Antioxidant Supplements: What You Need To Know

In general, except for age-related macular degeneration, there is currently no evidence that antioxidant supplements have a positive impact on these diseases.

On the other hand, there is extensive evidence that people who eat more vegetables and fruits—foods that are rich sources of antioxidants—have lower risks of chronic diseases. For example:

• A 2017 review of 95 observational studies, with more than 2 million total participants, showed that people who had higher intakes of fruits and vegetables had lower risks of cardiovascular disease and cancer.
• A 2023 study from the United Kingdom in which 72,160 people were followed for an average of 9 years showed that higher intakes of fruits and vegetables were associated with a lower risk of cataracts.

There are several possible reasons why antioxidant supplements may not prevent cardiovascular disease and cancer even though antioxidant-rich vegetables and fruits are associated with reduced risk:

• The beneficial health effects of a diet high in vegetables and fruits or other antioxidant-rich foods may be due to other substances in these foods or other aspects of people’s lifestyles that are associated with eating these foods. For example, in a study of adults living in rural areas in the United States, eating at least five servings of fruits and vegetables daily was associated with several other factors that might affect health, such as getting at least moderate physical activity and having had a routine medical exam in the past year.
• Antioxidants consumed as purified chemicals might act differently than those consumed in foods, which contain complex mixtures of substances.
• The high doses of antioxidants in dietary supplements may have different effects than the smaller amounts in foods.

• In 2022, the U.S. Preventive Services Task Force, an independent panel of experts that makes evidence-based recommendations about disease prevention, recommended against the use of beta-carotene or vitamin E supplements for cancer prevention. They also concluded that the evidence is insufficient to make recommendations about supplements of other single nutrients or pairs of nutrients. These recommendations are consistent with the Task Force’s previous recommendations, issued in 2014.
  • The Task Force’s recommendation against the use of beta-carotene for cancer prevention is based on studies of beta-carotene supplementation involving more than 90,000 people, which showed that the harms of beta-carotene outweigh its benefits. Beta-carotene supplementation led to an increase in risk of lung cancer, with the strongest evidence of an increase in risk in people at high risk of this type of cancer (smokers and people with occupational exposure to asbestos), as well as an increased risk of death from cardiovascular disease.
  • The Task Force’s recommendation against the use of vitamin E for cancer prevention is based on a combined analysis of 5 studies (76,777 participants) of vitamin E supplementation, which showed no benefit of the supplements in preventing cancer.
  • The Task Force’s decision not to make a recommendation about the use of supplements of other single or paired nutrients—including antioxidants such as vitamin C and selenium—is based on a lack of adequate evidence on the benefits and harms of the supplements.

• In 2022, the U.S. Preventive Services Task Force recommended against the use of beta-carotene or vitamin E supplements for prevention of cardiovascular disease. They also concluded that the evidence is insufficient to make recommendations about supplements of other single nutrients or pairs of nutrients. These recommendations are consistent with the Task Force’s previous recommendations, issued in 2014.
  • The Task Force’s recommendation against the use of beta-carotene for cardiovascular disease is based on studies of beta-carotene supplementation involving more than 90,000 people, which showed that the harms of beta-carotene outweigh its benefits. Beta-carotene supplementation led to an increase in risk of lung cancer, with the strongest evidence of an increase in risk in people at high risk of this type of cancer (smokers and people with occupational exposure to asbestos), and an increase in deaths from cardiovascular disease.
  • The Task Force’s recommendation against the use of vitamin E for cardiovascular disease prevention is based on a combined analysis of 4 studies (62,136 participants) of vitamin E supplementation, which showed no benefit of the supplements in preventing cardiovascular disease events.
  • The Task Force’s decision not to make a recommendation about the use of supplements of other single or paired nutrients—including antioxidants such as vitamin C and selenium—is based on a lack of adequate evidence on the benefits and harms of the supplements.

