Fish oil: fad or find?

Fish Oil: Fad or Find?

MaxEPA. Promega. Cardi-Omega. Proto-chol. Discovery. In 1987, sales of these and other fish oil supplements were flying high.

But in 1988 the roof fell in, when the Food and Drug Administration warned more than 60 companies to stop making drug claims, or risk lawsuits and seizure of their products. Advertising plunged from $10 million to $2 million. Sales slid from $45 million to $35 million.

Yet just as the fish oil fad is fading, new studies suggest--but don't yet prove--that the pills may in fact help prevent heart disease. And, though most labels and ads imply otherwise, their potential benefits may have little to do with lowering cholesterol.

It all started in Greenland. There, the local Eskimos, who typically eat one pound of whale and seal meat and fish a day, rarely suffer heart attacks.

In the 1970s, researchers in Denmark suggested that the polyunsaturated fats in the Eskimos' diet might be the key to their healthy hearts. If you eat enough of them, these omega-3 fats (eicosapentaenoic acid, or EPA; and docosahexaenoic acid, or DHA) lower cholesterol just like the polyunsaturated (omega-6) fats in vegetable oils.

But in smaller doses--say ten capsules a day--fish oil does not lower total cholesterol. (Neither would that amount--about two teaspoons--of safflower, corn, or other polyunsaturated fat.)

Ten capsules a day of fish oil--that's about 3 grams of EPA and DHA--does lower triglycerides, another unwanted fat in the blood (see "Zapping Triglycerides").(1) However, recent studies show that instead of lowering LDL ("bad") cholesterol, fish oil may actually cause it to rise slightly.(2)

Nevertheless, omega-3s may still help prevent heart disease.

"We have a tendency to look at heart disease as totally a function of LDL," says William Harris, of the University of Kansas Medical Center. "But there's other action on the vessel wall and on platelets that make fish oil beneficial." Adding Insult to Injury. Researchers now believe that before cholesterol gets deposited in an artery, the blood vessel wall suffers a microscopic "injury." It could be caused by a toxin, infection, oxidized cholesterol, or some other agent; no one knows. The body responds to the injury as it would to any other, sending in several armies of cells to patch things up.

But in fact, things get worse. Platelets stick to the lesion, setting the stage for blood clots. Smooth muscle cells, which belong on the outside of the artery wall, migrate to the inner layer. There, they grow rapidly, creating blockages. Meanwhile, white blood cells enter the artery, where they gobble up circulating cholesterol, giving it a foothold in the artery wall.

Fish oil may slow some of these events. For example, studies suggest it can make platelets less sticky and slow the proliferation of smooth muscle cells in the artery wall. It might also keep the immune system from calling in some of the white blood cells that cause further damage.(3)

In other words, says Alexander Leaf, of Massachusetts General Hospital in Boston, "fish oil works at the blood vessel wall to prevent the lesions [that must occur] for cholesterol to be deposited." Keeping Arteries Open. Demonstrating that fish oil (or anything else) prevents heart attacks isn't easy.

"We're talking about an extremely costly and difficult study," explains Gregory Dehmer, of North Carolina Memorial Hospital in Chapel Hill. "You would have to take a bunch of 30-to-40-years-olds in whom you could quantify [initial clogging] of the arteries. Then you'd treat half with fish oil and half with a placebo, and look ten years later to see if either half got fewer heart attacks, strokes, etc."

Instead, researchers have looked for evidence that fish oil keeps arteries clean. One clue comes from patients who undergo angioplasty to open a clogged artery.

This relatively new procedure is extremely popular because it is less risky than a coronary bypass, in which one or more clogged arteries that nourish the heart muscle are replaced with veins from the leg. That's major surgery.

In contrast, during angioplasty the patient stays awake. Cardiologists make an incision in the leg, through which they maneuver a small balloon all the way to the clogged artery. Then they inflate the balloon, which widens the opening in the blood vessel.

The problem is, in 25 to 40 percent of cases, the opening closes back up within six months. Of all the treatments tested so far, fish oil is the most effective at keeping arteries open.

"Fish oil is the first drug to have any effect," says Mark Milner of Washington (D.C.) Hospital Center. So far, his, Dehmer's, and a third study have found fewer relapses in patients taking a daily dose of 6 to 18 fish oil pills (1.8 to 5.4 grams of EPA and DHA).(3-5) Two other studies found no difference.(6,7)

The small size of the five studies probably accounts for the discrepancy, say researchers.

Leaf is seeking funding for a larger, definitive trial that would test fish oil's ability to keep arteries open after angioplasty. He thinks that it might because, in animals, omega-3s keep blood vessels from closing after procedures similar to angioplasty and by-pass.(8-10)

Leaf believes that fish oil might even keep blood vessels from closing in the first place. "The fact that you can actually prevent atherosclerosis in swine, monkeys, and dogs makes it seem almost unbelievable that if you do the study right, you won't find it in humans," he reasons.

But others disagree.

"In angioplasty, you're disrupting the inside of the blood vessel," explains Washington's Milner. "The response depends on factors such as how much inflammation and clotting occurs." Those factors may play a smaller role in the initial artery-clogging process. Cleaning Arteries Out. While some researchers are testing fish oil's ability to keep once-clogged arteries open, Frank Sacks, of Harvard Medical School, is studying whether omega-3s can clean arteries out.

Sacks is now enrolling people in the Harvard Atherosclerosis Reversibility Project (HARP). HARP consists of three studies, each of which tests to see if a treatment--drugs, diet, or fish oil--can actually help clear the arteries of people who have already had a coronary bypass or angioplasty.

In the fish oil study, patients will take either 12 capsules of Promega--that's 4.8 grams of EPA and DHA--or olive oil for two years. "The dose we're giving is equivalent to about a half pound of salmon every day," says Sacks.

But until his and other studies are completed, Sacks is not willing to recommend that people take fish oil to reverse or prevent heart disease.

"I don't think it would hurt to take fish oil, especially if you don't take huge doses, and no one's going to take 20 pills a day," he says. "But at the moment, we don't have enough data to recommend that everyone take it."

Dehmer and Milner advise their patients who are undergoing angioplasty to take fish oil. But they, too, stop short of recommending it to others.

"A lot of evidence from epidemiology and studies in animals suggests that fish oil might be beneficial in preventing heart disease, but no study shows you will be protected," says Dehmer. "It would be going on blind faith [to assume] that preliminary data will be shown to be true ten or 15 years from now."

And, he adds, "if you took as much as in our study [18 MaxEPAs a day], it would cost $1,000 a year."

Why are the researchers so reluctant to recommend that people take fish oil supplements? Probably because there's no proof that they're of any benefit. And, it will only be a few years before more studies are completed.

But some people don't want to wait that long. They see fish oil as "insurance." And that's fine, as long as they check with their doctors and keep track of their LDLs. (1)J. Am. Med. Assoc. 260: 665, 1988. (2)Ann. Intern. Med. 109: 465, 1988. (3)N. Eng. J. Med. 318: 549, 1988. (4)N. Eng. J. Med. 319: 733, 1988. (5)J. Am. Coll. Cardiol. 9: 64A, 1987. (6)Circ. 78 (Suppl 2): II-634, 1988. (7)Circ. 76: (Suppl. 4): IV-214, 1987. (8)N. Eng. J. Med. 315: 841, 1986. (9)Arterio. 7: 441, 1987. (10)J. Vasc. Surg. 7: 108, 1988.

PHOTO : Clogged Artery A is from a pig fed a high-fat diet. Clean Artery B is from a pig fed the

PHOTO : same diet plus cod liver oil.(8)