Adaptogens have been defined as compounds that increase the ability to adapt to environmental factors and to avoid damage from such factors. They are substances that increase attention and endurance in fatigue, and reduce stress-induced impairments and disorders related to the neuro-endocrine and immune systems.
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Historically, the supplemental use of adaptogens has not gained much traction in traditional western medicine but rather has been engaged by the naturopathic medicine, complementary and alternative medicine and functional medicine communities. However, in the last 10 years adaptogens have developed growing interest in traditional western medicine and research has begun to shed light on these botanical substances that have had widespread use for literally thousands of years.
Introduction – What are Adaptogens?
Adaptogens are natural bioregulators that facilitate adaptation to environmental and psychosocial oonditions that are stressful and threaten or cause damage or illness. This adaptation reduces the symptoms and damage from such conditions. Adaptogens lessen the negative impact of stress on the neuro-endocrine and immune systems, increase cognitive performance and reduce fatigue. The Food and Drug Administration (FDA) defines an adaptogen as “a new kind of metabolic regulator that has been proven to help in environmental adaptation and to prevent external harms.”
Characteristics of adaptogens:
- Increase bodily resistance to physical, chemical and/or biologically noxious agents or factors;
- Adaptogens have a normalizing influence and reduce the harm caused by stressed states such as fatigue, infection, and depression;
- Adaptogens have positive, excitatory (stimulating) effects on the body;
- In contrast to traditional stimulants, the excitatory effects produced by adaptogens must not cause side effects such as insomnia, low protein synthesis, or excessive energy consumption;
- Adaptogens do not harm the human body and not disturb body functions at normal levels.
Clinical Applications of Adaptogens
Adaptogens offer a wide range of benefits depending on the individual adaptogen and the dosing regimen. Most commonly, adaptogens are used to combat the effects of chronic stress including anxiety, insomnia, mental and physical fatigue, diminished sense of well-being and potential vulnerability to acute and chronic illness. Adaptogens are frequently recommended for use as general tonics in traditional Eastern and Asian medicine.
Adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly by increasing tolerance to mental exhaustion and enhanced attention. They reduce stress-induced impairments related to the neuro-endocrine and immune systems.
Because stress is known to impair the immune system, adaptogen’s stabilization of the stress response also supports the assertion that adaptogens improve the immune response during times of high stress. It has been proposed that adaptogens may be used prophylactically during COVID-19 to potentially reduce the impact of stress on the immune response and reduce vulnerability to infection.
Adaptogens and sleep
One of the major impacts of stress is the disruption of sleep, including including falling asleep, staying asleep and the quality or restfulness of sleep. One contributing factor is that stress impairs the normal secretion of circadian cortisol, a cause of sleep-related problems. The secretion of cortisol is regulated by the HPA axis and follows the biological clock and external circadian rhythms. The normal secretion of cortisol peaks in the morning and then decreases, reaching a minimum value at night. Proper exercise, diet and sleep help maintain stable cortisol levels but excessive stress becomes very disruptive to the normal rhythms of cortisol secretion. Adaptogens help stabilize cortisol levels. The following adaptogens have been shown to facilitate sleep, including the effects of the time zone differences: American Ginseng, As
hwagandha,, Schisandra chinensis and Rhodiola rosea.
Adaptogens and the neuroendocrine system
One of the most important functions of adaptogens is their ability to help stabilize the internal environment of the human body by modulating the neuroendocrine system. Adaptogens enhance the ability to adapt to external environments and avoid damage. A unique feature of adaptogens is that these substances affect both the neuroendocrine system and the cellular energy system. Adaptogens can increase the rates of oxygen, protein, fat and sugar utilization.
Adaptogens and adrenal fatigue
The adrenal glands, often considered the stress glands, provide various responses to physical, biochemical, hormonal, emotional and mental stress. Excessive stress, resulting from a single event or from the accumulation of chronic or repetitive stressors, can result in the adrenals not being able to secrete enough stress hormones to compensate for high levels of stress leads to adrenal fatigue. Adrenal fatigue occurs where the adrenal glands cannot maintain normal balance (homeostasis), including levels of the three major stress hormones: cortisol, adrenaline (epinephrine) and noradrenaline (norepinephrine). Adrenal fatigue is associated with nonspecific symptoms such as body aches, unexplained weight loss, fatigue, nervousness, sleep disturbances and digestive problems.
