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During aging, NAD+ declines and is linked to age-related diseases and inflammaging through effects on immune modulation, including macrophage polarization. Although NAD+ augmentation therapy is promising, optimizing NAD+ precursors for topical formulations remains insufficient. This study identifies nicotinic acid as a superior precursor for elevating NAD+ in cultured human epidermal keratinocytes, alongside evidence for improved mitochondrial function and reduced oxidative stress.",{"@graph":63,"@context":118},[64,80,101],{"@type":65,"itemListElement":66},"BreadcrumbList",[67,71,74,77],{"item":68,"name":69,"@type":70,"position":9},"https://docshare.wps.com","Home","ListItem",{"item":72,"name":10,"@type":70,"position":73},"https://docshare.wps.com/template/",2,{"item":75,"name":51,"@type":70,"position":76},"https://docshare.wps.com/template/general/",3,{"item":78,"name":59,"@type":70,"position":79},"https://docshare.wps.com/template/supplementation-of-nicotinic-acid-and-its-derivatives-up-regulates-cellular-nad-level-rather-than-nicotinamide-derivatives-in-cultured-normal-human-epidermal-keratinocytes/571128/",4,{"url":78,"name":59,"@type":81,"image":82,"author":87,"headline":59,"publisher":90,"fileFormat":93,"inLanguage":57,"description":61,"dateModified":94,"datePublished":95,"encodingFormat":93,"isAccessibleForFree":96,"interactionStatistic":97},"DigitalDocument",{"url":83,"@type":84,"width":85,"height":86},"https://docshare.wps.com/thumbnails/supplementation-of-nicotinic-acid-and-its-derivatives-up-regulates-cellular-nad-level-rather-than-nicotinamide-derivatives-in-cultured-normal-human-epidermal-keratinocytes/571128.png","ImageObject",442,249,{"name":88,"@type":89},"วิน","Person",{"url":68,"name":91,"@type":92},"DocShare","Organization","application/pdf","2026-10-23","2026-10-13",true,{"@type":98,"interactionType":99,"userInteractionCount":47},"InteractionCounter",{"@type":100},"ViewAction",{"@type":102,"mainEntity":103},"FAQPage",[104,110,114],{"name":105,"@type":106,"acceptedAnswer":107},"Why is NAD+ supplementation considered important in mammalian cells?","Question",{"text":108,"@type":109},"NAD+ supports energy metabolism, redox regulation, and gene expression. Declines in NAD+ during aging contribute to age-related diseases and inflammaging.","Answer",{"name":111,"@type":106,"acceptedAnswer":112},"Which NAD+ precursor showed the strongest effect in cultured normal human epidermal keratinocytes?",{"text":113,"@type":109},"Nicotinic acid supplementation significantly increased intracellular NAD+ levels, whereas nicotinamide and its derivatives did not induce a NAD+ response.",{"name":115,"@type":106,"acceptedAnswer":116},"What mitochondrial effects were observed after nicotinic acid supplementation?",{"text":117,"@type":109},"Nicotinic acid up-regulated mitochondrial SOD2 and SIRT3 and mitigated rotenone-induced mitochondrial reactive oxygen species (ROS) accumulation.","https://schema.org",{"og:url":78,"og:type":120,"og:title":59,"og:site_name":91,"og:description":61},"article",{"robots":122,"canonical":78},"index,follow",{"doc_id":124,"site_id":56},571128,1792109536,{"code":4,"msg":5,"data":127},{"doc_id":124,"user_id":128,"nickname":88,"user_avatar":129,"doc_module":9,"category_id":50,"category_name":51,"doc_title":59,"doc_description":61,"doc_content":130,"file_id":131,"file_url":132,"file_type":133,"file_size":134,"view_count":47,"is_deleted":4,"is_public":9,"is_downloadable":9,"audit_status":9,"page_count":135,"language":136,"language_code":57,"site_id":56,"html_lang":57,"table_of_contents":137,"faqs":138,"seo_title":139,"seo_description":61,"update_tm":140,"read_time":79},2336475104736,"https://ap-avatar.wpscdn.com/avatar/22000c4c5e0e5b17e70?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786591360781797222","life  \nCommunication  \nSupplementation of Nicotinic Acid and Its Derivatives  \nUp-Regulates Cellular NAD+ Level Rather than Nicotinamide Derivatives in Cultured Normal Human Epidermal Keratinocytes  \nTakahiro Oyama 1,2, *, Takumi Yamamoto 1, Takeshi Kameda 1, Takanori Kamiya 1, Hideaki Abe 1, Takehiko Abe 1 and Sei-ichi Tanuma 2  \nCitation: Oyama, T.; Yamamoto, T.; Kameda, T.; Kamiya, T.; Abe, H.; Abe, T.; Tanuma, S.