Omega-3 (Heart)

Unintentional doping, often caused by contaminated supplements or misinterpreted therapeutic prescriptions, poses significant health, ethical, and regulatory challenges in competitive sports. Understanding the cardiovascular risks associated with performance-enhancing substances (PESs) and the preventive role of nutrition requires integrated analysis. A systematic review was conducted in accordance with PRISMA guidelines. Searches of comprehensive bibliographic databases yielded studies published between 2015 and November 2025. Inclusion criteria encompassed peer-reviewed research on doping prevalence, cardiovascular outcomes, nutritional strategies, and supplement regulation. Data extraction focused on prevalence estimates, odds ratios (ORs), hazard ratios (HRs), and effect sizes for nutritional interventions. Quality assessment employed GRADE and risk-of-bias tools. From 1320 records screened, 60 studies were included in the qualitative synthesis and 31 in the meta-analysis. Surveys using indirect questioning estimated that 30-45% of elite athletes may engage in doping, while official anti-doping reports indicated that approximately 20-25% of confirmed rule violations are classified as unintentional. Supplement contamination accounted for 10-15% of unintentional cases. PES use significantly increased cardiovascular risk (HR for arrhythmias and myocardial infarction up to 3.5). Nutritional strategies-such as carbohydrate loading, optimized protein intake, omega-3 supplementation, and hydration-improved endurance by 8-12%, reduced resting heart rate by ~3 bpm, and lowered LDL cholesterol. Unintentional doping remains a major contributor to ADRVs, primarily driven by supplement contamination. Evidence-based nutrition offers safe alternatives to PESs (evidence-based nutritional strategies and structured hydration protocols), enhancing performance and cardiovascular health. Forensic toxicology and pharmacogenomic screening are essential for accurate detection and interpretation. Regulatory reforms, mandatory third-party supplement certification, and athlete education are critical to mitigate unintentional doping and ensure fair competition.

AIM: Many studies reported the effects of n-3 polyunsaturated fatty acids (PUFA) towards cardiovascular risk, but results are inconclusive. This meta-analysis systemically explored PUFA-mediated effects on representative cardiovascular-related metabolic markers, including glycolipid profile, adiponectin, and oxidative stress indicators in different people. DATA SYNTHESIS: Literature search on PubMed, EMBASE, Web of Science, and the Cochrane Library were performed up to October 11, 2024. Randomized controlled trials focusing on the effects of n-3 PUFA supplementation on triacylglycerol (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), apolipoprotein, adipokine, hemoglobin A1c (HbA1c), c-reactive protein (CRP), and oxidative stress biomarkers were chosen as outcome variables. There were 24 studies with 2043 subjects showed significant effects: (1)TG decreased by 16.95 mg/dl (21 trials, n = 1491; 95 % CI: 23.25, -10.66), (2)HDL increased by 1.55 mg/dl (22 trials, n = 1914; 95 % CI: 0.69, 2.42), (3)adiponectin increased by 0.96 μg/ml (3 trials, n = 198; 95 % CI: 0.03, 1.8), (4)HbA1c decreased by 0.17 % (3 trials, n = 283; 95 % CI: 0.29, -0.04), (5)LDL decreased by 10.98 mg/dl in women (4 trials, n = 236; 95 % CI: 19.41, -2.5) and by 13.77 mg/dl in the polycystic ovary syndrome (PCOS) (3 trials, n = 180; 95 % CI: 22.83, -4.7), (6)TC decreased by 15.58 mg/dl in women (4 trials, n = 236; 95 % CI: 24.64, -6.53). CONCLUSIONS: The meta-analysis indicates that n-3 PUFAs improve cardiovascular-related metabolic markers, potentially benefit cardiovascular health in patients with cardiovascular disease, PCOS, and kidney disease, especially in older women via reducing TG and HbA1c and increasing HDL and adiponectin.

AIMS: Omega-3 polyunsaturated fatty acids are routinely recommended as a lifestyle modification for preventing cardiovascular disease (CVD). It is not clear if any omega-3 polyunsaturated fatty acid formulations are favourable for patients with peripheral artery disease (PAD). DATA SYNTHESIS: A systematic review and meta-analysis (PROSPERO registration ID CRD42022336641) was conducted to determine the effects of omega-3 fatty acids on functional outcomes in people with PAD. Studies reporting any dose of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) supplementation versus placebo were assessed by two independent reviewers. Data including study design, number, age and sex of participants, period of assessment, diagnosis method for PAD, inclusion and exclusion criteria, method and formulation of omega-3 supplementation were analysed. Risk of bias was determined using the Newcastle-Ottawa scale. Of 1067 citations, 12 studies (n = 759 patients) met the predefined inclusion criteria. Supplementation of EPA, or EPA + DHA did not alter the primary outcome measures of pain-free walking distance, maximal walking distance; ankle brachial index, or flow mediated vasodilation versus placebo. There were no changes in secondary outcomes of circulating inflammatory markers, cholesterol, or blood pressure. CONCLUSION: Mixed omega-3 fatty acids, especially in low doses, are not effective in reducing symptoms of PAD. However, there is insufficient evidence to rule out effectiveness of specific omega 3 formulations, particularly for high-risk populations. Therefore, it is recommended that a large scale, randomised control trial with high dose EPA is conducted in patients with PAD.

BACKGROUND: Omega-3 polyunsaturated fatty acids are known for anti-inflammatory and cardiovascular benefits, but their impact on solid organ transplant outcomes is unclear. OBJECTIVES: To assess the effects of omega-3 supplementation on clinical outcomes in solid organ transplant recipients. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted according to PRISMA guidelines. Databases including PubMed, Scopus, and Web of Science were searched through May 2025. Eligible studies were evaluated for transplant-related outcomes, with the primary outcome being graft rejection at 30-day, 3-month, and 1-year post-transplant. Secondary outcomes included changes in lipid profile, blood pressure, renal function, and infection rates. RESULTS: Sixteen trials involving 1,020 patients were included. Omega-3 supplementation did not result in a statistically significant reduction in rejection rates at 30 days, 3 months, or 1 year post-transplant. Diastolic blood pressure decreased significantly (Hedges' g = -0.72; 95 % CI: -1.31 to -0.13), and total cholesterol levels also declined (Hedges' g = -0.64; 95 % CI: -1.04 to -0.24), particularly in kidney transplant recipients. In heart transplant recipients, systolic blood pressure decreased significantly (Hedges' g = -1.03; 95 % confidence interval: -1.53 to -0.54). Effects on high- and low-density lipoproteins, triglycerides, glomerular filtration rate, and creatinine clearance were inconsistent and largely non-significant. A single study reported reduced sepsis rates in kidney recipients (log odds ratio = -1.16; 95 % confidence interval: -2.25 to -0.07). No significant impact was seen on calcineurin inhibitor toxicity. CONCLUSION: Omega-3 supplementation may have benefits for solid organ transplant recipients in terms of improving lipid profiles and reducing blood pressure. However, study heterogeneity and limited outcome data highlight the need for larger, standardized trials.

