Fighting the Blues with Greens

Today, we look at the role diet plays in preventing and treating mood disorders.

Depression affects more than 150 million people worldwide, making it a leading cause of losing healthy years of life as a result of disability. Why is depression so common? Well, it is said, “Nothing in biology makes sense except in the light of evolution.” But, why would we evolve to get depressed?

Depression poses a baffling evolutionary puzzle. It has such negative effects, but remains so common and heritable, meaning a big chunk of risk is passed down through our genes. So, there must be some kind of adaptive benefit. Otherwise, presumably, it would have been naturally selected against. Maybe, depression is an evolutionary strategy for defense against infection.

Infection has been the leading cause of mortality throughout human history. The average life expectancy was 25, and it was not uncommon for half our kids to die. With such stark capabilities, infection has been a critical and potent driving force in natural selection.

When we become infected, there is a surge of inflammation as our body mounts a counterattack, and then what happens? We feel lousy. We feel sick.  We get weak, tired, slow, and sleepy. We don’t see anyone; we don’t want to do anything; all we want to do is sleep. It’s like we’re depressed—and that’s great for fighting infection. Not only does that help us conserve energy so we can put up a good fight, but it reduces social contact. We’re not running around infecting everyone.

It’s the same reason we evolved to think poop doesn’t smell good, or decaying flesh. That keeps us safe from infection. In fact, we see this phenomenon with other social animals, like honeybees and mole rats, who feel impelled to crawl off and die alone when they get sick, which reduces the risk to the rest of the community.

The relationship between mental health and inflammation was first noted in 1887, for which the only psychiatrist to ever win the award got a Nobel Prize. But what evidence have we accumulated in the century since that inflammation causes depression? Well, people who are depressed have raised inflammatory markers, such as C-reactive protein, and inflammatory illnesses are associated with greater rates of major depression. Indeed, that’s what’s found in a variety of inflammatory conditions including more benign inflammatory conditions, like asthma and allergies. And, that’s important, suggesting the mood symptoms are not simply ‘feeling bad about having a terrible disease,’ but may be directly tied to the inflammation. Most powerfully, you can actually induce depression by inducing inflammation, like when we give interferon for certain cancers or chronic infections—up to 50 percent go on to suffer major depression. Even just giving a vaccine can cause enough inflammation to trigger depressive symptoms. Taken together, these studies are strongly suggestive of inflammation being a causative factor of mood symptoms.

So, can an anti-inflammatory diet help prevent depression? We didn’t know, until about 43,000 women without depression were followed, along with their diets, for about a dozen years to see who became depressed, and it was those who ate a more inflammatory dietary pattern, characterized by more soda, refined grains, and meat, suggesting that chronic inflammation may underlie the association between diet and depression. Normally, we think of omega-3’s as anti-inflammatory, but they found fish to be pro-inflammatory, associated with increased C-reactive protein levels consistent with recent findings that omega-3’s don’t seem to help with either depression or inflammation. The most anti-inflammatory diet is plant-based, which can cut C-reactive protein levels by 30 percent within two weeks, perhaps because of the anti-inflammatory properties of antioxidants.

I’ve talked about this before, but never explained why antioxidants are anti-inflammatory. Oxidative damage caused by free radicals may cause an autoimmune response in the body by changing the chemical structure of otherwise ubiquitous molecules to generate new structures that the body attacks as foreign. For example, when LDL cholesterol gets oxidized, our body creates antibodies against it and attacks it. And, so, clinical depression can be accompanied by increased oxidative stress and the autoimmune inflammatory responses it creates.

Where else does inflammation come from in our diet? It’s worth reviewing how the endotoxins in animal products can cause a burst of inflammation within hours of consumption. What does that do to our mood? If you inject endotoxin into people, within a few hours, inflammation shoots up, and so do feelings of depression, as well as feelings of social disconnection between people.

Although previous research has demonstrated that inflammatory activity contributes to depressive symptoms, no work in humans has examined the effect of experimentally induced inflammation on anhedonia, the lack of reaction to pleasurable stimuli, an important symptom of depression.  No work has been done, that is, until now.  Within hours of endotoxin hitting their bloodstream, these experimental subjects not only started to feel depressed, but they had significant reductions in activity in the reward center of their brain. They were less excited about winning money playing video games, for example, in the study.

