Ingredient #7 + Research

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INCLUDING NEW RESEARCH INTO CORONAVIRUS SARS-COV-2

Scientific Evidence: Ingredient #7 - IRON

SARS-CoV-2 / COVID-19 Research results

FOR SCIENTIFIC EVIDENCE UPDATED TO JANUARY 2022, OBTAIN THE FOURTH EDITION OF 'AVD' (2022)

Potential Interventions for Novel Coronavirus in China: A Systematic Review - Lei Zhang & Yunhui Liu - Journal of Medical Virology (13 Feb. 2020):

“Iron is required for both host and pathogen and iron deficiency can impair host immunity, while iron overload can cause oxidative stress to propagate harmful viral mutations. Iron deficiency has been reported as a risk factor for the development of recurrent acute respiratory tract infections.”

Depriving Iron Supply to the Virus Represents a Promising Adjuvant Therapeutic Against Viral Survival - Wei Liu, Shuping Zhang, Sergei Nekhai & Sijin Liu - Current Clinical Microbiology Reports (20 Apr. 2020):

“Emerging studies indicate that iron manipulation, such as iron chelation, is a promising adjuvant therapy in treating viral infection. While the emerging viral infection by SARS-CoV-2 is much less understood compared with HIV-1 or SARS-CoV and MERS-CoV, based on the previous studies, it is plausible that deprivation of iron supply to the virus could serve as a beneficial adjuvant in treating the SARS-CoV-2 infection.”

Commentary: Could Iron Chelators Prove to be Useful as an Adjunct to COVID-19 Treatment Regimens? - Maria Dalamaga, Irene Karampela & Christos S. Mantzoros - Metabolism: Clinical and Experimental (10 May 2020):

“Here, we present evidence from the literature and a compelling hypothesis on the potential immunomodulatory, iron chelating and anti-oxidant effects of iron chelators in the treatment of COVID-19 and its complications. Interestingly, iron chelation has been shown in vitro to suppress endothelial inflammation in viral infection, which is the main pathophysiologic mechanism behind systemic organ involvement induced by SARS-CoV-2, by inhibiting IL-6 synthesis through decreasing NF-kB.”

COVID-19: Hemoglobin, Iron, and Hypoxia Beyond Inflammation. A Narrative Review - Attilio Cavezzi, Emidio Troiani & Salvatore Corrao - Clinics and Practice (19 May 2020):

“We speculated that in COVID-19, beyond the classical pulmonary immune-inflammation view, the occurrence of an oxygen-deprived blood disease, with iron metabolism dysregulation, should be taken in consideration. A more comprehensive diagnostic/therapeutic approach to COVID-19 is proposed, including potential adjuvant interventions aimed at improving hemoglobin dysfunction, iron over-deposit and generalized hypoxic state.”

Serum Iron Level as a Potential Predictor of Coronavirus Disease 2019 Severity and Mortality: A Retrospective Study - Kang Zhao, Jucun Huang, Dan Dai, Yuwei Feng, Liming Liu & Shuke Nie - Open Forum Infectious Diseases (21 Jun. 2020):

“Decreased serum iron level could predict the transition of COVID-19 from mild to severe and critical illness. Seven (53.8%) patients with a lower serum iron level after treatment in the critical group had died. There was a significant difference in posttreatment serum iron levels between COVID-19 survivors and non-survivors.”

COVID-19 Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism - Liu Wenzhong & Li Hualan - ChemRxiv (13 Jul. 2020).

“In this study, conserved domain analysis, homology modeling, and molecular docking were made to compare the biological roles of specific proteins belonging to the novel coronavirus. The conserved domain analysis showed envelope protein (E), nucleocapsid phosphoprotein (N) and ORF3a had heme linked sites, which Arg134 of ORF3a, Cys44 of E, Ile304 of N were the heme-iron linked site, respectively. ORF3a also possessed the conserved domains of human cytochrome C reductases and bacterial EFeB protein.”

Iron: Innocent Bystander or Vicious Culprit in COVID-19 Pathogenesis? - Marvin Edeasa, Jumana Saleh & Carole Peyssonnaux - International Journal of Infectious Diseases (Aug. 2020):

“[I]t is crucial to investigate coexisting iron parameters in COVID-19 patients including transferrin saturation, plasma iron levels, non-transferrin bound iron (NTBI) as well as hepcidin. The association of hyper-ferritinemia with increased transferrin saturation may reflect a state of iron overload. In this case, we suggest that targeting the intracellular iron overload may be a strategy of vital importance needed to be taken into consideration in future controlled clinical trials.”

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Earlier Scientific Evidence re: Iron

Anti-Viral / Immune Supportive Research

Antiviral Activities of Lactoferrin (A Review) - Barry van der Strate, Leonie Beljaars, G. Molema & Martin C. Harmsen - Antiviral Research (Jan. 2002):

“Lactoferrin (LF) is an iron binding glycoprotein that is present in several mucosal secretions. Many biological functions have been ascribed to LF. One of the functions of LF is the transport of metals, but LF is also an important component of the non-specific immune system, since LF has antimicrobial properties against bacteria, fungi and several viruses. This review gives an overview of the present knowledge about the antiviral activities and, when possible, the antiviral modes of action of this protein. Lactoferrin displays antiviral activity against both DNA- and RNA-viruses, including rotavirus, respiratory syncytial virus, herpes viruses and HIV. The antiviral effect of LF lies in the early phase of infection. Lactoferrin prevents entry of virus in the host cell, either by blocking cellular receptors, or by direct binding to the virus particles.”

