Oxidative stress: the most effective dietary supplements

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

Understanding oxidative stress

Within cells, energy production via cellular respiration is a vital process that occurs in the mitochondria, during which about 2% of the oxygen consumed is converted into oxygen-derived free radicals. These molecules also play an essential role in immune defense by helping to destroy pathogens. However, their chemically unstable nature, due to the presence of an unpaired electron, drives them to react with other molecules to regain stability. This behavior can cause damage to lipids, proteins, and DNA when they are not neutralized by antioxidant systems. Our body has enzymatic antioxidant defenses, such as superoxide dismutase, catalase, and glutathione peroxidase, and non-enzymatic ones such as vitamins C and E. These systems neutralize reactive species by limiting their oxidative potential 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 are often linked to our lifestyle: • Air pollution: Fine particles and toxic gases present in ambient air stimulate the production of reactive species, particularly in the lungs. • Ultraviolet (UV) radiation: Excessive UV exposure can induce oxidative damage in skin cells by triggering the formation of free radicals. • Tobacco: Smoking, active or passive, is a major source of reactive species generated by the toxic substances inhaled. • Alcohol consumption: Ethanol and its metabolites promote oxidative stress, notably 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. Certain 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, notably β-oxidation of fatty acids. • Cellular respiration: Although mitochondrial respiration is a normal source of reactive species production, mitochondrial dysfunction can lead to excessive electron leakage and increased generation of free radicals. • Excessive hormone 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 aging-related diseases: • Cardiovascular diseases: Oxidation of low-density lipoproteins (LDL) plays a central role in atherosclerosis, increasing the risk of heart attacks and strokes. • Cancer: Oxidative damage to DNA promotes genomic instability, an underlying mechanism in tumor transformation. • Diabetes: Excess reactive species impair pancreatic β cells, reducing insulin secretion, and contribute to the onset of diabetic complications, including retinopathy and nephropathy. • Neurodegenerative diseases: Oxidative stress is strongly involved in the progression of diseases such as 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 status of antioxidant defenses. • DNA damage: 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a key marker of oxidative damage to DNA. It is often used to evaluate the effect of free radicals on genetic material. • Lipid peroxidation: Malondialdehyde (MDA) and isoprostanes are reliable indicators of damage to membrane lipids caused by free radicals. • Protein oxidation: Protein oxidation products, such as protein carbonyls, reflect alterations of 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 assess the body’s capacity to neutralize reactive species.

Prevention

The human body has an endogenous enzymatic arsenal that neutralizes free radicals by converting 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 removes 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, thereby limiting its oxidative potential. These endogenous enzymes are activated in response to oxidative stress, but their capacities can be exceeded 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 scavenging free radicals. • Vitamin C: Water-soluble, it acts in aqueous environments to neutralize free radicals, thereby protecting DNA and proteins. • Vitamin E: Fat-soluble, it integrates into cell membranes to prevent oxidation of polyunsaturated fatty acids. • Vitamin A and carotenoids: These compounds neutralize specific reactive species such as singlet oxygen, protecting tissues and membranes (notably 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, such as vitamin E. • Minerals: Zinc, copper, manganese, and selenium support the activity of antioxidant enzymes as mentioned above. 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 can increase free radical production, regular moderate physical activity stimulates antioxidant defenses. Furthermore, tobacco, alcohol, and environmental pollutants should be limited, while managing stress is important.