Antioxidants: What They Really Do

“Packed with antioxidants” is one of the most popular phrases in food marketing. Blueberries, green tea, dark chocolate and red wine have all been sold on their antioxidant content. But what does an antioxidant actually do at the level of molecules? And why haven’t antioxidant pills lived up to the hype? The chemistry is a neat application of redox reactions and radical chain reactions — and it explains both the promise and the disappointment.

Oxidation, radicals and the need for defence

In chemistry, oxidation is loss of electrons (or gain of oxygen, or loss of hydrogen); reduction is gain of electrons (see oxidation and reduction). Many damaging oxidations in living things are carried out by free radicals — species with an unpaired electron, such as the hydroxyl radical, HO•. Radicals start chain reactions: each one that reacts creates a new radical, so a single event can damage many molecules (see the chemistry of ageing).

An antioxidant is a substance that, at low concentration, significantly slows or prevents the oxidation of another substance. It does this in one of three main ways:

1. Breaking chains: donating an electron or a hydrogen atom to a radical, turning it into a stable molecule, while itself becoming a radical that’s too unreactive to continue the chain.
2. Preventing initiation: removing the things that create radicals — for example, destroying hydrogen peroxide or locking up iron and copper ions.
3. Repairing or removing damaged molecules.

How a chain-breaking antioxidant works

The key requirement is that the antioxidant must form a stable, unreactive radical after it reacts. If it formed a reactive radical, it would just pass the damage on.

Vitamin E: the membrane guard

Vitamin E is a family of fat-soluble compounds; the most active form in humans is α-tocopherol. It has a long hydrocarbon tail that anchors it in cell membranes and a ring with an –OH group (a phenol) that faces the membrane surface.

When a lipid peroxyl radical (LOO•) forms during lipid peroxidation, vitamin E gives it a hydrogen atom:

LOO• + TOH → LOOH + TO•

The resulting tocopheroxyl radical (TO•) is stabilised because the unpaired electron is spread (delocalised) over the aromatic ring. It’s too sluggish to attack the next fatty acid, so the chain stops. One vitamin E molecule can protect hundreds of fatty acid molecules because the chain reactions it stops would otherwise have gone on and on.

Vitamin C: the recycler

Vitamin C (ascorbic acid) is water-soluble, so it works in blood plasma and the watery interior of cells (see vitamin C chemistry). It’s an excellent reducing agent. It can donate an electron directly to radicals, and — importantly — it can regenerate vitamin E at the membrane surface:

TO• + ascorbate → TOH + ascorbyl radical

The ascorbyl radical is also stabilised by delocalisation, and two of them can react to form ascorbate and dehydroascorbic acid. Cells then reduce dehydroascorbic acid back to ascorbate using glutathione. This forms a relay: the radical’s “damage” is passed from membrane to water to enzymes that can deal with it safely.

Glutathione: the cell’s own antioxidant

Glutathione is a small peptide of three amino acids (glutamate, cysteine and glycine) made in all our cells (see peptide bonds). Its cysteine carries a thiol group, –SH, which can donate a hydrogen atom or electrons. Two oxidised glutathione molecules join through a disulfide bridge (GSSG), and an enzyme uses NADPH to reduce them back to two GSH. The ratio of GSH to GSSG is a sensitive measure of a cell’s oxidative state.

Preventive antioxidants: enzymes and metal binders

The body’s most powerful antioxidant defences aren’t vitamins at all — they’re enzymes:

• Superoxide dismutase turns superoxide into hydrogen peroxide and oxygen.
• Catalase breaks hydrogen peroxide into water and oxygen.
• Glutathione peroxidase (which contains selenium) reduces peroxides using glutathione.

Because enzymes are catalysts, each molecule can destroy millions of reactive molecules, far more than any vitamin molecule used up once.

Metal-binding proteins such as ferritin and transferrin also act as antioxidants, because free iron and copper ions catalyse the formation of hydroxyl radicals from hydrogen peroxide.

Antioxidants in food

Plants are full of antioxidant molecules, because they’re exposed to strong sunlight and make oxygen in photosynthesis. Common groups:

• Polyphenols (including flavonoids) in berries, tea, coffee, cocoa, apples and onions. Their many phenol –OH groups can donate hydrogen atoms, forming stabilised radicals.
• Carotenoids such as β-carotene (carrots) and lycopene (tomatoes). Their long conjugated chains are good at absorbing the energy of a reactive form of oxygen called singlet oxygen.
• Vitamins C and E in fruits, vegetables, nuts and seeds.

Antioxidants in food preservation

Antioxidants aren’t only about health. They’re widely used to keep food from going rancid. Rancidity in fats and oils is lipid peroxidation — the same radical chain reaction that damages cell membranes. Food manufacturers add antioxidants such as:

• Ascorbic acid (E300) — also stops cut fruit browning.
• Tocopherols (E306–E309).
• Synthetic phenols such as BHA (E320) and BHT (E321), which work in the same way as vitamin E.

Oil in a clear bottle in sunlight goes rancid faster, because light helps start the radical chains. Oils rich in polyunsaturated fatty acids spoil faster than saturated fats, because their weaker C–H bonds next to double bonds are more easily attacked.

Why antioxidant supplements disappoint

If oxidative damage contributes to disease, shouldn’t swallowing antioxidants help? Large, well-designed trials in the 1990s and 2000s tested exactly that. The results were largely disappointing:

• Vitamin E and β-carotene supplements generally didn’t reduce heart disease or cancer.
• In two large trials among smokers and asbestos workers, high-dose β-carotene was associated with more lung cancer.
• Combined analyses suggest some high-dose antioxidant supplements may slightly increase overall mortality.

Chemistry and biology offer several explanations:

1. Antioxidants can become pro-oxidants. Vitamin C can reduce Fe³⁺ to Fe²⁺, which then drives the Fenton reaction to produce hydroxyl radicals. Whether a molecule acts as an antioxidant depends on its surroundings.
2. Radicals have useful jobs. Reactive oxygen species act as signals that trigger the body’s own protective enzymes, help muscles adapt to exercise, and help immune cells kill bacteria. Some studies found high-dose vitamins C and E blunted training adaptations.
3. The body regulates its levels. Excess vitamin C is excreted by the kidneys; plasma levels plateau at moderate intakes.
4. Food isn’t just antioxidants. Fruit and vegetables contain fibre, potassium, folate and many other compounds. Their health benefits can’t be pinned on antioxidants alone. Many polyphenols are poorly absorbed, and their benefits may come from other effects, such as on gut bacteria.

“Antioxidant capacity” scores for foods, measured in test tubes, were once widely advertised. The United States Department of Agriculture withdrew its database of such values in 2012, noting they didn’t reliably reflect effects in the body.

Common misconceptions

• “More antioxidants are always better.” Too much can disrupt useful signalling and, in some contexts, act as a pro-oxidant.
• “Antioxidants are a type of nutrient.” It’s a description of chemical behaviour, not a single class of molecules.
• “Free radicals are always harmful.” The body makes some on purpose.
• “A high test-tube antioxidant score means a healthier food.” Absorption and metabolism change everything.

Key takeaways

• An antioxidant slows oxidation, usually by breaking radical chains or preventing radical formation.
• It must form a stable, unreactive radical — vitamin E and polyphenols do this by delocalising the unpaired electron over an aromatic ring.
• Vitamin C recycles vitamin E; glutathione recycles vitamin C; enzymes like SOD and catalase do the heavy lifting.
• Antioxidants protect food from going rancid.
• Supplement trials have largely been disappointing; a diet rich in fruit and vegetables is the better-supported approach.