The Omega-3 Connection: The Groundbreaking Antidepression Diet and Brain Program

Andrew L. Stoll, M.D., is the director of the Psychopharmacology Research Laboratory at McLean Hospital in Boston and an assistant professor of Psychiatry at Harvard Medical School, as well as the recipient of the 1999 Klerman Award from the National Alliance for Research on Schizophrenia and Depression for the studies described in this book.

Chapter One: Nature's Mood Enhancers

During the course of reading this book you will learn about exciting research into a remarkable group of natural substances: the omega-3 fatty acids. Omega-3 fatty acids are essential for the optimal function of every cell in our bodies, yet we cannot manufacture them internally. Instead, along with vitamins, these essential oils can be obtained only in the diet.

Over the past century, people in developed countries, particularly in the United States, have largely eliminated omega-3 fatty acids from their diet. There is considerable evidence that this has had a very negative impact on the inner workings of many bodily systems, most notably the heart and the brain. We are learning that restoring the body's natural balance of omega-3 oils may improve a multitude of medical disorders, including coronary artery disease, major depression, and bipolar disorder (also called manic-depressive illness). My personal journey toward discovery of the omega-3 oils began in 1987, when I finished medical school and launched my career in psychiatric neuroscience with a residency and fellowship at Harvard Medical School and McLean Hospital in Belmont, Massachusetts. The focus of my clinical work and research was (and still is) bipolar disorder, one of the most complex, dangerous, and fascinating medical disorders -- and one of just a handful of afflictions that occur only in humans.

The prevalence of bipolar disorder suggests that it is not merely some random unlucky mutation, but that the genes involved might have been preferentially selected during the evolution of the human species. Without bipolar illness, our species would, at best, be uninteresting, even boring; at worst, the human race might not have survived the challenges of our evolutionary and society history at all.

Why would such a life-threatening disorder be necessary for our species? Viewed through the lens of history, some people believe its evolutionary value is clear. Kay Redfield Jamison, professor of psychiatry at Johns Hopkins University, has written extensively on the creative and leadership qualities of the many people throughout history who have been retrospectively diagnosed with bipolar disorder. From Winston Churchill and Ted Turner to Vincent van Gogh, Georgia O'Keefe, Virginia Woolf, and Charles Mingus, some of the volatile, grandiose individuals with this affliction have launched and dismantled empires, revolutionized cultures, and rendered hauntingly beautiful works of art. Bipolar disorder, characterized by alternating cycles of melancholy and mania, is especially prevalent among those in leadership and creative fields. A long list of writers, artists, and musicians -- Ernest Hemingway, Michelangelo, and Cole Porter, to name a few -- have produced visionary work, despite the crests and valleys of their mood states. According to Jamison, many prominent poets of our century have suffered from bipolar disorder, including Sylvia Plath and Hart Crane, and in the years before the advent of effective treatments, many killed themselves.

The occurrence of bipolar disorder is not limited to the arts. It is highly prevalent in the computer, biotechnology, and high finance fields, where some of the most creative and globally transforming work is currently being done.

Most people with bipolar disorder, of course, are not celebrities, but the wide swings between highs and lows disrupt their lives just as much, devastating relationships, school, jobs, and quality of life. Between 10 percent and 20 percent of bipolar patients will die of their illness, usually through suicide.

My career as a psychiatrist has been dedicated to relief and prevention of pain and suffering from these mood disorders. As a physician-neuroscientist, understanding and treating bipolar disorder has provided me with a profound yet still embryonic view of the biochemistry of the brain. In medical school, I was taught that if you can understand diabetes, you will understand all of medicine because those with diabetes fall prey to many other disorders, from cardiac disease to kidney failure to stroke. Similarly, if you understand bipolar disorder, you will have special insight into psychiatry because those with bipolar disorder manifest a wide variety of psychiatric symptoms. In the full-blown disorder, periods of suicidal depression alternate with episodes of mania: euphoria, irritability, increased energy, decreased need for sleep, and racing thoughts accompanied by impulsive behaviors and grandiose ideas. Symptoms of anxiety and even psychosis may occur during different phases of the illness.

