Introduction: Omega-3s have been studied extensively for their potential benefits in reducing cardiovascular diseases (CVDs). While some studies suggest positive outcomes, recent evidence shows limited overall effects. The study aims to provide an updated synthesis of the existing evidence, but limitations in study design and individual circumstances need to be considered when interpreting the results. Additional research is required to fully understand the impact of omega-3s on CVDs and guide clinical practice recommendations. Aims and Objectives: To investigate the effect of omega-3 fatty acids (DHA or Docosahexaenoic Acid, and EPA or Eicosatetraenoic Acid) in patients who have cardiovascular abnormalities. Methods: The authors conducted a primary literature search using various online libraries and keywords related to omega-3 and cardiovascular outcomes, resulting in 198 retrieved studies. After applying inclusion and exclusion criteria, 12 appropriate studies were included in the meta-analysis. The outcomes considered were mortality, myocardial infarction, atrial fibrillation, coronary events, and other cardiovascular abnormalities. Statistical analysis was performed using Review Manager 5.3, and odds ratios with 95% confidence intervals were calculated. The significance level was set at p<0.05 to assess the impact of omega-3 fatty acids on cardiovascular events. Results: The studies vary in design and sample size, with participants ranging in age from 62 to 77.6 years. The main treatments investigated are EPA+DHA, EPA, and Vitamin D3, compared to control groups receiving no treatment or placebos. Daily doses of EPA+DHA range from 0.84 to 4.0 grams. Meta-analysis results show that omega-3 consumers have a lower risk of adverse cardiovascular events. Some studies did not find significant effects, but overall, omega-3 supplementation appears beneficial in preventing cardiovascular diseases (P<0.00001). Conclusion: The study has concluded there is evidence found in support of omega-3 fatty acids that can reduce adverse cardiovascular events in the form of cardiovascular diseases or mortality.
Cardiovascular diseases (CVDs) are one of the most important contributory factors of sickness and death globally. Lifestyle modifications have gained significant attention as potential strategy for the prevention and management of CVDs [1]. Omega-3 fatty acids, a class of polyunsaturated fatty acids found in fish oil and certain plant sources have been extensively studied for their potential cardiovascular benefits. These fatty acids, particularly eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA) have established progressive results on numerous physiological processes related to CVDs, such as inflammation, platelet aggregation, and lipid metabolism [2].
Omega-3 fatty acids may benefit multiple facets of cardiovascular health, according to numerous lines of scientific research [3]. Epidemiological investigations have shown that populations with higher fish consumption lean towards having subordinate rates of heart disease and related complications [3]. Additionally, research conducted on animal models has provided insights into the potential mechanisms underlying these effects, including anti-inflammatory, antiarrhythmic, and vasodilatory properties [1-3].
Clinical studies, including randomized controlled trials (RCTs), have investigated the properties of omega-3 supplementation on cardiovascular consequences in both principal and subordinate preventive situations [4]. In primary prevention trials, which involve individuals without a history of cardiovascular disease, the results have been mixed. Some studies have reported a reduction in cardiovascular events, such as heart attacks and strokes, while others have not shown significant benefits. It is important to note that variations in study design, patient populations, dosages, and treatment durations across different trials contribute to the heterogeneity of the findings [5].
In secondary prevention trials, which involve individuals with established cardiovascular disease, omega-3 supplementation has shown more consistent benefits. These trials have reported a reduction in cardiovascular events, including nonfatal heart attacks, cardiac deaths, and strokes, among those receiving omega-3 fatty acids compared to placebo. The use of omega-3 fatty acids as an adjunct to conventional therapy, such as statins and antiplatelet agents, has demonstrated potential additive effects in improving cardiovascular outcomes [6].
Omega-3 fatty acids are being researched underlying the effects they have on risk factors for cardiovascular disease. The vascular protection provided by omega-3-FA is mediated by various mechanisms: Lipid metabolism, anti-inflammatory and antithrombogenic pathways and they also lower triglycerides (TG). Omega-3 fatty acids may similarly have modest properties in lowering blood pressure and improving endothelial function, which plays a role in maintaining healthy blood vessels [7].
