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Many patients present to our Tulsa Functional Medicine clinic with a complaint of fatigue. Adrenal fatigue is a potential cause for this fatigue.

Adrenal fatigue is not recognized by mainstream medicine due to a lack of firm scientific evidence.[3] This is a true shame as there are a number of conditions that also have a lack of firm scientific evidence yet are recognized by mainstream medicine. Examples include Fibromyalgia, Chronic Fatigue Syndrome, etc. Additionally, we should use caution in treating individual patients based on “firm scientific evidence” alone. See this article for more information.

Understand that the diagnosis of Adrenal Fatigue is NOT recognized by mainstream medicine. We believe this is a shame! If you’ll recall, in 1492 convention stated that the earth was flat…

If we are treating “firm scientific evidence” then I would agree that adrenal fatigue is not well substantiated in the scientific literature. However, we treat patients. Individual, unique patients.

Here is what one patient’s mom had to say about this topic…

“My daughter has all the symptons of Adrenal Fatigue, and had numerous tests, all coming back clear. I’ll be taking her to a herbalist or alternative doctor because I know IT’S NOT IN HER HEAD.”

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The Adrenal glands are small glands located just above the kidneys and they produce a number of hormones that are vital to normal health.

The adrenals glands consist of 2 primary regions: the outer layer is the adrenal cortex and the inner layer is the adrenal medulla.

Adrenal Medulla

The adrenal medulla produces our catecholamines: epinephrine, norepinephrine, and dopamine. These hormones help regulate blood flow, heart rate, blood pressure, and the “fight or flight” response required for acute stressors.

Adrenal Cortex

The adrenal cortex consists of 3 layers each producing a different set of hormones:

• Zona glomerulosa – the outermost layer of the adrenal cortex and primarily produces aldosterone which helps to regulate water and sodium in the kidney. This is also very important for the regulation of blood pressure as well as contributing to hypertension. 
• Zona fasciculata – the middle later of the cortex and primarily produces glucocorticoids. The primary hormone that we will be concerned with is Cortisol. More on this in a bit.
• Zona reticularis – the innermost layer and primarily produces the sex hormones: DHEA, DHEA(S), and androstenedione. Testosterone and Dihydrotestosterone (DHT) are also produced to a lesser extent here.

The adrenal glands help regulate the stress response required for optimal physiology and health.

It is important to understand that the body is not able to differentiate one form of stress from another. In other words, stress is stress. It doesn’t matter what the source of stress may be. Some common forms of ‘stress’ to which the adrenal glands respond include:

• psycho-emotional stressors
• tissue damage, inflammation, pain
• glucose dysregulation – low blood sugar is a very potent stimulus for the release of cortisol
• sympathetic overflow

Your brain evaluates stressors and increases the amount of adrenocorticotropic hormone (ACTH) released from the anterior pituitary gland. ACTH then stimulates the adrenal gland to produce and release cortisol in response.

The adrenal gland has receptors on its cells for ACTH. These receptors work like most other receptors in the body in that ACTH binds to them and stimulates the intra-cellular cascade to release the appropriate hormones.

Like other systems in the body the response can diminish over time if constantly bombarded with excessive levels. This results in a ‘resistance’ of the target tissue to the hormone. Examples of this type of resistance would be Leptin resistance leading to overeating and insulin resistance leading to Diabetes Type 2.

When your adrenal glands are bombarded with stimulation from ACTH over and over again it no longer responds in the usual manner. Think about a nagging spouse that won’t leave their partner alone. As you can imagine, over time, the constantly nagged spouse quits listening. The adrenal glands can become the constantly nagged spouse!

Cortisol

The adrenal gland typically secretes a baseline level of cortisol but is able to increase the release in a pulsatile response based on stimulation from the brain.

Cortisol is released in a circadian rhythm pattern. This means that the levels of cortisol change based on the time of day. We recommend testing cortisol levels at 4 times:

• AM – First thing in the morning, upon waking
• Noon – 30 minutes after eating lunch
• Afternoon – roughly 4pm
• Midnight – just before you go to bed

You’ll notice in the diagram (Figure 1) a green shaded area. This is the normal reference range for cortisol based on the time of day. Your cortisol levels should be within the green area at each interval.

Cortisol levels are generally highest in the morning, decline sharply by noon, flatten out in the afternoon, and slightly decline before bed. This diagram reflects a normal cortisol circadian rhythm pattern.

This type of pattern suggests a properly functioning Hypothalamic-Pituitary-Adrenal (HPA) Axis.

