|Year : 2012 | Volume
| Issue : 2 | Page : 83-86
Role of anti-oxidants in prevention of age-related macular degeneration
Department of Ophthalmology, MGM Medical College, Navi Mumbai, Maharashtra, India
|Date of Web Publication||22-Sep-2012|
Flat No 303, Shri sai sagar CHS, Plot No 80/81, Sector-19, Kharghar, Navi Mumbai-410210
Source of Support: None, Conflict of Interest: None
Age-related macular degeneration (ARMD) is the most common cause of severe, irreversible, vision loss in elderly people. It is estimated that 20 to 25 million people suffer from ARMD worldwide, of which 8 million people experience blindness. The treatment options are few and usually not successful in restoring the vision back. The anti-oxidants prevent the damage to the macula by free radicals and are beneficial in retarding the progress of ARMD. They also prevent the onset of ARMD. Anti-oxidant supplements are indicated to prevent the onset and retard the progression of ARMD. The Age-Related Eye Disease Study found that the daily supplementation of vitamin C 500 mg, vitamin E 400 IU and beta carotene 15 mg, zinc 80 mg and copper 2 mg for five years significantly retarded the progression of ARMD. Based on the results of this high quality, double blinded study, the American Academy of Ophthalmology recommends that patients with intermediate and severe ARMD consider taking antioxidants plus zinc on a daily basis.
Keywords: Age related macular degeneration, anti-oxidants, carotenoids, vitamin A, vitamin C, vitamin E
|How to cite this article:|
Deshpande S. Role of anti-oxidants in prevention of age-related macular degeneration. J Med Nutr Nutraceut 2012;1:83-6
|How to cite this URL:|
Deshpande S. Role of anti-oxidants in prevention of age-related macular degeneration. J Med Nutr Nutraceut [serial online] 2012 [cited 2020 Feb 26];1:83-6. Available from: http://www.jmnn.org/text.asp?2012/1/2/83/101292
| Introduction|| |
Age-related Macular Degeneration (ARMD), as its name suggests, is associated with the deterioration of function of the macula due to aging process. The macula is responsible for central vision, near vision, and color vision. This is possible because cones, the photoceptor cells are highly concentrated in macula. Slightest damage to fovea,the central part of macula causes profound disturbance in the vision.Due to the importance of macula, macular function is tested during every eye checkup.
ARMD is the most common cause of severe, irreversible, vision loss in elderly people. It is estimated that 20 to 25 million people suffer from ARMD worldwide, of which 8 million people experience blindness. 
The main symptoms of ARMD are a loss or blurring of vision, and a black area in our visual field (scotoma). Objects may appear distorted, small (micropsia), or large (macropsia) due to ARMD.
There are two main types of ARMD, dry and wet. Dry ARMD starts with the development of tiny, yellow deposits in the macula [Figure 1]. This ultimately results in the death of the nerve cells present in the macular area. The macula loses its normal yellow color and appears white, lusterless. Fundus examination in dry ARMD shows presence of drusen bodies in initial stages. Drusen bodies are discrete yellow deposits in macula due to degeneration of the retinal pigment epithelial cells. Atrophy and scarring is observed in late stages of dry ARMD. There is usually no effective treatment of dry ARMD in late stages.
In wet ARMD, abnormal, leaky, vessels grow in the macula, leading to the accumulation of blood and fluid. Fundus examination in wet ARMD may show hemorrhages and sub-retinal neo vascular membranes. Wet ARMD is usually associated with severe vision loss [Figure 2].The treatment options of wet ARMD include laser photo-coagulation or intravitreal injection of anti-vascular endothelial growth factor antibodies. However, once ARMD sets in, treatment is both difficult and expensive. 
|Figure 2: Fundus photograph of wet ARMD showing hemorrhages in macular area|
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Rationale of anti-oxidants in ARMD
In a majority of cases, loss of vision due to ARMD cannot be reversed by any treatment. It is therefore important to prevent it.Anti-oxidants offer hope in this regard, as they have the potential to prevent the occurrence or progression of ARMD. To understand how anti-oxidants work, we need to know more about the pathogenesis of ARMD. ARMD is the result of photo-oxidative-induced retinal injury and its inflammatory sequelae.
