Omega-3 Fish Oil Supplements Linked With Heart Rhythm Disorder

I agree with you that the outcome of the study is a bit counterintuitive. My response was more directed to the ones who replied that they would stop taking fish oil supplements because of the outcomes of this study.

For the last 20-odd years have I been eating fish multiple times per week (although not daily). I never felt the need to also use fish oil supplements.
 
More findings:

Warning: Combination of Omega-3s in Popular Supplements May Blunt Heart Benefits

https://scitechdaily.com/warning-co...popular-supplements-may-blunt-heart-benefits/

Doctors often recommend Omega-3s to help patients lower their cholesterol and improve heart health. Those Omega-3s can come from fatty fish like salmon and mackerel, or supplements that often contain a combination of the acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Now, new research from the Intermountain Healthcare Heart Institute in Salt Lake City finds that higher EPA blood levels alone lowered the risk of major cardiac events and death in patients, while DHA blunted the cardiovascular benefits of EPA. Higher DHA levels at any level of EPA, worsened health outcomes.


Results of the Intermountain study, which examined nearly 1,000 patients over a 10-year-period, will be presented virtually at the 2021 American College of Cardiology’s Scientific Session on Monday, May 17.

“The advice to take Omega-3s for the good of your heart is pervasive, but previous studies have shown that science doesn’t really back this up for every single omega-3,” said Viet T. Le, MPAS, PA, researcher and cardiovascular physician assistant at the Intermountain Heart Institute and principal investigator of the study. “Our findings show that not all Omega-3s are alike, and that EPA and DHA combined together, as they often are in supplements, may void the benefits that patients and their doctors hope to achieve.”

In this study, Intermountain researchers used the INSPIRE registry, an Intermountain Healthcare database started in 1993 that has more than 35,000 blood samples from nearly 25,000 patients.

Through INSPIRE, researchers identified 987 patients who underwent their first documented coronary angiographic study at Intermountain Healthcare between 1994 and 2012. From those blood samples, the circulating levels of EPA and DHA in their blood was measured. Researchers then tracked those patients for 10 years, looking for major cardiac adverse events, which included heart attack, stroke, heart failure requiring hospitalization or death.

They found that patients with the highest levels of EPA had reduced risk of major heart events. When evaluating how EPA and DHA affect one another, they found that higher DHA blunts the benefit of EPA. In particular, they also found that those patients with higher levels of DHA than EPA, were more at risk for heart problems.

Le said that these results raise further concerns about the use of combined EPA/DHA, particularly through supplements.

“Based on these and other findings, we can still tell our patients to eat Omega-3 rich foods, but we should not be recommending them in pill form as supplements or even as combined (EPA + DHA) prescription products,” he said. “Our data adds further strength to the findings of the recent REDUCE-IT (2018) study that EPA-only prescription products reduce heart disease events.”

Meeting: American College of Cardiology 2021

Other members of the research team include: Stacey Knight; Kirk Knowlton; Raymond McCubrey; Jeramie D. Watrous; Mahan Najhawan; Khoi Dao; Tami Bair, Benjamin Horne; J. Brent Muhlestein; Donald Lappe; Madisyn Taylor; John Nelson; John Carlquist; Mohit Jain; and Jeffrey Anderson.
 
There are some issues with this study, namely that they found an association (correlation) but that doesnt prove causation. But also, they reported a Incidence rate ratio of 1.37. What this means was an increase of 37% in the incident (atrial fibrillation) vs the placebo groups. It sounds like a lot but it really isn't. Smoking for instance, leads to a risk ratio (which is different from the Incidence rate ratio but it should resemble it enough to make the point) of around ~7.0 in terms of increase risk of lung cancer (according to one meta analysis I looked at). That means a 700% increase in the chance of the incident.

Its like if you are playing Bingo and your chance of winning is 2% then someone gives you the numbers that are a little more likely to come out because of a bug in the Bingo software, your chance then increases by 37%. Sounds like a lot but you are still only 2.74% likely to win.

And that raises the question, even if that correlation does indeed prove causation (which the study authors do not claim) doesnt the other benefits of O3 offset the 37% increase in odds of atrial fibrillation? The supplementation needs to be considered by looking at the overall benefits and costs, not just by looking at the costs. That would be like looking at a trade by only analyzing the size of the loss if you are wrong, but not considering how much you will win if you are correct

Non-organic Fruits and vegatables might have some downsides due the presence of pesticides and other toxic compounds but overall, its very likely they are a net positive to people due the presence of vitamins, fiber, other natural substances and the fact that they could be replacing much more dangerous junk food. That study didnt take that into account.

