Although the stratum corneum is biologically dead but biochemically very active. 70 -100 % of amino acids ( the building blocks of proteins) and their derivatives present in the stratum corneum are breakdown products from the lysis of a protein called Filaggrin, present in the basal layer of the epidermis. The conversion of filaggrin to NMF occurs as the corneocytes are moving to the more superficial layers of the stratum corneum. 

Components of NMF  

NMF is made up of a mixture of pyrrolidone carboxylic acid, urea, lactate (lactic acid)  hyaluronic acid, fatty acids (ceramides)  in addition to amino acids and exist naturally in normal skin. It makes up 20-30% of the dry weight of skin cells.  

a.      Urea is a major component of NMF and has been used in hand creams since the 1940s. In addition to being a strong moisturizing agent it also prevents scaling of the skin and is used to effectively treat dry skin.  

b.      Lactic acid or lactate belongs to a group of compounds called alpha hydroxy acids (AHAs), which are used for the treatment of dry skin-related disorders as well as for their anti-ageing benefits due to the positive effect they have on skin cell renewal and collagen production. They act as chemical exfoliants that remove dead skin cells from the outermost layer of the epidermis, in order to make way for new cell generation. This keeps the complexion looking brighter and evens out discoloration or pigmentation on the skin due to acne scars or age spots. It also improves the flow of blood to the skin, thereby improving the supply of nutrients through oxygen rich blood cells.  

c.       Long chain fatty acids like ceramides help to soothe skin irritation and provide additional barriers to prevent loss of moisture and dry skin. 

d.      Hyaluronic acid is a naturally occurring complex carbohydrate, that plays a pivotal role in wound healing. It is a powerful humectant that is capable of binding more than 1000 times its weight in water. It is also the compound that gives structure and elasticity to the skin . It is therefore often used for its anti-ageing properties, especially when dealing with wrinkles or sagging skin.  

Hyaluronic acid with molecular weight between 50 to 1000 kDA is believed to be the most beneficial for the skin. Studies have shown that if the size of the HA molecule is too large it does not show considerable benefits in skin treatments, and if the molecule is too small it may cause inflammation that in some cases worsen conditions like psoriasis.  

Functions of NMF   

Approximately one-third of the water contained within the stratum corneum is bound to NMF molecules. This hydration is what makes the skin appear healthy and supple, with elastic properties that prevent cracking or flaking due to mechanical stress. The components of NMF are strong humectants, that is they attract water like a magnet . NMF keeps the skin well moisturised by effectively decreasing trans epidermal water loss (TEWL). This moisture is bound and held in the stratum corneum in order to hydrate the skin.  

Atopic dermatitis, psoriasis, ichthyosis vulgaris, and xerosis all give rise to dry and flaky skin. In patients suffering from these  conditions, the levels of NMF in the stratum corneum are either reduced or absent. Ageing, routine soap washing of the skin or excessive exposure to UV light have also been known  to deplete the levels of NMF from the superficial layers of the stratum corneum addition.  

Hence, replacing or replenishing the supply of natural moisturizing components in the skin  by applying moisturizers rich in NMF has been used as a long standing approach for the treatment of dry skin. Interestingly, oils have been used to smoothen skin as early as 2300 B.C. In the 1950s however, research then evolved to focus  on water-imbibing substances or humectants to retain moisture in the skin.  

References 

1.Understanding the role of natural moisturizing factor in skin hydration - practical dermatology. [cited 2021b Jun 8]; Available from: https://practicaldermatology.com/articles/2012-jul/understanding-the-role-of-natural-moisturizing-factor-in-skin-hydration 

2.Rawlings CHV. 18 effects of natural moisturizing factor and lactic acid isomers on skin function [Internet]. Scientificspectator.com. [cited 2021 Jun 8] 

3.https://www.healthline.com/health/beauty-skin-care/ceramide#alongside-other-products 

4.https://www.healthline.com/hyaluronic-acid-for-skin#science-says 

5.Pavicic T, Gauglitz GG, Lersch P, et al. Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. J Drugs Dermatol. 2011;10(9):990-1000.