Interaction of Vitamin D Supplements and Marine n-3 Fatty Acids on Digestive Tract Cancer Prognosis.

A meta-analysis suggested that marine n-3 polyunsaturated fatty acids (PUFAs), e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), might reduce cancer mortality. However, a randomized clinical trial of marine n-3 PUFA and vitamin D supplementation failed to verify this benefit. This study aimed to investigate the potential interaction between vitamin D supplementation and serum EPA and DHA levels. This post hoc analysis of the AMATERASU trial (UMIN000001977), a randomized controlled trial (RCT), included 302 patients with digestive tract cancers divided into two subgroups stratified by median serum levels of EPA + DHA into higher and lower halves. The 5-year relapse-free survival (RFS) rate was significantly higher in the higher half (80.9%) than the lower half (67.8%; hazard ratio (HR), 2.15; 95% CI, 1.29-3.59). In the patients in the lower EPA + DHA group, the 5-year RFS was significantly higher in the vitamin D (74.9%) than the placebo group (49.9%; HR, 0.43; 95% CI, 0.24-0.78). Conversely, vitamin D had no effect in the higher half, suggesting that vitamin D supplementation only had a significant interactive effect on RFS in the lower half (p for interaction = 0.03). These results suggest that vitamin D supplementation may reduce the risk of relapse or death by interacting with marine n-3 PUFAs.

Joint effects of one year of marine omega-3 fatty acid supplementation and participant dietary fish intake upon circulating lipid mediators of inflammation resolution in a randomized controlled trial.

OBJECTIVES: We assessed the joint effects of omega (n)-3 fatty acid supplementation and dietary fish intake on systemic lipid mediators of inflammation among adults. METHODS: Within VITAL, a double-blind randomized controlled trial, adults were randomized to ω-3 fatty acids (460 mg EPA + 380 mg DHA/d) or placebo. We selected participants who reported low (<1 serving/mo) baseline dietary fish intake and matched them by age, sex, race, and trial arm to participants with self-reported highest fish intake (≥3.9 servings/wk). Baseline and 1-y plasma samples were tested for 9 ω-3 fatty acid-derived lipid mediators. Multivariable linear models assessed lipid mediator changes and joint effects of ω-3 fatty acid supplementation and dietary fish intake. RESULTS: Forty-eight participants with low baseline fish intake were matched to 48 with high fish intake. Mean age was 64.6 (±7.26), 50% were female, and 85% non-Hispanic white. One-year lipid mediator changes in expected directions were observed in those receiving ω-3 fatty acids versus placebo: reductions in proinflammatory mediators, PGD2, 5-HETE, and 12-HETE; increases in proresolving mediators, EPA and DHA. Larger 1-y lipid biomarker changes were seen in those with low baseline fish intake randomized to active ω-3 fatty acids for DHA, EPA, PGD2, Resolvin D1, and Resolvin D4 were observed, although no significant multiplicative interactions were detected. DISCUSSION: Beneficial changes in circulating proresolving and proinflammatory mediators were found with 1-y of ω-3 fatty acid supplementation versus placebo for all participants, with a trend toward larger effects among those with low baseline fish intake, although interactions were not significant.

Sex, Body Mass Index, and APOE4 Increase Plasma Phospholipid-Eicosapentaenoic Acid Response During an ω-3 Fatty Acid Supplementation: A Secondary Analysis.

