medical circles, many practitioners address the condition known
as "adrenal fatigue." Like many other functional medical
approaches, the concept of adrenal fatigue is gaining more and more
attention – with good reason, as our society continues to
push harder and harder at this game of life. Standard medical thinking
regarding the adrenal glands is like that of other organ systems
in the body; that is, adrenal glands are either considered to be
in satisfactory working order, or they are in failure. Rarely is
the diagnosis made of hypofunction in any organ system, without
the presence of notable pathologic tissue changes and function.
This is especially true of the adrenal glands. True adrenal failure
is also known as Addison's disease. In this condition, the cortical
tissue fails to produce both the mineralocorticoid and the glucocorticoid
hormones. The most common cause of Addison's disease is autoimmune
destruction of the adrenal cortex; tuberculosis is the second most
common cause.1 Currently, it is not known whether long-term adrenal
fatigue contributes to autoimmune destruction of the adrenal glands.
Despite this understanding, conventional medicine does not always
address adrenal dysfunction in the absence of these diagnoses.
In this scheme of normal functioning vs. a complete absence of function,
no middle ground (and thus room for the concept of adrenal fatigue)
is made possible, resulting in complete under-treatment of adrenal
fatigue. In mainstream conventional medicine, typically the only
patients who receive treatment (using adrenal steroid hormones)
for adrenal dysfunction are those with complete adrenal failure.
If a patient is not in complete adrenal failure, their condition
is considered "normal," and treatment may be difficult
for the patient to obtain. Only recently has conventional medicine
begun to demonstrate research that shows the existence of subclinical
adrenocortical disease not associated with complete adrenal failure.2
The precise etiology of adrenal fatigue has not been fully uncovered
at present, however, progressive medical practitioners have long
proclaimed that chronic severe stress can lead to clinical adrenal
fatigue.3,4 It is not the direction of this article to prove the
existence of adrenal fatigue. As many practitioners of complementary
and alternative medicine are aware, adrenal fatigue is a condition
that can be diagnosed using clinical signs and symptoms and laboratory
testing and, when properly addressed, lead to a path of renewed
health and vigor for our patients.
Stress is everywhere, and is increasingly categorized in any number
of ways. Chronic and acute, stressors are both physical and psychogenic.
Either way, the body is equipped with a highly complex system of
hormones and neurotransmitters specifically designed for dealing
with stress. Regardless of its form, stress can cause the body to
react in certain, predictable patterns. Hans Selye first mentioned
this response, known as the generalized adaptation syndrome, in
the 1930s. In the 70-plus years since its conceptual genesis, scientists
and physicians continue to learn ways to effectively modulate this
response in humans. Conventional and naturopathically oriented health
care practitioners both subscribe to the same biomedical model of
stress and its effects on physiology. However, this is where the
similarities between the two approaches stop, as major differences
in diagnostic and treatment methodologies are employed to discern
subclinical adrenal dysfunction.
Adrenal Response to Stress
Why do we respond to stress? Stress is the physical result of perceived
threats. Stress is in one sense, our body's reaction to a threat.
An excellent example of the mind-body link, numerous changes in
physiology occur due to our perceptions of the general safety or
danger of our environment, all of which occurs before any true harm
is inflicted upon the body. Although stressors have evolved over
time, our physical response to them has not. Many discussions regarding
this concept have taken place; early humans enjoyed relative proportions
of feast or famine, so to speak. It is arguable that today's humans,
with all the luxuries of our modern age, enjoy fewer of our ancestors'
acute stressors but definitely endure many more stressors, and these
may be experienced over a longer period of time.