Poststroke cognitive decline is a major form of disability in stroke survivors. Although dietary interventions have shown potential in improving cognitive outcomes in stroke-free populations, their effects on stroke survivors remain unclear. This review aimed to evaluate associations between diet and cognitive function in stroke survivors. MEDLINE, Embase, Scopus, and CINHAL were searched for studies from inception to 16 December, 2024. Eligible articles were observational and interventional studies on adult stroke survivors that evaluated the association/effect of any nutritional exposure/intervention on cognitive performance and dementia risk. Studies were excluded when an intervention was combined with nonnutritional treatment. Random-effects meta-analysis was used for similar randomized clinical trials. This review included 20 clinical trials and 14 observational studies assessing the intake of energy and proteins and a variety of single nutrients, as well as dietary patterns, single foods, and phytochemicals. Meta-analyses revealed a positive effect of energy-protein supplementation on global cognition [standardized mean difference (SMD): 0.62; 95% confidence interval (CI): 0.15, 1.08; P = 0.009], and a negative effect of B-vitamins (folic acid, vitamin B6, and vitamin B12) (SMD: -0.40; 95% CI: -0.72, -0.08; P = 0.02). Adherence to the Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay and plant-based diets, as well as higher consumption of fruits, milk, coffee, vitamin E, and selenium, were related to better cognitive outcomes; no significant association was observed for adherence to DASH and Mediterranean diets and consumption of vitamins D and C. Butter and sugar intake and calcium supplementation were associated with negative cognitive outcomes. Mixed results were seen for omega (ω)-3, tea, and plant extracts. The available evidence indicates that energy-protein supplementation may benefit cognition after stroke, whereas B-vitamin supplementation has no effect. The substantial heterogeneity among studies hinders conclusions about other dietary strategies. This review was registered with PROSPERO as CRD4

Heart failure is a progressive condition associated with a high mortality rate. Despite advancements in treatment, many patients continue to experience less-than-ideal outcomes. ω-3 (n-3) polyunsaturated fatty acids (PUFAs) have been studied as a potential supplementary therapy for heart failure, but the optimal dosage and duration of supplementation remain unclear. This network meta-analysis (NMA) aimed to assess the efficacy of various n-3 PUFA supplementation regimens in patients with heart failure, focusing on dose-dependent and time-dependent effects. We conducted a systematic search for randomized controlled trials (RCTs) on n-3 PUFA supplementation in heart failure till 13 September, 2024. The primary outcome was the change in heart function, specifically left ventricular ejection fraction. Secondary outcomes included changes in peak oxygen consumption (VO2), blood B-type natriuretic peptide concentrations, and quality of life. The safety analysis focused on dropout rates (i.e., patients leaving the study for any reason before completion) and all-cause mortality. A frequentist-based NMA was performed. This NMA, which included 14 RCTs with 9075 participants (mean age, 66.0 y; 23.3% female), found that high-dose n-3 PUFA supplementation (2000-4000 mg/d) over a duration of ≥1 y significantly improved left ventricular ejection fraction and peak VO2 compared with those of control groups. Lower doses and shorter treatment periods did not produce the same benefits. No significant differences were found in dropout rates or all-cause mortality between the n-3 PUFAs and control groups. Long-term, high-dose n-3 PUFA supplementation, particularly with a predominance of docosahexaenoic acid or eicosapentaenoic acid, enhances cardiac function in patients with heart failure without increasing risk of adverse events. Further well-designed RCTs with long treatment durations (i.e., >1 y) and stringent heart failure inclusion criteria are necessary to confirm these findings and reduce potential biases. This trial was registered at PROSPERO as CRD42024590476.

OBJECTIVE: Studies regarding effects of omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on risk of atrial fibrillation (AF) have reported discordant results. The aim of this review is to clarify effects of marine omega-3 intake on risk of AF. PATIENTS AND METHODS: A PubMed search was performed using terms: atrial fibrillation, omega-3, EPA, DHA, vagal tone. We summarized findings from randomized clinical trials (RCTs), epidemiology studies, and meta-analyses evaluating effects/associations of DHA + EPA on risk of AF. Also, vagal tone was explored as a mediator between omega-3 and risk of AF. RESULTS: Meta-analyses of 8 RCTs and 17 prospective cohort studies comprised of 83,112 and 54,799 individuals, respectively, investigated the link between omega-3 intake and incident AF. The RCTs reported that treatment with DHA and/or EPA was associated with a 24 % increased relative risk of AF (absolute risk 4.0 % vs 3.3 %; relative risk [RR] 1.24, 95 % confidence interval [CI] 1.11-1.38, p = 0.0002). This was dose-dependent; DHA + EPA doses of ∼1000 mg/d increased AF risk ∼12 %, whereas 1800 to 4000 mg/d increased AF risk by ∼50 %. In contrast, observational studies focused on DHA + EPA blood levels or dietary intake have generally reported that higher omega-3 levels/consumption are associated with lower AF risk. Maximal AF risk reduction. (12 %) occurred at ∼650 mg/d of dietary DHA + EPA. Other studies have indicated that omega-3 fatty acids can dose-dependently increase vagal tone, which could explain the biphasic relationship between DHA + EPA and AF risk. Experimental studies show that low-level vagal stimulation decreases risk of AF, whereas high-level vagal stimulation increases risk of AF. CONCLUSION: Higher consumption of dietary omega-3 is associated with decreased AF risk. In contrast, pharmaceutical dosing of omega-3 increases AF in a dose-dependent manner, which may be mediated by vagal tone.

