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Consequently, the development and validation of novel NAD-boosting strategies has been of central interest, along with the development of models that accurately represent the complexity of human NAD dynamics and deficiency levels. In this review, we discuss pioneering research and show how modern researchers have long since moved past believing that pellagra is the overt and most dramatic clinical presentation of NAD deficiency. The current research is centered on common human health conditions associated with moderate, but clinically relevant, NAD deficiency. In vitro and in vivo research models that have been developed specifically to study NAD deficiency are reviewed here, along with emerging strategies to increase the intracellular NAD concentrations.<\/jats:p>","DOI":"10.3390\/cells12030500","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T03:04:23Z","timestamp":1675393463000},"page":"500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Beyond Pellagra\u2014Research Models and Strategies Addressing the Enduring Clinical Relevance of NAD Deficiency in Aging and Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Morgan B.","family":"Feuz","sequence":"first","affiliation":[{"name":"Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT 84322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9949-8157","authenticated-orcid":false,"given":"Mirella L.","family":"Meyer-Ficca","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT 84322, USA"},{"name":"College of Veterinary Medicine, Utah State University, Logan, UT 84322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1518-4872","authenticated-orcid":false,"given":"Ralph G.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT 84322, USA"},{"name":"College of Veterinary Medicine, Utah State University, Logan, UT 84322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1098\/rspb.1906.0029","article-title":"The Alcoholic Ferment of Yeast-Juice","volume":"77","author":"Harden","year":"1906","journal-title":"Proc. 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