Fighting Depression

It’s crazy when you think about all of the different kinds of foods we eat.  We just swallow – and hope it all works out for the best. Well – as it turns out there are better ways to think about keeping our bodies humming healthfully along. Welcome to Nutrition Facts – I’m your host Dr. Michael Greger. 

Today – we look at ways to mitigate a serious mental health disorder: depression.

There is accumulating evidence that brain-derived neurotrophic factor (BDNF) may be playing a role in human depression. BDNF controls the growth of new nerve cells, and “so, low levels [may explain the] atrophy of specific brain areas…[you see] among depressed patients.” That may be one of the reasons exercise is so good for our brains. Start an hour-a-day exercise regimen, and within three months you can get a quadrupling of BDNF release from your brain.

This makes sense. Any time we were desperate to catch prey or desperate not to become prey ourselves, we needed to be cognitively sharp. And so, when we’re fasting or exercising and in a negative calorie balance, our brain starts churning out BDNF to make sure we’re firing on all cylinders. So, of course, Big Pharma is eager to create drugs to mimic this effect, but is there any way to boost BDNF naturally? Yes, I just said it—fasting and exercise! Okay, okay; but is there anything we can add to our diet to boost BDNF?

Well, higher intakes of dietary flavonoids appear to be protectively associated with symptoms of depression. The Harvard Nurses’ Study followed tens of thousands of women for years and found that those who were eating the most appeared to reduce their risk of coming down with depression. Flavonoids occur naturally in plants, and so there’s a substantial amount in a variety of healthy foods. But wait…how do we know the benefits are from the flavonoids, and not just from eating healthier in general? You don’t know until you put it to the test.

See, some fruits and vegetables have more than others. Apples have more than apricots, plums more than peaches, red cabbage more than white, kale more than cucumbers. So, if you randomize people into one of three groups: more high-flavonoid fruits and vegetables, more low-flavonoid fruits and vegetables, or no extra fruits and vegetables at all, after 18 weeks, only the high-flavonoid group got a significant boost in BDNF levels, which corresponded with an improvement in cognitive performance. The BDNF boost may help explain why each additional daily serving of fruits or vegetables is associated with a three percent decrease in the risk of depression.

A teaspoon a day of the spice turmeric may boost BNDF levels more than 50 percent within a month, consistent with the other randomized controlled trials that have so far been done.

Nuts may help too. In the PREDIMED study, where people were randomized to be sent weekly batches of nuts or extra virgin olive oil, the nut group lowered their risk of having low BDNF levels by 78 percent.

And, brain-derived neurotrophic factor is not just implicated in depression but schizophrenia as well. Have those with schizophrenia undergo a 12-week exercise program, and they get a significant boost in BDNF levels––leading the researchers to suggest “that exercise induced modulation of BDNF may play an important role in developing non-pharmacological treatment for chronic schizophreni[a] patients.” Okay, but what actually happened to their schizophrenia symptoms? Let’s find out.

Thirty individuals with schizophrenia randomized to ramp up to 40 minutes of aerobic exercise three times a week or not. And there did appear to be an improvement in psychiatric symptoms, such as hallucinations, as well as increasing their quality of life. In fact, you can actually visualize what happened in their brains. Loss of brain volume in a certain region appears to be a feature of schizophrenia, but 30 minutes of exercise three times a week, and you can get up to a 20 percent increase in size of that region within three months.

Calorie restriction may also increase BDNF levels in schizophrenics, but they didn’t just have them eat less, but eat healthier—less saturated fat and sugar, and more fruits and veggies. It’s like the Soviet fasting trials for schizophrenia. They reported these truly unbelievable results, supposedly restoring people to function: fasting described as an “unparalleled achievement in the treatment of schizophrenia.” Okay, but part of the problem is that the diagnostic system the Soviets used is completely different, making any results hard to interpret. But they do have a subgroup that does seem to correspond to the Western definition, and they still report between 40 and 60 percent improvement rates from fasting.

But that’s not all they did. After being fasted for up to a month, they were put on a meat- and egg-free diet, so when they report these remarkable effects even years later, that’s for those who stuck with the diet. Those who broke the diet evidently relapsed, and the closer the diet was followed, the better the effect. They note that “not all patients [were able to] remain vegetarian,” but they tried to keep meat to a minimum. And look, we know from randomized controlled trials that just removing meat and eggs can improve mental states within even just two weeks, and so it’s hard to know what role the fasting itself played in the reported improvements.

A single high-fat meal can drop BDNF levels within hours. And, you can prove it’s the fat itself by seeing the same thing injecting fat straight into their veins. Perhaps that helps explain why increased consumption of saturated fats in a high-fat diet may contribute to brain dysfunction—neurodegenerative diseases, long-term memory loss, cognitive impairment. Maybe that helps explain why the Standard American Diet has been linked to a higher risk of depression, dietary factors modulating the levels of brain-derived neurotrophic factor.

If depression can be induced with pro-inflammatory drugs, might an anti-inflammatory diet be effective 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. In fact, by 2020, depression may be the second leading cause of healthy years of life lost, second only to heart disease. 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, such as 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% 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 a plant-based diet, which can cut C-reactive protein levels by 30% 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? Endotoxins. It’s worth reviewing how the endotoxins in animal products can cause a burst of inflammation within hours of consumption. What does it 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 the 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.

The most comprehensive controlled trial of diet and mood finds that a plant-based nutrition program in a workplace setting across ten corporate sites significantly improves depression, anxiety, and productivity.

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 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? 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.

The overall amount of fat in their diet didn’t significantly 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 our 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 we 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. The plant-based group beat out controls on nearly every measure.

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 multicenter, 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.

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