Challenges in Oxidative Homeostasis and Supplementation (Episode 1)
Prof. Gabriele Costantino*
INTRODUCTION
During the two years of pandemics the quest and the demand for easy treatments to preserve and protect a status of health has significantly grown. As it usually happens when there is public interest and a mediatic over-exposition, the risk of jeopardizing concrete opportunities with unrealistic, if not fake, claims is high, and the scientific community, together with key stakeholders such as producers and consumers, is called to action to promote only evidence-based approaches.
Oxidative stress is commonly perceived as one of the most relevant phenomena leading to premature aging, chronic diseases, and tissue injuries. However, a proper classification of the concept is only seldom given, thus leading to incorrect statements concerning the need and the scope of antioxidant treatments. In this article, I would like to convince the readers that while oxidative stress can be associated with a variety of pathophysiological conditions, most of the scope of antioxidant treatments is directed to balancing and preservation rather than curing and restoring. Indeed, antioxidant food supplements are the case where a strong potential for preserving and promoting a healthy condition can be masked by unappropriated claims on therapeutic effects with unsubstantiated experimental validation.
Last, but not the least, I would like to point out that the mechanism by which antioxidant supplements exert their role in homeostasis is far more complex than ‘simple’ redox or radical scavenging mechanisms. While these latter are commonly used to experimentally characterize and rank naturally occurring antioxidants, they are unable to recapitulate their biologically observed properties. Rather, increasing data are accumulating that oxidative (and inflammatory) homeostasis is regulated through receptors and transcription factors. A systemic approach is thus required to fully understand and fully exploit the potential of antioxidant supplements.
AN OXIDANT WORLD
First, a definition for oxidative stress should be given. All the living organisms on Earth live under an oxidant atmosphere, characterized by a percentage of molecular oxygen of about 20%. We all know the fate of a piece of iron left outside: in a short time, it becomes completely oxidized (rusted). Why does the same not happen to us? Or, at least, it does not happen so fast to us? The reason is simple: we – living organisms- are made of carbon, hydrogen, and a few more atom types, which are ‘singlet species’ in their most stable electronic state. Molecular oxygen is an exception, being a ‘triplet species’. People may be scared by these terms, but it can be made easier by saying that bonding electrons are differently disposed in molecular oxygen compared to most of the biological molecules. This means that the reaction between biological, carbon-based, molecules and (triplet) molecular oxygen is ‘forbidden’ (which means, in reality, very slow).
However, you may easily counterargument that oxygen is everywhere in biological molecules: in amino acids, in proteins, in fats, in sugars, and so on. Even more: oxygenation is the preferred way to eliminate toxic or catabolic products from the body. Enzymes do this job, they are called oxygenases, and there are a plenty of them in our organism and, chemically, their task is to accelerate the slow reaction between molecular oxygen and carbon-based substrates. These enzymatic reactions proceed in most cases by forming reactive oxygen species (ROS). Among these, most are ‘radicals’ (very reactive, with unpaired electrons) such as superoxide ion, hydroxyl radical, peroxynitrite, others, such as hydrogen peroxide (H2O2) are not. And this happens at every moment in every single cell of our body! Thus, the first message to be taken is that production of oxidizing species and free radicals is a physiological process.
Not only! In most cases it is a beneficial physiological process. So, why should we bother with antioxidant supplementation?
Well, here comes the second point. Nature is often drastic in its behavior, and one has to keep in mind that living organisms are evolved to preserve genomic integrity. Individual cells can be easily sacrificed if endogenous check-point mechanisms suspect genomic damage. When this happens, and this does happen! We perceive it as a tissue lesion, as a weakness, as aging and wellness unbalance.
Take the case of atmospheric pollution. Aromatic hydrocarbon particles constantly challenge our skin. These particles have a high potential to harm the cell’s DNA and thus detoxifying mechanisms based on oxidation of these aromatic hydrocarbons are constantly activated. Observe that oxidation is a means to make molecules more polar, more hydrophilic, which can be washed out (from the skin or other organs). However, strong and massive oxidation produces a lot of reactive oxygen species (ROS), which severely harm the skin’s cells and we perceive this phenomenon as skin aging. On the other hand, under milder conditions, the same ‘oxidative’ pathways are able to produce anti-inflammatory molecules, regulate the immune response, and cope with pathogen infiltration. In a word, oxidative response contributes to a healthy organism.
As it happens with other conditions (think about chronic inflammation, or autoimmune diseases) a sustained oxidative response to a harmful stimulus may itself become harmful and in need of mitigation measures.
Hence, it is now apparent what is or should be the first scope of antioxidant supplementation: the scope is to balance the effect of oxidative activation by preserving its defensive role and at the same time by attenuating their unwanted effects in terms of cellular aging.