The macula needs a lot of oxygen, and at the same time is continuously exposed to light. This promotes the formation of a large number of free radicals, which are highly reactive chemicals produced by the body as a part of normal metabolism. Free radicals are toxic and unstable compounds, and they cause retinal cell damage by damaging the DNA and the cell membranes.Over a period of years, these free radicals injure the nerve cells in the macula, ultimately leading to its degeneration.They are produced in greater numbers when a person is exposed to UV radiation, tobacco smoke, and air pollution.  The longer one lives, the higher the risk of acquiring this condition. ARMD is present in around 46% of people aged 75 or above according to one population based study.
Although macular degeneration is closely related with the aging process, it is not inevitable with advancing age. This implies the involvement of other causative factors. These are hypertension, smoking, stress and dietary deficiency of anti-oxidants.
Anti-oxidants are nature's best defense against free radicals. They act as scavengers and neutralize the free radicals, thereby limiting the damage to the macula. Substances which act as anti-oxidants include vitamins (vitamin A, C and E), minerals (zinc and selenium), carotenoids (lutein and zeaxanthin), extracts from plants (bilberry and grape) etc.
There is negative correlation between serum levels of anti-oxidants and ARMD. Gale and colleagues reported that risk of ARMD was significantly higher in people with lower plasma concentrations of zeaxanthin. 
Dietary deficiency of anti-oxidants is an important and modifiable risk factor of AMD. Seventy-nine per cent of the patients with wet AMD were found to have a deficient daily intake in lutein-zeaxanthin in a study by Olea and colleagues. 
Most anti-oxidants are not produced in the body and therefore have to be consumed in our diet or via nutritional supplements. Antioxidant supplements are best taken in the form of combination products, as multiple antioxidants in synergy work far more effectively than a single antioxidant. A single antioxidant, even at high doses, does not provide the same degree of protection as a combination of antioxidants. Doses of multiple oxidants also help prevent the toxicity of a single agent.
Classification of anti-oxidants acting on the macula
The carotenoids, lutein and zeaxanthin are yellow colored pigments derived from plants. They are present in very high concentration in the macula, giving it a yellowish color. They protect the cones from damage by free radicals, and also filter out blue light, which is highly damaging to photoreceptors. Thus, they act like "sunglasses", protecting the critically important central sight from damaging light waves. They also protect the blood vessels in the macular area. By virtue of these actions, they prevent the onset and also retard the progression of ARMD. Lutein may also have additional anti-inflammatory action.
Zeaxanthin is predominantly present in the center of the macula, while lutein is present on the periphery. This may imply that they have different functions and should be taken in combination.Since carotenoids are not produced in the body, they need to be consumed in our diet or as nutritional supplements. Dietary sources of carotenoids include leafy green vegetables, corn, green peppers, carrots, peaches, and oranges. Most lutein supplements are derived from the extracts of marigold flowers.
Dietary carotenoids deficiency may be a causative factor for ARMD. Seddon and colleagues found abnormally low levels of carotenoids in blood in people suffering from ARMD in one study.  Zhou and colleagues in their study on 260 elderly Chinese subjects found that Serum levels of carotenoids and retinol were significantly lower in the cases with exudative AMD than in the controls.  Richer et al. reported that visual acuity improved after daily supplementation of lutein for 12 months in patients with atrophic ARMD.  These studies make a compelling case for lutein and zeaxanthin supplementation for the prevention and treatment of ARMD.
Carotenoid in Age-related Maculopathy Italian Study (CARMIS) was a two year randomized study carried out to find whether carotenoids have any effect on ARMD.Carotenoids Interventions used in this study was a combination of lutein (10 mg), zeaxanthin (1 mg), and astaxanthin (4 mg). In this study, carotenoids were associated with clinically meaningful stabilization/improvements in visual acuity and visual function through 24 months as compared with notreated subjects. 
