Enhancing brain health through omega fatty acids: Ahiflower oil and oleic acid as novel plant-based nootropic ingredients targeting the microbiome–Gut–Brain Axis

Experimental evidence suggests that dietary intakes of omega-3 and omega-6 polyunsaturated fatty acids have divergent effects on melanoma growth, but epidemiologic evidence on their combined effect is lacking. In 634 Australian patients with primary melanoma, we assessed prediagnosis consumption of 39 food groups by food frequency questionnaires completed within 2 months of diagnosis. We derived, by reduced rank regression, dietary patterns that explained variability in selected omega-3 and omega-6 fatty acid intakes. Prevalence ratios (PR) and 95% confidence intervals (CI) for the association between tertiles of dietary patterns and melanoma thickness >2 mm versus ≤2 mm were estimated using Poisson regression. Overall omega-3 fatty acid intakes were low. Two major fatty acid dietary patterns were identified: "meat, fish, and fat," positively correlated with intakes of all fatty acids; and "fish, low-meat, and low-fat," positively correlated with long-chain omega-3 fatty acid intake, and inversely with medium-chain omega-3 and omega-6 fatty acid intakes. Prevalence of thick melanomas was significantly higher in those in the highest compared with lowest tertile of the "meat, fish, and fat" pattern (PR, 1.40; 95% CI, 1.01-1.94), especially those with serious comorbidity (PR, 1.83; 95% CI, 1.15-2.92) or a family history (PR, 2.32; 95% CI, 1.00-5.35). The "fish, low-meat, and low-fat" pattern was not associated with melanoma thickness. People with high meat, fish, and fat intakes, who thus consumed relatively high levels of omega-3 and high omega-6 fatty acid intakes, are more likely to be diagnosed with thick than thin melanomas. High omega-3 and omega-6 fatty acid intakes may contribute to patients' presentation with thick melanomas.

Review question/objective The quantitative objectives are to identify the association of dietary intake and supplementation of specific polyunsaturated fatty acids (PUFA) with chronic inflammation and functional capacity outcomes in people with chronic obstructive pulmonary disease (COPD). More specifically, the objectives are: 1. To identify the association of low dietary intake of omega-3 fatty acids (docosahexaenoic acid [DHA], eicosapentaenoic acid [EPA] or α-linolenic acid [ALA]) and/or omega-6 (γ-linoleic acid [GLA] and arachidonic acid [AA]) fatty acids with chronic inflammation and functional capacity outcomes in people with COPD compared with controls (high dietary intake reference group). 2. To identify the effectiveness of omega-3 fatty acid supplementation (containing predominantly one or more omega-3 fatty acids) in reducing chronic inflammation and improving functional capacity outcomes compared with placebo/no intervention in people with COPD. Background Chronic obstructive pulmonary disease is currently ranked the fifth leading cause of global disability (health loss).1 The BOLD (Burden of Obstructive Lung Disease) study estimates that the prevalence of COPD, defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as stage 2 or higher, was 7.5% among Australian people aged 40 years or older in 2006-10.2 The prevalence of COPD was highest among people aged 75 years or older.2 A recent report by Access Economics estimates that COPD cost the Australian economy about $98 billion in 2008.3 Since Australia's population is ageing, the projected rise in the health burden of COPD will undoubtedly cause significant stress on the national healthcare system. Effective treatments to slow the progression of COPD and/or prevent exacerbations will likely result in significant health and economic benefits. Chronic obstructive pulmonary disease is characterized by persistent airflow limitation that is usually progressive and associated with