BACKGROUND:Preterm infants are associated with reduced levels of long-chain polyunsaturated fatty acids (LCPUFAs), particularly arachidonic acid (ARA) and docosahexaenoic acid (DHA), due to interrupted third-trimester transfer. FADS gene variants may further influence endogenous LCPUFA synthesis and exogenous LCPUFA supplementation. METHODS:This pilot randomized single-center study included 33 preterm infants assigned to control (n = 12), 120:60 (120 mg/kg ARA + 60 mg/kg DHA; n = 10), or 160:80 (160 mg/kg ARA + 80 mg/kg DHA; n = 11). Supplementation was provided from birth to 36 weeks postmenstrual age. Blood samples were collected at birth and at 36 weeks PMA. Plasma phospholipid fatty acids were quantified by gas chromatography (mol% of total fatty acids). FADS variants (rs174545, rs174546, and rs174602) and their combinations were genotyped from oral mucosa DNA. RESULTS:In the 160:80 group, rs174602 allele distribution differed from controls, with higher CC homozygosity. In controls, rs174545 CC homozygosity correlated with ARA at baseline (ρ=0.666) and T4 (ρ=0.768). In the 160:80 group, rs174602 CC homozygosity correlated with ARA (ρ=0.661) and DHA (ρ=0.731) at T4. The GTT allelic combination was negatively associated with baseline ARA and DHA and with ARA at T4 in controls. CONCLUSIONS:FADS genetic variability influences baseline LCPUFA status and response to ARA:DHA supplementation in preterm infants. rs174545, rs174546, rs174602, and their allelic combination are associated with differential fatty acid management, supporting the integration of genetic profiling into individualized nutritional strategies.
BACKGROUND:The FADS Indel insertion-deletion polymorphism (rs66698963) modulates fatty acid desaturase 1 (FADS1), which converts di-homo-γ-linolenic acid (DGLA) to arachidonic acid (ARA). Adults homozygous for the I allele (I/I) have up to 84% higher ARA/DGLA ratios than D homozygotes (D/D), with heterozygotes intermediate. Whether this relationship extends to preterm neonates is unknown. ARA is the precursor to prostaglandin E2 (PGE2), a key mediator of ductal patency. Elevated ARA synthesis may contribute to patent ductus arteriosus (PDA). HYPOTHESIS:I/I infants have greater ARA/DGLA ratios, higher PDA incidence, and more catheter-based closures than D/D genotype. METHODS:We prospectively enrolled 65 premature infants (mean gestational age 28 weeks). Blood fatty acids were analyzed by gas chromatography and genotype by PCR. Genotype associations with outcomes were assessed using Fisher's exact test, Cochran-Armitage trend test, and logistic regression. Fatty acid comparisons used Welch's t-test and one-way ANOVA. RESULTS:Genotypes were D/D in 26 infants (40%), I/D in 31 (48%), and I/I in 8 (12%). The ARA/DGLA ratio was 33% higher in I/I than D/D infants (ANOVA p=0.029; Welch's t-test p=0.04) and remained significant after gestational-age adjustment (p=0.025). PDA rates increased nonsignificantly from D/D (42%) to I/D (45%) to I/I (50%) (Cochran-Armitage p=0.70; OR=1.15, p=0.70). Among 29 with echo-confirmed PDA, spontaneous closure rates were 60%, 31%, and 50%; six required Piccolo occlusion. Gestational age did not differ by genotype (p=0.68). CONCLUSIONS:The FADS Indel significantly modulates ARA/DGLA in preterm infants, consistent with adults. PDA associations were nonsignificant, but trends warrant study in larger cohorts.
