The Truth About Adrenal Fatigue by Dr. Bryan Walsh I'm warning you now, folks: Dr. Walsh gets pretty technical in this one. And for good reason. You see, there are a lot of supposed experts out there talking about "adrenal fatigue" and cortisol. And most of them are either 1) giving you outdated and often misconstrued info, or 2) they're just full of shit, plain and simple. T NATION asked Dr. Walsh to cut through the BS and tell you the real truth about these issues. What he gave us is detailed and cutting edge. In fact, this is the first time a lot of this info has been made public. So strap on your thinking caps and get ready to dig in like your big bulgin' biceps depended on it... because they just might. — CS Adrenal Fatigue: The Real Story There's a lot of crap out there. Foot baths, colon cleanses, ear candling, liver/gall bladder cleanses... it's no wonder why people question alternative medicine. Well, here's another one: adrenal fatigue. To be honest, I feel sorry for the adrenal glands. They're the ultimate scapegoat for alternative practitioners today. When in doubt, blame the adrenal glands! No other part of the body garners as much attention and blame as the adrenal glands when something is amiss in the body. Can malfunctioning adrenal glands really cause issues? Perhaps most importantly, can supporting adrenal gland function improve one's health or performance in the gym? Yes and no. Dysfunctional adrenal gland physiology can cause a wide array of issues in the body that can negatively impact your training. However, it's not really the adrenal glands that are causing the problem! The adrenal glands are merely doing what they're told, mostly by the brain. Here's the real story about the adrenal glands, how they function, what can go wrong, and what you can do about it. Adrenal Physiology 101 You have a pair of triangular-shaped glands sitting on top of your kidneys called the adrenals. Their primary function is to help your body manage and survive during stressful situations. Here's a real life example of how they work. Let's say you're in your car, excitedly driving to the gym, and a truck bolts in front of you almost causing a collision. Fortunately, your cat-like reflexes help you swerve out of the way and avoid the accident. But, when you regain composure, you notice your heart is racing, you're sweating a little, and your hands are clammy and shaking. Here's what happened: At the sight of a near accident, your brain sent a nerve impulse directly via the preganglionic sympathetic fibers to your adrenal medulla to secrete adrenaline, otherwise known as epinephrine (or what's widely known as adrenaline). Epinephrine increases blood pressure, respiration rate, heart rate, increases glucose, and dilates the pupils, all for the purpose of enabling you to quickly and safely get out of a potentially life-threatening situation. This was a purely autonomic reaction that came straight from your brain. At the same time the brain was sending a nerve impulse, it was also releasing a hormone — corticotrophin releasing hormone (CRH) from the hypothalamus — which told the pituitary to release adrenocorticotropic hormone (ACTH), which then tells the adrenal glands to produce cortisol. This is obviously a much slower signal being that the hormone had to travel through the bloodstream. Cortisol's primary role is to increase blood glucose levels to provide fuel to your muscles and brain during a stressful situation. Now a third hormone is released from the adrenal glands called aldosterone, a mineralcorticoid, which helps regulate sodium and potassium levels in the body. Abnormal cortisol levels will wreck your efforts in the gym. Chronically elevated cortisol causes a number of issues including suppression of pituitary function, leading to low Testosterone levels. Oh, now I have your attention, huh? What The Adrenal Glands Don't Do Unfortunately, the adrenal gland model many alternative practitioners follow today is completely outdated. It basically says that the adrenal glands go through a progressive stress response like this: 1. Alarm reaction — This is the body's initial response to stress. It's typically characterized by elevated cortisol levels. 2. Resistance — If stress is prolonged, the adrenal glands will start to become more "fatigued" and therefore will use other hormones (i.e. pregnenolone) to help make cortisol. Cortisol levels may be normal or high during this phase, but DHEA levels may be low, which can negatively impact Testosterone levels. 3. Exhaustion — This final stage is typically characterized by low adrenal function, with low cortisol and DHEA levels. This phase is what most people refer to as "adrenal fatigue." Aside from the fact that this model is completely inaccurate, it also states that we must support or rebuild the adrenal glands by giving cofactors such as B vitamins, vitamin C and glandulars. This is wrong. It's now understood that people can go directly to the exhaustion phase and have low cortisol production without first going through the other two phases. People can also go directly from low cortisol to high cortisol, or people can live with either high or low cortisol their whole lives. Reasons for this have less to do with adrenal gland function and more to do with the connection between the brain, immune system, and endocrine system. The Updated Model There's a branch of medicine called neuroendocrineimmunology, which basically states that the nervous system, the endocrine system, and the immune system have an intimate connection with one another, and that it's impossible to talk about one system without considering the others. The adrenal glands are really nothing more than manufacturing plants that release hormones based on inputs from other areas of the body. In other words, if someone is having symptoms of low cortisol, perhaps it's not the adrenal glands that need help, but rather something in the body is actually telling the adrenal glands to produce less cortisol. The new model looks at the interconnection of neurotransmitters, hormones, and the immune system. But first, let's look at a few issues that can arise with the HPA axis. What Can Go Wrong High cortisol can be a real problem, especially with regard to getting results in the gym. A summary of the negative impacts of elevated cortisol includes: 1. Suppression of TSH, decreased conversion of T4 to T3, increased production reverse T3 (rT3) and decreased cellular thyroid receptor binding. (In other words, you get fat, among other things.) 