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Certain algae contain the (n-3) fatty acid DHA, yet the relation between algal oil supplementation and cardiovascular disease risk factors has not been systematically examined. Our objective was to examine the relation between algal oil supplementation and cardiovascular disease risk factors. We conducted a systematic review of randomized controlled trials published between 1996 and 2011 examining the relation between algal oil supplementation and cardiovascular disease risk factors and performed a meta-analysis of the association between algal oil DHA supplementation and changes in the concentrations of TG, LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C). We identified 11 randomized controlled trials with 485 healthy participants that evaluated the relation between algal oil DHA supplementation and TG, LDL-C, and HDL-C. The median dose of algal DHA was 1.68 g/d. The pooled estimate for the change in TG concentration was -0.20 mmol/L (95% CI: -0.27 to -0.14), 0.23 mmol/L (95% CI: 0.16-0.30) for LDL-C, and 0.07 mmol/L (95% CI: 0.05-0.10) for HDL-C. DHA supplementation from algal oil, a marine source of (n-3) fatty acids not extracted from fish, may reduce serum TG and increase HDL-C and LDL-C in persons without coronary heart disease.

Microalgae offer a promising sustainable source of essential nutrients, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). DHA and EPA are mainly obtained through fish, which are limited in number due to global climate change. Microalgal oil, on the other hand, has emerged as a sustainable and limitless source of DHA and EPA but the bioavailability of these nutrients has not been directly compared to fish oil. Therefore, the objective of this study is to evaluate and demonstrate the comparable DHA and EPA plasma bioavailability of microalgal and fish oil. We analyzed the plasma phospholipid levels of 74 adult men and women after 6 and 14 weeks of consuming omega-3 supplements derived from either microalgal or fish oil in a randomized double-blind placebo-controlled parallel-group clinical trial. We found that the bioavailability of DHA and EPA in plasma phospholipids from microalgal oil supplements are statistically non-inferior compared to fish oil supplements, despite the differences in production process and composition, indicating that microalgal oil is a reliable and bioavailable source of DHA and EPA.

Population research on the intervention of docosahexaenoic acid (DHA) supplementation in lactating women is in its infancy in China. This study investigated the effect of DHA supplementation on DHA concentrations in the breast milk of lactating women, and the intervention effect, with respect to different dietary patterns. In this trial, 160 healthy lactating women in Nanjing (30−50 days postpartum) were recruited and randomly divided into control (one placebo capsule of similar appearance per day) and supplement (one capsule with 200 mg of DHA from algal oil per day) groups for 8 weeks. Before and after the intervention, all subjects were asked to maintain basic information, maternal anthropometric parameters, breast milk (10−15 mL) sample collection, and a dietary survey using a food frequency questionnaire. The concentrations of DHA and other fatty acids in breast milk were detected using capillary gas chromatography. This study was completed by 137 subjects, with 60 in the control group and 77 in the supplement group. Compared with the DHA concentrations in the breast milk at enrollment, the absolute concentrations of the control group showed a significant decrease at the end of the trial (p = 0.037). In addition, after intervention, the absolute and relative DHA concentrations in the supplement group (10.07 mg/100 mL and 0.40%, respectively) were higher than those in the control group (7.57 mg/100 mL and 0.28%, respectively), being statistically significant (p = 0.012 and p = 0.001). Furthermore, the maternal diet in the supplement group was divided into four dietary patterns. Pattern 1 mainly included fruits and livestock meat. Pattern 2 was dominated by milk and its products, eggs, fish, shrimp and shellfish, and soybeans and its products. Pattern 3 chiefly comprised cereal and beans other than soybeans, potatoes, and nuts. Pattern 4 was high in poultry meat and low in cooking oils. The change in the absolute concentration of DHA in Pattern 3 was lower than that in other patterns (p < 0.05). In conclusion, DHA supplementation in lactating mothers increased breast milk DHA concentrations. The dietary pattern mainly characterized by cereal and beans other t

