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Eat More Fish

Heart-healthy omega-3 may be good for your brain
Washington Post Service

They occur naturally in fish, flaxseed, canola oil, nuts and avocados and are sold in dozens of dietary supplements. Increasingly, they are added to bread, dairy products, margarine, baby food and cereal.

Omega-3 fatty acids are already prized by cardiologists for protecting the heart against blocked arteries and for thwarting irregular, often fatal, heartbeats.

Now psychiatrists are taking a closer look. Omega-3s, dubbed the ''happy'' fats in some quarters, are under investigation for treating depression, bipolar disease and the so-called baby blues, or postpartum depression. Earlier this year, the American Psychiatric Association formed a committee to review the findings to make treatment recommendations for the use of omega-3s.

There's hope that omega-3s may help bridge the treatment gap in mental disorders -- up to 30 percent of people being treated for depression, for example, find drugs inadequate in controlling their symptoms.

''The main problem we have with depression is that we do not have treatment that [dependably] provides complete recovery,'' says David Kupfer, head of psychiatry at the University of Pittsburgh's Western Psychiatric Institute and Clinic. ``We're still leaving people mildly depressed or unable to function well. It's like trying to make the last 10 yards when you're in field-goal range. . . .''

The idea that omega-3 fatty acids might help treat mental disorders dawned on Joseph R. Hibbeln in an anatomy lab in 1984. ''I had cut open the brain, and it just very much struck me that it is mostly fat,'' says Hibbeln, chief of the outpatient clinic at the Laboratory of Membrane Biochemistry and Biophysics at the National Institute of Alcohol Abuse and Alcoholism (NIAAA) in Bethesda, Md.

Essential fatty acids can't be produced by the body but are required for good health. Playing key roles in brain cell structure, they're vital for each neuron's membrane, both its outer protection and its means of accessing key nutrients. It is these essential fats that regulate the growth of long tendrils called axons that enable neurons to communicate with each other.

One is an omega-3 fatty acid called alpha linolenic acid, which is found in fish, canola oil and flaxseed. The other is an omega-6 fatty acid, which is found in soybean, safflower and corn oils, as well as in meat, poultry, fish and processed foods. Omega-3s and omega-6s are close enough in chemical structure to be able to compete for the same molecular machinery that allows entry into the brain.

In 1909, Americans got most of their fat from free-range animals, which have higher levels of omega-3s than most of the meat and chicken eaten today. They also consumed about 0.02 pounds per year of soybean oil -- a number that increased gradually until about 1960, when ''soybean oil took over the U.S. food chain,'' says William Lands, a retired biochemist with NIAAA.


By 1999, per-capita consumption of soybean oil -- a major ingredient in crackers, bread, salad dressings, baked goods and processed food -- reached 25 pounds per year, according to the U.S. Department of Agriculture. ''That means that there has been a 1,000-fold increase in [consumption of] omega-6 fatty acids'' over 100 years, says Hibbeln. ``So we have literally changed the composition of people's bodies and their brains. A very interesting question, which we don't know the answer to yet, is to what degree the dietary change has changed overall behavior in our society.''

Flooding brains and bodies with a diet rich in omega-6 fatty acids theoretically could allow 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 -- had the lowest rates of depression. Nations with the lowest fish consumption -- New Zealand, Canada, Germany, France and the United States -- had the highest rates of depression.


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 suicide rates, while their counterparts in Japan, Portugal, Hong Kong, Korea and Norway ate the most fish and had the lowest suicide rates.

Since then, Hibbeln has examined patterns of postpartum depression. 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 a 2002 study 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. Nailing down a new scientific theory requires both basic science and clinical trials.

As director of a Boston-area psychopharmacology research lab, 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, 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.

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 a placebo in improving mood. (Both groups also received standard antidepressant medication.) Other studies found omega-3s helpful in controlling postpartum depression, impulsivity and even antisocial behavior in prisoners.


But the story is still unfolding. Exactly how omega-3s may work and which dosage of omega-3s may be most effective is not known, ''although it's probably going to be in the range of one to three grams per day,'' says Marlene Freeman, 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.''

And at least one trial, published earlier this year in the American Journal of Psychiatry by researchers at Baylor College of Medicine, found no significant effect of adding DHA to treatment for major depression.

Such findings explain why plenty of people -- even experts in the field -- are cautious about overbilling the benefits of omega-3 fatty acids.

''The biggest risk is for someone to try to treat themselves with these over the counter when what they really need is an evaluation,'' says Freeman. ``It scares me a little to have this in the media.''

''Is the evidence strong enough to use [omega-3s] for depression?'' asks Alice H. Lichtenstein, professor of nutrition at Tufts University. ``It's sufficient evidence to do human trials, but not to make dietary recommendations.''

Stoll is so convinced of the benefits of omega-3s that he jokes he nearly force-feeds food rich in omega-3s to his three children.

As Stoll says, ``Anything good for the heart seems to be good for the brain.''

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