This article is based on my conversation with Chris Miller MD, author of the Chris Miller, MD Substack, this is day 5 of the first-ever Brain Health Substack Summit hosted by The Habit Healers.

Click here to join, our final conversation tomorrow with Chef Martin Oswald and we will dive into all the delicious recipes he created for each of our Brain Health Substack Summit panelists.

If you missed Day 1 of our Brain Health Summit with Julie Fratantoni, PhD you can watch it here. We discussed how to exercise your brain day to day.

If you missed Day 2 of our Brain Health Summit with Annie Fenn, MD you can watch it here. We discussed foods to decrease dementia risks.

If you missed Day 3 of our Brain Health Summit with Jud Brewer MD PhD you can watch it here. We discussed how to unwind your anxiety.

If you missed Day 4 of our Brain Health Summit with Dr. Dominic Ng, you can watch it here. We discussed microplastics in your brain.

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There is a particular kind of tired that most people over 45 know well. You wake up and the day already feels heavy. You have a list of things to do and the motivation to do exactly none of them. You sit down to read something and the words just slide off the surface of your brain. You used to be sharp. You used to be a person who did things. And now you’re wondering what happened.

Most people chalk it up to aging. Or stress. Or some personal failing they can’t quite name. And what Chris Miller MD would tell you is that all of those people are wrong.

Chris is an emergency physician who spent over a decade working in the ER before her own body started fighting against her. It began with a swollen finger. Then more fingers. Then came the diagnosis: lupus, an autoimmune disease in which the immune system, the very thing designed to protect you, turns on your own tissue with alarming aggression. Her inflammation markers were sky-high. Her whole body was under siege. And eventually, the ER became too physically demanding to keep working in.

But what struck Chris most wasn’t the joint pain. It was what happened to her brain.

“I felt foggy,” she said during our discussion. “I was not motivated. I thought something was wrong with me, like I was lazy. But really, it was inflammation. My neurotransmitters were off.”

That distinction matters enormously. Because if you’re lying on the couch at 3 p.m. unable to will yourself into action, and the actual problem is an immune response happening inside your skull, then no amount of self-criticism will fix it. You’re yelling at yourself for something your brain chemistry is doing without your permission.

What’s Going on Exactly?

To understand what’s going on, you need to understand what inflammation actually is. And the simplest way to think about it is as a security system.

Your immune system runs 24 hours a day, patrolling your body for threats. A virus enters through your nose, the immune system grabs it. You cut your finger, the immune system repairs the wound. You breathe in polluted air, the immune system works to clear it out. Roughly 70 percent of your immune system sits in your gut, which makes sense when you consider that one of the biggest entry points for foreign substances is through the food you eat.

All of that is normal and necessary. The problem starts when the security system gets overstimulated.

If you’re eating highly processed food at every meal, breathing contaminated air, sleeping poorly, and running on stress hormones all day, your immune system never gets a break. It keeps releasing inflammatory signaling molecules called cytokines (think of them as alarm bells), which tell the rest of the body to ramp up the immune response even further. Normally, inflammation spikes when there’s a threat and then settles back down. But when the threats never stop coming, the inflammation goes up and stays up. That’s chronic inflammation. And that’s when things start breaking.

Fortunately, your brain has a built-in defense against all this: a structure called the blood-brain barrier. Picture the lining of a normal blood vessel as a single layer of cells. The blood-brain barrier is about 50 times tighter than that, reinforced with specialized support cells called astrocytes. It’s like a fortified wall around your brain, keeping out the inflammatory chaos happening in the rest of your body.

But here’s what Dr. Miller emphasized: when inflammation is chronically elevated, that wall starts to crack. The cytokines get through. And once they’re inside, they activate the brain’s own immune cells, called microglia, which then start releasing their own inflammatory signals. Now you have inflammation inside the fortress.

What Brain Inflammation Actually Feels Like

The symptoms are maddeningly vague, which is part of what makes this so tricky to spot. Chris described the most common ones from both her clinical practice and her own experience.