Long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation has shown potential benefits in the prevention of coronary heart disease (CHD); however, the impact of omega-3 fatty acid levels on CHD risk remains a subject of debate. Here, we aimed to investigate the association between n-3 PUFA levels and the risk of CHD, with particular reference to the subtypes of n-3 PUFA. METHODS: Prospective studies and retrospective case-control studies analyzing n-3 PUFA levels in CHD, published up to 30 July 2022, were selected. A random effects meta-analysis was used for pooled assessment, with relative risks (RRs) expressed as 95% confidence intervals (CIs) and standardized mean differences expressed as weight mean differences (WMDs). Subgroup and meta-regression analyses were conducted to assess the impact of n-3 PUFA exposure interval on the CHD subtype variables of the study. RESULTS: We included 20 prospective studies (cohort and nested case-control) and 16 retrospective case-control studies, in which n-3 PUFAs were measured. Higher levels of n-3 PUFAs (ALA, EPA, DPA, DHA, EPA + DHA, total n-3 PUFAs) were associated with a reduced risk of CHD, with RRs (95% CI) of 0.89 (0.81, 0.98), 0.83 (0.72, 0.96); 0.80 (0.67,0.95), 0.75 (0.64, 0.87), 0.83 (0.73, 0.95), and 0.80 (0.70, 0.93), respectively, p < 0.05. CHD patients had significantly lower n-3 PUFA levels compared to healthy controls (p < 0.05). In the subgroup analysis, a significant inverse trend was found for both fatal CHD and non-fatal CHD with n-3 PUFA (EPA + DHA) levels. Also, the link between n-3 PUFA levels in erythrocytes with total CHD was generally stronger than other lipid pools. CONCLUSIONS: n-3 PUFAs are significantly related to CHD risk, and these findings support the beneficial effects of n-3 PUFAs on CHD.

AIMS: Benefits of pharmacologic omega-3 fatty acid administration in cardiovascular prevention are controversial. Particularly, effects on coronary revascularization are unclear; also debated are specific benefits of eicosapentaenoic acid (EPA). We investigated incident coronary revascularizations, myocardial infarction (MI), stroke, heart failure (HF), unstable angina, and cardiovascular death, in subjects randomized to receive EPA or EPA + docosahexaenoic acid (EPA + DHA) vs. control. METHODS AND RESULTS: Meta-analysis of randomized controlled trials (RCTs) was conducted after MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library search. Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed for abstracting data and assessing data quality and validity. Data were pooled using a random effects model. Eighteen RCTs with 134 144 participants (primary and secondary cardiovascular prevention) receiving DHA + EPA (n = 52 498), EPA alone (n = 14 640), or control/placebo (n = 67 006) were included. Follow-up ranged from 4.5 months to 7.4 years. Overall, compared with controls, omega-3 supplementation reduced the risk of revascularization [0.90, 95% confidence interval (CI) 0.84-0.98; P = 0.001; P-heterogeneity = 0.0002; I2 = 68%], MI (0.89, 95% CI 0.81-0.98; P = 0.02; P-heterogeneity = 0.06; I2 = 41%), and cardiovascular death (0.92, 95% CI 0.85-0.99; P = 0.02; P-heterogeneity = 0.13; I2 = 33%). Lower risk was still observed in trials where most participants (≥60%) were on statin therapy. Compared with DHA + EPA, EPA alone showed a further significant risk reduction of revascularizations (0.76, 95% CI 0.65-0.88; P = 0.0002; P-interaction = 0.005) and all outcomes except HF. CONCLUSION: Omega-3 fatty acid supplementation reduced the risk of cardiovascular events and coronary revascularization, regardless of background statin use. Eicosapentaenoic acid alone produced greater benefits. The role of specific omega-3 molecules in primary vs. secondary prevention and the potential benefits of reduced revascularizations on overall health status and cost savings warrant further research. Plain Language Summary: It is debated whether

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.

Background. Research indicates that omega-3 fatty acids, resveratrol, astaxanthin, and coenzyme Q10 (CoQ10) possess anti-inflammatory properties, and their vascular benefits have been well-documented. This is a pilot study aimed at comprehensively evaluating the potential impact of the compound fish oil capsules on the microcirculation of multiple organs. Methods. In a triple-blind, randomized, placebo-controlled trial, 64 hypertensive patients were randomly assigned to either the compound fish oil (FO) group or the corn oil (CO) group (n = 32 per group) for a 3-week intervention. Participants were required to consume 2 capsules of the corresponding oil daily. The microcirculation functions of the heart, skin, and brain were examined by transthoracic Doppler echocardiography (TTDE), laser Doppler flowmetry (LDF), and magnetic resonance imaging (MRI), respectively. Data were primarily analyzed according to an intention-to-treat approach. Findings. In the left anterior descending artery (LAD), the end-diastolic velocity (EDV) and peak diastolic velocity (PDV) significantly increased in the FO group. The mean differences in change were 1.95 (0.13, 3.77; p = 0.036) and 2.95 (0.48, 5.41; p = 0.020), respectively. The resistance index (RI) showed a decreasing trend in the FO group, but the result was non-significant (p = 0.071). No significant differences were observed in blood pressure, brain and skin microcirculation parameters among the different groups. Interpretation. Compound fish oil capsules did not significantly improve RH. But compound fish oil capsules improved EDV and PDV levels in the LAD of hypertensive patients.

