β-Nicotinamide Mononucleotide (NMN)-

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1. Introduction

β-Nicotinamide Mononucleotide (NMN) is a direct precursor of nicotinamide adenine dinucleotide (NAD+), playing a pivotal role in energy metabolism, DNA repair, and cellular aging regulation. With the rise of anti-aging research, NMN has become a focal point in both scientific circles and the nutraceutical market due to its ability to significantly boost NAD+ levels in vivo.

Studies show that NAD+ levels in mammals decline markedly with age, while NMN supplementation can improve metabolic function and delay age-related diseases (Imai & Guarente, 2014). Currently, NMN has entered clinical trials and is marketed as a dietary supplement in several countries. This article provides a comprehensive analysis of NMN's chemical properties, biological activity, applications, and market competition.

 

 

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2. Chemical Properties and Production Process

1. Chemical Structure

NMN has the molecular formula C₁₁H₁₅N₂O₈P, a molecular weight of 334.22 g/mol, and appears as a white to light yellow crystalline powder at room temperature. It is highly soluble in water (>50 mg/mL) but prone to degradation in acidic or high-temperature environments (Sigma-Aldrich, 2023).

 

2. Primary production approaches include:

   • Enzymatic Catalysis: Uses nicotinamide (NAM) and 5-phosphoribosyl-1-pyrophosphate (PRPP) as substrates, catalyzed by nicotinamide phosphoribosyltransferase (NAMPT) (Revollo et al., 2004). This method yields high purity (>99%) but at a higher cost.

   • Chemical Synthesis: Generated through phosphorylation of ribose and nicotinamide, requiring multiple purification steps (Yoshino et al., 2018). Lower cost but may retain organic solvent residues.

 

 

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3. Mechanism of Action and Biological Activity 

NAD+ Biosynthesis Pathway

NMN enters cells via the Slc12a8 transporter and is converted to NAD+ by nicotinamide mononucleotide adenylyltransferase (NMNAT) (Grozio et al., 2019). NAD+ serves as a coenzyme in key processes:

   • Energy Metabolism: Supports mitochondrial TCA cycle and oxidative phosphorylation (Cantó et al., 2015).

   • DNA Repair: Activates PARP (poly-ADP-ribose polymerase) to repair DNA damage (Bai et al., 2011).

   • Aging Regulation: Enhances Sirtuins (deacetylases) activity, delaying cellular senescence (Imai & Guarente, 2016).

 

 

Experimental Evidence

   • Animal Studies: Mice orally administered 300 mg/kg/day NMN for 8 weeks showed 50% improved mitochondrial function and 10% lifespan extension (Mills et al., 2016).

   • Clinical Trials: A Phase I trial in healthy elderly subjects demonstrated that 250 mg/day NMN significantly improved insulin sensitivity and muscle function (Yoshino et al., 2021).).

 

 

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4. Applications

Research Applications

   • Aging Mechanism Studies: Investigates links between NAD+ metabolism and age-related diseases (e.g., diabetes, Alzheimer's) (Fang et al., 2017).

   • Metabolic Disease Models: Reverses hepatic steatosis in high-fat-diet-induced obese mice (Uddin et al., 2020).

 

 

Pharmaceutical Development

   • Clinical Trials:

  ——Diabetes: A Phase II trial combining NMN with metformin showed 30% better glycemic control (NCT03151239).

    ——Cardiovascular Disease: Preliminary data indicate NMN improves vascular endothelial function (de Picciotto et al., 2016).

 

Dietary Supplements

   • Market Products: Examples include Japan’s Shinkowa NMN 9000 (150 mg/capsule) and Elysium Health’s "Basis," marketed for "anti-aging."

  

 

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5. Comparative Analysis of Similar Products

1. NAD+ Precursor Comparison

Compound	Molecular Weight (g/mol)	Bioavailability	Clinical Stage	Side Effects	Price ($/g)
NMN	334.22	Moderate-High	Phase II (Anti-aging)	None severe reported	300-500
NR (Nicotinamide Riboside)	255.25	Low	Phase III (Cancer)	Flushing, GI upset	100-200
Niacin (NA)	123.11	Low	Marketed (Vitamin)	Skin flushing	10-20

   • Analysis:   

  ——NMN: Superior bioavailability but higher cost;

  ——NR: Requires conversion to NMN, less efficient;

  ——NA: Low-cost but may cause vasodilation at high doses (Trammell et al., 2016).

 

2. Commercial Anti-Aging Supplements Comparison

Brand	Key Ingredient	Dose per Serving	Monthly Cost ($)	Certifications
Elysium Health	NMN + Resveratrol	250 mg	60	FDA-GRAS, NSF
Shinkowa	Pure NMN	150 mg	120	Japan JHFA Certified
Tru Niagen	NR	300 mg	50	Self-reported

   • Analysis:   

  ——Combination Formulas (e.g., Elysium): Pair NMN with resveratrol to enhance Sirtuin activation;

  ——Pure NMN Products (e.g., Shinkowa): Target premium markets with higher pricing (Market Research Future, 2023).

 

 

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6. Safety and Toxicological Data

   • Acute Toxicity: Rat oral LD50 > 2000 mg/kg, no fatalities (Shade, 2020).

   • Chronic Toxicity: No liver/kidney damage in mice after 6 months at 500 mg/kg/day (Yoshino et al., 2021).

   • Human Tolerance: Mild headaches reported in a few subjects at 250 mg/day (NCT03151239).

 

 

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7. Market Status and Competitive Landscape

Per Global Market Insights (2023), the global NAD+ supplement market is projected to grow at 12.3% CAGR, reaching $350 million by 2030. NMN currently holds 40% market share, competing mainly with NR (35%) and emerging NAD+ injectables (15%).

Competitive Strategies:

   • Technology Optimization: Develop stabilized formulations (e.g., enteric-coated capsules) to improve absorption;

   • Indication Expansion: Explore NMN for neurodegenerative diseases (e.g., Parkinson’s).

 

 

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8. Future Prospects

1. Research Directions:

   • Targeted Delivery Systems: Nano-carriers to deliver NMN to specific tissues (e.g., brain);

   • Combination Therapies: Synergistic anti-aging effects with senolytics (Baker et al., 2023).

 

2. Regulatory Challenges:

   • FDA has not yet approved NMN as a dietary supplement; more long-term safety data needed (FDA, 2022).

 

 

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References

   • Imai, S., & Guarente, L. (2014). Cell Metabolism.

   • Yoshino, J., et al. (2018). Nature Communications.

   • Sigma-Aldrich. (2023). Product Information: β-Nicotinamide Mononucleotide.

   • Mills, K. F., et al. (2016). Cell Metabolism.

   • Global Market Insights. (2023). NAD+ Supplements Market Report.

 

β-Nicotinamide Mononucleotide (NMN) Specification

If you're interested in β-Nicotinamide Mononucleotide (NMN) into your supplement formulations, please reach out to JX Nutritional Chemical Co., Limited team. We will reply you as soon as possible.