On a physiological level, the body’s ability to adapt and maintain balance is largely regulated by the hypothalamic–pituitary-adrenal (HPA) axis. This axis is a convergence of the nervous and endocrine systems. It releases a cascade of hormones that culminates in the production of cortisol, which influences metabolic, immune, cardiovascular, and emotional health. The HPA axis maintains the body’s balance in the face of adversity, but too much adversity can cause the system to go haywire.
Supporting the healthy function of the HPA axis is foundational to building the body’s strength and flexibility to deal with everyday challenges. Here’s how the HPA axis accomplishes this physiologically, and seven adaptogenic herbs that support resilience and HPA axis balance.*
HPA AXIS AND CIRCADIAN RHYTHM
The hypothalamus sets the circadian rhythm for the HPA axis by releasing corticotropin-releasing factor (CRF) on a 24-hour cycle. CRF travels through blood vessels that feed directly to the pituitary gland. When CRF binds to receptors on the pituitary, adrenocorticotropic hormone (ACTH) enters the systemic circulation. At its principal target, the adrenal cortex, ACTH triggers the release of cortisol.
Cortisol is a member of the class of steroid hormones called glucocorticoids. Its primary effects are to preserve glucose for brain function, stimulate gluconeogenesis to raise blood sugar, and suppress the inflammatory and immune responses. Cortisol also promotes protein catabolism, stimulates gastric acid secretion, suppresses bone formation, and works as a diuretic. The appropriate release of cortisol is essential to support healthy metabolic, immune, cardiovascular, and behavioral health.
In people with a healthy HPA circadian rhythm, cortisol levels peak about 30 minutes after waking—which is referred to as the cortisol awakening response. This response triggers gluconeogenesis and helps people feel more alert and energetic on waking. Cortisol levels gradually decline throughout the day, reaching the lowest level around midnight.
HPA AXIS AND STRESS RESPONSE
In addition to following a circadian rhythm, the HPA axis responds to stress. Sitting in a traffic jam, hearing bad news, losing your wallet, sleeping three hours a night, skipping a meal or sustaining an injury will all trigger the HPA response.
The reason that physical, mental, and emotional stressors all trigger the same response is surprisingly simple. The hypothalamus kicks off the HPA cascade, but it receives input from a bundle of brainstem neurons. These neurons, in turn, receive input from behavioral centers (such as the amygdala in the limbic system), visceral centers (such as sensory tracts from the thoracic and abdominal organs), stress–response peptides (such as substance P and enkephalin), and inflammatory cytokines (such as interleukin-6). So no matter where the stress originates, the brainstem neurons integrate and translate it into a hypothalamic response.
This stress-induced HPA activation not only triggers the circadian rhythm cascade (CRH, ACTH, and cortisol), but it also activates the sympathetic nervous system. Sympathetic nerves release norepinephrine, and the adrenal medulla releases epinephrine. These catecholamines produce the racing heart, sweating skin, dry mouth, and feelings of fear or anxiety that are often associated with stress.
When the flush of catecholamines subsides, the HPA cascade follows suit with a spike in cortisol. Once cortisol concentrations reach a certain level, they’re brought back into check by a negative feedback mechanism, suppressing further release of hypothalamic CRH and pituitary ACTH. This physiological HPA stress response is a protective mechanism to keep us alive during times of distress, and does no lasting harm if activated on occasion.
STAGES OF THE STRESS RESPONSE
The sympathetic response and release of cortisol are adaptive mechanisms to maintain homeostasis, but over time and adversity, the HPA response can become maladaptive.
The concept of the stages of the stress response was first introduced in the 1950s by University of Montreal endocrinologist Hans Selye. He coined the term “General Adaptation Syndrome” to describe three stages of the stress response: alarm, resistance, and exhaustion.
Selye’s ideas are still relevant today, but we now have laboratory tests to confirm individual patterns of response. Hormone testing shows that some people with ongoing stress have elevated cortisol, others have flatlined cortisol, and some have flipped cortisol curves. The goal of supporting healthy HPA axis function is not to stimulate or suppress cortisol function, but rather to encourage its appropriate and adaptive response.
