Saturday Evening Post
Cory SerVaas, Patrick Perry

New scientific studies suggest that by increasing our consumption of certain "good" fats found in fish, flaxseed oil, and walnuts, we may improve the symptoms of a number of psychiatric illnesses, including depression, bipolar disorder, and schizophrenia. For years, investigators have been exploring the link between depression and diet, especially the association between the incidence of depression and fish consumption. Fish and some land-based foods are rich in omega-3-a nutritional building block critical for the healthy development and functioning of the brain and nervous system.

In the past 100 years, the American diet has shifted away from the diet of our human ancestors-wild plants and game, including fish-which was rich in omega-3 fatty acids to one relying on mass-produced and highly processed food. By reducing our consumption of omega-3s in favor of another fat called omega-6 fatty acid, found in vegetable oils such as corn and soy, we have upset a delicate balance that may underlie the increasing rate of depression and other chronic diseases in contemporary American society. In cross-national studies comparing diet, scientists found that in countries where fish is still a large part of the diet, such as in Taiwan and Japan, rates of depression were lower than in American and many European populations.

We spoke with Joseph R. Hibbeln, M.D., about this emerging field of scientific research. Dr. Hibbeln is an internationally recognized authority on the link between essential fatty acids and depression. Chief of the Outpatient Clinic, Laboratory of Clinical Studies at the National Institute on Alcohol Abuse and Alcoholism at the National Institutes of Health in Bethesda, Maryland, Dr. Hibbeln co-organized the first "NIH Workshop on Omega-3 Essential Fatty Acids and Psychiatric Disorders," held last September.

Q: In layman's terms, what are omega-3 fatty acids?

A: Omega-3 refers to a class of polyunsaturated fatty acids that are beneficial to many aspects of health. Polyunsaturated fatty acids are all essential fatty acids in that they must be derived from the diet-they can't be manufactured by the body. Among polyunsaturated fatty acids, there are two classes or families-an omega-6 and an omega- 3.

Balance between these two families is very important to proper human functioning and well-being.

The two families are not interchangeable. For example, if you eat foods high in omega-6 fatty acids, your body composition will change over to have lots of omega-6 fatty acids. If you eat foods high in omega-3 fatty acids, your body tissues will eventually develop a higher proportion of omega-3 fatty acids.

Q: Why are omega-3s so important?

A: Of the omega-3 fatty acids, two are especially biologically important-one is EPA, eicosapentaenoic acid, and the other is DHA, decosahexaenoic acid. In a nutshell, DHA is very biologically important because it is highly concentrated in the brain-in the synapses, where brain cells communicate with one another. And DHA is one of the important fats that make up the wall of the cell.

To illustrate this point, if you are building a house and pouring concrete, DHA would be what the concrete is made of-it is literally the wall of the cell. Depending on what kind of fatty acids you put into that cell wall, the wall or membrane will possess different physical properties. If you make the foundation out of saggy concrete, it will affect many different systems in the house-windows, electrical systems, etc. In a similar manner, the type of fatty acids that you eat will eventually create the cells of your membranes and therefore affect how they function. That is one reason why DHA is important.

Q: What role does the other omega-3 fatty acid - EPA - play in our health?

A: EPA becomes a very potent, biologically active molecule that keeps platelets from coagulating or clotting. When EPA gets into white blood cells, it helps reduce inflammation and immune responses. EPA affects the body in many other ways-sleep patterns, hormones, etc.-serving as a modulator.

Q: What function do omega-6s have in the body?

A: One omega-6 fatty acid, arachodonic acid (AHA), makes biological compounds which have the opposite effect from the compounds made from EPA. For example, if you have a platelet with a lot of arachodonic acid in its cell wall, it will clot more easily and you are therefore more likely to clot off a blood vessel during a stroke. If the platelet has EPA in its cell wall, it is less likely to clot.

Once again, the important factor here is achieving a balance between these two families-the omega-3s and the omega-6s.

Q: So people need both omega-3 and omega-6, but in what proportion?