Vegetarian and vegan diets are consistently associated with reduced cardiometabolic risk, despite providing minimal amounts of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs), key precursors of bioactive lipid mediators, raising questions about n-3 PUFAs metabolism and requirements in plant-based populations. This review examines current evidence on the metabolic fate of alpha-linolenic acid (ALA), its conversion to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the implications for n-3 PUFAs-derived signaling pathways. Although conversion efficiency is limited, it is influenced by dietary and non-dietary factors and may be supported by adaptive mechanisms that preserve tissue DHA. Individuals following plant-based diets exhibit lower EPA and DHA status, yet maintain favorable health profiles, suggesting that overall dietary context and endogenous regulation may mitigate reduced intake of preformed n-3 PUFAs. Targeted strategies, including optimizing ALA intake and using algae-derived EPA/DHA, effectively improve biomarker status. Understanding these mechanisms may help redefine n-3 PUFAs requirements in plant-based populations.
Polyunsaturated fatty acids (PUFA), particularly long-chain and very-long-chain PUFA (LC- and VLC-PUFA), are essential structural and functional compounds of the vertebrate retina. Their availability depends on dietary supply and endogenous biosynthesis, yet how environmental factors modulate retinal lipid composition fish species remains poorly understood. Here, we investigated the effects of diet quality, light regime, and temperature on retinal lipid composition in common carp (Cyprinus carpio), one of the most consumed fish species worldwide, using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to resolve lipid distributions across retinal layers.Carps were exposed for six months to a fully factorial combination of low vs. high LC-PUFA diets, light vs. dark conditions, and stable vs. fluctuating temperatures. Retinal lipidomes showed strong layer-specific organization, with outer retinal layers enriched in docosahexaenoic acid-containing phospholipids and VLC-PUFA. Across all layers, dietary PUFA exerted the strongest influence: high-LC-PUFA diets increased n-3 PUFA-containing phospholipids while consistently reducing arachidonic acid–containing species. Only two VLC-PUFA (30:6 and 32:6) were detected in the photoreceptor-associated regions of the retina.Low light conditions reduced the lipid abundance in the outer retina, including VLC-PUFA, suggesting reduced photoreceptor membrane turnover under diminished visual demand. Elevated temperatures induced subtler shifts, favouring shorter and less unsaturated fatty acids. These results demonstrate that the lipid composition of the retina in carp is highly plastic and sensitive to dietary PUFA supply, while light and then temperature act as secondary modulators. Our findings connect dietary lipid supply to retinal structure and function, offering an ecological perspective on sensory plasticity in heterogenous aquatic habitats, such as shallow and turbid fishponds.
Alcohol-associated liver disease (ALD) is a main health issue worldwide, which is reported as the second leading cause for liver transplantation. Chronic or heavy alcohol use exerts adverse effects on the liver, leading to dysregulated lipid metabolism, inflammatory response, generation of oxidative stress, and fibrosis. Emerging evidence has shown that chronic or heavy alcohol consumption alters the production of cyclooxygenase (COX)-mediated eicosanoids, including thromboxane A2 (TXA2), prostaglandin E2 (PGE2), prostaglandin I2 (PGI2), prostaglandin D2 (PGD2), and prostaglandin F2α (PGF2α), in the liver. These eicosanoids play diverse roles in altering steatosis, inflammation, oxidative stress, vascular dysfunction, fibrogenesis, and impaired liver regeneration in different liver diseases. In this review, we evaluate the roles of COX-mediated eicosanoids in mediating the pathogenesis of ALD. Of note, emerging evidence suggests that COX-mediated eicosanoids exert distinct effects in ALD: TXA2 largely drives inflammation and fibrosis, PGI2 and PGD2 show predominantly protective or reparative roles, and PGE2 displays effects that vary depending on receptor subtype and experimental model. Additionally, key knowledge gaps regarding those eicosanoids were identified, including poor understanding of receptor‑specific downstream signaling pathways, limited use of hepatic cell‑specific genetic models, and insufficient study of inter‑organ crosstalk in ALD progression. We also provide future directions aimed at answering these questions and eventually provide insight into the development of effective interventions for ALD by targeting COX‑mediated eicosanoid-related pathways.
