Macular degeneration (MD) is an eye disease that typically affects older adults and results in a loss of vision in the center of the visual field (the macula) due to damage of the retina. It is a major cause of blindness and visual impairment in older adults, afflicting 30-50 million people globally. Macular degeneration can make it difficult or impossible to read or recognize faces, although enough peripheral vision remains to allow other activities of daily life.
The complement system is a part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism. Certain genes impair that system and increase the risk of MD. For example, the lifetime risk of developing late-stage MD is 50% for people who have a relative with MD, versus 12% for people who do not have relatives with MD.
Recently, researchers from the University of Buffalo aimed to determine if vitamin D interacts with certain genes known to cause MD.
Millen AE, Meyers KJ, Liu Z, Engelman CD, Wallace RB, LeBlanc ES, Tinker LF, Iyengar SK, Robinson JG, Sarto GE, Mares JA. Association Between Vitamin D Status and Age-Related Macular Degeneration by Genetic Risk. JAMA Ophthalmol. 2015 Aug 27. doi: 10CF.1001/jamaophthalmol.2015.2715. [Epub ahead of print].
CFH and CFI genes are both associated with MD. For each gene, roughly 25% of the population have two good alleles, about 50 % of the population have one good and one bad allele, and about 25 % of the population have 2 bad alleles. However, the authors found that vitamin D status greatly modulated the individual’s risk of macular degeneration if they had two bad alleles, either CFH or CFI.
If a person had two bad alleles (CFH or CFI), their risk for MD was 6 times higher when vitamin D levels were less than 12 ng/ml, 4 times higher when 25(OH)D was between 12 and 20 ng/ml, 2 times higher when 25(OH)D was between 20 and 30 ng/ml and not elevated when their level was greater than 30 ng/ml. These findings were independent for the two genes.
The authors explain that CFI acts to inhibit the complement cascade by inactivating parts of the compliment cascade system. However, this regulation requires the cofactor of CFH, illustrating the interconnectedness of these two proteins in cascade inhibition. The results from this study suggest that being vitamin D deficient might impair one’s ability to suppress a localized inflammatory response. When coupled with a dysfunctional complement pathway response, vitamin D deficiency could lead to an increased risk of MD beyond that expected from either independent risk factor alone.
The authors concluded,
“Our study provides evidence of a suggestive joint effect between vitamin D status and genotypes of complement factor genes. Maintenance of an adequate vitamin D status and likely an overall healthy lifestyle may reduce the total burden of early AMD to the greatest extent in those with high genetic risk for genes in the complement cascade.”
This study suggests vitamin D can overcome genetic predispositions for MD. Some people may know if they have the genes that confer risk for the compliment cascade, but I doubt very many people do. So, if you want to reduce your risk of MD, make sure you have “adequate vitamin D status.” Since no one knows what that is, maintaining natural vitamin D levels using a combination of safe sensible sun exposure and supplements of at least 5,000 IU/day is a safe practice to reduce your risk of developing MD.