Advantages of NMNH
NMNH: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder. 2. Bontac is a very first manufacture in the world to produce the NMNH powder on the level of high purity, stability. 3. Exclusive “Bonpure” seven-step purification technology, high purity（up to 99%) and stability of production of NMNH powder 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMNH powder 5. Provide one-stop product solution customization service
Advantages of NADH
NADH: 1. Bonzyme whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive Bonpure seven-step purification technology, purity up higher than 98 % 3. Special patented process crystal form, higher stability 4. Obtained a number of international certifications to ensure high quality 5. 8 domestic and foreign NADH patents, leading the industry 6. Provide one-stop product solution customization service
Advantages of NAD
NAD: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Stable supplier of 1000+ enterprises around the world 3. Unique “Bonpure” seven-step purification technology, higher product content and higher conversion rate 4. Freeze drying technology to ensure stable product quality 5. Unique crystal technology, higher product solubility 6. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products
Advantages of MNM
NMN: 1. “Bonzyme”Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive“Bonpure”seven-step purification technology, high purity（up to 99.9%) and stability 3. Industrial leading technology: 15 domestic and international NMN patents 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products 5. Multiple in vivo studies show that Bontac NMN is safe and effective 6. Provide one-stop product solution customization service 7. NMN raw material supplier of famous David Sinclair team of Harvard University
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Bontac Bio-Engineering (Shenzhen) Co., Ltd. (hereafter referred to as BONTAC) is a high-tech enterprise established in July 2012. BONTAC integrates R&D, production and sales, with enzyme catalysis technology as the core and coenzyme and natural products as main products. There are six major series of products in BONTAC, involving coenzymes, natural products, sugar substitutes, cosmetics, dietary supplements and medical intermediates.
As the leader of the global NMN industry, BONTAC has the first whole-enzyme catalysis technology in China. Our coenzyme products are widely used in health industry, medical & beauty, green agriculture, biomedicine and other fields. BONTAC adheres to independent innovation, with more than 170 invention patents. Different from the traditional chemical synthesis and fermentation industry, BONTAC has advantages of green low-carbon and high-value-added biosynthesis technology. What’s more, BONTAC has established the first coenzyme engineering technology research center at the provincial level in China which also is the sole in Guangdong Province.
In the future, BONTAC will focus on its advantages of green, low-carbon and high-value-added biosynthesis technology, and build ecological relationship with academia as well as upstream/downstream partners, continuously leading the synthetic biological industry and creating a better life for human beings.
What NMN Supplements Do?
NMN supplements are mainly used to increase NAD+ levels to improve metabolic diseases and slow down the aging process.
Improve metabolic diseases: Studies have shown that NMN can improve the symptoms of metabolic diseases such as diabetes, fatty liver and obesity.
Delay the aging process: NMN can increase the vitality of cells, improve the metabolic process of cells, and delay the aging process.
Protect DNA: NAD+ is an important metabolic substance in cells and participates in various biological processes such as cellular energy metabolism and DNA repair. Supplementing NMN can increase NAD+ levels and protect DNA.
Improves Athletic Capacity: NMN has been shown to improve athletic performance and increase fat burning ability
Improve neurodegenerative diseases: Studies have shown that NMN can improve neurodegenerative diseases, such as Alzheimer's disease
However, these studies were small, and NMN has not been shown to be effective in clinical trials, so further research is needed to determine the effectiveness of NMN supplements.
What are the purposes of NMN supplements?
NMN supplements are mainly used to increase NAD+ levels to improve metabolic diseases and slow down the aging process.
Improve metabolic diseases: Studies have shown that NMN can improve the symptoms of metabolic diseases such as diabetes, fatty liver and obesity.
Delay the aging process: NMN can increase the vitality of cells, improve the metabolic process of cells, and delay the aging process.
Protect DNA: NAD+ is an important metabolic substance in cells and participates in various biological processes such as cellular energy metabolism and DNA repair. Supplementing NMN can increase NAD+ levels and protect DNA.
Improves Athletic Capacity: NMN has been shown to improve athletic performance and increase fat burning ability
Improve neurodegenerative diseases: Studies have shown that NMN can improve neurodegenerative diseases, such as Alzheimer's disease
What diseases can NMN supplements treat?
NMN (Nicotinamide Mononucleotide) is a substance similar to vitamin B3, which can produce NAD+ (a key metabolic intermediate) in the body. Therefore, studies have shown that NMN may help improve aging-related health issues such as metabolism, immunity, cell repair, brain health, and more.