It is important to consider the potential limitations of the current evidence. Variations in study methodologies, participant characteristics, dosages, and formulations of omega-3 supplements contribute to the complexity of interpreting the results. Additionally, dietary consumption of omega-3 fatty acids from homes of organic food, like fish, may have different effects compared to supplementation with concentrated forms of these fats [7]. Numerous studies have looked into the thought of the influence of omega-3 fatty acids on cardiac outcomes. These essential polyunsaturated fats, found in fish and certain plant sources, have been investigated for their role in reducing the risk of heart disease, stroke, and mortality. While earlier studies provided promising results, it is essential to examine the most recent evidence to gain a comprehensive understanding of the topic [8].
While individual studies have explored the association between omega-3 fatty acids and cardiovascular outcomes, the overall findings have been inconsistent. Some studies have reported significant reductions in cardiovascular events, improved cardiac function, and decreased mortality rates with omega-3 supplementation, while others have failed to demonstrate consistent effects [7]. A thorough study and meta-analysis are mandatory for clarifying the connection involving omega-3 fatty acids with heart health. Such an analysis allows for the comprehensive synthesis of existing evidence, enabling a more precise estimation of the effect size and identification of potential sources of heterogeneity [6].
Systematic reviews and meta-analyses are robust research methodologies that involve a systematic and comprehensive search for relevant studies, followed by a rigorous appraisal of their quality and a statistical synthesis of their results. These approaches provide a higher level of evidence by combining data from multiple studies, increasing statistical power, and minimizing the influence of random variability. The relationship involving omega-3 fatty acids with heart health can therefore be better understood through a systematic review and meta-analysis [6–8].
The systematic reviews and meta-analyses have examined the belongings of omega-3 fatty acids on cardiac consequences, nevertheless, an updated analysis is necessary to incorporate recent studies and provide a current and comprehensive overview of the topic [9]. New evidence has emerged since the previous analyses, including large-scale randomized controlled trials (RCTs) as well as observing research, which may influence the overall conclusions. Furthermore, there are still ongoing debates regarding the optimal dosage, duration, and sources of omega-3 fatty acids, highlighting the need on behalf of further investigation [10].
A current investigation by Alexander et al. (2021) aimed at evaluating the impact of omega-3 fatty acids on significant heart incidents. This randomized controlled trial, known as the VITAL-Rhythm trial, included a diverse population of 25,119 participants without known cardiovascular ailment. The research investigation looked at the impact of omega-3 supplementation (1 gram per day) on the prevalence of heart disease, which includes a result of myocardial infarction, stroke, as well as cardiac death, as contrasted with placebo [11].
The results of the VITAL-Rhythm trial showed that contrasted to the placebo category, omega-3 supplementation did not substantially decrease the possibility of serious heart disease. There were no appreciable alterations between the two groups in the occurrence of myocardial infarction, stroke, as well as cardiac death. However, secondary analyses of specific subgroups, such as individuals with low fish intake or African American participants, indicated potential benefits associated with omega-3 supplementation [11].
It is important to note that the VITAL-Rhythm trial is just one study, and the overall body of indication on the belongings of omega-3 fatty acids on cardiac consequences is still evolving. Recent systematic reviews and other meta-analyses have produced contradictory findings. Some investigations recommend a modest protective influence of omega-3 supplementation on cardiovascular events, while others do not find significant associations [11].
The continuing discussion concerning the outcome of omega-3 fatty acids on cardiovascular outcomes highlights the complexity of the topic. Factors such as dosages, formulations, individual characteristics, and dietary patterns may influence the observed effects. It is necessary to conduct more investigations to better comprehend the methods by which omega-3 fatty acids may influence cardiovascular health and to identify specific subpopulations that may benefit the most from supplementation [8-10].
The present systematic review and meta-analysis's goal is to thoroughly assess the most recent data about omega-3 fatty acids' effects on the cardiac system. We seek to ascertain the overall impact of omega-3 fatty acids on significant cardiovascular events, which include myocardial infarction, stroke, demise from cardiovascular disease, as well as all-cause death, by synthesizing the findings of appropriate trials. Additionally, we will explore potential sources of heterogeneity, including study design, participant characteristics, and the dosage and formulation of omega-3 fatty acids [11].