Immune Function is Impaired in Iron-Deficient, Homebound, Older Women - Namanjeet Ahluwalia, Jianqin Sun, Deanna Krause, Andrea Mastro & Gordon Handte - The American Journal of Clinical Nutrition (1 Mar. 2004).

Iron and Immunity: Immunological Consequences of Iron Deficiency and Overload - Bobby J. Cherayil - Archivum Immunologiae et Therapiae Experimentalis [Warsz.] (28 Sep. 2010):

“It is clear from the foregoing discussion that both iron deficiency and iron excess can influence the functioning of the innate and adaptive arms of the immune system. Iron can also have direct effects on the growth and virulence of microbial pathogens. Indeed, an important component of innate anti-microbial defense is based on depriving pathogens of this nutrient. Changes in iron status can thus affect the immune response in multiple ways, particularly in the context of infection, an idea that is worth remembering when considering the value of iron supplementation in areas of the world where infections such as malaria and tuberculosis are highly prevalent. Conversely, chronic immune activation can lead to alterations in iron homeostasis that may impair erythropoiesis and contribute to immunopathology.”

The Role of Iron in the Immune Response to Bacterial Infection - Cherayil B.J. - Immunologic Research (1 May 2011).

Antiviral Properties of Lactoferrin — A Natural Immunity Molecule - Francesca Berlutti, Fabrizio Pantanella, Tiziana Natalizi, Alessandra Frioni, Rosalba Paesano, Antonella Polimeni & Piera Valenti - Molecules (Aug. 2011).

Iron and the Immune System - Roberta J. Ward, Robert R. Crichton, Deanna L. Taylor, Laura Della Corte, Surjit K. Srai & David T. Dexter - Journal of Neural Transmission (29 Sep. 2011).

Iron in Infection and Immunity - James E. Cassat & Eric P. Skaar - Cell Host & Microbe (15 May 2013):

“Iron is an essential micronutrient for virtually all living cells. In infectious diseases, both invading pathogens and mammalian cells including those of the immune system require iron to sustain their function, metabolism and proliferation. On the one hand, microbial iron uptake is linked to the virulence of most human pathogens. On the other hand, the sequestration of iron from bacteria and other microorganisms is an efficient strategy of host defense in line with the principles of ‘nutritional immunity’. In an acute infection, host-driven iron withdrawal inhibits the growth of pathogens. Chronic immune activation due to persistent infection, autoimmune disease or malignancy however, sequesters iron not only from infectious agents, autoreactive lymphocytes and neoplastic cells but also from erythroid progenitors.”

The Role of Iron in Immunity and Inflammation: Implications for the Response to Infection - S.R. Kuvibidila, S.B. Baliga, L.C. Chandra & C.L. French - from Diet, Immunity and Inflammation (2013).

Iron Overload Effects on Immune System through the Cytokine Secretion by Macrophage - Keiko Matsui, Sachiko Ezoe, Takafumi Yokota, Tomohiko Ishibashi, Kenji Oritani & Yuzuru Kanakura - blood (16 Nov. 2013):

“In immune systems, many reports have shown the effects of iron, some of which are complex and controversial. Iron deficiency has been reported to be associated with increased susceptibility to infection, but iron overload caused by dietary excess abnormal hemolysis or inherited disorders is also associated with heightened susceptibility to infections. On the other hand, elevated ferritin levels, primarily related to RBC transfusions, have been reported to increase the risk of acute and chronic GVHD in patients received hematopoietic cell transplantation. Although this iron-related risk of GVHD may reflect the organ damage, such as liver, kidney, and pancreas, it also may be caused by imbalance in immune systems.”

Iron at the Interface of Immunity and Infection - Manfred Nairz, David Haschka, Egon Demetz & Günter Weiss - Frontiers in Pharmacology (16 Jul. 2014).

The Re-Emerging Role of Iron in Infection and Immunity - Mawieh Hamad & Khuloud Bajbouj - Open Access Text (29 Oct. 2016).

Antiviral Activities of Ferrous and Ferric Iron in Viral Prevention, Entry and Uncoating, Replication, mRNA Degradation and DNA/RNA Virus Replication, and Release and Budding along Viral Life Cycle - Tsuneo Ishida - Archives of Immunology and Allergy (2018):

“In this review, firstly cellular iron metabolism, iron homeostasis, and inflammation are dealt with important roles in pathophysiologic conditions. Secondly iron deficiency and overload, and iron host cell-virus pathogen interactions are described for both host and pathogen, complex systems of acquisition and utilization. Thirdly, antiviral activities of iron ions occur by the inhibitions of viral entry, replication, mRNA degradation and DNA/RNA virus replication, and release and budding along viral life cycle, and antiviral actions of ferritin, lactoferrin, and ferroportin are taken up specially.”

Bibliographic Research Information provided courtesy of The Academy of the Third Millennium (A3M) 2020