Role of omega-3 fatty acids in reducing proteinuria: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Proteinuria, a hallmark of renal and systemic disorders, is associated with adverse outcomes, especially in chronic kidney disease and cardiovascular disease. Omega-3 fatty acids have garnered attention for their cardiovascular benefits and potential therapeutic effects on proteinuria. This systematic review and meta-analysis aimed to evaluate the impact of omega-3 fatty acid supplementation on proteinuria levels across various kidney-related conditions. METHODS AND STUDY DESIGN: Studies published from 1989 to 2023 were systematically identified, including randomized controlled trials, cohort, case-control, and cross-sectional studies. Nine studies involving a total of 347 participants were included in the analysis. RESULTS: The meta-analysis revealed a neutral overall effect size of omega-3 fatty acid supplementation on proteinuria levels, assessed under both common and random effect models. Despite the lack of statistically significant evidence supporting the efficacy of omega-3 fatty acids in reducing proteinuria, the variability in interventions and patient populations suggests potential individual responses. CONCLUSIONS: The find-ings highlight the heterogeneity in responses to omega-3 fatty acid supplementation and emphasize the need for cautious interpretation. While no definitive conclusion can be drawn, the results underscore the importance of targeted research focusing on specific subgroups or conditions that may benefit from omega-3 supplementation. These findings contribute to the evolving understanding of personalized kidney health strategies and pave the way for further exploration and optimization of omega-3 fatty acids' therapeutic applications.

Nutritional effect on lipoproteins and their subfractions in patients with Psoriatic Arthritis: a 12-week randomized trial-the DIETA trial.

INTRODUCTION: Patients with psoriatic arthritis have some lipid metabolism changes and higher risk of metabolic syndrome (MetS) and cardiovascular diseases, regardless of traditional risk factors, suggesting that chronic inflammation itself plays a central role concerning the atherosclerosis. However, there is a lack of information regarding atherogenic pattern and lipoprotein subfractions burden in these individuals. AIM: To evaluate the HDL and LDL-cholesterol plasmatic levels and their subfractions after a nutritional intervention in patients with psoriatic arthritis (PsA). METHODS: This was a randomized, placebo-controlled clinical trial of a 12-week nutritional intervention. PsA patients were randomly assigned to 1-Placebo: 1 g of soybean oil daily, no dietetic intervention; 2-Diet + Supplementation: an individualized diet, supplemented with 604 mg of omega-3 fatty acids, three times a day; and 3-Diet + Placebo: individualized diet + 1 g of soybean oil. The LDL subfractions were classified as non-atherogenic (NAth), atherogenic (Ath) or highly atherogenic (HAth), whereas the HDL subfractions were classified as small, medium, or large particles, according to the current recommendation based on lipoproteins electrophoresis. RESULTS: A total of 91 patients were included in the study. About 62% of patients (n = 56) had an Ath or HAth profile and the main risk factors associated were male gender, longer skin disease duration and higher BMI. Thirty-two patients (35%) had a high-risk lipoprotein profile despite having LDL plasmatic levels below 100 mg/dL. The 12-week nutritional intervention did not alter the LDL subfractions. However, there were significant improvement of HDL subfractions. CONCLUSION: Recognizing the pro-atherogenic subfractions LDL pattern could be a relevant strategy for identifying PsA patients with higher cardiovascular risk, regardless total LDL plasmatic levels and disease activity. In addition, a short-term nutritional intervention based on supervised and individualized diet added to omega-3 fatty acids changed positively the HDLLARGE subfractions, while LDLLARGE subfraction was improved in hypercholesterolemic individuals. CLINICALTRIALS: gov identifier: NCT03142503 ( http://www. CLINICALTRIALS: gov/ ).

Effect of omega-3 fatty acid supplementation on markers of inflammation and endothelial function in patients with chronic heart disease: A systematic review and meta-analysis.

