Position Statement: The International Society of Sports Nutrition (ISSN) presents this position based on a critical examination of the literature surrounding the effects of long-chain omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation on exercise performance, recovery, and brain health. This position stand is intended to provide a scientific foundation for athletes, dietitians, trainers, and other practitioners regarding the effects of supplemental ω-3 PUFA in healthy and athletic populations. The following conclusions represent the official position of the ISSN: Athletes may be at a higher risk for ω-3 PUFA insufficiency.Diets rich in ω-3 PUFA, including supplements, are effective strategies for increasing ω-3 PUFA levels.ω-3 PUFA supplementation, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been shown to enhance endurance capacity and cardiovascular function during aerobic-type exercise.ω-3 PUFA supplementation may not confer a muscle hypertrophic benefit in young adults.ω-3 PUFA supplementation in combination with resistance training may improve strength in a dose- and duration-dependent manner.ω-3 PUFA supplementation may decrease subjective measures of muscle soreness following intense exercise.ω-3 PUFA supplementation can positively affect various immune cell responses in athletic populations.Prophylactic ω-3 PUFA supplementation may offer neuroprotective benefits in athletes exposed to repeated head impacts.ω-3 PUFA supplementation is associated with improved sleep quality.ω-3 PUFA are classified as prebiotics; however, studies on the gut microbiome and gut health in athletes are currently lacking.

The study compared the effects of hexane and 2-methyltetrahydrofuran (MeTHF) on oil yield, stability and bioactive compounds in fig, black cumin and rosehip oils. MeTHF increased oil yield in fig (11.7 %), black cumin (28.3 %) and rosehip (13.2 %). Solvent type did not change fatty acid and tocopherol composition and 18 fatty acids were identified. MeTHF increased number of phenolic compounds from 9 to 16 and amount of total tocopherol, phenolics, chlorophylls and carotenoids in oils. The antioxidant activity of oils was measured by CUPRAC and DPPH assays and MeTHF extracted oils had significantly higher antioxidant capacity. Oxidative stability test revealed that hexane-extracted oils peroxide value (PV) increased dramatically in fig (182.7 %) and rosehip (221.1 %) oils, while PV of MeTHF extracted oils was not significant in fig and rosehip oils. Black cumin oil was stable for both solvents. Results show that MeTHF is more efficient for obtaining oils with bioactive molecules to improve stability and quality.

According to previous studies, omega-3 polyunsaturated fatty acids (PUFAs) are controversial for the efficacy of treating depression.

This meta-analysis aims to investigate whether omega-3 PUFAs are able to treat depression, and find out the most beneficial clinical portrait.

More than two reviewers searched six registries, and 36 studies were eventually considered eligible. The PRISMA guidelines were used for data extraction, Cochrane Handbook for quality assessment, and random effects model for data pooling.

Significant heterogeneity and publication bias were observed. According to the results, significant efficacy was detected in the overall analysis [SMD = -0.26, 95 % CI = (-0.41, -0.11)] and several subgroups, while total daily dosage might be a potential heterogeneity source (P < 0.05). No between-group difference was observed in the rate of response [RR = 0.99, 95 % CI = (0.82, 1.20)], remission [RR = 1.17, 95 % CI = (0.92, 1.48)], and adverse events [RR = 1.07, 95 % CI = (0.90, 1.29)]. Total daily intake of eicosapentaenoic acid (EPA) and remission rate conformed to linear correlation (P < 0.05).

1) Omega-3 PUFAs might be effective in treating depression; 2) For Asian patients with mild to moderate depression and no other baseline medication, over 8 weeks of omega-3 PUFAs 1000-1500 mg/day with ratio of EPA/docosahexaenoic acid (DHA) between 1:1 and 2:1 might benefit the most; 3) Omega-3 PUFAs are no superior than placebo in rates of response, remission, and adverse events. Although several limitations exist, the evidence-based information provides guidance for clinical practice and directions for further research.

CRD42023464823.

The n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have a key role in maintaining fish growth and health. However, fish oil (FO), the main source of n-3 LC-PUFAs, is in relative shortage due to the rapid development of the aquaculture industry. In this study, we investigated the efficacy of replacing fish oil with mixtures of algal oil (AO) from Schizochytrium sp. and terrestrially sourced oils (animal oil poultry oil (PO) or vegetable oil rapeseed oil (RO)) in the diets of juvenile tiger puffer (average initial body weight 23.8 ± 1.51 g). An 8-week feeding trial was conducted using three experimental diets: a control diet containing 6% added FO (control FO-C) and two diets with 3% AO + 3% PO or RO (groups AO+PO and AO+RO, respectively), replacing FO. Each diet was fed to triplicate tanks with 25 fish in each tank. The weight gain, feed conversion ratio, body composition, and serum biochemical parameters were not significantly different among the three groups, except that the AO+PO group had a significantly lower muscle lipid content than the other two groups. The AO-added diets significantly increased the DHA content in whole fish, muscle, and liver samples but significantly reduced the EPA content. The oil mixture treatments significantly increased the contents of monounsaturated fatty acid (MUFA) but significantly decreased the contents of saturated fatty acids (SFAs) in the liver and whole fish samples. However, the MUFA and SFA contents in the muscle samples were not significantly different among the dietary groups. The diets with oil mixtures did not affect the hepatic histology but tended to result in the atrophy of intestinal villi. The treatment diets downregulated the hepatic gene expression of proinflammatory cytokines (il-1β and tnf-α) and the fibrosis marker gene, acta2. However, the AO+PO diet inhibited the intestinal gene expression of the tight junction protein, claudin 18. In the muscle, the treatment diets upregulated the expression of genes related to cell differentiation and apoptosis (myod, myog, myf6, myf5, bcl-2, and bax). In conclusion, Schizochytrium sp. oil in combination with terrestrial oils (poultry oil or rapeseed oil) can be an effective alternative to fish oil in the diets of tiger puffer, but the mixing strategy may be better modified in consideration of intestinal health.

