Gallstone Dissolution Effects of Combination Therapy with n-3 Polyunsaturated Fatty Acids and Ursodeoxycholic Acid: A Randomized, Prospective, Preliminary Clinical Trial.

Background/Aims: : Ursodeoxycholic acid (UDCA) is the only well-established and widely used agent for dissolving gallstones. Epidemiological and animal studies have suggested potential therapeutic benefits of n-3 polyunsaturated fatty acids (PUFA) for dissolving cholesterol gallstones. We evaluated whether adding PUFA to UDCA improves gallstone dissolution in patients with cholesterol gallstones. Methods: : This randomized, prospective, preliminary clinical trial compared the efficacy and safety of UDCA plus PUFA combination therapy (combination group) with those of UDCA monotherapy (monotherapy group). The inclusion criteria were a gallstone diameter ≤15 mm on ultrasonography, radiolucent stones on plain X-ray, and no to mild symptoms. Gallstone dissolution rates, response rates, and adverse events were evaluated. Results: : Of the 59 screened patients, 45 patients completed treatment (24 and 21 in the monotherapy and combination groups, respectively). The gallstone dissolution rate tended to be higher in the combination group than in the monotherapy group (45.7% vs 9.9%, p=0.070). The radiological response rate was also significantly higher in the combination group (90.5% vs 41.7%, p=0.007). In both groups, dissolution and response rates were higher in patients with gallbladder sludge than in those with distinct stones. Four adverse events (two in each group) were observed, none of which were study drug-related or led to drug discontinuation. The incidence of these adverse events was similar in both groups (combination vs monotherapy: 9.5% vs 8.3%, p=0.890). Conclusions: : UDCA plus PUFA therapy dissolves cholesterol gallstones more effectively than UDCA monotherapy, without significant complications. Further prospective, large-scale studies of this combination therapy are warranted.

Excesso de peso pré-gestacional e ácidos graxos poli-insaturados no leite humano: modelo teórico de causalidade / Pre-gestational overweight and polyunsaturated fatty acids in human milk: theoretical causality model

Resumo Inúmeros estudos têm se detido na avaliação da associação entre o excesso de peso pré-gestacional e os ácidos graxos poli-insaturados no leite humano. Todavia, diante da complexidade de fatores de risco potencialmente confundidores, é recomendável a utilização de ferramentas gráficas para identificar possíveis vieses. O objetivo deste artigo é propor um modelo teórico de causalidade utilizando o gráfico acíclico direcionado entre o excesso de peso pré-gestacional e os ácidos graxos poli-insaturados no leite humano. Foi realizada ampla revisão da literatura para identificar as variáveis com relações causais com a exposição e/ou desfecho. A escolha das variáveis para ajuste seguiu o algoritmo gráfico que compreende seis critérios para a seleção de um conjunto mínimo de variáveis potencialmente confundidoras. Condições socioeconômicas, intervalo interpartal, idade materna e padrão de consumo alimentar foram as variáveis ajustadas a fim de se estimar o efeito total do excesso de peso pré-gestacional sobre o conteúdo dos ácidos graxos poli-insaturados no leite humano. O conjunto mínimo de variáveis encontrado pelo presente estudo pode ser utilizado na análise de outros estudos que avaliem essa associação.

Abstract A number of studies have focused on the evaluation of the relationship between pre-pregnancy overweight and polyunsaturated fatty acids content in human milk. However, given the complexity of potentially confounding risk factors, the use of graphical tools is recommended to identify possible biases. This article aims to propose a theoretical model of causality using the directed acyclic graph between pre-pregnancy overweight and polyunsaturated fatty acids content in human milk. Methods: An extensive literature review was performed to identify variables with causal relationships with exposure and/or outcome. The choice of variables for adjustment followed the graphic algorithm that comprises six criteria for selecting a minimum set of potentially confounding variables. Socioeconomic conditions, interpartum interval, maternal age and food consumption pattern were the variables that would have to be adjusted in order to estimate the total effect of pre-pregnancy overweight on polyunsaturated fatty acids content in human milk. The minimum set of variables found in the present study can be used in the analysis of other studies that evaluate this association.

