By Marc Kaufman
Washington Post Staff Writer
Tuesday, April 27, 1999; Page Z07

Scientists believe they have found a surprising new ally in their efforts to understand and treat the sharp mood swings of manic depression--the fatty acids of fish oil.

A Harvard University clinical trial of 44 patients suffering from manic, or bipolar, depression had such positive results with fish oil that the experiment was stopped after four months and all patients were put on a treatment of 14 capsules per day.

"The group taking the fish oil was performing strikingly better than the placebo group, including significantly longer periods of remission," said Andrew L. Stoll, director of the Psychopharmacology Research Laboratory at Harvard Medical School/McLean Hospital. "A decision was made to stop the trial on ethical grounds."

Based on those promising findings, Stoll said, the National Institutes of Health (NIH) has given preliminary approval for a larger fish oil trial starting this summer. That trial, at McLean and Baylor College of Medicine in Houston, would include 120 people suffering from manic depression and would last for three years.

"If this works, it would be one of the most exciting findings in psychiatry in the past 20 years," said Jerry Cott, chief of the psychopharmacology research program at the National Institute of Mental Health. "This is the first time we would be testing a nutritional supplement that appears to be having efficacy about to the degree of a synthetic medication."

"This could give us real insight into what is the basis of this psychiatric disorder," Cott said. "Right now, we have no clue what it's really about."

In the Harvard study, all the patients continued on their other medications. About half were also treated with fish oil capsules, while the others got olive oil as a placebo. According to Stoll, 11 of the 15 patients taking the fish oil improved after four months, and only two had a recurrence. Six of 20 on the placebo responded positively, he said, and 11 had a relapse. Some patients were not counted because the trial was stopped before they had completed their four-month treatment.

Details of the study will be published in May in a major medical journal.

Stoll presented his findings this month at a meeting of fatty acid experts at NIH. Fish oil is especially high in omega-3 fatty acids, a family of long-chained polyunsaturated fats that have been associated with reduced cardiovascular disease and other health benefits.

The body's highest concentrations of omega-3 fatty acids are in the eyes and the brain, where neurobiologists believe they are essential to the proper functioning of cell membranes. If levels of omega-3 fatty acids are too low, they have theorized, then essential chemical pathways become overwhelmed and mental disorders can occur.

The Harvard study was the first significant scientific look at the effects of fish oil and its fatty acids on manic depression--which is estimated to affect between 1 and 2 percent of Americans at some point in their lives. The disease produces swings from the abnormally high energy and mood levels of mania to deep depression, and is generally treated with different drugs than those prescribed for unipolar depression, the more common form of depression. (An estimated 20 percent of Americans suffer from some form of depression during their lifetimes.)

But some researchers believe omega-3 fatty acids play an equally important role in unipolar depression.

Joseph Hibbeln of the National Institute on Alcohol Abuse and Alcoholism has found a striking correlation between fish consumption and depression. Societies where people eat a lot of fish, he found, have markedly lower levels of depression than societies where people don't eat much fish. He calls his work "suggestive" rather than conclusive.

Stoll said he stumbled across fish oil as a possible treatment of manic depression when he surveyed the literature on compounds with effects similar to traditional drugs such as lithium and valproate. "Everywhere we looked, we came up with omega-3s," he said. "I had heard about omega-3s in medical school, but there hadn't been a lot of attention paid to them since."

In the study, Stoll gave patients 10 grams of fish oil fatty acids a day, an extremely high dose. The capsules contained eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two primary molecules of the omega-3 family. There were only minor side effects--some gastric trouble and diarrhea--which he said were easily controlled.

While fish oil has long been used as a safe dietary supplement, doctors warn that it can oxidize if not properly stored. Experts in the field advise not taking fish oil capsules if they have more than a slightly fishy smell.

In addition, doctors worry about the unsupervised use of fish oils by bipolar patients.

"The ongoing studies suggest effectiveness, but at this point we don't know enough about how it works, about long-term consequences or about side effects to recommend its use," said Joseph Coyle, speaking for the American Psychiatric Association (APA).

Coyle, chairman of the psychiatry department at Harvard Medical School, said bipolar depression patients should only take fish oil capsules after conferring with their doctors. "Because a substance is natural," he said, "it is not necessarily harmless."

If a patient takes large doses of fish oil, doctors generally recommend taking vitamin E or C as an antioxidant as well.

One group already exploring the possibilities of fish oil is the Bipolar Kids Network, a collection of parents of bipolar children connected by the Internet. Promising information last fall from an NIH conference on the relation between fatty acids and psychiatric disorders caught the attention of some members of the network, and the word quickly spread that fish oil might help bipolar kids.

Elizabeth Cullen-Bryant, of Sherman Oaks, Calif., said her daughter, a young adult with a difficult-to-treat form of manic depression, improved significantly after she began taking large amounts of fish oil last year. The mother said her daughter had been treated with 28 different medications and scores of combinations, but never had an improvement as pronounced as the one she has had since she began taking megadoses of fish oil.

Psychiatrist Demitri Papolos, medical consultant to the network, said that many of the parents involved with the group have put their children on omega-3 supplements. Papolos, a researcher with the Albert Einstein College of Medicine in New York and author of an upcoming book on bipolar children, said he now gives fish oil capsules to his bipolar patients who have not been stabilized by other drugs.

"I'm very pleased by what I've seen," he said. "But everything about fish oil needs to be borne out with more rigorous study."

Coyle of APA said he understands the excitement about the promise of fish oil, but warned that there are additional risks to giving high dosages to children.

"Because the fish oils work through the nervous system, I would have special reservations about using them with children," he said. "We just don't know yet how they work."

Further research into fish oils is being undertaken by the Stanley Foundation, a private, nonprofit organization based in Washington. According to medical director Michael Knable, the foundation--which funds research into mental disorders--will soon begin fatty acid trials involving 160 patients with manic depression and 80 schizophrenics. The trial will use only eicosapentaenoic acid, Knable said, in an effort to learn whether it or docosahexaenoic acid is the compound affecting the patient's brain.

"The fish oil story has been spreading unofficially for a while, and many people are claiming it can do wonderful things," Knable said. "We're trying to find out the truth, in an independent kind of way."

Kay Redfield Jamison, a professor of psychiatry at Johns Hopkins School of Medicine and author of several books on depression, said she was surprised and intrigued by the possibilities of fish oil for manic depressives.

"If told a year ago [that] people would be talking seriously about the role of diet and nutrition in manic depression and depression, I would have thought it was hokey," she said during a Society for Neuroscience conference at the National Academy of Sciences this month. "In fact, the science has gotten very interesting."