Tuesday, May 22, 2018
Health

The fishy origins of the fish oil craze

In the 1970s, a pair of Danish researchers ventured north of the Arctic Circle and into medical lore. Studying a scattered Inuit population, they concluded that eating plenty of fish and other marine animals protected this group from heart disease. The researchers would eventually suggest that everyone else's hearts and arteries might also benefit from the "Eskimo diet," promoting a health food trend that continues to this day. The only trouble is, the two Danes never proved that the Inuit had low rates of heart disease. They never tested it at all. But today the market for fish oil pills is booming, even as scientists conduct trial after trial to hunt for a link to heart health that has never quite solidified.

Hans Olaf Bang and Jørn Dyerberg were clinical chemists at Aalborg Hospital North in Denmark. Curious about the nutrition of the Inuit, they "undertook an expedition" to the northwest coast of Greenland, which they described in a 1971 Lancet paper. They stopped at a town called Uummannaq. Counting the surrounding settlements, the population totaled 1,350 people, living off what they could hunt and fish from the unforgiving land.

The researchers drew blood from 130 natives. Compared to Danes, the Inuit had lower levels of lipids such as cholesterol and triglycerides. Yet they had a higher proportion of the molecules known as omega-3 fatty acids, which are common in oily, cold-water fish. On a subsequent journey north, Bang and Dyerberg asked the Inuit for samples of their meals for several days. Chemical analysis of the food samples showed that, compared to typical Danes, the Inuit ate more protein, more cholesterol, and a higher proportion of omega-3 fatty acids. None of this was too surprising — as the researchers described it, the Inuit diet was "mostly of meat of whales, seals, sea birds, and fish," with the main bread product being "some sort of ship biscuit."

You might expect such a carnivorous diet to be a recipe for heart disease. But, the authors speculated, plentiful omega-3 fatty acids seemed to be protecting the Inuit. By 1980 the researchers were suggesting that following a similar diet might prevent heart disease in people who, unlike the lucky Inuit, were prone to it.

How did they know the Inuit weren't prone to heart disease? Bang and Dyerberg were nutritionists, not cardiologists; they didn't examine anyone's heart themselves. Instead, they relied on numbers provided by Greenland's chief medical officer for parts of the 1960s and 1970s. These reports, based on death certificates and hospital admissions, included only a handful of confirmed heart disease cases from Uummannaq.

But there's a problem with relying on official medical records in a part of the world so remote that — according to a deputy chief medical officer in the 1970s — 30 percent of people lived in settlements with no medical officer at all. This meant many death certificates were filled out by whoever was nearby, without a doctor ever seeing the body. Someone experiencing heart attack symptoms might not be close enough to a hospital to attempt a trip. Even if he did, the hospital might have limited equipment for diagnosis. And 20 percent of heart attacks cause sudden death.

Given these circumstances, how could official records be expected to catch every heart attack that happens in an icy outpost far from any doctor? "It's highly unlikely," George Fodor says with a chuckle. He's a cardiologist at the University of Ottawa Heart Institute who has been studying heart disease and how to prevent it for more than four decades. What's more likely, he thinks, is that the numbers used by Bang and Dyerberg were a serious underestimate of Inuit heart disease.

For a recent review paper in the Canadian Journal of Cardiology, Fodor and his co-authors gathered all the studies they could find of Inuit cardiovascular health in Greenland, Canada, and the United States. A few of the studies found low heart disease rates. But most of them concluded that cardiovascular disease was just as common in the Inuit as in other populations — or more common. The more recent studies may represent an Inuit population that eats a more Western diet than in Bang and Dyerberg's day. But a report published by a Danish doctor in 1940 also described high rates of heart disease in the Greenland Inuit.

What matters most to a disease researcher, Fodor says, is overall mortality: "the number of corpses you count." A study found that from the late 1960s to early 1980s, Inuit died from all causes at twice the rate of Danes — hardly a lifestyle to aspire to.

When Bang and Dyerberg wrote about what they had seen and done in Greenland, they were straightforward. They didn't aim to deceive. Yet their message got twisted as it was cited and re-cited in generations of research articles. Bang and Dyerberg, other authors confidently declared, had gone to Greenland and found that the Inuit had low rates of heart disease. It was a fact.