Long-chain n-3 polyunsaturated fatty acid (PUFA) consumption in maternal and infants has been positively associated with cognitive and visual development. Tails even meta-analysis showed mixed results. To evaluate the effects of maternal and infant n-3 PUFA supplementation on childhood psychomotor and cognitive development, PubMed, Embase, the Cochrane Library, PsycINFO and clinicaltrials.gov were searched. Randomized controlled trials were included to evaluate the effect on child cognitive and psychomotor outcomes of n-3 PUFA supplementation in mothers or infants (age ≤ 2 years). Findings were pooled with mean differences (MD) with 95% confidence intervals (95% CIs). Heterogeneity was explored using I2 and subgroup analyses, stratified for maternal (pregnancy and/or lactation) and infant (preterm infant and term infant). We identified 47 articles, with 14 trials on mothers and 33 on infants. Pooled results showed that infants' mental development index (MDI) increased with n-3 PUFA supplementation (MD = 2.91, 95% CI: 1.32-4.51, I2 = 65.1%). Subgroup analysis of MDI also demonstrated a benefit in preterm infants (MD = 4.16, 95% CI: 1.40-6.93, I2 = 49.5%) and term infants (MD = 2.28, 95% CI: 0.27-4.29, I2 = 70.1%). No significant association was found in subgroup analyses of supplementation to mothers during pregnancy or lactation period. Supplementation did not increase the psychomotor development index (PDI) in the mother or infant group. Language composite score increased for infants whose mothers accepted supplementation in pregnancy or breastfeeding (MD = 8.57, 95% CI: 5.09-12.04, I2 = 70.2%). The cognitive composite score did not improve in any subgroup. Intelligence Quotient (IQ) increased in the infants' group with n-3 PUFA supplementation (MD = 2.54, 95% CI: 0.45-4.63, I2 = 66.0%). Furthermore, IQ in term infants also improved (MD = 2.91, 95% CI: 0.24-5.57, I2 = 69.2%). The funnel plot and Egger's test confirmed no publication bias in any endpoints. Supplementation with n-3 PUFA during pregnancy or breastfeeding in mothers has increased language abilities. Furthermore, direct supplementation in term infants can improve intelligence in later childhood. However, insufficient evidence supports the claim that supplementation improves cognitive abilities.

The incidence of depression is on the rise, and currently available antidepressants often exhibit limited efficacy in many patients. Additionally, the underlying mechanisms of depression remain poorly understood. Research has shown that neuroinflammation, driven by M1 microglial phenotypic polarization, contributes to neuronal abnormalities implicated in the development of depression. Eicosapentaenoic acid (EPA) has emerged as a promising therapeutic agent for depression. However, the specific target of EPA's anti-stress effects is yet to be identified. This study aimed to explore the pathogenesis of depression and elucidate the central regulatory mechanisms underlying EPA's antidepressant efficacy. In this study, mice were orally administered EPA for five consecutive weeks. During this period, they were subjected to daily chronic unpredictable mild stress (CUMS) and treated with lipopolysaccharide (LPS, 0.5 mg kg-1, intraperitoneally) every other week. The results demonstrated that EPA significantly alleviated neuronal degeneration in the medial prefrontal cortex. Furthermore, EPA improved synaptic plasticity impairments induced by CUMS combined with LPSs, as indicated by the increased protein levels of Nlgn1, PSD95, GAP43, and Syn. EPA also reduced neuroinflammation by inhibiting M1 microglial polarization and NLRP3 inflammasome activation. Notably, EPA exerted antidepressant-like effects by modulating GPR120. These findings suggest that EPA intake can mitigate abnormal mood and behavior induced by elevated immune-inflammatory signals. These findings suggest that EPA intake can attenuate abnormal moods and behaviors induced by elevated immune-inflammatory signals. Therefore, EPA may be a promising strategy for the clinical treatment of inflammatory depression.

Air pollution has been widely recognized as a risk factor for neurological disorders, and the gut microbiome may play a mediating role. However, current evidence remains limited. In this study, a mouse model was employed with continuous exposure to real-time air pollution from conception to late adolescence. Effects of growth-stage air pollution exposure on the gut microbiome, host metabolites, and brain tissue were assessed. Pathological damage in the hippocampus and cortex was observed. Fecal metagenomic sequencing revealed alterations in both compositions and functions of the gut microbiome. Metabolic disturbances in unsaturated fatty acids and glycerophospholipids were identified in the intestine, serum, and brain tissues, with significant changes in metabolites (e.g., gamma-linolenic acid, alpha-linolenic acid, docosahexaenoic acid (DHA), phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidylserine (PS). Serum levels of the pro-inflammatory mediator leukotriene C4 were also elevated. Correlation analysis identified a group of different gut microbiome species that were associated with host metabolites. Furthermore, mediation analysis showed that intestinal and serum metabolites mediated the associations between the key gut microbiome and brain microbiome. These findings indicate that the metabolic crosstalk in the gut-brain axis mediates the neuronal damage in mice induced by growth-stage air pollution exposure, potentially through pathways involving lipid metabolism and inflammation.

Pressure injuries (PIs) are a significant concern among the elderly and bedridden patients, often resulting from prolonged pressure on the skin. Various interventions, including plant and animal-based therapies, are used to prevent and treat PIs. However, there is a lack of comprehensive understanding of the effectiveness of these natural interventions.

This study aims to systematically review and conduct a meta-analysis of studies using plant and animal-based interventions to prevent and treat pressure injuries.

A systematic review and meta-analysis were performed according to the PRISMA guidelines. Searches were conducted in PubMed, Web of Science, SCOPUS, and Cochrane databases using keywords related to pressure injuries and natural interventions. Studies published between 2003 and 2023 were included. The inclusion criteria were experimental, quasi-experimental, and case-control studies. Data extraction and quality assessment were performed independently by two researchers. The effect size was calculated using Hedges' g, and heterogeneity was assessed using Cochrane Q and I2 tests.

A total of 13,563 records were identified, with 20 studies meeting the inclusion criteria after screening and full-text review. The total sample size was 2541 participants. The meta-analysis revealed a significant overall effect size (g = -0.614, 95 % CI: -0.890 to -0.337) indicating moderate effectiveness of plant and animal-based interventions in preventing and reducing PIs. Aloe vera, olive oil, and fish oil showed significant effects with p-values <0.05. High heterogeneity was observed among the studies (Q = 91.007, p < 0.05; I2 = 79.123 %), leading to the use of a random effects model.

