The Rise and Fall of Omega-3s

If this newsletter covered market trends, the title would be something like “The Never-ending Rise of Omega-3s”. The industry has grown rapidly since the 1990s and is expected to continue expanding.

What has fallen is the scientific reputation of omega-3 supplements. This month, you can hear a resounding thud as two new studies question their benefits for brain health. One of those studies shows that omega-3s actually accelerate cognitive decline.

Why has scientific enthusiasm for these supplements waned? Are they really bad for brain health? If not, should anyone be taking them?

Omega-3 supplements

“Omega-3” sounds like the newest transformer, or an expensive watch, but the term refers to a group of polyunsaturated fats that are essential for health. Here are the three types and some of their natural sources:

ALA is also found in canola oil, soybean oil, and, to a lesser extent, leafy green vegetables. Our bodies convert ALA into EPA and DHA, though in limited amounts.

After vitamins, omega-3s are the most commonly purchased supplement in the US. Over half of these supplements come from fish. (Any product labeled “fish oil” contains omega-3s.) Other sources include algae and krill, as well as non-marine foods like flaxseed. Most products contain ALA, EPA, and DHA, but each type can be purchased separately. And, as you’ve probably noticed, they’re also added to products ranging from multivitamins to fortified milk and eggs.

The origin story

The multibillion dollar omega-3 industry can trace its origins to research in the 1970s by Danish scientists Hans Olaf Bang and Jørn Dyerberg.

Bang and Dyerberg were intrigued by an apparent paradox: The Inuit people of Greenland have virtually no coronary artery disease, in spite of consuming prodigious quantities of animal fat (mostly seal and fatty fish, occasionally whale) and almost no fruits and vegetables.

Bang and Dyerberg found that the Inuit have healthy lipid profiles but unusually high EPA and DHA levels. They hypothesized that these omega-3s have anti-inflammatory and anti-thrombotic (i.e., blood thinning) properties that protect the Inuit against heart disease.

Hindsight is 20-20

Bang and Dyerberg’s work was exciting because it promised a simple solution to major public health problem.

In retrospect, their omega-3 hypothesis looks awfully weak.

Their own studies and others hint at alternative explanations, including a combination of active lifestyles (the Inuit hunted from daybreak through early afternoon) and minimal consumption of alcohol, sugar, and what we now call ultraprocessed foods.

These hints were overlooked, but no matter. It turns out that the Inuit aren’t especially heart healthy to begin with.

Bang and Dyerberg’s assumptions to the contrary were based on reports from Greenland’s Chief Medical Officer, which wouldn’t have been very credible.

Why not? Because the researchers studied Inuit in the Umanak area, roughly 300 miles north of the Arctic Circle. Most of these individuals lived in remote settings far from medical facilities. Experts have noted that least 20% of their death certificates were signed without examination by a doctor. Under such conditions, you wouldn’t expect accurate data on disease rates.

Indeed, later studies found that the Greenland Inuit experience the same rates of heart disease as Europeans and Americans do. But I’m getting ahead of the story.

A trickle becomes a flood

Following Bang and Dyerberg’s lead, evidence that EPA and DHA have cardioprotective effects started trickling in, and fish oil capsules began to be sold in niche markets such as health food stores.

During the 1990s, the trickle became a flood. Most prominently, the 1999 GISSI-Prevenzione study showed that among people who’d experienced a heart attack, one gram of omega-3s per day reduces the risk of subsequent heart attacks and deaths from cardiovascular causes. (One gram is about three times the amount of omega-3 found in most over-the counter supplements, though some contain that much or considerably more.)

By the first decade of the new millennium, fish oils and other omega-3 products had become America’s most popular supplements other than vitamins, though evidence of health benefits was already beginning to dwindle. Poorly-designed, industry-funded studies continued to show benefits; higher-quality research did not.

In fact, a 2020 study on the Inuit themselves, the first of its kind, found no association between omega-3 levels and cardiovascular disease.

Here’s how the authors of an influential Cochrane meta-analysis summarized the literature:

“Moderate‐ and high‐quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health [among the general population]... Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias...”

The current landscape

Scientists have come to realize that high doses of certain omega-3s might benefit certain at-risk groups, if not the general population.

In the US, two FDA-approved medicines contain omega-3s: Lovaza (EPA + DHA) and Vascepa (EPA only). Both help treat severely high triglyceride levels, and Vascepa is also prescribed to help lower the risk of heart attack and strokes among high-risk groups.

So, why are omega-3 supplements still growing in popularity? And why are scientists continuing to study their health impacts in the general population?

Consumers, presumably, are influenced by slick marketing, a preference for “natural” products, and a generally positive attitude toward fish oils that Paul Greenberg traces back to cod liver oil. (I highly recommend Greenberg’s book The Omega Principle. Among other things, it offers a close look at the environmental impacts of omega-3 production.)

Meanwhile, poorly-designed industry-funded studies continue to proliferate (and support the marketing), but there’s high-quality science too, most of it focusing on cardiovascular functioning or brain health.

I think cautiousness is the main reason why “good” science hasn’t given up on omega-3s. When new studies contradict existing ones, scientists don’t discard the older data right away, even if seems flawed. Rather, they refer to the evidence as “mixed”, and they continue gathering data. (Rome wasn’t built in a day; it wasn’t torn down in a day either.)

This brings me to the new study suggesting that omega-3s are bad for brain health.

Omega-3 supplements and cognitive decline

This study appears in the June issue of The Journal of Prevention of Alzheimer’s Disease, a top-tier journal in the field. The study was led by Zheng-Bin Liao at Third Military Medical University in Chongqing, China.

