How Antioxidants Actually Work (and Where Marketing Gets It Wrong)

The word “antioxidant” sells everything from face cream to coffee to dog food. The marketing works because the underlying story is real. Free radicals do damage cells. Antioxidants do neutralize free radicals. The product label just leaves out everything that makes the full picture more complicated.

Here’s the full picture.

What Free Radicals Are

Normal cell metabolism produces energy through oxidative phosphorylation in mitochondria. The process generates ATP (your cells’ energy currency) by moving electrons through a series of protein complexes. Some electrons leak out before completing the chain and react with oxygen to form reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and hydroxyl radicals.

Free radicals are molecules or atoms with one or more unpaired electrons. Electrons strongly prefer to exist in pairs, so free radicals are chemically reactive. They grab electrons from nearby molecules, stabilizing themselves but destabilizing whatever they stole from. If that’s a DNA base, it can cause a mutation. If it’s a protein, it can alter its shape and function. If it’s a cell membrane lipid, it starts a chain reaction of lipid peroxidation that damages membrane integrity.

The Sies and Jones 2020 review in Nature Reviews Molecular Cell Biology (PMID: 31996093) describes reactive oxygen species as “pleiotropic physiological signalling agents,” which is important: free radicals aren’t purely harmful. At normal physiological levels, they act as chemical messengers. They’re involved in immune defense (white blood cells use ROS to kill pathogens), insulin signaling, and exercise adaptation (some oxidative stress after exercise triggers muscle adaptation). The problem is chronic overproduction, not any ROS at all.

Oxidative stress happens when ROS production outpaces the body’s capacity to neutralize them.

How Antioxidants Neutralize Free Radicals

Antioxidants work by donating an electron to a free radical. The key is that antioxidants can give up an electron without becoming dangerously reactive themselves. They either stabilize easily or pass the electron to another antioxidant molecule in a recycling chain.

Vitamin C (ascorbic acid) is a classic example. It donates electrons to neutralize free radicals and becomes oxidized to dehydroascorbic acid, which cells can then reduce back to ascorbic acid and recycle. Vitamin E (alpha-tocopherol) works in cell membranes, where it intercepts lipid radicals and stops peroxidation chain reactions. Vitamin C can then regenerate vitamin E, linking the two systems.

Polyphenols (flavonoids, tannins, resveratrol, quercetin) are plant compounds that also neutralize free radicals, but their effects in the body are more complex than simple electron donation. Many polyphenols act on cell signaling pathways, activate the Nrf2 transcription factor (which upregulates the body’s own antioxidant enzymes), and have anti-inflammatory effects. Halliwell’s 2007 review in Cardiovascular Research (PMID: 17141179) noted that polyphenols probably confer health benefits less through direct antioxidant activity and more through these signaling effects.

Your Body’s Own Systems Do the Heavy Lifting

This part doesn’t make it onto supplement packaging.

Your body has its own enzymatic antioxidant systems that handle the vast majority of ROS. The three main ones:

Superoxide dismutase (SOD) converts superoxide radicals into hydrogen peroxide, which is less reactive. Catalase then converts hydrogen peroxide into water and oxygen. Glutathione peroxidase neutralizes hydrogen peroxide and lipid peroxides using glutathione as the electron donor.

These enzyme systems are continuously active and respond dynamically to oxidative load. They’re not fixed defenses waiting to be supplemented, they’re regulated systems that upregulate when needed. Dietary antioxidants add on top of these systems, but they’re not the foundation.

Why ORAC Scores Are Useless

ORAC (Oxygen Radical Absorbance Capacity) is a lab test that measures how quickly a food extract neutralizes a free radical in a test tube. Acai berries, goji berries, and cacao powder score very high. So does ground clove. The test is technically measuring something real.

The problem: ORAC scores in a test tube don’t predict what happens after you eat that food. Most dietary antioxidants are poorly absorbed, rapidly metabolized, or transformed by gut bacteria into different compounds before reaching cells. The bioavailability of polyphenols from most foods is under 10%. The free radical environment in a test tube has nothing to do with the regulated, complex redox environment of a living cell.

The USDA actually removed ORAC data from its National Nutrient Database in 2012, stating that it had “no relevance to the biology of human health.” The FDA has discouraged using ORAC values in food marketing for the same reason. When a food label highlights ORAC content, it’s using a number that regulatory agencies have explicitly said doesn’t mean what the marketing implies.

What Clinical Trials Found About Supplements

Here’s where the story gets clinically important.

The CARET trial (the study Omenn et al. published in NEJM in 1996, PMID: 8602180) gave high-risk smokers beta-carotene and vitamin A supplements, expecting to reduce lung cancer risk based on observational data linking high beta-carotene intake with lower cancer rates. The trial was stopped early because supplemented participants had 28% more lung cancers and 17% more deaths than the placebo group.

Beta-carotene in food tracks with good health outcomes. Beta-carotene as a large-dose supplement increased cancer risk in high-risk people. These are not the same exposure.

The Bjelakovic et al. 2007 systematic review in JAMA (PMID: 17327526) analyzed 68 randomized trials of antioxidant supplements (vitamin A, vitamin E, beta-carotene, vitamin C, selenium) for primary and secondary disease prevention. Overall mortality was slightly higher in groups given vitamin A, vitamin E, or beta-carotene supplements compared to placebo. Vitamin C and selenium didn’t show clear harm, but they also didn’t clearly reduce mortality.

The antioxidant paradox: high-dose antioxidant supplements can interfere with the redox signaling that cells use to communicate and adapt. Exercise-induced ROS triggers muscle adaptation signaling. Large doses of antioxidants during exercise training have been shown in some studies to blunt training adaptations. Too much antioxidant activity can disrupt normal cell signaling, not just neutralize excess free radicals.

What Actually Seems to Work

Polyphenol-rich whole foods consistently show favorable associations in observational research. Berries, olive oil, dark chocolate, colorful vegetables, and legumes all appear repeatedly in studies of dietary patterns associated with lower cardiovascular risk and slower cognitive decline.

But Halliwell’s argument is convincing: the mechanism probably isn’t simple antioxidant capacity. It’s the whole nutritional package. Fiber feeds gut bacteria that produce anti-inflammatory SCFAs. Polyphenols activate Nrf2 and modulate cell signaling pathways. Vitamins C and E contribute to their respective functions in collagen synthesis and membrane protection. The food does many things at once, and isolating one compound and scaling the dose up in a supplement doesn’t replicate that.

This is a theme across nutrition science. The nutrition science explained article covers the broader “food matrix” concept. Whole foods are more than the sum of their measured parts. Supplements extract one part and assume they’ve captured the benefit. The clinical trial record suggests they often haven’t.

This article is for educational purposes only and does not constitute medical advice. Consult a qualified health professional before making changes to your diet or health regimen.