Chronic heart disease (CHD) is still a major global cause of morbidity and mortality, necessitating effective therapeutic interventions to mitigate its progression. Omega-3 fatty acids (FAs) have garnered attention for their potential anti-inflammatory and endothelial-protective properties in CHD management. The present study aims to assess the efficacy of Omega-3 FA supplementation on markers of inflammation and endothelial function in patients with CHD. To achieve this, we used the relevant keywords to search international databases (Web of Science, PubMed, Embase, and Scopus) and extract publications evaluating the effectiveness of omega-3 FA supplementation on inflammation markers and endothelial function in patients with CHD. STATA (version 15) and the random and fixed-effects models were used to evaluate the collected data. Thirteen clinical trial studies met inclusion criteria, with a total sample size of 853 individuals (406 cases and 447 controls). The cases had a mean age of 58 ± 10.3 years. The pooled results indicated that omega-3 Omega-3 FA supplementation significantly reduced the level of circulating IL-6 (SMD = -0.47, 95% CI -1.29 to 0.35, %, p < 0.001), hs-CRP (SMD = -0.21, 95% CI -0.70 to 0.28, p = 0.01), and TNF-α (SMD = -0.56, 95% CI -1.14 to 0.01, p < 0.001) in patients with CHD. Also, findings revealed that a daily supplement of omega-3 significantly increased FMD by 0.34% (95% CI: 0.14-0.54%, p < 0.001) as compared with placebo by a fixed-effect model in patients with CHD. These findings underscore the potential therapeutic utility of omega-3 fatty acid supplementation in modulating inflammation and endothelial dysfunction in patients with CHD.

Efficacy and safety of omega-3 fatty acids supplementation for anxiety symptoms: a systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVES: There is uncertainty about the optimum dose of omega-3 fatty acids for anxiety symptoms. We aimed to find the dose-dependent effect of omega-3 supplementation on anxiety symptoms. METHODS: We systematically reviewed PubMed, Scopus, and Web of Science until December 2022 to find randomized trials that assessed the effects of omega-3 fatty acids supplementation on anxiety symptoms in adults. Investigators performed the literature search and screened the titles/abstracts and full-texts and between-reviewer agreement was assessed as Cohen's kappa coefficient. We conducted a random-effects dose-response meta-analysis to estimate standardized mean differences (SMD) and 95% confidence intervals (CIs) and assessed the certainty of evidence using the GRADE framework. RESULTS: A total of 23 trials with 2189 participants were included. Each 1 gram per day supplementation with omega-3 fatty acids resulted in a moderate decrease in anxiety symptoms (SMD: -0.70, 95%CI: -1.17, -0.22; GRADE = low). The non-linear dose-response analysis indicated the greatest improvement at 2 g/d (SMD: -0.93, 95%CI: -1.85, -0.01), and that supplementation in a dose lower than 2 g/d did not affect anxiety symptoms. Omega-3 fatty acids did not increase adverse events (odds ratio: 1.20, 95%CI: 0.89, 1.61; GRADE = moderate). CONCLUSIONS: The present dose-response meta-analysis suggested evidence of very low certainty that supplementation with omega-3 fatty acids may significantly improve anxiety symptoms, with the greatest improvements at 2 g/d. More trials with better methodological quality are needed to reach more robust evidence. PROTOCOL REGISTRATION: PROSPERO (CRD42022309636).

Effects of Omega-3 Polyunsaturated Fatty Acids, Docosahexaenoic Acid and Eicosapentaenoic Acid, on Post-Surgical Complications in Surgical Trauma Patients: Mechanisms, Nutrition, and Challenges.

This paper aims to provide an in-depth review of the specific outcomes associated with omega-3 polyunsaturated fatty acids (PUFAs), focusing on their purported effects on post-surgical complications in trauma patients. A comprehensive investigation of omega-3 polyunsaturated fatty acids was conducted until February 2023 using the PubMed database. Surgical trauma is characterized by a disruption in immune response post surgery, known to induce systemic inflammation. Omega-3 PUFAs are believed to offer potential improvements in multiple post-surgical complications because of their anti-inflammatory and antioxidant properties. Inconsistent findings have emerged in the context of cardiac surgeries, with the route of administration playing a mediating role in these outcomes. The effects of omega-3 PUFAs on post-operative atrial fibrillation have exhibited variability across various studies. Omega-3 PUFAs have demonstrated positive effects in liver surgery outcomes and in patients with acute respiratory distress syndrome. Omega-3 is suggested to offer potential benefits, particularly in the perioperative care of patients undergoing traumatic procedures. Incorporating omega-3 in such cases is hypothesized to contribute to a reduction in certain surgical outcomes, such as hospitalization duration and length of stay in the intensive care unit. Therefore, comprehensive assessments of adverse effects can aid in identifying the presence of subtle or inconspicuous side effects associated with omega-3.

