Adrenal Dysregulation Syndrome and Elevated Salivary Cortisol Levels

 

By Tori Hudson, ND

Practitioners of alternative medicine often use the term “adrenal fatigue” or “adrenal failure” to name the complex array of symptoms their patient is having, presumably related to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. I would assert that the term adrenal failure should be reserved for Addison’s disease. What we are looking to name is not adrenal failure, or even adrenal fatigue necessarily, but a syndrome with several phases and many different manifestations caused by dysregulation/dysfunction of the HPA axis. As such, I propose we avoid the terms adrenal failure and adrenal fatigue, and instead use the term “adrenal dysregulation syndrome.”

Adrenal functions and stress adaptation mechanisms are among the most far-reaching network of endocrine, nervous, and immune system interactions regulating our life. The HPA glands and their interactions are responsible for the secretion of hormones vital to the control of carefully orchestrated production, synthesis, and communication of these hormones. In response to stress, the hypothalamus secretes corticotropin-releasing hormone (CRH) that then stimulates the anterior lobe of the pituitary gland to secrete adrenocorticotropic hormone (ACTH). ACTH then reaches the adrenal cortex and cortisol is synthesized and secreted into the bloodstream. This hormone, cortisol, is the major glucocorticoid that acts as both mediator and inhibitor of the stress response. Cortisol is an insulin antagonist and maintains blood glucose levels by inhibiting glucose uptake and oxidation.¹ Its enhancement of catecholamine release leads to improved cardiac function and blood flow. Cortisol also suppresses collagen synthesis, osteoblast activity, hematopoiesis, protein synthesis, immune response, and kidney function.²

Under usual circumstances, our stress response and the acute/alarm phase is temporary. The HPA axis is under negative feedback control from cortisol. Cortisol then is the primary regulator of the HPA axis with negative feedback on ACTH and CRH, exerting its control of both the hypothalamus and the pituitary gland. Under prolonged stress or increasing intensity of the stress, the HPA axis no longer responds to this negative feedback. This prolonged stress response can then cause continuous cortisol synthesis and chronically elevated cortisol levels. In this state of prolonged stress, increased cortisol levels are linked to metabolic syndrome, overweight and obesity, chronic fatigue syndrome, chronic inflammatory states, coronary artery disease, anxiety, insomnia, depression, and more. This is referred to as the resistance phase of the stress adaptation syndrome. If allowed to persist, there is a significant increase in risk of these diseases. This can also lead to the final stage of the stress adaptation syndrome (ie, exhaustion). This exhaustion phase may manifest as more acute and serious collapse of vital organ systems and functions.

A comprehensive medical and social history will be the primary tool that will help to identify our patients’ phase of stress. Physical exams and select laboratory testing will help to not only determine underlying causes of stress, but also to diagnose current diseases and to evaluate for risk factors for other significant concerns. This in turn will help with prioritizing treatments and strategizing risk reduction with the goal of restoring HPA balance.

Many, if not most, of the manifestations of chronically elevated cortisol are more common in women. For example, chronic fatigue syndrome (CFS) occurs more frequently in women than in men. Most commonly, the onset is between 20 and 40 years of age. The majority of patients are middle class and in the helping professions such as nurses, doctors, and teachers. Overweight, obesity, insomnia, depression, anxiety, and metabolic syndrome, all associated with chronically elevated cortisol levels, are also among the health disorders more common in women. In addition, the hormonal influences of premenstrual syndrome, postpartum, perimenopause, and menopause add another layer of complexity and interaction unique to women and adrenal regulation. It is this chronically elevated cortisol state, most easily identified with salivary cortisol testing, that I address in this article.

The most effective way to manage chronically elevated cortisol levels is to ensure that the adrenal glands are supported with the proper nutrients. ¹ Vitamin B6, pantothenic acid, and vitamin C often become depleted when the demands on adrenal gland cortisol production are continuous.3 An abnormal adrenal response, whether it is deficient or excessive hormone release, can be in large part addressed with these key nutrients. These nutrients play a critical role in the optimal function of the adrenal gland and in the optimal manufacture of adrenal hormones. Levels of these nutrients can be diminished during times of stress. Urinary excretion of vitamin C is increased during stress. A deficiency of pantothenic acid results in fatigue, headaches, insomnia and more. L-tyrosine and L-theanine support the adrenal glands by combating fatigue and anxiety related to stress.4 In addition, the cortisol feedback control mechanism is dependent on adequate amounts of calcium, magnesium, potassium, manganese, and zinc.⁵

