The Secret Killer - How to Fight Inflammation

On February 23, 2004, the cover of Time magazine featured a burning silhouette with ominous text branded across it:

"The Secret Killer"

The lead article in this issue describes how inflammation underlies most chronic diseases, including 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 is behind 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 when camping: a match produces a small, well-contained fire that can perfectly light a barbecue. This would be physiological inflammation, a controlled inflammation, which the body activates for a specific purpose. However, an uncontrolled forest fire that spreads through the campsite will certainly ignite the barbecue, but it can also decimate the entire campsite and even the entire forest. When the fire goes uncontrolled 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, as we age, 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 the resources to control and extinguish the multiple fires they form. As a result, the net inflammatory burden increases, resulting in disastrous, multi-ignition wildfires. This cumulative inflammation is thought to drive age-related chronic diseases. While some of the matches struck are an inevitable part of aging, many other matches struck are a consequence of an unhealthy diet and lifestyle, 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, so far, has focused on suppressing inflammation. In other words, I focus exclusively on fires when they occur, without worrying about how to manage 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 prudent to focus equally on the little-known resolution process. Previously thought to be a passive process occurring as inflammatory mediators dissipated, the resolution of inflammation is now understood to be an active process involving a number of important cellular events, and emerging research recognizes that this other side of the inflammatory coin could be a game-changer for patients with chronic diseases. In short, inflammation is like your body's defense system, but you need it to be activated and deactivated at the right time. If it's activated 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. Imagine 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 this 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. Cleaning up the "debris": During the soldiers' actions, debris and damaged cells are generated. To restore the affected area, other cells (such as the "cleaners" called macrophages) come into play to clear away everything that is no longer useful. 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 making sure 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 the management of inflammation. 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 body's own cells and on nearby cells, helping to halt the inflammatory response and promote tissue repair. In short, they are like peace signals that cells send 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. Their names are resolvins, maresins, and protectins. They help clean the damaged area: Metabolites also facilitate the cleansing of damaged cells, allowing the body to get rid of what no longer serves a purpose. This is crucial for paving the way for tissue repair. In short, resolvins, maresins, and protectins act as directors that guide 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 promotes 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 to the body. The increase in SPM production, both endogenously and exogenously, represents a relevant objective in changing the balance of the inflammatory process to 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 internal (endogenous) production of Resolvins, Maresins and Protectins in the body 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 bodies produce more of these mediators internally. This may be beneficial in promoting the resolution of inflammation and maintaining health. The increase in SPMs in our bodies through 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 increasingly abundant scientific material.