Background
Chronic stress and resulting burnout are prevalent in modern 21st century life. Contributing stressors may be lifestyle factors, such as educational, professional, relationship, financial and health-related stressors and concerns. The human body has biological mechanisms which are supportive in times of short term stress, but not suited to long term, chronic stress. Over a prolonged period, chronic stress may exert serious effects on the body, and increase the risk for developing mental health conditions and chronic diseases.
Activation of HPA Axis
The HPA axis plays a key role in the stress response and mediates the effects of the stress response in the body. The HPA axis is regulated by neurotransmitters, such as GABA, which exerts a calming effect, and noradrenaline and serotonin, which exert neuro-excitatory effects. Therefore, the central nervous system and endocrine
Figure 1: The HPA Axis
systems work closely to regulate the stress response via this mechanism (1). In periods of stress, hypothalamic neurons, from the paraventricular nucleus, release corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) into the hypophysial portal blood, which connects the hypothalamus and pituitary gland. CRH and AVP produce and secrete adrenocorticotropic hormone (ACTH) and then release ACTH into circulation. ACTH has the function of inducing the synthesis of glucocorticoids and signalling cortisol release from the adrenal glands (1). As the HPA axis also increases the availability of glucose in times of stress, this mechanism may additionally cause blood glucose (sugar) levels to become imbalanced and cause weight gain (2).
The aforementioned HPA axis interacts with another integrative system known as the HPG axis, or hypothalamic-pituitary-gonadal), in a reciprocal, bi-directional relationship.
In response to chronic stress, the balance of hormones can therefore be disrupted via this mechanism (3). This section will discuss the effects of stress on three key sex hormones: oestrogen, progesterone and prolactin.
Figure 2: Female Ovaries
Oestrogen
Oestrogen has a modulating role on brain processes that are involved in changes related to the stress response, cognition and also emotional regulation, as oestrogen increases amygdala and hippocampus sensitivity (4). Oestrogen additionally has a modulatory effect on the HPA axis, and in periods of chronic stress, oestrogen secretion is decreased (3).
Progesterone
Chronic stress inhibits ovarian secretion of progesterone, whilst also causing noradrenaline to be released into the ovary (3). Progesterone has the function of modulating GABA, which has a calming effect on the brain (5).
Testosterone
There may be some variation on the effects of stress on testosterone levels, as differences have been observed depending on the variables of extroversion vs introversion, openness to challenges, and control and expression of emotion, as well as obvious sex-specific differences (6). However, in periods of chronic stress, testosterone secretion is generally decreased (3).
Impact of Stress of Health Span
Chronic stress and related disruptions to biological mechanisms, such as glucose homeostasis, have been indicated to increase levels of reactive oxygen species (ROS), resulting in elevated levels of oxidative stress (7) (8) (9) (10).
Oxidative stress may impact mitochondrial functioning, as ROS disrupts the Shelterin complex in neurovascular cells, which impairs the functioning of the genes human telomerase reverse transcriptase (hTERT) and human telomerase RNA component (hTERC). These genes are involved in modulating telomerase activity, which regulates telomere length. When hTERT and hTERC functioning becomes impaired due to excessive levels of oxidative stress, telomerase is inhibited and this causes telomere length to shorten (11) (12). Telomere shortening results in the activation of p53, a gene which downregulates PGC-1α and PGC-1β. The downregulation of PGC-1α and PGC-1β results in reduced mitochondrial biogenesis, and causes mitochondrial dysfunction, resulting in dysfunctional oxidative phosphorylation, which in turn causes defective generation of ATP, impacting on energy production (12) (13).
