Dietary Supplements for Eye Conditions: What the Science Says

The available data on efficacy of dietary supplements for delaying the progression of or reducing the risk of developing AMD consist of several randomized controlled trials and systematic reviews.

• A 2023 Cochrane review of 26 studies conducted in the United States, Europe, China, and Australia and involving a total of 11,952 people aged 65 to 75 years found moderate-certainty evidence suggesting that antioxidant vitamin and mineral supplementation (AREDS: vitamin C, E, beta-carotene, and zinc) probably slows progression to late AMD. The reviewers noted that people with intermediate AMD have a higher chance of benefiting from antioxidant supplements because their risk of progression is higher than people with early AMD. Although low-certainty evidence suggested little effect with lutein/zeaxanthin alone compared with placebo, subgroup analyses from a single large American study suggests that lutein/zeaxanthin may be a suitable replacement for the beta-carotene used in the original AREDS formula.
• A 2022 multicenter epidemiologic follow-up study of the AREDS2 clinical trial involving 3,882 participants found that lutein/zeaxanthin was a suitable replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer in those who were current smokers, and former smokers had higher rates of developing of lung cancer than nonsmokers; however, there was no statistically significant increased risk with lutein/zeaxanthin When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression. 
• A 2012 randomized controlled trial of 14,236 male physicians aged 50 years and older concluded that long-term (8 years) use of vitamin E and/or vitamin C has no appreciable beneficial or harmful effect on risk of incident diagnosis of AMD.
• A 2013 Cochrane review of two small randomized controlled trials involving a total of 119 participants concluded that current available research has not yet answered the question as to whether Ginkgo biloba supplements benefit people with AMD.
• A 2021 post hoc analysis of two controlled clinical trial cohorts—Age-Related Eye Disease Study (AREDS) and AREDS2—involving a total of 14,135 eyes, found that higher dietary intake of multiple nutrients, including minerals, vitamins, and carotenoids, is associated with decreased risk of progression to late AMD.  
• A 2015 Cochrane systematic review of two randomized controlled trials involving 2,343 participants found that omega-3 fatty acid supplementation in people with AMD for periods up to 5 years does not reduce the risk of progression to advanced AMD or the development of moderate-to-severe visual loss.
• A 2021 review found that there are some data from experimental studies in animals that Fructus lycii (F. lycii), a “berry-type” fruit of the plant Lycium barbarum, may show promise in preventing or delaying the onset of retinal diseases such as AMD. However, the reviewers noted that there is a paucity of data from human trials and that there are a number of concerns that need to be addressed before F. lycii establishes its place in the clinical management of retinal diseases. 

• Vitamin C has low toxicity and is not believed to cause serious adverse effects at high intakes. The most common complaints are diarrhea, nausea, abdominal cramps, and other gastrointestinal disturbances due to the osmotic effect of unabsorbed vitamin C in the gastrointestinal tract.
• Research has not found any adverse effects from consuming vitamin E in food. However, high doses of alpha-tocopherol supplements can cause hemorrhage and interrupt blood coagulation in animals, and in vitro data suggest that high doses inhibit platelet aggregation. Two meta-analyses of randomized trials have also raised questions about the safety of large doses of vitamin E, including doses lower than the Tolerable Upper Intake Level (UL). These meta-analyses linked supplementation to small but statistically significant increases in all-cause mortality. Results from the large SELECT trial show that vitamin E supplements (400 IU/day) may harm adult men in the general population by increasing their risk of prostate cancer.
• Use of beta-carotene has been linked to an increased risk of lung cancer in current and former smokers. In nonsmokers, however, large amounts of beta-carotene and other provitamin A carotenoids are not associated with major adverse effects. Even large supplemental doses (20–30 mg/day) of beta-carotene or diets with high levels of carotenoid-rich food for long periods are not associated with toxicity. The most significant effect of long-term, excess beta-carotene is carotenodermia, a harmless condition in which the skin becomes yellow-orange. Lutein and zeaxanthin appear to be safe regardless of smoking status.
• For many healthy adults, Ginkgo biloba appears to be safe when taken orally in moderate amounts. Adverse effects may include headache, gastrointestinal upset, and allergic skin reactions. In a 2013 study, rodents given ginkgo had an increased risk of developing liver and thyroid cancer at the end of the 2-year tests. Raw or roasted ginkgo seeds can be poisonous.
• Omega-3 fatty acid supplements usually do not have adverse effects. When side effects do occur, they typically consist of minor gastrointestinal symptoms. 
• F. lycii is generally considered to be a safe supplement when taken in the appropriate dosage. Allergic reactions to F. lycii are rare; however, a few cases have been reported with symptoms such as generalized urticaria, toxic hepatitis, and a rare life-threatening anaphylactic reaction.

