HPA Axis Dysregulation (AKA Adrenal Fatigue)

HPA Axis Dysregulation, also commonly known as Adrenal Fatigue, occurs whenever the body is under unrelenting stress due to a disproportionate response to a stressor, whatever that stressor may be, let it be physical (e.g. trauma, injury), emotional (e.g. grief, relationship issues, etc.), psychological (e.g. fears, negative thoughts/inner-conversations), or anticipatory (made up before a stressful situation).
 
As discussed in previous articles, everyone responds to stress differently and some people cannot cope at the littlest change or inconvenience to their routine. This does not in anyway undermine some people’s ability to understand what stress really is – as for them it is a reality –, and it has become a complete part of who they are. The more they stress about a situation the further stress sets into their core, fogging their thoughts and better judgement, and their stress response become disproportionate.
 
Adrenalin and Cortisol, our life-saving hormones, flood the blood stream, leading the way to High Blood Pressure and Heart Rate (to supply muscles with oxygen and nutrients, vital to “run away” from danger), high blood sugar (to supply energy to muscles) – our innate adaptive stress response mechanisms.
High level of sugar circulating in the blood is one of the leading causes of (systemic) inflammation, by making the blood acidic, which is exacerbated by the use of Stimulants, such as caffeine and pick-me-up sugary snacks throughout the day, forcing the body to leach out essentials minerals such as Calcium (from bones) to buffer blood pH changes.
For this reason, the Pancreas is also producing high levels of Insulin to get the sugar back in the cells as fast as possible, since it is not used (there is not an actual danger to run from, nor a beast to fight). But remember that Cortisol is also a master hormone and therefore, the spike in Insulin must be that much greater to overwhelm Cortisol receptors.
There are therefore several downside to High Cortisol and High Blood Sugar: 1) Inflammation in blood vessels (a leading cause of Atherosclerosis and Cardiovascular Disease); 2) Systemic Inflammation; 3) Reduced insulin sensitivity, Type-2 Diabetes, 4) Immuno-suppression (see previous articles for more details).
 
If this was not bad enough, Chronic Stress forces the Adrenals to work that much harder. Adrenals require many key nutrients and co-factors to produce Cortisol, including Vitamin C (as Ascorbate)1, and B vitamins (also necessary for the production of neurotransmitters), mainly B1 and B62, and these may become depleted, even more so if they are not replenished by a diet based on nutrient-dense food.
High-energy snacks or drinks are empty calories (no matter how healthy the manufacturers claim, no matter if you buy it in an health-store or a corner shop), mainly supplying energy through high doses of sugar (refined, or highly-processed from food – e.g. dates, coconut sugar, syrups, molasses) – too often the first ingredient listed on the label; and/or caffeine. 
 
   “With Lowered Cortisol levels, endogenous glucose production is compromised, and sugar and stimulant cravings are likely as a consequence of the resultant hypoglycaemia. If untreated, this can lead to adrenal burnout and chronic fatigue.
 
“The flow-on effect of these disturbances in neurotransmitters and stress hormones can lead to exhausted serotonin levels as well, potentially resulting in anxiety and sleep disturbances. The precursor of serotonin is tryptophan. The established link between carbohydrate cravings and depression is thought to be due to its tryptophan-increasing properties, with mood-elevating results.
 
“Agitation and anxiety can also be caused by glutamatergic activation. Note that the precursor for both the inhibitory and excitatory pathways is the same amino acid: glutamine. If zinc and B6 are in short supply then adequate amount of GABA, the inhibitory neurotransmitter, cannot be formed. Instead Glutamate, the excitatory neurotransmitter, accumulates, leading to the above-mentioned symptoms.” Writes Jerome Sarris in his book Clinical Naturopathy: An evidence-base guide to practice (2010. p. 278). Adding (p. 280): “While the SNS [Sympathetic Nervous System] is responsible for arousal, for fight and flight, the PNS [Parasympathetic Nervous System] facilitates rest, relaxation and healing (repair), it slows heart rate amd promotes digestion and elimination. Neurotransmitters activated by the SNS include adrenaline [Epinephrine] and noradrenaline [Norepinephrine], whereas acetylcholine is the predominant neurotransmitter of the PNS. In a healthy state there is a balance between the SNS and PNS. However, during stress the SNS is dominant, suppressing the action fo the PNS. This can lead to digestive and sleep disturbances and agitation. Repercussions of this may include reduced absorption of nutrients through diminished production of digestive juices, anxiety and further drain on energy through lack of restful sleep.
 
“The use of stimulants such as coffee increases the stress response and adrenal output, as shown by elevated Catecholamines, notably adrenaline, in urine. If coffee is used as a pick-me-up without having an effect, leading to increasingly greater consumption, it begs the question as to whether adrenaline production ability has been exhausted. This kind of stimulation may therefore hasten the decline in adrenal function, thus being a stressor in its own right. Adrenal exhaustion can be the result of multiple stressors, each of them not being enough to cause HPA dysfunction. However, the additive effects (if not addressed) can weaken the system to such an extant that other health problem could arise, such as chronic fatigue, clinical depression, hypothyroidism, inflammatory and autoimmune conditions, and hormonal disturbances, as outlined in Table 15.2 [contrasting with chronic diseases caused by high Cortisol table 15.1].”

