What is oxidative stress?

Oxidation, how does it work?

Oxidation is a chemical reaction that takes place in the presence of oxygen. You can see it when you cut an apple: once cut, the apple tends to turn brown because one of its enzymes reacts with oxygen and transforms a molecule (called phenol) into another molecule (called quinone) which will decompose into a brown pigment. The addition of lemon juice will slow down this browning because it contains vitamin C, a strong antioxidant, which will reduce the quantity of quinones and thus prevent the brown pigment from appearing.

It is the same balance between oxidation and anti-oxidation that takes place in each of our cells. Of course, we need oxygen to live and each of our cells uses it in many processes. During some of these reactions, for example when ATP cell energy is produced, free radicals (ROS – reactive oxygen species) are formed. Their presence – in small quantities – is normal, and they have certain functions such as communication between cells, the synthesis of cellular components or as a weapon of the immune system against pathogens. At the same time, ROS are constantly detoxified by certain antioxidant enzymes or by other mechanisms, to become harmless products, such as water H2O.^1,2 An oxidative balance is reached, and normally works very well! Except that this is not always the case…

It’s all a question of balance… Otherwise, it’s oxidative stress!

Oxidative stress is a phenomenon caused by an imbalance between the production and accumulation of free radicals (ROS) in cells and tissues, and our body’s ability to detoxify these reactive products.¹

While the presence of ROS created by our cellular metabolism is normal, certain environmental factors, such as UV rays, ionizing radiation, pollutants, heavy metals, tobacco, alcohol, certain drugs and chemicals, contribute to a significant increase in the production of ROS. This large amount of ROS cannot be fully detoxified by our antioxidant defences, and this imbalance leads to cell and tissue damage. This is called oxidative stress.

To counteract this, there are also exogenous antioxidants, such as vitamins C and E, flavonoids or polyphenols, which can react with ROS to render it harmless, prevent its production or activate antioxidant enzymes.^1,2

Why is oxidative stress negative?

When there is too much ROS in relation to our antioxidant defences, the membranes of our cells and our proteins, lipids, DNA etc. will be “attacked” and damaged.¹ Changes in the DNA of a cell lead to a deregulation of its functions and “behaviour”, which will impact the tissue in which it is located. Lipid damage can induce tissue permeability and disrupt communication between cells. The altered proteins can no longer perform their functions in the cell, which can no longer fulfil its role in the organ to which it belongs. Etc.³  

As ageing can be defined as “the progressive loss of our tissues’ functions”, the repetition of damage due to excess ROS can therefore accelerate it. ROS attacks could, for example, be involved in cell senescence, a physiological mechanism that stops cell proliferation when damage is present. These senescent cells can then secrete inflammatory molecules and extracellular matrix-degrading enzymes (MPP), and, if there are many of these, this can disrupt the functioning of the organ.⁴ In addition, the build-up of oxidative stress can lead to dysfunction of the mitochondria (the parts of our cells that produce cellular energy, regulate cell survival and oxidative balance), which means more ROS and fewer antioxidant defences, and unstable energy production and cell survival.⁵ Thus, over time, if oxidative stress is not resolved, damage builds up, tissue which can no longer maintain homeostasis become disordered, and chronic or degenerative diseases can occur.¹ In addition, as we age, antioxidant defences diminish, making us more susceptible to excess ROS.⁴

What is the impact of oxidative stress on our health?

Most of the chronic illnesses present in our civilisation are multifactorial diseases, which are triggered by a mixture of internal and external factors. Oxidative stress is often one of these factors, as it can damage tissues. Moreover, it is often coupled with chronic inflammation, as they amplify each other. Oxidative stress leads to inflammation that disrupts the immune system and produces more ROS etc. As this impacts the state of health in which we age, this phenomenon is sometimes called inflam-aging.⁴

Oxidative stress heightens chronic inflammation found for example in certain lung diseases such as asthma or obstructive lung diseases. The same applies to chronic inflammatory joint diseases such as rheumatoid arthritis, where oxidative stress is involved in the initiation and progression of the disease. In the kidneys, the presence of oxidative stress can induce the recruitment of inflammatory cells and molecules. This inflammation, if sustained, will eventually lead to tissue damage, kidney dysfunction and disease.^1,4