Omega-3 fatty acids and atrial fibrillation.

Although some clinical trials have demonstrated reduced incidence of cardiovascular disease with the use of omega-3 fatty acids, others have found an increased risk of atrial fibrillation (AF). AF is the most common sustained cardiac arrhythmia worldwide. It is associated with high morbidity and mortality rates and significant public health burden. Previous studies of the effect of omega-3 fatty acids on AF occurrence have reported contradictory results. Here we reviewed the effect of omega-3 fatty acids on the risk of AF.

Effects of omega-3 supplementation as an adjunct to non-surgical periodontal therapy on periodontal parameters in periodontitis patients: a randomized clinical trial.

OBJECTIVES: This study aimed to assess the effects of omega-3 fatty acid supplementation as an adjunct to non-surgical periodontal therapy in patients with periodontitis. MATERIALS AND METHODS: This randomized clinical trial was conducted on 30 patients with periodontitis. All patients received standard non-surgical periodontal therapy, and were randomly divided into two groups of intervention and control by a table of random numbers (n = 15). The intervention group consumed 1000 mg natural fish oil soft-gels daily (300 mg Omega-3 marine triglycerides, 180 mg Eicosapentaenoic acid and 120 mg Docosahexaenoic acid) while the control group used soft-gels contained only some soybean oil for 3 months. Clinical attachment loss (CAL), probing depth (PD), and bleeding index (BI) were recorded at baseline (before the intervention) and after 3 months. The two groups were compared regarding the clinical parameters by t-test (alpha = 0.05). RESULTS: All three clinical parameters decreased in both groups at 3 months compared with baseline (P = 0.001). The improvement in PD and CAL in the intervention group was significantly greater than that in the control group (P = 0.001); however, the difference in BI was not significant between the two groups (P = 0.283). CONCLUSION: Omega-3 supplementation as an adjunct to non-surgical periodontal therapy significantly improved the clinical parameters in periodontitis patients compared to soybean oil supplements.

Determination of n-3 index and arachidonic acid/eicosapentaenoic acid ratio in dried blood spot by gas chromatography.

Background: Clinical and epidemiological studies suggest that analysis of the polyunsaturated fatty acids (PUFAs) is essential to evaluate nutritional requirements and disease risk. We describe a simple, sensitive and non-invasive method for estimating the n-3 index and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in dried blood spots (DBSs). Experimental: After obtaining DBSs on a spot card, PUFAs were transesterified (direct, acidic transesterification) and subsequently extracted with n-hexane. Gas chromatography with flame ionization detection (GC-FID) was used to analyze the extracted PUFAs, and then n-3 index and AA/EPA ratio were calculated. Method validation showed satisfactory precision and linearity. Conclusion: This analysis is simple and reliable to estimate PUFA status, and it was successfully applied to samples from 20 subjects, demonstrating its applicability.

Urinary phthalate metabolite mixtures in pregnancy and fetal growth: Findings from the infant development and the environment study.

