Neuroinflammation: Causes, Signs, and How to Reduce It

Neuroinflammation is inflammation inside the brain and spinal cord. In conditions like Alzheimer’s disease or multiple sclerosis, it is a serious part of the picture. A short-lived, controlled version of neuroinflammation is also one of the ways a healthy brain protects and repairs itself.

What we see far more often in the clinic is lower-grade neuroinflammation that shows up as fatigue, low mood, anxiety, headaches, or trouble concentrating. It usually travels with inflammation elsewhere in the body, and the gut is frequently a major contributor. That’s useful to know, because the gut is one of the easiest places to start making changes.

In this article, I’ll explain what neuroinflammation is, what triggers it, and how it’s detected. Then I’ll walk through the stepwise approach we use to calm it, starting with the interventions most likely to help and escalating only when there’s a reason to.

What Is Neuroinflammation?

Neuroinflammation is an immune response within the central nervous system (the brain and spinal cord). It’s driven mainly by microglia, the brain’s resident immune cells, along with support cells called astrocytes. When these cells sense infection, injury, or other threats, they release signaling proteins called cytokines that coordinate defense and repair 1.

In the short term, this response is helpful. It fights infection, clears damaged tissue, and supports healing. It also produces the familiar “sickness behaviors” of fever, low appetite, reduced activity, and wanting to withdraw, which push the body to rest while the immune system works 1.

Helpful vs. Harmful Neuroinflammation

When activation doesn’t switch off, microglia keep releasing pro-inflammatory cytokines. These activate astrocytes, which amplify the response further 2. Over time, that cycle can harm neurons and weaken the blood-brain barrier, the protective filter between the bloodstream and brain tissue.

Chronic neuroinflammation is a shared feature of many brain conditions, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke, and traumatic brain injury. The relationship runs both ways: disease processes trigger inflammation, and inflammation can accelerate those processes 2. For practical purposes, that means lowering excess inflammation is a reasonable goal for anyone concerned about long-term brain health.

Neuroinflammation Symptoms: Common Signs to Know

No single symptom confirms neuroinflammation. The signs overlap with many other conditions, so they’re best viewed as a pattern, especially when they show up alongside gut symptoms or other signs of inflammation like joint pain.

Common symptoms linked with neuroinflammation include:

• Persistent fatigue that doesn’t improve much with rest
• Low mood or depression
• Anxiety or feeling constantly on edge
• Trouble concentrating, slower thinking, or memory lapses (sometimes described as brain fog)
• Headaches or migraines 3
• Disrupted or unrefreshing sleep
• A general sense of feeling unwell, achy, or withdrawn, similar to the early stage of a cold 1

The link with mood is one of the better-studied connections. A meta-analysis of 30 studies found that about 27% of people with depression had low-grade inflammation (measured by C-reactive protein, or CRP, above 3 mg/L), and 58% had at least mildly elevated CRP 4. Experimental research also shows that briefly raising inflammation in healthy volunteers changes how the brain handles attention tasks 5.

Over the long term, neuroinflammation is a consistent finding in mild cognitive impairment and Alzheimer’s disease 7. That doesn’t mean everyday symptoms are heading in that direction. In our experience, most people whose fatigue or low mood is tied to inflammation improve with the foundational steps covered below.

Red-Flag Symptoms That Need Prompt Medical Attention

Some neurological symptoms point to conditions that need a neurologist or emergency care rather than lifestyle changes. Seek care quickly if you notice:

• A sudden, unusually severe headache or migraine
• New weakness, numbness, or loss of coordination
• Vision loss or double vision
• Confusion or a sudden change in thinking or behavior
• A seizure
• Fever with a stiff neck

What Triggers Neuroinflammation?

Neuroinflammation usually reflects what’s happening in the rest of the body. Several factors can push the brain’s immune cells into a more reactive state, and most people with chronic symptoms have more than one in play.

Common triggers of neuroinflammation include:

• Gut imbalances: Dysbiosis 8, small intestinal bacterial overgrowth (SIBO) 9, and increased intestinal permeability (leaky gut) 10 can raise inflammation throughout the body.
• Infections: Viral and bacterial infections activate microglia directly or through the immune signals they produce 2.
• Poor or disrupted sleep: Sleep disturbance is consistently associated with higher inflammatory markers 11.
• A highly processed diet: Calorie-dense meals heavy in refined carbohydrates are associated with higher CRP and interleukin-6 (IL-6), markers of inflammation 12.
• Excess body fat: Obesity is linked with both systemic inflammation and neuroinflammation 13.
• Chronic stress and inactivity: Both shift the body toward a more inflammatory baseline, and both make the other triggers harder to manage 14 15.
• Head injury and aging: Brain injury and the gradual rise in baseline inflammation that comes with age both prime microglia to overreact 2.

