Fish oil to prevent cardiovascular diseases

Relation

Abdelhamid AS, Brown TJ, Brainard JS, et al. Omega-3 fatty acids for primary and secondary prevention of cardiovascular diseases. Cochrane Database Syst Rev. 2018;7:CD003177.

Objective

To evaluate the effects of increased intake of fish and plant-based omega-3 fatty acids on all-cause mortality, cardiovascular events, adiposity and lipids.

Draft

The authors conducted a systematic review of randomized controlled trials (RCTs) identified by searching multiple databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase databases up to April 2017, and ClinicalTrials.gov and World Health Organization International Clinical Trials registration up to September 2016. All languages ​​were recorded.

The authors only included RCTs that lasted at least 12 months and compared dietary supplementation and/or counseling to increase fish polyunsaturated omega-3 fatty acids (long-chain omega-3 fatty acids). [LCn3]) or plants (alpha-linolenic acid [ALA]) intake compared to usual or lower intake.

Participant

The literature search revealed 79 randomized controlled trials (RCTs) with a total of 112,059 adults with different cardiovascular risks; Most participants came from high-income countries.

Study methodology

Two review authors independently assessed studies for inclusion, extracted data, and assessed validity. The authors conducted separate random-effects meta-analyses for ALA and LCn3 interventions and assessed dose-response relationships by meta-regression.

The duration of the experiment was between 12 and 72 months. Most studies evaluated LCn3 supplementation with capsules, but some used LCn3-rich or ALA-rich or fortified foods or nutritional advice; Interventions were compared with either placebo or usual diet.

Target parameters

All-cause mortality, cardiovascular mortality, cardiovascular events, arrhythmia, stroke and coronary heart disease.

Key insights

The authors concluded that increasing fish oil (LCn3) had little or no effect on any of the following outcomes:

• Gesamtmortalität (relatives Risiko [RR]: 0,98; 95 % Konfidenzintervall [CI]: 0,90-1,03)
• Kardiovaskuläre Mortalität (RR: 0,95; 95 % KI: 0,87-1,03)
• Kardiovaskuläre Ereignisse (RR: 0,99; 95 % KI: 0,94-1,04)
• Koronare Herzkrankheit (KHK) Sterblichkeit (RR: 0,93; 95 % KI: 0,79-1,09)
• Schlaganfall (RR: 1,06; 95 % KI: 0,96-1,16)
• Arrhythmie (RR: 0,97, 95 % KI: 0,90-1,05)

Although LCn3 appeared to slightly reduce CHD events (RR: 0.93; 95% CI: 0.88–0.97), these effects were not maintained in sensitivity analyses.

Aside from preventing cardiovascular events, there are many reasons for patients to take fish oil.

They also concluded that increased intake of plant-based omega-3 fatty acids (ALA) is likely to have little to no effect on:

• Gesamtmortalität (RR: 1,01; 95 % KI: 0,84 -1,20)
• Kardiovaskuläre Mortalität (RR: 0,96; 95 % KI: 0,74-1,25)
• KHK-Ereignisse (RR: 1,00; 95 % KI: 0,80-1,22)

Increasing ALA intake may slightly reduce the risk of cardiovascular events (from 4.8% to 4.7%; RR: 0.95; 95% CI: 0.83-1.07) and it probably reduces the risk of CHD mortality (from 1.1% to 1.0%; RR: 0.95; 95% CI: 0.72-1.26). The effects of ALA on stroke are unclear.

Practice implications

This study is a Cochrane Review, a name probably familiar to most of us. Because the Cochrane database is a leading database of systematic reviews in healthcare,¹This study examining omega-3 fatty acids for primary and secondary prevention of cardiovascular disease carries weight in the world of evidence-based medicine.

