Antioxidants 101: What You Need to Know 2022
You may have heard a lot of talk about antioxidants. There are hundreds,
probably thousands, of different substances that can act as antioxidants. The
most familiar ones are the ACE vitamins (vitamin A, C and E), beta-carotene, and
other related carotenoids, along with the minerals selenium, manganese. They’re
joined by glutathione, coenzyme Q10, lipoic acid, flavonoids, phenols, polyphenols, phytoestrogens, molecular hydrogen and many more. Most are naturally occurring, and their presence in food is
likely to prevent oxidation or to serve as a natural defense against the local
environment. Antioxidants tend to work best in combination with other
antioxidants (R).
The body’s trillion or so cells face formidable threats, from lack of food to
infection with a virus. Another constant threat comes from chemicals called free
radicals. In very high levels, they are capable of damaging cells and genetic
material. The body generates free radicals as the inevitable byproducts of
turning food into energy. Free radicals are also formed after exercising or
exposure to cigarette smoke, air pollution, and sunlight. [R]
Free radicals come in many shapes, sizes, and chemical configurations. What they all share is a voracious appetite for electrons, stealing them from any nearby substances that will yield them. This electron theft can radically alter the “loser’s” structure or function. Free radical damage can change the instructions coded in a strand of DNA. It can make a circulating low-density lipoprotein (LDL, sometimes called bad cholesterol) molecule more likely to get trapped in an artery wall. Or it can alter a cell’s membrane, changing the flow of what enters the cell and what leaves it. An excessive chronic amount of free radicals in the body causes a condition called oxidative stress, which may damage cells and lead to chronic diseases. [R]
We aren’t defenseless against free radicals. The body, long used to this relentless attack, makes many molecules that quench free radicals as surely as water douses fire. We also extract free-radical fighters from food. These defenders are labeled “antioxidants.” They work by generously giving electrons to free radicals without turning into electron-scavenging substances themselves. They are also involved in mechanisms that repair DNA and maintain the health of cells.
There are hundreds, probably thousands, of different substances that can act as antioxidants. The most familiar ones are vitamin C, vitamin E, beta-carotene, and other related carotenoids, along with the minerals selenium and manganese. They’re joined by glutathione, coenzyme Q10, lipoic acid, flavonoids, phenols, polyphenols, phytoestrogens, and many more. Most are naturally occurring, and their presence in food is likely to prevent oxidation or to serve as a natural defense against the local environment.
But using the term “antioxidant” to refer to substances is misleading. It is really a chemical property, namely, the ability to act as an electron donor. Some substances that act as antioxidants in one situation may be pro-oxidants—electron grabbers—in a different situation. Another big misconception is that antioxidants are interchangeable. They aren’t. Each one has unique chemical behaviors and biological properties. They almost certainly evolved as parts of elaborate networks, with each different substance (or family of substances) playing slightly different roles. This means that no single substance can do the work of the whole crowd.
This article gives you an overview of what you need to know about
antioxidants.
What are antioxidants?
Free radicals come in many shapes, sizes, and chemical configurations. What they all share is a voracious appetite for electrons, stealing them from any nearby substances that will yield them. This electron theft can radically alter the “loser’s” structure or function. Free radical damage can change the instructions coded in a strand of DNA. It can make a circulating low-density lipoprotein (LDL, sometimes called bad cholesterol) molecule more likely to get trapped in an artery wall. Or it can alter a cell’s membrane, changing the flow of what enters the cell and what leaves it. An excessive chronic amount of free radicals in the body causes a condition called oxidative stress, which may damage cells and lead to chronic diseases. [R]
We aren’t defenseless against free radicals. The body, long used to this relentless attack, makes many molecules that quench free radicals as surely as water douses fire. We also extract free-radical fighters from food. These defenders are labeled “antioxidants.” They work by generously giving electrons to free radicals without turning into electron-scavenging substances themselves. They are also involved in mechanisms that repair DNA and maintain the health of cells.
There are hundreds, probably thousands, of different substances that can act as antioxidants. The most familiar ones are vitamin C, vitamin E, beta-carotene, and other related carotenoids, along with the minerals selenium and manganese. They’re joined by glutathione, coenzyme Q10, lipoic acid, flavonoids, phenols, polyphenols, phytoestrogens, and many more. Most are naturally occurring, and their presence in food is likely to prevent oxidation or to serve as a natural defense against the local environment.
