Sensible advice for aches, pains & injuries

Chronic, Subtle, Systemic Inflammation

A possible insidious cause of mysterious chronic pain

by Paul Ingraham, Vancouver, Canadabio
I am a science writer and a former Registered Massage Therapist with a decade of experience treating tough pain cases. I was the Assistant Editor of for several years. I’ve written hundreds of articles and several books, and I’m known for readable but heavily referenced analysis, with a touch of sass. I am a runner and ultimate player. • more about memore about
Close-up photograph of hot coals, representing inflammation.


Chronic, subtle, systemic inflammation is a possible factor in stubborn musculoskeletal pain. It can have many underlying causes, from bad genes to mild autoimmune disease (including allergies), smoking or other severe biological stresses, infections, and even just getting old (known as “inflammaging”). The greatest culprit is metabolic syndrome: a set of biological dysfunctions strongly linked to poor fitness, obesity, aging, and likely emotional stress and sleep disturbance as well.

full article 2500 words

Do you seem to have more than your fair share of aches and pains? It’s probably not your imagination, and there are many possible explanations for it, but this article is about one of the most insidious and interesting. It’s most relevant to you if you’re struggling with your weight and/or severe chronic stress… or if you’re just getting older. So really quite a lot of people.

Everyone over 40 knows that it gets more uncomfortable to get out of beds and chairs as we age, and we’re plagued by ever more pains that come and go without much rhyme or reason. Most people chalk this all up to “arthritis,” but that’s rarely a significant factor until much later in life.1 Conditions like fibromyalgia and myofascial pain syndrome, as common as they are, can’t account for all of it. Some medications cause widespread sensitivity as a side effect,2 but that still doesn’t explain such a widespread problem either. So what’s going on?

A little bit of inflammation spread all over the place is one possible culprit. And I have to strongly emphasize that this is an unproven idea, and there is plenty of guessing in this article: well-informed and evidence-based guessing, but guessing.

Chronic low grade inflammation is increasingly seen as a part of other orthopaedic conditions such as osteoarthritis — once considered a ‘cold’ wear and tear problem (as opposed to the far more overt and ‘hot’ inflammation of rheumatoid arthritis).

Summer is coming — Frozen Shoulder, Cocks (

Why would anyone be a little bit inflamed all over?

Chronic low-grade inflammation might happen as a consequence of “metabolic syndrome,” [NIH] a set of biological dysfunctions strongly linked to poor fitness, obesity, and aging. We know that metabolic syndrome is associated with at least some common pain problems, like neck pain.3

Metabolic syndrome may also be linked to severe chronic stress.4 If true, it means that metabolic syndrome could affect millions of people who would not otherwise be likely victims. But this is quite speculative.

Much less speculative: aging itself seems to be inflammatory — no matter how fit, skinny, and calm you are. This is known as “inflammaging.”5

Another possibility, more speculative again, is that chronic low-grade inflammation could be a symptom of mild autoimmune disease — diseases where our immune systems attacks our own tissues, the “why are you hitting yourself?” diseases.6 This could also have something in common with metabolic syndrome and aging, but it’s unknown.

Finally, there’s now good evidence that inflammaging is probably related to the gradual weakening of the immune system, which slowly allows some common minor infections to “reactivate” after lying dormant in our cells for years or even decades.7

If you’re on the far side of middle age, or you’re younger but struggling with your weight and/or major long-term stress, chronic inflammation could be your issue.

Can low-grade inflammation be diagnosed with blood tests?

Probably not easily, by definition, since the heart of the idea is that it’s a subtle problem. There are blood tests that are quite sensitive to inflammation, but — because biology is messy — they are not super reliable, and even people with serious inflammatory diseases do not always get a clear result. Nevertheless, it’s worth asking your doctor. Check your “CRP” (C-reactive protein). This is a common and easy test, and who knows: you might discover that you have not-so-low-grade inflammation.

Inflammation versus sensitization (fibromyalgia)

The pain of fibromyalgia. [Mayo] is caused by an unexplained neurological dysfunction, and results in widespread oversensitivity to stimuli, among other things. It is stigmatized and overdiagnosed,8 and all too often it is used as a way to dismiss the complaints of people who have unexplained pain, with the insinuation that they are “sensitive” or “dramatic” and don’t really have anything “real” wrong with their tissues. Of course this is great disservice to patients who don’t really have fibromyalgia and those who actually do.

You’re not paranoid if they’re really after you & you’re not “sensitive” if you’re actually inflamed.

But you’re not paranoid if they’re really after you, and you’re not “sensitive” if you’re actually inflamed. The pain of widespread inflammation is fundamentally different from the pain of fibromyalgia, yet the result is identical. Fibromyalgia is indeed a kind of sensitivity — the nervous system is over-reacting to stimuli. But inflammation constitutes an actual insult to tissues. Molecules produced by immune system activity, normally associated with infection and injury, are stimulating nerve endings (nociception). The information is sent to the spinal cord and brain for consideration, where the experience of pain may or may not be generated (but it probably will be).

