What is oxidative stress? The causes, symptoms, and how to combat it

What is oxidative stress? The causes, symptoms, and how to combat it 

In the modern Western world, stress can become a daily companion. Among the different forms in which it can present itself is oxidative stress. What is it all about? What are the causes of oxidative stress? And how is it combated?

Oxidative stress is the consequence of the loss of balance between oxidant and antioxidant factors within the cell. If prolonged over time, it can damage numerous cellular structures, increasing the risk of even serious health problems. The damage promoted by oxidative stress is itself a source of oxidant factors. Therefore, a vicious cycle can be created in which oxidative stress contributes to its own maintenance. Fortunately, to combat this enemy of health, one tool available to everyone may suffice: a lifestyle that is as healthy and balanced as possible.

Oxidative stress and free radicals

The two main classes of oxidizing molecules (or free radicals) are reactive oxygen species (ROS) and reactive nitrogen species (RSNs). Under conditions of physiological stress (eustress) ROS and RSNs are present in small amounts and regulate gene expression, receptor activation, pathogen recognition, cell survival and its ability to proliferate, migrate and differentiate. If, however, their production is high, a condition of toxic stress (distress) can be created.

In this condition, free radicals can oxidize molecules other than their natural targets, damaging them and impairing their functionality. The distress is accentuated when the excessive production of oxidizing molecules is associated with a weakening of the mechanisms that are supposed to protect cellular structures from oxidation. In fact, the cell is also equipped with the necessary paraphernalia to prevent free radicals from damaging it, including, for example, bilirubin, melatonin, uric acid, and a number of antioxidant enzymes.

What are the causes of oxidative stress?

In itself, the production of oxidant factors is a natural and necessary phenomenon; they are generated either while the cell is producing energy using oxygen or while various enzymes are doing their work. However, there are also causes of oxidative stress that come from the external environment and can promote the distressed condition.
Among the most common are included:

• tobacco smoke;
• pollution;
• infrared rays;
• the ultraviolet;
• sports.
  

Oxidative stress and sports

The first reason why sports and, more generally, the practice of physical activity are associated with increased oxidative stress is simple: with exercise, oxygen flow in the body increases. In addition, exercise-induced muscle microtrauma draws white blood cells whose activity promotes the increase of free radicals. These phenomena are entirely physiological, but if unpleasant side effects are to be avoided, their consequences must be limited in time.

In fact, oxidative stress is associated with inflammation. On the one hand, a certain degree of inflammation after physical activity is beneficial for both muscle regeneration and the apposition of new muscle mass. On the other, if inflammation is prolonged excessively, it can impair functional recovery, promoting symptoms such as muscle weakness and pain and reducing, for example, sports performance on subsequent days. Conversely, alleviating oxidative stress improves post-workout and post-race performance.

How does oxidative stress manifest itself?

Even before obvious symptoms such as reduced sports performance, high oxidative stress manifests itself in the form of damage to key biomolecules: lipids, proteins, and nucleic acids (DNA and RNA). Lipids can undergo peroxidation. It can also happen to fats in the Omega-3 series, which can lose their properties due to this phenomenon. Omega-3s and, more generally, peroxidized lipids are extremely reactive and can interact with proteins and DNA, changing them in undesirable ways. The building blocks that form DNA and RNA can also be oxidized; moreover, oxidative stress can literally break the DNA helix, promoting mutations and other dangerous rearrangements of genetic material. When, on the other hand, it is the proteins that are oxidized, their conformation changes and, as a result, so does their functionality.

In the long term, irreversible changes in lipids, proteins and nucleic acids and the structural and functional damage induced by them can promote the onset of health problems. Therefore, high and sustained oxidative stress over time can manifest itself in the form of:

• neurodegeneration: oxidative stress undoubtedly plays a role in Alzheimer's disease, and is also hypothesized to be involved in the development of Parkinson's.
• cardiovascular disorders: increased ROS are associated with functional and structural alterations that impair good circulation. For example, free radicals have been associated with atherosclerosis, stroke, heart attack, and peripheral arterial disease.
• diabetes: high oxidative stress can impair the synthesis and functioning of insulin, the hormone that allows blood sugar to be reduced. In addition, the mechanisms that lead to the vascular complications of diabetes also involve free radicals.
• tumors: moderate-level oxidative stress is sufficient to generate mutations that promote cancer development. In addition, oxidation of proteins and lipids has also been associated with the occurrence and progression of cancers.
• autoimmune diseases: oxidation can lead to the formation of molecules that are recognized as foreign by the immune system, which then attacks them resulting in autoimmunity.
• Rheumatoid arthritis: oxidative stress is both a cause and a consequence of the inflammation typical of this disease. In addition, ROS can induce cartilage cell death and thus promote degeneration of joints affected by the disease.
• kidney disease: oxidative stress is considered a major cause of kidney damage and is associated with several of the risk factors for kidney health (hypertension, diabetes, and atherosclerosis).
• eye diseases: age-related macular degeneration, cataracts, uveitis, premature retinopathy, keratitis, and ocular inflammation are just some of the eye problems associated with oxidative stress.

The analysis of oxidative stress

Possible approaches to oxidative stress analysis are of three types. On the one hand, there are tests for the assessment of oxidative stress based on the analysis of the levels of some of the products of oxidation. On the other, tests that directly assess levels of free radicals can be used. Such tests are, for example, used to assess levels of oxidative stress in the sperm of men with fertility problems. In this case, techniques used for direct measurement include chemoluminescence and cytoflurimetry, while examples of indirect measurements include assessments of lipid peroxidation, oxidoreductive potential, and total antioxidant capacity.

