Omega-3 supplementation reduces aggressive behavior: A meta-analytic review of randomized controlled trials

Relation Between Red Blood Cell Omega-3 Fatty Acid Index and Bleeding During Acute Myocardial Infarction

Omega-3 supplement use, fish intake, and risk of non-fatal coronary artery disease and ischemic stroke in the Million Veteran Program

Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions, including diet and exercise, to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively normal older adults (n = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed that self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.

Is self-reported use of omega-3 fatty acid supplements associated with fecundability, the probability of natural conception, in a given menstrual cycle? Prospectively recorded omega-3 supplement use was associated with an increased probability of conceiving. In infertile women, omega-3 fatty acid intake has been associated with increased probability of pregnancy following IVF. In natural fertility, studies are conflicting, and no study of natural fertility has evaluated omega-3 fatty acid supplementation and fecundity. Secondary data analysis of 900 women contributing 2510 cycles in Time to Conceive (TTC), a prospective, time to pregnancy cohort study from 2008 to December 2015. Women aged 30-44 years, trying to conceive <3 months, without history of infertility were followed using standardized pregnancy testing. While attempting to conceive, women daily recorded menstrual cycle events and supplement and medication intake using the Cerner Multum Drug Database. Supplements and vitamins containing omega-3 were identified. Omega-3 use, defined as use in at least 20% of days in a given menstrual cycle, in each pregnancy attempt cycle was determined. A discrete-time Cox proportional hazards model was used to calculate the fecundability ratio. Women taking omega-3 supplementation were more likely to be younger, thinner, nulligravid, white and to take vitamin D, prenatal and multivitamins compared to women not taking omega-3s. After adjusting for age, obesity, race, previous pregnancy, vitamin D and prenatal and multivitamin use, women taking omega-3 supplements had 1.51 (95% CI 1.12, 2.04) times the probability of conceiving compared to women not taking omega-3s. Our study was not a randomized controlled trial. The women who used omega-3 supplements may represent a more health-conscious population. We sought to address this by adjusting for multiple factors in our model. Additionally, the omega-3 fatty acid supplements that TTC participants used included multiple types and brands with varying dosages of omega-3 fatty acids. Women reported the type of supplement they were taking but not the concentration of omega-3s in that supplement. It is therefore not possible to compare dosing or a dose-response relationship in our study. Omega-3 supplementation may present a feasible and inexpensive modifiable factor to improve fertility. Randomized controlled trials are needed to further investigate the benefits of omega-3 supplementation for women trying to conceive naturally. This study was supported by the Division of Reproductive Endocrinology and Infertility at the University of North Carolina at Chapel Hill, the NIH/NICHD (R21 HD060229-01 and R01 HD067683-01), and in part by the Intramural Research Program of the National Institute of Environmental Health Sciences (Z01ES103333). The authors declare that there is no conflict of interest. N/A.

Objective: The aim of this study was to provide evidence-based recommendations for omega-3 supplementation during pregnancy through a systematic review of level-1 data published on this topic. Methods: We reviewed all randomized-controlled trials (RCTs) including women who were randomized to treatment with either omega-3 supplementation or control (placebo or no treatment) during pregnancy and analyzed all the outcomes reported in the trials, separately. We planned to evaluate the effect of omega-3 on: preterm birth (PTB); pre-eclampsia (PE) and intrauterine growth restriction (IUGR); gestational diabetes; perinatal mortality; small for gestational age (SGA) and birth weight; infant eye and brain development; and postpartum depression. Results: We identified 34 RCTs including 14 106 singletons and 2578 twins. These level-1 data showed that omega-3 was not associated with prevention of PTB, PE, IUGR, gestational diabetes, SGA, post-partum depression or better children development. Data about birth weight, perinatal mortality and childhood cognitive outcome were limited. Women with gestational diabetes who received omega-3 had significantly lower serum C-reactive protein concentrations, low incidence of hyperbilirubinemia in newborns and decreased newborns’ hospitalization rate. Conclusions: There was not enough evidence to support the routine use of omega-3 supplementation during pregnancy. Given the 73% significant decrease in perinatal death in the singleton gestations who started omega-3 supplementation ≤ 20 weeks, further research is needed. Large RCTs in multiple gestations and longer follow-up are also required.

