Free radicals are not just something that needs to be “neutralized.” In the right amounts, they are part of normal cell communication. The problem arises when this balance is lost.

When we hear the word antioxidant, the same simple story almost always follows: free radicals damage cells, and antioxidants neutralize them.

The biological reality is much more interesting.

Our cells do not try to eliminate all reactive oxygen molecules. On the contrary, they intentionally produce some of them because they serve as signals that help regulate metabolism, stress responses, immune processes, and cellular adaptation.

That is why the goal is not a life without oxidants.

The goal is redox balance. Nature

What are free radicals, really?

A free radical is a molecule or atom that contains an unpaired electron.

Such a structure can make it highly reactive, meaning it is prone to reacting with other molecules.

But the frequently used term ROS – reactive oxygen species is a broader concept.

It includes, for example:

superoxide anion (O₂•−)
hydroxyl radical (•OH)
hydrogen peroxide (H₂O₂)

An important nuance is that not all ROS are free radicals. Hydrogen peroxide, for example, does not have an unpaired electron, but it is a redox-active molecule and can participate in biological signaling. Nature

This already shows why the “free radicals = bad” story is too simplistic.

Why does the cell produce reactive molecules at all?

One source is located in the mitochondria.

As electrons pass through the electron transport chain to enable ATP production, a small fraction can react with oxygen and lead to the formation of superoxide.

But ROS can also be produced via other enzymatic systems in the cell.

This is not just a biological error.

In controlled concentrations, certain reactive molecules act as signaling molecules.

They can temporarily modify certain amino acids in proteins, especially cysteine residues, thereby changing the activity of enzymes, receptors, and transcription factors.

In this way, redox signals can convey information to the cell:

change metabolism

adapt to stress

activate defense systems

alter gene expression

Because of this, modern biology speaks less and less about just “oxidants vs. antioxidants” and more and more about redox signaling. Nature

When does a useful signal become oxidative stress?

The problem arises when the production of oxidants becomes greater than what the cell’s systems can control.

That is when redox signaling begins to turn into oxidative stress.

Reactive molecules can begin to uncontrollably react with:

cell membrane lipids,

proteins,

DNA,

and other important biomolecules.

The consequence is no longer precise signaling, but chemical damage. PubMed Central (PMC)

Interestingly, the threshold is not the same for every cell.

A neuron, a liver cell, and a muscle cell have different metabolism, different sources of oxidants, and different defense capacities.

Therefore, oxidative stress is not a single universal value that we can simply measure and declare as “high” or “low.”

It is a dynamic state of the entire system.

Redox balance is not a state of rest

The very term “balance” can create a wrong impression, as if the cell is trying to maintain one constant value.

In reality, the redox state is constantly changing.

After a meal.

During physical activity.

During an immune response.

In case of oxygen deficiency.

During energy production in the mitochondria.

The cell does not maintain a perfectly static equilibrium but is continuously adapting.

This is why researchers today also use the term redox homeodynamics – the dynamic regulation of the production, utilization, and removal of reactive molecules. Nature

How does the cell defend itself?

Our cells possess an extremely sophisticated internal antioxidant system.

Among the key components are enzymes such as:

superoxide dismutase (SOD)
catalase
glutathione peroxidase
peroxiredoxin

Alongside them work molecules like glutathione, one of the most important cellular redox systems.

These systems do not work in isolation.

One molecule can convert a reactive species into another, another enzyme then removes it, and the depleted antioxidant system must subsequently be regenerated.

In other words:

antioxidant defense is not a wall. It is a network. PubMed Central (PMC)

Glutathione: one of the central systems of redox balance

Glutathione is often cited as the cell's “master antioxidant,” but it is more accurate to describe it as part of one of the most important cellular redox buffers.

It exists mainly in a reduced form, GSH, and an oxidized form, GSSG.

The transition between these forms allows the cell to accept and donate electrons, thereby controlling the oxidation-reduction environment.

