An Overview of The HPA Axis + How It Can Affect Your Health - Vital Plan

An Overview of The HPA Axis + How It Can Affect Your Health

Stress has been a part of our human experience since the beginning of time. And while the types of stress have evolved throughout history, it’s clear that stress of some kind is here to stay. Luckily, our bodies have an innate system designed to keep us balanced in the face of stressful situations — the hypothalamic-pituitary-adrenal (HPA) axis.

But what if that system fails? Thirty-three percent of people report extreme stress, with over 70 percent experiencing a decline in their physical and mental health, according to the American Institute of Stress. If you’re having symptoms of stress, such as digestive upset, low energy, poor sleep, anxiety, or depression, your HPA axis might be struggling.

Here, you’ll learn how the HPA axis works in your body and what you can do to help keep it regulated. The result? A healthier response to stress and a healthier life.

What is the HPA Axis + What Does It Do?

Best known for regulating the body’s stress response, the HPA axis includes a group of glands from the nervous and endocrine systems — the hypothalamus and pituitary gland (located in the center of the brain) and the adrenal glands (located just above the kidneys).

The HPA axis constantly seeks to create homeostasis by regulating stress, explains Dr. Bill Rawls, medical director of Vital Plan. “It’s the job of the HPA axis to sense what’s going on inside and outside of the body — to create cellular homeostasis,” says Dr. Rawls. “So how well our cells are and if our cellular functions are balanced determines how well we feel.”

Humans have a unique ability to interpret what they sense, which can compound stress. “Our thinking brains can cause problems when it perceives a threat to be much greater than it actually is,” says Dr. Rawls. For example, your boss yelling at you at work doesn’t harm you directly, but the interpretation of being yelled at can cause harm and create a tense, uncomfortable environment.

How the HPA Axis Works

To get a good idea of how the HPA axis works, let’s look at the individual role of each gland and how they work together to create a healthy stress response.


The hypothalamus, a small neuroendocrine gland above the brainstem, acts as the head manager of incoming information from other parts of the brain. When a threat is perceived, the hypothalamus releases two hormones, vasopressin (AVP) and corticotropin-releasing hormone (CRH), both signaling different parts of the pituitary glands to send memos to avoid harm. “The brain wants to alter cellular function in different parts of the body to match the threat — to prepare for whatever change is confronting us,” explains Dr. Rawls.

Pituitary Gland

Sitting just below the hypothalamus is the pituitary gland. The size of a pea, this master endocrine gland releases hormones into the bloodstream to reach a wide variety of targets that can affect growth, metabolism, reproduction, and more. As part of the HPA axis, it releases adrenocorticotropic hormone (ACTH) in response to AVP and CRH, — triggering the adrenals into completing the stress response. “If the hypothalamus is the manager, the pituitary is the secretary. They’re both in constant communication with each other and the rest of the body to make things run smoothly,” says Dr. Rawls.

Adrenal Glands

Finally, propped upon the kidneys like little hats are the adrenal glands, which are made up of two main parts — the adrenal medulla (inner part) and the adrenal cortex (outer part). When stress hits, the cells in the adrenal medulla secrete epinephrine and norepinephrine (most often referred to as adrenaline and noradrenaline) into the bloodstream, triggering a fight-or-flight response.

At the same time, ACTH binds to receptors in the adrenal cortex, producing the more commonly known stress hormone — cortisol. This glucocorticoid mobilizes the energy the body needs to handle stress. When cortisol levels get too high, receptors in the hypothalamus and pituitary glands sense it’s time to shut down the stress response through what’s called the negative feedback mechanism, or negative feedback loop.

When Your HPA Axis Goes Haywire

When stress becomes chronic, elevated cortisol overloads the HPA axis, eventually leading to HPA axis dysfunction — most often referred to as adrenal fatigue. “Our brain works like a very complex computer. When you overload circuits for too long, signaling slows down and becomes distorted,” says Dr. Rawls.