ADAPTOGENS THAT SUPPORT ADRENAL HEALTH
The clinical key to supporting a healthy HPA response is not to stimulate or suppress it, but rather to encourage an adaptive response. And one of the best ways to encourage an adaptive response is to use—as the name implies—adaptogens.
Adaptogens normalize the HPA axis, modulate cortisol release, and support the body’s natural rhythm and response. Adaptogens can be taken singly or combined for their synergy. Consider the following seven adaptogens to support a healthy HPA axis in everyday practice.
Ashwagandha (Withania somnifera) is a member of the Solanaceae family. For centuries, Ayurvedic practitioners have revered this herb for its ability to support healthy energy, memory, mood, and libido. Ashwagandha translates to “smell of horse”—not only because of the scent of its fresh roots and leaves, but also because people who consumed the herb were thought to develop the strength and vitality of a horse.
Ashwagandha’s adaptogenic effects are attributed to its more than 40 steroidal lactone molecules, called withanolides. In a two-month clinical trial with stressed adults, , ashwagandha supported a healthy cortisol response and modulated their feelings of stress.* The study participants took 300 mg per day of ashwagandha root extract, standardized to 5 percent withanolide content.
Astragalus (Astragalus membranaceus) is a member of the legume family Fabaceae. A staple in traditional Chinese medicine, astragalus has been used for centuries to support energy and vitality. Astragalus root is also called huang qi and is said to tonify the qi. Animal studies suggest that astragalus supports the stress response by modulating cytokines and corticosteroids.*
Studies also suggest that this herb supports healthy immune function, heart function, and male fertility. And intriguing new research suggests that astragalus, in combination with other herbs or functional foods, might support healthy growth in children and healthy aging in adults.*
Holy basil (Ocimum sanctum) is native to India, where it’s cultivated for both spiritual and practical purposes. Also known as tulsi, holy basil is widely available as an herbal tea. Its active chemical constituents include a range of phytochemicals and essential oils. Animal studies show that holy basil supports a healthy stress response by helping balance cortisol and cortisol receptor function.*
In addition to supporting a healthy stress response, consuming 300 mg per day of holy basil ethanolic extract has been shown to support cognitive function and healthy immune biomarkers in older adults. And an impressive study found that taking 1,000 mg of holy basil extract per day for 60 days supported healthy mood in subjects in a hospital-based setting.*
Eleuthero (Eleutherococcus senticosus) is native to northern Asia and is sometimes called Siberian ginseng. Its use as an adaptogen to support energy, endurance, and a healthy stress response originated in the former Soviet Union. Eleuthero is also used in traditional Chinese medicine to support energy and stamina.
Chemical constituents called ginsenosides are thought to account for eleuthero’s physiological effects. Studies suggest that eleuthero supports adrenal function, stress tolerance, and immune health. One clinical trial found that Siberian ginseng supports mental health and social functioning in older adults. And another study found that taking 800 mg a day of the herb for eight weeks supported endurance, heart function, and metabolism in healthy men.
Rhodiola (Rhodiola rosea) is a flowering plant that grows in the arctic regions of Europe, Asia, and Alaska. Rhodiola has historically been used by Russians and Scandinavians to help them adapt to their countries’ cold and harsh living conditions. It has also been reported that the Russians have tested rhodiola in nearly every type of Olympic athlete to support energy and endurance.