BACKGROUND: The brain is concentrated with omega (ω)-3 (n-3) fatty acids (FAs), and these FAs must come from the plasma pool. The 2 main ω-3 FAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), must be in the form of nonesterified fatty acid (NEFA) or esterified within phospholipids (PLs) to reach the brain. We hypothesized that the plasma concentrations of these ω-3 FAs can be modulated by sex, body mass index (BMI, kg/m2), age, and the presence of the apolipoprotein (APO) E-ε4 allele in response to the supplementation. OBJECTIVES: This secondary analysis aimed to determine the concentration of EPA and DHA within plasma PL and in the NEFA form after an ω-3 FA or a placebo supplementation and to investigate whether the factors change the response to the supplement. METHODS: A randomized, double-blind, placebo-controlled trial was conducted. Participants were randomly assigned to either an ω-3 FA supplement (DHA 0.8 g and EPA 1.7 g daily) or to a placebo for 6 mo. FAs from fasting plasma samples were extracted and subsequently separated into PLs with esterified FAs and NEFAs using solid-phase extraction. DHA and EPA concentrations in plasma PLs and as NEFAs were quantified using gas chromatography. RESULTS: EPA and DHA concentrations in the NEFA pool significantly increased by 31%-71% and 42%-82%, respectively, after 1 and 6 mo of ω-3 FA supplementation. No factors influenced plasma DHA and EPA responses in the NEFA pool. In the plasma PL pool, DHA increased by 83%-109% and EPA by 387%-463% after 1 and 6 mo of ω-3 FA supplementation. APOE4 carriers, females, and individuals with a BMI of ≤25 had higher EPA concentrations than noncarriers, males, and those with a BMI of >25, respectively. CONCLUSIONS: The concentration of EPA in plasma PLs are modulated by APOE4, sex, and BMI. These factors should be considered when designing clinical trials involving ω-3 FA supplementation. This trial was registered at clinicaltrials.gov as NCT01625195.

Weight loss induced by a hypocaloric diet with or without fish oil supplementation re-established iron and omega-3 fatty acid homeostasis in middle-aged women with obesity: A post-hoc analysis of a randomized controlled trial.

OBJECTIVE: Middle-aged women with obesity are at increased risk of iron overload and iron disorder is known to disrupt n-3 polyunsaturated fatty acid homeostasis. We evaluated relationships between pretreatment hemoglobin and n-3 polyunsaturated fatty acid levels, and tested whether pretreatment hemoglobin contributed to inter-individual variability in weight loss with special focus on changes in body weight, iron and n-3 polyunsaturated fatty acid profiles. STUDY DESIGN: 117 middle and older aged women with obesity and more than two metabolic abnormalities were randomized to a 12-week hypocaloric diet without or with fish oil supplementation. Blood iron biomarker and erythrocyte membrane phospholipid profiles were evaluated. MAIN OUTCOME: The absolute change from baseline to week 12 in serum iron and erythrocyte n-3 polyunsaturated fatty acid levels according to pretreatment hemoglobin tertiles and fish oil supplementation. RESULTS: A Pearson correlation analysis showed that pretreatment hemoglobin levels were negatively correlated with linoleic acid (r = -0.231), α-linoleic acid (r = -0.279), and n-3 polyunsaturated fatty acid (r = -0.217) (all p < 0.05). Dietary weight loss markedly enhanced erythrocyte membrane lipids of linoleic acid, α-linoleic acid, and n-6 and n-3 polyunsaturated fatty acid only in those women with the highest pretreatment hemoglobin levels (tertile 3) (all p < 0.05). Fish oil supplementation increased bioavailable iron in women with moderate pretreatment hemoglobin levels (tertile 2) (p < 0.05) and, to a lesser extent, prevented a reduction in circulating iron in those with the lowest hemoglobin levels (tertile 1). CONCLUSION: Dietary weight loss is an effective treatment program to manage obesity-related iron and n-3 polyunsaturated fatty acid disorders, particularly for middle-aged women with obesity and iron overload.

Profiles of Serum Fatty Acids in Healthy Women on Different Types of Vegetarian Diets.

