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Objective: Previous research suggests a potential link between unsaturated fatty acids (UFAs) and ADHD, but the causal relationship remains uncertain. This study aims to investigate the causal association between ADHD and UFAs using Mendelian randomization (MR) analysis., Methods: Summary data from genome-wide association studies were used to estimate the concentration of circulating UFAs, including Monounsaturated Fatty Acids (MUFAs), Polyunsaturated Fatty Acids (PUFAs), Omega-3 PUFAs, Omega-6 PUFAs, Linoleic Acid (LA), and Docosahexaenoic Acid (DHA). Data from the Psychiatric Genomics Consortium, including both childhood and adult ADHD, were respectively used to examine the relationship between genetically predicted UFAs levels and ADHD. Various MR methods, including Inverse-variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier, MR-Egger, weighted median, and weighted mode, were employed to assess heterogeneity and pleiotropy., Results: The IVW revealed only nominal evidence suggesting a potential causal relationship between genetically predicted PUFAs (OR = 0.92, 95% CI [0.85, 0.99], p  = .031), Omega-6 PUFAs (OR = 0.90, 95% CI [0.83, 0.98], p  = .020), and LA levels (OR = 0.90, 95% CI [0.82, 0.98], p  = .021) with childhood ADHD risk. However, after false discovery rate correction, the p -values for PUFAs, Omega-6 PUFAs, and LA levels all exceeded the threshold for significance. For adult ADHD, we did not find any significant associations between the six circulating UFA levels and adult ADHD., Conclusion: Our findings do not support a causal relationship between UFAs levels and ADHD. This suggests that UFAs supplements may not be effective in improving ADHD symptoms and importantly, it appears that UFAs levels may not have a long-term effect on ADHD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Some research indicates that unsaturated fatty acids (UFAs) in the diet could enhance reproductive outcomes in infertile women. However, other research holds different views, possibly due to differences in the conversion rates of UFAs from various foods and bioavailability in the body. Therefore, this research examined the link between serum UFAs and infertility issues., Methods: This research included reproductive-age women participating in the 2013-2014 American National Health and Nutrition Examination Survey (NHANES). Serum levels of four UFAs, including palmitoleic acid (16:1n-7), vaccenic acid (18:1n-7), oleic acid (18:1n-9), and linoleic acid (18:2n-6) were measured through gas chromatography-mass spectrometry. Infertility data was collected by affirmative responses to targeted questionnaire items. Associations between serum UFA levels and infertility were evaluated utilizing Poisson regression models and smooth curve fitting methods. Sensitivity analysis was also conducted., Results: This study included 535 women, aged between 18 and 45. Poisson regression analysis, both adjusted and unadjusted for confounders, revealed no associations between palmitoleic acid, vaccenic acid, oleic acid, or linoleic acid and female infertility (all P > 0.05). However, four UFAs all showed non-linear relationships with infertility in smooth curve fitting analysis. Sensitivity analysis confirmed the stability of the findings., Conclusion: This research established non-linear associations between serum UFAs and infertility in American women. Specifically, maintaining appropriate serum levels of these UFAs may lower infertility risk. These findings offer new insights and practical dietary recommendations for improving female fertility., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Evidence supports associations between polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and psychosis. However, polyunsaturated fatty acid trajectories in the general population have not been characterized, and associations with psychosis spectrum outcomes in early adulthood are unknown., Methods: Plasma omega-6 to omega-3 ratio and DHA (expressed as percentage of total fatty acids) were measured by nuclear magnetic spectroscopy at 7, 15, 17, and 24 years of age in participants of ALSPAC (Avon Longitudinal Study of Parents and Children). Curvilinear growth mixture modeling evaluated body mass index-adjusted trajectories of both measures. Outcomes were assessed at 24 years. Psychotic experiences (PEs), at-risk mental state status, psychotic disorder, and number of PEs were assessed using the Psychosis-Like Symptoms interview (n = 3635; 2247 [61.8%] female). Negative symptoms score was measured using the Community Assessment of Psychic Experiences (n = 3484; 2161 [62.0%] female). Associations were adjusted for sex, ethnicity, parental social class, and cumulative smoking and alcohol use., Results: Relative to stable average, the persistently high omega-6 to omega-3 ratio trajectory was associated with increased odds of PEs and psychotic disorder, but attenuated on adjustment for covariates (PEs adjusted odds ratio [aOR] = 1.63, 95% CI = 0.92-2.89; psychotic disorder aOR = 1.69, 95% CI = 0.71-4.07). This was also the case for persistently low DHA (PEs aOR = 1.42, 95% CI = 0.84-2.37; psychotic disorder aOR = 1.14, 95% CI = 0.49-2.67). Following adjustment, persistently high omega-6 to omega-3 ratio was associated with increased number of PEs (β = 0.41, 95% CI = 0.05-0.78) and negative symptoms score (β = 0.43, 95% CI = 0.14-0.72), as was persistently low DHA (number of PEs β = 0.45, 95% CI = 0.14-0.76; negative symptoms β = 0.35, 95% CI = 0.12-0.58)., Conclusions: Optimization of polyunsaturated fatty acid status during development warrants further investigation in relation to psychotic symptoms in early adulthood., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Fatty acid (FA) metabolism plays an important role in the development of nonalcoholic fatty liver disease (NAFLD). However, data on the relationship between circulating FAs and NAFLD risk are limited. This study aims to assess the associations between specific circulating FAs and severe NAFLD risk among the general population. Overall 116 223 participants without NAFLD and other liver diseases from the UK Biobank were enrolled between 2006 and 2010 and were followed up until the end of 2021. Plasma concentrations of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were analyzed using an NMR-based biomarker profiling platform. Hazard ratios (HRs) and 95% confidence intervals (CIs) of NAFLD risk were estimated using Cox proportional-hazard models adjusted for other potential confounders. During a mean follow-up of 12.3 years, we documented 1394 cases of severe NAFLD. After multivariate adjustment, plasma SFAs and MUFAs were associated with a higher risk of severe NAFLD, whereas plasma n-3 PUFAs, n-6 PUFAs, and linoleic acid (LA) were associated with a lower risk. As compared with the lowest quartile, HRs (95% CIs) of severe NAFLD risk in the highest quartiles were 1.85 (1.45-2.36) for SFAs, 1.74 (1.23-2.44) for MUFAs, 0.79 (0.65-0.97) for n-3 PUFAs, 0.68 (0.48-0.96) for n-6 PUFAs, and 0.73 (0.54-0.99) for LA. The significant relationships were mainly mediated by serum TG for SFAs, HDL-C for MUFAs and n-6 PUFAs, and C-reactive protein for n-3 PUFAs. Plasma SFAs were associated with a more pronounced increase in the risk of severe NAFLD among participants with fewer SFA-associated alleles ( P interaction = 0.032). Dietary recommendations for reducing plasma SFAs and MUFAs while increasing n-3 and n-6 PUFAs may be protective for severe NAFLD, which could be mediated by lipid metabolism and inflammation.

