Role of polyunsaturated fatty acids in Japanese patients with coronary spastic angina.

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 ±â€¯37.7 µg/mL vs. 49.4 ±â€¯28.8 µg/mL, p = 0.015) and DHA (135.7 ±â€¯47.6 µg/mL vs. 117.4 ±â€¯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.

Relationship of circulating levels of long-chain fatty acids to persistent organ failure in acute pancreatitis.

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.

Puerarin improves OVX-induced osteoporosis by regulating phospholipid metabolism and biosynthesis of unsaturated fatty acids based on serum metabolomics.

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/ß-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.

Essential Polyunsaturated Fatty Acids in Blood from Patients with and without Catheter-Proven Coronary Artery Disease.

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.

Specialized Proresolving Mediators in Symptomatic Women With Coronary Microvascular Dysfunction (from the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD [WARRIOR] Trial).

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.

Acute severe SARS COVID-19 patients produce pro-resolving lipids mediators and eicosanoids.

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.

Changes in fatty acid levels (saturated, monounsaturated and polyunsaturated) during pregnancy.

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.

Use of Active Salmon-Lecithin Nanoliposomes to Increase Polyunsaturated Fatty Acid Bioavailability in Cortical Neurons and Mice.

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.

Proportions of Polyunsaturated Fatty Acids in Umbilical Cord Blood at Birth Are Related to Atopic Eczema Development in the First Year of Life.

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.

Perinatal Polyunsaturated Fatty Acid Status and Obesity Risk.

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.

Trimester-Specific Reference Ranges for Saturated, Monounsaturated and Polyunsaturated Fatty Acids in Serum of Pregnant Women: A Cohort Study from the ECLIPSES Group.

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.

The associations of circulating common and uncommon polyunsaturated fatty acids and modification effects on dietary quality with all-cause and disease-specific mortality in NHANES 2003-2004 and 2011-2012.

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, Ptrend = 0.011; ALA:0.626, 95%CI: 0.432-0.907, Ptrend = 0.008; EPA:0.535, 95%CI: 0.375-0.764, Ptrend = 0.001; DHA:0.669, 95%CI: 0.468-0.955, Ptrend = 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, Ptrend = 0.009; ALA:0.387, 95%CI: 0.167-0.900, Ptrend = 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.

Blood fatty acid analysis reveals similar n-3 fatty acid composition in non-pregnant and pregnant women and their neonates in an Israeli pilot study.

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.

The effect of omega-3 fatty acids on a biomarker of head trauma in NCAA football athletes: a multi-site, non-randomized study.

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 ).

A liquid chromatography-mass spectrometry workflow for in-depth quantitation of fatty acid double bond location isomers.

Tracing compositional changes of fatty acids (FAs) is frequently used as a means of monitoring metabolic alterations in perturbed biological states. Given that more than half of FAs in the mammalian lipidome are unsaturated, quantitation of FAs at a carbon-carbon double bond (C=C) location level is necessary. The use of 2-acetylpiridine (2-acpy) as the charge-tagging PB reagent led to a limit of identification in the subnanomolar range for mono- and polyunsaturated as well as conjugated FAs. Conjugated free FAs of low abundance such as FA 18:2 (n-7, n-9) and FA 18:2 (n-6, n-8) were quantified at concentrations of 0.61 ± 0.05 and 0.05 ± 0.01 mg per 100 g in yak milk powder, respectively. This workflow also enabled deep profiling of eight saturated and 37 unsaturated total FAs across a span of four orders of magnitude in concentration, including ten groups of C=C location isomers in pooled human plasma. A pilot survey on total FAs in plasma from patients with type 2 diabetes revealed that the relative compositions of FA 16:1 (n-10) and FA 18:1 (n-10) were significantly elevated compared with that of normal controls. In this work, we have developed a workflow for global quantitation of FAs, including C=C location isomers, via charge-tagging Paternò-Büchi (PB) derivatization and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Association between Preoperative Long-Chain Polyunsaturated Fatty Acids and Oxidative Stress Immediately after Total Knee Arthroplasty: A Pilot Study.

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.

Gestational diabetes mellitus decreased umbilical cord blood polyunsaturated fatty acids: a meta-analysis of observational studies.

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.

Long-chain polyunsaturated fatty acid (LC-PUFA) status in severe preeclampsia and preterm birth: a cross sectional study.

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.

Polyunsaturated Fatty Acid Levels and the Risk of Keratinocyte Cancer: A Mendelian Randomization Analysis.

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.