BACKGROUND: Prenatal phthalate exposure has been linked to reductions in fetal growth in animal and laboratory studies, but epidemiologic evidence is equivocal. OBJECTIVE: Examine the association between prenatal phthalate metabolite mixtures and fetal growth and evaluate whether that association is modified by fetal sex or omega-3 intake during pregnancy. METHODS: Analyses included 604 singleton pregnancies from TIDES, a prospective pregnancy cohort with spot urine samples and questionnaires collected in each trimester. Pregnancy-averaged phthalate exposure estimates were calculated as the geometric means of specific-gravity corrected phthalate metabolites. Fetal growth outcomes included birthweight and length, and ultrasound-derived size and velocity of estimated fetal weight, femur length, abdominal and head circumferences in the second and third trimesters. We used a novel application of quantile g-computation to estimate the joint association between pregnancy-averaged phthalate exposure and fetal growth, and to examine effect modification of that association by infant sex or omega-3 intake during pregnancy. RESULTS: There were few statistically significant differences in birth size and fetal growth by exposure. A one-quartile increase in the phthalate mixture was modestly associated with reduced birthweight(ß [95% confidence interval)]: -54.6 [-128.9, 19.7] grams; p = 0.15) and length (-0.2 [-0.6, 0.2] centimeters; p = 0.40). A one-quartile increase in the phthalate mixture was associated with reduced birth length in males (-0.5 [-1.0, 0.0] centimeters) but not for females (0.1 [-0.2, 0.3] centimeters); interaction p = 0.05. The phthalate metabolite mixture was inversely associated with ultrasound-derived fetal growth among those with adequate omega-3 intake. For example, a one-quartile increase in the phthalate mixture was associated with reduced abdominal circumference in the third trimesters in those with adequate omega-3 intake (-3.3 [-6.8, 0.1] millimeters) but not those with inadequate omega-3 intake (1.8 [-0.8, 4.5] millimeters); interaction p = 0.01. CONCLUSION: Prenatal phthalate exposure was not significantly associated with fetal growth outcomes, with some exceptions for certain subgroups.

Content of Docosahexaenoic Acid in Pectoral Muscles of Birds Correlates with Wing Beat Frequency.

Docosahexaenoic acid (22:6n-3, DHA) is a structural component of cell membranes and due to a peculiar form of its molecule exerts a high lateral pressure in the membranes enhancing activity of membrane-associated enzymes. A high content of DHA probably provides a high frequency of contraction and a continuous working of skeletal muscles. To estimate the probable physiological and biochemical role of DHA in muscle tissue, a relation of its contents in pectoral muscles of birds with wing beat frequency was evaluated. A high statistically significant correlation between the content of DHA in pectoral muscles of birds and species-specific wing beat frequency was found.

Effect of long-term intake of ω-3 polyunsaturated fatty acids on activation of hippocampal microglia in a mouse model of POCD / 中华麻醉学杂志

Objective:To evaluate the effect of long-term intake of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on the activation of hippocampal microglia in a mouse model of postoperative cognitive dysfunction (POCD).Methods:Ninety-six clean-grade healthy male C57BL/6 mice, aged 8 weeks, weighing 18-24 g, were stratified according to body weight and divided into 4 groups ( n=24 each) by a random number table method: control diet group (group C), ω-3 PUFAs group (group ω), control diet plus POCD group (group C+ P) and ω-3 PUFAs plus POCD group (group ω+ P). Mice were fed a special ω-3 PUFAs diet (DHA 0.14 g/100 g, EPA 0.03 g/100 g) for 12 weeks in group ω and group ω+ P, while mice were fed with a control diet for 12 weeks in group C and group C+ P.Tibial fracture procedures were performed under isoflurane anesthesia to develop the POCD model after 12 weeks of feeding.The fear conditioning test and Y maze test were performed on 1st and 3rd days after developing the model.The mice were sacrificed after behavioral tests, and the hippocampal tissues were removed for determination of the contents of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (by gas chromatography-mass spectroscopy), density of Iba-1 positive microglia (by immunofluorescence staining), and expression of mature brain-derived neurotrophic factor (mBDNF) and precursor brain-derived neurotrophic factor (pro-BDNF) (by Western blot), and contents of interleukin-1beta (IL-1β) and interleukin-6 (IL-6) (by enzyme-linked immunosorbent assay). Results:Compared with group C, the contents of DHA and EPA were significantly increased, the percentage of freezing time in the contextual test was increased, mBDNF/pro-BDNF ratio was increased ( P<0.05), no significant change was found in the rotation accuracy in Y maze test, density of Iba-1 positive microglia and contents of IL-1β and IL-6 in hippocampus ( P>0.05) in group ω ( P<0.05), and no significant change was found in the contents of DHA and EPA ( P>0.05), the percentage of freezing time in the contextual test and accuracy of rotation in Y maze test were decreased on 1st and 3rd days after operation, the density of Iba-1 positive microglia and contents of IL-1β and IL-6 were increased, and mBDNF/pro-BDNF ratio was decreased in group C+ P ( P<0.05). Compared with group C+ P, the contents of DHA and EPA were significantly increased, the percentage of freezing time in the contextual test and accuracy of rotation in Y maze test were increased on 1st and 3rd days after operation, the density of Iba-1 positive microglia and contents of IL-1β and IL-6 were decreased, and mBDNF/pro-BDNF ratio was increased in group ω+ P ( P<0.05). Conclusions:Long-term intake of ω-3 PUFAs can improve cognitive function in a mouse model of POCD, and the mechanism may be related to inhibition of activation of hippocampal microglia, reduction of inflammatory responses, and thus increasing the mBDNF/Pro-BDNF ratio.