chronic inflammation in the airways and lungs from exposure to noxious particles or gases.4 A lifetime of exposure to noxious particles and gases is likely to bring about a chronic (innate and adaptive) inflammatory response in COPD patients that increases production and accumulation of mucus, infiltration of the airway walls by inflammatory cells, as well as thickening of the airway wall and narrowing of the lumen.5 The progression of COPD (i.e. an increase in the severity of airflow limitation by the GOLD grading system) is positively associated with the degree of the inflammatory response,6 and the narrowing and disappearance of the small conducting airways.7 In addition, prospective cohort studies have shown that airway and systemic inflammation, independent of smoking, increases the risk of worsening lung function and exacerbations, which, in turn, are associated with reduced survival.8 Another cohort study observed decreases in airway and systemic inflammation in COPD patients hospitalized for acute exacerbation at the time of discharge (i.e. after treatment and remission of the exacerbation).9 Although there is considerable uncertainty about the origin and role of inflammation in COPD, this body of evidence suggests that new therapies for reducing the chronic inflammatory response may improve COPD prognosis. Low dietary intake of omega-3 fatty acids may be a reversible risk factor for chronic inflammation, and subsequent functional decline, in COPD patients through a variety of mechanisms including cell surface and intracellular receptors that control inflammatory cell signalling and gene expression.10 The major food sources of DHA and EPA omega-3 fatty acids are fish, fish oils and animal tissues (brain), whereas some plant oils contain ALA.11 Omega-6 fatty acids are predominately derived from plant oils, although small amounts of animal tissues contain GLA and AA.11 Omega-3 and omega-6 fatty acids have competitive (inhibiting) interactions that are important in controlling inflammation.12 Epidemiological evidence (cross-sectional and prospective cohort studies) consistently shows an inverse association between dietary intake of omega-3 fatty acids and systemic inflammation across different populations including people with COPD.13-16 Moreover, the most recent systematic review and meta-analysis of relevant randomized controlled trials (RCTs) shows that short-term marine-derived omega-3 supplementation significantly reduces systemic inflammatory biomarkers including C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) in different population groups.17 The effectiveness of omega-3 supplementation for lowering inflammatory markers was most evident in patients with cardiovascular risk factors which are highly prevalent in COPD patients.18 In contrast, two cross-sectional studies on omega-6 fatty acids reported opposing associations between dietary intake of AA and systemic inflammation.16,19 Although the systematic review by Li and colleagues17 is an excellent synthesis of evidence on effectiveness, none of the studies reviewed focussed on COPD patients. Furthermore, the equivocal results reported in one RCT raise questions about whether a reduction in chronic inflammation with PUFA supplementation is actually beneficial in patients with COPD.20 For instance, a cross-sectional study found no protective and several adverse associations between dietary intake of individual omega-3 and omega-6 fatty acids and airflow limitation in a regionally representative sample of Dutch adults.21 To our knowledge, there is no completed or in-progress systematic review of evidence on this topic. We therefore seek to systematically assess relevant studies on the association of dietary intake and supplementation of specific PUFA with inflammatory markers and functional capacity outcomes in COPD to inform guidelines and clinical practice.

