Search Results (2,520)

The Siberian sturgeon (Acipenser baerii, Brandt, 1869) is a potamodromous freshwater species with major ecological and commercial importance. Natural populations across the main Siberian River basins have declined so severely that the species is now classified as Critically Endangered on the IUCN Red List. This narrative analysis synthesizes current scientific knowledge regarding the ecology, reproductive biology, conservation status, and nutritional value of products derived from A. baerii, with the aim of providing an integrated perspective on this species, which has recently been introduced into Romanian aquaculture and occupies the interface between biodiversity and human consumption needs. The species’ remarkable ecological and morphological plasticity, which underlies its wide natural distribution in the Ob, Irtysh, Yenisei, and Lena River basins, has also made it the dominant species in global sturgeon aquaculture, commercially farmed in Europe, Asia, and South America. Reproductive management in farming systems relies on hormonal induction, non-invasive maturity assessment, and controlled hatchery practices, while emerging no-kill technologies enable repeated caviar harvesting without sacrificing the female, improving both ethical standards and economic efficiency. From a nutritional standpoint, A. baerii yields two high-value products: caviar, a rich source of the long-chain polyunsaturated fatty acids EPA and DHA, whose dietary intake has been associated with cardiovascular and neurodevelopmental benefits in the broader nutrition literature, and meat, characterized by high-biological-value protein, a favorable amino acid profile, and significant omega-3 content. By-products such as skin, swim bladders, glands, and cartilage contribute to the higher-value utilization of the species within the circular bioeconomy. Still, notable gaps remain in genetics and sex determination methods, in early life behavioral ecology, and in cryopreservation protocols. Future work should also look at more sustainable feed formulations and new value-added products. Full article

Background/Objectives: Autism Spectrum Disorder (ASD) affects approximately 60 × 10⁴ incident cases, 283.3 × 10⁵ prevalent cases, and 43.1 × 10⁵ DALYs globally and is frequently accompanied by irritability, hyperactivity, and social withdrawal linked to low-grade neuroinflammation. Omega-3 supplementation is among the most common complementary approaches used by families, but clinical evidence remains inconsistent, and prior meta-analyses have relied on a single outcome instrument. This study aimed to evaluate the efficacy of omega-3 supplementation on ASD-associated behavioral symptoms by harmonizing outcomes across multiple validated instruments. Methods: Twelve randomized controlled trials (number of studies per domain: k = 6–12) were identified through a systematic search of ten databases (CRD420261390092). Outcomes from eight instruments (ABC, CGI-I, BASC-2, SRS/SRS-2, GARS-2, CARS/SDQ, VABS/PLS-4/PDDBI, and CBCL) were mapped onto five behavioral domains: Irritability, Lethargy/Social Withdrawal, Stereotypy, Hyperactivity, and Inappropriate Speech/Communication. Random-effects models (REML, Knapp-Hartung adjustment) pooled Hedges’ g for each domain, with fixed-effects, subgroup, and PET-PEESE publication-bias sensitivity analyses. Results: Significant pooled effects favoring omega-3 supplementation were observed for Irritability (g = −0.287, 95% CI [−0.562, −0.013], p = 0.043) and Inappropriate Speech/Communication (g = −0.213, 95% CI [−0.363, −0.063], p = 0.010). Lethargy/Social Withdrawal, Stereotypy, and Hyperactivity showed trivial-to-small, non-significant effects. Heterogeneity was negligible (I² ≤ 0.83%) in four domains; Hyperactivity showed moderate heterogeneity (I² = 37.86%). Sensitivity analyses confirmed robustness, and no evidence of publication bias was detected. Conclusions: Expanding synthesis beyond a single outcome instrument revealed statistically significant, though clinically modest, benefits of omega-3 supplementation on irritability and communication symptoms in ASD, effects undetectable in prior smaller, single-instrument analyses. These findings support its consideration as a low-risk adjunctive option, while larger, adequately powered trials remain needed to confirm clinical relevance. Full article

