on November 05, 2026
The redox system: a fundamental communication network for cells
When talking about oxidative stress, people often think of a simple imbalance between free radicals and antioxidants. While useful for an initial understanding, this representation does not fully describe the complexity of the biological processes involved.
The body has a biochemical system called the redox system, present in all cells and extracellular compartments, which regulates numerous functions through oxidation and reduction reactions. The term redox itself comes from the combination of reduction and oxidation and identifies chemical reactions in which a transfer of electrons occurs between molecules.
This system is not only tasked with countering oxidizing substances. It participates in the regulation of energy metabolism, intracellular communication, immune response, gene expression, and adaptation processes to environmental stimuli.
Reactive oxygen species, commonly referred to by the acronym ROS, are important components of it. Among these are hydrogen peroxide, the superoxide anion, and the hydroxyl radical. Not all have the same reactivity, and not all exclusively play a harmful role.
At low concentrations and under controlled conditions, some reactive species act as true biological messengers. They can temporarily modify the activity of proteins, enzymes, and transcription factors, allowing the cell to adapt to changes in the internal and external environment.
Contemporary research therefore distinguishes between physiological oxidative stress, also defined as oxidative eustress, and harmful oxidative stress, or oxidative distress. The former is essential for cellular regulation; the latter manifests when the production and action of oxidizing species exceed the capacity of control and repair systems, promoting molecular alterations and loss of functionality.
Oxidation-reduction reactions: how electron transfer occurs
Oxidation-reduction reactions are chemical processes in which one species gives up electrons and another acquires them.
The molecule that gives up electrons is oxidized and acts as a reducing agent; the one that acquires them is reduced and acts as an oxidizing agent. The two processes occur simultaneously: oxidation cannot occur without a corresponding reduction.
It is important to remember that a substance is not necessarily oxidizing or reducing in every circumstance. Its behavior depends on the characteristics of the other species involved and the physicochemical conditions of the environment.
One example is ascorbic acid, or vitamin C, which in many biological conditions acts as a reducing agent, but can also participate in different reactions in the presence of particular metals and substrates.
Electron transfer is influenced by the reduction potential, expressed in volts. In general terms, electrons tend to transfer from the redox pair with the more negative reduction potential to the one with the more positive potential. In cells, however, the actual behavior also depends on the concentrations of the substances, the pH, the enzymes, and the organization of the cellular compartments.
From a biological point of view, redox reactions can involve the transfer of one or two electrons and assume different functions. Energy metabolism uses numerous electron transfer reactions, while cellular redox control also utilizes reversible modifications of specific chemical groups present in proteins.
These modifications allow for the regulation of the activity of enzymes and proteins involved in signal transmission.
When oxidizing species become biological messengers
One of the most important functions of the redox system is the ability to temporarily modify the activity of proteins.
One example is hydrogen peroxide, which can participate in the regulation of intracellular pathways through the reversible oxidation of particular sulfur-containing groups, especially those present in the cysteine residues of proteins.
These modifications can activate or inhibit enzymes, modify the function of receptors, and influence the activity of transcription factors, which are proteins that regulate gene expression.
Among the main systems involved are:
· Nrf2, a transcription factor that contributes to the regulation of antioxidant defenses and cellular detoxification systems;
· NF-κB, involved in the regulation of the inflammatory and immune response;
· MAPK, a family of signaling pathways that participates in the regulation of growth, differentiation, and response to stimuli;
· PI3K/Akt, a signaling system involved in cell survival, metabolism, and growth;
· HIF-1α, an important transcription factor in the cellular response to oxygen availability.
The redox system, therefore, should not be interpreted exclusively as a defense against free radicals. It is also a communication system that allows cells to recognize stimuli and adapt their behavior.
Research is deepening the role of peroxidoreductases and other antioxidant enzymes, which can also act as sensors and intermediaries in redox signal transmission.
