 It's crazy when you think about all the different kinds of foods we eat. We just swallow and hope it all works out for the best. Well, 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's accumulating evidence that brain-derived neurotrophic effect 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 errors you see among depressed patients. That may be one of the reasons exercise is so good for our brains. Starting our day exercise regimen, within three months you can get a quadrupling of BDNF reliefs from your brain. This makes sense. I mean, anytime 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, or 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 get 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? 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 the risk of coming down with depression. Flavonoids occur naturally in plants, 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 to an improvement in cognitive performance. The BDNF boost may help explain why each additional daily serving of fruits and vegetables is associated with a 3% decrease in the risk of depression. A teaspoon a day of the spiced turmeric may boost BDNF levels more than 50% within a month, consistent with the other randomized controlled trials that have so far been done. Nuts may help, too. In the Predomet 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%. 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 schizophrenia patients. OK, but what actually happened to their schizophrenia symptoms? Let's find out. 30 individuals with schizophrenia were 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% increase in size of that region within three months. Calorie restriction may also increase BDNF levels in schizophrenia, 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. OK, 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% improvement rates from fasting, but that's not all they did after being fasted for up to a month. They report 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 know 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 with 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, if it has such negative effects, but yet it remains so common. Inheritable, meaning a big chunk of risk is passed 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's a surge of inflammation as our body mounts a counter-attack. And then what happens? We feel lousy. We feel sick. We get weak, tired, slow, and sleepy. We don't want to 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 it help us conserve energy, so we can put up a good fight, but reduces social contact. We're not running around infecting everyone. It's the same reason we evolve 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 for the rest of the community. The relationship between mental health and inflammation was first noted in 1887, for which the only psychiatrist 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. 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. And 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 cause to 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 diet 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-3s as anti-inflammatory, but they found fish to be pro-inflammatory, associated with increased C-reactive protein levels, consistent with recent findings that Omega-3s 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% within two weeks, perhaps because of the anti-inflammatory properties of antioxidants. I've talked about this before, but never really explain why antioxidants are anti-inflammatory. See, 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 response that creates free radicals lead to autoimmune inflammation. 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 does 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. This is 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 this study. But by eliminating animal products and eating endoxin-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 10 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 the reduced odds of depression. But out of the 21 studies they could find in the medical literature, they were only able to find one randomized controlled trial considered the study design that provides the highest level of evidence. And 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 causing effect until you put it to the test, which they finally did. But 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 previously addressed, how consumption, even a single carbohydrate-rich meal, can improve depression, tension, anger, confusion, sadness, fatigue, alert, 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. These sustained improvements in mood in the low-fat group, compared with the low-carb group, are consistent with the results from epidemiological studies showing that diets high in carbohydrates and low in fat and protein are associated with lower levels of anxiety and depression and have beneficial effects on psychological well-being. 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 our brain. High blood levels in the bloodstream have been associated with a greater likelihood of suicide risk, for example in major depressive episodes. How can we stay away from this stuff? All 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 lettuce soup, minestrone, 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, 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, where the plant-based group beat out controls on nearly every measure. There was 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. 10 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. We would love it if you could share with us your stories about reinventing your health through evidence-based nutrition. Goodnutritionfacts.org slash testimonials, we may share it on our social media to help inspire others. To see any graphs, charts, graphics, images, or studies mentioned here, please go to the Nutrition Facts podcast landing page. There you'll find all the detailed information you need, plus links to all the sources we cite for each of these topics. For a timely text on the pathogens that cause pandemics, you can order the e-book, audio book, or hard copy of my latest book, How to Survive a Pandemic for Recipes. Check out my new How Not to Diet Cookbook. It's beautifully designed with more than 100 recipes for delicious and nutritious meals. And all the proceeds I receive from the sales of all my books goes to charity. Nutritionfacts.org itself is a non-profit, science-based public service where you can sign up for free daily updates on the latest in nutrition research via bite-sized videos and articles. Everything on the website is free. There's no ads, no corporate sponsorship. It's strictly non-commercial. I'm not selling anything. I just put it up as a public service as the labor of love as a tribute to my grandmother, whose own life was saved with evidence-based nutrition.