The authors did say this:
"The results of this meta-analysis show that individuals at high risk for, or with established CVD and elevated plasma triglycerides treated with O3FA supplementation have a significantly higher incidence of AF events, compared to placebo"

For individuals in that particular risk group, it COULD make sense use a lower dose or monitor risk factors for a stroke if they are on O3. And that would be a way to get the cake and eat it too. For others, it relative risk found seems unlikely to be anything to be worried about
 
Daal said:
For individuals in that particular risk group, it COULD make sense use a lower dose or monitor risk factors for a stroke if they are on O3. And that would be a way to get the cake and eat it too. For others, it relative risk found seems unlikely to be anything to be worried about
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My bottom line, IF the results can be accepted at face, is that fish oil supplements do not appear to benefit those at risk of CVD. That being the case, I wonder on what theoretical basis we can conclude that such supplements are beneficial for those who are not already at risk. Again, these musings are above my paygrade and on the assumption that the study results are valid. And so, in the meantime and until the dust settles, I will stick to whole foods rich in O3, both fish and plant.
 
Cardiologist follows the science to a new conclusion on fish oil supplements l Expert Opinion

"I used to think these pills were harmless. Now I’m thinking differently."

https://www.inquirer.com/health/exp...lements-heart-health-prevention-20210525.html

I have been a long-term proponent of fish oil supplements to prevent heart disease. I did a radio show every Sunday night for several years talking about the importance of lifestyle changes combined with taking high dose omega-3 fatty acids to help prevent coronary problems. There was good science behind it at the time, as fish oil had been shown to be anti-inflammatory, several studies had demonstrated a lower risk of heart attacks, and there seemed to be no downside risk. There were few side effects other than burping up an occasional taste of fish.

In 2019 the global market for omega-3 fatty acids reached $4.1 billion.

Over the last couple of years, there have been several studies that have questioned the benefit of fish oil supplements. The exception has been a trial called REDUCE-IT, in which a highly purified fish oil called Vascepa (icosapent ethyl) was used. This study examined people with high triglycerides and high cholesterol who were already on a statin to lower their cholesterol, and who had heart disease. It showed a 25% decrease in cardiac risk compared to half the participants in the study who took a placebo, which was mineral oil. The results were so impressive that Vascepa has become a hugely successful prescription product, with sales of $614 million in 2020, up 40% from 2019.

Another trial called STRENGTH looked at a similar group of people, and it used a slightly different fish oil preparation. It showed no difference between the fish oil and a placebo, which was corn oil.

No one has been able to reconcile the different results of these two trials.

Fish oil contains two omega-3 fatty acids called docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).

In a study released this month at the American College of Cardiology (ACC) meeting and simultaneously published in JAMA Cardiology, authors noted that while Vascepa is pure EPA, the STRENGTH oil was a mixture of DHA and EPA.

But the STRENGTH investigators looked at EPA and DHA blood levels in their participants. If EPA is good for you and DHA bad, then the group that had the highest blood levels of EPA, which was similar to the levels found in REDUCE-IT, would have been expected to do better. They did not.

Another reason has been suggested. It is possible that the placebo in REDUCE-IT was not a placebo at all. It was mineral oil, which can be inflammatory. In other words, the group that did well taking fish oil might have only done well because the placebo group was harmed, magnifying the difference.

Until a new trial is done comparing Vascepa to a different, inert placebo, we will not know if it is effective or it was compared to the wrong placebo.

One of the main reasons that I have recommended fish oil to patients for years has been the idea that it did no harm. In a recent meta-analysis (a review and analysis of multiple trials) published in the European Society of Cardiology, the authors found that people treated for high triglycerides with high dose (4 grams per /day) fish oil had more atrial fibrillation, an irregular heart rhythm. This analysis included everyone who participated in the STRENGTH and REDUCE-IT trials. The conclusion: People receiving fish oil had a significantly greater risk of atrial fibrillation, which can lead to a higher risk of stroke. The Vital Rhythm Study, published in JAMA in March, randomized 12,542 participants to receive a smaller dose of omega-3 fatty acids (847 mg of mixed DHA/EPA), and 12,577 people to receive a placebo containing olive oil. This trial did not show a significant incidence of atrial fibrillation, suggesting lower doses may be safer, but do not potentially help with prevention.

Fish oil can no longer be considered harmless. In high doses, it can increase the risk of developing atrial fibrillation.

It has been shown to be effective in just one major trial, and its results are now controversial. It was tested only in people with known coronary disease who already are taking a statin, and at high doses of 4 grams per day. Other groups of people either do not benefit or have never been tested.

In the future, based on these new studies, I will not be recommending fish oil to my patients to help prevent cardiac issues. Following the science can lead to unexpected places.