PURPOSE: To evaluate bioavailability of omega-3 long-chain polyunsaturated fatty acids (LCPUFA) from foods enriched with novel vegetable-based encapsulated algal oil across Australian and Singaporean populations. METHODS: 27 men (n = 12 Australian European; n = 15 Singaporean Chinese), 21-50 yr; 18-27.5 kg/m2, with low habitual intake of omega-3 LCPUFA completed a multicentre randomised controlled acute 3-way cross-over single-blind trial. They consumed, in random order 1-week apart after an overnight fast, standard breakfast meals including 400 mg docosahexanoic acid (DHA) from either extruded rice snacks or soup both containing cauliflower-encapsulated HiDHA® algal oil or gel capsules containing HiDHA® algal oil. Blood samples for analysis of plasma DHA and eicosapentaenoic acid (EPA) were taken pre-meal and after 2, 4, 6, 8 and 24 h. Primary analyses comparing 24-h incremental area under the plasma DHA, EPA and DHA + EPA concentration (µg/ml) curves (iAUC0-24 h) between test foods were performed using linear mixed models by including ethnicity as an interaction term. RESULTS: Plasma iAUC0-24 h did not differ significantly between test foods (adjusted mean [95% CI] plasma DHA + EPA: extruded rice snack, 8391 [5550, 11233] µg/mL*hour; soup, 8862 [6021, 11704] µg/mL*hour; capsules, 11,068 [8226, 13910] µg/mL*hour, P = 0.31) and did not differ significantly between Australian European and Singaporean Chinese (treatment*ethnicity interaction, P = 0.43). CONCLUSION: The vegetable-based omega-3 LCPUFA delivery system did not affect bioavailability of omega-3 LCPUFA in healthy young Australian and Singaporean men as assessed after a single meal over 24 h, nor was bioavailability affected by ethnicity. This novel delivery system may be an effective way to fortify foods/beverages with omega-3 LCPUFA. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov (NCT04610983), date of registration, 22 November 2020. © 2022. The Author(s).

The development of the infant brain relies on key nutrients such as choline and docosahexaenoic acid (DHA). However, their distinct physicochemical properties pose a challenge, as single supplementation typically results in poor stability and low bioavailability. In this study, DHA and choline were co-encapsulated using microencapsulation technology, resulting in stable microcapsules with an average particle size of approximately 590 nm and a DHA encapsulation efficiency of 85.2 %. Thermogravimetric analysis and Fourier-transform infrared spectroscopy further confirmed that DHA and choline were successfully encapsulated by the wall materials, thereby enhancing the thermal stability and structural integrity of the microcapsules. In addition, the content of fishy-flavor volatiles in the microcapsules was significantly lower than that in commercial DHA algal oil powder, making them more suitable for use in infant formula cereals. Animal experiments demonstrated that the DHA-choline microcapsules significantly improved the recognition index in the novel object recognition test and reduced escape latency in the Morris water maze, indicating enhanced learning and memory.

Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In the current experiments, levels of DHA and choline, two dietary ingredients that enhance neuronal membrane formation and function, were determined in plasma and red blood cells (RBC) from rats after dietary supplementation of DHA-containing oils with and without concomitant dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide experimental evidence for the hypothesized additive effects of dietary lecithin (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC. Dietary supplementation of DHA-containing oils, either as vegetable algae oil or as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin supplementation alone did not affect these levels. However, combined dietary supplementation of DHA and lecithin increased the changes induced by DHA supplementation alone. Animals receiving a lecithin-containing diet also had a higher plasma free choline concentration as compared to controls. In conclusion, dietary DHA-containing oils and crude lecithin have synergistic effects on increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing the systemic availability of dietary DHA, dietary lecithin may increase the efficacy of DHA supplementation when their intake is combined.

There is growing demand for functional food products enriched with long chain omega-3 polyunsaturated fatty acids (LCω3PUFA). Nanoemulsions, systems with extremely small droplet sizes have been shown to increase LCω3PUFA bioavailability. However, nanoemulsion creation and processing methods may impact on the oxidative stability of these systems. The present systematic review collates information from studies that evaluated the oxidative stability of LCω3PUFA nanoemulsions suitable for use in functional foods. The systematic search identified seventeen articles published during the last 10 years. Researchers used a range of surfactants and antioxidants to create systems which were evaluated from 7 to 100 days of storage. Nanoemulsions were created using synthetic and natural emulsifiers, with natural sources offering equivalent or increased oxidative stability compared to synthetic sources, which is useful as consumers are demanding natural, cleaner label food products. Equivalent vegetarian sources of LCω3PUFA found in fish oils such as algal oils are promising as they provide direct sources without the need for conversion in the human metabolic pathway. Quillaja saponin is a promising natural emulsifier that can produce nanoemulsion systems with equivalent/increased oxidative stability in comparison to other emulsifiers. Further studies to evaluate the oxidative stability of quillaja saponin nanoemulsions combined with algal sources of LCω3PUFA are warranted.