Plant and animal-based interventions are moderately effective in preventing and reducing pressure injuries. These findings support the integration of natural therapies into clinical practice for PI management. Further research is needed to standardize protocols and explore the long-term effects of these interventions.

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.

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.

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.

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.

Diet influences macronutrient availability to cells, and although mechanisms of sensing dietary glucose and amino acids are well characterized, less is known about sensing lipids. We defined a nutrient signaling mechanism involving fatty acid-binding protein 5 (FABP5) and mechanistic target of rapamycin complex 1 (mTORC1) that is activated by the essential polyunsaturated fatty acid (PUFA) ω-6 linoleic acid (LA). FABP5 directly bound to the regulatory-associated protein of mTOR (Raptor) to enhance formation of functional mTORC1 and substrate binding, ultimately converging on increased mTOR signaling and proliferation. The amounts of FABP5 protein were increased in tumors and serum from triple-negative compared with those from receptor-positive breast cancer patients, which highlights its potential role as a biomarker that mediates cellular responses to ω-6 LA intake in this disease subtype.

Glioma is the most common malignant tumor in the central nervous system with significant challenges for its treatment and prognosis. Based on publicly available genome-wide association study data, this study employed a bidirectional, two-sample Mendelian randomization (MR) analysis, combined with Bayesian weighted MR, to investigate the causal effect of 233 circulating metabolic traits on glioma and its subtypes, with the expectation of discovering new diagnostic and therapeutic targets. The MR study revealed that the Total cholesterol to total lipids ratio in large VLDL and the Ratio of polyunsaturated fatty acids to total fatty acids (PUFAbyFA) are risk factors for glioma, while free cholesterol or phospholipids in small HDL are protective against glioma. The free cholesterol to total lipids ratio in IDL, the ratios of total cholesterol or cholesteryl esters to total lipids in small or medium VLDL, as well as linoleic acid (LA 18:2), phosphatidylcholine, and sphingomyelins levels are risk factors for non-GBM glioma. Free cholesterol in small HDL is identified as a protective factor for non-GBM glioma. The results were robust to sensitivity analyses and Bayesian weighted mendelian randomization. The causal effects of glioma on circulating metabolites were explored through reverse mendelian randomization. The results provide potential biomarkers for the early diagnosis and treatment of glioma.

Marine phytoplankton is an emerging source of immunomodulatory bioactive lipids (BLs). Under physiological growth conditions and upon stress challenges, several eukaryotic microalgal species accumulate lipid metabolites that resemble the precursors of animal mediators of inflammation: eicosanoids and prostaglandins. Therefore, marine phytoplankton could serve as a biotechnological platform to produce functional BLs with therapeutic applications in the management of chronic inflammatory diseases and other clinical conditions. However, to be commercially competitive, the lipidic precursor yields should be enhanced. Beside tailoring the cultivation of native producers, genetic engineering is a feasible strategy to accrue the production of lipid metabolites and to introduce heterologous biosynthetic pathways in microalgal hosts. Here, we present the state-of-the-art clinical research on immunomodulatory lipids from eukaryotic marine phytoplankton and discuss synthetic biology approaches to boost their light-driven biosynthesis.

Celiac disease (CD) is a chronic autoimmune disorder driven by both genetic and environmental factors, with the HLA DQ2/DQ8 genotypes playing a central role in its development. Despite the genetic predisposition, only a small percentage of individuals carrying these genotypes develop the disease. Gluten, a protein found in wheat, rye, and barley, is the primary environmental trigger, but other factors, such as the intestinal microbiota, may also contribute to disease progression. While the gluten-free diet (GFD) remains the cornerstone of treatment, many CD patients experience persistent inflammation and gut dysbiosis, leading to ongoing symptoms and complications. This chronic inflammation, which impairs nutrient absorption, increases the risk of malnutrition, anemia, and other autoimmune disorders. Recent studies have identified an altered gut microbiota in CD patients, both on and off the GFD, highlighting the potential role of the microbiota in disease pathogenesis. An emerging area of interest is the supplementation of n-3 polyunsaturated fatty acids (PUFAs), known for their anti-inflammatory properties, as a potential therapeutic strategy. n-3 PUFAs, found in fish oil and certain plant oils, modulate the immune cell function and cytokine production, making them a promising intervention for controlling chronic inflammation in CD. This review explores the current understanding of n-3 PUFAs' effects on the gut microbiota's composition and inflammation in CD, with the goal of identifying new avenues for complementary treatments to improve disease management.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent joint inflammation, damage, and loss of function. In recent years, the role of gut microbiota and its metabolites in immune regulation has attracted increasing attention. The gut microbiota influences the host immune system's homeostasis through various mechanisms, regulating the differentiation, function, and immune tolerance of immune cells. Dysbiosis of the gut microbiota in RA patients is closely associated with abnormal activation of immune cells and excessive secretion of inflammatory cytokines. Metabolites produced by the gut microbiota, such as short-chain fatty acids (SCFAs), tryptophan metabolites, bile acids, and amino acid metabolites, play a critical role in immune responses, regulating the functions of immune cells like T cells, B cells, and macrophages, and inhibiting the release of pro-inflammatory cytokines. Restoring the balance of the gut microbiota and optimizing the production of metabolic products may become a new strategy for RA treatment. This review discusses the role of gut microbiota and its metabolites in the immune response of RA, exploring how they influence the immunopathological process of RA through the regulation of immune cells and key immune factors. It also provides a theoretical basis for future therapeutic strategies based on gut microbiota modulation.