But by eliminating animal products and eating antioxidant rich diets, we may be able to prevent or treat depression.

In our next story, we look at how the natural enzyme inhibitors in fruits and vegetables may help explain the improvement in mood associated with switching to a more plant-based diet.

Why does frequent consumption of vegetables appear to cut one’s odds of depression by more than half? And, by more frequent, they mean eating vegetables not three or more times a day, but just three or more times a week. But, even that seemed to cut the odds of developing depression by 60 percent, after controlling for a long list of variables.

In the 2012 study that found that eliminating animal products improved mood within two weeks, the researchers blamed arachidonic acid—primarily in chicken and eggs, which may adversely impact mental health via a cascade of brain inflammation. But, better moods on plant-based diets could also be from the good stuff in plants—a class of phytonutrients that crosses the blood-brain barrier into our heads. This recent review in the journal Nutritional Neuroscience suggests that eating lots of fruits and vegetables may present “a noninvasive, natural, and inexpensive therapeutic means to support a healthy brain.” Yeah, but how?

Well to understand the latest, we need to understand the underlying biology, the so-called monoamine theory of depression—the thought that depression may arise out of a chemical imbalance in the brain. Here’s the oversimplified version. One of the ways the billions of nerves in our brain communicate with one another is through chemical signals called neurotransmitters.

Note the two nerve cells don’t actually touch; there’s a physical gap between them. To bridge that gap, when one nerve wants to tap the other on the shoulder, it releases chemicals into that gap, including three monoamines: serotonin, dopamine, and norepinephrine. These neurotransmitters then float over to the other nerve, to get its attention. The first nerve then sucks them back up, to be reused the next time it wants to talk. But, it’s also constantly manufacturing more, and an enzyme—monoamine oxidase—is constantly chewing them up to maintain just the right amount.

The way cocaine appears to work is by acting as a monoamine reuptake inhibitor. It blocks the first nerve from sucking back up those three chemicals, and so, there’s this constant tapping on the shoulder, this constant signaling to the next nerve. Amphetamines work in the same way, but also increase monoamine release. Ecstasy works like speed, but just causes comparatively more serotonin release.

After a while, the next nerve may be like, enough already, and downregulate its receptors to turn down the volume. It puts in earplugs. So, you need more and more of the drug to get the same effect. And then, when you’re not on the drug, you may feel crappy—because normal volume transmission just isn’t getting through as much.

Antidepressants are thought to work along similar mechanisms. People who are depressed appear to have elevated levels of monoamine oxidase in their brain. That’s the enzyme that breaks down those neurotransmitters. If the levels of your neurotransmitter-eating enzyme is elevated, then your levels of neurotransmitters drops, and you become depressed, or so the theory goes.

So, a number of different classes of drugs have been developed. The tricyclic antidepressants—named because they have three rings, like a tricycle—appear to block norepinephrine and dopamine reuptake. And so, even though your enzymes may be eating these up at an accelerated rate, what gets released sticks around longer. Then, there came the SSRIs, like Prozac—the selective serotonin reuptake inhibitors. Now, you can know what that means—it just blocks the reuptake of serotonin.

Then, there are drugs that just block the reuptake of norepinephrine. Or, more dopamine. Or, the opposite. But, if the problem is too much high levels of monoamine oxidase, why not just block the enzyme? Make a monoamine oxidase inhibitor. And, of course, they did. But, they’re considered drugs of last resort because of serious side effects—not the least of which is the dreaded “cheese effect,” where eating certain foods (like certain cheeses) while on the drug can have potentially fatal consequences. If only there were a way to tamp down the activity of this enzyme, without the whole bleed-into-your-brain thing, and die thing.

