Biomarkers Nutrition

What is the HPA Axis? Dysregulation + Symptoms + Treatment

The HPA axis is a set of interactions among the hypothalamus, the pituitary gland, and the adrenal gland.

HPA stands for hypothalamic-pituitaryadrenal axis.

The HPA axis is a set of interactions among the hypothalamus, the pituitary gland, and the adrenal gland. HPA stands for hypothalamic-pituitary-adrenal axis.

Let’s look at these 3 words a little closer:

Hypothalamus: The hypothalamus is a small but really important area in the center of the brain. It plays an essential role in hormone production and helps to stimulate various important functions in the body, such as:

– body temperature

– thirst

– appetite and weight control

– emotions

– sleep cycles

– sex drive

– childbirth

– blood pressure and heart rate

– production of digestive juices

– balancing bodily fluids

The hypothalamus acts as the connector between the endocrine and nervous systems. It is located between the pituitary gland and the thalamus.

Pituitary gland: The pituitary gland is a tiny organ, the size of a pea, found at the base of the brain. As the “director gland” of the body, it produces many hormones that travel throughout the body, directing specific processes or communicating to other glands to produce certain hormones.

Adrenal glands: Your adrenal glands are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys.


Together these three above elements work together very much like an orchestra to regulate the following:

– stress response

– mood

– motivation

– metabolism

– energy levels

– and immune system.

There are 3 important hormones when it comes to the hypothalamic-pituitary-adrenal axis:

  • Corticotropin-Releasing Hormone (CRH) Released by the Hypothalamus in response to stress
  • Adrenocorticotropic Hormone (ACTH) Released by the Pituitary when it’s sensing CRH
  • Cortisol Released by the Adrenal glands when ACTH was able to dock onto them. With the rise in cortisol glucose is also being elevated as the body is triggered to make more energy (=ATP) to cope with the stress.

When any one part of the HPA axis isn’t running as it should, it can affect the other parts and various reactions. We call this an HPA axis dysfunction or dysregulation. External stressors are translated into biochemical signals, many of which influence the feedback loops of the HPA axis. Prolonged stress may continually activate the HPA axis and affect the balance of hormone and cell mediators. Cortisol is perhaps the most important hormone involved in the process. HPA axis activation and cortisol issues can persist for years, with effects on most major body systems including: gastrointestinal, neurological, musculoskeletal, endocrine, respiratory, and immune.

– Stress activates the HPA axis and sets off a cascade of neuroendocrine signals that ultimately leads to the release of hormones and neurotransmitters like cortisol, norepinephrine (noradrenaline), and epinephrine (adrenaline).

– Over time, the chronic activation of our stress–response system erodes resilience and depletes metabolic reserve. Resilience is the immediate capacity of cells, tissues, and organ systems to respond to changes in physiological need. Metabolic reserve refers to the long-term capacity of our body to respond to these changes.

– The loss of resilience and the depletion of metabolic reserve lead to changes in cortisol output (most commonly too much, but sometimes too little), disruption of the diurnal cortisol rhythm (too little cortisol in the morning or too much at night), and changes in the production of other hormones and neurotransmitters related to the HPA axis, such as DHEA, melatonin, and epinephrine.

– Previously, clinicians focused on the necessity of supporting adrenal function and coined terms such as “adrenal fatigue;” however, we have since learned that the effects of stress affect more than the adrenals.

– In addition, focusing only on cortisol and/or adrenal function may overly simplify complex interactions among several systems, and miss the contributions of the central nervous system, environmental factors, and other metabolic factors.

Lifestyle and Nutritional Support

The ability to respond to stress has the potential to interfere with the enjoyment of life and even the ability to perform ordinary daily activities. Incorporating lifestyle, nutritional, and behavioral recommendations can help support healthy HPA axis function. Although specific recommendations differ based on the stage of stress resistance, here are a few considerations:

  • Obtain regular exercise
  • Establish regular bedtimes and obtain sufficient sleep
  • Practice relaxation activities (e.g., meditation, yoga, hobbies)
  • Consider smoking cessation programs
  • Avoid or limit alcohol and sugar consumption
  • Identify and remove food intolerances

Supplemental support

Early Stage:

In the Early-Stage of stress resistance, patients can benefit from supplementation with herbs and nutrients that calm HPA axis activation, support healthy cortisol balance, and help relieve occasional anxiety and stress.

  • Ashwagandha (Withania somnifera) has been shown in clinical studies to reduce stress and occasional anxiety in adults.
  • L-Theanine, an amino acid found in green tea, has been shown to inhibit cortical neuron excitation, thereby creating feelings of calm, supporting blood pressure already within normal limits, and improving mood.
  • Magnolia (Magnolia officinalis) has been shown to provide calming effects, which can be in part attributed to its interaction with receptors for the neurotransmitter gamma-aminobutyric acid (GABA).
  • Phosphatidylserine (PS) has been shown to support an adaptive cortisol response to stress.


Patients in the Mid-Stage of the stress response can benefit from adaptogens, which are botanical ingredients that support the body’s ability to respond to stress and restore homeostasis. This may, in turn, influence mood, cognition, and energy levels.

  • Rhodiola (Rhodiola rosea) is an adaptogen that that helps to reduce occasional fatigue, improve mood, and promote psychological adaptation.
  • Holy basil (Ocimum tenuiflorum) prevents reductions in brain catecholamine and monoamine oxidase levels and may increase dopamine and serotonin levels during stress.
  • Eleuthero (Eleutherococcus senticosus) supports adrenal function, regulates neurotransmitters, and may increase resistance to stress.
  • Ashwagandha (Withania somnifera) may modulate hormonal changes that occur during stress.
  • Maca (Lepidium meyenii) has been shown in preliminary human research to have a positive influence on mood, feelings of occasional anxiety, and libido.


In the Late-Stage, patients can benefit from adrenal-supportive nutrients and botanicals to support healthy cortisol production. Fortifying the diet with essential vitamins that can be depleted by stress is also important in maintaining adrenal cortex function, combatting occasional stress-related fatigue, and promoting energy recovery.

  • Vitamin B1 (thiamine) is a water-soluble, sulfur-containing member of the B vitamins; the coenzyme form of thiamine plays a role in energy production.
  • Vitamin B2 (riboflavin) is necessary for energy production as well as normal cell function and growth. Animal research shows that a riboflavin deficiency leads to an initial increase, followed by a decrease, in adrenal cortex activity.
  • Vitamin B5 (pantothenic acid) is involved in numerous biological reactions, including the production of energy and the synthesis of steroid hormones, including cortisol.
  • Vitamin B6 (pyridoxine) is a cofactor for approximately fifty different enzymes and plays a role in the production of neurotransmitters, such as serotonin, dopamine, epinephrine, norepinephrine, and gamma-aminobutyric acid (GABA).
  • Licorice (Glycyrrhiza glabra) root extracts have been shown to influence cortisol production in both animals and humans by inhibiting 11beta-hydroxysteroid dehydrogenase, the enzyme responsible for converting cortisol to cortisone.



The information on is NOT intended to replace a one-on-one relationship with a qualified health care professional and is not intended as medical advice.

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