NMN Production Methods: Which is the best Manufacturing Process for purest NMN, Fermentation Method, Biological Enzyme method, or Chemical synthesis?

 

Although aging is inevitable, there are healthy opportunities to slow down the process, thanks to nicotinamide mononucleotide (NMN). Nicotinamide mononucleotide (NMN) is a precursor to Nicotinamide adenine dinucleotide (NAD+) which is an important biomarker in the human cell. As we get older, this chemical is depleted as a result of several enzyme functions. That's why the NAD+ levels start to decrease, so we need to replenish them for the cells to function properly.

 

One important thing to pay attention to is that, unlike most anti-aging supplements that have intolerable side effects, there are no adverse effects detected while taking NMN supplementation. Also, NMN extends lifespan. There are several ways for NMN production that we will address.

 

NMN production methods

 

When we are talking about the manufacturing process, we generally speak about synthesis. Synthesis is combining two or more small compounds to make one large compound. Biosynthesis is using a plant or microorganism to syntheses the target molecule. In both processes, the final product needs to undergo extraction, isolation, and purification to obtain high purity raw material.

 

NMN can be produced via three production methods, including:

 

Fermentation method

 

Fermentation is the biochemical decomposition of a substance by bacteria, yeast, or other microorganisms. A bioprocess that uses microorganisms to produce either acid or alcohol from carbohydrate sources such as sugars and fiber. These metabolites (substances obtained by "decomposition", in this case, acid or alcohol )preserve food and create unique flavors, textures, and increased nutritional value of products.

 

One way to produced NMN is by yeast fermentation. All the raw materials used in this process are at high prices. The NMN product at the end is of high purity, and it can be also difficult to mass-produce due to the high cost for the people. We know that NMN naturally can be found in many plants such as broccoli, cucumber, cabbage, and avocado. It is very hard to obtain NMN from these plants, because the presence of NMN in them is very small, so it will require tons of plants to get just a small amount of NMN, which also there will be losses through the extraction process. The product stability is really poor too. Because of the low yield of this method, and high cost, the fermentation method is not defined as the best method for NMN manufacturing.

 

Biological enzyme method

 

In the biological enzyme method, enzymes take place. Enzymes are proteins that act as catalysts for the reaction. The enzyme used in the process must be activated under certain conditions so the reaction can occur. Once the enzyme is inactivated or contaminated, the reaction can't proceed and that can impact the final product.

 

NMN is produced from NAM (nicotinamide) with the help of the NAMPT (nicotinamide phosphoribosyltransferase) enzyme, where NMN attaches a phosphate called PRPP (5’-phosphoribosyl-1-pyrophosphate). With this enzymatic process, it is obtained high purity NMN which can be also mass-produced. Not only high purity but high percent yield is improved as well. The final NMN product is stable, with a small molecule structure, lightweight, has poor fluidity, low density, and is easy to absorb. The level of purity is related to the purity of the enzyme used in the process, and also to the absorption effect. The only disadvantage is the low pH level of 3, which makes the product very unstable. That's why there are certain requirements for packaging and storing. With this method, the purity of NMN ranges from 99-99.99%, which makes it more expensive.

 

Chemical Synthesis

 

In chemical synthesis, two or more compounds are combined to form a single one. The raw materials used in this method are from unnatural sources. What makes this method better than others, is the fact that all raw ingredients, that undergo the reaction, can be accurately and carefully controlled. This offers better visibility of the temperature, pressure, solvents, and other steps.  The main problem is that the impurities and other by-products from this reaction can be hard to remove. This will lead to health problems in the future. The chemical method offers an extensive range of mass production and has the potential of increased yield with a faster way of production.

 

NMN is produced through Zincke's reaction. N-(2,4- dinitrophenyl)-3-carbamoylpyridinium chloride (compound A) and 2′,3′- O-isopropylidene-α/β-D-ribofuranosylamine (compound B) are the main two compound that takes place in the reaction. With these compounds, the yield ranges between 16-22%. If the Zincke’s reaction starts with 5-phospho ribose and is later converted to 5-phosphorylated aminoribose as a compound C, the yield ranges from 24-60%.

 

However, the raw ingredients used in the chemical synthesis can be harmful to the environment, and bring limitations in food and health products. This method has problematic compounds, which leads to decreased yield and high cost.

 

Which is the best method for purest NMN?

 

All these different methods have advantages and disadvantages. When talking about the best way for NMN production, we should consider all steps including the cost, mass production, the yield, safety, the raw ingredients used, their safety for the environment, and many other conditions.

 

In the manufacturing process, we want to ensure that we obtained high-purity NMN product. With the fermentation process is hard to produce large amounts of NMN because the ingredients used in the method are from a natural source and have a very little amount of NMN. This is a really long, high-cost, and low-yield process.

 

On the other hand, the chemical process is more practical because you have control over every step taken in the reaction. However, the product produced with this method is quite costly, because some of the ingredients are problematic, which is related to health safety and product purity.

 

To sum up, the better way to manufacture Nicotinamide mononucleotide (NMN) is by the biological enzyme method. The final NMN product has a purity of 99% to 99.99%, which means it can be easier and faster for absorption. Also, it can be mass-produced at a controllable and affordable price. It is safe to consume, and no adverse effects were reported. This kind of raw NMN substance is considered to have the best and most effective absorption power.

 

References

• Imai, Shin-ichiro. (2009). Nicotinamide Phosphoribosyltransferase (Nampt): A Link Between NAD Biology, Metabolism, and Diseases.
  Current Pharmaceutical Design, Volume 15, Number 1, 2009, pp. 20-28(9)

IMPORTANT: This infomation is not intended to diagnose, treat, cure, or prevent any disease, and it should not be used by anyone who is pregnant or under the care of a medical practitioner. Please consult your physician about which supplements may or may not be right for you.