AMD - Genetic and Environmental Risk

Macular degeneration (AMD) is the leading cause of vision loss in people over age fifty-five.  Genetic research from the Human Genome Project has shown that macular degeneration has one of the highest multi-genetic components of all common diseases.  But there are certain environmental elements that can reduce or increase individual risk of macular degeneration.  So, there are steps a person can take to reduce their genetic risk and there are things to avoid to keep from increasing their risk.

Genetically, it has been discovered that inheriting a certain form of complement factor H (CFH) gene can greatly influence risk of developing AMD^1,2.  The additional genetic variation, ARMS2, an oxidative stress gene in combination with the CFH gene can increase a person’s risk of developing macular degeneration by nearly ten times.  Smoking cigarettes increases this risk an additional three times.   Obesity also increases the risk of developing macular degeneration, but health habits of diet and exercise can reduce the risk.

Staying active, maintaining a healthy weight, good dietary habits and not smoking can improve the chances of developing the vision-disabling condition^2.. Other potential risk factors may include high blood pressure, elevated cholesterol levels, sunlight and blue light from computer screens, tablets and phones.

The Benefits of Nutrition: Antioxidants, Omega-3’s and B Vitamins

There are dietary nutrients that may slow the progression of AMD and even delay the onset of the disease in people with inherited risk.  While scientific evidence is always on-going and more studies are needed to determine certain risk reduction, there is a growing body of evidence that points to several nutrients that can likely make a significant difference.

In the Age-Related Eye Disease Study (AREDS) 1 and 2 over the past three decades, certain vitamin elements were studied to determine effect against a placebo-control to determine the best nutrient or nutrients.  In these trials, people with at least moderate AMD and deficient in carotenoids lutein and zeaxanthin were found to benefit from taking a supplement with lutein and zeaxanthin to replace their deficiencies.  The supplement also contained zinc, copper, vitamin C and E^3,4,5.  Subsequent genetic research from AREDS 1 data showed supplemental zinc in some people to be beneficial, while others it was detrimental. For this reason, it is recommended to take a genetic test to determine zinc’s effect on an individual based on your genes from our perspective^6,7.  Our doctors can assist you in testing your genes if you would like to pursue the need to avoid or take zinc supplements.  Otherwise, taking the most important of the substances in the AREDS trials seems to be the best supplement for protection without knowing your individual genetics.  

Several population-health studies have found consuming diets rich in green leafy vegetable sources of the nutrients lutein and zeaxanthin may reduce the risk of intermediate and advanced AMD^3,8,9.  Most recently, diets high in lutein/zeaxanthin as well as fish were found to be protective against AMD  in people with high genetic risk CFH and/or ARMS2¹⁰. Studies of a carotenoid blend of lutein, zeaxanthin and meso-zeaxanthin, Macuhealth, has shown to be the most effective carotenoids supplement blend - not only for healthy macular function, but for improved visual performance as measured by improved contrast sensitivity, glare recovery time, dark adaptation and temporal processing speed¹¹.

Getting enough of the omega-3 fatty acids, Eicosapentenoic Acid (EPA) and Docosopentenoic Acid (DHA) found in cold-water fish may also be protective.  In the strongest evidence to date, researchers report that regular intake of the omega-3’s, reduced the risk of developing AMD in women over a 10 year period¹². Another report giving greater credibility to this is a report that suggests higher intake of omega-3 fatty acids may help modify genetic susceptability for the progression to the dry AMD form¹³.

Evidence also supports beneficial effects of B-vitamins.  Supplemental folic acid with vitamins B6 and B12 taken over a 7-year period were shown to reduce the likelihood of AMD developing in women at risk of heart disease¹⁴.

Nutrient Rich Diets Recommended

Many clinicians advise those with AMD as well as younger patients with family members who have the disease to eat a diet that is plentiful in these nutrients.  

In addition to choosing cold-water wild-caught fish such as tuna, salmon or sardines for EPA/DHA, dark leafy green vegetables such as spinach and kale and orange vegetables such as peppers, carrots and pumpkin are good sources of carotenoids.

A recent study which looked at the dietary habits of over 16,000 individuals found that more than 80% of those 70 and older, and more than 90% of all others, ate too many calories from fats, added sugars and alcohol¹⁵.

Most of these individuals weren’t consuming enough of vitamins C, D and E from food alone, and nearly everyone failed to meet recommendations for dark green and organic vegetables, and whole grams – important sources of lutein, beta-carotene and zinc¹⁶.The use of dietary supplements dramatically improved intakes of many key nutrients – a good example of why a healthy diet along with dietary supplements is a good strategy to support ocular and overall health. 

References

1. Hadad W. et al.  The genetics of age-related macular degeneration: a review of progress to date.   Survey of Ophthalmology 51:316-63, 2008.
2. Mares JA. Et al Health lifestyles related to subsequent prevalence of age-related macular degeneration.  Archives of Ophthalmology 129:470-80, 2011.
3. Age-Related Eye Disease Study Research Group. The relationship of dietary carotenoids and vitamin A,E, and C intake with age-related macular degeneration in a case-control study AREDS report no 22 Arch Ophthalmology 125:1225-32 2007.
4. Age-Related Eye Disease Study 2 (AREDS2) Research Group  Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration profession; AREDS2 Report No.3 JAMA Ophthalmology (dec 5, 2013 132:142-49 2014.
5. Moeller SM. Et al. CAREDS Research Study Group.  Associations between intermediate age-related macular degeneration and lutein and zeaxanthin in the Carotenoids in Age-related Eye Disease Study (CAREDS) Archives of Ophthalmology 124:1151-62. 2006.
6. Awh C, et al.  CFH and ARMS Genetic Polymorphisms Predict Response to Antioxidants and Zinc in Patients with Age-related Macular Degeneration Ophthalmology 2013.
7. Vavvas D, et al.  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 of the United States of American, 2017.
8. Tan JSL, et al.  Dietary antioxidants and the long-term incidence of age-related macular degeneration.  The Blue Mountain Study.  Ophthalmology 115:334-41, 2008.
9. Wang JJ, et al.  Genetic susceptibility, dietary antioxidants, and long-term incidence of age-related macular degeneration in two populations.  Ophthalmology 121:667-75, 2014.
10. Ho L. et al.  Reducing the genetic reisk of age-related macular degeneration with dietary antioxidants, zinc, and omega-3 fatty acids.  The Rotterdan Study.  Ophthalmology 129:758-66, 2011.
11. Nelson, D.  Researchers emphasize Importance of Carotenoids in Visual Performance. Primary Eyecare News, December, 2018.
12. Christen WG et al.  Folic acid, pyridoxine and cyanocobalamin combination treatment and age-related macular degeneration in women; the Women’s Antioxidant and Folic Acid Cardiovascular Study Archives Internal Medicine 169:335-42, 2009.
13. Reynolds R, et al.  Dietary omega-3 fatty acids, other fat intake, genetic susceptivility, and profression to incident geographic atrophy.  Ophthalmology 120:1020-8, 2013.
14. Christen WG, et al.  Dietary omega-3 fatty acid and fish intake and incident age-related macular degeneration in women.  Archives Ophthalmology 129:921-29, 2011.
15. Fulgoni VL, et al.  Foods, fortificants and supplements; where do American get their nutrients?  Journal of Nutrition 141:1847-54, 2011.
16. Krebs-Smith SM. Et al.  American do not meet federal dietary recommendations.  Journal of Nutrition 140:1832-38, 2010.