The circadian rhythm influences many factors in the human body, including sleep-wake cycles, hormone production and release, hunger and satiety, mood, digestion, the immune system, and body temperature. As such, any dysfunction within this process increases the risk for long-term sequelae and chronic disease.
A normal, healthy rhythm begins with the cortisol awakening response (CAR). Upon waking in the morning, light enters the eyes and triggers the suprachiasmatic nucleus (SCN) in the brain to signal the adrenal glands to begin cortisol production. Immediately, cortisol levels rise sharply for the next 30-45 minutes, followed by a recovery period where cortisol gradually declines throughout the day. If the CAR is unable to properly rise and recover, several conditions and symptoms can arise, such as low energy, decreased alertness, poor resiliency, depression, anxiety, inflammation, blood sugar dysfunction, autoimmune development, and more.1-4 Add the stress of a global pandemic, and things can really take a turn for the worse.
Traditionally, cortisol is tested in serum, however, it only provides a single point in the day with a combination of free and bound cortisol in the results. Understanding this number is important because the free levels are active. As salivary testing became more widely available (followed by dried urine) it allowed for a sample to be taken on waking, two hours later (or at lunch), at dinner, and before bed. This gives a more comprehensive, broad sweeping view of the 4-point daily rhythm.
While cortisol testing throughout the day is important to understand the overall circadian rhythm, in some cases, it is even more critical to focus on the CAR, which requires more specific testing. The CAR is a discreet and distinct component of the circadian rhythm and is unrelated to the HPA axis cortisol signaling throughout the rest of the day.5 The CAR is a measure of overall HPA axis resiliency and can be viewed as an HPA axis “mini-stress test.”5,6
A true CAR assessment requires salivary samples to be collected at the “moment of waking,” and twice more at 30 and 60 minutes after waking. Salivette® collection devices make salivary sampling easy, convenient, and not stressful, which is critical to accurate results. As opposed to the typical (and sometimes difficult) process where saliva is supposed to drip into the collection device (most individuals spit), using Salivettes® is much easier. The included swab is placed in the mouth until saturated, then placed back in the collection device. To continue to evaluate the daily rhythm, a fourth collection is taken at dinner and a fifth before bed. In some cases, a sixth sample can be collected in the middle of the night if the patient suffers from insomnia.
This hyper-focused view of the cortisol rhythm, specifically the CAR, adds an important element of information for practitioners to personalize patient treatment plans. For example, a low CAR could increase the risk of autoimmune development through the glucocorticoid induced thymocyte apoptosis process, which relies on the waking spike in cortisol levels to work efficiently.3 This information is important to know when working with patients suffering from autoimmune diseases and struggling with worsening or progressing symptoms. Part of the treatment protocol focuses on improving the morning surge in cortisol.
In contrast, high CAR results could indicate major anticipatory stress.7 For patients struggling with feelings of anxiety, uneasiness, and fight-or-flight, this information is useful to determine the “why” behind their symptoms while allowing for appropriate lifestyle and supplemental interventions.
By taking the philosophy of “test, don’t guess,” and specifically looking at the health of the cortisol awakening response (CAR), practitioners can truly evaluate the health of the HPA axis and create personalized treatment plans that best fit their patients’ needs.
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Carrie Jones, ND, FABNE, MPH
Dr. Carrie Jones is an internationally recognized speaker, consultant, and educator on the topic of women's health and hormones. Dr. Jones graduated from the National University of Natural Medicine (NUNM) in Portland, Oregon where she also completed a two-year residency in women's health, hormones and endocrinology. Later, she graduated from Grand Canyon University's Master of Public Health program. Recently, Dr. Jones became board-certified through the American Board of Naturopathic Endocrinology. She was adjunct faculty at NUNM for many years, teaching gynecology and advanced endocrinology/fertility. While in practice, Dr. Jones served as medical director for two large integrative clinics in Portland. She has served as the medical director for Precision Analytical, Inc. and is currently the head of medical education at Rupa Health.
1 Contreras C and Gutierrez-Garcia A. Cortisol Awakening Response: An Ancient Adaptive Feature. Journal of Psychiatry and Psychiatric Disorders. 2 (2018): 29-40.
2. Ennis GE, Moffat SD, Hertzog C. The cortisol awakening response and cognition across the adult lifespan. Brain and cognition. 2016; 105:66-77.
3. Rocamora-Reverte L, et al. T-cell autonomous death induced by regeneration of inert glucocorticoid metabolites. Cell Death & Disease. 2017;(8): https://doi.org/10.1038/cddis.2017.344
4. Sephton SE. Diurnal Cortisol Rhythm as a Predictor of Breast Cancer Survival. 2000; 92(12):994-1000.
5. Smith RL, Soeters MR, Wust RCI, Houtkooper RH. Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease. Endocrine reviews. 2018; 39(4):489-517.
6. Taff CC, Vitousek MN. Endocrine Flexibility: Optimizing Phenotypes in a Dynamic World? Trends in Ecology & Evolution. 2016; 31(6):476-488
7. Powell DJ, Schlotz W. Daily life stress and the cortisol awakening response: testing the anticipation hypothesis. PloS one. 2012; 7(12):e52067.