Know It All: Adrenal Fatigue

Know It All: Adrenal Fatigue

Stress: it’s something we all deal with in one form or another, and it takes a major toll on our health. Prolonged stress (or an acute bout of major, major stress) can lead to something called hypoadrenalism or HPA axis dysfunction – more commonly referred to as “adrenal fatigue”. That term gets thrown around a lot, and there are arguments from both sides about whether it exists or not. In my opinion, it exists and it causes a lot of people to suffer. However, it can be induced by our own doing – for example, being too low carb (or being too low carb while exercising a lot) can really tax the adrenals and eventually lead to hypoadrenalism. Hypoadrenalism can also obviously be caused by excessive stress that we do nothing to combat. This article will focus on the causes of HPA axis dysfunction (adrenal fatigue), and exactly what you can do to heal.

Symptoms of Hypoadrenalism (Adrenal Fatigue):

  • Excessive fatigue.  This fatigue is usually most pronounced during the day and you may experience a “second wind” of energy later in the evening
  • In the earlier stages of adrenal fatigue, you may also have trouble sleeping at night. You may experience insomnia or wake up multiple times during the night.
  • Blood sugar crashes – low energy, shaky, “hangry” (angry and hungry!) feelings.
  • Postural hypotension – feeling dizzy or vision blacking out when you go from sitting or lying down to standing. This is due to blood pressure dropping (instead of rising) when you stand up.
  • Increased allergies or asthma symptoms.
  • Recurrent infections.
  • Cognition and memory problems – brain fog, forgetfulness, and cognitive issues are all possible signs of adrenal fatigue.
  • Salt cravings.

The HPA Axis: How We Respond to Stress

As soon as a stressor occurs, the body begins its reaction. The hypothalamic-pituitary-adrenal axis (HPA axis) is the control center for reactions to stress, and in turn regulates many other body functions like digestion and immunity. Upon interaction with a stressor, corticotropin-releasing hormone (CRH) is released from the hypothalamus. CRH travels within the blood to the anterior pituitary gland, where it stimulates the production of adrenocorticotropic hormone (ACTH). ACTH then travels through the blood to the adrenal cortex, where it ultimately stimulates the release of cortisol, the body’s main “stress hormone”, along with other hormones like DHEA. Cortisol works to keep blood glucose elevated and helps the body retain sodium and fluid so that our blood pressure stays high and our blood glucose levels can keep up with the fuel demands of the brain and other vital organs during times of stress. This process is hugely important in keeping us alive during a true “fight or flight” response, but what happens when we start activating the HPA-axis for every little stressor in our lives? The HPA-axis is not meant to be chronically activated and over time our adrenal health suffers.

Under normal circumstances, when the HPA-axis is activated only when truly necessary – negative feedback cycles stimulated by the glucocorticoids produced in the adrenals reduce CRH and ACTH production in the hypothalamus and pituitary, respectively. This feedback cycle serves to deactivate the HPA axis when the body doesn’t need it.[1] A healthy stress response is one that activates the HPA axis when needed, and shuts it down when the stressor ceases. Chronic stress, as experienced by many people in industrialized countries, has a negative effect on health as a result of chronic activation of the HPA axis.


One way of determining HPA axis function is to look at diurnal salivary cortisol curves. In a healthy person, activation of the HPA axis upon rising in the morning causes cortisol to peak, and then decline over the day to its lowest point at about midnight.[2] With increased allostatic load, this pattern starts to change. Allostatic load is defined as “the cost of chronic exposure to fluctuating or heightened neural or neuroendocrine response resulting from repeated or chronic environmental challenge that an individual reacts to as being particularly stressful.”[3] A high allostatic load can cause a flattened diurnal cortisol curve, indicating HPA axis deregulation.

Hans Selye, one of the forefathers of stress research, spoke of this phenomenon in 1950 when he described his “General Adaptation Syndrome” (GAS) concept. GAS develops in three stages: the alarm reaction, resistance stage, and the exhaustion stage.[4]  During the alarm reaction, the body senses a stressor and implements the “fight or flight” response. If the stressor continues for long enough, the body enters the resistance stage, where cortisol, blood glucose, and adrenaline levels stay elevated. If the stressor still persists, eventually the body enters the exhaustion stage where resources to fight the stressor have been depleted. See the chart below for a visual representation of the three stages.



