Inflammation and Your Brain: When a Natural Defence Becomes a Problem

Inflammation and Your Brain: When a Natural Defence Becomes a Problem

Chronic inflammation is increasingly recognised as an important factor in brain ageing, cognitive decline and dementia risk. Unlike the short-lived inflammation that helps us recover from injury or infection, chronic low-grade inflammation can persist quietly for years, potentially affecting how our brains function as we age.

Twist an ankle and within minutes it becomes hot, red, swollen and sore. That is inflammation doing its job: protecting the body and helping it heal. But what happens when this natural defence never fully switches off?

Researchers call this persistent, age-related inflammation inflammaging, and it may help explain how diet, sleep and lifestyle influence long-term brain health.

What Is Chronic Inflammation?

Inflammation is the immune system’s response to anything it reads as a threat: an injury, an infection, a damaged cell, an irritant. Immune cells release signalling molecules called cytokines, with names such as interleukin-6 (IL-6) and tumour necrosis factor (TNF), which call in reinforcements and switch on repair. The liver responds by making C-reactive protein (CRP), which is why CRP is one of the most widely used blood markers of inflammation.

Acute inflammation is designed to be short-lived. It flares, does its job and then actively resolves. Chronic, low-grade inflammation is different. There may be no redness, pain or swelling at all, just a modest but persistent rise in inflammatory signals in the blood. Our founder, Patrick Holford, describes this as a kind of internal global warming: not a single fire, but the whole system running slightly too hot for too long.

What Is Inflammaging?

The term inflammaging was coined in 2000 by the Italian immunologist Claudio Franceschi and colleagues to describe the gradual increase in this background inflammation that tends to accompany ageing (1). A major review in Nature Medicine later described systemic chronic inflammation as a common thread running through many of the leading non-communicable diseases, including heart disease, type 2 diabetes and neurodegenerative conditions, and pointed to largely modifiable drivers such as poor diet, physical inactivity, disrupted sleep, chronic stress, excess visceral fat and environmental toxins (2). Ageing makes us more prone to it. How we live seems to shape how much of it we carry.

How Does Chronic Inflammation Affect the Brain?

The brain has its own resident immune cells, called microglia. In health they act as caretakers, pruning unused connections, clearing away debris and responding to injury. Think of them as a night-watch patrol: invaluable when there is a genuine intruder, exhausting and disruptive if the alarm never stops ringing.

That is what researchers think may happen with long-term inflammation. Inflammatory signals from the rest of the body can reach the brain across, and sometimes through, the blood-brain barrier, and can nudge microglia into a more reactive state. Once activated, microglia release their own inflammatory chemicals. A landmark review in The Lancet Neurology concluded that neuroinflammation is not just a bystander in Alzheimer’s disease but appears to contribute to its progression, and identified systemic inflammation and obesity as external factors likely to influence that process (3). Much of this mechanistic picture comes from laboratory and animal work, so it explains a plausible pathway rather than proving cause and effect in people. Inflammation is one of several biological processes being investigated in Alzheimer’s disease. Explore our research into what’s driving Alzheimer’s and vascular dementia.

The human evidence is observational, but it is consistent. In the US Atherosclerosis Risk in Communities (ARIC) study, researchers measured inflammatory markers in 12,336 people in their mid-fifties and followed their thinking skills for 20 years. Those in the highest quarter for a combined inflammation score showed 7.8% steeper cognitive decline than those in the lowest quarter, and for CRP alone the figure was 11.6% (4). A meta-analysis of seven prospective studies, covering 5,717 older adults, found that people with the highest blood levels of CRP and IL-6 had a modestly higher risk of developing all-cause dementia (hazard ratios of 1.45 and 1.32 respectively), with a weaker and less consistent link to Alzheimer’s disease specifically (5).

These are associations, and they need to be read carefully. Raised inflammation could be a driver of brain ageing, an early consequence of disease processes already under way, or a marker of other risk factors such as diabetes, excess weight or inactivity. The most likely answer is some of each.

There is also a useful lesson from drug trials. Because people taking anti-inflammatory painkillers for arthritis appeared to develop Alzheimer’s less often, researchers tested whether these drugs could prevent it. In the ADAPT trial, 2,528 older adults with a family history of Alzheimer’s were randomised to naproxen, celecoxib or placebo, and neither drug reduced dementia risk (6). Inflammation is not a single switch that a single pill can turn off. It is the output of a whole system, which is why diet and lifestyle, acting on many inputs at once, are worth taking seriously.

What Causes Chronic Inflammation?

If chronic inflammation is the output of a system, the useful question is what feeds into it. Hippocrates is often quoted as saying that illnesses do not come upon us out of the blue but develop from small daily sins against nature. Whatever the origin of the quote, it describes inflammaging rather well. At Food for the Brain, we believe that protecting brain health starts long before symptoms appear. And many of the everyday factors that influence inflammation are the very things we can begin changing today.

