The Omega Principle

Flooding brains and bodies with a diet rich in omega-6 fatty acids theoretically could give an unfair advantage to these molecules, allowing them to block omega-3s from getting inside cells and replenishing stores in the brain and elsewhere in the body.

Intrigued by this possibility, Hibbeln charted fish consumption worldwide and compared those figures to rates of depression. In a paper published in 1998 in The Lancet, he showed that nations with the highest fish consumption -- Japan, Taiwan and Korea -- also had the lowest rates of depression. Nations with the lowest fish consumption -- New Zealand, Canada, West Germany, France and the United States -- had the highest rates of depression. "It becomes an interesting picture across countries," Hibbeln says.

Next, he took a look at homicide, suicide and aggression rates and compared them to seafood consumption. Similar patterns emerged. Using World Health Organization statistics, for example, Hibbeln found that men living in land-locked Hungary, Bulgaria and Austria had the lowest fish consumption and the highest rates of suicide, while their counterparts in Japan, Portugal, Hong Kong, Korea and Norway ate the most fish and had the lowest rates of suicide. Men living in the United States, Canada, Italy, Australia and Sweden fell between the two extremes on both seafood consumption and suicide rates.

Since then, Hibbeln has examined patterns of postpartum depression, which provides a particularly interesting window of opportunity for studying the psychological aspects of omega-3 fatty acids. That's because during pregnancy, mothers are the sole source of an omega-3 fatty acid known as docosahenaenoic acid (DHA) to the fetus. So key is this substance to fetal brain development that the mother's stores are depleted if she doesn't consume enough DHA in her diet. In a 2002 study published in the Journal of Affective Disorders, Hibbeln reported that "rates of postpartum depression are 50 times higher in countries where women don't eat fish," he says.

Of course, results from such population studies -- known as epidemiology -- can at best show only associations and trends, not cause and effect or a biological mechanism. To nail down any new scientific theory requires both basic science and clinical trials.

A Hard Sell

As director of the psychopharmacology research lab at McLean Hospital near Boston, psychiatrist Andrew Stoll often gets the most difficult patients to treat, the ones for whom standard therapy has failed.

In the late 1990s, research had already shown that depressed people seem to have lower levels of DHA in their brains than healthy people. Studies by Hussein Manji at the National Institute of Mental Health also found that people who respond well to antidepressants have neurons that exhibit greater plasticity, meaning that they are more receptive to changes that help them grow. Other laboratory work suggested that omega-3 fatty acids could help neurons be more plastic.

Stoll put all these elements together in a study of 30 people suffering from bipolar disorder, also known as manic depression. During the four-month study, which was published in 1999 in the Archives of General Psychiatry, he randomly assigned participants to receive either fish oil capsules containing omega-3 fatty acids along with their standard treatment or a placebo of olive oil plus the standard treatment. The study found that the omega-3s significantly lengthened the period of remission for those who received them.

Since then, a handful of other small, short-term studies have also found benefits to omega-3s. In England, Malcolm Peet and his colleagues at the Swallownest Court Hospital in Sheffield gave another type of omega-3 -- eicosapentaenoic acid (EPA) -- in varying doses to people with ongoing depression that was not well controlled with antidepressants. Peet found in this 12-week study that one gram per day of EPA was significantly better than placebo in improving mood. (Both groups also received standard antidepressant medication.) Other studies found that omega-3s were helpful in controlling postpartum depression, impulsivity and even antisocial behavior in prisoners.

To Stoll and other proponents of the benefits of omega-3 fatty acids in treating mental disorders, the results have been a kind of vindication. "We were laughed at five years ago and teased by our colleagues," says Stoll, an associate professor of psychiatry at Harvard Medical School. "Now this is in textbooks."

But the story is still unfolding. Exactly how omega-3s may work is not yet known. Scientists know that these fats break down into EPA and DHA in the body, while omega-6 fatty acids break down to a substance called arachidonic acid. Nothing is static in the body. So these products just continue a cascade of other biochemical reactions that produce more substances -- chemicals that act like a thermostat to raise and lower production of other key substances that in turn control blood clot formation, immune responses, bone health, smooth muscles and so on and so on.

Which dosages of omega-3s may be most effective is also not certain, "although it's probably going to be in the range of one to three grams per day," says Marlene Freeman, director of the Women's Mental Health Program at the University of Arizona Health Science Center in Tucson and lead investigator of two studies examining the use of omega-3s in pregnant women at high risk for postpartum depression. "It's all kind of theoretical, but then we don't truly know how antidepressants work, either."

Nor are omega-3s a panacea for mental disorders. In schizophrenia, for instance, there have been two studies showing benefit and one showing no effect. Studies of DHA "didn't do anything for people with attention-deficit disorder," Stoll notes. "But no one has tested EPA yet, and there's lots of evidence that kids with ADD are deficient in EPA."

Alcoholism is known to deplete the brain of omega-3 fatty acids. But whether supplementation might help reverse some of the ill effects is also not yet known. Omega-3s are also under investigation for treating Parkinson's and Alzheimer's diseases.