Schizophrenia, a complex psychiatric disorder, presents with multifaceted symptoms and important challenges in treatment, primarily due to its pathophysiological complexity, which involves oxidative stress and aberrant iron metabolism. Recent insights into ferroptosis, a unique form of iron‑dependent cell death characterized by lipid peroxidation and antioxidant system failures, open new avenues for understanding the neurobiological foundation of schizophrenia. The present review explores the interplay between ferroptosis and schizophrenia, emphasizing the potential contributions of disrupted iron homeostasis and oxidative mechanisms to the pathology and progression of this disease. The emerging evidence linking ferroptosis with the oxidative stress observed in schizophrenia provides a compelling narrative for re‑evaluating current therapeutic strategies and exploring novel interventions targeting these molecular pathways, such as the glutathione peroxidase 4 pathway and the ferroptosis suppressor protein 1 pathway. By integrating recent advances in ferroptosis research, the current review highlights innovative therapeutic potentials, including N‑acetylcysteine, selenium, omega‑3 fatty acids and iron chelation therapy, which could address the limitations of existing treatments and improve clinical outcomes for individuals with schizophrenia.

The lungs are a mucosal organ constantly exposed to potentially harmful compounds and pathogens. Beyond their role in gas exchange, they must perform a well-orchestrated protective response against foreign invaders. The lungs identify these foreign compounds, respond to them by eliciting an inflammatory response, and restore tissue homeostasis after inflammation to ensure the lungs continue to function. In addition, lung function can be affected by genetics, environmental exposures, and age, leading to pulmonary diseases that infringe on quality of life. Recent studies indicate that diet can influence pulmonary health including the incidence and/or severity of lung diseases. Specifically, long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) have gained attention because of their potential to reduce inflammation and promote resolution of inflammation. Docosahexaenoic acid and eicosapentaenoic acid are 2 potentially beneficial n-3 PUFAs primarily acquired through dietary intake. Here we review current literature examining the role of n-3 PUFAs and the biological mechanisms by which these fatty acids alter the incidence and pathologies of chronic lung diseases including asthma, chronic obstructive pulmonary disease, and interstitial lung disease. We also highlight the role of n-3 PUFAs in vulnerable populations such as pre/postnatal children, those with obesity, and the elderly. Lastly, we review the impact of n-3 PUFA intake and supplementation to evaluate if increasing consumption can mitigate mechanisms driving chronic lung diseases.

The existing evidence on the effect of dietary supplements for preventing migraines has generated conflicting results.

We assessed alterations in migraine clinical features corresponding to the intake of dietary supplements. Our main outcomes included the frequency (number of attacks), duration (in hours), the severity (intensity) and the monthly migraine days. Using a dose-response meta-analysis, we estimated the dose-dependent impact. The certainty of evidence was evaluated using the GRADE tool.

Finally, twenty-two trials were included in the systematic review and meta-analysis. Magnesium supplementation reduced migraine attacks (mean difference (MD) = -2.51), severity (MD = -0.88), and the monthly migraine days (MD = -1.66) compared with the control group. CoQ10 decreased the frequency (MD = -1.73), severity (MD = -1.35), and duration of migraine (MD = -1.72). Riboflavin decreased attack frequency (MD = -1.34). Alpha-lipoic acid decreased attack frequency (MD = -1.24) and severity (MD = -0.38). Probiotics decreased the frequency (MD = -1.16), severity (MD = -1.07) and the monthly migraine days (MD = -3.02). Vitamin D reduced migraine frequency (MD = -1.69) and the monthly migraine days (MD = -2.41). In adults, compared with placebo, these supplements did not significantly affect other outcomes, and omega-3 supplementation did not yield a statistically significant reduction in any of these outcomes.

The use of certain dietary supplements has resulted in a significant decrease in migraine prophylaxis. Further clinical trials of high quality appear to be beneficial.

Omega-3 fatty acids (ω-3-FAs) represent a group of essential nutrients, but modern diets often do not allow for a balanced ratio between the intakes of ω-6-FA and ω-3-FA, which is vital for health. ω-3-FA can be found primarily in algae and fish, while the intake of ω-3-FA dietary supplements can be seen as an efficient way of providing nutrients important for many physiological functions.

The aim of this research was to investigate the use of ω-3-FA-rich food and supplements, as well as the knowledge and attitudes on these nutrients among residents of the central Balkans-the Republic of Serbia and the Republic of Srpska.

The research was performed as a prospective, cross-section, online survey.

A total of 895 responses were collected, with relatively high usage of ω-3-FA supplements (34.2%). It was found that the respondents use these supplements due to inadequate dietary intake, but also in therapy or prevention of certain diseases and conditions. Users take the supplements on a regular basis, although for short periods of time. The respondents reported the dietary intake of food rich in ω-3-FA. It was found that more than half of parents give these supplements to their children, with similar purposes, although more frequently and for longer periods of time. The use of ω-3-FA via supplements in pregnant and breastfeeding women is also present.

The residents of the investigated territory seem to have an awareness of the importance of ω-3-FA use, with its consumption being registered in both the general population and specific subpopulations. Future steps would include further promotion and education on the given topic.

Autoimmune diseases pose significant health challenges worldwide and affect millions. In recent years, there has been growing interest in exploring preventive strategies through nutritional interventions using vitamins, antioxidants, and micronutrients to reduce the risk of developing autoimmune diseases. However, excessive supplementation has also been associated with toxicity.

We aim to assess how the intake of vitamins, antioxidants and micronutrients affect the risk of developing autoimmune diseases.

This PRISMA-adherent systematic review involved a systematic search of PubMed, Embase and Cochrane for controlled studies that evaluated the risk of incident autoimmune diseases after supplementation. Random effects meta-analyses were used for primary analysis.

18 studies were included. Overall meta-analyses observed that vitamin D did not influence the risk of autoimmune diseases (RR=0.99, 95%CI: 0.81-1.20). However, among the different vitamin D dosages, subgroup analysis demonstrated that those who were supplemented with 600-800IU/day may have a statistically significant reduction in risk (RR=0.55, 95%CI: 0.38; 0.82). Systematic review suggested that consumption of most vitamins, micronutrients and antioxidants may not have any effect on the risk of autoimmune diseases. Smoking, age, physical or outdoor activity and diet were significant confounding factors that affected the efficacy of such interventions.

We studied the effect of various vitamins, micronutrients and antioxidants on the risk of developing autoimmune diseases. Our study contributes to the evolving landscape of nutritional immunology, providing a foundation for future research to unravel more definite relationships with supplementation and the development of incident autoimmune diseases.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024504796.

