Joe Hibbeln, M.D., believes our diet is making us depressed, addicted and violent. He thinks he's found a simple solution.

Joe Hibbeln, M.D., believes our diet is making us depressed, addicted and violent. He thinks he's found a simple solution.

Joe Hibbeln maneuvers his small blue Mazda 626 around traffic on a wide boulevard in Bethesda, Maryland.

"How many people," he shouts over the noise from the open window, "even Miss America, say ‘I want to make the world a happier place'?" He turns the wheel sharply to the left. "Well, I'm doin' it!

I'm zeroing in on a nutritional deficiency that makes the world an unhappy place."

Hibbeln, a captain in the United States Public Health Service, one of the country's seven uniformed services ("army of the Surgeon General," says Hibbeln), is talking about omega-3 fatty acids. He has, in fact, devoted his entire career to studying the long-chain polyunsaturated fatty acids that are best known for their heart-health benefits. He loves them. He loves the fish they come from.

Hibbeln, 49, is average height, with dark, graying hair slightly longer on top and matching bushy eyebrows. His love affair with fats began simply. In a musty autopsy suite at the University of Illinois-Chicago medical school more than 25 years ago, Hibbeln, an aspiring psychiatrist, held a brain for the first time. It was jiggly and white, not what one would expect of a computing juggernaut. "What the heck is this thing made of?" Hibbeln asked. Mostly fat, his instructor replied.

Fascinated by the idea that the most complex organ in our bodies was, in large part, a type of tissue most of us want to get rid of, Hibbeln began scouring the scientific literature to learn more about how the fat comprising the brain influenced its function. He kept encountering the work of Norman Salem, Jr., Ph.D., a neurobiologist who studied docosahexaenoic acid (DHA), a particular type of omega-3 fat prevalent in the brain-and in fish. (Fish often consume a lot of omega-3-rich algae or eat other, smaller fish that do.)

During his last year of medical school, Hibbeln reached out to Salem, who told him something that forever changed his career path: our bodies do not produce DHA or other omega-3s from scratch; we have to get them from food. These words opened up a whole new avenue of inquiry for Hibbeln, and he jumped into researching how the fats we eat (or don't eat) might change our brain.

He was especially interested in mental illness. He has a family member with mental illness and in 1985, his parents, Raymond and Shirley, helped found the first national support group for families dealing with mental illness, what's now called the Depression and Bipolar Support Alliance.

We careen through the streets of Bethesda and finally pull up to a guard station at the National Naval Medical Center, where we are meeting Colonel Mike Lewis, M.D., M.P.H., one of Hibbeln's collaborators, to talk about some new studies. A soldier in dusty fatigues salutes and waves us in. "Sir, very good sir." Hibbeln returns the salute. Hibbeln tells me that post-traumatic stress disorder (PTSD) and depression in the U.S. military are affecting 20 percent of those who have been deployed. He points to construction vehicles and men in hard hats who swarm around the medical center. "They're building new treatment facilities to capture this flood of psychiatric distress," he says. "If I can get the military to change their diet, show that it works to reduce depression and suicide there, then there's a great potential for societal change."

After a few hair-raising attempts to secure parking, we find Lewis in the waiting area for Pulmonary Medicine. He and Hibbeln recently received Department of Defense funds to compare blood samples from 800 servicepeople who committed suicide between 2002 and 2008 to those of 800 healthy people in the military (matched by age, sex and rank) to see if low omega-3 levels are linked with likelihood of suicide. No results yet.

In addition, the U.S. Army recently awarded the duo almost $1 million to study the effects of giving omega-3 supplements to a special-operations unit that spends a third of the year in combat. They will give half the unit the omega-3 supplements and the other half a placebo, every day for a year, and then follow them for a couple of months to see if the omega-3s might prevent occurrences of depression and suicidal thinking. Hibbeln calls it giving "nutritional armor to the war fighter." They're also looking at whether it might protect a soldier should he or she suffer traumatic brain injury-not an unlikely occurrence for special-ops persons who jump from planes and engage in combat.

Hibbeln doesn't fight wars in the traditional sense, but as an officer in the public health service, he's been serving on the front lines of mental-health research for the last 17 years. "Joe truly wants to help people with his science," says Norman Salem, Hibbeln's former boss and mentor. "And he's got a lot of great ideas and great data."

What drives him? "I am motivated by a very strong sense of duty," says Hibbeln. (He mentions finding role models in his mother, a librarian; his father, a World War II vet who fought in Okinawa for 63 days straight; and his scoutmaster, Herb Wittenborn, also a WWII vet.) "Since I have the ability to do it, it is my duty to create the best science," says Hibbeln. "That's why I wear this uniform."