[The role of ω-3 polyunsaturated fatty acids in child development].

ω-3 polyunsaturated fatty acids (PUFAs) are incorporated in cell membranes and play an important role in the development and functioning of organs. Consolidation of data on the role of ω-3 PUFAs in child development may increase the professional's awareness, help to plan clinical studies, and develop recommendations for supplementation. The aim of the research was to analyze literature data on the effect of ω-3 PUFAs on the central nervous system, immune system, and vision in children. Material and methods. 86 literature sources have been analyzed, a keyword search was carried out in the PubMed, Scopus, Elsevier, eLibrary and Google Scholar databases. Results. ω-3 PUFAs (alpha-linolenic, docosahexaenoic and eicosapentaenoic acids) are not synthesized in the human organism, and should be obtained from food. The need for ω-3 PUFAs is especially high during periods of rapid growth (the first years of life and adolescence). ω-3 PUFAs play an important role in the anatomical and functional development of the brain, affecting the maturation and functioning of neurons, participating in the processes of neurogenesis, migration, synaptogenesis, and neurotransmission. The results of clinical studies on the effect of ω-3 PUFAs on the cognitive functions of healthy children and patients with attention deficit hyperactivity disorder are contradictory, which requ ires further research. PUFAs are substrates for the synthesis of bioactive compounds and take part in the control of acute and chronic inflammation, and also have a regulatory effect on immune cells. ω-3 PUFAs supplementation decreases the frequency and duration of acute respiratory viral infections in children. This indicates the potential effectiveness of ω-3 PUFAs in the prevention of acute respiratory viral infections. Сlinical studies demonstrated positive effects of ω-3 PUFAs on retinal development in premature infants. Conclusion. Adequate intake of ω-3 PUFAs is essential for the development and functioning of the central nervous system, immune system and vision in children. The body content of ω-3 PUFAs is closely related to the nutrition. In the Russian Federation, consumption of fish and other products containing ω-3 PUFAs is traditionally low. The majority of the Russian population has a deficiency in ω-3 PUFA consumption. With an unbalanced diet, supplementation of ω-3 PUFAs is necessary.

Addressing methodological concerns in omega-3 trial for bipolar disorder relapse prevention.

Our response addresses concerns raised about our pilot trial on omega-3 for bipolar disorder. We clarify randomization procedures, highlight the benefits of eicosapentaenoic-predominant formulations for a specific bipolar patients subgroup, and justify the use of Kaplan-Meier analysis despite limitations. We acknowledge analytical challenges due to strict inclusion criteria and encourage future research on specific bipolar subtypes and larger-scale trials for robust validation.

The efficacy of omega-3 fatty acids (O3FAs) as a complementary in colorectal cancer patients: A systematic review and meta-analysis.

BACKGROUND & AIMS: Colorectal cancer (CRC) is the third most common malignancy in developed countries. Therefore, omega-3 fatty acids (O3FAs) have been suggested as a beneficial complementary treatment due to their ability to regulate inflammatory responses and improve nutrition levels.This study aimed to evaluate the effects of O3FAs as a complementary treatment for inflammation, nutrition levels, post-operative infectious complications, and enhancement of recovery in CRC patients. METHODS: The literature search was carried out through three databases. The outcomes of interest were assessed by measuring pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and CRP levels, serum albumin levels for nutrition assessment, post-operative infectious complications, and length of stay for recovery evaluation. Quality appraisal and meta-analysis were performed using RoB 2.0 and RevMan 5.4, respectively. RESULTS: The result showed that O3FAs significantly reduced IL-6, CRP, and TNF-α, but did not affect IL-1ß. Furthermore, the variable slightly increased serum albumin levels and the supplementation led to a decrease in post-operative infectious complications and shortened hospital stays. CONCLUSION: O3FAs as a complementary treatment provided advantages for CRC patients, Further clinical trials and experiments should also be made emphasizing the impact and clinical implementation of O3FA in the nutritional status of CRC patients.

Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: There is a potential concern about increased bleeding risk in patients receiving omega-3 polyunsaturated fatty acids (PUFAs). The aims of this study-level meta-analysis were to determine the risk of bleeding and to assess whether this relationship is linked to the received dose of omega-3 PUFAs or the background use of antiplatelet treatment. METHODS AND RESULTS: Electronic databases were searched through May 2023 to identify randomized clinical trials of patients receiving omega-3 PUFAs. Overall bleeding events, including fatal and central nervous system events, were identified and compared with those of a control group. A total of 120 643 patients from 11 randomized clinical trials were included. There was no difference in the pooled meta-analytic events of bleeding among patients receiving omega-3 PUFAs and those in the control group (rate ratio [RR], 1.09 [95% CI, 0.91-1.31]; P=0.34). Likewise, the incidence of hemorrhagic stroke, intracranial bleeding, and gastrointestinal bleeding were similar. A prespecified analysis was performed in patients receiving high-dose purified eicosapentaenoic acid (EPA), which demonstrated a 50% increase in the relative risk of bleeding but only a modest increase in the absolute risk of bleeding (0.6%) when compared with placebo. Bleeding risk was associated with the dose of EPA (risk difference, 0.24 [95% CI, 0.05-0.43]; P=0.02) but not the background use of antiplatelet therapy (risk difference, -0.01 [95% CI, -0.02 to 0]; P=0.056). CONCLUSIONS: Omega-3 PUFAs were not associated with increased bleeding risk. Patients receiving high-dose purified EPA may incur additional bleeding risk, although its clinical significance is very modest.

Nutraceuticals in Psychiatric Disorders: A Systematic Review.

Correct nutrition and diet are directly correlated with mental health, functions of the immune system, and gut microbiota composition. Diets with a high content of some nutrients, such as fibers, phytochemicals, and short-chain fatty acids (omega-3 fatty acids), seem to have an anti-inflammatory and protective action on the nervous system. Among nutraceuticals, supplementation of probiotics and omega-3 fatty acids plays a role in improving symptoms of several mental disorders. In this review, we collect data on the efficacy of nutraceuticals in patients with schizophrenia, autism spectrum disorders, major depression, bipolar disorder, and personality disorders. This narrative review aims to provide an overview of recent evidence obtained on this topic, pointing out the direction for future research.

Can Nutraceuticals Support the Treatment of MASLD/MASH, and thus Affect the Process of Liver Fibrosis?

Currently, metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are considered to be the main causes of fibrosis. In turn, fibrosis may lead to the development of hepatocellular carcinoma or advanced cirrhosis, i.e., potentially life-threatening conditions. It is likely that therapy aimed at reducing the risk of developing hepatic steatosis and inflammation could be helpful in minimizing the threat/probability of organ fibrosis. In recent years, increasing attention has been paid to the influence of nutraceuticals in the prevention and treatment of liver diseases. Therefore, the aim of this review was to describe the precise role of selected ingredients such as vitamin C, beta-carotene, omega-3 fatty acids, and curcumin. It is likely that the use of these ingredients in the treatment of patients with MASLD/MASH, along with behavioral and pharmacological therapy, may have a beneficial effect on combating inflammation, reducing oxidative stress, and thereby preventing liver damage.

Expert consensus report on lipid mediators: Role in resolution of inflammation and muscle preservation.

This meeting report presents a consensus on the biological aspects of lipid emulsions in parenteral nutrition, emphasizing the unanimous support for the integration of lipid emulsions, particularly those containing fish oil, owing to their many potential benefits beyond caloric provision. Lipid emulsions have evolved from simple energy sources to complex formulations designed to improve safety profiles and offer therapeutic benefits. The consensus highlights the critical role of omega-3 polyunsaturated fatty acids (PUFAs), notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found in fish oil and other marine oils, for their anti-inflammatory properties, muscle mass preservation, and as precursors to the specialized pro-resolving mediators (SPMs). SPMs play a significant role in immune modulation, tissue repair, and the active resolution of inflammation without impairing host defense mechanisms. The panel's agreement underscores the importance of incorporating fish oil within clinical practices to facilitate recovery in conditions like surgery, critical illness, or immobility, while cautioning against therapies that might disrupt natural inflammation resolution processes. This consensus not only reaffirms the role of specific lipid components in enhancing patient outcomes, but also suggests a shift towards nutrition-based therapeutic strategies in clinical settings, advocating for the proactive evidence-based use of lipid emulsions enriched with omega-3 PUFAs. Furthermore, we should seek to apply our knowledge concerning DHA, EPA, and their SPM derivatives, to produce more informative randomized controlled trial protocols, thus allowing more authoritative clinical recommendations.