Ma and colleagues conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. They did not find significant association between dietary lutein and zeaxanthin and early AMD. However, they reported that an increase in the intake of these carotenoids may be protective against late ARMD. 
Bilberry (Vaccinium myrtillus) is a small shrub found growing mostly in the fields of Europe-England, Scandinavia, and Siberia. The bilberry extract contains blue colored pigments called as anthocyanins. These are very powerful anti-oxidants and also protect the blood vessels in the retina by making them less fragile. Grape seed extract is rich in another group of pigments called as flavonoids which also act as anti-oxidants and may help in ARMD.
Minerals such as zinc and selenium are used for the treatment of ARMD due to their anti-oxidant properties. Zinc is highly concentrated in the macula. Zinc activates many enzymes and plays an important role in the metabolism of proteins and nucleic acids. Dietary sources of zinc include meat, poultry, fish, whole grains, anddairy products . For many years now, zinc has been used as a component in ocular nutritional supplements. Zinc does not have significant adverse effects. However,zinc sulfate supplementation may depress copper levels and cause copper deficiency anemia. Therefore, zinc should always be taken with copper.
Vitamin E is the anti-oxidant vitamin as its main function is to prevent the damage of body tissues by free radicals. Serum vitamin E levels have been found to correlate negatively with severity of age related macular degeneration.  Due to its anti-oxidant properties, vitamin E is recommended by National Institute of Eye (NIE)at a dose of 400 IU/day in the treatment of ARMD. Selenium, a mineral, is required for the digestion and absorption of vitamin E. On the other hand, vitamin E reduces selenium requirements by preventing selenium loss from the body. Thus, vitamin E and selenium act synergistically and reduce the body's requirement for each other. Selenium also activates the antioxidant enzyme glutathione peroxidase, and protects cell membranes from oxidative damage.
Vitamin A, C and B 6 also have anti-oxidant properties.Vitamins when taken in isolation may not have beneficial effect in ARMD.Christen et al. In a large-scale, randomized trial of United States male physicians, alternate-day use of 400 IU of vitamin E and/or daily use of 500 mg of vitamin C for 8 years had no appreciable beneficial or harmful effect on risk of incident diagnosis of AMD. 
| Age-related Eye Disease Study|| |
Age-Related Eye Disease Study (AREDS) was a landmark study which was conducted across multiple centers in America to study the efficacy of anti-oxidant supplements in ARMD. In this study, some patients with ARMD received anti-oxidants plus zinc whereas the others received placebos. At the end of five years, it was found that the daily supplementation of anti-oxidants and zinc significantly retarded the progression of ARMD. The daily supplement used in this study contained vitamin C 500 mg, vitamin E 400 IU and beta carotene 15 mg, zinc 80 mg and copper 2 mg. This combination was found to be free from significant serious adverse effects.Based on the results of this high quality, double blinded study, the AmericanAcademy of Ophthalmology recommends that patients with intermediate and severe ARMDconsider taking antioxidants plus zinc on a daily basis. 
Sin and colleagues analyzed various risk factors and role of anti-oxidant supplements in treatment and prevention of AMD in asystematic review of the published studies. They found that smoking and obesity were significant risk factors associated with ARMD. Based on the evidence, they did not recommend routine anti-oxidants supplements for primary prevention of ARMD. However, patients with documented intermediate risk of AMD or advanced AMD in one eye are recommended to take AREDS-type vitamin supplements. 
Adverse effects of anti-oxidants
Potential harms of high-dose antioxidant supplementation must be considered before starting a patient on anti-oxidant supplements. Lutein and zeaxanthin are generally well tolerated without any major systemic adverse effects.  Adverse effects of anti-oxidants are an increased risk of lung cancer in smokers (beta-carotene), heart failure in people with vascular disease or diabetes (vitamin E) and hospitalization for genitourinary conditions (zinc). 
| Conclusion|| |
ARMD is a very common and dreaded disease of old age which may lead to irreparable vision loss. The treatment options are few and usually not successful in restoring the vision back. The anti-oxidants prevent the damage to the macula by free radicals and are beneficial in retarding the progress of ARMD. They also prevent the onset of ARMD.