DNA methylation clocks provide a tractable molecular readout for testing whether nutritional and natural-product interventions can modify biological aging. Natural-product-derived antioxidants are biologically plausible candidates because they influence redox signaling, inflammation, mitochondrial function, microbial metabolism and epigenetic regulation, yet their effects on DNA methylation-based aging remain difficult to interpret. Here, we systematically synthesize human intervention studies evaluating antioxidant-rich dietary patterns, botanical and food-derived extracts, marine omega-3 fatty acids, multi-component nutraceuticals and related lifestyle-based interventions with DNA methylation-clock outcomes. The available evidence does not support a uniform epigenetic anti-aging effect. Instead, methylation-age responses were clock-specific, exposure-dependent and often most apparent in metabolically or biologically responsive subgroups. Longer randomized or trial-embedded studies provided the most credible signals, whereas small uncontrolled studies mainly generated hypotheses. Future trials should move beyond claims of epigenetic age reversal and test whether objectively verified natural-product-derived antioxidant exposures produce reproducible, mechanistically linked, and clinically meaningful changes in aging biology. Full article

This research examines the effect of a 9-week feeding intervention on laying hens with flavonoid-enriched rations to modulate the colour and lipid quality of egg yolks. Triglycerides and phosphatidylcholine were the principal neutral and polar classes, respectively, as determined by TLC-FID. Oleic, palmitic, and linoleic were the major fatty acids (FAs) as determined by GC-FID/MS, while essential DHA predominated omega-3 FAs. Flavonoid supplementation did not markedly modify the total fat, lipid classes, or FA profile of yolks, whilst FAs were mostly affected by basal diet ingredients. However, higher-dose hesperidin and naringin improved the MUFA/PUFA ratio of yolk fatty acids. Egg yolks were not differentiated by colour or total carotenoid content irrespective of the feeding intervention. Study time, on the other hand, contributed to observed differences. Remarkably, a 1-week adaptation to a standardised regime proved adequate for the production of yolks with a homogenous colour profile, while incremental changes in the total carotenoids boosted red/yellow colouration. By completing the intervention, significant nutritional improvements emerged for all groups: (i) phosphatidylcholine levels increased; (ii) n-6/n-3 shifted to lower values; and (iii) peroxidisability indices diminished. The aforementioned findings, along with low atherogenic/thrombogenic indices and combined with the oxidative stability of yolk lipophilic constituents, feature eggs with consistent yolk colour and enhance lipid-rich yolks’ contribution towards a healthy diet. Full article

Acute and chronic inflammation underlies the pathogenesis of numerous diseases, including autoimmune disorders, atherosclerosis, infections, and cancer. Although non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are widely used to control inflammation, their clinical utility is limited by adverse effects such as gastrointestinal toxicity and immunosuppression. Specialized pro-resolving mediators (SPMs), a family of endogenous lipid mediators derived from omega-3 fatty acids, have emerged as promising therapeutics because they actively promote the resolution of inflammation without suppressing host immunity. However, their clinical translation is hindered by poor chemical stability, rapid metabolic degradation, and short circulation half-lives. To overcome these limitations, a variety of delivery platforms—including liposomes, extracellular vesicles, PLGA nanoparticles, and hydrogels—have been developed to improve SPM stability, pharmacokinetics, and therapeutic efficacy. This review summarizes the cellular targets of SPMs, current delivery challenges, and emerging strategies for cell- and tissue-specific SPM delivery. We also discuss future opportunities for targeted SPM therapies in the treatment of inflammatory diseases and cancer. Full article

Background: Precision nutrition and nutrigenomics have emerged as promising strategies to personalize dietary interventions according to individual genetic, metabolic, and molecular characteristics. However, the potential of nutrigenomic-guided nutraceutical interventions to modulate biological aging pathways remains poorly characterized. Objective: This study aimed to map and synthesize the available evidence from human studies evaluating personalized nutraceutical interventions based on nutrigenomic approaches and their effects on biomarkers associated with biological aging. Methods: A scoping review was conducted following the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched for studies published between 2021 and 2026. Eligible studies included adults aged ≥18 years receiving personalized nutraceutical interventions informed by genetic, genomic, metabolomic, or other molecular data. Outcomes included biomarkers of cellular aging, inflammation, oxidative stress, immunometabolism, and related pathways. Results: Twenty-one studies were included. Interventions involved omega-3 fatty acids, polyphenols, Nigella sativa, vitamin D, methyl-donor micronutrients, fermented papaya preparation, and other nutraceutical preparations and functional food-based interventions. Four major themes emerged: multi-omic stratification approaches, biological aging biomarkers, redox-inflammatory modulation, and applications in metabolic disorders. Most studies demonstrated favorable effects on intermediate molecular biomarkers, including inflammatory cytokines, oxidative stress markers, lipid metabolism, endothelial function, and DNA methylation signatures. However, evidence directly demonstrating slowing of biological aging through validated biomarkers such as epigenetic clocks or telomere dynamics remains limited. Conclusions: Personalized nutraceutical interventions exhibit biological plausibility for modulating pathways associated with healthy aging. Nevertheless, robust longitudinal studies incorporating validated biomarkers of biological aging and clinically meaningful outcomes are needed before their widespread implementation in precision medicine. Full article

