β-nicotinamide mononucleotide (NMN) is a naturally occurring biologically active nucleotide widely present in organisms and an inherent substance in the human body. As a critical intermediate in synthesizing coenzyme I (NAD+), it widely participates in multiple biochemical reactions in the human body and is closely related to immunity, metabolism, and other factors. In recent years, NMN has rapidly developed and made significant progress in medicine, food, and healthcare. However, there is currently a lack of comprehensive reports on the research progress of NMN, as well as exploration and analysis of the current research achievements and progress of NMN. Therefore, this review is based on retrieving relevant research on NMN from multiple databases at home and abroad, with the retrieval time from database establishment to 20 May 2024. Subsequently, literature search, reading, key information extraction, organization, and summarization were conducted with the aim of providing a comprehensive and in-depth analysis of the characteristics, metabolic pathways, pharmacological effects, progress in human clinical trials, and wide applications of NMN in drug development and food applications. Furthermore, it offers personal insights into NMN’s potential future developments and advancements to present the current development state and existing challenges comprehensively. Ultimately, this review aims to provide guidance and serve as a reference for the future application, innovation, and progression of NMN research.
Surgery, chemotherapy and radiotherapy constitute the main treatment methods against tumors. However, radiotherapy and chemotherapy may also bring some side effects during the treatment. Chemotherapy may affect multiple organ systems in the human body, such as digestive, blood, immune and respiratory systems. Since chemotherapy drugs are cytotoxic, they can damage normal cells in addition to cancer cells, which can result in undesirable adverse reactions. In addition, the radiation generated during radiotherapy may also damage normal tissues, exacerbating the risk of side effects. Common adverse reactions of radiotherapy include skin damage, nausea and vomiting, fatigue, bone marrow suppression, gastrointestinal reactions, etc.
β-Nicotinamide mononucleotide (β-NMN, the following will unify the β-NMN as NMN) is a natural active nucleotide. As a critical precursor for the production of coenzyme I (Nicotinamide adenine dinucleotide, NAD+), it is ubiquitous in various organisms. Recently, researchers have revealed the potential of NMN in alleviating the side effects of radiotherapy and chemotherapy. It can promote the energy metabolism process, strengthen the self-repair and renewal function of cells, and further reduce the damage of radiotherapy and chemotherapy to normal cells by improving the content of NAD+ in cells. Besides, NMN also has antioxidant and anti-inflammatory functions, which can help relieve oxidative stress and inflammatory responses triggered by radiotherapy and chemotherapy and further reduce the severity of side effects. However, although NMN has many effects, there is no systematic literature to report and analyze it. Hence, this article conducts a comprehensive search across multiple databases to gather relevant research reports on NMN, encompassing various fields such as pharmacokinetics, pharmacodynamics, pharmacology, clinical trials, and the intersecting realms of drugs and food. The core information from this literature is distilled to elucidate NMN’s characteristics, metabolism, pharmacological effects, applications in food and drug industries, and its progression in human clinical trials. The objective is to foster a deeper understanding of the research advancements in diverse NMN fields and present some personal perspectives on its future potential.
In order to comprehensively and systematically evaluate and review the unique characteristics, metabolic properties, pharmacological effects, human clinical trials, and various applications of NMN, this study adopted a rigorous and systematic literature search, query, and data extraction strategy. The specific method is as follows: Firstly, determine the search keywords: Based on the theme of this study, core search keywords including “β-nicotinamide mononucleotide”, “nicotinamide mononucleotide”, “NMN”, “NAD+“, “pharmacodynamics”, “pharmacology”, “metabolic characteristics”, “Chinses medicine”, “food” and “human clinical trials”. Secondly, selecting databases and resources: This study selected multiple authoritative academic databases and literature search platforms at home and abroad, such as Web of Science, PubMed, Embase, Clinical Trials Website, China National Knowledge Infrastructure (CNKI), Chinses Wanfang and Chinses VIP databases, etc. The language of the literature is English or Chinese. The retrieval covers the period from the establishment of the database to 20 May 2024. In addition, the types of literature include reviews, meta-analysis, original articles, conference papers, patents, dissertations, etc. Subsequently, text reading and data extraction: Read the titles and abstracts of the preliminarily screened literature to further confirm whether they fulfill the inclusion criteria. During the confirmation process, detailed information such as the author, publication year, research purpose, methods, results, and conclusions of each literature were recorded. Finally, data integration and analysis: After completing data extraction, integrate and analyze the collected information. Based on the different characteristics and application fields of NMN, classify and summarize relevant information to form a systematic review framework. Meanwhile, conduct a comprehensive analysis of key research findings. Furthermore, we have repeatedly verified and revised the preliminary conclusions to ensure the accuracy and comprehensiveness of the review content.
