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
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
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
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
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.
According to recent industrial report, only several products from worldwide NMN manufacturers came close to meeting label claim and contain not enough NMN. Almost products performed better, having at least 88% of the label claim up to small overages. A lone 250 mg product was identified as BRL. In sum, ChromaDex said that 64% of the products tested contained less than 1% of the stated amount of the active ingredient. which should give consumers pause. While this is a limited snapshot of the vast NMN finished product landscape. it does provide a glimpse into the high variability of product quality that is available. The majority of the products may purchase online contain such a small amount of NMN that there would be no clinical benefits achieved from the dose. Another concern with these adulterated products is that the actual contents are not known and could pose a risk to the user the company said in a statement.
1、“Bonzyme”Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder
2、Exclusive“Bonpure”seven-step purification technology, high purity(up to 99.9%) and stability of production of NMN powder
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 of NMN powder
5、Multiple in vivo studies show that Bontac NMN powder 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.
NMN powder in general is typically produced via chemical or enzymatic synthesis, or fermentation biosynthesis. There are pros and cons to all three methods.
Chemical synthesis is expensive and labor intensive, and all raw ingredients used are categorized as “unnatural,” i.e., not from biological systems. There are, however, some advantages from the manufacturer’s perspective. The yield is well suited to mass NMN powder production, and all of those unnatural raw ingredients can be carefully controlled. But there are a number of drawbacks as well. Some of the solvents used in the manufacturing process are seriously bad from an environmental standpoint, and impurities and by-products can be challenging to remove from the finished product – that’s seriously bad for the consumer.
Enzymatic production of NMN powder, on the other hand, is considered a “green preparation method.” Like the chemical route, it’s pricey, but it offers a higher yield and impressively high purity. The finished NMN ticks all the boxes – stable, easily absorbed, lightweight, low density, and a low molecular structure.
Fermentation has also been explored as a method of producing NMN, but yield, though high quality, is pretty abysmal, so many supplement companies quite sensibly look to other, more efficacious processes.
1.Raw material production process
Bioenzyme catalysis is a popular production method in the industry. It has a high threshold and several key catalytic enzymes are expensive, accounting for about 80% of the overall production process cost, but it is also the safest and most efficient production method. In the production of NMN by bioenzyme catalysis, the use of food-grade raw materials is an important part of the process to ensure product safety and to ensure that standards are followed.
2.High standard of production conditions
Production conditions refer to the standard of labor consumption required to complete the qualified products of the unit under certain production organization and production technology conditions. There are certifications issued by regulatory authorities, such as cGMP in the United States, TGA in Australia, GMP in Japan, etc.
3.High standard of product testing.
Product testing requires reliable test methods and reagents that are used throughout the production process. They are not only inspection standards for the final product, but also for the intermediate stages of control, including testing of active ingredients, testing of heavy metals such as lead, arsenic and mercury, and testing of pathogenic bacteria, microorganisms and processing by-products.
For NMN products, the commonly used method for active ingredient content testing is high performance liquid chromatography (HPLC), which is efficient, accurate and precise. For different manufacturers, the standards for testing reagents are different. Strict manufacturers will purchase high purity, analytically pure reagents from third party standards companies as controls.
4.Safety assessment
For relatively new raw materials such as NMN, it is not enough for consumers to judge the safety of the product on the side of the merchant alone. At this point, the third-party authoritative assessment report is particularly important.
Currently, there are two generic safety assessment reports, one is a toxicological assessment report and the other is a safety assessment report. In China, toxicological assessment reports usually account for the majority. However, there are still few NMN companies that can issue such reports
5.Storage and Packaging
NMNs are usually stored in sealed containers for up to 12 months. If it can be stored for 24 months with insignificant changes in purity, the stability of NMN is very reliable. Currently, the more common packaging materials are pet or hope, which are pharmaceutical packaging materials. They are non-toxic, odorless, lightweight, portable and effectively isolate air and moisture.