But using the term “antioxidant” to refer to substances is misleading. It is really a chemical property, namely, the ability to act as an electron donor. Some substances that act as antioxidants in one situation may be pro-oxidants—electron grabbers—in a different situation. Another big misconception is that antioxidants are interchangeable. They aren’t. Each one has unique chemical behaviors and biological properties. They almost certainly evolved as parts of elaborate networks, with each different substance (or family of substances) playing slightly different roles. This means that no single substance can do the work of the whole crowd.
How free radicals function
Free radicals are constantly being formed in your body. Without antioxidants,
free radicals would cause serious harm very quickly, eventually resulting in
death.
However, free radicals also serve important functions that are essential for health (Trusted Source). For example, your immune cells use free radicals to fight infections (Trusted Source). As a result, your body needs to maintain a certain balance of free radicals and antioxidants.
When free radicals outnumber antioxidants, it can lead to a state called oxidative stress. Prolonged oxidative stress can damage your DNA and other important molecules in your body. Sometimes it even leads to cell death.
Damage to your DNA increases your risk of cancer, and some scientists have theorized that it plays a pivotal role in the aging process (Trusted Source, Trusted Source).
Several lifestyle, stress, and environmental factors are known to promote excessive free radical formation and oxidative stress, including:
Epidemiological prospective studies show that higher intakes of antioxidant-rich fruits, vegetables, and legumes are associated with a lower risk of chronic oxidative stress-related diseases like cardiovascular diseases, cancer, and deaths from all causes. [Lancet 2017] A plant-based diet is believed to protect against chronic oxidative stress-related diseases. [R 2010] It is not clear if this protective effect is due to the antioxidants, other substances in the foods, or a combination of both. The following are nutrients with antioxidant activity and the foods in which they are found:
However, free radicals also serve important functions that are essential for health (Trusted Source). For example, your immune cells use free radicals to fight infections (Trusted Source). As a result, your body needs to maintain a certain balance of free radicals and antioxidants.
When free radicals outnumber antioxidants, it can lead to a state called oxidative stress. Prolonged oxidative stress can damage your DNA and other important molecules in your body. Sometimes it even leads to cell death.
Damage to your DNA increases your risk of cancer, and some scientists have theorized that it plays a pivotal role in the aging process (Trusted Source, Trusted Source).
Several lifestyle, stress, and environmental factors are known to promote excessive free radical formation and oxidative stress, including:
- air pollution
- cigarette smoke
- alcohol intake
- toxins
- high blood sugar levels (Trusted Source, Trusted Source)
- high intake of polyunsaturated fatty acids (Trusted Source)
- radiation, including excessive sunbathing
- bacterial, fungal, or viral infections
- excessive intake of iron, magnesium, copper, or zinc (Trusted Source)
- too much or too little oxygen in your body (Trusted Source)
- intense and prolonged exercise, which causes tissue damage (Trusted Source)
- excessive intake of antioxidants, such as vitamins C and E (Trusted Source)
- antioxidant deficiency (Trusted Source)
Prolonged oxidative stress leads to an increased risk of negative health
outcomes, such as cardiovascular disease and certain types of cancer.
Vitamin E, beta-carotene, and other antioxidants in supplement form aren’t
the silver bullet against heart disease and stroke that researchers were
hoping for. A modest effect of vitamin E has been found in some studies but
more research is needed.
If antioxidants were harmless, it wouldn’t much matter if you took
them “just in case.” A few studies, though, have raised the
possibility that taking antioxidant supplements, either single agents
or combinations, could interfere with health.
Antioxidants are essential for the survival of all living things. Your body
generates its own antioxidants, such as the cellular antioxidant
glutathione.
Plants and animals, as well as all other forms of life, have their own defenses against free radicals and oxidative damage.
Therefore, antioxidants are found in all whole foods of plant and animal origin.
One possible reason why many studies on antioxidant supplements do not show a
health benefit is because antioxidants tend to work best in combination with
other nutrients, plant chemicals, and even other antioxidants.
For example, a cup of fresh strawberries contains about 80 mg of vitamin C, a nutrient classified as having high antioxidant activity. But a supplement containing 500 mg of vitamin C (667% of the RDA) does not contain the plant chemicals (polyphenols) naturally found in strawberries like proanthocyanins and flavonoids, which also possess antioxidant activity and may team up with vitamin C to fight disease. Polyphenols also have many other chemical properties besides their ability to serve as antioxidants. There is a question if a nutrient with antioxidant activity can cause the opposite effect with pro-oxidant activity if too much is taken.
