Approximately 25% of Canadians and 33% of Americans report feeling somewhat or extremely stressed most days. (4)(30) While acute (short-term) stress is necessary for protecting the body from immediate threats, unmanaged chronic stress commonly experienced by many adults can result in numerous negative health effects over time. Chronic stress may result in dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and subsequent imbalances in cortisol, the body’s primary stress hormone produced by the adrenal glands. (12)
Certain nutrients, such as vitamin C, magnesium, and dietary supplements known as adaptogens may help support HPA axis function and modulate cortisol levels during times of physical or psychological stress. (21) This article will review the body’s physiological response to stress, outline the signs and symptoms of cortisol dysregulation, and provide an overview of various adrenal support supplements benefits.
The body’s stress response
A stressor is defined as a real (physical) or perceived (psychological/social) threat to an individual’s safety. Examples of stressors include physical pain or injury, work overload, social embarrassment, and financial stress. (12) When an individual perceives a threat, a physiological stress response occurs in the body.
In cases of acute stress, the amygdala, found in the brain’s limbic system, will trigger the first phase of the stress response in the sympathetic nervous system, known as the body’s fight-or-flight reaction. This response is followed by a response in the neuroendocrine system. The first phase involves the release of catecholamines into the bloodstream, which produces a number of effects, such as increased blood pressure, heart rate, respiration, and inflammation. (12)
The second phase of the stress response activates the HPA axis, which initiates a hormonal cascade that stimulates the release of cortisol from the cortex of the adrenal glands. Cortisol decreases inflammation, mobilizes glucose for use as energy, and suppresses non-vital organs. (12) All of these effects assist the body in coping with the stressor and returning to homeostasis, a state of physiological balance in the body.
Top 7 adrenal support supplements
When indicated, adaptogens, a type of herbal dietary supplement, can be used to improve resistance to stress and balance cortisol levels. Adaptogens, such as Withania somnifera, Rhodiola rosea, and Panax ginseng, have been shown to play a role in the regulation of the HPA axis as well as improve mental work capacity and tolerance to mental fatigue during periods of stress. (21) Additionally, certain nutrients, such as vitamin C, and magnesium, may play a role in adrenal health. (3)(25)(27)
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1. Ashwagandha (Withania somnifera)
Derived from a small shrub native to India and Southeast Asia, ashwagandha is a popular medicinal herb and adaptogen commonly used in Ayurvedic medicine. The therapeutic properties of ashwagandha are primarily attributed to the bioactive constituents found in the plant’s roots known as withanolides. (7)
Research suggests that supplementing with ashwagandha safely and effectively improves stress resistance. One study of 64 individuals with a history of chronic stress found that supplementing with ashwagandha for 60 days reduced perceived stress levels and lowered serum cortisol levels compared to the group receiving a placebo. (5) Specific to stress management, ashwagandha has clinical applications for individuals with stress-related nervous exhaustion, insomnia, and debility. (7)
2. Holy basil leaf (Ocimum sanctum)
Another adaptogen, holy basil leaf, sometimes referred to as tulsi, is a plant native to Southeast Asia. It has been found that supplementing with holy basil leaf may improve cognitive function and reduce salivary cortisol levels. (26) Tulsi may also combat psychological stress and normalize blood glucose (blood sugar), blood pressure, and blood lipid levels. (6)(15)
In a double-blind, placebo-controlled trial, subjects supplementing with holy basil for six weeks reported a 39% improvement in general stress symptoms compared to a placebo. (28)
3. Phosphatidylserine (PS)
Phosphatidylserine (PS), a phospholipid found in cell membranes, is primarily sourced from soy for its use in supplements. Research suggests that supplementing with PS may help normalize the HPA axis stress response and maintain normal levels of cortisol in the body. (14) In a six week trial, PS supplementation effectively normalized adrenocorticotropic hormone (ACTH) levels, a hormone produced by the pituitary gland that is responsible for controlling cortisol production. (14)
4. Rhodiola (Rhodiola rosea)