Studies suggest that rhodiola supports energy, mental performance, and concentration, and also helps modulate the cortisol awakening response. A human clinical trial found that taking 340 mg or 680 mg of rhodiola for six weeks supported healthy mood.*
Schisandra (Schisandra chinesis) berries grow on a woody, climbing vine that’s native to China and other areas of Asia. Lignans are among the berries’ most active chemical compounds. Studies show that schisandra acts as an adaptogen by supporting HPA axis function.*
Laboratory and animal studies suggest that schisandra supports liver health, immune health, blood flow, stamina, and mental performance. Human clinical trials suggest that schisandra may support healthy liver function, and also quality of life in menopausal women.*
Maca (Lepidium meyenii) is a cruciferous vegetable that grows in the Andes Mountains of Peru. Maca root is nutrient-dense and rich in amino acids, fatty acids, minerals, plant sterols, and glucosinolate. Macaridine, macamides, and maca alkaloids are compounds that are unique to this plant. The compounds in maca root have been shown to support the endocannabinoid system, antioxidant systems, and hormone pathways.*
Maca has been used for centuries to support healthy libido and fertility. Studies in animals and humans show that it has adaptogenic properties that support the HPA and reproductive hormone axes. Along with its libido and fertility supporting effects, human clinical trials suggest that maca also supports balanced mood.*
ADAPTOGENS AND STRESS
Adaptogens have a normalizing effect on variations in physiological function. The seven adaptogens listed above can be calming when the body needs calm and tonifying when the body needs tone. Supporting an adaptive stress response lays a foundation for everyday wellness, harmony, and health—and adaptogens can play a key role.
Bhattacharyya D, Sur TK, et al. Nepal Med Coll J 10, no. 3 (2008): 176–79.
Block KI and Mead MN. Integr Cancer Ther 2, no. 3 (2003): 247–67.
Chandrasekha, K, Kapoor J, and Anishetty S. Indian J Psychol Med 34, no. 3 (2012): 255–62.
Chiu HF, Chen TY, et al. Phytother Res 27, no. 3 (2013): 368–73.
Cicero AF, Derosa G, et al. Arch Gerontol Geriatr Suppl 9 (2004): 69–73.
Darbinyan V, Aslanyan G, et al. Nord J Psychiatry 61, no. 5 (2007): 343–48.
Dording CM, Fisher L, et al. CNS Neurosci Ther 14, no. 3 (2008): 182–91.Gaffney BT, Hügel HM, and Rich PA. Life Sci. 2001;70(4):431-442.
Gonzales GF, Gonzales C, and Gonzales-Castañeda C. Forsch Komplementmed 16, no. 6 (2009): 373–80.
Gonzales, GF. Evid Based Complement Alternat Med 2012 (2012): 193496.
Hajdu Z, Nicolussi S, et al. J Nat Prod 77, no. 7 (2014): 1663–69.
Hartz AJ, Bentler S, et al. Psychol Med 34, no. 1 (2004): 51–61.
Jothie Richard, E, R Illuri, B Bethapudi, S Anandhakumar, A Bhaskar, C Chinampudur Velusami, D Mundkinajeddu, and A Agarwal. Phytother Res 30, no. 5 (2016): 805–14.
Ku, J, Chen KW, et al. Chin J Physiol 53, no. 2 (2010): 105–11.
Lee MS, Shin BC, et al. Maturitas 70, no. 3 (2011): 227–33.
Lee D, Lee SH, et al. Phytother Res 32, no. 1 (2018): 49–57.
Mondal S, Varma S, et al. J Ethnopharmacol 136, no. 3 (2011): 452–56.
Park JY and Kim KH. Climacteric 19, no. 6 (2016): 574–80.
Salvado, L, Singaravelu G, et al. Rejuvenation Res 19, no. 6 (2016): 478–84.
Sampath S, Mahapatra SC, et al. Indian J Physiol Pharmacol 59, no. 1 (2015): 69–77.
Sinclair, S. Altern Med Rev 3, no. 5 (1998): 338–44.
Smith SM and Vale WW. Dialogues Clin Neurosci 8, no. 4 (2006): 383–95.
Szopa A, Ekiert R, and Ekiert H. Phytochem Rev 16, no. 2 (2017): 195–218.
Tan SY and Yip A. Singapore Med J 59, no. 4 (2018): 170–71.
Xia, N, J Li, H Wang, J Wang, and Y Wang. Exp Ther Med 11, no. 1 (2016): 353–59.