Omega-6 (GLA)

BACKGROUND: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication. Altered fatty acid (FA) metabolism may contribute to GDM development, yet evidence regarding specific circulating FAs remains inconclusive. OBJECTIVE: This systematic review and meta-analysis compared circulating FA profiles between pregnant women with and without GDM and examined their associations with GDM risk. METHODS: We searched PubMed, Scopus, and Web of Science for observational studies reported circulating FAs in relation to GDM risk. Pooled standardized mean differences (SMDs) and odds ratios (ORs) were calculated using random-effects models. Subgroup analyses explored heterogeneity sources, and the Newcastle-Ottawa Scale assessed risk of bias (RoB). RESULTS: Forty-four studies were included. Meta-analysis of ORs indicated that per one-SD increase, C16:0 was associated with higher GDM odds (OR: 1.20, 95%CI: 1.04, 1.38). Conversely, very-long-chain saturated FAs (C22:0 and C24:0), specific omega-6 FAs (C18:2, C20:2, and C22:4) were associated with lower odds. SMD analysis revealed significantly lower circulating levels of C22:0, C15:0, and C17:0 in women with GDM. Subgroup analyses identified FA form (e.g., free FAs vs. phospholipids) as a significant heterogeneity source for eight FAs, measurement unit (absolute concentration vs. relative percentage) for three FAs, while RoB, study design, and trimester were sources for limited specific FAs. CONCLUSIONS: GDM is associated with distinct circulating FAs patterns. C16:0 is associated with higher odds of GDM, whereas linoleic acid, very-long-chain Saturated FAs, and selected omega-6 FAs were related to lower odds. PROSPERO REGISTRATION CODE: CRD42025649380.

Inter-individual responses to omega-3 and omega-6 polyunsaturated fatty acid (PUFA) interventions vary substantially, complicating standardized dietary recommendations and suggesting a role for genetic differences that influence fatty acid biosynthesis, metabolism, and downstream health effects. A PRISMA 2020-guided systematic search of PubMed, Embase, and Web of Science identified adult studies assessing nutrigenetic interactions in the context of PUFA interventions and outcomes, yielding 132 eligible studies (79 Tier 1; 53 Tier 2) that collectively indicate pathway-specific genetic control of PUFA handling. Across 38 studies (combined n ≈ 500 000), variants in FADS1/FADS2 were consistently associated with genotype-dependent differences in long-chain PUFA synthesis, with minor allele carriers showing ∼40-60% lower conversion efficiency (14 studies reported significant interactions). In 25 studies (n ≈ 930 000), APOE ε4 carriage was associated with attenuated DHA responses to supplementation (≈20-31% lower) and markedly faster DHA turnover (≈77% shorter half-life), with significant interactions reported in 13 studies. Additional loci showed context-dependent effects, including lower type 2 diabetes odds among TCF7L2 TT carriers with high omega-3 intake (∼42% reduction) and substantially greater EPA uptake among FABP2 Thr54 carriers (up to ∼12-fold). Overall, genetic variation appears to shape omega-3 and omega-6 PUFA bioavailability and metabolism through mechanistically coherent pathways, providing a plausible explanation for inconsistent population-level intervention effects and supporting a shift toward genetically informed precision nutrition strategies for both PUFA families.

BACKGROUND: Diabetic Retinopathy is a significant microvascular complication of diabetes mellitus characterized by progressive damage to the retinal vasculature. Current management strategies focus on modifying risk factors and treating established disease. Omega-3 polyunsaturated fatty acids (PUFAs) demonstrate anti-inflammatory, antioxidative, and vasculoprotective properties. OBJECTIVES: To evaluate the protective effects of omega-3 fatty acids on DR incidence, progression, and microvascular health across diverse diabetic populations. METHODS: A comprehensive literature search was conducted via PubMed, EBSCO Open Research, ScienceDirect, Wiley Online Library, and Google Scholar. A reviewer screened the potential articles against prespecified eligibility criteria. The risk of bias in the eligible studies was then evaluated using the Newcastle Ottawa Scale (NOS), a Risk of Bias visualization tool developed by the Cochrane Collaboration (ROB 2.0). Data were then systematically extracted and analyzed. RESULTS: Fourteen studies involving 139,879 participants were analyzed. Omega-3 fatty acid intake of ≥500 mg/day significantly reduced the risk of sight-threatening diabetic retinopathy (DR) by 48% (HR = 0.52; 95% CI: 0.31-0.88; p = 0.001). Subgroup meta-analysis showed a stronger associated protective effect in type 2 diabetes (T2D) compared to type 1 (T1D), with a pooled hazard ratio of 0.71 (log HR = -0.339; SE = 0.0667; p < 0.000001). The antioxidant benefits were linked by a pooled mean difference of -1.399 in oxidative stress markers (MDA/TBARS) (95% CI: -1.432 to -1.366; Z = 83.29; p < 0.00001), with no significant heterogeneity (I² = 0%). Further stratification showed robust effects in both RCTs (HR = 0.743; p = 0.002) and non-RCTs (HR = 0.514; p = 0.005). These findings support omega-3s-especially in T2D-as a non-pharmacologic intervention for DR prevention, likely through anti-inflammatory and vasoprotective mechanisms. CONCLUSION: Omega-3 fatty acid intake is associated with dose-dependent protection against diabetic retinopathy, with the greatest benefits from whole food sources, optimal omega-6/omega-3 ratios, and in well-controlled T2D patients.

Findings on the associations of dietary/tissue levels of omega-6 polyunsaturated fatty acids (n-6 PUFAs) with the risk of colorectal cancer (CRC) are conflicting. We conducted a dose-response meta-analysis to assess the associations of dietary/tissue levels of n-6 PUFAs [total, linoleic acid (LA), and arachidonic acid (AA)] with CRC risk in adults. Twenty prospective cohort studies with a total sample size of 787,490 participants were included. Comparing extreme intake levels of LA revealed the summary relative risks (RR) of 1.15 (95% confidence interval (CI): 1.05-1.27) for CRC, and 1.30 (95% CI: 1.00-1.68) for rectal cancer, indicating a significant positive association for LA. However, neither total n-6 PUFAs nor AA were associated with cancers. A significant positive association was also found between a 1 gr/day increase in dietary LA intake and risk of colon cancer (RR: 1.01, 95% CI: 1.00-1.02). There were no significant associations between tissue levels of total n-6 PUFAs (RR: 0.94, 95% CI: 0.75-1.19), LA (RR: 0.93, 95% CI: 0.61-1.41), and AA (RR: 0.97, 95% CI: 0.70-1.33) and CRC risk. In conclusion, these findings suggest that dietary intake, but not tissue levels, of LA was associated with an increased risk of colorectal, colon, and rectal cancers. (PROSPERO registration: CRD42024516584). © 2025. The Author(s).

