A high intake of alpha linolenic acid (ALA) is associated with a lower risk of death

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A high intake of alpha linolenic acid (ALA) – found mainly in nuts, seeds, and plant oils – is associated with a lower risk of death from all causes, and specifically from diseases of the heart and blood vessels, finds a study published by The BMJ today.

Higher ALA intake was associated with a slightly higher risk of death from cancer, but the researchers say further studies are needed to confirm this.

Alpha-linolenic acid (ALA) is a type of omega-3 polyunsaturated fatty acid found in plants, such as soybean, nuts, canola oils and flaxseed.

Previous studies have shown that a high ALA intake is associated with a lower risk of fatal coronary heart disease, but findings from other studies on ALA and risk of death have been inconclusive.

To address this uncertainty, an international team of researchers analyzed the results of 41 studies published between 1991 and 2021 on the associations between ALA and risk of death from all causes, cardiovascular disease and cancer.

Together, these studies involved around 120,000 participants aged between 18 and 98 years who were monitored for between two and 32 years, and they accounted for factors such as age, weight, smoking status, alcohol consumption, and physical activity.

After thoroughly assessing each study for bias, the researchers found that a high intake of ALA was associated with a 10%, 8%, and 11% lower risk of mortality from all causes, cardiovascular disease, and coronary heart disease, respectively.

This is equivalent to 113 fewer deaths per 10,000 person years for all causes, 33 fewer cardiovascular disease deaths, and 23 fewer coronary heart disease deaths.

A higher intake of ALA, however, was associated with a slightly higher risk of cancer mortality, equivalent to 63 extra cancer deaths for the highest compared with lowest levels of ALA intake.

A dose-response effect was found for dietary ALA intake and cardiovascular disease mortality, such that a 1g per day increase in ALA intake (equivalent to one tablespoon of canola oil or 0.5 ounces of walnut oil) was associated with a 5% lower risk of cardiovascular disease mortality.

Higher blood levels of ALA were also associated with lower risks of mortality.

Due to the observational design of included studies, causality cannot be established, nor can the researchers rule out the possibility that other unknown factors or measurement errors of food and nutrient intakes might have affected their results.

Nevertheless, use of stringent study inclusion criteria together with rigorous and systematic evaluation of study quality suggests their conclusions are robust.

As such, they say their study adds to evidence of the potential health benefits of polyunsaturated fatty acids.

And they conclude: “Further studies should examine the association between ALA and a wider range of causes of death to provide a more comprehensive assessment of the potential health effects of ALA as well as to examine whether specific foods rich in ALA are differentially associated with mortality from cancer and other causes.”

A linked article summarizes the current evidence on dietary intakes of different types of fatty acids and death.

Despite the beneficial effects of omega 3 fatty acids, it suggests that recommendations for intakes should be made cautiously because ALA intake might slightly increase the risk of cancer mortality. Further studies are, however, needed to confirm the increased risk.


Omega-3 fatty acids (FAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, may reduce the risk of atherosclerotic cardiovascular disease (ASCVD) events through various mechanisms, including triglyceride (TG) lowering, membrane stabilization, and antithrombotic, anti-inflammatory, or antiarrhythmic properties [[1]]. Consequently, randomized controlled trials explored the cardiovascular effects of omega-3 FAs with considerable interest.

The JELIS (the JAPAN EPA Lipid Intervention Study) trial [[2]] showed a reduction in major coronary events in patients with hypercholesteremia using purified EPA. However, the study was limited by open-label design, lack of placebo group, the inclusion of potentially subjective endpoints in the primary composite outcome (e.g., unstable angina and elective revascularization), and lower intensity of statin therapy in participants with average low-density lipoprotein cholesterol (LDL-C) of ~180 mg/dL at baseline.

In 2018, three randomized controlled trials examining different preparations of omega-3 FAs showed divergent results [3, 4, 5]. The ASCEND (A Study of Cardiovascular Events in Diabetes) [[3]] and VITAL (Vitamin D and Omega-3 Trial) trials [[5]] using EPA+DHA did not significantly reduce the primary cardiovascular endpoints (ASCEND: non-fatal myocardial infarction [MI] or ischemic stroke, transient ischemic attack, or vascular death excluding confirmed intracranial hemorrhage [[3]]; VITAL: MI, stroke, or death from cardiovascular causes) [[5]].

Conversely, REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) [[4]] showed a significant 25% relative reduction in the primary composite efficacy endpoint of cardiovascular death, non-fatal MI, non-fatal stroke, coronary revascularization, or unstable angina (an absolute reduction of 4.8%) with icosapent ethyl a highly purified ethyl ester of EPA in patients with established ASCVD or those with high risk for ASCVD (diabetes with at least one additional risk factor).

The key secondary endpoint of cardiovascular death, MI, or stroke was significantly reduced by 26%, and death from cardiovascular causes was significantly reduced by 20%.

Two studies in 2020, STRENGTH (the Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia) [[6]] and OMEMI (the Omega-3 fatty acids in Elderly with Myocardial Infarction) [[7]], showed null results for combined EPA+DHA therapy on the primary endpoints (STRENGTH: composite of cardiovascular death, non-fatal MI, nonfatal stroke, emergent/elective coronary revascularization, or unstable angina requiring hospitalization [[6]], OMEMI: non-fatal MI, unscheduled revascularization, stroke or all-cause mortality) [[7]].

These discordant trial results have led to considerable uncertainty and debate about the potential role of omega-3 FAs in reducing ASCVD residual risk. Moreover, since EPA and DHA differ in their biological effects on membrane structure and lipid metabolism, this variability led to the hypothesis that combining DHA with the EPA might partially offset the beneficial clinical effects of EPA treatment alone [[1],[8]].

To explore this potential clinical heterogeneity across omega-3 FAs trials, we performed an updated systematic review and meta-analysis with a primary focus on determining the effectiveness and safety of omega-3 FAs on fatal and non-fatal cardiovascular outcomes in adults. The secondary focus was on examining the potential variability in the effects generated by EPA vs. EPA+DHA treatment.

reference link : https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00277-7/fulltext


More information: Sina Naghshi et al, Dietary intake and biomarkers of alpha linolenic acid and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of cohort studies, BMJ (2021). DOI: 10.1136/bmj.n2213

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