Since the early 1970s, when Bang and Dyerberg reported that Greenland Eskimos had enviable blood lipid levels and low rates of heart disease, fish oil and fish consumption have been suggested as a means of protection against cardiovascular disease.^2.3However, recently there has been debate about whether or not fish oil helps patients.⁴The cardiovascular benefits of eating fish are believed to be due to its fat content. Fats in fish are different from the fats found in most animal proteins; Commercially farmed animals are typically high in saturated fats and omega-6 fatty acids, while fish oil is high in omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These fatty acids are said to lower triglycerides, have a mild anticoagulant effect and are considered anti-inflammatory.^5.6

In recent years, the notion that fish oil influences important cardiovascular outcomes has been challenged. We know that fish appears to lower triglycerides. We know that fish oil can thin the blood a little, and we know that it can lower a person's high-sensitivity C-reactive protein (hsCRP), a hair.⁷However, some large studies have shown that fish may not have much of an impact on things that really matter, like heart disease rates or death rates from cardiovascular disease. This new systematic review by Abdelhamid et al. was extensive; it included 79 studies and over 100,000 participants. The authors examined the use of fish oil for both primary and secondary prevention of cardiovascular disease, and they looked at a range of outcomes that we would consider patient-important outcomes, including all-cause mortality, cardiovascular death, cardiovascular events, stroke, deep vein thrombosis (DVT), and bleeding.

You will note that none of the results presented in this review are surrogate markers. They didn't look at cholesterol; You haven't looked at triglycerides. However, they addressed the key endpoints that matter to our patients. They conducted a series of subgroup analyzes including duration of therapy dose, primary vs. secondary prevention, and type of intervention (i.e., did they give fish oil as a supplement, as nutritional advice, or as a fortified food?).

Let's consider the obvious questions that could fault the study results. As this is a Cochrane review, we assume that the study was probably well done; Therefore, we anticipate that the only real limitation will likely be the limitation of the data itself.

There was no lack of data collection. The authors searched multiple databases and reviewed gray literature (government, academic, and industry publications not controlled by commercial publishers⁸). They also included studies not published in English. There was no shortage of cardiovascular events in the composite cohort. They assessed the quality of the studies as they analyzed them and ensured that there were no strong methodological flaws that would affect the result.

The authors examined studies, all RCTs, that randomly assigned people to higher and lower exposure to omega-3 (LCn3) oils. Exposure to higher concentrations of LCn3 oils could arise through dietary supplements, fortified foods, or nutritional advice. However, in most studies, participants received nutritional supplementation. Study durations ranged from 12 to 74 months, but most were less than 24 months long. The dosage range was 1 to 3.3 grams of EPA/DHA per day. This is a pretty respectable dose even at the lower end of this range, so we're not too concerned that they underdosed fish oil in these studies. A risk of bias analysis was performed on each of the studies and 25 of the 79 studies were classified as low risk. Although it's not the majority, it's a pretty good number considering that it's fairly common for most studies in a systematic review to not have a low risk of bias. Most of the weight of this meta-analysis falls on just 11 larger studies. So most of the statistical power comes from just 11 studies, which were really large.

Does fish oil affect bleeding? Bleeding was considered a potential risk of fish oil, but this Cochrane review found that there was no difference in the risk of bleeding in the two groups. This is also confirmed in this review by the non-significant effect of fish oil on the risk of stroke. Together, these data points imply that fish oil is probably not a strong enough anticoagulant to produce such effects.

To recap: None of the meta-analysis results had statistical significance. The conclusion of this Cochrane review is that consuming higher amounts of omega-3 fatty acids is unlikely to have any effect on cardiovascular disease.

There are many of us who will be unhappy with these results. We have been telling patients to take fish oil for so long that it will be difficult to even consider changing our thinking.

Results of a new study (NCT01169259) are expected to be published later this year. These results may overturn other ideas we have about fish oil and cardiovascular disease. The new study is large, with 25,000 participants. It examined the effect of vitamin D and omega-3 fatty acids on the primary prevention of cardiovascular disease over a 5-year period. The largest study ever conducted on this topic looks at long-term fish oil supplementation and is robustly designed.⁹It will have the statistical power to call this current Cochrane review into question.

Aside from preventing cardiovascular events, there are many reasons for patients to take fish oil. Fish oil is prescribed for conditions ranging from depression to dementia. This review does not speak to any potential indication other than its impact on cardiovascular disease. The conclusion of this systematic review does not mean that fish oil is not beneficial for any disease; it just means that the best evidence currently available suggests that fish oil has no effect on the risk of cardiovascular disease.

Oh, what about the Eskimo study that sparked our near-obsession with fish oil and cardiovascular disease? An article published in 1992 offered an alternative explanation for why Eskimos have such good lipid profiles: Eskimos have significantly less lipoprotein (a), and this appears to be due to genetics rather than diet.¹⁰