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality worldwide, driven by complex interactions among dyslipidemia, chronic inflammation, insulin resistance, endothelial dysfunction, and gut microbiome-derived metabolites. This review synthesizes mechanistic and clinical evidence on non-pharmacological strategies that modulate these pathways and contribute to ASCVD risk reduction. Dietary patterns such as Mediterranean, DASH, and plant-based diets improve lipid metabolism, attenuate inflammation, and enhance endothelial function. Chrononutrition approaches, including time-restricted feeding and structured fasting protocols, influence circadian regulation of glucose and lipid homeostasis. Circadian misalignment—including irregular sleep timing, shift work, and disrupted feeding–fasting cycles—independently contributes to ASCVD through impaired glucose tolerance, dyslipidemia, endothelial dysfunction, and systemic inflammation. Modulation of the gut microbiome, particularly through increased short-chain fatty acid production and reduced TMAO formation, provides additional cardiometabolic benefits. Key nutraceuticals—phytosterols, omega-3 fatty acids, and berberine—demonstrate clinically meaningful effects through micellar competition, inflammation-resolving lipid mediators, and AMPK activation, respectively. When combined with evidence-based pharmacotherapy, these interventions exert synergistic effects on cardiometabolic risk factors. This integrative biomedical framework highlights the importance of combining lifestyle, metabolic, microbiome-targeted, and nutraceutical strategies for comprehensive ASCVD prevention. Full article

Mesenchymal stem/stromal cells (MSCs) are promising candidates in regenerative medicine, but their effectiveness is significantly influenced by the surrounding metabolic and nutritional conditions. Increasing evidence suggests that lipids act not only as energy sources but also as regulators of MSC fate. This review explores how lipid metabolism influences the balance among stemness, immunomodulation, and differentiation into adipogenic or osteogenic lineages. It does so through mechanisms such as fatty acid uptake, β-oxidation, de novo lipogenesis, and membrane remodeling, all orchestrated by CD36, carnitine palmitoyltransferase 1A, PPARγ, AMP-activated protein kinase, and the PI3K/AKT/mTOR pathway. We then examine how diet reshapes the MSC lipidome: obesity and high-fat diets promote adipogenesis and senescence, while omega-3 fatty acids, caloric restriction, micronutrients, and a balanced microbiota help preserve regenerative capacity. Lastly, we discuss how combining lipidomics with multi-omics could uncover lipid-metabolic signatures and regulatory nodes that connect diet to MSC function. Overall, the diet–lipid–MSC axis emerges as a modifiable determinant of MSC function. Full article

The flavor characteristics of three commercially important, cultivated mussel species (Mytilus coruscus, Mytilus galloprovincialis, and Perna viridis) were investigated through analyses of free amino acids, organic acids, 5′-nucleotides, fatty acids, and volatile organic compounds (VOCs). Distinct differences among species–sex groups were observed in both volatile and non-volatile flavor compounds. M. coruscus and M. galloprovincialis showed greater umami potential than P. viridis. Female M. galloprovincialis exhibited the highest equivalent umami concentration (EUC) (2.56 ± 0.21 g MSG/100 g), whereas male M. galloprovincialis and male M. coruscus contained the highest levels of sweet-tasting amino acids (605.42 ± 28.72 mg/100 g) and umami-tasting amino acids (209.29 ± 13.31 mg/100 g), respectively. Gas chromatography–ion mobility spectrometry (GC-IMS) analysis identified 67 volatile compounds, and 12 key discriminative volatiles were selected, including three aldehydes, four ketones, three alcohols, 2-ethylfuran, and acetic acid. Males generally showed higher omega-3 polyunsaturated fatty acids (ω-3 PUFAs)and omega-6 polyunsaturated fatty acids (ω-6 PUFAs) proportions than females, with the highest ω-3 PUFAs proportion in male M. coruscus (45.12 ± 0.22%) and the highest ω-6 PUFAs proportion in male P. viridis (8.13 ± 0.30%). Correlation analysis suggested that ω-6 PUFAs were more closely associated with aldehydes, whereas ω-3 PUFAs were more closely associated with alcohols and ketones. These associations provide preliminary evidence for understanding flavor differences among cultivated mussel groups. Full article