Based on current evidence, anti-oxidant supplements especially lutein and zeaxanthin are definitely indicated in patients with diagnosed ARMD to slow the progression of the disease. Anti-oxidants are more important in wet ARMD than dry ARMD. However, anti-oxidant supplements should not be routinely recommended in elderly people for primary prevention of ARMD due to lack of sufficient evidence in this regard. Further studies may shed light on this topic. An ideal ocular supplement should include all of the anti-oxidants described above to give maximum protection against free radicals without causing adverse effects.
| References|| |
|1.||Klein R, Klein BE, Tomany SC, Meuer SM, Huang GH. Ten-year incidence and progression of age-related maculopathy: The Beaver Dam eye study. Ophthalmology 2002;109:1767-79. |
|2.||Chopdar A, Chakravarthy U, Verma D. Age related macular degeneration. BMJ 2003;326:485-8. |
|3.||Beatty S, Koh H, Phil M, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 2000;45:115-34. |
|4.||Gale CR, Hall NF, Phillips DI, Martyn CN. Lutein and zeaxanthin status and risk of age-related macular degeneration. Invest Ophthalmol Vis Sci 2003;44:2461-5. |
|5.||Olea JL, Aragón JA, Zapata ME, Tur JA. [Characteristics of patients with wet age-related macular degeneration and low intake of lutein and zeaxanthin]. Arch Soc Esp Oftalmol 2012;87:112-8. |
|6.||Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA 1994;272:1413-20. |
|7.||Zhou H, Zhao X, Johnson EJ, Lim A, Sun E, Yu J, et al. Serum carotenoids and risk of age-related macular degeneration in a chinese population sample. Invest Ophthalmol Vis Sci 2011;52:4338-44. |
|8.||Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: The Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry 2004;75:216-30. |
|9.||Piermarocchi S, Saviano S, Parisi V, Tedeschi M, Panozzo G, Scarpa G, et al. Carotenoids in Age-related Maculopathy Italian Study (CARMIS): Two-year results of a randomized study. Eur J Ophthalmol 2012;22:216-225. |
|10.||Ma L, Dou HL, Wu YQ, Huang YM, Huang YB, Xu XR, et al. Lutein and zeaxanthin intake and the risk of age-related macular degeneration: A systematic review and meta-analysis. Br J Nutr 2012;107:350-9. |
|11.||Belda JI, Romá J, Vilela C, Puertas FJ, Díaz-Llopis M, Bosch-Morell F, et al. Serum vitamin E levels negatively correlate with severity of age-related macular degeneration. Mech Ageing Dev 1999;107:159-64. |
|12.||Christen WG, Glynn RJ, Sesso HD, Kurth T, Macfadyen J, Bubes V, et al. Vitamins E and C and Medical Record-Confirmed Age-Related Macular Degeneration in a Randomized Trial of Male Physicians. Ophthalmology 2012. |
|13.||Age-Related Eye Disease Study Research Group. 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: AREDS report no. 8. Arch Ophthalmol 2001;119:1417-36. |
|14.||Sin HP, Liu DT, Lam DS. Lifestyle modification, nutritional and vitamins supplements for age-related macular degeneration. Acta Ophthalmol 2012. |
|15.||Khachik F, de Moura FF, Chew EY, Douglass LW, Ferris FL 3 rd , Kim J, et al. The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older. Invest Ophthalmol Vis Sci 2006;47:5234-42. |
|16.||Evans J. Antioxidant supplements to prevent or slow down the progression of AMD: A systematic review and meta-analysis. Eye (Lond) 2008;22:751-60. |
[Figure 1], [Figure 2]
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