Abstract
Objective To review systematically the evidence for an effect of long chain and shorter chain omega 3 fatty acids on total mortality, cardiovascular events, and cancer. Data sources Electronic databases searched to February 2002; authors contacted and bibliographies of randomised controlled trials (RCTs) checked to locate studies. Review methods Review of RCTs of omega 3 intake for ≥6 months in adults (with or without risk factors for cardiovascular disease) with data on a relevant outcome. Cohort studies that estimated omega 3 intake and related this to clinical outcome during at least 6 months were also included. Application of inclusion criteria, data extraction, and quality assessments were performed independently in duplicate. Results Of 15 159 titles and abstracts assessed, 48 RCTS (36 913 participants) and 41 cohort studies were analysed. The trial results were inconsistent. The pooled estimate showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking additional omega 3 fats. The few studies at low risk of bias were more consistent, but they showed no effect of omega 3 on total mortality (0.98, 0.70 to 1.36) or cardiovascular events (1.09, 0.87 to 1.37). When data from the subgroup of studies of long chain omega 3 fats were analysed separately, total mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79 to 1.11) were not clearly reduced. Neither RCTs nor cohort studies suggested increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to 1.30; cohort studies: 1.02, 0.87 to 1.19), but clinically important harm could not be excluded. Conclusion Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.
Generated Summary
This systematic review and meta-analysis investigated the effects of long-chain and short-chain omega 3 fatty acids on total mortality, cardiovascular events, cancer, and stroke. The study encompassed randomized controlled trials (RCTs) and prospective cohort studies. Electronic databases were searched up to February 2002, and authors were contacted to locate studies. The review included RCTs of omega 3 intake for ≥6 months in adults (with or without risk factors for cardiovascular disease) with relevant outcome data, as well as cohort studies assessing omega 3 intake and related clinical outcomes over at least 6 months. Data extraction and quality assessments were performed independently in duplicate. The study aimed to determine the effects of these fatty acids on various health outcomes, including mortality, cardiovascular disease, cancer, and bleeding events, analyzing relevant RCTs and prospective cohort studies. The primary goal was to provide a comprehensive assessment of the benefits and risks associated with omega 3 fatty acid intake.
Key Findings & Statistics
- Out of 15,159 titles and abstracts assessed, 48 RCTs (36,913 participants) and 41 cohort studies were analyzed.
- The pooled estimate showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking additional omega 3 fats.
- Studies at low risk of bias showed no effect of omega 3 on total mortality (0.98, 0.70 to 1.36) or cardiovascular events (1.09, 0.87 to 1.37).
- When data from the subgroup of studies of long chain omega 3 fats were analyzed separately, total mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79 to 1.11) were not clearly reduced.
- Neither RCTs nor cohort studies suggested increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to 1.30; cohort studies: 1.02, 0.87 to 1.19).
- For RCTs, the numbers of participants experiencing each outcome and total numbers randomized for each study arm were extracted and combined using relative risks in random effects meta-analysis.
- For cohort studies, relative risk or odds ratio adjusted for the most confounding factors were used, comparing the most exposed quantile with the least exposed quantile.
- Meta-regression indicated that the risk of death increased as the length of the RCT increased (regression coefficient 0.008, 0.003 to 0.012).
- Cohort studies suggested that omega 3 protected against death (0.65, 0.48 to 0.88; I² = 36%), but it was unclear whether adjustment for confounders was adequate.
- The meta-analysis showed no definite effect of omega 3 fats on cardiovascular events, but confidence intervals were wide (0.95, 0.82 to 1.12) and inconsistency was high (I²=65%).
- Ten RCTs reported the incidence of cancer; 391 diagnoses of cancer or death from cancer occurred in 17,433 participants.
- The study found no evidence that omega 3 fats had an effect on the incidence of cancer (1.07, 0.88 to 1.30).
- Seven cohort studies provided data on cancer (832 events in the highest and lowest quantiles), and meta-analysis found no effect of high versus low intake of omega 3 (1.02, 0.87 to 1.19; I² = 21%).
- Nine RCTs reported at least one stroke (243 strokes in total), but little information was available specifically on haemorrhagic stroke. Omega 3 had no clear effect on the total numbers of strokes (1.17, 0.91 to 1.51; ²=0%), in sensitivity analysis (29 events), or in four cohort studies (0.87, 0.72 to 1.04).
Other Important Findings
- The study found no clear effect of long chain and shorter chain omega 3 fats on total mortality, combined cardiovascular events, or cancer.
- The few studies at low risk of bias were more consistent but they showed no effect of omega 3 on total mortality or cardiovascular events.
- Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.
Limitations Noted in the Document
- The largest studies reviewed had greater potential for bias than some of the smaller ones.
- The analysis of the effects of omega 3 on rarer outcomes such as stroke had insufficient power to detect clinically important effects.
- In cohort studies, the characteristics of participants with high and low intake of omega 3 fats differed, potentially leading to inadequate adjustment for confounding factors.
- The study by Burr et al., with the longest follow-up, contradicted other large studies by not suggesting a benefit of omega 3. Possible explanations include cumulative effects of methylmercury, the study population (men treated for angina), and performance bias due to differential care.
Conclusion
The systematic review of RCTs assessing the effects of increased omega 3 fats on total mortality found substantial variations between studies. Studies with stronger methodology had more consistent results, and the pooled relative risk of these studies was 0.98 (0.70 to 1.36; 138 events). The review found no evidence from RCTs or cohort studies that omega 3 fats have an effect on combined cardiovascular events. Neither RCTs nor cohort studies showed significantly increased risks of cancer or stroke with higher intake of omega 3, but there were too few events to rule out important effects. The findings suggest that long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer. Further research is needed to understand the effects of omega 3 fats on health, particularly with high-quality RCTs of long duration that report associated harms. Current guidelines recommending increased oily fish consumption should be regularly reviewed. The study emphasizes the importance of high-quality RCTs with adequate concealment of allocation and masking of participants and health providers to understand the effects of omega 3 fats on health. The review’s findings do not rule out an important effect of omega 3 fats on total mortality, but the evidence is not strong. The study’s results suggest that the benefits of omega 3 fats on cardiovascular health may be smaller than previously thought. The findings have implications for public health guidelines and the need for further rigorous research.