Background: Population aging is driving a convergent rise in three disorders historically managed in isolation: cardiovascular disease, neurocognitive decline, and osteoporotic bone loss. Mechanistic data indicate that these systems are coupled through shared regulators of calcium trafficking, inflammation resolution, vascular integrity, and inflammaging. On this basis, a “Heart–Brain–Bone” axis has been proposed; it should be understood as an integrative conceptual framework that organizes evidence drawn from three separate studies, not as a validated physiological entity with agreed diagnostic criteria or demonstrated modifiability. Three lipid-soluble nutrients—long-chain omega-3 polyunsaturated fatty acids (EPA/DHA), vitamin D3 (cholecalciferol), and vitamin K2 (menaquinone-7 [MK-7])—act on overlapping nodes of this network. Methods: We performed a structured narrative review. PubMed/MEDLINE, Embase, the Cochrane Library, and Web of Science were searched from database inception to 25 June 2026 using predefined term blocks for each nutrient, each organ domain, and each candidate mechanism, and the search was updated on 7 August 2026. Records were screened against prespecified inclusion and exclusion criteria by two authors independently, with disagreements resolved by a third. The strength of evidence for each nutrient–organ relationship was graded with an explicitly defined four-level scheme ((−) to (+++)) applied separately to preclinical, observational, randomized and meta-analytic evidence. Results: Vitamin K2-dependent gamma-carboxylation of matrix Gla protein (MGP) and osteocalcin has been proposed to influence whether calcium is incorporated into the bone matrix or deposited in the arterial wall, offering a candidate mechanistic account of the “calcium paradox” associated with isolated vitamin D3 supplementation; EPA/DHA-derived specialized pro-resolving mediators may support resolution of endothelial and neuronal inflammation; and bone-, vascular- and brain-derived signals (osteocalcin, FGF23, the neurovascular unit) interconnect the three organs. These mechanisms are biologically plausible but remain insufficiently confirmed in humans. The clinical evidence is heterogeneous, formulation- and population-dependent, and comprises positive, neutral and null results: cardiovascular omega-3 trials are discordant (REDUCE-IT, which used icosapent ethyl [an EPA ethyl ester], positive; VITAL/STRENGTH/ASCEND null, predominantly in lower-risk or replete cohorts); cognitive trials are largely null or subgroup-dependent (MAPT, DO-HEALTH, VITAL); and MK-7 improves surrogate bone and calcification biomarkers and slowed coronary artery calcification in one recent randomized imaging trial (VitaK-CAC), whereas combined MK-7 plus vitamin D3 did not slow aortic valve or coronary calcification in AVADEC and MK-7 did not reduce bone loss in early menopausal women. Recognized safety signals include a dose-dependent increase in atrial fibrillation with high-dose omega-3, adverse skeletal effects of high-dose or bolus vitamin D, and clinically relevant interference of even low-dose MK-7 with vitamin K antagonist therapy. Conclusions: No adequately powered randomized trial has demonstrated that the combination of long-chain omega-3, vitamin D3 and MK-7 is superior to its individual components or to placebo for any clinical endpoint. The combined regimen is therefore mechanistically rational and hypothesis-generating rather than clinically established; benefit appears most plausible in individuals with elevated risk or demonstrable nutritional insufficiency, and least in replete, low-risk populations. Findings should be interpreted within a broader healthy-aging context that includes lifestyle and psychosocial factors. Adequately powered factorial randomized controlled trials stratified by baseline Omega-3 index, 25(OH)D and vitamin K status, with prespecified mechanistic biomarkers and hard endpoints, are required. Full article