Blood sugar is one. Repeated spikes in glucose and insulin, and the excess visceral fat that often comes with a diet high in refined carbohydrates, are recognised drivers of systemic inflammation (2). Fat tissue around the organs is not inert storage; it actively produces inflammatory cytokines. This is one reason a low glycaemic load (GL) way of eating is one of the foundations of our approach to protecting brain health.

The balance of fats matters too. The omega-3 fats EPA and DHA, found mainly in oily fish, damp down several parts of the inflammatory response and are the raw material for a family of molecules, called resolvins, protectins and maresins, that help inflammation switch off once its job is done (7). Diets low in oily fish and high in processed oils shift that balance in the other direction.

The gut is a third input. A large share of the body’s immune cells sit in and around the lining of the digestive tract, which acts as a border checkpoint between what we eat and what reaches the bloodstream. A diet heavy in ultra-processed food, sugar and alcohol, and low in fibre and plant foods, can alter the gut microbiome and may weaken this barrier, allowing more immune-provoking material through. This gut-brain connection is an active and promising area of research, though much of the human evidence is still early and associative.

Finally, there is how we live. In the Multi-Ethnic Study of Atherosclerosis, which looked at 6,814 adults, chronic stress and cynical distrust were each linked to higher IL-6 and CRP. Revealingly, those links largely disappeared once body weight, diabetes and health behaviours were taken into account (8). Stress, in other words, seems to inflame us partly through what it does to how we eat, move and sleep. Sleep itself is part of the picture: a meta-analysis of 72 studies and more than 50,000 people found that disturbed sleep was associated with higher CRP and IL-6 (9). Regular physical activity, by contrast, has well-described anti-inflammatory effects, including reducing visceral fat and prompting working muscles to release anti-inflammatory signals (10).

How to Reduce Chronic Inflammation Through Diet and Lifestyle

If many small inputs keep inflammation simmering, many small changes can help turn it down. No single food is an anti-inflammatory switch, but the overall pattern of what we eat does appear to matter. In a Greek study of 1,059 older adults, those whose diets scored highest on a dietary inflammatory index, meaning more processed and refined foods and fewer vegetables, fruit, legumes and fish, were around three times more likely to develop dementia over roughly three years than those with the least inflammatory diets (11). It was a modest-sized observational study with wide margins of error, but it fits a broader body of research linking Mediterranean-style eating with better brain ageing.

You don’t need to understand every inflammatory pathway to start making a difference. What matters most is what you do consistently, day after day.

Eat to keep blood sugar steady. Build meals around whole foods, protein, healthy fats and fibre, and keep refined carbohydrates, sugary drinks and ultra-processed snacks to a minimum.
Eat oily fish two or three times a week. Salmon, mackerel, sardines, herring and anchovies are the richest sources of EPA and DHA. In a UK Biobank analysis of more than 267,000 people, those with the highest blood levels of omega-3 had about a 21% lower risk of developing dementia than those with the lowest (12). (Want to know if you are eating enough omega-3? Use one of our at-home blood tests to find out)
Fill up on colour. Vegetables, berries, herbs and spices such as turmeric and ginger, extra virgin olive oil, red onions, beans and nuts provide polyphenols and fibre that support both the gut and the body’s own antioxidant defences.
Feed your gut. Fibre-rich and fermented foods, such as oats, beans, live yoghurt, kefir and sauerkraut, help nourish a more diverse microbiome.
Move most days. Both aerobic exercise and strength training help reduce visceral fat and inflammatory signalling.
Protect your sleep and manage stress. Regular sleep times, daylight in the morning, social connection and activities that genuinely help you unwind all count.

None of these work in isolation, and that is the point. The 2024 Lancet Commission on dementia estimated that around 45% of dementia cases are potentially attributable to modifiable risk factors (13). Inflammation is one of the threads that ties many of them together, alongside blood sugar control, brain fats, B vitamins and homocysteine, and antioxidant status. Working on one tends to help the others.

Turning down the heat

Inflammation is not the enemy. Without it we could not heal a cut or fight off an infection. The problem is a defence system that never quite stands down, and the encouraging finding from decades of research is that many of the things keeping it switched on are within our influence. Rising inflammation with age is common, but it is not fixed.

If you would like to understand where you stand, Food for the Brain’s free online Cognitive Function Test™ looks at your cognitive performance alongside the diet and lifestyle factors linked to brain health, and gives you personalised, practical feedback.

Take the Free Cognitive Function Test

For those who want to go further, the DRIfT® home blood test measures biomarkers relevant to brain health and risk reduction, including your omega-3 index, HbA1c (a measure of long-term blood sugar control) and homocysteine.

Neither is a diagnostic test for dementia. They are tools for seeing which levers are most worth pulling, and for tracking whether the changes you make are working.

Explore the 8 Domains of Brain Health. Discover how simple changes to your diet and lifestyle can support brain health, with practical, evidence-informed guidance across our 8 Domains.