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Transcript
HPAT A XIS
ADRENAL BENEFITS ™
CORTISOL BENEFITS ™
The theory that chronic stress contributes to the long-term, overall health of the human body was
first publicly elucidated by Hans Selye in a 1950 British Medical Journal paper. Selye had observed a
predictable pattern in the human biological response to stress, one that was focused on restoration of
homeostasis.
He theorized that the amount of adaptive energy a body can devote to this process is limited in supply,
and that exposure to the “fight or flight” initial hormonal reaction could, if continuous, cause a decline
in that supply, leading to a variety of health concerns. (“Hans Selye’s general adaptation syndrome,”
n.d.).
Note: It is imperative that individual responses to stress are identified prior to beginning a regimen of
support for stress management and HPAT homeostasis. While all bodies do exhibit the same general
hormonal cascade, the impact of our reactions varies widely and should be determined based on
practitioner analysis of the individual patient.
THIS PAPER WILL PROVIDE:
An overview of the HPAT axis glands and their functions
A summary of the relationship between cortisol and DHEA
An explanation of how each stage of stress resistance (GAS stages) may present
An overview of how to support normal HPAT homeostasis with clinical nutrition
UNDERSTANDING THE HPAT AXIS
The HPAT axis is not a location, nor is it the compilation of the hypothalamus, pituitary, adrenal and
thyroid glands. Instead, the axis is the complex set of reactions and interactions that occurs between
these four glands. It is the compilation of all relevant relationships and signals. Because these interactions
form a good portion of the neuroendocrine system, which also regulates digestion, immune function,
emotional responses, sexual health and energy balance, the HPAT axis and its healthy function is
incredibly important to overall feelings of wellbeing.
The axis influences glucose regulation, hormones, cytokines and more. Cortisol is often the primary
focus of conversations about the HPAT axis, though other metabolic factors and contributions of the
central nervous system and individual environment are also important. Continued cortisol release, a
result of stress, affects the hypothalamic and pituitary feedback loops such that the axis may remain
persistently activated. Cortisol is also the end product of activation. We know, then, that the nature of
the relationship between cortisol and the axis is cyclical.
*These materials have not been reviewed by the U.S. Food and Drug Administration (FDA). This product is not intended to diagnose, treat,
cure or prevent any disease. These materials are for physician education purposes only. Not for consumer distribution. www.davincilabs.com.
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ADRENAL GLANDS
The adrenal functions regulate our responses to stress. The two main sections of the adrenal glands, the
adrenal cortex and the inner adrenal medulla, have different actions. The adrenal cortex is comprised
of three layers that include the sites of mineralcorticoid, glucocorticoid and sex hormone production.
The inner medulla actually has a direct connection to the brain, a rarity among the hormone-producing
glands, the others of which send messages about secretion through a chemical messenger in the
bloodstream. (Walsh, 2009). The inner medulla produces the hormones that dictate our fight or flight
response. The adrenal glands and the hormones they secrete have multiple effects on our bodies’
healthy functions.
An overactive or underactive set of adrenal glands will produce either excess or insufficient amounts
of hormones respectively, especially cortisol. The health of the adrenal cascade depends on various
nutrients, including the B vitamin complex. While larger (in proportion) quantities of vitamins B3, B5
and B6 are used in the adrenal hormone production process, B vitamins are known to work in concert,
meaning a full complex is recommended for healthy function. Each of the eight vitamins in the complex
is valuable during the adrenal cascade.
The adrenal gland boasts the highest concentration of vitamin C in the body. Interestingly, both the
adrenal cortex and the medulla accumulate high levels of ascorbate. Ascorbic acid is a cofactor required
both in catecholamine biosynthesis and in adrenal steroidogenesis.
