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The Physiology of ‘Adrenal Fatigue’, Pt I: What Does the Science Say?

This is Part One of a two-part series. For the second part,  The Adrenal-Endotoxemia Cycle and How Symptoms are Mediated by Inflammation, click here.

Adrenal Fatigue: An intro

If you’re reading my website, you’ve probably heard of ‘adrenal fatigue’. The label is given to a syndrome that involves fatigue as a primary symptom, but invariably also includes symptoms such as brain fog, low blood pressure, poor circulation, low sex drive and inflammatory symptoms that link into a daily pattern. However, the signature of adrenal fatigue is feeling ‘tired but wired’ and poor responses to exercise and stress.

The phrase began its journey into common parlance after Dr James Wilson published a seminal book, appropriately named “Adrenal Fatigue: 20th Century Stress Syndrome”. The doctor noticed a growing number of his patients that all presented with a similar pattern:

  • All were subject to long-term stressors
  • One day, they took on one stressor too many and ‘crashed’
  • From that point on, they had a wide range of symptoms (such as those mentioned above)
  • The one reliable way to help was to boost adrenal output and reduce stress load to the adrenals

Dr Wilson heavily backed the dual approach of reducing stress (reducing activation to the adrenal glands) plus use of adrenal extracts, Vitamin C and adaptogenic herbs (like Siberian Ginseng) with the aim of boosting response from the adrenal glands. The adaptogenic herbs were stars of the show, the commonly-repeated mantra that ‘they increase cortisol when it is low, and reduce it when it is high’… what’s not to like?

Naturally, given the role of fatigue and one crucial commonality (that interventions that boosted adrenal output were the only reliable way to improve symptoms), it was logical to conclude that this was an ‘adrenal problem’ and that ‘low adrenal output causes fatigue’. There was certainly no evidence to the contrary. Cue the entry of adrenal fatigue into patient vocabulary…


  • Many individuals who had been dismissed by the medical system were suddenly given an explanation for their symptoms
  • Introducing support for the adrenals was making a big difference for this population


The Controversy With Adrenal Fatigue


Dr Wilson’s book remains one of the highest-selling books in alternative healthcare. Thousands upon thousands of patients shared a similar experience. Did they have stressors loading their adrenals? Sure. Did their adrenals ‘crash’ one day? Yep. Did they fail to get better with all the normal interventions offered by the doctor and by alternative practitioners? Absolutely. Did they feel better for removing stress and boosting their adrenal output? Definitely. Of course, not all improved in this way but there was an overwhelming number of people that felt discarded by the medical system and got their life back after self-diagnosis and self-treatment for adrenal fatigue.

Logic states that, when a large number of unresponsive patients employ a particular protocol and – for the first time in many years – begin to improve, doctors would trip over themselves to better understand the issue. Not so. GPs were often outright hostile to the concept, and individuals who visited their doctor reported the same stock responses:

  • “There’s no scientific such thing as adrenal fatigue”. Depends on how you define it.
  • “It’s been proven that adrenal fatigue doesn’t exist”. In interesting one. It’s true that there was a 2016 study (ref) that went to the effort of searching the scientific literature for papers on ‘adrenal fatigue’ and found none. But this was the equivalent of if they searched for ‘belly ache’ instead of ‘intestinal pain’, or ‘fainting’ instead of ‘syncope’. However, if they were to use standardized terms like hypocortisolism or hypoadrenalism, they would find at least 25 studies that connect low adrenal output to the symptoms that patients commonly report.
  • “The adrenals don’t just break”. True.
  • “You’re clearly just depressed”. Hmm.
  • “I don’t know what suddenly made you better, I just know it wasn’t this protocol.” Yes, I’ve actually heard this. Many times.

As tempting is it is to bash the mainstream approach as callous and stubborn, should we really be surprised? It makes sense that practitioners would rightly approach new ideas with suspicion and especially so if they don’t make sense from a physiological perspective. And, unfortunately, the problem with the ‘adrenal fatigue’ concept is that it is physiologically incorrect. As my hours of research accumulated, the faults in the model were increasingly laid bare. What’s more, after over 1,000 adrenal tests – on both chronic fatigue patients, athletes and ‘the man in the street’ – it was very clear that there was more too it than “low cortisol = adrenal fatigue”. Of the patients with crippling fatigue, there were almost as many tests showing high cortisol output as there were with low readings.

It turned out that individuals could show a robust response from the adrenal cortex (as measured in ACTH Challenge tests) and still suffer an ‘adrenal crash’ after emotional or physical stressors (eg. exercise).

Equally, it turned out that there was no mechanism through which adaptogenic herbs could actually boost the adrenal output. They could reduce activation of the pituitary gland (through boosting levels of NPY, ref) but no study showed any improvement in cortisol production. So why were so many individuals reporting their low cortisol symptoms went away?

Equally, it turned out that Vitamin C rarely had any impact on the production of cortisol (I did a lot of before-and-after tests). Although the physiology textbooks clearly identified Vitamin C as a co-factor in manufacturing adrenal hormones, the research clearly indicated that Vitamin C actually helped lower cortisol levels in individuals under stress (ref). Yet, even where adrenal output was unaffected, we would often see improvements in ‘adrenal fatigue’ symptoms. It was helping… just not in the way described! So then, what was the Vitamin C doing?

The explanations proposed clearly didn’t actually play out… and yet, no other model offered such predictive value. There was no evidence that any adaptogenic herbs could increase output of cortisol (or any other adrenal hormone)… and yet, they sometimes helped relieve ‘low adrenal’ symptoms.




  • People who had symptoms of ‘adrenal fatigue’ got better when they introduced an ‘adrenal fatigue protocol’
  • The protocol was working for many, yet the physiology offered to explain these responses was weak
  • Mainstream medicine rejected the evidence to support this model but also refused to engage in dialogue or further investigation
  • Patients with these symptoms felt that they needed to choose between accepting a contrived diagnosis or self-treatment


This is Part One of a two-part series. For the second part,  The Adrenal-Endotoxemia Cycle and How Symptoms are Mediated by Inflammation, click here.

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