As devastating as bipolar disorder can be, it is treatable with drugs. But working with patients who have bipolar illness at McLean and Brigham and Women's Hospitals, I sometimes found the standard pharmaceutical agents ineffective or so harsh that they produced temporary discomfort or caused permanent medical problems of their own. Ongoing psychiatric symptoms, serious side effects, and noncompliance with medication therapy were the frequent results. These outcomes are even more pronounced in teaching hospitals like McLean and Brigham and Women's, where many of the patients have more severe or treatment-resistant conditions.

The long-term treatment of patients with bipolar disorder relies on the so-called mood stabilizers such as lithium and valproate. These often produce dramatically good results long term and have saved thousands of lives. Unfortunately, patients using lithium often experience weight gain, tremors, increased urination, drowsiness, and acne. Some 15 percent suffer reduced thyroid function, and as many as 5 percent develop kidney problems. Often the biggest problem for these innately creative individuals on lithium can be a loss of the creative spark. While their manias are under control, their emotions are frequently flattened, and they are, to use a clinical term, "cognitively dulled." What is more, one mood stabilizer used alone is often not effective over the long term. In an effort to control recurrent manias or depressions, patients might end up taking two or more mood stabilizers at once, increasing their risk of side effects and drug interactions.

As a psychopharmacologist (a psychiatrist specializing in medication treatments) and researcher with responsibility for treating these desperately ill people, my mandate was clear: to find newer medications with fewer side effects that worked as well as or better than the ones already in use, and to increase our understanding of the disorder.

Working with the German researcher W. Emanuel Severus, M.D., I started the hunt for a better treatment in 1993. Our strategy was to conduct extensive computer searches of medical research papers to identify substances whose biochemical properties were similar to the standard mood stabilizers, lithium and valproate. Reviewing hundreds of papers in search of a candidate molecule (one that had never been used in psychiatric disorders), we pulled up one match time and again: omega-3 fatty acids, or common fish oil!

At first our reaction was surprise and disbelief. We had no evidence that omega-3 fatty acids would be helpful in bipolar disorder, yet it made sense. Already used by some physicians in the treatment of heart disease, Crohn's disease, and rheumatoid arthritis, these oils are precursors to important signaling molecules in the body and are essential components of the healthy cell membrane -- the same membranes that appear to mediate the activity of lithium and valproate in the brain. The omega-3 fatty acids are found in unusually high concentration in the brain. Although almost nothing in the literature connected them with bipolar disorder, the possibility that they might act to stabilize mood was very real.

Our subsequent clinical study, ultimately published in The Archives of General Psychiatry, suggested that these safe and natural oils had therapeutic value in the treatment of bipolar disorder. In this one study, looking at thirty patients over four months, omega-3 fatty acids, used alone or with other medications, enabled a few seemingly incurable patients to lead normal lives and enhanced mood stability for those already gaining some benefit from other medications. Omega-3 fatty acids were also safer than valproate and lithium: they had few side effects, and, in my practice, at least, they have become one of the most frequently used "medications" for patients with mood disorders.

But there is more. While our discovery emerged from a search for a new treatment of bipolar disorder, evidence points to far wider applications for omega-3 fatty acids in the care and nurturing of the brain. Studies now under way indicate considerable potential as an antidepressant in the more common type of mood disorder, termed unipolar major depression. Other research suggests that omega-3 fatty acids may yield new treatments for postpartum depression, schizophrenia, attention deficit-hyperactivity disorder, and possibly many other disorders as well. They may be very appropriate for children and the elderly, whose bodies often cannot tolerate conventional psychiatric medications. Furthermore, it is possible that omega-3 fatty acids may actually prevent these disorders from developing at all.

For those of us engaging in neuroscience research, the possibility of global healing power for this natural lipid makes sense. Until the twentieth century, omega-3 fatty acids, derived largely from cold water oily fish from the ocean or freshwater lakes and rivers, as well as wild animals and plants, were common elements of the human diet. Today, with the advent of processed foods and the reduction of omega-3 fatty acids in the typical Western diet, that has changed.

