CELL STRESS: WHERE TO FIND IT?

Our life is in a state of continuous dynamic equilibrium. On a daily basis, our body is subjected to stresses of various kinds, stressors that undermine the physiological balance.

At the cell level, a stressor can:

• trigger an adaptive response >> stimulus to achieve a new balance with adaptive benefits
• create reversible damage >> stimulus to “fix” the condition that caused the stress
• create irreversible damage and lead to cell death (apoptosis).

Conditions such as intense sports, psychophysical stress, infections, exposure to pollutants, sun or other sources of radiation, and smoking, combined with unregulated lifestyles and poor dietary intake of antioxidants, can lead the cell to increase free radical production. Conditions in which antioxidant defences are depleted and the stressed condition may not be compensated for.

OXIDATIVE STRESS OR RADICAL STRESS: are the same?

The term oxidative stress is often used to refer to the formation of free radicals.

Oxidative stress and radical stress are two different molecular processes.

During the stress phenomenon, reactive oxygen species (ROS) of two types are formed in the cell:

1) oxidizing molecules, such as hydrogen peroxide

2) free radicals, such as the “famous” hydroxyl radicals (OH•). Free radicals are “transient,” i.e., unstable, species whose half-life is much shorter and reactivity quite different from oxidizing species.

Therefore, in the former case the term “oxidative stress” is used, while in the latter case it is more appropriate to speak of “radical stress.”

Recognizing whether one is dealing with oxidative stress or radical stress is important when one has to choose the ANTI-STRESS strategy, but this distinction can only be made by a specialist who will identify the most suitable ANTI-OXIDANT or ANTI-RADICAL synergy, including through membrane lipidomic analysis.

Consequently, “DO-IT-YOURSELF” in stress is definitely the worst choice, because resorting to antioxidants without knowing the molecular process may be useless or even deleterious.

ANTIOXIDANT-THEMED INSIGHTS:

Some in-depth readings on the topic of antioxidants and dietary supplementation:

• Before purchasing a supplement, it is important to know that…
  www.lipinutragen.it/en/food-supplements/
• Antioxidant action supplementation:
  www.lipinutragen.it/en/antioxidant-integration/
• Cell reinforcement with antioxidants:
  www.lipinutragen.it/en/strengthening-the-body/
• Easy homemade ice-cream recipe with natural antioxidant action ingredient:
  www.lipinutragen.it/en/antioxidant-ice-cream/

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Article edited by the Lipinutragen Editorial Group.

The information reported should in no way replace the direct relationship between health professional and patient.

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Immunity

The immune system acts through two components:

• The innate immune system, the first line of defense, fast, effective, but without memory;
• The adaptative immune system stores information, uses antibodies produced by B lymphocytes which are activated by T lymphocytes. It allows the development of an immune memory.

Immune tolerance

The immune system is normally tolerant of all body proteins, the so-called self-antigens. This tolerance develops as a result of contact with self-antigens by lymphocytes during their maturation in the primary lymphoid organs, i.e. bone marrow and thymus, as well as liver and spleen in fetal life. Tolerance can be lost and induce inappropriate activation of antibody-producing B lymphocytes with inflammatory processes involving organs or entire districts.

Autoimmunity

When the tolerance mechanisms are lacking, the T lymphocyte cells of the immune system can endure an erroneous activity that triggers a series of cascading phenomena. Consequence of the alteration and/or loss of tolerance towards self is autoimmunity, during which alterations in the immune response are clearly evident with production of autoantibodies, or antibodies directed against itself.

Autoimmunity can be a physiological or pathological response of the immune system and in the latter case it can lead to the development of clinical abnormalities, autoimmune diseases.

Autoimmune diseases

The autoimmune diseases can affect an organ (as in the cases of: Hashimoto’s thyroiditis, Graves’ thyrotoxicosis, type I diabetes, myasthenia gravis) or entire body systems or areas (for example: systemic lupus erythematosus, Sjogren’s syndrome).

The cells involved in the autoimmunity mechanism are mainly T helper lymphocytes and their mediators. These lymphocytes are responsible for instructing B lymphocytes and natural killer cells in their functions.

Autoimmune diseases are multifactorial and in recent decades there has been a continuous increase in their incidence, influenced by various risk factors including diet and stress.

Evidence and clinical studies suggest that stress may play an important role in the etiopathogenesis of these pathologies. In fact, psychological stress, as well as the mechanisms involved to deal with it, activate hormonal circuits that can also influence the activity of the immune system.

At least 50% of autoimmune diseases have been attributed to unknown triggers and most autoimmune patients reported experiencing extraordinary emotional stress before the onset of the disease. Stress would also have a role in maintaining and worsening the course of the disease.

The stress

The definition of stress dates back to Hans Seyle who already in 1936 defined it as “general adaptation syndrome”, that is, a physiological response of the organism to changes the disturb of its psychophysical balance.

