Super-Charging your HPA Axis: Research-Supported Natural Therapies – Vitamins

Super-charging your HPA axis Part I: Vitamins and Minerals

Tweaking our diet and lifestyle can nurture the HPA axis and give us a healthier body.


Key Points

  • The HPA axis involves the complex interaction of the hypothalamus, the pituitary gland and the adrenal glands.
  • The HPA axis regulates the release of multiple hormones involves in the body’s response to stress
  • Dysfunction of the HPA axis can lead to the development of diseases like to type 2 diabetes, obesity, and cardiovascular disease.
  • Alterations to the HPA axis can also increase our chances of developing infections, through its role with the body’s immune system.
  • There are multiple approaches to sustaining the optimal function of the HPA axis.
  • One key approach to maintaining an optimal HPA axis is through the thoughtful use of vitamins and minerals.


The hypothalamic-pituitary-adrenal (HPA) axis is a term used to describe the complex interaction of three major organs in the body: the hypothalamus, the pituitary gland and the adrenal glands.  The hypothalamus and pituitary gland can be found just above the brainstem, the part of the brain that connects with the spinal cord. The adrenal glands, in turn, are located on top of the kidneys. These three organs work together in the so-called HPA axis to regulate our body’s response to stress.



HPA axis and stress: the basics

Whenever our body is exposed to stressful factors, the brain is the first organ to respond through the sympathetic nervous system (SNS). This is the part of our autonomic nervous system that oversees the so-called fight or flight response, regulating the function of multiple organs during a stressful event. For example, the SNS system is responsible for the increased heart rate and perspiration we experience when exposed to stress.

Following a stressful event, the SNS releases the hormones epinephrine and norepinephrine, which activate the HPA axis, starting with the hypothalamus. This organ releases a hormone called corticotropin-releasing hormone or CRH, which keeps the SNS active during the body’s stress response and activates the rest of the HPA axis to produce a cascade of important hormones, such as cortisol, that drive the body’s response to stress.

Once the stressful factor disappears, our body deactivates the stress response, and regulate the production of hormones to normal levels. This is a very important step, because excessive and constant production of hormones like cortisol can have detrimental health effects. For example, chronic elevated cortisol can lead to reduced immune function1 and to an increased chance of infections. Constantly elevated levels of cortisol have also been linked to type 2 diabetes, obesity, and cardiovascular disease2.

Hence, it pays to maintain a healthy HPA axis and there are many ways to optimise your lifestyle and super-charge your body’s response to stress.



Supporting the HPA axis


One of the most obvious ways to optimise the function of the HPA axis is to avoid stressors and lead a healthy lifestyle that benefits your brain and body. In addition, there is a wide range of treatment options that help optimise the function of the brain, adrenal glands and help with the regulation of cortisol in specific tissues (Figure 1).

Below, we highlight the best research-backed treatments that improve the function of the HPA axis.

  • Vitamins and minerals

    Vitamins and minerals are important co-factors in the biological reactions that produce hormones and neurotransmitters, chemicals that allows communications between neurons. Below we highlight some of the most important vitamins and minerals that are available as dietary supplements and for which there is strong research evidence for their efficacy.

      • Vitamin C – Also known as ascorbic acid, this is an important cofactor needed for the function of the adrenal glands. In fact, studies have shown that adrenal glands hold the greatest concentration of vitamin C in their tissues. Vitamin C supplementation prior to intense exercise has been shown to regulate levels of the hormone cortisol, a key hormone produced by the adrenal glands.
        • For example, studies have shown that Vitamin C supplementation before a 90 km race resulted in clear changes in levels of cortisol and inflammatory cytokines (molecules involved with the inflammatory response). Runners that received 1,500 mg/day of Vitamin C for seven days showed significantly lower levels of cortisol and inflammatory cytokines after the race, compared to runners that received either lower levels of Vitamin C or a placebo3-4 (no treatment).
        • Similar results were obtained when measuring the effect of Vitamin C in stress levels. One study showed that participants who received 3,000 mg of Vitamin C for two weeks reported reduced levels of stress and blood pressure, relative to the placebo group.
      • B Vitamins – This group of vitamins include riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, inositol, and choline. They are important components needed for the synthesis of adrenal hormones and for the optimal function of neurotransmitters. During episodes of stress, levels of B-vitamins are depleted in the body, and patients experience significant improvement after treatment with B-vitamin supplements.
        • Sub-optimal levels of B-vitamins have been shown to contribute to poor metabolic responses to stress5-8.
        • A review of multiple studies showed that treatment with B vitamins in combination with other nutrients results in significant reduction of perceived stress, as well as improvement in mild psychiatric symptoms, subclinical anxiety, energy levels9.
      • Minerals – Sodium, potassium, calcium, magnesium, and zinc are among the most important minerals known to affect the function of the HPA axis.
        • Deficiencies on these minerals can result inf alterations in neurotransmitter and HPA axis dysfunctions10-12.
        • Magnesium supplementation has been shown to effectively improve sleep, metabolic function and measures of fatigue and energy in people with stress and HPA axis-related dysfunctions13-18.

According to the 2011-2012 Australian health survey, one in three people aged two years and over did not consume enough magnesium. Likewise, the same survey found that more than half of the Australian population over two years of age did not consume adequate levels of calcium.

There is extensive research supporting the important role of vitamins and minerals in the maintenance of an optimal HPA axis. Following a healthy diet rich in these nutrients or complementing your diet with supplements is a solid approach to improving your health. Consulting with your functional medicine practitioner is the first step to find your personalised pathway to health.





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  13. Nielsen FH, Johnson LK, Zeng H. Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Read it!
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