Efectos de Omega-3 en el Sueño: Revisión Sistemática / Effects of Omega 3 on Sleep: Systematic Review

RESUMEN: Objetivo: Determinar el efecto de omega-3 sobre la calidad/cantidad de sueño en humanos. Métodos: Se realizó la búsqueda sistemática de artículos (2010-2019), incluyendo pacientes sin limitación de edad/sexo, sometidos a cambio o suplemento de dieta con omega-3 y evaluaciones de sueño. La revisión se realizó bajo los criterios PICOT y PRISMA, la calidad de la evidencia y riego de sesgo fueron evaluados con criterios GRADE. Resultados: Seis ensayos superaron todos los filtros, dos estudios incluyeron pescado en la dieta y cuatro ingesta de cápsulas de omega-3. En cuatro estudios Omega-3 favorece el sueño presentando impacto moderadamente positivo en calidad y alto en cantidad. Los estudios fueron efectuados con variables de alta heterogeneidad, imposibilitando el análisis cuantitativo de los datos. El riesgo de sesgo fue moderado-alto. Conclusión: Omega-3, como suplemento dietético o directamente en los alimentos, interviene como coadyuvante para mejorar el sueño. No se pudo concluir sobre su recomendación de uso clínico en la gestión del sueño debido a la heterogeneidad de las metodologías para medir la intervención, las poblaciones estudiadas y cantidad de ingesta. Se necesitan estudios con mayor estandarización metodológica, para determinar dosis óptima, período de intervención y proporción de ácidos eicosapentaenoico/docosahexaenoico, necesarios para mejorar la calidad y la cantidad del sueño.

ABSTRACT: Objective: To determine the effect of omega-3 on the quality/quantity of sleep in humans. Methods: We conducted a systematic search for articles (2010-2019), including patients without age or sex limitation, undergoing omega-3 diet change or supplementation and sleep assessments. The review was conducted under the PICOT and PRISMA criteria, the quality of evidence and risk of bias were evaluated with GRADE criteria. Results: Six trials passed all filters. Two studies included dietary fish and four omega-3 capsule intake. In four studies, omega-3 favored sleep with moderately positive impact on quality and high impact on quantity. The studies were conducted with highly heterogeneous variables, making a quantitative analysis of the data impossible. The risk of bias was moderate to high. Conclusion: Omega-3 as a dietary supplement or directly in food intervenes as an adjuvant to improve sleep. We could not conclude on its recommendation for clinical use in sleep management due to the heterogeneity of the methodologies to measure the intervention, the populations studied and amount of intake. Studies with greater methodological standardization are needed, to determine optimal dose, intervention period and eicosapentaenoic/docosahexaenoic acid ratio, needed to improve sleep quality and quantity.

