Omega-3 supplementation and outcomes of heart failure: A systematic review of clinical trials

Backgrounds:Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits.A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials.The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events.Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.Heart failure (HF) is now a worldwide epidemic, with its prevalence and incidence increasing at a fast pace.[1] According to the American Heart Association data, 8.1 million individuals in the United States are currently suffering from this condition. By 2030, it is anticipated that the global incidence of HF will rise by 46%, emerging as a significant global health concern.[1] The World Health Organization (2016) has categorized HF as a major contributor to mortality in Europe, pinpointing diet, physical inactivity, smoking, alcohol consumption, hypertension, high cholesterol levels, excess weight, obesity, and diabetes as the primary risk factors.[1] HF is a consequence of various cardiovascular diseases (CVDs) and continues to be linked with a reduced quality of life (QoL), early mortality, and significant utilization of healthcare resources.[2-5] Despite the recent advancements in both pharmaceutical and interventional treatments, HF remains a leading cause of mortality and recurrent hospitalization.[6,7] It also serves as a predictor of lethality among geriatric patients.[8] Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have emerged as a vital category of dietary lipids that have demonstrated cardiovascular protective properties in HF patients.[3,9]Omega-3 polyunsaturated fatty acids obtained from marine sources (n-3 PUFAs), specifically Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have shown effectiveness in managing HF. Among the numerous nutraceuticals that have been studied for their potential impact on HF outcomes, only omega-3 PUFAs have received a favorable recommendation in the Australian HF guidelines.[10]Omega-3 fatty acids have shown an association with reducing myocardial fibrosis, left ventricular remodeling, and lowering systemic inflammation after myocardial infarction (MI). Additionally, significant decreases in events such as nonfatal MI, nonfatal stroke, cardiovascular-related deaths, coronary revascularization procedures, and unstable angina have been documented.[6] These findings carry particular importance since persistent inflammation is a significant contributor to the development of HF.[7,11,12] The most significant findings came from studies evaluating the impact of EPA/DHA supplementation on HF and other CVDs. [13] The researchers revealed the effectiveness of n-3 PUFA supplementation in preventing CVD events, such as HF and MI, with a particularly strong protective effect observed at higher dosage levels. However, accurately assessing the beneficial effects of n-3 PUFAs in clinical trials focusing on heterogeneous conditions like HF poses challenges. Several variables (e.g., race, age, sex, and dose of EPA/DHA) can influence the clinical outcomes in these trials. In addition, given the diverse effects of n-3 PUFAs in vivo, understanding their pathophysiologic effects on HF remains a complex endeavor.Significant benefits associated with the utilization of omega-3 in individuals with HF have been identified. Research has shown that omega-3 can lower the rate of patient readmissions.[14,15] Additionally, some studies have found that omega-3 supplementation can reduce mortality.[16,17] Multiple articles have confirmed the anti-inflammatory properties of omega-3.[16,18,19] Moreover, a limited set of studies has suggested that omega-3 supplementation may positively impact the QoL by ameliorating depressive symptoms among HF patients.[20-22] However, further investigations are necessary to draw a definitive conclusion.So far, several review studies have been undertaken regarding the effects of omega-3 on HF. These studies have assessed only a few outcomes, such as mortality and hospitalization.[16,19,23] They also reviewed the physiological effects and mechanism of omega-3 in HF patients.[16,19,23] However, clinical research has suggested that omega-3 may have an impact on a range of other HF-related outcomes. These include MI, stroke,[24,25] revascularization, and cardiac function in HF,[26,27] which have not been considered in previous studies.[13,14] In addition, the use of complementary and alternative medicine, which includes dietary supplements for preventing and treating illness, is a multibillion-dollar industry. Patients with HF commonly resort to complementary and alternative medicine, even without substantial evidence. Generally, there is inadequate high-quality evidence to support the significant therapeutic impact of these therapies.[28] Therefore, for the first time, we aimed to offer a comprehensive systematic review encompassing various outcomes associated with omega-3 supplementation among patients with HF, which helps clinicians be aware of the potential effects of omega-3 supplementation on improving HF outcomes. On the other hand, it allows researchers to be aware of the knowledge gaps and to consider them through further trials.Backgrounds:Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits.A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials.The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events. Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.Heart failure (HF) is now a worldwide epidemic, with its prevalence and incidence increasing at a fast pace.[1] According to the American Heart Association data, 8.1 million individuals in the United States are currently suffering from this condition. By 2030, it is anticipated that the global incidence of HF will rise by 46%, emerging as a significant global health concern.