Stress: The Silent Killer

Health can be conceptualised according to three dimensions: the physical, mental and social. However, the far-reaching impacts of mental health remain the most underappreciated. So much so that Public Health England has made it a primary objective to establish parity of importance between physical and mental health1.

While there are many factors at play behind poor mental health, without a doubt one of the most important elements is stress. Here, we’re going to talk about how stress affects our physiology and what you can do to set yourself up for long-term positive health.

What is stress?

‘Stress’ is a vague subjective term that is highly individual and reliant on situational factors; what is stressful for one person may not be so for another. Stress can therefore only be defined by what people typically find stressful, i.e. ‘stressors’, which we can divide into five broad categories:

  1. Acute time-limited stressors, such as public speaking or mental arithmetic.
  2. Brief naturalistic stressors, which might be real-life short term challenges, such as an exam.
  3. Stressful event sequences, perhaps centred around a focal event such as loss of a relationship or a natural disaster.
  4. Chronic stressors which pervade life, potentially forcing us to reformulate our identity and social roles. Examples include a major accident causing a disability or a chronic illness that suddenly stops you from working.
  5. Distant stressors, which include traumatic past experiences that continue to modify the immune system due to their long-lasting cognitive and emotional effects2.  

While stress comes in all shapes and sizes, it is still relevant to us, whatever its cause. This issue with stress is not just how we experience it but how well we ultimately respond too, which determines how well we survive and function in our lives. Our ability to cope through resources and strategies is not only biologically programmed into us but dictated by socialisation, major life transitions, personality dispositions, social and cultural contexts and life events3,4.

How does stress affect our health?

Stress can trigger ill mental health or, at any rate, poor mental health, which places psychological stress on the body. It is estimated that 60% of doctors’ appointments are triggered by stress-related symptoms5. Stress has been shown to exacerbate or initiate illnesses such as tension headaches, migraines, neurodermatitis, rheumatoid arthritis, asthma, regional enteritis and ulcerative colitis and many more6. Stress is also known to be a major contributor to coronary heart disease, cancer, lung illness and accidental injuries and suicide and is a trigger for five of the leading causes of death in the US7. So, what are the underlying mechanisms behind this?

Does stress affect the immune system?

A wealth of research has demonstrated links between stress and immunity in humans, showing that psychological challenges can modify our immune response8. Evolutionarily, we are primed to respond to environmental threats or stressors, such as predators or natural disasters. These responses include increased delivery of oxygen and glucose to the heart and large skeletal muscles, as well as changes in our immune system. Our bodies have developed a physiological adaptation for fight-or-flight situations, which would have likely involved a risk of injury and entry of infectious agents into the bloodstream or skin. This would trigger a stress-induced immune response to accelerate wound repair and help prevent infections. However, while these kinds of stimuli rarely occur today, our physiological response continues to reflect the demands of our ancestors’ environment and their ensuing immune system response9

To understand how stress impacts our immune system, we need to look a little closer at how it functions. Firstly, it is important to distinguish between the two types of immunity: natural and specific immunity.

What is natural immunity?

There are three types of cells involved in natural immunity: 

1. Granulocytes (neutrophils and macrophages)

Cells in natural immunity are one-size-fits-all, attacking multiple pathogens within a period of minutes to hours. In simplistic terms, these cells, known as granulocytes (including neutrophils and macrophages), eat their targets. The response they mount is known as inflammation. Neutrophils and macrophages gather at the site of an injury or infection, release toxic substances, such as oxygen radicals, to damage invaders and break down damaged tissue (phagocytosis). 

2. Natural killer cells

Natural killer cells recognise the lack of a self-tissue molecule on the surface of cells, as are found in virally-infected and some cancerous cells, destroying these cells by releasing toxic substances on them. It is believed that natural killer cells limit the early phases of viral infections before specific immunity becomes effective.

3. Complements 

Complements are a family of proteins involved in natural immunity. Complement proteins bind to microorganisms to enhance (or rather, complement) phagocytosis and inflammation. Complements can also aid in antibody-mediated immunity.

What is specific immunity?

Specific immunity is typically slower but more targeted than our natural immune response. This role is carried out by lymphocytes, which have receptor sites on their cell surfaces that fit with a single small molecular shape or antigen on an invader. When they recognise an invader, these antigen-specific cells divide to create a population called clonal proliferation or a proliferative response. While this process is efficient because the body needs to support fewer cells on a day-to-day basis, it normally takes several days for this process to kick in, during which the body has to rely on natural immunity.

How does stress affect the immune system? 

Stress affects the following areas of the body:

1. The sympathetic nervous system

Sympathetic fibres descend from the brain into both primary (bone marrow and thymus) and secondary (spleen and lymph nodes) lymphoid tissues10. These fibres release substances that influence immune responses by binding to receptors on white blood cells. 

