The hypothalamic–pituitary–adrenal (HPA)-axis is the major endocrine system that regulates the physiological response to stress and as a result drives how we adapt our own behaviour and physiology in order to accommodate that stress. When the HPA axis is functioning well the body adapts well to stressors and we feel strong, resilient, stable, fit and healthy. When there is dysregulation of the HPA and the body struggles to adapt to stressors it can rapidly display bipolar features with too little or too much hormone production, immune function, mental function and we are left feeling overwhelmed, tired, moody, weak and often fatigued with trouble sleeping. In this article we outline the key features of the HPA axis, how it works, how it mis-functions and what you can do to bring HPA balance back to your body.

What is the HPA axis?

When our body is placed under chemical, physical or emotional stress the master glands of the brain known as the Hypothalamus and Pituitary are given the task to help deal with the stress and they link with the distant adrenal glands situated above the kidneys to create a hormonal response cascade through what is called the hypothalamus-pituitary-adrenal axis or HPA for short.1 When faced with a stressor the body responds via the HPA as follows:

  1. The hypothalamus initially secretes corticotropin-releasing hormone into the bloodstream. Corticotropin-releasing hormone (CRF) itself increases the activity of the sympathetic nervous system perpetuating effects like elevated heart rate and tells the pituitary gland to secrete a substance called adrenocorticotropic hormone (ACTH)2.

  2. The pituitary gland releases ACTH into the bloodstream, and the hormone travels down to the adrenal cortex, which is a term for the outer layer of the adrenal glands. ACTH binds to receptors on the surface of the adrenal cortices, leading to a series of intracellular events that result in the adrenal glands secreting glucocorticoids like the hormone cortisol3.

  3. Cortisol has receptors in almost all cell types, and exerts widespread effects on digestion, immune function, emotions, energy metabolism, and sexual behaviour to help our body cope with the immediate stress4.

  4. Additionally, cortisol acts during the experience of a serious stressor to inhibit processes that are deemed to be of lesser importance at the time. It’s activity also provides negative feedback that can impact back on the function of the hypothalamus and pituitary (Figure 1).

THE HPA axis

Figure 1. The interactions of the Hypothalamus-Pituitary-Adrenal axis (HPA axis) in response to stress.

While proper functioning of the HPA axis is essential for dealing with stress, when the HPA axis is stimulated too much (for example in someone who faces extreme stress on a daily basis), it can lead to physical and psychiatric problems through dysregulation of the harmonious messaging between the three key glands (HPA)5.

How does HPA dysfunction occur?

The simple answer is prolonged and excessive stress that overloads the HPA axis. These forms of stress can come from psychological and emotional sources, infection, lack of sleep, processed foods, over or under-eating, over or under-exercising, toxins, lack of sun and proper Vitamin D, malnutrition, GI distress, gut inflammation (leaky gut), infections, viruses, bacteria…and much more (Figure 2)6.

stress

Figure 2. Examples of stressors that unbalance the HPA axis.

When chronic stress occurs in an individual, the HPA axis continues to release hormones on an accelerated basis. But after time, the overproduction of these hormones leaves the glands of the HPA axis desensitised and they stop recognising signals to stop producing hormones. The negative feedback loop is no longer functioning as it should and HPA axis dysfunction becomes the norm, with more and more over- or under-reaction to stressors occurring, finally leaving the body feeling burnt out and exhausted (figure 3).7

Figure 3. Cortisol production with HPA function leading to dysregulation.

What are the signs and symptoms of HPA dysfunction?

Common signs and symptoms that your HPA function is dysregulated may include:

  • Insomnia

  • Poor sleep quality (even if you’re sleeping, you don’t wake feeling rested)

  • Trouble sleeping (falling asleep or staying asleep)

  • Weight gain, especially in the mid-section

  • Brain fog

  • Thyroid dysfunction

  • Depression and/or anxiety

  • Hypoglycemia and other blood sugar problems

  • All-day fatigue, particularly in the morning and mid-afternoon

  • Cravings for salt or salty foods

  • Depressed immune system/recurrent illnesses or infections

  • Dizziness when standing (orthostatic hypotension)

  • Blood pressure issues

  • Inflammation

  • Rise in allergies – food, chemical, or environmental

  • Low libido

  • Poor muscle tone or loss of muscle mass

  • Dry skin

  • Slow wound healing

  • Inability to concentrate and focus

  • Memory problems — can’t remember why you walked into a room or where your car keys are

  • Cold hands and feet

How can you treat HPA dysregulation?

HPA axis dysfunction is reversible with changes in lifestyle, diet and some supplements can also assist. Our top tips 6 tips to nourish your HPA axis are listed below:

  • Practice an energy art like Yoga, Tai Chi, Qigong or Meditation

These energy arts can all be described as meditative exercises and all involve relaxation and concentration, a focus on the breath, and gradual and purposeful movement. Energy arts have the ability to bring peace and tranquility back to the mind, whilst allowing the HPA to gently find its harmonious rhythm again. For thousands of years cultures around the world have used such techniques to de-stress and maintain good health and well-being through protecting their healthy HPA function. Practicing for 30-45 minutes 2-3 times per week can go a long way to improving your HPA function.