This tale is still told in new studies of omega-3 fatty acids. Fodor found recent mentions in the New England Journal of Medicine ("Bang and Dyerberg ... confirmed a very low incidence of myocardial infarction"), Circulation ("epidemiologists observed a low coronary heart disease rate among native Alaskan and Greenland Eskimos who consumed a large amount of fish"), and other major journals.

Today, the American Heart Association says that people with coronary artery disease should take daily fish oil supplements. Nutritional guidelines in the United States, Canada, and Europe call for fish twice a week. Yet for all the enthusiasm that has surrounded these famed fatty acids in the past few decades, their performance in clinical trials has been mixed.

One of those clinical trials is going on right now, run by Brigham and Women's Hospital, an affiliate of Harvard Medical School. The Vitamin D and Omega-3 Trial, VITAL for short, is looking at the effect of both omega-3s and vitamin D in healthy adults. (An article about the trial that appeared in Nutrition Action Healthletter, the newsletter of the Center for Science in the Public Interest, name-checked Bang and Dyerberg.)

JoAnn Manson, principal investigator of VITAL and a professor at Harvard Medical School, doesn't think the details of the old Danish studies matter much to today's research. "I've never put a lot of stock in" that kind of research, she says. So-called ecological studies, which look at a whole population of people at once rather than individuals, are fraught with uncontrolled variables — even when, unlike Bang and Dyerberg, researchers actually measure the disease they're studying.

What matters is the next, more rigorous steps that those studies send scientists toward. "Whether those studies were valid, or appropriately done, or not, they generated a hypothesis," Manson says.

The hypothesis was that an "Eskimo diet" heavy in omega-3 fatty acids could protect against heart disease. The next step was laboratory research, Manson says, to look for possible mechanisms. Scientists turned up some evidence that omega-3s may lower triglycerides, prevent irregular heart rhythms, and reduce inflammation — all of which could be important to heart health. Then there were long-term observational studies like the Nurses' Health Study. These studies showed links between eating fish and having a healthy heart — but, Manson stresses, they didn't prove causation. People who eat more fish might eat less of other heart-damaging foods or have healthier lifestyles in other ways.

To truly learn whether omega-3s guard heart health or not, we need research that goes a step further: large-scale, randomized trials. A couple of early omega-3 trials got positive results, but they lacked a placebo control group. (That is, there were no subjects swallowing sham pills instead of the real thing.) More recently, randomized and placebo-controlled studies didn't find any benefit from fish oil. But these studies looked at patients who already had heart disease; they didn't ask whether omega-3s help healthy people. And medications like statins or aspirin could have masked any positive effects of fish oil in these trials, Manson says. VITAL will follow more than 25,000 healthy people taking real or placebo pills over the course of five years. By 2018, there will be an answer.

Manson believes that answer could easily go either way. "The vast majority of researchers who really know this field believe the jury's still out," she says. Fish oil might be a cheap, effective way for people to protect their health. Or it might be a red herring.

Even if the latest trial vindicates omega-3s at last, Fodor is disturbed that so many of his colleagues have bought into the myth of Bang and Dyerberg, asserting in their own papers that the Danes found low rates of cardiac disease in Inuit. "Nobody even, obviously, read this paper!" he says.

Fodor thinks it's all part of a habit we have of seeking cures in exotic populaces. In the early 20th century, there was hype surrounding the yogurt eaten by long-lived Bulgarians. More recently, the Yanomami Indians of Brazil, who consume barely any salt, got a lot of attention from hypertension researchers. Fodor compares fish oil, at least the way some people view it, to 19th-century snake oil: a miraculous food that can save us from disease and death.

Manson, too, wants to know once and for all whether fish oil is helpful or just hype. The fact that we haven't figured it out yet is what makes the study worth doing, she says. With any trial, researchers hope that the drug or treatment they're testing will prove to work. We hope that the next idea born in the Arctic dusk will hold up to the light of day. But, Manson says, "you can never become too attached to a hypothesis."

Elizabeth Preston blogs at Inkfish and is the editor of Muse, a science magazine for kids.

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