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How Do Stress and Inflammation Contribute to Chronic Disease?

The relationship between stress and inflammation has been studied rigorously in the past decade, with researchers finding evidence that the inflammatory pathway is pivotal in the pathogenesis of many chronic diseases.1 In fact, 75% to 90% of human disease is related to stress and inflammation, including cardiovascular and metabolic diseases, and neurodegenerative disorders.1 Studies suggest that chronic stress results in glucocorticoid receptor resistance that, in turn, results in failure to downregulate inflammatory responses.2,3

In this video, IFM educator Patrick Hanaway, MD, describes the role of stress and inflammation in cardiovascular and cardiometabolic health:

Large bodies of research indicate that chronic stress, whether experienced in early life or as an adult, is linked to increased coronary heart disease risk.1,4 In particular, childhood adversity, including physical and sexual abuse in childhood, has been shown to relate to higher morbidity of cardiovascular events in women.5 Work-related stressors, poor sleep, and emotional disturbances have been correlated with adult-related cardiovascular disease.1

A 2018 finding using data from the Jackson Heart Study suggested that in African American adults, global stress (overall stress level) and major life events were associated with increased risk of metabolic syndrome severity, while weekly stress (minor stressors over a week’s time) was not.6 Additionally, men and women’s stress responses varied in severity, with men’s metabolic syndrome severity increasing significantly at lower levels of major life event stress relative to women’s metabolic syndrome severity.6

Chronic psychological stress and inflammation are also associated with a greater risk of depression, autoimmune diseases, upper respiratory infections, and poor wound healing.2 For years, researchers have speculated that disorders of the gastrointestinal tract, such as Crohn’s disease and ulcerative colitis, are related to stress and inflammation,7 but the underlying mechanism remained largely unresolved. A groundbreaking 2018 study in mice suggests a clue, showing that chronic stress disturbs gut microbiota, triggering an immune system response and facilitating dextran sulfate sodium-induced colitis.8

With a wide range of chronic diseases on the rise, how can Functional Medicine clinicians target stress-related factors with interventions that improve the health of their patients? Accumulating evidence points to the beneficial effects of regular exercise in preventing or improving the metabolic and psychological comorbidities brought about by chronic stress.9 A recent meta-analysis indicates that physical exercise improves the inflammatory state in children with obesity; however, it is unclear whether this effect can reduce the risk of cardiovascular and metabolic diseases in adulthood.10

In 2017, a first-of-its-kind study on yoga and meditation showed improvement in biomarkers of cellular aging, which are associated with oxidative stress and complex lifestyle diseases like depression, diabetes, and cardiovascular disease.11 The researchers suggested that the improvement in stress and inflammatory response was mediated by changes in cortisol, ?-endorphin, IL-6, and other factors, with regulation by changes in the brain through the hypothalamic-pituitary-adrenal (HPA) axis.11

Many diseases stemming from chronic stress and inflammation have early warning signs, meaning some cases can be prevented or improved with lifestyle changes that help manage stress. The Functional Medicine model focuses in on identifying specific interventions like exercise, meditation, and yoga that work for the individual patient. Tools such as the Functional Medicine Timeline can also help clinicians identify areas of life where stress may be problematic and design treatments that focus on improving stress management.

Learn more about the research connecting stress and inflammation to disease and how Functional Medicine can help patients with chronic conditions at Applying Functional Medicine in Clinical Practice (AFMCP).

Learn More about Applying Functional Medicine in Clinical Practice (AFMCP)

References

  1. Liu YZ, Wang YX, Jiang CL. Inflammation: the common pathway of stress-related diseases. Front Hum Neurosci. 2017;11:316. doi:10.3389/fnhum.2017.00316.
  2. Cohen S, Janicki-Deverts D, Doyle WJ, et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci U S A. 2012;109(16):5995-5999. doi:10.1073/pnas.1118355109.
  3. Miller GE, Cohen S, Ritchey AK. Chronic psychological stress and the regulation of pro-inflammatory cytokines: a glucocorticoid-resistance model. Health Psychol. 2002;21(6):531-541.
  4. Su S, Jimenez MP, Roberts CTF, Loucks EB. The role of adverse childhood experiences in cardiovascular disease risk: a review with emphasis on plausible mechanisms. Curr Cardiol Rep. 2015;17(10):88. doi:10.1007/s11886-015-0645-1.
  5. Rich-Edwards JW, Mason S, Rexrode K, et al. Physical and sexual abuse in childhood as predictors of early-onset cardiovascular events in women. Circulation. 2012;126(8):920-927. doi:10.1161/CIRCULATIONAHA.111.076877.
  6. Cardel MI, Min YI, Sims M, et al. Association of psychosocial stressors with metabolic syndrome severity among African Americans in the Jackson Heart Study. Psychoneuroendocrinology. 2018;90:141-147. doi:10.1016/j.psyneuen.2018.02.014.
  7. Pereira C, Gracio D, Teixeira JP, Magro F. Oxidative stress and DNA damage: implications in inflammatory bowel disease. Inflamm Bowel Dis. 2015;21(10):2403-2417. doi:10.1097/MIB.0000000000000506.
  8. Gao X, Cao Q, Cheng Y, et al. Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response. Proc Natl Acad Sci U S A. 2018;115(13):E2960-E2969. doi:10.1073/pnas.1720696115.
  9. Tsatsoulis A, Fountoulakis S. The protective role of exercise on stress system dysregulation and comorbidities. Ann N Y Acad Sci. 2006;1083:196-213. doi:10.1196/annals.1367.020.
  10. Sirico F, Bianco A, D’Alicandro G, et al. Effects of physical exercise on adiponectin, leptin, and inflammatory markers in childhood obesity: systematic review and meta-analysis [published online May 15, 2018]. Child Obes. doi:10.1089/chi.2017.0269.
  11. Tolahunase M, Sagar R, Dada R. Impact of yoga and meditation on cellular aging in apparently healthy individuals: a prospective, open-label single-arm exploratory study. Oxid Med Cell Longev. 2017;2017:7928981. doi:10.1155/2017/7928981.

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