The safety of NMN powder cannot be assessed since required clinical and toxicological studies have not been completed yet to establish the recommended safe levels for long term administration. Nevertheless, their safety and efficacy are uncertain and unreliable since most of them have not been backed up by rigorous scientific preclinical and clinical testing. This issue has been arisen as manufacturers are hesitant to pay for research and clinical trials due to potential lower profit margin, and there is no authorizing agency to regulate NMN products because it is often sold as functional food product rather than heavily regulated therapeutic drug. Therefore, more strict approval process has been demanded by consumer advocacy groups requesting regulatory agencies to set standard and restrictions for marketing anti-aging health products, considering safety, health and wellbeing of consumers. NMN should not be considered as a panacea for the elderly, because boosting NAD levels when not required may yield some detrimental effects. Therefore, the dose and frequency of NMN supplementation should be carefully prescribed depending on the type of age-related deficiency and all other confronting health conditions of the people. Other NAD precursors have been studied to discover the efficacy for diverse age-related deficiencies and they are used for particular deficiencies, only after they are proven for effectiveness and safe to use. Therefore, the same principle should be applied to NMN as well
First, inspect the factory. After some screening, NMN companied that directly face consumers pay more attention to brand building. Therefore, for a good brand, quality is the most important thing, and the first thing to control the quality of raw materials is to inspect the factory. Bontac company actually manufacturing NMN powder of high quality with the caterias of SGS. Secondly, the purity is tested. Purity is one of the most important parameters of NMN powder. If high purity NMN cannot be guaranteed, the remaining substances are likely to exceed the relevant standards. As the attached certificates demonstrates that the NMN powder produced by Bontac reach the purity of 99.9%. Finally, a professional test spectrum is needed to prove it. Common methods for determining the structure of an organic compound include Nuclear Magnetic Resonance Spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). Usually through the analysis of these two spectra, the structure of the compound can be preliminarily determined.
With the epidemic control policies loosening worldwide, residents in China, India, Malaysia, Japan and Singapore have suffered a shortage of medicines to varying degrees. But on the other hand, the type of medicines available to the public is dynamically increasing, and at present the anti-Covid-19 stars available on the market include Paxlovid, NMN, etc. What are the similarities and differences between the two in terms of mechanism of preventing and treating the Coronavirus? It is necessary to briefly make out the principle of Covid-19 infection in human cells before discussing the mechanism of action of Paxlovid and NMN. How SARS-CoV-2 infect cells? First, the mature Covid-19 (as shown in Figure 1) is mainly composed of structure proteins including spike (S) protein, nucleocapsid (N) protein, membrane (M) protein and envelope (E) protein and RNA viral gene. Figure 1. SARS-Cov-2 structure The SARS-CoV-2 opens a channel into the cell by its S protein through recognizing and binding to the ACE2 protein receptor of host cells in vivo. After entering the host cell, the SARS-CoV-2 initiates transcription and translation activities, replicating plenty of SARS-CoV-2, disrupting the cell structure and interfering with the normal cell function. Under this mechanism of action, the supplement of medicine directly comes into play on the sides of spike S protein of the Covid-19 and the ACE2 protein of host cells in human body. Paxlovid prevents the synthesis of S proteins of SARS-CoV-2. The mechanism of Paxlovid to treat Covid-19 Paxlovid was made up with two main ingredients, Nirmatrelvir and Ritonavir. Nirmatrelvir combats SARS-CoV-2 by blocking the synthesis of S proteins.The gene information of all SARS-CoV-2 proteins only take over 1/3 of the right side of RNA strand (as shown in Figure 2), and the remaining 2/3 of the RNA gene strand is used for transcription and translation for multiple proteins to synthesize the polyprotein. After the polyprotein is synthesized, it will be cleaved into several functional proteins likely S protein by virus proteases. Figure 2. RNA structure In short, when the SARS-CoV-2 replicates, the RNA initiates transcription and translation for proteins in bulk and then proteases cleave it to form structural proteins (S protein). The main proteases used when replicating is CL3. Nirmatrelvir of Paxlovid binds to the CL3 protease to prevent the cleavage of the SARS-CoV-2 polyprotein so as to interrupt the protein synthesis of viral. (As shown in Figure 3). What’s more, another ingredient, Ritonavir, works by maintaining the concentration of Nirmatrelvir in the body, prolonging and enhancing its efficacy and maintaining the interruption strength for the replicating protease CL3. Figure 3.CL3 in translation The mechanism of NMN to prevent and treat Covid-19 NMN prevents Covid-19 infection by protecting DNA and reducing ACE2 expression, shutting down the pathway of ACE2 protein into human cells. The researchers found that DNA damages accumulates intracellular ACE2 receptor proteins. However, these two enzymes