Omega-3 fatty acids found in some foods have a wide-range of health benefits. The omega-3 supplementation results in higher antioxidant activity in human seminal fluid and enhanced sperm count, sperm motility, and sperm morphology. Considerable number of infertile men with idiopathic oligoasthenoteratozoospermia might be benefit from omega-3 fatty acids administration. Infertility caused by idiopathic oligoasthenoteratozoospermia(OAT) syndrome without any female factor represents one of the biggest patients group in the daily practice of urologists. Despite great advances in the field of infertility, still many cases of male infertility are diagnosed as idiopathic and remained untreated. In low-income communities where health service resources are restricted and basic health needs are unmet, health resources are not used to provide expensive technologies for the treatment of infertility. Social and family consequences of infertility, especially in developing and under developed communities are devastating. A decrease in male fertility has been occurred over the years.1 Sperm density had fallen by 40% over the past 50 years.2 One of the reasons for the impaired semen parameters over the years is dietary factors.3, 4 The significant effects of dietary fatty acids (FAs) on male fertility have been well documented both in animal and human studies.5, 6 There are three types of natural FAs: saturated, monounsaturated and polyunsaturated. Polyunsaturated fatty acids (PUFAs) are essential FAs, because they cannot be synthesized by the human body. Docosahexanoic acid (DHA), eicosapentanoic acid (EPA) and α-linolenic acid are the main omega-3 PUFAs. Linoleic acid, γ-linolenic acid and arachidonic acid (AA) are the main omega-6 PUFAs. The first mechanism by which omega-3 and omega-6 PUFAs affect spermatogenesis, is by the incorporation into spermatozoa cell membrane. Omega-3 and omega-6 PUFAs are structural components of cell membranes.7 The lipid bilayer of cellular membranes is maintained by the presence of these PUFAs.8 The successful fertilization of spermatozoa depends on the lipids of the spermatozoa membrane.9 Deleterious health effects of increased dietary omega-6/omega-3 ratios have been documented in many studies.10 The ideal ratio is 1:1. During the past 100 years, omega-6 PUFAs of Western diets have increased dramatically. This has resulted in an omega-6/omega-3 ratio of 25:1 to 40:1.11 Increased omega-6/omega-3 ratio in spermatozoa has also been implicated in impaired semen quality in oligozoospermic and/or asthenozoospermic men.12 Spermatozoa from asthenozoospermic and oligozoospermic men exhibit decreased concentrations of DHA compared with those from normozoospermic men. Conquer et al.13 demonstrated that, compared with normozoospermic men, spermatozoa from asthenozoospermic men have diminished concentrations of DHA and higher concentrations of oleic acid. Safarinejad et al.,14 investigated PUFA composition of the blood plasma and spermatozoa in men with idiopathic OAT. They found that, fertile men had higher blood and spermatozoa levels of omega-3 PUFAs compared with the infertile counterparts. Also, the serum omega-6/omega-3 PUFAs ratio was significantly higher in infertile men. These findings have also been replicated in human clinical trials. Attaman et al.15 evaluated the relation between dietary fats and semen quality in 99 men. They concluded that, higher intake of omega-3 PUFAs was positively correlated with sperm morphology. In another randomized clinical trial, 238 infertile men with idiopathic OAT were randomized to EPA and DHA, 1.84 g day−1 or placebo for 32 weeks.16 A significant improvement in total sperm count and sperm cell density was observed in the omega-3 group. The second mechanism by which omega-3 PUFAs improve semen quality, involves anti-oxidant activity. Oxidative stress is one of the main issues associated with male infertility. Reactive oxygen species (ROS) significantly and adversely affect sperm function at high concentrations. Imbalance between antioxidant capacity in seminal plasma and the production of ROS results in oxidative stress. The seminal plasma anti-oxidant capacity plays an important role in sperm function. Balanced seminal plasma antioxidant activity prevents the oxidation of various macromolecules such as DNA, proteins and lipids.7 Omega-3 PUFAs are among important antioxidants. In a study by Safarinejad et al.,14 seminal plasma enzymatic antioxidant levels of catalase, and superoxide dismutase (SOD) were measured. Significantly lower levels of catalase- and SOD-like activities were found in infertile men compared with fertile men. In addition, catalase- and SOD-like activities were significantly positively correlated with sperm density, sperm motility and sperm morphology. The omega-6/omega-3 ratio in spermatozoa cell membrane has outmost importance in maintaining normal sperm integrity and function. Oxidative stress to sperm DNA can result in increased DNA fragmentation. In humans, there is a positive strong correlation between sperm motility and sperm membrane DHA concentrations. Infertile men have higher mean AA/DHA ratio and AA/EPA ratio than fertile men.14 Also, other supplements with anti-oxidant activities such as selenium,17 coenzyme Q10,18 and pentoxifylline19 have demonstrated favorable efficacy in infertile men with idiopathic OAT. Recently supplementation with omega-3 PUFAs has received great attention in the course of psychiatric, neurologic and cardiovascular diseases.20 The incorporation of omega-3 PUFAs, including ALA, EPA and DHA, into the diets has also beneficial effects on fertility. As omega-3 PUFAs have excellent safety profiles, are widely available and cost effective, and have had beneficial effects on spermatogenesis in human studies, they might be considered as nutritional supplementation to improve semen quality. We frequently treat infertile men with idiopathic OAT who were candidate for assisted reproductive techniques (ARTs) using above mentioned supplementations. The cost of ART protocols is high. Selection of infertility treatment often interrelated to different issues such as efficacy, cost, mode of administration and its potential side effects. Legal, cultural, social, economical and religious inquiries have considerably restricted the available choices in some countries. Each community has own concerns. In some communities use of donor sperms or oocytes is not acceptable, and in poor-resource areas ART protocols have not been resulted in improvement of quality of infertility care. The prevalence of infertility is highest in countries that experience the severe conditions of war, poverty, and starvation. In developing and underdeveloped areas, if infertility occurs, it is the female partner who is frustrated, disinherited, and ostracized and suffers from unstable marriages, divorce, polygamy, domestic violence and economic deprivation, and may even endure life-threatening medical intervention. In some communities, female partners are discerned as a source of evil, subjected to physical and psychological violence and are even killed. We urgently need effective, inexpensive, and safe medications for dealing with OAT in idiopathic infertile men.

