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.
The preparation methods utilized by manufacturers worldwide of NAD powder are mainly divided into chemical synthesis method and biocatalytic method, among which biocatalytic method includes biological fermentation method and enzyme catalysis method. Enzyme catalysis method has gradually become the mainstream direction because of its advantages of green, environmental protection and pollution-free. And then the purity of NAD powder will reach 99% after the procedure of further purifying. But some NAD manufacturers tend to choose the multiple methods to develop the producing of NAD.
1、As an advanced technology NAD manufacturer, BONTAC choose the Enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder
2、High purity(up to 99%) and stability of production of NAD powder
3、Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NAD powder
4、Multiple in vivo studies show that Bontac NAD powder is safe and effective
5、Provide one-stop product solution customization service
Molecules that can be taken in supplement form to increase NAD levels in the body are referred to by some as “NAD boosters.” Studies conducted over the past six decades suggest that the following are some of the many benefits associated with taking an NAD supplement:
Can Help Restore Mitochondrial Function
Helps Repair Blood Vessels —A 2018 mice study found that supplementation could aid in repair and growth of aged blood vessels. There’s also some evidence it can help manage heart disease risk factors like high blood pressure and high cholesterol.
May Improve Muscle Function — One animal study conducted in 2016 found that degenerative muscles had improved muscle function when supplemented with NAD+ precursors.
Potentially Helps Repair Cells and Damaged DNA — Some studies have found evidence that NAD+ precursor supplementation leads to an increase in DNA damage repair. NAD+ is broken down into two component parts, nicotinamide and ADP-ribose, which combine with proteins to repair cells.
May Help Improve Cognitive Function — Several studies conducted on mice have found that mice treated with NAD+ precursors experienced improvements in cognitive function, learning and memory. Findings have led researchers to believe that NAD supplement may help protect against cognitive decline/Alzheimer’s disease.
May Help Prevent Age-Related Weight Gain — A 2012 study showed that when mice fed a high-fat diet were given an NAD supplement, they gained 60 percent less weight than they did on the same diets without the supplement. One reason this may be true is that nicotinamide adenine dinucleotide helps regulate production of stress- and appetite-related hormones, thanks to its effects on circadian rhythms.
Precursors are molecules used in chemical reactions inside the body to create other compounds. There are a number of precursors of NAD+ that result in higher levels when you consume enough of them.
1.Prevention and treatment of viral-induced inflammatory storms
Scientists have found after extensive research that neo-coronavirus has a mechanism similar to SARS virus to activate inflammatory vesicles NLRP3. and the activation of NLRP3 produces more inflammatory factors, generating excessive inflammation and thus triggering a deadly cytokine storm. This problem can be well addressed by NAD+, which inhibits the activity of NF-κB inflammatory pathway and NLRP3 inflammasome by increasing the activity of sirtuins (SIRT1, SIRT2 and SIRT3), thus preventing cytokine storm caused by excessive inflammation. Therefore, Sinclair and other scientists believe that increasing the concentration of NAD+ may play an important role in the prevention and treatment of neocoronavirus and other viral infections.
2.Restoration of virus-induced metabolic disorders
NAD+ is an essential coenzyme for many cellular energy metabolic pathways, present in every cell of the body, involved in thousands of reactions, and an important player in maintaining cellular viability. In the COVID-19 infection model, NAD+ and NMN supplementation was found to be effective in alleviating cell death and protecting the lung.
First, inspect the factory. After some screening, NAD manufactures 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 NAD powder of high quality with the caterias of SGS. Secondly, the purity is tested. Purity is one of the most important parameters of NAD powder. If high purity NAD cannot be guaranteed, the remaining substances are likely to exceed the relevant standards. As the attached certificates demonstrates that the NAD 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.
In the international market, NAD+ food supplements are in production in the United States, the Australian Food and Drug Administration has approved NAD+ products for sale, and Japanese NAD+ manufactures are devoted to extend the market share in China. Li Ka-shing invested HK$200 million in the US NAD manufacturer, whose NAD+ products are being sold by Watsons in Hong Kong! Then Mclane, a company owned by Warren Buffett also joined the NAD market.
