Oxidative Stress: Most Effective Dietary Supplements

Oxidative stress corresponds to a state in which reactive oxygen and nitrogen species, naturally produced during cellular respiration and immune responses, exceed the capacities of the body's antioxidant defense mechanisms. This imbalance leads to an accumulation of free radicals that can cause oxidative damage over time, implicated in the alteration of DNA, lipids, and proteins. These processes lead to cellular aging and the genesis of many chronic pathologies.

Understanding Oxidative Stress

In cells, the production of energy through cellular respiration is a vital process that takes place in the mitochondria, during which about 2% of the oxygen consumed is converted into oxygenated free radicals. These molecules also play an essential role in immune defense, helping to destroy pathogens. However, their unstable chemical nature, due to the presence of an unpaired electron, drives them to react with other molecules to regain stability. This behavior can lead to damage to lipids, proteins, and DNA when they are not neutralized by antioxidant systems. Our bodies have enzymatic antioxidant defenses, such as superoxide dismutase, catalase, and glutathione peroxidase, and non-enzymatic defenses such as vitamins C and E. These systems neutralize reactive species by limiting their oxidizing power and repairing the damage caused.

Factors Contributing to Oxidative Stress

Environmental factors play a key role in the accumulation of reactive species in the body. These elements, often related to our lifestyle:  Air pollution: Fine particles and toxic gases present in the ambient air stimulate the production of reactive species, especially in the lungs.  Ultraviolet (UV) rays: Excessive UV exposure can induce oxidative damage in skin cells by triggering the formation of free radicals.  Tobacco: Smoking, whether active or passive, is a major source of reactive species generated by inhaled toxic substances.  Alcohol consumption: Ethanol and its metabolites promote oxidative stress, particularly in the liver.  Unbalanced diet: A deficiency in antioxidant nutrients (vitamins C, E, selenium) or an excess of refined sugars and saturated fats can disrupt the balance between reactive species and antioxidant defenses. Some physiological or pathological processes within the body can also exacerbate the production of reactive species:  Chronic inflammation: When inflammation persists, immune cells (such as macrophages and neutrophils) release reactive species to eliminate pathogens, which can cause damage to healthy tissues.  Metabolic imbalances: Metabolic disorders such as obesity or diabetes increase levels of reactive species due to disruptions in metabolic pathways, especially fatty acid β-oxidation.  Cellular respiration: Although mitochondrial respiration is a normal source of reactive species production, mitochondrial dysfunction can lead to excessive electron leakage and increased free radical production.  Excessive hormonal production: Certain conditions, such as hyperthyroidism, can amplify metabolic processes and increase the generation of reactive species.

Consequences of Oxidative Stress

Oxidative stress is a key factor in the pathophysiology of many diseases associated with aging:  Cardiovascular diseases: The oxidation of low-density lipoproteins (LDL) plays a central role in atherosclerosis, increasing the risk of heart attacks and strokes.  Cancer: Oxidative DNA damage promotes genomic instability, an underlying mechanism in tumor transformation.  Diabetes: An excess of reactive species impairs pancreatic β-cells, reducing insulin secretion and contributing to the onset of diabetic complications, including retinopathy and nephropathy.  Neurodegenerative diseases: Oxidative stress is strongly implicated in the progression of diseases like Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, where it exacerbates neuronal death.

Biomarkers of Oxidative Stress

Oxidative stress can be assessed by specific biomarkers that reflect oxidative damage or the state of antioxidant defenses.  DNA damage: 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a key marker of oxidative DNA damage. It is often used to assess the effect of free radicals on genetic material.  Lipid peroxidation: Malondialdehyde (MDA) and isoprostanes are reliable indicators of lipid membrane damage caused by free radicals.  Protein oxidation: Protein oxidation products, such as protein carbonyls, reflect alterations in structural and enzymatic proteins due to oxidative stress.  Antioxidant defenses: Levels of enzymes like superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT), as well as concentrations of reduced glutathione (GSH) and antioxidant vitamins (C and E), are measured to evaluate the body's capacity to neutralize reactive species.

Prevention

The human body has an endogenous enzymatic arsenal that neutralizes free radicals by transforming them into less harmful compounds.  Superoxide dismutase (SOD): This enzyme catalyzes the conversion of the superoxide radical into hydrogen peroxide, a less reactive molecule. To function effectively, it requires cofactors such as manganese, copper, and zinc.  Glutathione peroxidase (GPx): It eliminates lipid peroxides and hydrogen peroxide using glutathione as a substrate. Selenium is essential for its activity.  Catalase: This enzyme converts hydrogen peroxide into water and oxygen, thus limiting its oxidizing potential. These endogenous enzymes are activated in response to oxidative stress, but their capacities can be overwhelmed in cases of prolonged or excessive exposure to external factors. When internal enzymatic systems are insufficient, dietary antioxidants come into play. These molecules act by directly trapping free radicals.  Vitamin C: Water-soluble, it acts in aqueous environments to neutralize free radicals, thus protecting DNA and proteins.  Vitamin E: Fat-soluble, it integrates into cell membranes to prevent the oxidation of polyunsaturated fatty acids.  Vitamin A and carotenoids: These compounds neutralize specific reactive species like singlet oxygen, protecting tissues and membranes (especially the skin).  Coenzyme Q10: In addition to its role in mitochondrial energy production, it acts as an antioxidant by inhibiting lipid peroxidation and regenerating other antioxidants, like vitamin E.  Minerals: Zinc, copper, manganese, and selenium support the activity of antioxidant enzymes as previously mentioned. A healthy lifestyle remains essential to reduce oxidative stress. Consuming fruits and vegetables rich in natural antioxidants such as polyphenols strengthens defenses against free radicals. Although intense exercise may increase the production of free radicals, regular moderate physical activity stimulates antioxidant defenses. Moreover, it is important to limit tobacco, alcohol, and environmental pollutants while ensuring stress control.