Updated on February 8, 2023
Systemic inflammation is detrimental to many of the body’s tissues and is implicated in countless diseases and health conditions ranging from the common flu to cancer. Emerging research is even linking systemic inflammation to unlikely conditions such as mood disorders and mild anxiety, expanding our understanding of the dangers posed by this circumstance. As more connections are discovered between systemic inflammation and various health conditions, researchers are increasingly seeking to shed light on the mechanisms responsible.
Currently, clinicians often direct patients presenting with inflammation issues to over-the-counter compounds, like non-steroidal anti-inflammatory drugs (NSAIDs), which are proven to address non-chronic inflammation safely. In more serious cases of chronic inflammation that don’t respond to NSAIDs, doctors often prescribe corticosteroids, which can safely address inflammation temporarily. However, these medications are not effective in all applications. Additionally, corticosteroids can cause a number of side effects with significant health implications, making them generally unsuitable for long-term use.
Research is now showing that alternative help is available and powerful. For example, there are currently a number compounds used in nutritional supplements that help maintain the body’s normal inflammatory response that have been proven safe and effective which could augment conventional therapies. Thanks to recent studies that have investigated these therapies, researchers and clinicians now know more about their mechanisms of action and beneficial effects than they ever have before, allowing more patients to benefit from natural alternatives. Because systemic inflammation itself is difficult to fully address with any one compound, it might be prudent to use natural inflammation support in combination with traditional therapies to ensure the problem is being approached from multiple physiological angles.
Systemic inflammation is a complex process, and scientists are striving to more deeply understand its full range of causes and effects. The working understanding of non-systemic inflammation is fairly simple. When local inflammation occurs, such as a cut or injury, small blood vessels in the inflamed area dilate, allowing more blood to rush in. This increased blood flow causes the tissue to become warmer, and external tissues take on a reddened color. Excess plasma from the blood permeates into the inflamed tissues, which then become swollen as a result of their higher-than-normal liquid volume. The body uses the additional blood flow and increased volume to traffick white blood cells, platelets, and other cells responsible for tissue repair to the inflamed area so the damage or external cause of the inflammation can be repaired.
As part of this process, white blood cells release an anti-pathogenic chemical package at the site of inflammation. Unfortunately, this often causes the healthy tissues at the inflamed site to be destroyed along with any pathogens and damaged tissues. The unintended destruction of healthy tissues makes inflammation a dangerous prospect, especially for sensitive organs like the intestines and brain. In these sensitive organs, a normal inflammatory response can evolve into systemic inflammation that can spiral out of control, which means that controlling inflammation must be a priority within medical practice. Additionally, the adverse effects of systemic inflammation are now understood to be implicated in a broad range of adverse health conditions, and clinicians and researchers are reinterpreting many diseases in the context of their inflammatory symptoms in hopes of finding new ways to help patients. As such, anti-inflammatories are an important site of inquiry.
Although drugs that control inflammation include common chemicals like ibuprofen and aspirin, these medications are not always effective and can have undesirable or even dangerous long-term side effects. In particular, members of the most common class of anti-inflammatories, NSAIDs are associated with gastric ulcers, thinned blood, and internal bleeding in the colon. Although most of these side effects only occur with extended periods of NSAID use, some patients might experience them more easily than others. NSAIDs are also associated with slower muscle regrowth following traumatic injury.
One study published in the South African Journal of Medicine found that for patients with acute traumatic hamstring injuries, NSAIDs performed only two percent better than placebo in terms of pain relief, and negligibly better than placebo for inflammation reduction. These two effects were consistent from the day after the injury until a week later. Ultimately, however, NSAIDs slowed the healing process and ultimately left the treatment group with more pain than the placebo group; a week after the initial injury and treatment with NSAIDs, the data showed that patients taking the NSAIDs had a median of 8.8 pain units out of 100 compared to those taking the placebo who experienced a median of 3.9 pain units. Additionally, the two groups exhibited similar reduction of swelling. Other studies have corroborated similar effects.
In contrast to NSAIDs, although corticosteroids have a broader array of side effects, they also have a greater degree of efficacy in reducing inflammation. Unlike NSAIDs, corticosteroids cause veins to constrict, which means they act faster to stop acute inflammatory episodes more effectively. However, vasoconstriction can also produce a number of significant side effects, and corticosteroids are linked to mild anxiety, immunosuppression, hypertension, and slower wound healing as a result of reduced blood access to wound sites. Because of their wider and more serious side effect profile, corticosteroids are typically a second-line therapy that is only used after NSAIDs have failed to control inflammation. After a patient is stabilized and inflammation is suppressed, doctors typically transfer patients back to NSAIDs.
In addition to NSAIDs and corticosteroids, some patients turn to over-the-counter pain relievers such as acetaminophen (Tylenol, for example) to cope with the pain of inflammation. Although acetaminophen can provide temporary pain relief, it does not address the underlying inflammation. Furthermore, acetaminophen can be toxic, causing profound liver damage and, in some cases, acute liver failure when taken in high doses. Overall, acetaminophen is acknowledged as the most common cause of liver injury, and its risk is heightened when taken in concert with alcohol use. It is critical that patients recognize the dangers of acetaminophen and focus their attention on seeking out safe anti-inflammatory remedies that address the root cause of pain rather than potentially damaging pain relievers that simply mask the root cause.
