clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
sponsored by the
National Eye Institute
The National Eye Institute (NEI) was established in 1968. It is located in Bethesda, Maryland, United States. The NEI is one of 27 institutes and centers of the US National Institutes of Health (NIH), an agency of the US Department of Health and ...
that ran from 1992-2001. 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. Over time, however, som ...
(AMD) and
cataract
A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
s, and
* evaluate the effects of high doses of
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
s and
zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc 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 periodi ...
on the progression of the two conditions in those with AMD.
The results were reported in the October 2001 issue of ''
Archives of Ophthalmology
''JAMA Ophthalmology'' (formerly ''Archives of Ophthalmology'') is a monthly peer-reviewed medical journal covering all aspects of ophthalmology. The editor-in-chief is Neil M. Bressler (Johns Hopkins School of Medicine). It is published by the ...
''. 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 kilogramme) is the unit of mass in the International System of Units (SI), having the unit symbol kg. It is a widely used measure in science, engineering and commerce worldwide, and is often simply called a kilo colloquially. ...
s of
vitamin C
Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...
;
*400
international unit
In pharmacology, the international unit (IU) is a unit of measurement for the effect, not mass of a substance; the variance is based on the biological activity or effect, for the purpose of easier comparison across similar ''forms'' of substance ...
s of
vitamin E
Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vitami ...
;
*15 milligrams of beta-carotene (or 25,000 international units of
vitamin A
Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably bet ...
);
*80 milligrams of the
dietary mineral
In the context of nutrition, a mineral is a chemical element required as an essential nutrient by organisms to perform functions necessary for life. However, the four major structural elements in the human body by weight (oxygen, hydrogen, carbon ...
zinc, in the form of
zinc oxide
Zinc oxide is an inorganic compound with the formula . It is a white powder that is insoluble in water. ZnO is used as an additive in numerous materials and products including cosmetics, food supplements, rubbers, plastics, ceramics, glass, cemen ...
; and
*two milligrams of
copper
Copper is a chemical element with the symbol Cu (from la, cuprum) 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 pinkis ...
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. It i ...
, added to prevent
copper deficiency
Copper deficiency, or hypocupremia, is defined either as insufficient copper to meet the needs of the body, or as a serum copper level below the normal range. Symptoms may include fatigue, decreased red blood cells, early greying of the hair, a ...
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
, a condition associated with high levels of zinc intake.
Bausch & Lomb
Bausch + Lomb is an 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, intraocular lenses, and other eye surgery products. The compan ...
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 chem ...
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.Age-Related Eye Disease Study 2 (AREDS2) /ref> 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."