Novel insight into nicotinamide adenine dinucleotide and related metabolites in cancer patients undergoing surgery

Sep 21, 2026

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Nicotinamide adenine dinucleotide (NAD+) is central to cellular homeostasis, and reduced levels have been linked to cancer. This prospective study examined NAD+ dynamics in patients undergoing surgery for eight digestive system cancer types. Ninety-nine patients provided fasting perioperative blood samples, with NAD+, nicotinamide mononucleotide (NMN), and nicotinamide riboside quantified by tandem mass spectrometry. NAD+ stayed relatively stable postoperatively after erythrocyte adjustment, while NMN dropped the day after surgery, then partially recovered; liver and pancreatic cancers showed poor NMN recovery. The findings identify low-level patterns and depletion timing, supporting the need for personalized NAD+ supplementation aligned to patient and treatment timelines.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Background and rationale

NAD+ biology and links to aging and cancer

NMN supplementation and metabolic salvage pathway

Study design and methods

Prospective cohort and perioperative sampling

Tandem mass spectrometry analysis

Results

NAD+ stability after surgery

NMN decrease and recovery patterns

Cancer type-specific NMN recovery deficits

Implications

Timing of depletion and personalized supplementation needs

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Novel insight into nicotinamide adenine dinucleotide and related metabolites in cancer patients undergoing surgery Hiroaki Fujita1,7, Taiichi Wakiya1,3,7, YotaTatara2,7, Keinosuke Ishido1, Yoshiyuki Sakamoto1, Norihisa Kimura1, Hajime Morohashi1, Takuya Miura1, Takahiro Muroya1, Harue Akasaka1, Hiroshi Yokoyama1, Taishu Kanda1, Shunsuke Kubota1, Aika Ichisawa1, Kenta Ogasawara1, Daisuke Kuwata1, Yoshiya Takahashi1, Akie Nakamura1, Keisuke Yamazaki1, Takahiro Yamada1, Ryo Matsuyama4,5, Masanobu Kanou4,6, Kei Yamana4,6, Ken Itoh2 & Kenichi Hakamada1* Nicotinamide adenine dinucleotide (NAD +) plays a pivotal role in numerous cellular functions. Reduced NAD + levels are postulated to be associated with cancer. As interest in understanding NAD + dynamics in cancer patients with therapeutic applications in mind grows, there remains a shortage of comprehensive data. This study delves into NAD + dynamics in patients undergoing surgery for different digestive system cancers. This prospective study enrolled 99 patients with eight different cancers. Fasting blood samples were obtained during the perioperative period. The concentrations of NAD + , nicotinamide mononucleotide (NMN), and nicotinamide riboside were analyzed using tandem mass spectrometry. After erythrocyte volume adjustment, NAD + remained relatively stable after surgery. Meanwhile, NMN decreased the day after surgery and displayed a recovery trend. Interestingly, liver and pancreatic cancer patients exhibited poor postoperative NMN recovery, suggesting a potential cancer type-specific influence on NAD + metabolism. This study illuminated the behavior of NAD + in surgically treated cancer patients. We identified which cancer types have particularly low levels and at what point depletion occurs during the perioperative period. These insights suggest the need for personalized NAD + supplementation strategies, calibrated to individual patient needs and treatment timelines. Clinical trial registration jRCT1020210066 . Keywords Cancer, Nicotinamide adenine dinucleotide, Nicotinamide mononucleotide, Surgery, Precision medicine, Metabolism Abbreviations Adm BMI Int LC–MS/MS MCV NAD+ NAMPT NMN Admission Body mass index Initial intake medical examination Liquid chromatography with tandem mass spectrometry Mean corpuscular volume Nicotinamide adenine dinucleotide Nicotinamide phosphoribosyl transferase Nicotinamide mononucleotide 1Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-Cho, Hirosaki City, Aomori 036-8562, Japan. 2Department of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan. 3Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan. 4Nutraceutical Group, New Business Development Unit, Teijin Limited, Hino, Tokyo, Japan. 5Discovery DMPK Research Group, Toxicology & DMPK Research Department, Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan. 6NOMON Co. Ltd., Kasumigaseki, Chiyoda-Ku, Tokyo, Japan. 7These authors contributed equally: Hiroaki Fujita, Taiichi Wakiya and YotaTatara.* email: [hakamada@hirosaki-u.ac.jp](hakamada@hirosaki-u.ac.jp) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) NR Nicotinamide riboside chloride PARP Poly (adenosine diphosphate-ribose) polymerases POD1 The day after surgery POD7 One week after surgery POD30 One month after surgery RBC Red blood cell SIRT Sirtuin Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite for maintaining cellular homeostasis. Multiple reduction–oxidation (redox) metabolic reactions for energy production are based on NAD+ . Moreover, NAD+ is essential for non-redox NAD-dependent enzymes, including sirtuins (SIRT), poly (adenosine diphosphate-ribose) polymerases (PARP), a

FAQs

What did the study measure in cancer patients undergoing surgery?

It measured concentrations of NAD+, nicotinamide mononucleotide (NMN), and nicotinamide riboside in fasting perioperative blood samples.

How did NAD+ levels change after surgery?

After erythrocyte volume adjustment, NAD+ remained relatively stable following surgery.

Which patients showed poor postoperative NMN recovery and what might it indicate?

Liver and pancreatic cancer patients exhibited poor postoperative NMN recovery, suggesting a cancer type-specific influence on NAD+ metabolism.

Sep 21, 2026

Upload by Noah