Subjectively, it is effectively impossible to tell the difference between the pain of an oversensitive nervous system and the pain of a nervous system that is actually detecting inflammation all over.9

And then of course there is the ominous possibility that you could have both things going on. And even worse still: it is also possible that constant exposure to the irritation of chronic systemic inflammation could actually cause fibromyalgia.

What can you do about inflammation and inflammaging?

No one really knows, of course, and quite possibly nothing. But here are some ideas…

Fitness: Undoubtedly critical! Regular moderate exercise really is the closest thing we have to a miracle drug or a fountain of youth.

Anti-inflammatory nutrition: It’s also possible to some extent to eat an “anti-inflammatory” diet — which isn’t as impressive as it sounds. It basically just means a healthy diet, particularly one that doesn’t give our system major blood sugar regulation challenges.

Ketogenic diets and fasting: Might be worth experimenting with. More below.

Reduce stress: Even though it’s not confirmed that there is a link between stress and inflammation, stress management has so many benefits that it is well pursuing regardless. You don’t have to meditate or do yoga (unless you want to). Often the best place to begin is troubleshooting major sources of chronic stress, like insomnia or anxiety.

Quitting bad habits: Consider finally ditching habits that are putting a strain on your biology, especially smoking (of course, smoking is a well known independent risk factor for pain), or drinking too much too regularly (anything more than a couple per day). Any kind of “hard living” is suspect. Coffee in reasonable doses, mercifully, is not an obvious suspect (it doesn’t dehydrate you, for instance10) — but if you’re drinking so much that it’s aggravating emotional stress with caffeine-powered agitation and anxiety, that’s another matter.

Reducing inflammation with a ketogenic (very low carb) diet

Diets that force you to mainly burn fat for energy, instead of carbohydrates — a “ketogenic” diet, like the infamous Atkins diet — may be anti-inflammatory and/or de-sensitizing.

Ketogenic diets are so low in carbohydrates (sugars) that they force the body to burn fat for fuel, a novel metabolic state, which is well-known to treat epilepsy in some children. We can infer from that success story that the biology of this treatment might also have an effect on some kinds of inflammation and pain (especially neuropathic pain, the pain of damaged nerves11). Although highly speculative, there are some reasons to think this might work, and some indirect (animal) evidence that it does.12 Like seizures, some kinds of pain may involve “overexcited” neurons, and can be treated with anticonvulsant drugs. Ketone metabolism “produces fewer reactive oxygen species,” a contributor to inflammation; and it produces adenosine signalling, which is a suspected pain-killer in other contexts (exercise, possibly acupuncture).

This is a completely experimental treatment. However, like an anti-inflammatory diet (AKA “healthy”), it has a non-crazy rationale, and it’s safe and inexpensive to dabble in. As long as you don’t get extreme, the worst case scenario is putting up with a fussy and unpleasant change in eating habits. Nevertheless, I am obliged to suggest that you run this by your physician and/or a nutritionist.

You should probably spend at least two to four weeks in a ketogenic state to be sure that you’ve given it an adequate chance. If you see a clear reduction in symptoms, that’s a strong sign that it’s working. In a spirit of moderation, I do not recommend trying to stay in a ketogenic state for any more more than a several weeks at a time, and you should probably take breaks — give your system a rest from ketogenesis once every week or two.

Fasting (or intermittent fasting)

Actual fasting might work simply because it includes ketogenesis, but it’s also harder and not as safe — so I’m less inclined to recommend it. But if you are keen on the idea fasting for whatever reason (e.g. meditative, emotional, spiritual reasons) it’s another possibility to consider. Of course, the subject of fasting is rife with pseudoscience and big claims, but here are two good sources to start with: Martin Berkhan’s (start with his myths of fasting), and Dr. Bojan Kostevski’s thesis paper, “The Effects of Intermittent Fasting on Human and Animal Health.”

About Paul Ingraham

Headshot of Paul Ingraham, short hair, neat beard, suit jacket.

I am a science writer, former massage therapist, and I was the assistant editor at for several years. I have had my share of injuries and pain challenges as a runner and ultimate player. My wife and I live in downtown Vancouver, Canada. See my full bio and qualifications, or my blog, Writerly. You might run into me on Facebook or Twitter.

Related Reading

What’s new in this article?

Added mobile summary, and a “perspective” sidebar warning against snake oily imposters.

Added another plausible explanation for inflammaging: the reactivation or dormant common infections. Also added a citation link metabolic syndrome to neck pain.

Many miscellaneous minor improvements.