INTRODUCTION: ASCEND assessed the effects of randomisation to aspirin versus placebo and, separately omega-3 fatty acid (FA) supplementation versus placebo on vascular events in 15480 adults with diabetes using mail-based remote methods. This analysis investigates factors associated with adherence to the allocated treatments. METHODS: Adherence was estimated from the 6-monthly follow-up forms and the supply of study treatment packs. A binary adherence variable, full versus less than full adherence during the period at risk of a serious vascular event (SVE), was investigated using logistic regression. Potential predictors of adherence considered were sex, age at randomisation, Hospital Frailty Risk Score, ethnicity, Townsend index, smoking status, type of diabetes, predicted 5-year vascular risk, number of other medications reported at study entry and treatment allocation. RESULTS: Seven thousand, three hundred twelve (47.2%) participants were fully adherent to aspirin/placebo and 8937 (57.7%) were fully adherent to omega-3 FA/placebo while at risk of a SVE. Women were less likely to be fully adherent than men (aspirin randomisation: 2509 [43.3%] vs. 4803 [49.6%]; OR, 0.73; 95% CI: 0.68 to 0.80; P < 0.0001; omega-3 FA randomisation: 3035 [52.4%] vs. 5902 [61.0%]; OR, 0.67; 95% CI: 0.61 to 0.72; P < 0.0001) and adherence decreased with increasing frailty (trend p-value < 0.0001), smoking (p-value < 0.0001), vascular risk score (p-value < 0.0001) and deprivation (trend p-value = 0.0211, p = 0.0011). CONCLUSION: We show this large, mail-based trial has comparable adherence with less streamlined trials in similar populations. In ASCEND, women and those with higher levels of frailty, smoking and vascular risk score had poorer adherence to trial medication. Trialists should consider strategies to improve adherence in these participant groups. © 2026. The Author(s).

Although preclinical studies suggest that omega-3 fatty acids may benefit skeletal health, there are few randomized controlled trials investigating effects of supplemental omega-3 on bone outcomes. This VITamin D and OmegA-3 TriaL (VITAL) ancillary study investigated effects of marine omega-3 (1 g/d; EPA+DHA in a 1.2:1 ratio) vs placebo supplements on fracture risk and bone density/structure. VITAL is a 2 × 2 factorial randomized placebo-controlled trial that studied effects of supplemental marine omega-3 fatty acids and/or vitamin D3 vs placebo on cancer and cardiovascular events. The intervention took place from November 2011 through December 2017; median follow-up was 5.3 yr. The study included 25 871 U.S. men (aged ≥50) and women (aged ≥55) without baseline cancer or cardiovascular disease, not selected for low bone density or fracture history. Primary outcomes were adjudicated incident total, nonvertebral, and hip fractures in the overall cohort. In a subcohort of 771 individuals, we measured 2-yr changes in areal BMD (aBMD) by DXA, and volumetric BMD (vBMD), cortical thickness, and bone strength indices at the radius and tibia by peripheral QCT. Supplemental omega-3 vs placebo had no effect on total (HR, 1.02; 95% CI, 0.92-1.13; p = .73), nonvertebral (HR, 1.01; 95% CI, 0.91-1.12; p = .80), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30; p = .55). In the subcohort, omega-3 supplementation resulted in a small increase in whole body aBMD (+0.03% vs -0.41%, p = .006) and no effect on aBMD at the spine or hip, or vBMD or bone strength indices at the radius or tibia. No serious adverse effects were observed. Supplementation with marine omega-3 fatty acids did not reduce incident fracture risk. It led to a small increase in whole body aBMD but had no other effects on BMD or bone strength measures compared to placebo in generally healthy midlife and older adults. Plain Language Summary: Animal studies suggest that omega-3 fatty acid supplements may help bone health. However, there are few human clinical trials assessing the impact of supplemental omega-3 on bone density and fracture risk. This ancillary study to the VITamin D and OmegA-3 TriaL investigated if sup

BACKGROUND: Cardiovascular disease is the leading cause of death in patients receiving hemodialysis, yet effective preventive therapies remain limited. Supplementation with n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have cardiovascular benefits in the general population, but efficacy among patients receiving hemodialysis is uncertain. METHODS: In a double-blind, randomized, placebo-controlled trial conducted at 26 sites in Canada and Australia, we assigned adult patients receiving maintenance hemodialysis to daily supplementation with fish oil (4 g of n-3 polyunsaturated fatty acids [1.6 g of EPA and 0.8 g of DHA]) or corn-oil placebo. The primary end point was a composite of all serious cardiovascular events including sudden and nonsudden cardiac death, fatal and nonfatal myocardial infarction, peripheral vascular disease leading to amputation, and fatal and nonfatal stroke. Secondary end points included extension of the primary end point to include noncardiac causes of death, the individual components of the primary end point, and a first cardiovascular event or death from any cause. RESULTS: Between November 28, 2013, and July 22, 2019, a total of 1228 participants underwent randomization; 610 were assigned to the fish-oil group and 618 to the placebo group. During 3.5 years of follow-up, the rate of serious cardiovascular events was significantly lower in the fish-oil group than in the placebo group (0.31 vs. 0.61 per 1000 patient-days; hazard ratio, 0.57; 95% confidence interval [CI], 0.47 to 0.70; P<0.001). The rate of the extended primary end point that included noncardiac causes of death appeared to be lower in the fish-oil group than in the placebo group, with a hazard ratio of 0.77 (95% CI, 0.65 to 0.90). The hazard ratio for cardiac death was 0.55 (95% CI, 0.40 to 0.75); for fatal and nonfatal myocardial infarction, 0.56 (95% CI, 0.40 to 0.80); for peripheral vascular disease leading to amputation, 0.57 (95% CI, 0.38 to 0.86); for fatal and nonfatal stroke, 0.37 (95% CI, 0.18 to 0.76); and for a first cardiovascular event or death from any cause, 0.73 (95% CI, 0.61 to 0.87). Adherence to

Prenatal supplementation with docosahexaenoic acid (DHA) has been reported to improve cognitive outcomes in infancy and early childhood in some studies. Existent studies have examined the effects of some dose of DHA against a true placebo; this report is the first to describe the effects of different doses of prenatal DHA on infant visual attention at 4 and 6 months of age. In a follow-up to a Phase III registered clinical trial (NCT02709239) designed to evaluate the effects of two prenatal doses of DHA supplementation (200 or 800 mg daily) on maternal physiology and fetal neurodevelopment, we assessed 215 infants delivered to these mothers at 4 and 6 months on a visual habituation task augmented with heart rate (HR) to assess visual stimulus processing, and a gap-overlap task to assess engagement and disengagement of attention. Infants of mothers supplemented with 800 mg/day of DHA had shorter look durations (indicative of more rapid visual learning) during habituation at both ages and a somewhat more mature pattern of HR-defined phases of attention. However, DHA dose did not affect infant HR, nor did it affect infant performance in the gap-overlap attention task. Results are consistent with positive effects of prenatal DHA supplementation on later outcomes, with higher benefit seen for a higher dose. © 2025 Wiley Periodicals LLC.