Currently, NMN supplements are mainly used to treat the following diseases:
Aging-related metabolic disorders such as diabetes, obesity, high cholesterol, etc.
Aging-related neurodegenerative diseases, such as Alzheimer's disease.
Aging-associated immune decline.
Aging-related cardiovascular disease.
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Frequently Asked Question
Do you have any question?
NMN supplements may cause side effects such as upset stomach, diarrhea, and nausea. There is also research showing that NMN supplements may affect insulin sensitivity and insulin levels, so people with diabetes should consult their doctor before taking them.
NMN supplements have not yet undergone large-scale clinical trials to verify their effectiveness. Currently, research on NMN supplements is mainly focused on animal and in vitro experiments. These studies show that NMN can improve the symptoms of metabolic diseases such as diabetes, fatty liver and obesity, and can delay the aging process.
The long-term health effects of NMN supplementation are not well studied. Existing studies mainly focus on animal and in vitro experiments, which show that NMN can improve the symptoms of metabolic diseases such as diabetes, fatty liver and obesity, and can delay the aging process. However, the results of these studies do not represent the long-term effects of NMN on human health.
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The latest research proves: Coenzyme NAD+ can enhance tumor immunity! Expert Comment from Chinese Academy of Sciences
On August 10, 2021, researchers from Shanghai University of Science and Technology published an article titled NAD+ supplement potentiates tumor killing function by rescuing defective TUBBY-mediated NAMPT transcription in tumor infiltrated T cells in Cell Reports, revealing that NAD+ in supplemented during CAR-T therapy and immune checkpoint inhibitor therapy, it can improve the anti-tumor activity of T. At present, the supplementary precursor of NAD+, as a nutritional product,has been verified for human consumption safety.This achievement provides a simply and feasible new method for improving the anti-tumor activity of T cells. Cancer immunotherapies including the adoptive transfer of naturally occurring tumor-infiltrating lymphocytes (TILs) and genetically engineered T cells, as well as the use of immune checkpoint blockade (ICB) to boost the function of T cells, have emerged as promising approaches to achieve durable clinical responses of otherwise treatment-refractory cancers (Lee et al., 2015; Rosenberg and Restifo, 2015; Sharma and Allison, 2015). Although immunotherapies have been successfully used in the clinic, the number of patients benefiting from them is still limited (Fradet et al., 2019; Newick et al., 2017). Tumor microenvironment (TME)-related immunosuppression has emerged as the major reason for low and/or no response to both immunotherapies (Ninomiya et al., 2015; Schoenfeld and Hellmann, 2020). Therefore, efforts to investigate and overcome TME-related limitations in immune therapies are of great urgency. The fact that immune cells and cancer cells share many fundamental metabolic pathways implies an irreconcilable competition for nutrients in TME (Andrejeva and Rathmell, 2017; Chang et al., 2015). During uncontrolled proliferation, cancer cells hijack alternative pathways for more rapid metabolite generation (Vander Heiden et al., 2009). As a consequence, nutrient depletion, hypoxia, acidity, and generation of metabolites that can be toxic in the TME may hinder successful immunotherapy (Weinberg et al., 2010). Indeed, TILs often experience mitochondrial stress within growing tumors and become exhausted (Scharping et al., 2016). Interestingly, multiple studies also indicate that metabolic changes in TME could re-shape T cell differentiation and functional activity (Bailis et al., 2019; Chang et al., 2013; Peng et al., 2016). All these evidences inspired us to hypothesize that metabolic reprogramming in T cells might rescue them from a stressed metabolic environment, thereby reinvigorating their anti-tumor activity (Buck et al., 2016; Zhang et al., 2017). In this current study, by integrating both genetic and chemical screens, we identified that NAMPT, a key gene involved in NAD+ biosynthesis, was essential for T cell activation. NAMPT inhibition led to robust NAD+ decline in T cells, thereby disrupting glycolysis regulation and mitochondrial function, blocking ATP synthesis, and dampening the T cell receptor (TCR) downstream signaling cascade. Building on the observation that TILs have relatively lower NAD+ and NAMPT expression levels than T cells from peripheral blood mononuclear cells (PBMCs) in ovarian cancer patients, we performed genetic screening in T cells and identified that Tubby (TUB) is a transcription factor for NAMPT. Finally, we applied this basic knowledge in the (pre) clinic and showed very strong evidence that supplementation with NAD+ dramatically improves the anti-tumor killing activity both in adoptively transferred CAR-T cells therapy and immune check point blockade therapy, indicating their promising potential for targeting NAD+ metabolism to better treat cancers. 