BACKGROUND: Plant-based dietary patterns are a source of different amounts and proportions of fatty acids (FAs) from those in traditional diets. Information about the full FAs profile provided by plant-based diets is widely lacking. The aim of this study was to present the exact serum profiles of FAs among people on a plant-based diet compared with omnivorous subjects. METHODS: FAs compositions and inflammation statuses (based on serum C-reactive protein (CRP) levels) were studied in serum samples obtained from 102 female volunteers (divided into four groups: vegans, vegetarians, pescatarians, and omnivores). The quality of the volunteers' diets was assessed based on seven-day dietary records. RESULTS: Both vegans and vegetarians had lower total n-3 PUFAs, EPA, and DHA serum levels than omnivores. Decreased levels of these FAs presumably did not cause inflammation in vegetarians and vegans, as vegetarians had similar serum levels of CRP compared to omnivores, and vegans had even lower levels. CONCLUSION: The analysis of serum FAs and CRP levels in vegetarians and vegans suggests that factors other than diet alone influence inflammation and overall health status. Further research on long-term plant-based diet users is needed to better understand this issue, and supplementation with EPA and DHA is worth considering in vegans and vegetarians.

Omega-3 eicosapentaenoic polar-lipid rich extract from microalgae Nannochloropsis decreases plasma triglycerides and cholesterol in a real-world normolipidemic supplement consumer population.

Introduction: AlmegaPL® is an oil rich in polar-lipid (> 15% w/w) derived from the microalga Nannochloropsis, that contains exclusively eicosapentaenoic acid (EPA > 25% w/w), without the DHA that is present in all other natural sources of omega-3. Previous findings from a randomized controlled clinical trial demonstrated the ability of AlmegaPL® supplementation to reduce cholesterol levels. Methods: In this post-market cohort study, we built upon previous findings and targeted the actual end-users of the supplement. Participants were recruited from a new subscriber database of AlmegaPL® capsules (1000-1100 mg/day) to capture the complexity of real-world clinical and consumer settings. Changes in circulating triglycerides (TG), remnant cholesterol (RC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), high-sensitivity C-reactive protein (hs-CRP), glucose and glycated hemoglobin (HbA1c) were monitored at baseline, Month 3, and Month 6 of supplementation using the at-home Baseline Heart Health Testing Kit by Imaware® (Houston, TX, USA). Results: Participants, who had, on average, normal TG level at baseline (1.62 ± 0.60 mmol/L), experienced a significant and progressive decrease in TG at Month 3 (8.0%; -0.13 ± 0.59 mmol/L; p < 0.001) and Month 6 (14.2%; -0.23 ± 0.64 mmol/L; p < 0.001) (primary outcome). Furthermore, after 6 months of supplementation, TC and non-HDL-cholesterol decreased by 5.0% (-0.26 ± 0.98 mmol/L; p < 0.001) and 5.5% (-0.21 ± 0.86 mmol/L; p < 0.001) respectively, primarily driven by a 14.9% reduction in RC (-0.11 ± 0.29 mmol/L; p < 0.001). Discussion: Consistent with our previous clinical trial, the decrease in RC was not coupled to an increase in LDL, which seems to be a benefit associated with EPA-only based formulations. In addition, this study demonstrated the AlmegaPL® capacity to maintain already healthy TG levels by further inducing a 14.9% decrease. Collectively, these findings highlight AlmegaPL® uniqueness as a natural over-the-counter option for EPA-only polar lipid that appears particularly effective in maintaining blood lipid levels in a generally healthy, normolipidemic population. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05267301.

A Preliminary Study on Hepatoprotective, Hypolipidemic and Aortic Morphometric Effects of Omega-3-Rich Fish Oil in Hypercholesterolemic Mice.

This study aims to evaluate the hepatoprotective, hypolipidemic and aortic morphometric effects of fish oil rich in omega-3 in hypercholesterolemic BALB/c mice. This is an experimental model that included 16 male BALB/c mice (Mus musculus) divided into three groups (G1 (standard commercial chow and 0.9% saline solution), G2 (hypercholesterolemic diet and 0.9% saline solution) and G3 (hypercholesterolemic diet and fish oil)) for 8 weeks. There was no significant difference in the treatment with omega-3-rich fish oil in the lipid profile (p > 0.05). In the histological analysis, group G2 detected the presence of hepatitis and liver tissue necrosis, but this was not observed in group G3. As for the morphometry in the light area of the vessel, the G1 group had a higher score (2.62 ± 0.36 mm2) when compared to G2 (2.10 ± 0.16 mm2) and G3 (2.26 ± 0.25 mm2) (p < 0.05). The vessel wall thickness did not differ between the groups (p > 0.05). It is concluded that supplementation with fish oil rich in omega-3 carried out in this study may have a protective effect on liver tissue, but it has not yet improved the lipid and morphometric profile. Despite this research being preliminary, it is a relevant study with future prospects for improving the doses of EPA and DHA in order to better elucidate the benefits of fish oil in models of dyslipidemia.