Yoga for chronic fatigue

  • Reduce Primary Stressors

If the main source of your stress is something you can cut out of your life (or reduce significantly), then you should consider doing so. This could mean a job change, speaking to a friend less often, a dietary change, eliminating an inflammatory source, eliminating stressors, taking up a new sport or hobby and eliminating a bad one or simply making the choice to find time for yourself instead of overextending your commitments. Also find a way to channel your stress into something positive that helps you relax, take it out at the gym in surfing in the ocean.

man stressed overworked

  • Make Sleep a Priority

Getting the recommended seven to nine hours of sleep each night can be difficult for some, but if you’re experiencing HPA axis dysfunction symptoms, it’s critical to make sleep a priority in your life. Getting the physical rest you need will help your body recover, and will do wonders for your mental state. If you struggle to get to sleep at night consider using a sleeping app like Sleepio or some meditative audio to gentle drift you off to sleep. Don’t eat or drink late at night and avoid working or using electronic devices before bed.

  • Maintain a Balanced Diet

It’s very important for people experiencing HPA axis symptoms to maintain a healthy balanced diet. The gut-brain connection and issues with leaky gut can rapidly unbalance the HPA axis. Now is not the time for extreme dieting. Stick to a natural whole food diet, eat plenty of fruits and vegetables, and stay away from processed foods, sugar and white flour as much as possible. And of course, drink plenty of water to maintain good hydration. One thing you may want to avoid (or limit) for at least a little while is alcohol. As alcohol is a depressant, it might be a good idea to limit your intake for a bit. For dietary ideas of what to eat and avoid download our HPA healthy food guide.

  • Exercise

Exercise can be a big stress reliever. Get up and get your body moving for at least 30 minutes 3-4 times per week. It doesn’t have to be rigorous or difficult, but you should do something you enjoy – something that helps you relax and clear your mind. It may be walking, hiking, swimming or biking (even if it’s on a stationary bike), or some light weight training. The point is to move your muscles, increase your circulation, breathe deeply and relax your mind. If you are suffering from chronic fatigue or find exercise creates post exertional fatigue then we advise you to focus on low impact forms like qigong or yoga that have a focus on meditative practice, strength building and breath-work. Exercising daily also helps you sleep better.

  • Use an adaptogenic plant like maca (lepidium meyenii)

Maca is a unique root vegetable from the Andes of Peru that has been used for centuries to bring balance and harmony back to the body during times of stress. Maca works as an adaptogen to regulate the HPA axis indirectly through the endocannabinoid system (ECS). Regular consumption of maca has been shown to improve components of the HPA axis, reduce down inflammatory levels, improve mitochondrial function, energy levels as well as cognition, mood and mental health.8 Not all maca is equal and there are also different colours of maca for different conditions. So to find the right maca for your condition we advise you to visit The Maca Experts to get a customised maca plan.

Buy Maca for your HPA

  1. (a) Tsigos C & Chrousos GP (2002) Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. J. Psychosom. Res. 53: 865–871. (b) Zavala E, Wedgwood KC, Voliotis M, Tabak J, Spiga F, Lightman SL & Tsaneva-Atanasova K (2019) Mathematical modelling of endocrine systems. Trends Endocrinol. Metab. (c) Melmed S, Polonsky KS, Larsen PR & Kronenberg HM (2015) Williams textbook of endocrinology Elsevier Health Sciences. (d) Hosseinichimeh N, Rahmandad H & Wittenborn AK (2015) Modeling the hypothalamus–pituitary–adrenal axis: A review and extension. Math. Biosci. 268: 52–65.
  2. Vale W., Spiess J., Rivier C., Rivier J. Characterization of a 41 -residue ovine hypothalamic peptide that stimulates secretion of corticotropin and betaendorphin. Science. 1981;213:1394–1397.
  3. Rivier C., Vale W. Modulation of stress-induced ACTH release by corticotropin-releasing factor, catecholamines and vasopressin. Nature. 1983;305:325–327.
  4. Munck A., Guyre PM., Holbrook NJ. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev. 1984;5:25–44.
  5. (a) Munck A., Guyre PM., Holbrook NJ. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev. 1984;5:25–44. (b) Bamberger CM., Schulte HM., Chrousos GP. Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev. 1996;17:245–261. 
  6. (a) Rutters, F., La Fleur, S., Lemmens, S. et al. The Hypothalamic-Pituitary-Adrenal Axis, Obesity, and Chronic Stress Exposure: Foods and HPA Axis. Curr Obes Rep 1, 199–207 (2012).)( Bose M, Oliván B, Laferrère B. Stress and obesity: the role of the hypothalamic-pituitary-adrenal axis in metabolic disease. Curr Opin Endocrinol Diabetes Obes. 2009;16(5):340-346. (b) Farzi A, Fröhlich EE, Holzer P. Gut Microbiota and the Neuroendocrine System. Neurotherapeutics. 2018;15(1):5-22. (c) Silverman MN, Pearce BD, Biron CA, Miller AH. Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection. Viral Immunol. 2005;18(1):41-78.
  7. (a) Fries, E., Hesse, J. et al. A new view on hypocortisolism. Psychoneuroendocrinology. 2005; 30(10):1010-1016. 40. (b) McEwen, B. S. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007; 87(3):873-904. (c) Raison, C. L. and Miller, A. H. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry. 2003; 160(9):1554-1565. (d) Gunnar, M. R. and Vazquez, D. M. Low cortisol and a flattening of expected daytime rhythm: potential indices of risk in human development. Dev Psychopathol. 2001; 13(3):515-538.
  8. https://themacaexperts.com/maca/learn-about-maca/10-amazing-health-benefits-of-maca/

Written by Dr Corin Storkey Founder and Director of Seleno Health. www.selenohealth.com

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