Eicosapentaenoic Acid Levels Research Articles

Relationships between erythrocyte membrane mono- and poly- unsaturated fatty acid composition and clinical/cognitive indices in antipsychotic-free schizophrenia patients.

Membrane phospholipid abnormalities are considered a pathophysiological background for schizophrenia. The aim of the study was to explore in detail the fatty acid (FA) composition in patients with antipsychotic-free schizophrenia and its association with clinical symptoms and cognitive function. Erythrocyte membrane FAs were measured in 29 antipsychotic-free patients with schizophrenia (male/female = 11/18; mean [standard deviation] age=26.7 [7.9] years) and age and sex-matched 32 healthy volunteers. Clinical symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), and the Schizophrenia Cognition Rating Scale (SCoRS). Eicosapentaenoic acid levels were lower in the schizophrenia group than in the healthy control group. In contrast, arachidonic acid and nervonic acid levels were higher in the schizophrenia group than in the control group. Nervonic acid levels were significantly associated with depression scores as measured by the PANSS. No FA levels were correlated with BACS score; however, oleic acid levels were significantly related to cognitive dysfunction, as measured by the SCoRS. These findings suggest that depressive symptoms along with cognitive dysfunction in daily living in schizophrenia may be linked to the FA composition abnormalities. Further studies will be needed to examine potential longitudinal FA changes during the course of schizophrenia as well as disease specificity.

Stearidonic acid improves eicosapentaenoic acid status: studies in humans and cultured hepatocytes.

Ahiflower oil from the seeds of Buglossoides arvensis is rich in α-linolenic acid (ALA) and stearidonic acid (SDA). ALA and SDA are potential precursor fatty acids for the endogenous synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are n3-long chain polyunsaturated fatty acids (n3-LC-PUFAS), in humans. Since taurine, an amino sulfonic acid, is often associated with tissues rich in n3-LC-PUFAS (e.g., in fatty fish, human retina), taurine may play a role in EPA- and DHA-metabolism. To examine the capacity of the plant-derived precursor fatty acids (ALA and SDA) and of the potential fatty acid metabolism modulator taurine to increase n3-LC-PUFAS and their respective oxylipins in human plasma and cultivated hepatocytes (HepG2 cells). In a monocentric, randomized crossover study 29 healthy male volunteers received three sequential interventions, namely ahiflower oil (9 g/day), taurine (1.5 g/day) and ahiflower oil (9 g/day) + taurine (1.5 g/day) for 20 days. In addition, cultivated HepG2 cells were treated with isolated fatty acids ALA, SDA, EPA, DHA as well as taurine alone or together with SDA. Oral ahiflower oil intake significantly improved plasma EPA levels (0.2 vs. 0.6% of total fatty acid methyl esters (FAMES)) in humans, whereas DHA levels were unaffected by treatments. EPA-levels in SDA-treated HepG2 cells were 65% higher (5.1 vs. 3.0% of total FAMES) than those in ALA-treated cells. Taurine did not affect fatty acid profiles in human plasma in vivo or in HepG2 cells in vitro. SDA-rich ahiflower oil and isolated SDA led to an increase in EPA-derived oxylipins in humans and in HepG2 cells, respectively. The consumption of ahiflower oil improves the circulating levels of EPA and EPA-derived oxylipins in humans. In cultivated hepatocytes, EPA and EPA-derived oxylipins are more effectively increased by SDA than ALA.

Molecular phylogenetics of the Umbelopsis genus-identification of new species and evaluation of their oil application value.