2. Increased blood glucose levels. 3. Suppressed pituitary function, leading to low luteinizing hormone and low Testosterone. 4. Decreased liver detoxification. 5. Suppressed secratory IgA, increasing potential of gut inflammation, infection and permeability. 6. Decreased immune system function, leading to increased risk of infection. 7. Insomnia. 8. Neurodegenerative disorders, including degradation of the blood-brain barrier and destruction of the hippocampus. Low cortisol also has negative health impacts including: 1. Suppression of the immune system. 2. Hypoglycemic tendencies, leading to increase in catecholamine release, fluctuations in blood sugar and insulin spikes. 3. Increased inflammation. Something not often talked about with cortisol is an abnormal circadian rhythm. This often indicates a hippocampus issue due to its regulation of the circadian rhythm. Cortisol should be highest in the morning and lowest at night. However, an inverted rhythm can result in: 1. Learning and memory issues. (Neuroendocrinologists are using cortisol circadian rhythm as an early biomarker for Alzheimer's.) 2. Insomnia and sleep difficulties. It All Starts In The Brain (The Really Technical Stuff) Adrenal gland function and release of cortisol is a coordination of three different structures in the brain: 1. Hippocampus — Inside the temporal lobe of your brain, the hippocampus regulates the circadian rhythm of the hypothalamus-pituitary-adrenal (HPA) axis. 2. Mesencephalic reticular formation (MRF) — Within the brain stem itself, the MRF is responsible for promoting a sympathetic response in the body. It does so via excitation of the intermediolateral cell column (IML) in the spinal cord, which stimulates the adrenal medulla to release epinephrine and norepinepherine. 3. Hypothalamus — There are a number of nuclei within the hypothalamus, one of which is called the paraventricular nucleus (PVN). The PVN of the hypothalamus receives a variety of inputs that ultimately results in secretion or suppression of cortisol by the adrenal glands. The Stress Response, 2010 The PVN is considered to be the final common structure where numerous different inputs initiate a stress response. Cytokines from the immune system, neurotransmitters from the nervous system, input from the limbic system (emotions), and hormones from the endocrine system all converge to elicit a stress response from the HPA axis at the PVN. There's a concept in neurology called the central integrative state, which basically states that the net output of a neurological structure is a summation of the excitatory inputs versus the inhibitory inputs. In other words, if a combination of stimulus from neurotransmitters, hormones, and cytokines all result in an excitatory state, the result will be an elevation of cortisol. On the other hand, if the combined total input is that of an inhibitory response, the results will be a low output of cortisol. This is how someone can go directly to the adrenal exhaustion phase: If the total summation of inputs is inhibitory to the PVN, there will be a diminished adrenal response and low cortisol. Using this model, there's no such thing as "adrenal fatigue." Rather, it's merely a lack of inputs that can generate an adequate adrenal response. The following can excite the PVN and therefore contribute to high cortisol: insulin, acetylcholine, elevated epinephrine and norepinepherine, and Th2 cytokines (IL-4, IL-5 and IL-10). The following can inhibit the PVN and therefore contribute to low cortisol: GABA, low epinephrine and norepinepherine, endothelial nitric oxide, interferon, tumor necrosis factor, and Th1 cytokines (IFG, IL-12, TNF). So the next time someone tells you, "Dude, you wore your adrenals out!" You can respond, "No, I probably inhibited my paraventricular nucleus." Symptoms and What To Do Symptoms can help point you in the right direction: Symptoms of hyperadrenal states include: difficulty falling asleep, allergies, excessive perspiration, and gastric ulcers. Symptoms of low adrenal states include: difficulty staying asleep (waking up during the night), dizziness when standing quickly, blurred vision, shakiness or lightheadedness between meals, and relief of fatigue after eating. Symptoms aside, laboratory testing is your best bet. The preferred method is salivary testing due to the ease of measuring circadian rhythm. This type of testing utilizes four salivary samples throughout the day and averages out the total production of DHEA to help evaluate adrenal function. The adrenal salivary test not only allows you to evaluate adrenal function, but can also give implications into the function of degree of hippocampus destruction as well. It's a great test. While the details of interpreting this test are beyond the scope of this article, here are some generalities you can use: 1) Chronically elevated cortisol: a. Phosphatidylserene — 2g a day in divided doses b. Adaptogenic herbs — panax ginseng, rhodiola, ashwaganda, eleutherococcus c. Cytokine support — resveratrol, pycnogenol, green tea extract, pine bark extract d. Neurotransmitter GABA support — taurine, valerian root, passion flower, L-theanine 2) Chronically depressed cortisol: a. Licorice root extract — Dosages depend on the type of licorice root extract used b. Adaptogenic herbs — panax ginseng, rhodiola, ashwaganda, eleutherococcus c. Cytokine support — Echinacea, astralagus, shiitake mushroom, beta-glucan, beta sitosterol d. Excitatory neurotransmitter support — acetylcholine (Alpha-GPC, huperzine, galantamine), serotonin (5-HTP), tryptophan, St. John's wort 3) Abnormal circadian rhythm: a. Acetylcholine support — Alpha GPC, huperzine, galantamine b. Phopshytidylseriene — 2g a day in divided doses for minimum of 6 months Summary Adrenal gland dysfunction is real. However, the way it's explained and treated by many integrated practitioners today is an outdated and incomplete model. With new research and a deeper understanding of how systems of the body work, our methods of treatment should evolve. Hopefully this article has lead to a greater degree of understanding of an otherwise misunderstood and overused concept!