By Chris Woolston
CONSUMER HEALTH INTERACTIVE

Can omega-3 fatty acids stabilize mood and combat depression?

We all have fat on the brain. Amazingly enough, more than half of the brain's dry weight comes from fat. Some of these fats are the key building blocks of cell membranes and play essential roles in the brain's function. Omega-3 fatty acids, for example, help form cell membranes, keep those membranes flexible, and regulate the flow of hormones and other chemical messengers, which may affect our mood.

Research has suggested that omega-3 fatty acids, or essential fatty acids (EFAs), can help lower cholesterol, regulate heartbeat, and thin the blood, thereby lessening the risk of heart disease. It's also possible that the omega-3 group may aid in treating depression, according to neuroscientist Andrew L. Stoll, MD, of Harvard Medical School, who has studied the effects of omega-3s on the illness. A few promising studies suggest that natural sources of omega-3s -- especially fish oil -- may help bring mood back into balance. Will fish oil ever join the ranks of Prozac as a remedy for depression? Here's a look at the latest information on omega-3s and the brain.

For many years, few scientists cared about the most abundant substance in the brain. Researchers hoping to understand depression usually talked about neurons and hormones and neurotransmitters -- not fats. But fats moved toward the spotlight in 1993 when Stoll, a psychiatrist at Harvard's McLean Hospital, started searching for a new treatment for bipolar disorder, also known as manic depression. Stoll is technically a psychopharmacologist (a psychiatrist specializing in medication treatments), and he knew that the most common drug treatment for bipolar disorder -- lithium -- had saved countless lives. But he also knew that some people with bipolar disorder couldn't tolerate lithium's frustrating side effects: weight gain, tremors, drowsiness, and in some cases a sensation of emotional "flatness." Those who experienced these discomforts often stopped taking the medication, putting themselves at risk of a severe manic episode.

The other medications for bipolar disorder are anticonvulsants (valproate, carbemazepine, gabapentin), which, like lithium, appear to work by stabilizing the membranes of nerve cells known as neurons. Like lithium, the anticonvulsants also have many side effects that lead patients to stop taking them. Working with German researchers, Stoll did an extensive computer search for a compound that was similar in action to lithium and anticonvulsants. After reviewing hundreds of papers, they found one especially good -- if unexpected -- match: fish oil. Like both the available treatments, fish oil worked to stabilize the walls of nerve cells.

"At first our reaction was surprise and disbelief," writes Stoll in his book, The Omega-3 Connection. At the time, only a handful of scientists had suspected that fish oil or any other source of omega-3 fatty acids could act to stabilize mood.

Stoll soon learned a lot more about omega-3s, which are among the essential nutrients humans need to survive but cannot synthesize. These essential nutrients include all vitamins and minerals, eight of the 20 amino acids (including lysine, valine, and luecine), and some (but not all) polyunsaturated fatty acids, including the omega-3 group. Just as a shortage of vitamin C can cause scurvy, there are signs that a shortage of omega-3s can be hard on the brain. A study published in the March 1999 issue of Psychiatry Research found that people suffering major depression tend to have relatively low levels of omega-3s.

Can fish oil ease depression? Stoll believes the answer is a cautious "yes," but is quick to add that more studies are needed. A 2007 review of ten clinical trials studying the effects of omega-3s on depression found a significant anti-depressant effect, but concluded that more large-scale studies are needed. Several teams of researchers are currently testing fish oil as a remedy for depression, bipolar disorder, and schizophrenia. Until those results come in, the jury on fish oil is still out. Still, the research that has been done to date suggest that omega-3s may have important implications for both depression and our overall health.

One small, preliminary study has already put fish oil to the test as a complementary treatment for bipolar disorder, with promising results. As reported in the May 1999 issue of the Archives of General Psychiatry, Stoll and colleagues found that large doses of fish oil significantly eased the symptoms of severe bipolar disorder, even in some patients who weren't responding to drug treatment. The study, which measured rates of relapse into mania, involved 30 patients whose symptoms were not abated by their medications. Fourteen of the subjects started taking a hefty 10 grams of fish oil every day, some while using other medications and some using the fish oil alone, while the rest took olive oil.

The study is what is known to scientists as a double-blind, placebo-controlled study -- that is, one set of patients was taking fish oil, while the other set was given a pill that had no physiological effect (a placebo); neither group knew which one they were taking. But after four months of treatment, 11 of the 14 patients taking fish oil capsules reported fewer symptoms of depression, and only two had suffered a manic-depressive episode since the study began. In contrast, only three of the 16 patients taking the olive oil placebo said they felt any better, and nine had major attacks. Researchers stopped the study early, partly because it seemed unethical to withhold fish oil from any of the patients.