With a decreased level of ascorbic acid available for the adrenal cortex and medulla, signs of depletion
of catecholamine storage vesicles, signs of apoptosis, and increased glycogen storage have been
observed. Further, decreased plasma levels of corticosterone and altered morphology of mitochondrial
membranes were found. This underscores the critical nature of adequate vitamin C levels for optimal
function of the adrenal gland (Patak, Willenberg, & Bornstein, 2004).
THYROID GLAND
NOTE: The thyroid gland is not always included in the HPA axis. Historically, the HPT axis, where the
T represents the thyroid gland, has been considered a separate set of complex interactions (between
the hypothalamus, pituitary and thyroid glands) which regulates metabolic health. For the purpose of
understanding how the neuroendocrine system responds to stress, we have chosen to include it in our
understanding of the HPA axis. Just like the other components of the neuroendocrine system outlined
in this paper, the thyroid gland affects our health and demands nutritional support for homeostasis. It’s
also been suggested that the end product of the HPA axis activation, corticosterone, may play a role
in the regulation of the HPT axis.
*These materials have not been reviewed by the U.S. Food and Drug Administration (FDA). This product is not intended to diagnose, treat,
cure or prevent any disease. These materials are for physician education purposes only. Not for consumer distribution. www.davincilabs.com.
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The hypothalamus’ relationship to thyroid hormones is incredibly relevant to the the body’s ability to
maintain hormone balance. The hypothalamus senses low circulating levels of thyroid hormones T3
and T4, and responds by releasing thyrotropin-releasing hormone (TRH). The release of TRH tells the
anterior pituitary gland to produce TSH, or thyroid stimulating hormone.
TSH is the stimulating factor for the thyroid’s production of T3 and T4 (the thyroid hormones), causing
blood levels to be restored. T3 and T4 then exert negative feedback over both the hypothalamus and
the pituitary, thereby controlling the releases of TRH and subsequently, TSH.
There are three areas of concern when we discuss the thyroid. The first is the health of the gland itself.
The second is the nutritional support it demands. The third is the impact of stress hormones, which can
cause increased reverse T3 and under conversion of T4 to T3, either due to liver function impairment
or to a need for selenium in the diet.
The T4 the body produces is converted to reverse T3 in the liver, in order to rid the body of excess T4
(which is normally produced in about an 4:1 ratio.) The percentage of T4 that is converted to RT3 may
increase when the body uses its energy for other functions, while T3 may decline.
Biological stress is one such use of energy. Excess cortisol, in fact, is known to inhibit conversion to
T3, instead elevating RT3 production. (Its hypothalamic precursor, cortico-tropin releasing hormone,
or CTRH, can also suppress TSH.) In this event, T3 and T4 levels can appear normal on a blood test,
but the adrenal glands may still be experiencing both slowed function and increased stress (which
can further slow function) due to hypothyroidism. Hypothyroidism also leads to an increase in cortisolbinding globulin, thereby making the cortisol inaccessible for use. So the cycle goes: low thyroid
function leads to low adrenal function leads to low thyroid function. (Simpson, 2011, p. 83).
On the other hand, ongoing stress can also cause eventual depletion of cortisol production from
the adrenals, meaning cortisol is low. Without that production, thyroid hormone blood levels are
increased, demanding that the body respond. It does respond: with conversion, from T4 to excess
RT3. So we see that excess cortisol production, which causes a high percentage of thyroid hormone
to be converted to RT3, can also eventually cause depletion of cortisol production, which then causes
the body to respond with elevated conversion of T4 to RT3.
WHY DOES EXCESS RT3 SEEM TO BE SUCH A BIG DEAL?
T3 is necessary for the body’s healthy metabolic function. RT3 is inactive but binds to T3 receptors,
thereby blocking them from T3’s binding and resulting metabolic effects.
There are a few key nutrients that support healthy thyroid function that should be part of any successful
HPAT support regimen.
*These materials have not been reviewed by the U.S. Food and Drug Administration (FDA). This product is not intended to diagnose, treat,
cure or prevent any disease. These materials are for physician education purposes only. Not for consumer distribution. www.davincilabs.com.
