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Evidence indicates link between hyperhomocysteinemia, AMD
This risk factor could be modified with diet and supplementation.
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Elevated levels of homocysteine have been implicated in arteriosclerosis, stroke and cardiovascular disease. More recently, there have been cross-sectional and case-controlled studies linking elevated plasma levels of homocysteine with neovascular age-related macular degeneration, suggesting a modifiable risk factor for AMD. Lowering these levels may be an interventional method in the prevention of the more visually debilitating type of AMD.
Homocysteine (Hcy) is an amino acid used in the synthesis of methionine and cysteine, two essential amino acids. When Hcy is not synthesized quickly or efficiently, total plasma Hcy levels rise, leading to a condition called hyperhomocysteinemia (hHcy). More severe cases may have a genetic link; the less severe form may be caused by diet. Hcy concentration also varies with age and geographical area, its concentration normally increasing with advancing age.
Epidemiological studies
Epidemiological studies have reported that an elevated level of Hcy is related to a higher risk of developing cardiovascular disease and stroke. Evidence suggests that Hcy has an effect on cardiovascular disease because it damages the inner lining of the arteries and promotes blood clots (Molloy, Ambati et al.), and elevated levels of Hcy leads to inflammatory and oxidative changes in tissues (Vine et al.). Many of these factors leading to cardiovascular disease have been found to be related to AMD. It is thought that oxidative stress disrupts the retinal pigment epithelial cell junctions along Bruch’s membrane, thus releasing angiogenic factors that stimulate neovascularization – a hallmark sign of neovascular AMD. The retina is particularly susceptible to oxidative stress because of its high consumption of oxygen, its high proportion of polyunsaturated fatty acids and its exposure to visible light.
A number of studies support the link between AMD and Hcy. In 2004, Axer-Siegel and colleagues published a cross-sectional study associating exudative or neovascular AMD with hHcy. They found that Hcy levels were higher by 27.9% in the neovascular group than the nonexudative AMD group.
Seddon and colleagues, in 2005, measured fasting plasma Hcy levels on 934 individuals participating in an ancillary study of the Age-Related Eye Disease Study (AREDS). Results of this cross-sectional, case-controlled study were consistent with the association between higher Hcy and AMD. The researchers determined that Hcy may be a “modifiable risk factor” for AMD.
Elisa F. de Junco
The Blue Mountains Eye Study assessed associations of Hcy, low vitamin B12, low folate and AMD. The results of this study showed that the participants who were age 75 and older with Hcy levels greater than 15 µmol/L had an increased likelihood of developing AMD. Nowak and colleagues similarly found a concentration of 14.89 µmol/L in neovascular AMD subjects, a significantly higher concentration than their control group. They concluded that hHcy might be one of the risk factors for the neovascular form of AMD.
In their study to determine which layers of the retina are affected by hHcy, Chang and colleagues subjected experimental mice to intravitreal injections of homocysteine-thiolactone and evaluated the retinas microscopically and with immunohistochemical analysis. Their results indicated that homocysteinylation was localized in the outer and inner segments of the photoreceptors and the ganglion cell layer. They concluded that patients with Hcy levels greater than 15 µmol/L could have a degeneration of the photoreceptors.
In 2012, Yu and colleagues also worked with experimental mice to determine whether elevated Hcy alters visual function. Their data suggested that elevated Hcy is associated with marked alterations in retinal function.
Thomas J.
de Junco
These studies show a link between elevated Hcy (greater than 15 µmol/L) and damage to retinal tissue. Can exudative AMD risk be reduced by reducing one’s Hcy level? Kamburoglu and colleagues showed that patients with both forms of AMD have increased Hcy levels, but those with the exudative type also had decreased vitamin B12 levels. There is a relationship between B12 and Hcy; O’Leary and colleagues and Satyanavayara and colleagues found B12 to be the major determinant of Hcy concentration.
Treatment with nutritional supplements
Treatment with folic acid, B6 and B12 has been shown to decrease Hcy concentration, and plasma Hcy levels can be safely lowered by 25% with folic acid and by 7% with B12 (Homocysteine Lowering Trialists’ Collaboration).
According to Alexander, recommended daily dosages for these important vitamins are 1,000 µg to 4,000 µg of folic acid, 10 mg to 50 mg of vitamin B6 and 50 mg to 1,000 mg of B12
Neovascular AMD affects 10% of Americans 65 to 74 years old and 13% 85 years and older (Dong Nguyen). Evidently, a better understanding of AMD and interventions in the early stages can reduce these unfortunate statistics and improve the quality of life for American seniors. Finding another modifiable risk factor such as elevated Hcy level can alert the practitioner in cases of early AMD to initiate diet modification and low-cost vitamin treatments.
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