The aim of this study was to reconstruct the evolutionary framework of the genus Umbelopsis by using modern taxonomic strategies and evaluating the quality of oil and prospective uses of three distinct species. Three species of Umbelopsis were identified based on morphological characteristics and phylogenetic evidence obtained from three genes (ITS, LSU, and ACT). A new species of Umbelopsis was described and illustrated, and subsequently named U. ophiocordycipiticola. The characteristics of U. ophiocordycipiticola exhibited sporangia with a diameter ranging from 8 to 17µm. and sporangiospores that were oval to ellipsoidal in shape, irregularly angular, with dimensions of ∼1.9-2.9×1.7-3.0µm. Gas chromatography and mass spectrometry (GC-MS) were used to examine the composition of fatty acids. Notably, U. ophiocordycipiticola showed a significantly higher oil content of 50.89% in dry cell weight (DCW) compared to U. vinacea and U. ramanniana. The mean proportion of polyunsaturated fatty acids (PUFAs) in U. ophiocordycipiticola was 32.38%, and the maximum levels of γ-linolenic acid (GLA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in U. ophiocordycipiticola were found to be 14.51, 0.24, 0.54, and 0.53%, respectively. The biodiesel quality from all three species complied with applicable standards set by the American Association for Testing and Materials (ASTM 6751) and the Brazilian National Petroleum Agency (ANP 255). The establishment of a novel species, U. ophiocordycipiticola, was strongly supported by morphological and molecular evidence. Umbelopsis ophiocordycipiticola exhibited a high-value PUFA content. Additionally, three Umbelopsis species demonstrated good quality for biodiesel production.

Interaction of Vitamin D Supplements and Marine n-3 Fatty Acids on Digestive Tract Cancer Prognosis.

A meta-analysis suggested that marine n-3 polyunsaturated fatty acids (PUFAs), e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), might reduce cancer mortality. However, a randomized clinical trial of marine n-3 PUFA and vitamin D supplementation failed to verify this benefit. This study aimed to investigate the potential interaction between vitamin D supplementation and serum EPA and DHA levels. This post hoc analysis of the AMATERASU trial (UMIN000001977), a randomized controlled trial (RCT), included 302 patients with digestive tract cancers divided into two subgroups stratified by median serum levels of EPA + DHA into higher and lower halves. The 5-year relapse-free survival (RFS) rate was significantly higher in the higher half (80.9%) than the lower half (67.8%; hazard ratio (HR), 2.15; 95% CI, 1.29-3.59). In the patients in the lower EPA + DHA group, the 5-year RFS was significantly higher in the vitamin D (74.9%) than the placebo group (49.9%; HR, 0.43; 95% CI, 0.24-0.78). Conversely, vitamin D had no effect in the higher half, suggesting that vitamin D supplementation only had a significant interactive effect on RFS in the lower half (p for interaction = 0.03). These results suggest that vitamin D supplementation may reduce the risk of relapse or death by interacting with marine n-3 PUFAs.

A phase IIb randomized placebo-controlled trial testing the effect of MAG-EPA long-chain omega-3 fatty acid dietary supplement on prostate cancer proliferation

BackgroundHigh prostate eicosapentaenoic fatty acid (EPA) levels were associated with a significant reduction of upgrading to grade group (GG) ≥ 2 prostate cancer in men under active surveillance. We aimed to evaluate the effect of MAG-EPA long-chain omega-3 fatty acid dietary supplement on prostate cancer proliferation.MethodsA phase II double-blind randomized placebo-controlled trial was conducted in 130 men diagnosed with GG ≥ 2 prostate cancer and undergoing radical prostatectomy between 2015–2017 (Clinicaltrials.gov: NCT02333435). Participants were randomized to receive 3 g daily of either MAG-EPA (n = 65) or placebo (n = 65) for 7 weeks (range 4–10) prior to radical prostatectomy. The primary outcome was the cancer proliferation index quantified by automated image analysis of tumor nuclear Ki-67 expression using standardized prostatectomy tissue microarrays. Additional planned outcomes at surgery are reported including plasma levels of 27 inflammatory cytokines and fatty acid profiles in circulating red blood cells membranes and prostate tissue.ResultsCancer proliferation index measured by Ki-67 expression was not statistically different between the intervention (3.10%) and placebo (2.85%) groups (p = 0.64). In the per protocol analyses, the adjusted estimated effect of MAG-EPA was greater but remained non-significant. Secondary outcome was the changes in plasma levels of 27 cytokines, of which only IL-7 was higher in MAG-EPA group compared to placebo (p = 0.026). Men randomized to MAG-EPA prior to surgery had four-fold higher EPA levels in prostate tissue compared to those on placebo.ConclusionsThis MAG-EPA intervention did not affect the primary outcome of prostate cancer proliferation according to nuclear Ki-67 expression. More studies are needed to decipher the effects of long-chain omega-3 fatty acid dietary supplementation in men with prostate cancer.

Differential DHA and EPA Levels in Women with Preterm and Term Births: A Tertiary Hospital Study in Indonesia.