[1] The World Health Organization (2016) has categorized HF as a major contributor to mortality in Europe, pinpointing diet, physical inactivity, smoking, alcohol consumption, hypertension, high cholesterol levels, excess weight, obesity, and diabetes as the primary risk factors.[1] HF is a consequence of various cardiovascular diseases (CVDs) and continues to be linked with a reduced quality of life (QoL), early mortality, and significant utilization of healthcare resources.[2-5] Despite the recent advancements in both pharmaceutical and interventional treatments, HF remains a leading cause of mortality and recurrent hospitalization.[6,7] It also serves as a predictor of lethality among geriatric patients.[8] Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have emerged as a vital category of dietary lipids that have demonstrated cardiovascular protective properties in HF patients.[3,9]Omega-3 polyunsaturated fatty acids obtained from marine sources (n-3 PUFAs), specifically Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have shown effectiveness in managing HF. Among the numerous nutraceuticals that have been studied for their potential impact on HF outcomes, only omega-3 PUFAs have received a favorable recommendation in the Australian HF guidelines.[10]Omega-3 fatty acids have shown an association with reducing myocardial fibrosis, left ventricular remodeling, and lowering systemic inflammation after myocardial infarction (MI). Additionally, significant decreases in events such as nonfatal MI, nonfatal stroke, cardiovascular-related deaths, coronary revascularization procedures, and unstable angina have been documented.[6] These findings carry particular importance since persistent inflammation is a significant contributor to the development of HF.[7,11,12] The most significant findings came from studies evaluating the impact of EPA/DHA supplementation on HF and other CVDs.[13] The researchers revealed the effectiveness of n-3 PUFA supplementation in preventing CVD events, such as HF and MI, with a particularly strong protective effect observed at higher dosage levels. However, accurately assessing the beneficial effects of n-3 PUFAs in clinical trials focusing on heterogeneous conditions like HF poses challenges. Several variables (e.g., race, age, sex, and dose of EPA/DHA) can influence the clinical outcomes in these trials. In addition, given the diverse effects of n-3 PUFAs in vivo, understanding their pathophysiologic effects on HF remains a complex endeavor.Significant benefits associated with the utilization of omega-3 in individuals with HF have been identified. Research has shown that omega-3 can lower the rate of patient readmissions.[14,15] Additionally, some studies have found that omega-3 supplementation can reduce mortality.[16,17] Multiple articles have confirmed the anti-inflammatory properties of omega-3. [16,18,19] Moreover, a limited set of studies has suggested that omega-3 supplementation may positively impact the QoL by ameliorating depressive symptoms among HF patients.[20-22] However, further investigations are necessary to draw a definitive conclusion.So far, several review studies have been undertaken regarding the effects of omega-3 on HF. These studies have assessed only a few outcomes, such as mortality and hospitalization.[16,19,23] They also reviewed the physiological effects and mechanism of omega-3 in HF patients.[16,19,23] However, clinical research has suggested that omega-3 may have an impact on a range of other HF-related outcomes. These include MI, stroke,[24,25] revascularization, and cardiac function in HF,[26,27] which have not been considered in previous studies.[13,14] In addition, the use of complementary and alternative medicine, which includes dietary supplements for preventing and treating illness, is a multibillion-dollar industry. Patients with HF commonly resort to complementary and alternative medicine, even without substantial evidence. Generally, there is inadequate high-quality evidence to support the significant therapeutic impact of these therapies.[28] Therefore, for the first time, we aimed to offer a comprehensive systematic review encompassing various outcomes associated with omega-3 supplementation among patients with HF, which helps clinicians be aware of the potential effects of omega-3 supplementation on improving HF outcomes. On the other hand, it allows researchers to be aware of the knowledge gaps and to consider them through further trials.Backgrounds:Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits.A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials.The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events.Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.Heart failure (HF) is now a worldwide epidemic, with its prevalence and incidence increasing at a fast pace.[1] According to the American Heart Association data, 8.1 million individuals in the United States are currently suffering from this condition. By 2030, it is anticipated that the global incidence of HF will rise by 46%, emerging as a significant global health concern.[1] The World Health Organization (2016) has categorized HF as a major contributor to mortality in Europe, pinpointing diet, physical inactivity, smoking, alcohol consumption, hypertension, high cholesterol levels, excess weight, obesity, and diabetes as the primary risk factors. [1] HF is a consequence of various cardiovascular diseases (CVDs) and continues to be linked with a reduced quality of life (QoL), early mortality, and significant utilization of healthcare resources.[2-5] Despite the recent advancements in both pharmaceutical and interventional treatments, HF remains a leading cause of mortality and recurrent hospitalization.