As stress piles on and allostatic load increases, patients go through the three stages of the General Adaptation Syndrome, the end result (exhaustion stage) being fatigue, depression, and low cortisol levels. Interestingly, as allostatic load increases and the body starts going through the three stages of the GAS, cortisol patterns look very much like the diagram above. Compare the stages of the General Adaptation Syndrome to that of the stages of “adrenal fatigue” or hypoadrenalism below.



Let’s also compare a normal diurnal cortisol curve to that of someone with HPA axis dysfunction or “adrenal fatigue”:



What to Do if You Have HPA Axis Dysfunction (Adrenal Fatigue)

You don’t need to do all of these things, but I thought it would be useful to give you all the options out there and you can work with your practitioner to determine what therapies might suit you best.

Diet: A general, healthful diet should be used to treat adrenal insufficiency: high intake vegetable and fruits, avoid sugars and other refined carbohydrates, adequate intake of fiber and water (i.e. a Paleo, Weston A. Price, real food type diet!). A diet like this will be high in many of the nutrients important for the hypoadrenalism patient, including Vitamin C, magnesium, pantothenic acid, and pyridoxine (read on for specific information regarding these nutrients). Patients should also be encouraged to make and eat fermented foods, which contain probiotics beneficial to the hypoadrenalism patient (probiotics are mentioned specifically below). Many patients with hypoadrenalism experience reactive hypoglycemia, thus dietary adjustments for this condition are usually helpful.[5] Reactive hypoglycemics should consume small, frequent meals that are low in simple carbohydrates and high in protein.[6] Nutritional factors that affect glycemic control should also be considered, such as chromium and l-arabinose.[7] Diets for hypoadrenalism patients are also usually not salt-restricted.40 Multivitamin/multimineral should be considered, especially if patients are not consuming a good diet

Medication/Supplementation: Listed below are some medical and nutritional factors that may affect hypoadrenalism.

Hydrocortisone: Cortisol may be used in the lowest effective dose for the patient.41 This is usually only for the most severe of cases, and all nutritional and lifestyle factors have not helped. This is the last resort.

Adaptogens: As defined by Brekhman in 1968, an adaptogen has four main characteristics:

1. The action of an adaptogen should be innocuous and cause minimal disturbance to the normal physiological functions of an organism. It must be absolutely harmless;

2. an adaptogenic agent should not be active only in a specific context or against a particular background. It must have a broad therapeutic spectrum of action;

3. the action of an adaptogen has to be non-specific, that is to say, resistance to a wide variety of action of harmful factors, whether of a physical, chemical or a biological nature, has to increase. In other words, the action of an adaptogen has to be more intense as unfavorable changes occur in an organism;

4. an adaptogen has to have a normalizing or stabilizing action independent of the direction of previous changes.[8]


Licorice root (glycyrrhia glabra), a HPA axis potentiator, is an 11beta-hydroxysteroid dehydrogenase (11B-HSD) inhibitor. 11B-HSD converts active cortisol to inactive cortisone, so when this enzyme is inhibited it enables a potentiated effect of cortisol.[9] In patients on cortisone acetate therapy, ingestion of licorice (or grapefruit juice) increased the amount of cortisol available to tissues after cortisone administration.[10] Licorice root can be taken as a tea, tincture or tablet.[11] (Please note: If you have high blood pressure, licorice root is contraindicated).

Other adaptogens such as eleutherococcus senticosus, ashwaganda, rhodiola rosea, and others have shown to be effective in reducing fatigue related to stress and are likely to be helpful in cases of HPA axis deregulation.[12]

Other Nutritional Factors

Vitamin C: The adrenal gland (specifically the cortex and medulla) contains a very high concentration of Vitamin C compared to all other organs. Vitamin C is required for catecholamine biosynthesis and adrenal steroidgenesis.[13] Vitamin C is released from the adrenals in response to ACTH, so every stressor the body faces causes the adrenals to lose Vitamin C.[14] Thus, Vitamin C intake is very important for the hypoadrenalism patient. Vitamin C infusion treatments have been shown to increase cortisol production[15], however oral Vitamin C is also likely to be effective. Vitamin C doses up to 2,000 – 4,000mg have been shown to be safe and have little adverse effects for the general population[16], so this is a good general guide to work from with the hypoadrenalism patient.