Central to the stress response are the adrenal glands. In addition
to the mineral-corticoids (hormones that assist in maintaining electrolyte
balance), the primary "stress" hormones that the glands
produce are epinephrine, norepinephrine, and cortisol. These hormones
assist in helping us to adapt to and survive stressors. In addition
to the aforementioned hormones (keeping in mind that cortisol, epinephrine,
and norepinephrine have numerous other physiologic uses), the adrenal
gland also produces hydrocortisone, testosterone, estrogen, dehydroepiandrosterone
(DHEA), pregnenalone, aldosterone, androstenedione, and progesterone,
as well as several other intermediary hormones. In the event of
an acute stressor, the body's immediate reaction is typically one
of alarm, during which the sympathetic nervous system prepares the
body for the well-known "fight or flight" state. When
in this mode, adrenal stress hormones lead to increased heart rate
and blood pressure, while blood is diverted from less crucial areas
such as the gastrointestinal tract to the heart, brain, and skeletal
muscles in preparation for survival mode. These physiologic events
are central to the development of adrenal fatigue.
Typically, the majority of individuals have little problem adjusting
to life stressors when they appear, and once these stressors dissipate,
these people display "healthy" psychophysiologic function
in that the hormone levels achieved to deal with the stressor return
to baseline levels. However, when one is unable to continually adapt
after prolonged periods of stress, adrenal dysfunction becomes clinically
apparent.5 Most often, these people are unable to maintain previous
levels of energy in all realms of life and progressively deteriorate
as times goes on. In fact, depression and substantial decreases
in performance are considered hallmark symptoms of maladaptation
During the early course of adaptation to long-term stressors, the
primary hormones released from the adrenal glands are the glucocorticoids.
Glucocorticoids can drastically change biologic functions and mainly
do so in the direction of preparing the body for both short and
long term survival. The glucocorticoids will mobilize stored proteins
(i.e., muscle tissue) and fatty acids, while increasing the liver's
ability to synthesize glucose, all in order to supply the body with
ample sources of fuel. A primary end-effect of these processes is
to raise blood sugar.7 As the exposure to the stressor continues,
and the adrenal glands continue to churn out glucocorticoids and
other stress-related hormones, the delicate feedback-induced balance
on the hypothalamic-pituitary-adrenal (HPA) axis becomes skewed.
Cortisol typically exhibits a diurnal rhythm during which it steadily
rises from its lowest point in the late evening to its highest level
in the early morning hours between 6 and 8 AM. As the day progresses,
cortisol levels should slowly decline to their low point again by
As the sympathetic nervous system continues to be stimulated by
stressors, the pituitary gland now begins secreting adrenocorticotropic
hormone (ACTH), which drives the adrenal gland to continue its output
of cortisol and dehydroepiandrosterone (DHEA). As the body attempts
to compensate for the hyperfunctioning of the adrenal glands, the
pituitary gland now begins to downregulate its sensitivity to cortisol.
Normally, as hormone levels rise, they act on other organs to decrease
their own production, much like a thermostat regulating heat in
a home. The pituitary gland does this in an attempt to turn down
its production of ACTH, the hormone that drives adrenal production.
However, if the stress exposure continues, the adrenals continue
to manufacture cortisol. Blood glucose levels continue to be elevated,
and cells become insensitive to insulin due to overproduction in
response to high blood glucose. Long-term elevations in cortisol
lead to two main divergent changes in the body. As mentioned previously,
muscle protein continues to be broken down in order to provide fuel
for the body, leading to decreased muscle mass. At the same time,
the body attempts to store fuel sources (as adipose tissue), primarily
around the abdomen. Adrenal hyperfunction is marked by insulin resistance,
mild obesity, hypertension, and elevated triglycerides and lipids.
In the final stages of the stress response, the adrenal glands begin
to fatigue, and cortisol output declines. The body's ability to
synthesize cortisol and other glucocorticoid hormones is severely
compensated, resulting in several physical changes. People experiencing
adrenal fatigue are excessively fatigued, may become depressed and
unable to concentrate, and may experience painful headaches, low
blood pressure, sensitivity to carbohydrates, and an inability to
tolerate alcohol.8 Furthermore, when cortisol production declines,
the body can become overburdened with inflammatory processes as
well; cortisol is an anti-inflammatory molecule and its absence
allows for increases in inflammatory eicosanoids and cytokines,
leading to eventual tissue damage and degeneration.9
Once a diagnosis of adrenal fatigue has been firmly established
(there are several methods for achieving this, each of them with
their own merits and disadvantages), treatment may be pursued. Note:
similar to thyroid dysfunction, one may obtain "normal"
hormone levels despite overt signs and symptoms that say otherwise.