Polyunsaturated fatty acids (PUFA) are known to have a regulatory effect on oxidative and inflammatory processes. This study aimed to identify the relationship between blood PUFA status and circulatory markers of oxidative stress and inflammation in a cohort of 172 subjects. The population was divided by sex and into three age groups: adults (18-64 years old, n = 69), older adults (65-89 years old, n = 54), and long-lived individuals (LLIs, 90-111 years old, n = 49). Whole blood PUFA content was quantified using gas chromatography. Additionally, serum levels of C-reactive protein (CRP), paraoxonase (PON), Trolox equivalent antioxidant capacity (TEAC), and malondialdehyde (MDA) were measured. Our results showed that a higher omega-3 (n-3) index in adult females was a predictor of lower MDA concentrations (p = 0.038). Conversely, total n-3 PUFA and total n-6 PUFA were positively related to MDA values among older adult females and LLI men (p < 0.05), while total n-6 PUFA was inversely correlated with MDA levels in LLI females (p < 0.05). Interestingly, increased concentrations of total n-3 PUFA and n-3 index were positively correlated with higher TEAC values in LLI men (p = 0.007), while the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio was inversely correlated with TEAC values among LLI females (p = 0.006). These findings suggest that cellular antioxidant capacity is inversely correlated with changes in the AA/EPA ratio in long-lived females, whereas n-3 PUFA may enhance blood antioxidant capacity in long-lived men. Overall, our study highlights the complex, sex-specific interactions between PUFA profiles and oxidative stress and inflammatory markers across different age groups., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Oxidative stress induces autooxidation of polyunsaturated fatty acids, producing numerous isoprostanoids and isofuranoids. These oxidized products are measurable in human plasma and urine and serve as oxidative stress biomarkers for chronic diseases. This chapter details the preparation and measurement of α-linolenic acid-derived phytoprostanes and phytofurans in human samples using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QToF-MS/MS)., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: The role of circulating polyunsaturated fatty acids (PUFAs) in preventing liver cirrhosis complications remains unclear., Methods: Between 2006 and 2010, 273,834 UK Biobank participants with plasma PUFA quantification data were enrolled and followed up until October 31, 2022. Plasma PUFAs were quantified using a high-throughput nuclear magnetic resonance-based metabolic profiling platform. Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with hepatocellular carcinoma., Results: During a median follow-up of 13.9 years, 2026 participants developed liver cirrhosis complications. Total plasma PUFAs, omega-3 PUFAs, docosahexaenoic acid (DHA), omega-6 PUFAs, and linoleic acid (LA) were inversely associated with the risk of liver cirrhosis complications, whereas the plasma omega-6/omega-3 ratio was positively associated. Nonparametrically restricted cubic spline regression showed nonlinear associations of plasma PUFAs with liver cirrhosis complications. The inflection points were 4.78 mmol/L for total PUFAs, 0.73 mmol/L for omega-3 PUFAs, 0.25 mmol/L for DHA, 4.07 mmol/L for omega-6 PUFAs, and 2.99 mmol/L for LA. Plasma omega-3 PUFAs were negatively associated with the risk of liver cirrhosis complications when omega-3 PUFAs were <0.73 mmol/L (adjusted hazard ratio [HR], 0.11 [0.08-0.16]), whereas the association was inverted when omega-3 PUFAs were ≥0.73 mmol/L (adjusted HR, 1.87 [1.20-2.92])., Conclusions: The protective effect of plasma omega-3 PUFAs on liver cirrhosis complications is reversed after passing the corresponding inflection point, suggesting an optimal dietary omega-3 PUFA supplementation dose., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Research on dietary fatty acids (FAs) and lung health has reported skeptical findings. This study aims to examine the causal relationship between circulating FAs and Chronic Obstructive Pulmonary Disease (COPD) onset and exacerbation, using a two-sample Mendelian Randomization (MR) analysis. Strong and independent genetic variants of FAs were obtained from the UK Biobank of European ancestry. The exposure traits included saturated FA (SFA), poly- and mono-unsaturated FA (PUFA and MUFA), omega-3 and omega-6 PUFA, docosahexaenoic acid (DHA), and linoleic acid (LA), all expressed as total FA (TFA) percentages. Summary statistics for COPD outcomes were obtained from the FinnGen consortium including COPD, COPD hospitalization, COPD/asthma-related infections, COPD-related respiratory insufficiency, and COPD/asthma/interstitial lung disease (ILD)-related pneumonia. The inverse-variance weighted (IVW) was the primary MR approach. MR-Egger regression and MR-PRESSO were utilized to evaluate heterogeneity and pleiotropy. MR-PRESSO tests suggested no obvious horizontal pleiotropy. MR results by the IVW approach indicated that the genetically high SFA/TFA levels were associated with an increased risk of COPD/asthma/ILD-related pneumonia (OR: 1.275, 95%CI: 1.103-1.474, p for FDR = 0.002). No significant relationship was observed between other types of FAs and COPD outcomes. Our MR analysis suggests that there is weak evidence that the genetically predicted high SFA/TFA was associated with an increased risk of pneumonia.

Osteoarthritis (OA) is a degenerative joint disease primarily affecting the cartilage. The therapeutic potential of the Dipsacus asper-Achyranthes bidentate herb pair for OA has been acknowledged, yet its precise mechanism remains elusive. In this study, we conducted a comprehensive analysis of metabolomic changes and therapeutic outcomes in osteoarthritic rats, employing a gas chromatography-mass spectrometry-based metabolomics approach in conjunction with histopathological and biochemical assessments. The rats were divided into six groups: control, model, positive control, Dipsacus asper treated, Achyranthes bidentata treated, and herb pair treated groups. Compared to the model group, significant reductions in levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and iNOS were observed in the treated groups. Multivariate statistical analyses were employed to investigate metabolite profile changes in serum samples and identify potential biomarkers, revealing 45 differential biomarkers, with eighteen validated using standard substances. These analytes exhibited excellent linearity across a wide concentration range (R 2 >0.9990), with intra- and inter-day precision RSD values below 4.69% and 4.83%, respectively. Recoveries of the eighteen analytes ranged from 93.97% to 106.59%, with RSD values under 5.72%, underscoring the method's reliability. Treatment with the herbal pair effectively restored levels of unsaturated fatty acids such as linoleic acid and arachidonic acid, along with glucogenic amino acids. Additionally, levels of phosphoric acid and citric acid were reversed, indicating restoration of energy metabolism. Collectively, these findings highlight the utility of metabolomic analysis in evaluating therapeutic efficacy and elucidating the underlying molecular mechanisms of herb pairs in OA treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rationale & Objective: Many studies have reported polyunsaturated fatty acids (PUFA) as significant predictors of cardiovascular disease, but little is known about the relationship between PUFA levels and chronic kidney disease (CKD). This study explored this relationship among individuals with and without CKD., Study Design: Prospective observational cohort study., Setting & Participants: 73,419 participants without CKD (cohort 1) and 6,735 participants with CKD (cohort 2) in the UK Biobank Study, with PUFA levels measured between 2007 and 2010., Exposure: Percentage of plasma PUFA, omega-3 fatty acid (FA), omega-6 FA, docosahexaenoic acid (DHA), and linoleic acid relative to total FA., Outcome: Incident CKD for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort 2., Analytical Approach: Cox proportional hazards regression analyses, including a cause-specific competing risk model., Results: In cohort 1, individuals with higher quartiles of plasma PUFA levels had healthier lifestyles and fewer comorbidities. During 841,007 person-years of follow-up (median 11.9 years), incident CKD occurred in 4.5% of participants (incidence rate, 39.1 per 10,000 person-years). For incident CKD in cohort 1, the adjusted cause-specific hazard ratios for quartiles 2, 3, and 4 were 0.83 (95% CI, 0.75-0.92), 0.85 (95% CI, 0.76-0.96), 0.71 (95% CI, 0.62-0.82), respectively, compared with quartile 1. This inverse relationship was consistently observed for all PUFA types. In cohort 2, although total PUFA levels were not associated with KFRT, higher PUFA subtype levels of DHA were associated with a lower risk of KFRT., Limitations: Observational design and limited generalizability to individuals with higher disease severity; no data on eicosapentaenoic acid., Conclusions: Among individuals without CKD, higher plasma PUFA levels and all 4 PUFA components were associated with a lower risk of incident CKD. In individuals with CKD, only the omega-3 component of PUFA, DHA, was associated with a lower risk of KFRT., Plain-Language Summary: Low amounts of polyunsaturated fatty acids (PUFA) in the blood are suspected of increasing the chances of heart disease, but it is not known whether the PUFA relates to kidney disease occurrence. In a large group without kidney disease in the United Kingdom, people with higher levels of PUFA in their blood tended to have a lower risk of developing kidney disease compared to those with lower PUFA levels. This relationship was consistently observed for all PUFA types. However, in the group with kidney disease, only higher levels of docosahexaenoic acid, a subtype of PUFAs, were associated with a lower risk of developing severe kidney problems that required kidney replacement therapy. These findings suggest that higher levels of PUFA, found in certain healthy fats, might protect against the development of kidney disease in the general population. As kidney function declines, only the docosahexaenoic acid, a subtype of PUFA, appears to be associated with preserved kidney function., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Lipids play integral roles in biological processes, with carbon-carbon double bonds (C═C) markedly influencing their structure and function. Precise characterization and quantification of unsaturated lipids are crucial for understanding lipid physiology and discovering disease biomarkers. However, using mass spectrometry for these purposes presents significant challenges. In this study, we developed a microwave-assisted magnesium monoperoxyphthalate hexahydrate (MMPP) epoxidation reaction, coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS), to analyze unsaturated lipids. Microwave irradiation expedited the MMPP epoxidation, achieving complete derivatization in 10 min without byproducts. A diagnostic ion pair, displaying a 16 Da mass difference, effectively identified the location of the C═C bond in mass spectra. Microwave irradiation also significantly facilitated the epoxidation reaction of polyunsaturated lipids, achieving yields greater than 85% and yielding a complete epoxidation product. This simplifies chromatographic separation and aids in accurate quantification. Additionally, a purification process was implemented to remove excess derivatization reagents, significantly reducing mass spectrometry response suppression and enhancing analytical reproducibility. The method's effectiveness was validated by analyzing unsaturated lipids in rat plasma from a type I diabetes model. We quantified nine unsaturated lipids and characterized 42 fatty acids and glycerophospholipids. The results indicated that unsaturated fatty acids increased in diabetic plasma while unsaturated glycerophospholipids decreased. Furthermore, the relative abundances of Δ9/Δ11 isomer pairs also exhibited a close association with diabetes. In conclusion, microwave-assisted MMPP epoxidation coupled with LC-MS/MS provides an effective strategy for characterization and quantification of polyunsaturated lipids, offering deeper insight into the physiological impact of unsaturated lipids in related diseases.

