Omega-3s: Meta-analysis finds no increase in bleeding risk

Writing in the Journal of the American Heart Association, ​researchers reported that pooled data from 120,643 patients from 11 RCTs did not support any increase in the risk of bleeding, including fatal and central nervous system events.

Researchers from the Cardiothoracic Centre Freeman Hospital in Newcastle‐upon‐Tyne did find an increased bleeding risk for high‐dose purified EPA but said the clinical significance of this finding was “debatable”.

Harry Rice, PhD, V.P., Regulatory & Scientific Affairs at Global Organization for EPA and DHA Omega-3s (GOED), told NutraIngredients that his organization is planning to submit an editorial for publication that will summarize the results from their own systematic review presented at the 2024 International Society for the Study of Fatty Acids and Lipids (ISSFAL) Congress and reference the results from the current publication.

“These combined results demonstrate that there is no relationship between increased EPA+DHA intake and bleeding events,” he said. “In addition, findings from observational studies report no increased risk for clinically meaningful bleeding with the use of omega-3 supplements, even when combined with anti-coagulant or anti-platelet drugs.

“While the publication reports that intake of high-dose EPA-only pharmaceuticals was associated with an increased relative risk of bleeding events, it’s important to point out that there was only a small increase in absolute risk. This finding was discussed extensively when the U.S. Food and Drug Administration (FDA) met in 2019 and allowed a label expansion for Amarin’s Vascepa omega-3 pharmaceutical.”

Consistent data​

Interest in fish oil and omega-3 fatty acids has increased over the decades since Dr. Jorn Dyerberg and his co-workers first reported the cardiovascular benefits of the fatty acids in the early 1970s. Dr. Dyerberg also reported that the Greenlandic Inuit, the people they studied for those early reports, had significantly longer bleed times than the general Danish population. This has been extensively studied over the years, and there is debate around whether fish oil supplementation should be stopped prior to surgery.

A 2017 systematic review, published in the Danish Medical Journal​​, also found that the overall body of science does not support any concerns around increased bleeding during or after surgery.

This was followed by a 2018 paper detailing a secondary analysis of data from the Omega-3 Fatty Acids for the Prevention of post-operative atrial fibrillation (OPERA) study, which also found omega-3s do not increase perioperative bleeding in surgery, but may be associated with a lessened risk of bleeding (Circulation: Cardiovascular Quality and Outcomes​​).

New meta-analysis​

The new meta-analysis included data from 11 randomized clinical trials, and the average age of participants in all the trials ranged from 61 to 75.

After crunching the numbers, the researchers found that there was no overall increase in the risk of bleeding from omega-3 supplementation.

“The antiplatelet effect of omega‐3 PUFAs is well‐recognized and subsequent bleeding has been a potential concern for patients receiving this treatment,” they wrote.  “[W]e demonstrate that there is no increased risk of overall bleeding events in patients receiving omega‐3 PUFAs. Moreover, the incidence of serious bleeding, including hemorrhagic stroke and intracranial bleeding, was comparable between the 2 groups.”

A modest increase of 0.6% was observed when the researchers focused on high‐dose EPA was very modest, and there was “no evidence to suggest an increase in serious bleeding such as intracranial or hemorrhagic stroke,” they said. “Furthermore, there was no relationship between bleeding events and the background use of antiplatelet treatment in patients receiving omega‐3 PUFAs.”

Source: Journal of the American Heart Association​
Volume 13, Number 10, doi: 10.1161/JAHA.123.032390​
“Bleeding Risk in Patients Receiving Omega‐3 Polyunsaturated Fatty Acids: A Systematic Review and Meta‐Analysis of Randomized Clinical Trials”
Authors: M. Javaid, et al.