June 26, 2013

ATHENS, Greece — Consumption of omega-3 polyunsaturated fatty acids (PUFAs) in fish does seem to cut the risk of incident atrial fibrillation (AF), but the associated AF risk follows a U-shaped curve, significantly reduced at the median level of fish consumption compared with higher and lower levels, according to a Danish cohort study [1].

Whether intake of omega-3 PUFAs, either in fish or supplements, can protect against AF or other arrhythmias has been often explored in randomized and observational studies, with widely varying outcomes.

"The U-shaped association found in our study may help to explain why studies have shown inconsistent results," Prof Thomas Andersen Rix (Aalborg University Hospital, Denmark) told heartwire in an email. The studies have looked at varying levels of omega-3 PUFA intake, which would presumably have a range of effects on AF risk. The current findings agree with those that found lower AF risk at moderate-intake levels.

Still, the median daily intake in the current analysis was 0.63 g/day. That corresponds to about 300 g of salmon, or two servings per week, according to Rix. That intake level, he said, is "higher than the previous observational studies, in which the mean intakes were around 0.2 to 0.3 g omega-3 PUFA per day. Therefore, our study has more information regarding a high intake."

The findings suggest that omega-3 PUFA at higher-intake levels could potentially have adverse effects, he said, but the study is observational and therefore can't say much about cause and effect.

As Rix presented here in a poster at the European Heart Rhythm Association EUROPACE 2013, people in Denmark from the Diet, Cancer, and Health Cohort Study enrolled at age 50 to 64 years from 1993 to 1997 were followed for a mean of 13.6 years. Of the 55 996 participants who at baseline were without a history of AF or atrial flutter or of cancer, 3425 developed new-onset AF.

The U-shaped curve reflecting risk of new AF by daily intake of omega-3 PUFA emerged in multivariate analyses, with the lowest risk near the median consumption of 0.63 g/day. An analysis of risk by intake quintiles showed a significant 13% reduction at the middle quintile (p=0.02) compared with quintile 1, the lowest-intake level. Risk wasn't significantly reduced or elevated at any of the other three quintiles.

Hazard Ratio* (95% CI) for New Onset AF by Omega-3 PUFA Intake Quintiles in the Diet, Cancer, and Health Cohort Study

Daily intake quintiles HR (95% CI)
Q1 <0.39 g (reference) 1.00
Q2 0.39–0.53 g 0.92 (0.82–1.02)
Q3 0.54–0.73 g 0.87 (0.77–0.97)
Q4 0.74–0.99 g 0.96 (0.85–1.07)
Q5 >0.99 g 1.06 (0.95–1.18)

*Adjusted for hypertension, systolic blood pressure, body-mass index, waist circumference, smoking, alcohol intake, years in school, hypercholesterolemia and/or cholesterol treatment, total serum cholesterol, angina pectoris, diabetes, MI, and heart failure

It isn't clear how there could be more AF risk at higher omega-3 PUFA intake levels, which is "difficult to explain," Rix said. "So far, we can only speculate that the balance between AF-inhibiting and AF-promoting effects may change depending on comorbidity and the intake of marine omega-3 PUFA. Other explanations might include potential risks from toxic compounds accumulated in fish, but a direct link of such compounds to AF has not been established."

The study was funded by the Danish Cancer Society. There were no other disclosures.

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