OBJECTIVES: To update a prior systematic review on the effects of omega-3 fatty acids (n-3 FA) on maternal and child health and to assess the evidence for their effects on, and associations with, additional outcomes. DATA SOURCES: MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Centre for Agriculture and Biosciences (CAB) Abstracts from 2000 to August 2015; eligible studies from the original report; and relevant systematic reviews. REVIEW METHODS: We included randomized controlled trials (RCTs) of any defined dose of n-3 FA (or combination) compared to placebo, any other n-3 FA, or alternative dose with an outcome of interest conducted in pregnant or breastfeeding women or neonates (preterm or term). We also included prospective observational studies that analyzed the association between baseline n-3 FA intake or biomarker level and followup outcomes. Postnatal interventions began within a week of birth for term infants and within a week of beginning enteral or oral feeding for preterm infants. Standard methods were used for data abstraction and analysis, according to the Evidence-based Practice Center Methods Guide. RESULTS: We identified 4,275 potentially relevant titles from our searches, of which 95 RCTs and 48 observational studies met the inclusion criteria. Risk of bias was a concern with both RCTs and observational studies. Outcomes for which evidence was sufficient to draw a conclusion are summarized here with the Strength of Evidence (SoE). (Outcomes for which the evidence was insufficient to draw a conclusion are summarized in Appendix G of the report.). Maternal Exposures and Outcomes: Gestational length and risk for preterm birth: Prenatal algal docosahexaenoic acid (DHA) or DHA-enriched fish oil supplementation had a small positive effect on length of gestation (moderate SoE), but no effect on risk for preterm birth (low SoE). Prenatal EPA (eicosapentaenoic acid) plus DHA-containing fish oil supplementation has no effect on length of gestation (low SoE). Supplementation with DHA, or EPA plus DHA-, or DHA-enriched fish oil does not decreaserisk for preterm birth (low SoE). Birth wei

Presently alpha-linolenic acid (ALA) is the most widely used vegetarian LC3PUFA, but only marginal amounts are converted into eicosapentaenoic (EPA) and docosahexaenoic acid (DHA); both of which are strongly related to human health. Currently, fish oils represent the most prominent dietary sources of EPA and DHA; however, these are unsuitable for vegetarians. Alternative sources include flaxseed, echium, walnut, and algal oil but their conversion to EPA and DHA must be considered. The present systematic review sets out to collate information from intervention studies examining the bioavailability of alternative vegetarian long chain omega-3 (n-3) polyunsaturated fatty acids (LC3PUFA) sources. Ten key papers published over the last 10 years were identified with seven intervention studies reporting that ALA from nut and seed oils was not converted to DHA at all. Three studies showed that ingestion of micro-algae oil led to significant increases in blood erythrocyte and plasma DHA. Further work is now needed to identify optimal doses of alternative vegetarian LC3PUFAs and how these can be integrated within daily diets. The potential role of algal oils appears to be particularly promising and an area in which further research is warranted.

Background: There is a growing number of studies suggesting the effectiveness of dietary supplements in preventing and treating endometriosis. It has been suggested that deficiencies in vitamins D and E as well as zinc are associated with the increased risk of endometriosis development. Beneficial effects of magnesium, curcumin, resveratrol and epigallocatechin-3-gallate were found in experimental animal studies. A reduction in pain related to endometriosis was shown in women using omega-3 and alpha-lipoic acid. Meanwhile, decreasing endometriotic lesion size after the supplementation of omega-3, N-acetylcysteine, vitamin C and epigallocatechin-3-gallate was observed in animal and human studies. Thus, the aim of this critical review was to summarize the available data describing the effects of dietary supplements used in the treatment of endometriosis. Material and Methods: The PubMed, Embase, Cochrane, and Web of Science databases were searched for related studies until 15 December 2025. Finally, 34 studies were included in the synthesis. Results: Of these 34 studies, only 23 were randomized, placebo-controlled trials. There have been no RCTs evaluating the effectiveness of vitamin E, zinc, alpha-LA, EGCG and DIM in the treatment of endometriosis. Single studies evaluating the effectiveness of vitamin C, magnesium, resveratrol, NAC and PEA with PLD have not confirmed it. Meanwhile single studies evaluating the effectiveness of selenium, propolis and quercetin have confirmed it. Of the four studies assessing the effectiveness of vitamin D, two confirmed it and two did not; of the two studies assessing probiotics, one confirmed its effectiveness and one did not; of the two studies assessing curcumin, one confirmed its effectiveness and one did not; and of the three studies assessing omega-3, two confirmed its effectiveness and one did not. All four RCTs assessing the combination of vitamins C and E confirmed their effectiveness. Conclusions: Despite encouraging observations from experimental studies, the results of RCTs are less encouraging and do not allow for the formulation of recommendations concerning the use of supplements in the treatment of endometriosis

