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Natural moisturizing factor (NMF) is found inside keratinocytes and helps regulate stratum corneum (SC) hydration. NMF is a mixture of amino acids including pyrrolidone carboxylic and urocanic acids,1,2 which are water-soluble byproducts of filaggrin.

Filaggrin, also known as filament aggregating protein, has two different cutaneous functions. In lower levels of the skin, filaggrin plays a structural role; however, higher up in the skin, it is broken down into amino acids that are hygroscopic and strongly bind water. Histidine, glutamine, and arginine are metabolites of filaggrin in the SC that are metabolized into trans-urocanic acid, pyrrolidone carboxylic acid, and citrulline, respectively. They create the osmotically active component that regulates skin hydration known as NMF.1,3 Other constituents of NMF include lactic acid, urea, and inorganic ions such as sodium, potassium, calcium, and chloride, all of which contribute to epidermal hydration. The osmotically active and humectant properties of NMF allow the epidermis to retain hydration even in dry environments. Extraction of NMF components results in a decrease in the moisture accumulation rate (MAT) of the epidermis,4 emphasizing the importance of NMF in skin hydration. Interestingly, NMF constituents undergo seasonal changes: the breakdown of filaggrin and production of NMF increase in low humidity and decrease in high humidity. NMF is intracellular and at this time it is not known if exogenously applied NMF or its precursors would result in increased NMF levels.

Patients with atopic dermatitis exhibit a reduction in NMF and have been found to have mutations in the filaggrin gene.6,7 A defect in filaggrin also results in a structural impairment that is seen in atopic dermatitis because filaggrin plays a structural role in lower levels of the epidermis.8 NMF levels are decreased by ultraviolet exposure, surfactants, and prolonged water immersion.


1. +
Scott  IR, Harding  CR, Barrett  JG. Histidine-rich protein of the keratohyalin granules. Source of the free amino acid, urocanic acid and pyrrolidone carboxylic acid in the stratum corneum. Biochim Biophys Acta. 1982;719:110.  [PubMed: 7171620]
2. +
Horii  I, Kawasaki  K, Koyama  J,  et al. Histidine-rich protein as a possible origin of free amino acids of stratum corneum. Curr Probl Dermatol. 1983;11:301.  [PubMed: 6653157]
3. +
Elias  PM. Stratum corneum defensive functions: an integrated view. J Invest Dermatol. 2005;125:183.  [PubMed: 16098026]
4. +
Visscher  MO, Tolia  GT, Wickett  RR,  et al. Effect of soaking and natural moisturizing factor on stratum corneum water-handling properties. J Cosmet Sci. 2003;54:289.  [PubMed: 12858228]
5. +
Nakagawa  N, Sakai  S, Matsumoto  M,  et al. Relationship between NMF (lactate and potassium) content and the physical properties of the stratum corneum in healthy subjects. J Invest Dermatol. 2004;122:755.  [PubMed: 15086563]
6. +
Weidinger  S, Illig  T, Baurecht  H,  et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic ...

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