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Stress Biomarkers and Consequences Part 7: Biomarkers of Stress Overview

Welcome to part 7 of the ODX Stress Biomarkers Series. In this post, the ODX Research team the major biomarkers and patterns associated with stress, including those reflecting acute and chronic stress, oxidative stress, and inflammation.

The ODX Stress Biomarkers Series

  1. Stress Part 1: A Quick Overview
  2. Stress Part 2: How Do We Get Stressed Out?
  3. Stress Part 3: The Physiology of Stress
  4. Stress Part 4: Hormonal Control of the Stress Response
  5. Stress Part 5: Identifying Stress
  6. Stress Part 6: Disorders Associated with Stress
  7. Stress Part 7: Biomarkers of Stress Overview
  8. Stress Part 8: Biomarkers of Stress, Individual Markers
  9. Stress Part 9: Addressing Stress: Can We Treat It or Beat It?
  10. Stress Part 10: Nutrition and Stress
  11. Stress Part 11: Optimal Takeaways

Biomarkers of Stress - Overview

A biomarker reflects underlying physiology and reflects either homeostasis or dysfunction. Blood chemistry biomarkers that reflect HPA axis activity and the physiological stress response include cortisol and DHEA/DHEA-S, corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), anti-diuretic hormone (also known as vasopressin or arginine vasopressin), epinephrine, norepinephrine, and aldosterone. Prolonged stress can also prolong disruption to the HPA axis and promote metabolic and cardiovascular consequences.[1]

Examples of the association between biomarker changes and stress include: [2]

  • Four weeks of intense combat training, a source of stress, were found to increase serum IL-6, TNF-a, and cortisol. These changes were associated with gastrointestinal distress.
  • Elevated cortisol in healthy adults predicted the development of hypertension up to three years later.
  • In a group of breast cancer patients, stress management, yoga, and meditation were found to reduce proinflammatory cytokines.

Ultimately, stress manifests as an increase in blood glucose, blood pressure, heart rate, cardiac contractility, and pupil dilation, and a decrease in gastrointestinal function. Prolongation of this sympathetic nervous system activation can become detrimental and damage tissues and organs.[3]

Biomarker Changes and Stress

The stress response is characterized by measurable biochemical changes including:[4] [5] [6] [7] [8] [9] [10] [11]

Increased

  • ACTH
  • Advanced glycosylation products
  • Aldosterone
  • Antidiuretic hormone (vasopressin)
  • Catalase
  • Copeptin
  • Clotting factors
  • Corticotropin-releasing hormone
  • Cortisol
  • DHEA (increases acutely)
  • Epinephrine and norepinephrine
  • Glucagon
  • Glucose
  • Glutathione peroxidase
  • Growth hormone (physical stress)
  • Hemoglobin A1C
  • Histamine
  • Inflammatory cytokines
  • Isoprostanes
  • Malondi-aldehyde
  • Myelo-peroxidase
  • Oxidized glutathione  
  • Oxidized LDL
  • Oxytocin
  • Prooxidant enzymes
  • Protein carbonyl groups (from cell membrane lipid oxidation)
  • NADPH oxidase
  • Renin
  • Superoxide dismutase
  • T3, T4 (Graves’)
  • Thiobarbituric acid-reactive substances (TBARS)
  • Uric acid
  • White blood cells
  • Xanthine oxidase

Decreased

  • Acetylcholine
  • Albumin (acute stress)
  • Basophils
  • Bilirubin
  • Gonadotropins
  • Growth hormone (prolonged psychological stress)
  • Insulin
  • Lysozyme
  • Prolactin (may increase or decrease)
  • Reduced glutathione
  • Secretory IgA  
  • TSH and T3, T4 in non-Graves’
  • Thyroid-binding globulin (major stress)

Biomarker Patterns of Adrenal Stress and Exhaustion

Recognition of the patterns associated with acute or chronic stress may help address which phase of the stress response an individual is experiencing. Note the biomarker shifts as one transitions from acute to chronic stress:

Acute stress, adrenal hyperfunction:

  • Elevated catecholamines, ACTH, cortisol, DHEA (initially), aldosterone, sodium, chloride, sodium:potassium ratio
  • Decreased potassium
  • Decreased triglycerides and cholesterol (though they may increase acutely as well)

Chronic stress, adrenal hypofunction:

  • Elevated ACTH, potassium, triglycerides, cholesterol
  • Decreased cortisol, DHEA, aldosterone, sodium, chloride

The biochemical changes associated with stress clearly reflect the body’s shift into fight or flight mode and the mobilization of resources to fuel this response. It is important to resolve the changes that take place during acute stress and support the changes that can occur with prolonged stress and exhaustion Healthy lifestyle changes can factor into both stages.

References

[1] Burford, Natalie G et al. “Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System.” International journal of molecular sciences vol. 18,10 2150. 16 Oct. 2017, doi:10.3390/ijms18102150

[2] Nater, Urs M et al. “Biomarkers of stress in behavioural medicine.” Current opinion in psychiatry vol. 26,5 (2013): 440-5. doi:10.1097/YCO.0b013e328363b4ed

[3] Piazza, Jennifer R et al. “Frontiers in the use of biomarkers of health in research on stress and aging.” The journals of gerontology. Series B, Psychological sciences and social sciences vol. 65,5 (2010): 513-25. doi:10.1093/geronb/gbq049

[4] Dhama, Kuldeep et al. “Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values.” Frontiers in molecular biosciences vol. 6 91. 18 Oct. 2019, doi:10.3389/fmolb.2019.00091

[5] Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.

[6] Singh, K. "Nutrient and stress management." J Nutr Food Sci 6.4 (2016): 528.

[7] Noland, Diana, Jeanne A. Drisko, and Leigh Wagner, eds. Integrative and functional medical nutrition therapy: principles and practices. Springer Nature, 2020.

[8] Ranabir, Salam, and K Reetu. “Stress and hormones.” Indian journal of endocrinology and metabolism vol. 15,1 (2011): 18-22. doi:10.4103/2230-8210.77573

[9] Vita, Roberto et al. “Stress triggers the onset and the recurrences of hyperthyroidism in patients with Graves' disease.” Endocrine vol. 48,1 (2015): 254-63. doi:10.1007/s12020-014-0289-8

[10] Wardle, Jon, and Jerome Sarris. Clinical naturopathy: an evidence-based guide to practice. Elsevier Health Sciences, 2019. 3rd edition.

[11] Noushad, Shamoon et al. “Physiological biomarkers of chronic stress: A systematic review.” International journal of health sciences vol. 15,5 (2021): 46-59.

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