Now, lets consider an abnormal pattern.

Here, you’ll notice 2 problems:

1. The levels for the first 3 specimens are below the green shaded area. There is a very low level of cortisol being released when the levels should be much higher. This is very abnormal!
2. The pattern is very flat! Remember that the brain and adrenals are supposed to be communicating. This flat pattern suggests that the adrenals are not responding to the brain stimulus via ACTH. Another explanation could be that the brain is not secreting ACTH appropriately. Regardless of the actual cause, the pattern is abnormal and the HPA Axis is inappropriate. This must be fixed.

So, we’ve established normal function of the adrenals and the HPA Axis and abnormal function. There are definitely other patterns that can be very abnormal as well.

The 4pm spike noted on this pattern could be due to anything that causes cortisol to elevate. Common reasons would be psychoemotional stress, glucose dysregulation, pain, inflammation, etc.

When we see patterns like this we often start with blood glucose control as part of a comprehensive plan to treat the adrenals.

When looking at the function of the adrenal glands we also like to evaluate the common causes of adrenal dysfunction.

Therefore, we have to address the primary causes of increased ACTH release from the anterior pituitary gland causing release of cortisol from the adrenal cortex as mentioned above.

Psychoemotional Stressors: It is difficult to evaluate psychoemotional stressors from a medical perspective. The best way we know of is a good history obtained in the office visit. This is one of the many reasons that we need, and spend, a little more time with our patients.

Glycemic Regulation: As mentioned above, low blood sugar is a very potent stimulus for the release of cortisol. The biggest problem that we see in this area is eating high glycemic index foods and too many carbs in general. This causes insulin spikes with subsequent drops in blood sugar due to the fact that insulin follows behind glucose levels.

We will often check fasting insulin levels as well as post-prandial (after meals) insulin levels to see how your physiology is adapting to your diet. This helps us understand the full impact of stress on the adrenals and better enables us to tailor the plan to you for optimal results.

Tissue Damage, Inflammation, & Pain: Secretory IgA (SIgA) is an antibody secreted along the GI tract as a first line of defense against potentially problematic substances. These levels are suppressed in response to elevated cortisol levels, sympathetic stimulation, chronic deficits in cortisol or DHEA, immune insufficiency, and poor gut health.

SIgA complexes are generally not inflammatory when they combine with their antigen. However, when SIgA levels are low the body must rely on other immune components to maintain appropriate defenses. This often causes increased inflammation which is another stressor on the adrenal glands.

Sympathetic Overflow: We can evaluate the balance of the sympathetic and parasympathetic nervous systems by measuring Heart Rate Variability (HRV). This is an in office test that only takes a few minutes and can help us determine neurologic status.

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How Do We Fix Adrenal Fatigue?

Reading the information above on the basis of adrenal fatigue will help you understand what we need to do to fix this problem.

Adrenal fatigue therapy is a 2 step process:

1. Reduce (if not eliminate) the sources of adrenal stress & fatigue – this means turning off the source of stress. There are 4 primary stimuli of cortisol release from the adrenals which need to be optimized in order to turn off this fatigue.
   1. Glycemic dysregulation – lack of blood sugar control
   2. Psychoemotional stressors – mental and emotional stress
   3. Sympathetic overflow – increased sympathetic nervous system tone, too much “fight or flight”
   4. Tissue damage, inflammation, and pain – any tissue inflammation or damage as well as any source of pain can increase cortisol
2. Adrenal support with meds, supplements, etc.

If you know anything about our approach then you understand the ‘Healthy Trinity’. We will address the specifics of how the Healthy Trinity applies to the treatment of adrenal fatigue here.

Nutrition & Glucose Control

As with most health issues, proper nutrition is essential when it comes to adrenal fatigue.

I mentioned that glucose control is very important with adrenal fatigue as low blood sugar causes an increase in cortisol. We generally recommend a fairly low carbohydrate diet but adrenal fatigue presents an exception. This is not a pass to go crazy on carbs though. We simply need to make sure that we get enough carbs at the right times.

• 5-6 small meals per day, eat every 3-4 hours
• Low glycemic-index foods with every meal, along with protein & fat every time
• No blood sugar spikes which should prevent blood sugar drops
• Make sure you get some carbs (following the rules above) immediately after any exercise
• Gymnema sylvestre can help with carb cravings, pancreas function, and insulin function.

Nutritional Supplements

Vitamins B5 & B6 are very important for energy production and for optimal adrenal function and these 2 vitamins are generally part of any adrenal support supplement.