Effect of Long-Term Marine É·-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine É·-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose-related. METHODS: The MEDLINE and Embase databases were searched for articles and abstracts published between January 1, 2012, and December 31, 2020, in addition to a meta-analysis of large cardiovascular RCTs published in 2019. RCTs of cardiovascular outcomes of marine É·-3 fatty acids that reported results for AF, either as a prespecified outcome, an adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median follow-up of at least 1 year were included. RCTs specifically examining shorter-term effects of É·-3 fatty acids on recurrent AF in patients with established AF or postoperative AF were not included. The hazard ratio (HR) for the reported AF outcomes within each trial was meta-analyzed using random effects model with Knapp-Hartung adjustment and evaluated a dose-response relationship with a meta-regression model. RESULTS: Of 4049 screened records, 7 studies were included in the meta-analysis. Of those, 5 were already detected in a previous meta-analysis of cardiovascular RCTs. Among the 81 210 patients from 7 trials, 58 939 (72.6%) were enrolled in trials testing ≤1 g/d and 22 271 (27.4%) in trials testing >1 g/d of É·-3 fatty acids. The mean age was 65 years, and 31 842 (39%) were female. The weighted average follow-up was 4.9 years. In meta-analysis, the use of marine É·-3 fatty acid supplements was associated with an increased risk of AF (n=2905; HR, 1.25 [95% CI, 1.07-1.46]; P=0.013). In analyses stratified by dose, the HR was greater in the trials testing >1 g/d (HR, 1.49 [95% CI, 1.04-2.15]; P=0.042) compared with those testing ≤1 g/d (HR, 1.12 [95% CI, 1.03-1.22]; P=0.024; P for interaction <0.001). In meta-regression, the HR for AF increased per 1 g higher dosage of É·-3 fatty acids dosage (HR, 1.11 [95% CI, 1.06-1.15]; P=0.001). CONCLUSIONS: In RCTs examining cardiovascular outcomes, marine É·-3 supplementation was associated with an increased risk of AF. The risk appeared to be greater in trials testing >1 g/d.

Benefits of Icosapent Ethyl Across the Range of Kidney Function in Patients With Established Cardiovascular Disease or Diabetes: REDUCE-IT RENAL.

BACKGROUND: Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function. METHODS: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was a multicenter, double-blind, placebo-controlled trial that randomly assigned statin-treated patients with elevated triglycerides (135-499 mg/dL) who had CVD or diabetes and 1 additional risk factor to treatment with icosapent ethyl (4 g daily) or placebo. Patients from REDUCE-IT were categorized by prespecified estimated glomerular filtration rate (eGFR) categories to analyze the effect of icosapent ethyl on the primary end point (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina) and key secondary end point (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). RESULTS: Among the 8179 REDUCE-IT patients, median baseline eGFR was 75 mL·min-1·1.73 m-2 (range, 17-123 mL·min-1·1.73 m-2). There were no meaningful changes in median eGFR for icosapent ethyl versus placebo across study visits. Treatment with icosapent ethyl led to consistent reduction in both the primary and key secondary composite end points across baseline eGFR categories. Patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the largest absolute and similar relative risk reduction for the primary composite end point (icosapent ethyl versus placebo, 21.8% versus 28.9%; hazard ratio [HR], 0.71 [95% CI, 0.59-0.85]; P=0.0002) and key secondary composite end point (16.8% versus 22.5%; HR 0.71 [95% CI, 0.57-0.88]; P=0.001). The numeric reduction in cardiovascular death was greatest in the eGFR <60 mL·min-1·1.73 m-2 group (icosapent ethyl: 7.6%; placebo: 10.6%; HR, 0.70 [95% CI, 0.51-0.95]; P=0.02). Although patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the highest numeric rates of atrial fibrillation/flutter (icosapent ethyl: 4.2%; placebo 3.0%; HR 1.42 [95% CI, 0.86-2.32]; P=0.17) and serious bleeding (icosapent ethyl: 5.4%; placebo 3.6%; HR, 1.40 [95% CI, 0.90-2.18]; P=0.13), HRs for atrial fibrillation/flutter and serious bleeding were similar across eGFR categories (P-interaction for atrial fibrillation/flutter=0.92; P-interaction for serious bleeding=0.76). CONCLUSIONS: In REDUCE-IT, icosapent ethyl reduced fatal and nonfatal ischemic events across the broad range of baseline eGFR categories. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG.

