"Adrenal Fatigue" does NOT exist; here's why
Updated: Jan 23, 2022
“Adrenal Fatigue” is a common term used in the alternative medicine space to describe chronic fatigue
Cortisol is the main hormone released by the adrenal glands that is thought to be implicated with the stress hormone
Many organs other than the adrenals can synthesize and release cortisol
Cortisol levels do no correlated with energy levels
Low cortisol can lead to symptoms
There are many causes of low cortisol that needs to be addressed
“Adrenal Fatigue” does not exist
Do you have "adrenal fatigue"?
Do you struggle with:
Low energy levels
Trouble falling or staying asleep
Perhaps you’ve done some research on your symptoms and came to the conclusion that you have “adrenal fatigue”.
“Adrenal Fatigue” is a common term that has become very popular in the alternative medicine space. This is a theoretical condition popularized in some health circles that characterizes a state of low energy induced by chronic stress. This has lead many over-zealous clinicians to throw out this diagnosis to patients. In addition, many patients are self-diagnosing themselves with this condition.
The thinking is that the adrenal glands “fatigue” and are unable to meet the demands of the body because of high stress levels. This leads to a reduced amount of cortisol to be produced by the adrenal glands and the subsequent low energy levels.
Understandably, this makes sense at the surface level. However, one of my responsibilities is to give my patients evidence-informed solutions to their health concerns. With that said, I gathered some of the latest up-to-date research on this topic to examine the question, “Is adrenal fatigue a real condition” And if not, what can cause low cortisol levels?”
What we are going to cover in this article is a brief overview of the stress response, an overview of why adrenal fatigue does not exist, and a few causes for low cortisol that is validated in the literature.
What is the stress response?
As mentioned before, the notion of adrenal fatigue implies that the organs responsible for secreting the stress hormone, cortisol, eventually become “fatigued” and “burned out” because of chronic stress.
In order to evaluate this claim, it’s important to look at the conventional model of the body’s stress response. I’ll try to make this is as simple, yet interesting, as possible.
A stressor is a perceived or real threat to the body. This can be psychological (losing job, ending a relationship, stuck in traffic, etc.) or physical (high blood sugar, infection, inflammation, poor sleep, etc.). Part of the brain called the hypothalamus senses this threat. Through a series of hormones, the brain tells the hat-shaped organs on top of the kidneys called the adrenal glands to produce cortisol. This is called the HPA-system, or Hypothalamus-Pituitary-Adrenal system, to explain the connections of the multiple parts of the body that orchestrate this stress response.
Cortisol is the main “stress hormone” released by the body after it senses a threat (either psychological or physical). The brain and adrenal glands also release epinephrine and norepinephrine- these hormones kick in the “fight or flight” part of the brain.
This picture below depicts this hormonal communication between the brain (hypothalamus and pituitary gland) and the multitude of downstream hormone-producing glands, including the adrenal glands.
It may make sense that an overactive stress response may eventually lead to the poor adrenal glands to become “burned out”. However, let’s examine this claim first-hand to see if it has any merit in managing your energy levels.
Examining the evidence for “Adrenal Fatigue”
Historically, adrenal fatigue has been used to explain other health conditions such as diabetes, mental health disorders, obesity, weight gain, sleep disturbances, low energy, and cardiovascular disease.
Some clinicians may tell you that it takes an average of 6-12 months to “recover your adrenal glands”. They might give you 20 different supplements to get your adrenal glands to start working again. However, this practice is not rooted in what the literature says about chronic fatigue and cortisol levels.
Why “Adrenal Fatigue” does NOT exist
Long-story short is that “adrenal fatigue” does not exist. Here’s the evidence to support this claim.
1. Many organs synthesize and release cortisol
You might be surprised to know that many organs synthesize cortisol. That’s right, organs other than the adrenal glands can produce and secrete cortisol. For example, there is a whole HPA system that has been found in the skin. This means that the hormones released by the brain and the adrenal glands can all be produced by the skin alone. Dysfunction of the HPA axis in the skin has been associated with acne, psoriasis, and atopic dermatitis.
One study found that enzymes responsible for synthesis and conversion of cortisol are found within the immune system, gut, skin, brain, and even the heart. Moreover, fat tissue and the liver are able to recycle inactive cortisol into its active form.
In one study, cortisol production by organs other than the adrenal glands accounted for 50% of total cortisol measured in the body. This indicates that the cortisol produced elsewhere in the body actually makes a difference in hormonal levels. Another study noted that cortisol produced from places other than the adrenal glands have concentrations sometimes much higher than levels found in the blood.
