The Therapeutic Need to Support Chronic Stress

Article Highlights

  • Stress has 3 phases: Alarm reaction, resistant and persistent.
  • Chronic stress occurs when the body does not have the resources to maintain the resistant phase and can lead to many detrimental health effects including increase in oxidative stress and depletion of immune defence.
  • Certain antioxidants and adaptogens may help the body cope with the health effects of chronic stress.

Stress, whether acute or chronic, causes biochemical and physiological reactions throughout numerous organ systems, tissues and cells and involves a multitude of hormones and mediators.1,2 The complex chain of events triggered by physical, environmental, emotional or self-driven stressors (collectively called the allostatic load) initially mobilises resources to try to restore homeostasis. This stage is the alarm reaction (or flight or fight response) phase.3

Once out of the initial alarm phase the body moves into the second defensive stage called the resistant phase. 3 However, if the stressor is ongoing or persistent (chronic) or is a major event, the body may not have the resources available to sustain the defensive phase. The continual allostatic overload can lead to a stage of depletion, exhaustion and burnout. 3,4 It is therefore crucial to support the body’s resilience so it has optimal protection against stress and can sustain the resistant phase. 3

Fatigue and exhaustion are key symptoms of unmanaged chronic stress. However, there are numerous other physical and psychological effects including gastrointestinal complaints, musculoskeletal issues, immune dysfunction, nervousness, irritability, anxiety and changes in cognition, such as memory, learning and concentration. 1,3

In addition, the ongoing production of glucocorticoids in the resistance phase of chronic stress adversely affects neurons and the mitochondria (the main generators of ROS). Induced stress models show that ROS mitochondrial levels are increased significantly, including the superoxide free radical anion, with a detrimental effect on cell survival and viability. The excess cortisol and resulting oxidative stress state highlights the importance of antioxidants in chronic stress.1

The benefits of adaptogens

Adaptogens, such as Withania somnifera, Eleutherococcus senticosus, Schisandra chinensis and Rhodiola rosea are key herbs in combating stress, due to their stimulatory effect on the resistance phase, and their ability to relieve mental and physical fatigue, increase energy production and promote endurance. 2,3,5,6

The mechanisms of action of adaptogens in stress resilience is complex but involves modulation of the hypothalamic-pituitary-adrenal axis and the regulation of key mediators. 1,6,7

In chronic stress or the resistance phase of stress, ongoing release of glucocorticoids, such as cortisol and inflammatory mediators, have a detrimental effect on multiple physiological functions, including reducing the important brain-derived neurotrophic factor (BDNF) – a factor that plays an important role in synaptic plasticity and mitochondrial function. 1-3 Adaptogens have been shown to reduce the excess cortisol produced during stress; 2,6 however, they have many more functions.

Rhodiola rosea extract, for example, at the standardised dose of 3.5% rosavin and 1% salidroside commonly used in clinical trials, has been extensively studied and found to increase BDNF levels, which leads to:

  • increased mitochondrial bioenergetic activity and production of ATP
  • increased cell viability, survival and neuroplasticity
  • decreased levels of mitochondrial reactive oxygen species (ROS) by upregulating antioxidant enzymes
  • neurite outgrowth promotion. 1,7,8

Rhodiola is also anti-inflammatory and neuroprotective, modulating nitric oxide (NO) levels- a main mediator of neuroinflammation and pro-inflammatory cytokines.9,10 These actions also support the research showing rhodiola improves memory, learning, mental performance and the ability to concentrate, especially as neurons rely solely on adequate ATP for synaptic function. 1,2,10

Antioxidants are important in chronic stress

Although adaptogens often have antioxidant capacity, the metalloenzyme superoxide dismutase (SOD) acts on this free radical directly by catalysing its breakdown into oxygen and hydrogen peroxide. 1,11 Additionally, the supplemental use of SOD in stress is supported by two randomised, placebo-controlled trials showing a specific extract, Extramel® – a proprietary concentrated source of SOD from melon, is effective in reducing stress levels and fatigue and improving quality of life in healthy individuals.12,13

Immune support in prolonged stress

Cortisol downregulates inflammatory cytokines in normal activity. However, in chronic stress the ongoing release of glucocorticoids triggers an adaptive process that reduces cell immune response to cortisol (called glucocorticoid resistance). As the cells become unresponsive, the body is unable to regulate or turn down the inflammatory response, which increases inflammation and reduces the ability to combat infections and overall resilience. 4

Plant extracts such as the ancient reishi mushroom can support chronic stress responses through its strong antioxidant capacity, anti-inflammatory and immunodulatory effects. As an immune regulator, reishi can significantly affect a variety of immune cells, including macrophages, B and T lymphocytes, dendritic cells and natural killer cells, while modulating inflammatory cytokines.  Its traditional uses of relaxing the body physically and psychologically, soothing the nerves, enhancing energy, strengthening muscles and improving memory also supports its benefits for reducing stress symptoms and increasing resilience.14,15

*References available on request