Marine omega-3 fatty acid (omega-3) supplements have been used to treat depression but their ability to prevent depression in the general adult population is unknown. To test effects of omega-3 supplementation on late-life depression risk and mood scores. A total of 18 353 adults participated in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized trial of cardiovascular disease and cancer prevention among 25 871 US adults. There were 16 657 at risk of incident depression (no previous depression) and 1696 at risk of recurrent depression (previous depression, but not for the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017. Randomized 2 × 2 factorial assignment to vitamin D3 (2000 IU/d), marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid and 375 mg of docosahexaenoic acid) or placebo; 9171 were randomized to omega-3 and 9182 were randomized to matching placebo. Prespecified coprimary outcomes were risk of depression or clinically relevant depressive symptoms (total of incident + recurrent cases); mean difference in mood score (8-item Patient Health Questionnaire [PHQ-8] depression scale). Among 18 353 participants who were randomized (mean age, 67.5 [SD, 7.1] years; 49.2% women), 90.3% completed the trial (93.5% among those alive at the end of the trial); the median treatment duration was 5.3 years. The test for interaction between the omega-3 and the vitamin D agents was not significant (P for interaction = .14). Depression risk was significantly higher comparing omega-3 (651 events, 13.9 per 1000 person-years) with placebo (583 events, 12.3 per 1000 person-years; hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P = .03). No significant differences were observed comparing omega-3 with placebo groups in longitudinal mood scores: the mean difference in change in PHQ-8 score was 0.03 points (95% CI, -0.01 to 0.07; P = .19). Regarding serious and common adverse events, the respective prevalence values in omega-3 vs placebo groups were major cardiovascular events (2.7% vs 2.9%), all-cause mortality (3.3% vs 3.1%), suicide (0.02% vs 0.01%), gastrointestinal bleeding (2.6% vs 2.7%), easy bruising (24.8% vs 25.1%), and stomach upset or pain (35.2% vs 35.1%). Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with omega-3 supplements compared with placebo yielded mixed results, with a small but statistically significant increase in risk of depression or clinically relevant depressive symptoms but no difference in mood scores, over a median follow-up of 5.3 years. These findings do not support the use of omega-3 supplements in adults to prevent depression. ClinicalTrials.gov Identifiers: NCT01696435 and NCT01169259.

To assess whether omega-3 fatty acid (FA) supplementation is more efficacious than placebo in amelioration of signs and symptoms of dry eye disease. We performed a systematic literature search in PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. We included randomized clinical trials comparing omega-3 FA supplementation with placebo in patients with dry eye disease. The outcome measures were dry eye symptoms, breakup time (BUT), Schirmer test, and corneal fluorescein staining. The pooled effect sizes were estimated using a random-effects model. Heterogeneity was evaluated using the Q and I tests. Sensitivity analysis and assessment of publication bias were performed. Meta-regression was performed to evaluate the source of heterogeneity. Seventeen randomized clinical trials involving 3363 patients were included. Compared with placebo, omega-3 FA supplementation decreased dry eye symptoms [standardized difference in mean values (SDM) = 0.968; 95% confidence interval (CI) 0.554-1.383; P < 0.001] and corneal fluorescein staining (SDM = 0.517; 95% CI, 0.043-0.991; P = 0.032), whereas it increased the BUT (SDM = 0.905; 95% CI, 0.564-1.246; P < 0.001) and Schirmer test values (SDM = 0.905; 95% CI, 0.564-1.246; P < 0.001). No evidence of publication bias was observed, and sensitivity analyses indicated the robustness of results obtained. Meta-regression analysis showed a higher improvement of dry eye symptoms and BUT in studies conducted in India. This meta-analysis provides evidence that omega-3 FA supplementation significantly improves dry eye symptoms and signs in patients with dry eye disease. Therefore, our findings indicate that omega-3 FA supplementation may be an effective treatment for dry eye disease.

BackgroundOmega-3 fatty acids reportedly improve child learning and behavioral outcomes. However, sociodemographic factors and parental perceptions driving omega-3 supplementation in children are not fully understood. MethodsIn a cross-sectional study design, we examined factors associated with use of a commercial omega-3 supplement for children (1–18 years) among 280 Thai, Chinese and Vietnamese parents. ResultsAfter adjustment for demographic and lifestyle factors, multivariable logistic regression showed that omega-3 supplement use was higher in children with greater quality of life [OR, 4.81 (95% CI: 1.64, 14.10)] and whose parents had more advanced education [OR, 2.29 (95% CI: 1.02, 5.15)]. Parents who viewed the omega-3 supplement as proven by research [OR, 5.01 (95% CI: 1.83, 13.74)], safe [OR, 7.44 (95% CI: 2.66, 20.80)] and natural [OR, 2.47 (95% CI: 1.09, 5.60)] were more likely to use the product for their child, as were those who reported positive social feedback regarding the product [OR, 2.44 (95% CI: 1.33, 4.48)]. ConclusionOmega-3 supplement use among children residing in Asia was associated with better socio-demographic and lifestyle characteristics. Parental views concerning the safety and efficacy of the omega-3 product were major predictors of supplementation practices.