BACKGROUND Preterm birth is one of the main causes of neonatal death worldwide. One strategy focused on preventing preterm birth is the administration of long chain polyunsaturated fatty acids (LCPUFAs) during pregnancy. Omega-3 LCPUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential in metabolic and physiological processes during embryonic and fetal development. This study aimed to compare DHA and EPA levels in 44 women with preterm births and 44 women with term births at a tertiary hospital in West Java Province, Indonesia, between November 2022 and March 2023. MATERIAL AND METHODS A total of 88 patients in this study consisted of 44 patients with term births (≥37 gestational weeks) and 44 patients with preterm births (<37 gestational weeks) at a tertiary hospital in West Java Province, Indonesia. This observational, cross-sectional study was conducted from November 2022 to March 2023. Using the enzyme-linked immunosorbent assay test, maternal DHA and EPA levels were investigated. IBM SPSS 24.0 was used to statistically measure outcomes. RESULTS Average maternal DHA and EPA levels in patients with preterm births were significantly lower than those in term births. Preterm labor risk was further increased by DHA levels of ≤5.70 µg/mL (OR=441.00, P=0.000) and EPA levels ≤3971.54 µg/mL (OR=441.00, P=0.000). CONCLUSIONS Since the average maternal DHA and EPA levels were significantly lower in patients with preterm births, adequate intake of omega-3 LCPUFA in early pregnancy and consistency with existing nutritional guidelines was associated with a lower risk of preterm delivery for pregnant women.

The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose–response meta-analysis

BackgroundOmega-3 polyunsaturated fatty acids (n-3 PUFA) have been suggested as a cognitive enhancing agent, though their effect is doubtful. We aimed to examine the effect of n-3 PUFA on the cognitive function of middle-aged or older adults without dementia.MethodsWe reviewed randomized controlled trials of individuals aged 40 years or older. We systematically searched PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Library databases. We used the restricted cubic splines model for non-linear dose–response meta-analysis in terms of the standardized mean difference with 95% confidence intervals.ResultsThe current meta-analysis on 24 studies (n 9660; follow-up 3 to 36 months) found that the beneficial effect on executive function demonstrates an upward trend within the initial 12 months of intervention. This effect is prominently observed with a daily intake surpassing 500 mg of n-3 PUFA and up to 420 mg of eicosapentaenoic acid (EPA). Furthermore, these trends exhibit heightened significance in regions where the levels of blood docosahexaenoic acid (DHA) + EPA are not very low.ConclusionsSupplementation of n-3 PUFA may confer potential benefits to executive function among the middle-aged and elderly demographic, particularly in individuals whose dietary DHA + EPA level is not substantially diminished.

Prognostic Significance of Sarcopenia and Eicosapentaenoic Acid (EPA) Levels in Patients With Unresectable Pancreatic or Biliary Tract Cancer.

This study aimed to investigate the relationship between prechemotherapy blood eicosapentaenoic acid (EPA) levels, sarcopenia, and overall survival in patients with pancreatic and biliary tract cancer undergoing chemotherapy. Forty-five patients with recurrent, non-resected pancreatic or biliary tract cancer undergoing chemotherapy were retrospectively analyzed. The skeletal muscle mass was measured at the third lumbar vertebra. Sarcopenia cut-off values were based on the Japanese Society of Hepatology sarcopenia assessment criteria. Two months after starting chemotherapy, the patients received enteral nutrition containing omega-3 fatty acids. Patients with pancreatic and biliary tract cancers with low pre-treatment blood EPA levels had significantly more intense sarcopenia than those with high EPA levels (p=0.023). Patients with sarcopenia before chemotherapy had significantly lower overall survival than those without sarcopenia. Multivariate analysis revealed blood EPA concentration as an independent prognostic factor (p<0.01). Lumbar muscle volume, a marker of sarcopenia, showed a clear positive correlation with prechemotherapy EPA concentration (p=0.008). In patients administered with enteral nutrition containing omega-3 fatty acids, both EPA concentration and lumbar muscle volume were significantly higher than those prior to intervention, indicating sarcopenia improvement due to the intervention. In patients with recurrent non-resected pancreatic and biliary tract cancer, low blood EPA levels before chemotherapy are associated with sarcopenia and poor prognosis.