PURPOSE: This study aims to comprehensively analyze the intricate relationship between unsaturated fatty acids (UFAs, particularly omega-3 and omega-6 UFAs) and acne, from their clinical therapeutic effects to their underlying genetic regulatory mechanisms, to elucidate the role of UFAs in acne pathogenesis. METHODS: Clinical evidence synthesis: we systematically reviewed randomized controlled trials (RCTs) to evaluate the impact of UFA supplementation on acne treatment outcomes. Genetic analysis: two-sample Mendelian randomization (MR) analysis we used to investigate causal relationships between serum UFA metabolites and acne, identifying potential key regulatory enzymes. RESULTS: The synthesis of these RCT studies confirmed that UFA supplementation improved acne conditions. MR analysis revealed causal links between three serum UFA metabolites and acne, with dihomo-gamma-linolenic acid (DGLA) (OR = 8.457; 95% CI: 2.367-30.214; P-value = 0.001) as a risk factor and arachidonic acid (AA) (OR = 0.209; 95% CI: 0.071-0.618; P-value = 0.005) and eicosapentaenoic acid (EPA) (OR = 0.318; 95% CI: 0.102-0.991; P-value = 0.048) as protective factors. Functional annotation suggested enzymes such as Δ5 desaturase (FADS1) and Δ6 desaturase (FADS2) may play a role in acne regulation. CONCLUSION: This study offers evidence that supports a connection between UFAs and acne, examining this relationship from both clinical and genetic angles. These findings highlight the role of specific UFAs and their associated metabolic enzymes in the development of acne. Omega-3 UFAs seem to have a protective effect against acne, whereas certain types and ratios of omega-6 UFAs might contribute to acne formation. The varied impacts of UFAs on acne could be attributed to disease processes mediated by specific enzymes. However, the study's limitations include its genetic analysis being primarily based on European populations, which limits the applicability of the findings to other groups. Future research should aim to include a more diverse range of participants to improve the generalizability of the results. © 2025. Springer-Verlag GmbH Germany, part of Springer Nature.

BACKGROUND: Despite the significant increase in omega-6 fatty acid consumption, evidence regarding their health impacts remains inconsistent. This study performs an umbrella review and updated meta-analysis to evaluate the association between dietary and circulating omega-6 levels and the risks of cardiovascular diseases (CVDs), cancer, and mortality. METHODS: A systematic search was conducted in PubMed, Scopus, and Web of Science until January 2024 to identify eligible meta-analyses of prospective observational studies. The Cochrane risk of bias and GRADE tools were used to assess the risk of bias and certainty of the evidence, respectively. RESULTS: Analysis of 150 publications revealed that higher dietary intake and circulating levels of omega-6 were associated with lower risks of CVDs, cancer incidence, and all-cause mortality in the general population, particularly for coronary heart disease and stroke. While omega-6 intake was linked to lower risks of lung and prostate cancers, it was associated with higher risks of ovarian and endometrial cancers. Subgroup analyses revealed that these protective associations were more pronounced in cohort studies and absent in populations with pre-existing health conditions. CONCLUSIONS: Higher dietary intake and circulating levels of omega-6 fatty acids were associated with lower risks of CVDs, cancers, and all-cause mortality. However, the associations vary by cancer type and are less evident in individuals with pre-existing health conditions. These findings highlight the potential benefits of omega-6 fatty acids for public health while underscoring the need for further research to address specific risks and underlying mechanisms. TRIAL REGISTRATION: Registration number (PROSPERO): CRD42024522842. © 2025. The Author(s).

CONTEXT: Migraines are a prevalent neurological condition that significantly impacts the quality of life. Although narrative reviews and clinical trials suggest the potential effects of fatty acid supplementation as a promising approach for migraine prophylaxis, the findings remain inconsistent. OBJECTIVE: The aim was to evaluate the efficacy of fatty acid supplementation on migraine clinical outcomes through a systematic review and meta-analysis. DATA SOURCES: This systematic review and meta-analysis was conducted using electronic databases including Medline, Scopus, Web of Science, and CINAHL from their inception up to October 7, 2024. DATA EXTRACTION: Studies meeting the PICOS criteria were included: adults diagnosed with migraine, dietary supplementation with fatty acids, assessing migraine clinical outcomes, and only randomized controlled trials. Methodological quality and risk of bias were assessed independently by 2 reviewers using the Cochrane Risk of Bias 2 tool. DATA ANALYSIS: Meta-analyses were conducted using Review Manager software. A random-effects model was applied to account for heterogeneity among studies. A standardized mean difference (SMD) of 0.2, 0.5, and 0.8 was interpreted as small, moderate, and large effects, respectively. Six randomized controlled trials, including 407 participants with chronic migraines, were analyzed. Interventions varied, including omega-3 supplementation with or without omega-6 restriction, lasting from 8 to 16 weeks, and 1 trial assessing alpha-lipoic acid. The overall risk of bias was assessed as low. The pooled analysis demonstrated significant reductions in headache intensity (SMD = -1.77; 95% CI: -3.32 to -0.21; P = .03), headache duration (SMD = -0.77; 95% CI: -1.05 to -0.50; P < .00001), headache frequency (SMD = -1.91; 95% CI: -2.61 to -1.21; P < .00001), and HIT-6 score (SMD = -2.44; 95% CI: -4.13 to -0.76; P = .004). CONCLUSION: This meta-analysis provides moderate evidence that fatty acid supplementation, particularly omega-3, improves migraine clinical outcomes. Additional high-quality, randomized controlled trials are needed to confirm these findings, particularly for the promising effects of alpha-lipo