Erythrocyte membrane n-3 PUFA are inversely associated with breast cancer risk among Chinese women.

The relationship between erythrocyte membrane n-3 PUFA and breast cancer risk is controversial. We aimed to examine the associations of erythrocyte membrane n-3 PUFA with odds of breast cancer among Chinese women by using a relatively large sample size. A case-control study was conducted including 853 newly diagnosed, histologically confirmed breast cancer cases and 892 frequency-matched controls (5-year interval). Erythrocyte membrane n-3 PUFA were measured by GC. Logistic regression and restricted cubic spline were used to quantify the association between erythrocyte membrane n-3 PUFA and odds of breast cancer. Erythrocyte membrane α-linolenic acid (ALA), docosapentaenoic acid (DPA) and total n-3 PUFA were inversely and non-linearly associated with odds of breast cancer. The OR values (95 % CI), comparing the highest with the lowest quartile (Q), were 0·57 (0·43, 0·76), 0·43 (0·32, 0·58) and 0·36 (0·27, 0·49) for ALA, DPA and total n-3 PUFA, respectively. Erythrocyte membrane EPA and DHA were linearly and inversely associated with odds of breast cancer ((EPA: ORQ4 v. Q1 (95 % CI) = 0·59 (0·45, 0·79); DHA: ORQ4 v. Q1 (95 % CI) = 0·50 (0·37, 0·67)). The inverse associations were observed between ALA and odds of breast cancer in postmenopausal women, and between DHA and oestrogen receptor+ breast cancer. This study showed that erythrocyte membrane total and individual n-3 PUFA were inversely associated with odds of breast cancer. Other factors, such as menopause and hormone receptor status, may warrant further investigation when examining the association between n-3 PUFA and odds of breast cancer.

Eicosapentaenoic Acid: between Cardiovascular Benefits and the Risk of Atrial Fibrillation.

In recent years, scientific research has increasingly focused on the cardiovascular benefits of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements. The most promising results emerged from the new trials on a high-dose eicosapentaenoic acid (EPA)-only approach, instead of the previously prescribed therapy with EPA + docosahexaenoic acid (DHA). The evidence of the reduction of cardiovascular events in patients at high cardiovascular risk with EPA is intriguing. However, physicians have expressed concern about the potential high risk of atrial fibrillation (AF) occurrence due to such an approach. This study aims to investigate the current evidence on the cardiovascular benefits of EPA and its association with atrial arrhythmogenesis. Current guidelines consider EPA (as IPE) treatment for selected patients but with no specific indication regarding AF risk evaluation. We propose a flowchart that could be a starting point for the future development of an algorithm to help clinicians to prescribe EPA safely and effectively, especially in patients at high risk of incipient AF.

n-3 PUFAs Show Promise as Adjuvants in Chemotherapy, Enhancing their Efficacy while Safeguarding Hematopoiesis and Promoting Bone Generation.