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The most well-known of these nutrients is iodine. It is necessary for our bodies to produce thyroid
hormone. Hypothyroidism in unborn children can be caused by a deficiency of iodine, and deficiencies
are often related to mental retardation. Pregnancy itself demands higher daily requirements for
iodine intake, due to the fact that T4 production doubles in the gestation period.
It is important to bear in mind, though, that both diets high and low in iodine are associated with
hypothyroidism. That tells us that a diet high in iodine may only be useful in hypothyroidism treatment
when a deficiency is present.
Another mineral that affects thyroid function: selenium. Without selenium’s contribution to the
enzymes that remove iodine molecules from T4, converting to T3, the thyroid hormone would never
activate. Some of the most important features of the mineral’s relationship to thyroid function include:
• Research has revealed that patients with varied thyroid concerns tend to exhibit lower
selenium levels. Further, selenium plays a role in free radical scavenging, which is
fortunate because thyroid cells generation hydrogen peroxide, a free radical, as part
of their normal function, in order to make thyroid hormones.
• Selenium acts a balance to high iodine levels. It also supports normal efficacy of
glutathione peroxidase, an enzyme whose inefficiency is linked to Hashimoto’s.
• A hypothyroid state may be induced when, during a prolonged infection, levels of T4, T3,
TSH and selenium all decrease.
Zinc is important to thyroid function due to its relationship with conversion from T4 to T3. In animal
studies, researchers found that zinc deficiency significantly lowered T3 and free T4 concentrations,
though total T4 levels remained unaffected (Karlik, Eder, & Kirchgessner, 1996).
Zinc, though, just like iodine, could suppress function of the thyroid if the amount of zinc in the body
is too high. (Taneja & Mandal, 2008). Taking copper and zinc in concert is advised, as high zinc doses
can disrupt copper absorption.
Copper deficiency depletes the hypothalamus’s ability to regulate thyroid hormone. In one rat study,
mothers who were copper deficient produced infant rats who produced 48% less T3 than rats from
mothers without such a deficiency (Bastian, Prohaska, Georgieff, & Anderson, 2010).
Elements aside, some vitamins also have important supportive actions for thyroid function. Vitamin E
acts as a free radical scavenger.* Oxidative stress is an effect of hypothyroidism, so it’s important to
support oxidative balance.* Vitamin D, too, is important, as evidence shows that vitamin D deficiency
is more prevalent in people with thyroid cancer or nodules (Laney, Meza, Lyden, Erickson, Treude, &
Goldner, 2010).
Vitamin B12 may also be considered a key nutrient to support the thyroid’s healthy function. The link
between B12 deficiency and lowered thyroid function has not been fully elucidated.
*These materials have not been reviewed by the U.S. Food and Drug Administration (FDA). This product is not intended to diagnose, treat,
cure or prevent any disease. These materials are for physician education purposes only. Not for consumer distribution. www.davincilabs.com.
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THE GLUTEN CONNECTION
A deficiency in iron also interferes with hormone production through reduced thyroid peroxidase
activity. And while the etiologies of iron deficiency are many, one of the more common presently
involved gluten.
Anemia secondary to malabsorption of iron, folic acid, and/or vitamin B12 is a common complication
of celiac disease and many patients have anemia at the time of diagnosis.
(Halfdanarson, Litzow, & Murray, 2007).
A 2010 study in the Journal of Pediatrics found that 11 of 15 children with celiac disease who had
elevated thyroid-stimulating hormone levels at diagnosis with celiac saw these numbers normalize
after 12 to 18 months on a gluten-free diet. The Naiyer study noted that among people with celiac
disease, significantly more people have thyroid antibodies before going gluten free than after (37.5%
vs. 4.4%). The study also showed a positive correlation between anti-tTG and thyroid antibody titers in
patients with active celiac disease. The only way to reduce anti-tTG levels is to eat a gluten-free diet.