Finding the right compound, however, can be a challenge. Although most local inflammation can be addressed effectively with NSAIDs or corticosteroids, the drugs’ limitations have left a growing number of patients searching for natural remedies that can be used to supplement or replace pharmaceuticals. These natural compounds include substances have long been renowned for their ability to support the body’s natural response to inflammation, as well as innovative new supplements that are emerging to give patients more modern ways of coping with systemic inflammation.
Fish oil is composed of omega-3 fatty acids. As a nutritional supplement, omega-3 fatty acids inhibit the body’s ability to convert fatty acids like arachidonic acid into prostaglandin E2, which is highly proinflammatory. Because fish oil inhibits the metabolic step necessary to generate proinflammatory molecules, the entire body experiences a lower level of inflammation. The ability of omega-3 fatty acids to inhibit inflammation is so marked that some researchers have proposed using the blood concentrations of omega-3s as a diagnostic indicator for the risk of coronary heart disease, which is exacerbated by systemic inflammation. Other researchers have proposed a link between consumption of fish oil and a lower risk of Alzheimer’s disease and stroke, both of which are associated with creating inflammation or being caused by systemic inflammation.
Unlike pharmaceutical anti-inflammatories, fish oil is primarily preventative rather than reactive with regard to reducing inflammation, which means it helps maintain long-term health rather than helping a patient during an acute, local inflammation episode.
Humans have a long relationship with polyphenols, dating back to the prehistoric era of the Indus River Valley civilization. Since then, polyphenols have been renowned for their tissue-shrinking properties, which can help address chronic inflammation safely and effectively. Derived from plants like the green tea leaf, turmeric, and the pine tree, most polyphenols are confirmed to be bioactive, which makes them a natural area for scientists performing drug discovery.
Recently, polyphenols like turmeric have been studied in the context of mitigating systemic inflammation, like in arthritis. A 2006 study found that daily administration of turmeric-derived compounds addressed inflammation caused by subsequent arthritic episodes by as much as 75 percent due to its inhibition of white blood cells’ secretion of damaging chemicals. On average, patients who used turmeric in a preventive capacity experienced a 68-percent reduction in joint inflammation, and scientists who replicated this experiment found an average of 65-percent inflammation reduction. However, the initial study also found that turmeric’s effect on the body’s inflammatory response was heavily impacted and delayed when administered only after injuries. This means that like fish oil, turmeric is best used preventively because it won’t have a therapeutic impact when used to address an acute incident.
Aside from turmeric, other polyphenol-containing plants include green tea extract. Green tea extract contains compounds that inhibit one of the body’s primary pro-inflammatory signaling molecules, the nuclear factor kappa light chain enhancer of activated B cells (NF-kB). Because cells that secrete NF-kB are inhibited by green tea extract from modifying their protein production to generate other inflammatory molecules, systemic inflammation can be addressed. Although these beneficial effects are under active study, researchers state that green tea extract consumed in quantities as high as 400 mg per day is safe and effective.
Botanicals like ginkgo biloba also contain polyphenols that exhibit similar effects. In particular, the polyphenol quercetin is associated with fewer aging-linked inflammatory markers when consumed daily by Japanese adults. Furthermore, quercetin is also associated with lower levels of LDL cholesterol, oxidative stress markers, a slightly longer lifespan, and lower blood pressure in hypertensive patients. These effects are especially pronounced in obese patients, who benefit more than patients of a healthy weight from quercetin supplementation. Like other polyphenols, quercetin is under active investigation by researchers who hope to exploit its medicinal effects.
Butyric acid is perhaps the newest and most promising natural compound. Also known as butyrate, butyric acid is a cellular signaling molecule produced in large volumes in the human gut and subsequently consumed by the gut microbiota for energy. Butyric acid is potent because it inhibits secretion of the critical pro-inflammatory molecules IL-1B, TNF-a, and IL-6. These molecules are secreted by dying cells, creating systemic inflammation that causes circulating white blood cells to clear any pathogens in their vicinity. Because butyric acid inhibits these signals from being secreted and causes proinflammatory t-cells to self-destruct, systemic inflammation is beneficially down-regulated. One study found that administration of butyric acid to cells in vitro reduced their secretion of certain proinflammatory molecules by more than 70 percent.
Historically, butyric acid’s beneficial effects were impossible to access due to the compound’s inability to survive metabolism and produce its systemic physiological effects. As a result, researchers have long sought a way to administer butyric acid in such a way that it could circulate everywhere in the body after oral administration and first pass metabolism. Thanks to recent breakthroughs in high bioavailability delivery systems, patients can now take butyric acid supplements to enjoy its benefits. Rather than losing most of the ingredient’s activity to first-pass metabolism, bioavailability systems like erodible pill coatings or molecule-specific drug release triggers enable the butyric acid to get where it needs to go and remain there longer. Although butyric acid is under active research and many questions remain to be answered, its undeniable efficacy in vitro and safety profile in vivo make it an excellent choice for supporting the body’s natural response to inflammation.
Natural compounds with a beneficial inflammatory response profile are becoming more understood by the day, and evolving knowledge brings new hope and expanded therapy options for patients seeking natural alternatives to conventional pharmaceutical therapies. However, patients who want to take advantage of natural inflammation support must seek out the most appropriate and highest quality supplements to realize optimal benefits; many supplements have been tested in specific disease contexts, and patients should strive to find those that are proven effective for their needs. Natural substances with beneficial inflammatory response characteristics are also often more effective when used in combination with each other and with traditional therapies. With this in mind, clinicians should tailor combination therapies to the specific needs of their patients to achieve the best outcomes, while minimizing side effects and promoting overall wellness.
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