by Bradley Bush, ND
Specialty: Naturopathy with focus on neuroimmunology and endocrinology
Company Affiliation: Clinical Advisory Board Member for NeuroScience, Inc.

Not every person experiences adrenal fatigue in the same way, so your treatments should reflect that. While the black and white extremes of adrenal fatigue are easily recognized as acute fight-or-flight at one end and complete exhaustion at the other, the majority of people display ‘5 shades’ of grey (not 50) that are slightly different from one another.
The adrenal glands are comprised of two parts that are anatomically and functionally quite different. The adrenal cortex produces cortisol, dehydroepiandrosterone (DHEA), androstenedione, and aldosterone. It is formed in the embryo from intermediate mesoderm, along with the kidneys and gonads, and is under the direct control of the hypothalamus-pituitary axis. The adrenal medulla converts tyrosine to dopamine, norepinephrine and epinephrine. It is formed in the embryo by neural crest cells therefore, medulla cells are basically modified neurons. The medulla is hardwired to the sympathetic nervous system, allowing it to respond immediately to stressors.
This dynamic structure allows for both immediate responses to stress for short-term survival and stress adaptability for long-term survival. Our modern environment challenges the adrenal glands, disrupting its functioning in a variety of ways. I have listed out 5 shades of adrenal fatigue and nutritional support for each one.
1.) Early stage: This is the stage that most people love; heightened awareness, high energy and a sense of invincibility. Many successful people operate in this stage, but it is only a matter of time until adrenal function becomes affected. On a biochemical level, early stage tends to have higher-than-normal output of epinephrine, norepinephrine and cortisol. Phosphatidylserine, at high doses, can reduce pituitary stimulation in addition to supporting the repair of any cortisol receptors, which is vital for cortisol’s negative feedback throughout the hypothalamic-pituitary-adrenal (HPA) axis.*
2.) Early mid-stage: As the body’s adaptive stress mechanisms gradually degrade, the adrenal’s ability to maintain healthy levels of cortisol and/or epinephrine is diminished. Epinephrine is converted from norepinephrine in the adrenal medulla, in the presence of endogenously produced cortisol, and can be supported with tyrosine and methionine. Tyrosine is the amino acid precursor to the catecholamine neurotransmitters epinephrine, norepinephrine, and dopamine.* L-methionine is the precursor to S-adenosylmethionine (SAMe),* which is a rate-limiting co-factor for the conversion of norepinephrine to epinephrine.
Epigallocatechin gallate (EGCG) is a powerful antioxidant that supports catecholamine neurotransmitter levels by blocking the enzyme that breaks them down, catechol-O-methyltransferase (COMT).* Rhodiola rosea is an adaptogenic herb that I use to support norepinephrine production in the adrenals and works synergistically with tyrosine, L – methionine, EGCG and general adrenal support (B-vitamins, vitamin C, etc.)*
3.) Late mid-stage: It is only a matter of time until norepinephrine synthesis and hypothalamic modulation of the adrenal glands declines (Aguilera, 2011; Young 2005; Herman 2012). The hypothalamus is stimulated to initiate the HPA axis via neurotransmitter signals, especially norepinephrine, from specific brain nuclei (Flak, 2014). Fatigue symptoms become more pronounced at this time and stronger tyrosine support is required to support norepinephrine synthesis in the adrenals and areas of the brain that initiate the HPA axis cascade, ultimately resulting in adrenal activation.* Symptoms including low energy, sleep disturbances, mood changes, altered weight metabolism and declining cognition become more pronounced. Stronger precursor supplementation for catecholamine synthesis helps support healthier levels of these neurotransmitters and boosts activation and functioning of the adrenals.*
4.) End stage: This darker shade of grey is present once adrenal stimulation by the hypothalamus has declined and production of cortisol and the catecholamines is severely reduced. At this point, patients tend to suffer from pronounced fatigue and have difficulties maintaining healthy blood sugar levels. Licorice root containing glycyrrhizic acid will provide immediate relief by boosting cortisol levels.* Glycyrrhizic acid inhibits the enzyme (11- beta hydroxysteroid dehydrogenase type 2) that converts cortisol to inactive cortisone allowing more cortisol to circulate throughout the body (Zhang, 1999; Al-Dujaili, 2010).* Licorice root has also been shown to support the neuronal health and sympathetic regulation of the hypothalamus (Kim, 2012, Duax, 2000; Zhang, 2006).*
5.) End stage due to genetic predispositions: Some people have predispositions making them more susceptible to adrenal fatigue. Compromised methylation pathways with lower levels of active folate or methyl donors may result in lower levels of monoamine neurotransmitter synthesis including adrenal epinephrine and norepinephrine (Bottiglieri, 2002). Methylenetetrahydrofolate reductase (MTHFR) is a rate-limiting enzyme in the synthesis of the active metabolite of folate, 5-methyltetrahydrofolate (5-MTHF). 5-MTHF supplementation may be required for some patients to respond to adrenal fatigue support. SAMe is a major methyl donor, especially in the brain, and has been shown to support healthy levels of neurotransmitter synthesis (Miller, 2008).*
Nothing is black and white in this world and your clinical approach to adrenal fatigue is not an exception. There are many shades of adrenal fatigue, and once you identify where your patients’ statuses, your treatments can be personalized to their specific needs.

Aguilera, G. (2011). Exp Gerontol., 46(2-3), 90–95.
Al-Dujaili, E.A., Kenyon, C.J., Nico,l M.R., & Mason, J.I. (2010). Mol Cell Endocrinol., 336(1-2), 102-9.
Bottiglieri, T. (2002). Am J ClinNutr., 76, 1151S–7S.
Duax, W.L., Ghosh, D., & Pletnev, V. (2000). Vitam Horm., 58, 121-48.
Flak JN, Myers B, Solomon MB, McKlveen JM, Krause EG, Herman JP. Eur J Neurosci. 2014 Jun;39(11):1903-11.
Herman, J.P., McKlveen, J.M., Solomon, M.B., Carvalho-Netto, E., & Myers, B. (2012). Braz J Med Biol Res., 45, 292-8.
Kim, S.W., Jin, Y., Shin, J.H., Kim, I.D., Lee, H.K., Park, S., Han, P.L., & Lee, J.K. (2012). Neurobiol Dis., 46(1), 147-56.
Miller AL. Altern Med Rev. 2008 Sep;13(3):216-26.
Young EA, Abelson JL, Cameron OG. 2005 Sep;30(8):807-14.
Zhang, Y., Wu, P., Liu, Y., Wang, X., Liang, X., Guo, Z.,& Lai, W. (1999). Zhonghua NeiKe ZaZhi., 38(5), 302-5.
Zhang, Z.H., Kang, Y.M., Yu, Y., Wei, S.G., Schmidt, T.J., Johnson, A.K., & Felder, R.B. (2006). Hypertension. 48(1), 127-33.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.**This blog was written by an outside source. This blog does not necessarily reflect the views or positions of Natural Partners.