Age-Related Eye Disease Study

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The Age-Related Eye Disease Study (AREDS) was a clinical trial sponsored by the National Eye Institute that ran from 1992 to 2001. [1] The study was designed to:

Contents

The results were reported in the October 2001 issue of Archives of Ophthalmology . [1] The study followed 3640 individuals for an average of 6.3 years between 1992 and 2001. The researchers concluded that high levels of antioxidants and zinc can reduce some people's risk of developing advanced AMD by about 25 percent. [1] Advanced AMD is defined as either choroidal neovascularization (wet macular degeneration) or atrophic age-related macular degeneration (geographic atrophy). The anti-oxidants and zinc supplements only reduced the risk of progression to wet macular degeneration. Those that benefited from the dietary supplements included those with intermediate-stage AMD and those with advanced AMD in one eye only. The supplements had no significant effect on the development or progression of cataracts. "High levels" in this case were defined to be:

Bausch & Lomb was a collaborator in the study. [2] They and other suppliers provide supplements pre-packaged with formulations based on this study.

Studies in 2016 [3] and 2018 [4] later showed that this average 25 percent reduction in risk from the combination of anti-oxidants and zinc varies by genotype.

AREDS2

Changes in the formulation [5]
IngredientAREDSAREDS2
Vitamin C 500mg500mg
Vitamin E 400IU400IU
Beta-carotene 15mg Crystal Clear action edit remove.png  Removed
Cupric oxide 2mg2mg
Lutein 10mg
Zeaxanthin 2mg
Zinc 80mg80mg

The original AREDS study was followed by AREDS2, a five-year study that started in 2006 to test whether the original AREDS formulation would be improved by adding omega-3 fatty acids; adding lutein and zeaxanthin; removing beta-carotene; or reducing zinc. [6] [7] [8] In AREDS2, participants took one of four AREDS formulations: the original AREDS formulation, AREDS formulation with no beta-carotene, AREDS with low zinc, AREDS with no beta-carotene and low zinc. In addition, they took one of four additional supplement or combinations including lutein and zeaxanthin (10 mg and 2 mg), omega-3 fatty acids (1,000 mg), lutein/zeaxanthin and omega-3 fatty acids, or placebo. [6] [8]

The study reported that there was no overall additional benefit from adding omega-3 fatty acids or lutein and zeaxanthin to the formulation. However, the study did find benefits in two subgroups of participants: those not given beta-carotene, and those who had very little lutein and zeaxanthin in their diets. Removing beta-carotene did not curb the formulation's protective effect against developing advanced AMD, [6] which is important given that high doses of beta-carotene have been linked to higher risk of lung cancers in smokers. [9] According to Dr. Emily Chew, "Because carotenoids can compete with each other for absorption in the body, beta-carotene may have masked the effect of the lutein and zeaxanthin in the overall analysis." [6]

The AREDS2 trial did not find a difference in the effects of 80mg versus 25mg zinc. The UK National Health Service suggests that people may take the lower dose if the higher dose upsets their stomach. [10] The 25mg zinc level has not been compared to a placebo, as of 2020, and 80mg remains the standard. [5]

Packaging

The AREDS2 formulation is often sold with all the ingredients packaged together in one pill, for convenience. These formulations may be labelled as "AREDS2", the pharmaceutical generic name, or they may be labelled with trademarked brand names, or they may be labelled with both. Some preparations not explicitly labelled as AREDS2 may not contain the correct ingredients in the correct quantities, and may contain additional, non-AREDS2 ingredients, which have no proven benefit. [10]

The AREDS2 formulation can also be taken as a set of pills which contain the individual components in the correct quantities. [10]

Related Research Articles

Omega−3 fatty acids, also called Omega−3 oils, ω−3 fatty acids, Ω-3 Fatty acids or n−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their chemical structure. They are widely distributed in nature, being important constituents of animal lipid metabolism, and they play an important role in the human diet and in human physiology. The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA can be found in plants, while DHA and EPA are found in algae and fish. Marine algae and phytoplankton are primary sources of omega−3 fatty acids. DHA and EPA accumulate in fish that eat these algae. Common sources of plant oils containing ALA include walnuts, edible seeds, and flaxseeds as well as hempseed oil, while sources of EPA and DHA include fish and fish oils, and algae oil.

Tocopherols are a class of organic compounds comprising various methylated phenols, many of which have vitamin E activity. Because the vitamin activity was first identified in 1936 from a dietary fertility factor in rats, it was named tocopherol, from Greek τόκοςtókos 'birth' and φέρεινphérein 'to bear or carry', that is 'to carry a pregnancy', with the ending -ol signifying its status as a chemical alcohol.