Cancer ranks as the second leading cause of mortality in high-income countries, underscoring the critical need for effective therapeutic strategies. One prominent approach, chemotherapy, is widely employed for treating solid tumors. However, the significant adverse effects associated with chemotherapy, notably myeloablation and osteonecrosis, impart considerable challenges by compromising immune function and diminishing patients' quality of life. Furthermore, the emergence of chemotherapy resistance poses a formidable hurdle in achieving successful cancer treatment outcomes. In this context, the focus is on exploring alternative approaches to enhance the efficacy of cancer treatment and mitigate its adverse consequences. Among these approaches, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), two n-3 polyunsaturated fatty acids (PUFAs), have garnered substantial interest. These PUFAs exhibit the potential to influence membrane lipid composition and modulate critical gene expressions associated with cancer, such as Bcl-2, PI3K, NF-κB, and phosphorylated Akt, thereby potentially reducing cancer risk. Moreover, emerging evidence highlights their ability to augment chemotherapy efficacy, particularly in drug-resistant cancer cells. Importantly, both preclinical and clinical investigations have provided compelling evidence supporting the protective effects of n-3 PUFAs on healthy cells. Leveraging these findings, there has been growing attention on the exploration of n-3 PUFAs as adjuvants to chemotherapy. This strategic approach holds promise in mitigating the adverse effects linked to chemotherapy, notably myeloablation and osteonecrosis, while simultaneously enhancing its effectiveness in combating cancer. This comprehensive review delves into the multifaceted attributes of n-3 PUFAs, encompassing their cytotoxic properties, potential as chemopreventive agents, and their prospective role in ameliorating the adverse effects commonly associated with chemotherapy, with a particular emphasis on myeloablation and osteonecrosis. By elucidating the intricate interplay between n-3 PUFAs and cancer treatment paradigms, this review contributes to the expanding body of knowledge aimed at refining cancer therapeutic strategies and enhancing patient outcomes.

Omega-3 Polyunsaturated Fatty Acids are not associated with Peripheral Artery Disease in a Meta-Analysis from the Multi-Ethnic Study of Atherosclerosis and Atherosclerosis Risk in Communities Study Cohorts.

BACKGROUND: Research suggests omega-3 polyunsaturated fatty acids (PUFAs) exert favorable effects on several biological processes involved in the development and progression of atherosclerotic cardiovascular disease (ASCVD). However, studies examining the relationship between omega-3 PUFAs and peripheral artery disease (PAD) are scarce. OBJECTIVES: We evaluated the associations between omega-3 PUFAs and incident PAD in a meta-analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) study cohorts. METHODS: Omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured at baseline for all MESA (n = 6495) and Minnesota ARIC participants (n = 3612). Incident clinical PAD events (MESA n = 106; ARIC n = 149) identified primarily through ICD discharge codes were assessed through follow-up of each cohort. Associations between omega-3 PUFAs (EPA, DHA, and EPA+DHA) and incident PAD were modeled in MESA and ARIC as quartiles and continuously using Cox proportional hazards regression, respectively. A fixed-effects meta-analysis was conducted to evaluate associations in the 2 cohorts combined. RESULTS: In the fully adjusted model, in 10,107 participants, no significant associations were observed between EPA, DHA, or EPA+DHA, and incident PAD modeled as quartiles or continuously for either MESA or ARIC cohorts separately or in the meta-analysis after a follow-up of approximately 15 y. CONCLUSION: This study is consistent with previous literature indicating that the beneficial effects of omega-3 PUFAs on the markers of ASCVD may not translate to a clinically meaningful decrease in PAD risk.

Clinical impacts of n-3 fatty acids supplementation on depression symptoms: an umbrella review of meta-analyses.

Several meta-analyses investigating the efficacy of n-3 PUFA in alleviating depression symptoms have reported conflicting findings. In the present study, we aimed to perform an umbrella meta-analysis to provide a definite conclusion. A comprehensive systematic search of PubMed, Scopus, Embase, Web of Science and Cochrane Central Library was performed up to June 2021. Meta-analysis studies evaluating the effects of n-3 PUFA on depression symptoms were included. The quality of the included meta-analyses was assessed using AMSTAR questionnaire. Out of 101 studies, twenty-two studies with twenty-six effect sizes (ES) were eligible for inclusion. Sixteen ES showed significant improving effect of n-3 supplementation on depression symptoms among which eleven ES had small ES. The other studies observed no significant effect. Available evidence suggests that n-3 PUFA (EPA, DHA) supplementation could be considered as an effective add-on therapeutic approach in relieving depression symptoms.