Figure 3: Mechanisms of Oxidative Stress in Telomere Attrition
Blood glucose levels may become imbalanced and insulin sensitivity decreased due to downregulation of PGC1 α and β, as they coordinate insulin-sensitising gene expression, (12) (14) . Additionally, downregulated PGC1 α and PGC1 β results in decreased detoxification of ROS, due to reduced availability of superoxide dismutase 2 and glutathione peroxidase 1 (14) (15). Furthermore, PGC1- α is essential for the transcription of SIRT1, and therefore downregulation results in increased cell senescence. Reduced expression of SIRT1 may reduce the stimulation of essential antioxidant enzymes (16) (17). Telomere length shortening – or telomere attrition – due to chronic stress has been associated with accelerated ageing, increased risk of developing chronic diseases and shortened lifespan.
Effects of Chronic Stress on Nutritional Status and Food Preferences
Chronic stress increases the body’s metabolic needs, which may result in increased uptake and excretion of nutrients. Chronic stress therefore can increase requirements for nutrients, and also exacerbate already existing deficiencies.
During periods of prolonged stress, food choices may alter and consumption of sugar and processed foods increase. One reason for this may be that during periods of stress, preferences for higher fat and sugar foods may increase. Theoretically, in evolutionary terms, this mechanism may have been beneficial initially during prehistoric times, for when early humans were experiencing stress, such as food scarcity, as fat provides 9 calories per gram and sugar affords a quick release of glucose and therefore energy. However, in modern times, many experience chronic stress over significant periods of time. Moreover, food availability is more abundant, and there is an ever growing array of processed foods, microwave meals, and high sugar and high fat snacks cheaply and readily available.
Blood Glucose Imbalance
Caffeine, and sugary so called “energy” drinks, which are readily available, are often employed as a coping mechanism for stress and stress-related exhaustion. Increased consumption of caffeine causes blood glucose levels to fluctuate, through increasing cortisol levels and dysregulating insulinotropic polypeptide and GLP-1, which are both involved in regulating appetite control and insulin levels. Refined carbohydrates and caffeine increase blood glucose levels (18). Consuming a high amount of refined carbohydrates daily causes blood glucose to be constantly rapidly rising and falling postprandially. This dysregulation of blood glucose may cause energy levels to be affected due to persistent rising and falling of blood glucose levels through the day (18).
Nutrition can be used as a means of supporting the body during times of stress, increasing resilience, building strength and re-equipping the body with nutrients which may become depleted during periods of chronic stress.
Blood Glucose Balance
To support blood glucose balance:
Magnesium and Vitamin B6
Research has indicated that Magnesium and Vitamin B6 may be supportive to individuals experiencing stress. A recent study indicated that combined supplementation helped to alleviate stress levels in subjects who were experiencing chronic, long term stress (19).
Increasing Magnesium
Possible side effects: nausea, vomiting, diarrhoea, and other gastrointestinal disruptions
Contraindications: When taken with antibiotics, Magnesium may affect their absorption and / or cause muscle aches. Magnesium can also rescue the absorption of bisphosphonates, so in terms of timing they should not be taken together. Furthermore, Magnesium can lower blood pressure so caution should be exerted if someone is on medication for hypertension.
Increasing Vitamin B6
Possible side effects: some possible side effects of B6 supplementation are nausea, vomiting, diarrhoea, stomach pain, loss of appetite, headache, tingling and sleepiness
Contraindications: Vitamin B6 may interact moderately with the following drugs: Amiodarone, phenytoin, phenobarbital. Vitamin B6 may also interact with levodopa.
Omega 3 Fatty Acids
A recent study indicated that individuals who were administered omega 3 fatty acids demonstrated reduced markers of psychological and physiological burnout, including decreased cortisol levels, compared with controls (20).
Increasing Omega 3 Fatty Acids
Possible side effects: loose stools, nausea, fish taste in mouth
Contraindications: omega 3 fatty acids may interact moderately with birth control pills, reducing their effectiveness and blood pressure lowering medications. Omega 3 fatty acids may also have minor interactions with blood clotting medications.
Disclaimer: before beginning any new supplement, always consult a doctor and proceed under their supervision, and ideally also the supervision of a qualified nutrition practitioner.
Researched by: Alice Elizabeth Benskin, MSc
Published: October 2021
Review date: October 2022
References
