The Secret Killer - How to Fight Inflammation

"The Secret Killer"

The lead article in this issue describes how inflammation underlies most chronic diseases, such as coronary heart disease, cancer, and Alzheimer's disease. This influential article helped raise public awareness about the importance of inflammation. The research that has accumulated since then has strongly reinforced the notion that inflammation underlies most chronic diseases.

Physiological Inflammation and Chronic Inflammation

To understand this we have to distinguish between Physiological Inflammation and Chronic Inflammation (also known as Iflammaging) An analogy would be needing a fire to cook dinner while camping: a match produces a small, well-contained campfire that can perfectly light a barbecue. This would be physiological inflammation, a controlled inflammation that the body activates for a specific purpose. However, an uncontrolled forest fire that spreads through the camp will undoubtedly light the barbecue, but it can also decimate the entire camp and even the entire forest. When inflammation is not controlled and goes beyond its specific physiological purpose, that's when "inflammaging" comes into play. Essentially, inflammatory mediators, such as proinflammatory signaling cytokines, are necessary for normal cell maintenance. However, if excessive and prolonged, cytokine signaling leads to disease and even death.

Continuing with our analogy, what we find is the “Death by a thousand matches”

Unfortunately, during aging, inflammatory triggers accumulate, a process researchers have termed "inflammaging." This occurs when thousands of matches are lit to start a fire, and we don't have sufficient resources to control and extinguish the multiple fires that form. As a consequence, the net inflammatory burden increases, resulting in a disastrous, multi-ignition wildfire. This cumulative inflammation is thought to drive age-related chronic diseases. While some of the matches lit are an inevitable part of aging, many other matches are a consequence of unhealthy diet and lifestyle choices, and therefore we can act on them to mitigate inflammation—or, in other words, aging and chronic disease.

There are solutions. What are they?

There is a unanimous consensus in both conventional and integrative medicine that inflammation needs to be firmly attenuated with their respective remedies. The entire strategy, until now, has focused on suppressing inflammation. In other words, I focus exclusively on the fire when it occurs without worrying about how to resolve the impact of those fires or bring them under control. I focus on the problem, not on how to solve the problem. Chemical mediators of inflammation (whether NSAIDs such as ibuprofen or corticosteroids) are, at best, an incomplete and limited strategy, while, in some scenarios, they could prolong the inflammatory disease due to their inability to address all the sources of the fire.

The other side of the coin

While minimizing inflammatory triggers is an important strategy for keeping inflammatory tone in check, it would be wise to focus just as much attention on the little-known resolution process. Once thought to be a passive process that occurred when inflammatory mediators dissipated, the resolution of inflammation is now understood to be an active process involving several important cellular events. Emerging research recognizes that this other side of the inflammatory coin could be a game-changer for patients with chronic conditions. In short, inflammation is like your body’s defense system, but you need it to be turned on and off at the right time. If it’s on for too long, it can cause more problems than it solves. This state is called chronic inflammation and is what the Time magazine article referred to as the secret killer. Ideally, the resolution phase should follow shortly after the initiation phase to prevent progression to chronic inflammation. After the body initiates the inflammatory response to an injury or infection, a resolution phase is essential. During this phase, immune system cells receive signals to change their behavior. Instead of promoting inflammation, they shift into an anti-inflammatory, pro-resolution mode. Think of inflammation as the body's "alarm" when there's a problem, such as a wound or infection. After the alarm is triggered and the immune system's "soldiers" (neutrophils) rush to the affected area to fight the problem, there comes a time when it's necessary to stop that process and begin repairing the damage. Stopping the Excessive Arrival of "Soldiers": After a while, we need to slow the arrival of these soldiers (neutrophils) to prevent too many of them from arriving in one place. Clearing the "Debris": During the action of the soldiers, debris and damaged cells are generated. To restore the affected area, other cells (such as "cleaners" called macrophages) kick in to clean up everything that no longer serves a purpose. Repairing the "Building": Once the cleaning is done, it's time to repair. Cells work together to rebuild and heal damaged tissue, much like repairing a building after a storm. In short, the resolution phase is like the part where we turn off the alarm, clean up the mess, and begin rebuilding to get everything back to normal after a problem. It's the body ensuring that, once it faces a difficult situation, it can recover and continue functioning as it should.

What are SPMs (Resolvins, Maresins and Protectins)?

In 2000, just a few years before the Time article was published, a veteran prostaglandin researcher with more than two decades of laboratory experience identified a class of lipid mediators that are now beginning to revolutionize inflammation management. Professor Charles Serhan of Harvard Medical School discovered that fatty acid metabolites, particularly omega-3s, are key signaling molecules that coordinate the resolution phase of inflammation. When inflammation occurs, certain cells, such as macrophages and neutrophils, release substances called metabolites. These metabolites act as chemical messengers that help calm inflammation. They work both on the cells themselves and on nearby cells, helping to halt the inflammatory response and promote tissue repair. In short, they are like peace signals that cells send out to resolve inflammation and allow the body to heal.

"The Masters of Inflammation Resolution"

Serhan named this group of metabolites SPMs (specialized pro-resolving mediators), which include several classes of lipid mediators. They are called resolvins, maresins, and protectins. They help clean up the damaged area: Metabolites also facilitate the cleanup of damaged cells, allowing the body to get rid of what no longer serves a purpose. This is crucial for setting the stage for tissue repair. In short, resolvins, maresins, and protectins are like conductors, guiding macrophages, a type of immune cell, to end inflammation. They do this by shifting macrophages from an "M1" state (which promotes inflammation) to an "M2" state (which favors resolution and a return to normalcy in the body). They are the conductors of the orchestra, ensuring that immune cells play the right tune to resolve inflammation and restore balance in the body. Increasing the production of SPMs, both endogenously and exogenously, represents a relevant objective in shifting the balance of the inflammatory process toward resolution. Modern technology has made it possible to discover external SPMs, which are precursors to substances such as resolvins, maresins, and protectins. These precursors are 17-HDHA, 14-HDHA, and 18-HEPE, and can be found in fish oil. Taking these external compounds, properly concentrated and isolated from fish oil, can increase the body's internal (endogenous) production of resolvins, maresins, and protectins and ensure proper natural resolution of inflammation without resorting to NSAIDs such as ibuprofen or corticosteroids. In simple terms, we can now identify external substances that act as "resolution masters," and when consumed, help our body produce more of these mediators internally. This can be beneficial for promoting inflammation resolution and maintaining health. The increase in SPMs in our body via supplementation is measurable and objective. Numerous scientific studies validate this. Work is already underway on the synthesis of these metabolites to obtain the anti-inflammatory drugs of the future, focused on resolution. Meanwhile, supplementation with the precursors of resolvins, maresins, and protectins (17-HDHA, 14-HDHA, and 18-HEPE) is already a reality, with efficacy validated by an ever-increasing body of scientific evidence.