In this randomized, double-blind, placebo-controlled trial, 72 healthy vegan adults (aged 19–57 years) received a multinutrient supplement consisting of a vitamin and mineral supplement (providing 26 µg vitamin D) and an omega-3 supplement administered in either a single dose (EPA 98.7 mg, DHA 171.0 mg, additional vitamin D 36 µg, vitamin E 3.7 mg) or a double dose (EPA 197.4 mg, DHA 342.0 mg, additional vitamin D 72 µg, vitamin E 7.4 mg) or placebo capsules for 4 months. Nutrient biomarkers were assessed at baseline and at the end of the intervention after 4 months. An analysis of covariance was employed to test for between-group differences (p < 0.05) and adjusted for multiple testing using the Bonferroni-Holm method. Compared to the control group, which showed on average a significant decline in both the omega-3-index and 25-hydroxyvitamin D, participants in both intervention groups demonstrated significant increase in these parameters (p < 0.001). Although the double dose group exhibited numerically greater increases in omega-3 index and vitamin D compared to the simple dose group, the differences between these dosing regimens were not statistically significant. As expected, vitamin E levels remained unchanged, reflecting its inclusion solely for antioxidative protection in the omega-3 supplement rather than as a critical nutrient in vegan diets. In conclusion, supplementation significantly improved omega-3 and vitamin D status in healthy vegans, with no significant benefit from doubling the dose. Although clinical endpoints were not evaluated, improved nutrient status may have potential implications for health.The study has been registered at the German Clinical Trials Register (DRKS00028151).
Obesity and overweight are characterized by persistent low-grade inflammation. Specialized pro-resolving mediators (SPMs), polyunsaturated fatty acid-derived metabolites, actively promote inflammatory resolution, and their dysregulation has been linked to unresolved inflammation and metabolic disturbances in obesity. This systematic review synthesized human and animal evidence on adiposity-related differences and associations in SPMs and SPM precursors. The protocol was prospectively registered in PROSPERO (CRD420251067464). PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched up to 22 May 2026. Eligible studies included human and animal research comparing SPMs and/or SPM precursors between overweight/obese and normal-weight/lean groups or assessing their associations with adiposity indices. Due to heterogeneity across matrices and analytical platforms, findings were synthesized narratively. Twenty-seven unique studies were included, providing 28 experimental datasets (14 animal and 14 human). The most consistent alterations were observed in adipose tissue and circulation, where overweight/obesity was frequently associated with lower concentrations of SPMs and/or SPM precursors. In humans, circulating Resolvin E1 showed reproducible reductions and was inversely associated with adiposity measures in several cohorts. In contrast, selected metabolites, including SPM Lipoxin A4 and the SPM precursors 15-HETE and 18-HEPE, exhibited mixed directionality across studies. Evidence for hepatic and central nervous system compartments was limited and heterogeneous. Overall, available evidence suggests that excess adiposity is associated with altered SPM and precursor profiles, most consistently in adipose tissue and circulation, whereas hepatic and central nervous system findings remain inconsistent. Future studies using standardized quantification and tissue-specific designs are needed to clarify whether targeting pro-resolving pathways has translational potential in obesity-related metabolic dysfunction.