Often, the diagnosis of adrenal fatigue is made based on resting
cortisol levels obtained throughout the day. These levels do not
necessarily discern the adrenal glands' ability to increase production
to counter the effects of stress. A more accurate measure of adrenal
capacity can be obtained using ACTH. When ACTH is administered in
a trial dose, output of cortisol should at least double. If this
does not occur, then true adrenal fatigue is likely. However, adrenal
fatigue can be strongly suspected if a person reports high amounts
of stress with many adrenal fatigue symptoms and normal or low cortisol
levels are measured. Alternatively, a person with symptoms of adrenal
dysfunction may have high levels of cortisol. In this case, these
persons should receive adrenal supportive treatment from the standpoint
that eventually they will reach a place of adrenal fatigue. Each
of these clinical scenarios is reflective of different stages in
adrenal dysfunction. The reader should also keep in mind that these
are oversimplified for the purposes of this article.
Often, practitioners are faced with several projects when treating
patients with adrenal dysfunction. In addition to the symptomology
of adrenal fatigue, practitioners will often find themselves treating
the additional damage caused by overuse of stimulatory products.
These are often recruited by the patient in response to the incredible
fatigue associated with this condition. Left unrecognized and untreated,
people with adrenal fatigue do what most do when faced with insurmountable
fatigue: they continually increase the amount of cheap energy sources
such as coffee and caffeinated beverages and simple carbohydrates
due to their sugar content. Sugary and high glycemic foods only
confound the blood sugar problems associated with this condition,
while caffeine only serves to increase the rate at which energy
is consumed, thereby leading to even greater demand on the adrenal
From a naturopathic perspective, treatment of adrenal fatigue rests
on using therapeutic nutrition, botanical medicines, and lifestyle
adjustments. All of these treatments are designed to support adrenal
gland function, and depending on where a patient is along the spectrum
of adrenal dysfunction, differentiation in the general treatment
protocol is made. In extreme cases of adrenal fatigue, small amounts
of bioidentical hormones may be used to support the adrenal glands
in their initial recovery process.
This approach is the most basic, yet of course, the most difficult
to achieve. The stressors that a person faces today are many and
are generally of a long-term duration. Long gone are the brief,
alarm phase reactions to acute stressors. Modern people, instead
of fighting for survival against predators, exposure, and starvation,
are faced with stressors that seem to be ever present (bills, career,
the IRS, etc.). More easily stated than achieved, the underlying
theme is the same: in order to reduce the toll on the adrenal glands,
one must reduce or place into perspective their own individual life
stressors. Although one may not have absolute control over the origin
of some stressors, there are other choices that can be made. These
include obtaining enough sleep, making healthy dietary choices,
and engaging in stress-reducing activities such as gentle exercise.
Another powerful means of reducing stress involves learning to change
our perceptions of the stress, an exciting topic for another day.
All of these "medicines" serve to reduce the overall stress
burden, thereby preserving adrenal function.
Widely recommended as part of adrenal supportive therapies, use
of vitamins may be key to assisting adrenal function:
Vitamin B5 (Pantothenic
Vitamin B5 is nearly ubiquitous in nature, found in many foods and
every cell in the body. This vitamin carries out its many vital
functions in the body as part of the enzyme complex coenzyme A (CoA).
CoA is involved in adrenal cortex function, as it serves in increasing
production of glucocorticoids and other adrenal hormones.10 Because
of this association with production of adrenal hormones, B5 is commonly
referred to as an antistress vitamin and is mentioned as a treatment
in nearly all conditions in which proper adrenal gland function
has a demonstrated role (stress, allergies, asthma, arthritis, psoriasis,
and infectious processes). In addition, research utilizing B5 in
laboratory animals has been shown to enhance adrenal cortical function.11
In human subjects, B5 was shown to attenuate the elevation in urinary
cortisol metabolites that were expected to be produced as a by-product
of adrenal stimulation using ACTH.12 This experiment suggests that
B5 may also lower secretion of cortisol during times of stress.