Profiling of Oxylipins as Markers of Oxidative Stress in Biological Samples.

Oxylipins are oxidized metabolites of polyunsaturated fatty acids (PUFAs). They represent a class of risk markers and/or therapeutic targets for diseases associated with inflammation, including cardiovascular disease and brain disorders. Because the biological activities of free PUFAs and oxylipins depend on their chemical structures and concentrations, monitoring PUFAs and oxylipin levels in biological systems is critical for understanding their roles in health and disease. Traditionally, accurate quantification of free PUFAs and oxylipins in biological samples was performed separately, as PUFAs are often 1000-fold more abundant than the derived oxidized fatty acids (oxylipins). This article describes a liquid chromatography multiple reaction monitoring tandem mass spectrometry method for the quantitative analysis of five free PUFAs and 88 oxylipins in various biological fluids, including plasma, platelet supernatants, and tissues. The same approach can also be used in conjunction with an alkaline hydrolysis step to quantify total oxylipins in fish oils. We observed that in some samples, linoleic acid levels in plasma and eicosapentaenoic acid and arachidonic acid levels in brain tissue were above the upper limit of quantification. To address this issue, we developed a data analysis method to obtain PUFA and oxylipin concentrations in these samples without additional sample preparation, thus significantly saving time and labor. © 2024 Wiley Periodicals LLC. Basic Protocol: Quantification of polyunsaturated fatty acids (PUFAs) and oxylipins using liquid chromatography multiple reaction monitoring tandem mass spectrometry Support Protocol 1: Preparation of internal standard mixed working solution Support Protocol 2: Preparation of standard mixed stock solution Support Protocol 3: Preparation of standard mixed working solution Alternate Protocol 1: Extraction and quantitation of free PUFAs and oxylipins from mouse brain tissue Alternate Protocol 2: Extraction and quantitation of total PUFAs and oxylipins from fish oil.

Developmental and Nutritional Changes in Children with Severe Acute Malnutrition Provided with n-3 Fatty Acids Improved Ready-to-Use Therapeutic Food and Psychosocial Support: A Pilot Study in Tanzania.

Children with severe acute malnutrition (SAM) are at high risk of impaired development. Contributing causes include the inadequate intake of specific nutrients such as polyunsaturated fatty acids (PUFAs) and a lack of adequate stimulation. We conducted a pilot study assessing developmental and nutritional changes in children with SAM provided with a modified ready-to-use therapeutic food and context-specific psychosocial intervention in Mwanza, Tanzania. We recruited 82 children with SAM (6-36 months) and 88 sex- and age-matched non-malnourished children. We measured child development, using the Malawi Development Assessment Tool (MDAT), measures of family and maternal care for children, and whole-blood PUFA levels. At baseline, the mean total MDAT z-score of children with SAM was lower than non-malnourished children; -2.37 (95% confidence interval: -2.92; -1.82), as were their total n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. After 8 weeks of intervention, MDAT z-scores improved in all domains, especially fine motor, among children with SAM. Total n-3 and EPA levels increased, total n-6 fatty acids decreased, and DHA remained unchanged. Family and maternal care also improved. The suggested benefits of the combined interventions on the developmental and nutritional status of children with SAM will be tested in a future trial.

The Effect of Acute Knee Injuries and Related Knee Surgery on Serum Levels of Pro- and Anti-inflammatory Lipid Mediators and Their Associations With Knee Symptoms