Rhodiola rosea is an adaptogenic herb that has been shown to decrease cortisol levels. The roots and rhizome of the plant contain approximately 140 different active compounds, such as monoterpene alcohols and their glycosides, flavonoids, flavonolignans, proanthocyanidins, and gallic acid derivatives. (22)
In one double-blind, randomized controlled trial, subjects with stress-related fatigue were given two daily doses of Rhodiola rosea for a duration of 28 days. The subjects experienced improved mental performance, concentration, and morning-time cortisol secretion, known as the cortisol awakening response (CAR). (19)
5. Asian ginseng (Panax ginseng)
Panax ginseng, also referred to as Asian or Korean ginseng, is an adaptogenic herb that possesses antioxidant and anti-inflammatory benefits. (18) Ginsenosides, a group of steroid-like saponins, have been identified as the primary active components of the herb. Panax ginseng exerts many therapeutic actions, such as neuroprotective, antioxidant, anti-inflammatory, antiapoptotic (prevents cell death), immunostimulant, and anticancer effects. (31)
Research has shown that supplemental Panax ginseng may improve chronic fatigue and reduce the HPA axis response to stress. (9)(17) In one study, Panax ginseng supplementation reduced circulating cortisol and increased enzymatic and nonspecific antioxidant activity in response to physical stress. (9)
6. Vitamin C
The adrenal glands contain one of the highest concentrations of vitamin C in the body, and research indicates that stress can cause the adrenal glands to secrete vitamin C. (20)(23) A randomized, placebo-controlled trial of 120 participants showed that a high dose of sustained-release vitamin C (ascorbic acid) lowered blood pressure, improved salivary cortisol recovery, and improved subjective psychological stress responses compared to the control group. (3)
It is estimated magnesium deficiency affects up to 20% of the global population. (8) Insufficient magnesium levels in the body can lead to low stress tolerance and manifest in a number of ways, including fatigue and depression. (11)(29)
The bottom line
Supplements such as Withania somnifera, Rhodiola rosea, Panax ginseng, vitamin C, and magnesium have been shown to help the body adjust to stress, balance cortisol levels, and support the function of the HPA axis. If you are a patient, we recommend speaking with your healthcare provider to find out whether these adrenal supplements are right for your wellness plan.
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- Aguilar Cordero, M. J., Sánchez López, A. M., Mur Villar, N., García García, I., & Rodríguez López, M. A. (2014). Salivary cortisol as an indicator of phycological stress in children and adults; a systematic review. Nutr Hosp, 29(5), 960–968.
- Allen, M. J., & Sharma, S. (2019). Physiology, adrenocorticotropic hormone (ACTH). In StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK500031/
- Brody, S., Preut, R., Schommer, K., & Schürmeyer, T. H. (2001). A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress. Psychopharmacology, 159(3), 319–324.
- Canadian Mental Health Association. (2014). Stress. https://cmha.bc.ca/documents/stress/
- Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized Double-Blind, Placebo-Controlled study of safety and efficacy of a High-Concentration Full-Spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian Journal of Psychological Medicine, 34(3), 255–262.
- Cohen, M. (2014). Tulsi – Ocimum sanctum: A herb for all reasons. Journal of Ayurveda and Integrative Medicine, 5(4), 251.
- Cooley, K., Szczurko, O., Perri, D., Mills, E. J., Bernhardt, B., Zhou, Q., & Seely, D. (2009). Naturopathic care for anxiety: A randomized controlled trial ISRCTN78958974. PLoS ONE, 4(8), e6628.
- DiNicolantonio, J. J., O’Keefe, J. H., & Wilson, W. (2018). Subclinical magnesium deficiency: A principal driver of cardiovascular disease and a public health crisis. Open Heart, 5(1), e000668.
- Flanagan, S. D., DuPont, W. H., Caldwell, L. K., Hardesty, V. H., Barnhart, E. C., Beeler, M. K., Post, E. M., Volek, J. S., & Kraemer, W. J. (2018). The effects of a Korean ginseng, GINST15, on Hypo-Pituitary-Adrenal and oxidative activity induced by intense work stress. Journal of Medicinal Food, 21(1), 104–112.
- Fries, E., Hesse, J., Hellhammer, J., & Hellhammer, D. H. (2005). A new view on hypocortisolism. Psychoneuroendocrinology, 30(10), 1010–1016.
- Gröber, U., Schmidt, J., & Kisters, K. (2015). Magnesium in prevention and therapy. Nutrients, 7(9), 8199–8226.
- Hannibal, K. E., & Bishop, M. D. (2014). Chronic stress, cortisol dysfunction, and pain: A psychoneuroendocrine rationale for stress management in pain rehabilitation. Physical Therapy, 94(12), 1816–1825.
- Hellhammer, J., Schlotz, W., Stone, A. A., Pirke, K. M., & Hellhammer, D. (2004). Allostatic load, perceived stress, and health: A prospective study in two age groups. Annals of the New York Academy of Sciences, 1032(1), 8–13.