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 On July 2023, the World Health Organization (WHO) has classified the soda sweetener aspartame as a possible carcinogen, but said that aspartame is safe to consume within a daily limit of 40 milligrams per kilogram of a person’s body weight according to the latest assessment results regarding the impacts of the non-sugar sweetener aspartame upon the health. How about another sweetener stevioside? Is stevioside a sugar reducer or a health killer? 2. Current situation on stevioside Stevioside (also termed stevia glycoside) has been regarded as “the third largest source of natural sugar across the world” by virtue of its low calorie, high sweetness, good stability and low price, which is widely used in medicine, daily chemicals, beverage, food, brewing and other industries. 3. Regulatory application and control of stevioside The aforementioned report of WHO on the possible carcinogenesis of soda sweetener aspartame is based on high intake. An adult weighing 70 kilograms or 154 pounds would have to drink more than 9 to 14 cans of aspartame-containing soda daily to exceed the limit and potentially face health risks. There is no need to be worry about the risk of carcinogenesis in the case of healthy intake. The same situation is applicable to another sweetener stevioside. Stevioside is approved to be sweetener in food in countries like Mainland China, Japan, Korea, Australia, New Zealand, the USA and European Union. In China, there are detail specifications on the food additive stevioside (GB 2760-2014). 4. The therapeutic properties of stevioside 4.1 Antitumor effect Stevioside can be applied as a valuable chemotherapy candidate to be further investigated for cancer therapy. The activity of the well-known tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), is successfully inhibited with stevioside in a murine skin-cancer model. In addition, stevioside can reduce mammary adenoma incidence in F344 rats. 4.2 Anti-hypertensive activity The hypotensive effect observed in rats after chronic oral administration (30 days) of 2.67 g stevia leaves/day has been confirmed in spontaneously hypertensive rats. In that murine model, stevioside (100 mg/kg; i.v.) is able to reduce blood pressure with no change in serum epinephrine, norepinephrine, or dopamine levels. 4.3 Anti-diabetics In diabetic rats, stevioside (0.2 g/kg; i.v. administration) decreases glucose blood levels, yet increases insulin responses and reactions to an intravenous glucose tolerance test (IVGT). Also, stevioside enhances insulin levels above basal during the IVGT, without altering blood glucose response, in normal rats, hinting its potential as a drug candidate for type 2 diabetes. 4.4 Inhibition of pathogenic bacteria Stevioside has demonstrated antibacterial action on various foodborne pathogenic bacteria, including Escherichia coli, a wellknown etiologic agent of severe diarrhea. Regarding antiviral properties, stevioside seems to impede binding of rotavirus to host cells. Rotavirus is commonly associated with pediatric gastroenteritis. 4.5 Anti-inflammatory property In lipopolysaccharide (LPS)-stimulated THP1 cells, stevioside (1mM) inhibits NF-κB. Moreover, stevioside prevents in vitro upregulation of genes involved in liver inflammation. In addition, silico assays demonstrate its antagonistic action in two proinflammatory receptors: tumor necrosis factor receptor (TNFR)-1 and Toll-like receptor (TLR)-4-MD2. 4.6 Antioxidant capability The antioxidant effects of stevioside and rebaudioside A have been confirmed in a fish model, both of which effectively control lipoperoxidation and protein carbonylation. Furthermore, stevioside prevents oxidative DNA damage in the livers and kidneys of a type 2 diabetes murine model. 5 Conclusion As long as the intake is properly controlled, stevioside can be very useful. Stevioside holds a great promise in the clinical treatment and daily health care. Reference Orellana-Paucar A. M. (2023). Steviosides from Stevia rebaudiana: An Updated Overview of Their Sweetening Activity, Pharmacological Properties, and Safety Aspects. Molecules (Basel, Switzerland), 28(3), 1258. https://doi.org/10.3390/molecules28031258 BONTAC Stevioside Reb-D product features and advantages BONTAC possesses the international application and authorized patents on Stevioside Reb-D (US11312948B2 & ZL2018800019752), where the product quality (purity and stability) can be better ensured. Disclaimer BONTAC shall hold no responsibility for any claims arising directly or indirectly from your reliance on the information and material on this website.