to repair DNA damage, sirtuins and PARP, need to be to motivated by NAD+. Studies showed that NMN supplementation is effective in increasing NAD+ levels and thus reducing ACE2 protein expression. As it demonstrates that experiment proved that a reduction in ACE2 expression after infected with the SARS-CoV-2, along with a reduction in viral load and tissue damage in the lungs (as shown in Figure 4) based on the situation that 200mg/kg of NMN fed to old mice aged 12 months for 7 days. Figure 4. NMN performance in recuding viral loads The study not only reaffirms the convincing for NMN to treat Covid-19 infection, but based on its proven ability to reduce lung pathological damage and even death in mice infected with neointima, NMN may be used in clinical trials to treat patients with Covid-19 infection. It is clear from the above principles of action that both Paxlovid and NMN work on original source of infection to treat and prevent Covid-19. The difference between the two is that Paxlovid interferes with the replication of the virus while NMN closes the door to the entry of Covid-19 into human cells. Both different mechanisms of action are in principle effective in preventing the invasion of Covid-19. References 1. FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR PAXLOVID, 2022 2. Jin R., Niu C.,et al. DNA damage contributes to age-associated differences in SARS-CoV-2 infection, Aging Cell, 2022
Introduction Nicotinamide mononucleotide (NMN), one precursor of nicotinamide adenine dinucleotide (NAD+), has been ascertained to be implicated with multiple biological processes such as cellular redox regulation and metabolism as well as DNA repair. Herein, post-hoc analysis of a double-blinded clinical trial is carried out. On the premise of safety, to optimize NMN utilization, personalized dosage regimen can be developed by monitoring the NAD concentration. Research protocol A total of 80 healthy middle-aged adults (age: 40 to 65) are enrolled in the randomized, double-blinded, controlled clinical trial of NMN supplementation, who are randomly assigned into four groups and administrated with placebo or NMN (300 mg, 600 mg, or 900 mg) for 60 days. The clinical data including age, sex, body mass index (BMI), blood biological age, homeostatic model assessment for insulin resistance (HOMA-IR), blood NAD concentration, 6-minute walk test and 36-item short-form survey (SF-36), along with adverse events, are collected at baseline and after supplement, followed by comparison and correlation analysis. The association of participant clinical data at baseline and after supplement of NMN NAD concentration change (NADΔ) is dose-dependently increased post NMN supplementation, with a large coefficient of variation (29.2–113.3%) within group. Notably, only HOMA-IR has a prominent association with blood baseline NAD. As a whole, NMN supplementation has a positive impact on the physical endurance and general health conditions of healthy adults, as evidenced by the obvious improvement of six-minute walking distance, blood biological age, and SF-36 score. In addition, the increase of about 15 nmol/L in NADΔ is related to clinically improvements in the walking distance of 6-minute walk test and the SF-36 score. The safety oral dose of NMN in clinical trials As demonstrated by the registered clinical trials NCT04823260 and CTRI/2021/03/032421, NMN supplementation can boost blood NAD concentration, which is safe and well tolerated with daily oral administration of 900 mg. Strikingly, clinical efficacy expressed by blood NAD concentration and physical performance reaches highest at a dose of 600 mg daily oral intake. Conclusion Blood NAD concentration is increased by NMN supplement at a dose-dependent manner. Personalized regimen of NMN supplement should be based on the close monitoring of NAD concentration change. In addition to longer follow-up duration and large sample size, future trials on the efficacy of NMN supplement should pay much attention to the factors affecting baseline NAD concentration. Reference [1] Kuerec AH, Wang W, Yi L, et al. Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration. Mech Ageing Dev. 2024;218:111917. doi:10.1016/j.mad.2024.111917 [2] Song Q, Zhou X, Xu K, Liu S, Zhu X, Yang J. The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update. Adv Nutr. 2023;14(6):1416-1435. doi:10.1016/j.advnut.2023.08.008 BONTAC NMN As David Sinclair, a famous professor of genetics at Harvard University, once pointed out in an interview, NMN has unstable molecular structure, which is easily degraded into nicotinamide if stored in the conventional environment. The satisfactory efficacy of NMN cannot be guaranteed if the quality and purity NMN products are not high. BONTAC is the first choice of NMN raw material suppliers worldwide, who has dedicated to the manufacture of raw material for enzyme and natural products for 12 years, with self-owned factory, 173 patents and professional R&D team. The purity of BONTAC NMN can reach up to 99.5%. Also, BONTAC is the NMN raw material supplier of David Sinclair team, who uses the raw materials of BONTAC in a paper titled “Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging”. Our services and products have been highly recognized by global partners. The coenzyme products of BONTAC are widely used in fields such as nutritional health, biomedicine, medical beauty, daily chemicals and green agriculture. Disclaimer This article is based on the reference in the academic journal. The relevant information is provided 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.
