⚡ Oxidative Stress and Free Radicals: How the Antioxidant Network Works
Reactive oxygen species, causes of oxidative stress, and the three levels of cellular protection
Free radicals and oxidative stress are among the most popular topics in nutrition science. But what do they actually mean? A free radical is a molecule with an unpaired electron that tends to "steal" an electron from neighbors. Reactive oxygen species (ROS) form constantly in cells — as a byproduct of respiration in the mitochondria.
Oxidative stress itself is not a "breakdown" but a state of imbalance: when more reactive oxygen species are produced than the antioxidant system can neutralize. It is balance — not the complete absence of radicals — that matters for health.
What are free radicals and ROS
A free radical is a molecule or atom with one or more unpaired electrons on its outer orbital. Such a molecule is chemically very active: it tends to "take" an electron, damaging DNA, proteins and membrane lipids in the process.
The key reactive oxygen species: superoxide anion (O₂•⁻), hydrogen peroxide (H₂O₂) and the hydroxyl radical (OH•) — the most reactive and dangerous. They form mainly in the mitochondria during electron transport chain activity.
| ROS | Formula | Danger |
|---|---|---|
| Superoxide anion | O₂•⁻ | Moderate; a precursor of many other radicals |
| Hydrogen peroxide | H₂O₂ | Crosses membranes; source of the hydroxyl radical |
| Hydroxyl radical | OH• | Very reactive; damages DNA and lipids |
Where and why they form
ROS form in cells constantly, and that is a normal process. The main sources:
Respiration
The main source: during electron transfer, a small portion "leaks" and produces superoxide.
Defense
Phagocytes deliberately generate ROS to destroy bacteria and viruses.
Xenobiotics
Oxidative enzymes (for example, cytochromes) in the liver produce radicals while detoxifying substances.
UV, smoking, alcohol
Ultraviolet light, cigarette smoke, alcohol and some drugs increase ROS production.
The antioxidant network: three levels of defense
The cell defends itself against ROS not with a single substance but with a coordinated "network" of three levels:
| Level | Components | Role |
|---|---|---|
| 1. Enzymatic | SOD, catalase, glutathione peroxidase | Neutralize ROS itself, turning them into water and oxygen |
| 2. Small molecules | Glutathione, vitamins C and E, coenzyme Q10 | "Quench" radicals, restore damaged molecules |
| 3. Repair | DNA repair enzymes, proteasomes | Remove already damaged DNA and proteins |
Glutathione — the main intracellular antioxidant
Glutathione is a tripeptide made of glycine, cysteine and glutamic acid. It is the most abundant intracellular antioxidant: its concentration in cells reaches millimolar levels. It directly neutralizes radicals and is a cofactor of the enzyme glutathione peroxidase, which removes hydrogen peroxide and lipid peroxides.
With age and stress, glutathione levels may decline. Some studies associate higher glutathione levels with better health, although direct "glutathione" supplements are poorly absorbed — precursors (NAC) and substrates are more commonly used.
Superoxide dismutase and catalase — the enzyme arm
Superoxide dismutase (SOD) is the enzyme that neutralizes the first and most abundant radical — superoxide — converting it into hydrogen peroxide and oxygen. There are several forms of SOD requiring different metals: copper/zinc (in the cytoplasm) and manganese (in the mitochondria).
Catalase is an enzyme that breaks down hydrogen peroxide into water and oxygen. Together with glutathione peroxidase, it removes H₂O₂, preventing it from becoming a hydroxyl radical.
| Enzyme | Neutralizes | Required cofactors |
|---|---|---|
| SOD | Superoxide anion | Zinc, copper, manganese |
| Catalase | Hydrogen peroxide | Iron (heme) |
| Glutathione peroxidase | Hydrogen peroxide, lipid peroxides | Selenium |
Vitamins and polyphenols: antioxidants from food
From food we get both vitamin antioxidants and thousands of plant compounds (polyphenols). Here are the key ones and their sources with approximate content:
| Antioxidant | Foods | Approximate in 100 g |
|---|---|---|
| Vitamin C | Rose hips, kiwi, bell pepper, citrus | Pepper ~80 mg, rose hips up to 400–1000 mg |
| Vitamin E | Sunflower oil, almonds, nuts | Oil ~40 mg, almonds ~26 mg |
| Selenium | Brazil nuts, tuna, eggs | Brazil nut ~68–90 mcg (1–2 nuts) |
| Zinc | Oysters, beef, pumpkin seeds | Oysters ~30–60 mg, seeds ~7 mg |
| Polyphenols | Berries, green tea, dark chocolate, spices | Cocoa powder ~3000+ mg flavonoids |
What to do: practical conclusions
Oxidative stress is not "enemy number one" but a matter of balance. Practical steps to support the antioxidant network:
A diet rich in antioxidants
Berries, vegetables, nuts, greens and spices provide a broad spectrum of polyphenols and vitamins.
Adequate trace elements
Zinc, selenium, copper, manganese — the "raw material" for SOD, catalase and glutathione peroxidase.
Physical activity
Moderate training boosts your own antioxidant defense through adaptation (hormesis).
Reduce excess sources
Quitting smoking, moderating alcohol and protecting skin from excess UV reduce the load.
Full sleep
Cell recovery and repair depend heavily on sleep, including antioxidant processes.
What are free radicals?
Molecules with an unpaired electron that tend to "take" an electron from neighbors, damaging DNA, proteins and lipids.
What is oxidative stress?
An imbalance where more reactive oxygen species are produced than the antioxidant system can neutralize.
Are all free radicals harmful?
No. In moderate amounts they participate in signaling and immune defense. Chronic excess is the danger.
What is the antioxidant network?
Three levels of defense: enzymes (SOD, catalase), small molecules (glutathione, vitamins C and E) and repair systems.
Which antioxidant is the main one?
Glutathione is the most abundant intracellular antioxidant, but it works together with enzymes and trace elements.
Do antioxidant supplements help?
Not always. High doses of individual antioxidants did not reduce risk in studies and sometimes increased it. Food is more balanced.
Which trace elements are needed?
Zinc, copper, manganese (for SOD), selenium (for glutathione peroxidase), iron (for catalase).
Does exercise increase or reduce oxidative stress?
Moderate training boosts your own antioxidant defense. Excessive training without recovery can overload.
How to reduce oxidative stress?
Quit smoking, moderate alcohol, eat an antioxidant-rich diet, sleep well and stay active.
Is N-acetylcysteine (NAC) beneficial?
NAC is a cysteine precursor for glutathione synthesis and is often used as a mucolytic and antioxidant, but consult a doctor.