Photoprotective effects of various nutritional components and supplements have been demonstrated in animal and in vitro studies. The objective of this systematic review is to assess the photoprotective effects of various dietary supplements. A systematic review of studies assessing dietary supplements on photoprotective outcomes was performed. Human studies were retrieved from PubMed, Embase, and Cochrane in February 2023. Supplement keywords included "dietary supplements," "vitamins," "minerals," "carotenoids," "lutein," "isoflavones," "polyphenols," "Polypodium leucotomos," "heliocare," "herbal medicine," "probiotics," "prebiotics," "astaxanthin," "rosmarinic acid," "botanical," and "herb," and outcome keywords included "photoprotection," "ultraviolet rays," UVA," "UVB," and "blue light." A total of 47 studies were included in the systematic review. Studied supplements included carotenoids, polyphenols, Polypodium leucotomos (PL), melon concentrate, vitamins, coenzyme Q, squalene, and omega-3 and omega-6 fatty acids. Some studies evaluated mixed supplementation and incorporated other active ingredients such as selenium and probiotics. The greatest evidence of photoprotection exists for polyphenols, carotenoid-based, and PL supplementation. While flavanol supplementation exhibited dose-dependency, dose-dependency could not be consistently demonstrated for polyphenol supplementation. The weakest evidence exists for photoprotective effects of isolated vitamin or coenzyme Q supplementation. Dietary supplements may promote enhanced photoprotection, although current evidence is limited by small sample size and short duration. Supplementation with photoprotective active ingredients may be especially favorable for individuals with predisposed ultraviolet sensitivity, such as those with polymorphic light eruption. Future research is necessary to determine optimal dosing and supplementation duration for intended photoprotective outcomes.

The associations between circulating PUFA and cardiovascular risk factors and events in healthy Asian populations have been less examined robustly compared with Western populations. This systematic review aimed to summarise current evidence on the associations between n-3 and n-6 PUFA biomarkers and cardiovascular risk factors and events in healthy Asian populations. Four databases were searched for observational studies from 2010 until 2024. Twenty-three studies were eligible, which covered six Asian countries and included events (n 7), traditional risk factors such as blood pressure and lipids (n 4), physical signs such as arterial stiffness (n 4), non-traditional lipid markers (n 1), markers of inflammation (n 4), markers of thrombosis (n 2) and non-invasive imaging-based markers (n 5). Biological sample types included plasma (n 6), serum (n 14) and erythrocyte (n 3). Higher circulating total n-3 PUFA appeared to be associated with lower hypertension risk and specifically EPA and DHA to be associated with lower myocardial infarction risk, reduction in TAG and inflammation. Higher circulating linoleic acid was associated with improved lipid profiles and lower inflammation. Limited evidence led to inconclusive associations between circulating n-6 PUFA biomarkers and CVD events and blood pressure. No consistent associations with arterial stiffness, obesity, thrombosis and imaging-based biomarkers were observed for circulating PUFA biomarkers in Asian populations. Limited studies exist for each outcome; hence, results should be interpreted with caution. More high-quality and prospective studies in Asian populations are warranted. Several recommendations such as sample size justification and reporting of non-respondents rate are proposed for future studies.

INTRODUCTION: Omega-3 possesses anti-inflammatory and lipid metabolism modifying effects in rheumatoid arthritis (RA), but inconsistency exists among previous studies. This meta-analysis intended to explore the effects of omega-3 supplementation on fatty acid distribution, blood lipid profiles, inflammation, and disease activity in RA patients. METHODS: This meta-analysis followed the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) protocol. PubMed, Web of Science, and Embase databases were searched until August 31, 2023. RESULTS: Eighteen randomized controlled trials with 1018 RA patients were included. Regarding fatty acid distribution, omega-3 supplementation increased eicosapentaenoic acid (EPA) [standardized mean difference (SMD): 0.74; 95% confidence interval (CI): 0.46, 1.01; P < 0.001] and docosahexanoic acid (DHA) (SMD: 0.62; 95% CI: 0.35, 0.89; P < 0.001), but reduced omega-6:omega-3 ratio (SMD: -1.06; 95% CI: -1.39, -0.73; P < 0.001) in RA patients. Regarding blood lipid, omega-3 supplementation decreased triglyceride (TG) in RA patients (SMD: -0.47; 95% CI: -0.78, -0.16; P = 0.003). Regarding clinical symptoms, omega-3 supplementation reduced tender joint count (TJC) in RA patients (SMD: -0.59; 95% CI: -0.79, -0.39; P < 0.001). Notably, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score on 28 joints (DAS28) score were slightly decreased by omega-3 supplementation but without statistical significance (all P > 0.05). Publication bias was low, and stability assessed by sensitivity analysis was good. CONCLUSION: Omega-3 supplementation increases EPA and DHA, but reduces the omega-6:omega-3 ratio, TG, and TJC in RA patients. © 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).

BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have unique properties that are advantageous for female. However, no study has explored the effects of omega-3 PUFA supplementation on serum ferritin levels. Thus, the objective of this study was to investigate the effects of omega-3 PUFA supplementation on serum ferritin levels in university female students. METHODS: Thirty-nine iron-deficient university female students aged 18-29 years randomly assigned in a 1:1 ratio to either the intervention group (receiving 525 mg eicosapentaenoic acid [EPA] and 175 mg docosahexaenoic acid [DHA] daily for 8 weeks) or the control group. Hemoglobin and serum ferritin levels, dietary intake, and lipidomics were assessed at baseline and after the 8-week intervention period. Analyses were performed by an independent, blinded statistician. RESULTS: The adherence rate in the study was 94.9 %. n-3 PUFA supplementation increased the omega-3 index (1.8 ± 1.7 vs. 0.4 ± 1.1; p = 0.007), while it decreased the omega-6/3 ratio (-2.6 ± 2.5 vs. -0.9 ± 1.5; p = 0.016) and arachidonic acid/EPA ratio (-9.1 ± 11.6 vs. 1.4 ± 8.5; p = 0.004) compared to those in the control group. These supplementation increased serum ferritin levels (7.8 ± 9.1 vs. 1.8 ± 8.0 ng/mL; p = 0.041); however, it did not change hemoglobin and hepcidin levels compared to those in the control group. No adverse events were observed. CONCLUSION: In this pilot study, omega-3 PUFA supplementation was associated with modest changes in iron status markers in young healthy females. These findings are exploratory, and further placebo-controlled trials are needed to confirm the effects. NAME OF TRIAL REGISTRY: The effect of omega-3 fatty acids intake on hepcidin and anemia Identifying number: UMIN000050570. DATE OF REGISTRATION: 2023/03/14.