[6,7] It also serves as a predictor of lethality among geriatric patients.[8] Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have emerged as a vital category of dietary lipids that have demonstrated cardiovascular protective properties in HF patients.[3,9]Omega-3 polyunsaturated fatty acids obtained from marine sources (n-3 PUFAs), specifically Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have shown effectiveness in managing HF. Among the numerous nutraceuticals that have been studied for their potential impact on HF outcomes, only omega-3 PUFAs have received a favorable recommendation in the Australian HF guidelines.[10]Omega-3 fatty acids have shown an association with reducing myocardial fibrosis, left ventricular remodeling, and lowering systemic inflammation after myocardial infarction (MI). Additionally, significant decreases in events such as nonfatal MI, nonfatal stroke, cardiovascular-related deaths, coronary revascularization procedures, and unstable angina have been documented.[6] These findings carry particular importance since persistent inflammation is a significant contributor to the development of HF.[7,11,12] The most significant findings came from studies evaluating the impact of EPA/DHA supplementation on HF and other CVDs.[13] The researchers revealed the effectiveness of n-3 PUFA supplementation in preventing CVD events, such as HF and MI, with a particularly strong protective effect observed at higher dosage levels. However, accurately assessing the beneficial effects of n-3 PUFAs in clinical trials focusing on heterogeneous conditions like HF poses challenges. Several variables (e.g., race, age, sex, and dose of EPA/DHA) can influence the clinical outcomes in these trials. In addition, given the diverse effects of n-3 PUFAs in vivo, understanding their pathophysiologic effects on HF remains a complex endeavor.Significant benefits associated with the utilization of omega-3 in individuals with HF have been identified. Research has shown that omega-3 can lower the rate of patient readmissions.[14,15] Additionally, some studies have found that omega-3 supplementation can reduce mortality.[16,17] Multiple articles have confirmed the anti-inflammatory properties of omega-3.[16,18,19] Moreover, a limited set of studies has suggested that omega-3 supplementation may positively impact the QoL by ameliorating depressive symptoms among HF patients.[20-22] However, further investigations are necessary to draw a definitive conclusion.So far, several review studies have been undertaken regarding the effects of omega-3 on HF. These studies have assessed only a few outcomes, such as mortality and hospitalization.[16,19,23] They also reviewed the physiological effects and mechanism of omega-3 in HF patients.[16,19,23] However, clinical research has suggested that omega-3 may have an impact on a range of other HF-related outcomes. These include MI, stroke,[24,25] revascularization, and cardiac function in HF,[26,27] which have not been considered in previous studies.[13,14] In addition, the use of complementary and alternative medicine, which includes dietary supplements for preventing and treating illness, is a multibillion-dollar industry. Patients with HF commonly resort to complementary and alternative medicine, even without substantial evidence. Generally, there is inadequate high-quality evidence to support the significant therapeutic impact of these therapies.[28] Therefore, for the first time, we aimed to offer a comprehensive systematic review encompassing various outcomes associated with omega-3 supplementation among patients with HF, which helps clinicians be aware of the potential effects of omega-3 supplementation on improving HF outcomes. On the other hand, it allows researchers to be aware of the knowledge gaps and to consider them through further trials.Backgrounds:Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits.A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials.The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events.Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.Heart failure (HF) is now a worldwide epidemic, with its prevalence and incidence increasing at a fast pace.[1] According to the American Heart Association data, 8.1 million individuals in the United States are currently suffering from this condition. By 2030, it is anticipated that the global incidence of HF will rise by 46%, emerging as a significant global health concern.[1] The World Health Organization (2016) has categorized HF as a major contributor to mortality in Europe, pinpointing diet, physical inactivity, smoking, alcohol consumption, hypertension, high cholesterol levels, excess weight, obesity, and diabetes as the primary risk factors.[1] HF is a consequence of various cardiovascular diseases (CVDs) and continues to be linked with a reduced quality of life (QoL), early mortality, and significant utilization of healthcare resources.[2-5] Despite the recent advancements in both pharmaceutical and interventional treatments, HF remains a leading cause of mortality and recurrent hospitalization.[6,7] It also serves as a predictor of lethality among geriatric patients.[8] Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have emerged as a vital category of dietary lipids that have demonstrated cardiovascular protective properties in HF patients.