High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis.

Migraine is a highly prevalent neurologic disorder with prevalence rates ranging from 9% to 18% worldwide. Current pharmacologic prophylactic strategies for migraine have limited efficacy and acceptability, with relatively low response rates of 40% to 50% and limited safety profiles. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered promising therapeutic agents for migraine prophylaxis. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various dosages of EPA/DHA and other current Food and Drug Administration-approved or guideline-recommended prophylactic pharmacologic interventions for migraine. Randomized controlled trials (RCTs) were eligible for inclusion if they enrolled participants with a diagnosis of either episodic or chronic migraine. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed were 1) changes in migraine frequency and 2) acceptability (i.e., dropout for any reason). Secondary outcomes included response rates, changes in migraine severity, changes in the frequency of using rescue medications, and frequency of any adverse events. Forty RCTs were included (N = 6616; mean age = 35.0 y; 78.9% women). Our analysis showed that supplementation with high dosage EPA/DHA yields the highest decrease in migraine frequency [standardized mean difference (SMD): -1.36; 95% confidence interval (CI): -2.32, -0.39 compared with placebo] and the largest decrease in migraine severity (SMD: -2.23; 95% CI: -3.17, -1.30 compared with placebo) in all studied interventions. Furthermore, supplementation with high dosage EPA/DHA showed the most favorable acceptability rates (odds ratio: 1.00; 95% CI: 0.06, 17.41 compared with placebo) of all examined prophylactic treatments. This study provides compelling evidence that high dosage EPA/DHA supplementation can be considered a first-choice treatment of migraine prophylaxis because this treatment displayed the highest efficacy and highest acceptability of all studied treatments. This study was registered in PROSPERO as CRD42022319577.

Hexachlorobenzene and omega-3 fatty acid intake from traditional foods in the northern Yukon: A risk and benefit analysis.

A human biomonitoring study was conducted in the community of Old Crow, Yukon, in 2019, finding that levels of hexachlorobenzene (HCB) in plasma were elevated in the community relative to the general Canadian population. The aim of this study was to estimate dietary intake of both hexachlorobenzene, and the nutrient omega-3 fatty acids from locally harvested traditional foods in Old Crow, with the aim of identifying possible regional sources of exposure. A stochastic model was constructed to estimate intake of both hexachlorobenzene and the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Average predicted hexachlorobenzene exposure levels from traditional food consumption in Old Crow were below the tolerable daily intake of 1600-1700 ng/kg body weight/day in both average (18 ng/kg body weight/day) and short-term maximum (27 ng/kg body weight/day) exposure models. The primary contributors to average hexachlorobenzene intake were caribou fat, bone marrow, ribs, and kidneys, and Chinook salmon muscle. Average estimated dietary EPA + DHA intake levels from traditional foods were below the recommendation of 2.1 to 3.2 g of EPA + DHA per week in the average (1.6 g/week) exposure model, but above this recommendation in the short-term maximum model (3.3 g/week). The primary contributors to average EPA + DHA intake were the meat of Chinook, coho, and, chum salmon muscle, and whitefish muscle and eggs. The results of this study support the message that traditional foods continue to be an important source of nutrients and other health benefits and that the health benefits of traditional foods generally outweigh contaminant risks.

Effect of age and dietary habits on Red Blood Cell membrane fatty acids in a Southern Europe population (Basque Country).

The levels of blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are very variable and, in general, low in most of the world population. In this study, the effects of age, sex, COVID-19, and dietary habits on the lipid profile of the erythrocyte membranes were assessed in a sub-cohort of healthy population (N = 203) from a large cohort of individuals from the Basque Country, Spain, (AKRIBEA). Sex did not have an effect on RBC lipid profile. COVID-19 infected participants showed higher levels of DGLA. Oldest participants showed higher oleic acid, EPA and DHA levels. Arachidonic acid in RBC correlated positively with the intake of sunflower oil, butter, eggs, processed and red meat, whereas DHA and EPA correlated positively with oily and lean fish. Basque Country population showed lipid profiles similar to other high fish consuming countries, such as Italy and Japan. Baseline levels of the whole lipidomic profile of the RBC including SFA, MUFA and PUFA should be examined to obtain a better description of the health and nutritional status.

