The Definitive Guide to Inflammation

November 6, 2019

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Inflammation gets a bad rap in the alternative health world: “Inflammation causes heart disease, cancer, and autoimmune disease! It’s at the root of depression.” These are all true—to some extent.

Name a disease, and inflammation is involved.

Crohn’s disease is inflammatory.

Major depression is inflammatory.

Heart disease is inflammatory.

Autoimmune diseases, which involve an inflammatory response directed at your own tissues, are inflammatory.

Arthritis is inflammatory.

Even obesity is inflammatory, with fat cells literally secreting inflammatory cytokines.

Yes, but the story is more complicated than that. Inflammation, after all, is a natural process developed through millions of years of evolution. It can’t be wholly negative. Just like our bodies didn’t evolve to manufacture cholesterol to give us heart disease, inflammation isn’t there to give us degenerative diseases.

So, Why Does Inflammation Happen?

When pain, injury, or illness hit, the first responder is the acute inflammatory response. In other words, it is brief, lasting several days or less. All sorts of things can cause an acute inflammatory response. Here are a few:

Trauma (punch, kick, golf ball to the head)
Infection by pathogens (bacterial, viral)
Burn (sun, fire, seat belt buckle on a summer day)
Chemical irritants
Frostbite
Stabbing/Cut/Laceration
Allergic reaction

Things happen pretty fast in an acute inflammatory response and involve several different players, including the vascular system (veins, arteries, capillaries and such), the immune system, and the cells local to the injury.

First, something painful and unpleasant happens; choose one of the above injury options.
Then, pattern recognition receptors (PRR) located at the injury site initiate the release of various inflammatory mediators, which in turn initiate vasodilation (or widening of the blood vessels). This allows increased blood flow to the injury site, which warms the site, turns it the familiar red, and carries plasma and leukocytes to the site of the injured tissue.
The blood vessels become more permeable, thus allowing the plasma and leukocytes to flow through the vessel walls and into the injured tissue to do their work. Emigration of plasma into tissue also means fluid buildup, which means swelling.
At the same time, the body releases an inflammatory mediator called bradykinin, which increases pain sensitivity at the site and discourages usage of the injured area. These sensations—heat, redness, swelling, pain, and a loss of function—are annoying and familiar, but they’re absolutely necessary for proper healing.

Why Is (Acute) Inflammation Essential?

Allow me to explain why the four primary symptoms of acute inflammation are necessary, despite being unpleasant:

Increased blood flow warms the injury and turns it red, which can be irritating and unsightly, but it also carries the guys—leukocytes—that will be cleaning up the injury site, mopping up pathogens, and overseeing the inflammatory process.
Swollen body parts don’t fit into gloves, are really sensitive, and don’t work as well as their slim counterparts, but a swollen finger is a finger that’s full of a plasma and leukocyte slurry and therefore on the road to recovery.
Pain hurts, but if an injury doesn’t hurt and it’s serious, you’ll keep damaging it because you won’t know not to use it.
Loss of function prevents you from using what could be one of your favorite body parts, but you don’t want to make it worse be re-injuring it. Besides, it’s only temporary.

What About Chronic Inflammation?

These symptoms both indicate and enable inflammation (and, thus, healing), but what’s the deal with inflammation being linked with all those chronic illnesses—like obesity, heart disease, and depression? How does something normal and helpful go haywire and become implicated in some of the most crushing, tragic diseases of our time?

When inflammation becomes chronic and systemic, when it ceases to be an acute response, when it becomes a constant low-level feature of your physiology that’s always on and always engaged, the big problems arise.

The inflammatory response is supposed to be short and to the point. And because a big part of inflammation is breaking the tissue down, targeting damaged tissue and invading pathogens, before building it back up, the inflammatory response has the potential to damage the body. That’s why it’s normally a tightly regulated system: because we don’t want it getting out of hand and targeting healthy tissue. But if it’s on all the time—if chronic inflammation sets in—regulation becomes a lot harder.

Acute vs. Chronic Inflammation

A perfect example of the acute inflammation versus chronic inflammation dichotomy is exercise.

A single hard workout raises inflammation. It’s a stressor, a damaging event imposed upon your body. See for yourself.

A hard run spikes C-reactive protein for up to two days.

During exercise, skeletal muscle releases the inflammatory cytokine IL-6, a marker of damage.

Volleyball practice elicits spikes in IL-6 in both male and female elite volleyball players.

Acute exercise spiked CRP in cardiovascular disease patients (but a four-month exercise program lowered it).

This table of inflammatory responses to strenuous endurance events shows some massive spikes in CRP, some up to 20-fold the baseline value.

Yet, study after study (epidemiological and clinical alike) shows that extended exercise programs generally reduce markers of inflammation (like C-reactive protein) over the long-term:

In elderly Japanese women, a 12-week resistance training program reduced circulating levels of inflammatory markers compared to baseline; reductions in CRP were associated with increases in muscle thickness.
American adults who engaged in frequent physical activity tended to have lower CRPs than adults who were more sedentary.
In type 2 diabetics, (key term coming up) long-term high intensity resistance and aerobic training reduced inflammatory markers over the course of a year (independent of changes in body weight, meaning activity was the key factor).
Endurance combined with resistance training reduced CRP in young, healthy women better than endurance training alone.
In obese, post-menopausal women, a basic moderate cardio program lowered CRP without really affecting body weight either way over the course of a year.

There are many more out there, but the general gist is that regular exercise tends to lower markers of systemic inflammation while acute exercise increases markers of acute inflammation. And sometimes what’s acute can become chronic. How do we make sense of this? How do we avoid making those acute spikes a chronic, constant thing?

Identifying Chronic Inflammation: Objective Markers

First, we need to be able to identify chronic inflammation. What symptoms and biomarkers can we use to track our inflammation levels?

CRP, or C-Reactive Protein

CRP is a protein that binds with dead and dying cells and bacteria in order to clear them from the body. It can always be found (and measured) in the bloodstream, but levels spike when inflammation is at hand. During acute inflammation caused by infection, for example, CRP can spike by up to 50,000-fold. CRP spikes due to acute inflammation peak at around 48 hours and declines pretty quickly thereafter (post acute-phase inflammation CRP has a half life of 18 hours). Thus, if the incident causing the inflammation is resolved, CRP goes back to normal within a few days. If it persists, the infection/trauma/etc. probably persists as well.

Highly sensitive to many different kinds of stressors, CRP rises in response to essentially anything that causes inflammation. This makes it valuable for determining that inflammation is occurring, but it makes it difficult to determine why that inflammation is occurring—because it could be almost anything. But if you’re looking for confirmation that you are chronically, systemically inflamed, an elevated CRP (in absence of any acute infections, injuries, burns, or stressors) is a useful barometer.

“Normal” CRP levels are supposedly 10 mg/L. Absent infection or acute stressors, however, ideal CRP levels are well under 1 mg/L. You want to stay well below 1; you don’t want “normal.” Between 10-40 mg/L (and perhaps even 1-9 mg/L, too) indicates systemic inflammation (or pregnancy), while anything above that is associated with real acute stuff. Note that exercise can elevate CRP, so don’t get tested if you’ve worked out in the last couple days.

IL-6, or Interleukin-6

T cells (type of white blood cell that plays a huge role in the immune response) and macrophages (cells that engulf and digest—also known as phagocytosing—stray tissue and pathogens) both secrete IL-6 as part of the inflammatory response, so elevated IL-6 can indicate systemic inflammation.

Tissue Omega-3 Content

This is a direct measurement of the omega-3 content of your bodily tissue. It’s not widely available, but it is very useful. Remember that anti-inflammatory eicosanoids draw upon the omega-3 fats in your tissues and that inflammatory eicosanoids draw upon the omega-6 fats. People having a higher proportion of omega-6 fats will thus produce more inflammatory eicosanoids. Now, we absolutely need both inflammatory and anti-inflammatory eicosanoids for proper inflammatory responses, but people with high omega-6 tissue levels make way too many inflammatory eicosanoids. Studies indicate that people with the highest omega-3 tissue levels suffer fewer inflammatory diseases (like coronary heart disease).

Research (highlighted and explicated here by Chris Kresser) suggests that omega-3 tissue concentrations of around 60% are ideal, which is a level commonly seen in Japan—the seemingly paradoxical land of high blood pressure, heavy smoking, and low coronary heart disease rates.

Omega-3 Index

This measures the EPA and DHA, the two important omega-3 fatty acids, as a percentage of total fatty acids present in your red blood cells. It doesn’t correlate exactly to tissue amounts, but it’s pretty good and a powerful predictor of cardiovascular disease risk. The omega-3 index doesn’t measure omega-6 content, but those with a low omega-3 index are probably sporting excessive omega-6 in their red blood cells.

Anything above 8% corresponds to a “low risk,” but levels of 12-15% are ideal and roughly correspond to the 60% tissue content mentioned by Chris’ article. Four percent and below is higher risk and can be viewed as a proxy for increased inflammation (or at least the risk of harmful systemic inflammation developing from normal inflammation).

Heart Rate Variability

I’ve written extensively on HRV in the past. Long story short, high HRV predicts lower levels of inflammation.

Systemic Inflammatory Response Syndrome Score

There’s the systemic inflammatory response syndrome, which is incredibly serious and has four criteria. If you have two or more of them at once, congratulations: you qualify—and should probably see a health professional immediately. This isn’t relevant for low-grade systemic inflammation, like the kind associated with obesity or autoimmune disease.

Body temperature less than 96.8 F (36 C) or greater than 100.4 F (38 C).
Heart rate above 90 beats per minute.
High respiratory rate, 20 breaths per minute or higher.
White blood cell count fewer than 4000 cells/mm³ or greater than 12,000 cells/mm³.

Of these objective markers to test, I’d lean toward CRP, HRV, and one of the omega-3 tests. CRP is pretty comprehensive, HRV is a two-fer (inflammation and general stress/recovery), and, while omega-3 tissue or blood cell content doesn’t necessarily indicate the existence of systemic inflammation in your body, it does indicate the severity of the inflammatory response you can expect your body to have. Taken together, these tests will give you an idea of where you stand.

Identifying Inflammation: Subjective Markers

There are also subjective markers. They may be harmless artifacts, but they may indicate that something systemic is going on.

Flare-up of Autoimmune Conditions You Haven’t Heard From In Ages

Sore joints, dry, patchy, and/or red skin, and anything else that indicates a flare-up. For me, this is usually mild arthritis.

Water Retention

Acute inflammation is often characterized by swelling at the site of injury. The same effect seems to occur in states of systemic inflammation, although they aren’t localized, but rather generalized.

Stress Load

If you feel stressed, you’re probably inflamed. I’m talking about the kind that has you rubbing your temples, face palming, sighing every couple minutes, and pinching the space between your eyes very, very hard.

Persistent But Unexplained Nasal Congestion

Could be allergies, sure, but I’ve always noticed that when I’m under a lot of stress and generally in an inflamed state, my nose gets clogged. Certain foods will trigger this, too, and I think it can all be linked to a persistent but subtle state of inflammation.

Overtraining

If you fit the bill for the eight signs of overtraining listed in this post, you’re probably inflamed.

Ultimately, though? It comes down to the simple question you must ask yourself: How do you feel?

I mean, this seems like an obvious marker, but a lot of people ignore it in pursuit of numbers. If you feel run down, lethargic, unhappy, your workouts are suffering, you struggle to get out of bed, you’re putting on a little extra weight around the waist, sex isn’t as interesting, etc., etc., etc., you may be suffering from some manner of systemic, low-grade inflammation. Conversely, if you’re full of energy, generally pleased and/or content with life, killing it in the gym, bounding out of bed, lean as ever or on your way there, and your sex drive is powerful and age appropriate (or inappropriate), you’re probably not suffering from chronic inflammation.

Causes of Chronic Inflammation

We need to determine why inflammation is “on” all the time—and then take the steps to counter it. I’m going to fire off a few things that both induce inflammation and tend toward prevalence in developed countries. You let me know if anything sounds familiar to you.

Toxic diets: High-sugar, high-processed carb, high-industrial fat, high-gluten, high-CAFO meat, low-nutrient food is a pretty accurate descriptor of the modern Western diet.
Insufficient omega-3 intake: Omega-3 fats form the precursors for anti-inflammatory eicosanoids, which are an integral part of the inflammatory response. Poor omega-3 status means insufficient production of anti-inflammatory eicosanoids and a lopsided inflammatory response to normal stimuli.
Excessive omega-6 intake: Omega-6 fats form the precursors for inflammatory eicosanoids, which are an integral part of the inflammatory response. High omega-6 status (especially when combined with poor omega-3 status) means excessive production of inflammatory eicosanoids and a lopsided inflammatory response to normal stimuli. The more omega-6 you eat, the more omega-3 you crowd out for anti-inflammatory eicasonoid formation.
Lack of sleep: Poor sleep is linked to elevated inflammatory markers. Poor sleep is a chronic problem in developed nations. Either we go to bed too late, wake up too early, or we use too many electronics late at night and disrupt the quality of what little sleep we get. Or all three at once.
Lack of movement: People lead sedentary lives, by and large, and a lack of activity is strongly linked to systemic, low-grade inflammation. People don’t have to walk to get places, they take escalators and elevators, they sit for hours on end, and they don’t have time for regular exercise.
Poor recovery: Other people move too much, with too little rest and recovery. When I ran 100+ miles a week, I certainly wasn’t sedentary, but I was chronically inflamed. Overtraining is a form of chronic inflammation.
Chronic stress: Modern life is stressful. Bills, work, commuting, politics, exercise that you hate – it all adds up and it doesn’t seem to let up or go away. And if it becomes too much for you to handle (I know it’s too much for me at times), your body will have a physiological, inflammatory response to emotional stress.
Lack of down time: When you’re always on the computer, always checking your email/Facebook/smartphone, you are always “on.” You may think you’re relaxing because your body is stationary, but you’re not relaxing.
Lack of nature time: We spend too much time contained in cubicles, cars, trains, and cities, away from trees, leaves, and soft earth. In a way, nature is home for us. Going home certainly has its measured benefits.
Poor gut health: The gut houses the bulk of the human immune system. When it’s unhealthy, so is your inflammatory regulation. A healthy gut is also selectively permeable, allowing beneficial compounds passage into the body and keeping toxins out. An unhealthy gut often becomes leaky, allowing toxins into the body to stimulate an immune, inflammatory response.
Poor acute stressor/chronic stress ratio: We respond far better to acute stressors than repeated, sustained stress – even if the latter is of a lower intensity.

See what I mean? Since we’re set up for acute stressors requiring an acute inflammatory response, all this other low-level, evolutionarily-discordant, superficially mild stuff set against a backdrop of misaligned fatty acid ratios and impaired gut health throws us off and sets us up for a lifetime of chronic inflammation.

Inflammation is a complex physiological process that can go wrong in a lot of ways. But luckily, sticking to the tried and true dietary and lifestyle measures will get you most of the way toward preventing inflammation from becoming chronic and untamed.

If you have any further questions about inflammation, fire away down below! Thanks for reading.