2. The hypothalamic-pituitary-adrenal axis, sympathetic-adrenal-medullary axis and hypothalamic-pituitary-ovarian axis

These three systems secrete the adrenal hormones epinephrine, norepinephrine and cortisol, the pituitary hormones prolactin and growth hormone, and the brain peptides melatonin, β-endorphin, and enkephalin. These substances bind to receptors on white blood cells and regulate their distribution and function11

3. Our behaviour 

Often when we are stressed we turn to behaviours that modify the immune system, such as drinking alcohol, sleeping less or eating poor quality foods.

It has also been suggested that immunological changes due to stress are an adaptation from changes that respond to infection. When mammals’ immune systems are activated, they can display what is known as ‘sickness behaviour’, which includes a reduction in activity, social interaction and sexual activity as well as increased sensitivity to pain, low mood and low appetite. It is thought that this could be a mechanism to preserve energy for fighting infection12

What is clear from both the natural and specific models of immunity is that we need to mobilise and redirect energy according to the need to fight attackers internally and externally. It was initially thought that chronic stress always weakens our immune system by reducing cytotoxicity in natural killer cells, impairing proliferative responses and blunting humoral responses to immunisation13

There is also thought to be behind a greater incidence of infectious and neoplastic diseases in chronically stressed individuals14,15. However, from an evolutionary perspective, this would have meant we would have become extinct long ago in the face of life-threatening circumstances, famine or major global events, such as wars. It is now believed that fight-or-flight stressors cause immune cells to be redistributed to places that they can act most effectively and efficiently against invaders16, 17. In experiments on mice, they found that during acute stress, T-cells selectively redistributed into the skin and contributed to enhanced immune response. In contrast, during chronic stress, T cells were shunted away from the skin and there was a lesser immune response to the skin test18

Based on these experiments, it was proposed that acute stress enhances immune responses while chronic stress suppresses them. However, subsequent research has shown that short-term changes in the natural and specific components of the immune system would expend too much energy to be adaptive in life-threatening circumstances and are therefore unlikely. Instead, stress shifts the balance of the immune response toward activating natural immunity and diminishing specific immunity. This is because our fast-acting natural immune responses are better placed to manage life-threatening situations more quickly and effectively than specific immune responses and require less energy from other bodily systems to do so19, 20

How does the impact that stress has on our immune system affect our overall health?

While there is little to no evidence that stress causes immune changes or increases vulnerability to disease in healthy humans, it has been shown that older adults are especially vulnerable to life-event-induced immune change. In a meta-analysis of 300 studies spanning 30 years, those that included samples of adults with a mean age of 55 and over showed a correlation between life events and noticeable declines in both natural and specific immunity. These effects were much weaker in studies that had a mean age of 55 and below21.

It seems that chronic stress may elicit prolonged secretion of cortisol. This triggers white blood cells to mount a counterregulatory response by downregulating cortisol receptors, reducing these cells’ capacity to respond to anti-inflammatory signals and allowing cytokine-related inflammatory processes to flourish. Stress, therefore, might contribute to diseases involving excessive, non-specific inflammation, such as multiple sclerosis, rheumatoid arthritis and coronary heart disease, thereby decreasing life expectancy22

Does stress affect gut health?

As we have seen, stress triggers the release of systemic pro-inflammatory cytokines, whether its cause is psychological or physiological. This stimulates the pituitary gland to release what is known as adrenocorticotropic hormone (ACTH), which in turn signals to the adrenal glands to release one of the main stress hormones, cortisol23.

Cortisol has wide-ranging effects throughout the body and the brain in particular. The brain uses a network of hormonal and neural systems to control a range of gut functions, from motility, secretion of stomach acid, mucus, intestinal fluid and our immune response. In studies on dogs, it has been shown that these elements are vital for the correct functioning of the microbiota in the gut24. When the gut-brain axis becomes dysregulated, this can disturb the mucosal habitat in our gut. This is because the alterations that accompany stress mean that virulent bacteria can proliferate. This has partially been demonstrated through studies into patients’ gut health post surgery; the release of norepinephrine can induce the expression of pseudomonas aeruginosa, a disease-causing bacterium, which can cause life-threatening gut sepsis25.

A body of research has demonstrated that gut microbiota has a highly influential role in influencing anxiety and depressive behaviour26,27. There is also evidence that dysbiosis, an imbalance in gut bacteria, is linked to autism; autistic patients have been shown to have specific microbiota alterations, which vary according to the severity of their condition28,29. Researchers have also demonstrated that chronic stress also contributes to insulin resistance30, increasing the risk of developing metabolic disease and diabetes. 

