1. Direct NAD+ Administration (SubQ/IM) Has Poor Cellular Uptake

NAD+ (nicotinamide adenine dinucleotide) is a large, charged molecule that struggles to penetrate cell membranes when injected intramuscularly (IM) or subcutaneously (SubQ). This is due to:

• Polarity and Size: NAD+ is highly hydrophilic, meaning it does not easily cross lipid bilayers.

• Extracellular Degradation: Once in circulation, NAD+ is rapidly broken down by ectonucleotidases (CD38 and CD73) into its precursors, such as NMN and nicotinamide (NAM), before cells can absorb it.

Scientific Evidence:

• Camacho-Pereira et al. (2016) demonstrated that CD38 degrades NAD+ within minutes in vivo, limiting its bioavailability.

• Grozio et al. (2013) showed that extracellular NAD+ does not efficiently enter cells and must first be degraded into NMN or NAM before uptake.

2. NMN is a More Efficient Precursor for Boosting Intracellular NAD+

Nicotinamide mononucleotide (NMN) is the direct precursor to NAD+ and has a dedicated transporter (Slc12a8) that allows for rapid and efficient uptake into cells, particularly in the small intestine.

• Sublingual Bioavailability:

• NMN is absorbed directly into the bloodstream through the oral mucosa, bypassing first-pass metabolism, leading to higher cellular uptake compared to injections.

• Sublingual absorption allows for immediate NMN uptake into circulation, while injected NAD+ is largely broken down before utilization.

Scientific Evidence:

• Research by Yao et al. (2018) identified Slc12a8 as an NMN transporter, demonstrating direct uptake into enterocytes and subsequent NAD+ synthesis.

• Mills et al. (2016) showed that NMN supplementation increased NAD+ levels in muscle and liver within minutes, proving its rapid bioavailability.

3. Biofermented NMN is More Biologically Compatible

Biofermented NMN has higher purity, better stability, and improved bioavailability compared to synthetic versions. This allows for sustained NAD+ elevation without the instability and degradation issues of injected NAD+.

• Unlike synthetic NMN, biofermented NMN mimics natural biosynthetic pathways, leading to higher intracellular retention and utilization.

• Injected NAD+ lacks direct transport mechanisms and is quickly broken down, making biofermented NMN the far superior option for maintaining NAD+ homeostasis.

Scientific Evidence:

• Chini et al. (2020) highlighted how NMN supplementation preserves NAD+ pools without excessive degradation compared to direct NAD+ administration.

• Yoshino et al. (2011) demonstrated that NMN enhances mitochondrial function and energy metabolism more effectively than NAD+ injections.

Conclusion: Why Sublingual Biofermented NMN is Superior

✅ Better Bioavailability – Sublingual NMN is absorbed directly into circulation without degradation.

✅ Efficient Cellular Uptake – Uses Slc12a8 transporters, ensuring rapid intracellular conversion to NAD+.

✅ Sustained NAD+ Levels – Bypasses CD38 degradation and supports longer-lasting NAD+ elevation.

✅ Mitochondrial Support – NMN supplementation is proven to enhance ATP production and cellular energy.

❌ SubQ/IM NAD+ is Inefficient – Rapid degradation and poor cellular permeability make it a wasteful and less effective method.