BACKGROUND: Inflammation is a common mechanism for atrial fibrillation (AF). 2-Hydroxybenzylamine (2-HOBA) is a novel therapeutic that scavenges isolevuglandins-a downstream mediator of inflammation and oxidative stress. 2-HOBA is safe and reduces AF in mice, prompting a first-in-human pilot clinical trial. METHODS: Participants were enrolled and randomized 1:1 to placebo or 2-HOBA (750 mg p.o. TID) 3 days before a planned AF ablation. Participants were monitored for 28 days after their ablation for recurrence of AF as detected by smartwatch single-lead ECG recordings. Blood was collected at the time of ablation for measurement of isolevuglandin levels. The study drug was stopped at 28 days. A 12-month extended follow-up period was used to monitor for any residual effect of the study drug on AF recurrence. RESULTS: 2-HOBA increased the risk of AF recurrence in the postablation population (odds ratio, 3.65 [95% CI, 1.31-10.16]; P=0.013) after prespecified adjustment for potential confounders. This increased risk of recurrence remained despite post hoc adjustment for other clinical risk factors. There was no difference in isolevuglandin levels between the 2-HOBA and placebo groups. After the study drug was stopped, there was no difference in AF recurrence between the 2-HOBA and placebo groups during the 12-month extended follow-up. CONCLUSIONS: 2-HOBA was associated with a higher risk of AF recurrence when tested early after AF ablation. This result was unexpected based on preclinical data, but paradoxical associations with AF have been previously reported for other drugs that target inflammation and oxidative stress pathways, such as omega-3 fatty acids. The mechanisms for AF immediately following ablation may be different from AF that occurs under other conditions, and the generalizability of these results to all forms of AF remains unknown.

BACKGROUND AND PURPOSE: Dietary intakes of omega-3 polyunsaturated fatty acids (ω-3 PUFA) are below what is recommended. Meat from grass finished ruminants contains higher levels of ω-3 PUFAs, particularly, alpha-linolenic acid (C18:3 ω-3). The impact of consuming grass finished lamb meat rich in ω-3 PUFA on blood fatty acid (FA) response in humans is not well established. This study investigated the impact of consuming grass finished lamb on total blood plasma and blood plasma phospholipids (PL) FA and on cardiovascular risk factors, including heart rate, blood pressure (BP), HDL, LDL, total cholesterol, and TAG, in humans. METHODS: A single blinded, randomised controlled trial was conducted. Two portions of lamb chops and one portion of lamb mince from lambs finished on a grass or concentrate diet were consumed per week by 34 healthy participants for four consecutive weeks. Blood samples were taken at baseline and post-intervention. Approximately ~ 328 mg/100 g of total ω-3 PUFA was present in grass finished lamb portions per week. RESULTS: Greater levels of ω-3 PUFA, namely C18:3 ω-3, eicosapentaenoic acid (C20:5 ω-3) and docosapentaenoic acid (C22:5 ω-3), were detected in total blood plasma from participants who consumed grass finished lamb (P < 0.05), while consuming concentrate finished lamb higher levels of linoleic acid (C18:2 ω-6) in plasma PL (P < 0.01). There were no differences of consuming grass or concentrate finished lamb on cardiovascular risk factors. CONCLUSION: This study demonstrates that ω-3 PUFA from lamb meat finished on grass is reflected in blood ω-3 PUFA response. Grass finished lamb is a useful matrix for increasing intake of ω-3 PUFA into the human body alongside little required change to customary dietary habits. CLINICALTRIALS: gov ID: NCT06607354. Retrospectively registered 24/09/2024. © 2025. The Author(s).

Background/Objectives: Familial hypercholesterolemia (FH) is an increasingly common inherited disorder that increases cardiovascular risk. Despite the importance of lifestyle interventions, adherence to a healthy diet among individuals with FH remains suboptimal. This pilot, multicenter, double-blind, placebo-controlled randomized trial aimed to evaluate the feasibility and preliminary effects of a culturally adapted cardioprotective diet (DICA-FH), alone or in combination with phytosterol and/or krill oil supplementation, on lipid parameters in Brazilian adults with probable or definitive FH. Methods: Between May and August 2023, 58 participants were enrolled across nine Brazilian centers and randomized (1:1:1:1) into four groups: DICA-FH + phytosterol placebo + krill oil placebo; DICA-FH + phytosterol 2 g/day + krill oil placebo; DICA-FH + phytosterol placebo + krill oil 2 g/day; and DICA-FH + phytosterol 2 g/day + krill oil 2 g/day. Interventions lasted 120 days. The primary outcomes were mean low-density lipoprotein cholesterol (LDL-c) and lipoprotein(a) (Lp[a]) levels, as well as adherence to treatment at follow-up. Secondary outcomes included mean levels of other lipids, frequency of adverse events, and assessment of protocol implementation components. All data were presented separately for the allocation groups: phytosterol vs. placebo and krill oil vs. placebo. Results: Mean age was 54.5 ± 13.7 years, and 58.6% were women. Both adherence to protocol (91.8% attendance; 79.1% investigational product intake) and retention (86.2%) were high. No significant differences between groups were found for LDL-c or Lp(a). However, regardless of allocation to active supplementation or placebo, a significant reduction in Lp(a) concentrations was observed following the DICA-FH intervention (median difference: -3.8 mg/dL [interquartile range: -7.5 to -1.2]; p < 0.01). Significant reductions in oxidized LDL (LDL-ox) and LDL-ox/LDL-c ratio were also observed in the overall sample (p < 0.01). Although not statistically significant, all groups showed improvements in diet quality after 120 days. No serious adverse events related to the interventions were reported. Additionall