BACKGROUND:Preclinical and limited human data suggest long-chain omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may be protective of brain volume and amyloid-beta (Aβ) accumulation, hallmarks of Alzheimer's disease (AD), which may be modulated by Apolipoprotein E ε4 (APOE4) carriage. METHODS:This cross-sectional study was conducted using baseline data from a clinical trial at the University of Kansas Medical Center that included cognitively normal older adults, enriched for preclinical AD. We investigated serum DHA+EPA's (% total triacylglycerol fatty acids) relationship with MRI-derived gray matter volume and PET-derived Aβ burden (Florbetapir F18) overall and by APOE4 carriage status. RESULTS:Among all participants (n = 104, 67.3% female, 69.2% preclinical AD, 44.2% APOE4), higher DHA+EPA was related to larger gray matter volume in a left precuneus/postcentral gyrus cluster, with similar relationships between APOE4 carriers and non-carriers. Higher DHA+EPA was also related to lower brain Aβ in the frontoparietal cortex, bilaterally. In APOE sensitivity analyses, higher DHA+EPA was related to lower global and AD-related regional brain Aβ among APOE4 carriers . CONCLUSIONS:Higher DHA+EPA was associated with larger gray matter volume and lower Aβ in AD-susceptible regions, especially among APOE4 carriers. These findings are consistent with the hypothesis that omega-3 fatty acids influence brain volume and Aβ. Well-designed DHA+EPA supplementation RCTs are needed as DHA supplementation RCTs have inconsistently impacted brain volume and no RCTs investigating the impact of omega-3 on brain Aβ have been reported. TRIAL REGISTRATION:NCT02000583 (https://clinicaltrials.gov/study/NCT02000583?term=NCT02000583&viewType=Card&rank=1) registered on November 26, 2013.
Arachidonic acid is a long chain polyunsaturated fatty acid and precursor to bioactive lipid molecules contributing to inflammation and vasoregulation. Placental arachidonic acid metabolites (including oxylipins) are involved in maternal adaptation to pregnancy and fetoplacental development, and are considered biomarkers of pregnancy complications and delivery timing. Arachidonic acid metabolic pathway enzymes (including COX, LOX, CYP) have been studied in human placenta, but the role of epoxide hydrolases (responsible for degradation of CYP-dependent metabolites-epoxyeicosatrienoic acids) is not as widely researched. We hypothesized that fetal growth restriction (FGR) and gestational age both independently affect placental arachidonic acid metabolism and expression and activity of epoxide hydrolases. Placenta tissue samples were collected: Cohort 1 included women with healthy term pregnancy (HT), preterm birth (PT), or FGR (birth weight <5th centile). Cohort 2 included women with HT pregnancy or FGR (same criteria). Cohorts were analyzed separately. Placental lipids (arachidonic acid-derived oxylipins) were extracted and quantified using LC-MS/MS. Placental abundance of arachidonic acid metabolites in COX, LOX, sEH and autooxidation pathways were lower in PT compared to HT (p<0.05). No differences were found in CYP pathway lipids and no significant differences detected between HT and FGR for any measured lipid. Increased placental content of oxylipins across the second half of pregnancy likely contributes to labor initiation signaling, xenobiotic protection and, importantly, increased lipid transfer to support fetal brain and somatic growth. Our data indicates that studies of placental lipid signaling must include carefully gestational age-matched controls in order to correctly identify changes of pathologic interest.
OBJECTIVE:Intermittent fasting (IF) has emerged as a dietary intervention with potential effects on metabolic health and inflammatory processes. However, clinical evidence for its benefits remains inconsistent, despite numerous biochemical indications. Polyunsaturated fatty acids (PUFAs), as precursors of bioactive lipid mediators, may represent a potential mechanism through which dietary interventions such as IF exert anti-inflammatory and metabolic effects. Therefore, we investigated changes in blood fatty acid (FA) composition and associated metabolic endpoints during IF. METHODS:Thirty-nine normal-weight and overweight/obese participants followed a 16:8 IF regimen. Body weight, body mass index (BMI), routine lipid and liver parameters, and blood FA composition, quantified by gas chromatography with flame ionization detection (GC-FID), with a focus on omega-6 and omega-3 PUFAs (n-6 and n-3 PUFAs), were assessed at baseline and after 4 weeks. RESULTS:IF induced plasma FA mobilization and a higher n-6/n-3 ratio in normal-weight participants. Across the cohort, arachidonic acid (AA) and the Delta-5-desaturase (D5D) index increased while the eicosapentaenoic acid/AA (EPA/AA) ratio decreased. Red blood cell FA composition remained largely unchanged. In contrast, overweight/obese participants showed minimal changes in FA profiles but significant metabolic improvements, including reductions in body weight, BMI, liver fat content, and γ-glutamyl transferase (GGT). CONCLUSION:IF results in weight-dependent alterations in plasma FAs. Normal-weight individuals showed a predominance of n-6 PUFAs, whereas FA profiles in overweight/obese participants remained stable despite metabolic improvements. Overall, IF may exert a more pronounced effect on inflammatory pathways in normal-weight individuals, reflected by increased availability of AA, whose inflammatory significance remains unclear.
Prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), prostacyclin and their analogues are widely used in clinical practice for their potent biological effects. PGE1/PGE2 analogues, including misoprostol and sulprostone, are primarily used in obstetrics for labour induction, abortion, and postpartum haemorrhage management, whereas PGI2 analogues such as iloprost and treprostinil are key drugs in pulmonary arterial hypertension treatment. Despite structural similarities, these compounds produce contrasting vascular effects due to differences in receptor selectivity, signalling pathways, and tissue distribution. PGE1/PGE2 analogues activate EP receptors, particularly EP1 and EP3 with varying selectivity profile, promoting vasoconstriction and have been associated with cardiovascular complications such as coronary vasospasm. In contrast, PGI2 analogues act mainly on IP receptors, promoting vasodilation, inhibition of platelet aggregation, and beneficial vascular remodelling, with a generally favourable cardiovascular safety profile. Although cardiovascular effects have been reported with both classes of analogues, the underlying mechanisms, and especially their direct effects on human coronary arteries (HCA) remain insufficiently explored. In this context, we combined a review of the clinical and experimental literature that integrates clinical reports with original ex vivo pharmacological investigations on isolated HCA. Both PGE2 and misoprostol induce concentration-dependent vasoconstriction, primarily via EP3 receptors, which is significantly reduced by a TP receptor antagonist, suggesting a potential EP3-TP pathway interaction. All tested PGI2 analogues consistently induced relaxation in our HCA preparations, a finding that aligns with their general improvement of cardiovascular clinical parameters, with only rare exceptions. Together, these findings summarize the cardiovascular effects of clinically-used prostanoids and provide mechanistic insights to optimize their therapeutic use while minimizing cardiovascular risk.
BACKGROUND:Despite evidence that omega-3 supplementation reduces early preterm birth, population-level data on the distribution of fatty acids in pregnancy are limited. Statewide early-pregnancy screening data were used to describe serum fatty acid profiles. METHODS:We analysed serum fatty acid classes (saturated, monounsaturated, omega-6 polyunsaturated fatty acids [PUFA] and omega-3 PUFA) from women in South Australia's Omega-3 Test-and-Treat Program (Apr 2021-Apr 2025). Samples collected at <20 weeks' gestation were measured by gas chromatography (% total fatty acids). Total omega-3 PUFA (alpha-linolenic acid + eicosapentaenoic acid [EPA] + docosapentaenoic acid + docosahexaenoic acid [DHA]) was classified as low (<3.7%), moderate (3.7-4.3%) or sufficient (>4.3%). RESULTS:Among 26,389 samples, omega-6 PUFA was highest (median 36.9%), followed by saturated fatty acids (31.6%), monounsaturated fatty acids (26.2%), and omega-3 PUFA (4.4%). Total omega-3 PUFA, DHA and EPA were right-skewed, whereas arachidonic acid (AA) had a narrow distribution. Overall, 16.1% were classified as low total omega-3, 26.7% were moderate and 57.2% sufficient. Compared with samples classified as sufficient, those with low omega-3 had higher linoleic acid (29.0%vs 26.9%) and slightly lower AA (6.2%vs 7.1%). The clinically validated cut-off for low omega-3 (<3.7%) was similar to one standard deviation below the cohort mean (mean -1 SD = 3.47%). CONCLUSION:Around one in six samples had low serum total omega-3 status. These data quantify early-pregnancy serum fatty acid profiles and demonstrate the clinically validated low omega-3 cut-off lies in the lower tail of the population distribution, providing context for biomarker-guided screening in pregnancy.
