Atrial fibrillation, often referred to as AFib or AF, is the most common type of heart arrhythmia. Simply put, a heart arrhythmia occurs when the heart’s electrical systems responsible for telling the heart how and when to beat is faulty. In the case of AFib, what happens is that the upper (the atria) and lower (the ventricles) chambers of the heart are not in working sync, resulting in the heart beating too slowly, too quickly or inconsistently.

According to the Heart Rhythm Society, the impact of AFib is global, with nearly 40 million individuals affected worldwide including six million in the U.S. What’s more, the Centers for Disease Control and Prevention (CDC) estimates that by 2030 that U.S. figure will double.

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The risk for AFib increases with age. About 2% of the U.S. population younger than 65 years old have AFib, while that stat more than quadruples to 9% for those 65 and older.

Some people with AFib may experience one or more of these symptoms:

  • Irregular heartbeat
  • Heart palpitations, either rapid, fluttering or pounding
  • Lightheadedness
  • Extreme fatigue
  • Shortness of breath
  • Chest pain

But approximately 15-30% don’t have any symptoms and don’t even know they have AFib. In those cases, AFib may be discovered during a physical exam or while testing for another medical condition.

 

Enter Omega-3 

Here’s where we bring omega-3 fatty acids into the story. Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients with a variety of associated potential health benefits, including some related to heart health. Learn more here.

For today’s blog, it’s relevant to share the omega-3 origin story from our blog on Eskimos in Greenland studied by two Danish investigators whose scientific hypothesis was published in The Lancet in 1978. It’s this heart hypothesis from the late 1970s that truly put omega-3 EPA and DHA on the map, igniting a flame for more and more research on omega-3 EPA and DHA that continues to this day.

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In summary, the hypothesis from Drs. Dyerberg and Bang, opines that EPA, a main component of omega-3s, could reduce risk for thrombosis and atherosclerosis. Since this publication, that theory has since been well-confirmed and other beneficial mechanisms for omega-3 EPA and DHA have been discovered as well. To date, omega-3 fatty acids have become the most researched nutrients in biology, with the number of studies on omega-3 surpassing that of statins and aspirin combined.

So, it should come as no surprise that studying omega-3s and AFib was, and continues to be, of great interest to the scientific, medical and nutrition communities.

 

What is the Relationship Between Omega-3 and AFib?

To say the least, the relationship is complicated. As often happens in science, the relationship is a see-saw of sorts. In other words, we don’t have consistent answers at this point, much as we would like to. But the story, with its ebbs and flows, is something we, at OmegaQuant, are following with interest.

We’re about to get to the science, but first an introduction to one of the world’s preeminent experts on omega-3 PUFAs, William S. Harris, Ph.D., someone we will be quoting throughout this blog. In 2004, Dr. Harris co-developed an omega-3 blood test called the Omega-3 Index and five years later founded OmegaQuant Analytics to offer the test to researchers, clinicians and consumers. Learn more here.

In 2020, Dr. Harris started the Fatty Acid Research Institute (FARI) to accelerate the discovery of fatty acid and health relationships, and his scientific productivity was recently ranked among the top 2% in a survey of scientists worldwide.

In a recent webinar for healthcare professionals and health-minded individuals, Dr. Harris reviewed the key science surrounding the association between omega-3 and AFib.

If you’re hoping for a clear-cut answer about that association, we’re sorry we can’t answer that at this time. But if you’re curious as we are as to where the science is going, let’s take a look.

 

What Has Some of the Research Found?

Dr. Harris said that “AFib is a big problem that’s been around for a long time.” Starting in the mid-to late 1990s, there was great interest in trying to control or treat AFib with omega-3, he added.

With regard to omega-3 and AFib, the early studies were in animals, with one in particular in rabbits that showed less incidence of AFib in the rabbits given fish oil, compared to sunflower oil or placebo.

Observational studies in humans followed that compared the risk for AFib from either supplemental omega-3, fish intake or circulating blood levels of omega-3. The early results found only favorable or neutral relationships between AFib and omega-3. At this point, there was no adverse relationship between the pair.

One such study from Mozaffarian et al., was published in 2004 in Circulation. The large prospective, population-based cohort followed 4815 adults ages 65 years and older and assessed dietary intake assessments at baseline. Consumption of tuna and other broiled or baked fish correlated with higher plasma phospholipid long-chain omega-3 fatty acids; consumption of fried fish or fish sandwiches/burgers did not.