Thus, the utility of -5 in adrenal fatigue is due to its supportive
nature in producing adrenal corticosteroids. Additionally, as part
of the enzyme CoA, B5 is necessary for proper metabolism of carbohydrates
and fats (leading to energy production) and the synthesis of the
neurotransmitter acetylcholine. B5 is found in many non-processed
foods such as brewer's yeast, egg yolks, cheese, peanuts, fish,
chicken, and numerous vegetables, to name a few. B5 is even made
in the intestines by the bacterial flora. Despite the widespread
availability of this vitamin, supplementation with B5 is recommended
for adrenal support.
Vitamin C (Ascorbic
Vitamin C is a vitamin with multiple functions and uses in the body.
In fact, reading about the benefits of vitamin C in the research
leads one to believe that this vitamin is useful in nearly all aspects
of health! Indeed, vitamin C benefits adrenal function as well.
Because of the vitamin's water-soluble status, it doesn't stay in
the body long before being used or lost through elimination. However,
there are areas of the body where vitamin C concentrates; these
are typically areas that are very metabolically active. The adrenal
glands are one area, typically storing close to 30 milligrams on
average. Vitamin C is quickly utilized in the body and replacement
is necessary--especially when one is exposed to high amounts of
activity or oxidative processes. Long-term stress is also thought
to compromise the amount of stored vitamin C in the adrenal glands.
In one study, researchers looked at the ability of vitamin C to
improve adrenal function in a surgical setting. In this study, patients
with lung cancer were able to better adapt to the stress of surgery
when supplemented by vitamin C as manifested by normalized levels
of cortisol and ACTH.13 In another study, when vitamin C was given
at a modest dose of 1 gram three times a day, researchers noted
a blunting of the effect of exogenously administered ACTH in raising
cortisol levels.14 Additionally, vitamin C is needed for the synthesis
of two important "stress" hormones, norepinephrine and
epinephrine, both of which are produced in states of high stress.
Because of its supportive function in the production of adrenal
hormones and the fact that large amounts are stored and utilized
by the adrenal glands, supplementation with vitamin C in the treatment
of adrenal dysfunction is recommended.
Phosphatidylserine is phospholipid with fat-soluble properties.
PS is found throughout the human brain and is vital to neuron membrane
function.15 PS is also found in the mitochondrial membrane, where
it is thought to serve as a storage supply for other phospholipids.16
PS is synthesized in the body, however at a high metabolic cost.
PS can also be obtained from dietary sources and is found in most
foods, albeit in small amounts. PS can increase levels of the neurotransmitters
acetylcholine, norepinephrine, serotonin, and dopamine as well.17 PS is considered to enhance neuron function and acts as a compensatory
adaptive mechanism to cell deterioration. PS may be helpful in optimizing
the stress response and at the same time providing substrate for
tissue repair as a result of the catabolic actions of stress hormones.
PS is also thought to blunt the activation of the HPA axis in response
to stress; PS may be able to prevent the production of high amounts
of ACTH and cortisol in response to physical stress.18 In one study,
PS was given to a small group of healthy men prior to the start
of exercise. These men displayed a leveling of ACTH and cortisol
in comparison exercising without being pretreated with PS.19 Another
experiment involved treating subjects who were exposed to two weeks
of an intense weight-training program with PS. Treatment led to
decreased levels of cortisol after the exercise session, and interestingly,
subjects reported a lower incidence of muscle soreness and depression,
both hallmarks of overtraining.20 The effectiveness of PS in attenuating
stress-related hormone elevations appears to be dose-dependent,
Mentioned earlier, often the first (and incorrect) approach to treating
fatigue that results from adrenal dysfunction is to use ergogenic
aids such as coffee or other stimulants. While the herbs Coffea
arabica and ephedra do have useful purposes as stimulants, these
substances should not be employed in cases of adrenal dysfunction.