Randomized controlled trials (RCTs) have demonstrated benefits of marine omega-3 polyunsaturated fatty acids (omega-3 FA) supplementation for the prevention of coronary heart disease (CHD). However, it has not been clear which individuals benefit the most from supplementation. We sought to develop an omega-3 effect score to stratify individuals according to their expected benefit from supplementation. Among the 25,871 randomized participants without a history of cardiovascular disease in the VITamin D and OmegA-3 TriaL (VITAL), we applied machine-learning (ML) approaches to predict individual treatment effect of omega-3 FA supplementation on 5-year CHD risk using 11 covariates pre-specified in the VITAL protocol. An omega-3 effect score was developed such that each covariate contributed linearly. ML algorithms effectively stratified participants by their expected benefit according to individual factors; for example, there was 1.21% absolute CHD risk reduction in the top tertile of the expected benefit, compared with the average effect of 0.47% risk reduction. Baseline diabetes, race, hypertension, sex, and fish intake contributed the most to the omega-3 effect score. Five-year CHD risk was 2.5% among those in the omega-3 arm and 3.2% among those in the placebo arm with omega-3 effect score ≥ 4 (upper 70th percentile), and 1.4% among the omega-3 arm and 1.3% among the placebo arm in those with the score < 4, respectively. The transportability of the score to the National Health and Nutrition Examination Survey (NHANES) data was confirmed. Although testing of the score in a new RCT is warranted, the proposed omega-3 effect score holds promise for guiding decision making for omega-3 FA supplementation in the US primary prevention population. © 2025. Springer Nature B.V.

Comment in Atherosclerosis. 2025 Sep;408:120461. doi: 10.1016/j.atherosclerosis.2025.120461. BACKGROUND/AIMS: Racial differences in lipid and cardiovascular risk profiles are well-established, including for Asians. We compared cardiovascular treatment effects of ω-3 carboxylic acid (CA) between Asians and non-Asians in this post-hoc analysis of the STRENGTH trial. METHODS: The STRENGTH trial was a double-blinded randomized controlled trial of 13,078 high cardiovascular risk patients enrolled at 675 global centers. Efficacy and interactions of ω-3 CA for Asians (n = 1355) and non-Asians (n = 11,723) were assessed. The primary endpoint is a 5-point composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, and unstable angina hospitalizations. RESULTS: In Asians, ω-3 CA was associated with significantly reduction in the primary endpoint during 3.6 ± 0.7 years follow-up with 81/698 (Kaplan-Meier estimate (KME): 14.8 %) events in the ω-3 CA group, 103/657 (KME: 20.4 %) events in the corn oil group, hazard ratio (HR) 0.72, 95 %CI 0.54-0.96, p = 0.03. In non-Asians, there was not a significant difference in primary endpoint rates, 704/5841 (KME: 15.6 %) events in the ω-3 CA group, 692/5882 (KME: 15.9 %) events in the corn oil group, HR 1.03 95 %CI 0.93-1.14, p = 0.60. There were significant interactions between race (Asian vs non-Asian) and treatment group for the primary endpoint (p = 0.02) and non-fatal stroke (p = 0.02). CONCLUSION: In this exploratory analysis from the neutral STRENGTH trial, ω-3 CA was associated with significant reduction in the primary endpoint in Asians but not in non-Asian patients with high cardiovascular risk. Further, ideally randomized, research is necessary to assess these hypothesis-generating findings and elucidate potential mechanisms for beneficial effects of ω-3 CA in Asians.

BACKGROUND: Cholecalciferol (D3) may improve inflammation, and thus provide protection from cardiometabolic diseases (CMD), although controversy remains. Omega-3 fatty acids (ω-3FA) may also prevent the development of CMD, but the combined effects of ω-3FA and D3 are not fully understood. OBJECTIVES: We determined the chronic independent and combined effects of D3 and ω-3FA on body weight, glucose homeostasis, and markers of inflammation in obese mice. METHODS: We gave 8-week-old male C57BL/6J mice, which had been fed a high-fat, high-sucrose (HF) diet (65.5% kcal fat, 19.8% kcal carbohydrate, and 14% kcal protein) for 12 weeks, either a standard D3 dose (+SD3; 1400 IU D3/kg diet) or a high D3 dose (+HD3; 15,000 IU D3/kg diet). We fed 1 +SD3 group and 1 +HD3 group with 4.36% (w/w) fish oil (+ω-3FA; 44% eicosapentaenoic acid, 25% docosahexaenoic acid), and fed the other 2 groups with corn oil [+omega-6 fatty acids (ω-6FA)]. A fifth group was fed a low-fat (LF; 15.5% kcal) diet. LF and HF+ω-6+SD3 differences were tested by a Student's t-test and HF treatment differences were tested by a 2-way ANOVA. RESULTS: D3 supplementation in the +HD3 groups did not significantly increase plasma total 25-hydroxyvitamin D and 25-hydroxyvitamin D3 [25(OH)D3] versus the +SD3 groups, but it increased 3-epi-25-hydroxyvitamin D3 levels by 3.4 ng/mL in the HF+ω-6+HD3 group and 4.0 ng/mL in the HF+ω-3+HD3 group, representing 30% and 70%, respectively, of the total 25(OH)D3 increase. Energy expenditure increased in those mice fed diets +ω-3FA, by 3.9% in the HF+ω-3+SD3 group and 7.4% in the HF+ω-3+HD3 group, but it did not translate into lower body weight. The glucose tolerance curves of the HF+ω-3+SD3 and HF+ω-3+HD3 groups were improved by 11% and 17%, respectively, as compared to the respective +ω-6FA groups. D3 supplementation, within the ω-3FA groups, altered the gut microbiota by increasing the abundance of S24-7 and Lachnospiraceae taxa compared to the standard dose, while within the ω-6FA groups, D3 supplementation did not modulate specific taxa. CONCLUSIONS: Overall, D3 supplementation does not prevent CMD or enhance the beneficial effects of ω-3FA in vitamin D-sufficient obese