1.NAD+ regulates the activation of T cells by affecting energy metabolism After antigen stimulation, T cells undergo metabolic reprogramming, from mitochondrial oxidation to glycolysis as the main source of ATP. While maintaining sufficient mitochondrial functions to support cell proliferation and effector functions.Given that NAD+ is the main coenzyme for redox, the researchers verified the effect of NAD+ on the level of metabolism in T cells through experiments such as metabolic mass spectrometry and isotope labeling. The results of in vitro experiments show that NAD+ deficiency will significantly reduce the level of glycolysis, TCA cycle and electron transport chain metabolism in T cells. Through the experiment of replenishing ATP, the researchers found that the lack of NAD+ mainly inhibits the production of ATP in T cells, thereby reducing the level of T cell activation. 2.The NAD+ salvage synthesis pathway regulated by NAMPT is essential for T cell activation The metabolic reprogramming process regulates the activation and differentiation of immune cells. Targeting T cell metabolism provides an opportunity to modulate the immune response in a cellular way. Immune cells in the tumor microenvironment, their own metabolic level will also be correspondingly affected. The researchers in this article have discovered the important role of NAMPT in the activation of T cells through genome-wide sgRNA screening and metabolism-related small molecule inhibitor screening experiments. Nicotinamide adenine dinucleotide (NAD+) is a coenzyme for redox reactions and can be synthesized through the salvage pathway, de novo synthesis pathway, and Preiss-Handler pathway. The NAMPT metabolic enzyme is mainly involved in the NAD+ salvage synthesis pathway. Analysis of clinical tumor samples found that in tumor-infiltrating T cells, their NAD+ levels and NAMPT levels were lower than other T cells. Researchers speculate that NAD+ levels may be one of the factors that affect the anti-tumor activity of tumor-infiltrating T cells. 3.Supplement NAD+ to enhance the anti-tumor activity of T cells Immunotherapy has been exploratory research in cancer treatment, but the main problem is the best treatment strategy and the effectiveness of immunotherapy in the overall population. Researchers want to study whether enhancing the activation ability of T cells by supplementing NAD+ levels can enhance the effect of T cell-based immunotherapy. At the same time, in the anti-CD19 CAR-T therapy model and anti-PD-1 immune checkpoint inhibitor therapy model, it was verified that supplementation of NAD+ significantly enhanced the tumor-killing effect of T cells. The researchers found that in the anti-CD19 CAR-T treatment model, almost all mice in the CAR-T treatment group supplemented with NAD+ achieved tumor clearance, while the CAR-T treatment group without NAD+ supplemented only about 20 % Of mice achieved tumor clearance. Consistent with this, in the anti-PD-1 immune checkpoint inhibitor treatment model, B16F10 tumors are relatively tolerant to anti-PD-1 treatment, and the inhibitory effect is not significant. However, the growth of B16F10 tumors in the anti-PD-1 and NAD+ treatment group could be significantly inhibited. Based on this, NAD+ supplementation can enhance the anti-tumor effect of T cell-based immunotherapy. 4.How to supplement NAD+ The NAD+ molecule is large and cannot be directly absorbed and utilized by the human body. The NAD+ directly ingested orally is mainly hydrolyzed by brush border cells in the small intestine. In terms of thinking, there is indeed another way to supplement NAD+, which is to find a way to supplement a certain substance so that it can synthesize NAD+ autonomously in the human body. There are three ways to synthesize NAD+ in the human body: Preiss-Handler pathway, de novo synthesis pathway and salvage synthesis pathway. Although the three ways can synthesize NAD+, there is also a primary and secondary distinction. Among them, the NAD+ produced by the first two synthetic pathways only accounts for about 15% of the total human NAD+, and the remaining 85% is achieved through the way of remedial synthesis. In other words, the salvage synthesis pathway is the key to the human body to supplement NAD+. Among the precursors of NAD+, nicotinamide (NAM), NMN and nicotinamide ribose (NR) all synthesize NAD+ through a salvage synthesis pathway, so these three substances have become the body's choice for supplementing NAD+. Although NR itself has no side effects, in the process of NAD+ synthesis, most of it is not directly converted into NMN, but needs to be digested into NAM first, and then participate in the synthesis of NMN, which still cannot escape the limitation of rate-limiting enzymes. Therefore, the ability to supplement NAD+ through oral administration of NR is also limited . As a precursor for supplementing NAD+, NMN not only bypasses the restriction of rate-limiting enzymes, but is also absorbed very quickly in the body and can be directly converted into NAD+. Therefore, it can be used as a direct, rapid and effective method to supplement NAD+. Expert Reviews: Xu Chenqi (Excellence and Innovation Center of Molecular Cell Science, Chinese Academy of Sciences, Immunology Research Expert) Cancer treatment is a problem in the world. The development of immunotherapy has made up for the limitations of traditional cancer treatment and expanded the treatment methods of doctors. Cancer immunotherapy can be divided into immune checkpoint blocking therapy, engineered T cell therapy, tumor vaccine, etc. These treatment methods have played a certain role in the clinical treatment of cancer. At the same time, this also makes the current focus of immunotherapy research on how to further enhance the effect of immunotherapy and expand the beneficiaries of immunotherapy.