A more appropriate class of herbs (and the most misunderstood, perhaps)
are the adaptogens. In general, adaptogens are medical herbs that
allow an organism to attain a state of nonspecific, increased resistance
in order for the organism to combat stressors and adapt to challenges,
whether they are chemical, physical, or biological. This grouping
of herbs play an important role in the practice of holistically
minded physicians in that they are useful for enhancing an individual's
resistive powers to the chronic effects of high amounts of stress.
Much of the original research into plant adaptogens involved looking
at their effects in athletes. Beneficial results were found, and
with the recent resurgence of natural medicines, adaptogenic herbs
are becoming popular among many patient populations that have a
large stress component as a common circumstance. While much research
is underway that is designed to elucidate the exact mechanism of
these herbs, some evidence points to modulation of hormone and neurotransmitter
production and degradation as a major effect. It is important to
note that adaptogens are not stimulatory in nature. This is a relatively
common misperception and is key to their use in adrenal dysfunction.
Adaptogens can be used in all patients along the spectrum of adrenal
dysfunction to support their adaptive capabilities. It is important
to note, however, that in extremely fatigued and debilitated patients,
some adaptogenic botanicals may be physically perceived as stimulatory
in their effect. For this reason, moderate caution and low doses
should be used in the completely fatigued patient.
The adaptogenic approach to adrenal fatigue is perhaps one of the
most remarkable concepts in naturopathic medicine. To approach the
patient from this perspective (bolstering their adaptive capabilities
through modulation of hormone and neurotransmitter physiology) is
a true approach to assisting the body in healing itself, rather
than approaching symptoms directly. In fact, treatment of symptoms
only in adrenal dysfunction is highly unlikely to produce any lasting
benefit for the patient.
Many botanicals are considered to have adaptogenic effects, some
more than others. Some of the most researched adaptogenic herbs
are licorice (Glycyrrhiza glabra) and Korean Ginseng (Panax ginseng).
One of the main mechanisms of action of both herbs is the ability
to decrease the amount of endogenously produced hydrocortisone that
is degraded by the liver. In this way, hydrocortisone and cortisol
are preserved, thereby reducing the demand on the adrenals to produce
more. The constituents in licorice have the ability to inhibit the
enzyme 11-beta-hydroxysteroid dehydrogenase, which converts active
cortisol to inactive cortisone.22 Panax ginseng complements this
effect by increasing serum cortisol concentrations23 and by stimulating
As mentioned previously, there are many botanicals with adaptogenic
capabilities; a brief listing include the following:25
American ginseng (Panax quinquefolium)
Ashwaganda (Withania somnifera)
Astragalus (Astragalus membranaceus) root
Borage (Borago officinalis)
Bupleurum (Bupleurum chinense)
Cola nut (Cola nitida)
Devil's club (Oplopanax horridum)
Echinacea (Echinacea spp.)
Ginseng (Panax spp.)
Licorice (Glycyrrhiza glabra)
Oats (Avena sativa)
Prickly ash (Xanthoxylum clava-herculis) bark
Rhodiola (Rhodiola rosea)
Siberian ginseng (Eleutherococcus senticosus)
Scullcap (Scutellaria lateriflora)
Suma (Pfaffia paniculata)
Turmeric (Curcuma longa)
The concept of adrenal fatigue is gaining more and more attention
as naturopathically minded clinicians and laboratories have discerned
useful diagnostic and treatment methods for this condition. Much
work remains to be done regarding this approach, however, the treatment
of adrenal fatigue leads to considerable health improvements in
those affected. This approach is further proof that physical structure
cannot be separated from physical function; both are interrelated
and must be approached in this manner for true clinical improvement
to take place. The treatment of adrenal fatigue is of course not
limited to the treatments described herein. Many other approaches
are available and should be explored.
1. Porterfield S. Endocrine Physiology.
St. Louis, Missouri: Mosby; 1997:142.
2. Terzolo M, Osella G, Ali A, Borretta G, Cesario F, Paccotti P,
Angeli A. Subclinical Cushing's syndrome in adrenal incidentaloma.