Background: Despite an acute knee injury being a major risk factor for osteoarthritis, the factors that initiate and maintain this risk of longer-term knee symptoms are poorly understood. Bioactive lipids derived from omega-3 and -6 polyunsaturated fatty acids have key roles in the regulation of the inflammatory response and have been linked to joint damage and osteoarthritis pain in translational models. Hypothesis: There would be associations between systemic levels of bioactive lipids and knee symptoms longitudinally after an acute knee injury and related knee surgery. Study Design: Controlled laboratory study. Methods: This study analyzed a subset of young, active adults who had sustained an acute knee injury (recruited via a surgical care pathway) and healthy age- and sex-matched controls. Surgery, if performed, was conducted after the baseline serum sample was taken and before the 3-month and 2-year visits. Liquid chromatography–tandem mass spectrometry of 41 bioactive lipids was carried out in sera of (1) 47 injured participants (median age, 28 years) collected at baseline (median, 24 days after injury), 3 months, and 2 years, along with the Knee injury and Osteoarthritis Outcome Score, and (2) age- and sex-matched controls. Results: Levels of the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (P≤ .0001) and docosahexaenoic acid (P≤ .0001) and the pro-resolving lipid mediators 17– and 14–hydroxydocosahexaenoic acid, and 18-hydroxyeicosapentaenoic acid were all significantly greater at baseline in injured participants compared with the later time points and also higher than in healthy controls (P = .0019 and P≤ .0001, respectively). Levels of pro-inflammatory prostaglandins E2 and D2, leukotriene B4, and thromboxane B2 were significantly lower at baseline compared with the later time points. Higher levels of 8,9–, 11,12–, and 14,15–dihydroxyeicosatrienoic acid (DHET) were cross-sectionally associated with more severe knee pain/symptoms according to the Knee injury and Osteoarthritis Outcome Score at 2 years (P = .0004, R2 = 0.251; P = .0002, R2 = 0.278; and P = .0012, R2 = 0.214, respectively). Conclusion: The profile of pro-resolving versus pro-inflammatory lipids at baseline suggests an initial activation of pro-resolution pathways, followed by the later activation of pro-inflammatory pathways. Clinical Relevance: In this largely surgically managed cohort, the association of soluble epoxide hydrolase metabolites, the DHETs, with more severe knee symptoms at 2 years provides a rationale for further investigation into the role of this pathway in persisting knee symptoms in this population, including potential therapeutic strategies.

Effects of microalgae diets on growth, proximate, and fatty acid composition of black mussel, Mytilus galloprovincialis

AbstractThis study evaluates the growth, proximate, and fatty acid composition of black mussel, Mytilus galloprovincialis fed four marine microalgae (Pavlova lutheri, Nannochloropsis oculata, Diacronema vlkianum and Rhinomonas reticulata) diets for 21 days. Black mussel is a common bivalve species that has been recognized as important for marine aquaculture with increasing production in the last two decades. The mussel group fed N. oculata showed a significantly lower survival rate than the other groups (p &lt; 0.05). Shell height, length, and width of mussels were measured. The height and length of the mussel group fed N. oculata were statistically higher than other experimental groups (p &lt; 0.05). Shell width did not show any significant differences among groups (p &gt; 0.05). The microalgae N. oculata showed the highest protein content whereas P. lutheri had the highest crude lipid content among dietary treatments. The group fed P. lutheri showed significantly higher protein, lipid, and ash contents among experimental groups (p &lt; 0.05). The D. vlkianum diet enhanced the highest docosahexaenoic acid level in black mussels. Black mussel fed P. lutheri showed the highest eicosapentaenoic acid and polyunsaturated fatty acid levels. Arachidonic acid was found to be similar among experimental groups. In our study, P. lutheri and D. vlkianum had outstanding results on survival, growth, and essential fatty acid accumulation in mussel culture.

Fatty acid profiles reveal dietary variability of a large calanoid copepod Limnocalanus macrurus in the northern Baltic Sea

Eutrophication, climate-induced warming, and salinity fluctuations are altering the fatty acid profiles and the availability of essential polyunsaturated fatty acids (PUFAs) in marine zooplankton communities. Limnocalanus macrurus Sars G.O., 1863 is a large calanoid copepod inhabiting the low-salinity areas in the Baltic Sea, where it is a major source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to commercially important fish. L. macrurus is sensitive to warming, eutrophication and hypoxia. As an opportunistic feeder, it is capable of dietary shifts, which affects its fatty acid profiles. Although much studied in boreal lakes, there are only a few studies on the fatty acid profiles of the Baltic Sea populations. This study aimed to compare the fatty acid profiles of L. macrurus in three basins of the Baltic Sea, in relation to the community fatty acids and environmental variables. We collected samples of L. macrurus and filtered plankton community for gas chromatographic fatty acid analyses in August 2021 on R/V Aranda. The nutritional quality of L. macrurus to consumers was lower in the Gulf of Finland (GoF) compared to the Gulf of Bothnia, indicated by the low levels of DHA and EPA, as well as the low n-3/n-6 ratio of PUFAs. The lower ratio of 18:1n-7 to 18:1n-9 implied higher degree of omnivory in GoF. In contrast, a diatom marker 16:1n-7 had high proportion in the Bothnian Bay. High temperatures in GoF may have restricted feeding in the upper water column, possibly forcing a shift towards cyanobacteria or seston-based diet, as interpreted from a high proportion of 18:2n-6 and 18:3n-3. We conclude that the ability of L. macrurus to utilize multiple food sources increases its resilience to environmental change, while the consequences on the nutritional quality may have further cascading effects on the food webs.