The following adaptogens support adrenal function by increasing the effectiveness of adrenal gland secretion and stabilizing stress hormone production: Ashwagandha, American Ginseng, Asian ginseng (Panax), Siberian ginseng, Licorice root (Glycyrrhizae radix), and Rhodiola rosea.
Of note, adrenal fatigue is a diagnosis supported by alternative medicine clinicians, but isn’t a generally accepted medical diagnosis in traditional western medicine. The traditional medical term is adrenal insufficiency (Addison’s disease), referring to inadequate production of one or more of these hormones. The theory behind adrenal fatigue is that the adrenal glands are unable to keep up with the demands of severe or chronic stress and as a result, symptoms develop. Existing blood tests, according to the adrenal fatigue theory, aren’t sensitive enough to detect such a small decline in adrenal function. Adrenal insufficiency, it is argued, can be diagnosed by blood tests and special stimulation tests that show inadequate levels of adrenal hormones. The debate has not been resolved.
The stimulating effects of adaptogens
Some adaptogens are noted for their stimulating effects. Stimulants, defined as drugs that increase the activity of the sympathetic nervous system, can be used to increase alertness and the ability to concentrate on mental tasks. Traditional stimulants such as caffeine, nicotine, amphetamines and cocaine, can with short term use boost endurance and productivity. However, long-term stimulant use can impair mental function and lead to psychotic symptoms. Furthermore, some stimulants are prone to abuse and addiction, have a negative effect on sleep structure and cause rebound hypersomnolence or ‘come down’ effects.
The stimulating adaptogens do not exhibit these negative effects and may actually regulate certain sleep disorders and improve sleep quality. This is because these adaptogens stimulate the nervous system by mechanisms that are totally different from those of traditional stimulants. Adaptogens modulate the response to stressful stimuli and regulate various metabolic elements of the stress system, particularly the SAS.
Depending on the mediators of the stress system involved in the adaptogen-induced stress response, an immediate (single dose effect) or a long term (after multiple administration) stimulating effect may result. While the effectiveness of repeated administration of adaptogens in improving mental performance over various time periods is well documented, research on single dose effects is less well established.
Single dose use of adaptogens
Single dose use of adaptogens are reported to increase:
(i) mental working capacity
(ii) physical working capacity
(iii) the accuracy of movement
Stimulating adaptogens for single dose use
Three of the known plant adaptogens, Rhodiola rosea, Schizandra Berry (Schisandra chinensis) and Siberian Ginseng (Eleutherococcus senticosus), offer a safe, ‘adaptogen-type’ stimulating effect providing improvements in mental performance and learning efficiency after single dose use. The most activating stimulant is Rhodiola rosea. The stimulating effects of these adaptogens are apparent within 30 minutes after administration and last for at least 4–6 hours.
A number of botanicals have been identified as adaptogens, each with their unique properties and clinical benefits. Commonly used adaptogens include:
Ginseng (Panax ginseng)
There are at least nine species of ginseng, mostly named by their geographical origins, such as Asian ginseng (Panax ginseng), American ginseng (Panax quinquefolium), and Japanese ginseng (Panax japonicus). Panax ginseng, also called Asian or Korean ginseng, has been reported to have diverse physiological effects in multiple systems, including cardiovascular, immune, and neuronal. It has also been used to enhance sex performance. The main active components of Panax ginseng are ginsenosides, which have been shown to have a
variety of beneficial effects, including anti-inflammatory, antioxidant, and anticancer effects.