1. Introduction Gastric cancer (GC) represents a global health-care challenge, which is the fifth most common cancer and the fourth leading cause of cancer death across the world in 2020, with a significant incidence rate. Despite the efficacy of improved chemotherapy and surgical options, the prognosis of GC patients remains unsatisfactory. Remarkably, NAD+ is an intriguing target for cancer therapy by leverage of its impacts upon energy metabolism and pathway regulation. This research is engineered to probe into the magic roles of NAD+ metabolism-associated genes (NMRGs) in GC. 2. The establishment of prognostic risk model for GC patients Based on the expression levels of NAD+ metabolism-related genes in GC cell lines, a prognostic model is established for GC patients. Simply put, a total of 13 lncRNAs related to NMRGs are singled out by LASSO regression to construct prognostic risk model, with seven markedly up-regulated lncRNAs and six prominently down-regulated lncRNAs in GC tissues, as confirmed by real-time polymerase chain reaction. On this basis, six lncRNAs with the minimum likelihood of deviance corresponding to the first-rank value of Log (k) are chosen, followed by the plotting of model AUC and calculation of the risk score. The detailed calculation formula is listed below: risk score = AL139147.1 × (0.416) + AC107021.2 × (0.3119) + AC090825.1 × (0.1218) + AC005726.2 × (−0.0.0062) + AC012615.1 × (−0.0130) + AP001107.6 × (−0.0451). It is found that patients with high-risk scores have a poor prognosis. 3. The correlation between immune factors and risk scores The levels of immune cell infiltration, including CD8 T cells, CD4 naïve T cells, CD4 memory-activated T cells, B memory cells, and naïve B cells, are markedly associated with risk scores. Besides, high-risk patients show activated immune checkpoints as well as high immune and stromal scores. 4. The role of NAD+ in the metabolism of GC patients NAD+ not only promotes GC progression, but also promotes immune cell infiltration into tumors. The modulation of NAD+ is significant for the metabolism of GC patients. 5. Conclusion NMRGs may be promising biomarkers for predicting clinical outcomes of GC patients and ultimately facilitating their precise management. Reference Sun, X., Wen, H., Li, F., Bukhari, I., Ren, F., Xue, X., Zheng, P., & Mi, Y. (2023). NAD+ associated genes as potential biomarkers for predicting the prognosis of gastric cancer. Oncology research, 32(2), 283–296. https://doi.org/10.32604/or.2023.044618 BONTAC NAD and NMN BONTAC has rich R&D experience and advanced technology in the biosynthesis of NAD and NMN. Bonzyme whole-enzymatic method is adopted, which is environmental-friendly, with no harmful solvent residues. The purity of products can reach up to 95%, which is benefited from the exclusive Bonpure seven-step purification technology. BONTAC has self-owned factories and has obtained a number of international certifications, where high quality and stable supply of products can be ensured. BONTAC has over 170 domestic and foreign patents, leading the industry of coenzyme and natural products. 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.