[3,9]Omega-3 polyunsaturated fatty acids obtained from marine sources (n-3 PUFAs), specifically Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have shown effectiveness in managing HF. Among the numerous nutraceuticals that have been studied for their potential impact on HF outcomes, only omega-3 PUFAs have received a favorable recommendation in the Australian HF guidelines. [10]Omega-3 fatty acids have shown an association with reducing myocardial fibrosis, left ventricular remodeling, and lowering systemic inflammation after myocardial infarction (MI). Additionally, significant decreases in events such as nonfatal MI, nonfatal stroke, cardiovascular-related deaths, coronary revascularization procedures, and unstable angina have been documented.[6] These findings carry particular importance since persistent inflammation is a significant contributor to the development of HF.[7,11,12] The most significant findings came from studies evaluating the impact of EPA/DHA supplementation on HF and other CVDs.[13] The researchers revealed the effectiveness of n-3 PUFA supplementation in preventing CVD events, such as HF and MI, with a particularly strong protective effect observed at higher dosage levels. However, accurately assessing the beneficial effects of n-3 PUFAs in clinical trials focusing on heterogeneous conditions like HF poses challenges. Several variables (e.g., race, age, sex, and dose of EPA/DHA) can influence the clinical outcomes in these trials. In addition, given the diverse effects of n-3 PUFAs in vivo, understanding their pathophysiologic effects on HF remains a complex endeavor.Significant benefits associated with the utilization of omega-3 in individuals with HF have been identified. Research has shown that omega-3 can lower the rate of patient readmissions.[14,15] Additionally, some studies have found that omega-3 supplementation can reduce mortality.[16,17] Multiple articles have confirmed the anti-inflammatory properties of omega-3.[16,18,19] Moreover, a limited set of studies has suggested that omega-3 supplementation may positively impact the QoL by ameliorating depressive symptoms among HF patients.[20-22] However, further investigations are necessary to draw a definitive conclusion.So far, several review studies have been undertaken regarding the effects of omega-3 on HF. These studies have assessed only a few outcomes, such as mortality and hospitalization.[16,19,23] They also reviewed the physiological effects and mechanism of omega-3 in HF patients.[16,19,23] However, clinical research has suggested that omega-3 may have an impact on a range of other HF-related outcomes. These include MI, stroke,[24,25] revascularization, and cardiac function in HF,[26,27] which have not been considered in previous studies.[13,14] In addition, the use of complementary and alternative medicine, which includes dietary supplements for preventing and treating illness, is a multibillion-dollar industry. Patients with HF commonly resort to complementary and alternative medicine, even without substantial evidence. Generally, there is inadequate high-quality evidence to support the significant therapeutic impact of these therapies.[28] Therefore, for the first time, we aimed to offer a comprehensive systematic review encompassing various outcomes associated with omega-3 supplementation among patients with HF, which helps clinicians be aware of the potential effects of omega-3 supplementation on improving HF outcomes. On the other hand, it allows researchers to be aware of the knowledge gaps and to consider them through further trials.Backgrounds:Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits.A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials.The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events.Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.Heart failure (HF) is now a worldwide epidemic, with its prevalence and incidence increasing at a fast pace.[1] According to the American Heart Association data, 8.1 million individuals in the United States are currently suffering from this condition. By 2030, it is anticipated that the global incidence of HF will rise by 46%, emerging as a significant global health concern.[1] The World Health Organization (2016) has categorized HF as a major contributor to mortality in Europe, pinpointing diet, physical inactivity, smoking, alcohol consumption, hypertension, high cholesterol levels, excess weight, obesity, and diabetes as the primary risk factors.[1] HF is a consequence of various cardiovascular diseases (CVDs) and continues to be linked with a reduced quality of life (QoL), early mortality, and significant utilization of healthcare resources.[2-5] Despite the recent advancements in both pharmaceutical and interventional treatments, HF remains a leading cause of mortality and recurrent hospitalization.[6,7] It also serves as a predictor of lethality among geriatric patients.[8] Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have emerged as a vital category of dietary lipids that have demonstrated cardiovascular protective properties in HF patients.[3,9]Omega-3 polyunsaturated fatty acids obtained from marine sources (n-3 PUFAs), specifically Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have shown effectiveness in managing HF. Among the numerous nutraceuticals that have been studied for their potential impact on HF outcomes, only omega-3 PUFAs have received a favorable recommendation in the Australian HF guidelines.[10]Omega-3 fatty acids have shown an association with reducing myocardial fibrosis, left ventricular remodeling, and lowering systemic inflammation after myocardial infarction (MI). Additionally, significant decreases in events such as nonfatal MI, nonfatal stroke, cardiovascular-related deaths, coronary revascularization procedures, and unstable angina have been documented.[6] These findings carry particular importance since persistent inflammation is a significant contributor to the development of HF.[7,11,12] The most significant findings came from studies evaluating the impact of EPA/DHA supplementation on HF and other CVDs.