The five main mechanisms involved in redox imbalance
Alterations in the redox system can have different origins. There is no single mechanism responsible for oxidative stress: different cellular sources can contribute to the production of reactive species and the modification of antioxidant defenses.
A useful interpretive model consists in identifying some of the main enzymatic and metabolic systems involved.
1. NADPH oxidase: the production of reactive species during inflammation
NADPH oxidases are membrane and intracellular enzymes that produce reactive oxygen species using NADPH as an electron donor.
These enzymes perform an important physiological function in the immune response. Some immune system cells, in fact, use the production of oxidizing species to help neutralize microorganisms.
The problem can arise when the activity of NADPH oxidases becomes excessive or inadequately regulated. In the presence of persistent inflammation, metabolic alterations, and vascular dysfunction, the production of reactive species can contribute to the maintenance of a pro-oxidant cellular environment.
Metabolic syndrome, some chronic inflammatory conditions, and alterations in endothelial function are among the areas in which the involvement of these enzymes is studied.
2. Mitochondria: the relationship between energy production and oxidative stress
Mitochondria are essential organelles for energy production. Through the electron transport chain and oxidative phosphorylation, they allow the cell to produce ATP, the main molecule used to provide energy to biological processes.
During this metabolism, some of the electrons can transfer to oxygen, contributing to the formation of the superoxide anion and other reactive species.
Under physiological conditions, the production of mitochondrial ROS also participates in the regulation of metabolism and adaptive responses. When, however, mitochondrial function is altered, the production of reactive species can increase and contribute to damage to membranes, proteins, and mitochondrial DNA.
Alterations in thyroid function, some metabolic conditions, and sedentary lifestyle can influence mitochondrial function, although the relationship between these factors and oxidative stress depends on the clinical context.
Regular physical activity represents an important adaptive stimulus: it can promote mitochondrial biogenesis and improve the efficiency of defense systems. Conversely, excessive exertion relative to the training level can cause a transient increase in the production of reactive species.
3. Hepatic microsomal systems: drug and xenobiotic metabolism
The liver represents one of the main organs for the transformation of substances introduced into the body.
Hepatic microsomes contain numerous enzymes, including those belonging to the cytochrome P450 family, which participate in the metabolism of drugs, environmental substances, and other compounds foreign to the body, defined as xenobiotics.
These enzymatic systems can generate reactive intermediates and contribute to the production of oxidizing species. Under physiological conditions, these processes are counterbalanced by detoxification systems and antioxidant defenses.
Some drugs can modify hepatic metabolism and the oxidative load, but it is not correct to consider every pharmacological treatment a cause of clinically significant oxidative stress. The effect depends on the substance, the dose, the duration of treatment, individual characteristics, and liver conditions.
This aspect is particularly important in patients who take multiple drugs or undergo oncological treatments: any nutritional or integrative interventions must be evaluated by a doctor, also to avoid interactions with therapies.
4. Xanthine oxidase: ischemia and reperfusion
Xanthine oxidase is an enzyme involved in purine metabolism. During the degradation of some molecules, it can contribute to the production of reactive oxygen species.
Its role has been studied particularly in ischemia-reperfusion phenomena. When a tissue receives an insufficient amount of blood and is subsequently re-perfused, metabolic changes can occur that promote the production of oxidizing species.
This phenomenon can contribute to cellular damage in several tissues, including cardiac and vascular tissues.
The relationship between ischemia, reperfusion, and ROS production is complex and also involves mitochondria, immune cells, and other enzymatic systems. It therefore cannot be attributed exclusively to xanthine oxidase.
5. Nervous system and glia: the relationship between emotional stress and redox signals
The nervous system also uses redox reactions to regulate communication between neurons and glial cells.
Monoamine oxidases, enzymes present mainly in mitochondria, participate in the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. During these reactions, hydrogen peroxide can be produced.
The nervous system has specific antioxidant mechanisms to control these molecules. However, metabolic alterations, inflammation, mitochondrial dysfunctions, and changes in neuronal regulation can contribute to a redox imbalance.