Background : Gout is a nutrition-related, highly prevalent inflammatory arthritis with undesirable effects on the quality of life. The relationships between circulating fatty acids (FAs) and gout remain poorly understood. Method : We included 268 174 participants with plasma FAs measured using nuclear magnetic resonance at the baseline (2006-2010) from the UK Biobank, of which 15 194 participants had repeated measures of FAs between 2012 and 2013. Cox proportional hazards models were used to assess the association of the baseline and longitudinal changes in relative levels of plasma FAs ( % total FAs) with incident gout. Mendelian randomization (MR) analyses were conducted to assess the potential causality of the examined association. Results : Over a median follow-up of 12.8 years, 5160 incident cases of gout occurred. Baseline polyunsaturated fatty acids (PUFAs), n-6 PUFAs, and linoleic acids (LAs) were inversely associated with incident gout (all P -trend values < 0.0001). Baseline monounsaturated fatty acids (MUFAs), n-3 PUFAs, and docosahexaenoic acids (DHAs) were positively associated with incident gout (all P -trend values < 0.0001). Longitudinal increments of n-6 PUFAs and LAs were associated with a lower risk of subsequent gout, whereas an increment of n-3 PUFAs was associated with a higher risk. In two-sample MR analyses, genetically determined higher levels of PUFAs, n-6 PUFAs, and LAs were associated with a decreased risk of gout (all P values < 0.05). Conclusions : Our findings consistently indicate a causal relationship of elevated levels of n-6 PUFAs, especially LAs, with a reduced risk of gout.

Aims: This study aimed to investigate the association between serum levels of common and uncommon unsaturated fatty acids and prediabetes risk., Methods: Data were collected from the National Health and Nutrition Examination Survey for 2003-2004 and 2011-2012. Weighted proportional and multivariate logistic regression analyses were performed to assess the association of serum PUFAs and MUFAs with prediabetes risk after adjusting for potential confounders., Results: A total of 3575 individuals were enrolled in this study. Serum levels of PUFAs EPA (20:5 n3) and GLA (18:3 n6) were associated with increased prediabetes risk (EPA (20:5 n3): OR = 1.878, 95% CI: 1.177-2.996, P trend  = 0.002; GLA (18:3 n6): 1.702, 95% CI: 1.140-2.541, P trend  = 0.016). The MUFAs PA (16:1 n7) and EA (20:1 n9) were associated with the risk of prediabetes (OR in quintile5: PA (16:1 n7): 1.780, 95% CI: 1.056-3.001, P trend  = 0.003; EA (20:1 n9): 0.587, 95% CI: 0.347-0.994, P trend  = 0.010). Moreover, nonlinear analysis revealed that serum levels of EPA (20:5 n3) and EA (20:1 n-9) were nonlinearly associated with prediabetes risk., Conclusion: Some serum n-3 PUFAs are positively associated with prediabetes, several serum n-6 PUFAs are inversely associated with prediabetes. Regulating individual serum USFA levels may help prevent prediabetes, thereby providing evidence for clinical and nutritional practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The objective was to determine whether baseline fatty acid intake and erythrocyte omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can predict risk of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in older women., Methods: This was a prospective analysis of 34,990 women in the Women's Health Initiative. Dietary fatty acids were estimated from food frequency questionnaires. Imputed erythrocyte PUFAs were available in a subcohort of 3,428 women. Arthroplasty (THA and TKA), used as a surrogate of severe osteoarthritis, was identified via linked Medicare data. Cox proportional hazards models were constructed to estimate risk of arthroplasty., Results: Risk of THA was associated with higher intake of arachidonic acid, (multivariable hazard ratio [HR] quartile 4 [Q4] vs Q1: 1.16; 95% confidence interval [CI] 1.01-1.34; P = 0.03) and higher intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; HR Q4 vs Q1: 1.20; 95% CI 1.05-1.39; P = 0.003). There was a linear trend (P = 0.04) for patients to have a higher risk of THA with higher erythrocyte EPA and DHA in body mass index-adjusted models; however, there was no significant difference in patients who had THAs by quartiles of erythrocyte EPA and DHA (P = 0.10). Dietary fatty acids and erythrocyte PUFAs were not significantly associated with risk of TKA., Conclusion: Higher baseline intakes of arachidonic acid and EPA and DHA were associated with a modestly higher risk of THA. No association was found between fatty acids and patients who had TKAs. Further research in populations with direct measures of osteoarthritis severity is needed to better understand the importance of PUFAs in modulating osteoarthritis and arthroplasty risk., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Intake of polyunsaturated fatty acids (PUFA) may affect mortality following breast cancer; however, epidemiological studies have relied on the self-reported assessment of PUFA intake. Herein, we examined the associations between red blood cell (RBC) PUFAs and mortality., Methods: This nested case-control study included 1,104 women from the Women's Healthy Eating and Living study, a multistate randomized controlled trial. Cases (n = 290) comprised women who died from 1995 to 2006. Matched controls (n = 814) comprised women who were alive at the end of follow-up. PUFAs were measured in baseline RBC samples and included four ω-3 and seven ω-6 PUFAs. We examined each PUFA individually and principal components factor analysis (PCFA)-derived scores in association with all-cause mortality (ACM) and breast cancer-specific mortality (BCM) using conditional logistic regression to estimate ORs and 95% confidence intervals (CIs)., Results: In fully adjusted models, ACM ORs were elevated among women with PUFAs above the median  (>median) versus at the median or below (≤median) for α-linolenic acid (ALA; OR = 1.63, 95% CI, 1.18-2.24) and linolenic acid (LA; OR = 1.56, 95% CI, 1.16-2.09). BCM ORs were elevated for ALA (OR = 1.83, 95% CI, 1.27-2.63), LA (OR = 1.70, 95% CI, 1.23-2.37), and γ-linolenic acid (GLA; OR = 1.50, 95% CI, 1.04-2.16). PCFA Factor 1 (arachidonic acid-adrenic acid-docosapentaenoic acid) scores above the median (vs. ≤median) were associated with lower odds of ACM (OR = 0.71, 95% CI, 0.52-0.97) and BCM (OR = 0.69, 95% CI, 0.49-0.97). PCFA Factor 4 (ALA/GLA) scores above the median (vs. ≤median) were associated with increased odds of BCM (OR = 1.47, 95% CI, 1.04-2.09)., Conclusions: RBC ALA, LA, and GLA may be prognostic indicators among breast cancer survivors., Impact: These results are important for understanding the associations between a biomarker of PUFA intake and mortality among BC survivors., (©2024 American Association for Cancer Research.)

Background: Exposure to different concentration levels of fatty acids (FAs) may have an impact on depression. However, previous studies using individual FAs may not reflect the performance of mixtures of various FAs, and the associations of FA patterns with depression remain unclear., Methods: We conducted the cross-sectional analysis in 792 adults aged 18 and older with available serum FAs and depression screening data in the National Health and Nutrition Examination Survey (NHANES) 2011-2012. The serum concentrations of thirty FAs were measured using gas chromatography-mass spectrometry and their percentage compositions were subsequently calculated. Depression was defined as the Patient Health Questionnaire-9 score ≥ 10. We employed principal component analysis to derive serum FA patterns. We examined the association between these patterns and depression in the overall population and various subgroups through survey-weighted logistic regression., Results: Four distinct patterns of serum FAs were identified: 'high eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); low docosatetraenoic acid (DTA) and docosapentaenoic acid (DPA) n-6', 'high long-chain saturated FA and long chain FA', 'low median-chain saturated FA and myristoleic acid' and 'low capric acid and lauric acid; high gamma-linolenic acid (GLA) and stearidonic acid (SDA)' pattern. Individuals in the high tertile of 'high EPA and DHA; low DTA and DPA n-6' pattern score had 0.46 (95% CI: 0.22, 0.93) lower odds of developing depression compared to individuals in the lowest tertile after adjusting for confounders such as age, sex, physical activity and total energy intake, etc. The odds ratio (OR) of depression was increased in the population with the highest tertile of 'low capric acid and lauric acid; high GLA and SDA' pattern (OR: 2.45, 95% CI: 1.24, 4.83). In subgroup analyses, we observed that the association between 'high EPA and DHA; low DTA and DPA n-6' and depression persisted among specific demographic and lifestyle subgroups, including females, non-Mexican Americans, non-obese, those aged over 60 years, smokers and drinkers. Similarly, 'low capric acid and lauric acid; high GLA and SDA' showed stable associations in female, non-Mexican Americans and smokers., Conclusions: Serum FA patterns are associated with depression, and their relationships vary across sex, race, BMI, age, smoking and drinking subgroups, highlighting the importance of considering specific FA patterns within these demographic and lifestyle categories. Utilization of combined FA administration may serve as a mitigation measure against depression in these specific populations., (© 2024. The Author(s).)