A: Proportion is a critical question. One way to answer the question is to study human evolution and look at the diet human beings evolved on. It's quite clear that even if you don't account for fish in the diet, the ratio of omega-6s to omega-3s in our paleolithic diet was about one-to-one. During our evolution, we ate a variety of different plant sources and leafy green vegetables, nuts, and free-range animals that ate leafy green vegetables: wild game has about a one-to-one ratio of omega-6 to omega-3.

Q: How has our diet changed?

A: In the past 100 years, the balance of omega-6s to omega-3s has radically changed from the diet we evolved on and what, it could be argued, we are optimally suited for. We now grow seed oils, such as corn and soybeans, in great abundance. As seed oils, they have much higher ratios of omega-6s to omega-3s. Corn oil, for example, has a ratio of about 74 or 75 omega-6s to one omega-3.

Q: Flaxseed is a seed, but it contains more omega-3, right?

A: Yes, flaxseed is an exception.


Q: Tell us about your current research findings on depression. Is depression less common in countries where they consume more omega- 3 fatty acids?

A: In April 1998, I published a paper in Lancet in which I compared the annual prevalence of depression across countries to a measure of their fish intake. I took the data points from a paper, published in the Journal of the American Medical Association by Myrna Weissman, M.D.-an epidemiologist at Yale University who is recognized as the world's expert in psychiatric epidemiology; the quality of the epidemiological data is really the gold standard.

The country with the lowest prevalence of depression was Japan at about 0.12, and the highest was New Zealand at almost 6 percent. The paper describes nearly a 60-fold difference in the prevalence of depression-not double or times five-but a 60-fold difference. Virtually all of the differences across those countries appeared to be predicted by how much fish people were eating.

Q: Has the prevalence of depression changed over the past century?

A: I mentioned the differences in incidence of depression across countries, but another way of testing the hypothesis that depression is related to our dietary intake of omega-3s is to look at differences in depression across time, especially in the past century. Long before I began this work, psychiatrists noted, and described very well, that the prevalence of depression has been on a marked increase in the past century depending on what birth cohort you were born in. You are about 100-fold less likely to be depressed by the age of 35 if you were born before 1914, than becoming depressed by the age of 35 if you were born after 1945.

As I mentioned to you, 100 years ago we were eating much closer to our paleolithic diet, because the world was still a much more rural community. We didn't yet have mass agricultural production of corn and soybeans or hydrogenation. My parents still remember when they were eating only butter, which has few omega-6s, instead of margarine.

Q: Have studies demonstrated how depression is affected by fish consumption?

A: I have, for example, done an epidemiological comparison with postpartum depression, although the study is as yet unpublished. It appears that countries where more fish is consumed have much lower rates of postpartum depression. The finding makes sense, because mothers deplete themselves of omega-3 fatty acids while supplying them to the developing infant, presumably for their neuronal development. During gestation and lactation-it is well known-women can become depleted of omega-3 fatty acids. It can take up to 36 months for women to return to their normal levels, so depleted levels of omega-3 fatty acids may very well be one of the factors contributing to postpartum depression. The prevalence of postpartum depression is also much lower in countries where more fish is consumed.

Q: Can omega-3 supplementation help relieve the depression?

A: At the NIH workshop last September, data was presented from a study done by Dr. Antolin Llorente, Ph.D., at Baylor University, where women were given DHA during pregnancy. The study was originally devised to be a biochemical study; it wasn't really designed to study depression or moods. They did, however, recruit depressed women. The women in the study were basically very healthy, normal, upper-class, well-nourished women. Nonetheless, they found that those women receiving the DHA supplements had better measures of attention and concentration than women receiving placebos.

Q: How much DHA were they given?

A: They were given about 200 mg per day of DHA. It was a double-blind, placebo-controlled study in capsules versus a placebo oil.

Q: We've recently read that there is a link between depression and cardiovascular disease. Are the two connected?

A: My data relating countries and their fish consumption, published in the Lancet, suggest that fish consumption protects against depression and cardiovascular disease.

Second, psychologists have known for a long time that there is a link between either depression and/or hostility and cardiovascular disease. If you have one, you are more likely to have the other.