The Clinical Promise of Microalgae in Rheumatoid Arthritis: From Natural Compounds to Recombinant Therapeutics.

Rheumatoid arthritis (RA) is an invalidating chronic autoimmune disorder characterized by joint inflammation and progressive bone damage. Dietary intervention is an important component in the treatment of RA to mitigate oxidative stress, a major pathogenic driver of the disease. Alongside traditional sources of antioxidants, microalgae-a diverse group of photosynthetic prokaryotes and eukaryotes-are emerging as anti-inflammatory and immunomodulatory food supplements. Several species accumulate therapeutic metabolites-mainly lipids and pigments-which interfere in the pro-inflammatory pathways involved in RA and other chronic inflammatory conditions. The advancement of the clinical uses of microalgae requires the continuous exploration of phytoplankton biodiversity and chemodiversity, followed by the domestication of wild strains into reliable producers of said metabolites. In addition, the tractability of microalgal genomes offers unprecedented possibilities to establish photosynthetic microbes as light-driven biofactories of heterologous immunotherapeutics. Here, we review the evidence-based anti-inflammatory mechanisms of microalgal metabolites and provide a detailed coverage of the genetic engineering strategies to enhance the yields of endogenous compounds and to develop innovative bioproducts.

DHA and EPA Alleviate Epileptic Depression in PTZ-Treated Young Mice Model by Inhibiting Neuroinflammation through Regulating Microglial M2 Polarization and Improving Mitochondrial Metabolism.

Depression is the most common complication of childhood epilepsy, leading to a poor prognosis for seizure control and poor quality of life. However, the molecular mechanisms underlying epileptic depression have not been completely elucidated. Increasing evidence suggests that oxidative stress and neuroinflammation are major contributors to depression. The positive effects of dietary supplementation with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on depression have been previously reported. However, knowledge regarding the effects of EPA and DHA in managing depressive symptoms in pediatric patients with epilepsy is limited. Therefore, this study aims to investigate the effects of EPA and DHA on epileptic depression in a pentylenetetrazole (PTZ)-treated young mouse model. Three-week-old mice were fed a DHA- or EPA-enriched diet for 21 days and treated with PTZ (35 mg/kg, i.p.) every other day for a total of 10 times. EPA was more effective than DHA at alleviating PTZ-induced depressive symptoms. Pathological results revealed that DHA and EPA significantly improved neuronal degeneration in the hippocampus. Analysis of the mechanism revealed that DHA and EPA mitigated PTZ-induced myelin damage by increasing the protein levels of CNPase, Olig2, and MBP. Furthermore, both DHA and EPA reduced neuroinflammation by promoting microglial M2 polarization and suppressing the LCN2-NLRP3 inflammasome pathway. Notably, EPA polarized microglia towards the M2 phenotype. In addition, DHA and EPA decreased oxidative stress by inhibiting NOX2 and enhancing mitochondrial metabolism through the increased expression of mitochondrial respiratory chain complex I-V proteins. These findings suggest that DHA and EPA can be used as effective interventions to improve depression in children with epilepsy, with EPA being a particularly favorable option.

Effects of Omega-3 Fatty Acid Supplementation on Skeletal Muscle Mass and Strength in Adults: A Systematic Review.