Prenatal alcohol exposure (PAE) leads to fetal alcohol spectrum disorder (FASD), the most common preventable cause of neurodevelopmental impairment. The classical narrative attributes the clinical picture of FASD exclusively to direct ethanol-induced brain injury. In the present review, we argue that this perspective is incomplete and leads to diagnostic errors, most often to the misdiagnosis of ADHD in children who in fact have FASD. We propose that, alongside the direct neurotoxicity of ethanol, an important and clinically under-recognized complementary mechanism is gut–brain axis dysfunction: alcohol damages the enteric nervous system and enteric glial cells, induces dysbiosis with deep deficits of butyrate and other short-chain fatty acids (SCFAs), damages the enterochromaffin cells responsible for 90% of peripheral serotonin production, and—through translocation of lipopolysaccharide (LPS) and activation of the Toll-like receptor 4 (TLR4)—sustains a neuroinflammatory brain signature. This cascade—superimposed on direct ethanol neurotoxicity—may account for the high rates of depression, anxiety, self-injurious behavior, and suicide attempts observed in individuals with FASD and for the limited efficacy of traditional interventions focused solely on the central nervous system. The 2024 Polish Institute of Mother and Child (Okulicz-Kozaryn et al.) study showed that 50.3% of pregnant women consumed alcohol, and 11% did so regularly, against only 7% who admitted so in questionnaires. The real clinical picture of children with FASD is further complicated by three factors to which we devote separate sections in this paper: prenatal co-exposure to nicotine, cannabinoids, and opioids; the loss of vertical microbiota transmission and breastfeeding in children transferred to foster care (where the prevalence of FASD is 18.8% and in children’s homes in some regions reaches up to 80%); and the substantial over-representation of preterm and small-for-gestational-age (SGA) infants (in the Hasken et al. cohort, 18.4% of children with FASD were born preterm and 51.4% were born SGA). In the final section, we present a structured, staged protocol for nutritional and microbiological intervention grounded in a hierarchy of evidence: from interventions supported by randomized controlled trials (RCT-level; choline) through interventions supported by strong mechanistic rationale and RCTs in related populations (sodium butyrate, Lactobacillus rhamnosus GG, GOS/FOS prebiotics—galacto-oligosaccharides and fructo-oligosaccharides, and omega-3 fatty acids) to experimental interventions. The protocol also covers the window before 2 years of age: we argue that, given the over-representation of preterm and SGA infants among children with FASD, the analogy to preterm infants on parenteral nutrition and to post-institutional infants applies in substantial part to the same patients, which justifies extending the indications for choline and other nutritional interventions. The paper includes a compact table of dosing proposals for each age window (from pregnancy to school-age child) and provides clinicians with concrete answers: where to start, what to avoid, and what to monitor, with explicit signposting of regulatory limitations for individual substances in Poland and the European Union. Full article

α-Linolenic acid (ALA) is an essential omega-3 polyunsaturated fatty acid, yet how dietary ALA enrichment interacts with population-specific gastrointestinal physiology to dictate bioaccessibility and lipid peroxidation remains insufficiently understood. This study systematically evaluated the in vitro digestive behaviors and oxidation risks of flaxseed oils containing 52% and 68% ALA using simulated models representative of distinct population groups (infants, adults, and the elderly). Digestive efficiency peaked in the adult model, achieving ALA bioaccessibility of 49.2% (52% ALA oil) and 46.5% (68% ALA oil), significantly outperforming those observed in infants (23.1% and 19.5%) and the elderly (39.4% and 37.3%). Crucially, malondialdehyde (MDA) accumulation directly correlated with digestive lipolysis efficiency across population groups, reaching its maximum in adults (5.00 nmol/mL for 52% ALA oil; 7.54 nmol/mL for 68% ALA oil), followed by the elderly (3.06 nmol/mL and 4.02 nmol/mL), and remaining lowest in infants (0.92 nmol/mL and 1.49 nmol/mL). Within each population cohort, although the 68% ALA oil yielded a higher absolute ALA release amount, its relative bioaccessibility was slightly lower while generating elevated MDA levels. These findings demonstrate that increasing ALA concentration imposes a critical trade-off between lipolytic efficiency and oxidative safety across different population groups, providing a solid scientific rationale for designing population-tailored flaxseed oil products optimized for both nutrient delivery and safety. Full article

Background/Objectives: Obesity is paradoxically associated with iron deficiency despite adequate dietary intake, driven by chronic inflammation and elevated hepcidin. Different dietary patterns may differentially affect iron metabolism in obese individuals, yet comparative evidence remains limited. Methods: We conducted a systematic literature review following PRISMA 2020 guidelines. Four databases (SciSpace, Google Scholar, PubMed) were searched through 2025 using terms related to obesity, iron deficiency, and three dietary patterns: Mediterranean diet, ketogenic diet, and intermittent fasting. Studies were screened using seven predefined criteria (three inclusion, four exclusion) with thresholds of ≥4.0/5.0 for abstract screening and ≥4.5/5.0 for full-text screening. Results: From 396 identified records (SciSpace n = 325, Google Scholar n = 57, PubMed n = 14), 38 studies were included after removing 62 duplicates and screening 334 unique records. Studies without accessible full text were excluded.The Mediterranean diet appears most protective for iron status due to its anti-inflammatory profile (omega-3 fatty acids, polyphenols, vitamin C) and bioavailable iron sources. Ketogenic diets may impair duodenal iron absorption through hepcidin-independent mechanisms and restrict dietary iron diversity. Intermittent fasting shows complex effects, remodeling iron metabolism with increased transferrin and decreased ferritin within physiological ranges. Weight loss per se consistently improves iron status by reducing adipose-driven inflammation and lowering hepcidin. Conclusions: Among the three dietary patterns examined, the Mediterranean diet appears most protective for iron status in obese individuals. The ketogenic diet may pose the highest risk due to restricted dietary iron diversity and potential hepcidin-independent absorption impairment. Direct comparative randomized controlled trials are urgently needed. Clinicians should routinely monitor iron biomarkers, including hepcidin, in obese patients undertaking any dietary intervention. Quantitative biomarker data from the 38 included studies showed serum ferritin reductions of 8–28%, hemoglobin levels remaining within clinically stable ranges, and IL-6 decreases of 15–42% across dietary patterns. Full article