Stress also tends to go hand-in-hand with poor sleep, creating a vicious cycle. Ever find yourself struggling to sleep because of a stressful day, leaving you feeling even more run-down the next day? This also has serious consequences for your gut health amongst other long-term implications. We now know that the diversity of our gut microbiome is heavily influenced by sleep quality and quantity31. All these factors demonstrate that it is vital to look at health with a holistic view covering multiple, inter-connecting dimensions rather than purely one element. To understand how to become physically, mentally and socially healthier, looking at the causes rather than purely the symptoms, could be the key to unlocking positive health for life.

How can I manage stress to protect my health?

The evidence seems overwhelming that stress is a major contributor to several negative outcomes, both for our mental and physical health. While the underlying mechanisms may be complex, the solutions need not be. 

1. Make necessary dietary changes

While it may be tempting to turn to food or alcohol to relieve stress, this simply compounds the problem. High-calorie, highly inflammatory foods, such as junk food, cause intestinal distress and alcohol disturbs sleep, hitting you with a double whammy. Make it a priority to focus on anti-inflammatories that you know work for you, for instance:
 

  • Avoid processed foods and food sources that don’t work for you. For some people this may include dairy and gluten, others may not experience issues. Use a process of trial and error to adapt as you go.
  • Include a tonne of bright, colourful vegetables with every meal, 
  • Avoid high-inflammatory oils, like sunflower oil, peanut oil, corn oil, soybean oil, margarine or vegetable oils.
  • Enjoy healthy fat sources such as olives, avocados, nuts, and seeds. 
  • Eat a high-fibre diet, such as green leafy vegetables, berries, nuts and seeds.
  • Prioritise high-quality, unprocessed protein sources. 

2. Improve your sleep 

This is a factor that many find difficult, particularly if you have a demanding job or small children at home. However, getting to bed just 15-30 minutes earlier each night will soon have a dramatically positive impact on your health.

  • Install blackout blinds or curtains or consider investing in a sleep mask. 
  • Keep your room cool and quiet; invest in earplugs if you live with a lot of ambient noise.
  • Avoid heavy meals close to bedtime.
  • Set up a strong bedtime routine: in the hour before bed, avoid your phone and chores. Use this time to read a book, take a bath or meditate.
  • Supplement with our sleep supplement stack.

3. Practise gratitude 

However you choose to do it, gratitude and mindfulness have many positive impacts on stress and mental health.

  • Invest in a journal and write down 3-5 things you are grateful for every day. You will improve at this with time if it feels difficult at first. 
  • Make time to meditate or carry out guided breathing, whether before bed or in the morning. Ten minutes is just 1% of your day and this 1% investment will reap far greater rewards for your productivity, mindset and long term health.

4. Overhaul your morning routine 

Do you check your phone for work emails, social media or news as soon as you wake up? This habit can set you up for a negative mindset before the day has fully begun. 

  • Create a routine that works for you, whether that’s journaling, doing a 20-minute yoga class online, a stretching routine or some guided-breathing. 
  • Make time to sit and eat a nutritious breakfast with zero distractions.
  • Give yourself an hour undisturbed before diving into work or other activities.
  • Consider what news sources you use. Often this stream of negativity feeds into our mindset and stress levels without us even realizing it.

5. Supplement

For the most part, the key to minimising stress is lifestyle changes. However, stress is sometimes inevitable, which is where supplementation can provide a valuable tool. Our stress supplement stack supports you when you need it:

  • Amplify – the ingredients in our unique BCAA blend suppress myostatin caused by chronic cortisol elevation, vital for stressed thirty-plus executives.
  • Phosphatidylserine – which allows the brain to adapt to stress.
  • Taurine Powder – this helps to maintain neurotransmitters and reduce anxiety.
  • UltraMag – Magnesium is involved in over 300 processes in the body and relaxes the central nervous system. If you often have disturbed sleep or anxiety, take it before going to bed.
  • Zinc NT – provides the cofactors and minerals required for full production and activity of neurotransmitters.
  • Drive – provides the precursor to dopamine to prevent the feeling of being overwhelmed.
  • Serotonin Support – helps support the production of serotonin and ensure satisfying, refreshing sleep.
  • Inflammation Support – prevents cortisol production in response to inflammation.
  • D3 Replenish – helps maintain a healthy circadian rhythm, which may be disturbed by elevated cortisol.

References

1.  Department of Health (2011). No Health Without Mental Health, available at https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/215811/dh_124057.pdf [last accessed 11.09.2020].

2.  Elliot, G. R., & Eisdorfer, C. (1982). Stress and human health: An analysis and implications of research. A study by the Institute of Medicine, National Academy of Sciences. New York: Springer Publishing.

3.  Friedman, H. S. et al. (1995). Psychosocial and behavioral predictors of longevity. The aging and death of the “termites”, American Psychology, 50 (2), pp. 69-78.