[13] The researchers revealed the effectiveness of n-3 PUFA supplementation in preventing CVD events, such as HF and MI, with a particularly strong protective effect observed at higher dosage levels. However, accurately assessing the beneficial effects of n-3 PUFAs in clinical trials focusing on heterogeneous conditions like HF poses challenges. Several variables (e.g. , race, age, sex, and dose of EPA/DHA) can influence the clinical outcomes in these trials. In addition, given the diverse effects of n-3 PUFAs in vivo, understanding their pathophysiologic effects on HF remains a complex endeavor.Significant benefits associated with the utilization of omega-3 in individuals with HF have been identified. Research has shown that omega-3 can lower the rate of patient readmissions.[14,15] Additionally, some studies have found that omega-3 supplementation can reduce mortality.[16,17] Multiple articles have confirmed the anti-inflammatory properties of omega-3.[16,18,19] Moreover, a limited set of studies has suggested that omega-3 supplementation may positively impact the QoL by ameliorating depressive symptoms among HF patients.[20-22] However, further investigations are necessary to draw a definitive conclusion.So far, several review studies have been undertaken regarding the effects of omega-3 on HF. These studies have assessed only a few outcomes, such as mortality and hospitalization.[16,19,23] They also reviewed the physiological effects and mechanism of omega-3 in HF patients.[16,19,23] However, clinical research has suggested that omega-3 may have an impact on a range of other HF-related outcomes. These include MI, stroke,[24,25] revascularization, and cardiac function in HF,[26,27] which have not been considered in previous studies.[13,14] In addition, the use of complementary and alternative medicine, which includes dietary supplements for preventing and treating illness, is a multibillion-dollar industry. Patients with HF commonly resort to complementary and alternative medicine, even without substantial evidence. Generally, there is inadequate high-quality evidence to support the significant therapeutic impact of these therapies.[28] Therefore, for the first time, we aimed to offer a comprehensive systematic review encompassing various outcomes associated with omega-3 supplementation among patients with HF, which helps clinicians be aware of the potential effects of omega-3 supplementation on improving HF outcomes. On the other hand, it allows researchers to be aware of the knowledge gaps and to consider them through further trials.Backgrounds:Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits.A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials.The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events.Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.Heart failure (HF) is now a worldwide epidemic, with its prevalence and incidence increasing at a fast pace.[1] According to the American Heart Association data, 8. 1 million individuals in the United States are currently suffering from this condition. By 2030, it is anticipated that the global incidence of HF will rise by 46%, emerging as a significant global health concern.[1] The World Health Organization (2016) has categorized HF as a major contributor to mortality in Europe, pinpointing diet, physical inactivity, smoking, alcohol consumption, hypertension, high cholesterol levels, excess weight, obesity, and diabetes as the primary risk factors.[1] HF is a consequence of various cardiovascular diseases (CVDs) and continues to be linked with a reduced quality of life (QoL), early mortality, and significant utilization of healthcare resources.[2-5] Despite the recent advancements in both pharmaceutical and interventional treatments, HF remains a leading cause of mortality and recurrent hospitalization.[6,7] It also serves as a predictor of lethality among geriatric patients.[8] Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have emerged as a vital category of dietary lipids that have demonstrated cardiovascular protective properties in HF patients.[3,9]Omega-3 polyunsaturated fatty acids obtained from marine sources (n-3 PUFAs), specifically Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have shown effectiveness in managing HF. Among the numerous nutraceuticals that have been studied for their potential impact on HF outcomes, only omega-3 PUFAs have received a favorable recommendation in the Australian HF guidelines.[10]Omega-3 fatty acids have shown an association with reducing myocardial fibrosis, left ventricular remodeling, and lowering systemic inflammation after myocardial infarction (MI). Additionally, significant decreases in events such as nonfatal MI, nonfatal stroke, cardiovascular-related deaths, coronary revascularization procedures, and unstable angina have been documented.[6] These findings carry particular importance since persistent inflammation is a significant contributor to the development of HF.[7,11,12] The most significant findings came from studies evaluating the impact of EPA/DHA supplementation on HF and other CVDs.[13] The researchers revealed the effectiveness of n-3 PUFA supplementation in preventing CVD events, such as HF and MI, with a particularly strong protective effect observed at higher dosage levels. However, accurately assessing the beneficial effects of n-3 PUFAs in clinical trials focusing on heterogeneous conditions like HF poses challenges. Several variables (e.g., race, age, sex, and dose of EPA/DHA) can influence the clinical outcomes in these trials. In addition, given the diverse effects of n-3 PUFAs in vivo, understanding their pathophysiologic effects on HF remains a complex endeavor.Significant benefits associated with the utilization of omega-3 in individuals with HF have been identified. Research has shown that omega-3 can lower the rate of patient readmissions.