Krill Oil and Its Bioactive Components as a Potential Therapy for Inflammatory Bowel Disease: Insights from In Vivo and In Vitro Studies.

Krill oil is extracted from krill, a small crustacean in the Antarctic Ocean. It has received growing attention because of krill oil's unique properties and diverse health benefits. Recent experimental and clinical studies suggest that it has potential therapeutic benefits in preventing the development of a range of chronic conditions, including inflammatory bowel disease (IBD). Krill oil is enriched with long-chain n-3 polyunsaturated fatty acids, especially eicosapentaenoic and docosahexaenoic acids, and the potent antioxidant astaxanthin, contributing to its therapeutic properties. The possible underlying mechanisms of krill oil's health benefits include anti-inflammatory and antioxidant actions, maintaining intestinal barrier functions, and modulating gut microbiota. This review aims to provide an overview of the beneficial effects of krill oil and its bioactive components on intestinal inflammation and to discuss the findings on the molecular mechanisms associated with the role of krill oil in IBD prevention and treatment.

Omega-3 polyunsaturated fatty acids play a protective role in a mouse model of Parkinson's disease by increasing intestinal inducible Treg cells.

Parkinson's disease (PD) is defined as a progressive neurodegenerative disease in middle-aged and elderly people. The therapeutic effect of ω-3 PUFAs in several neurodegenerative diseases has been well recognized. Nevertheless, whether nutrition supplementing ω-3 PUFAs exerts a neuroprotective role in PD remains elusive. Bioinformatics revealed 2D chemical structural formula of three components. Mice received indicated treatment with saline, MPTP or ω-3 PUFAs according to grouping. Behavioral function of mice was measured through motor tests such as rearing, akinesia, and rotarod tests. OFT test measured anxiety-like behaviors of mice. Western blotting and TUNEL staining measured dopaminergic fibers and neurons of mice. Western blotting measured inflammation and apoptosis-related protein levels in mouse tissue. FACS measured iTreg cell proportion in colon and brain tissues of mice. ω-3 PUFAs repaired MPTP-stimulated motor function damage in PD mice. ω-3 PUFAs mitigated MPTP-stimulated comorbid anxiety in PD mice. ω-3 PUFAs relieved MPTP-stimulated deficits of dopaminergic fibers and neurons in PD mice. ω-3 PUFAs repressed MPTP-stimulated inflammation and apoptosis pathway activation in PD mice. ω-3 PUFAs repaired MPTP-stimulated immune function damage in PD mice. ω-3 PUFAs exert a protective role in PD mice through alleviating motor function impairment and neuroinflammation by increasing intestinal inducible Treg cells, which may provide a new direction for seeking targeted therapy plans for PD in humans.

Omega-3 and omega-6 polyunsaturated fatty acids and their potential therapeutic role in protozoan infections.

