HPA axis dysregulation is fundamentally caused by stress, which can take many forms:
- Psychosocial stress (relationships, finances, housing insecurity, discrimination, etc.)
- Inflammation (diet, small intestinal bacterial overgrowth, infection, insulin resistance)
- High or low blood sugar
- Insufficient sleep (sleep apnea, poor sleep habits)
Interventions should first and foremost target these root causes of stress in order to regulate the HPA axis.
Get more rest! Inadequate sleep profoundly potentiates the stress reactivity of the HPA axis (van Dalfsen and Markus, 2018)
Identify and treat underlying conditions. Infections, sleep apnea, autoimmunity, anemia, and more.
- Identify and avoid allergens (food and environmental)
- Practice mental health hygiene (Counseling! Boundary-setting! Cultivate healthy relationships and community!)
- Balance blood sugar (Mosili et al., 2020)
- Exercise (Zschucke et al., 2015), (Stranahan, Lee, and Mattson, 2008)
Cognitive interventions. Our perceptions of stress modulate our physiological responses to it. Check out this TED Talk by health psychologist Kelly McGonigal “How to Make Stress Your Friend.” According to her research, study participants who envisioned their body’s stress response as an adaptive strategy that supports them in rising to a challenge did not suffer from the ill effects of stress on cardiovascular health. She believes, based on her research, that resilience can be learned; that we are capable of “getting better at stress.” It’s amazing — the way we think about stress literally transforms our biology. Mind-body… it’s really just one thing.
Plant-based interventions to support the HPA axis. Essential oils excel at reducing stress and improving sleep (Lillehei and Halcon, 2014), (Karadag et al., 2017), (Ren et al., 2019), (Farrar and Farrar, 2020).
Several recent studies also indicate that essential oils directly regulate the HPA axis and offset the pathologies that result from chronic stress and HPA axis dysregulation.
A 2021 study published in Frontiers in Pharmacology explored the effect of the combined volatile oils of Aquilaria sinensis and Aucklandia costus, an herbal pairing commonly used in traditional Chinese medicine to treat depression, on rats exposed to chronic unpredictable mild stress (CUMS). Inhalation of the combined oils was found to exert an antidepressant effect via modulation of the HPA axis.
In this study researchers stressed rats over the course of 28 days with various nefarious measures (restraint stress, “strange object stimulation,” wet bedding, cage tilting, etc.) and measured subsequent immobility time in an open field test — stressed and depressed rats lose interest in exploring an open space — to assess the rats “degree of despair.” Treatment with volatile oils was found to ameliorate the depressive behaviors induced by the stress condition.
In order to assess the role of the HPA axis in mediating chronic stress-induced depression, the researchers investigated levels of ACTH, corticosterone (the rodent equivalent of cortisol), and the expression of CRH mRNA. All three measures were increased significantly in CUMS rats, indicating, as expected, activation of the HPA axis in response to chronic stress. Administration of the volatile oils significantly decreased the levels of serum ACTH and corticosterone in stressed rats. The authors hypothesize that this may be due to inhibition of HPA axis hyperactivity via restoration of the negative feedback loop between adrenal glucocorticoids and the hypothalamus and pituitary.
Treatment with the volatile oils was also found to impact neurotransmitter concentrations, as well as the expression of their receptors. Researchers found that the levels of 5-HT (serotonin), norepinephrine, dopamine, and acetylcholine were significantly decreased in CUMS rats. Intervention with volatile oils significantly increased levels of these neurotransmitters, and also upregulated expression of the 5-HT1A receptor subtype. This indicates that the volatile oils may also exert their antidepressant effect via regulation of neurotransmitters and their receptors (Li et al., 2021).
A 2018 study published in the International Journal of Molecular Sciences explored the connection between stress-induced anxiety and depression, inflammation, and HPA activation. In this study, agarwood (Aquilaria spp.) essential oil exerted anxiolytic and antidepressant effects in mice stressed by restraint. Researchers theorized that this effect was primarily mediated via agarwood’s anti-inflammatory activity.
Let’s unpack that a bit. Previous research shows that inflammatory messengers known as cytokines are capable of activating the HPA axis, which leads to increased release of CRH from the hypothalamus, ACTH from the pituitary, and cortisol from the adrenals. Restraint stress, which was used to activate the HPA axis in mice, can increase cytokine concentrations in the cerebral cortex, hippocampus, hypothalamus, and the blood. In this study, administration of agarwood essential oil lowered the concentrations of several types of cytokines in a dose-dependent manner, and significantly inhibited gene expression of CRH in the cerebral cortex and hippocampus, and ACTH and cortisol levels in serum (Wang et al., 2018).
