clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
sponsored by the
National Eye Institute
The National Eye Institute (NEI) is part of the National Institutes of Health, U.S. National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services, U.S. Department of Health and Human Services. The mi ...
that ran from 1992 to 2001. The study was designed to:
* investigate the natural history and
risk factor
In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection.
Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...
s of
age-related macular degeneration
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), 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. Some people experien ...
(AMD) and
cataract
A cataract is a cloudy area in the lens (anatomy), lens of the eye that leads to a visual impairment, decrease in vision of the eye. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colours, blurry or ...
s, and
* evaluate the effects of high doses of
antioxidant
Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...
s and
zinc
Zinc is a chemical element; it has symbol Zn and atomic number 30. It is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic tabl ...
on the progression of the two conditions in those with AMD.
The results were reported in the October 2001 issue of ''
Archives of Ophthalmology
An archive is an accumulation of historical records or materials, in any medium, or the physical facility in which they are located.
Archives contain primary source documents that have accumulated over the course of an individual or organi ...
''. 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. 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:
*500
milligram
The kilogram (also spelled kilogramme) is the base unit of mass in the International System of Units (SI), equal to one thousand grams. It has the unit symbol kg. The word "kilogram" is formed from the combination of the metric prefix kilo- (m ...
s of
vitamin C
Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits, berries and vegetables. It is also a generic prescription medication and in some countries is sold as a non-prescription di ...
;
*400
international unit
In pharmacology, the international unit (IU) is a unit of measurement for the effect or biological activity of a substance, for the purpose of easier comparison across similar ''forms'' of substances. International units are used to quantify vi ...
s of
vitamin E
Vitamin E is a group of eight compounds related in molecular structure that includes four tocopherols and four tocotrienols. The tocopherols function as fat-soluble antioxidants which may help protect cell membranes from reactive oxygen speci ...
;
*15 milligrams of beta-carotene (or 25,000 international units of
vitamin A
Vitamin A is a fat-soluble vitamin that is an essential nutrient. The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinyl esters, and several provitamin (precursor) carotenoids, most not ...
);
*80 milligrams of the
dietary mineral
In the context of nutrition, a mineral is a chemical element. Some "minerals" are essential for life, but most are not. ''Minerals'' are one of the four groups of essential nutrients; the others are vitamins, essential fatty acids, and essent ...
zinc, in the form of
zinc oxide
Zinc oxide is an inorganic compound with the Chemical formula, formula . It is a white powder which is insoluble in water. ZnO is used as an additive in numerous materials and products including cosmetics, Zinc metabolism, food supplements, rubbe ...
; and
*two milligrams of
copper
Copper is a chemical element; it has symbol Cu (from Latin ) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkish-orang ...
as
cupric oxide
Copper(II) oxide or cupric oxide is an inorganic compound with the formula CuO. A black solid, it is one of the two stable oxides of copper, the other being Cu2O or copper(I) oxide (cuprous oxide). As a mineral, it is known as tenorite, or so ...
, added to prevent
copper deficiency
Copper deficiency, or hypocupremia, is defined as insufficient copper to meet the body's needs, or as a serum copper level below the normal range. Symptoms may include fatigue, Anemia, decreased red blood cells, early greying of the hair, and neu ...
anemia
Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
, a condition associated with high levels of zinc intake.
Bausch & Lomb
Bausch & Lomb (since 2010 stylized as Bausch + Lomb) is an American-Canadian eye health products company based in Vaughan, Ontario, Canada. It is one of the world's largest suppliers of contact lenses, lens care products, pharmaceuticals, intra ...
was a collaborator in the study. They and other suppliers provide supplements pre-packaged with formulations based on this study.
Studies in 2016 and 2018 later showed that this average 25 percent reduction in risk from the combination of anti-oxidants and zinc varies by genotype.
AREDS2
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
Omega−3 fatty acids, also called omega−3 oils, 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 c ...
zeaxanthin
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 (made from bell peppers), corn, saffron, goji ( wolfberries) ...
; removing beta-carotene; or reducing zinc. 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.
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, which is important given that high doses of beta-carotene have been linked to higher risk of lung cancers in smokers. 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."
The AREDS2 trial did not find a difference in the effects of 80mg versus 25mg zinc. The UK
National Health Service
The National Health Service (NHS) is the term for the publicly funded health care, publicly funded healthcare systems of the United Kingdom: the National Health Service (England), NHS Scotland, NHS Wales, and Health and Social Care (Northern ...
suggests that people may take the lower dose if the higher dose upsets their stomach. The 25mg zinc level has not been compared to a placebo, , and 80mg remains the standard.
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
A trademark (also written trade mark or trade-mark) is a form of intellectual property that consists of a word, phrase, symbol, design, or a combination that identifies a product or service from a particular source and distinguishes it from ot ...
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.
The AREDS2 formulation can also be taken as a set of pills which contain the individual components in the correct quantities.