By Kim Ross, DCN, CNS, LDN, IFMCP⁺

Cortisol: How It Shapes Occasional Anxiety and Mood

1. Introduction
2. Overview of the HPA Axis
3. Spotlight on Cortisol -The Master Stress Hormone
4. Recognizing Symptoms of High Cortisol
5. Pure Encapsulations Nutrient Solutions
6. Conclusion
7. Resources

Introduction

Stress and occasional anxiousness are increasingly common experiences in today's high-demand world. A poll conducted in 2024 by the American Psychiatric Association revealed that 43% of adults in the United States experience increased feelings of anxiousness, with 53% of those polled attributing this feeling to stress.¹ Although short-term stress responses are adaptive and essential for survival, dysregulated stress responses can significantly impact mood and mental clarity. Central to this physiological stress response is the hormone cortisol.

This blog highlights how cortisol, particularly when levels fluctuate, becomes an underlying driver of changes in mood and emotion. It will also provide targeted, evidence-based interventions that healthcare providers may consider for patients experiencing occasional anxiousness due to stress.

Overview of the Hypothalamus-Pituitary-Adrenal (HPA) Axis

The HPA axis is the body's primary neuroendocrine pathway for responding to stress, governed by a multi-layer negative feedback system. Signaling begins in the hypothalamus, which consolidates internal and external signals to determine the overall "threat" to the body. The hypothalamus releases corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in response to a perceived, physical or emotional stressor.

Next, CRH stimulates the anterior pituitary to secrete adrenocorticotropic hormone (ACTH). The pituitary gland comprises the posterior, intermediate and anterior lobes, each responsible for releasing multiple hormones.

Finally, the release of ACTH prompts the adrenal glands to produce cortisol and dehydroepiandrosterone (DHEA) in the adrenal cortex and to release two catecholamines, epinephrine (adrenaline) and norepinephrine (noradrenaline), from the adrenal medulla.

Once the "threat" (stress) is removed, a negative feedback loop reduces CRH and ACTH production, lowering cortisol levels and returning the system to homeostasis.

While this system is adaptive in the short term, chronic activation of the HPA axis leads to sustained cortisol production, as seen in prolonged stress states. Over time, this can impair receptor sensitivity and disrupt the negative feedback loop, resulting in cortisol fluctuation. Long-term, this fluctuation has been associated with emotional lability, poor resilience, fatigue, cognitive fog, increased cytokine production, changes of glycemic control and circadian rhythm disturbances.^2,3

Spotlight on Cortisol: The Master Stress Hormone

Cortisol is a steroid hormone, specifically a glucocorticoid, synthesized in the zona fasciculata of the adrenal cortex. It exerts its effects by binding to glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs), which are widely distributed throughout the central nervous system and peripheral tissues.⁴

Cortisol prepares the body for a "fight or flight" response. It increases blood glucose levels, enhances alertness and temporarily suppresses non-essential processes like digestion and reproduction. DHEA, also produced in the adrenal cortex, is a modulating hormone that buffers the effects of increased cortisol.^3,4

Functions of Cortisol

Cortisol plays a vital role in many physiological processes since most cells in the body have glucocorticoid receptors (GRs).²

Diurnal Cortisol Rhythm

Cortisol follows a distinct circadian rhythm governed by the suprachiasmatic nucleus (SCN) of the hypothalamus. This rhythm includes:^2,4

• A sharp increase within 30 – 45 minutes after waking (the cortisol awakening response, or CAR). A healthy cortisol awakening response can cause a 35-60% rapid increase in cortisol production, followed by a decline within 60 minutes.
• A gradual decline continues throughout the day, reaching its lowest point near midnight.

Of importance, cortisol has an inverse relationship with melatonin, commonly called the sleep hormone.

When Cortisol Fluctuates: Its Impact on Mood

When cortisol regulation changes, either through hypersecretion, receptor desensitization or circadian misalignment, the consequences of mood regulation can be profound.

Elevated cortisol patterns have been linked to³:

• Changes of the HPA axis leads to ongoing elevations in cortisol.
• Disruptions in the production of the inhibitory neurotransmitters GABA and serotonin, which are responsible for creating a sense of calmness.
• Changes in brain structure and function, particularly in the area responsible for mood regulation.
• Hypersensitivity to stressors with increased vigilance and threat perception, leading to increased anxious feelings

The Bi-Directional Relationship Between Cortisol and Occasional Anxiety

Prolonged psychological or physiological stress activates the HPA axis, leading to sustained cortisol secretion. The ongoing elevation of cortisol can cause changes to key brain regions involved in mood and emotional regulation, heightening vigilance, worry and symptoms of anxiousness. This state of occasional anxiousness, in turn, acts as a persistent internal stressor, perpetuating further HPA axis activation and continued cortisol release.

The result is a self-reinforcing feedback loop.