Psoriasis is a chronic systemic disease with a multifaceted pathomechanism and immunological basis, with the presence of inflammatory skin lesions and joint ailments. Diseases accompanying psoriasis include metabolic and cardiovascular disorders. It has been suggested that inflammation is involved in the development of each of these conditions. The main objective of this study was to analyse the fatty acid profile, including polyunsaturated fatty acids, in the erythrocyte membranes of patients suffering from psoriasis. A total of 58 adult patients of the Department of Skin and Venereal Diseases of the Pomeranian Medical University in Szczecin, suffering from psoriasis, were qualified for this study. The patients had undergone an interview and physical examination, during which the severity of psoriasis was assessed. All patients had their weight and height measured to assess their body mass index (BMI). After 3 months of treatment, biochemical parameters (ALT, AST, total cholesterol) and inflammatory markers (CRP) in the blood were assessed. In addition, the isolation of fatty acids (PUFAs, SFAs, MUFAs) from erythrocyte membranes and the qualitative and quantitative analysis of their profile using a gas chromatograph were carried out. In patients with severe psoriasis requiring systemic treatment, an altered profile of fatty acids in erythrocyte membranes was found, including a significantly lower concentration of polyunsaturated fatty acids (omega-3), which have an anti-inflammatory effect; a significantly higher concentration of saturated fatty acids; and a decreased concentration of oleic acid (omega-9), compared to the results obtained in patients with less severe psoriasis receiving topical treatment. In patients with psoriasis and BMI ≥ 25, significantly higher concentrations of AST and ALT in the blood and significantly higher concentrations of pro-inflammatory arachidonic acid in erythrocyte membranes were found. Elevated concentrations of saturated (R = 0.31) and monounsaturated fatty acids (R = 0.29) may correlate with a greater severity of psoriasis., Competing Interests: The authors declare no conflicts of interest.

Background & Aims: High mortality rate of pancreatic cancer (PC) as one of the most common cancers worldwide made it a center of attention for recent researches on its pathology, etiology, screening and early diagnosis. In previous researches, association of dietary intake and plasma levels of fatty acids with risk of pancreatic cancer was investigated. In this study we aimed to evaluate the correlation between dietary and plasma fatty acids in case and control groups., Methods: From 50,045 adults between 40-75 years old participated in Golestan cohort study, fifty incident cases of PC were diagnosed and 150 controls matched by age, sex and residence place were randomly selected. Dietary intakes and plasma levels of fatty acids was evaluated by validated food-frequency questionnaire (FFQ) and Gas Chromatography - Flame Ionization Detector (GC-FID), respectively. Then, Spearman's correlation was used to measure the correlation between dietary and plasma levels of fatty acids in case and control groups., Results: Among all the fatty acids, there was a significant association between plasma and dietary intake of a few fatty acids including trans fatty acids (TFA), polyunsaturated fatty acids (PUFA), 22:6n-3 and 14:0 only in control group. Only total PUFA intake modified plasma level of some fatty acids in case group. There was no difference between association of desaturase enzymes and fatty acids in case and controls., Conclusions: Since, plasma levels of fatty acids might be influenced by recent diet, we did not find any specific differences between the associations of plasma levels of fatty acids with dietary intake of fats in case and control groups., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) may play an important role in the development of atherosclerotic cardiovascular disease (ASCVD). Increased plasma levels of Lp-PLA2 may predict future cardiovascular (CV) events in type 2 diabetes (T2D). The potential beneficial effects of polyunsaturated fatty acids (PUFA) on ASCVD have been widely investigated. However, the impact of different PUFA concentrations on Lp-PLA2 remains uncertain., Objectives: We sought to determine the intergender differences in a population of patients with both T2D and ASCVD regarding Lp-PLA2 mass and the association between Lp-PLA2 mass and plasma levels of PUFA., Material and Methods: In this cross-sectional study, we measured the Lp-PLA2 mass, PUFA concentrations and inflammatory markers in 74 patients (49 males and 25 females) with T2D and ASCVD., Results: In this very high-risk population, males had, on average, 33.6% higher levels of Lp-PLA2 than females. The Lp-PLA2 mass was positively associated with interleukin 6 (IL-6) (r = 0.27, p = 0.019), creatinine (r = 0.29, p = 0.03) and triglyceride levels (r = 0.41, p = 0.002). Additionally, male gender and higher levels of triglycerides, leptin, oxidized low-density lipoprotein (oxLDL), and intercellular adhesion molecule 1 (ICAM-1) were independent predictors for an increased Lp-PLA2. Moreover, arachidonic acid (AA) negatively correlated with Lp-PLA2 (r = -0.26, p = 0.024), which was especially apparent in the female subgroup., Conclusions: In the population of patients with ASCVD and T2D, males present with higher plasma levels of Lp-PLA2 than females. Additionally, higher plasma levels of AA were associated with lower Lp-PLA2 levels. Our findings support the utilization of Lp-PLA2 as a novel biomarker in ASCVD risk assessment in a very high CV risk population.

Polyunsaturated fatty acids (PUFAs) are vital nutrients in human physiology and are implicated in various chronic diseases. However, the relationship between PUFAs and gastric polyps remains unclear. This study employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess PUFA levels in the serum of 350 patients, along with analyzing the ω-6 to ω-3 ratio. The results revealed significant differences in the levels of C16:1, C18:1, C18:2, α-C18:3, γ-C18:3, C20:1, C20:4, C20:5, ω-3-C22:5, ω-6-C22:5, and C22:6, as well as ω-6 to ω-3 ratio between the control and gasteic polyp groups. Moreover, setting the threshold for ω-6: ω-3 at 10 revealed a close correlation between polyp occurrence and this ratio. These findings suggest that PUFAs and the ω-6 to ω-3 ratio hold promise as potential early screening markers for gastric polyps. However, further research is imperative to elucidate the underlying mechanisms and therapeutic potential of PUFAs in managing gastric polyps., Competing Interests: The authors declare that they have no competing interests., (© 2024 Li et al.)

Non-invasive diagnostics are crucial for the timely detection of renal cell carcinoma (RCC), significantly improving survival rates. Despite advancements, specific lipid markers for RCC remain unidentified. We aimed to discover and validate potent plasma markers and their association with dietary fats. Using lipid metabolite quantification, machine-learning algorithms, and marker validation, we identified RCC diagnostic markers in studies involving 60 RCC and 167 healthy controls (HC), as well as 27 RCC and 74 HC, by analyzing their correlation with dietary fats. RCC was associated with altered metabolism in amino acids, glycerophospholipids, and glutathione. We validated seven markers (l-tryptophan, various lysophosphatidylcholines [LysoPCs], decanoylcarnitine, and l-glutamic acid), achieving a 96.9% AUC, effectively distinguishing RCC from HC. Decreased decanoylcarnitine, due to reduced carnitine palmitoyltransferase 1 (CPT1) activity, was identified as affecting RCC risk. High intake of polyunsaturated fatty acids (PUFAs) was negatively correlated with LysoPC (18:1) and LysoPC (18:2), influencing RCC risk. We validated seven potential markers for RCC diagnosis, highlighting the influence of high PUFA intake on LysoPC levels and its impact on RCC occurrence via CPT1 downregulation. These insights support the efficient and accurate diagnosis of RCC, thereby facilitating risk mitigation and improving patient outcomes.

The growing interest in Omega-3 fatty acids as diagnostic markers or new therapeutic approaches also for COVID-19 disease, led us to investigate the presence of potential correlations between Omega-3 fatty acids' levels in whole blood and days of hospitalization or admission to the paediatric intensive care unit (PICU) in 51 children with MIS-C diagnosis following SARS-CoV-2 infection. A statistically significant negative correlation was observed between days of hospitalization and docosapentaenoic acid (22:5n-3,DPA), docosahexaenoic acid (DHA) and total Omega-3 FA levels. Dividing the study group into quartiles according to Omega-3-Index (O3I), no statistically significant difference was observed with respect to the PICU admission rate. In contrast, the number of days of hospitalization in Q4 (O3I ≥ 2.51 %) was different from the number observed in groups Q1-3 (O3I < 2.51 %), with subjects showing higher O3I needing shorter hospitalizations than the subjects with lower O3I. According to previous study investigating O3I in adults affected by Sars-cov-2 we explored the levels of this nutrients in children with MIS-C. Our exploratory study shows that high DPA, DHA and O3I levels could be effective in reducing the length of hospitalization., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Several observational studies have indicated that polyunsaturated fatty acid serum levels (PUFAs) are associated with vascular dementia (VaD), but their causal relationships remain elusive. Therefore, we attempted to evaluate the causal effect of PUFAs on VaD in a two-sample Mendelian randomization (MR) analysis by using summary statistics from aggregated genome-wide association studies., Methods: The inverse-variance weighted (IVW) method was performed as the primary analysis. Sensitivity analyses (MR-Egger regression, weighted median, penalized weighted median, and MR pleiotropy residual sum and outlier methods) were also implemented to estimate the effects of potential violations of MR hypotheses., Results: No causality was found for PUFAs (odds ratio, 1.14; 95% confidence interval, 0.91-1.42; p = 0.25) on VaD in the IVW model. The results were consistent in sensitivity analyses. There was no notable horizontal pleiotropy or heterogeneity., Conclusion: In this two-sample MR analysis, our findings did not support the assumption that PUFAs play causal role in the occurrence or development of VaD., (© 2023 S. Karger AG, Basel.)