Exclusion of meat and fish from the diet can lead to low levels of omega-3 (n-3) long chain polyunsaturated fatty acids (LCPUFAs), leaving the body reliant on dietary intake of n-3 α-linolenic acid (ALA) for endogenous conversion. This study compared dried blood spot fatty acid profiles from a large cohort of pregnant Indian women in Bengaluru, Karnataka, with self-reported vegetarian (n = 332) or omnivorous (n = 691) diets in the first trimester, to those of pregnant Australian women (n = 454) at a similar gestational age. Indian vegetarians and omnivores showed similar fatty acid profiles in dried blood spots but both had markedly lower n-3 fatty acids (mean total n-3 values: Indian 2.01% and 2.36% of total fatty acids respectively; 4.75% in Australian) with ALA, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid all less than half the Australian values. Both Indian groups also had lower arachidonic acid levels (mean 7.65% and 7.91% respectively, vs 8.50% in Australian omnivores), and higher linoleic acid levels (mean 22.53% and 22.41% respectively, vs 19.96% in Australian omnivores) compared with the Australian participants. In general, the relationships between n-3 fatty acids were stronger in Indian vegetarians than Indian omnivores, and weakest in Australian omnivores. These findings suggest that regardless of diet, Indian women in early pregnancy have lower n-3 LCPUFA status than Australian pregnant women. Our data are consistent with the idea that increasing intake of n-3 ALA-rich oils and reducing n-6 linoleic acid-rich oils in the diet of Indian women could be an efficient way of increasing their n-3 LCPUFA status. CLINICAL TRIAL REGISTRATIONS: ORIP, Australian New Zealand Clinical Trials Registry number, ACTRN12613001142729; BORN, Clinical Trials Registry-India CTRI/2020/08/027146.

BACKGROUND AND PURPOSE: Dietary intakes of omega-3 polyunsaturated fatty acids (ω-3 PUFA) are below what is recommended. Meat from grass finished ruminants contains higher levels of ω-3 PUFAs, particularly, alpha-linolenic acid (C18:3 ω-3). The impact of consuming grass finished lamb meat rich in ω-3 PUFA on blood fatty acid (FA) response in humans is not well established. This study investigated the impact of consuming grass finished lamb on total blood plasma and blood plasma phospholipids (PL) FA and on cardiovascular risk factors, including heart rate, blood pressure (BP), HDL, LDL, total cholesterol, and TAG, in humans. METHODS: A single blinded, randomised controlled trial was conducted. Two portions of lamb chops and one portion of lamb mince from lambs finished on a grass or concentrate diet were consumed per week by 34 healthy participants for four consecutive weeks. Blood samples were taken at baseline and post-intervention. Approximately ~ 328 mg/100 g of total ω-3 PUFA was present in grass finished lamb portions per week. RESULTS: Greater levels of ω-3 PUFA, namely C18:3 ω-3, eicosapentaenoic acid (C20:5 ω-3) and docosapentaenoic acid (C22:5 ω-3), were detected in total blood plasma from participants who consumed grass finished lamb (P < 0.05), while consuming concentrate finished lamb higher levels of linoleic acid (C18:2 ω-6) in plasma PL (P < 0.01). There were no differences of consuming grass or concentrate finished lamb on cardiovascular risk factors. CONCLUSION: This study demonstrates that ω-3 PUFA from lamb meat finished on grass is reflected in blood ω-3 PUFA response. Grass finished lamb is a useful matrix for increasing intake of ω-3 PUFA into the human body alongside little required change to customary dietary habits. CLINICALTRIALS: gov ID: NCT06607354. Retrospectively registered 24/09/2024. © 2025. The Author(s).

Targeted manipulation of dietary omega-3 and omega-6 fatty acids has previously been shown to decrease nontraumatic headaches in controlled trials. This study assessed the effects of a diet high in omega-3 fatty acids and low in omega-6 linoleic acid (H3L6 diet) on headache frequency and severity, headache impact, and plasma nociceptive mediators in a persistent post-traumatic headache (pPTH) population. One hundred and twenty-two participants with pPTH were randomized 1:1 to 12 weeks of either the H3L6 (n = 62) or a control (n = 60) diet. A priori primary end-points were the plasma levels of the antinociceptive docosahexaenoic acid (DHA) derivative 17-hydroxy-DHA and the Headache Impact Test (HIT-6) score. Secondary end-points included headache days/month and average daily headache pain intensity (0-10 scale). Statistical analyses followed intention-to-treat principles and were adjusted for baseline values. Relative to the control group, the H3L6 group significantly reduced headache days/month (-2.1, 95% confidence interval [CI]: -3.5 to -0.8, p = 0.002) and average headache intensity (-0.9, 95% CI: -1.2 to -0.5, p < 0.001) and increased circulating 17-hydroxy-DHA (nanograms/milliliter; difference 0.07, 95% CI: 0.02-0.11, p = 0.003), although it did not significantly improve HIT-6 scores (-1.6, 95% CI: -4.0 to 0.8, p = 0.18). In conclusion, the H3L6 diet reduced headache pain and increased antinociceptive mediators, supporting its potential as an adjunct nonpharmacological pPTH therapy.