Fatty acids and bipolar disorder

Pre-pregnancy Dietary Intake of Omega-3 and Omega-6 Fatty Acids and the Risk of Hypertensive Disorders of Pregnancy

Cod liver oil supplements in infancy have been associated with a decreased risk of type 1 diabetes mellitus in a retrospective study. To examine whether intakes of omega-3 and omega-6 fatty acids are associated with the development of islet autoimmunity (IA) in children. A longitudinal, observational study, the Diabetes Autoimmunity Study in the Young (DAISY), conducted in Denver, Colorado, between January 1994 and November 2006, of 1770 children at increased risk for type 1 diabetes, defined as either possession of a high diabetes risk HLA genotype or having a sibling or parent with type 1 diabetes. The mean age at follow-up was 6.2 years. Islet autoimmunity was assessed in association with reported dietary intake of polyunsaturated fatty acids starting at age 1 year. A case-cohort study (N = 244) was also conducted in which risk of IA by polyunsaturated fatty acid content of erythrocyte membranes (as a percentage of total lipids) was examined. Risk of IA, defined as being positive for insulin, glutamic acid decarboxylase, or insulinoma-associated antigen-2 autoantibodies on 2 consecutive visits and still autoantibody positive or having diabetes at last follow-up visit. Fifty-eight children developed IA. Adjusting for HLA genotype, family history of type 1 diabetes, caloric intake, and omega-6 fatty acid intake, omega-3 fatty acid intake was inversely associated with risk of IA (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21-0.96; P = .04). The association was strengthened when the definition of the outcome was limited to those positive for 2 or more autoantibodies (HR, 0.23; 95% CI, 0.09-0.58; P = .002). In the case-cohort study, omega-3 fatty acid content of erythrocyte membranes was also inversely associated with IA risk (HR, 0.63; 95% CI, 0.41-0.96; P = .03). Dietary intake of omega-3 fatty acids is associated with reduced risk of IA in children at increased genetic risk for type 1 diabetes.

Background: Omega-3 fatty acid supplementation has been shown to help maintain muscle function and reduce muscle soreness after exercise-induced muscle damage. However, the relationship between the dietary and biological status of omega-3 fatty acids in rugby players remains unclear. Objectives: This study aimed to investigate the connection between the dietary and biological status of omega-3 fatty acids in university rugby players. Methods: We conducted a cross-sectional study involving university rugby players and age-matched sedentary controls. We assessed diets, including omega-3 and omega-6 polyunsaturated fatty acids, using self-administered dietary questionnaires. Whole blood lipidomics was performed before and after a single training session. Results: The rugby group (n = 29) had significantly higher intakes of omega-3 and omega-6 fatty acids compared to the control group (n = 31). While the blood omega-6 relative concentration did not differ between the groups, the rugby group had lower omega-3 fatty acid levels than the control group (4.4 ± 1.1 vs. 6.2 ± 1.8%). Approximately 48% of rugby players had an omega-3 index (O3i) considered as high risk for cardiovascular disease, and 52% were classified as intermediate risk. None of the players had a low-risk O3i. A single training session had an impact on the omega-3 and omega-6 metabolic pathways. Conclusions: Despite having a higher omega-3 fatty acid intake than controls, rugby football players may still be deficient in omega-3 fatty acids. Further nutritional interventions are needed to address these issues.

There are no well-established modifiable risk factors for pancreatic cancer except smoking. Some dietary factors have been associated with pancreatic cancer risk and require further study. We examined the associations among intake of specific fatty acids and antioxidants and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area. Unconditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CI) as estimates of relative risk. Positive associations were observed for high levels of the 8 individual saturated fatty acids (4th vs. 1st quartile: ORs ranged from 1.6 to 2.6; all p(trend) < 0.01), monounsaturated palmitoleic and oleic fatty acids [OR = 1.6 (95% CI: 1.2-2.1) and 1.4 (95% CI: 1.1-1.9); both p(trend) < 0.01], and polyunsaturated linolenic acid [OR = 1.5 (95% CI: 1.1-2.0); p(trend) = 0.02]. Inverse associations were observed for high levels of gadolic acid [4th vs. 1st quartile: OR = 0.68 (95% CI: 0.50-0.92); p(trend) = 0.007] and omega-3 fatty acids [>or=0.85 g/day vs. 1st quartile: OR = 0.47 (95% CI: 0.25-0.90)]. An inverse association was also observed for high total intake of vitamin C [4th vs. 1st quartile: OR = 0.69 (95% CI: 0.51-0.94); p(trend) = 0.004] and of vitamin E [OR = 0.67 (95% CI: 0.49-0.92); p(trend) = 0.01]. Although similar decreased risks were also observed for high supplemental intake of these 2 vitamins (both p(trend) < 0.01), no association was observed for intake from food alone. These results support the hypotheses that a high intake of saturated and certain monounsaturated fatty acids may increase the risk of pancreatic cancer, whereas greater intake of omega-3 fatty acids, vitamins C and E may reduce the risk.

