NCCIH Clinical Digest

for health professionals

Dietary Supplements for Eye Conditions: What the Science Says

October 2020

Clinical Guidelines, Scientific Literature, Info for Patients: 
Dietary Supplements for Eye Conditions

What Does the Research Show?

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 2017 Cochrane review of 5 randomized controlled trials involving 55,614 participants concluded that taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD. The reviewers also noted that the same probably applies to vitamin C and the multivitamin (Centrum Silver) investigated in the one trial included in the review.
  • A 2012 Cochrane systematic review of 13 trials involving 6,150 participants concluded that people with AMD may experience delay in progression of the disease with antioxidant vitamin and mineral supplementation. However, the finding is drawn from a single, large trial conducted in a “relatively well-nourished American population,” and the generalizability of these findings to other populations is unknown.
  • 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.
  • Findings from a 2014 secondary analyses of the Age-Related Eye Disease Study 2 (AREDS2), involving 4,203 participants aged 50 to 85 years who were at risk for developing late AMD, suggest that lutein/zeaxanthin could be more appropriate than beta-carotene for the new AREDS2 formulation, but the differences were not large.
  • 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.

Safety

  • 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 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 non-smokers, 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. Eating 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. It is uncertain whether people with fish or shellfish allergies can safely consume fish oil supplements. Omega-3 supplements may extend bleeding time.

Cataract

In the Age-Related Eye Disease Studies (AREDS and AREDS2), neither omega-3 fatty acids nor lutein/zeaxanthin, when added to the original AREDS formulation (vitamins E and C, beta-carotene, and zinc), had any overall effect on the need for cataract surgery. However, when the participants were ranked into five equal-sized groups according to their dietary lutein/zeaxanthin intake, supplementation with lutein/zeaxanthin appeared to make a difference for the group with the lowest dietary levels. Within that group, lutein/zeaxanthin was associated with a 32 percent reduction in progression to cataract surgery.

Although there are some data from observational research that dietary vitamin B12 supplements may slow or prevent cataract development, no dietary supplements have been recommended for the treatment of cataracts.

What Does the Research Show?

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, cataract progression, or slows the loss of visual acuity.
  • A 2013 randomized controlled trial (Age-Related Eye Disease Study—AREDS) 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.

Safety

  • 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 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.
  • 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. Current smokers and asbestos-exposed individuals should be discouraged from taking supplemental beta-carotene (and the combination of β-carotene with vitamin A) as it may increase the risk of developing lung cancer.
  • 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.

Glaucoma

Current data do not support the use of dietary supplementation with vitamins A, C, and E or cannabinoids as glaucoma treatments.

What Does the Research Show?

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 (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.     

Safety

  • 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 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.
  • 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.
  • 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.”

References

  • Age-Related Eye Disease Study 2 (AREDS2) Research Group, Chew EY, SanGiovanni JP, et al. Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report n. 4. JAMA Ophthalmol. 2013;131(7):843-850.
  • Age-Related Eye Disease Study 2 (AREDS2) Research Group, Chew EY, Clemons TE, et al. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report no. 3. JAMA Ophthalmol. 2014;132(2):142-149.
  • Christen WG, Glynn RJ, Gaziano JM, et al. Age-related cataract in men in the selenium and vitamin E cancer prevention trial eye endpoint study: a randomized clinical trial. JAMA Ophthalmol. 2015;133(1):17-24.
  • Christen WG, Glynn RJ, Sesso HD, et al. Vitamins E and C and medical record-confirmed age-related macular degeneration in a randomized trial of male physicians. Ophthalmology. 2012;119(8):1642-1649.
  • Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database Syst Rev. 2017;7(7):CD000253.
  • Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. 2012;11:CD000254.
  • Evans JR. Ginkgo biloba extract for age-related macular degeneration. Cochrane Database Syst Rev. 2013;1:CD001775.
  • Glaser TS, Doss LE, Shih G, et al. The association of dietary lutein plus zeaxanthin and B vitamins with cataracts in the Age-Related Eye Disease Study: AREDS report no. 37. Ophthalmology. 2015;122(7):1471-1479.
  • Lawrenson JG, Evans JR. Omega-3 fatty acids for preventing or slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. 2015;4:CD10015.
  • Matthew MC, Ervin AM, Tao J, et al. Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract. Cochrane Database Syst Rev. 2012;6:CD004567.
  • Millen AE, Sahli MW, Nie J, et al. Adequate vitamin D status is associated with the reduced odds of prevalent diabetic retinopathy in African Americans and Caucasians. Cardiovasc Diabetol. 2016;15(1):128.
  • Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. Journal of the National Cancer Institute. 1996;88(21):1550-1559.
  • Patrick PA, Visintainer PF, Shi Q, et al. Vitamin D and retinopathy in adults with diabetes mellitus. Arch Opthalmol. 2012;130(6):756-760.
  • Tomida I, Azuara-Blanco A, House H, et al. Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. J Glaucoma. 2006;15(5):349-353.
  • Wang SY, Singh K, Lin SC. Glaucoma and vitamins A, C, and E supplement intake and serum levels in a population-based sample of the United States. Eye (Lond). 2013;27(4):487-494.
  • Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systemic review and meta-analysis. JAMA. 2015;313(24):2456-2473.

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