-i. Supplementation of Nicotinic Acid and Its Derivatives  \nUp-Regulates Cellular NAD+ Level Rather than Nicotinamide Derivativesin Cultured Normal Human Epidermal Keratinocytes. Life 2024, 14, 413 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)life14030413  \nAcademic Editor: Alin Laurentiu Tatu  \nReceived: 9 January 2024  \nRevised: 22 February 2024  \nAccepted: 19 March 2024  \nPublished: 20 March 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Hinoki Shinyaku Co., Ltd., 9-6 Nibancho, Chiyoda-ku, Tokyo 102-0084, Japan; [t.kameda@hinoki.co.jp](t.kameda@hinoki.co.jp) (T.K.); [hideaki.abe@aibliss.co.jp](hideaki.abe@aibliss.co.jp) (H.A.)  \n2 Laboratory of Genomic Medicinal Science, Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki Noda, Chiba 278-8510, Japan; [tanuma@rs.tus.ac.jp](tanuma@rs.tus.ac.jp)  \n* Correspondence: [takahiro.oyama@hinoki.co.jp](takahiro.oyama@hinoki.co.jp); Tel.: +81-055-948-4111; Fax: +81-055-948-6111  \nAbstract: Nicotinamide adenine dinucleotide (NAD+ ) plays a pivotal role in various physiological processes within mammalian cells, including energy metabolism, redox homeostasis, and genetic regulation. In the majority of mammalian cellular contexts, NAD+ biosynthesis primarily relies on vitamin B3, including nicotinamide (NAM) and nicotinic acid (NA) . The concept of NAD+ augmentation therapy has recently emerged as a promising strategy to mitigate aging-associated phenomena, termed rejuvenation. Despite the involvement of diverse enzymatic cascades in NAD+ biosynthesis, certain cellular environments exhibit deficiencies in specific enzymes, suggesting cell type-dependent variability in optimal NAD+ precursor selection. However, the optimization of NAD+ precursors for topical formulations has received scant attention thus far. In the present investigation, we sought to delineate the most efficacious precursor for augmenting NAD+ levels inhuman skin keratinocytes. Remarkably, NA supplementation led to a significant 1.3-fold elevation in intracellular NAD+ levels, even in the presence of nicotinamide phosphoribosyltransferase inhibition by FK866 . Additionally, NA mononucleotide demonstrated a 1.5-fold increase (but not significant) in NAD+ levels following 100 µM application. Conversely, NAM and its derivatives failed toelicit a NAD+ response in keratinocytes. Notably, NA supplementation elicited up-regulation of mitochondrial superoxide dismutase (SOD2) and sirtuin 3 (SIRT3), indicative of its beneficial impact on mitochondrial function. Furthermore, NA mitigated rotenone-induced mitochondrial reactive oxygen species (ROS) accumulation. Collectively, these findings advocate for the potential utility of NA in topical applications aimed at skin rejuvenation.  \nKeywords: nicotinic acid; NAD+; keratinocyte; rejuvenation; inflammaging  \n1. Introduction  \nNicotinamide adenine dinucleotide (NAD+ ) is a crucial component for cellular maintenance, including energy metabolism, redox regulation, and gene expression [1,2] . During the aging process, there is a decline in NAD+ levels, which has been implicated in the onset and progression of age-related diseases. Low levels of NAD+ have been associated with various dis","cbCailfthgDtz75z","https://ap.wps.com/l/cbCailfthgDtz75z","pdf",1561978,10,"English","# Abstract\n# Introduction","[{\"question\":\"Why is NAD+ supplementation considered important in mammalian cells?\",\"answer\":\"NAD+ supports energy metabolism, redox regulation, and gene expression. Declines in NAD+ during aging contribute to age-related diseases and inflammaging.\"},{\"question\":\"Which NAD+ precursor showed the strongest effect in cultured normal human epidermal keratinocytes?\",\"answer\":\"Nicotinic acid supplementation significantly increased intracellular NAD+ levels, whereas nicotinamide and its derivatives did not induce a NAD+ response.\"},{\"question\":\"What mitochondrial effects were observed after nicotinic acid supplementation?\",\"answer\":\"Nicotinic acid up-regulated mitochondrial SOD2 and SIRT3 and mitigated rotenone-induced mitochondrial reactive oxygen species (ROS) accumulation.\"}]","Supplementation of Nicotinic Acid and Its Derivatives - Up-Regulates Cellular NAD+ Level Rather than Nicotinamide Derivatives in Cultured Normal Human Epidermal Keratinocytes | PDF",1791894628]