Of note: Every study done to date affirms the importance of diet, exercise, and weight loss to prevent cardiac problems, albeit without the use of fish oil supplements.


David Becker is a board-certified cardiologist with Chestnut Hill Temple Cardiology in Flourtown. He has been in practice for more than 30 years.
 
I’m not buying this is a controlled study. I mean, they would have to follow around and monitor 50,277 people and Record every single thing they consumed. And then there’s the matter of genetics. I tend to believe some animal rights activist funded this bunk low limit study.
BTW, doesn’t big Pharma have some synthetic omega-3’s they’re trying sell?
 
A cardiologist answers 10 questions from readers about fish oil and heart disease - Expert Opinion

https://www.inquirer.com/health/exp...iovascular-disease-afib-vascepa-20210707.html

I’m still not recommending the supplement to prevent heart disease. But that’s only the start of questions from readers of a recent Inquirer column.

I have written several articles about fish oil supplements, but none has generated the response that I received after my most recent piece, published in The Inquirer in late May. I evaluated a study that questioned the evidence for taking fish oil to prevent heart disease and concluded that I would no longer be recommending it to my patients. I clearly hit a nerve, especially in the pro-supplement crowd.

One reader said the column “is a scientific travesty and medically irresponsible, given the proven science behind high-strength icosapent ethyl (Vascepa) in reducing cardiac risk. At times, Dr. Becker wants to negligently conflate high-dose prescription icosapent ethyl (EPA) with all the fish oil supplements that can be bought off the shelf, which may be pretty much worthless.”

Another reader sent me an explanation by Deepak Bhatt (the primary author of the Vascepa trial) showing a 25% risk reduction in heart attacks and said, “I was a little surprised to see you’ve joined the attack on Amarin’s Vascepa by short sellers in the stock market and others trying to derail the outcome of a $600 million study of 8,000 people performed over seven years under the close watch of the FDA, which approved the use of mineral oil as the placebo.”

It is hard to know whether these responses are motivated by an understanding of the science or the financial markets. Vascepa is big business, and its success is largely dependent on the differentiation between it and other fish oils. There seem to be conflict of interests everywhere. The STRENGTH study, showing no cardiovascular benefit of fish oil, was run by cardiologist Steven Nissan. He often speaks about the dangers of conflicts but has received grants from multiple industry sources, including the manufacturer of the main Vascepa competitor. Bhatt, the principal investigator of the REDUCE-IT trial, has received grants from Amarin, the main sponsor.

The article that I wrote (I have no financial backing to disclose) raised many other questions from readers, not all of which were negative. Among them:

  1. “I was wondering if any of the studies took into the account the ick burp taste” of fish oil. The answer is yes, especially the purified prescription versions. If you do have this symptom, you can try keeping your fish oil in the refrigerator, as this will help prevent the “burp” taste.

  2. “Wouldn’t seeds and nuts be a more optimal choice?” Yes, nuts, seeds and olive oil have all been shown to decrease cardiac risk with moderate consumption. Fish, especially the more oily fishes, such as salmon, has also been shown to promote cardiac health. Eating fish with high levels of omega 3 fatty acids two or three times a week is good for you.

  3. “Absolutely beautiful clear-eyed analysis of the fish oil conundrum. Great contribution to soothe the confusion”

  4. “I take one teaspoon of cod liver oil daily and am wondering if this is chemically the same as fish oil.” It is not. Cod liver oil contains large amounts of Vitamins A and D, which at high levels may be toxic.

  5. “I am still wondering if the intake of omega 3 through algae and not fish oil will lead to the same results?” The beneficial effects (which are controversial) are probably from EPA and DHA, which primarily come from fish sources, and not algae.

  6. “One study and it’s over for you? … What if the study had faults?” I share this frustration. It can seem that medicine flip-flops with every new study. In this case, it is the increased risk of developing atrial fibrillation with high doses of omega 3 fatty acids that led to my conclusion that most people should not be taking fish oil supplements.

  7. “How can fish oil, especially from cold water (Alaska, Canada) be harmful or nonproductive to your health?” High-dose fish oil (2 grams twice a day) may cause a higher risk of atrial fibrillation. There is no way to eat that much fish at one sitting.

  8. “I often feel chest pains, palpitations and tiredness and fear that it may be a heart issue.” I wrote back right away to this man suggesting he see a doctor ASAP. The time to make a lifestyle change or consider a supplement is not when you are having symptoms suggesting heart disease.

  9. “Fish oil can still be useful in Ob-Gyn. Please avoid media sensationalism and black-and-white thinking in considering this study.” The studies that I have discussed relate only to the lack of cardiac benefits and should not be generalized to other possible benefits/harms of fish oil.