OBJECTIVE:Low inflammation associated with fish intake may reflect not only the amount of fish consumed but also its nutrient composition and related lifestyle factors. This study investigated the relationship between fish intake, estimated n-3 polyunsaturated fatty acid (n-3 PUFA) intake, lifestyle behaviors, and the systemic immune-inflammation index (SII), a composite marker of atherosclerotic cardiovascular disease (ASCVD). METHODS:We conducted a cross-sectional study of 8675 participants (mean age: 46.7 ± 13.0 years; 59% men) undergoing health check-ups between April 2019 and March 2020. Fish intake was assessed using a self-reported questionnaire on weekly consumption frequency. Estimated weekly fish and n-3 PUFA intake were calculated by combining intake frequency with age- and sex-specific average intake data derived from the Japanese National Health and Nutrition Survey. RESULTS:The average fish intake was 143 ± 88 g/week. Higher fish intake was significantly associated with lower SII levels (p < 0.0001). In multivariable regression analysis, higher fish intake and aerobic exercise were independently associated with lower SII, whereas shorter sleep duration was associated with higher SII. The proportion of participants engaging in aerobic exercise increased across fish intake categories. Mediation analysis suggested that estimated n-3 PUFA intake substantially contributed to the association between fish intake and lower SII. CONCLUSION:The anti-inflammatory effects associated with fish intake may be partly explained by n-3 PUFA intake, along with related lifestyle factors. These findings highlight the importance of considering fish consumption alongside broader dietary and behavioral patterns that influence systemic inflammation.
BACKGROUND:Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are important long-chain polyunsaturated fatty acids involved in fetal and infant brain development, synaptogenesis, neurogenesis, and neuronal membrane function. DHA accretion is highest from the third trimester of pregnancy through the first two years of life, representing a critical period for neurodevelopment. OBJECTIVE:This narrative review summarizes current evidence on the role of maternal DHA in infant neurodevelopment, with particular emphasis on Indian populations, including maternal dietary intake, maternal-fetal transfer, human milk composition, pregnancy outcomes, and supplementation studies. METHODS:Relevant pre-clinical and clinical studies were identified through searches of PubMed, Embase, Google Scholar, and related databases. Studies addressing maternal dietary patterns, fatty acid composition in maternal blood and human milk, placental transfer, and infant neurodevelopmental outcomes were reviewed, with special focus on evidence from India. RESULTS:Available evidence indicates that maternal omega-3 fatty acid intake and human milk DHA concentrations in Indian populations are generally lower than those reported in many Western populations, likely due to limited seafood consumption and higher intake of omega-6-rich vegetable oils. Maternal DHA supplementation has been shown to improve maternal DHA status; however, evidence regarding benefits on infant neurodevelopmental outcomes remains inconsistent. Experimental studies also suggest potential interactions of DHA with other nutrients, including vitamin B12 and folate, which may influence neurodevelopment. CONCLUSION:Suboptimal maternal DHA intake and imbalanced dietary n-6/n-3 fatty acid ratios may contribute to lower maternal and human milk DHA status in Indian populations. Further well-designed studies are required to clarify the effects of maternal DHA supplementation on infant neurodevelopment and to evaluate integrated nutritional strategies during pregnancy and lactation.