Antioxidant supplements and disease prevention: Clinical Evidence Review
Heart Disease
- In the Women’s Health Study, 39,876 initially healthy women took 600 IU of natural source vitamin E or a placebo every other day for 10 years. At the study’s end, the rates of major cardiovascular events and cancer were no lower among those taking vitamin E than those taking the placebo. However, the trial did observe a significant 24% reduction in total cardiovascular mortality. Although this was not a primary endpoint for the trial, it nevertheless represents an important outcome. [R]
- Earlier large vitamin E trials, conducted among individuals with previously diagnosed coronary disease or at high risk for it, generally showed no benefit. In the Heart Outcomes Prevention Evaluation (HOPE) trial, the rates of major cardiovascular events were essentially the same in the vitamin E (21.5%) and placebo (20.6%) groups, although participants taking vitamin E had higher risks of heart failure and hospitalization for heart failure. [R] In the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI) trial, the results were mixed but mostly showed no preventive effects after more than three years of treatment with vitamin E among 11,000 heart attack survivors. [R] However, some studies suggest potential benefits among certain subgroups. A recent trial of vitamin E in Israel, for example, showed a marked reduction in coronary heart disease among people with type 2 diabetes who have a common genetic predisposition for greater oxidative stress. [R]
- Beta-carotene, meanwhile, did not provide any protection against heart disease or stroke, as demonstrated by the Physicians’ Health Study. [NEJM 1996]
- What about combinations? In the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study, 13,017 French men and women took a single daily capsule that contained 120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 mcg selenium, and 20 mg zinc, or a placebo, for seven and a half years. The vitamins had no effect on overall rates of cardiovascular disease. [R]
- In the Women’s Antioxidant Cardiovascular Study, vitamin E, vitamin C, and beta-carotene had similar effects as a placebo on myocardial infarction, stroke, coronary revascularization, and cardiovascular death, although there was a modest and significant benefit for vitamin E among women with existing cardiovascular disease. [R]
Cancer
When it comes to cancer prevention, the picture remains
inconclusive for antioxidant supplements. Few trials have gone on long
enough to provide an adequate test for cancer.
- In the long-term Physicians’ Health Study, cancer rates were similar among men taking beta-carotene and among those taking a placebo. [NEJM 1996] Other trials have also largely shown no effect, including HOPE. [JAMA 2005]
- The SU.VI.MAX randomized placebo-controlled trial showed a reduction in cancer risk and all-cause mortality among men taking an antioxidant cocktail (low doses of vitamins C and E, beta-carotene, selenium, and zinc) but no apparent effect in women, possibly because men tended to have low blood levels of beta-carotene and other vitamins at the beginning of the study. [R]
- A randomized trial of selenium in people with skin cancer demonstrated significant reductions in cancer and cancer mortality at various sites, including colon, lung, and prostate. [R 2002] The effects were strongest among those with low selenium levels at baseline.
Eye Health
- Lutein, a naturally occurring carotenoid found in green, leafy vegetables such as spinach and kale, may protect vision. However, relatively short trials of lutein supplementation for age-related macular degeneration have yielded conflicting findings. [R 2007] A follow-up trial to the AREDS, the AREDS2, examined lutein/zeaxanthin supplementation on late age-related macular degeneration (AMD) in men and women for up to five years. [AREDS2 2014] It found that adding omega-3 fatty acids (fish oil) to the combination of supplements did not improve its effectiveness. However, adding lutein and zeaxanthin (two carotenoids found in the eye) improved the supplement’s effectiveness in people who were not taking beta-carotene and those who consumed only small amounts of lutein and zeaxanthin in foods.
- A Cochrane review of 19 randomized controlled trials compared antioxidant vitamin/mineral supplements (multivitamin, vitamin E, lutein, zeaxanthin, zinc) with placebo or no intervention in people with AMD. [Cochrane 2017] The participants were generally well-nourished. The study found that people taking the vitamins were less likely to progress to late-stage AMD and vision loss. However, the study authors noted that taking lutein and zeaxanthin alone or vitamin E alone did not have a beneficial effect on these eye conditions.
- The Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study, which followed 11,267 men for a mean of five years, did not find that vitamin E and selenium supplements, in combination or alone, protected from age-related cataracts. [R 2015]
Brain Health
- The Physicians’ Health Study II, a randomized trial giving 50 mg beta-carotene supplements or a placebo to 5,956 men older than 65 years, found that longer-term supplementation for at least 15 years provided cognitive benefits. [R 2007]
- The Prevention of Alzheimer’s Disease by Vitamin E and Selenium (PREADViSE) trial followed more than 3,700 men ages 60 and older for six years. It did not find that antioxidant supplements of vitamin E or selenium, alone or in combination, protected against dementia compared with a placebo. [JAMA Neurology 2017]
Anti Aging
- A meta-analysis of 68 antioxidant supplement trials found that taking beta-carotene and vitamin A and E supplements increased the risk of dying. [JAMA 2007] Although healthy participants were included in 21 of the trials, most of the studies included people who already had some type of serious illness. It was also difficult to compare interventions because the types of supplements, the dosages taken, and the length of time they were taken varied widely.