Long COVID and Neuroinflammation

Neuroinflammation has been proposed as one explanation for lingering long COVID symptoms like fatigue and trouble concentrating. A recent controlled study found no evidence of this. Researchers compared 48 people with long COVID to 48 matched controls who recovered without lasting symptoms, about 69 weeks after infection. Blood markers of neuronal damage (NfL), glial activation (GFAP and TREM2), and systemic inflammation showed no significant differences between the groups 16. The researchers suggest that symptoms of long COVID may be caused by systems beyond conventional inflammatory pathways 16.

Blood tests can miss inflammation confined to the brain, and the authors describe their findings as preliminary, meaning more research is needed. Even so, the results suggest that persistent long COVID symptoms are unlikely to reflect ongoing brain injury for most people. That’s reassuring, and it supports focusing on the gut, sleep, and nervous system regulation rather than searching for active brain damage.

How the Gut-Brain Axis Drives Neuroinflammation

The gut and brain are in constant two-way communication. Signals travel through the vagus nerve, through immune messengers, and through compounds produced by gut bacteria 17. This network is often called the gut-brain axis.

When the gut microbiome is out of balance, the intestinal lining can become more permeable (leaky gut). Bacterial fragments such as lipopolysaccharide (LPS) can then cross into the bloodstream and drive systemic inflammation. Those inflammatory signals reach the brain and, over time, they may also weaken the blood-brain barrier, allowing more inflammatory material through 17 18.

This matches what we see clinically. Patients who come to us for bloating, irritable bowel syndrome (IBS), or leaky gut symptoms frequently mention fatigue, anxiety, or poor focus as well, and those symptoms often improve as the gut improves. It’s one reason we start with the gut even when the main complaint isn’t digestive.

How Is Neuroinflammation Detected?

Neuroinflammation is difficult to measure directly. In research settings, it’s detected with specialized PET brain scans that track activated immune cells and with spinal fluid analysis. These tools aren’t used routinely, and even PET imaging has meaningful limitations, including results that vary based on a person’s genetics 19.

The main ways neuroinflammation is assessed include:

• PET imaging: Uses tracers (most often targeting a protein called TSPO) to highlight activated glial cells. It’s mainly a research tool.
• Spinal fluid (CSF) testing: Measures immune cells, proteins, and cytokines in the fluid around the brain. It’s used to diagnose specific conditions like multiple sclerosis, encephalitis, or meningitis.
• MRI: Shows inflammation-related damage in conditions like multiple sclerosis, but it doesn’t detect low-grade neuroinflammation.
• Blood markers: CRP, IL-6, and TNF-α reflect inflammation in the body as a whole. They aren’t brain-specific, but elevated levels are common in people with mood and cognitive symptoms 4.
• Symptom pattern and treatment response: In everyday care, this is often the most practical tool.

Do You Need Testing for Neuroinflammation?

For most people, chasing a confirmed neuroinflammation diagnosis isn’t the right first step. A useful question is whether the result would change what you do next. If the plan is to improve diet, sleep, exercise, and gut health either way, testing adds cost without adding much direction.

Certain types of tests make more sense in a few situations:

• You have any of the red-flag symptoms listed above. These warrant a medical or neurological workup, which may include MRI or spinal fluid testing.
• Gut symptoms persist after the foundational steps. Testing for SIBO or other gut drivers can guide more targeted treatment.
• You want a baseline to track. A high-sensitivity CRP test is inexpensive and can show whether systemic inflammation is trending down over time.

You don’t need to know the exact cause of your symptoms before you start improving them. Watching how you respond to foundational care often tells you more than any single test.

How to Reduce Neuroinflammation Naturally

The most effective way to reduce neuroinflammation is to start with low-risk changes that help the greatest number of people, give them time to work, and add targeted options only if needed. The steps below are listed in the order we generally use them in the clinic.

1. Start With an Anti-Inflammatory Diet

Diet is the first place I’d look. Meals heavy in refined starches, trans fats, and calorie-dense processed foods are associated with higher inflammatory markers 12. Moving away from ultra-processed food is a step in the right direction, no matter what diet you choose.