Objectives An appropriate nutritional environment is crucial for both the mother’s health and that of the developing fetus. Alpha-linolenic acid (ALA) serves as a precursor to docosahexaenoic acid (DHA), a n-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) required for placentation and fetal brain development. Chia seeds are particularly rich in ALA, however, although its benefits to offspring’s health are well established, the extent to which ALA is converted into fetal n-3 LCPUFA, particularly DHA, remains unclear. The high-fat, high-sugar Western diet is a major contributor to obesity and typically contains low levels of n-3 LCPUFA and DHA. Using a rat model of diet-induced obesity, we investigated whether supplementing chia seeds to a high-fat-high-sugar (HFS) diet enhances DHA levels in maternal tissue and circulation, and increases its availability in the placenta and fetal brain at gestational days 15 (G15) and 20 (G20). Methods Female Wistar rats were fed an HFS diet for 6 weeks before mating. They were then divided into two groups during gestation until G15 or G20. One group continued on the HFS diet (n=7), while the other group was fed a HFS diet supplemented with chia seeds (HFSChia, n=7-9). Results We demonstrated that the HFSChia diet increased ALA, eicosapentanoic acid (EPA) and DHA levels in the liver at G15 and G20. This increased the incorporation of DHA into lipid complexes in the maternal liver, adipose tissue, and peripheral circulation. Furthermore, placental enrichment of n-3 LCPUFA, accompanied by enhanced expression of lipid transporters suggested an increased capacity of n-3 LCPUFA transfer to the fetus, as did enhanced DHA concentrations in fetal brain phospholipids from mid-gestation onwards. Conclusion Supplementing a HFS diet with chia seeds increased maternal n-3 LCPUFA levels and enhanced the placental transfer capacity of DHA to the fetal brain, which may support optimal neurodevelopment in a context of obesity.
Cancer therapy remains challenged by limited treatment efficacy, cancer-related malnutrition and substantial toxicity, underscoring the need for novel strategies to improve therapeutic responses. Omega-3 fatty acids, particularly docosahexaenoic acid (DHA), exhibit both nutritional and bioactive properties, including anti-inflammatory effects and the ability to enhance tumor cell susceptibility to oxidative stress and ferroptosis. To improve stability and delivery, omega-3 fatty acids can be formulated into nanoemulsions that facilitate cellular uptake and may potentiate anticancer therapies. Therefore, we developed a panel of nanoemulsions with defined omega-3 and 9 fatty acid profiles derived from algae, fish and olive oils. All formulations exhibited high physicochemical stability, nanoscale droplet sizes and compendial quality. While pure oil showed minimal biological activity, nanoemulsification markedly increased cytotoxicity, and the novel DHA-rich algae oil emulsion displayed strong and selective antitumor effects without affecting normal fibroblasts. Combination studies indicated tumor type-dependent enhancement of chemotherapeutic efficacy. RNA sequencing indicated activation of ferroptosis-associated pathways and suppression of DNA replication and cell-cycle progression by the novel DHA-rich algae oil emulsion. To expand translational relevance for tumor specific target therapies, a HER2⁺/ER⁻ patient-derived breast cancer cell line and matched cancer-associated fibroblasts were established and characterized. In conclusion, these findings identify the new formulation prototype as a selective and biologically active nanocarrier for DHA which is capable of enhancing tumor type specific therapies, selective chemotherapeutic efficacy and potentially inducing ferroptosis-driven antiproliferative programs. These results highlight the promising potential of DHA as lipid component in a nanoscale droplet size formulation for future combination cancer therapies.
Intravenous lipid emulsions are essential components of nutrition for preterm infants. The aim of this scoping review was to assess the evidence base for intravenous lipid emulsions with and without fish oil for preterm infant health outcomes. We searched PubMed up to May 2024 and found six systematic reviews with meta-analyses (synthesizing results of 22 randomized controlled trials and five observational studies), one narrative review (including four publications from three randomized controlled trials and four observational studies, without meta-analysis) reporting 10 infant outcomes. Results were largely null but limited by small samples, study quality, and heterogeneity in duration, dose, and timing of intravenous lipid emulsions, as well as participants characteristics and measurement of outcomes. The evidence does not support or refute that parenteral nutrition with or without fish oil is better for preterm infants, but further research is needed for robust evidence.