[14,15] Additionally, some studies have found that omega-3 supplementation can reduce mortality.[16,17] Multiple articles have confirmed the anti-inflammatory properties of omega-3.[16,18,19] Moreover, a limited set of studies has suggested that omega-3 supplementation may positively impact the QoL by ameliorating depressive symptoms among HF patients.[20-22] However, further investigations are necessary to draw a definitive conclusion.So far, several review studies have been undertaken regarding the effects of omega-3 on HF. These studies have assessed only a few outcomes, such as mortality and hospitalization. [16,19,23] They also reviewed the physiological effects and mechanism of omega-3 in HF patients.[16,19,23] However, clinical research has suggested that omega-3 may have an impact on a range of other HF-related outcomes. These include MI, stroke,[24,25] revascularization, and cardiac function in HF,[26,27] which have not been considered in previous studies.[13,14] In addition, the use of complementary and alternative medicine, which includes dietary supplements for preventing and treating illness, is a multibillion-dollar industry. Patients with HF commonly resort to complementary and alternative medicine, even without substantial evidence. Generally, there is inadequate high-quality evidence to support the significant therapeutic impact of these therapies.[28] Therefore, for the first time, we aimed to offer a comprehensive systematic review encompassing various outcomes associated with omega-3 supplementation among patients with HF, which helps clinicians be aware of the potential effects of omega-3 supplementation on improving HF outcomes. On the other hand, it allows researchers to be aware of the knowledge gaps and to consider them through further trials.Backgrounds:Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits.A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials.The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events.Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.Heart failure (HF) is now a worldwide epidemic, with its prevalence and incidence increasing at a fast pace.[1] According to the American Heart Association data, 8.1 million individuals in the United States are currently suffering from this condition. By 2030, it is anticipated that the global incidence of HF will rise by 46%, emerging as a significant global health concern.[1] The World Health Organization (2016) has categorized HF as a major contributor to mortality in Europe, pinpointing diet, physical inactivity, smoking, alcohol consumption, hypertension, high cholesterol levels, excess weight, obesity, and diabetes as the primary risk factors.[1] HF is a consequence of various cardiovascular diseases (CVDs) and continues to be linked with a reduced quality of life (QoL), early mortality, and significant utilization of healthcare resources.[2-5] Despite the recent advancements in both pharmaceutical and interventional treatments, HF remains a leading cause of mortality and recurrent hospitalization.[6,7] It also serves as a predictor of lethality among geriatric patients. [8] Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have emerged as a vital category of dietary lipids that have demonstrated cardiovascular protective properties in HF patients.[3,9]Omega-3 polyunsaturated fatty acids obtained from marine sources (n-3 PUFAs), specifically Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have shown effectiveness in managing HF. Among the numerous nutraceuticals that have been studied for their potential impact on HF outcomes, only omega-3 PUFAs have received a favorable recommendation in the Australian HF guidelines.[10]Omega-3 fatty acids have shown an association with reducing myocardial fibrosis, left ventricular remodeling, and lowering systemic inflammation after myocardial infarction (MI). Additionally, significant decreases in events such as nonfatal MI, nonfatal stroke, cardiovascular-related deaths, coronary revascularization procedures, and unstable angina have been documented.[6] These findings carry particular importance since persistent inflammation is a significant contributor to the development of HF.[7,11,12] The most significant findings came from studies evaluating the impact of EPA/DHA supplementation on HF and other CVDs.[13] The researchers revealed the effectiveness of n-3 PUFA supplementation in preventing CVD events, such as HF and MI, with a particularly strong protective effect observed at higher dosage levels. However, accurately assessing the beneficial effects of n-3 PUFAs in clinical trials focusing on heterogeneous conditions like HF poses challenges. Several variables (e.g., race, age, sex, and dose of EPA/DHA) can influence the clinical outcomes in these trials. In addition, given the diverse effects of n-3 PUFAs in vivo, understanding their pathophysiologic effects on HF remains a complex endeavor.Significant benefits associated with the utilization of omega-3 in individuals with HF have been identified. Research has shown that omega-3 can lower the rate of patient readmissions.[14,15] Additionally, some studies have found that omega-3 supplementation can reduce mortality.[16,17] Multiple articles have confirmed the anti-inflammatory properties of omega-3.[16,18,19] Moreover, a limited set of studies has suggested that omega-3 supplementation may positively impact the QoL by ameliorating depressive symptoms among HF patients.[20-22] However, further investigations are necessary to draw a definitive conclusion.So far, several review studies have been undertaken regarding the effects of omega-3 on HF. These studies have assessed only a few outcomes, such as mortality and hospitalization.