Treating Depression with Diet

Today, we look at how plant-based nutrition may play a role in alleviating symptoms of depression. And, in our first story, we ask, “Do vegetarians have more or less depression and anxiety?”

Mental illness is among the leading causes of disability. Pharmacotherapy and psychotherapy, such as antidepressants and Cognitive Behavioral Therapy, are cornerstones of treatment. However, they avert less than half of the disease burden, suggesting that additional strategies to prevent and treat mental disorders are needed. A new field of nutritional psychiatry provides evidence for diet quality as a modifiable risk factor for mental illnesses.

Cited mechanisms include chronic low-grade inflammation. That’s been implicated in the development of depression, schizophrenia, and bipolar disorder. Oxidative stress—free radicals may also be relevant to mental illness. And then, there’s compelling evidence, though predominantly from animal studies, indicating the gut microbiome can affect the brain. What kind of compelling evidence? Fecal transplant studies found that feeding rats feces from depressed people induces depression-like behavior. Now, if I got force-fed feces every day, I might be depressed too—but rats fed feces from non-depressed people didn’t act as depressed.

How might we sow the seeds of good mental health through our microbiome? Dietary factors that help our good gut bugs include eating more Mediterranean, more plant-based, fruits and vegetables, fermented foods, nuts, fiber and other prebiotics, plant-based proteins, predominantly plant-based fats, and polyphenols, which are also plant-based compounds. Bad for our microbiome is the Western diet, animal protein, saturated fat, which is concentrated in meat, dairy, and junk, and sweeteners and emulsifiers, which may help explain why greater ultra-processed food intake is associated with increased risk of subsequent depression. And the animal protein and animal fat may help explain why greater meat consumption is also associated with a higher risk of depression.

So, if plants may be good and meat bad, then vegetarians must be feeling great! But some compilations of studies found that vegetarians tend to show higher depression scores than non-vegetarians, and not just reviews funded by the National Cattlemen’s Beef Association. Other systematic reviews of vegetarian diets and risk of depression, anxiety, and stress found no significant associations with depression or anxiety, and the only study finding a significant difference in stress found a lower level of stress in those eating strictly plant-based.

Other reviews found mixed findings––for example, higher rates of depression, but lower rates of anxiety. Basically, the evidence on the effect of plant-based diets on depression is contradictory. For example, out of 25 studies, 11 found higher rates of depression, seven found lower rates of depression, and another seven found no overall correlation. If you drill down, though, and just consider the best quality studies, of the four, one found that veg diets had either no risk or a higher risk of depression (depending on the population), and the other three good studies found a lower risk of depression among those eating more plant-based.

Drilling down geographically, vegetarianism was not associated with mental health in the United States, Russia, or Germany, but was associated with anxiety and depression in China––though the association was small, explaining less than 1% of the variance in depression and anxiety between individuals. And if you drill down by type of vegetarian, only the so-called semi-vegetarians, or flexitarians, had higher rates of depression, rather than actual vegetarians and vegans.

Study results suggested that semi- and pesco-vegetarians, who include fish and/or poultry, had a higher risk for depression, whereas no significant association was found for lacto-ovo vegetarians who eat no meat. And there were similar findings with studies using relative mood scoring, though technically, none of the groups achieved statistical significance.

The bottom line is that some systematic reviews have shown no association between vegan and vegetarian diets and mental health outcomes, whereas others have shown associations between vegetarian diets and more depression, while others associate vegetarian diets with less depression.

And even if it did go one way or the other, the majority of the studies were just snapshot-in-time cross-sectional studies. So, they are unable to determine cause and effect. Even if following a vegetarian diet was consistently associated with higher or lower rates of depression, there is the possibility of reverse causation. Maybe being depressed leads people to eat vegetarian, rather than eating vegetarian leads to depression. What we need are studies over time to see which came first and interventional studies to put it to the test, both of which I’ll explore, next.

In our next story, we look at how vegetarians have a 30% lower chance of developing depression over time.

