Calming Inflammation, Soothing Depression
By Erica Zelfand

Smart choices for a happy brain

In last week’s post I explored the ways in which inflammation can cause depression. The science shows that we cannot blame genetics alone for depression, and that’s a good thing: it means there is a lot we can do to heal our brains. Here are some evidence-based strategies to quell inflammation and support mental health:


Quit smoking

It is no secret that smoking cigarettes is a major driver of inflammation. Not only does smoking cause inflammation in the obvious locations of the lungs and airways, but also in the mouth, the digestive system, and – you guessed it – in ways that affect the brain.[1] Although less particulate matter is inhaled into the lungs with vaping than with smoking cigarettes, vape smoking is also a culprit of inflammatory damage.[2] As a significant source of toxic chemical exposure, furthermore, smoking is the number one cause of preventable illness in humans.

Smoking is the number one cause of preventable illness in humans.

While there is no shortage of studies confirming the connection between cigarette smoking and depression,[3],[4],[5],[6] a recent (2021) case-control study revealed a significant causal relationship between smoking-related inflammation and depression. The study compared 26,894 people who had been diagnosed with major depressive disorder at some point in their lives to 59,001 control subjects without depression, and found that genetics actually played a negligible role in inflammation-mediated depression. Rather, the researchers explain that the “increased inflammation in depression is due to… eating and smoking habits.”[7]

In another study examining the effects of smoking on the mental health of 462,690 people, there was strong evidence to suggest that smoking is a risk factor not only for depression, but also for schizophrenia.[8]

In short: smoking can harm mental health, in significant ways.


Maintain a healthy weight

Like many of the studies summarized in our last article, a 2019 study found a significant correlation between high levels of hs-CRP (an inflammatory marker measured in the blood) and treatment-resistant depression (TRD). Upon deeper consideration of the data, the authors found that high body mass index (BMI) (aka: being overweight or obese) was strongly correlated with hs-CRP elevations.[9] Other studies have likewise connected elevated C-reactive protein (CRP) levels and obesity, suggesting that overweight and obese individuals are living in a state of low-grade, chronic, systemic inflammation.[10]

The habits that cause weight gain (like eating sugary foods) are the same behaviors that drive inflammation, but fat also drives inflammation in and of itself: adipose (fat) cells produce inflammatory chemicals. In other words, the more fat you have on your body, the more inflammation those fat cells will pump into your system.[11]

Overweight and obese individuals live in a state of low-grade, chronic, systemic inflammation.

This is even the case among overweight and obese young adults ages 17 to 38,[12] which is significant, as the rate of depression is highest among those 18 to 29 years of age,[13] and the rate of major depression (MDD) is most prevalent among those 18 to 25.[14]

Fortunately, a systemic literature review of 76 studies (including data from a total of 6,742 patients) reports that most studies found that weight loss caused a significant drop in inflammatory markers. This was true whether the weight loss was due to eating a low-calorie diet, exercising, or undergoing weight loss surgery.[15]

Other reviews have found that weight loss (regardless of the method) improves inflammation profiles by reducing harmful markers like CRP, TNF-alpha, IL-6 and leptin, and by enhancing the anti-inflammatory chemicals interleukin-10 and adiponectin.[16],[17]

Many of the inflammation-reducing strategies explained in this article can also help with sustainable weight loss.


Break up with booze

Numerous studies have confirmed that alcohol consumption and depression go hand-in-hand, [18],[19],[20],[21],[22] and the relationship is bi-directional: alcohol consumption drives depression, and depression drives drinking.[23] While this is a documented trend in all adult age groups, alcohol consumption causes substantially greater harm in the elderly than in younger adult groups.[24],[25]

Alcohol consumption causes leaky gut.

There are many mechanisms by which alcohol hurts the central nervous system and fuels depression, anxiety, and other mood troubles – and most of those mechanisms have to do with inflammation. One way this happens is at the level of the gut, where chronic alcohol consumption increases intestinal permeability (ie: causes “leaky gut”) and changes the composition of the gut microbiome (the mix of good and bad “bugs” in the gut), thus allowing harmful gut bacteria to pass through the weakened gut lining and into the circulation.[26] The immune system recognizes that these gut-derived bacteria are now in places where they don’t belong within the body, and responds in turn by producing pro-inflammatory cytokines (chemicals). These cytokines can then reach the central nervous system and trigger neuroinflammation, thus driving mood imbalances, cognitive struggles (such as those seen in Alzheimer’s disease[27]), and addictive behaviors.[28],[29],[30]


Take a break from bread

Alcohol isn’t the only food known to degrade the gut lining: gluten, the protein found in rye, barley, wheat, and spelt, is also notorious for causing leaky gut and in turn driving neuroinflammation in many individuals.[31],[32]

Although most people think of digestive trouble when they hear the word “gluten sensitivity,” many people with gluten sensitivity experience little to no intestinal issues from the protein. Symptoms like brain fog, fatigue, joint pain, skin problems, and depression are common in those with both celiac disease and non-celiac gluten sensitivity (NCGS).[33],[34]

In a meta-analysis pooling results from 1,139 patients, a gluten-free diet (GFD) was found to significantly improve the symptoms of depression. Interestingly, even those who did not have celiac disease tended to have a worsening of their depressive symptoms after they unknowingly ate food containing gluten.[35]

There’s another reason to take a break from wheat: gluten aside, high carbohydrate diets may exacerbate depression.