Inflammation represents a critical factor in carcinogenesis, and cysteinyl leukotrienes (CysLTs) have been associated with tumor development and progression. Thus, it has been hypothesized that leukotriene receptor antagonists (LTRAs), widely used in the treatment of asthma, could exert a chemopreventive effect due to the modulation of inflammatory pathways. However, the association between LTRAs and cancer risk among asthma patients is still not fully understood. Medline, Scopus, Web of Science, and the Cochrane Library were searched from inception to August 2, 2025 for studies including patients with asthma that have used LTRAs reporting cancer risk. Statistical analysis was made in R software, with hazard outcomes using hazard ratio (HR) by applying Inverse variance random-effect models. P values <0.05 were set as statistical significance. Five studies involving 281,420 individuals, of which 128,188 were LTRAs users. The use of LTRAs significantly reduced cancer risk (HR: 0.60; 95 % CI: 0.40-0.89; p = 0.011), and this was consistent in individuals <65 years (HR: 0.8729; 95 % CI: 0.8479-0.8985; p < 0.001) as well as in those ≥65 years (HR: 0.7510; 95 % CI: 0.7110-0.7933; p < 0.001). Additionally, our data support that the use of LTRAs decreases the risk of urological cancer (HR: 0.91; 95 % CI: 0.8593-0.98;p = 0.014). Moreover, our study showed that the use of LTRAs does not appear to influence the risk of lung cancer (HR: 0.64; p = 0.086), brain cancer (HR: 0.78; p = 0.343), breast cancer (HR: 0.28; p = 0.239), colorectal cancer (HR: 0.56; p = 0.183), gastric cancer (HR: 0.57; p = 0.108), liver cancer (HR: 0.54; p = 0.099), pancreatic cancer (HR: 0.64; p = 0.432), or skin cancer (HR: 1; p = 0.95).This is the first meta-analysis to mention the potential chemopreventive action of LTRAs and their impact on cancer risk among patients with asthma. Our findings support that LTRAs are safe and that their prolonged use in asthma may reduce the overall risk of cancer, especially urological cancers.
BACKGROUND:Metabolism of docosahexaenoic acid (DHA), an omega-3 (Ω3) fatty acid (FA), differs between carriers of the epsilon 4 allele of the apolipoprotein E (APOE4)-the main genetic risk factor for late-onset Alzheimer's disease-and APOE3 carriers. Dietary DHA has been shown to prevent cognitive decline in APOE4 carriers. However, whether DHA must be consumed the whole life is unclear. We hypothesized that a DHA intake started later in life and for a shorter duration prevents cognitive decline in APOE4 mice. OBJECTIVE:To investigate three dietary durations of DHA on the prevention of cognitive decline in APOE4 mice. METHODS:Mice knock-in for the human APOE3 (control, n = 84; 34 males/50 females) or APOE4 (n = 84; 39 males/45 females) allele were fed either a DHA-free control diet for 8 months or a diet rich in calcium salt DHA (0.5 g DHA/100 g diet) for 2, 4 or 8 months. Recognition memory was assessed using the novel object recognition test. DHA was quantified using gas chromatography. RESULTS:APOE4 mice fed the control diet did not recognize the novel object as the APOE3 mice did suggesting cognitive decline in APOE4 mice. However, a DHA-Ca rich diet for 2 and 4 months prevented cognitive deficits in males (2M-P = 0.0414, 4M-P = 0.0073) and females (2M-P < 0.0001). 2-months DHA-Ca rich diet was associated with 18-25% higher cortical relative percentage of DHA in females and males compared to the control diet (Females-P = 0.0031; Males-P = 0.0010). CONCLUSION:In APOE4 mice, it is not necessary to consume DHA-calcium salt throughout life to prevent cognitive decline.