Fatigue is at the top of the list. Not the kind of tired you feel after a bad night’s sleep, but a bone-deep exhaustion that doesn’t lift. More than 80 percent of people with autoimmune conditions describe fatigue as their number one symptom, and Dr. Miller points directly to brain inflammation as the reason.

Then there’s the motivation problem. When microglia are activated and releasing cytokines inside the brain, they suppress dopamine, the chemical that drives you to start and complete tasks. Less dopamine means less motivation. They also reduce serotonin, the chemical involved in mood regulation. So now you’re tired, unmotivated, and a little depressed. The problem is biological, not personal.

And then there’s brain fog. Chris struggled to even describe it, which she acknowledged was sort of the point. “It feels like things are distant,” she said. “Like you want to calculate something and you almost can’t get there. Even though you know what you want to do, you just can’t.” I’ve dealt with Hashimoto’s thyroiditis (an autoimmune condition affecting the thyroid gland) for nearly 30 years, and I know exactly what she means. It feels like wading through molasses. You can see the thought arriving. You watch it come toward you. And then it either takes forever to land or it drifts right past.

Headaches can also be a sign. So can anxiety. The overall picture is of a brain that isn’t broken in any dramatic way but is running on degraded hardware.

The Surprising List of Things That Set Your Brain on Fire

Some of the causes of neuroinflammation (the medical term for inflammation specifically in the brain) are predictable. Autoimmune diseases. Head injuries. COVID and other serious infections. When you have a bad flu and feel that total withdrawal from the world, the foggy detachment, that’s your brain responding to the inflammatory cascade in your body.

But some causes are less obvious.

Blood sugar spikes, for instance. You don’t need to be diabetic for this to matter. Even if your fasting blood sugar and your A1C (a measure of average blood sugar over three months) look normal, the spikes that happen after meals can still damage the blood-brain barrier. Every time your blood sugar shoots up after eating, your insulin surges to bring it back down, and that surge creates a small hit of inflammation that chips away at the barrier over time.

Low estrogen is another one. Estrogen is strongly anti-inflammatory, which helps explain why so many women experience sudden cognitive changes during perimenopause and menopause. I lived this firsthand. I had such an abrupt cliff from perimenopause to menopause that I went from fine one week to not fine the next. That rapid drop in estrogen removes a major source of inflammation protection for the brain.

Chronically elevated cortisol, the stress hormone, directly activates the microglia. So living in a constant state of stress doesn’t just feel bad. It is physically inflaming your brain.

Air pollution is a culprit too. Chris described reading studies linking air pollution to dementia through glial cell activation. She even mentioned her frustration with neighbors whose wood-burning fireplace pollutes the air in her neighborhood. It’s one of those things that feels insignificant, a neighbor’s fireplace, but breathing contaminated air over months and years adds up.

And poor sleep. Sleep is arguably the most important factor in this whole equation, which brings us to one of the most remarkable discoveries in neuroscience in the last two decades.

The Brain’s Nighttime Cleaning Crew

Until about 2012, scientists didn’t know the brain had its own waste-clearance system. The rest of your body has the lymphatic system, a network of vessels that filters out waste and toxins. But the brain was thought to operate differently. Then researchers discovered the glymphatic system (the “g” comes from glial cells, which play a central role in the process), and it changed the way we think about sleep.

The glymphatic system surrounds the brain. During deep sleep, it activates, flowing through and around brain cells to clear out metabolic waste, damaged proteins, inflammatory debris, all the byproducts of a brain that’s been thinking and firing all day. Every time your neurons fire, they produce a form of cellular exhaust called reactive oxidative stress. The glymphatic system is what takes out that trash.

I like to use an analogy when I explain this to patients. During the day, the office workers are busy at their desks, tossing things into the trash can as they go. At night, the cleaning crew comes in and empties the bins, mops the floors, hauls everything away. If the cleaning crew never shows up, or only gets 20 minutes to do a full night’s work, the garbage piles up.

That’s exactly what happens when you don’t get enough deep sleep. The microglia that were activated during a stressful day, or by blood sugar spikes, or by any of the other triggers, are supposed to calm down during deep sleep and switch from their inflammatory mode back into their cleaning and repair mode. Without that reset, they stay activated. The inflammation compounds. And night after night, the damage accumulates.

