Photo credit: Andrei Armiagov/Shutterstock.com

By Kim Ross, DCN, CNS, IFMCP
Reviewed by Deanna Minich, PhD, CNS, IFMCP

June 19, 2023

Adaptogens

In the 1950s, the term “adaptogen” was coined by a Russian physician and pharmacist conducting research on botanicals. While the term is relatively new, using plants and herbs for human health is rooted in history across many cultures. Adaptogens refer to substances that have the ability to increase non-specific resistance to stress and maintain normal metabolic functions (1,2). It is worth noting that there are two classes of adaptogens: plant and synthetic. Synthetic adaptogens were first introduced in the 1970s with the development of bemethyl, with others that followed (1). Bemethyl (also called bemitil), is sold as a dietary supplement in some parts of the world and has evidence of improved physical performance and reduced recovery time. However, in 2018, the World Anti-Doping Agency listed it as a banned substance (3).

This article focuses on plant adaptogens, which are naturally-occurring compounds or extracts from plants.

Since the discovery of plant adaptogens, scientific evidence has expanded our knowledge of the pharmacological and molecular mechanisms of action (2).

In general, these features define adaptogens: (1,2)

• They help with the physiological response to various physical, chemical, or even biological factors.
• They are non-toxic compounds that assist with cellular activities, allowing them to be optimized for adaptability and survival.
• They protect against environmental assaults and psychological distress.
• They help with increased attention and endurance in states of fatigue.
• They can increase energy.
• They work through the endocrine system to modulate stress' physical, mental, and emotional effects and increase resistance to physiological imbalances and disease by strengthening the immune system.

"Adaptogens are natural compounds or plant extracts that increase adaptability, resilience, and survival of organisms to stress." (2)

Image 1: Adaptogenic effect on homeostasis.
Image Adapted From: Panossian AG, Efferth T, Shikov AN, et al. Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases. Med Res Rev. 2021;41(1):630-703. doi:10.1002/med.21743.

While the mechanism of action is not fully understood, they are described to have effects on the neuroendocrine-immune system (2) and it is accepted that adaptogens (1,2,4):

• influence and support the hypothalamus-pituitary-adrenal (HPA) axis.
• display anti-inflammatory and antioxidant effects.
• activate the cerebral cortex for the release of norepinephrine and serotonin.
• impact some stress mediators, such as cortisol and nitric oxide.
• influence gene regulation modulating multiple pathways involved in stress regulation and cell signaling and pathways involved in detoxification (2).

Additionally, plant adaptogens have a rich phytochemical composition that varies based on each plant but may include ginsenosides, flavonoids, lignans, saponins, phenols, and phenolic acids (1). Not only do these phytochemicals display multiple physiological functions, such as acting as an anti-inflammatory agent, but they are also structurally similar to hormones and catecholamines. For example, flavonoids are structurally similar to estradiol and other steroid hormones, and lignans are structurally similar to catecholamines (5,6).

Adaptogens are widely used in traditional Chinese, Korean, Japanese, and Ayurvedic medicines (1,2), with some of the reported health benefits highlighted in Table 1. (1):

Table 1: Reported health benefits of adaptogens

*Due to the positive effect that some adaptogens have on physical performance, some are included on the World Anti-Doping Agency (WADA) prohibited substances list, though they are primarily synthetic adaptogens rather than plant adaptogens (1).

Adaptogens vs. Stimulants

Stress, the Adrenal Glands, and Adaptogens

It is increasingly known and accepted that chronic stress contributes to a plethora of health concerns, including but not limited to sleep disturbances, gastrointestinal distress, cardiovascular issues, anxiety, and depression (7).

Stress, defined as a “disturbance in an individual’s homeostatic balance” (7), can be

• Acute – immediate response to stress, such as jumping out of the way of a moving vehicle as you cross the road.
• Chronic – constant response to a stressor/stimulus, such as financial concerns, social isolation, traumatic events, difficult relationships (personal or work), or physical illnesses.