Siberian Ginseng (Eleutherococcus senticosus)
Siberian Ginseng, or Eleuthero, is an Asian herb that has been widely used in China for thousands of years as a healing remedy in folk medicine to combat stress and improve stress resilience, support memory and increase work capacity during strenuous aerobic activity. It is different from, and only distantly related to the “true” ginseng species (Panax ginseng and P. quinquefolius) and possesses entirely different, unrelated chemical constituents. Eleuthero helps stabilize stress hormones, at least in part by inhibiting catechol-O-methyl transferase (COMT), the enzyme that metabolizes the stress hormones adrenaline and noradrenaline. Eleuthero has also been shown to support the immune system. Syringin is one of the most important bioactive compounds found in Eleuthero, with pharmacological properties that include scavenging free radicals, protection against neuronal cell
damage, inhibition of apoptosis, anti-diabetic effect, anti-inflammatory potential, anti-pain action and anti-allergic effects.
Ashwagandha has strong adaptogenic properties with many benefits that include improving stress resilience, supporting immune response, regulating the sleep cycle, supporting healthy thyroid function and protecting against exhaustion of the nervous system. Ashwagandha may also be beneficial in supporting mood regulation and restoring a sense of calmness under stress.
Rhodiola has been studied extensively and is widely used in Eastern Europe and Asia to reduce fatigue, regulate mood, improve mental clarity, work performance and the sleep cycle. It increases resistance to a variety of stressors. Rhodiola supports levels of neurotransmitters in the central nervous system such as serotonin, dopamine and norepinephrine. Salidroside, rosavin and triandrin are the constituents in rhodiola that are best studied and the substances which most benefits are attributed to, including Rhodiola’s neuroprotective and stimulating effects.
Licorice root (Glycyrrhizae radix)
Schizandra Berry (Schisandra chinensis)
Schizandra is an adaptogenic botanical that has been used for centuries in China and Russia to help support mental clarity, stress response and emotional wellness. It is believed to improve physical performance in athletes, support learning and memory and may have some protective factors that support brain health.
Understanding Adaptogens and Their Impact on the Stress Response
An excellent review article, “Stimulating Effect of Adaptogens: An Overview with Particular Reference to their Efficacy following Single Dose Administration” published in 2005 in Phytotherapy Research, provides a comprehensive introduction to the concepts surrounding the benefits and use of adaptogens for therapeutic benefit.
Physiological adaptation is defined as a biochemical change in an organism that results from exposure to certain environmental conditions or stressors and generates a more effective response to them. Such adaptive changes take the the stress system (a function of the neuroendocrine-immune complex) from its normal steady state (homeostasis) to a heightened level of dynamic equilibrium (heterostasis) or to the state of non-specific resistance (SNSR), the state in which one has greater resistance to the disruptive and potentially damaging effects of stress, offering greater potential for survival. Allostasis is the process of achieving stability, or homeostasis, through physiological or behavioral change. This can be carried out by means of alteration in HPA axis hormones, the autonomic nervous system, cytokines, or other systems.
The general adaptation syndrome, or response to stress, has three stages: the alarm response, the point at which the body identifies a stressor; adaptation, in which the body engages defensive countermeasures against the stressor; and exhaustion, where the body begins to run out of defences. Stress can be considered as challenging but not overwhelming (eustress), or as overloading (distress). Stress can result from positive (desirable) or negative (undesirable) events. Eustress can be beneficial but distress can be harmful and contribute to disease. Eustress may raise levels of adrenaline and prostaglandins in the body, which in turn increases the heart rate, respiration and blood pressure and may promote survival. Long-term stress, however, contributes to heart disease, high blood pressure, strokes and other illnesses.
Early research suggested that a state of non-specific resistance (SNSR) could be achieved either by gradually training the organism to withstand the effect of the stressor or through use of pharmacologically active compounds named ‘adaptogens’ that modify the body’s response to stress.
Repeated use of adaptogens may be stress-protective, in a manner similar to that produced by repeated physical exercise, and lead to prolonged SNSR with increased endurance and stamina under extreme conditions. Repeated doses of adaptogens have been shown to be effective in sports with fatigue reduction and increased endurance in long distance runners with a more rapid recovery from strenuous exercise – even a single dose of an adaptogen may produce a stimulating effect.