Protozoa exert a serious global threat of growing concern to human, and animal, and there is a need for the advancement of novel therapeutic strategies to effectively treat or mitigate the impact of associated diseases. Omega polyunsaturated fatty acids (ω-PUFAs), including Omega-3 (ω-3) and omega-6 (ω-6), are constituents derived from various natural sources, have gained significant attention for their therapeutic role in parasitic infections and a variety of essential structural and regulatory functions in animals and humans. Both ω-3 and ω-6 decrease the growth and survival rate of parasites through metabolized anti-inflammatory mediators, such as lipoxins, resolvins, and protectins, and have both in vivo and in vitro protective effects against various protozoan infections. The ω-PUFAs have been shown to modulate the host immune response by a commonly known mechanism such as (inhibition of arachidonic acid (AA) metabolic process, production of anti-inflammatory mediators, modification of intracellular lipids, and activation of the nuclear receptor), and promotion of a shift towards a more effective immune defense against parasitic invaders by regulation the inflammation like prostaglandins, leukotrienes, thromboxane, are involved in controlling the inflammatory reaction. The immune modulation may involve reducing inflammation, enhancing phagocytosis, and suppressing parasitic virulence factors. The unique properties of ω-PUFAs could prevent protozoan infections, representing an important area of study. This review explores the clinical impact of ω-PUFAs against some protozoan infections, elucidating possible mechanisms of action and supportive therapy for preventing various parasitic infections in humans and animals, such as toxoplasmosis, malaria, coccidiosis, and chagas disease. ω-PUFAs show promise as a therapeutic approach for parasitic infections due to their direct anti-parasitic effects and their ability to modulate the host immune response. Additionally, we discuss current treatment options and suggest perspectives for future studies. This could potentially provide an alternative or supplementary treatment option for these complex global health problems.

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review.

Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance. For dry AMD, no real effective treatment is available in Europe. It is, therefore, essential to look for new approaches. Recently, the use of long-chain and very long-chain polyunsaturated fatty acids was identified as an interesting new therapeutic alternative. Indeed, the levels of these fatty acids, core components of photoreceptors, are significantly decreased in AMD patients. To better understand this pathology and to evaluate the efficacy of various molecules, in vitro and in vivo models reproducing the mechanisms of both types of AMD were developed. This article reviews the anatomy and the physiological aging of the retina and summarizes the clinical aspects, pathophysiological mechanisms of AMD and potential treatment strategies. In vitro and in vivo models of AMD are also presented. Finally, this manuscript focuses on the application of omega-3 fatty acids for the prevention and treatment of both types of AMD.

Omega-3 (n-3) Fatty Acid-Statin Interaction: Evidence for a Novel Therapeutic Strategy for Atherosclerotic Cardiovascular Disease.

Managing atherosclerotic cardiovascular disease (ASCVD) often involves a combination of lifestyle modifications and medications aiming to decrease the risk of cardiovascular outcomes, such as myocardial infarction and stroke. The aim of this article is to discuss possible omega-3 (n-3) fatty acid-statin interactions in the prevention and treatment of ASCVD and to provide evidence to consider for clinical practice, highlighting novel insights in this field. Statins and n-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) are commonly used to control cardiovascular risk factors in order to treat ASCVD. Statins are an important lipid-lowering therapy, primarily targeting low-density lipoprotein cholesterol (LDL-C) levels, while n-3 fatty acids address triglyceride (TG) concentrations. Both statins and n-3 fatty acids have pleiotropic actions which overlap, including improving endothelial function, modulation of inflammation, and stabilizing atherosclerotic plaques. Thus, both statins and n-3 fatty acids potentially mitigate the residual cardiovascular risk that remains beyond lipid lowering, such as persistent inflammation. EPA and DHA are both substrates for the synthesis of so-called specialized pro-resolving mediators (SPMs), a relatively recently recognized feature of their ability to combat inflammation. Interestingly, statins seem to have the ability to promote the production of some SPMs, suggesting a largely unrecognized interaction between statins and n-3 fatty acids with relevance to the control of inflammation. Although n-3 fatty acids are the major substrates for the production of SPMs, these signaling molecules may have additional therapeutic benefits beyond those provided by the precursor n-3 fatty acids themselves. In this article, we discuss the accumulating evidence that supports SPMs as a novel therapeutic tool and the possible statin-n-3 fatty acid interactions relevant to the prevention and treatment of ASCVD.

Parenteral n-3 polyunsaturated fatty acids supplementation improves postoperative recovery for patients with Crohn's disease after bowel resection: a randomized, unblinded controlled clinical trial.