The effect of fish oil rich in cetoleic acid on the omega-3 index and skin quality

Objective: The objective of the study was to provide preliminary data on the effect of a long chain monounsaturated oil rich in cetoleic acid on the omega-3 index, a validated measure of EPA and DHA in blood cells, as well as a potential effect of the oil on skin quality.Design: Two intervention studies were performed, each as double blinded, placebo controlled, randomised nutritional trials. The CetoIndex study (N = 55) measured omega-3 index using a blood spot collection kit (Omegaquant). The Optihud study (N = 28) measured skin quality parameters in healthy women using the VISIA system. The cetoleic-rich-oil (CRO) was an oil derived from North Atlantic fish with a predominance of long chain mono-unsaturated fatty acids including cetoleic acid (C22:1 n-11) and gondoic acid (C20:1 n-9).Results: In a placebo-controlled study, the omega-3 index in healthy volunteers was increased similar to that seen with an oil with higher levels of omega-3 fatty acids. In a separate placebo-controlled study, the CRO reduced erythema in skin, which is a marker of inflammation.Conclusions: The results of this pilot study suggest that the use of a CRO increases the omega-3 index more than expected from the levels of EPA and DHA in the oil. The CRO may potentially have benefits on skin inflammation.Summary: Long chain polyunsaturated fatty acids (LCPUFA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are commonly taken as dietary supplements for a range of health benefits. Other marine fatty acids may also provide health benefits and it is of interest to understand their activity. Long chain mono-unsaturated fatty acids (LCMUFA) have shown biological activity in studies of metabolic health in animal models. Here, we report two intervention studies using a fish oil with a high LCMUFA content where cetoleic acid is the predominant fatty acid (Cetoleic rich oil: CRO). In CetoIndex, a placebo-controlled study in 55 healthy volunteers, the omega-3 index increased similarly to that seen with an oil containing higher levels of omega-3 fatty acids. In Optihud, a placebo-controlled study in 28 female volunteers, the CRO reduced erythema in skin, which is a marker of inflammation. The results of this pilot study support the use of a CRO for increasing the omega-3 index with potential benefits on skin inflammation.

Metabolomic insights into the therapeutic mechanisms of costus (Saussurea costus (Falc.) Lipsch.) root extract in propylthiouracil-induced hypothyroidism rat model

Ethnopharmacological relevanceSaussurea costus (Falc.) Lipschitz. is one of the most reputed medicinal plants as a traditional medicine in the Arab and Middle East regions in the treatment of thyroid disorders, however, more investigations are needed to fully understand its effectiveness and mechanism of action. Aim of the studyThe primary objective of the study was to assess the impact of Saussurea costus (COST) on the metabolic profiles of propylthiouracil (PTU)-induced hypothyroidism in rats. This involves a comprehensive examination of serum metabolites using UPLC/QqQ-MS analysis aiming to identify differential metabolites, elucidate underlying mechanisms, and evaluate the potential pharmacological effect of COST in restoring metabolic homeostasis. Materials and methodsHypothyroidism was induced in female Sprague-Dawley rats by oral administration of propylthiouracil (PTU). UPLC/QqQ MS analysis of serum samples from normal, PTU, and PTU + COST rats was utilized for annotation of intrinsic metabolites with the aid of online Human metabolome database (HMDB) and extensive literature surfing. Multivariate statistical analyses, including orthogonal partial least squares discriminant analysis (OPLS-DA), discerned variations between the different groups. Serum levels of T3, T4 and TSH in addition to arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels in thyroid gland tissues; Phospholipase A2 group IIA (PLA2G2A), and lipoprotein lipase (LPL) in liver tissues were assessed by specific ELISA kits. Gene expression for key proteins of the primary evolved pathwayswere quantified by one-step qRT-PCR technique. Histopathological evaluation of thyroid gland tissue was performed by an investigator blinded to the experimental group using light microscope. ResultsDistinct clustering in multivariate statistical analysis models indicated significant variations in serum chemical profiles among normal, disease, and treated groups. VIP values guided the selection of differential metabolites, revealing significant changes in metabolite concentrations. Subsequent to COST treatment, 43 differential intrinsic metabolites exhibited a notable tendency to revert towards normal levels. Annotated metabolites, such as lysophosphatidylcholine (LPC), L-acetylcarnitine, gamma-glutamylserine, and others, showed differential regulation in response to PTU and subsequent S. costus treatment. Notably, 21 metabolites were associated with polyunsaturated fatty acids (PUFAs) biosynthesis, arachidonic acid (ARA) metabolism, and glycerophospholipid metabolism exhibited significant changes on conducting metabolic pathway analysis. ConclusionsCOST improves PTU-induced hypothyroidism by regulating biosynthesis of PUFAs signified by n-3/n-6, ARA and glycerophospholipid metabolism. The study provides us a novel mechanism to explain the improvement of hypothyroidism and associated dyslipidemia by COST, depicts a metabolic profile of hypothyroidism, and gives us another point cut for further exploring the biomarkers and pathogenesis of hypothyroidism.