The stress-protective effect obtained by multiple administrations of adaptogens is not the result of inhibition of the stress response, but a result of the adaptive changes in the organism as a consequence of the repeated stress-response modifying effect of the drug. In pharmacological terminology, adaptogens are stress-agonists and not stress-antagonists. Adaptogens function mainly by affecting the stress response system, primarily the hypothalamic–pituitary–adrenal (HPA axis), in response to stimulation by external stress.
The Physiologic Basis of the Stress Response
The stress response system is complex, primarily consisting of the central nervous system (CNS) which includes the hypothalamus and the pituitary gland, the peripheral nervous system which includes the autonomic nervous system (sympathetic and parasympathetic) and the adrenal glands. In times of stress, the hypothalamus releases corticotropin releasing hormone (CRH – also known as corticotropin-releasing factor (CRF), a peptide hormone that stimulates the pituitary to release ACTH (adrenocorticotropic hormone), which acts on the adrenal glands to release the steroid hormone cortisol. Cortisol is a steroid hormone that regulates a wide range of processes throughout the body, including metabolism and the immune response. It has a very important role in helping the body respond to stress.
The Hypothalamic–Pituitary–Adrenal (HPA) Axis
Adaptogens function in response to stress mainly by affecting the HPA axis, which consists of the hypothalamus, the pituitary gland and the adrenal gland. The HPA axis is the primary component of the body’s stress system that responds to repeated stress and contributes to the adaptation to stress. When stimulated by the hypothalamus via homeostatic feedback mechanisms, the pituitary gland secretes ACTH. The release of ACTH regulates levels of the corticosteroid hormone cortisol, which is manufactured and released from the adrenal gland. The HPA also functions to balance the release of adrenaline from the adrenal gland and corticosteroids and nitric oxide (that modulates many hormones and other physiologically active substances. The HPA axis modulates the nervous, cardiovascular, immune, gastrointestinal and endocrine systems.
The Sympatho-Adrenal–System (SAS)
In addition to chronic stress adaptation, acute stress adaptations are important in situations that require a rapid response to a stressful situation. In these acute cases, the effects are generally associated with another part of the body’s stress system, namely, the Sympatho-Adrenal-System (SAS). The SAS is a physiological connection between the sympathetic nervous system and the adrenal gland which is crucial to the physiological response to stress. The sympathetic nervous system (SNS) and HPA system interact in terms of functions and systematic anatomy. When responding to the external environment, these systems can interact on different levels, for example, catecholamine can stimulate the HPA axis by releasing of CRH, and the hormones produced by the HPA axis can act on the SNS system. This system’s rapid response to a stressor results in increased levels of the catecholamine stress hormones (adrenaline and noradrenaline) and other physiologically active substances (neuropeptides, ATP, nitric oxide and eicosanoids) that have a variety of effects including inflammation, blood pressure regulation, and the immune response.
Research has shown that the inhibitory effects and long-term overexpression of cortisol causes stimulatory effects that are adjusted by the sympathetic nervous system (SNS) under stress. The secretion of CRH increases, promoting the secretion of cortisol and adrenocorticotropic hormone. The SNS provides a fast response mechanism to stress. In addition to adrenaline and noradrenaline, the SNS and the parasympathetic nervous systems also secrete a variety of neuropeptides, ATP and nitric oxide (NO). In addition, other agents including angiotensin, cytokines and arachidonic acid metabolites participate in the stress response. When these adjustments to the HPA axis occur with use of adaptogens, an increase in energy occurs along with a reduction in the feeling of stress, improvement of mental concentration and facilitation of sleep. These are all considered the primary function of adaptogens.
Adaptogens and their ability to modify gene expression
Based on recent research published in 2018, adaptogens presumably worked as eustressors (“stress-vaccines”) to activate the cellular adaptive system by inducing the expression of adaptive stress-response signaling pathways (ASRSPs), which then protect cells from damage caused by distress. Adaptogens activate neuroglia cells to modulate adaptive homeostasis by modifying gene expression to prevent stress-induced and aging-related disorders such as chronic inflammation, cardiovascular health, neurodegenerative cognitive impairment, metabolic disorders, and cancer.