In one case, a participant came to the study with a treatment-resistant case of bipolar disorder marked by what Stoll described as violent rages and crime sprees. "When given the opportunity to participate in our fish oil study, he was eager indeed," Stoll writes. "The fish oil was a charm. Participating in our double-blind study, he had no way of knowing whether his capsules contained fish oil or placebo, yet he announced almost immediately that whatever we were giving him, it worked! His mood swings and rages stopped abruptly, and he felt well for the first time in his life. He has remained on fish oil supplements for three years."

The conclusions that may be drawn from Stoll's study, some observers say, are that omega-3s may be useful to bipolar patients as a complement to their traditional mood-stabilizing medications (which are mainly thought to prevent mania and not to prevent depression). Due to the small number of participants in Stoll's research project, however, his results are minimally statistically significant and need to be reproduced in a larger study.

It's hard to get enough omega-3 fatty acids just by eating a normal diet. Foods that contain them in abundant amounts include salmon and other cold-water fish, wild game, and free-range livestock -- not exactly the most popular items on the typical American's menu.

To get the amount of omega-3s used by Stoll and other researchers in his study, you'd have to eat six to 32 cans of tuna a day -- a fairly unappetizing prospect, no matter how much you like tuna melts. (Since some tuna is contaminated with PCBs and small amounts of heavy metals such as mercury, you'd also put yourself at risk to eat that much.)

That said, eating fish three to four times a week is certainly good for you, and would greatly increase the amount of essential fatty acids in your diet. But for the amount that may be needed for mood stabilization, the most practical way to obtain it would be fish oil or flaxseed oil supplements.

Essential fatty acids come in two main types: omega-6s, which promote inflammation, which is sometimes necessary to fight invaders in the body; and omega-3s, which decrease inflammation and promote flexible cell membranes. Omega-6s can be found in corn oil and other vegetable and seed oils; omega-3s are in cold-water fish, wild game, walnuts, and certain kinds of seeds and vegetables. Both types are necessary for good health, and at a recent international conference, omega-3 researchers agreed that for optimum health, omega-3 and omega-6 fatty acids should be eaten in roughly equal proportions, or a one-to-one ratio.

Unfortunately, with the advent of processed and "fast" food, the modern Western diet is heavily slanted toward omega-6s, typically providing a ratio of 10 or 20 to one. Researchers speculate, in fact, that this imbalance has contributed to inflammatory diseases and a rise in the rates of depression in the United States.

You shouldn't take fish oil capsules for depression or any other condition without consulting a doctor, according to Stoll. He also cautions depressed or bipolar patients not to stop using their medications. That step could cause serious problems, and it must be remembered that fish oil supplements are generally used as an addition to therapy rather than as a replacement. But fish oil may be a welcome addition to current treatments, he adds. If you are depressed, talk with your doctor about omega-3s: You may be able to take fish oil as a valuable adjunct to your therapy.

Aside from the hit to the pocketbook, there's little downside to fish oil supplements. The over-the-counter supplements combine well with most medications, with one notable exception: blood thinners. People taking warfarin (Coumadin), high-dose aspirin, or any other blood thinner should always consult their physicians prior to taking fish oil, since omega-3s also act to temporarily block platelet clumping.

The majority of people taking fish oil supplements develop loose stools, and some experience problematic diarrhea or nausea. (In Stoll's study, 62 percent of the subjects complained of gastrointestinal symptoms, usually loose stools. More than half of the subjects taking the olive oil pills also had gastrointestinal symptoms.) You can help minimize these side effects by taking a small dose with every meal instead of one big dose on an empty stomach. You should also take vitamin C and vitamin E supplements to prevent oxidization of the fatty acids, says Stoll.

A few other cautions: Be sure to read the labels carefully. Don't take cod liver oil or any other oil made from fish liver for your omega-3s, as this can result in hazardous doses of vitamin A. Stoll recommends finding fish oil capsules that are highly concentrated in omega-3 fatty acids. Some brands are over 92 percent omega-3s, while others contain only 30 percent. Whatever product you buy, try to ingest one or two grams (1,000 to 2,000 milligrams) of omega-3s every day. The results may surprise you.

-- Chris Woolston, M.S., is a health and medical writer with a master's degree in biology. He is a contributing editor at Consumer Health Interactive, and was the staff writer at Hippocrates, a magazine for physicians. He has also covered science issues for Time Inc. Health, WebMD, and the Chronicle of Higher Education. His reporting on occupational health earned him an award from the northern California Society of Professional Journalists.

Further Resources

National Institute of Mental Health 5600 Fishers Lane Rockville, MD 20857 Phone: (800) 421-4211

International Foundation for Research and Education on Depression, Phone: (410) 268-0044

References

First published June 29, 2001
Last updated November 30, 2007
Copyright © 2001 Consumer Health Interactive

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