To recreate reduced glutathione, the cell uses enzymes and the reducing power of molecules like NADPH.

Therefore, a cell’s antioxidant capacity is not just a question of how much of a certain “antioxidant substance” is present.

What matters is whether the entire system can regenerate.

Nrf2: when the cell boosts its own defense

One of the most interesting parts of redox biology is the Nrf2 protein.

We can think of it in simple terms as a regulator that helps the cell react when its chemical environment changes.

Under normal conditions, its activity is strictly controlled.

When certain redox signals rise, Nrf2 can become more active and enter the cell nucleus, where it influences the expression of a range of genes associated with defense against oxidative and chemical stress.

Among these are genes linked to glutathione synthesis and other protective enzymatic systems. PubMed Central (PMC)

This changes the way we can think about antioxidants.

Sometimes the most interesting question is not:

“How many radicals can this molecule neutralize?”

but:

“How does this molecule affect the way the cell defends itself?”

Where does alpha-lipoic acid fit into this story?

Alpha-lipoic acid (ALA) is particularly interesting because it sits at the intersection of energy metabolism and redox biology.

Lipoic acid, which the body produces itself, acts as an important cofactor for several mitochondrial enzyme complexes, including the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes.

These enzymes participate in converting nutrients into energy and connecting different parts of metabolism. PubMed Central (PMC)

But lipoic acid can also exist in a free form, in which case it exhibits other redox properties.

That is why calling it just an “antioxidant” is quite limiting.

Why R-alpha-lipoic acid?

Alpha-lipoic acid exists in two spatial forms, or enantiomers:

R-ALA and S-ALA.

Naturally produced lipoic acid in biological systems is found in the R-configuration.

It is precisely the R-form that is bound to certain mitochondrial enzymes and acts as their physiological cofactor.

The S-form does not occur naturally in the same way and is mainly the result of chemical synthesis; conventional synthetic alpha-lipoic acid is often produced as a mixture of R and S forms. PubMed Central (PMC)

It is important, however, to distinguish two things:

endogenous R-lipoic acid bound to mitochondrial enzymes

and

free R-ALA taken orally as a dietary supplement.

Their biology is not entirely the same.

ALA and DHLA: a redox pair

Alpha-lipoic acid can be reduced to dihydrolipoic acid – DHLA.

ALA and DHLA together form a redox pair that can accept and donate electrons.

In experimental systems, ALA/DHLA can participate in reactions with various reactive species, influence the availability of glutathione, and participate in the regeneration of other redox systems. PubMed Central (PMC)

But this is precisely where an important difference arises between the popular and the more precise explanation.

ALA is not just a molecular “sponge” that travels through the body catching free radicals.

Its influence can be much more indirect.

Instead of just neutralization: supporting the network

Experimental research shows that alpha-lipoic acid can influence glutathione levels.

One of the possible mechanisms involves increasing the availability of cysteine, an amino acid required for its synthesis.

ALA is also associated with the regulation of the Nrf2 signaling pathway and the expression of some genes involved in endogenous antioxidant defense. PubMed Central (PMC)

In other words, the potential value of such a molecule is not just:

ALA + free radical → neutralized radical

but it can include:

redox signal → cellular response → change in defense systems

This is much closer to how modern biology views antioxidant defense.

And more antioxidants are not necessarily better

This is perhaps the most important part of the entire story.

If oxidants were always bad, the logical conclusion would be that we should eliminate as many as possible.

But that is not how the cell functions.

Too low a level of certain reactive molecules can also interfere with normal signaling.

There is even an opposite condition to oxidative stress, called reductive stress, in which the cellular environment is excessively shifted toward reduction.

Modern redox biology therefore distinguishes between useful, physiological redox signaling and a state in which it becomes excessive and harmful. Nature

That is why the formula:

more antioxidants = more protection

is not scientifically precise enough.

The goal of a biological system is not to maximally neutralize oxidation.

The goal is to control it.