Previous studies have suggested that omega-3 polyunsaturated fatty acids, predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have several health benefits. However, their effect on changes in skeletal muscle mass and strength has not been established, owing to differences in study designs. This systematic review aimed to investigate the recent evidence regarding the role of dietary EPA and DHA in muscle mass changes and their association with muscle strength. Databases including PubMed and Google Scholar were searched for randomized controlled trials and single-arm interventions that investigated the effects of omega-3 fatty acids on skeletal muscle mass, strength, and body composition in adults aged 18 years and older. A total of 18,521 studies were retrieved from the databases and manual searches; 21 studies were quality assessed, and the findings were summarized. Studies were categorized into 3 main categories according to the type of omega-3 fatty acid supplementation: pure compounds such as oil tablets, formulated forms with protein, leucine, and vitamin D, and ingredients added to enteral nutrition support products. Overall, the majority of the study results appeared to indicate that omega-3 fatty acids are beneficial for muscle health. However, meta-analysis was not conducted because of the heterogeneity of the study participants, evaluation method of muscle indices, and intervention periods among the studies. High-quality studies are required to validate our conclusions. However, this systematic review of the effects of EPA and DHA on skeletal muscle and body composition provides evidence that can be applied in both clinical and industrial settings.

n-3 PUFAs synergistically enhance the efficacy of doxorubicin by inhibiting the proliferation and invasion of breast cancer cells.

Breast cancer stands as a prominent contributor to cancer-related fatalities among women globally, characterized by an unfavorable prognosis, low survival rates, and its conventional treatment approach involving chemotherapy. Doxorubicin (DOXO) represents a potent anti-tumor agent widely employed in combating breast cancer. Regrettably, a substantial proportion of patients eventually develop resistance to DOXO treatment, elevating the risk of relapse and adverse clinical outcomes. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), recognized as essential components of the human diet, have exhibited considerable promise in targeting malignant cells, initiating apoptosis, and impeding tumor proliferation and metastatic dissemination. Combining these nutritional supplements, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with DOXO presents a compelling strategy to augment treatment efficacy. The present study was conducted employing a breast cancer cell line, MCF-7, to assess the synergistic potential of DHA, EPA, and DOXO. Remarkably, the combination treatment yielded a substantial increase in cytotoxicity compared to the administration of DOXO alone. Furthermore, an enhancement in the suppression of metastasis was evident in the combination treatment relative to the exclusive use of DOXO. Cell cycle analysis unveiled that cells subjected to the combination treatment exhibited a more pronounced arrest in the G1 phase, signifying the combination's heightened effectiveness in impeding cell progression into the doubling phase. Collectively, the amalgamation of n-3 polyunsaturated fatty acids (n-3 PUFAs) emerges as a potent strategy for enhancing the therapeutic potential of DOXO, effectively restraining the growth and dissemination of breast cancer cells.

Immunomodulatory effect of marine lipids on food allergy.

Seafood is highly enriched in n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), particularly eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3), in contrast to the ultra-processed foods included in the modern Western diet that have high levels of n-6 linoleic acid (LA, 18:2 n-6), precursor for the pro-inflammatory n-6 arachidonic acid (ARA, 20:4 n-6). The capacity of marine lipids to reduce plasmatic triglycerides and blood pressure have been well-described. Moreover, recent studies have also raised evidence of a potential regulatory action of marine lipids on inflammation, the immune system, and food allergy (FA). FA is considered one of the main concerns to become life threatening in food safety. The prevalence of this emerging global problem has been increasing during the last two decades, especially in industrialized countries. About a 6-8% of young children and 2-4% of adults is estimated to be affected by FA. The main objective of the current study is to update the existing knowledge, but also the limitations, on the potential impact of marine lipids and their lipid mediators in regulating immunity, inflammation, and ultimately, food allergies. In particular, the focus is on the effect of marine lipids in modulating the key factors that control the sensitization and effector phases of FA, including gut microbiota (GM), inflammation, and immune system response. Results in animal models highlight the positive effect that consuming marine lipids, whether as a supplement or through seafood consumption, may have a relevant role in improving gut dysbiosis and inflammation, and preventing or reducing the severity of FA. However, more systematic studies in humans are needed to optimize such beneficial actions to each particular FA, age, and medical condition to reach an effective clinical application of marine lipids to improve FAs and their outcomes.