As a baseline approach to adrenal support I generally recommend:

• Herbal adaptogens:
  • Adrenal Essence – 2 caps twice a day
  • Cortisolv – 1 capsule twice daily
  • Ashwagandha twice daily

Depending on the cortisol pattern we may prescribe:

• Licorice Root – helps decrease the breakdown of cortisol thereby effectively increasing cortisol levels. If your cortisol levels are very low then you may benefit from licorice root supplementation at the appropriate times. We have a Licorice root liquid with a dose of 5-10 drops at the time when cortisol levels are low. We also carry it in a capsule form. This is generally in the morning but can be any time.
  
• Phosphatidyl (or phosphorylated) serine – this helps to re-sensitize the hypothalamus to the cortisol in circulation which helps re-establish the HPA Axis. We recommend this at periods when your cortisol levels are elevated.

Herbal Adaptogens: these are herbs that decrease cellular sensitivity to stress.

“The stress-protective activity of adaptogens has been found to be associated with activation of molecular chaperonin Hsp70,and other key mediators of the stress response such as cortisol, nitric oxide, stress-activated protein kinase JNK and DAF-16. Studies have demonstrated that heat-shock factor 1 (HSF1) and Neuropeptide Y might be primary upstream molecular targets of adaptogens in neuroglia cells, but the results were only suggestive, not conclusive. One recent analysis revealed that a claimed adaptogen extract, ADAPT-232, and some of its components individually, regulated the transcription of genes involved in cellular signaling pathways, most notably those of G protein-coupled receptors.“[1]

Examples of herbal adaptogens include:

• Ashwagandha
• Rhodiola
• Cordyceps
• Panax ginseng

Adrenal Glandulars: These are simply dessicated and powdered forms of adrenal glands that help to provide the raw materials for optimal adrenal function. Some practitioners prefer to not use glandulars initially and reserve them for those that do not respond to adaptogens, nutritional supplementation, and appropriate stress reduction.

Hormones: Depending on the stage of adrenal fatigue and the amount of steroid precursors some patient will require supplementation with these. Pregnenolone is the foundational hormonal precursor from which all adrenal hormones are produced. Some patients have very low levels of some of these precursors and benefit from supplementation with pregnenolone.

Hydrocortisone – this is bioidentical cortisol. On rare occasions we use hydrocortisone to assist with appropriate hormone levels as a very low dose.

Exercise

Exercise is very important but we have to be careful in the setting of adrenal fatigue. Remember, we are trying to minimize the stress on the body to allow the adrenals to recover and to help re-establish the HPA Axis. While we typically recommend high-intensity exercise, adrenal fatigue is one case where we may want to decrease the intensity just a little. This needs to be evaluated on a case by case basis.

The 3 R’s

This is probably one of the biggest areas of concentration for the patient with adrenal fatigue.

Rest: Sleep is absolutely critical for adrenal fatigue patients. If these patients are not sleeping appropriately then this may become one of the first priorities. The foundation of sleep intervention is through sleep hygiene and we increase the interventions as needed. RelaxMax is an excellent supplement that helps with both sleep and cortisol regulation.

Recovery from Exercise: It is very important to ensure that we allow for adequate recovery from exercise. Excessive exercise (relative term) with inadequate recovery can place significant loads on the adrenals. Again, ensure adequate nutrition after exercise.

Reduce Stress: This is the basis of much that was discussed above in regards to reducing the total stress encountered.

 

These recommendations are intended for educational purposes only. The specific recommendations for individual patients are based on a thorough history and physical exam that can only be established through an appropriate doctor-patient relationship. This information is in no way intended to circumvent any recommendations by your personal physician.

 

References:

1. http://en.wikipedia.org/wiki/Adaptogen
2. http://www.adrenalfatigue.org
3. http://www.sciencebasedmedicine.org/fatigued-by-a-fake-disease/
4. http://www.bmj.com/content/327/7429/1459
5. http://www.mayoclinic.com/health/adrenal-fatigue/AN01583
6. http://robbwolf.com/2012/04/09/real-deal-adrenal-fatigue/
7. http://thyroid.about.com/cs/endocrinology/a/adrenalfatigue.htm
8. http://www.drlam.com/articles/adrenal_fatigue.asp
9. http://gokaleo.com/2013/01/25/adrenal-fatigue-as-a-cover-for-starvation/
10. http://www.foxnews.com/health/2012/09/07/how-to-combat-stress-from-adrenal-fatigue/