In reality, the human species constantly interacts and responds to the outside world with an adaptive behavior that has the survival of the species as its ultimate goal. Stress, understood in this way, is therefore not a negative event because it is commensurate with the individual’s ability to control and adapt to events.

When the events remain within the limits of tolerability by the individual, the psychophysical activation induced by stress results in an improvement of various mental performances of the subject. On the other hand, it becomes a negative event when, lasting for more or less long times, with situations that question the individual regarding his real ability to deal with situations, it produces an abnormal adjustment and induce it to give excessive charge to the events and their evaluation.

The relationship between stress and autoimmune diseases is complex and is still under study. For rheumatoid arthritis, systemic lupus erythematosus, chronic inflammatory bowel diseases (Chron’s disease, ulcerative colitis and pancolitis), multiple sclerosis and Graves’ disease, it has been shown that stress is associated with the onset and exacerbation of the disease. In subjects with psoriasis, stress appears to delay the healing of lesions during therapy.

The stress response

The stress response is orchestrated by the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system. The coordination of them occurs through neuro hormonal responses mediated by the following hormones:

• adrenaline
• noradrenaline
• corticotrophin-releasing hormone (CRH)
• adrenocorticotropic hormone (ACTH)
• glucocorticoids, especially cortisol.

Catecholamine and colrtisol exert, among other things, control over various cells of the immune system.

Under physiological conditions, the immune system, following stimulation by stress hormones, will be activated by reducing the production of pro-inflammatory cytokines and stimulating the production of anti-inflammatory cytokines.

An inadequate answer

In the presence of an adequate and efficient regulation mechanism, a negative feedback system will send the deactivation signal of the hypothalamus-pituitary-adrenal axis, protecting the body from the effect of an excess secretion of pro inflammatory cytokines potentially harmful to the body.

In chronic stress conditions, especially in subjects in which the physiological adaptive stress response is inadequate, the stress mediators will send the wrong signal for stress management.

Such dysfunctions of the hypothalamus-pituitary-adrenal axis can therefore lead to greater susceptibility to inflammatory diseases and the severity of the inflammation itself. Furthermore, an overactive axis in the absence of inflammation causes immunosuppression and increases susceptibility to inflammation.

The inadequate response will not only keep the hypothalamus-pituitary-adrenal axis activated, but will indirectly affect other regulatory systems such as the sympathetic-adrenal axis and the hypothalamus-pituitary-ovary axis and obviously the immune system.

Stress and lifestyle habits

It would therefore be advisable for the treatment of autoimmune disease to include adherence to useful behaviors to prevent stress-related immune imbalance. A good quality of sleep, a correct diet, which brings all the antioxidant micronutrients of vegetables, essential fatty acids of fishery products and some vegetable foods, low saturated fats and processed foods, together with an adequate intake of water, seem to be a strategy in the prevention and management of stress.

In particular, it is necessary to pay close attention to the quality of the fatty acids introduced in the diet, especially EPA and DHA, directly responsible for the modulation of the inflammatory cascade, a key physiological phenomenon of autoimmune diseases. Their food income is unbalanced and very often insufficient. The Western diet does not help us and too often we make up for it by supplementing with omega-3s incorrectly. It would be appropriate to define the lipid profile of our cell membranes through a membrane lipidomic analysis in order to properly manage the delicate balance underlying the health of our cells and make personalized food and supplement choices, aimed at prevention and treatment.

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Bibliography:

www.febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3
www.frontiersin.org August 4, 2020 Volume 11 Article 1823
www.sciencedirect.com/science/article/abs/pii/S1568997218301770#!
www.onlinelibrary.wiley.com/doi/epdf/10.1111/pcn.12820
medcraveonline.com/MOJI/the-role-of-il-17-secretion-in-mediating-the-influence-of-stress-on-cancer-and-other-human-systemic-diseases.html
www.clinicaltrials.gov/ct2/show/NCT01115621
www.ncbi.nlm.nih.gov/pmc/articles/PMC5498122/
www.pnas.org/content/115/13/E2960.short
www.pnas.org/content/109/16/5995.short
www.imbio.it/possible-mechanisms-responsible-for-stress-predisposition-to-cancer-or-to-autoimmune-diseases/

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Article by:

Dr. Nicoletta Bocchino – Nutritionist Biologist

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Photo: 123RF Archivio Fotografico: 148499302 : ©GANNA MARTYSHEVA / 123rf.com | 146429617 : ©Ignacio Roca Benito / 123rf.com

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Manage stress and stay healthy:

According to the American College of Lifestyle Medicine*, stress management is an essential component on which to intervene to maintain health. The other fundamental elements are:

• the correct diet;
• physical and motor activity;
• cessation of smoking habit;
• the quality of sleep;
• healthy interpersonal relationships.

(*) Lifestyle Medicine is a new discipline born as a systemic approach to the prevention and treatment of chronic degenerative diseases (1).

What is “Stress”?