BACKGROUND: The first 1000 days of life, from conception to 2 years of age, represent a critical window during which nutrition can exert long-lasting effects on neurodevelopment, immune maturation, and susceptibility to prematurity-related morbidity. Docosahexaenoic acid (DHA) is a key structural n-3 long-chain polyunsaturated fatty acid of the brain and retina, characterized by rapid fetal accretion during the third trimester. METHODS: We conducted a narrative review of studies published from March 2015 up to December 2025, including randomized controlled trials, follow-up studies, and systematic reviews/meta-analyses about DHA supplementation during pregnancy, lactation, infancy and early childhood, and its role on development. RESULTS: Across the first 1000 days, DHA supplementation improves biochemical DHA status, particularly in populations with low baseline levels (moderate to high level of evidence), while clinical outcomes remain heterogeneous. During pregnancy, some benefits in specific cognitive and behavioral domains have been demonstrated, whereas effects on global cognition and long-term behavior are frequently null (moderate evidence). Visual outcomes appear favorable, with improvements in visual acuity (moderate evidence). In preterm infants, enteral DHA-often combined with arachidonic acid (ARA)-is feasible and well tolerated. DHA may reduce inflammatory markers and necrotizing enterocolitis risk when in equilibrium with ARA (low to moderate evidence), while no evidence supports the link between DHA and reduced risk of bronchopulmonary dysplasia and retinopathy of prematurity (moderate evidence). Neurodevelopmental outcomes are mixed: neuroimaging studies suggest enhanced white matter maturation with DHA + ARA, whereas most trials show no clear benefit regarding standardized developmental scores (moderate evidence). CONCLUSIONS: DHA is biologically essential during the first 1000 days, but its clinical impact depends on timing, dose, baseline status, and prematurity-related context. The balance between DHA and ARA, rather than DHA supplementation alone, emerges as a key determinant of clinical efficacy, supporting a shift toward precision-based n

Chronic kidney disease (CKD) is closely associated with systemic inflammation. This randomized controlled trial aimed to evaluate the effects of omega-3 fatty acids supplementation on inflammatory markers in patients with CKD undergoing hemodialysis. Eligible participants with CKD receiving hemodialysis were randomly assigned to either an intervention group or a control group. The intervention group received three capsules of omega-3 fatty acids (3 g/day) for two months, while the control group received placebo capsules containing medium-chain triglyceride (MCT) oil. Inflammatory markers, including C-reactive protein (CRP) and interleukin-6 (IL-6), were measured both before and after the interventions. The results showed that CRP levels increased from 9.86 ± 12.64 to 11.46 ± 22.23 mg/L in the intervention group and from 5.24 ± 9.01 to 5.61 ± 7.93 mg/L in the control group (p = 0.11). Similarly, IL-6 levels increased from 17.84 ± 14.08 to 81.82 ± 66.22 pg/mL in the intervention group and from 14.96 ± 18.41 to 56.73 ± 115.45 pg/mL in the control group (p = 0.53). No statistically significant group differences were observed after adjusting for confounders such as age, sex, body mass index (BMI), smoking, dietary intake, and pre-existing diseases. The study findings showed that a two-month intake of omega-3 fatty acids supplements did not have a significant impact on reducing the levels of inflammatory markers in CKD patients undergoing hemodialysis. Larger trials with longer durations are warranted. Study Highlights What is the Current Knowledge on the Topic? ○ Omega-3 fatty acids have anti-inflammatory properties and are reported to be potentially beneficial in reducing inflammation associated with CKD, but the evidence regarding the effectiveness of omega-3 supplements in reducing inflammatory markers in this population remains inconsistent. What Question did this Study Address? ○ What is the effect of omega-3 fatty acids supplementation for 2 months on CRP and IL-6 levels in patients with CKD undergoing hemodialysis? What Does This Study Add to Our Knowledge? ○ Contrary to previous studies, this study found that omega-3 fatty acids supplementation did not signif

BACKGROUND: Tobacco use and its smoke produces oxidative stress in the body, which eventually triggers cell damage by lipid peroxidation. Smokers report lower levels of omega-3 fatty acids (FAs) in their serum as compared to nonsmokers. Omega-3 deficiency impairs neurotransmission, resulting in hypofunctioning of the mesocortical system, which is a reward and dependency system that can raise tobacco cravings, disrupting tobacco quitting efforts. Omega-3 polyunsaturated fatty acid (PUFA) regulates stress, anxiety, and negative emotions that are associated with tobacco urges. Limited research has assessed the supplementation effect of omega-3 PUFA [in the form of alpha-linolenic acid (ALA)] on tobacco craving. AIM: We aimed to explore the effects of omega-3 PUFA (ALA) on the frequency of tobacco use per day, tobacco dependence, and tobacco craving when compared to placebo in regular tobacco users. MATERIALS AND METHODS: Regular tobacco users (n = 83) recruited from the Tobacco Cessation Clinic were randomly allocated to two groups. Group I was the omega-3 PUFA group, supplemented with 10 mL/day of omega-3 PUFA in the form of ALA (5.1 gm) for 180 days, and the other group received a placebo for the same duration. The outcome was evaluated by means of a case record form (for demographic parameters), self-reports of tobacco use (for frequency of tobacco use per day), as well as psychometric measures (for tobacco dependence and tobacco craving). The evaluations were carried out at baseline and after 180 days of intervention. RESULTS AND CONCLUSION: The frequency of tobacco use per day, tobacco dependence, and tobacco craving were found to be significantly decreased (p < 0.0001) in the group receiving omega-3 PUFA (ALA) at the end of supplementation. This is a novel approach that ALA supplementation reduces tobacco cravings in regular tobacco users in comparison to a placebo. Thus, omega-3 FAs may be an adjuvant tool in quitting tobacco use by reducing nicotine dependence and tobacco craving. Further studies are necessary with large samples to understand the possible association and explore the probable nonpharmacological approaches for tobacco cessation. © Journal of

