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7 reasons to think that Zinc should fight COVID-19 – July 2020

Front. Immunol. 11:1736. doi: 10.3389/fimmu.2020.01736
Ander Mayor-lbarguren1*t, Carmen Busca-Arenzana22 andAngel Robles-Marhuenda2t
1 Department of Dermatology, La Paz University Hospital, Madrid, Spain,
2 Department of Internal Medicine, La Paz University Hospital, Madrid, Spain
KEY POINTS

  • Zinc deficiency may be common and associated with severe infection.
  • Zinc helps to enhance the interferon type 1 response to the virus and participates in many regulatory pathways.
  • Low levels of zinc have been associated with higher IL-6 responses.
  • IL-6 plays an important role in severe lung injury due to COVID-19 infection.
  • Zinc inhibits SARS-CoV RNA polymerase, and thus its replication capacity.
  • Zinc may increase the efficacy of antimalarial agents, since they are zinc ionophores.
  • Differences in mortality due to COVID-19 infection may be explained to some degree by-174 IL-6 gene polymorphism.

Zinc (Zn) is the second most abundant trace metal in the human body after iron. However, unlike iron, there is no specialized zinc store (1). Zinc's functions can be classified as catalytic, structural, and regulatory (2). For example, important zinc metalloenzymes include alkaline phosphatase, RNA polymerases, and alcohol dehydrogenase (3). Zinc deficiency can precipitate an immune system imbalance, exemplified in severe deficiency by high susceptibility to infections, skin disorders, gastrointestinal disorders, weight loss, growth retardation and male hypogonadism, amongst other symptoms (4).
While severe zinc deficiency is rare, mild to moderate deficiency is more common worldwide ⑸.There are very low levels of free zinc in plasma, since it is mostly bound to proteins such as albumin, alpha-2-macroglobulin (A2M), and transferrin. Plasma zinc levels are therefore only around 1 ug/ml, equal to 0.1% of total body zinc, but are still the most important reservoir for zinc homeostasis, which requires “free” or “labile” zinc mobilization (6, 7). Kinetic studies suggest that only a small proportion of total body zinc (10%) represents the “functional pool” of zinc, located within the liver and other tissues, that exchanges rapidly with that found in the plasma (8, 9).
When this functional pool is depleted, zinc deficiency ensues (8). Intracellular zinc is distributed in zinc-storing vesicles called zincosomes, the nucleus and other organelles. In cytoplasm, zinc mostly binds zinc-chelating proteins called metallothioneins (MTs). Zinc homeostasis is understood to be the correct balance of zinc distribution. Internal zinc homeostasis is regulated by the cooperative activities of two metal transporter protein families. One family consists of 10 solute-linked carrier 30 (SLC30 or ZnT) exporters, and the other family consists of 14 solute-linked carrier 39 (SLC39 or ZIP) importers (10, 11). For instance, most labile zinc in the body is absorbed by intestinal epithelial cells via SLC39a4 protein, and excessive zinc is excreted through the kidneys, and the intestine via SLC39a5 (12).
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Created by admin. Last Modification: Saturday August 8, 2020 21:51:10 GMT-0000 by admin. (Version 9)

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