When the Adrenals are not able to produce enough Cortisol because nutrients necessary for its production are lacking or not able to cope with the demand, they may simply become exhausted. Cortisol levels in the blood drop, and its affect on the nervous system is also greatly reduced, a leading cause of (unexplained) Fatigue. Remember that high levels of Cortisol are required to get up in the morning and go up about our day. Not being able to feel refreshed in the morning is also a sign of HPA Axis Dysregulation.
 
When DHEA levels are also affected (remember the Pregnenolone Steal? When Cholesterol is shunted towards the production of Cortisol, and little, if none, is available for the production of DHEA and Sex Hormones), usually with Low levels in the morning and High Cortisol in the evening, is a sign that the Adrenals are fatigued. When both levels of Cortisol and DHEA remain low, a person will be unable to move, let alone get up from bed in the morning – a typical sign of Adrenal Exhaustion (and associated with major depression)3. The Central Nervous System is no longer aroused and subsequent processes, including smooth muscles and heart muscles contraction, clear thinking and concentration, are all altered.
When Adrenal Exhaustion has set, an individual may require hospitalisation, and complete rest, so that the stress response can be weakened enough and Adrenals function restored. Usually, a person will find hard to execute the simplest of movement, and rest is the only option left.
If this last cry for help is still ignored, or the stress response remains disproportionate, the body will no longer be able to:

• Fight infections (due to suppressed immunity)4,
• Digest food and assimilate nutrients (due to suppressed digestive and enzyme function)4,
• Heal and repair (due to sleep disturbances and key nutrient missing)4,
• Balance hormones (especially sex hormones, involved in healing and repair, arterial wall health (protecting from free radical damage), Oestrogen Dominance Syndrome (involved in Cancer, especially Breast Cancer; exacerbated by chronic constipation (due to stress and a diet low in fibre) and recirculation of oestrogen into the bloodstream from the bowel), and other hormones such as Melatonin (Neuroprotective against oxidative stress-induced cell death) and Serotonin),
• Produce vital neurotransmitters (e.g. GABA, Serotonin)4,
• Prevent thyroid dysfunction (due to stress impacting on T4 to T3 conversion towards rT3, the emergency break on metabolism, the thyroid exhausting itself producing more and more thyroid hormones as the cells are not receiving hormones essential for their functioning)4,
• Prevent Mitochondrial dysfunction (the cell energy production factories)5,
• Clean up the accumulation of acidic compounds within interstitial Fluid (the liquid bathing all cells) (to keep blood pH within range – a leading cause of cancer),
• Prevent osteoporosis (due to mineral leaching out into the blood to buffer acidity)5,
• Repair free radical damage (due to overwhelmed enzymatic antioxidants (e.g. SOD), and a diet often void of antioxidant-rich foods, also necessary for liver detoxification and elimination of toxins),
• Prevent Systemic inflammation (due to a greater production of inflammatory cells by visceral fatty tissue, and from inflammation occurring in the gut due to Dysbiosis, and in the arteries),
• Prevent Autoimmune Conditions4, and
• Cell death4,5 – ultimately leading towards (early ageing and) inevitable death.

 
And… The list is not exhaustive!
 
For the impact of Stress on Digestion and immune system, refer to previous articles.

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References:
 
1 Patak, P. Willenberg, HS. Bornstein, SR. (2004). Vitamin C is an important cofactor for both adrenal cortex and adrenal medulla. Endocrine research. 30 (4), pp. 871–875.
2 Kathleen, AH. Kelly, GS. (2009). Nutrients and Botanicals for Treatment of Stress: Adrenal Fatigue, Neurotransmitter Imbalance, Anxiety, and Restless Sleep. Alternative Medicine Review. 14 (2), pp. 114–140.
Available at: https://www.spectracell.com/media/uploaded/2/0e2016801_266fullpaper2009altmedrevnutrientsforthetreatmentofstressfatigueandinsomnia.pdf.
Last accessed: 25th April 2017.
 3 Goodyer, IM. et al. (1996). Adrenal secretion during major depression in 8- to 16-year-olds. Altered diurnal rhythms in salivary cortisol and Dehydroepiandrosterone (DHEA) at presentation. Psychological Medicine. 26 (2), pp. 245–256.
4 Sarris, J. (2010). Adrenal Exhaustion. In: Window, J Clinical Naturopathy: An evidence-based guide to practice. Chatswood: Elsevier. pp. 275–298.
5 Suwanjang, W. et al. (2016). Melatonin prevents cytosolic calcium overload, mitochondrial damage and cell death due to toxically high doses of dexamethasone-induced oxidative stress in human neuroblastoma SH-SY5Y cells. Neurochemistry International. 97, pp. 34–41.