Doxorubicin (DOX) is widely used in cancer treatment, however, its use is often limited due to its side effects. To avoid these shortcomings, the encapsulation of DOX into nanocarriers has been suggested. Herein, we proposed a novel nanostructured lipid carrier (NLC) formulation loading DOX, docosahexaenoic acid (DHA), and α-tocopherol succinate (TS) for cancer treatment. DHA is an omega-3 fatty acid and TS is a vitamin E derivative. It has been proposed that these compounds can enhance the antitumor activity of chemotherapeutics. Thus, we hypothesized that the combination of DOX, DHA, and TS in NLC (NLC-DHA-DOX-TS) could increase antitumor efficacy and also reduce toxicity. NLC-DHA-DOX-TS was prepared using emulsification-ultrasound. DOX was incorporated after preparing the NLC, which prevented its degradation during manufacture. High DOX encapsulation efficiency was obtained due to the ion-pairing with TS. This ion-pairing increases lipophilicity of DOX and reduces its crystallinity, contributing to its encapsulation in the lipid matrix. Controlled DOX release from the NLC was observed in vitro, with increased drug release at the acidic environment. In vitro cell studies indicated that DOX, DHA, and TS have synergistic effects against 4T1 tumor cells. The in vivo study showed that NLC-DHA-DOX-TS exhibited the greatest antitumor efficacy by reducing tumor growth in 4T1 tumor-bearing mice. In addition, this formulation reduced mice mortality, prevented lung metastasis, and decreased DOX-induced toxicity to the heart and liver, which was demonstrated by hematologic, biochemical, and histologic analyses. These results indicate that NLC-DHA-DOX-TS may be a promising carrier for breast cancer treatment.

OBJECTIVE: Studies of depressed psychiatric patients have suggested that antidepressant efficacy can be increased by adding eicosapentaenoic acid (EPA), one of the omega-3 fatty acids found in fish oils. The purpose of this study was to determine whether the addition of EPA improves the response to sertraline in depressed patients with or at high risk for coronary heart disease (CHD). METHODS: Between May 2014 and June 2018, 144 patients with DSM-5 major depressive disorder seen at the Washington University School of Medicine with or at high risk for CHD were randomized to receive either 50 mg/d of sertraline and 2 g/d of EPA or 50 mg/d of sertraline and corn oil placebo capsules for 10 weeks. The Beck Depression Inventory II (BDI-II) was the primary outcome measure. RESULTS: After 10 weeks of treatment, there were no differences between the arms on the mean baseline-adjusted BDI-II (placebo, 10.3; EPA, 12.1; P = .22), the 17-item Hamilton Depression Rating Scale (placebo, 7.2; EPA, 8.0; P = .40), or the 10-week remission rate (BDI-II score ≤ 8: placebo, 50.6%; EPA, 46.7%; odds ratio = 0.85; 95% CI, 0.43 to 1.68; P = .63). CONCLUSIONS: Augmentation of sertraline with 2 g/d of EPA for 10 weeks did not result in greater improvement in depressive symptoms compared to sertraline and corn oil placebo in patients with major depressive disorder and CHD or CHD risk factors. Identifying the characteristics of cardiac patients whose depression may benefit from omega-3 and clarifying the pathways linking omega-3 to improvement in depression symptoms are important directions for future research. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02021669; FDA IND registration number: 121107. © Copyright 2019 Physicians Postgraduate Press, Inc.

Cardiovascular disease remains the leading cause of morbidity and mortality in the United States and other developed countries, and is fast growing in developing countries, particularly as life expectancy in all parts of the world increases. Current recommendations for the prevention of cardiovascular disease issued jointly from the American Academy of Cardiology and American Heart Association emphasize that lifestyle modification should be incorporated into any treatment plan, including those on statin drugs. However, there is a dearth of data on the interaction between diet and statins with respect to additive, complementary or antagonistic effects. This review collates the available data on the interaction of statins and dietary patterns, cognition, genetics and individual nutrients, including vitamin D, niacin, omega-3 fatty acids, fiber, phytochemicals (polyphenols and stanols) and alcohol. Of note, although the available data is summarized, the scope is limited, conflicting and disparate. In some cases it is likely there is unrecognized synergism. Virtually no data are available describing the interactions of statins with dietary components or dietary pattern in subgroups of the population, particularly those who may benefit most were positive effects identified. Hence, it is virtually impossible to draw any firm conclusions at this time. Nevertheless, this area is important because were the effects of statins and diet additive or synergistic harnessing the effect could potentially lead to the use of a lower intensity statin or dose.

BACKGROUND: Antiplatelet properties of omega-3 polyunsaturated fatty acids (PUFA) have been demonstrated in patients with coronary artery disease (CAD). It is unknown whether omega-3 PUFA can enhance platelet inhibition on standard aspirin and clopidogrel treatment in the setting of CYP2C19 loss-of-function polymorphism. AIM: To investigate whether omega-3 PUFA are able to modify platelet responsiveness to clopidogrel therapy in patients with CYP2C19 loss-of-function polymorphism undergoing percutaneous coronary intervention (PCI). METHODS: 63 patients with stable CAD undergoing PCI (48 males, mean age 63.2 ± 9.6 years) were enrolled into an investigator- initiated, prospective, single-centre, double-blind, placebo-controlled, randomised study. Patients on standard dual antiplatelet therapy (aspirin 75 mg daily and clopidogrel 600 mg loading dose followed by 75 mg daily) were assigned to receive the addition of 1 g of omega-3 ethyl esters (n = 33) or placebo (n = 30) for 1 month. Platelet function was measured serially by light transmittance aggregometry in response to 5 and 20 μmol/L ADP at baseline, 12 h, 3-5 days and 30 days after randomisation. CYP2C19*2 was genotyped at baseline. RESULTS: No significant differences were found in baseline variables, including the frequency of CYP2C19 genetic variants. At least one loss-of-function variant of CYP2C19*2 was found in 19 (30.2%) patients. In patients with CYP2C19*1/*2 and *2/*2 variants, maximal platelet aggregation induced by 5 and 20 μmol/L ADP was reduced by 21.4% (p = 0.006) and 14.3% (p = 0.041), respectively, after 1 month of treatment with omega-3 PUFA as compared to placebo. The beneficial effect of omega-3 PUFA was demonstrated in carriers of CYP2C19 loss-of-function polymorphism, whereas no differences in platelet aggregation between the omega-3 PUFA and placebo groups were found in patients with the 1*/1* variant. CONCLUSIONS: The addition of omega-3 ethyl esters significantly potentiates platelet response to clopidogrel after PCI mostly in patients with CYP2C19 loss-of-function polymorphism.