BACKGROUND: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. METHODS: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. RESULTS: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63-0.92]; P=0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56-0.87]; P=0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50-0.81]; P=0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%-10.2%) in first events, with a number needed to treat of 16 (95% CI, 10-44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P=0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. CONCLUSIONS: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Maternal Intake of Flaxseed During Lactation and Exercise Training Protect Against Salt Overload-Induced Aortic Remodeling in Adult Offspring

Abstract Background High dietary sodium intake can induce endothelial stiffness even without changes in blood pressure. Objectives To evaluate the effects of exercise training and chronic intake of sodium chloride solution on aortic morphology of male offspring of rat dams who consumed flaxseed during lactation. Methods Female rats were fed with a control diet or a flaxseed diet during lactation. At weaning, two male offspring of each rat dam were allocated into eight groups for 180 days: four groups received a control diet e four received a flaxseed diet, with /without exercise and with/without NaCl solution supply. Aorta was collected for histomorphometric analysis. The one-way analysis of variance was used and P value < 0.05 was considered statistically significant. Results The chronic use of 1% NaCl solution led to changes in aortic histoarchitecture in the control group: increase in aortic intima-media thickness (10,4%, p<0.0001) and reduced number of elastic lamellae (-8,1%, p<0.0001). Groups of offspring of mother that consumed flaxseed during lactation, the chronic use of 1% NaCl alone did not lead to an increase in the aortic intima-media thickness. Exercise training of adult offspring increased aortic intima-media thickness (13.3%, p<0.0001), with preservation of elastic components and aortic flexibility. Conclusion Chronic salt overload caused adverse effects on the aorta of rats, and maternal consumption of the flaxseed diet during lactation protected against aortic remodeling. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials.

BACKGROUND: There is strong public belief that polyunsaturated fats protect against and ameliorate depression and anxiety. AIMS: To assess effects of increasing omega-3, omega-6 or total polyunsaturated fat on prevention and treatment of depression and anxiety symptoms. METHOD: We searched widely (Central, Medline and EMBASE to April 2017, trial registers to September 2016, ongoing trials updated to August 2019), including trials of adults with or without depression or anxiety, randomised to increased omega-3, omega-6 or total polyunsaturated fat for ≥24 weeks, excluding multifactorial interventions. Inclusion, data extraction and risk of bias were assessed independently in duplicate, and authors contacted for further data. We used random-effects meta-analysis, sensitivity analyses, subgrouping and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment. RESULTS: We included 31 trials assessing effects of long-chain omega-3 (n = 41 470), one of alpha-linolenic acid (n = 4837), one of total polyunsaturated fat (n = 4997) and none of omega-6. Meta-analysis suggested that increasing long-chain omega-3 probably has little or no effect on risk of depression symptoms (risk ratio 1.01, 95% CI 0.92-1.10, I2 = 0%, median dose 0.95 g/d, duration 12 months) or anxiety symptoms (standardised mean difference 0.15, 95% CI 0.05-0.26, I2 = 0%, median dose 1.1 g/d, duration 6 months; both moderate-quality evidence). Evidence of effects on depression severity and remission in existing depression were unclear (very-low-quality evidence). Results did not differ by risk of bias, omega-3 dose, duration or nutrients replaced. Increasing alpha-linolenic acid by 2 g/d may increase risk of depression symptoms very slightly over 40 months (number needed to harm, 1000). CONCLUSIONS: Long-chain omega-3 supplementation probably has little or no effect in preventing depression or anxiety symptoms. DECLARATION OF INTEREST: L.H. and A.A. were funded to attend the World Health Organization Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health meetings and present review results. The authors report no other conflicts of interest.

Effects of n-3 Fatty Acid Supplements in Elderly Patients After Myocardial Infarction: A Randomized, Controlled Trial.

