Inuit Study Adds Twist to Omega-3 Fatty Acids’ Health Story

As the Inuit people spread across the Arctic, they developed one of the most extreme diets on Earth. They didn’t farm fruits, vegetables or grains. There weren’t many wild plants to forage, aside from the occasional patch of berries on the tundra.

For the most part, the Inuit ate what they could hunt, and they mostly hunted at sea, catching whales, seals and fish. Western scientists have long been fascinated by their distinctly un-Western diet. Despite eating so much fatty meat and fish, the Inuit didn’t have a lot of heart attacks.

In the 1970s, Danish researchers studying Inuit metabolism proposed that omega-3 fatty acids found in fish were protective. Those conclusions eventually led to the recommendation that Westerners eat more fish to help prevent heart disease and sent tens of millions scrambling for fish oil pills.

Today, at least 10 percent of Americans regularly take fish oil supplements. But recent trials have failed to confirm that the pills prevent heart attacks or stroke. And now the story has an intriguing new twist.

A study published last week in the journal Science reported that the ancestors of the Inuit evolved unique genetic adaptations for metabolizing omega-3s and other fatty acids. Those gene variants had drastic effects on Inuit bodies, reducing their heights and weights.

Rasmus Nielsen, a geneticist at the University of California, Berkeley, and an author of the new study, said that the discovery raised questions about whether omega-3 fats really were protective for everyone, despite decades of health advice. “The same diet may have different effects on different people,” he said.

Food is a powerful force in evolution. The more nutrients an animal can get, the more likely it is to survive and reproduce. Humans are no exception. When we encounter a new kind of food, natural selection may well favor those of us with genetic mutations that help us thrive on it.

Some people, for example, are able to digest milk throughout their lives. This genetic adaptation arose in societies that domesticated cattle thousands of years ago, in such places as Northern Europe and East Africa. People who trace their ancestry to other regions, by contrast, tend to more often be lactose-intolerant.

Dr. Nielsen wondered if the Inuit had a similar evolutionary change when they shifted to a diet made up mainly of meat.

In recent years, he and his colleagues have been collaborating with researchers at the University of Greenland to study Inuit DNA. Originally, they searched for mutations that raise the risk of developing diseases such as diabetes.

But then Dr. Nielsen and his colleagues took a different tack, searching for mutations that might have provided the Inuit with some benefit.

To sharpen the focus of their search, the scientists selected 191 Greenlanders whose ancestry was 95 percent Inuit or greater. (Many Greenlanders can trace some of their ancestry to Europe because of the island’s colonization by Denmark.) The researchers looked at the DNA of these people for variations in genes important to metabolism.

“We wanted to scan the genome and ask, where do we find the strongest signals of natural selection?” Dr. Nielsen said.

The researchers found several genetic variants at different locations in the genome that were unusually common in the Inuit, compared with people in Europe or China. Several of these variations occurred within a cluster of genes that direct construction of enzymes called fatty acid desaturases. (The genes are called FADS, for short.)

This discovery was particularly tantalizing, because the scientists knew that these enzymes helped regulate the different fats in our bodies, including omega-3 fatty acids.

Even more intriguing was the fact that one of these gene variants was present in almost every Inuit in the study. It is much less common in other populations: About a quarter of Chinese people have it, compared with just 2 percent of Europeans.

Natural selection is the only known way this gene variant could have become so common in the Inuit. Dr. Nielsen said this adaptation might have arisen as long ago as 20,000 years, when the ancestors of the Inuit were living in the Beringia region, which straddles Alaska and Siberia.

To uncover the effect of this variant gene, the scientists compared the Inuit in their study with others with more European ancestry. Some had inherited a European version of the variant. People with two copies of the Inuit gene had different blood levels of fatty acids than people without them, the researchers found.

It’s possible that with so much extra omega-3 in their diet, the Inuit evolved a way to bring blood levels of fatty acids back into a healthy balance. “It seems that a genetic adaptation has counteracted the high intake of omega-3 fatty acids,” said Marit E. Jorgensen, an author of the new study from the University of South Denmark.

The adaptation did more than just change blood levels of fatty acids, the scientists found. Inuit who carried two copies of the variant gene were on average an inch shorter and 10 pounds lighter than those without a copy.

“That’s quite extreme,” said Dr. Nielsen.

Indeed, it’s rare to find a single gene that can influence height and weight so drastically. In recent years, scientists have run a number of large studies pinpointing hundreds of genes that affect height and weight, but each one played a minuscule role in the variation from person to person.

Those studies missed this influential gene variant because they focused mostly on people of European ancestry. So Dr. Nielsen and his colleagues also investigated how it affects Europeans. As it turns out, the gene variant is linked to a drastic drop in height and weight in that population, too.

The idea that the Inuit adapted to eating fatty food was very plausible, said Anthony G. Comuzzie, a geneticist at the Texas Biomedical Research Institute in San Antonio who was not involved in the study. But he cautioned that natural selection might not have favored the FADS variant but a neighboring, as yet unknown piece of DNA that conferred evolutionary advantages.

As that gene spread through the Inuit population, the FADS variant might simply have been passed down with it.

Dr. Nielsen and his colleagues are planning to investigate the long-term health effects of the gene variants they’ve found. They may help explain why some of us metabolize fats more effectively than others, and why omega-3s haven’t been the heart panacea once hoped.

But the research may also shed light on what sort of dietary changes might benefit the Inuit in particular. “Very soon, these results could be translated into help for people with their dietary choices,” Dr. Nielsen said.