- The same authors conducted another systematic review of 78 randomized clinical trials on antioxidant supplements including beta-carotene, vitamin A, vitamin C, vitamin E, and selenium (alone or in combination). [Cochrane 2012] Again, the majority of trials included people with various established diseases. The study found that both people who were healthy and those with diseases taking beta-carotene and vitamin E supplements had a higher rate of death. The duration of the studies varied widely from one month to 12 years, with varying dosages.
Potential hazards of antioxidant supplements
- The first inkling came in a large trial of beta-carotene conducted among men in Finland who were heavy smokers, and therefore at high risk for developing lung cancer. The trial was stopped early when researchers saw a significant increase in lung cancer among those taking the supplement compared to those taking the placebo. [R 1996]
- In another trial among heavy smokers and people exposed to asbestos, beta-carotene was combined with vitamin A. Again, an increase in lung cancer was seen in the supplement group. [NEJM 1996] Not all trials of beta-carotene show this harmful effect, however. In the Physicians’ Health Study, which included few active smokers, no increase in lung cancer or any other adverse affect was seen even after 18 years of follow-up. [NEJM 1996]
- In the SU.VI.MAX trial, rates of skin cancer were higher in women who were assigned to take vitamin C, vitamin E, beta-carotene, selenium, and zinc. [R 2007]
- Vitamin E supplements were found to significantly increase the risk of prostate cancer by 17% in healthy men compared with those who took a placebo. These results came from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) that followed 35,533 men for up to 12 years. [JAMA 2011]
Antioxidants in foods
Plants and animals, as well as all other forms of life, have their own defenses against free radicals and oxidative damage.
Therefore, antioxidants are found in all whole foods of plant and animal origin.
For example, a cup of fresh strawberries contains about 80 mg of vitamin C, a nutrient classified as having high antioxidant activity. But a supplement containing 500 mg of vitamin C (667% of the RDA) does not contain the plant chemicals (polyphenols) naturally found in strawberries like proanthocyanins and flavonoids, which also possess antioxidant activity and may team up with vitamin C to fight disease. Polyphenols also have many other chemical properties besides their ability to serve as antioxidants. There is a question if a nutrient with antioxidant activity can cause the opposite effect with pro-oxidant activity if too much is taken.
This is why using an antioxidant supplement with a single isolated substance
may not be an effective strategy for everyone.
Differences in the amount and type of antioxidants in foods versus those in supplements might also influence their effects. For example, there are eight chemical forms of vitamin E present in foods. However, vitamin E supplements typically only include one form, alpha-tocopherol. [NIH 2013]
Differences in the amount and type of antioxidants in foods versus those in supplements might also influence their effects. For example, there are eight chemical forms of vitamin E present in foods. However, vitamin E supplements typically only include one form, alpha-tocopherol. [NIH 2013]
Epidemiological prospective studies show that higher intakes of antioxidant-rich fruits, vegetables, and legumes are associated with a lower risk of chronic oxidative stress-related diseases like cardiovascular diseases, cancer, and deaths from all causes. [Lancet 2017] A plant-based diet is believed to protect against chronic oxidative stress-related diseases. [R 2010] It is not clear if this protective effect is due to the antioxidants, other substances in the foods, or a combination of both. The following are nutrients with antioxidant activity and the foods in which they are found:
- Vitamin C: Broccoli, Brussels sprouts, cantaloupe, cauliflower, grapefruit, leafy greens (turnip, mustard, beet, collards), honeydew, kale, kiwi, lemon, orange, papaya, snow peas, strawberries, sweet potato, tomatoes, and bell peppers (all colors)
- Vitamin E: Almonds, avocado, Swiss chard, leafy greens (beet, mustard, turnip), peanuts, red peppers, spinach (boiled), and sunflower seeds
- Carotenoids including beta-carotene and lycopene: Apricots, asparagus, beets, broccoli, cantaloupe, carrots, bell peppers, kale, mangos, turnip and collard greens, oranges, peaches, pink grapefruit, pumpkin, winter squash, spinach, sweet potato, tangerines, tomatoes, and watermelon
- Selenium: Brazil nuts, fish, shellfish, beef, poultry, barley, brown rice
- Zinc: Beef, poultry, oysters, shrimp, sesame seeds, pumpkin seeds, chickpeas, lentils, cashews, fortified cereals
- Phenolic compounds: Quercetin (apples, red wine, onions), catechins (tea, cocoa, berries), resveratrol (red and white wine, grapes, peanuts, berries), coumaric acid (spices, berries), anthocyanins (blueberries, strawberries)
Types of dietary antioxidants
Antioxidants can be categorized as either water- or fat-soluble.