Inflammation causes the progressive destruction of the supporting tissues around teeth in patients with periodontitis. Therefore, this study aimed to investigate the immunological effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as adjunctive therapy in patients with periodontal disease and identify potential biomarkers for the disease.

This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to investigate the impact of omega-3 therapy with or without acetylsalicylic acid on the immunological parameters of periodontal treatment. Eligible studies included those conducted on patients with normoglycemia and diabetes, published after 2002 in English, and containing relevant keywords. The exclusion criteria included pre-2002 publications, literature reviews, animal studies, and articles without immunological analysis. This review involved careful study selection by two double-blind researchers using the Rayyan software, with data extraction and analysis performed by the third and fourth reviewers.

Seven randomized clinical trials that compared control/placebo and n-3 PUFA groups or the follow-ups of the n-3 PUFA groups were included. The concentration of inflammatory cytokines was reduced following dietary supplementation with n-3 PUFA in the reviewed studies. Specifically, IL-1β, TNF-α, IL-6, and RANKL levels were reduced after dietary supplementation with n-3 PUFA as an adjunctive therapy for periodontitis. Changes in inflammatory outcomes were associated with the clinical benefits of periodontitis. However, significant divergence in the evaluated inflammatory markers, samples, and methods impairs direct comparisons and quantitative analyses in the available literature.

This study highlights the need for clinical trials to advance our understanding and assessment of inflammatory outcomes in patients with periodontitis.

Recent studies indicate that oxidative/nitrosative stress is involved in the pathogenesis of asthma, allergic rhinitis, atopic dermatitis, and urticaria. The article aimed to review the latest literature on disruptions in redox homeostasis and protein glycation in allergy patients. It has been shown that enzymatic and non-enzymatic antioxidant systems are impaired in allergic conditions, which increases cell susceptibility to oxidative damage. Reactive oxygen/nitrogen species exacerbate the severity of asthma symptoms by activating inflammatory mediators that cause airway smooth muscle contraction, promote mucus hypersecretion, increase the permeability of lung capillaries, and damage cell membranes. Redox biomarkers could have considerable diagnostic potential in allergy patients. There is no compelling evidence to indicate that antioxidants reduce allergy symptoms' severity or slow disease progression.

Background: Periodontitis presents as a chronic inflammatory disease that affects the gingival tissues and structures surrounding the tooth. However, the existing approaches for periodontitis do not allow complete control of the disease. In this regard, an active search is being carried out both in preclinical and clinical studies for new approaches based, among other things, on nutraceuticals. Aim: This systematic review aimed to summarize and systematize data from preclinical studies on the effects of the use of polyunsaturated omega-3 fatty acids in experimentally induced periodontitis. Methods: A systematic search for research articles was performed using electronic scientific databases. Only original in vivo experimental studies investigating the use of omega-3 polyunsaturated fatty acids in experimentally induced periodontitis were included. Quality and risk of bias assessment (Systematic Review Centre for Laboratory Animal Experimentation) and quality of evidence assessment (using the modified Grading of Recommendations Assessment, Development and Evaluation approach) were performed. Results: Nineteen studies were included in this systematic review. It has been shown that omega-3 polyunsaturated fatty acids may decrease the progression of periodontitis with amelioration of alveolar bone loss along with decreased pro-inflammatory response and inhibition of osteoclasts. Despite the promising results, most of the analyzed studies were characterized by low to moderate quality and a significant risk of bias. Conclusion: Based on the retrieved data, the possibility of extrapolating the obtained results to humans is limited, indicating the need for additional studies to elucidate the key patterns and mechanisms of action of omega-3 polyunsaturated fatty acids and their endogenous metabolites in experimentally induced periodontitis.

Female reproductive aging remains irreversible. More evidence is needed on how polyunsaturated fatty acids (PUFAs) affect the female reproductive lifespan.

To identify and validate specific PUFAs that can influence the timing of menarche and menopause in women.

We utilized a two-sample Mendelian randomization (MR) framework to evaluate the causal relationships between various PUFAs and female reproductive longevity, defined by age at menarche (AAM) and age at natural menopause (ANM). Our analyses leveraged summary statistics from four genome-wide association studies (GWASs) on the plasma concentrations of 10 plasma PUFAs, including 8866 to 121,633 European individuals and 1361 East Asian individuals. Large-scale GWASs for reproductive traits provided the genetic data of AAM and ANM from over 202,323 European females and 43,861 East Asian females. Causal effects were estimated by beta coefficients, representing, for each increase in the standard deviation (SD) of plasma PUFA concentration, the yearly increase in AAM or ANM. Replications, meta-analyses, and cross-ancestry effects were assessed to validate the inference.

Higher plasma DHA was identified to be associated with delayed natural menopause without affecting menarche, offering a potential intervention target for extending reproductive longevity.

The presence of industrial trans-fatty acids (iTFAs) in processed foods poses significant public health concerns, necessitating comprehensive regulatory frameworks. In this study, the current legal landscape governing iTFA in the European Union and Spain is analyzed, with a particular focus on regulatory effectiveness and implementation challenges. The research methodology combines a systematic review of existing regulations, including EU Regulation No. 1169/2011 and Spanish Law 17/2011, with the analysis of the scientific literature on iTFA health impacts. The results reveal significant regulatory gaps, particularly in enforcement mechanisms and iTFA detection methods. Key challenges are also identified in the present study, including inconsistent compliance monitoring, varying analytical methods for iTFA detection, and contradictions between EU and Spanish regulatory frameworks. Additionally, in this work, the need for harmonized approaches to ultra-processed food regulation is emphasized. Further, the conclusion is that despite the current regulations providing a foundation for iTFA control, it is compulsory to enhance the monitoring systems, and clearer regulatory guidelines are necessary. These would contribute valuable insights for policymakers, food industry stakeholders, and public health professionals working towards effective iTFA regulation.

