And driving all of these billions and billions of dollars in sales in stimulant drinks is the underlying condition of adrenal fatigue. In today’s newsletter, we will explore the anatomy and physiology of the adrenal glands, and how the abuse of these glands has led to a dependency on stimulants that goes far beyond the world’s illicit drug trade.

General anatomy

The adrenal glands are located on top of each kidney; hence, the terms “ad renal” — as in “added” to the renal glands. They are small glands, about 2 inches (5 cm) in length, and weighing about 5 gm each. As part of the kidneys, they are located way, way to the back of the body (as any good martial artist knows) and are abundantly supplied by three sets of blood vessels to ensure redundancy:

• Inferior phrenic arteries off the aorta.
• Middle suprarenal arteries off the aorta.
• Inferior suprarenal arteries of each renal artery.

Like the pituitary gland, the adrenal glands are composed of two entirely separate sections (the cortex and the medulla), and like the pituitary gland, the two sections actually evolve during embryology from two entirely different types of tissue. The adrenal cortex evolves from fetalmesodermal cells (essentially cells that produce connective tissue). The adrenal medulla, on the other hand, evolves from the nervous system. In fact, the adrenal medulla actually consists of modified neurons (neural crest cells). In the fifth week of fetal development, neuroblast cells migrate from the neural crest to form the sympathetic chain and preaortic ganglia. The cells then migrate a second time to the adrenal medulla. Forgetting all the technical names of cells and cell sources, the key point to remember here is that the two parts of the adrenal glands form two entirely different types of cells and share little in common — other than location.

• The adrenal cortex is the outer layer.
• The adrenal medulla is the inner layer.

The adrenal glands, or at least the cortex of the glands, are absolutely essential for life. Then again, although it is possible to survive without the inner layer, the adrenal medulla, the quality of life would be severely compromised.

Let’s now examine the adrenal cortex and medulla in more detail.

Adrenal cortex

The adrenal cortex produces three hormones in three separate zones.

Mineralocorticoids
Aldosterone is 96% of this group, and it controls water and electrolyte (sodium and potassium) balance in the body. Without the action of the mineralocorticoids in maintaining electrolyte homeostasis, you would die since this has a direct effect on regulating blood pressure. The action of the mineralocorticoids is on the kidneys, which under the direction of these hormones excrete sodium or potassium as required to maintain optimal balance. Adrenal adenomas (benign, actively secreting growths in the cortex) cause hyper-production of aldosterone, which may account for as much as 25% of high blood pressure patients. Treatment involves removal of the tumor, and positive results are virtually instantaneous. The trick, of course, is arriving at the correct diagnosis. Most adrenal adenomas are discovered by chance when an abdominal computed-tomography (CT) or magnetic-resonance imaging (MRI) scan is done for unrelated symptoms.

Glucocorticoids
Cortisol (also called hydrocortisone) is 95% of the total, plus corticosterone, and cortisone.

• Cortisol depresses the immune system.
• It is an anti-inflammatory (as a result of depressing the immune system).
• It retards allergic overreactions, but as a result slows wound repair.
• It promotes the breakdown of protein (catabolism).
• It promotes lipolysis, the conversion of triglycerides to stored fatty acids.
  • Many weight-loss supplements sold today theoretically address this problem by relieving stress, thereby reducing cortisol production and correspondingly eliminating excess fat storage. Although the theory is sound, how well any individual supplement works, of course, is open to debate.
• It promotes glucose formation (gluconeogenesis).
• It promotes resistance to stress, resulting in higher blood pressure.

Addison’s disease results from acute adrenocortical insufficiency.

• The symptoms are lethargy, low blood pressure, weight loss, anorexia, and low blood sugar.
• Addison’s disease is treated with a steroid hormone (cortisol in various forms, natural and synthetic) replacement.
• John F. Kennedy may be history’s most famous Addison’s disease patient and required regular cortisone injections to deal with stress. Since one of the side effects of cortisol injections is a “tanning” of the skin, JFK looked his best (tanned and relaxed) during times of stress — immediately after injections.
• Full blown Addison’s disease is extremely rare. However, “low level” adrenal fatigue is extremely common, and we will be discussing it in more detail later.