Background: n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of ischemic heart disease. However, there are few reports of a relationship between n-3 PUFAs and coronary spastic angina (CSA). This study aimed to assess the age-dependent role of serum levels of fatty acid in patients with CSA., Methods and Results: We enrolled 406 patients who underwent ergonovine tolerance test (ETT) during coronary angiography for evaluation of CSA. All ETT-positive subjects were diagnosed as having CSA. We categorized the patients by age and results of ETT as follows: (1) young (age ≤ 65 years) CSA-positive (n = 32), (2) young CSA-negative (n = 134), (3) elderly (age > 66 years) CSA-positive (n = 36), and (4) elderly CSA-negative (n = 204) groups. We evaluated the serum levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, and dihomo-gamma-linolenic acid. In the young groups, the serum levels of EPA (64.3 ± 37.7 μg/mL vs. 49.4 ± 28.8 μg/mL, p = 0.015) and DHA (135.7 ± 47.6 μg/mL vs. 117.4 ± 37.6 μg/mL, p = 0.020) were significantly higher in the CSA-positive group than in the CSA-negative group, respectively. However, this was not the case with elderly groups. In the multivariate analysis in young groups, the serum levels of EPA (p = 0.028) and DHA (p = 0.049) were independently associated with the presence of CSA, respectively., Conclusion: Our results suggested that the higher serum levels of EPA and/or DHA might be involved in the pathophysiology of CSA in the young population but not in the elderly population., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

During acute pancreatitis (AP), free fatty acids (FFAs) are liberated from circulating triglycerides (TG) and injured adipocytes by pancreatic lipase. Circulating FFAs have been suspected as a source of systemic lipotoxicity in AP. However, assessment of FFAs is difficult and time-consuming, and little is known about relative levels of FFAs between patients with different severities of AP and controls. This study's aims were to assess early circulating levels of FFAs, (both saturated and unsaturated) in patients with AP vs. controls, and associations between FFA levels and AP severity. Serum samples from patients with AP were collected at enrollment ( day 1 of hospital stay); serum samples were also collected from controls. FFAs including palmitic, palmitoleic, stearic, oleic, and linoleic acid were extracted and quantitated using gas chromatography separation. Severity of AP was determined by Revised Atlanta Classification. Differences in FFA levels and percentages of total FFAs were assessed between patients with AP and controls and patients with AP of different severity grades. A total of 93 patients with AP (48 female, 52%) and 29 controls (20 female, 69%) were enrolled. Of the patients with AP, 74 had mild/moderate and 19 had severe AP. Serum levels of all FFAs except stearic acid were significantly higher in patients with AP compared with controls. A strong and independent association between elevated palmitoleic acid levels and severe AP was found. Serum unsaturated FFA levels, specifically palmitoleic acid, appear to correlate with severe AP. These findings have potential clinical implications for targeted AP therapies. NEW & NOTEWORTHY Drivers of the inflammatory response in acute pancreatitis remain incompletely understood. Unsaturated fatty acids, specifically palmitoleic, appear to have an association with more severe acute pancreatitis. This finding presents a new clinical understanding of fatty acid toxicity and highlights a potential future target for treatment in severe acute pancreatitis.

Background: Postmenopausal osteoporosis (PMOP) is a serious problem for the women over 50 years old. Natural product puerarin (PUE) has been proven to improve PMOP with high safety. PMOP is a metabolic disorder affecting bone metabolism, indicating that endogenous metabolites amelioration may be a novel strategy for PMOP therapy. However, what the metabolic profile of POMP will be after PUE treatment is still obscure., Purpose: We purpose to figure out the metabolic characteristics of PMOP and to explore the intrinsic mechanism on the anti-osteoporosis efficacy after PUE treatment based on the serum metabolomics., Methods: We established OVX rats as osteoporosis model, and the animals were distributed into Sham, OVX, and OVX+PUE (100 mg/kg/d) group. The femurs were analyzed by μ-CT and three-point bending test. Serum metabolomics was performed by UPLC/Q-TOF-MS. We also determined the body weight, liver weight, and the levels of serum TC, TG, LDL-C, and HDL-C. The key proteins of the PPARγ pathway and Wnt pathway were analyzed by Western blot and qPCR experiments., Results: PUE treatment for 14 weeks both improved the bone structure and ameliorated lipid metabolism in ovariectomized rats. By determination and further analysis of serum metabolomics, we revealed that the endogenous metabolites was significantly changed in ovariectomized rats, and PUE treatment adjusted 23 differential metabolites, which were involved in phospholipid metabolism metabolism and PUFAs metabolic pathways. Close correlationships were futher found between the indexes of bone metabolism, lipid metabolism and the differential metabolites, particularly LysoPA, S1P and n-3/n-6 PUFAs. Further, we discovered that PUE regulated differentiation of BMSCs to elicit anti-osteoporosis efficacy, attributing to Wnt/β-catenin signaling activation and PPARγ pathway inhibition initiated by metabolomics., Conclusion: PUE improves OVX-induced osteoporosis and lipid metabolism by regulating phospholipid metabolism and biosynthesis of PUFAs, resulting in reducing the adipogenic differentiation and promoting osteogenic differentiation of BMSCs via Wnt pathway activation and PPARγ pathway inhibition in ovariectomized rats. The study provides us a novel mechanism to explain the improvement of osteoporosis by PUE, depicts a metabolic profile of PMOP, and gives us another point cut for further exploring the pathogenesis of PMOP and looking for biomarkers of osteoporosis., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Coronary artery disease (CAD) is the leading cause of death worldwide. Statins reduce morbidity and mortality of CAD. Intake of n-3 polyunsaturated fatty acid (n-3 PUFAs), particularly eicosapentaenoic acid (EPA), is associated with reduced morbidity and mortality in patients with CAD. Previous data indicate that a higher conversion of precursor fatty acids (FAs) to arachidonic acid (AA) is associated with increased CAD prevalence. Our study explored the FA composition in blood to assess n-3 PUFA levels from patients with and without CAD. We analyzed blood samples from 273 patients undergoing cardiac catheterization. Patients were stratified according to clinically relevant CAD ( n = 192) and those without ( n = 81). FA analysis in full blood was performed by gas chromatography. Indicating increased formation of AA from precursors, the ratio of dihomo-gamma-linolenic acid (DGLA) to AA, the delta-5 desaturase index (D5D index) was higher in CAD patients. CAD patients had significantly lower levels of omega-6 polyunsaturated FAs (n-6 PUFA) and n-3 PUFA, particularly EPA, in the blood. Thus, our study supports a role of increased EPA levels for cardioprotection.

Resolvins and maresins, members of the specialized proresolving mediator (SPM) family, are omega-3 fatty acid-derived lipid mediators that attenuate inflammation. We hypothesized that they play a role in the pathophysiology of coronary microvascular dysfunction (CMD) in women with ischemia and no obstructive coronary disease. In a pilot study, we measured the D-series resolvins (D1, D2, D3, and D5), resolvin E1, maresin 1, docosahexaenoic acid, eicosapentaenoic acid (precursor of resolvin E1), and 18-hydroxyeicosapentaenoic acid by mass spectrometry in the peripheral blood of 31 women enrolled in the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD (WARRIOR) trial who had confirmed CMD assessed by coronary flow reserve. We compared SPM levels with 12 gender and age-matched reference subjects. Compared with the reference subject group, those with CMD had significantly lower plasma concentrations of resolvin D1 and maresin 1 and significantly higher levels of docosahexaenoic acid and 18-hydroxyeicosapentaenoic acid. In conclusion, insufficient or ineffective SPM production may play a role in the pathophysiology of CMD. If our results are validated in a larger cohort, omega-3 fatty acid supplementation could be tested as a novel treatment for these patients., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Associations of dietary or supplementary intake of several unsaturated fatty acids and mortality have been widely studied but the results were still hitherto inconsistent or limited. It is still need to explore the effects of these fatty acids by using the objective biomarkers., Objective: We aimed to investigate the relevancy of several serum n-3 and n-6 fatty acids with all-cause and disease-specific mortality to confirm their health effects and effects on the associations between dietary quality and all-cause mortality., Methods: A total of 4132 people from NHANES 2003-2004 and 2011-2012 and the mortality information was confirmed from the NDI. CPH models adjusted for known risk factors were conducted to explore the associations between circulating n-3 and n-6 fatty acids and all-cause or CVD or cancer mortality under complex sampling. We further evaluated their effects on association between dietary quality and all-cause mortality., Results: A total of 437 deaths occurred during the mean follow-up of 83.34 months, including 157 CVD death and 100 cancer death. Serum LA, ALA, EPA and DHA were associated with all-cause mortality (HR in quintile5: LA:0.584, 95%CI: 0.387-0.882, P trend  = 0.011; ALA:0.626, 95%CI: 0.432-0.907, P trend  = 0.008; EPA:0.535, 95%CI: 0.375-0.764, P trend  = 0.001; DHA:0.669, 95%CI: 0.468-0.955, P trend  = 0.031). Additionally, serum EPA and ALA were respectively related to CVD and cancer mortality (Q5 HR: EPA:0.450, 95%CI: 0.23-0.854, P trend  = 0.009; ALA:0.387, 95%CI: 0.167-0.900, P trend  = 0.022). Serum AA, GLA, DGLA and SDA were not associated with any risk of mortality. The effect on all-cause mortality of the lower AHEI scores can be improved by adherence to a higher serum LA, EPA and DHA (in the lowest AHEI strata, LA in tertile3 compared to tertile1 HR:0.596, 95%CI: 0.366-0.970; EPA:0.660, 95%CI: 0.454-0.959; DHA:0.666, 95%CI; 0.444-1.000)., Conclusions: Our results support the recent dietary recommendations to increase the intake of plant-derived and marine-derived n-6 and n-3 to improve the ability of primary and secondary prevention.