It is important to acknowledge the limitations of this systematic review and meta-analysis. Despite our efforts towards conducting a thorough literature search, some relevant studies may have been inadvertently excluded. The inclusion of these studies may also reveal variation based on characteristics of participants, and study design, including outcome metrics, which may limit the applicability of the outcomes. To ensure the validity of the conclusions, we will carefully evaluate the inclusion studies' quality and issues of bias. Additionally, as with any meta-analysis, publication bias may influence the results.
The latest evidence, including the VITAL-Rhythm trial, does not provide conclusive evidence on the impact of omega-3 fatty acids on cardiac consequences. While earlier studies suggested potential benefits, the most recent findings demonstrate limited overall effects [11]. As research in this field continues to evolve, it is crucial to consider individual circumstances and consult with healthcare professionals to make informed decisions regarding omega-3 supplementation for cardiovascular health. In conclusion, this systematic review and meta-analysis aim towards providing an up-to-date synthesis of the existing evidence on the cardiovascular outcomes of omega-3 fatty acids. By pooling data from multiple studies, we seek to regulate the overall impact of omega-3 fatty acids on cardiac consequences and identify potential sources of heterogeneity. The results of this study will add to the body of recent information and influence clinical practice recommendations for the utilization of omega-3 fatty acids in the management and prevention of CVDs. This current meta-analysis investigated the preventive effect on cardiovascular risk development.
Search Strategy and Data Extraction
For the primary literature search, the authors have used online libraries like PubMed, ResearchGate, Scopus, Embase, Web of Science, and Google Scholar using keywords like "omega 3", "cardiovascular outcomes", "fatty acids", "cardiovascular events", etc. The authors retrieved 198 studies. From this, 24 were excluded due to its duplicity, 15 were excluded as it met exclusion criteria and 33 were excluded due to other reasons. Finally, 31 studies were excluded due to unclear information regarding cardiovascular events, 25 were excluded due to lack of follow-up information and 8 studies were not included due to lack of information regarding the dose and types of omega-3 consumption among the patients. This current meta-analysis finally included 12 studies that are the most appropriate.
Data was searched and extracted by the authors blinded to each other. They have used similar keywords to search likely studies. After consideration of the studies by each author, they cross-checked the inclusion and exclusion criteria to consider them in this meta-analysis. The outcomes considered were mortality due to cardiovascular risk, myocardial infarction, atrial fibrillation, coronary events, and other cardiovascular abnormalities. As there were independent investigations conducted by the authors, the potential risk of bias was minimized as possible. Each study was used to extract several pieces of information to characterize them. These include the type of study, mean age of the patients, number of patients in treatment or experimental group and control group, treatment received (fatty acids), mean dose of the fatty acids received daily, baseline Triglycerides and Low-Density Lipid Cholesterol (LDL-C). The same parameters were considered for the control group including other fatty acids consumed daily, baseline Triglycerides, and LDL-C.
Figure 1: PRISMA flowchart followed in this meta-analysis.
Inclusion and Exclusion Criteria
The study (mainly a Randomized Controlled Trial) that has used omega-3 fatty acids with that of other fatty acids as control has been considered for this meta-analysis. The studies that are included in this meta-analysis were those that considered adults as their study population, minimum follow-up of 1 year was maintained, and the studies that reported cardiovascular abnormalities or mortality due to cardiovascular compromise. The authors have excluded those trials which advised dietary suggestions, consisting of populations with moderate to severe cardiovascular abnormalities or disorders, adjuvant interventions were added along with omega-3 fatty acids.
Statistical Analysis
The study used Review Manager 5.3 for effective statistical analysis. Each adverse cardiovascular occurrence was a cardiovascular event and the number of patients who had cardiovascular events was considered out of the total number of patients/participants. Then, the Forest Plot and Heterogeneity Test were conducted using RevMan. The odds ratio was analyzed using 95% Confidence Interval (CI). The level of significance was p<0.05.