These studies suggest that a gluten-free diet has the potential to improve thyroid function by reducing
autoimmune reactions in the body (Cassio et al., 2010)
THE THYROID-GUT CONNECTION
T3 and T4 have other important connections in the body, such as their influence on gut health through
their protection of gut mucosal lining, which has been proven in conditions of stress-induced ulcer
formation.(Koyuncu et al., 2002). Further, TSH and TRH both influence the development of a large
portion of the immune system contained in the gut, called GALT (Kresser, n.d.).
Yet another thyroid-gut connection exists in the gut bacteria’s relationship with T4 and T3. Gut bacteria
assist in the conversion from T4 to T3, which makes sense because about 20% of that conversion
occurs in the GI tract, in T3 sulfate (T3S) and triidothyroacetic acid (T3AC) forms. Their conversion
to active T3 is dependent on an enzyme called intestinal sulfatase. That enzyme comes from the
presence of healthy gut bacteria. An imbalance in the gut can reduce the conversion of T3S and T3AC
to active (Stratakis & Chrousos, 1995), a possible explanation for why people with unhealthy guts may
have thyroid symptoms despite normal lab results.
Finally, gut inflammation contributes to reduced active T3 through increasing cortisol (Braverman &
Stockigt, 1997).
All of this means that to support healthy gut function and healthy thyroid function, the two should be
addressed in concert.(Kresser, n.d.).
*These materials have not been reviewed by the U.S. Food and Drug Administration (FDA). This product is not intended to diagnose, treat,
cure or prevent any disease. These materials are for physician education purposes only. Not for consumer distribution. www.davincilabs.com.
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CORTISOL AND THE IMPORTANCE OF BALANCE
Cortisol has one main role: release glucose into the bloodstream to effect the fight or flight response.
It also has many other roles, in suppression and modulation of the digestive, reproductive and immune
systems. (“hypothalamic-pituitary-adrenal (HPA) axis,” n.d.).
Simply knowing that excess cortisol eventually may lead to low cortisol tells us just how important
balance is. But cortisol doesn’t stand alone in the body. In fact, maintaining its proper ratio with DHEA
is considered one of the major balancing acts of human biology.
DHEA and cortisol are both synthesized from the master steroid hormone, pregnenelone (derived
from cholesterol). DHEA is a testosterone and estrogen precursor produced in the adrenals. It acts
antagonistically to cortisol, meaning maintenance of the ratio between the two is an obvious health
goal. If adrenal function is low (perhaps due to ongoing stress/elevated cortisol), a resulting imbalance
is likely. Writes Kathleen McCormick for Connections, a publication of Women’s International Pharmacy:
“The link between cortisol production and DHEA is an important one because, with long periods of
chronically high cortisol levels, the ability to produce DHEA diminishes. One of the most significant
effects of restoring DHEA seems to be the restoration of the normal balance between DHEA and
cortisol. As DHEA levels increase, the propensity to overproduce cortisol is dampened.” (McCormick,
2012).
From a clinical perspective, we may find that if cortisol levels are elevated at night, the body will exist
in a catabolic state (the mechanism behind this lies in the fact that nighttime cortisol levels will impair
the body’s ability to release adequate growth hormone levels necessary for repair and rebuilding body
tissues).
The brain may also fall victim to elevated cortisol levels. A recent series of studies was published by
Daniela Kaufer, UC Berkeley associate professor of integrative biology, and the findings suggested that
chronic stress and elevated levels of cortisol can generate more overproduction of oligodendrocytes
and fewer neurons than is necessary for optimal function. This was specific to the hippocampus, a part
of the brain which ‘regulates memory and emotions, and plays a role in various emotional disorders’
and whose size and functionality has been known to affected under extended periods of acute stress’.