Finally, oxidative stress analysis can be based on genetic tests; however, these do not assess oxidative stress levels as such but the predisposition to accumulate free radicals as written in the genes. 

How do you combat oxidative stress? 

As mentioned, cellular defense weapons are not always sufficient to effectively fight free radicals, especially when they are produced in high amounts. What can be done, then, to decrease oxidative stress? On the one hand, you can try to prevent oxidative stress by limiting exposure to agents that promote free radical formation, such as tobacco smoke. On the other, it is possible to enrich one's anti-free radical armamentarium with foods that are sources of exogenous (i.e., from outside the body) antioxidants and anti-oxidative stress supplements.

How do antioxidants taken in food and supplements work?

There are different types of antioxidants:

- primary antioxidants prevent the formation of free radicals;
- secondary antioxidants eliminate them;
- tertiary antioxidants repair molecules damaged by oxidative stress.

What are the best natural antioxidants?

The best natural exogenous antioxidants include vitamin C, vitamin E, carotenoids, selenium, zinc, phenolic compounds, lecithins, and coenzyme Q10. They are found in foods, especially those of plant origin; not surprisingly, a diet rich in fruits and vegetables can effectively counteract the consequences of oxidative stress.

Omega-3 fatty acids are also attributed antioxidant properties. This is one of the reasons why they are considered allies of athletes' health: they can help manage post-workout and post-competition oxidative stress and, more importantly, the inflammatory phenomena associated with it.

What are the best antioxidant supplements?

Today, many of the antioxidants found in food can also be taken in the form of supplements against oxidative stress. Unfortunately, their effectiveness is not always comparable to that of consuming fruits and vegetables. In some cases, completely unexpected side effects have also been established. This is why, for example, beta-carotene supplements are not recommended for smokers: despite their antioxidant potential, they may increase the risk of lung cancer in smokers. In other cases, as with vitamin E, adverse effects are associated with taking very high doses of antioxidants.

It is therefore essential that supplements against oxidative stress be taken only after making sure thereare no contraindications (such as smoking in the case of beta-carotene). At the same time, it is important to make sure that the doses of antioxidants contributed are not excessive. These expedients, together with the preference for products that guarantee high standards of purity and freshness of the ingredients, makes it possible to derive the maximum possible benefits from antioxidant supplements without health risks.

Finally, a curiosity. In some supplements, the presence of antioxidants has a specific collateral function: to protect other ingredients from oxidation. For example, it is precisely vitamin E, used in non-dangerous concentrations, that can be exploited to prevent oxidation of the Omega-3s present in fish oil supplements and thus ensure the quality of the product. In Omega-3 supplements from krill oil, this action is carried out by another natural antioxidant, astaxanthin, a carotenoid naturally present in this oil.

Sources:

Agarwal A and Majzoub A. Laboratory tests for oxidative stress. Indian J Urol. 2017 Jul-Sep;33(3):199-206. doi: 10.4103/iju.IJU_9_17

Alabdali A et al. Antioxidant activity of Curcumin. Research Journal of Pharmacy and Technology. 2021; 14(12):6741-6. doi: 10.52711/0974-360X.2021.01164

Albert BB et al. Oxidation of Marine Omega-3 Supplements and Human Health. Biomed Res Int. 2013; 2013: 464921. doi: 10.1155/2013/464921 

do Nascimento Marreiro D et al. Zinc and Oxidative Stress: Current Mechanisms. Antioxidants (Basel). 2017 Jun; 6(2): 24. doi: 10.3390/antiox6020024

Gammone MA et al. Omega-3 Polyunsaturated Fatty Acids: Benefits and Endpoints in Sport. Nutrients. 2018 Dec 27;11(1):46. doi: 10.3390/nu11010046

Mehta SK and Gowder SJT. Members of Antioxidant Machinery and Their Functions, in SJT Gowder (ed.), Basic Principles and Clinical Significance of Oxidative Stress, IntechOpen, London. 2015. doi: 10.5772/61884

NIH. Antioxidant: In Depth. https://www.nccih.nih.gov/health/antioxidants-in-depth. Last viewed: 7/27/22 

O'Connor E et al. Nutritional Compounds to Improve Post-Exercise Recovery. Nutrients. 2022 Nov 29;14(23):5069. doi: 10.3390/nu14235069

Pereira CPM et al. Antioxidant and anti-inflammatory mechanisms of action of astaxanthin in cardiovascular diseases (Review). Int J Mol Med. 2021 Jan; 47(1): 37-48. doi: 10.3892/ijmm.2020.4783

Pisoschi AM et al. Oxidative stress mitigation by antioxidants - An overview on their chemistry and influences on health status. Eur J Med Chem. 2021 Jan 1;209:112891. doi: 10.1016/j.ejmech.2020.112891

Saini R. Coenzyme Q10: The essential nutrient. J Pharm Bioallied Sci. 2011 Jul-Sep; 3(3): 466-467. doi: 10.4103/0975-7406.84471

Tinggi U. Selenium: its role as antioxidant in human health. Environ Health Prev Med. 2008 Mar; 13(2): 102-108. doi: 10.1007/s12199-007-0019-4

Tomczyk M et al. Athletes Can Benefit from Increased Intake of EPA and DHA-Evaluating the Evidence. Nutrients. 2023 Nov 26;15(23):4925. doi: 10.3390/nu15234925