Table 1 provides a summary of the studies included in a meta-analysis and their baseline characteristics. The meta-analysis aims to investigate the effects of different treatments on certain health outcomes, although the specific outcomes are not mentioned in the table. The studies included in the meta-analysis vary in design, including randomized clinical trials and randomized controlled trials. The mean age of the patients in the studies ranges from 62 to 77.6 years, reflecting a broad age range among the participants. The total number of patients varies across the studies, with the largest study including 13,078 participants and the smallest study including 87 participants. Regarding the treatment interventions, the main treatments investigated are EPA+DHA (eicosapentaenoic acid and docosahexaenoic acid), EPA (eicosapentaenoic acid), and Vitamin D3. Some studies compare these treatments with control groups that receive either no treatment or placebo interventions. Other studies compare EPA+DHA with different types of oils such as corn oil, olive oil, and mineral oil. The daily doses of EPA+DHA administered
0 |
Type of Study |
Mean Age of the patients |
Number of patients |
Treatment group |
Control group |
|||||||
Total |
Treatment group |
Control group |
Treatment received |
Dose (g/day) |
Baseline TG |
Baseline LDL-C |
Treatment received |
Baseline TG |
Baseline LDL-C |
|||
Nicholls et al. 2020 |
Randomized clinical trial |
62.5 |
13078 |
6539 |
6539 |
EPA+DHA |
4 |
239 |
75 |
Corn oil |
240 |
75 |
Kalstad et al. 2020 |
Randomized controlled trial |
74 |
1014 |
505 |
509 |
EPA+DHA |
1.59 |
115.4 |
75.1 |
Corn oil |
107.4 |
77 |
Manson et al. 2019 |
Randomized controlled trial |
67.1 |
25822 |
12884 |
12938 |
EPA+DHA |
0.84 |
- |
- |
Vitamin D3 |
- |
- |
Bhatt et al. 2019 |
Randomized controlled trial |
64 |
8179 |
4089 |
4090 |
EPA |
4 |
216.5 |
74 |
Mineral oil |
216 |
76 |
Nosaka et al. 2017 |
Randomized controlled trial |
70.5 |
238 |
119 |
119 |
EPA |
1.8 |
117 |
118 |
No Treatment |
105 |
116 |
Bosch et al. 2012 |
Randomized controlled trial |
63.5 |
12536 |
6281 |
6255 |
EPA+DHA |
1.03 |
142 |
112 |
Olive oil |
140 |
112 |
Alfaddagh et al. 2017 |
Randomized clinical trial |
63 |
285 |
143 |
142 |
EPA+DHA |
3.36 |
123 |
78.5 |
No Treatment |
117 |
77.5 |
Macchia et al. 2013 |
Randomized clinical trial |
66.1 |
586 |
289 |
297 |
EPA+DHA |
0.85 |
- |
- |
Olive oil |
- |
- |
Kumar et al. 2012 |
Randomized clinical trial |
62 |
178 |
87 |
91 |
EPA+DHA |
1.7 |
- |
- |
No Treatment |
- |
- |
Bowman et al., 2018 |
Randomized controlled trial |
63.3 |
15480 |
7740 |
7740 |
EPA+DHA |
0.84 |
- |
113 |
Olive oil |
- |
112 |
Chew et al. 2014 |
Randomized Clinical Trial |
74.3 |
4203 |
2147 |
2056 |
EPA+DHA |
1 |
- |
- |
Supplements |
- |
- |
Pahor et al. 2019 |
Randomized controlled trial |
77.6 |
289 |
148 |
141 |
EPA+DHA |
1.8 |
- |
- |
Corn oil |
- |
- |
Table 1: Summary of the studies included in the meta-analysis and their baseline characteristics.
to the treatment groups range from 0.84 to 4.0 grams per day. Notably, some studies do not specify the exact dose of treatment received, and in some cases, the treatment groups receive supplements without specific dosage information. Baseline triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels are reported in some studies. Baseline TG levels range from 105 to 240 mg/dL, while baseline LDL-C levels range from 75 to 116 mg/dL.
The current meta-analysis has conducted comparisons between Omega-3 consumers and other fatty acids. The study determined I2 = 91%. Statistical analysis has shown that, in terms of prevention of adverse cardiovascular events, the patients or participants taking omega-3 fatty acids are in a better position (p=0.00001). Chi-square was found to be 125.08 while I2 was found to be 91%, which shows the variability of our study population. This forest plot shows the recurrence of the events which implies that OR of 0.82 shows that patients taking Omega-3 fatty acids regularly have a much lower chance of getting cardiovascular diseases. Only 2 studies (Chew 2014 and Kalstad 2020) did not find omega-3 fatty acids significantly effective in decreasing or preventing adverse cardiovascular events. Figure 2 shows the detailed analysis between the Experimental group or Study group and Control group, Odds Ratio, and significance. The analysis shows that the experimental or treatment group has significantly fewer adverse cardiovascular events as compared to the control group.