The human body has an adaptive stress response built in as a survival mechanism. This is the body’s ability to resist the damage caused by stress through prior exposures. For example, a mild exercise stressor can activate cellular signaling to aid in reducing chronic inflammation and promote healthy aging (2).

The body is equipped to deal with stress through the adrenal glands. The adrenal glands comprise the adrenal cortex (80-90%) and the adrenal medulla (10-20%), with each area having distinct roles. Within seconds of an acute stress response, the adrenal medulla secretes catecholamines, which include epinephrine and norepinephrine, to prepare for the familiar “fight or flight” response (8). Each of the three layers of the cortex is responsible for releasing specific hormones, including cortisol, DHEA, and aldosterone. Extra cortisol is released from the adrenals within minutes to hours of the stressful event to support the intricate stress adaptation response.

Table 2: Adrenal hormone descriptions

In addition to the release of hormones, the body responds to stress in a number of physiological ways:

Image 4: Effects of Cortisol
Image Credit: Effects of Cortisol on Human Body. Shutterstock.com/MedicalStocks. Vector ID 1431043022

When the body cannot keep up with the demands of the various stressors, adrenal dysfunction and multiple health concerns can present, such as increased blood pressure, increased blood glucose, and the suppression of the immune system (8).

There are three phases to the stress response, according to Hans Selye’s theory of stress and adaptation (4):

1. The alarm phase: Sometimes called “stressed and wired” or “stressed and worried”, this phase is often accompanied by increased cortisol and DHEA output (12,13). During this stage, sleeplessness, and an inability to calm down is common.
2. The resistance phase: This phase may present with lowering DHEA levels, while cortisol levels may remain within normal ranges or begin to shift downward. Symptoms of the alarm phase or exhaustion phase can present.
3. The exhaustion phase: Sometimes called “stressed and mentally exhausted” or “stressed and tired”. Both low DHEA and cortisol levels are often present (14). As the name implies, individuals feel exhausted and have little energy for daily tasks, often sleep longer, may get sick more often due to a suppressed immune system, and may experience increased pain and inflammation (8).

In 2021,109 plants have been classified as having adaptogenic activity (2).

Table 3: Partial list of plants classified as adaptogens

Extensive literature reports the multiple benefits each adaptogenic plant can provide to the body. Depending on the plant, this includes, but is not limited to, cognitive function, cardiovascular health, prevention of and reducing the duration of the common cold, positive effects on glucose, and insulin levels, improvement in energy and physical and mental performance, and reducing inflammation (2).

Assessing Stress

Multiple options are available to assess the level of stress an individual is experiencing, with only a sample of possible assessments provided in Table 4. (7).

Table 4: Clinical assessments of stress

Maca-GO^® and Maca-OG^® - more than an adrenal modulator

Most traditional plant adaptogens (including standard maca products) modify the stress response through the hypothalamus-pituitary-adrenal (HPA) axis, primarily impacting cortisol output.

Why are FemmenessencePRO™ and RevolutionPRO™ so different?

The FemmenessencePRO™ line contains a proprietary Lepidium peruvianum phenotype combination called Maca-GO^®, formulated specifically for women that nourishes the hypothalamus-pituitary-thyroid-adrenal-ovarian (HPTAO) axis.

The published clinical trials using Maca-GO^® (FemmenessencePRO™) demonstrated improvements that expand past adrenal health (cortisol) and into ovarian health (estradiol, progesterone), pituitary health (ACTH, FSH), and thyroid health (T3), making it an endocrine modulator.

RevolutionPRO™ contains a proprietary Lepidium peruvianum phenotype combination, called Maca-OG^®, formulated specifically for men that supports the hypothalamus-pituitary-thyroid-adrenal-testes (HPTAT) axis. As a result, RevolutionPRO™ supports the body’s production of hormones, such as testosterone, while also supporting adrenal health.

*This statement is not meant to diagnose.