This study aims to comprehensively and objectively evaluate and summarize the unique characteristics, metabolic properties, pharmacological effects, human clinical research, and diverse applications of NMN. Through the literature search, query, and data extraction methods outlined in the above system, it provides valuable reference information for researchers and clinical practitioners in related fields.
NMN is one of the isomers of nicotinamide mononucleotide. Nicotinamide mononucleotide includes two isomers, α and β, but only β is an active isomer, as shown in Figure 1. The chemical molecular formula of NMN is C 11 H 15 N 2 O 8 P, and the molecular structure consists of three parts: nicotinamide base, ribose sugar and a phosphate group. In appearance, NMN is a crystalline powder from white to slightly yellow, with no significant odour, and should be stored in a dry environment at a temperature of −20°C under dark conditions. It has a melting point of about 166°C and a boiling point of °C at a pressure of 760 mmHg. NMN can be rapidly dissolved in water, but its solubility in acetone is extremely low. Its pH value is usually between 3.0 and 4.0. As a natural active nucleotide, NMN is an inherent substance in the human body and is widely distributed in certain fruits and vegetables.
NMN is a metabolic intermediate of the coenzyme NAD+ in the body. NAD+, as an essential coenzyme in the human body, participates in thousands of reactions within cells. However, with age and other factors, the level of NAD+ in the human body will gradually decrease, which may lead to a series of health problems. The human body mainly supplements 85% of NAD + through the Salvage synthesis pathway, and the Denovo and Preiss Handler pathways are also in vivo synthesis pathways for NMN. In the Preiss Handler pathway, niacin (NA) is catalytically converted to nicotinic acid mononucleotide (NAMN). In the Denovo pathway, tryptophan (Trp) is converted to quinoline acid (QA), followed by the generation of NAMN. These two paths intersect at the nicotinic acid mononucleotide (NAMN) point, ultimately transforming into nicotinamide adenine dinucleotide (NAAD) and NAD+. In this way, organisms ensure a stable supply of NAD + to support their various important physiological functions through different synthetic pathways. The generation and metabolic pathways of NMN and NAD+ in the human body are shown in Figure 2.
Aging is a natural process, and with the consumption of NAD+, the energy of organ mitochondria decreases. NAD+ is crucial for cellular energy metabolism and repair, and its reduction can impair mitochondrial function and accelerate aging. Aging is characterized by decreased mitochondrial function, DNA damage, cognitive decline, osteoporosis, immune deficiency, etc. Supplementing with NAD + can alleviate these symptoms. Research has shown that NAD + precursors (NMN and NR) can maintain the number of melanocyte stem cells, enhance function, prolong mouse lifespan, and open up new directions for anti-aging science. NAD+ and its precursors show potential in extending lifespan. The reasons for the decrease in NAD + levels during the aging process and the anti-aging mechanism of NMN are shown in Figure 3.
However, there are also some potential limitations and conflicting results in the anti-aging research of NMN. Firstly, NMN products produced by different brands and research institutions may have differences in purity and content, leading to inconsistencies in research results. Secondly, there is no unified standard for the dosage and usage of NMN, and there may be differences in dosage and usage in different studies, which can affect the research results. Besides, the long-term safety and efficacy of NMN still needs further research and validation, especially regarding potential adverse reactions and drug interactions that may occur when used at high doses. More importantly, aging is a complex process that involves changes in multiple physiological systems, and a single substance (such as NMN) can not comprehensively solve all problems. Therefore, combining other methods, such as a healthy diet, moderate exercise, and good lifestyle habits, is necessary to enhance the body’s anti-aging ability.
Currently, type 2 diabetes has generally become a metabolic health problem around the world. One of its hallmark features is insulin resistance caused by increased oxidative stress, inflammation, and lipid metabolism disorders. When pancreatic β-cell dysfunction or inability to secrete sufficient insulin, it will cause insulin deficiency and eventually lead to type II diabetes. Pancreatic β cells are susceptible to the decrease of NAD + concentration. Once the level of NAD + decreases, it may interfere with the metabolic activity of these cells, resulting in a reduction of insulin production, which in turn increases the possibility of diabetes. Studies have shown that NMN supplementation can promote insulin release from pancreatic β cells and increase the responsiveness of peripheral tissues to insulin, effectively improve diabetes caused by age and poor eating habits, and glucose tolerance and insulin sensitivity observed in elderly mice, opening up a new method for the treatment and management of diabetes. At the same time, NMN can also regulate the metabolism of adipose tissue, promote lipolysis and its oxidation process, reduce body fat accumulation, and alleviate fat antagonism to insulin. Additionally, long-term intake of NMN can increase the concentration of NAD+ in the body, which helps to improve the