• A 2017 review that examined the results of 5 studies (76,756 participants) did not find any significant benefit of vitamin E, vitamin C, or beta-carotene supplementation in preventing or delaying the onset of AMD.
• For people who already have AMD, supplements containing a combination of antioxidants and zinc may slow the progression of the disease. The evidence for this comes from two large studies sponsored by the National Institutes of Health—the Age-Related Eye Disease Study (AREDS) and Age-Related Eye Disease Study 2 (AREDS2).
  • AREDS evaluated the effects of a dietary supplement containing high doses of vitamins C and E, beta-carotene, zinc, and copper on the progression of AMD. Almost 4,800 people participated in this study, including 3,640 who had AMD. Among people with intermediate AMD, the supplement reduced the risk of developing advanced AMD by about 25 percent.
  • AREDS2 tested modifications to the original AREDS formula in about 4,200 people who were at high risk of progressing to advanced AMD. Participants were randomly assigned to groups that received the original formula or various modified versions. The modifications included removing beta-carotene and adding lutein and zeaxanthin (two carotenoids that are found in the eye). Because the link between beta-carotene and an increased risk of lung cancer in smokers was known before this study started, current smokers were not assigned to groups that received beta-carotene; only nonsmokers and former smokers were included in those groups. After 10 years of follow-up, lutein and zeaxanthin proved to be more effective than beta-carotene in reducing the risk of progression to advanced AMD. Beta-carotene increased lung cancer risk among former smokers, but lutein and zeaxanthin did not.

• A 2017 review concluded that supplements containing vitamin E with no other nutrients or lutein (with or without zeaxanthin) with no other nutrients may have little or no effect on progression to late AMD, but the evidence (from one study for vitamin E and six for lutein or lutein/zeaxanthin) was of low certainty.                       

• A 2018 review examined 8 studies of antioxidant supplements (beta-carotene/vitamin A, vitamin C, and/or beta-carotene) that included about 47,000 total participants, all of whom were 40 years old or older at the beginning of the studies. There was low-certainty evidence of better overall cognitive function after taking beta-carotene for 18 years and after taking vitamin C for 5 to 10 years, but no effects were seen after shorter periods of supplementation or after taking vitamin E. The effects seen in the studies were small.
• Another 2018 review looked at studies of vitamin and mineral supplementation in people who already have mild cognitive impairment. Two of the studies involved antioxidants. In one study (516 participants), high-dose supplementation with vitamin E for 3 years did not have a significant effect on progression of mild cognitive impairment to dementia. In the other study, which involved combined vitamin E and C supplementation (256 participants), the evidence was too low in quality for any conclusions to be reached about cognitive effects. 

• As discussed earlier, high-dose beta-carotene supplementation can increase people’s risks of lung cancer and cardiovascular disease. These effects have been seen primarily in people at high risk, such as smokers.
• High doses of vitamin E supplements may increase the risk of bleeding by reducing the blood’s ability to form clots after an injury. Vitamin E supplements may also interact with certain medicines, including anticoagulant or antiplatelet medicines.
• High doses of vitamin C can cause diarrhea, nausea, and stomach cramps. Vitamin C supplements may also interact with cancer treatments, such as chemotherapy and radiation therapy, and they can worsen iron overload in people with hemochromatosis, a condition that causes the body to store too much iron.
• Combinations of antioxidants may have undesirable effects. For example, in one study, a combination of vitamin E, vitamin C, selenium, and beta-carotene reduced the cholesterol-lowering effects of two drugs taken together for this purpose.

• It’s common for people with cancer to take antioxidants and other dietary supplements, but the antioxidants might interact in unfavorable ways with cancer treatments. The mechanism by which some cancer treatments exert their effects involves generating reactive substances that contain oxygen. Antioxidants might reduce the effectiveness of these types of treatments.
• In a 2019 study, 1,134 women with breast cancer who were participating in a clinical trial of different chemotherapy treatment schedules were asked to fill out questionnaires about their use of dietary supplements when they joined the trial and again when they finished chemotherapy. The use of any antioxidant supplement (vitamins A, C, and E; carotenoids; or coenzyme Q10) or iron or vitamin B12 supplements during chemotherapy was linked with higher risks of breast cancer recurrence and death. Although the results of this study may be biased because the participants made their own choices about whether to use supplements, the findings support the idea that the use of antioxidant supplements during cancer chemotherapy may interfere with treatment.