<span class="mw-page-title-main">Vitamin A</span> Essential nutrient

Vitamin A is a fat-soluble vitamin, hence an essential nutrient. The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinal, retinoic acid, and several provitamin (precursor) carotenoids, most notably beta-carotene. Vitamin A has multiple functions: essential in embryo development for growth, maintaining the immune system, and healthy vision, where it combines with the protein opsin to form rhodopsin – the light-absorbing molecule necessary for both low-light and color vision.

<span class="mw-page-title-main">Abetalipoproteinemia</span> Medical condition

Abetalipoproteinemia is a disorder characterized by abnormal absorption of fat and fat-soluble vitamins from food. It is caused by a mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively. It is not to be confused with familial dysbetalipoproteinemia.

<span class="mw-page-title-main">Macula</span> Oval-shaped pigmented area near the center of the retina

The macula (/ˈmakjʊlə/) or macula lutea is an oval-shaped pigmented area in the center of the retina of the human eye and in other animals. The macula in humans has a diameter of around 5.5 mm (0.22 in) and is subdivided into the umbo, foveola, foveal avascular zone, fovea, parafovea, and perifovea areas.

The National Eye Institute (NEI) is part of the U.S. National Institutes of Health (NIH), an agency of the U.S. Department of Health and Human Services. The mission of NEI is "to eliminate vision loss and improve quality of life through vision research." NEI consists of two major branches for research: an extramural branch that funds studies outside NIH and an intramural branch that funds research on the NIH campus in Bethesda, Maryland. Most of the NEI budget funds extramural research.

β-Carotene Red-orange pigment of the terpenoids class

β-Carotene (beta-carotene) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. It is a member of the carotenes, which are terpenoids (isoprenoids), synthesized biochemically from eight isoprene units and thus having 40 carbons.

<span class="mw-page-title-main">Xanthophyll</span> Chemical compounds subclass

Xanthophylls are yellow pigments that occur widely in nature and form one of two major divisions of the carotenoid group; the other division is formed by the carotenes. The name is from Greek: xanthos (ξανθός), meaning "yellow", and phyllon (φύλλον), meaning "leaf"), due to their formation of the yellow band seen in early chromatography of leaf pigments.

<span class="mw-page-title-main">Multivitamin</span> Dietary supplement containing vitamins

A multivitamin is a preparation intended to serve as a dietary supplement with vitamins, dietary minerals, and other nutritional elements. Such preparations are available in the form of tablets, capsules, pastilles, powders, liquids, or injectable formulations. Other than injectable formulations, which are only available and administered under medical supervision, multivitamins are recognized by the Codex Alimentarius Commission as a category of food.

<span class="mw-page-title-main">Macular degeneration</span> Medical condition associated with vision loss

Macular degeneration, also known as age-related macular degeneration, is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, some people experience a gradual worsening of vision that may affect one or both eyes. While it does not result in complete blindness, loss of central vision can make it hard to recognize faces, drive, read, or perform other activities of daily life. Visual hallucinations may also occur.

<span class="mw-page-title-main">Vegetarian nutrition</span> Nutritional and human health aspects of vegetarian diets

Vegetarian nutrition is the set of health-related challenges and advantages of vegetarian diets.

<span class="mw-page-title-main">Lutein</span> Yellow organic pigment created by plants

Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. Lutein is synthesized only by plants, and like other xanthophylls is found in high quantities in green leafy vegetables such as spinach, kale and yellow carrots. In green plants, xanthophylls act to modulate light energy and serve as non-photochemical quenching agents to deal with triplet chlorophyll, an excited form of chlorophyll which is overproduced at very high light levels during photosynthesis. See xanthophyll cycle for this topic.

<span class="mw-page-title-main">Cone dystrophy</span> Medical condition

A cone dystrophy is an inherited ocular disorder characterized by the loss of cone cells, the photoreceptors responsible for both central and color vision.

<span class="mw-page-title-main">Zeaxanthin</span> Chemical compound

Zeaxanthin is one of the most common carotenoids in nature, and is used in the xanthophyll cycle. Synthesized in plants and some micro-organisms, it is the pigment that gives paprika, corn, saffron, goji (wolfberries), and many other plants and microbes their characteristic color.

David Anthony Newsome M.D. FARVO was a scientist, ophthalmologist, inventor, and author. He studied the treatment of age-related macular degeneration and proposed the usefulness of zinc supplements to slow the rate of vision loss from age-related macular degeneration.

Vitamin D and Omega-3 Trial (VITAL) was a clinical trial designed to investigate the use of daily dietary supplements of vitamin D and fish oil.

<i>meso</i>-Zeaxanthin Xanthophyll carotenoid

meso-Zeaxanthin (3R,3′S-Zeaxanthin) is a xanthophyll carotenoid, and is one of the three stereoisomers of zeaxanthin. Of these three stereoisomers, meso-zeaxanthin is the second most abundant in nature, after 3R,3′R-zeaxanthin, which is produced by plants and algae. meso-Zeaxanthin has been identified in specific tissues of marine organisms and in the macula lutea, also known as the "yellow spot", of the human retina.