BackgroundMany commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been controversial in this regard. In this systematic review, we assessed the effect of these medications as adjunctive therapy in COVID-19 by the inclusion of randomized controlled trials (RCTs).MethodsWe searched four international databases including PubMed, the Web of Science, Scopus, and Embase for RCTs in April 2023. The primary outcome was mortality, while other efficacy indices were considered secondary outcomes. In order to estimate the pooled effect size of the outcomes, considering the odds ratio (OR) or standardized mean difference (SMD) and 95% confidence interval (CI), random-effect meta-analyses was conducted.ResultsTen studies involving 2,167 COVID-19 patients using statins, omega-3 fatty acids, fenofibrate, PCSK9 inhibitors, and nicotinamide as intervention compared to control or placebo, were included. No significant difference was found in terms of mortality (OR 0.96, 95% CI 0.58 to 1.59, p-value = 0.86, I2 = 20.4%) or length of hospital stay (SMD -0.10, 95% CI -0.78 to 0.59, p-value = 0.78, I2 = 92.4%) by adding a statin to the standard of care. The trend was similar for fenofibrate and nicotinamide. PCSK9 inhibition, however, led to decreased mortality and an overall better prognosis. Omega-3 supplementation showed contradicting results in two trials, suggesting the need for further evaluation.ConclusionAlthough some observational studies found improved outcomes in patients using lipid-lowering agents, our study found no benefit in adding statins, fenofibrate, or nicotinamide to COVID-19 treatment. On the other hand, PCSK9 inhibitors can be a good candidate for further assessment. Finally, there are major limitations in the use of omega-3 supplements in treating COVID-19 and more trials are warranted to evaluate this efficacy.

Multiple sclerosis (MS), a neuroinflammatory disorder, occurs as non-progressive or progressive phenotypes; both forms present with diverse symptoms that may reduce quality of life (QoL). Adherence to healthy lifestyle behaviors has been associated with higher QoL in people with MS; whether these associations differ based on MS phenotype is unknown. Cross-sectional self-reported observational data from 1108 iConquerMS participants were analysed. Associations between lifestyle behaviors and QoL were assessed by linear regression, and phenotype differences via moderation analyses. Diet, wellness, and physical activity, but not vitamin D or omega-3 supplement use, were associated with QoL. Specifically, certain diet types were negatively associated with QoL in relapsing-remitting MS (RRMS), and positively associated in progressive MS (ProgMS). Participation in wellness activities had mixed associations with QoL in RRMS but was not associated in ProgMS. Physical activity was positively associated with QoL in RRMS and ProgMS. Phenotype differences were observed in diet and wellness with physical QoL, and physical activity with most QoL subdomains. Our findings show lifestyle behaviors are associated with QoL and appear to differ based on MS phenotype. Future studies assessing timing, duration, and adherence of adopting lifestyle behaviors may better inform their role in MS management.

Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population. To investigate whether omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis. Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n-3 PUFA levels predicted change in cognitive performance. The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months. We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n-3 PUFAs.

The cross-sectional relationship among omega-3 fatty acid levels, cardiorespiratory fitness, and depressive symptoms from the Cooper Center Longitudinal Study

Omega-3 supplements may be efficacious in reducing symptoms of depression and anxiety in adults, particularly as an adjunct to antidepressant medication. However, research in young people is limited. Thus, this scoping review aimed to summarise existing evidence on the efficacy of omega-3 supplementation in treating depression and anxiety symptoms in young people aged 14-24. A secondary aim was to determine whether grey literature intended for the general public accurately reflects the evidence. Four databases (Cochrane CENTRAL, EmBASE, PsycINFO, PubMed) were searched from inception to 4th August 2021. Eligible peer-reviewed studies were empirical studies which examined the efficacy of omega-3 supplements in preventing/treating anxiety and/or depression symptoms in young people aged 14-24. Risk of bias was assessed for randomised studies using the Cochrane Risk of Bias Tool. Selected grey literature databases were also searched, with eligible sources assessed for quality. A stakeholder group including young people with lived experience of anxiety/depression, parents/carers and mental health professionals informed the research questions and data interpretation. Findings were summarised using narrative synthesis. 17 empirical studies (N = 1240 participants) meeting inclusion criteria were identified. Studies varied in treatment and participant characteristics. In general, the data did not support the view that omega-3 supplements were efficacious in improving symptoms of anxiety or depression in young people aged 14-24. In contrast, most grey literature sources recommended the use of omega-3 supplements in young people. Evidence for efficacy of omega-3 supplementation in reducing symptoms of depression and anxiety in young people was inconclusive. More research is needed to identify potential mechanisms and moderators of the effect of omega-3 supplements on depression and anxiety symptoms in young people.

Paola Bozzatello et al. [1] have done a comprehensive qualitative review of the potential use of long-chain polyunsaturated fatty acids in the prevention and treatment of mental disorders.[...].

The role of omega-3 polyunsaturated fatty acid supplementation in the management of type 2 diabetes mellitus: A narrative review