BACKGROUND: High intake of marine n-3 polyunsaturated fatty acids (PUFA) has been associated with reduced risk of cardiovascular events; however, this has not been confirmed in patients with a recent acute myocardial infarction (AMI). Elderly patients are at particularly increased cardiovascular risk after myocardial infarction, but few trials address this group specifically. Omega-3 fatty acids hold the potential to reduce cardiovascular events with limited adverse effects in this vulnerable group. The hypothesis was that daily addition of 1.8g n-3 PUFA to standard of care secondary prophylaxis in elderly patients who have survived an AMI would reduce the risk of subsequent cardiovascular events during 2 years follow-up. METHODS: The OMEMI trial (Omega-3 Fatty acids in Elderly with Myocardial Infarction) is an investigator-initiated, multicenter, randomized clinical trial adding 1.8 g n-3 PUFA (930 mg eicosapentaenoic acid and 660 mg docosohexaenoic acid) versus placebo (corn oil) daily to standard of care in patients aged 70 to 82 years with recent (2-8 weeks) AMI. The primary endpoint was a composite of nonfatal AMI, unscheduled revascularization, stroke, all-cause death, heart failure hospitalization after 2 years. The secondary outcome was new atrial fibrillation. The safety outcome was major bleeding. Serum fatty acids were measured as biomarkers of adherence. RESULTS: In total, 1027 patients were randomized. Follow-up data were available for 1014 patients who were included in the intention-to-treat analysis. Mean±SD age was 75±3.6 years, 294 (29%) were female, and mean triglycerides were 111.4±61.9 mg/dL. The primary endpoint occurred in 108 (21.4%) patients on n-3 PUFA versus 102 (20.0%) on placebo (hazard ratio, 1.08 [95% CI, 0.82-1.41]; P=0.60). The secondary endpoint occurred in 28 (7.2%) patients on n-3 PUFA versus 15 (4.0%) on placebo (1.84 [0.98-3.45]; P=0.06). Median changes in eicosapentaenoic acid and docosahexaenoic acid were +87% and +16% for n-3 PUFA versus -13% and -8% for placebo. Major bleeding occurred in 54 (10.7%) and 56 (11.0%) in the n-3 PUFA and placebo groups, respectively (P=0.87). Similar results were found in per-protocol analysis (n=893). CONCLUSIONS: We could not detect reduction in clinical events in our elderly patients with recent AMI who were treated with 1.8 g n-3 PUFAs daily for 2 years. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01841944.

Long-term effects of increasing omega-3, omega-6 and total polyunsaturated fats on inflammatory bowel disease and markers of inflammation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Effects of long-chain omega-3 (LCn3) and omega-6 fatty acids on prevention and treatment of inflammatory bowel diseases (IBD, including Crohn's Disease, CD and ulcerative colitis, UC), and inflammation are unclear. We systematically reviewed long-term effects of omega-3, omega-6 and total polyunsaturated fats (PUFA) on IBD diagnosis, relapse, severity, pharmacotherapy, quality of life and key inflammatory markers. METHODS: We searched Medline, Embase, Cochrane CENTRAL, and trials registries, including RCTs in adults with or without IBD comparing higher with lower omega-3, omega-6 and/or total PUFA intake for ≥ 24 weeks that assessed IBD-specific outcomes or inflammatory biomarkers. RESULTS: We included 83 RCTs (41,751 participants), of which 13 recruited participants with IBD. Increasing LCn3 may reduce risk of IBD relapse (RR 0.85, 95% CI 0.72-1.01) and IBD worsening (RR 0.85, 95% CI 0.71-1.03), and reduce erythrocyte sedimentation rate (ESR, SMD - 0.23, 95% CI - 0.44 to - 0.01), but may increase IBD diagnosis risk (RR 1.10, 95% CI 0.63-1.92), and faecal calprotectin, a specific inflammatory marker for IBD (MD 16.1 µg/g, 95% CI - 37.6 to 69.8, all low-quality evidence). Outcomes for alpha-linolenic acid, omega-6 and total PUFA were sparse, but suggested little or no effect where data were available. CONCLUSION: This is the most comprehensive meta-analysis of RCTs investigating long-term effects of omega-3, omega-6 and total PUFA on IBD and inflammatory markers. Our findings suggest that supplementation with PUFAs has little or no effect on prevention or treatment of IBD and provides little support for modification of long-term inflammatory status.