BACKGROUND: This study aimed to investigate sensitization to eggs and other common allergenic foods, allergic symptoms, and fatty acid status among infants after introducing daily eggs as a complementary food for 6 months. METHODS: This secondary analysis used data from a randomized controlled trial of 500 infants aged 6-9 months in Jouberton, South Africa, who were randomly assigned to receive one egg daily, n = 250 (treatment) or no egg, n = 250 (control) for 6 months. Clinical allergy symptoms were assessed with the Childhood Allergy and Immunology Research questionnaire. Infants were tested with a skin prick test for egg sensitization at baseline and at the end of the study for additional food allergens. The fatty acid composition was analyzed in whole blood at the endpoint. RESULTS: At the endpoint, egg sensitization was 1.9% in the egg intervention group and 2.0% in the control group (aOR 0.936 [95% CI 0.229, 3.822]; p = .926) and all foods sensitization was 7.5% in the egg intervention group and 12.9% in the control group (aOR 0.515 [0.264, 1.005]; p = .052). There were no reported acute egg-related allergy symptoms at baseline and midpoint in the two groups. The incidence of allergic disease during the study was 7.5% in the egg intervention group and 13.4% in the control group (aOR = 0.545 [95% CI: 0.283, 1.048]; p = .069). The total and long-chain polyunsaturated fatty acid omega-6/omega-3 ratios were higher in the intervention group (β = .173 [0.291, 2.898], p = .021 and β = .198 [0.149, 0.902], p = .007) with no effect on omega-3 fatty acid composition. CONCLUSION: Complementary feeding with daily eggs may reduce overall allergic sensitization to common allergenic foods. © 2025 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Omega-3 (n-3) (e.g., EPA/DHA) and omega-6 (n-6) (e.g., linoleic acid [LA]) FAs are suggested to have opposite effects on inflammation, but results are inconsistent and direct comparisons of n-3 and n-6 are lacking. In a double-blind, randomized, and crossover study, females (n = 16) and males (n = 23) aged 30-70 years with abdominal obesity were supplemented with 3-4 g/d EPA/DHA (fish oil) or 15-20 g/d LA (safflower oil) for 7 weeks, with a 9-week washout phase. Cytokines and chemokines (multiplex assay), acute-phase proteins (MALDI-TOF mass spectrometry), endothelial function (vascular reaction index), blood pressure, FA composition (red blood cell membranes/serum/adipose tissue, GC-MS/MS), and adipose gene expression (microarrays, quantitative PCR) were measured. While significant differences between treatments in relative change scores were found for systolic blood pressure (n-3 vs. n-6: -1.81% vs. 2.61%, P = 0.003), no differences between n-3 and n-6 were found for any circulatory inflammatory markers. However, compared with baseline, n-3 was followed by reductions in circulating TNF (-24.9%, P < 0.001), regulated upon activation, normal T cell expressed and secreted (-12.1%, P < 0.001), and macrophage inflammatory protein 1-beta (-12.5%, P = 0.014), and n-6 by lowered TNF (-18.8%, P < 0.001), regulated upon activation, normal T cell expressed and secreted (-7.37%, P = 0.027), monocyte chemoattractant protein-1 (-7.81%, P = 0.020), and macrophage inflammatory protein 1-beta (-14.2%, P = 0.010). Adipose tissue showed significant treatment differences in weight percent of EPA (n-3 vs. n-6: 50.2%∗ vs. -1.38%, P < 0.001, ∗: significant within-treatment change score), DHA (16.0%∗ vs. -3.67%, P < 0.001), and LA (-0.033 vs. 4.91%∗, P < 0.001). Adipose transcriptomics revealed overall downregulation of genes related to inflammatory processes after n-3 and upregulation after n-6, partly correlating with changes in circulatory markers. These data point to tissue-specific proinflammatory effects of high n-6 intake, but a net systemic anti-inflammatory effect as for n-3.

BACKGROUND/OBJECTIVE: Zinc deficiency is common worldwide and has been linked to reduced growth and immune function, increased risk of and slower recovery from infections, and increased risk of non-communicable diseases. To address the issue, zinc biofortification of wheat has been proposed as a sustainable approach to increase dietary zinc intake in countries like Pakistan, where zinc deficiency rates are high and wheat is the primary staple crop. Since plasma zinc concentration (PZC) does not reliably respond to small changes in zinc intake, biomarkers sensitive to small changes in zinc intake achievable though biofortification are needed. Activity indices for zinc-dependent metabolic steps of desaturation and elongation of omega-6 fatty acids (FAs) have been proposed as sensitive zinc biomarkers. Oxylipin metabolites of polyunsaturated FAs may also respond to changes in zinc intake and further mediate metabolic response to oxidative stress. The objective of the current study was to assess the effects of consuming zinc-biofortified wheat flour on plasma markers of fatty acid (FA) metabolism in females aged 10-16 years. METHODS: A nested secondary analysis was conducted in samples from a double-blind, cluster-randomized controlled trial conducted in rural Pakistan, whereparticipants (n = 517) consumed either zinc-biofortified wheat flour or control flour for 25 weeks. Total plasma FAs and oxylipins were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Activity indices were estimated from the ratios of product to precursor FAs. RESULTS: Except for docosahexaenoic acid (DHA, p < 0.05), no significant intervention effect was observed on plasma FAs and FA activity index endpoints. Zinc-biofortified wheat intake reduced pro-inflammatory oxylipins and biomarkers of oxidative stress, 5-HETE (p < 0.05), 9-HETE (p < 0.05), 11-HETE (p < 0.05), and 15-HETE (p < 0.05), compared with the control. However, after adjustment for multiple comparisons, none of the intervention effects remained significant. CONCLUSIONS: Further study of the responsiveness and specificity of plasma oxylipins to changes in zinc intake is warranted.

PURPOSE: Men on active surveillance (AS) for prostate cancer are extremely interested in dietary changes or supplements to prevent progression of their disease. We sought to determine whether a high omega-3, low omega-6 fatty acid diet with fish oil capsules (D + FO) decreases proliferation (Ki-67) in prostate biopsies in men with prostate cancer on AS over a 1-year time period. METHODS: In this phase II, prospective randomized trial, men (N = 100) with grade group 1 or 2 prostate cancer who elected AS were randomly assigned to the D + FO or a control group. Same-site prostate biopsies were obtained at baseline and 1 year. The primary end point was the change in Ki-67 index from baseline to 1 year from same-site biopsies compared between the groups. RESULTS: The Ki-67 index decreased in the D + FO group by approximately 15% from baseline to 1 year (1.34% at baseline, 1.14% at 1 year) and increased in the control group by approximately 24% from baseline to 1 year (1.23% at baseline, 1.52% at 1 year), resulting in a statistically significant difference in the change of Ki-67 index between the groups (95% CI, 2% to 52%, P = .043). There was no significant difference in the secondary outcomes grade group, tumor length, Decipher genomic score, or prostate-specific antigen between the two groups. Four patients in the D + FO group were withdrawn from the trial because of adverse events related to the FO. CONCLUSION: A high omega-3, low omega-6 diet with FO for 1 year resulted in a significant reduction in Ki-67 index, a biomarker for prostate cancer progression, metastasis, and death. These findings support future phase III trials incorporating this intervention in men on AS.