For many years, people have asked the question: Does depression cause cardiovascular disease, or does cardiovascular disease cause depression? What I put forth as a hypothesis is that depression and cardiovascular disease are both manifestations of a common nutritional deficiency.

Depressed patients have been shown to have higher cardiac risk factors from their diets and are, for example, more likely to die of arrhythmias, excessive platelet clotting, or to have elevated cytokines-an immune reaction. All of these conditions parallel what could happen in people with low levels of omega-3 fatty acids.

Most of the work that I have done, and described to you, has largely been theoretical and hypothesis-building. But since that hypothesis, there are five published studies showing that depressed patients have lower levels of omega-3 fatty acids than do control subjects.

Q: Do studies suggest that increasing consumption of omega-3 fatty acids-through diet or supplementation-could have a positive effect for patients with depression?

A: Yes. Some chemistry data also suggest it, as do data among suicide patients and data on hostility and violence. That aside, it took me a while to really come to this opinion. During a conversation with a person at one of the nutritional journals, the interviewer asked, "What's the harm of a depressed patient taking three grams of omega- 3s per day?" Well, there is no harm that we know of. There's no risk and a possible benefit. In other words, it can't hurt and it might help.

Q: How are omega-3 levels measured?

A: Omega-3 levels are measured by analyzing plasma or red blood cells. The test will indicate what concentrations of omega-3 fatty acids are in your blood.

Q: Is the test expensive?

A: It is about a $100 or $150 lab test.

Q: Is the test widely available?

A: No. It is largely a research test at this point. Johns Hopkins' Kennedy Kreger Institute, for example, can do it reliably. The trouble with getting your plasma drawn right now is that while we can analyze the level, we don't know what level is optimal for depressed patients as yet. If you take what is normal for the United States right now in the latter half of the 20th century, I can't tell you if that level is optimal.


Q: Are omega-3s helpful for patients with manic-depression or bipolar disorder?

A: The most exciting and best clinical data from double-blind, placebo- controlled treatment trials is in schizophrenia and manic depression.

In manic depression, the treatments of choice with the best record of efficacy are lithium, valproic acid, and carbamazapine. The action of these drugs in these conditions is well known, and they are still the treatments of choice.

Q: But do higher serum levels of omega-3 play a role in efficacy of these treatments for bipolar disorder?

A: Andrew Stoll, M.D., at Harvard did a double-blind, placebo-controlled trial in bipolar disease. In the study, patients had recently been hospitalized and had either a severe mania or severe depression. All the patients were on medications-lithium and valproic acid. One half of the patients were assigned to take six grams of omega-3 fatty acids a day; the other half were assigned to placebos. After four months, researchers did a preliminary review of the data, and the ethics committee made them stop the trial and put everybody on the active agent, because only one out of 16 of the people taking the omega-3s relapsed into a mania or depression, whereas 8 or 9 out of 15 relapsed on the placebo.

Q: Is six grams a very large dose?

A: Yes, but Eskimos ate diets that were almost completely omega-3 fatty acids, and they had low rates of heart diseases and arthritis.

Q: Is depression common among Eskimos?

A: We don't know. I have looked for that data. But by the time people were doing epidemiological studies of Eskimos, they were eating Western diets.

Q: Is there a toxic level of omega-3?

A: The FDA recognizes up to 3 grams per day of omega-3s as GRAS, or Generally Recognized As Safe.

Q: What are the side effects if you consume more than three grams?

A: It will definitely have a greater effect in thinning your blood and making your platelets not coagulate.

Q: If you had a hemorrhagic stroke, you would be in trouble.

A: Right. That's why Japanese people die more frequently of hemorrhagic stroke, but have lower death rates overall.

Q: And lower rates of depression?

A: Right. And apparently also lower hostility and violence.

Q: That finding is very interesting, especially for countries where there is more hostility and violence.

A: One very reasonable question people ask me is, "Isn't it possible that it's just the Japanese culture that is different and less hostile?" I say, "Well, Japan has approximately onehalf the population of the United States living on an arable land mass the size of Connecticut. And it's a stressful society. Just on the basis of crowding, you would expect higher rates of depression and hostility."