Cushing’s syndrome, on the other hand, results from excessive adrenal cortical function. It results in spindly arms and legs, a moon-face,a buffalo hump on the back, flushed skin, hypertension, osteoporosis, and decreased resistance to infection or stress.

Androgens
Androgens are masculinizing hormones that occur in insignificant amounts in the adult male. The primary and most well-known androgen is testosterone. In men, the vast majority of androgens are produced in the testes, but in women, the adrenal glands are responsible for the overwhelming quantity of androgen production. Surprisingly, for women, the masculinizing hormones produced by the adrenal glands are essential for well being. In females, androgen accounts for sexual drive, energy, and “joie de vivre.” It is converted into female hormones (estrogens) after menopause.

Incidentally, old treatments for breast cancer involved removing the pituitary gland to prevent the adrenal glands from producing estrogen by stopping release of ACTH that would normally have stimulated the adrenals. Nowadays, this is accomplished with pharmaceuticals.

Adrenal medulla

Hormones in the medulla are produced in the chromaffin cells (“chromium + affinity”). They get their name from the fact that they stain readily in the presence of chromium salts. Chromaffin cells are neuroendocrine in that they are activated by neurotransmitters released by nerve cells located in the autonomic nerve fibers coming directly from the central nervous system. In response to this input, the chromaffin cells of the medulla release hormone messenger molecules into the blood. In this way, they integrate the nervous system and the endocrine system, a process known as neuroendocrine integration.

Because the chromaffin cells are directly activated by the nerve fibers from the autonomic nervous system, they respond very quickly — as is necessary in a system that responds to emergency situations. On the other hand, chromaffin cells continue to secrete adrenal hormones “long” after nervous stimulation has passed. In fact, hormonal effects can last up to ten times longer than those of neurotransmitters. In a sense, neurotransmitters respond in the short term to emergencies, whereas the medullary hormones cover the longer term. In this way the sympathetic division of theautonomic nervous system and the medullary secretions function together.

So which hormones are we talking about?

The adrenal medulla releases two hormones: adrenaline (80%) and noradrenaline (20%), more commonly known among the medical establishment as epinephrine and norepinephrine. Collectively, they are called catecholamines. As I mentioned earlier, unlike the adrenocortical hormones, the medullary hormones are not essential for life — at least when the body is in the resting state. Without stress, you don’t need these hormones — with one primary exception. Standing up from a reclining or sitting position would entail an unsustainable drop in blood pressure, as blood pooled in the feet and legs, if not for a compensating action governed by the medullary hormones. (We will talk more about this in a moment.)

Adrenaline

Epinephrine (also known as adrenaline) increases heart rate, contracts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. As a hormone, epinephrine acts on nearly all body tissues. Its actions vary by tissue type and by the differing responses of the various receptor sites scattered throughout the body. For example, epinephrine causes smooth muscle relaxation in the airways, but causes contraction of the smooth muscle that lines most arterioles.

Noradrenaline

Norepinephrine (also known as noradrenaline) both complements the actions of adrenaline and adds its own stimulus to the brain. Along with adrenaline, noradrenaline also responds to the fight-or-flight stimulus by directly increasing heart rate, triggering the release of glucose from energy stores, and increasing blood flow to skeletal muscle. In addition, though, noradrenaline affects parts of the brain where attention and responding actions are controlled. Noradrenaline also works as an anti-inflammatory agent in the brain.

I’ve fallen down, and I can’t get up

When a healthy individual stands up, gravity, if not accounted for, would cause approximately 10-15% of their blood to settle in the stomach and limbs. This blood pooling would mean that less blood reaches the brain — resulting in lightheadedness, seeing stars, tunneled vision/darkening, and even fainting. In healthy individuals, however, this does not happen because special pressure sensors in blood vessels instantaneously act (via the involuntary nervous system) to trigger important responses in the body. These responses maintain normal blood pressure and flow to the brain and body primarily by pumping adrenaline and noradrenaline into the bloodstream. As we discussed earlier, these hormones cause the smooth muscle that lines most arterioles to contract. They also cause the veins of the lower body to contract. The net result of all this contraction is the raising of blood pressure and the forcing of blood up into the head. Also, the heart is stimulated to increase its output by increasing the number of heart beats per minute, the volume of blood pumped per beat, and the force with which each beat squeezes. We can actually feel this happening, from time to time. (Pay special attention and check it out the next time you stand up.) The end result is more blood returning to the brain and heart. Usually, if all components of the circulatory reflexes are working properly, the move from lying to standing proceeds without symptoms.