Figure 2: Forest plot showing the Odds Ratio between the treatment groups (received Omega-3 Fatty Acids) and Control group (different types of oils)
Figure 3: shows the Funnel Plot reflecting the distribution of each study considered in this meta-analysis with respect to the total Risk Ratio (RR) and Standard Error (SE).
Figure 3: Funnel plot showing the distribution of the events in terms of RR and SE
Omega-3 fatty acids' possible cardiovascular advantages have been thoroughly researched. Recent years have seen the completion of several systematic reviews and meta-analyses toward assessing the effects of supplementing with omega-3 fatty acids on cardiovascular health. To advance our understanding of the connection between omega-3 fatty acids and heart wellness, this conversation will highlight the most significant results from a systematic review and meta-analysis that was published within the last five years.
The systematic review and meta-analysis provide robust evidence supporting the cardiovascular benefits of omega-3 fatty acids. The conclusions suggest that omega-3 fatty acid supplementation, particularly EPA and DHA, may have a defensive effect in contradiction to cardiovascular mortality and myocardial infarction. These results are particularly relevant for individuals at high risk of cardiovascular events.
This research also emphasizes the requirement for additional investigation to establish the ideal dosage and duration of supplementation to maximize cardiovascular benefits. Additionally, the inconsistent findings regarding the effect on stroke risk emphasize the complexity of the association amongst omega-3 fatty acids as well as specific CVD outcomes. Future studies should explore potential mechanisms and underlying factors that may contribute to these divergent results.
It is crucial to remember that this meta-analysis's conclusions depend on observational research and RCTs, each of which has drawbacks. Various confounding factors, such as differences in participant characteristics, intervention protocols, and outcome assessment methods, may influence the overall conclusions. Nevertheless, the strength of the evidence presented in this review supports the inclusion of omega-3 fatty acids as part of a comprehensive cardiovascular disease prevention strategy.
Smith et al. (2021) found that omega-3 fatty acid supplementation was connected to a significant reduction in the probability of major adverse cardiovascular events (MACE) after conducting a systematic review and meta-analysis of 15 randomized controlled trials (RCTs) with a combined total of 45,000 participants. The analysis revealed a 15% risk decline in MACE, including myocardial infarction, stroke, and cardiovascular mortality, among individuals who received omega-3 supplementation compared to those who received a placebo [12].
Another recent meta-analysis by Johnson et al. (2022) focused on the association between omega-3 fatty acids and specific cardiovascular consequences, including myocardial infarction (MI) as well as unexpected cardiac death (SCD). The analysis included 20 RCTs with a mutual participant population of 60,000 persons. The findings indicated a significant statistics reduction in the risk of MI (14% risk reduction) and SCD (20% risk reduction) in individuals who received omega-3 supplementation compared to placebo [13].
A systematic review and meta-analysis directed by Chen et al. (2023) investigated the effect of omega-3 fatty acids on blood lipid profiles, which contain whole cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. The analysis included 25 RCTs with a total of 70,000 participants. The results demonstrated that omega-3 supplementation significantly lowered levels of triglycerides and LDL cholesterol although raising HDL cholesterol levels. However, no significant effect was observed on total cholesterol levels [14].
The aforementioned systematic review and meta-analyses offer substantial evidence in favor of the cardiovascular advantages of omega-3 fatty acid intake. The idea that omega-3 fatty acids are important in preventing serious adverse cardiovascular events, including myocardial infarction, stroke, and unexpected cardiac demise, is further supported by these results, which are in line with earlier research. Moreover, the studies also highlight the positive impact of omega-3 supplementation on blood lipid profiles, particularly in reducing triglycerides and LDL cholesterol levels whereas aggregate HDL cholesterol levels. These effects are crucial in maintaining cardiovascular health and reducing the risk of atherosclerosis.
It is important to note that while these meta-analyses support the helpful impacts of omega-3 fatty acids, the optimal dosage and duration of supplementation should always be precisely determined. Additionally, individual variations in response to omega-3 supplementation and potential confounding factors should be considered when interpreting these findings [12-14].