The available data on efficacy of dietary supplements for preventing or slowing the progression of cataracts consist of several randomized controlled trials, observational studies, and systematic reviews.

• A 2012 Cochrane review of 9 randomized controlled trials involving 117,272 participants aged 35 years or older found no evidence that antioxidant vitamin supplementation (vitamin C, vitamin E, or beta-carotene) reduced the risk of cataract, cataract extraction, or cataract progression or slowed the loss of visual acuity.
• A 2013 randomized controlled trial (Age-Related Eye Disease Study—AREDS2) of 3,159 participants found that daily supplementation with lutein/zeaxanthin had no statistically significant overall effect on rates of cataract surgery or vision loss.
• Findings from 2015 observational data (Age-Related Eye Disease Study—AREDS) of 3,159 participants examining the association of dietary lutein plus zeaxanthin and B12 vitamins with cataracts suggest that dietary intake of B12 vitamins may affect the occurrence of age-related lens opacities. Specifically, the study showed increased dietary riboflavin and B12 were associated with less nuclear and cortical lens opacities.
• Findings from a 2015 randomized controlled trial of 11,267 men from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age-related cataract.
• A 2020 review concluded that in general, clinical trials have not been able to show convincing therapeutic effects of vitamin C supplementation on cataract incidence, except in those cases in which individuals may have had low vitamin C levels at the start of the trial.

• Vitamin C has low toxicity and is not believed to cause serious adverse effects at high intakes. The most common complaints are diarrhea, nausea, abdominal cramps, and other gastrointestinal disturbances due to the osmotic effect of unabsorbed vitamin C in the gastrointestinal tract.
• Research has not found any adverse effects from consuming vitamin E in food. However, high doses of alpha-tocopherol supplements can cause hemorrhage and interrupt blood coagulation in animals, and in vitro data suggest that high doses inhibit platelet aggregation. Two meta-analyses of randomized trials have also raised questions about the safety of large doses of vitamin E, including doses lower than the Tolerable Upper Intake Level (UL). These meta-analyses linked supplementation to small but statistically significant increases in all-cause mortality. Results from the large SELECT trial show that vitamin E supplements (400 IU/day) may harm adult men in the general population by increasing their risk of prostate cancer.
• Use of beta-carotene has been linked to an increased risk of lung cancer in current and former smokers. In nonsmokers, however, large amounts of beta-carotene and other provitamin A carotenoids are not associated with major adverse effects. Even large supplemental doses (20–30 mg/day) of beta-carotene or diets with high levels of carotenoid-rich food for long periods are not associated with toxicity. The most significant effect of long-term, excess beta-carotene is carotenodermia, a harmless condition in which the skin becomes yellow-orange. 
• No adverse effects have been associated with excess vitamin B12 intake from food and supplements in healthy individuals.
• Chronically high intakes of the organic and inorganic forms of selenium have similar effects. Early indicators of excess intake are a garlic odor in the breath and a metallic taste in the mouth. The most common clinical signs of chronically high selenium intakes, or selenosis, are hair and nail loss or brittleness. Other symptoms include lesions of the skin and nervous system, nausea, diarrhea, skin rashes, mottled teeth, fatigue, irritability, and nervous system abnormalities.

