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How Do Stress and Inflammation Contribute to Chronic Disease?

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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:

Patrick Hanaway, MD, is a board certified family physician who teaches on the clinical application of nutritional biochemistry, with an emphasis on digestion, immunology, mitochondrial function, and wellness. Dr. Hanaway is the former medical director of the Center for Functional Medicine at the Cleveland Clinic.

The Impact of Stress

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

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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 (MetS) severity, while weekly stress (minor stressors over a week’s time) was not.6 Additionally, men and women’s MetS and stress responses varied in severity. For example, men significantly increase their MetS severity at medium levels of stress, whereas women significantly increase their MetS severity at high levels of stress.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 In a large study published in 2019 in the journal Molecular Psychiatry, a team of researchers from Cambridge examined the link between depression and coronary heart disease.7 Their findings suggest that the connection between these two conditions cannot be explained by a common genetic predisposition; rather, it is environmentally related. They used Mendelian randomization to investigate 15 biomarkers associated with the risk of coronary heart disease; of these biomarkers, they found that triglycerides and the inflammation-related proteins IL-6 and CRP were also risk factors for depression. What’s more, the authors note that with regard to shared environmental factors, the depression–coronary heart disease comorbidity could be linked with early-life factors influencing inflammatory regulation, such as impaired fetal development or childhood maltreatment/trauma. Low birth weight and childhood maltreatment are associated with increased levels of circulating inflammatory markers, depression, and coronary heart disease in adulthood.7

“Taking a holistic view of a person’s health—such as looking at heart disease and depression together—enables us to understand how factors like traumatic experiences and the environment impact on both our physical and mental health,” said Dr. Sophie Dix, director of research at MQ, in a press release issued by the University of Cambridge.8

Similarly, researchers have for years speculated that disorders of the gastrointestinal tract, such as Crohn’s disease and ulcerative colitis, are related to stress and inflammation,9 but the underlying mechanism remained largely unresolved. An elegant 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.10

Managing Stress

With a wide range of stress-related 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.11 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.12

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.12 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.13

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 stress as a cause of dysfunction and utilizing 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.

For more information about inflammation and stress in the body, consider reading the following IFM-authored articles.

Learn More About Functional Medicine

Beneficial effects of meditation on inflammation

The microbiome, stress hormones, and gut function

Making connections: chronic stress, pain, and addiction

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. Khandaker GM, Zuber V, Rees JMB, et al. Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort. Mol Psychiatry. Published online March 19, 2019. doi:10.1038/s41380-019-0395-3
  8. University of Cambridge. Inflammation links heart disease and depression, study finds. Published March 19, 2019. Accessed October 10, 2019. https://www.cam.ac.uk/research/news/inflammation-links-heart-disease-and-depression-study-finds
  9. Pereira C, Grácio 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
  10. 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
  11. 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
  12. 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. Child Obes. 2018;14(4):207-217. doi:10.1089/chi.2017.0269
  13. 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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