All nutritional and supplemental recommendations should be personalized for your individual client or patient.

These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease.

References

1. Todorova V, Ivanov K, Delattre C, Nalbantova V, Karcheva-Bahchevanska D, Ivanova S. Plant Adaptogens—History and Future Perspectives. Nutrients. 2021 Aug 20;13(8):2861.
2. Panossian AG, Efferth T, Shikov AN, Pozharitskaya ON, Kuchta K, Mukherjee PK, et al. Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress‐ and aging‐related diseases. Med Res Rev. 2021 Jan 25;41(1):630–703.
3. Kwiatkowska D, Kowalczyk K, Grucza K, Szutowski M, Bulska E, Wicka M. Detection of bemitil and its metabolite in urine by means of LC–MS/MS in view of doping control analysis. Drug Test Anal. 2018;10(11–12).
4. Panossian A, Wikman G. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity. Pharmaceuticals. 2010 Jan 19;3(1):188–224.
5. Morales-Quintana L, Ramos P. A talk between flavonoids and hormones to reorient the growth of gymnosperms. Vol. 22, International Journal of Molecular Sciences. 2021.
6. Liao L ying, He Y fan, Li L, Meng H, Dong Y mao, Yi F, et al. A preliminary review of studies on adaptogens: comparison of their bioactivity in TCM with that of ginseng-like herbs used worldwide. Chin Med. 2018 Dec 16;13(1):57.
7. Iqbal T, Elahi A, Redon P, Vazquez P, Wijns W, Shahzad A. A Review of Biophysiological and Biochemical Indicators of Stress for Connected and Preventive Healthcare. Diagnostics. 2021 Mar 19;11(3):556.
8. Hannibal KE, Bishop MD. Chronic Stress, Cortisol Dysfunction, and Pain: A Psychoneuroendocrine Rationale for Stress Management in Pain Rehabilitation. Phys Ther. 2014 Dec 1;94(12):1816–25.
9. Thau L, Gandhi J, Sharma S. Physiology, Cortisol [Internet]. StatPearls; 2023 [cited 2023 Jun 11]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538239/
10. Dutt M, Wehrle CJ, Jialal I. Physiology, Adrenal Gland [Internet]. 2023 [cited 2023 Jun 11]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537260/
11. Scott J, Menouar M, Dunn R. Physiology, Aldosterone. [Internet]. StatPearls; 2023 [cited 2023 Jun 11]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470339/
12. Dutheil F, de Saint Vincent S, Pereira B, Schmidt J, Moustafa F, Charkhabi M, et al. DHEA as a Biomarker of Stress: A Systematic Review and Meta-Analysis. Front Psychiatry. 2021 Jul 6;12.
13. Çay M. The Effect of Cortisol Level Increasing Due to Stress in Healthy Young Individuals on Dynamic and Static Balance Scores. North Clin Istanb. 2017;
14. Lennartsson AK, Arvidson E, Börjesson M, Jonsdottir IH. DHEA-S production capacity in relation to perceived prolonged stress. Stress. 2022 Jan 2;25(1):105–12.
15. Grossman A. Hyperaldosteronism [Internet]. Merck Manual Consumer Version. 2022 [cited 2023 Jun 15]. Available from: https://www.merckmanuals.com/home/hormonal-and-metabolic-disorders/adrenal-gland-disorders/hyperaldosteronism
16. Lewis J. Hypernatremia [Internet]. Merck Manual Professional Version. 2022 [cited 2023 Jun 15]. Available from: https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypernatremia?query=Hypernatremia%20(High%20Level%20of%20Sodium%20in%20the%20Blood)
17. Grossman A. Adrenal Insufficiency [Internet]. Merck Manual Consumer Version. 2022 [cited 2023 Jun 15]. Available from: https://www.merckmanuals.com/home/hormonal-and-metabolic-disorders/adrenal-gland-disorders/adrenal-insufficiency