The good news, Dr. Miller was careful to point out, is that a bad night here and there won’t ruin you. The brain is resilient. But chronic sleep deprivation is a different story, and improving your deep sleep is one of the most powerful interventions available for reducing neuroinflammation.

What You Can Actually Do About It

Dr. Miller outlined a set of strategies that collectively form a strong defense against brain inflammation. None of them are exotic. All of them are backed by research. And the cumulative effect of stacking them together is significant.

Lower your overall inflammation first. This is the foundation. If your body is chronically inflamed, those cytokines will keep battering the blood-brain barrier. Get tested: a high-sensitivity C-reactive protein (hs-CRP) blood test measures a protein your liver produces in response to inflammation, and an erythrocyte sedimentation rate (ESR) test measures how quickly red blood cells settle in a tube, which speeds up when inflammation is present. These are simple blood tests you can ask your doctor to order. They won’t catch every type of inflammation (some inflammation is localized and won’t show up on these tests), but they’re a solid starting point.

Prioritize deep sleep. This is when the glymphatic system does its work and the microglia switch back to their calm, repair-focused state. If you’re not sleeping well, start asking why. The solution will be different for everyone, but the importance of getting there is universal.

Manage stress actively. This means concrete daily practices. Deep breathing, time in nature, walking, yoga, laughter. All of these lower cortisol. Chris also mentioned the vagus nerve, a major nerve that runs from the brainstem to the gut and plays a key role in calming the body’s stress response. Stimulating it through practices like gargling, singing, or cold water exposure can help lower inflammation in the brain. I’ve recently started walking three times a day instead of just once, and the effect on my cognitive load has been noticeable.

Eat to fight inflammation. Omega-3 fatty acids are critical. Your brain’s cell membranes need them, and low omega-3 levels leave the brain vulnerable to inflammation. Fatty fish like salmon, mackerel, sardines, and herring are the most concentrated food sources. For people who don’t eat fish, flaxseeds and chia seeds provide a plant-based form (called ALA) that the body partially converts to the usable forms. Algae-based omega-3 supplements are another option. Beyond omega-3s, fiber-rich foods feed your gut microbiome, which produces short-chain fatty acids that travel to the brain and actively fight inflammation. Sulforaphane, a compound found in broccoli and broccoli sprouts, is particularly potent for brain health. Turmeric and ginger directly reduce inflammation by turning off a gene pathway called NF-kappa B (a master switch that controls dozens of inflammatory genes). Blueberries, tea, dark chocolate, and polyphenol-rich olive oil all contribute as well.

Build muscle. This one surprises people, but the research is clear. When you build muscle through resistance training, the muscle tissue releases signaling molecules called myokines, which are essentially anti-inflammatory cytokines. Muscle also triggers the release of brain-derived neurotrophic factor, or BDNF, a protein that promotes the growth of new nerve cells and strengthens the connections between existing ones. On top of that, more muscle mass improves your body’s ability to handle blood sugar, reducing those insulin spikes that damage the blood-brain barrier. Chris called it one of the biggest levers we have for slowing aging and protecting the brain.

Do cardio too. Aerobic exercise protects the endothelium (the lining of blood vessels), including the blood vessels that form the blood-brain barrier. Research has shown that people with good cardiovascular fitness maintain larger brain volume as they age.

Watch your blood pressure. High blood pressure is one of the most damaging forces acting on the blood-brain barrier, and it’s also one of the most commonly undertreated. Dr. Miller recommended keeping blood pressure below 120/80, and noted that some people have a genetic predisposition to stiffer blood vessels, which makes them more prone to hypertension. And I want to stress this: rising blood pressure with age isn’t inevitable. In populations studied in blue zones (regions of the world where people routinely live past 100), people maintain the blood pressure of their youth well into old age.

The Labs Worth Asking About

Beyond hs-CRP and ESR, Chris and I highlighted several other tests worth discussing with your doctor.

Vitamin D should be checked and optimized. Most people don’t get enough from sunlight alone, and supplementation is often necessary.