Long-term, chronic stress, however, also resulted in a potentially damaging overproduction of the
myelin while decreasing the number of stem cells that mature into neurons (Chetty et al., 2014).
The immune system can also be affected by altered cortisol/DHEA levels, in particular the surface of
the mucosal lining, which acts as a first-line immune defense. This barrier function, specifically the
modulation of the production and turnover of immunocytes (plasmacytes) which produce antibodies
(secretory IgA or sIgA), is dictated by the both cortisol and DHEA. When cortisol is elevated and DHEA
is low, sIgA output is suppressed. This was demonstrated in a study in 2009 in Stress & Health Journal.
*These materials have not been reviewed by the U.S. Food and Drug Administration (FDA). This product is not intended to diagnose, treat,
cure or prevent any disease. These materials are for physician education purposes only. Not for consumer distribution. www.davincilabs.com.
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It was found that the sIgA decrease significantly correlated with the cortisol rise during the 20 min after
the stress induction. (Stress and Health HYPERLINK “http://onlinelibrary.wiley.com/doi/10.1002/smi.
v25:2/issuetoc” Volume 25, Issue 2, pages 189–194, April 2009)
When observing patients physical traits, one may theorize a cortisol/DHEA imbalance based on excess
adiposity around the hips, thighs and/or waist. This pattern presents in the absence of overt obesity
and should be considered along with symptomology and appropriate diagnostic testing. However,
when patients complain of exhibiting abnormal energy levels and referring to themselves as ‘wired
and tired’ and display this pattern of weight gain, there is a strong likelihood of a need to balance
cortisol and DHEA levels.
Understanding cortisol and its many effects on health is crucial to the HPAT axis conversation, as HPA
axis activation results, ultimately, in increased blood levels of cortisol at times of stress. (“hypothalamicpituitary-adrenal (HPA) axis,” n.d.).
THE THREE STAGES OF STRESS RESISTANCE
In his 1950 paper, Hans Selye theorized that the body’s continuous stress response could cause major
health concerns. He coined the body’s response to prolonged stress “GAS,” or General Adaptation
Syndrome, and identified three stages of stress resistance associated with this response: alarm,
resistance and exhaustion.
STAGE 1: THE ALARM/EARLY STAGE
When your older brother jumps out from behind a door to scare you, your reaction occurs in the
alarm stage. Do you punch him? Do you run? Do you scream? The fight/flight/freeze reactions occur
as axis activation occurs. Cortisol, adrenaline and noradrenaline are released, giving you the energy
to address the threat. Too much of this energy, without expenditure through physical activity, can be
harmful. Symptoms of early stage stress include anxiousness, a high pulse, and a “tired but wired”
feeling.
Important nutrients:
Ashwagandha - Active constituents are withanolides which serve as important hormone precursors
that can convert into human physiologic hormones as needed
L-Theanine - Supports GABA levels through its action as an excitatory neurotransmitter antagonist
Magnolia - Supports the inhibitory neurotransmitter effect at the level of the GABA receptor site
Phosphatidylserine - Supports metabolism and stimulation of acetylcholine production
*These materials have not been reviewed by the U.S. Food and Drug Administration (FDA). This product is not intended to diagnose, treat,
cure or prevent any disease. These materials are for physician education purposes only. Not for consumer distribution. www.davincilabs.com.
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STAGE 2: THE RESISTANCE/MID STAGE
When the source of the stress is potentially resolved, the body moves into the resistance phase. While
stress hormone levels may have returned to normal values, the amount of adaptive energy the body
has to use may leave the body with diminished defenses. Should the condition of stress persist, the
body will remain aroused. Without proper recovery (for example, if the body is inaccurately perceiving
constant threats), the body moves into the exhaustion phase.