BACKGROUND AND OBJECTIVE: Obesity rates continue to rise globally, highlighting the need for prevention and targeted treatment strategies. Chronic systemic low-grade inflammation and gut microbiota dysbiosis are key contributors to obesity-associated metabolic diseases. Anti-inflammatory dietary components, such as fish oil rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), reduce inflammation and improve metabolic outcomes. Similarly, physical activity improves metabolic health and attenuates chronic systemic inflammation, with varying benefits according to exercise intensity. While both interventions independently modulate inflammation and gut microbiota, their combined effects warrant further research. This study investigates the combined impact of n-3 PUFA supplementation and high-intensity interval training (HIIT) on obesity-related inflammation and gut microbiota dysbiosis, hypothesizing that improvements in gut microbiota composition driven by n-3 PUFAs may enhance the metabolic benefits of exercise. DESIGN AND METHODS: Adults with a body mass index (BMI) ≥ 25 kg/m2 are randomized to receive either 4 g/day n-3 PUFA or safflower oil (placebo) for 10 weeks. During weeks 0-4, participants take the assigned supplement. Beginning in week 4, one n-3 PUFA group and one placebo group will additionally complete 4-weeks of HIIT. Control groups perform low-intensity training (LIT) for 4 weeks. The last two weeks are a detraining phase with continued supplementation. DISCUSSION: This study explores the benefits of combining short-term HIIT and n-3 PUFA supplementation in individuals with overweight or obesity. The findings inform measurable, time-efficient interventions that target systemic inflammation, gut microbiota dysbiosis, and metabolic dysfunctions.

BACKGROUND: Structured triglycerides (STGs), in which eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are esterified with medium-chain triglycerides (MCTs), have demonstrated greater bioavailability and potential benefits in improving endurance and reducing post-exercise strength loss compared with physical mixtures (PMs) of EPA and MCTs. However, it remains unclear whether STGs have superior effects on blood EPA levels and muscular endurance and fatigue. This study compared the effects of 8-week STG and PM intake on blood EPA levels, muscular endurance, and fatigue following resistance exercise. METHODS: Twenty-eight healthy young men were randomly assigned to an STG group (n = 15) or a PM group (n = 13) in a double-blind, parallel-group, active comparator trial. Participants consumed 4,560 mg/day of the test oil (600 mg EPA, 260 mg DHA) for 8 weeks. After the intervention, the participants performed four sets of leg extensions to exhaustion at 40% of their body weight. Muscular endurance was assessed by the number of repetitions, and fatigue was evaluated by changes in maximal voluntary contraction, range of motion, thigh circumference, muscle thickness, echo intensity, and jump performance. RESULTS: The STG group showed a significantly greater increase in the serum EPA/arachidonic acid (AA) ratio compared with the PM group. However, no significant differences were found between groups in repetition counts or fatigue-related measures. CONCLUSION: Eight weeks of STG supplementation improved the blood EPA/AA ratio more than a PM, but did not yield superior effects on muscle endurance or fatigue.