The modern concept of stress dates back to 1936 when doctor Hans Selye defined it as “the body’s non-specific response to any request for change”. The term stress then undergoes its own evolution and, conceptually, is linked to homeostasis, or the state of dynamic balance that every living being tries to maintain, in response to any disturbing agent internal or external, called stressor.

In other words, stress is a phenomenon that can be psychological/emotional or physiological and that involves the perception, evaluation and response to stimuli or harmful situations (2).

How does the human body respond to stress?

In response to stress, the body has evolved physiological and behavioral compensatory mechanisms to restore homeostasis. These include increased vigilance, attention and excitement, increased oxygenation and nutrition of the organs essential for the fight or flight mechanism: the brain, heart and skeletal muscles. On the other hand, the neuronal pathways underlying functions such as reproduction, nutrition and growth, which are not strictly necessary to resolve a dangerous situation, are inhibited.

The “stress system” is located both in the Central Nervous System (CNS) and in the peripheral organs. Among the main components of this system are the hypothalamic hormonal axes, including in particular the adrenal (HPA) with the production of glucocorticoids and the efferent part of the Autonomous Nervous System (SNA) with the release of catecholamines.

Cortisol is the main hormone of the HPA axis and regulates many functions including anti-inflammatory responses, metabolism of carbohydrates, fats, proteins and also gluconeogenesis.

The catecholamines (adrenaline, noradrenaline) activated by SNA, influence the regulation of the cardiovascular, pulmonary, hepatic, muscular and immune system.

Intense and chronic Stress

If the stress-reducing stimulus is particularly intense or if it becomes chronic over time, it causes imbalances in the regulation of equilibrium in other physiological systems such as: the sleep-wake cycle (circadian rhythm), the reproductive and thyroid axes, the reward centres, etc., the human being has not been faced with continuous situations of danger and therefore has not adapted to the needs of the human body.

During the course of evolution, the human being has not been faced continually with dangerous situations and therefore has not adapted to handle phenomena of chronic stress, as is currently the case.

The typical modern scenario, characterized by very fast rhythms and numerous external stimuli, places our stress system in constant alarm and is a new condition for which we have not been prepared by the adaptive selection of thousands of years.

The relation between food and stress:

The individual under stress can have two very different reactions depending on whether they are acute or chronic stimuli. In the first case, a “fight or flight” response is generated, mediated mainly by the Corticotropin Release Hormone (CRH) and by catecholamines that block non-essential immediate stimuli, such as hunger.

In the case of persistent stress over time, the activation of the HPA axis will produce cortisol which, together with other mechanisms, will stimulate phenomena of catabolism and the search for food with high energy density. It has recently been discovered that the continuous presence of glucocorticoids in the circulation, instead of their fluctuation in 24 hours, induces the body to produce adipocytes (fat cells) from undifferentiated cells (3). This molecular mechanism is in addition to other changes in human physiology related to stress phenomena that lead to the metabolic syndrome.

Main relapses of stress in relation to food:

• Increase of alarm and danger hormones (fight or flight);
• Hunger for “comfort food” (sugars and fats), food dependence and consequent eating disorder;
• Stimulation of brain areas of pleasure with consolatory function that reinforce incorrect behavior;
• Less motivation to do physical activity;
• Increased blood sugar and insulinemia;
• Alteration of intestinal permeability and microbiota (brain-intestine axis);
• Reduction of heart rate variability (HRV);
• Increased water retention;
• Increased risk of osteopenia and osteoporosis;
• Increased abdominal fat, insulin resistance and oxidative stress.

The response to stress can be directed not only at food, but also at alcohol, smoking or abuse drugs.

“To be used” to control stress relapses:

To break the vicious circle of health-related stress relapses, it would be desirable to adopt balanced eating styles that lead to a control of glycemic peaks and insulin fluctuations.

It is also important to observe the right sleep-wake cycles, meal times and their breakdown into macronutrients and also the timing of physical-motor activity during the day, in accordance with circadian rhythms.

Other possible interventions concern the behavioural sphere, with stress-reducing techniques such as mindfulness, yoga, etc., and which are fully included in the modifiable elements of the lifestyle.

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Bibliography:

(1) Kushner RF, Sorensen KW. Lifestyle medicine: the future of chronic disease management. Current Opinion in Endocrinology & Diabetes and Obesity. 20(5):389–395, Oct 2013.
(2) Fink G. Stress: Definition and history. Stress Science: Neuroendocrinology. 2010:3–9.
(3) Bahrami-Nejad Z et al. A Transcriptional Circuit Filters Oscillating Circadian Hormonal Inputs to Regulate Fat Cell Differentiation. Cell Metab. 2018 Apr 3;27(4):854-868.e8.

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Article by:
Nutritionist Dr. Francesco Bonucci

The diet tips, written in the article, are not intended to be a substitute for a personal nutrition plan and are to be adapted to specific cases.

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Photo: 123RF Archivio Fotografico | ©Andriy Popov, 43306810 , 2018-09-28 | ©robuart, 51249161 , 2018-09-28 | ©lightwise, 63825904, 2018-09-28

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