Cardiovascular and metabolic diseases (e.g. diabetes) are also multifactorial, with internal and lifestyle-related triggers, but oxidative stress is often considered one of the main risk factors (along with diet, physical inactivity, smoking, etc.) and may promote certain complications.^1,4,6 The consequences of oxidative stress, which damages our DNA, combined with other internal and external factors, can lead to cellular abnormalities that promote cancer. Oxidative stress in the muscles, particularly due to physical inactivity, could be a common determinant of muscle wasting and loss of strength, or even sarcopenia. Finally, the presence of oxidative stress has also been linked to neurological diseases (Alzheimer’s, Parkinson’s, multiple sclerosis, dementia, depression, sickly anxiety…), as it plays an important role in the death of neurons.^1,4 Indeed, as the brain has an enormous consumption of oxygen and energy to function and is very rich in lipids (neuronal membranes), this makes it very vulnerable to the accumulation of ROS, which can lead to its functional decline.⁵

Thus, a high excess of ROS over the long run, combined with other risk factors (which sometimes have the same causes as ROS accumulation), can be involved in a wide variety of conditions. Fortunately, it is never too late to get involved in reducing oxidative stress in our bodies. It is possible to reduce the generation of exogenous ROS as much as possible by avoiding exposure to radiation, pollutants, heavy metals, tobacco and alcohol, certain medicines and chemicals. And of course, it is a good idea to regularly strengthen our antioxidant defences.

The benefits of exogenous antioxidants

There are many sources of antioxidants in nature, all of which are useful. Here are the most common:

Vitamin E is one of the best-known antioxidants. This name encompasses various molecules, of which α-tocopherol is one of the most effective. It is able to regulate certain cellular pathways that produce ROS or induce inflammation.¹ Vitamin C is also a widely used natural antioxidant. It reacts with the ROS and promotes their conversion into a non-reactive, and therefore harmless, substance.¹ Carotenoids and vitamin A react with certain free radicals, converting them into harmless H2O water. They are also able to regulate certain cellular pathways, such as inhibiting certain inflammatory pathways or acting on cell survival.³

Polyphenols are found in many plants. Flavonoids are one type of polyphenol and contain different molecules. Non-flavonoids include, for example, resveratrol from grapes. All of them are powerful antioxidants, often possessing certain anti-inflammatory properties and having many benefits for our health.⁴ The specific activity of flavonoids depends on each specific molecule, acting on the suppression of ROS synthesis, on the detoxification of ROS and/or on the improvement of antioxidant defences.¹

Coenzyme Q10, also known as ubiquinone, is naturally found in our mitochondria, the parts of our cells that are used to produce energy, reduce oxidative stress and regulate the survival of our cells. Taking Q10 appears to be effective against oxidative stress and some of the chronic diseases mentioned above.⁴

The presence of selenium, an essential component of selenoproteins, is required for many functions in our body, including the reduction of oxidative stress. Some clinical trials have also highlighted its positive effect in the prevention and treatment of certain chronic conditions.⁴

Moderate and regular aerobic physical activity (long, low-intensity aerobic exercise using oxygen in the muscles) is also important to limit the accumulation of oxidative stress because it stimulates antioxidant defences, especially in the muscles. It is also essential for maintaining good health in general. However, high-intensity physical activity will increase oxidative stress in our bodies.⁴

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1. Pizzino, G. et al. Oxidative Stress: Harms and Benefits for Human Health. Oxidative Medicine and Cellular Longevity vol. 2017 (2017).
2. Burton, G. J. & Jauniaux, E. Oxidative stress. Best Practice and Research: Clinical Obstetrics and Gynaecology vol. 25 287–299 (2011).
3. Birben, E., Sahiner, U. M., Sackesen, C., Erzurum, S. & Kalayci, O. Oxidative stress and antioxidant defense. World Allergy Organization Journal vol. 5 9–19 (2012).
4. Liguori, I. et al. Oxidative stress, aging, and diseases. Clinical Interventions in Aging vol. 13 757–772 (2018).
5. Salim, S. Oxidative stress and the central nervous system. Journal of Pharmacology and Experimental Therapeutics vol. 360 201–205 (2017).
6. Betteridge, D. J. What is oxidative stress? in Metabolism: Clinical and Experimental vol. 49 3–8 (W.B. Saunders, 2000).