His government-issued dress, he tells me, is a daily reminder of the people he's committed to serving: veterans with PTSD, violent alcoholics, people with depression, underprivileged mothers who need access to foods that will maximize their children's potential. He points out the window to a man on the island of a busy intersection, holding a sign asking for money. "That's my boss. That's the guy I'm working for."

Diet-induced epidemic of distress?

In 1995, Hibbeln and Salem published the paper that launched Hibbeln's career in this field, an article in the American Journal of Clinical Nutrition presenting the theory he had been working out ever since he first held that lump of brain in his hands: mental illness could very well be a result of omega-3 deficiency.

His reasoning is this: The modern American diet is vastly different from the one upon which our ancestors evolved. Our ancestors consumed about equal amounts of omega-3 fats and omega-6 fats, the other polyunsaturated fats (found in vegetable oils) that compete with omega-3s for space in the brain. Today, Americans get 10 to 25 times more omega-6s than omega-3s, partly because we don't eat as many omega-3-rich fish, such as salmon and sardines (or wild animals, which are also higher in omega-3s), but mostly because our diets now contain processed foods that are packed with omega-6-rich oils, including oils made from soybeans, safflower and corn.

Hibbeln presented the possibility that this dramatic shift could have changed the way our brains function-sort of as if a car designed to run on unleaded gas suddenly started using diesel. Might it even trigger or perpetuate psychiatric illnesses? Hibbeln offers an interesting correlation: statistics suggest that depression and homicide rates have risen steadily over the past century-the same time period during which Americans' annual per capita intake of omega-6-rich oils increased by nearly 500 percent, from 11 pounds to 64 pounds.

"When the brain becomes deficient in nutrients, the first things to go are mood, the expression of emotion and concentration," Hibbeln explains. Though the idea of a nutritional deficiency affecting mood isn't exclusive to omega-3s (the Institute of Medicine mentions depression and irritability as symptoms of numerous nutrient deficiencies, including iodine and vitamin B12), Hibbeln's theory is unique in that it proposes too few omega-3s-or too many omega-6s-may be at least partly responsible for a national epidemic of psychiatric illness.

Fifteen years after the publication of that first paper, Hibbeln, who is now Acting Chief, Section on Nutritional Neurosciences at the National Institute on Alcohol Abuse and Alcoholism, is even more passionate about his hypothesis. Now, he has a growing body of scientific research to support it.

Hibbeln started building his case with broad observational studies and in 1998, he compared fish consumption to the prevalence of major depression in nine countries. He found that in countries with higher fish consumption, like Japan, the prevalence of major depression was lower than in countries with lower fish consumption, like the U.S. In 2001, he showed that among 3,204 Finnish people, those who rarely ate seafood were more likely to suffer symptoms of depression than those who ate it all the time. Later, Hibbeln showed that low fish consumption was also associated with bipolar disorder in 11 countries and schizophrenia in 14 countries. Furthermore, countries where people ate less fish tended to also have higher rates of homicide.

Hibbeln and others soon started testing the theory in clinical trials. The results were compelling enough to prompt the American Psychiatric Association (APA), in 2006, to recommend that people with major depression consume a daily omega-3 supplement in addition to their regular medications. (Recommended daily dose: 1 gram of DHA+EPA, eicosapentaenoic acid, another omega-3 fat in fish. That's the equivalent of what you would get eating 1 pound of oily fish, such as salmon, every week.) Additionally, the APA suggested that people with other mental-health conditions, including schizophrenia, bipolar disorder and ADHD, might also benefit from this complementary treatment.

Hibbeln likes these recommendations. He mentions them often. He also mentions the people who call, thanking him for his dedicated work. He played me a voicemail from a colleague whose sister's severe, treatment-resistant depression improved significantly after she began taking omega-3 supplements at the suggestion of her psychopharmacologist, who happened to be a big follower of Hibbeln's work.

I asked if he gets that a lot. "There are certainly people who have suffered from debilitating depression for 20 years, despite having gone through every reasonable pharmacological therapy," he says, leaning forward. "They take the omega-3s at high levels (2 to 3 grams per day), and suddenly their brain is freed."

Healthy fats make happy brain chemicals

Hibbeln explains that omega-3 fats help keep the membranes surrounding brain cells supple. This flexibility is important because the proteins that stick in the membrane need to twist to do their jobs, which include helping brain cells communicate. Studies suggest that omega-3s also may improve mental health by altering concentrations of brain chemicals called neurotransmitters-specifically dopamine and serotonin-perhaps by switching "on" or "off" genes that regulate these chemicals. Low levels of serotonin are linked with depression, aggression and suicidal tendencies, while dopamine is a "reward" chemical that the brain releases in response to pleasurable experiences, such as eating or having sex-or taking drugs like cocaine. Depletion of dopamine as a result of low omega-3 levels could cause an addict to seek more and more drugs to get high, worsening the addiction, says Hibbeln.