BACKGROUND: Tools to measure omega-3 (n-3) polyunsaturated fatty acid (PUFA) half-lives and turnover deserve attention, as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play vital roles in the body. Plants and marine life vary in fixed carbon-13 signatures (δ13C), allowing in vivo tracing. OBJECTIVES: To determine the half-lives and turnover of n-3 PUFAs using δ13C in this secondary analysis. METHODS: During a 28-d randomized crossover study (6-wk wash-in phase/washout phase), 12 participants (aged 19-34 y) were supplemented with 4.2 g/d α-linolenic acid (ALA) (flax oil) or 4.3 g/d DHA, 1.0 g/d EPA, and 0.2 g/d docosapentaenoic acid (n-3 DPA) (fish oil). Blood was collected on days 0, 1, 3, 7, 14, and 28. Plasma n-3 PUFA δ13C signatures were analyzed by gas chromatography-isotope ratio mass spectrometry (GC-IRMS) to calculate half-lives and turnover. RESULTS: δ13C signatures of flax oil ALA, fish oil EPA, n-3 DPA, and DHA were -33.2 ± 1.4, -26.3 ± 2.2, -26.2 ± 1.5, and -25.4 ± 1.3 mUr, respectively. Baseline signatures were not statistically different. Over time, δ13C of EPA, n-3 DPA, and DHA converged toward the isotopic signature of the fish oil supplement (P < 0.05). Using δ13C signatures, half-lives of EPA, n-3 DPA, and DHA (3.4 ± 2.7, 6.4 ± 5.3, and 6.3 ± 8.9 d, mean ± SD, respectively) and turnover rates (61.9 ± 53.1, 6.0 ± 2.9, and 78.0 ± 44.5 nmol/mL/d, respectively) were calculated. CONCLUSIONS: This is the first study to investigate n-3 PUFA half-lives and turnover in humans using GC-IRMS and the natural variance of 13C in commercial fish oils. These results were similar to preclinical model values and other clinically used methods but added the first estimate for n-3 DPA half-life and turnover rate. Compound-specific isotope analysis is a valuable tool in human studies for determining n-3 PUFA half-lives and turnover rate, as well as factors affecting them, including diet, exercise, sex, genetics, and disease.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron loss, with limited effective therapies. Docosahexaenoic acid (DHA) exhibits neuroprotective effects, but its limited transport across the blood-brain barrier (BBB) restricts clinical utility. Major facilitator superfamily domain-containing protein 2A (MFSD2A) is the primary transporter of DHA into the central nervous system, yet its role in ALS remains unclear. This study investigated the therapeutic potential and mechanisms of MFSD2A overexpression combined with DHA supplementation in male SOD1^G93A ALS mice. We found that MFSD2A expression was markedly reduced in ALS mice and correlated with impaired motor function and neuronal damage. DHA supplementation or MFSD2A overexpression partially improved behavioral deficits, while their combination produced synergistic benefits. Histological analyses revealed attenuated neuronal degeneration and reduced muscle fibrosis following combined treatment. Furthermore, MFSD2A physically interacted with the E3 ubiquitin ligase TRIM21, regulating glycolytic metabolism by modulating key enzymes (GLUT1, HK2, LDHA, PDK1) and products (lactate/pyruvate and NADH/NADPH ratio). TRIM21 knockdown reversed MFSD2A-mediated neuroprotection and impaired glycolytic metabolism, indicating its critical role in this pathway. The combined intervention also suppressed systemic inflammation and oxidative stress by decreasing pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and restoring antioxidant enzyme activities (GSH-Px), while reducing lipid peroxidation (MDA). These findings suggest that MFSD2A facilitates DHA's neuroprotective effects by enhancing glycolytic metabolism and mitigating neuroinflammation. This study highlights MFSD2A and DHA as promising therapeutic targets in ALS and provides novel insights into overcoming BBB transport limitations for neurodegenerative disease treatment. © 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Omega-3 fatty acid supplementation may influence lipid mediators that regulate inflammation, but its effects in older adults are not well defined. This secondary analysis examined the effects of omega-3 supplementation on lipid mediators and inflammatory markers in older adults performing a home-based and vibration exercise program. We hypothesized that omega-3 supplementation would reduce circulating prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) and increase resolvin E1 (RvE1). Forty participants (mean age 69 years, 50% women) were randomly assigned to receive an algae-oil omega-3 supplementation (1397 mg docosahexaenoic acid, 749 mg eicosapentaenoic acid) or no supplementation for 8 weeks. Plasma PGE2, LTB4, RvE1, and inflammatory markers were measured before and after the intervention. Directional changes were classified as increase, no change, or decrease, and correlations between lipid mediator and inflammatory marker responses were analyzed. PGE2 decreased more in the omega-3 group than in controls (time × group P = .043), whereas LTB4 (time P < .001) and RvE1 (time P = .003) declined similarly in both groups. Supplementation was associated with greater reductions in interleukin 10 and interleukin 1 receptor antagonist, and a larger increase in insulin-like growth factor 1. Changes in PGE2 correlated with C reactive protein (ρ = -0.412, P = .008) and like growth factor 1 (ρ = 0.345, P = .029). Omega-3 supplementation selectively lowered PGE2 independent of exercise effects, while exercise contributed to decreases in LTB4 and RvE1. These findings indicate that omega-3 supplementation modifies lipid mediators linked to inflammation in older adults.