Maternal NAD Precursor Supplementation to Reduce the Risk of Developing CNDD
1. Introduction Nicotinamide adenine dinucleotide (NAD) has been unveiled to be essential for embryonic development. Patients with genetic variants in the NAD+ de novo synthesis pathway often have congenital NAD deficiency disorder (CNDD), a multisystem condition inherited in an autosomal recessive manner. In the context of NAD+ deficiency, all organs and systems, not just vertebrae, heart, kidneys, and limbs, may be affected. 2. The association between NAD synthetase 1 (NADSYN1) and CNDD Individuals delivering biallelic NADSYN1 variants share similar clinical features to those with CNDD. Up till now, almost all of the identified CNDD cases can be attributed to biallelic loss-of-function variants in any of 3 nonredundant genes of the NAD de novo synthesis pathway, including kynureninase (KYNU), 3-hydroxyanthranilate 3,4-dioxygenase (HAAO), or NADSYN1. Among individuals with CNDD identified to date, those with biallelic pathogenic NADSYN1 variants are the most diverse in phenotype. 3. The impact of NADSYN1 variants upon enzymatic activity and phenotype Specifically, NADSYN1 can catalyse the amidation of nicotinic acid adenine dinucleotide (NaAD) to NAD. Biallelic pathogenic variants in NADSYN1 cause a metabolic block in both the de novo pathway and the Preiss-Handler pathway, leading to NAD deficiency. Biallelic NADSYN1 loss-of-function variants impact the NAD metabolome of humans. Post-birth phenotypes involve feeding difficulties, developmental delay, short stature, etc. 4. Mouse embryogenesis disrupted by the loss of NADSYN1 In NADSYN1-/- mouse embryos, NAD-dependent malformations occur when maternal dietary NAD precursors are limited during gestation. The affected Nadsyn1-/- embryos most frequently present malformations of the kidneys, eyes, and lungs. 5. The preventative effect of amidated NAD precursor supplementation against CNDD NADSYN1-dependent embryo loss and malformation in mice are preventable by dietary supplementation of amidated NAD precursors (NMN and NAM) during pregnancy. Maternal diet–derived NAD precursors primarily determine the development of healthy embryos. 6. Conclusion NAD-boosting supplements are essential for individuals with biallelic loss-of-function variants in NADSYN1. Maternal NAD precursor supplementation, to some extent, can reduce the risk of developing CNDD. Reference Szot JO, Cuny H, Martin EM, et al. A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder. J Clin Invest. 2024;134(4):e174824. Published 2024 Feb 15. doi:10.1172/JCI174824 About BONTAC BONTAC has been dedicated to the R&D, manufacture and sale of raw materials for coenzyme and natural products since 2012, with self-owned factories, over 170 global patents as well as strong R&D team consisting of Doctors and Masters. BONTAC has rich R&D experience and advanced technology in the biosynthesis of NAD and its precursors (eg. NMN and NR), with various forms to be selected (eg. endoxin-free IVD-grade NAD, Na-free or Na-containing NAD; NR-CL or NR-Malate). High quality and stable supply of products can be better ensured here with the exclusive Bonpure seven-step purification technology and Bonzyme Whole-enzymatic method. Disclaimer This article is based on the reference in the academic journal. The relevant information is provide for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC. Under no circumstances will BONTAC be held responsible or liable in any way for any claims, damages, losses, expenses, costs or liabilities whatsoever (including, without limitation, any direct or indirect damages for loss of profits, business interruption or loss of information) resulting or arising directly or indirectly from your reliance on the information and material on this website.
