Age-related macular degeneration (AMD) is an eye disease: Is your eye health supplement helping?

High dose eye supplements may be used to protect eyesight in age-related macular degeneration or AMD [1]. But there are recent concerns that AREDS-based supplements may be harmful in certain patients with specific genetic makeup.

Based on results of a recent pharmacogenetic study, there are concerns that macular degeneration AREDS formulation may be harmful in patients with particular variants of the genes CFH and ARMS2 genes [2].  The recent studies that analysed genetic profile of patients that have been taking macular degeneration AREDS formulations, showed that 13% of patients carry a specific genetic profile (2 high-risk CFH alleles and 0 ARMS2 risk alleles), and in these group of patients the macular degeneration AREDS formula was actually harmful to their AMD and in fact accelerated vision loss faster than placebo [3,4] .

Now the concern is whether the macular degeneration AREDS supplement is safe and effective in 13% of Caucasians that have the specific genetic variants of ARMS2 and CFH genes?

Lengyel [5, 4] et al published results of studies that showed that high dose daily supplementation with zinc accelerates the formation of complement protein aggregates into drusen, causing dry macular degeneration in patients with high-risk CFH genotypes. It means that zinc may be harmful to patients with a certain CFH genetic profile.

There have been studies that showed high dose zinc provided by macular degeneration AREDS products promotes a pro-inflammatory state in patients with high-risk CFH genotypes, which leads to macular degeneration [6].

In other words, these data suggest that patients with specific CFH and ARMS2 genetic profiles (13% of macular degeneration AMD populations) should not take AREDS eye supplements because they may in fact, experience an increased progression to vision loss from age-related macular degeneration or AMD [7,8].

The effects of saffron supplementation in macular degeneration are independent of the CFH and ARMS2 genetic variations

Saffron is unique for protecting vision in age-related macular degeneration.

A new study (9) worked to determine whether the functional effects of oral supplementation with saffron are influenced by variations of specific genes in patients particularly by the complement factor H (CFH) and age-related maculopathy susceptibility (2) (ARMS2) risk genotypes. This study showed that the effects of saffron supplementation, evaluated by means of electroretinogram, was not influenced by the two major AMD risk polymorphisms in CHF and ARMS2 genes.

Therefore, the individual’s response to saffron supplementation is not dependent on CFH or ARMS2 genotypes. Saffron treatment provided a long term efficacy in two major genotypes. Improvements in macular function remained stable for 15 months in all patients, regardless of their genotype. 

Clinical management of early AMD patients with saffron supplementation is easier now as the effects are independent of CFH and ARMS2 genetic variations.



Age-related eye disease study (AREDS), age-related macular degeneration (AMD), eye health supplement, eye health vitamins, eye health nutrients, macular degeneration supplement, eye vitamins:

  1. Age-Related Eye Disease Study Research, G., 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(10): p. 1417-36.
  1. Lechanteur Y et al: Association of Smoking and CFH and ARMS2 Risk Variants With Younger Age at Onset of Neovascular Age-Related Macular Degeneration; JAMA Ophthalmol. May 15 2015;133(5):533-541
  2. Imre Lengyel et al.
 Correlations in distribution and concentration of calcium, copper and iron with zinc in isolated extracellular deposits associated with age-related macular degeneration: Royal Society of Chemistry, Volume 6 Number 7 July 2014 Pages 1167–1302.
  3. Klein ML et al. CFH and LOC3087715/ARMS2 Genotypes and Treatment with Antioxidants and Zinc for Age-Related Macular Degeneration. Ophthalmology 2008;115:1019-1025.
  4. Imre Lengyel et al; Experimental Eye Research 84 (2007) 772-780.
  5. Seddon JM et al; Prediction Model for Prevalence and Incidence of Advanced Age-Related Macular Degeneration Based on Genetic, Demographic and Environmental Variables. IOVS 2009;50(5):2044-2053.
  6. Awh, C.C. et al, Treatment response to antioxidants and zinc based on CFH and ARMS2 genetic risk allele number in the Age-Related Eye Disease Study. Ophthalmology, 2015. 122(1): p. 162-9.
  7. Awh, C.C. et al, CFH and ARMS2 Genetic Polymorphisms Predict Response to Antioxidants and Zinc in Patients with Age-related Macular Degeneration. Ophthalmology, 2013 Nov;120(11):2317-23. doi: 10.1016/j.ophtha.2013.07.039.
  8. Marangoni et al. Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report  Journal of Translational Medicine 2013, 11:228