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.
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.
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.
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.
Introduction NADH (reduced form of NAD+) serves as a carrier of biological hydrogen and an electron donor, which participates in diverse physiological processes such as protein synthesis, DNA repair, insulin synthesis and secretion, immune response and cell division, playing a critical role in promoting health span and mitigating various disease states. Major enzymatic reactions in substrate metabolism that are dependent upon NAD+/NADH ratio The equilibrium of the NAD+/NADH ratio is vital for maintaining cellular reduction–oxidation (redox) homeostasis and modulating energy metabolism. Several enzymatic reactions in substrate metabolism are carried out in a NAD+/NADH ratio-dependent way. For instance, ketones suppress the increased mitochondrial production of ROS associated with excitotoxic injury by enhancing NADH oxidation (i.e. elevated NAD+/NADH ratio) in the electron transport chain, directly affecting NADH level . NADH in Krebs cycle and glycolysis NADH is produced in glycolysis and the Krebs cycle (also known as citric acid cycle or tricarboxylic acid cycle), which can transfer energy to supply ATP synthesis through the process of oxidative phosphorylation in the inner membrane of the mitochondria. Krebs cycle supplies NADH as an electron carrier to the electron transport chain in mitochondria, while glycolysis-produced NADH can be used by L-lactate dehydrogenase (LDH) or transported to the mitochondria for redox homeostasis. The effects of NADH on the mitochondria are accomplished by specialized shuttle systems (e.g., malate-aspartate or glycerol-3-phosphate). The possible strategies to modulate NADH level The main NAD/NADH biosynthetic pathways include de novo synthesis from tryptophan (TRP), synthesis from either form of vitamin B3, nicotinamide (NAM) or nicotinic acid (NA), or conversion of nicotinamide riboside (NR). Correspondingly, NADH level can be regulated by replenishing NADH precursors (eg. NR and NMN), applying NADH dehydrogenase inhibitors, having diets rich in certain nutrients (eg. vitamin B3), administrating mitochondrial targeting agents and supplementing exogenous NADH. Conclusion NADH may be a versatile therapeutic candidate by leverage of its ability to affect redox homeostasis, mitochondrial functions, and enzymatic reactions. Reference Schiuma G, Lara D, Clement J, Narducci M, Rizzo R. NADH: the redox sensor in aging-related disorders. Antioxid Redox Signal. Published online February 17, 2024. doi:10.1089/ars.2023.0375 BONTAC NADH 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 and over 170 global patents including 8 NADH patents. The purity of BONTAC NADH can reach over 98%. BONTAC NADH has been widely applied in anti-aging health products, diagnostic reagent raw materials, HCY Homocysteine Test Kit, Biomedical R&D, and functional food and beverage. Our products are subjected to strict third-party self-inspection, which are worth of trustworthy. 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.
