Abstract
Objective- To examine the associations between dietary intake and tissue biomarkers of alpha linolenic acid (ALA) and risk of mortality from all causes, cardiovascular disease (CVD), and cancer.
Design Systematic review and meta-analysis of prospective cohort studies. Data sources – PubMed, Scopus, ISI Web of Science, and Google Scholar to 30 April 2021. Study selection Prospective cohort studies that reported the risk estimates for death from all causes, CVD, and cancer. Data synthesis – Summary relative risks and 95% confidence intervals were calculated for the highest versus lowest categories of ALA intake using random effects and fixed effects models. Linear and non-linear dose-response analyses were conducted to assess the dose-response associations between ALA intake and mortality. Results – 41 articles from prospective cohort studies were included in this systematic review and meta-analysis, totalling 1 197 564 participants. During follow-up ranging from two to 32 years, 198 113 deaths from all causes, 62 773 from CVD, and 65 954 from cancer were recorded. High intake of ALA compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled relative risk 0.90, 95% confidence interval 0.83 to 0.97, I2=77.8%, 15 studies), CVD (0.92, 0.86 to 0.99, I2=48.2%, n=16), and coronary heart disease (CHD) (0.89, 0.81 to 0.97, I2=5.6%, n=9), and a slightly higher risk of cancer mortality (1.06, 1.02 to 1.11, I2=3.8%, n=10). In the dose-response analysis, a 1 g/day increase in ALA intake (equivalent to one tablespoon of canola oil or 0.5 ounces of walnut) was associated with a 5% lower risk of all cause (0.95, 0.91 to 0.99, I2=76.2%, n=12) and CVD mortality (0.95, 0.91 to 0.98, I2=30.7%, n=14). The pooled relative risks for the highest compared with lowest tissue levels of ALA indicated a significant inverse association with all cause mortality (0.95, 0.90 to 0.99, I2=8.2%, n=26). Also, based on the dose-response analysis, each 1 standard deviation increment in blood concentrations of ALA was associated with a lower risk of CHD mortality (0.92, 0.86 to 0.98, I2=37.1%, n=14). Conclusions – The findings show that dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD, and CHD, and a slightly higher risk of cancer mortality, whereas higher blood levels of ALA are associated with a reduced risk of all cause and CHD mortality only.
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Key Points
This meta-analysis of 41 studies found that a high intake of the omega-3 fatty acid alpha linolenic acid (ALA) is associated with a lower risk of death from all causes, and specifically from diseases of the heart and blood vessels. The study showed that dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD (cardiovascular disease) and CHD (coronary heart disease), and a slightly higher risk of cancer mortality. Higher blood levels of ALA correlated to a reduced risk of all cause and CHD mortality only. In this systemic review and meta-analysis, a higher intake of ALA was significantly associated with a 10%, 8% and 11% lower risk of mortality from all causes, CVD and CHD, respectively.
Conversely, a higher ALA intake was linked to a slightly higher risk of death from cancer, but said that this could be due to the existence of trans forms of ALA in certain foods.
Previous studies had already established a link between a high ALA intake and a lower risk of fatal CHD. However, no study had examined the association between ALA and the risk of all cause mortality. Moreover, previous studies had mainly focused on dietary intake of ALA, rather than on the tissue biomarkers of ALA, and no information was available on the dose-response relationship between ALA intake and the risk of mortality. To address these knowledge gaps, an international team of researchers analysed 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. Each 1 SD increment in blood and total plasma or serum levels of ALA was associated with a reduced risk of CHD and CVD mortality.