- Hellhammer, J., Vogt, D., Franz, N., Freitas, U., & Rutenberg, D. (2014). A soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal-axis in chronically stressed male subjects: A randomized, placebo-controlled study. Lipids in Health and Disease, 13(1), 121.
- Jamshidi, N., & Cohen, M. M. (2017). The clinical efficacy and safety of tulsi in humans: A systematic review of the literature. Evidence-Based Complementary and Alternative Medicine, 2017, 1–13.
- Janssens, K. A., Oldehinkel, A. J., Verhulst, F. C., Hunfeld, J. A., Ormel, J., & Rosmalen, J. G. (2012). Symptom-specific associations between low cortisol responses and functional somatic symptoms: The TRAILS study. Psychoneuroendocrinology, 37(3), 332–340.
- Kim, H. G., Cho, J. H., Yoo, S. R., Lee, J. S., Han, J. M., Lee, N. H., Ahn, Y. C., & Son, C. G. (2013). Antifatigue effects of Panax ginseng C.A. meyer: A randomised, Double-Blind, Placebo-Controlled trial. PLoS ONE, 8(4), e61271.
- Kim, J. H. (2018). Pharmacological and medical applications of Panax ginseng and ginsenosides: A review for use in cardiovascular diseases. Journal of Ginseng Research, 42(3), 264–269.
- Olsson, E., von Schéele, B., & Panossian, A. (2008). A randomised, Double-Blind, Placebo-Controlled, Parallel-Group study of the standardised extract SHR-5 of the roots of Rhodiola rosea in the treatment of subjects with Stress-Related fatigue. Planta Medica, 75(02), 105–112.
- Padayatty, S. J., Doppman, J. L., Chang, R., Wang, Y., Gill, J., Papanicolaou, D. A., & Levine, M. (2007). Human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone. The American Journal of Clinical Nutrition, 86(1), 145–149.
- Panossian, A., & Wikman, G. (2010). Effects of adaptogens on the central nervous system and the molecular mechanisms associated with their Stress—Protective activity. Pharmaceuticals, 3(1), 188–224.
- Panossian, A., Wikman, G., & Sarris, J. (2010). Rosenroot (Rhodiola rosea): Traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine, 17(7), 481–493.
- Patak, P., Willenberg, H. S., & Bornstein, S. R. (2004). Vitamin C is an important cofactor for both adrenal cortex and adrenal medulla. Endocrine Research, 30(4), 871–875.
- Poleszak, E., Szewczyk, B., Kędzierska, E., Wlaź, P., Pilc, A., & Nowak, G. (2004). Antidepressant- and anxiolytic-like activity of magnesium in mice. Pharmacology Biochemistry and Behavior, 78(1), 7–12.
- Rolf, L., Damoiseaux, J., Huitinga, I., Kimenai, D., van den Ouweland, J., Hupperts, R., & Smolders, J. (2018). Stress-Axis regulation by vitamin D3 in multiple sclerosis. Frontiers in Neurology, 9, 263.
- Sampath, S., Mahapatra, S. C., Padhi, M. M., Sharma, R., & Talwar, A. (2015). Holy basil (Ocimum sanctum Linn.) leaf extract enhances specific cognitive parameters in healthy adult volunteers: A placebo controlled study. Indian J Physiol Pharmacol, 59(1), 69–77.
- Sartori, S., Whittle, N., Hetzenauer, A., & Singewald, N. (2012a). Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment. Neuropharmacology, 62(1), 304–312.
- Saxena, R. C., Singh, R., Kumar, P., Negi, M. P. S., Saxena, V. S., Geetharani, P., Allan, J. J., & Venkateshwarlu, K. (2012). Efficacy of an extract of Ocimum tenuiflorum (OciBest) in the management of general stress: A Double-Blind, Placebo-Controlled study. Evidence-Based Complementary and Alternative Medicine, 2012, 1–7.
- Schwalfenberg, G. K., & Genuis, S. J. (2017). The importance of magnesium in clinical healthcare. Scientifica, 2017, 1–14.
- The American Institute of Stress. (2019, December 18). What is stress? https://www.stress.org/daily-life
- Xiang, Y. Z., Shang, H. C., Gao, X. M., & Zhang, B. L. (2008). A comparison of the ancient use of ginseng in traditional Chinese medicine with modern pharmacological experiments and clinical trials. Phytotherapy Research, 22(7), 851–858.