Newsletter #250

Depression is estimated to affect a staggering 300 million people around the world, costing the global economy as much as $1 trillion in lost productivity every year. Unfortunately, it is a difficult problem to solve. A tremendous portion of people battling depression is treatment-resistant, likely because it is a complex, multifactorial disease process.

Observational evidence, as well as some intervention studies, have suggested that a healthy diet, and particularly a higher intake of foods rich in dietary fiber, may decrease the risk of depression. However, there hasn't been very much research that directly examines how dietary fiber might interact with mental health outcomes…until quite recently. I stumbled upon a few new-ish studies that not only show a link between higher fiber intake and lower risk of depression but also suggest that fiber (as well as some other health-promoting dietary components) may exert this effect by dampening inflammation, which I thought was worth diving into.

Of course, this association has to be interpreted cautiously. It's not hard to imagine that people who are depressed are more likely to engage in behaviors that tend to ramp up systemic inflammation (inactivity, ultra-processed foods, drugs, etc). In other words, is it possible that depression (indirectly) leads to inflammation, rather than inflammation-causing depression? Well, longitudinal studies seem to suggest that the former might be the case. For instance, British civil servants who started out with higher CRP levels (indicating greater inflammation) but who were not depressed were more likely to go on to be diagnosed with depression when they were followed for 12 years. But those who began the study with depression were not more likely to show increasing markers of inflammation over the same follow-up period.

Finally, before I jump into the research, I'd like to let y'all know about an exciting new project that we are working on now and which we will be launching in the near future. If you've followed us for a while, you must know that our greatest passion is finding ways to modify lifestyle to improve health and performance. But over time, we've realized that knowledge isn't necessarily quite enough, by itself, to drive behavior change. To that end, we will be opening up a coaching program to help folks transform their lives and meet their goals. Stay tuned for more info on that 👀

Prior studies have suggested that a high intake of fruits and vegetables is associated with a lower risk of depression. To discern the specific role of dietary fiber, researchers in Iran performed a comprehensive search for observational studies that examined the association between depressive symptoms and fiber intake. They ultimately included nine articles in the meta-analysis. Four of the studies were case-control (meaning that the researchers compared patients with depression to otherwise similar individuals who didn't have depression). They determined, sure enough, that consumption of dietary fiber in people with depression was significantly lower than in healthy controls. The other five studies were cross-sectional, meaning that the researchers collected data on diet and mental health from lots of different people at a single point in time. After pooling data from all of these studies (a total of 97,023 subjects), they determined that higher consumption of fiber was linked to 24% lower odds of depression. This is the first meta-analysis to specifically investigate the association between dietary fiber intake and odds of depression, and the finding is fairly persuasive in light of other evidence.

Acute inflammation is a normal and healthy response to injury or infection. However, dysregulation of anti-inflammatory pathways in the body can lead to chronic low-grade inflammation, which is thought to drive a number of pathologies, including perhaps conditions of the brain. We've known for some time that components of the diet may influence systemic inflammation. To comprehensively capture the inflammatory potential of a given diet, experts have developed a Dietary Inflammation Index (DII). Basically, researchers analyzed thousands of studies reporting the effects of various dietary parameters on inflammation based on whether they increased or decreased inflammatory biomarkers. (Notably, dietary fiber is one of the anti-inflammatory parameters of this score.) To see how this score might predict mental health outcomes, researchers affiliated with Hebei Medical University in China performed a literature search for articles related to dietary inflammatory potential and the risk of depression and anxiety. In total, 17 studies with a total of 157,409 participants were included in the final analysis. The researchers determined that compared to those consuming the least inflammatory diet, eating a diet with higher inflammatory potential was associated with 45% greater odds of depression and 66% greater odds of anxiety. When the scientists broke down these results by gender, they found that the association was stronger in women (who are also more vulnerable to depression and anxiety). For depression, the increased risk was 49% in women and 27% in men. For anxiety, the increased risk was 80% in women and 47% in men.

So, we've seen that inflammation, and in particular pro-inflammatory diets, appear to be linked to greater depressive symptoms, while dietary fiber and anti-inflammatory diets reduce the risk of depression. To untangle the relationship between these variables, researchers affiliated with Gannon Medical University in China analyzed data from a total of 8430 National Health and Nutrition Examination Survey (NHANES) samples. The researchers extracted 22 nutrients (including fiber) from the dietary recall interviews and calculated the inflammatory scores for these samples, wherein higher scores indicated greater diet-associated inflammation and lower scores indicated lower levels. They also analyzed patient health questionnaires to determine the frequency of depressive symptoms in the cohort. The researchers determined higher dietary inflammatory scores, as well as the inflammatory biomarker CRP, were both associated with depression. In subjects with lower dietary fiber intake, a higher dietary inflammatory index was linked to 2.7 times higher odds of depressive symptoms. However, the dietary inflammatory score was not linked to depressive symptoms in participants consuming a high-fiber diet. After the researchers crunched the numbers, they determined that inflammation partially mediated the effect of dietary fiber on depressive symptoms. The scientists suggest that dietary fiber may affect inflammation by reducing intestinal permeability, as well as altering the production and reuptake of neurotransmitters. For some more insight in this mind-bogglingly complex process, refer to the figure below.

This week, our friends Josh and Tommy tackled a listener-submitted question, one that we've occasionally addressed in this newsletter as well: What supplements are best for brain health?

One example Tommy touches on here is B vitamins, which are known to lower plasma concentrations of homocysteine. Elevated homocysteine is a well-established risk factor for cognitive impairment and dementia. In a randomized, double-blind controlled trial, participants were treated with either folic acid/vitamin B12/vitamin B6 or a placebo. After two years, the mean rate of brain atrophy was significantly slower in the active treatment group, and this appeared to be mediated by how high their homocysteine was at the beginning of the trial. In participants who started out with high homocysteine, the rate of atrophy was attenuated by 53% if they were taking the B vitamins. Pretty impressive result for a very cheap and readily accessible supplement regimen.

By the way, if you'd like to submit a question for the guys, you can head on over to brainjo.academy/question.

(And if you've been paying attention to the footage from the aftermath of the Turkey-Syria earthquake earlier this month, you can probably see why someone who survived such a disaster might react this way. Deaths due to earthquakes are generally not directly caused by ground vibrations. It's actually caused by falling objects, glass, and collapsing walls from the structures surrounding victims. So, in theory, a tent would seem like a safer place to be if one were to strike again.)

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