Important Nutrients:
Rhodiola - Restores the normal sensitivity of cortisol receptors by modulation of stress activated
protein Kinase which ultimately supports healthy cortisol levels
ETAS™ (Proprietary extract of Asparagus officinalis) - Increases the production of HSP70, which
supports cell structure and repair and the balance of excitatory and inhibitory cytokines
Ashwagandha - See above
STAGE 3: THE EXHAUSTION/LATE STAGE
The supply of adaptive energy has depleted and the body cannot resist, causing what we commonly
refer to as “burnout.” Because the late stage of GAS is the stage in which stress levels will stay
increased, the resistance stage is often considered the best point of nutritional intervention. Latestage symptoms include low pulse, fatigue, impaired thinking and anxiety.
Important Nutrients:
Eleuthero - Possibly supports the enzyme catechol-O-methyltransferase, which ultimately impacts the
body’s supply of catecholamines (Braun & Cohen, 2015).
Vitamin B5 - B5 helps to produce co-enzyme A, which contributes to cellular respiration and the
breakdown of macronutrients for energy
Vitamin B12 - B12 supports energy production, cell repair and the maintenance of our red blood cells
Vitamin C - Directly involved in the production of cortisol in your adrenals
HOW TO SUPPORT HPAT OPTIMIZATION WITH CLINICAL NUTRITION
A diet and lifestyle regimen that includes appropriate physical activity, nutritional factors and
supplementation is the first step to supporting HPAT axis health and homeostasis. DaVinci’s Thyroid,
Adrenal and Estrogen Metabolism protocols are designed to support your patients as they work toward
balance. The protocols include ingredients to promote restorative sleep, the health of energy recovery
processes and cortisol/DHEA balance.
Read our Clinical Protocol Guide to learn more about each ingredient and how to start your patients
on the path to a healthy HPAT axis and stress response.
*These materials have not been reviewed by the U.S. Food and Drug Administration (FDA). This product is not intended to diagnose, treat,
cure or prevent any disease. These materials are for physician education purposes only. Not for consumer distribution. www.davincilabs.com.
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ADRENAL BENEFITS™
SUPPLEMENT FACTS
Serving Size 2 Capsules
Servings Per Container 60
Amount Per Serving
% Daily Value
PureWay-C®
[proprietary formulation of ascorbic acid USP combined with lipid metabolites (fatty acids) from vegetable waxes] 250 mg 375%
Vitamin B6 (as Pyridoxal 5-Phosphate) 25 mg 1,250%
Folate
(as [6s]-5-methyltetrahydrofolic acid from 800 mcg of
Quatrefolic® [6s]-5-methyltetrahydrofolic acid,
glucosamine salt) 400 mcg 100%
Vitamin B12 (as MecobalActive™) 250 mcg 4,167%
Pantothenic Acid (as Calcium d-Pantothenate) 250 mg 2,500%
Adrenal Cortex (Bovine) Eleutherococcus senticosus Root Extract Adrenal Whole (Bovine) 250 mg
250 mg 200 mg *
*
*
*Daily Value not established.
Other ingredients: hypromellose (caspule), microcrystalline cellulose,
vegetarian leucine.
Mecobalactive™ is a trademark of INTERQUIM, S.A.
®
®
PureWay-C is a Trademark of Innovation
Laboratories, Inc., Miami, FL, U.S.A.
Quatrefolic® is a registered trademark of Gnosis S.p.A.
U.S. Patent No. 7,947,662
CORTISOL BENEFITS™
SUPPLEMENT FACTS
Serving Size 2 Capsules
Servings Per Container 30
Amount Per Serving
% Daily Value
Sensoril® Ashwagandha (Withania somnifera) Root and Leaf Extract ETAS™ (proprietary extract of Asparagus officinalis) Rhodiola rosea Root Extract (std. to 3% rosavins and 1% salidrosides) Magnolia officinalis Bark Extract 250 mg *
200 mg
*
150 mg
100 mg *
*
*Daily Value not established.
Other ingredients: hypromellose (caspule), microcrystalline cellulose,
vegetarian leucine.