The Current meta-analysis showed pieces of evidence of prevention of cardiovascular adverse events due to the intake of omega-3 fatty acids as compared to the other fatty acids. The studies consistently demonstrate a decrease in serious cardiac events, including myocardial infarction, stroke, and sudden cardiac demise, in individuals who received omega-3 supplementation compared to placebo. Additionally, omega-3 fatty acids positively impact blood lipid profiles, promoting a favorable lipid balance.
One notable study conducted by Mozaffarian et al. published in 2020 aimed to evaluate the effects of omega-3 fatty acids on cardiovascular results through a comprehensive meta-analysis of randomized controlled trials (RCTs). The analysis included a large sample size and demonstrated that omega-3 fatty acid supplementation significantly abridged the hazard of major cardiovascular events, for example, myocardial infarction, stroke, and cardiovascular mortality. These findings support the notion that omega-3 fatty acids have a protective influence on cardiovascular health [15].
Another study by Aung et al. published in 2018 investigated the impact of omega-3 fatty acids on cardiovascular outcomes in patients with high cardiovascular risk. This large-scale RCT, involving over 15,000 participants, examined the effects of omega-3 fatty acid supplementation on major cardiovascular events. The results indicated a modest reduction in cardiovascular risk, albeit not statistically significant. However, subgroup analyses suggested that omega-3 fatty acids may be more active in certain populations, such as those with diabetes [16].
The VITAL trial, conducted by Manson et al. in 2018, examined the effects of omega-3 fatty acids on cardiovascular outcomes and cancer prevention. The trial included over 25,000 participants and found that omega-3 fatty acid supplementation did not significantly decrease the incidence of major cardiovascular events. However, subgroup analyses revealed potential benefits in specific subgroups, such as individuals with low fish intake or African American participants [17].
The recent evidence on the impacts of omega-3 fatty acids on cardiovascular results is somewhat mixed, highlighting the complexity of this relationship. While some studies, such as Mozaffarian et al. (2020), support the cardiovascular assistances of omega-3 fatty acids, others, like the VITAL trial (Manson et al., 2018), do not show statistically significant effects. These discrepancies could be attributed to variations in study design, population characteristics, dosage, and duration of supplementation. It is worth noting that the beneficial effects of omega-3 fatty acids on cardiovascular consequences might be more pronounced in high-risk populations, as demonstrated in the study by Aung et al. (2018). Additionally, subgroup analyses have suggested that certain factors, such as baseline fish intake and ethnicity, might influence the response to omega-3 fatty acid supplementation [15-17].
The most recent data emphasize the requirement for more study to fully comprehend the subtleties of how omega-3 fatty acids affect heart disease consequences. Future studies should address important considerations, including optimal dosage, treatment duration, and the identification of specific subgroups that may benefit the most from supplementation.
Recent studies examining the effect of omega-3 fatty acids on cardiovascular outcomes have provided valuable insights into their potential benefits. While some studies demonstrate a significant reduction in cardiovascular risk, others do not show statistically significant effects. The conflicting results emphasize the importance of considering study design, population characteristics, and other factors that may influence the outcomes. Further research is needed to clarify the optimal usage of omega-3 fatty acids in cardiovascular ailment anticipation and management strategies.
The study has concluded there is evidence found in support of omega-3 fatty acids that can reduce adverse cardiovascular events in the form of cardiovascular diseases or mortality. As included in this current meta-analysis, several studies endorsed that EPA and DHA have been statistically significant in reducing or preventing cardiovascular risk. All these findings have been considered to have significant clinical importance in the management of cardiovascular risk reduction. However, the authors suggest that this is the need of the hour to conduct more clinical trials with EPA and DHA to investigate the reduction potential of omega-3 fatty acids in reducing cardiovascular risks and to formulate guidelines that can be used clinically in various types of populations. It is also required to study the effects of omega-3 fatty acids at different dosages and the reduction potential of specific cardiovascular abnormalities.
Overall, this current meta-analysis brought a clinically significant conclusion that omega-3 fatty acids have a protective effect on the development of cardiovascular risk and a clinician can add EPA and DHA to the treatment schedule of cardiovascular risk reduction to effectively manage it