In 2003, Hibbeln and colleagues looked at omega-3 levels in 38 cocaine addicts in a rehabilitation clinic. Some kicked their addiction; others relapsed after discharge. Hibbeln found that those who relapsed had lower levels of omega-3s in their blood. Whether they recovered or relapsed, addicts with aggressive tendencies also had lower omega-3s. Hibbeln followed up with a controlled trial in 2008, and found that giving omega-3s to substance abusers made them less angry and anxious.

Now Hibbeln and some colleagues are looking at whether the same thing may hold true for alcoholics. (Alcohol breaks down omega-3 fats, depleting the body's supply.) To find out, Hibbeln and his team recruited 90 aggressive alcoholics. The volunteers underwent 30 days of in-patient rehabilitation, followed by 90 days of out-patient therapy with or without DHA+EPA supplements (the "without" group got placebo pills). By changing levels of neurotransmitters, omega-3s might help remedy issues underlying these subjects' alcoholism, namely depression, says Hibbeln, noting that it might also make them less violent. "If you treat their underlying depression and irritability and restore their brain DHA," Hibbeln asks, "will that assist them in reducing their drinking?"

Hibbeln can't say yet, as he's still analyzing the results of the study. He does, however, offer up an anecdotal account of one man for whom the omega-3 doses seemed to make a profound, positive impact.

When "Mr. D.," in his early sixties, was referred to Hibbeln's study by a homeless shelter, he'd been living on the streets or in prison for 25 years and had a long history of arrests for physical violence and multiple assault convictions. Basically, says Hibbeln, his daily routine consisted of "panhandling enough money to buy the booze he needed to get really drunk and go to sleep."

After "drying out" for 30 days, Mr. D. underwent baseline tests that found the omega-3 levels in his body to be "profoundly low," says Hibbeln. He was randomly assigned to the group that got the omega-3 supplements. The first thing the nurses and staff noted was that he looked healthier and happier.

He got a job for the first time in 20 years-at a car wash-and he showed up to work every day, says Hibbeln, who recalls: "He came in at one point in the study and pulled $650 out of a sock and says, ‘Doc, this is the most money I've had at one time in 25 years. I used to spend all of my panhandling money at the liquor store. I still go there to buy cigarettes and lottery tickets, but I don't crave any of the booze in the store.'" (This never happened the other times Mr. D. went through detox without omega-3s, says Hibbeln.)

As for Mr. D.'s aggression issues: "Here was a guy who'd had an impossibly long record for drunk and disorderly conduct transformed," says Hibbeln, into "a complete pussycat."

Diet of evolution

It's midday and we're standing in one of the medical center's public waiting areas, when Hibbeln suddenly gets a smile on his face and announces it's time for lunch. "EatingWell Magazine offers to take me out to lunch. Most people are smart enough to go to the fanciest restaurant in Bethesda. I have a twisted sense of humor, so we're going to eat what the military eats." He laughs.

We take the elevator to the basement, walk down a long hallway to the galley. It looks like any hospital cafeteria. There's fish on the menu today-cod.

But all that's left of the fish is a steaming tray of broth.

"Ten minutes till it's ready," the lady tells us.

"Glad to see it's popular," says Hibbeln.

"Yeah, it is," she says. "It's healthy."

"It's healthy, there you go," Hibbeln replies.

Hibbeln chooses pepper steak with rice instead. (His normal lunch is "hardtack [Scandinavian flatbread] and a can of tuna.") I have the same. Mike Lewis, who has joined us for lunch, selects a salad with soup.

After talking about Lewis's ideas for providing omega-3s to protect soldiers' brains from traumatic injury, Hibbeln reveals his grandest plan, one that applies all his research toward helping people in the "real world." Hibbeln wants to create what he calls a modern-day "Diet of Evolution." He is designing this diet-which he plans to someday introduce into the Naval hospital's cafeteria-to boost the ratio of omega-3s to omega-6s in the brain, not so much by increasing omega-3s but rather by dramatically reducing omega-6 fats-from about 10 percent to 1 percent of total calories. (On 2,000 calories a day, that's 2 to 2.5 grams versus the 17 to 20 that a typical Western diet delivers.)

For years, Hibbeln and others have advocated eating lots of omega-3-rich fish to restore the omega balance in the brain. But they haven't lost sight of the fact that animal studies suggest slashing the omega-6s may work just as well. "We don't need to increase the world's fisheries production tenfold to achieve the same goal," says Hibbeln. Eating a traditional Mediterranean-style diet that's centered on vegetables and fruits, legumes and olive oil, provides plenty of seafood and is limited in meat, will help to lower omega-6 intake dramatically, says Hibbeln. (Vegetables, fruits, legumes and olive oil don't contain significant amounts of omega-6s or omega-3s; seafood provides plenty of omega-3s; and meat tends to deliver more 6s than 3s. The diet as a whole is low in omega-6-rich processed foods. But overhauling an institutional menu is expensive, he says, "so the question is how do we make the same menus, backing off the omega-6 fatty acids?"