2. Low cortisol does not correlate with energy levels
A groundbreaking review of 58 studies concluded that there is no such thing adrenal fatigue. The authors boldly state, “This systematic review proves that there is no substantiation that ‘adrenal fatigue’’ is an actual medical condition. Therefore, adrenal fatigue is still a myth” (Cadegiani et al). In this review, the authors found that those with chronic fatigue syndrome (characterized by fatigue lasting longer than 6 months) had no different cortisol levels compared to healthy controls. In fact, a good amount of those with chronic fatigue syndrome had higher cortisol levels. This, in and of itself, puts a big hole in the adrenal fatigue hypothesis.
Another study of 165 participants with adrenal insufficiency (severe lack of cortisol production) were noted to have high rates of severe fatigue. However, fatigue was not correlated with cortisol levels. The authors state that “our results indicate that there are no significant correlations between salivary cortisol levels and momentary fatigue… and that cortisol is not a significant predictor for momentary fatigue during the day” (Giebels et al).
A Dutch researcher of chronic fatigue syndrome found that correlations between cortisol responses and perceived emotional stress variables were found in merely 25% of studies (Jonsdottir et al).
The adrenal fatigue hypothesis would have us believe that stress levels would be associated with cortisol levels. However, multiple studies have shown that psychological stress scores are not correlated with energy levels. This might be due to the fact that each person’s response to stress is very different given their perspective, spiritual life, early life experiences, social factors, and personality.
3. Cortisol is also controlled at the local level
Most studies do not confirm HPA system dysfunction in those with chronic fatigue or “adrenal fatigue”. Instead of the brain being the master regulator of cortisol production and release, there may be other factors that affect the adrenal glands locally.
For example, specific white blood cells have been found to infiltrate the adrenal glands and produce pro-inflammatory molecules that affect cortisol secretion.
Similarly, testosterone production (also produced in the adrenal glands as well as the testes) are affected by inflammatory molecules. This makes sense given the notion that your body is not going to worry about reproduction when it’s fighting an infection or recovering from a severe illness.
4. Low cortisol can be a sign of another issue
As we will soon discuss, low cortisol is a real lab finding. However, this is usually a cause of another problem.
In 20 patients with sepsis (a severe bacterial infection), low cortisol levels were noted. However, the levels went back to a normal baseline after the patients recovered. This confirms other studies that show low adrenal gland activity in up to 75% of those with sepsis. This might be because those with sepsis who had increased cortisol had higher rates of mortality and disease severity. Perhaps, a less-severe form of inflammation or infection can contribute to lower cortisol levels.
Addressing the root cause of low cortisol
Don’t get me wrong, I’ve identified many patients with suspected sub-optimal levels of cortisol in practice. This doesn’t mean that their adrenal glands were “fatigued”. And I’m not talking about those with Addison’s disease who have a severe inability to produce cortisol.
A better term for “adrenal fatigue” may be “cortisol suppression” or “cortisol inhibition”. Let’s discuss the reasons for sub-optimal cortisol levels. In other words, what are the reasons your adrenal glands may be producing less than optimal amount of cortisol.
1. Toxins and cortisol
One paper noted that the “adrenal gland is the most common toxicological target organ in the endocrine system” (Harvey et al). Many medications and toxins have been found to inhibit key enzymes responsible for not only cortisol, but also sex hormones (testosterone, estrogen, progesterone) as well. Such medications and toxins include ketoconazole, glyphosate (found in Roundup), alcohol, and PCB (a toxin that can accumulate in fat tissue). One study listed over 60 chemicals that inhibit cortisol production. Here is that list of toxins (including some medications) along with the enzymes that they inhibit and the other studies that support these findings (Harvey et al).
2. Oxidative stress and cortisol
Oxidative stress is like rusting that occurs inside your body.
The adrenal glands have a high concentration of a type of fat called polyunsaturated fatty acids that are very susceptible to oxidation. Also, enzymes responsible for cortisol production are very sensitive to oxidative stress. This is why the adrenals have also have a high concentration of antioxidants such as vitamin C and vitamin A. One study depleted these key antioxidants in rats which lead to adrenal gland degeneration. Poor antioxidant capacity has also been linked with impaired fertility. It’s important to assess what the source of oxidative stress is from. Sources of oxidative stress include toxins, eating more than what your cells can handle, poor mitochondrial function, and insulin resistance/diabetes. Fortunately, oxidative stress levels can be assessed using some basic blood chemistry markers.
