Negative Effects of Stress & Cortisol

Cortisol: The Stress Hormone

Cortisol is a hormone released by the adrenals in response to stress. Cortisol is the only hormone in the human body that increases with age.

Cortisol is released by the adrenal glands in response to stress. The release of cortisol is a normal, healthy process which can be beneficial in stressful situations as part of the “flight-or-fight” response. However, when cortisol is elevated for extended periods of time it can have some negative effects, particularly for anyone trying to lose weight or build muscle.

Cortisol’s functions include blood pressure regulation, glucose metabolism, blood sugar management, and immune system regulation. Cortisol plays a critical role in the stress response by facilitating a release of glucose and diverting activity away from non-survival related processes such as immune function.

Adrenal fatigue occurs when the adrenals can no longer produce sufficient levels of cortisol necessary for optimal function. This happens as a result of chronically elevated cortisol response. Adrenal fatigue can cause patients to feel unwell and exhausted, causing them to turn to sugar and caffeine – which can magnify the effects of adrenal fatigue.

Insulin Resistance

Cortisol increases blood glucose via activation of gluconeogenesis. At the same time, coritsol makes fat and muscle cells resistant to the action of insulin by inhibiting insulin release and blocking glucose uptake. “Healthy adults appear able to compensate for glucocorticoid-induced insulin resistance with increased β-cell function or increased insulin release” (Adam et al, 2010). In individuals who are obese or already experience some level of insulin resistance these compensatory mechanisms fail to counteract the effects of cortisol, resulting in hyperglycemia.


Studies have found that cortisol injections are associated with increased appetite and cravings (Yale, 2000). The explanation of this association may have multiple mechanisms: The first explanation is that increased cortisol can deplete levels of neurotransmitters serotonin and dopamine. Serotonin plays an important role in quality of sleep, as well as appetite. Another way that cortisol can effect appetite has to do with its effects on glucose uptake. High blood glucose levels combined with insulin suppression means cells are starved for energy, which leads to an increased hunger response.

Fat Storage

Consistently high cortisol levels impacts fat storage and can result in increased belly fat. Cortisol can cause stored triglycerides to be relocated to the visceral fat cells, primarily the ones in the abdomen and under muscle. The results of this mechanism was illustrated in a study which found correlation between abdominal fat and elevated cortisol levels (Yale, 2000).


Elevated Cortisol inhibits collagen production (Canalis, 1983).

Natural Ingredients Support Healthy Stress Response


Adaptogens are plants and herbs that help your body respond to stress, anxiety, fatigue and overall wellbeing. Traditionally used to reduce stress and enhance wellbeing, adaptogens help modulate stress responses, resulting in enahncced energy production, sleep quality, and immune function. “Adaptogens were recently defined as herbal preparations that increased attention and endurance in fatigue, and reduced stress-induced impairments and disorders related to the neuro-endocrine and immune systems“ (Panossian & Wikman, 2010).

Ashwagandha – adaptogen. Can re-balance neurotransmitters and reduce cortisol response. “Ashwagandha intake was associated with greater reductions in morning cortisol” (Lopresti et al, 2019). Studies have shown positive effects on stress assessment scales. “ Ashwagandha root extract safely and effectively improves an individual’s resistance towards stress and thereby improves self-assessed quality of life” (Chandrasekhar et al, 2012).

Works by activating receptors for the calming neurotransmitter GABA. Potent mood regulator – helps to restore a sense of calmness under stress. Has been shown to improve resilience to emotional and physical stress, supporting immune system response, and regulating sleep.

Rhodiola Rosea – adaptogen. Can increase resistance to a variety of stressors. Used to support the nervous system, mood regulation, mental clarity, and the sleep cycle. Studies have shown improvements in mental performance, mood stability, and sleep patterns: “The plant’s dual actions of cognitive stimulation and emotional calming create benefits for both immediate cognitive and memory performance, as well as for the long-term preservation of brain functions” (Stojcheva & Quintela, 2022). Rhodiola “exerts an anti-fatigue effect that increases mental performance, particularly the ability to concentrate, and decreases cortisol response“ (Olsson et al, 2009).

Eleuthero Root (Eleutherococcus senticosus)– adaptogen. Asian herb which has been used for thousands of years as a healing remedy in folk medicine. Commonly called Siberian ginseng as it is known for having Panax ginseng-like effects. Eleutherococcus is reported to affect responses in the brain to help blunt the stress response, and studies have shown that “treatment with Eleutherococcus senticosus is able to reduce cardiovascular responses to stress” (Facchinetti et al, 2002).