We often think of depression and bipolar disorder as purely hereditary in nature, but research on the omega-3 fatty acids indicates that some of what is inherited may not be in the genes. In studies of omega-3-deprived mice, scientists learned that it may take several generations for offspring to deplete their brains of omega-3 fatty acids. This is because the body tenaciously holds on to the omega-3s throughout life, and also because most of the omega-3s in young animals come from what their mother (and her mother) have consumed and stored. Over time, of course, depletion occurs. Could this possibly be one reason that depression and other mood disorders are on the rise in the United States, or be a factor in the apparently low rate of depression in Japan and other countries where the consumption of fish has remained high for generations?

Researchers in psychiatric epidemiology have found that the prevalence of depression varies as much as sixty-fold from country to country. In a fascinating study from Joseph Hibbeln, M.D., of the National Institute on Alcohol Abuse and Alcoholism, data shows that the international pattern of major depression corresponds strongly to cross-national differences in coronary artery disease, suggesting similar dietary risk factors. Of all the dietary variables, fish consumption appears to be the most significant, with fish-eating nations at lower risk for both major depression and heart disease.

There is evidence that omega-3 deficiency may play a role in postpartum depression as well. The developing fetus and newborn require high amounts of omega-3 fatty acids and receive them through the placenta and breast milk, respectively. The baby's ability to import and incorporate omega-3 oils outweighs the typical Western mother's ability to replace what she has lost. It is well-documented that infants and toddlers who were breast fed rather than bottle fed score higher on cognitive and visual system tests. It has been determined that one reason is the high levels of long-chain omega-3 fatty acids in breast milk. (There are none in U.S. formula.) If the mother does not maintain sufficient levels of omega-3 fatty acids in her diet, she puts her body at risk of depletion during the pregnancy and breast-feeding period. Low levels of omega-3 in her brain and body may put her at greater risk for depression and possibly other disorders.

In studies of children with attention deficit-hyperactivity disorder (ADHD), meanwhile, Jay R. Burgess of Purdue University has found that some 40 percent showed evidence of omega-3 fatty acid deficiency. Research into use of omega-3 supplements as an adjunctive treatment for ADHD is currently under way.

Although the results of the ADHD studies are not yet in, research with healthy populations indicate that omega-3 fatty acids may indeed play a role in attention as well as cognitive abilities like memory and response time. In a fifty-day study of 285 normal women, with a particular focus on EPA, David Benton, Ph.D., a researcher at the University of Wales Swansea, found that omega-3 fatty acid supplements improved measurements of memory, vigilance, and mood.

The jury will remain out on many of these treatments and applications until controlled clinical studies are completed and replicated. In the meantime if you are already receiving drug therapy for a psychiatric disorder and would like to start taking omega-3 fatty acids, it is important that you continue current treatment and consult with your clinician. In most cases, the omega-3 fatty acids are used "adjunctively"; that is, added to what you already take. There are some patients with mood disorders doing very well on omega-3 fatty acids alone but until more data are in, I do not recommend treatment based solely on omega-3 fatty acid therapy, except for the mildest forms of depression or bipolar disorder, or for the general population, to enhance well-being, mood, and health. If you think you might have a mood disorder, you should consult a mental health care professional to review your treatment options.

The chapters that follow present the latest findings on omega-3 fatty acids and mood enhancement -- not just for those who suffer from bipolar disorder, but possibly for everyone. And because the use of this supplement in psychiatry is so new, I'll deliver a road map for use in my Omega-3 Renewal Plan. What foods are especially rich in omega-3 fatty acids, and how much should you eat? What should you look for in a supplement? What can labels tell you? How much should you take and when?

I understand that some readers may be skeptical. Who is to say this is not just another supplement flavor of the month, another bogus claim in the continual stream of magic elixirs and miracle cures? Who is to say that fish oil is not really snake oil, a fad that will pass as others have before? Well, it may. The case we present to you is not yet solid. Many more studies are needed. But serious scientists at many prestigious institutions like Harvard Medical School, Oregon Health Sciences University, Purdue University, the University Hospital of Ghent in Belgium, and the University of Sheffield in the United Kingdom are impressed enough to be dedicating themselves to the study of the omega-3 fatty acids.

Every so often, scientists really do discover a substance of transformative power, one with the ability to cure the previously incurable and improve the quality of life for the rest of us. Omega-3 fatty acids -- a component of simple fish oil, once so prevalent in our diet but now largely absent -- could be such a substance.

Copyright © 2001 by Andrew L. Stoll, M.D.