Ashwaganda (Withania somnifera), also known as Indian ginseng, has been in historical use in the Ayurvedic medical system for more than 3,000 years. It has been shown to reduce corticosterone, a glucocorticoid hormone structurally similar to cortisol.^{1, 6, 7} An array of clinical trials and laboratory research also support the use of ashwaganda in enhancing mood, reducing anxiety, and increasing energy. ^{8, 9, 10 , 11}

Magnolia (Magnolia officinalis), also known as Holly Bay and White Laurel, has been historically used for weight loss, obesity, anxiety, stress, depression, and inflammation. A randomized, parallel, placebo-controlled study in overweight, premenopausal women showed magnolia use led to a decrease in transitory anxiety, although salivary cortisol levels were not significantly reduced.¹² Through some of its reported antidepressant and anxiolytic effects, magnolia can improve mood, increase relaxation, induce a restful sleep, and enhance stress reduction. ¹³

A proprietary blend of two plant extracts, one from magnolia and the other from Amur cork tree (Phellodendron amurense) shows promise in lowering cortisol. Initial evaluations by the research and development company behind this proprietary product found that 8 out of 10 stressed individuals felt more relaxed, 7 out of 10 enjoyed more restful sleep, and 9 out of 10 said it was gentle on the stomach.

In an unpublished study conducted at the Living Longer clinic in Cincinnati, Ohio, by LaValle, the same proprietary blend was shown clinically to normalize the hormone levels associated with stress-induced obesity. This combination lowered cortisol levels by 37 percent and increased DHEA by 227 percent. Phosphatidylserine (PS), also known as lecithin phosphatidylserine, is a fat-soluble phospholipid that is the most abundant phospholipid in the human brain. PS is a component of the mitochondrial membrane, where it serves as a reservoir for other phospholipids. It is vital in neuronal membrane functions, signal transduction, cell-to-cell communication, cell-growth regulation, and secretory vesicle release. We obtain most of our PS from dietary sources, although we do synthesize PS as well. PS is known to blunt the rise in cortisol and ACTH following strenuous training and significantly reduce both ACTH and cortisol levels after exposure to physical stress.^{14, 15} Phosphatidylserine also has been shown to improve mood.^{16, 17}

Combinations of the above-mentioned ingredients can be used together and in multiple-ingredient formulations as part of a whole-system approach to correcting adrenal dysregulation with elevated cortisol levels. In a recent unpublished study of another proprietary formula, study subjects took a product containing ashwagandha, PS, magnolia, and L-theanine. The nutritional/botanical supplement consistently decreased salivary cortisol levels in relation to baseline levels. In addition, participants reported increased relaxation, improved sleep, deeper sleep, and reduced stress levels.¹⁸

Numerous other adaptogens may be useful in cases of adrenal dysregulation. Traditional herbal medicine defines an adaptogen as an agent that produces a nonspecific response to counter physical, chemical, or biological stressors, thus allowing the body to “adapt” to the stressful circumstance. This normalizing influence on physiology is irrespective of hyperfunction or hypofunction of an organ or organ system. Western botanical researchers look at the effect of adaptogens on regulating the HPA axis and use them to regulate the neuroendocrine and immune systems. Adaptogenic herbs support the entire neuroendocrine system, in particular the adrenal function and the stress response, which results in a modulating and regulating effect on the use of cortisol. Adaptogens known for their anti-stress qualities and stabilizing effect on the HPA axis include American ginseng, ashwagandha, Asian ginseng, astragalus, cordyceps, reishi, eleutherococcus, holy basil, rhodiola, schisandra, and licorice. Again, combination/multi-ingredient formulations are common in a whole-system approach to restoring adrenal regulation.

Reducing cortisol levels and restoring adrenal regulation can be a very effective management approach to addressing stress management, chronic fatigue, sleep disturbances, and anxiety, while also reducing the long term risks associated with elevated cortisol levels.

Tori Hudson, ND, graduated from the National College of Naturopathic Medicine and has served the college in several capacities, including: Medical Director, Associate Academic Dean, and Academic Dean. She has been practicing for 25 years, is currently a clinical professor at The National College of Naturopathic Medicine and Bastyr University, is medical director of her clinic in Portland, Ore., and director of product research and education for VITANICA. She is the author of Women's Encyclopedia of Natural Medicine second edition. Dr. Hudson serves on several editorial boards, advisory panels, and as a consultant to the natural products industry.

    

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¹⁸ Author not listed. An open label pilot study of the safety and effectiveness of a cortisol-reducing combination in healthy adults. 2006. Unpublished.