Common adrenal problems

For the most part, the adrenal glands function so well, and can handle almost any abuse we throw at them, that we barely give them a thought. But if pushed too far, they will crack. Addison’s disease, which we’ve already discussed, is the primary “disease” of the adrenals, but there are several “lesser” problems worth discussion. Although not normally recognized by the medical community, they actually represent the vast majority of adrenal problems people face in today’s high stress world. We’re talking about non-clinical adrenal fatigue, weight gain, and caffeine addiction.

Adrenal Fatigue

According to the Mayo Clinic, adrenal fatigue is a term applied to a collection of nonspecific symptoms, such as body aches, fatigue, nervousness, sleep disturbances, and digestive problems. The term often shows up in popular health books and on alternative medicine Web sites, but it isn’t an accepted medical diagnosis. The “unproven theory” behind adrenal fatigue is that your adrenal glands are unable to keep pace with the demands of perpetual fight-or-flight arousal. As a result, they can’t produce quite enough of the hormones you need to feel good. Existing blood tests, according to this theory, aren’t sensitive enough to detect such a small decline in adrenal function — but your body is. That’s why you feel tired, weak, and depressed. However, the only real, diagnosable, medically accepted form of adrenal fatigue is Addison’s disease (discussed earlier).

But is that true?

What I find absolutely delicious in the Mayo Clinic’s commentary on adrenal fatigue is their conclusion. “Unproven remedies for so-called “adrenal fatigue” may leave you feeling sicker, while the real cause — such as depression or fibromyalgia — continues to take its toll.” How wonderful to include fibromyalgia as a “real” condition. Lest anyone forget, it was just a few years ago that the medical establishment was dismissing fibromyalgia as an alternative health fantasy…just like adrenal fatigue. And many doctors still dismiss it as such. So with that in mind, what is adrenal fatigue?

First of all, contrary to what the Mayo Clinic claims, adrenal fatigue probably affects as many as 80% of adults at some point in their lives. These patients often end up going from doctor to doctor trying to find out why they feel exhausted and sick. Too often they’re told after extensive testing, as the Mayo Clinic would do, that there is nothing wrong with them — or perhaps that they are suffering from stress and need to relax more. The problem is that, from a medical point of view, adrenal fatigue has a broad spectrum of non-specific, yet often debilitating symptoms, including:

• Fatigue, lethargy:
  • Difficulties getting up in the morning.
  • Lack of energy in the mornings, and also in the afternoon between 3 and 5 pm.
  • Often feel tired between 9 and 10 pm, but resist going to bed.
  • Sleep difficulties.
  • Difficulty concentrating or remembering (brain fog).
• Need coffee or stimulants to get going in the morning.
• Feel better suddenly for a brief period after a meal.
• Cravings for salty, fatty, and high protein food such as meat and cheese.
• Lowered blood pressure and blood sugar.
• Lightheadedness (including dizziness and fainting) when rising from a sitting or lying-down position.
• High frequency of getting the flu and other respiratory diseases — plus a tendency for them to last longer than usual.
• Tendency to tremble when under pressure.
• Pain in the upper back or neck with no apparent reason.
• Increased symptoms of PMS for women; periods are heavy and then stop, or are almost stopped on the 4th day, only to start flow again on the 5th or 6th day.
• Reduced sex drive — particularly in women.
• Tendency to gain weight and unable to lose it, especially around the waist.

The bottom line is that being consistently under stress eventually exhausts the ability of the adrenal glands to produce sufficient amounts of hormones — particularly cortisol. As the Mayo Clinic indicated, because they are prepared only to diagnose extreme dysfunction in the adrenals such as Addison’s disease, conventional endocrinologists and medical tests cannot diagnose adrenal fatigue. But that does not mean that it is untestable. Beyond the symptoms themselves, natural healers can conduct a saliva cortisol test to evaluate your adrenal function. This will pick up more subtle dysfunctions in your adrenal glands than the typical medical tests.