Good starting templates include:

• Mediterranean diet: Rich in vegetables, fruit, olive oil, nuts, and fish. It has well-documented anti-inflammatory effects and is a strong default for people without major gut symptoms 20.
• Paleo diet: Removes most processed foods, grains, and dairy. It’s a practical framework for people who suspect food sensitivities.
• Low FODMAP diet: One of the diets I use most in the clinic, largely because most people who come to us have significant gut symptoms like bloating, IBS, or SIBO.
• Short-term elemental diet: For more stubborn gut cases, a few days to two weeks on a formula like Elemental Heal gives the gut a reset before reintroducing foods.

Start with the fewest restrictions that work for you. Cut out additional foods only if your symptoms show you need to.

2. Add Probiotics

Probiotics have reasonably strong evidence for lowering systemic inflammation. A meta-analysis of 42 randomized controlled trials found that probiotic supplementation significantly reduced the inflammatory compounds CRP, IL-6, and TNF-α in adults 21.

The evidence for brain-related outcomes is earlier but encouraging:

• A meta-analysis of five small trials in people with mild cognitive impairment or Alzheimer’s disease found that probiotics improved cognitive scores and lowered CRP 22.
• In a 12-week randomized trial of stressed adults, a Lactobacillus plantarum probiotic reduced stress and anxiety, lowered pro-inflammatory cytokines, and improved memory and cognition compared with placebo 23.

Research hasn’t identified a single best strain for neuroinflammation. In the clinic, we’ve had the best results across gut, inflammation, and mood symptoms by combining one probiotic from each of the three main probiotic categories:

1. Lactobacillus and Bifidobacterium blends, such as our Lacto-Bifido Probiotic Blend
2. Saccharomyces boulardii, a beneficial yeast, such as our Saccharomyces Boulardii Probiotic
3. Soil-based Bacillus species, such as our Soil-Based Probiotic

If you’d rather take one product, Triple Therapy Probiotic Powder Sticks combine all three categories. For patients who tried a single probiotic in the past without much change, this broader approach often makes the difference.

3. Prioritize Sleep

Sleep quality matters as much as sleep quantity. A meta-analysis of 72 studies with more than 50,000 participants found that sleep disturbance was associated with higher CRP and IL-6. Regularly sleeping longer than 8 hours was also linked with higher inflammation 11, and sleep disruption triggers neuroinflammation 24. 

Practical ways to improve sleep:

• Keep a consistent bedtime and wake time, including weekends
• Aim for about 7 to 8 hours in a dark, quiet, cool room
• Get morning daylight to anchor your circadian rhythm
• Limit caffeine after midday and alcohol close to bedtime
• If racing thoughts keep you up, try a short mindfulness meditation practice before bed

4. Exercise at a Moderate Intensity

Exercise doesn’t need to be intense to calm inflammation. In a study of 47 adults, a single 20-minute session of moderate treadmill walking reduced the number of immune cells producing TNF, a key inflammatory signal, by about 5% 25.

Moderate exercise ranges from brisk walking to a slow jog. If fatigue is a major symptom, start with shorter sessions and build gradually. Consistency matters more than intensity.

5. Manage Chronic Stress

Chronic stress keeps the nervous system on alert, and in our experience it’s one of the more common reasons people plateau. Daily practices such as meditation, slow breathing, time outdoors, and regular social connection are simple places to start. Many of the same practices that improve sleep also help here.

6. Consider Targeted Supplements

Once the foundations are in place, a few supplements may offer additional support:

• Curcumin: A meta-analysis of 66 randomized trials found that curcumin or turmeric supplementation significantly reduced CRP, IL-6, and TNF-α 26. CurcuSelect uses a well-absorbed form of curcumin called Meriva.
• Luteolin: A plant flavonoid that has been studied for its ability to calm microglia and mast cells 27. I cover the evidence in more detail in my article on luteolin benefits.

Supplements work best layered on top of diet, probiotics, sleep, and exercise, not as a substitute for them.

What the Research Shows About Neuroinflammation

The research is strongest on two points. Chronic inflammation is consistently tied to mood, cognitive, and neurological symptoms, and everyday interventions can meaningfully lower inflammatory markers. Evidence that those changes directly calm inflammation inside the brain is still limited, mostly because neuroinflammation is so hard to measure in living people 19.

Evidence at a Glance

Lowering Inflammation Can Improve Mood

One of the more convincing findings comes from medication research. A meta-analysis of 36 randomized trials with more than 9,000 participants found that anti-inflammatory medications improved depressive symptoms compared with placebo, both on their own and when added to antidepressants 6.