[16,19,23] They also reviewed the physiological effects and mechanism of omega-3 in HF patients.[16,19,23] However, clinical research has suggested that omega-3 may have an impact on a range of other HF-related outcomes. These include MI, stroke,[24,25] revascularization, and cardiac function in HF,[26,27] which have not been considered in previous studies.[13,14] In addition, the use of complementary and alternative medicine, which includes dietary supplements for preventing and treating illness, is a multibillion-dollar industry. Patients with HF commonly resort to complementary and alternative medicine, even without substantial evidence. Generally, there is inadequate high-quality evidence to support the significant therapeutic impact of these therapies. [28] Therefore, for the first time, we aimed to offer a comprehensive systematic review encompassing various outcomes associated with omega-3 supplementation among patients with HF, which helps clinicians be aware of the potential effects of omega-3 supplementation on improving HF outcomes. On the other hand, it allows researchers to be aware of the knowledge gaps and to consider them through further trials.Backgrounds:Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits.A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials.The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events.Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.Heart failure (HF) is now a worldwide epidemic, with its prevalence and incidence increasing at a fast pace.[1] According to the American Heart Association data, 8.1 million individuals in the United States are currently suffering from this condition. By 2030, it is anticipated that the global incidence of HF will rise by 46%, emerging as a significant global health concern.[1] The World Health Organization (2016) has categorized HF as a major contributor to mortality in Europe, pinpointing diet, physical inactivity, smoking, alcohol consumption, hypertension, high cholesterol levels, excess weight, obesity, and diabetes as the primary risk factors.[1] HF is a consequence of various cardiovascular diseases (CVDs) and continues to be linked with a reduced quality of life (QoL), early mortality, and significant utilization of healthcare resources.[2-5] Despite the recent advancements in both pharmaceutical and interventional treatments, HF remains a leading cause of mortality and recurrent hospitalization.[6,7] It also serves as a predictor of lethality among geriatric patients.[8] Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have emerged as a vital category of dietary lipids that have demonstrated cardiovascular protective properties in HF patients.[3,9]Omega-3 polyunsaturated fatty acids obtained from marine sources (n-3 PUFAs), specifically Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have shown effectiveness in managing HF. Among the numerous nutraceuticals that have been studied for their potential impact on HF outcomes, only omega-3 PUFAs have received a favorable recommendation in the Australian HF guidelines.[10]Omega-3 fatty acids have shown an association with reducing myocardial fibrosis, left ventricular remodeling, and lowering systemic inflammation after myocardial infarction (MI). Additionally, significant decreases in events such as nonfatal MI, nonfatal stroke, cardiovascular-related deaths, coronary revascularization procedures, and unstable angina have been documented.[6] These findings carry particular importance since persistent inflammation is a significant contributor to the development of HF.[7,11,12] The most significant findings came from studies evaluating the impact of EPA/DHA supplementation on HF and other CVDs.[13] The researchers revealed the effectiveness of n-3 PUFA supplementation in preventing CVD events, such as HF and MI, with a particularly strong protective effect observed at higher dosage levels. However, accurately assessing the beneficial effects of n-3 PUFAs in clinical trials focusing on heterogeneous conditions like HF poses challenges. Several variables (e.g., race, age, sex, and dose of EPA/DHA) can influence the clinical outcomes in these trials. In addition, given the diverse effects of n-3 PUFAs in vivo, understanding their pathophysiologic effects on HF remains a complex endeavor.Significant benefits associated with the utilization of omega-3 in individuals with HF have been identified. Research has shown that omega-3 can lower the rate of patient readmissions.[14,15] Additionally, some studies have found that omega-3 supplementation can reduce mortality.[16,17] Multiple articles have confirmed the anti-inflammatory properties of omega-3.[16,18,19] Moreover, a limited set of studies has suggested that omega-3 supplementation may positively impact the QoL by ameliorating depressive symptoms among HF patients.[20-22] However, further investigations are necessary to draw a definitive conclusion.So far, several review studies have been undertaken regarding the effects of omega-3 on HF. These studies have assessed only a few outcomes, such as mortality and hospitalization.[16,19,23] They also reviewed the physiological effects and mechanism of omega-3 in HF patients.[16,19,23] However, clinical research has suggested that omega-3 may have an impact on a range of other HF-related outcomes. These include MI, stroke,[24,25] revascularization, and cardiac function in HF,[26,27] which have not been considered in previous studies.