The Role of Inflammation in Fatigue

Fatigue remedies that address inflammation are key to getting your energy back.

woman exhausted at her laptop

A problem with inflammation could be the cause of your excessive tiredness.

© Ginasanders |

As a doctor, I hear this question a lot. When a patient asks me, “Why am I tired all the time?” I think of inflammation. It may surprise you, as it does many of my patients, that you could have a problem with inflammation and not even know it, and that it could be the cause of your excessive tiredness. When there is fatigue, inflammation is usually the reason. Fatigue remedies that address inflammation are key to getting your energy back.

This type of inflammation is often described as “silent,” “low-grade,” “chronic,” and “systemic” because it is relatively mild and is present throughout the entire body for long stretches of time. Compare this to the kind of acute inflammation you would notice with, say, a severely sprained ankle, which is characterized by heat, redness, and swelling in the localized area around the ankle.

Does Inflammation Cause Fatigue?

So how can inflammation make you tired? Medical researchers have known for some time now that low-level inflammation over time is deleterious and is connected to diabetes, increased risk of cardiovascular disease, cancer and other chronic illnesses. Newer evidence also links chronic inflammation to chronic fatigue syndrome, depression, and general fatigue. In fact, there has been an explosion in recent knowledge of the pathways and mechanisms by which inflammation levels can influence your body, brain, and even your behavior, leading to fatigue. [12]

Numerous studies show that chronically fatigued individuals have significantly higher blood markers of inflammation, such as the protein known as C-reactive protein (CRP) and other pro-inflammatory compounds known as cytokines.[1,2] In addition to general fatigue, higher levels of CRP and certain pro-inflammatory cytokines are associated with other symptoms linked with excessive tiredness, such as fatigue following physical exertion, as well as poorer physical performance and poorer self-rated health.[3,4]

Compared to people who feel well, blood levels of CRP are higher both in those who meet the strict definition of chronic fatigue syndrome (CFS) and in those with chronic fatigue who do not meet the diagnostic criteria for CFS.[5,6] In a sample of 70-year old women, CRP levels were 40% higher in those with fatigue compared to those without fatigue.[7] Many other fatigue-related conditions, such as depression, type 2 diabetes, being a breast cancer survivor, and routinely getting inadequate (less than six hours) sleep, are also associated with higher CRP levels.[8,9,10]

One interesting recent study showed one way in which inflammation likely interacts with the brain and the nervous system in causing fatigue. Researchers think inflammation may be the cause of the decreased activation of the brain’s reward center, known as the basal ganglia, seen in patients with CFS. In studying a group of CFS patients, they have found that the lower the basal ganglia’s activation, the higher fatigue level.[11] The basal ganglia at the base of the brain help control motion and motivation and are vulnerable to the effects of pro-inflammatory compounds made by the body known as cytokines.

In addition to affecting the brain and nervous system, inflammation promotes fatigue through many biological pathways involving the immune system, mitochondria, oxidative stress, and the stress-response system known as the HPA axis. Each of these systems has been implicated in chronic inflammation and the symptom of excessive tiredness.

How to Treat Exhaustion or Fatigue Due to Inflammation

So, in answer to the question, “Does inflammation cause fatigue?” it is most likely the primary underlying cause. The good news is that chronic inflammation is not only easy to test for, it is most effectively treated using natural and lifestyle therapies involving nutrition, stress reduction techniques, exercise, lifestyle changes, and supplements. No drugs or surgeries are typically needed. If you want to test your own blood for its C-reactive protein level (general inflammation level), you can do so inexpensively using one of the direct access laboratories such as LEF or US BioTek. In part 2 of this article, we explore some of the causes of chronic inflammation as well as some of these natural fatigue-beating, anti-inflammatory therapies in greater detail.

[1] Spence VA, Kennedy G, Belch JJ, Hill A, Khan F. Low-grade inflammation and arterial wave reflection in patients with chronic fatigue syndrome. Clin Sci (Lond). 2008 Apr;114(8):561-6.

[2] Raison CL, Lin JM, Reeves WC. Association of peripheral inflammatory markers with chronic fatigue in a population-based sample. Brain Behav Immun. 2009 Mar;23(3):327-37.

[3] Brinkley TE, Leng X, et al. Chronic inflammation is associated with low physical function in older adults across multiple comorbidities. J Gerontol A Biol Sci Med Sci. 2009 Apr;64(4):455-61.

[4] Christian LM, Glaser R, et al. Poorer self-rated health is associated with elevated inflammatory markers among older adults. Psychoneuroendocrinology. 2011 Nov;36(10):1495-504.

[5] Maes M, Twisk FN, Kubera M, Ringel K. Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin. J Affect Disord. 2012 Feb;136(3):933-9.

[6] Valentine RJ, McAuley E, et al. Sex differences in the relationship between obesity, C-reactive protein, physical activity, depression, sleep quality and fatigue in older adults. Brain Behav Immun. 2009 Jul;23(5):643-8.

[7] Orre IJ, Reinertsen KV, et al. Higher levels of fatigue are associated with higher CRP levels in disease-free breast cancer survivors. J Psychosom Res. 2011 Sep;71(3):136-41.

[8] Faraut B, Boudjeltia KZ, et al. Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery. Sleep Med Rev. 2012 Apr;16(2):137-49.

[9] Lasselin J, Layé S, et al. Fatigue symptoms relate to systemic inflammation in patients with type 2 diabetes. Brain Behav Immun. 2012 Mar 25. [Epub ahead of print] PubMed PMID: 22469909.

[10] Unger ER, et al. Decreased basal ganglia activation in chronic fatigue syndrome subjects is associated with increased fatigue. FASEB 2012. Abstract 4833.

[11] Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther. 2011 May;130(2):226-38.

[12] Naik E, Dixit VM. Mitochondrial reactive oxygen species drive proinflammatory cytokine production. J Exp Med. 2011 Mar 14;208(3):417-20.

[13] Salminen A, Ojala J, et al. Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases. Cell Mol Life Sci. 2012 Mar 25. [Epub ahead of print] PubMed PMID: 22446749.

This post was published in 2012 and has been updated. 

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UHN Staff

University Health News is produced by the award-winning editors and authors of Belvoir Media Group’s Health & Wellness Division. Headquartered in Norwalk, Conn., with editorial offices in Florida, Cleveland, Pittsburgh, … Read More

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