  1. Not many middle-aged people have enough arthritis to account for the sheer number of variety of aches and pains that they often report. Arthritic pain is typically well localized to specific joints, and usually not serious in middle age (unless the joint is vulnerable to early arthritis due to an injury). BACK TO TEXT
  2. The main ones to watch out for are the bisphosphonates (Alendronate, risedronate, Actonel, Atelvia) and statins (Lipitor, Crestor, Mevacor, Zocor, Lescol). For more information, see 10 Surprising Causes of Pain. BACK TO TEXT
  3. Mäntyselkä P, Kautiainen H, Vanhala M. Prevalence of neck pain in subjects with metabolic syndrome--a cross-sectional population-based study. BMC Musculoskelet Disord. 2010;11:171. PubMed #20670458. PainSci #53456. This study found that neck pain is prevalent in people with metabolic syndrome. The relationship is definitely not necessarily causal, but it certainly might be. This evidence certainly suggests a need for more research to find out. BACK TO TEXT
  4. Gohil BC, Rosenblum LA, Coplan JD, Kral JG. Hypothalamic-pituitary-adrenal axis function and the metabolic syndrome X of obesity. CNS Spectr. 2001 Jul;6(7):581–6, 589. PubMed #15573024. Prolonged chronic stress can probably contribute to metabolic syndrome by messing with the hormonal balance of the hypothalamic-pituitary-adrenal axis (HPA-axis). BACK TO TEXT
  5. Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4–9. PubMed #24833586. PainSci #53291. “Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging." Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown.” BACK TO TEXT
  6. Autoimmune disease is inflammatory by definition, and is extremely unpredictable. Even full-blown autoimmune diseases are notoriously difficult to diagnose, because they tend to erratically affect many systems. It’s likely that some people have minor autoimmune disease, effectively undiagnosable. It’s not even a case of having “early” autoimmune disease: AD is so unpredictable that it might well permanently back off before getting severe enough to be diagnosed. BACK TO TEXT
  7. Bennett JM, Glaser R, Malarkey WB, et al. Inflammation and reactivation of latent herpesviruses in older adults. Brain Behav Immun. 2012 Jul;26(5):739–46. PubMed #22155500. PainSci #53327. “Persistent pathogens such as latent herpesviruses and chronic bacterial infections can act as a source of inflammation. Herpesviruses, including Epstein-Barr virus (EBV) and cytomegalovirus (CMV), establish latent infections following primary infection and reactivate when the cellular immune system is compromised.” In this study of 222 older adults (~64), activity of these two viruses was associated with more inflammatory markets (CRP and IL-6). “Thus, reactivation of multiple herpesviruses may drive inflammation and could contribute to poorer health among older adults.” BACK TO TEXT
  8. Walitt B, Katz RS, Bergman MJ, Wolfe F. Three-Quarters of Persons in the US Population Reporting a Clinical Diagnosis of Fibromyalgia Do Not Satisfy Fibromyalgia Criteria: The 2012 National Health Interview Survey. PLoS One. 2016;11(6):e0157235. PubMed #27281286. PainSci #53271.The majority of clinically diagnosed fibromyalgia cases in the US do not reach levels of severity necessary and sufficient for diagnosis. The clinical diagnosis of fibromyalgia is disproportionally dependent on demographic and social factors rather than the symptoms themselves. Diagnostic criteria for fibromyalgia appear to be used as a vague guide by clinicians and patients, and allow for substantial diagnostic expansion of fibromyalgia.” BACK TO TEXT
  9. In theory, the way to tell the difference would be the absence of other classic fibromyalgia symptoms like poor quality sleep, fatigue, memory and mood issues — the infamous “fibrofog.” In practice, those are common, messy, and overlapping sensations (even more so in people who’ve had a lot of aches and pains for years). The sensations in an inflamed person could strongly resemble those in someone with fibromyalgia. BACK TO TEXT
  10. Killer SC, Blannin AK, Jeukendrup AE. No evidence of dehydration with moderate daily coffee intake: a counterbalanced cross-over study in a free-living population. PLoS One. 2014;9(1):e84154. PubMed #24416202. PainSci #53892. “These data suggest that coffee, when consumed in moderation by caffeine habituated males provides similar hydrating qualities to water.” BACK TO TEXT
  11. There are two main kinds of pain: nociceptive and neuropathic, or the more familiar pain of tissue damage and the more exotic pain caused by a damaged nervous system. Some pain isn’t easy to classify (fibromyalgia). For more information, see The Basic Types of Pain: Nociceptive, neuropathic, and “other”. BACK TO TEXT
  12. Masino SA, Ruskin DN. Ketogenic diets and pain. J Child Neurol. 2013 Aug;28(8):993–1001. PubMed #23680946. PainSci #53476.

    Ketogenic diets are well established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain.