Higher circulating and tissue levels of Linoleic Acid associated with lower risk of major cardiovascular events

A recent study found that higher levels of circulating Linoleic Acid (LA) were significantly associated with lower risks of total cardiovascular disease (CVD), cardiovascular mortality, and ischemic stroke. Arachidonic Acid (AA) levels were not associated with higher risk of cardiovascular outcomes. In fact, comparing extreme quintiles, higher levels were associated with lower risk of total CVD. 

Previous evidence from clinical trials and cohort studies suggests a moderate benefit of consuming n-6 PUFA, predominantly LA, for coronary heart disease (CHD) risk, whether replacing saturated fat or total carbohydrate. In contrast, recent secondary analyses of clinical trials of LA-rich corn oil (although not LA-rich soybean oil) conducted in the 1960s-1970s suggest a possible increased risk of overall and CHD mortality. However, findings from these latter studies are hampered by a number of methodological factors. Concerns have also been raised that n-6 PUFA could actually increase CVD risk, due to potential pro-inflammatory effects. Yet, stable isotope studies suggest very limited conversion of LA to AA in humans, and trials show limited effects of increasing dietary LA on plasma and adipose tissue AA levels. Few studies have evaluated the relationship between in vivo levels of LA and AA and CVD outcomes and so this study was conducted to address these knowledge gaps.

This current study pooled analysis of 30 cohort studies, across 13 countries, in the Fatty Acid and Outcome Research Consortium (FORCE) to evaluate associations of LA and AA levels with incident total CVD and subtypes (CHD, ischemic stroke, CVD mortality). Almost 70,000 individuals were included (average age at baseline ranged from 49 to 77 years) and 10,000 total CVD events were reported. Median follow-up ranged between 2.5 to 31.9 years. Fatty acids were measured in both blood and adipose tissues.

Higher LA levels were associated with a 7%, 22% and 12% lower incidence of total CVD, CVD mortality, and ischemic stroke, respectively. AA levels were not associated with higher risk of CV outcomes and when comparing extreme quintiles, higher levels were associated with lower risk of total CVD.

The findings from this study support potential benefits of the main dietary omega-6 fatty acid, i.e.linoleic acid, for CVD prevention. Furthermore, the results do not support any theorized cardiovascular harms of omega-6 fatty acids. As such they can help inform currently inconsistent global dietary recommendations on n-6 PUFA consumption.

Marklund et al (2019) Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality. Circulation May 21;139(21):2422-2436