Reducing cortisol secretion in response to stress is just one way of protecting the HPA axis against the harmful effects of chronic stress. A 2017 study published in the International Journal of Environmental Research and Public Health found that inhalation of Japanese cedarwood (Cryptomeria japonica) essential oil following the stressor of monotonous work increased salivary DHEA in humans. As you’ll recall, DHEA is another adrenal hormone secreted in response to stress that plays a protective role against the damaging effects of excessive cortisol activity. The sample size was fairly small, and exclusively male, so we need to hold off on making generalizations until more information is available. That being said, the idea that essential oils promote DHEA secretion is an exciting mechanism of HPA regulation to explore (Matsubara et al., 2017).
Essential oils have been found to buffer against chronic stress-induced pathologies, including skin ailments. A 2012 study published in Chemical Senses found that treatment with rose (Rosa alba) essential oil limited chronic stress-induced skin barrier disruption in rats and humans. Researchers measured transepidermal water loss (TEWL) as a marker of skin barrier disruption and found that chronic stress-induced elevation of TEWL was prevented in subjects that inhaled rose essential oil. Inhalation of rose essential oil significantly reduced the overall cortisol response induced by acute stress, which indicates HPA axis involvement (Fukada et al., 2012).
A 2012 study published in Human & Experimental Toxicology explored the effect of propolis essential oil on restraint-stressed rats. Propolis is a resinous substance harvested by honeybees (Apis mellifera) from leaf buds and cracks in the bark of plants, mixed with wax and bee enzymes. Researchers found that volatile oil extracted from propolis significantly reversed the anxiety-like behavior of restraint-stressed mice, and significantly decreased plasma levels of ACTH and corticosterone (Li, et al., 2012).
The neurotransmitter GABA has also been linked to HPA axis regulation. A 2011 study published in Phytotherapy Research explored the effect of bergamot essential oil (Citrus aurantium subsp. bergamia) on the HPA response to acute stress in rats. In this study, inhalation of bergamot essential oil was found to exert anxiolytic effects on behavior, and reduce corticosterone levels in acutely stressed rats. The authors theorize that this was due to GABA-mediated inhibition of the HPA axis at the level of the paraventricular nucleus of the hypothalamus. Previous studies have shown that GABAergic axons terminate on corticotropin-releasing hormone neurons, and that blockade of GABAergic neurotransmission increases CRH release. This indicates involvement of GABA in the regulation of HPA activity.
Linalool, a constituent of bergamot and many other essential oils, has been found to modulate GABA neurotransmission by increasing GABA concentrations, as well as by potentiating the GABAA receptor. Bergamot essential oil is hypothesized to ameliorate anxiety in acutely stressed rats by reducing HPA axis hyperactivity via GABAergic pathways (Saiyudthong and Marsden, 2011).
To sum it up, research in the last decade indicates that essential oils offer great therapeutic value in supporting healthy HPA axis functionality by promoting sleep, reducing stress, stimulating DHEA production, modulating neurotransmission, and reducing HPA hyperactivity in response to stress.
When we’re talking about “adrenal fatigue,” what we’re really talking about is, simply, “fatigue.” Maybe you’ve got a lifestyle of overwork, burnout, and exhaustion. Or maybe you’ve got an undiagnosed condition. If you’re experiencing any of the symptoms attributed to adrenal fatigue, do yourself a favor and find the actual root cause. Check in with a healthcare practitioner to exclude potential underlying disorders like anemia, obstructive sleep apnea, irritable bowel syndrome, depression, anxiety, diabetes, or other systemic illness.
Work with complementary practitioners — herbalists, aromatherapists, nutritionists, naturopaths — to optimize your diet, reduce and manage stress, improve sleep quality, and foster resilience in the HPA axis with herbs and essential oils.
The temptation to buy into the story of adrenal fatigue is clear: if there’s a defective organ we can fix, who wouldn’t want that? It’s empowering to think that you can reclaim your energy and your life back with a pill. It’s so much easier to blame a body part, or an individual body, than to name and dismantle the systemic cultural causes of exhaustion and illness arising from chronic stress.
It’s grind culture that’s broken, not your adrenals. Seriously, get your symptoms checked out. Then go get some rest.
