The chemistry of oxidative stress

Oxidation-reduction reactions are natural processes within the body, and occur in any energy process in which oxygen is involved. These are necessary reactions but they rely on a delicate balance that, if altered, triggers a pathological condition called oxidative stress. When a particular organ or tissue in the body is said to be damaged, there is always an underlying alteration of a chemical process, and, more simply, we can say that the damage is almost always oxidative. The chemistry of oxidation-reduction reactions is a very complicated world, and what is presented in this article aims only to give some basic information to understand what is meant when we talk about oxidative stress and how it can be measured, without running the risk of trivializing the topic.

Free radicals vs. antioxidants

Free radicalsA free radical is a particularly reactive molecule or atom that contains at least one odd electron in its outermost orbital. Because of this chemical characteristic, free radicals are highly unstable and try to return to equilibrium by stealing from the nearby atom the electron needed to equalize its electromagnetic charge. This mechanism gives rise to new unstable molecules, triggering a chain reaction that, if not stopped in time, ends up damaging cellular structures and metabolic processes. accumulate during oxidation reactions. These, too, when in an condition of equilibrium, are balanced by the production of antioxidant molecules that can neutralize them. However, if their production becomes uncontrolled and excessive due to external factors such as pollution, an unhealthy lifestyle, unhealthy diet, sedentary lifestyle or, on the contrary, excessive physical exertion, a condition of oxidative stress is provoked. The damage always begins in the mitochondria, the so-called powerhouses of cells, which provide energy for reactions that rely on oxygen consumption.

Oxidation-reduction reactions are natural in the body, but they rely on a delicate balance that, if altered, triggers a pathological condition called oxidative-stress

What are the “best” antioxidants?

Among the most publicized substances to combat aging and the much-demonized free radicals are antioxidants. Natural or chemical, we often tend to abuse antioxidants, considering them almost the panacea for all ills. Obviously this is not the case, and the first reason is that many of the antioxidants found on the market are not effective.

One of the most valuable and readily available antioxidants, both in the diet and commercially, is vitamin C. Making sure we are getting the right amount of vitamin C, which is found as we know in many fruits and vegetables, is a good way to protect ourselves from oxidative stress. Then there are more powerful antioxidants. One among them is glutathione, a molecule that exists in both oxidized and reduced forms. To neutralize free radicals, of course, it is necessary to focus on the reduced form, the one that has antioxidant power.

What is the best way to take glutathione?

It is a molecule produced largely by the liver and composed of three amino acidsAmino acids are the basic substances that make up proteins. Each protein is characterized by a precise sequence of amino acid "bricks". Some are produced by the body by processing food, others, which the body cannot synthesize, must be taken directly with food.. In addition to blocking free radicals very efficiently, glutathione activates “detoxifying” processes in cells. Pharmacologically, however, it is difficult to manage. In fact, if the endogenous glutathione produced by the liver manages to reach all tissues and cells without difficulty, thereby counteracting free radical activity and aging processes, the synthetic exogenous glutathione taken orally comes to a very different end. Enzymes (called gamma-glutamyl transferases) are present in the intestines that hydrolyze it and drastically reduce its bioavailability. The bioavailability of glutathione also appears to be further reduced by the first-pass effect in both the intestine and liver. Gut and liver cells, in essence, sequester it. In addition, glutathione itself has a poor ability to enter cells because it lacks a specific receptor. In other words, it is not very “bioavailable.”

Therefore, in some specific cases (for example, in the presence of liver disease), and under strict medical indication, glutathione is administered at high doses intravenously. Lately, however, partly because of the pandemic, we often hear of people taking it this way without medical indication. “Personally, I am against this approach for two reasons,” says Alberto Beretta, immunologist and Scientific Director of SoLongevity: “First, because measuring how much glutathione is already present in the body is difficult and for this reason, proper dosing is not given. The second reason is a direct consequence: if too much glutathione is injected, the excess amount will act in the opposite way to what is desired. It becomes pro-oxidant. Instead, the best way to work with glutathione is to provide the three amino acids of which it is composed and let the body make exactly the amount of glutathione it needs on its own.”

“If too much glutathione is injected, the excess amount will act in the opposite way to that desired. It becomes, insead, pro-oxidant.”

