Permeation Performance of NMN in an Artificial Membrane

Nicotinamide mononucleotide (NMN), the direct precursor of NAD⁺, has recently become the centerpiece of anti-aging cosmetics. Yet its cutaneous penetration efficiency and stability remain the chief bottlenecks. A 2025 study systematically evaluated NMN permeation behavior in yeast ferment filtrate (YFF) using the Strat-M artificial membrane model.

Artificial-Membrane Validation
Franz diffusion cells coupled with Strat-M membranes—mimicking human skin’s three-layer architecture (stratum corneum, epidermis, dermis)—revealed pronounced region-specific permeation. MALDI-IMS imaging confirmed that NMN accumulated exclusively in the papillary dermis, the fibroblast-rich active zone, without reaching the deeper reticular dermis or subcutaneous tissue. This settles the long-standing debate over NMN’s ability to breach the stratum corneum: its 334 Da molecular weight (< 500 Da) falls within the ideal range for transdermal uptake, but its hydrophilicity restricts deeper diffusion, directing it precisely to the key site of collagen synthesis.

Stability Breakthrough
Free NMN hydrolyzes rapidly in aqueous media to nicotinamide (NAM) with a half-life of only weeks. The study demonstrated that YFF prolongs NMN activity via three synergistic mechanisms:
Molecular shielding: polysaccharides and organic acids in the yeast ferment stabilize NMN through hydrogen bonding.
Sustained release: the colloidal nature of YFF slows NMN diffusion, extending the half-life to 7 months at 20 °C.
Cooperative degradation: NAM, the degradation product, itself possesses skin-brightening properties, yielding a “dual-benefit” delivery system.

Functional Verification
In vitro, 1 mM NMN-YFF treatment of human fibroblasts for 24 h boosted type I collagen secretion by 120 % (p < 0.05). Mechanistically, NMN elevated intracellular NAD⁺, activated the SIRT1/AMPK pathway, and thereby up-regulated COL1A1 gene expression. Notably, amino acids in YFF—particularly proline and glycine—may serve as collagen-building substrates, creating an additional synergy with NMN.
Paradigms for NMN Skincare Development

Findings provide three design principles:
• Precision delivery: use artificial membranes to screen optimal carriers.
• Formulation engineering: adjust concentration and pH to balance NMN stability versus permeation.
• Benefit extension: exploit the skin-brightening value of NAM, enabling “anti-aging + whitening” hybrid products.

Although artificial membranes cannot fully replicate the dynamic metabolism of living skin, this work is the first to quantify the link between NMN’s transdermal behavior and its biological efficacy, laying the groundwork for clinical trials. Future research should dissect which specific bioactives in YFF modulate NMN permeation and assess long-term safety.

Reference
[1] Betsuno R, Yamane T, Tsuji H, et al. Permeation of Nicotinamide Mononucleotide (NMN) in an Artificial Membrane as a Cosmetic Skin Permeability Test Model. J Cosmet Dermatol. 2025;24(5):e70222.

*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.

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