Sensoril® is a trademark of Natreon, Inc. and is protected under U.S. Patents 6,153,198 and 7,318,938.
ETAS™ is a trademark of Amino Up.
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REFERENCES
Bastian,T.W., Prohaska, J.R., Georgieff, M.K., Anderson, G.W. Perinatal iron and copper deficiencies alter
neonatal rat circulating and brain thyroid hormone concentrations. Endocrinology. 2010 Aug;151(8):4055-65.
Braun, L., & Cohen, M. (2015). Herbs & natural supplements: An evidence-based guide. Volume 2 (4th ed.).
Chatswood, NSW, Australia: Elsevier: Churchill Livingstone.
Braverman, L. E., & Stockigt, J. R. (1997). Update on the sick euthyroid syndrome. In Diseases of the thyroid
(pp. 49-68).
Chetty, S., Friedman, A. R., Taravosh-Lahn, K., Kirby, E. D., Mirescu, C., Guo, F., … Kaufer, D. (2014). Stress and
glucocorticoids promote oligodendrogenesis in the adult hippocampus. Molecular Psychiatry, 19(12), 12751283. doi:10.1038/mp.2013.190
Halfdanarson, T. R., Litzow, M. R., & Murray, J. A. (2007). Hematologic manifestations of celiac disease. Blood,
109(2), 412-421. doi:10.1182/blood-2006-07-031104
Hans Selye’s general adaptation syndrome: Classic stages of chronic stress. (n.d.). Retrieved from http://www.
essenceofstressrelief.com/general-adaptation-syndrome.html
The hypothalamic-pituitary-adrenal (HPA) axis. (n.d.). Retrieved from http://www.mind-body-health.net/hpaaxis.shtml
Koyuncu, A., Aydintug, S., Kocak, S., Aydin, C., Demirer, S., Topcu, O., & Kuterdem, E. (2002). Effect of thyroid
hormones on stress ulcer formation. Anz Journal of Surgery, 72(9), 672-5. doi:10.1046/j.1445-2197.2002.02519.x
Kralik, A., Eder, K., Kirchgessner, M. Influence of zinc and selenium deficiency on parameters relating to thyroid
hormone metabolism. Horm Metab Res. 1996 May;28(5):223-6.
Kresser, C. (n.d.). The thyroid-gut connection. Retrieved from http://chriskresser.com/the-thyroid-gut-connection/
Laney, N., Meza, J., Lyden, E., Erickson, J., Treude, K., Goldner, W. The Prevalence of Vitamin D Deficiency Is
Similar between Thyroid Nodule and Thyroid Cancer Patients. Int J Endocrinol. 2010;2010:805716.
McCormick, K. (2012, March). DHEA newsletter. Retrieved from https://www.womensinternational.com/
connections/dhea.html
Patak, P., Willenberg, H. S., & Bornstein, S. R. (2004). Vitamin C is an important cofactor for both adrenal cortex
and adrenal medulla. Endocr Res, 30(4), 871-875. doi:10.1081/erc-200044126
Simpson, K. R. (2011). Overcoming adrenal fatigue: How to restore hormonal balance and feel renewed,
energized, and stress free. Oakland, CA: New Harbinger Publications.
Stratakis, C. A., & Chrousos, G. P. (1995). Neuroendocrinology and Pathophysiology of the Stress System.
Annals of The New York Academy of Sciences, 771, 1-18. doi:10.1111/j.1749-6632.1995.tb44666.x
Taneja, S.K., Manda,l R. Beneficial effect of modified egg on serum T3, T4 and dyslipidaemia following dietary
Zn-supplementation in Wistar rat. Indian J Exp Biol. 2008 Mar;46(3):171-9.
Walsh, B. (2009, March 27). The adrenal glands | Precision Nutrition [Web log post]. Retrieved from http://www.
precisionnutrition.com/what-do-the-adrenal-glands-do
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