Background/Objectives: The beneficial effects of ω-3 fatty acids on the cardiovascular system have been observed in many epidemiological studies; however, their effects on the skeleton and in particular on postmenopausal bone loss appear to vary. The present study's purpose was to investigate the effects of oral fish oil (rich in ω-3 fatty acids) consumption on bone, plasma, and inflammation parameters in the ovariectomized (Ovx) rat model of osteopenia. Methods: Four Groups of ten rats each were separated into Non-Ovx receiving fish oil (2.8 g/kg body weight) (Non-Ovx + FO), Non-Ovx receiving isocaloric corn oil (Non-Ovx + CO), Ovx receiving fish oil (Ovx + FO), and Ovx receiving corn oil (Ovx + CO) daily for 4 months. Results: Tibial bone mineral density percentage changes from baseline were +4.09% in Non-Ovx + FO rats versus -2.99% in Non-Ovx + CO rats (p NS), and -5.73% in Ovx + FO rats versus -14.12% in Ovx + CO rats (p = 0.070), indicating a tendency to protect from bone loss. Fish oil exerted a beneficial effect on bone strength, as shown by significantly increased femoral fracture stress in Ovx + FO, compared to Ovx + CO rats (p = 0.05). The plasma's total cholesterol was significantly reduced in both FO Groups versus the CO Groups (p < 0.001), while HDL-cholesterol decreased slightly in both FO Groups, significantly (p < 0.001) between Non-Ovx + FO versus Non-Ovx + CO. Interleukin 6 was reduced in both FO Groups, indicating the anti-inflammatory effect of fish oil consumption, which was highly significant (p < 0.001) between Non-Ovx + FO versus Non-Ovx + CO. Interleukin 10, TNF-α, and RANKL displayed non-significant changes. Conclusions: Among the skeletal and blood parameters studied, several, but not all, demonstrated a mild to significant beneficial effect of four-month fish oil consumption.

Bread consumption dates back thousands of years, being one of the oldest and most widespread staple food worldwide. While bread is often associated with taste, pleasure, and tradition, its perception as a vehicle of nutrition and health remains complex. Today, there is no scientific consensus on whether bread consumption is beneficial or deleterious to human health. The objective of this review is therefore to present and discuss epidemiological and clinical evidence on the nutritional contribution of bread and its relationship with health. We also present different aspects of bread such as flour type and inclusions that may modulate this relationship. Studies included in this review investigate bread as part of a dietary pattern as well as the effect of bread alone on overweight, cardiometabolic health, and digestive health. Bread is an integral part of diets around the world, with a significant contribution to key nutrients. Although evidence on the impact of bread consumption on health is still lacking and depends on the overall diet, whole grain breads have shown consistent beneficial effects on human health. Substitution modeling studies and well-designed clinical trials are warranted to fill the research gaps and understand the role of bread consumption in health and disease.

Background/Objectives: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited effective treatments, prompting the need for investigation of novel therapeutic approaches. Eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) have demonstrated potential anti-inflammatory properties, but their combined effects on UC have not been thoroughly investigated. This study aimed to evaluate the effect of the combined administration of EPA and GLA on clinical and histopathologic features of experimental UC models. Methods: Thirty-six male Wistar rats were randomized in three groups (DSS group, Ensure Plus group, and Oxepa group), with twelve rats in each group. Experimental colitis was induced by administrating dextran sulfate sodium (DSS) 8%. The DSS group received tap water, the Ensure Plus group was given a high caloric diet, and the Oxepa group received a special diet containing high levels of EPA and GLA. Disease activity index (DAI) and microscopic activity index (MAI) were measured. Inflammatory markers were calculated both in blood and large intestine, liver, spleen, and lung tissue samples. Neutrophil and macrophage populations were assessed with immunohistochemistry. Results: No significant differences in the DAI index were found between the groups, but the MAI revealed statistically significant differences (p < 0.001). While no significant differences were observed in tumor necrosis factor-alpha (TNF-α) levels, interleukin-17 (IL-17) levels in the large intestine showed statistically significant differences (p = 0.05), with the Ensure Plus and Oxepa groups displaying lower levels compared to the DSS group (p = 0.021 and p = 0.043, respectively). Significant differences in neutrophil infiltration were found in both the large intestine (p < 0.001) and lungs (p = 0.002), with the Oxepa group showing fewer cells. Similarly, significant differences in macrophage infiltration were observed in the large intestine (p = 0.038) and spleen (p < 0.001), with the Oxepa group having lower macrophage counts. Conclusions: In conclusion, the combination of EPA and GLA demonstrates local anti-inflammatory effects and improves the histopathological outcomes in UC.

Autoimmune diseases are a group of disorders characterized by abnormal immune responses that mistakenly target and attack healthy cells, tissues, and organs, resulting in inflammation and tissue damage. Omega-3 fatty acids possess anti-inflammatory activities and may decrease abnormal immune activity. However, the role of omega-3 fatty acids in various autoimmune diseases is still unclear. This umbrella review and Mendelian randomization (MR) study aims to summarize the highest available evidence on omega-3 fatty acids and autoimmune disease.

We conducted an umbrella review by searching electronic databases to identify systematic reviews and meta-analyses. The selection criteria included systematic reviews with or without meta-analysis, which evaluated omega-3 fatty acids as the exposure and autoimmune disease as the outcome variable. Two authors independently assessed the overlapping and quality of the reviews using the AMSTAR-2 tool. We also performed MR studies to investigate the potential causal effect of fatty acids on the risk of various autoimmune diseases, utilizing data from the meta-analysis of the UKB-TOPMed and FinnGen cohorts.

The umbrella review identified 21 studies (8 systematic reviews and 13 meta-analyses) on 9 autoimmune diseases and 30 diseases in the MR study. AMSTAR 2 categorized the quality of evidence in six studies as critically low, six studies as low, eight studies as moderate, and one as high-quality evidence. The consistent result between the review and the MR study demonstrated the benefit of omega-3 fatty acids on rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Additionally, in our summary review, omega-3 fatty acids can improve disease activity and inflammation biomarkers; however, MR studies provided no consistent evidence for the causal effects of omega-3 fatty acids on psoriasis, multiple sclerosis (MS), type 1 diabetes (T1D), IgA nephropathy (IgAN), juvenile idiopathic arthritis (JIA), Crohn's disease (CD), and ulcerative colitis (UC).

The current study presented solid evidence highlighting the advantageous impact of omega-3 fatty acids on SLE and RA. This was achieved through the reduction of disease risk, the decrease of disease activity, and the mitigation of inflammatory biomarkers. To stratify another autoimmune illness, it is necessary to carry out rigorous evaluations to surpass the existing findings and enhance understanding in this domain.