Just as there are a variety of life stressors, causes of HPA axis dysfunction widely vary — as do its symptoms. Below are among the most common.

Causes of HPA Axis Dysfunction:

  • Inflammation
  • Emotional stress
  • Microbial infections
  • Environmental toxins
  • Sleep deprivation
  • Poor diet
  • Medication use
  • Drug or alcohol dependence
  • Post-traumatic Stress Disorder (PTSD)

Symptoms of HPA Axis Dysfunction:

  • Feeling irritable or moody
  • Frequently ill
  • Difficulty handling stress
  • Easily overwhelmed
  • Unexplained fatigue

It’s important to note there is a difference between adrenal disease and adrenal fatigue. “True adrenal diseases, like Cushing’s syndrome (overactive adrenals) or Addison’s disease (underactive adrenals), occur when the cells of the adrenal glands have been damaged,” Dr. Rawls says, “Adrenal fatigue is the result of pushing too hard, causing the cells to be overworked, but the glands themselves aren’t diseased.”

6 Ways to Regulate the HPA Axis

So what can you do to support and restore your HPA axis? Comb through the following tools to see which ones you might be missing in your daily routine.

1. Eat a Balanced Diet

With all the fad diets that come and go sharing their must-dos and don’ts, it can be hard to know what eating balanced even means. A seasonal diet consisting mostly of vegetables, quality protein, healthy fats, and complex carbohydrates (with a focus on balancing blood sugar levels) is a great starting point in supporting your HPA axis. Age-old medical systems like Ayurveda suggest that eating meals at the same time every day is just as important as what you’re eating. A predictable routine stabilizes and calms the nervous system.

2. Cut Back on Caffeine

A study published in Scientific Reports links caffeine use with HPA axis dysfunction due to its ability to spike adrenaline and cortisol levels. If you want to cut caffeine but find it difficult to let go of, consider switching to green tea or drinking more water to crowd out the desire. Caffeine isn’t bad in moderation, but it does have a dehydrating effect on the body, so if you’re going to include it in your daily routine — be sure to hydrate a bit extra. Also, nix caffeine after noon as it can lead to low-quality sleep, causing you to think you need more caffeine to function (when you probably just need more rest).

3. Regulate Your Sleep

Cortisol may seem like a “bad guy,” but only when in excess. Balanced levels of cortisol are key to maintaining a healthy sleep-wake cycle, also known as our circadian rhythm. Research shows a direct link between stress and sleep, pointing to deep sleep reducing overactivity in the HPA axis and a lack of sleep-promoting overactivity. A general rule of thumb to regulate your sleep is to go to bed shortly after dark and rise with the sun when cortisol is naturally at its peak.

4. Exercise Your Body

Exercise helps stabilize your HPA axis in many ways, and one is by normalizing blood sugar. “When you move your body, your muscles contract, which sets off a chain reaction that mobilizes glucose and allows cells to absorb it better,” says Dr. Rawls. It doesn’t take much to reap the benefits, either.

Make it a habit to get 30-60 minutes of exercise three times per week, but be sure to keep the intensity and duration manageable. Studies have found that cortisol increases during aerobic exercise, so avoid extraneous activity in the evening to ensure a restful night’s sleep.

5. Supplement with Adaptogenic Herbs

Calming herbs such as passionflower can promote rest by increasing calming neurotransmitters like gamma-aminobutyric acid (GABA). Adaptogens, though, are a different class of herb that directly impact the HPA axis due to their similarity to the steroid-like hormones the hypothalamus uses to transmit messages. “When we use adaptogens, they send a message to the brain that things are turned up or down, and there’s no longer a need to keep sending out messages to boost cortisol,” says Dr. Rawls.

While all adaptogens help regulate the HPA axis in some way, ashwagandha has a special affinity for protection against mental stress. Published in Medicine (Baltimore), the research found ashwagandha directly reduced morning cortisol levels, proving effective in lowering reactivity to stress by directly affecting the HPA axis.