Introduction: IgA nephropathy (IgAN) is a leading cause of end-stage renal disease. Given the significant adverse effects and inconsistent long-term efficacy of conventional immunosuppressive strategies, there is an unmet need for safer adjunctive therapies. Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed as potential candidates to address this therapeutic gap. Purpose: This narrative review summarizes the proposed mechanisms of action of omega-3 PUFAs in IgAN and critically evaluates the current clinical evidence regarding their therapeutic potential and limitations. Mechanisms: Emerging experimental data suggest that omega-3 PUFAs may modulate inflammatory and fibrotic pathways relevant to kidney injury. Proposed mechanisms include modulation of eicosanoid metabolism, attenuation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, and generation of specialized pro-resolving mediators. In experimental studies, omega-3 PUFAs may also suppress nuclear factor kappa B (NF-κB)-driven transcription and attenuate mesangial cell proliferation, IgA immune-complex deposition, and transforming growth factor beta 1 (TGF-β1)/Smad3-mediated fibrotic signaling. Clinical Evidence: Conclusions: Omega-3 PUFAs have biological plausibility as adjunctive therapy in IgAN, but their clinical benefit remains uncertain. Available randomized trials and meta-analyses suggest possible modest effects on proteinuria in some settings, whereas evidence for preservation of kidney function or prevention of kidney failure is inconsistent and of low certainty. Future well-designed trials incorporating guideline-directed background therapy and biomarker-guided patient selection are essential to determine optimal dosing, formulation, biological exposure, and whether any patient subgroups derive clinically meaningful benefit. Full article

Background/Objectives: Omega-3 and omega-9 fatty acid supplementation has shown metabolic and immunomodulatory benefits, but evidence in pediatric insulin resistance is limited, and the persistence of effects after treatment discontinuation remains uncharacterized. This study evaluated the independent and combined effects of omega-3 and omega-9 supplementation on the metabolic and inflammatory profile of children with obesity and insulin resistance, during and after active treatment. Methods: This prespecified secondary analysis of a multicenter, randomized, triple-blind, three-arm parallel trial (NCT05488223) included 97 children (8–17 years) with overweight/obesity and baseline insulin resistance (HOMA-IR > 3.0). Participants received 1.8 g/day of omega-3 (n = 32), omega-9 (n = 34), or combined supplementation (n = 31) for 3 months, followed by a 2-month post-intervention follow-up. Metabolic and inflammatory markers were assessed at baseline (T1), end of treatment (T2), and follow-up (T3). The primary outcome was the change in HOMA-IR from T1 to T2. Results: Active supplementation significantly reduced fasting insulin and HOMA-IR in the Combined (p < 0.001) and Omega-9 (p = 0.010 and p = 0.006) groups; at month 5, only the Combined group maintained significant reductions in both. IL-6 and leptin decreased across all groups during intervention and remained reduced at follow-up. Multivariable regression (n = 96) showed the metabolic response was most strongly associated with baseline metabolic status and concurrent BMI reduction rather than intervention group, which was not an independent predictor of metabolic response, nor consistently of inflammatory outcomes (one exception: a smaller IL-4 increase with omega-9, p = 0.043, unconfirmed in GEE). Conclusions: Within-group reductions in HOMA-IR and fasting insulin persisted after discontinuation only in the Combined group, but without significant between-group differences at any timepoint, consistent with response magnitude reflecting baseline status and adiposity reduction rather than treatment group per se. This positions combined supplementation as a potential metabolic adjuvant—not a standalone therapy—for HOMA-IR-defined insulin resistance in pediatric obesity, assessed here via anthropometric and biochemical rather than imaging-based measures. Full article