During a 12 year follow-up period, 980 cases of AFib were diagnosed, with AF incidence prospectively ascertained based on hospital discharge records and annual electrocardiograms.

In multivariate analyses, consumption of tuna or other broiled or baked fish was inversely associated with incidence of AF, with 28% lower risk with intake 1 to 4 times per week and 31% lower risk with intake of ≥5 times per week compared to <1 time per month.

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The opposite results were found with fried fish or fish sandwiches. After adjustment for potential confounders, intake ≥1 time per week was associated with 24% higher risk compared with <1 time month.

The findings led the authors to conclude that fish intake may influence the risk of AFib.

In another earlier study, this one a randomized control study (RCT) published in 2005 in the Journal of the American College of Cardiology (JACC), the study authors noted that postoperative AF is a common complication of Coronary Artery Bypass Graft (CABG) surgery and that there was growing clinical evidence that PUFAs have cardiac antiarrhythmic effects.

So, Calo et al., set as the study objectives to assess the efficacy of preoperative and postoperative treatment with omega-3 PUFAs in preventing the occurrence of AFib after CABG.

A total of 160 male and female patients were randomized to two groups: 81 patients, 13 female, ages 64.9 ± 9.1 years in the control group and 79 patients, 11 female, 66.2 ± 8.0 years in the PUFA treatment group (2 g/day for at least 5 days before elective CABG and until the day of discharge from the hospital).

The results of this trial indicated the use of PUFAs during hospitalization in patients undergoing CABG significantly reduced the incidence of postoperative AF (18.1% absolute risk reduction, 54.4% relative risk reduction) and was associated with a shorter hospital stay. Further, except for a single case of allergic response, no significant adverse reactions were observed.

According to Dr. Harris, the assumption in the research community based on these two encouraging studies and others was that these safe and beneficial results would continue to be the norm as research progressed.

 

Why is There a Concern Regarding Omega-3 and Afib?

But instead, the story took a turn. In 2010, a prospective, randomized, double-blind placebo-controlled study from Kowey et al., designed to evaluate the safety and efficacy of prescription omega-3 fatty acids for the prevention of recurrent symptomatic AFib was published in JAMA.

The 650+ U.S.-based outpatient participants included 542 with confirmed symptomatic paroxysmal AFib (also known as intermittent AFib) and 121 with persistent AFib, no substantial structural heart disease, and in normal sinus rhythm at baseline.

Patients received prescription 8g/d or placebo for the first 7 days, followed by prescription omega-3 (4 g/d) or placebo thereafter through week 24.

The authors concluded that “among participants with paroxysmal AF, 24-week treatment with prescription omega-3 compared with placebo did not reduce recurrent AF over 6 months.”

That was a disappointing result but Dr. Harris saw something more surprising in the results. He noted that although not statistically significant, there was a trend towards more AFib in the treated group. Surprising because as the authors contextualized in their study, “limited data from small trials suggest omega-3 PUFAs may provide a safe, effective treatment option for AF patients.”

Then another study, this one co-authored by Mozaffarian et al., published in JAMA in 2012, set out to determine whether perioperative omega-3 supplementation could reduce postoperative AFib.

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Over 1500 patients scheduled for cardiac surgery in 28 centers in the U.S., Italy and Argentina were enrolled. The main exclusions were regular use of fish oil or the absence of sinus rhythm at enrollment.

Patients were randomized to receive 1g capsules of fish oil containing ≥840 mg omega-3 fatty acids or placebo, with preoperative loading of 10g over 3 to 5 days (or 8g over 2 days) followed postoperatively by 2g/d until hospital discharge or postoperative day 10, whichever came first.

The authors reported the results:  when compared with placebo, the omega-3 PUFAs did not reduce the reduce the risk of postoperative AF.

Although it was a null result, Dr. Harris pointed out that there was no suggestion of any increased risk for AFib in the treated group.

More recent studies have seen similar inconsistent results, which is often the case with science. Generally, one study does not trump another, but rather adds to the overall literature library.

Here are two more studies that shifted thoughts about omega-3 and AFib.

A meta-analysis by Gencer et al., published in Circulation in 2021, pooled results from seven RCTs (81,210 patients) following a literature search of 4049 screened records. The criteria for the included studies were RCTs with cardiovascular outcomes of marine omega-3 fatty acids that reported results for AF, either as a prespecified outcome, an adverse event, or a cause for hospitalization. (In other words, not trials that targeted AFib as the primary outcome.)