Background: During pregnancy a high amount of fatty acids (FA) is necessary to meet foetus demands, which vary during gestation. The present study describes the changes in maternal fatty acid concentrations during pregnancy in a sample of pregnant women., Methods: This is a longitudinal study of 479 pregnant women who were monitored from the first trimester to third trimester of pregnancy. Data on maternal characteristics were recorded and a serum sample was collected in each trimester. The fatty acid profile (saturated (SFA: total, lauric acid, myristic acid, palmitic acid, stearic acid), monounsaturated (MUFA: total, palmitoleic acid, oleic acid) and polyunsaturated fatty acids (PUFA: total omega-6 (n-6), linoleic acid, dihomo-γ-linolenic acid, arachidonic acid (AA), total omega-3 (n-3), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)) was analysed with a gas chromatography-mass spectrometry combination., Results: From the first trimester to third trimester of pregnancy, a significant increase in total SFA, total MUFA and total n-6 PUFA was found. (p < 0.001). Nevertheless, the serum concentration of arachidonic acid (AA), eicosapentaenoic acid (EPA) and total n-3 PUFA decreased during gestation (p < 0.001). A statistically non-significant result was observed for the docosahexaenoic acid (DHA) serum concentration between the first and third trimesters of pregnancy. Significant correlations were observed between each total fatty acid concentrations of the first and third trimesters., Conclusion: The circulating serum concentration of SFA, MUFA and n-6 PUFA increases during pregnancy, whereas essential fatty acids such as AA and EPA decrease, and DHA remains unchanged. Further research is necessary to understand the role played by FA throughout gestation., (© 2021. The Author(s).)

In the course of pregnancy, increasing importance is being placed on maintaining optimal fatty acid (FA) levels and particularly n-3 PUFAs to ensure correct fetal development. However, reference ranges for FA have been reported in only a few studies. Our objective is to provide quantitative reference intervals for SFAs, MUFAs, and PUFAs (n-6 and n-3) in a large population of healthy pregnant women from a developed country. A prospective study of pregnant women ( n = 479) was conducted from the first trimester (T1) to the third trimester (T3). A total of 11 fatty acids were analyzed in serum by gas chromatography mass spectrometry and were expressed as absolute (µmol/L) and relative (percentage of total FA) concentration units. Serum concentrations of SFAs, MUFAs, n-6 PUFAs, n-3 PUFAs, various FA ratios, and the EFA index were determined. The reference intervals (2.5/97.5 percentiles) in absolute values from T1 ranged from 1884.32 to 8802.81 µmol/L for SFAs, from 959.91 to 2979.46 µmol/L for MUFAs, from 2325.77 to 7735.74 µmol/L for n-6 PUFAs, and from 129.01 to 495.58 µmol/L for n-3 PUFAs. These intervals mainly include the values of other studies from European populations. However, reference ranges vary according to some maternal factors. The FA levels proposed, obtained from a large sample of pregnant women, will be a useful tool for assessing the degree of adequacy of FAs in pregnant women and will help to carry out dietary interventions based on certain maternal factors.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) play an important role in the development, maintenance, and function of the brain. Dietary supplementation of n-3 PUFAs in neurological diseases has been a subject of particular interest in preventing cognitive deficits, and particularly in age-related neurodegeneration. Developing strategies for the efficient delivery of these lipids to the brain has presented a challenge in recent years. We recently reported the preparation of n-3 PUFA-rich nanoliposomes (NLs) from salmon lecithin, and demonstrated their neurotrophic effects in rat embryo cortical neurons. The objective of this study was to assess the ability of these NLs to deliver PUFAs in cellulo and in vivo (in mice). NLs were prepared using salmon lecithin rich in n-3 PUFAs (29.13%), and characterized with an average size of 107.90 ± 0.35 nm, a polydispersity index of 0.25 ± 0.01, and a negative particle-surface electrical charge (-50.4 ± 0.2 mV). Incubation of rat embryo cortical neurons with NLs led to a significant increase in docosahexaenoic acid (DHA) (51.5%, p < 0.01), as well as palmitic acid, and a small decrease in oleic acid after 72 h (12.2%, p < 0.05). Twenty mice on a standard diet received oral administration of NLs (12 mg/mouse/day; 5 days per week) for 8 weeks. Fatty acid profiles obtained via gas chromatography revealed significant increases in cortical levels of saturated, monounsaturated, and n-3 (docosahexaenoic acid,) and n-6 (docosapentaenoic acid and arachidonic acid) PUFAs. This was not the case for the hippocampus or in the liver. There were no effects on plasma lipid levels, and daily monitoring confirmed NL biocompatibility. These results demonstrate that NLs can be used for delivery of PUFAs to the brain. This study opens new research possibilities in the development of preventive as well as therapeutic strategies for age-related neurodegeneration.

Agricultural workers, especially those who work in swine confinement facilities, are at increased risk for developing pulmonary diseases including asthma, chronic obstructive pulmonary disease, and chronic bronchitis due to exposures to fumes, vapors, and organic dust. Repetitive exposure to agricultural dust leads to unresolved inflammation, a common underlying mechanism that worsens lung disease. Besides occupational exposure to dusts, diet also significantly contributes to inflammation and disease progression. Since DHA (docosahexaenoic acid), a polyunsaturated omega-3 fatty acid and its bioactive metabolites have key roles in inflammation resolution, we rationalized that individuals chronically exposed to organic dusts can benefit from dietary modifications. Here, we evaluated the role of DHA in modifying airway inflammation in a murine model of repetitive exposure to an aqueous extract of agricultural dust (three-week exposure to swine confinement dust extract, HDE) and after a one-week resolution/recovery period. We found that mice fed a high DHA diet had significantly increased bronchoalveolar lavage fluid (BALF) levels of DHA-derived resolvins and lower TNFα along with altered plasma levels of endocannabinoids and related lipid mediators. Following the one-week recovery we identified significantly reduced BALF cellularity and cytokine/chemokine release along with increased BALF amphiregulin and resolvins in DHA diet-fed versus control diet-fed mice challenged with HDE. We further report observations on the effects of repetitive HDE exposure on lung Ym1+ and Arg-1+ macrophages. Overall, our findings support a protective role for DHA and identify DHA-derived resolvins and endocannabinoids among the potential mediators of DHA in altering airway inflammation in chronic agricultural dust exposure., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to evaluate the eicosanoid and pro resolutive parameters in SARS COVID-19 patients with the severe acute respiratory syndrome., Patients and Methods: Fourteen male patients with an acute respiratory syndrome caused by SARS COVID-19 and four healthy controls were evaluated by measuring the following parameters in plasma: Polyunsaturated fatty acids: EPA, DHA, ARA, and DPA. Specialized Pro-resolving mediators (SPMs) (including monohydroxy-containing precursors 17-HDHA, 18-HEPE, 14-HDHA) resolvins, maresins, protectins, and lipoxins. The eicosanoids group included prostaglandins, thromboxanes, and leukotrienes., Results: Plasma from COVID-19 patients presented higher amounts of pro-inflammatory and pro-thrombotic lipid mediators as compared to healthy subjects (65.7 pg/ml vs. 10.2 pg/ml), including thromboxane (2142.6 pg/ml vs. 10.4 pg/ml), and the ratio between total plasma pro-inflammatory mediators versus total SPM's was 13.2 to 0,4, respectively., Conclusions: A clear disbalance favoring the pro-inflammatory axis is described, showing the need to perform future clinical interventions in these patients using SPM's or monohydroxylated lipid mediators derivates from fatty acids.

High obesity rates in almost all regions of the world prompt an urgent need for effective obesity prevention. Very good scientific evidence from cell culture and rodent studies show that the availability of essential polyunsaturated fatty acids (PUFA) and their long-chain polyunsaturated derivatives, namely, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, influence adipogenesis; for this reason, early life status may influence later obesity risk. The respective PUFA effects could be mediated via their eicosanoid derivatives, their influence on cell membrane properties, the browning of white adipose tissue, changes to the offspring gut microbiome, their influence on developing regulatory circuits, and gene expression during critical periods. Randomized clinical trials and observational studies show divergent findings in humans, with mostly null findings but also the positive and negative effects of an increased n-3 to n-6 PUFA ratio on BMI and fat mass development. Hence, animal study findings cannot be directly extrapolated to humans. Even though the mechanistic data basis for the effects of n-3 PUFA on obesity risk appears promising, no recommendations for humans can be derived at present.

