Oxidative Stress: What It Is, Why It Arises, What It Causes, How to Reduce It

by luciano

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Oxidative stress is a biological condition characterized by an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them through antioxidant systems.
When this imbalance persists over time, the risk of molecular damage, cellular dysfunction, and the development of numerous chronic diseases increases.

What Is Oxidative Stress

Oxidative stress occurs when ROS production exceeds the capacity of endogenous and exogenous antioxidant systems to keep them within a physiological range.

ROS include:

  • true free radicals (e.g., superoxide O₂•⁻, hydroxyl radical •OH)

  • non-radical reactive species (e.g., hydrogen peroxide H₂O₂)

ROS are continuously produced during cellular metabolism, particularly in the mitochondrial electron transport chain.

BOX — ROS does not mean “toxic”
ROS are not intrinsically harmful. At low concentrations they perform essential functions:

  • cellular signaling

  • immune defense

  • adaptation to physical exercise

They become pathological only when they exceed redox control capacity.

Where ROS Come From

Endogenous production

  • mitochondrial respiration

  • nutrient metabolism

  • immune system activity

  • metabolism of drugs and xenobiotics

Factors that increase production

  • mitochondrial dysfunction

  • altered circadian rhythms

  • chronic psychophysiological stress

  • hyperglycemia and lipotoxicity

  • smoking, pollutants, UV radiation

  • unbalanced diet

What Is Redox Imbalance

Under normal conditions, the body possesses:

  • antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase)

  • non-enzymatic antioxidants (glutathione, vitamin C, vitamin E, polyphenols)

Oxidative stress arises when ROS production exceeds these defenses.

What Oxidative Stress Damages

DNA

  • oxidation of bases (e.g., 8-oxo-guanine)

  • strand breaks

  • mutations if repair is incomplete

Proteins

  • oxidation of amino acid residues

  • loss of three-dimensional structure

  • reduced enzymatic activity

Membrane lipids

  • lipid peroxidation

  • loss of fluidity

  • increased membrane permeability

Long-Term Consequences

The accumulation of oxidative damage is associated with:

  • cellular aging

  • cardiovascular diseases

  • type 2 diabetes

  • neurodegenerative diseases (Alzheimer’s, Parkinson’s)

  • increased cancer risk

Oxidative stress is not the only cause of these conditions, but it represents an important contributing biological factor.

BOX — Relationship between oxidative stress and inflammation
Oxidative damage is a direct mechanism.
Inflammation is a response to damage that, once established, can amplify it.
A vicious cycle often develops:

ROS → molecular damage → inflammatory activation → production of additional ROS → further damage

How to Reduce Oxidative Stress

The goal is not to eliminate ROS, but to restore redox balance.

Nutrition

  • high intake of vegetables

  • adequate protein intake

  • control of refined carbohydrates

  • reduction of oxidized and ultra-processed foods

Physical activity

  • moderate and regular

  • avoids both inactivity and overtraining

Sleep and biological rhythms

  • sufficient sleep

  • exposure to natural daylight

  • reduction of evening artificial light

Stress management

  • relaxation techniques

  • sustainable workload

Lifestyle

  • smoking cessation

  • alcohol moderation

BOX — Antioxidants: key point
The main objective is not to consume large amounts of exogenous antioxidants, but to strengthen endogenous antioxidant systems (e.g., via Nrf2).
Indiscriminate high-dose supplementation is not always beneficial.

Final Message

Oxidative stress represents a functional imbalance of the cellular redox system.
Its prevention requires an integrated approach addressing nutrition, movement, sleep, stress, and mitochondrial function.

RELATED ARTICLES published in:

(In-depth of “Oxidative Stress: What It Is, Why It Arises, What It Causes, How to Reduce It”)

  1. Mitochondria and oxidative stress

    • why they are the main source of ROS

    • mitochondrial dysfunction and chronic diseases

  2. Circadian rhythm and redox metabolism

    • sleep, light, meal timing

  3. Exercise, hormesis, and Nrf2

    • why physical activity is “antioxidant training”

  4. Low-grade chronic inflammation

    • what it is

    • relationship with oxidative stress

  5. Biomarkers of oxidative stress

    • F2-isoprostanes

    • 8-OHdG

    • GSH/GSSG

    • hs-CRP

    • integrated interpretation

  6. Antioxidant supplements: when they truly help

    • limits

    • risks of high doses

    • personalized approach

ESSENTIAL BIBLIOGRAPHY

Birben E. et al., Oxidative Stress and Antioxidant Defense, 2012
Betteridge DJ., What is oxidative stress?, 2000
Roberts LJ & Milne GL., Isoprostanes as markers of lipid peroxidation, 2000
Ristow M. et al., Antioxidants prevent health-promoting effects of exercise, 2009
Powers SK., Exercise-induced activation of Nrf2 signaling, 2024