Increased the consumption of polyunsaturated (PUFA) and omega-3 fatty acid may be one of the strategies to prevent morbidity and mortality among elderly. This study aimed to identify the plasma fatty acid profile and intake among older adults who aged successfully (SA) as compared to the usual agers (UA). This cross-sectional comparative study was conducted among 48 SA (mean age 66.4+4.7 years old) and 42 UA (mean age 68.4+4.8 years old). The plasma fatty acid profile was determined using gas chromatography. Fatty acid intake was measured by using the validated Fatty Acid Omega-3 intake food frequency questionnaire. The percentage of saturated fatty acids (SFA) in blood plasma of UA (men 62.2+6.4%, women 62.9+7.0%) were significantly higher (p<0.05) compared to SA (men 53.7+15.8%, women 57.1+9.5%). On the other hand, the percentage of monounsaturated (MUFA), polyunsaturated (PUFA) omega-3 and omega-6 fatty acids were the opposites. Fatty acids intake among SA was higher compared to UA. SFA (SA=5.0+2.5%, UA=4.6+2.9%) and total omega-3 (SA=0.5+0.4%, UA=0.4+0.3%) intakes met the recommended nutrient intake (RNI). However, mean intakes of MUFA (SA=5.3+2.4%, UA=4.7+2.7%) and linoleic acid (LA) (SA=0.5+0.7%, UA=0.3+0.5%) were below than the RNI. Percentages of subjects who did not meet the RNI for omega-3 and MUFA were 44.2% and 97.7% for SA and 47.4% and 95% for UA, respectively. SA had a higher level of plasma PUFA and MUFA, but lower in SFA when compared to UA. MUFA and LA were more likely to be inadequate in the diet of older adults, particularly the UA.

Association between Ω3 and Ω6 fatty acid intakes and serum inflammatory markers in COPD

Fatty acids, inflammation, and asthma

There is growing evidence that inflammation is an important mediator of pathophysiology in bipolar disorder. The omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acid (PUFA) metabolic pathways participate in several inflammatory processes and have been linked through epidemiologic and clinical studies to bipolar disorder and its response to treatment. We review the data on PUFAs as biomarkers in bipolar disorder and n-3 PUFA used as treatment for bipolar disorder. PubMed and CINAHL were searched for articles on PUFA and bipolar disorder published in the English language through November 6, 2013, with an updated search conducted on August 20, 2015. Keywords searched included omega 3 fatty acids and bipolar disorder, omega 3 fatty acids and bipolar mania, omega 3 fatty acids and bipolar depression, omega 3 fatty acids and mania, omega 3 fatty acids and cyclothymia, omega 3 fatty acids and hypomania, fatty acids and bipolar disorder, essential fatty acids and bipolar disorder, polyunsaturated fatty acids and bipolar disorder, DHA and bipolar disorder, and EPA and bipolar disorder. Studies selected measured PUFAs as biomarkers or introduced n-3 PUFA as treatment. We identified 17 relevant human clinical articles that either compared PUFA levels between a bipolar disorder group and a control group or used a PUFA intervention to treat depression or mania in bipolar disorder. Human studies suggest low n-3 red blood cell PUFA concentrations and correlations with clinical severity in studies of plasma concentrations in symptomatic bipolar disorder. Results of published n-3 PUFA dietary supplementation trials for bipolar disorder indicate efficacy in treatment for mania or depression in 5 of 5 open-label trials, efficacy in treatment of depression in 1 of 7 randomized controlled trials, and a signal for treatment of depression in 1 meta-analysis. Biomarker studies of PUFA and treatment studies of n-3 PUFA in bipolar disorder show promise for indicating a way forward in the study of PUFA in bipolar disorder. Investigation of the intake and metabolism of the n-3 and n-6 PUFA when supplementation is provided in treatment trials might offer clues for identification of when and how PUFA may be important for treatment in bipolar disorder.

