Natural Moisturising Factor

Natural moisturising factor (NMF) is a mix of small water-soluble molecules packed inside the corneocytes (the flattened dead cells of the stratum corneum). Its main parts are free amino acids, the amino-acid derivatives pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA), inorganic salts (chlorides, phosphates and citrates of sodium, potassium, calcium and magnesium), sugars, lactic acid (lactate) and urea. It makes up about 10% of corneocyte mass and 20–30% of the dry weight of the stratum corneum (Practical Dermatology review). NMF components are strong humectants. They pull water into the corneocytes even at 50% relative humidity, and the bound water keeps the skin barrier elastic and stops it cracking. NMF also supplies the water that the desquamation enzymes need to work. PCA is the largest single component.

Natural Moisturising Factor [part-of] skin barrier Natural Moisturising Factor [prevents] Transepidermal Water Loss

Derivation from filaggrin. Most NMF comes from breakdown of Filaggrin. Profilaggrin is cut into filaggrin, which lines up keratin filaments. Its arginines are then converted to citrulline, which loosens the filaggrin–keratin complex. Proteases (caspase-14 and others) then break it down completely into free amino acids. Filaggrin provides 70–100% of the free amino acids in the stratum corneum. Glutamine turns into PCA, and histidine turns into urocanic acid (Practical Dermatology review; Agrawal & Woodfolk 2014). Filaggrin breakdown depends on humidity. In dry air it happens deeper in the stratum corneum. Occlusive patches can stop it altogether, which suggests that heavy, constant occlusion may slow the skin’s own NMF production (Practical Dermatology review). This has not been studied in children with eczema.

Filaggrin [causes] Natural Moisturising Factor

NMF in eczema. Kezic et al. (Allergy 2011) used tape strips to compare 96 patients with moderate–severe Atopic Dermatitis and 24 controls. Levels of PCA, UCA and histidine followed FLG genotype: carriers of loss-of-function mutations had the least. Levels were also lower in AD patients without mutations than in controls. The authors concluded that “decreased NMF is a global feature of moderate-to-severe AD”, with FLG genotype as the main determinant and disease severity as a secondary one. This fits the idea that Th2 inflammation itself suppresses filaggrin (Th2 Immune Response). NMF is almost absent in Ichthyosis Vulgaris, which is caused by FLG mutations. Soap washing and UV remove NMF from the outermost layers (Practical Dermatology review). This is one reason for using Soap Substitutes and sealing in moisture straight after the bath (Soak and Seal).

Atopic Dermatitis [worsens] Natural Moisturising Factor Ichthyosis Vulgaris [relates] Natural Moisturising Factor Sodium Lauryl Sulfate [worsens] Natural Moisturising Factor Soak and Seal [relates] Natural Moisturising Factor

Link to skin pH. Amino acids from filaggrin and their acidic derivatives (UCA, PCA) help keep the stratum corneum acidic (Skin pH). When NMF is low, pH rises. A higher pH activates serine proteases (kallikreins) that break down corneodesmosomes and downstream lipid processing that makes Ceramides, and favours colonisation by Staphylococcus aureus (Elias & Wakefield 2011; Agrawal & Woodfolk 2014; Acta Derm Venereol review). The Filaggrin note sets out the disagreement over whether this chain starts eczema or follows from inflammation.

Natural Moisturising Factor [regulates] Skin pH Skin pH [relates] Staphylococcus aureus Skin pH [relates] Ceramides

What this means for emollient choice in toddlers. Several NMF components have long been added to moisturisers as humectants. Urea has been used since 1943 and lactate since 1946. Skin urea is low in AD, and topical urea (or its precursor arginine) corrects this (Practical Dermatology review). Lactic acid may also stimulate ceramide synthesis. In young children the trade-off is stinging. Medscape notes that children with acute or fissured eczema feel urea sting, and prefers 10% over higher strengths. In a split-arm RCT of excoriated eczema in children aged 8–16, a ceramide-based cream caused less irritation than 5% urea cream (VAS 0.69 vs 1.43, p=0.035; Ho et al. 2020). No equivalent trial in under-5s was found. A practical approach is a bland or ceramide-containing emollient on broken or inflamed toddler skin, with low-strength urea (≤5–10%) kept for intact, dry, rough skin if tolerated (Urea Creams, Ceramides). This is an inference from the sources, not a guideline recommendation. The BEE Trial found no emollient type (lotion, cream, gel, ointment) better overall, and it did not compare active ingredients such as urea or ceramides (Emollient Therapy).

Urea Creams [supports] Natural Moisturising Factor Ceramides [relates] Emollient Therapy Urea Creams [part-of] Emollient Therapy

Connections

• Skin Barrier Dysfunction — loss contributes to dryness and raised pH, source: Agrawal & Woodfolk 2014
• Filaggrin — source of 70–100% of stratum corneum free amino acids, PCA and UCA, source: Practical Dermatology; Kezic 2011
• Atopic Dermatitis — NMF reduced globally in moderate–severe AD, source: Kezic 2011
• Skin pH — NMF acids keep stratum corneum acidic, source: Agrawal & Woodfolk 2014
• Urea Creams — urea is an NMF component replaced topically; stings in children, source: Practical Dermatology; Ho 2020
• Ceramides — lactate may stimulate ceramide synthesis; ceramide cream less irritating than urea, source: Practical Dermatology; Ho 2020
• Soak and Seal — soap washing strips NMF; seal step holds water, source: Practical Dermatology
• Ichthyosis Vulgaris — FLG-mutation disorder with near-absent NMF, source: Practical Dermatology
• Transepidermal Water Loss — NMF-bound water limits evaporation, source: Agrawal & Woodfolk 2014