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Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy

DiGuilio et al., International Journal of Molecular Sciences, doi:10.3390/ijms23062995
Mar 2022  
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Zinc for COVID-19
2nd treatment shown to reduce risk in July 2020
*, now known with p = 0.0000013 from 44 studies, recognized in 11 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,200+ studies for 70+ treatments.
Review of epithelial and endothelial barrier compromise and associated disease risk including COVID-19, and the potential benefits of vitamin A, vitamin D, and zinc for improving barrier function.
Reviews covering zinc for COVID-19 include Arora, Briassoulis, Derwand, DiGuilio, Foshati, Jin, Joachimiak, Schloss, Sethuram, Wessels.
Review covers vitamin D, vitamin A, and zinc.
DiGuilio et al., 10 Mar 2022, peer-reviewed, 8 authors.
This PaperZincAll
Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy
Katherine M Diguilio, Elizabeth Rybakovsky, Reza Abdavies, Romy Chamoun, Colleen A Flounders, Ariel Shepley-Mctaggart, Ronald N Harty, James M Mullin
International Journal of Molecular Sciences, doi:10.3390/ijms23062995
The published literature makes a very strong case that a wide range of disease morbidity associates with and may in part be due to epithelial barrier leak. An equally large body of published literature substantiates that a diverse group of micronutrients can reduce barrier leak across a wide array of epithelial tissue types, stemming from both cell culture as well as animal and human tissue models. Conversely, micronutrient deficiencies can exacerbate both barrier leak and morbidity. Focusing on zinc, Vitamin A and Vitamin D, this review shows that at concentrations above RDA levels but well below toxicity limits, these micronutrients can induce cell-and tissue-specific molecular-level changes in tight junctional complexes (and by other mechanisms) that reduce barrier leak. An opportunity now exists in critical care-but also medical prophylactic and therapeutic care in general-to consider implementation of select micronutrients at elevated dosages as adjuvant therapeutics in a variety of disease management. This consideration is particularly pointed amidst the COVID-19 pandemic.
Conflicts of Interest: The authors have declared that no conflict of interest exists.
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An opportunity now ' 'exists in critical care—but also medical prophylactic and therapeutic care in general—to ' 'consider implementation of select micronutrients at elevated dosages as adjuvant therapeutics ' 'in a variety of disease management. This consideration is particularly pointed amidst the ' 'COVID-19 pandemic.</jats:p>', 'alternative-id': ['ijms23062995'], 'author': [ {'affiliation': [], 'family': 'DiGuilio', 'given': 'Katherine M.', 'sequence': 'first'}, {'affiliation': [], 'family': 'Rybakovsky', 'given': 'Elizabeth', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Abdavies', 'given': 'Reza', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Chamoun', 'given': 'Romy', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Flounders', 'given': 'Colleen A.', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Shepley-McTaggart', 'given': 'Ariel', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Harty', 'given': 'Ronald N.', 'sequence': 'additional'}, { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Mullin', 'given': 'James M.', 'sequence': 'additional'}], 'container-title': ['International Journal of Molecular Sciences'], 'content-domain': {'crossmark-restriction': False, 'domain': []}, 'created': {'date-parts': [[2022, 3, 10]], 'date-time': '2022-03-10T16:46:47Z', 'timestamp': 1646930807000}, 'deposited': { 'date-parts': [[2022, 3, 10]], 'date-time': '2022-03-10T17:52:24Z', 'timestamp': 1646934744000}, 'indexed': {'date-parts': [[2022, 3, 11]], 'date-time': '2022-03-11T12:42:24Z', 'timestamp': 1647002544614}, 'is-referenced-by-count': 0, 'issn-type': [{'type': 'electronic', 'value': '1422-0067'}], 'issue': '6', 'issued': {'date-parts': [[2022, 3, 10]]}, 'journal-issue': {'issue': '6', 'published-online': {'date-parts': [[2022, 3]]}}, 'language': 'en', 'license': [ { 'URL': '', 'content-version': 'vor', 'delay-in-days': 0, 'start': { 'date-parts': [[2022, 3, 10]], 'date-time': '2022-03-10T00:00:00Z', 'timestamp': 1646870400000}}], 'link': [ { 'URL': '', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'member': '1968', 'original-title': [], 'page': '2995', 'prefix': '10.3390', 'published': {'date-parts': [[2022, 3, 10]]}, 'published-online': {'date-parts': [[2022, 3, 10]]}, 'publisher': 'MDPI AG', 'reference': [ {'DOI': '10.1093/jn/130.5.1367S', 'doi-asserted-by': 'publisher', 'key': 'ref1'}, {'DOI': '10.1017/S0007114508006818', 'doi-asserted-by': 'publisher', 'key': 'ref2'}, {'DOI': '10.1021/acs.jafc.7b04203', 'doi-asserted-by': 'publisher', 'key': 'ref3'}, {'DOI': '10.1007/s10620-012-2328-8', 'doi-asserted-by': 'publisher', 'key': 'ref4'}, {'DOI': '10.1017/S0007114512005508', 'doi-asserted-by': 'publisher', 'key': 'ref5'}, {'DOI': '10.3390/ijms20236020', 'doi-asserted-by': 'publisher', 'key': 'ref6'}, {'DOI': '10.1111/asj.13357', 'doi-asserted-by': 'publisher', 'key': 'ref7'}, {'DOI': '10.3390/genes11030290', 'doi-asserted-by': 'publisher', 'key': 'ref8'}, {'DOI': '10.3390/ijms21030972', 'doi-asserted-by': 'publisher', 'key': 'ref9'}, {'DOI': '10.1111/1759-7714.13344', 'doi-asserted-by': 'publisher', 'key': 'ref10'}, {'DOI': '10.1016/j.cellsig.2019.109485', 'doi-asserted-by': 'publisher', 'key': 'ref11'}, {'DOI': '10.1007/s10620-019-05777-2', 'doi-asserted-by': 'publisher', 'key': 'ref12'}, {'DOI': '10.1017/S0007114521000738', 'doi-asserted-by': 'publisher', 'key': 'ref13'}, {'DOI': '10.1042/BSR20201532', 'doi-asserted-by': 'publisher', 'key': 'ref14'}, {'DOI': '10.1053/j.gastro.2019.07.058', 'doi-asserted-by': 'publisher', 'key': 'ref15'}, { 'article-title': 'Spontaneous and cytokine-induced hole formation in epithelial cell ' 'layers: Implications for barrier function studies with the gingival ' 'cell culture, Gie-3B11, and other epithelial models', 'author': 'Rybakovsky', 'first-page': '99', 'journal-title': 'Trends Cell Mol. 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