Well, now we can finally talk about the latest theory as to why fruits and vegetables may improve our mood. There are inhibitors of that depression-associated enzyme in various plants. There are phytonutrients in spices, such as cloves, oregano, cinnamon, nutmeg. But, people don’t eat enough spices to get enough into the brain. This dark green leafy has a lot, but its name is tobacco—which may actually be one of the reasons cigarettes make smokers feel so good.

Okay, but what if you don’t want brain bleeds or lung cancer? Well, there is a phytonutrient found in apples, berries, and grapes, and kale, onions, and green tea that may indeed affect our brain biology enough to improve our mood.

Finally today, the results of an interventional trial of diet and mood.

A 2014 systematic review and meta-analysis of dietary patterns and depression concluded that a healthy diet pattern was significantly associated with reduced odds of depression, but out of the 21 studies they could find in the medical literature, they were able to find only one randomized controlled trial, considered the study design that provides the highest level of evidence. It was the study I profiled in Improving Mood Through Diet, in which removing meat, fish, poultry, and eggs improved several mood scores in just two weeks.

We’ve known that those eating plant-based tend to have healthier mood states—less tension, anxiety, depression, anger, hostility, and fatigue. But you couldn’t tell if it was cause and effect until you put it to the test, which they finally did. What could account for such rapid results? Well, eating vegetarian does give you a better antioxidant status, which may help with depression.

Also, as I’ve previously addressed, consumption of even a single carbohydrate-rich meal can improve depression, tension, anger, confusion, sadness, fatigue, alertness, and calmness scores among patients with PMS—but what about long term?

Overweight men and women were randomized into a low-carb, high-fat diet, or a high-carb, low-fat diet for a year. By the end of the year, who had less depression, anxiety, anger, and hostility, feelings of dejection, tension, fatigue, better vigor, less confusion, or mood disturbances? The low-carb dieters are represented by the black circles, and the low-fat dieters are represented in the white. These sustained improvements in mood in the low-fat group compared with the low-carb group are consistent with results from epidemiological studies showing that diets high in carbohydrate and low in fat and protein are associated with lower levels of anxiety and depression, and have beneficial effects on psychological wellbeing.

But the overall amount of fat in their diet didn’t change in this study, though. But the type of fat did; their arachidonic acid intake fell to zero.

Arachidonic acid is an inflammatory omega-6 fatty acid that can adversely impact mental health via a cascade of neuroinflammation. It may inflame your brain. High blood levels in the bloodstream have been associated with a greater likelihood of suicide risk, for example, and major depressive episodes. How can we stay away from the stuff?

Americans are exposed to arachidonic acid primarily through chicken and eggs. But when you remove chicken and eggs, and other meat, we can eliminate preformed arachidonic acid from our diet.

So, while high-quality treatment studies investigating the impact of diet on depression are scarce, there is that successful two-week trial, but even better, how about 22 weeks?

Overweight or diabetic employees of a major insurance corporation received either weekly group instruction on a whole food, plant-based diet or no diet instruction for five and a half months. There was no portion size restriction, no calorie counting, no carb counting. No change in exercise. No meals were provided, but the company cafeteria did start offering daily options such as lentil soup, minestrone, and bean burritos.

No meat, eggs, dairy, oil, or junk; yet, they reported greater diet satisfaction compared with the control group participants who had no diet restrictions. How’d they do though? More participants in the plant-based intervention group reported improved digestion, increased energy, and better sleep than usual at week 22 compared with the control group. They also reported a significant increase in physical functioning, general health, vitality, and mental health.

There were also significant improvements in work productivity, thought to be due, in large part, to their improvements in health. So, what this study demonstrated was that a cholesterol-free diet is acceptable, not only in research settings, but in a typical corporate environment, improving quality of life and productivity at little cost. All we need now is a large, randomized trial for confirmation, but we didn’t have such a thing—until now.

Ten corporate sites across the country from San Diego to Macon, Georgia. Same kind of setup as before. Can a plant-based nutrition program in a multi-center, corporate setting improve depression, anxiety, and productivity? Yes, significant improvements in depression, anxiety, fatigue, emotional well-being, and daily functioning. Lifestyle interventions have an increasingly apparent role in physical and mental health, and among the most effective of these is the use of plant-based diets.