Fish Oil, Particularly EPA, Linked to Reduced Ischemic Stroke

January 17, 2019

A new study of fish oils and ischemic stroke that included data on adipose tissue levels of the key fatty acids has suggested a greater benefit with eicosapentaenoic acid (EPA) than with docosahexaenoic acid (DHA) or total fish oil intake.

"Our results show that higher dietary intakes of fish oils — and higher adipose tissue levels of EPA in particular — are related to a reduction in ischemic stroke," lead author Stine Krogh Venø, MD, Department of Cardiology at Aalborg University Hospital, Denmark, told Medscape Medical News

"This is more of a study of dietary fish intake rather than omega 3 oil supplementation, and I think we can say from these results it is still a good thing to eat fish regularly," she added. "But when we looked at the individual fatty acids separately we showed more benefits with EPA than with DHA."

The current observational study was published online January 3 in Stroke.

The results are of particular interest given the recent reporting of the REDUCE-IT trial, a large randomized study showing a dramatic lowering of cardiovascular events with a high-dose purified EPA product vs placebo.

Lead investigator of REDUCE-IT, Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, Massachusetts, commented on the current study for Medscape Medical News.

"The authors have conducted a very insightful study," Bhatt said. "It is quite remarkable that we saw a significant 28% reduction in stroke in REDUCE-IT with a highly purified ethyl ester of EPA (icosapent ethyl), and in this study they found a 26% lower rate of stroke associated with higher EPA levels.

"It is also worth noting in this study that while EPA was associated consistently with cardiovascular benefits, the case for DHA was more mixed. This latter observation may in part help explain why all the recent studies of omega-3 fatty acids had been neutral – until REDUCE-IT," Bhatt pointed out.

"It may take a while, as it did for the LDL-cholesterol story to unfold fully, but I anticipate, in years to come, there will be even more data supporting the protective role of EPA in cardiovascular health," he added. 

For the current study, the authors analyzed data from of 55,000 participants in the Danish Diet, Cancer and Health study who completed detailed food questionnaires, including 3400 who had fatty acid composition of their adipose tissue analyzed at baseline. Information on ischemic stroke during 13.5 years of follow-up was obtained from The Danish National Patient Register, and all cases were validated.

During follow-up, 1879 participants developed an ischemic stroke from whom 1755 adipose biopsies were available.

Results showed that neither dietary intake nor adipose tissue content of total marine n-3 polyunsaturated fatty acids (PUFA) showed any association with total ischemic stroke. Likewise, dietary intake of EPA and DHA, as well as adipose tissue content of DHA, showed no association with total ischemic stroke.

However, adipose tissue content of EPA showed a statistically significant inverse association with total ischemic stroke (hazard ratio [HR] 0.74) when comparing the highest with the lowest quartile.

Also, lower rates of large artery atherosclerosis were seen with higher intakes of total marine n-3 PUFA (HR 0.69); EPA (HR 0.66); and DHA (HR, 0.72) and higher adipose tissue content of EPA (HR 0.52), but not with higher adipose tissue content of total marine n-3 PUFA or DHA.

Intake of total marine n-3 PUFA, EPA, and DHA and adipose tissue content of total marine n-3 PUFA and DHA were statistically significantly associated with higher rates of cardioembolic stroke.

No consistent associations were found between intake of total marine n-3 PUFA, EPA, or DHA and small-vessel occlusion. However, a statistically significant inverse association was found between adipose tissue content of EPA and small-vessel occlusion (HR 0.69).

The current study is unusual in that rather than just trying to assess intake of key fish oil fatty acids by asking participants about dietary fish consumption, the researchers actually had data on tissue levels of these fatty acids. 

"It is very unusual to have data on tissue levels and this makes our results much more reliable," Venø said.

She noted that some previous studies have measured fatty acid levels in red blood cells, but adipose tissue measurements are more informative as they reflect dietary habits over the past 1 to 3 years, whereas red blood cell levels correlate more with the last couple of months. "Therefore, adipose tissue levels are a good and reliable indicator of long-term diet."

In the paper, the researchers suggest that different effects on lipids may explain the different results seen for DHA and EPA in this study. "Both EPA and DHA lower plasma triglycerides, but DHA may raise low-density lipoprotein [LDL] cholesterol, which could be an explanation for the difference between associations of EPA and DHA in relation to large artery atherosclerosis stroke," they write.

They say the increase in cardioembolic stroke was unexpected as "EPA and DHA are generally believed to have antithrombotic effects."

However, Venø warned that the cardioembolic stroke results should be interpreted with caution because there were relatively few such events — with just 99 cardioembolic strokes out of a total of 1879 ischemic strokes in the study.

The authors note, however, that some previous studies have reported a higher risk of atrial fibrillation with high intakes of marine n-3 PUFA, and as AF is a risk factor of cardioembolism, this could provide a possible explanation for the findings.

"This again fits in with observations in REDUCE-IT, which showed a higher risk of AF with EPA," Venø added.

In the paper, the authors conclude that "our study suggests that intake of marine n-3 PUFAs may protect middle-aged subjects against the development of ischemic stroke of atherosclerotic origin, which supports recent guidelines."

They note that these results should be viewed together with evidence on other atherosclerotic vascular events, adding that "there is solid epidemiological evidence that fish consumption protects against ischemic heart disease, and we recently reported that marine n-3 PUFA may also lower the risk of the third major atherosclerotic disorder, peripheral arterial disease."

This study was supported by a research grant from the Danish Heart Foundation. The primary data collection for the Diet, Cancer and Health study was funded by the Danish Cancer Society. Venø has disclosed no relevant financial relationships.

Stroke. Published online January 3, 2019. Abstract

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