Supplementation of Nicotinic Acid and Its Derivatives - Up-Regulates Cellular NAD+ Level Rather than Nicotinamide Derivatives in Cultured Normal Human Epidermal Keratinocytes

Oct 13, 2026

Nicotinamide adenine dinucleotide (NAD+) underpins energy metabolism, redox homeostasis, and genetic regulation in mammalian cells. 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.

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Introduction

life Communication Supplementation of Nicotinic Acid and Its Derivatives Up-Regulates Cellular NAD+ Level Rather than Nicotinamide Derivatives in Cultured Normal Human Epidermal Keratinocytes Takahiro Oyama 1,2, *, Takumi Yamamoto 1, Takeshi Kameda 1, Takanori Kamiya 1, Hideaki Abe 1, Takehiko Abe 1 and Sei-ichi Tanuma 2 Citation: Oyama, T.; Yamamoto, T.; Kameda, T.; Kamiya, T.; Abe, H.; Abe, T.; Tanuma, S.-i. Supplementation of Nicotinic Acid and Its Derivatives Up-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 Academic Editor: Alin Laurentiu Tatu Received: 9 January 2024 Revised: 22 February 2024 Accepted: 19 March 2024 Published: 20 March 2024 Copyright: © 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/)) . 1 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.) 2 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) * Correspondence: [takahiro.oyama@hinoki.co.jp](takahiro.oyama@hinoki.co.jp); Tel.: +81-055-948-4111; Fax: +81-055-948-6111 Abstract: 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. Keywords: nicotinic acid; NAD+; keratinocyte; rejuvenation; inflammaging 1. Introduction Nicotinamide 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

FAQs

Why is NAD+ supplementation considered important in mammalian cells?

NAD+ supports energy metabolism, redox regulation, and gene expression. Declines in NAD+ during aging contribute to age-related diseases and inflammaging.

Which NAD+ precursor showed the strongest effect in cultured normal human epidermal keratinocytes?

Nicotinic acid supplementation significantly increased intracellular NAD+ levels, whereas nicotinamide and its derivatives did not induce a NAD+ response.

What mitochondrial effects were observed after nicotinic acid supplementation?

Nicotinic acid up-regulated mitochondrial SOD2 and SIRT3 and mitigated rotenone-induced mitochondrial reactive oxygen species (ROS) accumulation.

Oct 13, 2026

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