Answer: Replace the inexpensive high-omega-6 oils the military currently uses, such as soybean oil, with lower-omega-6 oils, such as high-oleic safflower and high-oleic sunflower oil (which have been bred or engineered to have more monounsaturated fats and fewer omega-6s).

If Hibbeln can show that balancing the omega-3/omega-6 equation in the medical center cafeteria can reduce risks of depression and suicide, it might convince the entire military to switch to lower-omega-6 oils (which cost a little more than, say, soy oil, but far less than the expense of changing the entire military diet). This could open the door to wider-reaching changes-like commercial product reformulations. Hibbeln is already preparing for that. His research team is figuring out how many omega-3s and omega-6s are in foods on supermarket shelves: Different brands of salad dressings. Mayo. Peanut butter. Chicken. Pork. "Pretty much everything," says Hibbeln.

What if he's wrong?

Near the end of our long day together, Hibbeln's conviction of the extreme importance of his work had not waned. After saying good-bye to Lewis and ending up in another of Hibbeln's several offices, this one at the NIH main campus, I asked: What would it take for him to discard his theory that a lack of omega-3s causes mental illness? He sat quietly for a few seconds, then said steadily, "I could ask Jeremy [the student sitting with us] to find all of the published scientific studies on omega-3s in humans-I think the total is somewhere between three and four thousand. So you're asking me to override the published data on several thousand studies?"

But, I say, most of the studies are not gold-standard randomized controlled trials (and they're not all in psychiatric illness; many are in cardiovascular disease).

"You have to take every piece of science for what it's worth," he says.

OK-but there are quite a few pieces of science, and researchers, who don't support Hibbeln's theories. Critics argue that Hibbeln's initial observational studies simply show associations and note there could be plenty of other reasons why-besides high fish consumption. For example, people in Japan seem less prone to depression than those in the United States. They also argue that the clinical science is equivocal: of the handful of controlled trials examining the effects of omega-3s on people with major depression, the most well-studied of these psychiatric illnesses, only about half suggest they help. In studies of people with milder depression, omega-3 supplementation has worked even less well. The same is true for mentally healthy people, though there have been even fewer studies.

Peter Rogers, Ph.D., an experimental psychologist who specializes in food and nutrition at the University of Bristol in the UK, is one of the skeptics. "I was very excited by this field, when I read the very first studies nearly 10 years ago now," says Rogers. "But the more I've been involved in this, the less I'm convinced about the impact" of omega-3s on mental illness. In a 2008 study, Rogers found omega-3 supplements did not improve the moods of people with mild to moderate depression. Rogers also reviewed hundreds of studies on omega-3s and various mental conditions, including depression, anxiety, aggression, ADHD and schizophrenia. That paper, published in Nutrition Research Reviews in 2008, concluded that, while early observational studies were promising, clinical trials have produced inconsistent and inconclusive results overall; much more evidence is needed to recommend omega-3 fats as a way to boost mental health.

Hibbeln waves all this off, acknowledging that the field is still young. What's important, he says, is finding the conditions under which omega-3s do work. Michel Lucas, Ph.D., M.P.H., a research fellow in the department of nutrition at the Harvard School of Public Health, agrees. "Even antidepressant drugs do not work for everybody," says Lucas, who thinks that, for people with mild to moderate depression, omega-3s might work about as well as antidepressants. Hibbeln, Lucas and Rogers all see the same data but come to different conclusions. Hibbeln's are the rosiest.

We get back into Hibbeln's Mazda, which has an ichthys (one of those religious fish tags) on the back-only this one says "sushi"-and drive back to my rental car. Hibbeln draws me a shortcut on my notepad-while driving-so that I can avoid D.C. rush-hour traffic and make my flight. We talk about his hobbies: serving as Cub Scout master, taking his school-age kids to historic presidential homes on vacation, cooking in his open-fire brick oven.

As we circle the garage looking for my car, he starts speaking almost out of nowhere, as if in response to the naysayers I would talk to later. "I think my role is not to provide definitive answers, although I do that on some level," he says, a bit more subdued than he'd been earlier. "My bigger contribution has been to ask the best questions. Open up new fields for inquiry. I'm a psychiatrist. If I only practice medicine, I can only affect hundreds, maybe thousands, of people. But if I do research that shifts the paradigm of treatment, I can create useful therapies that could impact millions."

May/June 2010