Other Ingredients:

L-Theanine Naturally occurring amino acid found in green tea that promotes relaxation by reducing stress and anxiety levels. ‘The key to quieting the mind’. Helpful when you begin to feel overwhelmed and your mind begins to race. L-Theanine binds to glutatamate receptors in the brain protecting brain cells from excitotoxicity, calming the brain’s nerve networks. (Cho, 2008)

Phosphatidylserine A phospholipid found in high concentrations in the brain. Can reduce stress-induced excretion of cortisol and can reduce the cortisol response to overtraining in athletes. Supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate.

Chinese Skullcap Root Used as a medicine in several East Asian countries for more than 2000 years, this herb is a member of the lamiaceae (mint) family and native to China. Contains antioxidants known as flavones, which include Baicalin and Baicalein. These antioxidants appear to down-regulate the effects of stress on various tissues in the body including the liver. Chinese Skullcap is also known for supporting a healthy inflammatory response and normal cellular growth.

DHEA is a base hormone used to manufacture all of the steroid hormones. Levels deplete after the age of 25. DHEA effectively antagonizes the effects of cortisol.

Evidence suggests that DHEA acts to moderate the stress response and the ratio between cortisol and DHEA has been correlated with tolerance for stress.

The ratio between cortisol and DHEA has numerous effects on the body. An elevated ratio (high cortisol) can lead to suppressed immune function, impaired metabolism, loss of memory, breakdown of collagen and bone, and other undesirable effects.

A study of over 4000 US army veterans found a direct correlation between the cortisol/DHEA ratio and metabolic syndrome. “high cortisol concentrations were associated with an increased risk of [Metabolic Syndrome] … the higher the ratio [of cortisol:DHEA], the greater the risk” (6).


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Adam, T. C., Hasson, R. E., Ventura, E. E., Toledo-Corral, C., Le, K. A., Mahurkar, S., Lane, C. J., Weigensberg, M. J., & Goran, M. I. (2010). Cortisol is negatively associated with insulin sensitivity in overweight Latino youth. The Journal of clinical endocrinology and metabolism, 95(10), 4729–4735. https://doi.org/10.1210/jc.2010-0322

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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. https://doi.org/10.4103/0253-7176.106022

Lopresti, Adrian L. PhDa,b,∗; Smith, Stephen J. MAa,b; Malvi, Hakeemudin MBBS, MDc; Kodgule, Rahul MBBSd. (2019). An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine: Volume 98 – Issue 37 – p e17186
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Salve, J., Pate, S., Debnath, K., & Langade, D. (2019). Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study. Cureus, 11(12), e6466. https://doi.org/10.7759/cureus.6466
Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979308/

Olsson, E. M., von Schéele, B., & Panossian, A. G. (2009). 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(2), 105–112. https://doi.org/10.1055/s-0028-1088346

Ivanova Stojcheva, E., & Quintela, J. C. (2022). The Effectiveness of Rhodiola rosea L. Preparations in Alleviating Various Aspects of Life-Stress Symptoms and Stress-Induced Conditions-Encouraging Clinical Evidence. Molecules (Basel, Switzerland), 27(12), 3902. https://doi.org/10.3390/molecules27123902
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Facchinetti, Fabio & Neri, I. & Tarabusi, M.. (2002). Eleutherococcus senticosus reduces cardiovascular stress response in healthy subjects: A randomized, placebo-controlled trial. Stress and Health. 18. 11 – 17. 10.1002/smi.914.

Cho, H. S., Kim, S., Lee, S. Y., Park, J. A., Kim, S. J., & Chun, H. S. (2008). Protective effect of the green tea component, L-theanine on environmental toxins-induced neuronal cell death. Neurotoxicology, 29(4), 656–662. https://doi.org/10.1016/j.neuro.2008.03.004

Glade, M. J., & Smith, K. (2015). Phosphatidylserine and the human brain. Nutrition (Burbank, Los Angeles County, Calif.), 31(6), 781–786. https://doi.org/10.1016/j.nut.2014.10.014

Canalis E. (1983). Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity, and deoxyribonucleic acid content in cultured rat calvariae. Endocrinology, 112(3), 931–939. https://doi.org/10.1210/endo-112-3-931

Taylor Froiland is the president of Legere Pharmaceuticals in Scottsdale, Arizona and serves on the Board of Directors for RK Logistics Group. He also owns and operates Medmetrics Compounding Pharmacy in Chandler, Arizona, specializing in various pharmaceutical services. Taylor holds a PharmD and has expertise in compounding, medicinal chemistry, and quality control.
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