BackgroundThe use of several glucose-lowering drugs (GLDs) in individuals with type 2 diabetes mellitus is common, but their effects on dietary intake have been little explored.AimOur study aimed to examine the association between the number of GLDs used by adults with type 2 diabetes mellitus and their diet quality and nutrient intake.MethodsThis is a cross-sectional analysis of baseline data from a Brazilian national multicenter randomized clinical trial involving participants with type 2 diabetes mellitus aged >30 years. We collected sociodemographic, clinical, biochemical, and anthropometric information and food intake data (24-h dietary recall). Diet quality was assessed by the modified Alternative Healthy Eating Index. Multiple linear regression models were used to examine the association of dietary intake with the number of GLDs in use.ResultsOur analysis included data from a total of 363 participants, mean age of 60.8 ± 9.5 years, and mean glycated hemoglobin of 8.7 ± 1.5%. Of these, 28.1% were taking one GLD; 48.8% were taking two GLDs; and 23.1% were taking ≥3 GLDs. We found no difference in diet quality, but the intake of total polyunsaturated fatty acids and omega-3 and omega-6 fatty acids was different between the three groups (p ≤ 0.03). However, this association was no longer seen after adjusting for age, sex, duration of diabetes, prior diagnosis of dyslipidemia, physical activity and mean monthly family income.ConclusionsWe did not find an association between the number of GLDs in use and either diet quality or nutrient intake in individuals with type 2 diabetes mellitus.

BACKGROUND: Managing metabolism for optimal training, performance, and recovery in medium-to-high-level endurance runners involves enhancing energy systems through strategic nutrient intake. Optimal carbohydrate intake before, during, and after endurance running can enhance glycogen stores and maintain optimal blood glucose levels, influencing various physiological responses and adaptations, including transitory post-endurance inflammation. This randomized trial investigates the impact of a high-dose 2:1 maltodextrin-fructose supplementation to medium-to-high-level endurance runners immediately before, during, and after a 15 km run at 90% VO2max intensity on post-exercise inflammatory stress. METHODS: We evaluated inflammatory biomarkers and lipidomic profiles before the endurance tests and up to 24 h after. We focused on the effects of high-dose 2:1 maltodextrin-fructose supplementation on white blood cell count, neutrophil number, IL-6, cortisol, and CRP levels, as well as polyunsaturated fatty acids, ω-3 index, and AA/EPA ratio. RESULTS: This supplementation significantly reduced inflammatory markers and metabolic stress. Additionally, it may enhance the post-activity increase in blood ω-3 fatty acid levels and reduce the increase in ω-6 levels, resulting in a lower trend of AA/EPA ratio at 24 h in the treated arm. CONCLUSIONS: Adequate carbohydrate supplementation may acutely mitigate inflammation during a one-hour endurance activity of moderate-to-high intensity. These effects could be beneficial for athletes engaging in frequent, high-intensity activities.

The effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on cancer remains controversial. This study aimed to investigate the causal relationship between SGLT2 inhibition, circulating metabolites and cancer through Mendelian randomization. Genetic instruments for SGLT2 inhibition were identified as genetic variants. A two-sample, two-step Mendelian randomization approach was adopted to determine the causal relationship between SGLT2 inhibition and cancer, as well as the mediating role of circulating metabolites that link SGLT2 inhibition to cancer. SGLT2 inhibition was associated with an increased risk of lung cancer, colorectal cancer, skin cancer, and basal cell carcinoma, and a decreased risk of brain cancer. The mediation proportions of SGLT2 inhibition through polyunsaturated fatty acids and omega-6 fatty acids concerning colorectal cancer were 2.388% and 2.131% of the total effect, respectively. The mediation proportion of SGLT2 inhibition through acetone concerning skin cancer was 5.127%. For brain cancer, the mediation proportions of SGLT2 inhibition through medium-high-density lipoprotein triglycerides, high-density lipoprotein triglycerides, and very-low-density lipoprotein triglycerides were 2.648%, 2.131%, and 2.095%, respectively. Our study established the causal effects of SGLT2 inhibition on circulating metabolites. SGLT2 inhibition can influence cancer through various metabolites.

Fatty acids, such as short-chain fatty acids, medium-chain fatty acids and long-chain fatty acids, exist in different chain lengths and with various modifications, which determine their physical, metabolic and biological properties. They serve as important nutrients in energy production via mitochondrial beta-oxidation in various cell types including immune cells. At optimal levels in the body, fatty acids support normal differentiation and function of immune cells. However, at excessive levels, they can cause dysregulation of immune cells and inflammation. The three types of fatty acids regulate cells, in part, via the activation of G protein-coupled receptors, such as GPR41, GPR43, GPR109A, and Olfr78 for short-chain, GPR40 and GPR120 for both medium- and long-chain fatty acids, and GPR84 for medium-chain fatty acids. Activation of these receptors by fatty acids regulates cell proliferation and cell-specific functions. Importantly, fatty acids induce the production of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide through activation of G-protein coupled receptors. Short-chain fatty acids additionally control epigenetic regulators such as histone deacetylases and histone acetyltransferases. Saturated long-chain fatty acids and omega-6 polyunsaturated fatty acids are implicated in metabolic diseases and inflammatory conditions, whereas short-chain fatty acids, monounsaturated fatty acids, and omega-3 polyunsaturated fatty acids are generally associated with functional immunity with anti-inflammatory effects. This article explores how fatty acids regulate the immune system, focusing on their common and unique roles, as well as their opposing functions. © 2026. The Author(s).