• A 2019 Cochrane review of 34 randomized controlled trials involving more than 4,314 adult participants concluded that long-chain omega-3 supplements may have a role in managing dry eye; however, the evidence is currently inconsistent and more research is needed.
• A 2022 randomized clinical trial of 23,523 adults without dry eye disease found that daily supplementation with 1 g of marine omega-3 fatty acids for a median of 5.3 years had no significant effect on the incidence of diagnosed dry eye disease or reported dry eye disease symptoms.

• Omega-3 fatty acid supplements usually do not have adverse effects. When side effects do occur, they typically consist of minor gastrointestinal symptoms. 

The available data on efficacy of dietary supplements for delaying the progression of glaucoma consist of several laboratory studies, but only a few randomized controlled trials and a cross-sectional study.

• Findings from a 2013 cross-sectional study involving 2,912 participants aged 40 years and older in the 2005–2006 National Health and Nutrition Examination Survey indicate that neither supplementary consumption with nor serum levels of vitamins A and E were found to be associated with glaucoma prevalence. However, individuals reporting either low vitamin C (≤100 mg/day) and or high (>900 mg/day) supplementation levels had significantly lower adjusted odds of being diagnosed with glaucoma than those reporting no vitamin C supplementation. No dose-response relationship was demonstrated, and serum levels of vitamin C did not correlate with glaucoma prevalence. Low- and high-dose supplementary consumption of vitamin C, however, was found to be associated with decreased odds of developing glaucoma. While vitamin C intake, relative to no vitamin C intake, may be associated with decreased odds of glaucoma development, findings should be reproducible in further studies before therapeutic recommendations can be made.
• Studies conducted in the 1970s and 1980s showed that cannabis or substances derived from it could lower pressure in the eye, but not as effectively as treatments already in use (see NCCIH’s fact sheet, “Cannabis (Marijuana) and Cannabinoids: What You Need To Know” for more information). 
• A 2006 small crossover trial compared delta-9-tetrahydrocannabinol (delta-9-THC; 5mg), cannabidiol (CBD; 20 mg and 40 mg) oromucosal spray, and placebo with six patients with ocular hypertension or early primary open angle glaucoma. The study found an intraocular pressure (IOP)-lowering effect of delta-9-THC, but it was not considered to be clinically relevant. CBD did not reduce IOP.     
• A 2020 crossover randomized trial involving 57 participants with glaucoma found that nicotinamide (vitamin B3) supplementation may improve inner retinal function in glaucoma. Additional studies are underway to determine the effects of long-term nicotinamide supplementation.

• Vitamin C has low toxicity and is not believed to cause serious adverse effects at high intakes. The most common complaints are diarrhea, nausea, abdominal cramps, and other gastrointestinal disturbances due to the osmotic effect of unabsorbed vitamin C in the gastrointestinal tract.
• Research has not found any adverse effects from consuming vitamin E in food. However, high doses of alpha-tocopherol supplements can cause hemorrhage and interrupt blood coagulation in animals, and in vitro data suggest that high doses inhibit platelet aggregation. Two meta-analyses of randomized trials have also raised questions about the safety of large doses of vitamin E, including doses lower than the Tolerable Upper Intake Level (UL). These meta-analyses linked supplementation to small but statistically significant increases in all-cause mortality. Results from the large SELECT trial show that vitamin E supplements (400 IU/day) may harm adult men in the general population by increasing their risk of prostate cancer.
• There is risk of adverse events with cannabinoid use, including asthenia, balance problems, confusion, dizziness, disorientation, diarrhea, euphoria, drowsiness, dry mouth, fatigue, hallucination, nausea, somnolence, and vomiting. For additional information on safety, see NCCIH’s fact sheet, “Cannabis (Marijuana) and Cannabinoids: What You Need To Know.”