Scientists Explains How Fasting Protect Against Inflammation

Cambridge researchers may have identified a new approach for fasting to lower inflammation, a potentially harmful side effect of the immune system that underpins a variety of chronic diseases.

In a report published in Cell Reports titled “Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting,” the team discusses how fasting increases levels of arachidonic acid, a molecule in the blood that inhibits inflammation. According to the researchers, it could also help explain some of the benefits of medications like aspirin.

Scientists have long known that our food, particularly a high-calorie Western diet, might increase our risk of diseases such as obesity, type 2 diabetes, and heart disease, all of which are associated to chronic inflammation in the body.

Inflammation is our body’s natural response to injury or illness, but it may also be triggered by other systems, such as the so-called “inflammasome,” which functions as an alarm within our cells, causing inflammation to help defend our body when it detects damage. However, the inflammasome can unintentionally cause inflammation—one of its jobs is to eliminate undesirable cells, which can result in the discharge of the cell’s contents into the body, triggering inflammation.

“We’re very interested in trying to understand the causes of chronic inflammation in the context of many human diseases, and in particular the role of the inflammasome”, said Professor Clare Bryant from the Department of Medicine at the University of Cambridge.

“What’s become apparent over recent years is that one inflammasome in particular—the NLRP3 inflammasome—is very important in a number of major diseases such as obesity and atherosclerosis, but also in diseases like Alzheimer’s and Parkinson’s disease, many of the diseases of older age people, particularly in the Western world.”

Fasting has been shown to lower inflammation, however the exact mechanism is unknown. To help address this question, a team led by Professor Bryant and colleagues from the University of Cambridge and the National Institute for Health in the United States examined blood samples from 21 volunteers who ate a 500-kcal meal and then fasted for 24 hours before eating another 500-kcal meal.

The researchers discovered that calorie restriction boosted levels of arachidonic acid, a type of lipid. Lipids are chemicals that serve crucial functions in our bodies, such as storing energy and conveying information between cells. When they ate again, their arachidonic acid levels decreased.

When the researchers investigated arachidonic acid’s effect on immune cells cultivated in the lab, they discovered that it inhibits the activity of the NLRP3 inflammasome. This startled the scientists because arachidonic acid was previously assumed to be associated with increased inflammation rather than lower levels.

More information: Milton Pereira et al, Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting, Cell Reports, DOI: 10.1016/j.celrep.2024.113700

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