3. Tintera JW. Hypoadrenocorticism.
Troy, NY: Hypoglycemia Foundation, Inc.; 1980.
4. Opstad K. Circadian rhythm of hormones is extinguished during
prolonged physical stress, sleep and energy deficiency in young
men. Eur J Endocrinol. 1994;131:56-66.
5. Morgan WP, Brown DR, Raglin JS, O'Connor PJ, Ellickson KA. Psychological
monitoring of overtraining and staleness. Br
J Sports Med. 1987;21:408-414.
6. Szabo S. Hans Selye and the development of the stress concept.
Ann NY Acad Sci. 1998;851:19-27.
7. Ronizo RA. Nutritional support for adrenal function. Am J Nat
8. Smith LL. Cytokine hypothesis of overtraining: A physiological
adaptation to excessive stress? Med Sci
Sports Exerc. 2000; 32(2):317-331.
9. Heiderscheit BC, Hamil J. Van Emmerik REA. Q-angle influences
on the variability of lower extremity coordination during running.
Med Sci Sports Exerc.1999;31(9):1313-1319.
10. McKevoy GK, ed. AHFS Drug Information.
Bethesda, MD: American Society of Health-System Pharmacists, 1998.
11. Kosaka C, Okida M, Kaneyuki T, et al. Action of pantethine on
the adrenal cortex of hypophysectomized rats. Horumon
To Rinsho.1973;21:517-525. [In Japanese]
12. Onuki M, Suzawa A. Effect of pantethine on the function of the
adrenal cortex: Clinical experience using pantethine in cases under
steroid hormone treatment. Horumon To Rinsho.1970;18:937-940.
13. Gromova EG, Sviridova SP, Kushlinskii NE, et al. Regulation
of the indices of neuroendocrine status in surgical patients with
lung cancer using optimal doses of ascorbic acid. Anesteziol
Reanimatol. 1990;5:71-74. [In Russian]
14. Liakakos D, Doulas NL, Ikkos D, et al. Inhibitory effect of
ascorbic acid (vitamin C) on cortisol secretion following adrenal
stimulation in children. Clin Chim Actab.
15. Blokland A, Honig W, Brouns F, Jolles J. Cognition-enhancing
properties of subchronic phosphatidylserine (PS) treatment in middle-aged
rats: comparison of bovine cortex PS with egg PS and soybean PS.
16. Kidd PM. Phosphatidylserine; Membrane nutrient for memory. A
clinical and mechanistic assessment. Altern
Med Rev. 1996;1:70-84.
17. Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine
in Alzheimer's disease. Psychopharmacol
18. Kelly GS. Nutritional and botanical interventions to assist
with the adaptation to stress. Altern Med
Rev. 1999 Aug;4(4):249-65.
19. Monteleone P, Beinat L, Tanzillo C, et al. Effects of phosphatidylserine
on the neuroendocrine response to physical stress in humans. Neuroendocrinology.
20. Fahey TD, Pearl MS. The hormonal and perceptive effects of phosphatidylserine
administration during two weeks of resistive exercise-induced overtraining.
Biol Sport. 1998;15:135-144.
21. Monteleone P, Maj M, Beinat L, et al. Blunting by chronic phosphatidylserine
administration of the stress-induced activation of the hypothalamo-pituitary-adrenal
axis in healthy men. Eur J Clin Pharmacol.
22. Krahenbuhl S, Hasler F, Frey BM, et al. Kinetics and dynamics
of orally administered 18 beta-glycyrrhetinic acid in humans. J
Clin Endocrinol Metab. 1994;78:581-5.
23. Hiai S, Yokoyama H, Oura H, et al. Stimulation of pituitary-adrenocortical
system by ginseng saponin. Endocrinol Jpn.
24. Robbers JE, Speedie MK, Tyler VE. Pharmacognosy
and Pharmacobiotechnology. Baltimore, MD: Williams &
25. Listing partially adapted from: Tilgner S. Herbal
Medicine: From the Heart of the Earth. Oregon: Wise Acres