Adrenal fatigue. (2020, May). Hormone Health Network; The Endocrine Society. https://www.hormone.org/diseases-and-conditions/adrenal-fatigue
Cadegiani, F. A., & Kater, C. E. (2016). Adrenal fatigue does not exist: A systematic review. BMC Endocrine Disorders, 16(1). https://doi.org/10.1186/s12902-016-0128-4
Cortisol. (2019, January). You and Your Hormones; The Society for Endocrinology. https://www.yourhormones.info/hormones/cortisol/
Ciato, D., & Albani, A. (2020). Molecular mechanisms of glucocorticoid resistance in corticotropinomas: New developments and drug targets. Frontiers in Endocrinology, 11. https://doi.org/10.3389/fendo.2020.00021
Debunking adrenal fatigue. (2018, January 16). Cedars-Sinai Blog; Cedars-Sinai. https://www.cedars-sinai.org/blog/debunking-adrenal-fatigue.html
Farrar, A. J., & Farrar, F. C. (2020). Clinical aromatherapy. The Nursing Clinics of North America, 55(4), 489–504. https://doi.org/10.1016/j.cnur.2020.06.015
Fukada, M., Kano, E., Miyoshi, M., Komaki, R., & Watanabe, T. (2012). Effect of “rose essential oil” inhalation on stress-induced skin-barrier disruption in rats and humans. Chemical Senses, 37(4), 347–356. https://doi.org/10.1093/chemse/bjr108
Hébert, S., & Lupien, S. J. (2007). The sound of stress: Blunted cortisol reactivity to psychosocial stress in tinnitus sufferers. Neuroscience Letters, 411(2), 138–142. https://doi.org/10.1016/j.neulet.2006.10.028
Hewagalamulage, S. D., Clarke, I. J., Rao, A., & Henry, B. A. (2016). Ewes with divergent cortisol responses to acth exhibit functional differences in the hypothalamo-pituitary-adrenal (Hpa) axis. Endocrinology, 157(9), 3540–3549. https://doi.org/10.1210/en.2016-1287
Karin, O., Raz, M., Tendler, A., Bar, A., Korem Kohanim, Y., Milo, T., & Alon, U. (2020). A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks. Molecular Systems Biology, 16(7). https://doi.org/10.15252/msb.20209510
Karadag, E., Samancioglu, S., Ozden, D., & Bakir, E. (2017). Effects of aromatherapy on sleep quality and anxiety of patients. Nursing in Critical Care, 22(2), 105–112. https://doi.org/10.1111/nicc.12198
Lam, J. C. W., Shields, G. S., Trainor, B. C., Slavich, G. M., & Yonelinas, A. P. (2019). Greater lifetime stress exposure predicts blunted cortisol but heightened DHEA responses to acute stress. Stress and Health, 35(1), 15–26. https://doi.org/10.1002/smi.2835
Li, H., Li, Y., Zhang, X., Ren, G., Wang, L., Li, J., Wang, M., Ren, T., Zhao, Y., Yang, M., & Huang, X. (2021). The combination of aquilaria sinensis (Lour.) gilg and aucklandia costus falc. Volatile oils exerts antidepressant effects in a cums-induced rat model by regulating the hpa axis and levels of neurotransmitters. Frontiers in Pharmacology, 11. https://doi.org/10.3389/fphar.2020.614413
Li, J., Bidlingmaier, M., Petru, R., Pedrosa Gil, F., Loerbroks, A., & Angerer, P. (2018). Impact of shift work on the diurnal cortisol rhythm: A one-year longitudinal study in junior physicians. Journal of Occupational Medicine and Toxicology (London, England), 13. https://doi.org/10.1186/s12995-018-0204-y
Li, Y.-J., Xuan, H.-Z., Shou, Q.-Y., Zhan, Z.-G., Lu, X., & Hu, F.-L. (2012). Therapeutic effects of propolis essential oil on anxiety of restraint-stressed mice. Human & Experimental Toxicology, 31(2), 157–165. https://doi.org/10.1177/0960327111412805
Lillehei, A. S., & Halcon, L. L. (2014). A systematic review of the effect of inhaled essential oils on sleep. Journal of Alternative and Complementary Medicine (New York, N.Y.), 20(6), 441–451. https://doi.org/10.1089/acm.2013.0311
