The Good, The Bad, & The Ugly

by Women’s Brain Health Initiative:

INFLAMMATION IN THE BRAIN.

We hear a lot about inflammation, and usually in negative terms. But inflammation isn’t always something to be concerned about. In fact, it’s a remarkable way the body responds to infection and injury. This immune response can heal the body by repairing wounds, destroying pathogens, and clearing pollutants or damaged cells.

But too much of a good thing can sometimes have negative consequences.

Inflammation can also occur with the onset and flare up of chronic diseases, like heart disease, arthritis, diabetes, bowel diseases, and certain types of cancer (e.g., colon cancer).

WHEN THE IMMUNE RESPONSE IS ACTIVATED AND GETS STUCK IN THE “ON” POSITION BECAUSE OF AN ONGOING FIGHT WITH CHRONIC DISEASE, THIS CAN LEAD TO THE CHRONIC PRESENCE OF INFLAMMATION, CAUSING HARM TO HEALTHY CELLS AND TISSUES.

This relationship can work in the other direction as well, where chronic inflammation can worsen or trigger flare ups of chronic disease.

NEUROINFLAMMATION & NEURODEGENERATIVE DISEASE

Taking a deeper look at brain health, ongoing research shows that neuroinflammation – an inflammatory response in the brain or the spinal cord – can negatively affect regions of the brain involved in thinking, memory, and movement.

Neurodegenerative diseases like multiple sclerosis, Parkinson’s disease, Alzheimer’s disease (AD), and other forms of dementia have been shown to worsen with neuroinflammation, where the immune system goes rogue and attacks healthy brain tissue.

One possible way this occurs is connected to a type of brain cell called an astrocyte and how it communicates with T-cells, which are white blood cells. When things are working well, T-cells can help regulate a sub-type of astrocyte, which will then regulate inflammation in the brain. However, those same T-cells can also secrete proteins that cause the astrocytes to release potentially brain-damaging free radicals into the central nervous system.

Cells outside of the immune system have also been shown to communicate with astrocytes. A growing amount of research is being done on the way this happens along what’s known as the “gut-CNS axis” (gut-central nervous system axis).

Research has shown that chemical signals produced by gut bacteria and metabolites can activate astrocytes to trigger (positive) anti-inflammatory processes or (destructive) neuroinflammation (inflammation in the brain), depending on the signal sent.

SEX DIFFERENCES IN IMMUNE RESPONSES

A solid base of evidence shows that females have stronger peripheral immune responses than males. A 2016 review by Drs. Sabra Klein and Katie Flanagan in Nature Reviews Immunology explains women clear pathogens faster and tend to have better antibody responses to vaccines when compared to men (making vaccines, like the seasonal flu vaccine, more effective for women).

AT THE SAME TIME, STRONGER IMMUNE RESPONSES PLACE WOMEN AT A HIGHER SUSCEPTIBILITY TO AUTOIMMUNE DISEASES, WITH 80% OF AUTOIMMUNE DISEASES OCCURRING IN FEMALES.

When it comes to neuroinflammation, the opposite seems to be true, where males show a stronger response when compared to females. In their 2021 article published in Journal of Neuroinflammation, Dr. Caitlin Posillico and colleagues identified sex differences in protein release, chemical signalling, and gene expression within brain cells of mice.

The authors explained that sex differences in neuroinflammation is a relatively new area of research, with the bulk of previous research looking at only males or only females. Future studies are needed to learn more about how sex differences in neuroinflammation may affect outcomes like cognitive function and mood disorders so that new targets for treatment may be identified.

Sex differences have also been noted along the gut-CNS axis, playing potential roles in the incidence of neurodegenerative diseases (e.g., AD and Parkinson’s disease) and mental health disorders (e.g., anxiety and depression).

A 2020 review of evidence by Dr. Calliope Holingue and colleagues in Current Psychiatry Reports explains that although there are known differences in hormones (e.g., estrogens), metabolism, and gut microbes between men and women, we are in the early stages of identifying how these sex differences influence the brain, mental health, and physical health.

ANTI-INFLAMMATORY DIETS & BRAIN HEALTH

With clear evidence pointing to the harmful nature of chronic inflammation in the brain and body, and emerging findings on the gut-CNS axis, attention has turned toward anti-inflammatory strategies to mitigate disease progression or reduce risk of disease.