Persistent psycho-emotional stress can influence several physiological systems, including the hypothalamus-pituitary-adrenal axis, the autonomic nervous system, and the inflammatory response. The link between emotional stress and redox alterations is a subject of research, but it cannot be reduced to a single biochemical reaction.
This aspect underscores the importance of also considering the psychological and behavioral dimension in the overall assessment of health.
Antioxidants: why not all substances behave the same
Antioxidants constitute a very heterogeneous family of molecules, which can be classified based on their chemical nature, function, and origin.
Among the main endogenous systems are:
· Superoxide dismutase (SOD), which transforms the superoxide anion into hydrogen peroxide;
· Catalase, which contributes to the conversion of hydrogen peroxide into water and oxygen;
· Glutathione peroxidase, which uses glutathione to reduce peroxides;
· Glutathione, a key molecule for maintaining the intracellular reducing environment;
· Thioredoxin and thioredoxin reductase, involved in controlling the redox state of proteins.
To these are added substances obtained from food, such as vitamin C, vitamin E, curcumin, carotenoids, and polyphenols.
However, not all substances defined as antioxidants act in the same way. Some directly neutralize certain reactive species, others participate in the regeneration of oxidized molecules, while others modulate the expression of enzymes and defense systems.
It is also important to consider that an antioxidant substance can exhibit pro-oxidant behavior under specific chemical and biological conditions. This phenomenon depends on the concentration, the presence of transition metals, the type of substrate, and the cellular environment.
Vitamin C, for example, primarily performs a reducing function in the body, but under certain experimental conditions it can participate in reactions that promote the formation of reactive species.
This leads to an important principle: taking more antioxidants does not necessarily mean achieving greater biological protection. The goal is not to eliminate all oxidizing species, but to maintain the proper functioning of regulatory mechanisms.
From physiological oxidative stress to cellular damage
The difference between oxidative eustress and distress is essential to understanding the biological significance of redox reactions.
Physiological oxidative stress represents an adaptive response. During physical activity, for example, the controlled production of reactive species can stimulate the activation of defense systems and promote muscular and metabolic adaptation.
When the production of oxidizing species becomes excessive or persistent, however, more extensive and less easily reversible changes can occur.
The main molecular targets include:
· Membrane lipids: the peroxidation of polyunsaturated fatty acids can alter the structure and functionality of cell membranes.
· Proteins: oxidation can alter the three-dimensional structure and activity of enzymes, receptors, and transport proteins.
· DNA: reactive species can cause modifications of nitrogenous bases and damage to genetic material.
· Mitochondria: alterations to the membranes and components of the respiratory chain can impair energy production.
If repair systems fail to compensate for the damage, cell communication, energy metabolism, immune response capacity, and tissue renewal processes can be compromised.
Oxidative stress has been associated with numerous pathological conditions, including cardiovascular diseases, diabetes, neurodegenerative diseases, chronic inflammatory diseases, and some cancers.
However, this association must be correctly interpreted: oxidative stress can contribute to the pathogenesis and progression of some diseases, but it is not necessarily their primary cause. In many cases, there is a bidirectional relationship, in which the disease promotes redox alterations and these, in turn, can aggravate the pathological process.
The causes of redox imbalance: environment, metabolism, and lifestyle
The redox system is continuously influenced by internal and external factors.
Environmental factors may include:
· exposure to tobacco smoke;
· air pollution;
· ultraviolet and ionizing radiation;
· certain chemicals and contaminants;
· infections and inflammatory processes.
Lifestyle factors of particular importance include excessive alcohol consumption, a sedentary lifestyle, smoking, a limited diet, and the difficulty of recovery associated with persistent stress and insufficient sleep.
Metabolic conditions and chronic diseases can also alter the production of reactive species and the efficiency of defense systems.