Impact of serum eicosapentaenoic acid/arachidonic acid ratio on overall survival in lung cancer patients treated with pembrolizumab: a pilot study

This pilot study analyzed the dietary patterns of patients with non-small cell lung cancer undergoing initial pembrolizumab, an immune checkpoint inhibitor (ICI), treatment in the month before treatment. Serum fatty acid fractions and their associations with ICI treatment efficacy were also investigated. The results showed that long-term survivors (those who survived for ≥ 3 years) consumed significantly more seafood than short-term survivors (those who survived for < 3 years). Furthermore, the serum levels of eicosapentaenoic acid (EPA) as well as the ratio of EPA to arachidonic acid (EPA/AA) were higher in the long-term survivors than those in the short-term survivors. The group with a high serum EPA/AA ratio had a significantly higher overall survival rate after ICI treatment than the group with a low serum EPA/AA ratio. In conclusion, higher dietary seafood consumption may improve OS in lung cancer patients treated with ICI and the serum EPA/AA ratio may be a useful biomarker for determining the efficacy of ICI treatment. Thus, supplements that increase the serum EPA/AA ratio could serve as new nutritional interventions for enhancing the efficacy of ICI treatment. However, further large-scale case and intervention studies are required.

Antioxidant Status, Lipid Metabolism, Egg Fatty Acids, and Nutritional Index of White-Egg Laying Hens Fed Flaxseed Cake.

Flaxseed cake contains high levels of phenolic compounds, which have numerous biological activities, as well as a considerable amount of omega-3 fatty acids, such as α-linolenic acid, which remains after oil extraction. In this study, we examined the effects of flaxseed cake meal (FSCM) on the antioxidative status, lipid metabolism, egg fatty acid profile, and egg health index of white-egg laying hens. A total of 63 Hisex White laying hens were divided into three experimental treatment groups and fed diets containing 0, 5, or 10% FSCM from 48 to 58 weeks of age. Feeding with 5 and 10% FSCM did not significantly (p>0.05) influence total lipid, triglyceride, total cholesterol, very low-density lipoprotein-cholesterol, or low-density lipoprotein-cholesterol concentrations, or the high-/low-density lipoprotein ratio in the serum and egg yolk; however, 10% FSCM significantly (P<0.05) increased serum high-density lipoprotein. Dietary FSCM also did not affect (P>0.05) antioxidant markers in the eggs and blood plasma. Notably, dietary inclusion of FSCM significantly increased (P<0.05) total n-3 polyunsaturated fatty acids (PUFAs), α-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid levels in egg yolk, whereas the n-6:n-3 PUFAs ratio was markedly (P<0.05) decreased in a dose-dependent manner. Moreover, including 5-10% FSCM improved (P<0.05) egg health indices, with 10% being the most beneficial. Together, these findings indicated that the inclusion of up to 10% FSCM in laying hen diets improved egg yolk lipid and fatty acid profiles, as well as egg quality and nutritional and metabolic indices.