While research on the timing and target of anti-inflammatory pharmaceutical approaches for chronic inflammation is ongoing, parallel research has been exploring alternate approaches, with considerable attention on the role of diet.

In 2009, researchers at the University of South Carolina developed a dietary inflammatory index (DII) to quantify the ways that food parameters (components) affected chemical markers of inflammation.

Published in The Journal of Nutrition, Dr. Philip Cavicchia and colleagues reviewed 929 research studies on diet and inflammation and derived a list of 45 different parameters. The DII included macronutrients (e.g., fat, carbohydrate, protein), vitamins (e.g., vitamins C, D), minerals (e.g., magnesium, zinc, iron), specific foods (e.g., garlic, ginger, turmeric), alcohol, and food constituents abundant in fruits and vegetables (e.g., fibre, beta carotene).

The inflammatory potential of diet was calculated as a single DII score; a lower value indicated a more anti-inflammatory diet that is rich in antioxidants. Over time, the DII has been updated and is even available as an online calculator.

IT SEEMS THAT EATING FEWER INFLAMMATORY FOODS AND PLENTY OF ANTI-INFLAMMATORY SOURCES APPEARS TO BE HEALTH PROTECTIVE.

Over the last decade, population studies from around the world have confirmed that a high DII score is related to a higher presence of inflammatory markers and is also linked to poorer health outcomes.

For example, a 2021 systematic review of meta-analyses published in Frontiers in Nutrition by Fang-Hua Liu and colleagues showed that there is a strong evidence base linking high DII to several forms of cancer (e.g., digestive and colorectal) and cardiovascular disease, and suggestive evidence linking high DII to other forms of cancer (e.g., breast and prostate), all-cause mortality, and depression. The researchers suggest that randomized controlled trials should be done to determine if these results are causal versus correlated.

Focusing on brain health, emerging research published over the last few years has found relationships between high DII and smaller brain volume, poor cognition, cognitive decline, dementia diagnosis, and risk of AD.

A growing number of randomized controlled trials examining the effect of low DII diets on disease outcomes are also underway, which will hopefully help researchers determine DII levels that offer health protection.

REDUCING THE BAD & INCREASING THE GOOD

New understandings of inflammation and immune responses give rise to future possibilities to manage and prevent chronic inflammation in the brain and body.

Over the last decade, we’ve learned there are detrimental and beneficial subgroups of cells involved in our immune systems, but what’s missing is information about how to isolate and amplify the beneficial parts of inflammation and suppress the destructive ones.

At this point, though, what can be said is that a diet rich in anti-oxidants with limited inflammatory foods appears to be protective for overall health and promotes proper functioning of the immune system. So go ahead and eat the rainbow, and some beans and fatty fish, too! Your body and mind will thank you for it.

SIDEBAR

Chronic inflammation may result from a variety of conditions, including uncontrolled infection or injury, autoimmune disorders, exposure to toxins, and lifestyle factors like chronic stress, poor eating habits, excessive alcohol consumption, smoking, low levels of physical activity, and sedentary behaviour.

Free Radicals & Antioxidants

Free radicals are unstable molecules that are highly reactive. Free radicals are generated by the body during essential metabolic processes, like inflammation and breathing, but can also result from exposure to external sources like cigarette smoke, some medications, and air pollution. An abundance of free radicals can cause large-chain chemical reactions that damage DNA and cells, leading to oxidative stress and illness/disease. Thus, free radicals must be kept in balance by antioxidants.

Antioxidants stabilize free radicals, essentially “disarming” them from causing damage to the body. As with free radicals, there are internal and external sources of antioxidants. Antioxidants are produced in the body during essential metabolic processes like energy production and can also be ingested from foods rich in vitamins (e.g., vitamins C and E) and phytochemicals (e.g., lycopene from tomatoes and flavanols in cocoa).

Not surprisingly, diets with plenty of colourful fruits and vegetables, plant sources of protein (e.g., lentils, nuts, and seeds), fatty fish (e.g., salmon), and unsaturated oils (e.g., olive, avocado) yield a low DII score. Diets with a lot of red meat, fried foods, refined sugars, and saturated fats yield a high DII score.