If you are diagnosed with adrenal fatigue, or simply believe you have it, you will want to consider the following steps.

• Relax! Chill out! Find some way to reduce your stress levels. Remember, adrenal fatigue is almost always the result of unrelenting stress.
• Eliminate or cut way back, on your use of stimulants such as coffee and energy drinks. They work by stimulating the adrenals. If your adrenals are already exhausted, stimulants merely drive your adrenals further into “the red.”
• Switch to a low glycemic diet since high sugar levels increase stress on the body and consequently increase cortisol levels. In turn, elevated cortisol levels interfere with the body’s ability to handle sugar — thus raising blood sugar levels and locking you into a vicious circle.
• Consider using a formula such as Standard Process’ Drenamin to “feed” the adrenals.
• Supplement with a formula that contains adaptogenic herbs to help rebuild the adrenals. It would also be useful if the formula helped free up bound testosterone since this would take a burden off of the adrenals as they would no longer have to “make up the difference” caused by low free testosterone levels.

Weight gain

Cortisol is elevated in response to stress. The adrenal glands are not particular, any kind of stress will do. The stress can be physical, environmental, chemical, dietary, or imaginary. The human brain is hard wired with automatic responses to protect the body from harm. All forms of stress produce the same physiological consequences.

As we mentioned earlier, one of the primary roles of cortisol is to promote the conversion of triglycerides into stored fatty acids. It also promotes glucose formation (gluconeogenesis). The bottom line is that chronically elevated cortisol levels contribute to the accumulation of abdominal fat and make it very difficult to eliminate.

• Lowering cortisol levels requires the same five steps mentioned above for relieving adrenal fatigue.

Caffeine

Last year, I devoted an entire newsletter tocaffeine. In summary, the way caffeine works on the adrenal glands is as follows:

Caffeine works by blocking adenosine’s ability to slow nerve cell activity in preparation for sleep, and instead increases the speed of nerve cell activity and of the neuron firing in the brain. (The caffeine molecule is structurally similar to adenosine, and binds to adenosine receptors on the surface of cells without activating them — an “antagonist” mechanism of action.) The pituitary gland “sees” all of the increased neuron firing in the brain and thinks some sort of emergency must be occurring, so it releases hormones that tell the adrenal glands to produce adrenaline, which gives your body a boost, so it can remain active and alert in response to the perceived “emergency.”

If you’re drinking five, six, ten cups of coffee a day, or if you’re slugging down five or six energy drinks a day, you’ve put your body in a state of continual “alert.” This produces a constant drain on the adrenals — eventually leading to adrenal fatigue.

So yes or no on consuming caffeine? Unfortunately, when it comes to caffeine, the devil is in the details.

• Natural caffeine is preferable to “added” caffeine. Natural caffeine comes packaged with a number of powerful antioxidants such as:
  • Chocolate: flavonoids, procyanidins, epicatechin, cocoa phenols.
  • Tea: epigallocatechin, epicatechin gallate, and epicatechin. Not to mention theanine, which is not an antioxidant, but rather, a profoundly beneficial amino acid.
  • Coffee: chlorogenic acid, caffeic acid, and melanoidins.
• The Mayo Clinic says under 300 mg a day is fine. I set the figure much lower — at about 100 mg a day. That still allows for 3 cups of green tea a day. The exception to this guideline is that if you take your caffeine bound to fiber, as in guarana (not guarana extract), the caffeine releases over time rather than in powerful bursts, which allows you to consume more without the negative side effects.
• Don’t use caffeine as part of a daily ritual such as “every morning” to start the day. Use it selectively, if possible, to get a boost only when needed. And take at least two days off each week — totally caffeine free — to allow all caffeine to clear from your body on a weekly basis.
• And if you’re already in a state of adrenal fatigue, you might want to consider stopping all caffeine consumption at least until you give your adrenals a chance to rebuild some of their lost reserves.