How to Reconcile the Axonal Degeneration Caused by NMN Accumulation with the Anti-ageing Effect of NMN
1. Introduction The NAD precursor nicotinamide mononucleotide (NMN) shows a beneficial effect on ageing, yet excessive NMN accumulation may lead to axon degeneration. How to make the anti-ageing effect of NMN compatible with axonal degeneration caused by NMN accumulation is still a challenge. A preliminary discussion on this issue is conducted in this study. 2. The definition and pathological changes of axonal degeneration Axonal degeneration refers to degenerative changes in the axon as a result of direct damage to the primary or as a result of diseases such as neuronal metabolic disorders, which is a common pathological change of the nervous system. The pathological changes after axonal injury include axonal swelling, fracture, retraction and atrophy. 3. The relationship between NMN and sterile alpha and TIR motif–containing 1 (SARM1) SARM1 is a multi-functional enzyme with base exchange activity, which can cleave nicotinamide adenine dinucleotide (NAD) into adenosine diphosphate ribose (ADPR), cyclic adenosine diphosphate ribose (cADPR) and nicotinamide (NAM). A substantial body of evidence mirrors that the degenerative enzyme SARM1 will be bound to and be activated by NMN. Hence, failed conversion of sufficient NMN into NAD may give rise to toxic NMN accumulation and axon degeneration. 4. The specific pathway of axon degeneration NMN only induces axon degeneration in the presence of SARM1, placing the toxic accumulation on a common pathway of axon death. Notably, nicotinamide mononucleotideadenylyltransferases (NMNATs) has a broader, compartment-specific regulatory role in SARM1 activity. For instance, NMNAT2 depletion is associated with SARM1 activation in axons. In a nutshell, NMNAT2 depletion can give rise to NMN accumulation. Next, NMN binds to and activates the pro-degenerative protein SARM1, leading to rapid NAD consumption and axon degeneration. 5. The impacts of NAD precursors upon axonal health NAD precursors are likely to be safe for most people, but there is a risk for people with compromised NMNAT activity, as these supplements could cause SARM1 activation and neurodegeneration. In healthy individuals, rapid conversion from NMN into NAD can be accomplished by NMNAT2, which is conductive to the prevention of NMN toxic accumulation and maintenance of healthy neurons and axons. Yet, downregulation of NMNAT2 level or activity may result in the upregulation of NMN, thereby leading to SARM1 activation, increased axonal vulnerability and/or axon degeneration. 6. The factors for SARM1 activity SARM1 activity is regulated by a ratio between NMN and NAD. When NMN rises, partial inhibition of SARM1 is only seen at high concentrations of NAD. Inefficient conversion of NMN into NAD because of compromised NMNAT activity is the most likely scenario in which NMN can become toxic. The change in NMN level close to the physiological concentration has a much more significant impact on SARM1 activity than NAD level. A twofold increase in NAD level is not sufficient to delay axon degeneration after injury, and even higher NAD level only temporarily delays axon degeneration. 7. The interaction between SARM1 activation and ageing effect of NMN Sub-lethal/chronic SARM1 activation could increase axonal vulnerability or have a significant impact upon NAD homeostasis and important intracellular signalling pathways in neurons.It is pivotal for life to preserve NAD homeostasis. Maintaining NAD homeostasis could be a viable anti-ageing strategy. Similarly, NMNAT2 depletion increases axon vulnerability and the level of the NMNAT2 is declined with ageing. These findings signify that SARM1 and NMNAT2 may be the key factor to reconcile the axonal degeneration caused by the accumulation of the NAD precursor NMN and ageing effect of NMN. 8. Conclusion Efficient conversion of NMN into NAD is key to preventing SARM1 activation and neurotoxicity. SARM1 and NMNAT2 may be the intersection factors between axon degeneration and anti-ageing therapy. Reference Loreto, Andrea et al. “NMN: The NAD precursor at the intersection between axon degeneration and anti-ageing therapies.” Neuroscience research vol. 197 (2023): 18-24. doi:10.1016/j.neures.2023.01.004 BONTAC NMN product features and advantages * Industrial leading technology: 15 domestic and international NMN patents * Self-owned factories and a number of international certifications to ensure high quality and stable supply of products * NMN raw material supplier of famous David Sinclair team of Harvard University Disclaimer BONTAC shall hold no responsibility for any claims arising directly or indirectly from your reliance on the information and material on this website.