Magnesium: During chronic stress, plasma magnesium is depleted.[17] Magnesium affects the adrenal glands’ sensitivity to ACTH – the start of the activation of the HPA axis.[18] Most Americans do not consume enough magnesium from their diet[19], thus supplementation can be useful, especially for the hypoadrenalism patient. Patients should also eat a magnesium-rich diet containing plenty of green leafy vegetables. Refining or processing food removes up to 85% of magnesium[20], so the hypoadrenalism patient should be encouraged to eat a whole foods, unprocessed diet as much as possible.

Pantothenic acid:Pantothenic acid is required for the structural integrity of the adrenal glands, and pantothenic acid-deficient mice have been shown to have decreased adrenal function.[21] There have been limited studies done on humans in this regard, but it is not far-fetched to imagine that given pantothenic acid’s important role in the structural integrity of the adrenal glands that this vitamin is necessary for proper adrenal health. Hypoadrenalism patients should eat a diet high in this vitamin and/or supplement with a B-vitamin complex.

Pyrodoxine (Vitamin B6): The glucocorticoid action of cortisol is decreased in pyridoxine-deficient animals[22] , indicating that pyrodoxine is important to cortisol production and function. As mentioned with pantothenic acid, hypoadrenalism patients should be encouraged to take a B-vitamin supplement. Women who are using oral contraceptives should supplement with B6, as they have been shown to have lower stores of this important vitamin.[23]

Probiotics: Gut health is important to overall health, and it has recently been shown that the gut flora of rats has an affect on the HPA axis. Rats that had no exposure to microorganisms (germfree; GF) had significantly higher ACTH and corticosterone responses to restraint stress than did rats with normal gut bacteria.[24] Another study in rats showed that those exposed to endotoxin (like that which a human would be exposed to if they acquired a pathogen) displayed altered HPA axis activity.[25]  Stress is known to alter the gut microbiota, and in turn this change alters the HPA axis.[26] It seems that normal gut flora is required for proper HPA axis activity and that clearing of pathogens and replacing lost beneficial bacteria with probiotic supplementation will likely benefit those suffering from HPA axis dysfunction.

Anxiolytic Herbal Preparations: To reduce anxiety experienced by many with hypoadrenalism, anxiolytic herbs may be used. Some of these include L-theanine, Passiflora incarnata, Valeriana officinalis, Humulus lupulus, Matricaria chomomilla, Galphimia glauca, Bacopa monniera, Centella asiatica, Melissa officinalis, Piper methysticum, Scutellaria lateriflora, and Ziziphus jujuba.48 Preparations may be made from one or more herbs and used as needed for anxiety relief.

Lifestyle Changes

Mind-body medicine techniques: Exercise can help to attenuate the cortisol response to stress, especially as women age.[27] Yoga, in particular, can help to reduce anxiety, depression, perceived stress, and morning salivary cortisol levels.[28] Tai chi has been shown to decrease salivary cortisol after a stressful event.[29] In a study on mindfulness-based stress reduction, 40% of participants had abnormal cortisol secretion patterns before intervention. After the intervention, there was a shift from “inverted-V shaped” patterns to “V-shaped” patterns of secretion, indicating change to a more normal cortisol rhythm.[30] Guided imagery has been shown to reduce salivary cortisol levels in overweight Latino adolescents.[31] Patients with hypoadrenalism should be encouraged to find a mind-body medicine technique that they enjoy and do it on a regular basis to promote appropriate responses to major and minor stressful events.

Sleep: The hypoadrenalism patient should be encouraged to wake and sleep at approximately the same time every night to help the HPA axis function properly. Lack of sleep and/or shift work disrupting sleeping patterns were likely instrumental in precipitating HPA axis dysfunction (bringing the patient into the Resistance phase), as sleep deprivation and disordered sleeping cause HPA axis hyperactivity.[32] Normalizing sleep patterns should have a beneficial effect on HPA axis activity. Use of blue-blocker glasses at nighttime (if the patient is exposed to blue light, such as that emanating from a computer or TV screen) can prevent the light-induced melatonin suppression.[33] If possible, patients should be advised to avoid blue light sources prior to bedtime.

Religiosity/Spirituality: Those who show medium or high religiosity or spirituality show normal cortisol rhythms (high in the morning, low at night) compared to those with low religiosity or spirituality whose cortisol rhythms appear flattened.[34] It is likely that those with hypoadrenalism may find additional benefit to spiritual or religious support in their lives.