Liao and colleagues analyzed data on 819 adults in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), an ongoing project whose participants are all American or Canadian. Just over half of these individuals are carriers of the APOE ε4 gene, meaning they’re at risk of Alzheimer’s disease. The others have no known genetic risks.

The researchers used a technique called propensity score matching to create two groups of adults who were as similar as possible, except that one group reported taking omega-3 supplements and the other group did not. The groups consisted of 273 and 546 individuals, respectively, each with a median age of around 73 years.

Liao and colleagues’ looked at changes in scores on three tests of cognitive functioning:

• The Mini-Mental State Examination (MMSE). This is a quick, informal screener asking test-takers to identify the date, copy geometric figures, count backwards from 100 by 7s, and so forth.

• The Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADASC-Cog13). This also tests basic cognitive skills, but it’s more sensitive to changes in functioning than the MMSE.

• The Clinical Dementia Rating–Sum of Boxes (CDR-SB). This is a cognitive test that includes a look at functioning in everyday contexts such as work, social interactions, and personal care.

Participants were tested multiple times (median followup was 5 years; the range was not provided). MRI and PET imaging data were also recorded.

Main findings

1. People taking omega-3 supplements showed more rapid decline on each of the three cognitive tests than the comparison group did.

To put that finding in context, the omega-3 group exhibited roughly 8 to 15% of the annual decline ordinarily seen among people diagnosed with Alzheimer’s disease.

2. Decline in cognitive function was linked to poorer brain glucose metabolism, but not to an accumulation of amyloid or tau, or to grey matter atrophy.

In other words, what happened among the omega-3 group wasn’t the accumulation of proteins or the loss of grey matter that accompanies Alzheimer’s disease, but rather a reduction in neural uptake of glucose, meaning that brain cells weren’t communicating as actively or efficiently.

How to interpret the findings?

The findings may sound grim if you happen to take omega-3 supplements – but don’t throw them away just yet.

A key limitation of this study is that information wasn’t available on the types and quantities of omega-3s that people consumed.

Thus, even if we trust the findings, we can’t rule out the possibility that the effects were driven by a few people in the omega-3 group who were taking too much of the supplement. (Or, taking fairly large amounts plus eating a lot of fish.)

I’m not sure I trust the findings in the first place. It’s unclear why the omega-3 group started taking supplements in the first place – perhaps they were already noticing some cognitive decline. More importantly, most RCTs with humans show that omega-3 supplements don’t affect cognition one way or the other.

A particularly good example is an RCT published in The Lancet one week ago. This study, conducted by researchers at USC, showed that DHA taken in supplement form reaches the brain but – at least within a 2.5 year period – does not reduce grey matter or affect cognitive functioning.

Should you take omega-3 supplements?

I don’t see good evidence that over-the-counter omega-3 supplements are inherently harmful, assuming you don’t exceed the recommended dosage.

Still, I find it hard to justify taking them, unless they’re prescribed by your doctor, or recommended because you’re pregnant, or your diet happens to be unusually low in omega-3s. A vegan with certain food allergies, for instance, might benefit from supplementation.

Assuming you do take omega-3s, what exactly should you be aiming for?

For ALA, the National Academy of Medicine recommends 1.6 grams per day for males and 1.1 grams per day for female. (This is for individuals 14 and older.)

To put those numbers in context, a person would get more than 1.3 grams of ALA from two tablespoons of soy oil, canola oil, flaxseed oil, or mayonnaise, or an ounce of walnuts or chia seeds, or three and a half cups of beans or edamame. (More details can be found in a large USDA database here.)

NAM doesn’t provide recommendations for EPA and DHA because our body synthesizes them from ALA, but since fairly little is synthesized, other professional organizations offer advice such as 250-500 mg per day of EPA and DHA combined.

Honestly, I’m not sure what to do with that, since you can only make, at best, a crude guess as to how much EPA and DHA you’re getting from ALA in your food. The current Dietary Guidelines for Americans takes the more practical approach of recommending 8 to 12 ounces of seafood per week. That seems reasonable, keeping in mind that the best sources would be smaller, fatty fish (salmon, mackerel, tuna, herring, sardines, etc.).

Final thoughts

Over the past century our society has been statisfied, or transformed by modern statistics. The omega-3 saga illustrates why this can be a mixed blessing. For instance:

Statistics helped 20th and 21st-century scientists determine, for the first time in history, how specific nutrients such as omega-3s influence our health. In the Lancet study, and others like it, statistics also help rule out certain influences (i.e., no cognitive benefits from DHA intake).

At the same time, statistics allow some industry-funded scientists to misrepresent data in way that make nutrients seem more beneficial than they probably are. (Emphasis on “some”. Industry funding doesn’t guarantee industry-friendly data.)

Another positive is that statistics help translate scientific data into concrete practical guidelines, such as the recommendation that we eat 1.1 or 1.6 grams of ALA per day.

Here too, there’s a downside. I don’t carry a little scale everywhere I go. Even if I did, I wouldn’t want to consult the USDA database for an estimate of exactly how much of the omega-3s each food provides. After all, recommendations for daily intake come from statistical generalizations that don’t necessarily apply well to individuals.

You can be Bryan Johnson, if you wish, and analyze the micro- and macro-nutrient content of everything you eat. Johnson, famous for devoting his life to living forever, surely knows his omega-3 intake better than you and I know our own. But he’s not going to live forever. He’ll enjoy a long and healthy life, I expect, but I believe we can too, if we take the best of what science and statistics tell us and not attempt to micromanage every last detail of our diets and other lifestyle choices.

(As you might guess, I applaud the squishiness of Michael Pollan’s famous dictum “Eat food. Mostly plants. Not too much.” It’s hard to imagine better nutritional advice in just seven words, and I don’t think a numerical definition of “mostly” would be an improvement.)

Thanks for reading!