It’s all about balance

“It should be understood,” Beretta continues, “that when working in this area there is always a reaction and a counter-reaction. It is the balance between the two that generates well-being. The clinical studies we conducted on our supplement CellFasting, which contains glutathione precursors, show that the oxidized and reduced species in plasma are perfectly balanced.”

In physics it is said that for every action there is an equal and opposite reaction, and the maxim seems to apply well to antioxidants. Certain therapies-such asozone therapy-also work on the basis of a similar mechanism: they are actually pro-oxidants, but they stimulate the antioxidant reaction. Finally, it is well known thatphysical activity triggers oxidative processes at the muscle level, but if carried out in moderation and constancy it actually stimulates the production of anti-oxidants and is found to have a protective and beneficial effect on the body.

Exercise is a powerful antioxidant. If excessive and exhausting, however, it has the opposite effect and produces free radicals

How is oxidative stress measured?

Oxidative stress is a pre-pathological condition and gives no signal, but it is usually assessed on the basis of risk factors. It is therefore difficult to detect clinically although several techniques have been developed over the years. They are used in the world of research or clinical practice to measure excess free radicals in the body.

SoLongevity researchers, for example, use high-pressure liquid chromatography. The examination is based on the fact that different chemical species, separated through special chemical processes in a special machine, have different detection times. In the case of free radicals, this is a reliable but complex and expensive test, which is why it is not used in clinical practice but only in research.

A widely used test, however, was developed by an Italian chemist, Mauro Carratelli, and involves the analysis of different species of reactive oxygen radicals. The test is called d-ROMs(Reactive Oxygen-Free Radical Metabolites) and specifically measures the amount of lipid peroxides or hydroperoxides generated in cells by free radical attack in the patient’s blood. This is a measurement that correlates well with oxidative stress damage, and only one drop of blood is needed to obtain it. In the near future, it could also be used in Longevity Pharmacies, pharmacies that adopt SoLongevity’s check-up solutions for primary prevention.

While the d-ROMs test directly quantifies the body’s level of oxidative stress, there is another test called BAP that measures the body’s ability to counteract the formation of oxygen free radicals. What, in jargon, is called plasma antioxidant potential, manages to consider both antioxidants of an exogenous nature (such as Vitamin C or E) and those of an endogenous nature produced, for example, by the liver.

Another of the consequences of increased free radicals in the body is theoxidation of LDL lipoproteins, or cholesterol. The risk, when these are present, is mainly in terms of the onset of cardiovascular disease or atherosclerosis. These cause damage to the inner walls of blood vessels and can also induce a rupture of atherosclerotic plaques and cause thrombi. An indirect-and less widespread-measure of the body’s state of oxidation, and thus of excess free radicals, is therefore precisely the measurement of oxidized cholesterol.

Still another way is based on measuring thiols, or plasma thiol groups, organic compounds that can be found in the reduced (protective) and oxidized form in the blood. If the two forms are in balance, we have an indication of balance of the organism as well.

Prevention and antiaging medicine

Investigations such as those described above are usually prescribed for heavy smokers, since smoking is one of the most powerful oxidants. They can also be indicated for professional athletes, since, as we have seen, excess physical activity leads to great oxygen consumption and, therefore, oxidative stress, which might be balanced by taking antioxidants. And they are, in any case, a useful diagnostic aid for early identification for all people who, whether due to age or lifestyle, may be at risk of developing oxidative stress and inflammation

Acting on oxidative stress, however, is a practice that is carried as a means of prevention, when there is not yet a disease to cure. Therefore, considering one’s lifestyle is crucial. Once an inflammatory disease, such as chronic gut diseases, for example, or a chronic cardiovascular disease, or even diabetes, is established, acting only on oxidative stress serves little purpose. Rebalancing oxidative stress is a topic primarily addressed in antiaging medicine, which when necessary, provides both diagnostics and planning for subsequent targeted intervention.

Finally, it should be emphasized that oxidative stress generates inflammatory processes because it stimulates the transcription of particular genes that, in turn, increase oxidative stress, thus triggering a vicious cycle. Often, therefore, to “treat” inflammation, it is necessary to see if there is an underlying oxidative stress condition, and to intervene accordingly.