However, there is no single oxidative stress profile applicable to all people. The response depends on age, genetics, metabolic conditions, physical activity, diet, environmental exposures, and the presence of any diseases.
For this reason, it is more accurate to speak of a dynamic redox balance, rather than imagining an unchanging ideal value to be achieved through the intake of antioxidant substances.
How oxidative stress is measured: the role of biomarkers
The assessment of oxidative stress is an important area of research, but it presents methodological difficulties.
Reactive species are often unstable, have a very short lifespan, and can be produced in different cellular compartments. Their direct measurement in the human body is therefore complex.
For this reason, various indirect biomarkers are used, which can measure oxidation products, antioxidant capacity, or specific molecular modifications.
Among the studied indicators are:
· malondialdehyde (MDA), associated with lipid peroxidation;
· isoprostanes, products of fatty acid oxidation;
· 8-OHdG, an indicator of oxidative modifications of DNA;
· carbonyl proteins, used to assess protein oxidation;
· reduced and oxidized glutathione, to further assess the cellular redox state.
No single indicator completely describes the organism's redox balance. The choice of test depends on the clinical or experimental question and must consider sensitivity, specificity, reproducibility, and possible interferences.
d-ROMs test: what it measures
The d-ROMs test is a colorimetric test used to assess the presence of reactive oxygen derivatives, in particular compounds attributable to hydroperoxides present in the biological sample.
The analytical principle is based on reactions involving iron and the formation of species capable of oxidizing a chromogenic reagent. The color change is measured through a photometric reading.
The result is generally expressed in Carratelli units (U.CARR), according to the system used by the method.
The test can be useful for obtaining an indirect indicator of the circulating oxidant load, but it does not directly measure all reactive species present in the tissues and does not identify the cellular source of the phenomenon.
Furthermore, the scientific literature has highlighted possible interferences due to serum components, including ceruloplasmin, iron, and other substances. For this reason, the result must be interpreted considering the analytical method and the conditions of the sample.
BAP test: the reducing capacity of plasma
The BAP test, an acronym for Biological Antioxidant Potential, assesses the reducing capacity of the biological sample through the ability to transform ferric iron (Fe³⁺) into ferrous iron (Fe²⁺).
The result provides an indication of the overall reducing capacity of the plasma, but it does not individually identify all antioxidant molecules and does not directly measure their activity in the different tissues.
The association between d-ROMs and BAP can offer complementary information: the former provides an indication of the oxidant load detected by the method, while the latter assesses the overall reducing capacity of the sample.
This combination can be used in some research and monitoring contexts, but should not be interpreted as an independent diagnosis of disease or as a complete measure of the redox status of each organ.
How to interpret the results
Reference values depend on the method used, the laboratory, the equipment, and the preanalytical conditions.
Scientific and popular literature on d-ROMs and BAP tests often reports indicative ranges, such as d-ROMs values between 250 and 300 U.CARR and BAP values above 2,200 micromoles of reduced iron per liter.
However, these numbers should not be considered universal diagnostic thresholds. On their own, they are not sufficient to establish the presence of a pathology, predict its onset, or prescribe a treatment.
An altered result must be evaluated by the doctor in the context of the patient's medical history, risk factors, other tests, and overall condition.
It is also important to emphasize that oxidative stress measurement is not currently a recommended annual screening test for the general population. Its potential usefulness must be evaluated in relation to the clinical situation and the purpose of the investigation.
Lifestyle and the redox system: how to support physiological defenses
Maintaining redox balance depends on a network of mechanisms involving metabolism, diet, movement, rest, and stress response.
No single food or supplement can correct every form of redox imbalance. The most rational strategies are those that support normal physiological functions and reduce harmful exposures.
Varied and balanced diet
Fruit, vegetables, legumes, whole grains, nuts, and sources of unsaturated fats provide vitamins, minerals, and bioactive compounds involved in metabolic processes and cellular defense systems.