Recognizing Symptoms of High Cortisol

Biomarker assessment (e.g., salivary cortisol curve including CAR) may help evaluate diurnal rhythm and identify disruptions. Integrating this data with symptom patterns can help guide personalized nutrition and lifestyle strategies to support healthy HPA axis function.

Pure Encapsulations Nutrient Solutions

Daily Calm combines GABA with clinically backed saffron (affron^®), ashwagandha (KSM-66^®) and l-theanine (Suntheanine^®) to relieve feelings of occasional stress and anxiety. Together, these ingredients address common mental health needs while supporting mood and sleep quality with continued use. Research highlights include a significant reduction in perceived stress after 8 weeks of KSM-66^® and a reduction of occasional anxiousness after 4 weeks of Suntheanine^®.^6,7‡

Suggested Dose: Take 1 capsule two times daily, between meals.

Rapid Calm provides rapid-acting support (<1 hour) for occasional anxiety. It combines vitamin B6 with two clinically researched ingredients, Zembrin^®, a patented extract of Sceletium tortuosum, and Suntheanine^® l-theanine, to help moderate feelings of stress and occasional anxiety. This formula is ideal for as-needed relief from occasional everyday stressors. Research highlights that a single dose of 25 mg Zembrin^® reduced perceived anxiety levels and moderated fear responsivity.^{8,9 ‡}

Suggested Use: Take 1 capsule, as needed, with or between meals.

Cortisol Calm combines vitamin D3, Sensoril^® ashwagandha extract, Rhodiola rosea extract, Magnolia officinalis extract and l-theanine to promote relaxation and a healthy cortisol response. It provides support for occasional stress, calm and emotional well-being. Sensoril^® promotes relaxation and a healthy cortisol response as well as the reduction of perceived stress scale score and plasma cortisol and ACTH levels.^{10,11 ‡}

Suggested Use: As a dietary supplement, take 1 capsule in the morning and 1 capsule in the evening, with meals.

Amino Replete contains a blend of free-form amino acids, provided in the ratios found naturally in high biological value (BV) protein sources, made with high-quality vegetarian ingredients. It enhances healthy neurotransmitter synthesis with amino acid precursors to support cognitive function and positive mood.^‡

Suggested Use: As a dietary supplement, take 1 scoop daily, mixed with 8 ounces of water or juice, between meals, or as directed by a health professional.

Conclusion

Cortisol plays a central role in the body's adaptive response to stress, exerting wide-reaching effects on metabolism, immune function, circadian regulation and mood. For healthcare practitioners, understanding the bi-directional relationship between cortisol and mood and the symptoms of high cortisol is essential for comprehensive assessment and early intervention to interrupt the self-reinforcing cycle of stress and anxiousness.

Resources

For additional resources that include diet and lifestyle recommendations for supporting occasional anxiety, refer to the protocols listed below:

Positive Mood Protocol: Designed by our scientific and medical advisors in collaboration with Dr. James Greenblatt to help you deliver the most effective care and support for your patient's mood and emotional well-being.

For more details on the research on the selected nutrient solutions, download the product information sheets:

• Daily Calm
• Rapid Calm
• Cortisol Calm
• Amino Replete

Drug-Nutrient Interactions Checker: Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.

PureInsight^™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals.

Virtual Dispensary: Our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

You can also explore Pure Encapsulations^® to find On-Demand Learning, Clinical Protocols and other resources developed with our medical and scientific advisors.

1. American Psychiatric Association. May 1, 2024. Accessed November 11, 2024. https://www.psychiatry.org/news-room/news-releases/annual-poll-adults-express-increasing-anxiousness
2. Jones C, Gwenin C. Physiol Rep. 2021;8(24):e14644. doi:10.14814/phy2.14644
3. Sic A, Cvetkovic K, Manchanda E, Knezevic NN. Diseases. 2024;12(9):220. doi:10.3390/diseases12090220
4. Guilliams T. Principles and Protocols for Healthcare Professionals. Point Institute; 2018.
5. Azmi NASM, Juliana N, Azmani S, et al. Int J Environ Res Public Health. 2021;18(2). doi:10.3390/ijerph18020676
6. Salve J, Pate S, Debnath K, Langade D. Cureus. Published online 2019. doi:10.7759/cureus.6466
7. Hidese S, Ogawa S, Ota M, et al. Nutrients. 2019;11(10). doi:10.3390/nu11102362
8. Reay J, Wetherell MA, Morton E, Lillis J, Badmaev V. Hum Psychopharmacol. 2020;35(6). doi:10.1002/hup.2753
9. Terburg D, Syal S, Rosenberger LA, et al. Neuropsychopharmacology. 2013;38(13). doi:10.1038/npp.2013.183
10. Auddy B, Hazra J, Mitra A, Abedon B, Ghosal S. Journal of the American Nutraceutical Association. 2008;11(1).
11. Pandit S, Srivastav AK, Sur TK, Chaudhuri S, Wang Y, Biswas TK. Nutrients. 2024;16(9):1293. doi:10.3390/nu16091293

⁺Kim Ross is a paid consultant for Pure Encapsulations.