minor allele carriers of the SNP and haplotypes described above had lower concentrations of GLA and AA. In the FADS2 gene, the 3-locus haplotype rs3834458-rs1535-rs174575, significantly affected concentrations of GLA but not AA. Pairwise comparison showed that individuals major homozygous for the SNP rs1000778 in the FADS3 gene had lower concentrations of ALA and linoleic acid (LA) in their breast milk. ConclusionPolymorphisms in the FADS gene cluster influence PUFA concentrations in the breast milk of Chinese Han lactating women.

Associations of polyunsaturated fatty acids with residual depression or anxiety in older people with major depression

Depression in late life often follows a chronic course with residual depressive and anxiety symptoms. Levels of omega-3 polyunsaturated fatty acids (PUFAs) have been found to be depleted in people with major depression in the acute stage. Additionally, lower omega-3 PUFA levels have been suggested to be associated with anxiety. The aim of this study was to investigate whether PUFAs levels (omega-3 or omega-6) are correlated with residual depressive or anxiety symptoms in older people with previous depression. Participants aged 60 years or over with previous major depression in remission were enrolled from outpatient psychiatric services of four hospitals. Participants with residual depressive symptoms were defined as the Hamilton Depression Rating Scale (HDRS) scores>5, and those with anxiety were defined as sum of scores for the two anxiety subscale of HDRS≧2. The levels of fatty acids in erythrocyte membranes and in plasma were measured separately by gas chromatography. One hundred and thirty two older people with previous major depression (mean age of 68 years, range 60-86 years) were analyzed. Erythrocyte membrane linoleic acid levels had a curvilinear association with depressive symptoms and anxiety symptoms. Plasma linoleic acid levels were found to have a negative linear relationship with depressive symptoms. No significant associations were found between any omega-3 fatty acid level and depressive or anxiety symptoms. Linoleic acid levels may be a possible biomarker for residual depression and anxiety in older people with previous depression. Possible clinical applications need further investigation.

Intake and Adipose Tissue Composition of Fatty Acids and Risk of Myocardial Infarction in a Male Portuguese Community Sample

Objective To evaluate the relation between intake and adipose tissue composition of fatty acids and acute myocardial infarction in Portuguese men. Design Case-control study. Diet was assessed using a semiquantitative food frequency questionnaire. In 49 case and 49 control subjects, adipose tissue composition was assessed by gas-liquid chromatography. Subjects/Setting Population-based; subjects were 297 consecutively admitted cases of first acute myocardial infarction in a tertiary care hospital who were aged ≥40 years. Three hundred ten community controls were selected by random-digit dialing. Main Outcome Measure Odds ratio (OR). Statistical Analysis Performed Logistic regression, adjusting for age, education, family history of acute myocardial infarction, smoking, physical activity, body mass index, and energy intake. Results Total fat intake (OR 0.45, fourth quartile, P=0.02), lauric acid (OR 0.44, fourth quartile, P=0.02), palmitic acid (OR 0.58, fourth quartile, P=0.03), and oleic acid (OR 0.42, fourth quartile, P=0.03) were inversely associated with acute myocardial infarction. No significant effects were found for the remaining fatty acids. In the adipose tissue composition data, the adjusted risk estimates of acute myocardial infarction for the highest vs the lowest tertile were 0.16, 0.14, and 0.04 for lauric, oleic, and trans-fatty acids, respectively. A significant direct association was found for palmitic and linoleic acids (adjusted ORs for the highest tertile were 9.02 and 3.63, respectively). Conclusions Low intake of total fat and lauric acid from dairy products was associated with acute myocardial infarction. The association of polyunsaturated fatty acids with risk of acute myocardial infarction was nonsignificant after adjustment for energy intake and confounders. Recommendations on fatty acid intake should aim for both an upper and lower limit.

We-P14:465 The association of polyunsaturated fatty acids and blood pressure in men with coronary artery disease

We-P14:465 The association of polyunsaturated fatty acids and blood pressure in men with coronary artery disease