Antioxidant Evidence by Use: Eye Health (AREDS2), Heart, Exercise, Skin and Aging

Two different questions

"Do antioxidants work?" mixes two questions. One is whether a specific formula tested in a trial helps a specific group of people. The other is whether antioxidant supplements in general keep healthy people well. The first has an answer for eye disease. For the second, the NCCIH says that, except for age-related macular degeneration, there is currently no evidence that antioxidant supplements have a positive impact on chronic disease. [1]

Labels: established, evidence in adequately nourished people, promising but limited, mixed, insufficient evidence, preclinical, marketing claim. See Antioxidants Explained.

Summary table

Eye health: AREDS2 is a formula, not "antioxidants"

The NEI ran AREDS (4,757 people) and AREDS2 (4,203 people with intermediate AMD in both eyes, or intermediate AMD in one eye and advanced in the other). [2] The AREDS formula has vitamin C 500 mg, vitamin E 400 IU, beta-carotene 15 mg, zinc 80 mg and copper 2 mg; the AREDS2 formula swaps beta-carotene for lutein 10 mg and zeaxanthin 2 mg. [2] These are amounts used in a specific eye-disease trial, not general recommendations.

• AREDS: people with intermediate or one-eye advanced AMD had about 25% lower risk of advanced AMD and 19% lower risk of central vision loss. [2]
• AREDS2: adding lutein/zeaxanthin or omega-3 to the AREDS formula did not give a significant overall extra effect in the main analyses. [7] The formula without beta-carotene and with lutein/zeaxanthin still showed an incremental benefit. [2]
• Long-term follow-up: odds of lung cancer were 1.82 with beta-carotene and not significantly raised with lutein/zeaxanthin; the NEI advises current and former smokers to use the AREDS2 formula, not the formula with beta-carotene. [8][2]
• Cochrane 2023: moderate-certainty evidence that the AREDS formula probably slows progression to late AMD; lutein/zeaxanthin alone had low-certainty, small or no effect. [9]
• It does not show benefit for people without AMD. Anyone with AMD should ask an eye doctor whether it fits their case. [1]

Heart and cancer

The NCCIH reports that in 2022 the US Preventive Services Task Force recommended against beta-carotene or vitamin E supplements for preventing cardiovascular disease and cancer, and found insufficient evidence for other single or paired nutrients such as vitamin C and selenium. [1] In SELECT (35,533 men), vitamin E 400 IU a day was linked with more prostate cancer (hazard ratio 1.17). [10] A Cochrane review of 78 trials found no support for antioxidant supplements and signs of higher mortality with beta-carotene and vitamin E. [11] CoQ10 in heart failure is separate: see CoQ10.

Exercise and recovery

In 39 healthy young men, vitamin C (1,000 mg) plus vitamin E (400 IU) for 4 weeks blocked the improvement in insulin sensitivity that exercise produced without antioxidants. [4] In 54 young adults on 11 weeks of endurance training, vitamin C (1,000 mg) plus E (235 mg) did not change gains in VO2 max or running performance but reduced increases in muscle mitochondrial markers. [5] Proper evidence not found in the sources read for antioxidant supplements speeding recovery. See recovery after exercise.

Skin

A review of 47 human studies found the strongest photoprotection evidence for polyphenols, carotenoids and Polypodium leucotomos, and the weakest for isolated vitamins or CoQ10; studies were small and short. [6] See astaxanthin, carotenoids and skin aging and appearance. Supplements do not replace sun protection.

Healthy aging

In the NCCIH summary, two 2018 reviews of antioxidants and cognition found small, low-certainty effects, no benefit of vitamin E, and no significant effect of high-dose vitamin E on progression from mild cognitive impairment to dementia. [1] "Anti-aging" claims are covered on antioxidant safety and marketing claims and supplements for healthy aging.

Safety

See medication interactions and talking with a health professional.