[13,14] In addition, the use of complementary and alternative medicine, which includes dietary supplements for preventing and treating illness, is a multibillion-dollar industry. Patients with HF commonly resort to complementary and alternative medicine, even without substantial evidence. Generally, there is inadequate high-quality evidence to support the significant therapeutic impact of these therapies.[28] Therefore, for the first time, we aimed to offer a comprehensive systematic review encompassing various outcomes associated with omega-3 supplementation among patients with HF, which helps clinicians be aware of the potential effects of omega-3 supplementation on improving HF outcomes. On the other hand, it allows researchers to be aware of the knowledge gaps and to consider them through further trials.Backgrounds:Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits.A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials. The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events.Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.Heart failure (HF) is now a worldwide epidemic, with its prevalence and incidence increasing at a fast pace.[1] According to the American Heart Association data, 8.1 million individuals in the United States are currently suffering from this condition. By 2030, it is anticipated that the global incidence of HF will rise by 46%, emerging as a significant global health concern.[1] The World Health Organization (2016) has categorized HF as a major contributor to mortality in Europe, pinpointing diet, physical inactivity, smoking, alcohol consumption, hypertension, high cholesterol levels, excess weight, obesity, and diabetes as the primary risk factors.[1] HF is a consequence of various cardiovascular diseases (CVDs) and continues to be linked with a reduced quality of life (QoL), early mortality, and significant utilization of healthcare resources.[2-5] Despite the recent advancements in both pharmaceutical and interventional treatments, HF remains a leading cause of mortality and recurrent hospitalization.[6,7] It also serves as a predictor of lethality among geriatric patients.[8] Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have emerged as a vital category of dietary lipids that have demonstrated cardiovascular protective properties in HF patients.[3,9]Omega-3 polyunsaturated fatty acids obtained from marine sources (n-3 PUFAs), specifically Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have shown effectiveness in managing HF. Among the numerous nutraceuticals that have been studied for their potential impact on HF outcomes, only omega-3 PUFAs have received a favorable recommendation in the Australian HF guidelines.[10]Omega-3 fatty acids have shown an association with reducing myocardial fibrosis, left ventricular remodeling, and lowering systemic inflammation after myocardial infarction (MI). Additionally, significant decreases in events such as nonfatal MI, nonfatal stroke, cardiovascular-related deaths, coronary revascularization procedures, and unstable angina have been documented.[6] These findings carry particular importance since persistent inflammation is a significant contributor to the development of HF.[7,11,12] The most significant findings came from studies evaluating the impact of EPA/DHA supplementation on HF and other CVDs.[13] The researchers revealed the effectiveness of n-3 PUFA supplementation in preventing CVD events, such as HF and MI, with a particularly strong protective effect observed at higher dosage levels. However, accurately assessing the beneficial effects of n-3 PUFAs in clinical trials focusing on heterogeneous conditions like HF poses challenges. Several variables (e.g., race, age, sex, and dose of EPA/DHA) can influence the clinical outcomes in these trials. In addition, given the diverse effects of n-3 PUFAs in vivo, understanding their pathophysiologic effects on HF remains a complex endeavor. Significant benefits associated with the utilization of omega-3 in individuals with HF have been identified. Research has shown that omega-3 can lower the rate of patient readmissions.[14,15] Additionally, some studies have found that omega-3 supplementation can reduce mortality.[16,17] Multiple articles have confirmed the anti-inflammatory properties of omega-3.[16,18,19] Moreover, a limited set of studies has suggested that omega-3 supplementation may positively impact the QoL by ameliorating depressive symptoms among HF patients.[20-22] However, further investigations are necessary to draw a definitive conclusion.So far, several review studies have been undertaken regarding the effects of omega-3 on HF. These studies have assessed only a few outcomes, such as mortality and hospitalization.[16,19,23] They also reviewed the physiological effects and mechanism of omega-3 in HF patients.[16,19,23] However, clinical research has suggested that omega-3 may have an impact on a range of other HF-related outcomes. These include MI, stroke,[24,25] revascularization, and cardiac function in HF,[26,27] which have not been considered in previous studies.[13,14] In addition, the use of complementary and alternative medicine, which includes dietary supplements for preventing and treating illness, is a multibillion-dollar industry. Patients with HF commonly resort to complementary and alternative medicine, even without substantial evidence. Generally, there is inadequate high-quality evidence to support the significant therapeutic impact of these therapies.[28] Therefore, for the first time, we aimed to offer a comprehensive systematic review encompassing various outcomes associated with omega-3 supplementation among patients with HF, which helps clinicians be aware of the potential effects of omega-3 supplementation on improving HF outcomes. On the other hand, it allows researchers to be aware of the knowledge gaps and to consider them through further trials.