Other criteria included a minimum sample of 500 patients and a median follow-up of at least one year. About 73% of those enrolled were in trials testing ≤1 g/d and about 27% in trials testing >1 g/d of omega-3 fatty acids supplementation. The mean age was 65 years, and 31,842 (39%) were female. The weighted average follow-up period was 4.9 years.

In meta-analysis, the use of marine omega-3 fatty acid supplements was associated with an increased risk of AF (n=2905; HR, 1.25 [95% CI, 1.07-1.46]; P=0.013). In analyses stratified by dose, the HR was greater in the trials testing >1 g/d (HR, 1.49 [95% CI, 1.04-2.15]; P=0.042) compared with those testing ≤1 g/d (HR, 1.12 [95% CI, 1.03-1.22]; P=0.024; P for interaction <0.001). In meta-regression, the HR for AF increased per 1 g higher dosage of marine omega-3 fatty acids dosage.

The authors concluded this: In RCTs examining cardiovascular outcomes, marine omega-3 supplementation was associated with an increased risk of AFib. The risk appeared to be greater in trials testing >1 g/d.

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Then there is another case of scientific whiplash with this study from Qian et al. from JACC published in 2023 with the authors conclusion: “In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AFib. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AFib risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.”

This study looked at the question of whether there was a relationship between blood levels of omega-3 at baseline and risk for AFib. Pooling data from a global consortium of 17 prospective cohort studies, this analysis involved 7,720 incident cases of AF among 54,799 participants ascertained after a median 13.3 years of follow-up.

The multivariable analysis showed this: EPA levels were not associated with incident AF, HR per interquintile range (i.e., the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively.

The prospective studies included very large, long studies such as the Women’s Health Initiative and the Framingham Study, where the participants were AFib-free at the beginning of the study and then tested for everything under the sun and followed for many years for the development of different diseases, commented Dr. Harris. He added that this follow-up period was much longer than any randomized trial goes.

In this study, “if we compare the people with the highest omega-3 level versus the lowest,” said Dr. Harris, “if we look just at plasma level or circulating levels of EPA/DHA, there’s roughly a statistically significant 12% lower risk of developing AFib in the highest omega-3 levels versus the lowest.”

Dr. Harris noted that this is not a dietary supplement study, but rather the blood levels are driven by the different intake of omega-3 fatty acids and maybe some genetic factors that may raise or lower omega-3 levels.

VIDEO: OmegaMatters – Episode 31 – Omega-3 and Stroke Risk

 

What to Keep in Mind About Omega-3s and AFib Risk

One thing we haven’t touched on is that AFib is a major risk factor for ischemic strokes, those caused by blood clots. Read more here.

When making decisions about omega-3s and AFib it’s important to also consider your own individual risks for AFib. Here are some of those risk factors.

  • Coronary artery disease or previous heart surgery
  • High blood pressure
  • Heart problems at birth
  • Thyroid disease
  • Obstructive sleep apnea
  • Electrolyte imbalance
  • Some medications and supplements
  • Excessive alcohol use
  • Caffeine, nicotine or illegal drug use

Bottom Line: Here’s our best current advice, although we believe the story is not yet finished. Or as Dr. Harris says “we don’t know the full answers yet.” Having said that, consumption of omega-3s EPA and DHA from fatty fish and seafood has been consistently associated with lower risk for developing AF, whereas perhaps an ideal daily dose of EPA+DHA in supplement form would be ~600 to 750 mg/d. In contrast, higher dose omega-3 interventions (>1800 mg/d) appear to increase the risk of AF, though the absolute risk is small (~1%).

If you have a history of AF, discuss with your doctor whether to avoid omega-3 prescription drugs. Do what you can to decrease your risk factors for AF and try to follow the American Heart Association’s guidelines of at least 2 servings of fatty fish weekly.

These statements have not been evaluated by the Food and Drug Administration. This test is not intended to diagnose, treat, cure, prevent or mitigate any disease. This site does not offer medical advice, and nothing contained herein is intended to establish a doctor/patient relationship. OmegaQuant, LLC is regulated under the Clinical Laboratory improvement Amendments of 1988 (CLIA) and is qualified to perform high complexity clinical testing. The performance characteristics of this test were determined by OmegaQuant, LLC. It has not been cleared or approved by the U.S. Food and Drug Administration.

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