In the present study, we analysed the effects of SNP rs174547 (T/C) in the fatty acid desaturase 1 (FADS1) gene on long-chain PUFA levels. Four databases were searched to retrieve related literature with keywords such as fatty acid (FA), SNP, FADS1 and rs174547. A meta-analysis of the data was performed using Stata12.0 software, including summary statistics, test for heterogeneity, evaluation of publication bias, subgroup analysis and sensitivity analysis. The associations between rs174547 in FADS1 and seven types of FA, and Δ-5 (D5D) and Δ-6 fatty acid desaturase (D6D) activity were assessed based on the pooled results from eleven papers. A total of 3713 individuals (1529 TT and 2184 TC + CC) were included. The results demonstrated that minor C allele carriers of rs174547 had higher linoleic acid (LA; P < 0·001) and α-linolenic acid (P = 0·020) levels, lower γ-linolenic acid (GLA; P = 0·001) and arachidonic acid (P = 0·024) levels, and lower D5D (P = 0·005) and D6D (P = 0·004) activities than the TT genotype group. Stratification analysis showed that minor C allele carriers of rs174547 had higher LA and lower GLA levels and lower D6D activities in plasma (LA, P < 0·001; GLA, P < 0·001; D6D activity, P < 0·001) samples and in Asian populations (LA, P < 0·001; GLA, P = 0·001; D6D activity, P = 0·001) than the TT genotype group. In conclusion, minor C allele carriers of the SNP rs174547 were associated with decreased activity of D5D and D6D.

Atopic eczema, the most common atopic disease in infants, may pave the way for sensitization and allergy later in childhood. Fatty acids have immune-regulating properties and may regulate skin permeability. Here we examine whether the proportions of fatty acids among the infant and maternal plasma phospholipids at birth were associated with maternal dietary intake during pregnancy and development of atopic eczema during the first year of age in the Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE) birth cohort. Dietary data were collected with a semi-quantitative food frequency questionnaire, fatty acids were measured with GC-MS and atopic eczema was diagnosed by a pediatric allergologist at 12 months of age. We found that higher proportions of n-6 PUFAs (including arachidonic acid) but lower proportions of n-3 PUFAs (including DPA) in the infant's phospholipids at birth were associated with an increased risk of atopic eczema at 12 months of age. The n-6 and n-3 PUFAs were related to maternal intake of meat and fish, respectively. Our results suggest that prenatal exposure to unsaturated fatty acids is associated with eczema development in the infant. Maternal diet during pregnancy may partly explain the fatty acid profiles in utero .

Maternal docosahexaenoic acid (DHA) is required during pregnancy to supply for normal fetal growth and development. This pilot study aimed to assess the unknown fatty acid (FA) composition in a cohort of non-pregnant and pregnant Israeli women at term and their offspring on a normal diet without n-3 FA supplementation. The fatty acid profile, analyzed using gas chromatography, showed significantly higher plasma monounsaturated (MUFA) and lower n-6 FA percent distribution with similar n-3 index, in pregnant compared to non-pregnant women. RBC exhibited significantly higher MUFA with similar n-3 index, in pregnant compared to non-pregnant women. N-3 FA significantly correlated between neonates' plasma, with higher n-3 index, and pregnant women's DHA. Conclusion: DHA levels in non-pregnant and pregnant Israeli women at term were comparable and the DHA in pregnant women's plasma positively correlated with their neonate's level, suggesting an efficient mother-fetus FA transfer and/or fetal fatty acid metabolism to longer FA products., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: American-style football (ASF) athletes are at risk for cardiovascular disease (CVD) and exhibit elevated levels of serum neurofilament light (Nf-L), a biomarker of axonal injury that is associated with repetitive head impact exposure over the course of a season of competition. Supplementation with the w-3 fatty acid (FA) docosahexaenoic acid (DHA) attenuates serum Nf-L elevations and improves aspects of CVD, such as the omega-3 index (O3I). However, the effect of combining the w-3 FA eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) with DHA on, specifically, serum Nf-L in ASF athletes is unknown. Therefore, this study assessed the effect of supplemental w-3 FA (EPA+DPA+DHA) on serum Nf-L, plasma w-3 FAs, the O3I, and surrogate markers of inflammation over the course of a season., Methods: A multi-site, non-randomized design, utilizing two American football teams was employed. One team (n = 3 1) received supplementation with a highly bioavailablew-3 FA formulation (2000mg DHA, 560mg EPA, 320mg DPA, Mindset®, Struct Nutrition, Missoula, MT) during pre-season and throughout the regular season, while the second team served as the control (n = 35) and did not undergo supplementation. Blood was sampled at specific times throughout pre- and regular season coincident w ith changes in intensity, physical contact, and changes in the incidence and severity of head impacts. Group differences were determined via a mixed-model between-within subjects ANOVA. Effect sizes were calculated using Cohen's dfor all between-group differences. Significance was set a priori at p< .05., Results: Compared to the control group, ASF athletes in the treatment group experienced large increases in plasma EPA (p < .001, d = 1.71) and DHA (p < .001, d = 2.10) which contributed to increases in the O3I (p < .001, d = 2.16) and the EPA:AA ratio (p = .001, d = 0.83) and a reduction in the w-6: w-3 ratio (p < .001, d = 1.80). w-3 FA supplementation attenuated elevations in Nf-L (p = .024). The control group experienced a significant increase in Nf-L compared to baseline at several measurement time points (T2, T3, and T4 [p range < .001 - .005, drange = 0.59-0.85])., Conclusions: These findings suggest a cardio- and neuroprotective effect of combined EPA+DPA+DHA w-3 FA supplementation in American-style football athletes., Trial Registration: This trial was registered with the ISRCTN registry ( ISRCTN90306741 )., (© 2021. The Author(s).)

Background: Polyunsaturated fatty acid (PUFA) is important for the development of the fetal brain, and the retina. Gestational diabetes mellitus (GDM) may influence maternal and fetal fatty acid metabolism, in turn affecting fetal growth and development. In several studies, maternal and fetal PUFA metabolic differences have been reported between mothers with and without GDM, but not in other studies. Thus, the aim of this meta-analysis (registration number: CRD42020220448) was to compare levels of linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA), docosahexaenoic acid (DHA), and total n-3 and n-6 PUFA between mothers with and without GMD and their fetuses., Methods: We performed a meta-analysis of observational studies on maternal and fetal fatty acid metabolism, published until May 2021. In addition, we performed subgroup analysis depending on the analyzed tissues (plasma/serum, erythrocyte membrane, or placenta) and the expression modes of fatty acids (concentration or percentage)., Results: We included 24 observational studies involving 4335 maternal datasets and 12 studies involving 1675 fetal datasets in the meta-analysis. Levels of AA, DHA, and n-6 and n-3 PUFA were lower in the cord blood of mothers with GDM than in controls (P  <  0.05). Compared to that in controls, in erythrocyte membranes, the percentages of AA, DHA, and n-6 and n-3 PUFA in total fatty acid were lower in mothers with GDM (P  <  0.05), but in plasma/serum, the percentages of AA, DHA, and n-6 PUFA in total fatty acid were higher in mothers with GDM (P  <  0.05)., Conclusions: GDM appears to influence the transfer of PUFAs from mothers to fetuses. The percentage of PUFAs in maternal plasma/serum was higher, and that in erythrocyte membranes was lower in mothers with GDM compared to those with normal glucose tolerance., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Keratinocyte cancer is the commonest cancer, imposing a high economic burden on the health care system. Observational studies have shown mixed associations between polyunsaturated fatty acids (PUFA) and keratinocyte cancer, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). We explored whether genetically predicted PUFA levels are associated with BCC and SCC risks., Methods: We conducted a two-sample Mendelian randomization study using PUFA level genome-wide association studies (GWAS) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium ( n > 8,000), and the meta-analysis GWASs from UKB, 23andMe, and Qskin for BCC ( n = 651,138) and SCC ( n = 635,331) risk., Results: One SD increase in genetically predicted levels of linoleic acid [OR = 0.94, 95% confidence interval (CI) = 0.91-0.97, P = 1.4 × 10 -4 ] and alpha-linolenic acid (OR = 0.91, 95% CI = 0.86-0.96, P = 5.1 × 10 -4 ) was associated with a reduced BCC risk, while arachidonic acid (OR = 1.04, 95% CI = 1.02-1.06, P = 3.2 × 10 -4 ) and eicosapentaenoic acid (OR = 1.10, 95% CI = 1.04-1.16, P = 1.5 × 10 -3 ) were associated with an increased BCC risk., Conclusions: Higher genetically predicted levels of linoleic acid and alpha-linolenic acid were associated with a reduced BCC risk, but arachidonic acid and eicosapentaenoic acid were associated with a higher BCC risk., Impact: PUFA-related diet and supplementation could influence BCC etiology., (©2021 The Authors; Published by the American Association for Cancer Research.)