Oxidation is not an enemy of life

Oxidation-reduction reactions are at the very foundation of life.

Without electron transfer, we would not have normal ATP production.

Without certain ROS signals, cells would not properly react to changes in the environment.

Without the oxidative activity of immune cells, some defense processes would not function in the same way.

The problem, therefore, is not the existence of oxidation.

The problem is the loss of control over it.

That is what the concept of oxidative stress is actually trying to describe.

An antioxidant is part of a system, not its replacement

R-alpha-lipoic acid is a good example of why the word “antioxidant” can be too narrow.

Natural R-lipoic acid is simultaneously linked to mitochondrial metabolism, electron transport, redox reactions, and the regulation of cellular defense systems. PubMed Central (PMC)

This does not mean that oral R-ALA consumption automatically produces a specific health effect, nor that a higher dose will necessarily mean better protection. Clinical results of supplementation vary depending on the population, dose, duration of the study, and observed outcome. For example, meta-analyses in certain clinical populations find changes in some metabolic or oxidative biomarkers, but it is not justified to automatically apply such results to healthy individuals. PubMed

A scientifically more interesting conclusion is something else:

antioxidant protection is not a single molecule. It is a coordinated network.

The cell does not want to eliminate oxidation. It wants to keep it under control.

ROS are created continuously.

Antioxidant systems react continuously.

Glutathione transitions between reduced and oxidized states.

Proteins change their activity.

Nrf2 changes gene expression.

Mitochondria adapt their metabolism.

This is redox biology.

Not a battle between “good antioxidants” and “bad free radicals,” but an extremely precise biochemical balance in which the same molecules at one concentration can serve as useful signals, and at another, become a source of damage.

That is why perhaps the most precise question is less:

“How can we remove free radicals?”

and more:

“How does the cell maintain the balance between signals, energy, and protection?”

Literature and sources

[1] Sies H, Mailloux RJ, Jakob U. Fundamentals of redox regulation in biology. Nature Reviews Molecular Cell Biology. 2024;25:701–719. A modern review of redox signaling, redox homeodynamics, and the difference between physiological redox signals and oxidative or reductive distress. Nature

[2] Mitochondrial Physiology of Cellular Redox Regulations. 2024. A review of mitochondrial sources of superoxide, H₂O₂, antioxidant systems, and redox signaling. PubMed Central (PMC)

[3] Reactive oxygen species in biological systems: Pathways, associated diseases, and potential inhibitors—A review.Food Science & Nutrition. 2024;12:675–693. Overview of physiological and potentially harmful functions of ROS. PubMed Central (PMC)

[4] Total Antioxidant Capacity: Biochemical Aspects and Clinical Significance. 2023. Overview of redox homeostasis, oxidative stress, and endogenous antioxidant systems. PubMed Central (PMC)

[5] The bridge between cell survival and cell death: reactive oxygen species-mediated cellular stress. 2023. Overview of the Nrf2 system and the role of redox balance in cell signaling. PubMed Central (PMC)

[6] Solmonson A, DeBerardinis RJ. Lipoic acid metabolism and mitochondrial redox regulation. Journal of Biological Chemistry. 2018. Fundamental overview of the role of lipoic acid as a mitochondrial cofactor and regulator of energy metabolism. PubMed Central (PMC)

[7] Alpha-Lipoic Acid: Biological Mechanisms and Health Benefits. 2024. Overview of the ALA/DHLA redox pair, glutathione, and molecular mechanisms of alpha-lipoic acid. PubMed Central (PMC)

[8] Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential. Overview of the differences between R- and S-enantiomers and the biological role of the natural R-form. PubMed Central (PMC)

[9] Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling. Overview of R-ALA as part of mitochondrial metabolism and the effects of free lipoic acid on redox signaling. PubMed Central (PMC)

[10] Alpha-Lipoic Acid: Biological Mechanisms and Health Benefits. Data on the interactions of ALA/DHLA with glutathione and other redox systems.