6. Be Present

Whether it’s by practicing meditation, taking a walk, or deep breathing — there are a hundred ways you can cultivate being present in your daily life. The key to relaxing an anxious HPA axis is to affirm safety constantly.

Incorporating any of these tools can be more challenging if you’re bombarded with chronic stress or are diagnosed with post-traumatic stress disorder (PTSD). If this is you, consider working with a trained therapist for a few sessions using tools like Internal Family Systems (IFS) Therapy or Eye Movement Desensitization and Reprocessing (EMDR).

While the science behind IFS is still in its infancy, it has been shown to be a strong alternative to Cognitive Behavioral Therapy (CBT) — especially in those with complex-PTSD (CPTSD). On the other hand, EMDR has been proven effective at positively influencing the HPA axis in trauma survivors by lowering levels of cortisol, research reveals.

Check out Dr. Rawls’ favorite adaptogenic herbal formulations for all-around, daily health support and for more targeted stress and sleep support.

The Takeaway

When it comes to stabilizing the HPA axis, there is no magic bullet that works for everyone. It can also take consistent effort to employ the above practices before noticing lasting results. But be patient, and rest assured, whatever you can do to lighten your stress load will support your HPA axis to function as it’s designed to — leading to healthier responses to stress and more energy to use for things you enjoy doing the most.

The Cellular Wellness Solution

Discover more in Dr. Bill Rawls' new #1 Bestselling book: The Cellular Wellness Solution: Tap Into Your Full Health Potential with the Science-Backed Power of Herbs.

"An eye-opening and empowering book that the world needs right now: The Cellular Wellness Solution will fundamentally change how you think about herbs and the powerful role they play in cultivating wellness at the cellular level."

Mark Hyman 5 stars
Mark Hyman, MD
Fourteen-time #1 New York Times Bestselling Author

Looking for More Wellness Tips?

Join our newsletter for bi-weekly tools, education, and savings to boost your health.


1. Batalha VL, Ferreira DG, Coelho JE, et al. The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function. Sci Rep. 2016;6:31493. Published 2016 Aug 11. doi:10.1038/srep31493
2. Do P, Guo F, Warburton D. Effect of aerobic fitness on cortisol response and hpa-axis reactivity at different aerobic exercise intensities. The Health & Fitness Journal of Canada. Accessed December 14, 2022.
3. Gerardi M, Rothbaum BO, Astin MC, Kelley M. Cortisol Response Following Exposure Treatment for PTSD in Rape Victims. J Aggress Maltreat Trauma. 2010;19(4):349-356. doi:10.1080/10926771003781297
4. Haddock SA, Weiler LM, Trump LJ, Henry KL. The efficacy of Internal Family Systems therapy in the treatment of depression among female college students: A pilot study. Journal of Marital and Family Therapy. 2016;43(1):131-144. doi:10.1111/jmft.12184
5. Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 2019;98(37):e17186. doi:10.1097/MD.0000000000017186
6. Nicolaides NC, Vgontzas AN, Kritikou I, et al. HPA Axis and Sleep. . In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext . South Dartmouth (MA):, Inc.; 2000-. Available from:
7. Nidich S. Picture of Health: Transform your self-care and health care through Ayurvedic and Integrative Medicine: Written by Charles R Elder, MD, MPH, FACP, & Leslie D Elder, MD. Perm J. 2019;23:19.179. Published 2019 Nov 1. doi:10.7812/TPP/19.179

Cellular-Wellness-Solution-bestseller-2_fdcb5886-026d-46ce-84d8-1444caa7185a - Vital Plan

Want to know more about cellular wellness?

We wrote the book on it.

Discover more in Dr. Bill Rawls' new #1 Bestselling book, The Cellular Wellness Solution: Tap into Your Full Health Potential with the Science-Backed Power of Herbs.

Learn More