Matsubara, E., Tsunetsugu, Y., Ohira, T., & Sugiyama, M. (2017). Essential oil of japanese cedar (Cryptomeria japonica) wood increases salivary dehydroepiandrosterone sulfate levels after monotonous work. International Journal of Environmental Research and Public Health, 14(1). https://doi.org/10.3390/ijerph14010097
Merkulov, V. M., Merkulova, T. I., & Bondar, N. P. (2017). Mechanisms of brain glucocorticoid resistance in stress-induced psychopathologies. Biochemistry (Moscow), 82(3), 351–365. https://doi.org/10.1134/S0006297917030142
Miller, A. L., Clifford, C., Sturza, J., Rosenblum, K., Vazquez, D. M., Kaciroti, N., & Lumeng, J. C. (2013). Blunted cortisol response to stress is associated with higher body mass index in low-income preschool-aged children. Psychoneuroendocrinology, 38(11). https://doi.org/10.1016/j.psyneuen.2013.06.014
Mosili, P., Mkhize, B. C., Ngubane, P., Sibiya, N., & Khathi, A. (2020). The dysregulation of the hypothalamic–pituitary–adrenal axis in diet-induced prediabetic male Sprague Dawley rats. Nutrition & Metabolism, 17(1), 104. https://doi.org/10.1186/s12986-020-00532-1
Ouellet-Morin, I., Odgers, C. L., Danese, A., Bowes, L., Shakoor, S., Papadopoulos, A. S., Caspi, A., Moffitt, T. E., & Arseneault, L. (2011). Blunted cortisol responses to stress signal social and behavioral problems among maltreated/bullied 12-year-old children. Biological Psychiatry, 70(11). https://doi.org/10.1016/j.biopsych.2011.06.017
Palumbo, M. L., Prochnik, A., Wald, M. R., & Genaro, A. M. (2020). Chronic stress and glucocorticoid receptor resistance in asthma. Clinical Therapeutics, 42(6), 993–1006. https://doi.org/10.1016/j.clinthera.2020.03.002
Powell, D. J. H., Liossi, C., Moss-Morris, R., & Schlotz, W. (2013). Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: A systematic review and subset meta-analysis. Psychoneuroendocrinology, 38(11), 2405–2422. https://doi.org/10.1016/j.psyneuen.2013.07.004
Seaborg, E. (2017, September 7). Treating the Symptoms that are believed to be Adrenal Fatigue. Endocrine News; The Endocrine Society. https://endocrinenews.endocrine.org/myth-adrenal-fatigue/
Ren, G., Zhong, Y., Ke, G., Liu, X., Li, H., Li, X., Zheng, Q., & Yang, M. (2019). The mechanism of compound anshen essential oil in the treatment of insomnia was examined by network pharmacology. Evidence-Based Complementary and Alternative Medicine : ECAM, 2019. https://doi.org/10.1155/2019/9241403
Saiyudthong, S., & Marsden, C. A. (2011). Acute effects of bergamot oil on anxiety-related behaviour and corticosterone level in rats: ACUTE EFFECTS OF BERGAMOT OIL ON ANXIETY-RELATED BEHAVIOUR. Phytotherapy Research, 25(6), 858–862. https://doi.org/10.1002/ptr.3325
Stranahan, A. M., Lee, K., & Mattson, M. P. (2008). Central mechanisms of hpa axis regulation by voluntary exercise. Neuromolecular Medicine, 10(2), 118–127. https://doi.org/10.1007/s12017-008-8027-0
Thau, L., Gandhi, J., & Sharma, S. (2021). Physiology, cortisol. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK538239/
van Dalfsen, J. H., & Markus, C. R. (2018). The influence of sleep on human hypothalamic-pituitary-adrenal (Hpa) axis reactivity: A systematic review. Sleep Medicine Reviews, 39, 187–194. https://doi.org/10.1016/j.smrv.2017.10.002
Wang, S., Wang, C., Yu, Z., Wu, C., Peng, D., Liu, X., Liu, Y., Yang, Y., Guo, P., & Wei, J. (2018). Agarwood essential oil ameliorates restrain stress-induced anxiety and depression by inhibiting hpa axis hyperactivity. International Journal of Molecular Sciences, 19(11). https://doi.org/10.3390/ijms19113468
Zschucke, E., Renneberg, B., Dimeo, F., Wüstenberg, T., & Ströhle, A. (2015). The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback. Psychoneuroendocrinology, 51, 414–425. https://doi.org/10.1016/j.psyneuen.2014.10.019