To examine whether the intake of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) is associated with periodontal condition. The study population consisted of non-smoking, non-diabetic and non-rheumatoid individuals in the Health 2000 Survey in Finland. Analyses were made in two age groups: 30-49years (n=1212) and 50-79years (n=980). Clinically determined sextants with gingival bleeding and teeth with periodontal pockets were used as outcome variables. Dietary data were collected by a validated food frequency questionnaire. Energy-adjusted intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), omega-3 and omega-6 PUFAs, as well as ratios of EPA/AA and of DHA/AA, and omega-3/omega-6 PUFAs were used as exposures. Prevalence rate ratios were estimated using Poisson regression models. In this population, there were no statistically significant associations between the examined omega-3 or omega-6 fatty acids or their ratios and the periodontal outcome variables. This cross-sectional study provided evidence that individual omega-3 or omega-6 fatty acids, their subclasses or ratios are not associated with periodontal health among a non-diabetic, non-rheumatoid and non-smoking population.

Omega-3 polyunsaturated fatty acids (PUFAs) play important roles in cardiometabolic and mental health, and the dietary omega-6/omega-3 ratio has emerged as a key determinant of inflammatory and psychological outcomes. Despite generally low omega-3 intake in Iran, little is known about how dietary fatty acid patterns relate to mental health in young adults, who may be particularly vulnerable due to nutritional constraints and high rates of depressive symptoms. Moreover, prior studies in Iran have not simultaneously examined omega-3 intake, the omega-6/omega-3 ratio, BMI, and depressive symptoms within the same analytical framework. This cross-sectional study aims to investigate the associations between the intake of omega-6 and omega-3 fatty acids, the omega-6:3 ratio, body mass index, and depressive symptoms in young Iranian adults. Dietary data on omega-3 and omega-6 fatty acids were obtained through semi-quantitative food-frequency questionnaire (FFQ). The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptom. We applied logistic regression to assess the relationships between variables. A total of 440 university students aged 18-30 years were included. After adjustment for age, sex, and total energy intake, higher BMI was associated with greater odds of depressive symptoms (OR: 1.11; 95% CI: 1.04-1.20). Compared with the lowest quintile, participants in the highest quintile of omega-3 intake had lower odds of depressive symptoms (OR: 0.34; 95% CI: 0.17-0.71). In contrast, a higher omega-6/omega-3 ratio was associated with greater odds of depressive symptoms, with nearly tenfold higher odds observed in the highest versus lowest quintile (OR: 9.94; 95% CI: 3.89-25.43). Higher omega-3 intake was associated with lower odds of depressive symptoms, whereas higher BMI and a greater omega-6/omega-3 ratio were associated with higher odds. These findings suggest that dietary fatty-acid balance and body weight may be relevant correlates of mental health in young adults. Prospective and interventional studies are needed to clarify causal relationships.

Background: Uncertainty exists about the link between omega-3 fatty acid, omega-6 fatty acid, and total polyunsaturated fatty acid (PUFA) intake and mortality in atherosclerotic cardiovascular disease (ASCVD) patients, and no meta-analyses summarize the relationship between these various types of PUFAs and ASCVD. Methods: Web of Science, PubMed, EBSCO and Cochrane Library up to November 30, 2022 were searched for prospective randomized controlled studies investigating the relationships among omega-3, omega-6, and PUFA intake and mortality and cardiovascular events in ASCVD patients. This study has been registered at PROSPERO (No. CRD42023407566). Results: This meta-analysis included 21 publications from 17 studies involving 40 861 participants published between 1965 and 2022. In ASCVD patients, omega-3 may lower all-cause mortality (RR: 0.90, 95% CI [0.83, 0.98], I2 = 8%), CVD mortality (RR: 0.82, 95% CI [0.73, 0.91], I2 = 34%) and CVD events (RR: 0.90, 95% CI [0.86, 0.93], I2 = 79%). Subgroup analyses showed that EPA or EPA ethyl ester supplementation reduced CVD events, while the mixture of EPA and DHA had no significant impact. Long-chain omega-3 consumption of 1.0-4.0 g per d reduced death risk by 3.5% for each 1 g per d increase. Omega-6 and PUFA had no significant effect on mortality or CVD events, with low-quality evidence and significant heterogeneity. Conclusions: omega-3 intake is associated with a reduced risk of all-cause mortality, CVD mortality, and CVD events in ASCVD patients, while omega-6 or total PUFA intake showed no significant association. Increasing the omega-3 intake by 1 g per d resulted in a 3.5% decrease in the risk of death. These findings support the recommendation of supplements with omega-3 fatty acids for the secondary prevention of ASCVD.