Despite widespread use in the USA, little is known about the impact of multivitamin-multimineral (MVM) supplementation on metabolomic profiles and how this may translate to biological aging and long-term risk of age-related chronic diseases. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a 2 × 2 factorial, placebo-controlled, double-blinded, randomized clinical trial testing daily MVM (Centrum Silver®) in US older adults. In 399 participants with metabolomics profiles quantified using the Nightingale Health nuclear magnetic resonance platform at baseline, year 1, and year 2 (70.3 ± 5.7 years; 50.1% female), we evaluate the effects of MVM versus placebo on 168 metabolites, 7 metabolomics clocks of biological aging, and 24 metabolomic risk scores (MRS) for chronic diseases. Compared with placebo, 2-year daily MVM supplementation increased the concentrations of docosahexaenoic acid (Cohen's d for between-group differences in changes from baseline to 2 years, 0.212 [95% CI, 0.02 to 0.404]) and omega-3 fatty acids (0.193 [0.003 to 0.382]) as well as delayed the increase in concentrations of creatinine (-0.222 [-0.424 to -0.019]). MVM also reduced MRS for 16 chronic diseases, including major cardiovascular events, renal disease, all-cause dementia, asthma, cataracts, glaucoma, liver disease, non-melanoma skin cancer, and prostate cancer (Cohen's d range, -0.206 to -0.277). However, all these effects were only significant at nominal levels, not after multiple-testing correction (p < 0.05; FDR > 0.05). Additionally, MVM led to a non-significant decrease across all metabolomic aging clocks, ranging from 0.496 to 1.054 years. Despite the limited sample size, COSMOS provides preliminary evidence that daily MVM supplementation may modestly improve metabolomic profiles in older adults. Further expansion within COSMOS is still warranted to confirm whether these alterations contribute to the benefits of MVM supplementation for healthy aging. Trial registration number: NCT02422745. © 2026. The Author(s), under exclusive licence to American Aging Association.

This systematic review and network meta-analysis aimed to compare the effects of dietary protein, creatine, and omega-3 fatty acid supplementation on muscle strength, endurance performance, and recovery outcomes in trained athletes. A comprehensive literature search across MEDLINE, Embase, Cochrane CENTRAL, Web of Science, SPORTDiscus, and Scopus identified randomized controlled trials evaluating these supplements in individuals engaged in structured training for a minimum of six months. Network meta-analysis employing a frequentist random-effects model synthesized direct and indirect evidence, with treatment rankings determined using Surface Under the Cumulative Ranking curve probabilities. The analysis incorporated 35 trials enrolling 1211 participants. Creatine supplementation demonstrated superior effects for muscle strength (SMD = 0.46, 95% CI: 0.29 to 0.63, SUCRA = 82.4%), protein supplementation proved most effective for endurance performance (SMD = 0.28, 95% CI: 0.08 to 0.48, SUCRA = 85.2%), and omega-3 supplementation yielded the greatest benefits for recovery outcomes (SMD = 0.40, 95% CI: 0.18 to 0.62, SUCRA = 88.7%). Network consistency assessment revealed no significant disagreement between direct and indirect evidence across all outcomes. These findings reveal an outcome-specific efficacy pattern supporting targeted supplementation strategies aligned with primary training objectives in athletic populations.

Omega-3 polyunsaturated fatty acids (PUFAs) are known to modulate inflammatory signaling and enhance muscle recovery from exercise-induced stress. In this work, a meta-analysis was conducted that adhered to the PRISMA 2020 criteria, incorporating evidence from 41 randomized controlled trials on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation, all of which had been conducted as evidence between 2011 and 2025 and evaluated the effects of EPA and DHA supplementation on the primary markers of the impact of exercise on inflammation and muscle injury, including the random-effects model with moderator dose, intervention duration, sex, and training status. The integrated findings showed that interleukin-6, tumor necrosis factor-α, creatine kinase, and delayed-onset muscle soreness (standardized mean difference = -0.4 to -0.7) were significantly and moderately reduced, indicating a uniform response to omega-3 supplementation's anti-inflammatory and recovery-promoting effects. C-reactive protein responses were more dispersed, suggesting that baseline inflammation differed and that the sampling protocols did as well. Subgroup analyses showed that doses of 2 g/day or more of mixed EPA + DHA, with a minimum duration of 6 weeks of administration, produced the strongest effects, especially among recreational athletes rather than elite athletes. Mechanistically, nuclear factor-kappa B activation and the ensuing synthesis of specialized pro-resolving mediators (resolvins, protectins, and maresins), as well as an increase in cellular antioxidant capacity, appear to be moderated by omega-3 supplementation and support efficient resolution of inflammation and tissue repair. These results form a body of evidence over more than 10 years, showing that omega-3 fatty acids are a strong, evidence-based nutritional tool for reducing the effects of post-exercise inflammation, supporting functional recovery, and sustaining long-term athletic performance. © 2026 Federation of American Societies for Experimental Biology.