3. Diabetes/Obesity and cortisol
Diabetes and obesity can also suppress cortisol production. Leptin is a hormone produced by fat tissue that tells the brain the levels of long-term fat storage. Leptin has been found to suppress cortisol production at both the level of the brain and the adrenal glands.
4. Nutrition and cortisol
The part of the brain responsible for starting the cascade that leads to cortisol production is also the part of the brain that acts as the “gas pedal and brake” for eating. When this system becomes dysfunctional from either too much or too little of food, hormonal imbalances can result. Furthermore, macronutrient ratios (balance of protein, carbohydrates, and fat) can change how much and where cortisol is secreted.
5. Inflammation and cortisol
Inflammatory molecules called cytokines also affect cortisol production. One paper stated that, “Cytokines interact and modulate steroidogenesis at the levels of the adrenal glands, testes, and ovaries, influencing function and development of these glands in a complex and systematic manner” (Bornstein et al). This can be a downward spiral where inflammation leads to low cortisol and testosterone which can then lead to more inflammation (since cortisol and testosterone are “anti-inflammatory).
6. Gut health and cortisol
“Bad” gut bacteria release toxins called LPS. When researchers inject LPS into mice, the adrenal glands suppressed cortisol production within 4 hours of administration. This means that “adrenal fatigue” should not take 6-12 months to recover if you get rid of the thing causing suppressed levels in the first place. Addressing gut health remains a stable of my practice.
7. Viruses and cortisol
Viruses can also cause cortisol suppression. In one paper, the authors noted that the SARS family of viruses (this includes COVID) induces autoimmunity against the hormone that causes cortisol secretion. This has also been noted in influenza family of viruses as well.
8. Mitochondria and Cortisol
The mitochondria are the “kidney bean” shaped part of the cell that makes energy. The mitochondria are also responsible for producing cortisol and sex hormones from cholesterol. Many factors can cause dysfunctional mitochondria. For example, many micronutrients (copper, manganese, zinc, selenium) are needed for the mitochondria to process the harmful molecules that can accumulate within the mitochondria. Deficiencies of these micronutrients can impair this processing which can lead to poor energy production and low-grade inflammation.
9. Mental health and cortisol
There is a bi-directional relationship between mental health and cortisol response. This means that they both affect each other. In fact, HPA system dysfunction has been implicated in a multitude of psychiatric conditions including bipolar disorder, depression, and anxiety. This also may mean that assessing your perspective on life is an important step in improving your biology and overall health.
10. Gender and cortisol
Gender can also affect cortisol production. Females have been found to be more responsive to stressful stimuli. This may be due to the action of estrogen on the brain. In fact, when researchers take the ovaries out of rats, the whole HPA system is suppressed. On the other hand, testosterone may mitigate the brain’s response to stress. When researchers take out the testes of male rats, the stress response become more sensitive. This highlights the far-reaching impact of hormones on multiple organ systems of the body.
Other causes of chronic fatigue
There are other causes of chronic fatigue that have nothing to do with the adrenal glands, cortisol, of the stress response. Here are some possible causes to look into.
Hormonal imbalances (testosterone, thyroid, female hormones)
Liver and kidney dysfunction
Chronic lung conditions
Sleep apnea and other sleep disorders
Gut issues including IBS
The Bottom Line
In this article, we reviewed what the stress response is, the notion of “adrenal fatigue”, and why it is not a validated term when we look at the research.
The idea that it takes 6-12 months for your adrenal glands to “recover” is ill-founded. It shouldn’t take $200 tests to assess cortisol levels. In fact, a basic blood chemistry and good history can give me a good idea of cortisol levels and potential issues causing suppressed levels.
In my practice, I focus on identifying and treating the root cause of symptoms commonly associated with “adrenal fatigue” including chronic fatigue, poor sleep, hormonal imbalances, and weight gain. This means using validated tests including blood chemistry tests and focusing on nutrition, diet, lifestyle, supplemental, and medications (when necessary) to address the factors discussed above that may be suppressing/inhibiting cortisol production.
I hope you found this information useful and helpful in your journey back to a healthier and happier life.
Like what you are reading? Learn more about how to take control of your health by signing up for the "5 Minute Health Makeover" below where I coach you through 3 pivotal strategies for better health.
1. Bornstein SR, Rutkowski H, Vrezas I. Cytokines and steroidogenesis. Mol Cell Endocrinol. 2004;215(1-2):135-141. doi:10.1016/j.mce.2003.11.022
2. Briegel J, Schelling G, Haller M, Mraz W, Forst H, Peter K. A comparison of the adrenocortical response during septic shock and after complete recovery. Intensive Care Med. 1996;22(9):894-899. doi:10.1007/BF02044113
3. Buss NA, Gavins FN, Cover PO, Terron A, Buckingham JC. Targeting the annexin 1-formyl peptide receptor 2/ALX pathway affords protection against bacterial LPS-induced pathologic changes in the murine adrenal cortex. FASEB J. 2015;29(7):2930-2942. doi:10.1096/fj.14-268375
4. Cadegiani FA, Kater CE. Adrenal fatigue does not exist: a systematic review [published correction appears in BMC Endocr Disord. 2016 Nov 16;16(1):63]. BMC Endocr Disord. 2016;16(1):48. Published 2016 Aug 24. doi:10.1186/s12902-016-0128-4
5. Dalegrave D, Silva RL, Becker M, Gehrke LV, Friedman G. Relative adrenal insufficiency as a predictor of disease severity and mortality in severe septic shock. Rev Bras Ter Intensiva. 2012;24(4):362-368. doi:10.1590/s0103-507x2012000400012
6. Giebels V, Repping-Wuts H, Bleijenberg G, Kroese JM, Stikkelbroeck N, Hermus A. Severe fatigue in patients with adrenal insufficiency: physical, psychosocial and endocrine determinants. J Endocrinol Invest. 2014;37(3):293-301. doi:10.1007/s40618-013-0042-9
7. Harvey PW, Everett DJ, Springall CJ. Adrenal toxicology: a strategy for assessment of functional toxicity to the adrenal cortex and steroidogenesis. J Appl Toxicol. 2007;27(2):103-115. doi:10.1002/jat.1221
8. Herrmann M, Scholmerich J, Straub RH. Influence of cytokines and growth factors on distinct steroidogenic enzymes in vitro: a short tabular data collection. Ann N Y Acad Sci. 2002;966:166-186. doi:10.1111/j.1749-6632.2002.tb04213.x
9. Jonsdottir IH, Sjörs Dahlman A. MECHANISMS IN ENDOCRINOLOGY: Endocrine and immunological aspects of burnout: a narrative review. Eur J Endocrinol. 2019;180(3):R147-R158. doi:10.1530/EJE-18-0741
10. Kim JE, Cho BK, Cho DH, Park HJ. Expression of hypothalamic-pituitary-adrenal axis in common skin diseases: evidence of its association with stress-related disease activity. Acta Derm Venereol. 2013;93(4):387-393. doi:10.2340/00015555-1557
11. Oyola MG, Handa RJ. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity. Stress. 2017;20(5):476-494. doi:10.1080/10253890.2017.1369523
12. Pralong FP, Roduit R, Waeber G, et al. Leptin inhibits directly glucocorticoid secretion by normal human and rat adrenal gland. Endocrinology. 1998;139(10):4264-4268. doi:10.1210/endo.139.10.6254
13. Prasad R, Kowalczyk JC, Meimaridou E, Storr HL, Metherell LA. Oxidative stress and adrenocortical insufficiency. J Endocrinol. 2014;221(3):R63-R73. doi:10.1530/JOE-13-0346
14. Stimson RH, Mohd-Shukri NA, Bolton JL, Andrew R, Reynolds RM, Walker BR. The postprandial rise in plasma cortisol in men is mediated by macronutrient-specific stimulation of adrenal and extra-adrenal cortisol production. J Clin Endocrinol Metab. 2014;99(1):160-168. doi:10.1210/jc.2013-2307
15. Takemura T, Makino S, Takao T, Asaba K, Suemaru S, Hashimoto K. Hypothalamic-pituitary-adrenocortical responses to single vs. repeated endotoxin lipopolysaccharide administration in the rat. Brain Res. 1997;767(2):181-191. doi:10.1016/s0006-8993(97)00460-5
16. Taves MD, Gomez-Sanchez CE, Soma KK. Extra-adrenal glucocorticoids and mineralocorticoids: evidence for local synthesis, regulation, and function. Am J Physiol Endocrinol Metab. 2011;301(1):E11-E24. doi:10.1152/ajpendo.00100.2011
17. Wheatland R. Molecular mimicry of ACTH in SARS - implications for corticosteroid treatment and prophylaxis. Med Hypotheses. 2004;63(5):855-862. doi:10.1016/j.mehy.2004.04.009