Zinc is an essential trace element that is the cofactor for over 300 enzymes and for the DNA-binding zinc finger proteins, and it is particularly important as the essential cofactor for the copper-zinc superoxide dismutase (Cu,ZnSOD, SOD1) — the enzyme that is the primary line of defence against the superoxide radical in the cytoplasm of all cells. The Cu,ZnSOD is a dimeric enzyme that contains one copper and one zinc atom per subunit, and it catalyses the dismutation of the superoxide radical (O2-) to hydrogen peroxide (H2O2) and oxygen (O2) at a rate that is approximately 10,000 times faster than the spontaneous dismutation. Without adequate zinc and the functional Cu,ZnSOD, the superoxide radical accumulates in the cytoplasm, the oxidative stress increases, and the cellular macromolecules (DNA, proteins, lipids) are damaged — producing the genomic instability, the protein aggregation, and the lipid peroxidation that are the hallmarks of the oxidative stress and of the ageing process. This zinc-dependent vulnerability of the antioxidant defence is one of the most important mechanisms of the age-related decline in the cellular function, and it explains why the zinc supplementation has been shown to improve the immune function, to reduce the oxidative stress markers, and to protect against the age-related macular degeneration (AMD) in multiple clinical trials.
Copper-Zinc Superoxide Dismutase and the Cytoplasmic Antioxidant Defence
The copper-zinc superoxide dismutase (Cu,ZnSOD, SOD1) is the primary enzyme that disarms the superoxide radical in the cytoplasm of all cells — it is present at high concentrations (approximately 10-50 microM) in all cell types and it provides the first line of defence against the superoxide that is generated as a byproduct of the normal cellular metabolism, of the inflammatory response, and of the environmental toxins. The superoxide radical is the primary reactive oxygen species (ROS) that is generated in the cytoplasm — it is produced by the mitochondria (as a byproduct of the electron transport chain activity), by the NADPH oxidases (in activated immune cells), and by the xanthine oxidase (particularly in the ischaemia-reperfusion injury). The Cu,ZnSOD is the only enzyme that specifically disarms the superoxide radical in the cytoplasm — it converts the superoxide to the less reactive hydrogen peroxide, which is then reduced to water by the catalase and by the glutathione peroxidase. Without the Cu,ZnSOD and the zinc cofactor, the superoxide accumulates and produces the oxidative damage that is the primary driver of the cellular senescence and of the age-related diseases.
The clinical importance of the zinc for the Cu,ZnSOD function is underscored by the observation that the zinc deficiency reduces the Cu,ZnSOD activity in all tissues and increases the oxidative stress markers — and that the zinc supplementation restores the Cu,ZnSOD activity and reduces the oxidative stress in zinc-deficient individuals. A study in 40 healthy older adults found that zinc supplementation at 45mg daily (as zinc gluconate) for 12 weeks significantly increased the Cu,ZnSOD activity in the erythrocytes (by 20%), reduced the oxidative stress markers (by 15%, as measured by the 8-hydroxy-2-deoxyguanosine in the urine), and improved the immune function (as measured by the T cell-mediated immune response) — demonstrating the essential role of zinc in the antioxidant defence and in the immune function.
Zinc and the Age-Related Macular Degeneration
The age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world, and it is characterised by the progressive degeneration of the macula (the central part of the retina that is responsible for the high-acuity vision). The pathogenesis of the AMD involves the oxidative stress, the chronic inflammation, and the accumulation of the lipofuscin in the retinal pigment epithelium (RPE) cells — all of which are exacerbated by the zinc deficiency and are attenuated by the zinc supplementation. The retina is one of the most metabolically active tissues in the body and is particularly vulnerable to the oxidative stress — it has a high concentration of the polyunsaturated fatty acids (which are the preferred targets of the lipid peroxidation), it is exposed to the high-energy blue light (which generates the ROS in the retina), and it has a relatively low activity of the antioxidant enzymes (including the Cu,ZnSOD, the catalase, and the glutathione peroxidase). The zinc is particularly important for the retinal function because it is required for the Cu,ZnSOD activity and for the visual pigment regeneration (zinc is a cofactor for the retinol dehydrogenase enzyme).
The clinical importance of the zinc for the AMD prevention is underscored by the observation that the zinc supplementation reduces the risk of the AMD progression in people with the intermediate AMD. The Age-Related Eye Disease Study (AREDS) found that the zinc supplementation (at 80mg daily, as zinc oxide) reduced the risk of the AMD progression by approximately 25% in people with the intermediate AMD — making it one of the most effective interventions for the prevention of the AMD progression. The AREDS formulation (which contains zinc, copper, vitamin C, vitamin E, beta-carotene, and lutein-zeaxanthin) is now the standard of care for the management of the intermediate AMD.
Practical Application
For general zinc supplementation, the evidence-based approach is to supplement with 15-30mg of zinc daily (as zinc citrate, zinc picolinate, or zinc gluconate — the forms that are well absorbed and well tolerated). The RDA of zinc is 8mg daily for women and 11mg daily for men, and the tolerable upper intake level is 40mg daily for adults (above which the zinc can interfere with the copper absorption and produce the copper deficiency anaemia). For comprehensive antioxidant and immune support, zinc pairs well with the copper (which is required for the Cu,ZnSOD and which should be supplemented at 1-2mg daily when high-dose zinc is used), with the vitamin C (which has antioxidant and immune-enhancing effects), with the vitamin D (which has immunomodulatory effects and which is particularly important for the T cell function), and with the selenium (which is required for the glutathione peroxidase enzyme and which works synergistically with zinc for the antioxidant defence).
A quality supplement routine can make a real difference to your results.
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