Pulmonary arterial hypertension (PAH) is a rare and progressive disorder that affects the pulmonary vasculature. Although recent developments in pharmacotherapy have extended the life expectancy of PAH patients, their 5-year survival remains unacceptably low, underscoring the need for multitarget and more comprehensive approaches to managing the disease. This should incorporate not only medical, but also lifestyle interventions, including dietary changes and the use of nutraceutical support. Among these strategies, n-3 polyunsaturated fatty acids (n-3 PUFAs) are emerging as promising agents able to counteract the inflammatory component of PAH. In this narrative review, we aim at analysing the preclinical evidence for the impact of n-3 PUFAs on the pathogenesis and the course of PAH. Although evidence for the role of n-3 PUFAs deficiencies in the development and progression of PAH in humans is limited, preclinical studies suggest that these dietary components may influence several aspects of the pathobiology of PAH. Further clinical research should test the efficacy of n-3 PUFAs on top of approved clinical management. These studies will provide evidence on whether n-3 PUFAs can genuinely serve as a valuable tool to enhance the efficacy of pharmacotherapy in the treatment of PAH.

Autoimmune diseases encompass a wide range of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, which cause inflammation and multiple organ involvement. However, its pathogenesis remains unelucidated. Furthermore, the cumulative medical and economic burden of autoimmune diseases is on the rise, making these diseases a ubiquitous global phenomenon that is predicted to further increase in the coming decades. Coumarins, a class of aromatic natural products with benzene and alpha-pyrone as their basic structures, has good therapeutic effects on autoimmune diseases. In this review, we systematically highlighted the latest evidence on coumarins and autoimmune diseases data from clinical and animal studies. Coumarin acts on immune cells and cytokines and plays a role in the treatment of autoimmune diseases by regulating NF-κB, Keap1/Nrf2, MAPKs, JAK/STAT, Wnt/β-catenin, PI3K/AKT, Notch and TGF-β/Smad signaling pathways. This systematic review will provide insight into the interaction of coumarin and autoimmune diseases, and will lay a groundwork for the development of new drugs for autoimmune diseases.

Identification of the chemical compositions of fatty acids and tocopherols shows the high content of linum usitatissimum oil (LO) by linolenic acid 55.3735% and γ-tocopherol 570.927 mg/kg, while argania spinosa oil (AO) is known by the dominance of oleic acid 47.77% followed by linoleic acid 31.08% as well as tocopherols by γ-tocopherols 687.485 mg/kg and δ-tocopherols 51.035 mg/kg. This difference in compositions enables us to enrich the low-stability oil and monitor its behavior during storage at a specific time and under specific conditions. In this study, pure linum usitatissimum and argania spinosa oils extracted by cold pressing as well as their formulations at proportions of (LO: AO) respectively: (80:20; 60:40, 50:50; 40:60; 20: 80) were oxidized at 60 °C for 28 days of storage, during which time the pure oils and blends were assessed for oxidative stability by studying their different fatty acid and tocopherol profiles and physicochemical characteristics such as acidity, peroxide value and chlorophyll and carotenoid pigments, as well as nutritional indexes such as the atherogenic index (AI), the thrombogenic index (TI), and the hypocholesterolemic: hypercholesterolemic ratio (HH), ω3:ω6 ratio, also the oxidative susceptibility (OS), and oxidazability value (Cox), and total phenolic compounds (TPC).

Migraine is one of the most debilitating neurological disorders that causes frequent attacks of headaches and affects approximately 11% of the global population. Deficient or even insufficient levels of vital nutrients would increase the severity and frequency of migraine attacks. Therefore, we aimed to examine the practical supplements for the prevention and management of migraine attacks.

This narrative review study was conducted by searching PubMed, ISI web of science, EMBASE, Google Scholar, and Scopus using the keywords of "dietary supplement" and "migraine" plus their MeSH terms. Original articles published in English language from their inception to July 27th, 2024, studies that investigated adult population (aged >18 years), and those assessing the impact of intended nutrient supplementation on clinical symptoms of migraine were included in the study.

Oxidative stress and low intake of antioxidants would be risk factors for migraine attacks by inducing inflammation. The secretion of inflammatory cytokines, such as tumor necrosis factor (TNF)-a, would lead to neuroinflammation and migraine episodes by increasing the cellular permeability and interactions. Evidence also indicated a direct association between phases of migraine attacks and calcitonin gene-related peptide (CGRP), mitochondrial disorders, monoaminergic pathway, disruption in brain energy metabolism, and higher serum levels of glutamate and homocysteine. Therefore, supplementation with nutrients involved in mitochondrial function, brain energy metabolism, and even methyl donors would relieve migraine attacks.

Evidence indicated that supplementation with riboflavin, omega-3 fatty acids, alpha lipoic acid, magnesium, probiotics, coenzyme Q10, ginger, and caffeine would have favorable effects on migraine patients. However, more prospective studies are required to evaluate the effect of other nutrients on migraine patients.

Sacha Inchi (Plukenetia volubilis L) (SI) is a traditional natural medicine from tropical rainforests of Amazon region in South America. As a raw material for edible oil, it has various pharmacological effects such as antioxidant, anti-inflammatory, hypolipidemia, and blood pressure lowering, which have attracted increasing attentions of pharmacists. This has prompted researchers to explore its pharmacological effects for potential applications in certain diseases. Among these, the study of its anti-inflammatory effects has become a particularly interesting topic, especially in rheumatoid arthritis (RA). RA is a systemic autoimmune disease, and often accompanied by chronic inflammatory reactions. Despite significant progress in its treatment, there is still an urgent need to find effective anti-RA drugs in regard to safety. This review summarizes the potential therapeutic effects of SI on RA by modulating gut microbiota, targeting inflammatory cells and pathways, and mimicking biologic antibody drugs, predicting the application prospects of SI in RA, and providing references for research aimed at using SI to treat RA.

Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions. The causal relationship between olfaction with memory dysfunction deserves particular attention because this sensory system has the only direct projection to memory centers. Mechanisms that may underlie the connections between medical conditions and olfactory loss include inflammation as well as neuroanatomical and environmental factors, and all 139 of the medical conditions listed here are also associated with inflammation. Olfactory enrichment shows efficacy for both prevention and treatment, potentially mediated by decreasing inflammation.

The aim of this work is to develop an ω-3 fatty acid fraction mapping method at 3 T based on a chemical shift encoding model, to assess its performance in a phantom and in vitro study, and to further demonstrate its feasibility in vivo.

A signal model was heuristically derived based on spectral appearance and theoretical considerations of the corresponding molecular structures to differentiate between ω-3 and non-ω-3 fatty acid substituents in triacylglycerols in addition to the number of double bonds (ndb), the number of methylene-interrupted double bonds (nmidb), and the mean fatty acid chain length (CL). First, the signal model was validated using single-voxel spectroscopy and a time-interleaved multi-echo gradient-echo (TIMGRE) sequence in gas chromatography-mass spectrometry (GC-MS)-calibrated oil phantoms. Second, the TIMGRE-based method was validated in vitro in 21 adipose tissue samples with corresponding GC-MS measurements. Third, an in vivo feasibility study was performed for the TIMGRE-based method in the gluteal region of two healthy volunteers. Phantom and in vitro data was analyzed using a Bland-Altman analysis.

Compared with GC-MS, MRS showed in the phantom study significant correlations in estimating the ω-3 fraction (p < 0.001), ndb (p < 0.001), nmidb (p < 0.001), and CL (p = 0.001); MRI showed in the phantom study significant correlations (all p < 0.001) for the ω-3 fraction, ndb, and nmidb, but no correlation for CL. Also in the in vitro study, significant correlations (all p < 0.001) between MRI and GC-MS were observed for the ω-3 fraction, ndb, and nmidb, but not for CL. An exemplary ROI measurement in vivo in the gluteal subcutaneous adipose tissue yielded (mean ± standard deviation) 0.8% ± 1.9% ω-3 fraction.

The present study demonstrated strong correlations between gradient-echo imaging-based ω-3 fatty acid fraction mapping and GC-MS in the phantom and in vitro study. Furthermore, feasibility was demonstrated for characterizing adipose tissue in vivo.

The inclusion of by-product coconut mesocarp skins (CMS) in diets was evaluated in feedlot lambs. The objective of this study was to evaluate CMS levels effects on carcass traits and meat quality of lambs. Thirty-five male lambs with an initial body weight of 16.9 ± 2.93 kg were distributed in a completely randomized design with five CMS levels in total dry matter (0; 4.8; 9.6; 14.4 and 19.2%) and fed during 71 d until slaughter. High levels of CMS decreased the intake of dry matter and negatively affected the performance of lambs. Fat and protein contents of Longissimus lumborum muscle (P < 0.05) and the saturated fatty acid (FA) decreased (P < 0.001) whereas polyunsaturated FA increased (P < 0.01) with the inclusion of CMS. The ratio t10/t11-18:1 increased with the inclusion of CMS (P < 0.001). The instrumental color descriptors were unaffected by CMS levels. According to the effects on the investigated meat quality traits we recommend up to 4.8% CMS in diets of confined lambs.

This study was carried out to analyze the fatty acid and amino acid compositions of three economically important freshwater fish species, Mali (Wallago attu), Raho (Labeo rohita), and Mahseer (Tor putitora), indigenous to Indus River, Pakistan.. Amino acid profiling was done by high-performance liquid chromatography (HPLC) while gas chromatography (GC) was used for fatty acid analysis. Glutamic acid, aspartic acid, arginine, alanine, leucine, lysine and isoleucine were the most predominant amino acid while palmitic acid (C16:0), oleic acid (C18:1c), palmitoliec acid (C16:1c), linolenic acids (C18:2c) and docosahexaenoic acids (DHA C22:6) were the notable fatty acids present in these species. Our results indicated that all species have comparable nutritional composition and are good source of healthy human diet. Our findings will help the people to make informed choice while selecting fish for consumption and will pave the way for future researchers in planning new strategies to enhance the growth and production of commercial fish species. It will also be helpful for theFrom the current finding it was concluded that all fish species under discussion are rich in amino acids and fatty acids. These species contain essential amino acids and important fatty acid such as omega3 and omega 6, thus raising the nutritional quality of these species.

The use of edible insect protein in food products is contingent on their biological effects. Conventional protein extraction methods are not only time-consuming and costly but also energy-intensive. There is a need for alternative techniques that maintain the bioactivities of insect proteins and are environmentally sustainable. This study compares the health functionality of mealworm (Tenebrio molitor larvae) concentrates obtained by conventional methods-alkali and salt (MS) extraction-and nonconventional methods-enzyme (ME) and screw press (MP)-to enhance their applicability despite lower protein concentration. Overall, MP exhibited the highest essential amino acids content, whereas ME showed the highest in vitro digestibility, total phenolic contents, and antioxidant capacities among all the concentrates. ME also had a significant cell proliferative capacity at concentrations ≥500 µg/mL. MS significantly inhibited tumor necrosis factor-alpha and interleukin-1beta secretion in lipopolysaccharide-treated Hep3B cells compared to other samples. As for anti-hyperglycemia effects, treatment with MS and ME for 2 and 5 min significantly increased the p-Akt/Akt ratio (MS, 1.34- and 1.61-fold; ME, 2.26- and 2.70-fold, respectively). In conclusion, enzyme treatment enhanced nutritional value and antioxidant capacity, whereas salt treatment potentially contributed to anti-inflammatory and anti-hyperglycemia activities. Hybrid extraction techniques combining conventional and nonconventional methods are suggested based on target applications, considering health benefits, environmental impact, costs, and efficiencies. PRACTICAL APPLICATION: Four mealworm protein extraction methods (alkali/salt/enzyme/screw press) were compared for their nutritional and biological properties. Alkali extraction enhanced protein content, enzyme treatment improved nutritional value and antioxidant capacity, and salt-assisted extraction exhibited immunomodulatory effects in vitro. Notably, enzyme and salt treatments produced protein concentrates with significant antidiabetic and anti-hyperglycemic properties.