Polyphenols, carotenoids, and vitamins contribute to the protection of cellular structures through different mechanisms. However, the benefit of diet does not depend on a single active ingredient, but on the combination of nutrients and the overall quality of the dietary pattern.
Regular physical activity
Movement provides an adaptive stimulus for the redox system. Physical exercise can promote mitochondrial function and the activation of endogenous defense systems.
Intensity and duration must be appropriate to individual conditions. Excessive load, especially in untrained individuals or those with particular clinical conditions, can cause physiological stress that is not adequately compensated.
Sleep quality
Sleep plays a role in regulating metabolism, immune response, and recovery processes. Its insufficiency or fragmentation can be associated with metabolic and inflammatory alterations that also affect redox regulation.
Management of psycho-emotional stress
Persistent stress can affect the neuroendocrine response, the autonomic nervous system, and inflammatory processes. Relaxation techniques, breathing exercises, meditation, and psychological support, when necessary, can contribute to overall well-being.
Reduction of harmful exposures
Avoiding smoking, limiting alcohol consumption, reducing exposure to pollutants when possible, and adopting protective behaviors against ultraviolet radiation are measures consistent with health protection.
Antioxidant supplements: why personalization is important
The use of antioxidant supplements must be carefully evaluated. The presence of a substance with laboratory-proven antioxidant activity does not automatically mean that its intake produces a clinical benefit.
The response depends on the molecule, dose, bioavailability, duration of intake, and the person's physiological conditions.
Furthermore, the unnecessary intake of high doses of certain antioxidants can interfere with normal redox signaling and, in certain conditions, with adaptation to physical activity or specific therapies.
This aspect is particularly relevant for cancer patients, who should not take antioxidant supplements during treatment without first consulting their oncologist. Some anticancer therapies use oxidative mechanisms to exert their effect, and interactions with supplements must be evaluated on a case-by-case basis.
The choice of a nutraceutical should therefore stem from an assessment of nutritional needs, clinical conditions, ongoing therapies, and available evidence, avoiding standardized protocols and self-medication.
Integrated Medicine: understanding the person beyond a single parameter
The redox system represents a meeting point between energy metabolism, inflammation, immune function, mitochondrial activity, and cellular communication.
For this reason, its study is particularly interesting in the field of Integrated Medicine, which considers health as the result of the interaction between different biological systems and individual factors.
A personalized assessment should not be based exclusively on a single test or the search for a presumed excess of free radicals. It must consider medical history, diet, physical activity level, sleep quality, emotional stress, environmental exposures, and any therapies.
The Moltitudo consultation fits into this perspective of personalizing the health journey: understanding the person's characteristics and identifying the priorities to address through diet, lifestyle, and, when appropriate, selected nutraceutical supports.
The goal is not to eliminate oxidation, because redox reactions are essential for life, but to promote the conditions that allow the body to maintain efficient physiological regulation.
Knowledge of the redox system therefore offers an important key to understanding: cellular health does not depend on eliminating every reactive species, but on the ability to produce, control, and use it correctly.
Future perspectives: from redox research to personalized medicine
Research on the redox system is developing increasingly sophisticated tools to identify reactive species, their molecular targets, and the modifications that occur in different tissues.
Mass spectrometry techniques, methods based on electron paramagnetic resonance, and molecular imaging systems allow for a deeper understanding of aspects that indirect tests cannot fully describe.
Another area of research involves the development of sensors capable of detecting redox changes in specific cellular compartments. These tools could help better understand the relationship between oxidative signals, metabolism, inflammation, and adaptation.
Laboratory tests already available can also be evaluated through further studies on reproducibility, reference values, and their actual usefulness in guiding clinical decisions.
The most interesting perspective is not to search for a single oxidative stress value valid for everyone, but to understand how the redox system changes under different physiological and pathological conditions.
This knowledge can contribute to medicine that is increasingly oriented toward personalization, in which interventions are chosen based on reliable clinical data and not merely the presence of an altered indicator.
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