BACKGROUND: The postoperative inflammatory response is associated with postoperative recovery in surgery. n-3 (ω-3) polyunsaturated fatty acids have been reported to lower inflammation. The postoperative role of parenteral n-3 polyunsaturated fatty acids supplementation on outcomes in Crohn's disease after bowel resection is unclear. OBJECTIVES: We aimed to investigate the effects of postoperative parenteral n-3 polyunsaturated fatty acids supplementation in Crohn's disease. METHODS: A prospective randomized, unblinded controlled clinical trial was conducted for patients with Crohn's disease who underwent bowel resection between May 2019 and February 2022. Postoperative complications, complete blood count, serum biochemical values, and cytokine concentrations were compared in patients with and without parenteral n-3 polyunsaturated fatty acids supplementation for 5 d postoperatively. RESULTS: There were 268 patients randomly assigned in the analysis, with 134 in the control group (a mix of long-chain and medium-chain fats at 1.0 g/kg/d) and 134 in the treatment group (long-chain, medium-chain, and n-3 polyunsaturated fats at 1.2 g/kg/d). Twenty-six did not complete the allocated treatment, and 8 patients were lost to follow-up. The intention-to-treat analysis and the per-protocol analysis showed that there were a significant reduction in overall complication rates (22.4% compared with 49.3%; P < 0.001 and 21.8% compared with 38.2%; P = 0.006) and postoperative stay (8.8 ± 4.5 d compared with 11.2 ± 6.8 d; P = 0.001 and 8.7 ± 4.0 d compared with 11.5 ± 7.3 d; P < 0.001) in patients with parenteral n-3 polyunsaturated fatty acids supplementation compared with patients in the control group. In the secondary outcomes, the mean ± standard deviation of interleukin (IL)-6 (17.11 ± 2.14 pg/mL compared with 30.50 ± 5.14 pg/mL; P = 0.014), IL-1ß (2.01 ± 0.05 pg/mL compared with 2.24 ± 0.09 pg/mL; P = 0.019), tumor necrosis factor-α (2.09 ± 0.06 pg/mL compared with 2.29 ± 0.06 pg/mL; P = 0.029), and C-reactive protein concentrations (51.3 ± 4.2 mg/L compared with 64.4 ± 5.3 mg/L; P = 0.050) on postoperative day 5 in the treatment group were much lower than those in the control group. CONCLUSIONS: Parenteral n-3 polyunsaturated fatty acids supplementation promotes postoperative recovery in patients with Crohn's disease following bowel resection, with fewer complications and reduced inflammatory cytokines. This trial was registered at clinicaltrials.gov as NCT03901937 at https://classic. CLINICALTRIALS: gov/ct2/show/NCT03901937?term=NCT03901937&cond=Crohn+Disease&draw=2&rank=1.

Omega-3 fatty acids for inflamed depression - A match/mismatch study.

Despite decades of research on the pathophysiology of depression, the development of new therapeutic interventions has been slow, and no biomarkers of treatment response have been clinically implemented. Several lines of evidence suggest that the clinical and biological heterogeneity among patients with major depressive disorder (MDD) has hampered progress in this field. MDD with low-grade inflammation - "inflamed depression" - is a subtype of depression that may be associated with a superior antidepressant treatment response to anti-inflammatory compounds. Omega-3 fatty acid eicosapentaenoic acid (EPA) has anti-inflammatory properties, and preliminary data suggest that it may be particularly efficacious in inflamed depression. In this study we tested the hypothesis that add-on EPA has greater antidepressant efficacy in MDD patients with high baseline high-sensitivity C-reactive protein (hs-CRP) compared to MDD patients with low hs-CRP. All subjects received 2.2 g EPA, 400 mg docosahexaenoic acid and 800 mg of other fatty acids daily for 8 weeks, added to stable ongoing antidepressant treatment. The primary outcome was change in the 17-item Hamilton Depression Rating Scale (HAMD-17). Patients and raters were blind to baseline hs-CRP status. In an intention-to-treat analysis including all subjects with at least one post baseline visit (n = 101), ahs-CRPcut-off of ≥1 mg/L, but not ≥3 mg/L, was associated with a greater improvement in HAMD-17 total score. In addition to a general antidepressant effect among patients with hs-CRP ≥ 1 mg/L, adjuvant EPA treatment improved symptoms putatively related to inflamed depression such as fatigue and sleep difficulties. This adds to the mounting evidence that delineation of MDD subgroups based on inflammation may be clinically relevant to predict treatment response to anti-inflammatory interventions.