Diabetic retinopathy (DR) is a leading cause of preventable vision loss, yet current therapies primarily address late, VEGF-driven vascular complications rather than early upstream drivers. Emerging evidence indicates that early DR originates from metabolic stress within the retinal neurovascular unit, where dysregulated lipid metabolism, oxidative stress, and inflammation precede visible microvascular damage. Disturbances in polyunsaturated fatty acid (PUFA) metabolism, together with related metabolic stressors such as elevated homocysteine (Hcy), drive lipid dysregulation, oxidative stress, and inflammation preceding visible microvascular damage, promoting endothelial dysfunction and blood-retinal barrier (BRB) breakdown. Hyperglycemia shifts retinal lipid composition toward oxidation-prone omega-6 PUFAs and activates lipoxygenase (LOX), cyclooxygenase (COX), and cytochrome P450 (CYP450) eicosanoid pathways. LOX-derived metabolites such as 12- and 15-HETE stimulate NADPH oxidase, disrupt tight junctions, and promote inflammatory signaling in endothelial and Müller cells. COX-2-driven prostaglandin E2 signaling increases vascular permeability, while CYP450 metabolites and their soluble epoxide hydrolase (sEH) derived products exert context-dependent effects on vascular integrity. Elevated Hcy further enhances oxidative stress and NF-κB activation, amplifying PUFA-mediated inflammatory signaling. These mechanisms identify modifiable upstream targets that complement glycemic control. Higher dietary omega-3 intake and lower omega-6:omega-3 ratios are associated with reduced DR risk, particularly in well-controlled diabetes. Omega-3-rich diets, exercise, and correction of folate and B-vitamin deficiencies may help improve systemic inflammation and retinal barrier integrity. Integrating lipid pathway modulation, nutritional support, and metabolic control with careful ocular monitoring may help slow the progression of DR before irreversible blindness occurs.

Docosahexaenoic acid (DHA) is an essential ω-3 polyunsaturated fatty acid (PUFA) with high nutritional and pharmaceutical value. The marine protist Aurantiochytrium is a promising industrial DHA producer; however, its DHA biosynthesis via the PUFA synthase pathway co-produces ω-6 docosapentaenoic acid (DPA), limiting DHA purity. Here, we introduced an ω-3 desaturase from Phytophthora infestans (Pin-O3D) into Aurantiochytrium sp. SD116. Functional validation in an Escherichia coli system co-expressing the native PUFA synthase confirmed that Pin-O3D converts DPA to DHA, shifting the DHA/DPA ratio from 1:1 to 2:1. Pin-O3D was then integrated into the fatty acid synthase (FAS) locus, simultaneously attenuating FAS activity and enabling heterologous gene expression. The engineered strain ΔFAS-Pin-O3D exhibited significantly (p < 0.0001 in t-test) increased DHA content (55.2% of total fatty acids) and DHA/DPA ratio (5.91) in shake flasks, with no negative impact on biomass or lipid accumulation. Fed-batch fermentation confirmed the scalability of this strategy, achieving a >20% increase in DHA/DPA ratio. This study demonstrates that combining heterologous ω-3 desaturase expression with FAS attenuation is an effective approach for optimizing PUFA profiles in Aurantiochytrium.

Bladder cancer is a major public health concern worldwide. While smoking and occupational exposures are established risk factors, the role of dietary fatty acids (FAs) in bladder cancer risk remains unclear. Data were collected from 711 bladder cancer cases and 3,297 controls in the IROPICAN study (2017-2020) across ten Iranian provinces. Dietary intake was assessed using a validated food frequency questionnaire. Intakes of total fat, saturated FAs (SFAs), monounsaturated FAs (MUFAs), polyunsaturated FAs (PUFAs), and trans FAs (TFAs) were analyzed. Principal component analysis (PCA) identified fatty acid consumption patterns. Multivariable logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for confounders. PCA suggested that balancing FA intake, specifically increasing omega-3 FAs, moderating omega-6, and reducing saturated fats, was associated with a favorable profile for bladder cancer risk. OR for stearic acid intake was 0.28 (95% CI: 0.12-0.67). Conversely, OR for high intake of palmitoleic acid, alpha-linolenic acid (ALA), and docosapentaenoic acid (DPA) was elevated. Sex-specific effects were found stearic acid was protective in men, while PUFAs were protective in women. No associations were observed for total fat or cholesterol. These results highlight the importance of FA subtypes, rather than total fat intake, in dietary recommendations.

This research assessed the impact of Radix Isatidis polysaccharides (RIPS) supplementation on the growth, meat quality, lipid metabolism, and gut microbiota of broiler chickens. A total of 320 AA broilers were separated into four groups and given either a basic diet or diets with 250, 500, or 1000 mg/kg RIPS for 42 days. We employed various multi-omics approaches, including serum biochemistry, lipidomics, transcriptomics, and 16S rRNA sequencing, to investigate the underlying mechanisms. The results indicated that 1000 mg/kg RIPS markedly enhanced meat color, elevated ω-3 and ω-6 polyunsaturated fatty acids, and augmented antioxidant activity in breast muscle. In the 500 mg/kg and 1000 mg/kg groups, alanine aminotransferase (ALT) activity was significantly decreased, and triglyceride (TG) levels were significantly reduced in the 1000 mg/kg group. Lipidomic analysis revealed that in the 1000 mg/kg group, the accumulation of triglycerides and ceramides in the chicken breast was lower, indicating an optimization of lipid metabolism. Transcriptomic analysis showed that in the ileum, the expression of FABP1 and APOA1 genes was significantly upregulated in the 1000 mg/kg group, suggesting improved fatty acid transport and cholesterol metabolism. RIPS also significantly improved the gut microbiota, particularly increasing the abundance of g__Actinomarinales and p__DTB120 in the 1000 mg/kg group, which were positively correlated with antioxidant capacity and meat quality. In summary, RIPS regulates lipid metabolism and antioxidant defense through the "gut-muscle axis," leading to significant improvements in both meat quality and health in broiler chickens. This study emphasizes the potential of plant polysaccharides in animal nutrition and suggests 1000 mg/kg RIPS as an appropriate supplementation amount.