4.  Moos, R. H., and Schaefer, J. A. (1993). Coping resources and processes: Current concepts and measures. In L. Goldberger & S. Breznitz (Eds.), Handbook of stress: Theoretical and clinical aspects

5.  Sachs, B. C. (1991). Coping with stress. Stress Medicine, 7, pp. 61–63.

6.  Brantley, P. J., & Jones, G. N. (1993). Daily stress and stress-related disorders. Annals of Behavioral Medicine, 15 (1), pp. 17–25.

7.  Sachs, B. C. (1991). Coping with stress. Stress Medicine, 7, pg. 62.

8.  Segerstrom, S.C. and Miller, G.E. (2004).  Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry, Psychological Bulletin,  Vol. 130 (4).

9.  Segerstrom, S.C. and Miller, G.E. (2004). Psychological Stress and the Human Immune System.

10.  Felten, S. Y., & Felten, D. (1994). Neural-immune interaction. Progress in Brain Research, 100, pp. 157–162.

11.  Ader, R., Cohen, N., & Felten, D. (1995). Psychoneuroimmunology: Interactions between the nervous system and the immune system. The Lancet, 345, 99–103.

12.  Maier, S. F., Watkins, L. R., & Fleshner, M. (1994). Psychoneuroimmunology: The interface between behavior, brain, and immunity. American Psychologist, 49, 1004–1017.

13.  Selye, H. (1975). The stress of life. New York: McGraw-Hill.

14.  Andersen, B. L., Kiecolt-Glaser, J. K., & Glaser, R. (1994). A biobehavioral model of cancer stress and disease course. American Psychologist, 49, 389–404.

15.  Cohen, S., & Williamson, G. M. (1991). Stress and infectious disease in humans. Psychological Bulletin, 109, 5–24.

16.  Dhabhar, F. S., & McEwen, B. S. (1997). Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: A potential role for leukocyte trafficking. Brain, Behavior, and Immunity, 11, pp. 286–306.

17.  Dhabhar, F. S., & McEwen, B. S. (2001). Bidirectional effects of stress and glucocorticoid hormones on immune function: Possible explanations for paradoxical observations. In Ader, R., Felten, D. L., and Cohen, N. (Eds.), Psychoneuroimmunology, third edition, San Diego, California, Academic Press, pp. 301–338. 

18.  Dhabhar, F. S., and McEwen, B. S. (1997). Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: A potential role for leukocyte trafficking.

19.  Dopp, J. M., Miller, G. E., Myers, H. F., & Fahey, J. L. (2000). Increased natural killer-cell mobilization and cytotoxicity during marital conflict. Brain, Behavior, and Immunity, 14, pp. 10–26.

20.  Sapolsky, R. M. (1998). Why zebras don’t get ulcers: An updated guide to stress, stress-related disease, and coping. New York, Freeman.

21.  Segerstrom, S.C. and Miller, G.E. (2004). Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry.

22.  Ershler, W.B., and Keller, E.T. (2000). Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annual Review of Medicine, 51, pp. 245–270.

23.  Carabotti, M., et al. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of Gastroenterology, 28 (2), pp. 203-209.

24.  Gué, M. et al. (1989). Stress-induced changes in gastric emptying, postprandial motility, and plasma gut hormone levels in dogs. Gastroenterology, 97, pp. 1101–1107.

25.  Alverdy, J. et al. (2000). Gut-derived sepsis occurs when the right pathogen with the right virulence genes meets the right host: evidence for in vivo virulence expression in Pseudomonas aeruginosa. Annals of Surgery, 232 (4), pp. 480-489. 

26.  Cryan, J.F. and Dinan, T.G. (2012). Mind-altering microorganisms: The impact of the gut microbiota on brain and Behavior. National Review of Neuroscience,13, pp. 701-712.

27.  Collins, S.M., Kassam, Z., Bercik, P. (2013). The adoptive transfer of behavioral phenotype via the intestinal microbiota: Experimental evidence and clinical implications. Current Opinion in Microbiology, 16, pp. 240-245.

28.  Foster, J.A. and McVey Neufeld, K.A. (2013). Gut-brain axis: How the microbiome influences anxiety and depression. Trends in Neuroscience, 36, pp. 305-312.

29.  Lyte, M. (2013). Microbial endocrinology in the microbiome-gut-brain axis: How bacterial production and utilization of neurochemicals influence behavior. PLOS Pathogens, 9(11).

30.  Yan, Y.X., Xiao, H.B., Wang, S.S., et al. (2016). Investigation of the Relationship Between Chronic Stress and Insulin Resistance in a Chinese Population. Journal of Epidemiology, 26 (7), pp. 355-360. 

31.  Smith, R.P., Easson, C., Lyle, S.M., et al. (2019). Gut microbiome diversity is associated with sleep physiology in humans. PLoS One, 14 (10).