PURPOSE: Developing approaches that will increase the selectivity of anticancer drugs remains a challenge. Docosahexaenoic acid (DHA) has the potential to increase tumor sensitivity to chemotherapy with no sensitization of normal tissues. This study was aimed at exploring the mechanism involved in this differential sensitization with a focus on oxidative stress, one of the main determinants involved in DHA enhancement of anthracycline-based chemotherapy. METHODS: In a previously validated model of chemically induced mammary tumors in rats where supplemental DHA sensitized tumors to epirubicin, DHA level, lipid hydroperoxides (LPO), total antioxidant activity, glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities were measured in tumors, intestine, liver, and heart in rats treated with DHA+epirubicin and in control rats (palm oil, no chemotherapy). RESULTS: At baseline, the level of LPO was similar in tumors, liver, heart, and small intestine. The proportion of DHA was higher in non-tumor tissues compared to tumors (liver or heart, p < 0.0001; intestine, p = 0.01). DHA and epirubicin induced a significant increase in LPO in tumors (p = 0.03), but no increase was detected in liver, heart, or intestine. The difference in LPO production between these tissues was associated with differences in their antioxidant defenses. In tumors, the adjustment of GPx activity was possible but limited, and no adjustment of their total antioxidant and SOD activities was observed compared to other tissues. CONCLUSION: Supplementing DHA during an anthracycline-based chemotherapy induced a selective increase of LPO in tumors. This selectivity might result from a differential handling of oxidative stress between tumor and non-tumor tissues.

OBJECTIVES: N-3 fatty acids reduce the risks of cardiovascular morbidity and mortality. Administration of N-3 fatty acids to patients treated with statins may potentiate the treatment effects. We examined the operating mechanisms underlying such a combination. METHODS: Thirty-two hypercholesterolemic patients aged 30-70 years with hypercholesterolemia controlled by statins, received sequential treatments with placebo followed by 1.9 g/day of N-3 fatty acids for 23 weeks. Scheduled clinical visits included physical examination, 24-h blood pressure measurement, endothelial function evaluated by pulse wave analysis, analyses for platelet function, inflammation markers [interleukin (IL)-6, plasminogen activator inhibitor-1 (PAI-1)] and oxidative stress parameters (STAT-8-Isoprostane) were undertaken at baseline, after placebo treatment, and after 6 and 20 weeks of N-3 fatty acid intake. RESULTS: Platelets functions were significantly inhibited, whereas endothelial function parameters were unaltered. IL-6 significantly decreased whereas PAI-1and STAT-8-Isoprostane levels remained unaffected. Daytime blood pressure significantly decreased; however, nighttime pressure and heart rate remained unchanged. No evidence of lipid-profile improvement was observed following combined treatment with statins and N-3 fatty acids. CONCLUSIONS: In hypercholesterolemic patients, combination of statins and N-3 fatty acid inhibits platelet aggregation, alters inflammatory status, and positively affects daytime blood pressure. Close long-term follow-up might reveal additional beneficial effects of N-3 fatty acids in this patient population.

AIMS: Recent secondary prevention trials have failed to demonstrate a beneficial effect of n-3 fatty acids on cardiovascular outcomes, which may be due to the growing use of statins since the mid-1990s. The aim of the present study was to assess whether statins modify the effects of n-3 fatty acids on major adverse cardiovascular events in patients with a history of myocardial infarction (MI). METHODS AND RESULTS: Patients who participated in the Alpha Omega Trial were divided into consistent statin users (n = 3740) and consistent statin non-users (n = 413). In these two groups of patients, the effects of an additional daily amount of 400 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA), 2 g α-linolenic acid (ALA), or both on major cardiovascular events were evaluated. Multivariable Cox's proportional hazard models were used to calculate adjusted hazard rate ratios (HR(adj)). Among the statin users 495 (13%) and among the statin non-users 62 (15%) developed a major cardiovascular event. In statin users, an additional amount of n-3 fatty acids did not reduce cardiovascular events [HR(adj) 1.02; 95% confidence interval (CI): 0.80, 1.31; P = 0.88]. In statin non-users, however, only 9% of those who received EPA-DHA plus ALA experienced an event compared with 18% in the placebo group (HR(adj) 0.46; 95% CI: 0.21, 1.01; P= 0.051). CONCLUSION: In patients with a history of MI who are not treated with statins, low-dose supplementation with n-3 fatty acids may reduce major cardiovascular events. This study suggests that statin treatment modifies the effects of n-3 fatty acids on the incidence of major cardiovascular events.

With its increasing prevalence throughout the world, heart failure continues to be associated with high morbidity and mortality. Patients with heart failure develop progressive metabolic abnormalities, inflammation, and atrophy in the myocardium and skeletal muscle. Improvement in functional capacity as defined by exercise tolerance is essential for better quality of life and potentially survival of these patients. Therapeutic management options aimed at improving peripheral organ function are limited. Nutritional approaches with dietary supplementation in addition to current therapies are particularly appealing as they are novel and mechanistically different. In this article, we review the role of glutamine and omega-3 polyunsaturated fatty acids on metabolism and functional capacity in heart failure. These two compounds are of particular interest due to their synergistic role on oxidative metabolism, lipolysis and inflammation.

Fish and fish oil supplements are often used to lower triglycerides; however, recent studies suggest the beneficial use of fish oil for other cardiovascular reasons. Studies have shown that in addition to decreasing triglycerides, fish oil has shown benefit in providing antiplatelet activity, improving heart failure, and improving vascular function in diabetes. Fish oil was shown to improve triglycerides in combination with other lipid-lowering therapy such as a statin or fibrate. Fish oil also had effects on lowering total cholesterol, very-low-density lipoprotein (VLDL), and increasing high-density lipoprotein (HDL). In terms of its antiplatelet activity, fish oil was shown to lower platelet aggregation when given in combination with clopidogrel and aspirin therapy during PCI, thus fish oil appears to enhance platelet response to clopidogrel. Fish oil has a role in heart failure as well.Fish oil was shown to slightly decrease morbidity and mortality in patients with class II-IV heart failure compared to placebo.Finally, fish oil showed benefit in patients with type II diabetes in terms of improving micro- and macrovascular function.