Water-soluble antioxidants perform their actions in the fluid inside and outside cells, whereas fat-soluble ones act primarily in cell membranes.
Important dietary antioxidants include:
Notable examples include curcuminoids in turmeric and oleocanthal in extra virgin olive oil. These substances function as antioxidants but also have potent anti-inflammatory activity (Trusted Source, Trusted Source).
Excessive intake of isolated antioxidants can have toxic effects and may even promote rather than prevent oxidative damage — a phenomenon termed the “antioxidant paradox” (Trusted Source, Trusted Source).
Some studies even show that high doses of antioxidants increase your risk of death (Trusted Source, Trusted Source).
For this reason, most health professionals advise people to avoid high-dose antioxidant supplements, although further studies are needed before solid conclusions can be reached.
Eating plenty of antioxidant-rich whole food is a much better idea. Studies indicate that foods reduce oxidative damage to a greater extent than supplements.
For example, one study compared the effects of drinking blood-orange juice and sugar water, both of which contained equal amounts of vitamin C. It found that the juice had significantly greater antioxidant power (Trusted Source).
These results suggest that foods’ compounds work synergistically. Taking just one or two isolated nutrients won’t have the same beneficial effects.
The best strategy to ensure adequate antioxidant intake is to follow a diet rich in various vegetables and fruits, alongside other healthy habits (Trusted Source).
However, low-dose supplements, such as multivitamins, may be beneficial if you are deficient in certain nutrients or unable to follow a healthy diet.
Water-soluble antioxidants perform their actions in the fluid inside and outside cells, whereas fat-soluble ones act primarily in cell membranes.
Important dietary antioxidants include:
- Vitamin C. This water-soluble antioxidant is an essential dietary nutrient.
- Vitamin E. This fat-soluble antioxidant plays a critical role in protecting cell membranes against oxidative damage.
- Flavonoids. This group of plant antioxidants has many beneficial health effects (Trusted Source).
Notable examples include curcuminoids in turmeric and oleocanthal in extra virgin olive oil. These substances function as antioxidants but also have potent anti-inflammatory activity (Trusted Source, Trusted Source).
Dietary intake of antioxidants is essential for optimal health, but more is not always better.
Excessive intake of isolated antioxidants can have toxic effects and may even promote rather than prevent oxidative damage — a phenomenon termed the “antioxidant paradox” (Trusted Source, Trusted Source).
Some studies even show that high doses of antioxidants increase your risk of death (Trusted Source, Trusted Source).
For this reason, most health professionals advise people to avoid high-dose antioxidant supplements, although further studies are needed before solid conclusions can be reached.
Eating plenty of antioxidant-rich whole food is a much better idea. Studies indicate that foods reduce oxidative damage to a greater extent than supplements.
For example, one study compared the effects of drinking blood-orange juice and sugar water, both of which contained equal amounts of vitamin C. It found that the juice had significantly greater antioxidant power (Trusted Source).
These results suggest that foods’ compounds work synergistically. Taking just one or two isolated nutrients won’t have the same beneficial effects.
The best strategy to ensure adequate antioxidant intake is to follow a diet rich in various vegetables and fruits, alongside other healthy habits (Trusted Source).
However, low-dose supplements, such as multivitamins, may be beneficial if you are deficient in certain nutrients or unable to follow a healthy diet.
Adequate antioxidant intake is essential to a healthy diet, although some studies suggest that high-dose supplements may be harmful.
Excessive free radicals contribute to chronic diseases including cancer,
heart disease, cognitive decline, and vision loss. This doesn’t
automatically mean that substances with antioxidant properties will fix the
problem, especially if they are taken out of their natural context. The
studies so far are inconclusive but generally don’t provide strong evidence
that antioxidant supplements have a substantial impact on disease. Keep in
mind that most of the trials conducted have had fundamental limitations due
to their relatively short duration and inclusion of people with existing
disease. At the same time, abundant evidence suggests that eating whole in
fruits, vegetables, and whole grains—all rich in networks of naturally
occurring antioxidants and their helper molecules—provides protection
against many scourges of aging.
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