The Skeptical Cardiologist

Omega-3 Fatty Acids and Cardiovascular Disease Risk: Has the Story Ended or Only Just Begun?

The skeptical cardiologist recently gave a virtual presentation for the Saint Louis University School of Medicine Grand Rounds which was an update on recent studies examining the therapeutic benefit of omega-3 fatty acids and fish oil supplements.

The talk is about 45 minutes and is absolutely mesmerizing. Just kidding. Actually, I’m always amazed at how oddly and slowly I speak even when I’m totally at ease and know the topic backwards and forwards.

I start with reminiscing on my training at SLU: “It’s a great pleasure to be back here at SLU where I did all my medical and cardiology training in the clinical crucibles of fire known as City Hospital, the John Cochran VA Hospital and Fermin Desloge.”

City Hospital has long been gone and the building and area, both of which were quite scary in the 1980s have long been gentrified. Fermin Desloge hospital, per Wikipedia, was opened in 1932 by the Jesuits of Saint Louis University and the Sisters of Saint Mary and was established to serve the poor and needy.

Fermin Desloge Hospital on left where I did my training. The brand new SLU/SSM on the right. Inpatient SLU operations shifted to the new hospital in late 2020.

I began by indicating that I would be talking on “a weirdly interesting topic which spans the disciplines of nutrition, business, the nutraceutical-industrial complex, quackery and preventive cardiology and yields fascinating insights into the glaring weaknesses of nutritional epidemiology, the hidden weaknesses of randomized clinical trials, and the many sources of bias in scientific research.”

Here’s the video of my talk which was followed by about 30 minutes of questions and comments, including a discussion on cooking oils.

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I wrote out the beginning of the talk and that transcript is below:

What I’ll address in the next 40 minutes can be boiled down to a question most of us over the age of 40 have asked ourselves: Should I take fish oil supplements to prevent cardiovascular disease.?

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Although almost all my academic research and publications have been in the field of echocardography, for the last dozen years I have evolved into a clinical cardiologist with major interests in preventive cardiology and enlightened medical management of atrial fibrillation

Over the years I’ve cultivated a healthy skepticism for medical and scientific information that has potential bias.

To educate my patients, myself and the public at large I started writing a blog in 2013 which began by looking at the scientific underpinning (or lack thereof) of current dietary guidelines relating to cardioprotection

One of the first topics I tackled was fish oil supplements which seemed to have a solid scientific and guideline support. Before I looked deeply into the topic I was advising patients with CAD or at high risk for CAD to take fish oil supplements but after I began taking patients off them.

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The fish oil story begins with observations that Eskimos in Greenland who consumed an extremely high fat diet rarely had evidence of coronary heart disease

In the 70s, two Danish doctors, Hans Olaf Bang and Jørn Dyerberg, went to Greenland because they’d read there were very low levels of cardiovascular disease among the Inuit eating seals and whales and fish. 

When they did blood lipid analyses of Inuit samples, they found very high amounts of omega-3 fatty acids and formed a hypothesis that omega-3s might be responsible for the lower levels of coronary heart disease among Greenland Inuit.

These observations have triggered tens of thousands of studies which have attempted to determine if omega-3 fatty acids (OMFAs) are the key to cardio protection. 

In the last 40 years there has been a pronounced movement to proclaim all saturated fats as bad and all PUFAs as good. Simplifying nutritional advice in this way makes for simple public health messaging but blurs the truth. For example, there is no solid evidence that dairy fat which is predominantly saturated has any negative cardiac effects.

Likewise, with PUFAs, many researchers have concluded that humans are consuming far too many omega-6 PUFAs which are predominantly obtained from corn, safflower and soybean oil. Canola oil, a product of factory ultra processing and genetic manipulation is widely promoted as very good for the heart.

The Omega-3 fatty acid family consists of long-chain (18 to 22 carbons) PUFA with a double bond at the third carbon from the omega end. The marine OMFAs of interest are EPA and DHA which are predominantly derived from seafood consumption

DPA levels aren’t associated with fish consumption and have minimal relevant physiologic or clinical effects. DHA is a primary structural component of the human brain, cerebral cortex, skin, and retina. For organisms that do not eat algae containing DHA nor animal products containing DHA, DHA is instead produced internally from α-linolenic acid. Alpha-linolenic acid is an 18-carbon essential n-3 polyunsaturated fatty acid (PUFA) derived from plant sources.

In addition to long-chain-3 PUFA, fish provide specific proteins, vitamin D, selenium, and other minerals and elements.

Observational studies have demonstrated an inverse association between dietary consumption of either fatty fish or omega-3 fatty acids and incident cardiovascular events and that circulating concentrations of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) inversely correlate with cardiovascular risk.

Of course all these studies did not prove that eating fish or taking OMFA supplements reduces your risk of CVD.

 This doesn’t stop press releases and news stories related to these observational studies from promoting them as showing causality and implying an important role for supplementation in reducing heart disease. Nutrition guidelines from the AHA in 2005 co-authored by Bill Harris, arguably the world’s foremost expert on OMFA concluded that Everyone in the population should eat “a variety of (preferably oily) fish at least twice a week” and that their diet should include “oils and food rich in ALA (flaxseed, canola and soybean oils” flaxseed and walnuts.”

What are the “oily fish” all Americans should be consuming twice per week. The amount of EPA+DHA in the recommended portion size of 3.5 oz of fish varies wildly

To make things more complicated with fish consumption, one has to consider mercury content and the sustainability of the species one is consuming. The EDF has a seafood selector that rates each type of fish on these 3 items. But even within something you might think would be incredibly healthy, the mackerel, depending on the specific kind the levels of mercury vary wildly

As a result, most Americans through up their arms in frustration and confusion and prodded on by a burgeoning fish oil supplement industry which was freed from any constraints of the FDA by legislation in 1994, they began buying millions of fish oil supplements

Thus began the era of fish oil as snake oil, promoted widely by quacks like Dr. Oz who recommended “FISH OIL FOR ALL!”

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Thus ends the “transcript.”

For the remainder of the presentation I spoke without script, analyzing in detail recent large randomized controlled trials of large dosage omega-3 fish oil supplementation. Spoiler alert, the STRENGTH trial found no cardiovascular benefits.

Along the way I touch on the weaknesses of observational epidemiology and the sneaky ways the fish oil supplement industry biases scientific publications.

My conclusion is that there is no compelling evidence for you to take over the counter fish oil supplements for primary or secondary prevention of cardiovascular disease.

I also discuss the reasons behind questioning the benefits of icosapent ethyl (Vascepa) which were demonstrated in the REDUCE-IT trial and why there needs to be another trial that compares icosapent ethyl to a neutral oil like corn oil rather than mineral oil.

Just prior to giving my talk I came across a study published in late 2020 which is the first prospective study in Inuit on the cardiovascular effects of long-chain n-3 polyunsaturated fatty acids. No effect was found, as summarized in this cute graphic, which I believe brings us full circle in our OMFA journey.

Pescatorially Yours,

-ACP

Feature image Evidently Cochrane

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