As I noted in the last video, the association between vegetarian diets and depressive symptoms is ambiguous and lacks consensus. Some systematic reviews found no association between vegetarian diets and symptoms of depression, while others suggest that those following a vegetarian diet are less likely to be depressed, but even that doesn’t mean that eating vegetarian makes people feel better. Maybe those who feel better are just more likely to eat healthier. Maybe we’re less likely to need comfort foods if we’re already comforted. Or, it could go the other way, where individuals who experience problems may be more inclined to follow a vegetarian or vegan diet in order to improve their mental health. For example, most medications used to treat depression cause weight gain; so, maybe depression led to antidepressants, which led to weight gain, which then led people to try eating healthier diets. What we need are prospective studies that follow people over time to see, in the very least, which came first. There’s been a few.

This study in Germany found that the mental disorders came first, followed by the adoption of the vegetarian diet, suggesting that those with mental health issues may try to clean up their diets in hopes it will benefit their condition. It was the same in the UK; psychological distress predicted later vegetarianism, and not the other way around.

By far the biggest study was in Taiwan, a prospective cohort study following more than 3,500 vegetarians for about nine years, and compared with non-vegetarians, those in the vegetarian group had a 30% lower chance of developing a depressive disorder in that time. Thus, Taiwanese vegetarians were at lower risk. Rates remained about the same for the first two years, and then the curves separate. What might be the mechanism? Well, the sleep quality of vegetarians may be significantly better, and maybe that helps mood, or maybe they’re just sleeping better because they’re less depressed.

On the one hand, consumption of vegetarian diets could increase the risk of depression if the vegetarians weren’t getting enough vitamin B12 or long-chain omega-3 fats. At the same time, there are aspects about their diet that could reduce the risk of depression. Like all the antioxidant, anti-inflammatory foods, like fruits and vegetables, may help to counteract the inflammation in the brain associated with depression.

In the United States, those eating vegetarian may only have half the odds of depression. But if you adjust for factors such as inflammation and body weight, the association is no longer significant. Now, it’s totally legitimate to control for things like educational level and smoking status, but since vegetarians are less likely to be obese and inflamed, maybe that played a role in their better mental health. So, by effectively erasing those benefits, one may be undercutting part of the causal pathway.

It’s not actually clear what role inflammation plays in depression, though. Check out this study: a double-blind, randomized, placebo-controlled trial on the effect of the anti-inflammatory drug aspirin for the long-term management of depression in older people. Those randomized to aspirin actually had a worsening of their depression, and diminished quality of life compared to placebo.

There are certainly confounding factors that need to be taken into account. Otherwise, we don’t know if some of the associated lifestyle factors are the cause, rather than the diet itself. For example, in this study of plant-based health professionals, besides eating fewer animal foods, they also tended not to smoke or drink as much, exercised and slept regularly, and also ate less junk. And one can imagine them feeling better mentally if only because they felt better physically. They lost weight, up to 120 pounds (55 kg); some reversed their health conditions and were able to stop medications. No wonder they felt less depressed.

It’s like when you look at the effectiveness of plant-based diets in promoting well-being in the management of type 2 diabetes. Yes, compared to traditional diets for diabetes, eating plant-based was associated with significant improvement in emotional well-being, depression, and quality of life, but maybe it’s just because their diabetes improved significantly more.

And finally, when we’re talking about well-being, we’re talking about well-being through self-report. So, for example, in this study, the vegetarians reported significantly better well-being than omnivores, and vegans were about twice as likely to report good well-being, but maybe they were just ideologically motivated to say so. It’s like this study on the self-reported health status of those following the carnivore diet. If you do a social media survey of communities like the World Carnivore Tribe, they also report feeling great. They also reported shockingly high LDL cholesterol levels, but you can see how self-selection bias in various communities could skew the results. This is all to say why it’s critical we have interventional trials. Randomize people to eat different diets and see what happens: interventional trials, which I’ll cover, next.

Finally today, dietary interventions are put to the test for major mental illness.

Psychiatry is at an important juncture, with the current drug-focused model having only achieved modest benefits. So, what about using nutritional interventions? Diet may be as important to psychiatry as it is to cardiology. That’s quite the bar. You don’t know if diet can help, until you put it to the test.

For example, the famous Geico study, a multicenter, randomized, controlled trial of a nutrition intervention program in a multiethnic adult population in the corporate setting, looked at reducing depression and anxiety, and improving quality of life. Researchers found that advice to eat a strictly plant-based diet improved indicators of depression, anxiety, and work productivity—specifically, significant improvements in depression, anxiety, fatigue, emotional well-being, daily functioning because of emotional health, improvement in impairments while working because of health, overall work impairments because of health, and non-work related activity impairment because of health, compared with the control group at 18 weeks.