Homocysteine is an amino acid your body produces as a byproduct of normal metabolism. It gets broken down by B vitamins (specifically B6, B9, and B12), but some people have genetic variations that make them poor methylators, meaning they can’t process homocysteine efficiently. High homocysteine damages blood vessel walls, including the ones feeding your brain, and is associated with increased risk of heart attack, stroke, and cognitive decline. If your level is above 10, it’s worth investigating. I’ve been checking homocysteine in my patients for a long time, and I recommend keeping B12 between 500 and 1,000 in lab results. Even when B12 looks adequate, homocysteine can still be elevated, which means something further up the metabolic chain needs attention.

Blood sugar markers including fasting blood sugar, hemoglobin A1C, and fasting insulin paint a fuller picture of metabolic health and its effect on the brain.

Thyroid function should be assessed, especially given the connection between thyroid inflammation and brain fog.

Nutrient levels for things like zinc and iodine are worth checking, particularly if you’ve changed your diet recently or have gut issues that could impair absorption.

The One-Habit Starting Point

It would be easy to read all of this and feel overwhelmed. Chris and I both anticipated that reaction. The advice isn’t to overhaul your entire life by next Tuesday.

“Find the one easiest lever that you can move,” I told the summit audience, “and make it the tiniest piece.” For one person, that might be a five-minute walk in the morning. For another, it might be turning off the TV 30 minutes earlier and going to bed. For another, it might be adding ground flaxseed to a morning smoothie.

The brain is remarkably sensitive to changes in both directions. When you’re not taking care of your body, it suffers. But when you start making even small improvements, it responds. Chris put it simply: “Every small change does add up and does help. And we can protect our brains. There’s a lot we can do.”

One of our Habit Healers readers had blood sugar in the prediabetic range. After four months of incorporating small daily habits she’d learned from the newsletter, her fasting blood sugar dropped to 91 and she’d lost weight. No dramatic overhaul. Just consistent small choices, compounding.

That’s the real takeaway from this conversation. The fog, the fatigue, the creeping sense that your brain isn’t what it used to be: these aren’t inevitable. They have a biological explanation. And the biology can be changed.

Key Takeaways from Day 5

Brain inflammation is real and underdiagnosed. Chronic fatigue, lack of motivation, brain fog, low mood, and anxiety can all stem from an overactive immune response inside the brain, not from personal weakness.

The blood-brain barrier protects you, but it has limits. When chronic inflammation, high blood sugar, elevated cortisol, or high blood pressure persist over time, this barrier breaks down and allows inflammatory signals into the brain.

The glymphatic system is your brain’s cleaning crew. Discovered only in the last 15 years, it clears waste and calms activated immune cells during deep sleep. Without adequate deep sleep, the trash piles up.

Muscle is medicine for the brain. Resistance training releases anti-inflammatory myokines and BDNF, which promote new nerve growth and strengthen brain connections.

Food is a direct lever. Omega-3 fats, fiber, sulforaphane (from broccoli and broccoli sprouts), turmeric, ginger, blueberries, and polyphenol-rich foods actively reduce brain inflammation.

Blood pressure is a brain health issue. Keeping it below 120/80 protects the blood-brain barrier. Rising blood pressure with age is not inevitable.

Key labs to discuss with your doctor: hs-CRP, ESR, vitamin D, homocysteine, B12, fasting blood sugar, hemoglobin A1C, fasting insulin, thyroid panel, and nutrient levels (zinc, iodine).

Start with one small change. The brain responds to improvements quickly. Pick the easiest thing you can do, make it tiny, and build from there.

Chris Miller MD writes on Substack, where she shares her journey leaving emergency medicine and discovering integrative medicine, after experiencing significant autoimmune and other health concerns.

Inspired by Dr. Millers’s brain health food recommendations, Chef Martin Oswald created the Anti-inflammatory Super Bowl packing incredible anti-inflammatory ingredients into a single dish for the Brain Health Summit.

This interview is part of The Habit Healers Brain Health Substack Summit. For more expert conversations on protecting and improving your brain health, subscribe to The Habit Healers.

PS. Want to train your brain with games backed by science? Check out my free weekly Substack, Train the Brain Games, where I share cognitive challenges focused on processing speed and other skills the research actually supports.

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