This matters because it suggests inflammation actively contributes to mood symptoms rather than simply showing up alongside them. Those medications carry side effects that limit routine use, though. That’s a large part of why we lean on diet, gut health, sleep, and exercise first: they lower the same inflammatory signals with far less risk.

Where the Evidence Is Still Thin

• Most studies measure blood markers. CRP, IL-6, and TNF-α reflect inflammation in the body as a whole, not inside the brain specifically.
• Many trials are small. Probiotic and supplement studies often use different strains, doses, and populations, which makes them harder to compare.
• Few studies use brain imaging. Very little research has tested whether lifestyle changes reduce neuroinflammation as measured on PET scans.

These gaps don’t make the foundational interventions less worthwhile. They’re low-risk, they improve overall health, and they target the systemic inflammation that feeds neuroinflammation in the first place.

Clinical Perspective: How We Approach Neuroinflammation

Most patients don’t come to us asking about neuroinflammation. They come in for bloating, IBS, or SIBO, and mention fatigue, anxiety, low mood, or poor focus as a secondary complaint. As we treat the gut, those secondary symptoms often improve along with it. That pattern is a big reason I see the gut as one of the most practical entry points for calming neuroinflammation.

What We Do First

• Start with diet and probiotics before specialized testing. For most patients, the first step is an anti-inflammatory diet matched to their gut symptoms plus a triple therapy probiotic.
• Track how symptoms respond. We ask patients to note energy, mood, focus, and sleep week to week. That response tells us more than a single lab value.
• Keep the diet as broad as possible. We restrict only what symptoms show needs restricting, then reintroduce foods once things settle.

Common Mistakes We See

• Ordering tests that won’t change the plan. Cytokine panels and specialty brain inflammation tests rarely shift what we’d recommend for someone without red-flag symptoms.
• Stacking too many supplements at once. Starting five anti-inflammatory products together makes it impossible to tell what’s helping.
• Staying on a restrictive diet too long. Long-term restriction can narrow food variety and add stress around eating, which works against recovery.
• Switching protocols too quickly. Changing course every week or two doesn’t give treatment time to work.
• Skipping the sleep and stress steps because they seem basic. In our experience, these are often what separates people who plateau from people who keep improving.

My overall view is that neuroinflammation is real and worth taking seriously, but for most people it doesn’t call for a complicated diagnostic workup. The interventions most likely to help are the same ones that improve gut and overall health, and they’re worth trying first.

What to Do if Neuroinflammation Symptoms Don’t Improve

Give the foundational steps a fair trial before changing course. In the clinic, we generally look for meaningful progress over about 4 to 8 weeks. Constantly switching protocols makes it hard to tell what’s helping.

If you’ve been consistent and symptoms haven’t budged, these are reasonable next steps:

• Look for ongoing gut drivers. Testing for SIBO or other gut imbalances can uncover a source of inflammation that diet and probiotics alone haven’t resolved. A low FODMAP diet for SIBO, herbal antimicrobials such as Biota-Clear 1a, and a plan to heal leaky gut may be appropriate depending on what testing shows.
• Consider nervous system retraining. For patients stuck in a cycle of anxiety about their symptoms, limbic system retraining can help calm an overactive stress response. A small pilot randomized trial found that a mindfulness program combined with amygdala and insula retraining reduced pain, anxiety, and depression in women with fibromyalgia 28. I explain how this works in my article on neuroplasticity healing.
• Get individualized care. If you’ve gone through several rounds of treatment without the progress you expected, that’s the type of case our virtual clinic is designed to investigate.
• See a neurologist for red-flag symptoms. New neurological symptoms, or symptoms that worsen quickly, need a medical evaluation regardless of what else you’re trying.

For most people, neuroinflammation responds to the same fundamentals that improve overall health. Starting with the gut, sleep, and movement gives you a clear plan without needing to identify every possible cause first.

The Bottom Line on Neuroinflammation

Neuroinflammation is the brain’s immune response. It becomes a problem when it stays switched on, and chronic neuroinflammation is linked with fatigue, low mood, anxiety, headaches, and cognitive symptoms. It usually reflects inflammation elsewhere in the body, with the gut, sleep, diet, and stress among the most common contributors.

You don’t need a confirmed diagnosis or specialized testing to start improving it. An anti-inflammatory diet, a multi-category probiotic, consistent sleep, and moderate exercise are low-risk and help most people. Give those steps several weeks to work, then look at gut testing, nervous system retraining, or individualized care if you’re still struggling. New or rapidly worsening neurological symptoms should always be evaluated by a doctor.

If you’d like help putting a plan together, our virtual clinic team works with patients on exactly these kinds of cases.

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