BACKGROUND: Donor human milk (DHM) is commonly used to supplement feeds for preterm and sick infants with insufficient breastmilk. It is unclear whether DHM provides the same amounts of omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA) and arachidonic acid (AA), as maternal breastmilk. OBJECTIVE: To conduct a systematic review summarizing the evidence on the LCPUFA composition of DHM. METHODS: PubMed was searched up to January 2026 to identify studies reporting DHA and AA profiles of DHM. Where possible, potential influences of DHM LCPUFA composition such as milk collection methods and pasteurization were summarized. We performed meta-analyses sub-grouped on the fatty acid expression modes (molar% or weight%). RESULTS: Twenty studies were included in this systematic review; sixteen were eligible for meta-analysis. Sample sizes ranged from three to 168 DHM samples per study and LCPUFAs were generally reported as relative rather than absolute concentrations. Pooled means were 0.25% DHA (95% CI 0.19, 0.31) and 0.50% AA (95% CI 0.41, 0.58). Higher DHA proportions were associated with omnivorous diets and earlier lactation stages. Compared to preterm colostrum and transitional (7-14 days postpartum) milk, DHM contained lower relative levels of DHA and AA. Pasteurization had little effect on relative LCPUFA levels. CONCLUSIONS: DHM has an LCPUFA profile similar to mature breastmilk but has lower proportions of DHA and AA than preterm colostrum or transitional breastmilk. Due to limitations in reporting of LCPUFA composition, absolute amounts delivered to infants given DHM are unclear, but it is likely preterm infants require supplemental DHA and AA. REGISTRATION: This review was registered on Open Science Framework (DOI: 10.17605/OSF.IO/HMX2F).

Nutritional psychiatry is an emerging field. Micro- and macro-nutrients play a role in energy metabolism and the regulation of inflammation; particularly, an insufficient dietary intake of omega-3 fatty acids and an imbalanced intake of omega-6/omega-3 fatty acids, with a shift toward increased inflammation, are of relevance for the pathophysiology of mental disorders. This review summarizes evidence on the role of omega-3 fatty acids in the pathophysiology of mental disorders (schizophrenia, affective and anxiety disorders, post-traumatic stress disorder, and eating disorders), neurodevelopmental disorders (attention-deficit/hyperactivity disorder and autism spectrum disorder) and neurodegenerative disorders (Alzheimer's disease) and explores potential treatment implications. In addition, the underlying neurobiological mechanisms through which omega-3 fatty acids might exert a protective effect are also discussed. Despite methodological variability and heterogeneous results, an increasing body of evidence suggests that omega-3 deficiency and altered fatty acid profiles are modifiable risk factors and potential biomarkers for mental disorders. The integration of omega-3 supplementation as an adjuvant to state-of-the-art therapy offers the potential for a low-risk intervention with meaningful clinical outcomes. However, clinical monitoring is recommended to avoid adverse effects and to adjust the dosage according to individual and disease-specific factors.

The imbalance in the dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratio contributes to chronic low-grade inflammation, a key pathological basis for degenerative musculoskeletal conditions such as osteoporosis and osteoarthritis. While individual reviews have explored aspects of ω-3 PUFAs in bone or muscle, a comprehensive narrative review integrating their multidimensional mechanisms with translational evidence across orthopedics and sports medicine is less common. This review consolidates evidence from fundamental science, clinical trials, and translational research, employing an interdisciplinary approach to systematically elucidate their mechanisms and application values. ω-3 PUFAs exert multi-layered anti-inflammatory and pro-repair effects through mechanisms including cell membrane remodeling, reprogramming of lipid mediator profiles (promoting the generation of specialized pro-resolving mediators), and inhibition of key pathways such as NF-κB and the NLRP3 inflammasome. Clinical studies indicate that ω-3 PUFA supplementation can improve bone metabolic markers, alleviate pain in osteoarthritis, and reduce inflammation and muscle loss in the perioperative period. In sports medicine, ω-3 PUFAs enhance muscle anabolic metabolism, optimize energy utilization, promote recovery, and demonstrate neuroprotective potential. Their extended application value lies in regulating the "bone-muscle axis," providing targeted nutritional support for athletes, and serving as a nutritional countermeasure in extreme environment medicine. Statement of Significance: This review constructs an integrative framework linking molecular mechanisms to clinical translation, positioning ω-3 PUFAs as key physiological modulators for musculoskeletal health and delineating future directions for precision nutrition-based intervention strategies.

The uncinate fasciculus (UF) is a long-range association fiber tract connecting the anterior temporal lobe with the orbitofrontal cortex and has been linked to a multitude of physiological and pathophysiological conditions such as aging, epilepsy, and the vulnerability to psychopathology posed by a history of childhood abuse (CA). Since the myelin sheath is highly enriched in lipids, changes in white matter (WM) microstructure observed via neuroimaging may reflect alterations in the myelin lipid profile. Given that the UF does not exist in rodents, its molecular properties are highly understudied. Therefore, we sought to quantify the phospholipid FA and cholesterol quantities of the human postmortem UF and evaluate any lipid-related or myelin-constituent gene/protein changes associated with age and history of CA. UF samples were analyzed from individuals with depression who died by suicide with (DS-CA) or without (DS) severe CA, and control individuals (CTRL), with an age span of 15 to 85 years. Phospholipids were separated by thin-layer chromatography; FAs and nonderivatized cholesterol were quantified by gas chromatography-flame ionization detection. The relative expression of myelin-constituent genes and proteins was measured by RT-qPCR and immunoblotting, respectively. We found no robust relationships between CA or depression and lipid measures or myelin-constituent gene/protein levels. In contrast, phospholipids showed pronounced age effects that differed by fraction, with an overall trend of monounsaturated FAs increasing and long-chain omega-6 polyunsaturated FAs decreasing with age. The expression of most myelin-constituent genes and proteins declined with age; PLP1 and MAG showed significant decreases. Therefore, changes in lipid composition and lipid-protein interactions likely contribute to age-related myelin deficits and may in part underlie age-associated cognitive decline. © 2026 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.