One thing also to consider about the culture is what would happen to a culture, or group of people, if you gave them a psychotropic drug that made them calmer for a couple hundred years. It's quite possible that these brain-specific nutrients have had an effect on culture over a long period of time.

Q: We have interviewed researcher and author Kay Redfield Jamison, M.D., who is manic-depressive. She is at Johns Hopkins and would probably be very interested in your work.

A: Some of my data were recently presented to a National Institutes of Mental Health group. Apparently, Kay was there, or heard about it. I have data of EPA levels in suicide attempters. It looks very much like the curve with depression, in that high plasma levels of EPA predict much lower psychological risk factors toward suicide. Dr. Jamison is doing work on suicide right now, so she called me up and we had a long talk. I sent her information. She actually just sent me a copy of her book, so I have had contact with her.

Q: What is rapid-cycling bipolar disease, and is it common?

A: Rapid cycling is anything more frequent than four times per year, but it can be as frequent as every other day or minute-to-minute in some cases. It is not common and very difficult to treat, often treatment-resistant.

Q: In rapid cycling every other day, for example, it is hard to understand how omega-3s could be a factor. If the tissues are deficient in omega- 3s, how would that trigger the depression, then euphoria, every other day?

A: The brain works in a series of interlinked neural networks, trained to cycles of biological rhythms. What occurs in patients with rapid- cycling bipolar disease is that the brake-the modulator of cycles-is gone. Although not well-defined biochemically, the theory is that omega-3s help put back a brake on that cycling or disrupted, endogenous biological rhythm. In no way are omega-3s proven to be effective in rapid-cycling bipolar disorder. All we have are anecdotal reports in rapid-cycling disorder at this point.

Q: What about the influence of omega-3s in schizophrenia?

A: Malcolm Peet, M.D., in England has given omega-3 fatty acids to patients suffering from schizophrenia. He found a good effect in reducing psychosis and negative symptoms, such as diminished social function. Omega-3s improved their social functioning. It has shown very good effect in this regard.

Q: Can it help people with attention deficit hyperactivity disorder (ADHD)?

A: There has been a lot of discussion about using omega-3 fatty acids in attention deficit hyperactivity disorder. At the NIH conference, everybody who has done a clinical study was present. Two of the three studies discussed showed no effect. The third study showed a good effect, using a combination of omega-3s and omega-6s. What was troubling about this study was that they also sell the product that they investigated.

At this point, there is no strong, compelling double-blind data that shows omega-3s are effective for people with ADHD. Scientific data aside, however, I have heard some impressive stories of efficacy from parents in anecdotal reports. The jury is still out on ADHD.

Q: It would seem that if a parent had a schizophrenic child or a child with ADHD, it wouldn't hurt to give omega-3s.

A: Right, it won't hurt and it might help.


Q: Do you think people in the United States need to be concerned about getting more omega-3s into their diet?

A: Yes. A very good description of the whole omega-3 phenomenon is in a book called The Omega Plan by Artemis P. Simopoulos, M.D., and Jo Robinson. I don't endorse the book, but I think it is a good layman' s literature and reference. Your readers would probably appreciate it.

Dr. Simopoulos bases much of her work on the Crete diet and study. In the seven-country Crete study, men from the Greek island of Crete had the longest lifespans and lowest incidence of cardiovascular disease of men studied. [The six other countries in the study were Italy, the Netherlands, Finland, Yugoslavia, Japan, and the United States.]

The Crete men basically achieved this state of health and longevity by consuming fish, or foods that contain omega-3s, with almost every meal. Secondarily, they used olive oil for their salad dressings, instead of corn oil or soybean oil, as we do in the typical American diet, in which vegetable-oil-based salad dressings and margarines are rich sources of omega-6s.

Q: If fish are farm-fed using corn, would the fish then contain higher levels of omega-6s?

A: That's quite right. Fish farmers have realized that if they just feed their fish with corn and soybeans, the fish don't grow as well and don't reproduce. Fish farmers now give a minimum amount of fish protein by farming menhaden-a source of fish protein-from the ocean. Apparently, the menhaden provides just enough omega-3s so that the farm-raised fish will reproduce.