Introduction Solute carrier family 25 member 51 (SLC25A51) is perceived as a mammalian transporter, which is capable of importing oxidized nicotinamide adenine dinucleotide (NAD+) into mitochondrial matrix. Remarkably, upregulation of SLC25A51 has correlation with poorer outcomes in patients with acute myeloid leukemia (AML), a clinically aggressive haematological disease with a mortality rate of over 70% within the first 5 years following an initial diagnosis. The association between NAD+/NADH ratio and SLC25A51 in AML cells Both NAD+ (oxidative form) and NADH (reduced form) are essential coenzymes for cellular energy metabolism, and the ratio of NAD+/NADH reflects the metabolic activity and health state, which has a direct impact on cellular rhythms, senescence, carcinogenesis and death. Importing mitochondrial NAD+ by SLC25A51 could be a critical aspect supporting mitochondrial metabolism in AML tumorigenesis. Concretely, the decreased mitochondrial NAD+/NADH ratio and specific loss of reduced ubiquinol are observed post the depletion of SLC25A51 in AML cells U937. SLC25A51 as an NAD+/NADH redox decoupler in AML SLC25A51 functions as an NAD+/NADH redox decoupler in AML tumorigenesis to sustain an oxidative TCA cycle and promote glutaminolysis. Depletion of SLC25A51 results in increased usage of non-glutamine carbon sources to support the TCA cycle, as determined by increased proportions of unlabeled TCA intermediates. SLC25A51 is required for robust glutaminolysis. In the context of SLC25A51 depletion, AML cells are forced to rely more on glutamine for aspartate synthesis. Alleviation of AML by SLC25A51 depletion and 5-azacytidine Loss of SLC25A51 leads to a subcellular redistribution of NAD+ in AML cells to limit proliferation. The combination of SLC25A51 depletion and 5-azacytidine is much effective in repressing the viability of AML cells and prolonging the survival time of mice. Conclusion SLC25A51 can maintain mitochondrial oxidative phosphorylation and boost the proliferation of AML cells by regulating NAD+/NADH ratio in mitochondria, with promising efficacy in treating AML, especially in combination with 5-azacytidine. BONTAC NAD 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 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 Mitochondria are the center of energy metabolism in cardiomyocytes, which are necessary for maintaining normal myocardial contractility and cardiac function. Typically, the development of cardiovascular disease is usually accompanied by mitochondrial dysfunction. Impaired autophagy is known to cause mitochondrial dysfunction and heart failure, in part due to altered mitophagy and protein quality control. Notably, external replenishment of nicotinamide adenine dinucleotide (NAD+) precursors can enhance autophagy and mitochondrial quality control to maintain metabolic health, thereby regulate mitochondrial and cardiac function. 2. NAD+ metabolism in mitochondrial and cardiac function Cardiomyocytes accumulate NAD+ mostly within their mitochondria, where the bulk of cellular oxidation-reduction reactions occur. However, NAD+ is also present in the cytosol and nucleus, in which NAD+-derived metabolites and NAD+-dependent enzymes contribute to various cellular functions. 3. Mitochondrial and cardiac dysfunction induced by NAD+ deficiency Mitochondrial and cardiac dysfunction triggered by NAD+ deficiency is alleviated in cAtg3-KO mouse hearts post the administration of β-nicotinamide mononucleotide (NMN), as evidenced by the restoration of citrate synthase (CS) activity, partial normalization of ATP level and NPPB mRNA expression in cAtg3-KO mice as well as upregulation of ADP level in WT mouse hearts. Besides, NNMT inhibition can rescue mitochondrial and cardiac dysfunction in cAtg3-KO mice by restoring NAD+ level. 4. The impact of autophagic flux upon cardiac and mitochondrial function Autophagy is an intracellular degradation pathway that recycles subcellular components, playing a critical in modulating metabolic homeostasis. Autophagic flux, a central homeostatic mechanism that degrades materials toxic to cardiomyocytes, can mediate SQSTM1-NF-κB-NNMT signal transduction to control the cellular level of NAD+, thereby maintaining the mitochondrial and cardiac function. 5. Conclusion Autophagic flux may be a potential way to maintain the cellular level of NAD to regulate mitochondrial and cardiac fiunction. . Reference [1] Abdellatif M, Sedej S, Kroemer G. NAD+ Metabolism in Cardiac Health, Aging, and Disease. Circulation. 2021;144(22):1795-1817. doi:10.1161/CIRCULATIONAHA.121.056589 [2] Zhang Q, Li Z, Li Q, et al. Control of NAD+ homeostasis by autophagic flux modulates mitochondrial and cardiac function. EMBO J. Published online January 11, 2024. doi:10.1038/s44318-023-00009-w About BONTAC 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 160 domestic and foreign patents, leading the industry of coenzyme and natural products. In the future, BONTAC will actively expand the international market, and work with global partners to promote the prosperous development of synthetic biology industry. In this era full of challenges and opportunities, BONTAC is confident to make greater contributions to the cause of human health. 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.