Article
Zinc supplementation inhibits complement activation in AMD
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Published: | October 1, 2015 |
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Background: Zinc supplementation can reduce the progression of AMD but the precise mechanism of this protective effect is as yet unclear. Complement-mediated inflammation plays a fundamental role in the etiology of AMD. We designed the present study to investigate whether zinc affects the activity of the alternative complement pathway— defined as the C3d/C3 and C5a— in patients with AMD. Secondly, we correlate the response to the CFH and ARMS2 genotype.
Methods: A sample size of 70 was calculated to detect a decrease in serum complement of 10% with α=0.05 and power of 80. In this clinical study, 72 AMD patients received a daily supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months. One blood samples was collected prior to zinc supplementation. Three samples were collected at the end of months 1, 2 and 3 of the period of zinc supplementation. To check for any reversible effects of zinc, we collected a two blood sample after ending the zinc administration. All patients were genotype for the CFH and ARMS2.
Results: Serum zinc concentration increased significantly (p<0.001). The patients with high serum complement catabolism had a steep decline in C3d/C3 ratio during the administration of zinc sulphate (p<0.001). C5a showed also a significant decrease during zinc supplementation. Measurements performed when zinc administration was ended, showed that C3d/C3 had returned to prior baseline levels. Change in complement catabolism were not related to CFH or ARMS2 genotypes.
Conclusions: Our findings demonstrate that increased levels of complement catabolism in AMD patients can be normalized by the daily oral administration of 50 mg zinc sulphate. The C3d/C3 ratio returned to ist baseline value after ending the zinc administration, indicating a reversible effect of zinc on complement. Continuous zinc supplementation may therefore be necessary to inhibit disease over longer periods of time.