  10. “What do you recommend?” I am concerned about the cardiac risk of taking high doses of fish oil (4 grams a day}. I think it is interesting that I received very few comments about this risk. Unless you have high triglycerides and heart disease, the data suggest that the dose should be decreased to lower the risk of developing atrial fibrillation. There is no evidence that 1 gram a day causes afib, and that is what I have suggested to my patients if they wish to continue taking fish oil. Rather than supplementing, a better approach may be a diet rich in omega 3s, daily exercise, decreased intake of sugars and junk carbohydrates, not smoking, weight loss, and practicing relaxation techniques.
David Becker is a board-certified cardiologist with Chestnut Hill Temple Cardiology in Flourtown. He has been in practice for more than 30 years.
 
More of the same:

EPA vs. DHA: The new research on the health benefits of omega-3 fish oil

https://newatlas.com/health-wellbeing/epa-dha-omega3-fish-oil-heart-health-metastudy/

The ongoing debate over the health benefits of omega-3 fatty acids is divisive to say the least. Several studies over the past few years have suggested fish oil supplements, commonly taken to reduce a person’s risk of cardiovascular disease, may not be effective. A new meta-analysis of 38 randomized controlled trials is now suggesting the key to beneficial cardiovascular outcomes from omega-3 supplements could come down to the specific kind of fatty acid being consumed.

Three kinds of omega-3 fatty acids are known to play a role in human health. Alpha-linolenic acid (ALA) is perhaps the most common, primarily found in plant foods. The other two, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are the classic “fish oil” omega-3 fatty acids regularly found in health supplements.

Many over-the-counter fish oil supplements contain a combination of EPA and DHA. This has traditionally been thought to offer the best health benefits, particularly from the standpoint of preventing cardiovascular disease.

Last year a large Phase 3 clinical trial was discontinued after early data indicated a purified concentrated combination of EPA and DHA did not reduce the risk of adverse cardiovascular events. The trial failure was contrasted against another already FDA-approved drug called Vascepa, which was reporting increasingly positive cardiovascular effects.

Vascepa is a purified and concentrated form of EPA, and a growing hypothesis is suggesting the cardiovascular benefits of omega-3 fish oil could be solely due to EPA. And those benefits may be offset when EPA is administered alongside DHA.

The new research adds weight to that idea comparing the results of trials testing EPA + DHA supplements against trials looking solely at EPA monotherapy. The results confidently showed reduced mortality and improved cardiovascular health when EPA was administered alone.

The researchers note it is plausible to suggest the cardiovascular benefits of omega-3 fish oil are limited to EPA. The two fatty acids have distinctly different properties and interact with human cells in unique ways.

A compelling recent study, yet to be peer-reviewed and published, offers evidence backing up the EPA hypothesis. The research followed nearly 1,000 patients at a high risk of adverse cardiovascular events for 10 years. Circulating levels of both EPA and DHA were measured in their blood and the research found those with the highest levels of EPA showed the lowest risk for adverse cardiac events. But high DHA levels blunted the benefits seen in patients with high EPA levels.

"Our findings show that not all Omega-3s are alike, and that EPA and DHA combined together, as they often are in supplements, may void the benefits that patients and their doctors hope to achieve,” says Viet T. Le, principal investigator on the study.

Of course, continuing the trend of confusingly inconsistent omega-3 research, another recent study looked at the differences in EPA and DHA blood levels in subjects from a large omega-3 clinical trial. It reported no difference in cardiovascular events between those with high EPA blood levels taking EPA supplements and those in the placebo group. Even those subjects with high DHA levels in the trial showed no difference to the placebo group.

"To be thorough, we looked at the data multiple ways--absolute EPA and DHA levels, change in levels of these omega-3 fatty acids, red blood cell levels, and by primary and secondary prevention subgroups," explains lead author Steven Nissen. "All of these analyses showed no benefits or harms."

Deepak Bhatt, a co-author on the new meta-analysis, is confident in suggesting EPA is the source of omega-3 fish oil’s cardiovascular benefits. Bhatt was also lead investigator on a large trial called REDUCE-IT, focusing solely on the cardiovascular effects of high doses from a purified ethyl ester of EPA.

"REDUCE-IT was the largest and most rigorous contemporary trial of EPA, but there have been other ones as well,” Bhatt says. "Now, we can see that the totality of evidence supports a robust and consistent benefit of EPA. This meta-analysis provides reassurance about the role of omega-3 fatty acids, specifically prescription EPA. It should encourage investigators to explore further the cardiovascular effects of EPA across different clinical settings."


The new study was published in the Lancet journal, EClinicalMedicine.
 
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