Long-Chain Polyunsaturated Fatty Acid (LCPUFA) is essential throughout pregnancy, since deficiency of LPUFA may linked to obstetrical complications. This study aimed to investigate LCPUFA status in severe preeclampsia and preterm birth. A cross sectional study was conducted in 104 pregnant women, which divided into normal pregnancy, severe preeclampsia and preterm birth groups. Serum percentage and concentration of total LCPUFA, omega-3, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), omega-6, linoleic acid (LA), and arachidonic acid (AA) were measured using gas chromatography/mass spectrometry. Receiver operating characteristic (ROC), bivariate and multivariate analysis were performed. Severe preeclampsia showed the highest concentration of total PUFA and the lowest DHA percentage, with significantly higher Omega-6/Omega-3 ratio (p = 0.004) and lower omega-3 index (p < 0.002) compared to control. Preterm birth showed the least omega-3 concentrations, with significantly low omega-6 derivates (LA (p = 0.014) and AA (p = 0.025)) compared to control. LCPUFA parameters have shown to increase the risk in both conditions, particularly ALA ≤ 53 µmol/L in preeclampsia with OR 5.44, 95%CI 1.16-25.42 and preterm birth with OR 4.68, 95%CI 1.52-14.38. These findings suggest that severe preeclampsia and preterm birth have an imbalance in LCPUFA status., (© 2021. The Author(s).)

Long-chain omega-3 polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) play an essential role in cognitive and behavioural changes among school going children. This study delineates the dietary omega-3 PUFA [alpha-Linolenic acid (ALA), DHA, and EPA] intake and plasma fatty acids levels among school-going children. This is a cross-sectional study purely observational in nature, wherein 625 apparently healthy boys and girls aged between 7 and 13 years were selected from five different schools of Hyderabad. Dietary information on omega-3 PUFA (ALA, DHA, and EPA) intake was collected using a food frequency questionnaire. Plasma fatty acid concentrations were measured in 34% of sub-sample using standard gas chromatography. The study revealed that the average dietary intakes of omega-3 PUFA, ALA, DHA, and EPA were 55.46, 15.82, 35.59, 4.06 mg/day, respectively. There was a significant difference in mean DHA intake among gender and age group [girls (38.64±1.45 mg/day), boys (31.80±1.38 mg/day) p < 0.001] and [7-10 years (31.75±1.38 mg/day), 11-13 years (38.07±1.40 mg/day) p < 0.01]. The mean plasma DHA and DPA levels of overall subjects were 0.98 nmol% and 0.18nmol% respectively which was comparable among different gender, age and BMI-for age groups. There was a positive correlation between dietary DHA intake and plasma DHA level [ρ=0.376 (p < 0.001)]. The current study demonstrated that the omega-3 PUFA intake in school going children was less and reinforces the importance of increasing the omega-3 PUFA intake through diet and supplements., (Copyright © 2021. Published by Elsevier Ltd.)

Background: There has been no study systematically assessing the causal effects of putative modifiable risk factors on lung cancer. In this study, we aimed to construct a modifiable risk factors atlas of lung cancer by using the two-sample Mendelian randomization framework., Methods: We included 46 modifiable risk factors identified in previous studies. Traits with p-value smaller than 0.05 were considered as suggestive risk factors. While the Bonferroni corrected p-value for significant risk factors was set to be 8.33 × 10 -4 ., Results: In this two-sample Mendelian randomization analysis, we found that higher socioeconomic status was significantly correlated with lower risk of lung cancer, including years of schooling, college or university degree, and household income. While cigarettes smoked per day, time spent watching TV, polyunsaturated fatty acids, docosapentaenoic acid, eicosapentaenoic acid, and arachidonic acid in blood were significantly associated with higher risk of lung cancer. Suggestive risk factors for lung cancer were found to be serum vitamin A1, copper in blood, docosahexaenoic acid in blood, and body fat percentage., Conclusions: This study provided the first Mendelian randomization assessment of the causality between previously reported risk factors and lung cancer risk. Several modifiable targets, concerning socioeconomic status, lifestyle, dietary, and obesity, should be taken into consideration for the development of primary prevention strategies for lung cancer., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

[Figure: see text].

Background: Emerging evidence suggests an association of maternal PUFA concentrations during pregnancy with child cognitive and neuropsychiatric outcomes such as intelligence and autistic traits. However, little is known about prenatal maternal PUFAs in relation to child brain development, which may underlie these associations., Objectives: We aimed to investigate the association of maternal PUFA status during pregnancy with child brain morphology, including volumetric and white matter microstructure measures., Methods: This study was embedded in a prospective population-based study. In total, 1553 mother-child dyads of Dutch origin were included. Maternal plasma glycerophospholipid PUFAs were assessed in midpregnancy. Child brain morphologic outcomes, including total gray and white matter volumes, as well as white matter microstructure quantified by global fractional anisotropy and mean diffusivity, were measured using MRI (including diffusion tensor imaging) at age 9-11 y., Results: Maternal ω-3 (n-3) long-chain PUFA (LC-PUFA) concentrations during pregnancy had an inverted U-shaped relation with child total gray volume (linear term: β: 16.7; 95% CI: 2.0, 31.5; quadratic term: β: -1.1; 95% CI: -2.1, -0.07) and total white matter volume (linear term: β: 15.7; 95% CI: 3.6, 27.8; quadratic term: β: -1.0; 95% CI: -1.8, -0.16). Maternal gestational ω-6 LC-PUFA concentrations did not predict brain volumetric differences in children, albeit the linolenic acid concentration was inversely associated with child total white matter volume. Maternal PUFA status during pregnancy was not related to child white matter microstructure., Conclusions: Sufficient maternal ω-3 PUFAs during pregnancy may be related to more optimal child brain development in the long term. In particular, exposure to lower ω-3 PUFA concentrations in fetal life was associated with less brain volume in childhood. Maternal ω-6 LC-PUFAs were not related to child brain morphology., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Quadriceps muscle atrophy following total knee arthroplasty (TKA) can be caused by tourniquet-induced ischemia-reperfusion (IR) injury, which is often accompanied by oxidative stress and inflammatory responses. n -3 long-chain polyunsaturated fatty acids (LCPUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert antioxidant and anti-inflammatory effects against IR injury, whereas n -6 LCPUFAs, particularly arachidonic acid (AA), exhibit pro-inflammatory effects and promote IR injury. This study aimed to examine whether preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio are associated with oxidative stress immediately after TKA. Fourteen eligible patients with knee osteoarthritis scheduled for unilateral TKA participated in this study. The levels of serum EPA, DHA, and AA were measured immediately before surgery. Derivatives of reactive oxygen metabolites (d-ROMs) were used as biomarkers for oxidative stress. The preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio were found to be significantly negatively correlated with the serum d-ROM levels at 96 h after surgery, and the rate of increase in serum d-ROM levels between baseline and 96 h postoperatively. This study suggested the preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio can be negatively associated with oxidative stress immediately after TKA.

Background: Gestational diabetes mellitus (GDM) is associated with increased risks of disease for mother and child during pregnancy and after that. Early diagnosis of GDM would promote both maternal and fetal health. Metabolomics can simplify and develop our understanding of the etiology, manifestation, or pathophysiology of the disease. This systematic review investigates the association of circulating omega 3, 6, and 9 fatty acids with GDM., Methods: We conducted a systematic search of PubMed, Scopus, Web of Science, and EMBASE databases up to May 8, 2020, using the key term combinations of all types of omega fatty acids with gestational diabetes mellitus. Additional articles were identified through searching the reference lists of included studies., Results: This systematic review included 15 articles. Five were cohort studies, four included nested case-control studies and four were case-control studies. The results of this study demonstrate an increasing trend in the amount of oleic acid and palmitoleic acid in the second trimester and an increase in decosahexanoic acid in the third trimester of GDM mothers. The changes in other fatty acids of interest are either not significant or if significant, their results are inconsistent with the other existing articles., Conclusions: Omega fatty acids, as potential biomarkers, are considered to be associated with GDM risk and thus provide useful information regarding the prevention and early diagnosis of GDM. Moreover, existing metabolomic studies on GDM are shown to provide conflicting results about metabolite profile characteristics. This systematic review was registered at PROSPERO ( www.crd.york.ac.uk/PROSPERO ) as CRD42020196122.

Polyunsaturated fatty acids (PUFA) are important for neuronal function and may contribute to the development of neurodegenerative diseases. Here, we investigated the correlation between dietary intake and plasma concentrations of PUFA and their associations with clinical severity in early-stage Parkinson's disease (PD). In a case-control study with 38 patients with PD and 33 controls, we assessed dietary intake using food frequency questionnaires and simultaneously measured the plasma levels of five PUFA. No differences were observed in dietary total energy and lipid intake, including PUFA, between patients with PD and controls. However, α-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA) plasma levels were lower in patients with PD. The association between dietary intake and plasma PUFA concentrations was not significant in patients with PD. ALA and LA plasma levels were inversely correlated with motor severity in patients with PD, while docosahexaenoic acid and AA plasma levels were positively correlated with non-motor symptoms after controlling for age and sex.