Fish Oil and Depression

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 triglycerides, slow the hardening of arteries, regulate heartbeat, and lessen the risk of death in people with known 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.

The case for fish oil

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, carbamazepine, 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.

What is the research on depression and 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. In 2009, researchers found higher consumption of omega-3s is associated with lower depressive symptoms in women. Different researchers found the flip side of the same coin: lower blood serum levels of omega-3s are related to major depression. A meta-analysis purported that omega-3s could potentially treat depressive disorders, but not mania, while another study found that omega-3s significantly reduced mania and depression in juveniles.

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 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.

And in 2010, a case-control study from Canada, found that omega-3s were effective in treating major depression, as long as it was not accompanied by an anxiety disorder.

Can I get enough omega-3s just by eating fish?

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.

What’s the difference between omega-3s and other essential fatty acids?

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.

It has been estimated that the diet of early humans contained about equal amounts of omega-3s and omega-6s. 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. Correcting the balance – by increasing omega-3s and/or or decreasing omega-6s – may have a host of health benefits.

Should I take fish oil?

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. Cod liver oil or any other oil made from fish liver may increase the risk of vitamin A or D toxicity. 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.

Further Resources

National Institute of Mental Health

International Foundation for Research and Education on Depression


Franois Lesprance, Nancy Frasure-Smith, Elise St-Andr, Gustavo Turecki, Paul Lesprance, Stephen R. Wisniewski. The Efficacy of Omega-3 Supplementation for Major Depression: A Randomized Controlled Trial. Journal of Clinical Psychiatry, 2010

Interview with Andrew L. Stoll, MD, of Harvard Medical School

Natural Standard Research Collaboration. Omega-3 fatty acids, fish oil, alpha-linolenic acid.

Edwards, R. et al. Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients, Journal of Affective Disorders.

Hibbeln, J.R.. Fish consumption and major depression.

Hibbeln, J.R.. Long-chain polyunsaturated fatty acids in depression and related conditions, in Phospholipid Spectrum Disorder (Lancashire, England: Marius Press, 1999), pp. 195-210.

Maes, M. et al. Fatty acid composition in major depression. Journal of Affective Disorders, 1996; 38: 35-46.

Maes, M. and R.S. Smith, Fatty acids, cytokines, and major depression. Biological Psychiatry, 1998; 43: 313-14.

Mischoulon, D. and M. Fava. Docosahexanoic acid and omega-3 fatty acids in depression. The Psychiatric Clinics of North America. December 2000; 23(4): 785-794.

Stoll, A.E., et al. Omega-3 fatty acids in bipolar disorder: A preliminary double-blind, placebo-controlled trial, Archives of General Psychiatry 1999; 56: 407-12.

The Omega-3 Connection. Andrew Stoll, M.D. Simon and Schuster, 2000.

Linus Pauling Institute. Essential Fatty Acids. December 2005.

Lin, PY, Su, KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. Journal of Clinical Psychiatry, July 2007; 68 (7): 1056-1061.

Colangelo, LA et al., Higher dietary intake of long-chain omega-3 polyunsaturated fatty acids is inversely associated with depressive symptoms in women. Nutrition. Oct. 2009; 25(10): 1011-19.

Clayton EH, et al. Reduced mania and depression in juvenile bipolar disorder associated with long-chain omega-3 polyunsaturated fatty acid supplementation. European Journal of Clinical Nutrition. Aug 20098; 63(8): 1037-40.

Kraguljac, NV, et al. Efficacy of omega-3 fatty acids in mood disorders a systematic review and meta analysis. Psychopharmacological Bulletin. 2009; 42(3): 39-54.

Osher, Y and Belmaker, RH. Omega-3 fatty acids in depression: a review of three studies. CNS Neuroscience Ther. 2009 Summer; 15(2): 128-33.

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