Kick the sugar and refined carbohydrates

While it’s common for folks with depression to gravitate towards eating toast, cereal, and other processed foods high in sugar and carbohydrates, this practice may be doing more harm than good.[36]

A number of studies have illuminated the connection between diabetes and depression.[37],[38],[39],[40] In fact, depression is more than three times more prevalent in people with type 1 diabetes than in the general population, and the rate of depression is almost double in those with type 2 diabetes.[41],[42]

The rate of depression is almost double in those with type 2 diabetes.

Although some studies on the topic have yielded contradictory results,[43],[44] a highly significant correlation has been identified between sugar consumption and the annual rate of depression in several countries.[45]

What virtually every study on sugar agrees upon, however, is that the sweet stuff drives oxidative stress and inflammation.[46],[47],[48]


Eat protein

A 2019 study examining markers of oxidative stress and inflammation in 2,061 participants of the Framingham Heart Study Offspring cohort found an inverse relationship between protein intake and high levels of oxidation and inflammation.[49] In other words, the overall levels of inflammation and oxidative stress were the lowest in the people who ate the most protein. Plant-based protein was protective, but animal protein (e.g.: meat) was even more significant.

The overall levels of inflammation and oxidative stress were the lowest in the people who ate the most protein.

In other words: having a pea protein shake, a burger made from grass-fed beef, or some poached chicken breast is likely to support brain health and mood.



Although exercise produces a brief inflammatory response in the short term, both cross-sectional and longitudinal studies have shown that exercise has long-term anti-inflammatory effects.[50] This inflammation-soothing response may in fact be part of the magic that is exercise.[51]

Specifically, a protein known as interleukin-6 (IL-6) is produced by the muscle fibers during exercise. IL-6 in turn stimulates the circulation of anti-inflammatory cytokines and suppresses the production of the pro-inflammatory cytokine TNF-alpha. IL-6 also helps bust up fat cells, in turn helping burn fat and lose weight in a healthy way.[52]

Moderate intensity exercise is likely the best bet for sustainably battling depression and quelling inflammation.

The type of exercise matters, however – or rather the intensity of the exercise. In a study on the subject, 61 university students were assigned to a six-week regimen of either high-intensity interval training (HIIT), moderate continuous training, or no exercise at all. While the students who didn’t exercise had a worsening of their depression, those who did continuous training not only enjoyed better mood, but also lower blood levels of pro inflammatory cytokines (TNF-α, IL-6, IL-1β, and CRP). Although those who did HIIT had a drop in their depressive symptoms, they reported higher levels of perceived stress, and had higher inflammatory cytokine levels than those who did moderate continuous training. These findings suggest that moderate intensity exercise is likely the best bet for sustainably battling depression and quelling inflammation.[53]

“Get up offa that thing, and dance ‘til you feel better.”

Exercise not only combats depression and anxiety, but also improves physical wellbeing, body image, stress coping strategies, quality of life, and cognitive functioning – all of which in turn reinforce mental health.[54],[55] Physical inactivity, on the other hand, is associated with the development of mental health disorders.[56]

So, in short, James Brown was truly onto something when he said, “Get up offa that thing, and dance ‘til you feel better.”



Mindfulness practice has been shown to reduce stress hormone levels and fight inflammation, thereby dampening two major players in anxiety and depression.[57],[58] In addition to helping with mood imbalances,[59],[60] meditation can also trigger the release of endorphins, the body’s homemade natural pain relievers.[61]

Meditation doesn’t need to be complicated or difficult. It can simply entail sitting in a chair or on the floor and breathing calmly with the eyes closed or open (with a soft gaze) for ten minutes a day.



Many inflammatory markers and hormones are influenced by sleep – as well as the lack thereof. Even short-term sleep deprivation can affect markers of inflammation like CRP, IL-1β, IL-6, and IL-17 – with the increases in CRP and IL-17 lasting as long as two days after just one night of reduced sleep.[62],[63],[64]

Sleep deprivation is associated with poor performance on cognitive tasks and decreased motor skills,[65],[66] depression, feelings of burnout, increased vulnerability to infection,[67] weight gain,[68] and decreased ability to balance blood sugar levels.[69]

Most adults need seven to nine hours of uninterrupted sleep in a dark room each night for optimal wellbeing. If you have trouble falling or staying asleep, there are thankfully natural allies to help with rest. Supplements like melatonin, magnesium, and honokiol may come in handy, along with putting away smartphones, computers, and other glowing screens shortly after sunset.


You can help your brain

In closing, depression may have less to do with genetics than it does with inflammation. That’s good news: it means that through some mindful choices, we can give both our physical and mental health a major upgrade. Lay down the cigarettes and booze, eat healthy, move your body, and meditate – this might just be the recipe for a healthy mind.



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[This article by Dr. Erica Zelfand was first published at Allergy Research Group and is reposted here with permission.]