Even just cutting out meat can improve mood. Omnivores were randomly assigned to a control group to consume meat, including fish and poultry, daily, or just the fish, or no meat at all. And compared to the control group, some mood improvements were found in the total meat elimination group within just two weeks.

However, just replacing three servings of meat a week with plant-based meat alternatives was not found sufficient to affect psychological measures. Why not at least a serving a day? Researchers gave people as much red meat as could conscientiously be imposed, given the associated cancer risks.

The problem with all these studies, though, is they were all on people who started out mentally healthy. If nutritional psychiatry is going to be a thing, we need to know if can actually help people with major mental illness. To date, only two trials have put dietary interventions to the test for major depression: the SMILES trial and the HELFIMED trial.

The SMILES trial was the first randomized, controlled trial to explicitly seek to answer the question: If I improve my diet, will my mental health improve? It was a 12-week trial consisting of nutritional consulting sessions delivered by a clinical dietician vs a control group “social support protocol” called befriending. So, instead of seeing the dietician, study participants hung out with someone to talk sports, news, or music, or just play cards or board games, with the intention of keeping them engaged and feeling positive. Befriending aims to control for four factors: time, expectancy, therapeutic alliance, and therapist factors, often used as a control condition for clinical trials of psychotherapy. It’s like placebo therapy.

What were they told to eat? It was a Mediterranean-ish diet with lots of whole grains—five to eight servings a day––lots of vegetables, fruits, nuts every day, olive oil, with restrictions on meat, eggs, sweets, refined cereals, fried foods, fast foods, and sugary drinks. They used the MADRS depression rating scale, which rates 0 to 6 as normal, no depression, 7 to 19 mild depression, and 20 to 34 moderate depression. So, study participants in both the diet and control groups started out, on average, with moderate depression. And after three months of social support, the control group felt better, but still technically moderately depressed, whereas the diet group ended up with only mild depression, on average. If one defines remission as scoring less than 10, that was achieved by 32.3% in the diet group, compared to only 8% in the control group.

The HELFIMED study was a similar Mediterranean-style dietary intervention versus social support for three months. The diet groups successfully consumed more vegetables, fruits, nuts, legumes, whole grains, and a greater diversity of vegetables, while eating fewer unhealthy snacks, and less red meat and less chicken. And they indeed appeared to reap mental health benefits in terms of reduced depression and improved quality of life, which was notably sustained to at least six months. Now, they also supplemented with fish oil, but that is unlikely to have a meaningful antidepressant effect. And indeed, in the study, there was no correlation between increased omega-3 levels and improved depressive symptoms. But improvements in a range of mental health outcomes were significantly correlated with the greater diversity of vegetables and fruits, intake of legumes and nuts, and reduced consumption of unhealthy snacks, takeout, and meat.

Any foods in particular that may be beneficial? In this study, men and women diagnosed with major depression were randomized to receive either about two-thirds of a teaspoon of lemon balm leaf powder or lavender flower powder—both disguised in capsules—or an identical looking capsule filled with a typical dose of Prozac. And, both of the herbs appeared to work as well as the drug. Which group is which? Exactly. Now, what they didn’t have is a placebo group, where people essentially took nothing. But there are placebo-controlled trials of lemon balm, showing it can significantly improve anxiety and depression symptoms.

This trial used lavender flower tea on anxiety and depression in the elderly––the same amount in a teabag, but twice a day. Sadly, the control group didn’t receive anything; so, the reduction in depression and anxiety may have just been a placebo effect. But since it’s cheap, simple, and side-effect free, it might be worth giving lavender flower tea a try.

What about vinegar? Now, this study was about improving mood in healthy adults, but two tablespoons of vinegar diluted in a cup (240 ml) of water twice daily with meals for four weeks appeared to lead to a reduction in self-reported depression scores compared to those randomized to instead take vinegar pills with a 100 times less acetic acid, the presumed active ingredient. And finally, wild blueberries. Adolescents were randomized to about five teaspoons a day of wild blueberry powder, versus a placebo powder matched for sugars and vitamin C, and those getting the blueberries had a significantly greater drop in depression scores. But the difference in anxiety did not reach statistical significance.