Q: What about ersatz, or imitation, fish sold in the fish market as sea legs?

A: Almost any seafood, even if farmed, will probably have more omega- 3 fatty acids in it than will, for example, hamburger meat. Of course, wild seafood will probably have more omega-3s than farmed seafood, but you almost have to analyze omega-3 content on a case-by-case basis.

Overall, you are better off getting omega-3s from seafood.

Q: Are there manufacturers of fish-oil products who are superior to others? Are there products that our readers should look out for?

A: The general rule of thumb is that if you cut the capsule open and it smells like rotten, spoiled fish, it is spoiled fish. When you buy fish from the store and it is fresh, it doesn't smell fishy. I don't feel that I should pick on anybody in particular.

I will tell you that a good, common concentration in a one gram capsule would be 300 mg of EPA and 200 mg of DHA per gram. That's pretty good. That concentration gives 0.5 g omega-3 fatty acids per gram tablet. It makes it pretty easy to calculate. If you take two capsules, you are getting one gram of omega 3s. If you take four of them, you get two grams. With six, you get three grams, etc.

Q: In our grandparents' day, parents gave their children cod liver oil.

A: Yes, but they didn't give six grams. I want to mention that people should not consume large amounts of cod liver oil in order to get omega-3s into their diet. Cod liver oil also contains a lot of vitamin A. If you were going to get three grams of omega-3s from cod liver oil, you would quickly reach toxic levels of vitamin A, so avoid cod liver oil.

Q: Do fish oil supplements provide the same benefits?

A: Your body pretty much doesn't know whether you are getting it from fresh fish or a fish oil supplement.

Q: What about canola oil?

A: Canola oil is better; it has a better ratio of omega-6s to omega- 3s-around five or seven omega-6s to one omega-3.

Q: Is flaxseed oil the best source of omega-3?

A: Right, of the direct oil sources.

Q: What about nuts, such as walnuts?

A: Walnuts are good. I haven't looked at the data carefully. But nuts, in general, are a pretty good bet. If you go with the principles of the paleolithic diet, it's clear that we were eating a lot more fruits and nuts than wild game.

Q: How much omega-3 do you take?

A: I take about one gram per day and eat a lot of different types of fish.

Q: Deep-sea fish, not farm-fed catfish?

A: Farm-fed catfish are going to have less omega-3s, but they are going to have some.

Q: What is your next research project?

A: I am looking at whether consuming these omega-3 fatty acids reduces hostility and aggression. We looked at 235 subjects on whom we have performed lumbar punctures and taken cerebrospinal fluid for analysis. One of the markers of brain neurochemistry in the cerebrospinal fluid is a metabolite, or breakdown, of serotonin called 5HIAA. It is well known in biological psychiatry that people who have low concentrations of this 5HIAA are especially prone to suicidal and impulsive behaviors. What I found among normal subjects was that low concentrations of DHA in the plasma correlated to low concentrations of 5HIAA in their cerebrospinal fluid. This finding is important because 5HIAA predicts serotonin levels, and serotonin is really key to the biochemistry of depression and the biochemistry of suicide and violence.

Q: Serotonin levels should be high, right?

A: Right.

Q: Do you have access to prison inmates who have been given spinal- fluid taps from which you could determine whether the impulsive, violent person is low in omega-3s?

A: We are engaged in that work right now. We are taking cerebrospinal fluid samples before and after giving them either the omega-3s or placebos.


Cory SerVaas, M.D., & Patrick Perry

Walnuts are especially good for their omega-3 content.

Flaxseed for salads and baking.

"The research being conducted is fascinating and potentially very important to the understanding and treatment of bipolar disorder," commented Kay Redfield Jamison, M.D., of Johns Hopkins University on the role of omega-3 essential fatty acids and psychiatric illnesses. Dr. Jamison, who controls her manic-depressive illness, is a prominent researcher and has authored several books on the disorder.

An omega-3 fatty acid called DHA is highly concentrated in the synapses where brain cells communicate and plays a key role in brain development and function. A vast communications network within our brain is formed when chemical messengers, or neurotransmitters, are released from the axon, cross the synapse, and bind to receptors on another neuron.