Many of the genes regulated by adaptogens are closely associated with adaptive stress-response signaling pathways (ASRSPs) related to corticotropin-releasing hormone, melatonin, nitric oxide synthase, neuroinflammation, neuropathic pain, opioids, and renin-angiotensin and many others.
Adaptogens in context of Eastern Medicine: Ayerveda and Traditional Oriental Medicine
Evaluation of Eastern medical systems including Indian Ayurvedic medicine and traditional Oriental medical systems including Traditional Chinese Medicine (TCM), traditional Japanese medicine (Kampo) and traditional Korean medicine reveals that the tonics they incorporate are often adaptogens.
Indian Ayurvedic Medicine
Ayurveda, the traditional medical system of India, recognizes dos
has, or functional principles. It is the combination of the doshas characteristics based on a five-element philosophy that drives mental and physical well-being. When the doshas are out of balance in quality or quantity, well-being is impaired and symptoms occur. Research suggests that some of the diagnoses established in Ayurveda overlap in many ways with western medical diagnoses, particularly related to anxiety and stress. As such, traditional Ayurveda treatment may offer benefit in the management of anxiety and stress. For example, the adaptogen Ashwagandha is commonly used in Ayerveda to treat conditions associated with stress and anxiety.
Traditional Chinese Medicine (TCM)
In traditional Chinese medicine, it is believed that harmony and balance are required for optimal health and the concepts of yin and yang in the balance of Qi (life energy) are used to diagnose and cure disease. In TCM, medicines that can improve deficiency and weakness caused by deficiency of qi are used to treat the syndrome of qi deficiency and are called tonics.
Tonics have wide range of applications in TCM and are used under the conditions of low body resistance and weak constitution or when the body is finding it difficult to fight severe diseases. This function of tonics is similar to that of adaptogens and tonics typically are adaptogens, but not always. Chinese herbs considered to be both adaptogens and tonics include the following: Panax ginseng, Panax quniquefolius, Eleutherococcus senticosus, Rhodiola rosea and Schisandra chinensis. According to the terminology used in TCM, the mechanism of action of plant-based adaptogens is to achieve equilibrium in both yin and yang, resulting in great vitality.
Barriers to the understanding of adaptogens
There are multiple challenges to the study of the stress response. First, it is difficult to quantify external stressors, especially psychological stressors such as grief. In addition, little is known about the interactions between stressors and the body. Second, the hormones, neurotransmitters, neuro-regulators and cytokines, which are involved in the stress response have been identified, but the specific functions of these agents remain poorly understood. Furthermore, it has not been determined whether there are different mechanisms of action for different stressors. As a result, it is not possible to differentiate and measure the stress response (including adaptation), making the response stress difficult to quantify.
Asian Traditional Medicine
Adaptogens – Overviews
- Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity – 2010
- Relationships Among Classifications of Ayurvedic Medicine Diagnostics for Imbalances and Western Measures of Psychological States – An Exploratory Study – 2019
- Stimulating Effect of Adaptogens- An Overview With Particular Reference to Their Efficacy Following Single Dose Administration – 2005
- A preliminary review of studies on adaptogens – comparison of their bioactivity in TCM with that of ginseng-like herbs used worldwide – 2018
- Novel Molecular Mechanisms for the Adaptogenic Effects of Herbal Extracts on Isolated Brain Cells Using Systems Biology – 2018
- Adaptogens Exert a Stress-Protective Effect by Modulation of Expression of Molecular Chaperones – 2009
- Understanding Adaptogenic Activity- Specificity of the Pharmacological Action of Adaptogens and Other Phytochemicals – 2017′
- Adaptogens in Mental and Behavioral Disorders – 2013
- Evidence-based Efficacy of Adaptogens in Fatigue, and Molecular Mechanisms Related to Their Stress-Protective Activity – 2009
- Chemistry and Pharmacology of Syringin, A Novel Bioglycoside – A Review – 2015
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