Tyrosol regulates hepatic lipid metabolism in high-fat diet-induced NAFLD mice.

This study aimed to elucidate the effect of tyrosol (TYR) on the amelioration of nonalcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were fed a low-fat diet (LFD), a high-fat diet (HFD), or a HFD supplemented with 0.025% (w/w) TYR (TYR) for 16 weeks. Following a 16-week intervention, the TYR cohort exhibited diminished final body weight and hepatic lipid accumulation, compared to HFD fed mice. Liver metabolomics analysis revealed that TYR increased the hepatic levels of spermidine, taurine, linoleic acid, malic acid and eicosapentaenoic acid (EPA), indicating the beneficial effect of TYR on lipid homeostasis. Using molecular docking analysis and the luciferase assay, we found that TYR acts as a ligand and binds with peroxisome proliferator-activated receptor-α (PPARα), which plays a pivotal role in the modulation of hepatic lipid metabolism, thereby activating the transcription of downstream genes. Our results suggest that TYR alleviates NAFLD in HFD-fed mice probably by the modulation of the PPARα signaling pathway.

Higher Plasma Omega-3 Levels are Associated With Improved Exacerbation Risk and Respiratory-Specific Quality of Life in COPD.

Omega-3 polyunsaturated fatty acids (PUFAs) have been associated with systemic anti-inflammatory responses. Dietary intake of omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has also been associated with lower chronic obstructive pulmonary disease (COPD) morbidity using self-report food frequency questionnaires. The objective of this study was to investigate the relationship between measured PUFA intake using plasma EPA+DHA levels and COPD morbidity. Former smokers with moderate-to-severe COPD living in low-income communities were enrolled in a 6-month prospective cohort study. Participants completed standardized questionnaires, spirometry, and plasma samples at 3-month intervals. Total plasma PUFAs were analyzed using gas chromatography/mass spectrometry for DHA and EPA concentrations. Linear or logistic mixed model regression was used to evaluate EPA+DHA's and COPD morbidity's association, accounting for demographics, lung function, pack years, comorbidities, and neighborhood poverty. A total of 133 plasma EPA+DHA samples from 57 participants were available. Participants exhibited average plasma EPA and DHA levels of 14.7±7.3µg/mL and 40.2±17.2µg/mL, respectively, across the 3 clinic visits. Each standard deviation increase in EPA+DHA levels was associated with 2.7 points lower St George's Respiratory Questionnaire score (95% confidence interval [CI] -5.2, -0.2) and lower odds of moderate exacerbation (odds ratio 0.4; 95% CI 0.2, 0.9), but lacked significant association with the COPD Assessment Test score (95% CI -2.4, 0.8), modified Medical Research Council dyspnea scale (95% CI -02, 0.2), or severe exacerbations (95% CI 0.3, 1.4). Plasma EPA+DHA levels are associated with better respiratory-specific quality of life and lower odds of moderate exacerbations in patients with moderate-to-severe COPD. Further research is warranted to investigate the efficacy of an omega-3 dietary intervention in the management of COPD morbidities.

Fatty acids profile in pregnancies affected by neural tube defects

Abstract This study aimed to determine if maternal fatty acids (FA) levels during pregnancy are associated with the occurrence of neural tube defects (NTDs) and to explore the correlation between FA and maternal vitamin D, homocysteine, vitamin B12, and folate in cases. Plasma FA composition was assessed using capillary gas chromatography. Comparisons between cases and controls were performed by independent samples t-test for continuous variables. Cases had significantly higher levels of heptadecanoic acid, linolelaidic acid, and arachidonic acid (ARA):(eicosapentaenoic acid+docosahexaenoic acid) ratio than controls (p &lt; 0.05). Nervonic acid, ARA, adrenic acid, eicosapentaenoic acid, docosahexaenoic acid, and omega-3 polyunsaturated fatty acids (n-3 PUFA) levels were significantly lower in cases (p &lt; 0.05). Maternal 25-hydroxyvitamin D (25(OH)D) levels were positively correlated with maternal polyunsaturated fatty acids and omega-6 polyunsaturated fatty acids. RBC folate levels were negatively correlated with n-3 PUFA. Further research is required to clarify the association of FA metabolism with NTDs.