<span class="mw-page-title-main">Emily Chew</span> American ophthalmologist

Emily Ying Chew is an American ophthalmologist and an expert on the human retina with a strong clinical and research interest in diabetic eye disease and age-related eye diseases. She currently works for the National Eye Institute (NEI) at the National Institutes of Health (NIH) in Bethesda, Maryland, where she serves as deputy director of the Division of Epidemiology and Clinical Applications (DECA) and the Institute's deputy clinical director. She designs and implements Phase 1, 2 and 3 clinical trials at the NIH Clinical Center. Chew is board certified in ophthalmology.

<span class="mw-page-title-main">Senior dog diet</span>

Senior dog food diets are pet foods that are catered toward the senior or mature pet population. The senior dog population consists of dogs that are over the age of seven for most dog breeds, though in general large and giant breed dogs tend to reach this life stage earlier when compared to smaller breed dogs. Senior dog foods contain nutrients and characteristics that are used to improve the health of the aging dog. Aging in dogs causes many changes to occur physiologically that will require a change in nutrient composition of their diet.

In general, cognitive support diets are formulated to include nutrients that have a known role in brain development, function and/or maintenance, with the goal of improving and preserving mental processes such as attentiveness, short-term and long-term memory, learning, and problem solving. Currently, there is very little conclusive research available regarding cat cognition as standardized tests for evaluating cognitive ability are less established and less reliable than cognitive testing apparatus used in other mammalian species, like dogs. Much of what is known about feline cognition has been inferred from a combination of owner-reported behaviour, brain necropsies, and comparative cognitive neurology of related animal models. Cognition claims appear primarily on kitten diets which include elevated levels of nutrients associated with optimal brain development, although there are now diets available for senior cats that include nutrients to help slow the progression of age-related changes and prevent cognitive decline. Cognition diets for cats contain a greater portion of omega-3 fatty acids, especially docosahexaenoic acid (DHA) as well as eicosapentaenoic acid (EPA), and usually feature a variety of antioxidants and other supporting nutrients thought to have positive effects on cognition.

References

  1. 1 2 3 Age-Related Eye Disease Study Research Group (October 2001). "AREDS Report No. 8: A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E, Beta Carotene, and Zinc for Age-Related Macular Degeneration and Vision Loss". Archives of Ophthalmology . 119 (10): 1417–1436. doi: 10.1001/archopht.119.10.1417 . PMC   1462955 . PMID   11594942.
  2. The Age-Related Eye Disease Study Research Group (June 2006). "The Age-Related Eye Disease Study (AREDS): Design Implications AREDS Report No. 1". Controlled Clinical Trials. 20 (6): 573–600. doi:10.1016/S0197-2456(99)00031-8. PMC   1473211 . PMID   10588299.
  3. Seddon, Johanna M.; Silver, Rachel E.; Rosner, Bernard (July 2016). "Response to AREDS supplements according to genetic factors: survival analysis approach using the eye as the unit of analysis". British Journal of Ophthalmology. 100 (12): 1731–1737. doi: 10.1136/bjophthalmol-2016-308624 . PMC   6570490 . PMID   27471039.
  4. Vavvas, Demetrios G.; Small, Kent W.; Awh, Carl C.; Zanke, Brent W.; Tibshirani, Robert J.; Kustra, Rafal (January 2018). "CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation". Proceedings of the National Academy of Sciences. 115 (4): E696–E704. doi: 10.1073/pnas.1718059115 . PMC   5789949 . PMID   29311295.
  5. 1 2 "AREDS/AREDS2 Frequently Asked Questions | National Eye Institute". www.nei.nih.gov. National Eye Institute/National Institutes of Health . Retrieved 14 July 2024.
  6. 1 2 3 4 "NIH study provides clarity on supplements for protection against blinding eye disease". May 2013. Archived from the original on 2013-06-07. Retrieved 2024-02-21.
  7. Age-Related Eye Disease Study 2 Research Group (May 5, 2013). "Lutein/Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration. The Age-Related Eye Disease Study 2 (AREDS2) Controlled Randomized Clinical Trial" . JAMA. 309 (19): 2005–2015. doi:10.1001/jama.2013.4997. PMID   23644932.
  8. 1 2 "Age-Related Eye Disease Study 2 (AREDS2) - Full Text View". clinicaltrials.gov.
  9. Omenn, Gilbert S.; et al. (1996). "Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease" (PDF). New England Journal of Medicine. 334 (18): 1150–155. doi:10.1056/NEJM199605023341802. PMID   8602180.
  10. 1 2 3 "AREDS 2 trial of vitamins and minerals for macular degeneration". Milton Keynes University Hospital. UK National Health Service . Retrieved 14 July 2024.