A recent mouse study has shown that deficiency in 12-hydroxyeicosatetraenoic acid (12-HETE) affects neonatal alveolar macrophage imprinting and associates with increased respiratory morbidity, but this has not been investigated in humans. Utilizing data from two mother-child cohorts, COPSAC2010 and VDAART, we demonstrate that undetectable maternal plasma 12-HETE during pregnancy associates with increased risk of childhood asthma and respiratory infections alongside an altered infant airway microbiota structure and airway immune profile. Further, we observed an interaction between maternal 12-HETE levels and maternal N-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation in a randomized clinical trial in COPSAC2010 and maternal dietary n-3 LCPUFA intake in VDAART in relation to offspring respiratory morbidity; higher prenatal n-3 LCPUFA exposure reduced asthma and respiratory infection among mothers with detectable 12-HETE levels. These findings identify maternal 12-HETE as a potential biomarker for risk of offspring respiratory morbidity and suggest that maternal 12-HETE status may determine responsiveness to prenatal n-3 LCPUFA supplementation.

Despite well-documented benefits of omega-3 for maternal and child health, evidence on high-docosahexaenoic acid (DHA) supplementation in low-risk pregnant women is limited. A randomized, double-blind, placebo-controlled trial was conducted among low-risk pregnant women aged 20-40 years at 22-24 weeks of gestation to evaluate the effects of high-DHA omega-3 supplementation on maternal and neonatal health outcomes. The control group (CG, n = 30) received oral olive oil supplementation, and the intervention group (IG, n = 30) received omega-3 [1700 mg, 260 mg of eicosapentaenoic acid (EPA), and 1440 mg of DHA] for ∼16 weeks or until delivery. Maternal and neonatal health outcomes were collected by telephone 15 days after delivery. Forty-five pregnant women completed the study (IG: 20; CG: 25). Adherence to supplementation was above 90% and did not differ between groups (P > .05). There were no differences between groups in mean gestational age (CG: 39.3 ± 1.6; IG: 39.2 ± 1.6; P = .877), adequate gestational weight gain (CG: 24.0%; IG: 50.0%; P = .088), adequate gestational BMI before delivery (CG: 33.3%; IG: 27.8%; P = .261), vaginal delivery (CG: 72.0%; IG: 60.0%; P = .396), full-term birth (CG: 92%; IG: 90%; P = .815), adequate weight (CG: 91.3%; IG: 94.7%; P = .237), and adequate length for gestational age (CG: 82.6%; IG: 100%; P = .056). Omega-3 supplementation with a higher concentration of DHA had no effect on the maternal and neonatal health outcomes investigated in a Brazilian sample of low-risk pregnant women. Further studies are needed to evaluate this effect in pregnant women at higher nutritional risk and with low dietary intake of omega-3. © The Author(s) [2026]. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition that affects attention, impulse control, and the ability to remain still. These challenges can make it harder for individuals with ADHD to succeed at school, work, and in social situations. Stimulant medications, such as methylphenidate and amphetamines, are commonly used as first-line treatments and are effective at reducing symptoms. However, their use can be limited by side effects, such as insomnia, appetite loss, cardiovascular risks, potential for misuse, and variability in individual response. Since current treatments have drawbacks, many people are exploring nonstimulant options, such as behavioral therapy, dietary changes, and neurofeedback. These approaches may be safer and easier to maintain, but research on their effectiveness remains uncertain. This systematic review and meta-analysis aim to compare the effectiveness of pharmacological and nonpharmacological therapies for ADHD. METHOD: We systematically searched PubMed, PsycINFO, Cochrane Library, ClinicalTrials.gov, and IEEE Xplore for randomized controlled trials (2008-2023) evaluating pharmacological (e.g., stimulant medications), non-pharmacological (e.g., behavioral therapy, cognitive training), or combined interventions in children and adolescents with ADHD. The search yielded 318 records. After screening titles and abstracts, 249 were excluded. Sixty-nine full-text articles were assessed, and 18 RCTs met the inclusion criteria for analysis. Primary outcomes were reductions in ADHD symptoms measured by standardized rating scales; secondary outcomes included academic performance, social functioning, and clinical global impression. RESULTS: Eighteen RCTs were pooled. ADHD symptoms were consistently reduced with stimulant medications (methylphenidate and amphetamines), although effects on academic performance were modest. Non-stimulants, such as viloxazine and guanfacine, showed significant improvements on ADHD-RS scores, but these improvements were only clinically modest. In contrast, some nutritional supplements, particularly iron and omega-3 fatty acids, showed more pronounced benefits in sympt