Social Interaction: Oxytocin and social support protect against the negative effects of stress.[35] It is thought that community and social ties and their association with increased health and longevity is due in part to their attenuation of the stress response.[36] Intimacy with partners showed decreases in salivary cortisol levels.[37] In the earlier stages of HPA axis dysfunction (when cortisol levels are high), social interaction and support can be an effective strategy for bringing cortisol rhythm back to normal. Even in the late stages of adrenal fatigue when cortisol is low, finding support is likely effective in regulating cortisol production. It is very important for those who suffer from hypoadrenalism to find support in their community.

Avoidance of toxic compounds: In animals, DDT analogues and metabolites have been shown to inhibit the synthesis of cortisol as well as cause adrenocorticol toxicity.[38] Organochlorines effect cortisol production in polar bears, a species regularly exposed to these contaminants.[39] This is certainly an area that needs further research, but the hypoadrenalism patient would be wise to avoid known toxins in the environment such as BPA, PCBs, organochlorines, among others.

There you have it! I hope this posts answers a lot of your questions related to “adrenal fatigue”. If you have any further questions, feel free to post a comment!


[1] Jones, David S. “Clinical Approaches to Hormonal and Neuroendocrine Imbalances.” Textbook of Functional Medicine. Gig Harbor, WA.: Institute for Functional Medicine, 2010. 611-14. Print.

[2] Stone, Arthur A., et al. “Individual differences in the diurnal cycle of salivary free cortisol: a replication of flattened cycles for some individuals.” Psychoneuroendocrinology 26.3 (2001): 295-306.

[3] McEwen, Bruce S., and Eliot Stellar. “Stress and the individual: mechanisms leading to disease.” Archives of internal medicine 153.18 (1993): 2093.

[4] Selye, Hans. “Stress and the general adaptation syndrome.” British Medical Journal 1.4667 (1950): 1383-1392.

[5] Gaby, Alan. “Hypoadrenalism (adrenocortical Insufficiency).” Nutritional Medicine. Concord, N.H: Fritz Perlberg, 2011. 1118-120. Print.

[6] Sanders, LEONARD R., et al. “Refined carbohydrate as a contributing factor in reactive hypoglycemia.” Southern medical journal 75.9 (1982): 1072.

[7] Kaats, Gilbert R., et al. “A combination of l-arabinose and chromium lowers circulating glucose and insulin levels after an acute oral sucrose challenge.” Nutrition journal 10 (2011): 42-42.

[8] Davydov, Marina, and A. D. Krikorian. “< i> Eleutherococcus senticosus</i>(Rupr. & Maxim.) Maxim.(Araliaceae) as an adaptogen: a closer look.” Journal of ethnopharmacology 72.3 (2000): 345-393.

[9] Anderson, D. “Assessment and nutraceutical management of stress-induced adrenal dysfunction.” Integrative Medicine 7.5 (2008).

[10] Methlie, Paal, et al. “Grapefruit juice and licorice increase cortisol availability in patients with Addison’s disease.” European Journal of Endocrinology 165.5 (2011): 761-769.

[11] “Licorice.” NYU Langone Medical Center. N.p., July 2012. Web. 23 Feb. 2013.

[12] Sleep, Restless. “Nutrients and botanicals for treatment of stress: adrenal fatigue, neurotransmitter imbalance, anxiety, and restless sleep.” Alternative Medicine Review 14.2 (2009): 114-140.

[13] Patak, P., H. S. Willenberg, and S. R. Bornstein. “Vitamin C is an important cofactor for both adrenal cortex and adrenal medulla.” Endocrine research 30.4 (2004): 871-875.

[14] Padayatty, Sebastian J., et al. “Human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone.” The American journal of clinical nutrition 86.1 (2007): 145-149.

[15] Kodama, M., T. Kodama, and M. Murakami. “Vitamin C infusion treatment enhances cortisol production of the adrenal via the pituitary ACTH route.” In vivo (Athens, Greece) 8.6 (1994): 1079.

[16] Hathcock, John N., et al. “Vitamins E and C are safe across a broad range of intakes.” The American journal of clinical nutrition 81.4 (2005): 736-745.

