Options to Accurately Measure the Body’s Stress Response

The hypothalamus-pituitary-adrenal (HPA) axis is a biological system involved in our stress response. In response to stress (physical, mental, real, or imagined), the hypothalamus releases corticotrophin-releasing hormone (CRH), which then triggers the pituitary gland to release adrenocorticotropic hormone (ACTH), which in turn activates the adrenal cortex to release cortisol. When the system works well, a negative feedback loop is in play. This means that when there is too much release of cortisol, the hypothalamus reduces the release of CRH. This helps to ‘turn down’ the release of cortisol. However, if there is not enough cortisol, the hypothalamus will increase its release of CRH.

This negative feedback system is in place to restore levels of various hormones to normal levels. The HPA axis relies on the ‘Goldilocks principle’. Not too much and not too little. It should be just right. Unfortunately, many disorders and conditions seem to have a dysregulated stress response. Some examples include Cushing syndrome (extreme dysregulation), depression, anxiety disorders, some pain conditions, burnout, and sleep disorders.

There are various ways activity in the HPA-axis can be assessed; however, there is no perfect test. In the dexamethasone/corticotropin-releasing hormone test and dexamethasone suppression test, CRH and/or dexamethasone are injected into the body. Changes in ACTH and cortisol then indicate HPA-axis activity. Other tests include measuring 24-hour urinary-free cortisol concentrations, but this test can be cumbersome and generally requires people to remain home for the day. Excess stress on the day of testing could also alter the results. Midnight plasma cortisol levels can be measured, but this requires an overnight stay in a hospital/clinic. Late-night salivary cortisol concentrations can be collected. This can be done at home, but again, concentrations can be altered by stress before testing. Other factors such as food, exercise, light, medications, and illness can also affect cortisol levels. The exact timing of collection also dramatically affects the results as cortisol is released on a circadian rhythm, with the highest concentrations occurring in the morning and lowest levels at night. Therefore, relying on single-point measures on a single day can lead to erroneous conclusions. Another option is to measure the cortisol awakening response (CAR). This involves collecting multiple saliva samples upon awakening, and the rise and fall in cortisol provides an indication of HPA axis activity. However, stress, timing, and sleep quality can affect the CAR.

Increasingly, researchers and clinicians are relying on single cortisol measures to examine changes in HPA axis activity following a treatment. However, as already mentioned, this can lead to inaccurate conclusions. Moreover, decreases in cortisol are often seen as positive and increases as unfavourable. Unfortunately, this does not take into account the HPA-axis Goldilocks principle. In clinical trials, we have been utilising experimental stress procedures to measure activity in the HPA-axis and sympathetic nervous system to measure the stress response. Before and after exposing people to a stressor (e.g., the Maastricht Acute Stress Test), we collect several stress-related measures to see how people respond. This can include changes in cortisol, saliva α-amylase, heart rate, heart rate variability, blood pressure, temperature, sweat responses, and self-rating of stress. Using these combinational measures after exposure to a real-time stressor can help more accurately determine a person’s stress response and assess if an intervention affects this response over time.

How we respond to stress has important implications on physical and mental health, and using reliable measures of this response is essential. If you are interested in conducting a clinical trial examining how your ingredient/ intervention affects the stress response, do not hesitate to contact us to discuss this further. Contact Us Page