[17] Cernak, I., et al. “Alterations in magnesium and oxidative status during chronic emotional stress.” Magnesium research: official organ of the International Society for the Development of Research on Magnesium 13.1 (2000): 29.

[18] Eby, George A., and Karen L. Eby. “Magnesium for treatment-resistant depression: a review and hypothesis.” Medical hypotheses 74.4 (2010): 649.

[19] Ford, Earl S., and Ali H. Mokdad. “Dietary magnesium intake in a national sample of US adults.” The Journal of nutrition 133.9 (2003): 2879-2882.

[20] Swaminathan, R. “Magnesium metabolism and its disorders.” The Clinical Biochemist Reviews 24.2 (2003): 47.

[21] Hurley, Lucille S., and Julia B. Mackenzie. “Adrenal Function in the Pantothenic Acid-Deficient Rat Liver Glycogen, Blood Glucose, Adrenal Cholesterol and Adrenal Ascorbic Acid Levels.” The Journal of nutrition 54.3 (1954): 403-415.


[23] Wilson, Stephanie, et al. “Oral contraceptive use: impact on folate, vitamin B6, and vitamin B12 status.” Nutrition reviews 69.10 (2011): 572-583.

[24] Sudo, Nobuyuki, et al. “Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice.” The Journal of physiology 558.1 (2004): 263-275.

[25] Shanks, Nola, et al. “Early-life exposure to endotoxin alters hypothalamic–pituitary–adrenal function and predisposition to inflammation.” Proceedings of the National Academy of Sciences 97.10 (2000): 5645-5650.

[26] Foster, Jane A., and Karen-Anne McVey Neufeld. “Gut–brain axis: how the microbiome influences anxiety and depression.” Trends in neurosciences (2013).

[27] Traustadóttir, Tinna, Pamela R. Bosch, and Kathleen S. Matt. “The HPA axis response to stress in women: effects of aging and fitness.” Psychoneuroendocrinology 30.4 (2005): 392-402.

[28] Raghavendra, Rao M., et al. “Effects of a yoga program on cortisol rhythm and mood states in early breast cancer patients undergoing adjuvant radiotherapy: a randomized controlled trial.” Integrative Cancer Therapies 8.1 (2009): 37-46.

[29] Jin, Putai. “Efficacy of Tai Chi, brisk walking, meditation, and reading in reducing mental and emotional stress.” Journal of psychosomatic research 36.4 (1992): 361-370.

[30] Carlson, Linda E., et al. “Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate cancer outpatients.” Psychoneuroendocrinology 29.4 (2004): 448-474.

[31] Weigensberg, Marc J., et al. “Acute Effects of Stress-Reduction Interactive Guided ImagerySM on Salivary Cortisol in Overweight Latino Adolescents.” The Journal of Alternative and Complementary Medicine 15.3 (2009): 297-303.

[32] Balbo, Marcella, Rachel Leproult, and Eve Van Cauter. “Impact of sleep and its disturbances on hypothalamo-pituitary-adrenal axis activity.” International journal of endocrinology 2010 (2010).

[33] Sasseville, Alexandre, et al. “Blue blocker glasses impede the capacity of bright light to suppress melatonin production.” Journal of pineal research 41.1 (2006): 73-78.

[34] Dedert, Eric A., et al. “Religiosity may help preserve the cortisol rhythm in women with stress-related illness.” The International Journal of Psychiatry in Medicine 34.1 (2004): 61-77.

[35] Heinrichs, Markus, et al. “Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress.” Biological psychiatry 54.12 (2003): 1389-1398.

[36] Seeman, Teresa E., and Bruce S. McEwen. “Impact of social environment characteristics on neuroendocrine regulation.” Psychosomatic medicine 58.5 (1996): 459-471.

[37] Ditzen, Beate, Christiane Hoppmann, and Petra Klumb. “Positive couple interactions and daily cortisol: On the stress-protecting role of intimacy.” Psychosomatic Medicine 70.8 (2008): 883-889.

[38] Sanderson, J. Thomas. “The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals.” Toxicological sciences 94.1 (2006): 3-21.

[39] Oskam, Irma, et al. “Organochlorines affect the steroid hormone cortisol in free-ranging polar bears (Ursus maritimus) at Svalbard, Norway.” Journal of Toxicology and Environmental Health 67.12 (2004): 959-977.

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